TARGETED IMMUNOCONJUGATES

[0001] This application claims the benefit of U.S. Prov. Appl. No. 61/234,584, filed Aug. 17, 2009, and European Appl. No. 10162410, filed May 10, 2010, each of which is incorporated herein by reference in its entirety.

[0002] The content of the electronically submitted sequence listing (Name: 19750640001_Sequence_Listing.ascii.txt; Size: 431,626 bytes; Date of Creation: Aug. 16, 2010) filed with this application is incorporated herein by reference in its entirety.

[0003] 1. Field of the Invention

[0004] The present invention generally relates to antigen-specific immunoconjugates for selectively delivering effector moieties that influence cellular activity. In addition, the present invention relates to nucleic acid molecules encoding such immunoconjugates, and vectors and host cells comprising such nucleic acid molecules. The invention further relates to methods for producing the immunoconjugates of the invention, and to methods of using these immunoconjugates in the treatment of disease.

[0005] 2. Background Art

[0006] The selective destruction of an individual cell or a specific cell type is often desirable in a variety of clinical settings. For example, it is a primary goal of cancer therapy to specifically destroy tumor cells, while leaving healthy cells and tissues intact and undamaged. A multitude of signal transduction pathways in the cell are linked to the cell's survival and/or death. Accordingly, the direct delivery of a pathway factor involved in cell survival or death can be used to contribute to the cell's maintenance or destruction.

[0007] Cytokines are cell signaling molecules that participate in regulation of the immune system. When used in cancer therapy, cytokines can act as immunomodulatory agents that have anti-tumor effects and which can increase the immunogenicity of some types of tumors. However, rapid blood clearance and lack of tumor specificity require systemic administration of high doses of the cytokine in order to achieve a concentration of the cytokine at the tumor site sufficient to activate an immune response or have an anti-tumor effect. These high levels of systemic cytokine can lead to severe toxicity and adverse reactions.

[0008] One way to deliver a signal transduction pathway factor, such as a cytokine, to a specific site in vivo (e.g., a tumor or tumor microenvironment) is to conjugate the factor to an immunoglobulin specific for the site. Early strategies aimed at delivering signal transduction pathway factors, such as cytokines, to a specific site in vivo included immunoglobulin heavy chains conjugated to various cytokines, including lymphotoxin, tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and granulocyte macrophage-colony stimulating factor (GM-CSF). The immunoglobulin heavy chains were either chemically conjugated to a cytokine or the immunogobulin-cytokine conjugate was expressed as a fusion protein. See Nakamura K. and Kubo, A. Cancer Supplement 80:2650-2655 (1997); Jun, L. et al., Chin. Med. J. 113:151-153 (2000); and Becker J. C., et al., Proc. Natl. Acad. Sci. USA 93:7826-7831 (1996). Researchers observed that, not only were they able to target cytokines to specific sites in vivo, they were also able to take advantage of the fact that monoclonal antibodies have longer serum half-lives than most other proteins. Due to the systemic toxicity associated with high doses of certain unconjugated cytokines, i.e. IL-2, the ability of an immunoglobulin-cytokine fusion protein to maximize immunostimulatory activities at the site of a tumor whilst keeping systemic side effects to a minimum at a lower dose led researchers to believe that immunoglobulin-cytokine immunoconjugates were optimal therapeutic agents. However, one of the major limitations in the clinical utility of immunoglobulins as delivery agents is their inadequate uptake and poor distribution in tumors, partially due to the large size of the immunoglobulin molecule. See Xiang, J. et al., Immunol. Cell Biol. 72:275-285 (1994). Additionally, it has been suggested that immunoglobulin-cytokine immunoconjugates can activate complement and interact with Fc receptors. This inherent immunoglobulin feature has been viewed unfavorably because therapeutic immunoconjugates may be targeted to cells expressing Fc receptors rather than the preferred antigen-bearing cells.

[0009] One approach to overcoming these problems is the use of engineered immunoglobulin fragments. Numerous studies have detailed the characteristics of immunoglobulin fragment-cytokine immunoconjugates. See Savage, P. et al., Br. J. Cancer 67:304-310 (1993); Harvill, E. T. and Morrison S. L., Immunotechnol. 1:95-105 (1995); and Yang J. et al., Mol. Immunol. 32:873-881 (1995). In general, there are two common immunoglobulin fragment-cytokine fusion protein constructs, the F(ab′)₂-cytokine expressed in mammalian cells and the scFv-cytokine expressed in Escherichia coli. See Xiang, J. Hum. Antibodies 9:23-36 (1999). Both the tumor-binding reactivity of the immunoglobulin parent molecule and the functional activity of the cytokine are maintained in most of these types of immunoconjugates. Recent preclinical studies have shown that these fusion proteins are able to target cytokines to tumors expressing the tumor-associated antigen in vivo, and to inhibit both primary and metastatic tumors in an immune competent animal model.

[0010] Examples of immunoglobulin fragment-cytokine immunoconjugates include the scFv-IL-2 immunoconjugate as set forth in PCT publication WO 2001/062298 A2; the immunoglobulin heavy chain fragment-GM-CSF immunoconjugate as set forth in U.S. Pat. No. 5,650,150; the immunoconjugate as set forth in PCT publication WO 2006/119897 A2, wherein scFv-IL-12 first subunit shares only disulfide bond(s) with IL-12 second subunit-scFv, and the immunoconjugate as described in PCT publication WO 99/29732 A2, wherein Ig heavy chain fragment-IL-12 first subunit shares only disulfide bond(s) with Ig heavy chain fragment-IL-12 second subunit. While these second generation immunoconjugates have some improved properties as compared to the first generation immunoglobulin-cytokine conjugates, development of more and even safer specific therapeutic agents is desirable for greater effectiveness against tumor cells and a decrease in the number and severity of the side effects of these products (e.g., toxicity, destruction of non-tumor cells, etc.). Additionally, it is desirable to identify ways to further stabilize immunoconjugates while maintaining acceptable therapeutic activity levels.

[0011] The present invention provides immunoconjugates that exhibit improved efficacy, high specificity of action, reduced toxicity, and improved stability in blood relative to known immunoconjugates.

[0012] One aspect of the present invention is directed to immunoconjugates that exhibit improved efficacy, high specificity of action, reduced toxicity and improved stability as compared to known immunoconjugates. The immunoconjugates of the present invention can be used to selectively deliver effector moieties to a target site in vivo. In another embodiment, the immunoconjugate delivers a cytokine to a target site, wherein the cytokine can exert a localized biological effect, such as a local inflammatory response, stimulation of T cell growth and activation, and/or activation of B and/or NK cells.

[0013] One aspect of the present invention relates to an immunoconjugate that comprises at least a first effector moiety and at least a first and a second antigen binding moiety independently selected from the group consisting of an Fv and an Fab, wherein a first effector moiety shares an amino- or carboxy-terminal peptide bond with a first antigen binding moiety and a second antigen binding moiety shares an amino- or carboxy-terminal peptide bond with either i) the first effector moiety or ii) the first antigen binding moiety.

[0014] Another aspect of the present invention is an immunoconjugate that comprises at least a first single-chain effector moiety joined at its amino-terminal amino acid to one or more scFv molecules and wherein the first-single-chain effector moiety is joined at its carboxy-terminal amino acids to one or more scFv molecules.

[0015] Another aspect of the present invention is an immunoconjugate that comprises at least a first single-chain effector moiety and first and second antigen binding moieties, wherein each of the first and second antigen binding moieties comprises an scFv molecule joined at its carboxy-terminal amino acid to a constant region comprising a immunoglobulin constant domain independently selected from the group consisting of: IgG CH1, IgG C_kappa, and IgE CH4, and wherein the first antigen binding moiety is joined at its constant region carboxy-terminal amino acid to the amino-terminal amino acid of one of the effector moieties, and wherein the first and second antigen binding moieties are covalently linked through at least one disulfide bond.

[0016] Another aspect of the present invention is an immunoconjugate that comprises at least a first single-chain effector moiety and first and second antigen binding moieties, wherein each of the first and second antigen binding moieties comprises an scFv molecule joined at its carboxy-terminal amino acid to an IgG1 CH3 domain, and wherein the first antigen binding moiety is joined at its carboxy-terminal amino acid to the amino-terminal amino acid of one of the effector moieties, and wherein the first and second antigen binding moieties are covalently linked through at least one disulfide bond.

[0017] Another aspect of the present invention is directed to an immunoconjugate that comprises first and second single-chain effector moieties and first and second antigen binding moieties, wherein each of the antigen binding moieties comprises an Fab molecule joined at its heavy or light chain carboxy-terminal amino acid to an IgG1 CH3 domain, and wherein each of the IgG1 CH3 domains is joined at its carboxy-terminal amino acid to the amino-terminal amino acid of one of the effector moieties, and wherein the first and second antigen binding moieties are covalently linked through at least one disulfide bond.

[0018] In one embodiment, the immunoconjugate comprises the polypeptide sequence of SEQ ID NO: 95. In another embodiment, the immunoconjugate comprises the polypeptide sequence of SEQ ID NO: 104. In another embodiment, the immunoconjugate comprises the polypeptide sequence of SEQ ID NO: 105. In another embodiment, the immunoconjugate comprises the polypeptide sequence of SEQ ID NO: 106. In another embodiment, the immunoconjugate comprises the polypeptide sequence of SEQ ID NO: 107. In another embodiment, the immunoconjugate comprises the polypeptide sequence of SEQ ID NO: 96. In a further embodiment, the immunoconjugate comprises the polypeptide sequence of SEQ ID NO: 96 and a polypeptide sequence selected from the group consisting of SEQ ID NOs: 95 and 104-107. In another embodiment, the immunoconjugate comprises a polypeptide having a sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group consisting of SEQ ID NOs: 95, 96, and 104-107.

[0019] In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 108. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of SEQ ID NO: 108. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 117. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of SEQ ID NO: 117. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 118. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of SEQ ID NO: 118. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 119. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of SEQ ID NO: 119. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 120. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of SEQ ID NO: 120. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 109. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of SEQ ID NO: 109.

[0020] In one embodiment, the immunoconjugate comprises a heavy chain variable region that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 13 or SEQ ID NO: 15. In another embodiment, the immunoconjugate comprises a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 9 or SEQ ID NO: 11. In a further embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 13 or SEQ ID NO: 15, and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 9 or SEQ ID NO: 11.

[0021] In one embodiment, the immunoconjugate comprises a heavy chain variable region sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to either SEQ ID NO: 14 or SEQ ID NO: 16. In another embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is encoded by the polynucleotide sequence of either SEQ ID NO: 14 or SEQ ID NO: 16. In one embodiment, the immunoconjugate comprises a light chain variable region sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to either SEQ ID NO: 10 or SEQ ID NO: 12. In another embodiment, the immunoconjugate comprises a light chain variable region sequence that is encoded by the polynucleotide sequence of either SEQ ID NO: 10 or SEQ ID NO: 12.

[0022] In one embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 99. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 100 or SEQ ID NO: 215. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 101 or SEQ ID NO: 235. In a further embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 100, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 101. In a further embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 215, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 235.

[0023] In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 112. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of SEQ ID NO: 112. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to either SEQ ID NO: 113 or SEQ ID NO: 216. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of either SEQ ID NO: 113 or SEQ ID NO: 216. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to either SEQ ID NO: 114 or SEQ ID NO: 236. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of either SEQ ID NO: 114 or SEQ ID NO: 236.

[0024] In one embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 7, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 187, SEQ ID NO: 191, SEQ ID NO:195, SEQ ID NO: 199, SEQ ID NO: 203 and SEQ ID NO: 207. In another embodiment, the immunoconjugate comprises a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 177, SEQ ID NO: 181, SEQ ID NO:185, SEQ ID NO: 189, SEQ ID NO: 193, SEQ ID NO: 197, SEQ ID NO: 201 and SEQ ID NO: 205. In a further embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 7, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 187, SEQ ID NO: 191, SEQ ID NO:195, SEQ ID NO: 199, SEQ ID NO: 203 and SEQ ID NO: 207 and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 177, SEQ ID NO: 181, SEQ ID NO:185, SEQ ID NO: 189, SEQ ID NO: 193, SEQ ID NO: 197, SEQ ID NO: 201 and SEQ ID NO: 205.

[0025] In one embodiment, the immunoconjugate comprises a heavy chain variable region sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 8, SEQ ID NO: 180, SEQ ID NO: 184, SEQ ID NO: 188, SEQ ID NO: 192, SEQ ID NO: 196, SEQ ID NO: 200, SEQ ID NO: 204 and SEQ ID NO: 208. In another embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is encoded by a polynucleotide sequence selected from the group of SEQ ID NO: 8, SEQ ID NO: 180, SEQ ID NO: 184, SEQ ID NO: 188, SEQ ID NO: 192, SEQ ID NO: 196, SEQ ID NO: 200, SEQ ID NO: 204 and SEQ ID NO: 208. In one embodiment, the immunoconjugate comprises a light chain variable region sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 178, SEQ ID NO: 182, SEQ ID NO: 186, SEQ ID NO: 190, SEQ ID NO: 194, SEQ ID NO: 198, SEQ ID NO: 202 and SEQ ID NO: 206. In another embodiment, the immunoconjugate comprises a light chain variable region sequence that is cncoded by a polynucleotide sequence selected from the group of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 178, SEQ ID NO: 182, SEQ ID NO: 186, SEQ ID NO: 190, SEQ ID NO: 194, SEQ ID NO: 198, SEQ ID NO: 202 and SEQ ID NO: 206.

[0026] In one embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 239, SEQ ID NO: 241 and SEQ ID NO: 243. In another embodiment, the conjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 245, SEQ ID NO: 247 and SEQ ID NO:249. In a further embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 239, SEQ ID NO: 241 and SEQ ID NO: 243, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 245, SEQ ID NO: 247 and SEQ ID NO:249.

[0027] In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 240, SEQ ID NO: 242 and SEQ ID NO: 244. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by a polynucleotide sequence selected from the group of SEQ ID NO: 240, SEQ ID NO: 242 and SEQ ID NO: 244. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 246, SEQ ID NO: 248 and SEQ ID NO: 250. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence selected from the group of SEQ ID NO: 246, SEQ ID NO: 248 and SEQ ID NO: 250.

[0028] In one embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group consisting of: SEQ ID NO: 21, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 31, SEQ ID NO: 35, SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, SEQ ID NO: 69, SEQ ID NO: 73, SEQ ID NO: 77, SEQ ID NO: 81, SEQ ID NO: 85, SEQ ID NO: 89, SEQ ID NO: 93, SEQ ID NO: 123, SEQ ID NO: 127, SEQ ID NO: 131, SEQ ID NO: 135, SEQ ID NO: 139, SEQ ID NO: 143, SEQ ID NO: 147, SEQ ID NO: 151, SEQ ID NO: 155, SEQ ID NO: 159, SEQ ID NO: 163, SEQ ID NO: 167, SEQ ID NO: 171 and SEQ ID NO: 175. In another embodiment, the immunoconjugate comprises a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group consisting of: SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 23, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 37, SEQ ID NO: 41, SEQ ID NO: 45, SEQ ID NO: 49, SEQ ID NO: 67, SEQ ID NO: 71, SEQ ID NO: 75, SEQ ID NO: 79, SEQ ID NO: 83, SEQ ID NO: 87, SEQ ID NO: 91, SEQ ID NO: 121, SEQ ID NO: 125, SEQ ID NO: 129, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ID NO: 141, SEQ ID NO: 145, SEQ ID NO: 149, SEQ ID NO: 153, SEQ ID NO: 157, SEQ ID NO: 161, SEQ ID NO: 165, SEQ ID NO: 169 and SEQ ID NO: 173. In a further embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group consisting of: SEQ ID NO: 21, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 31, SEQ ID NO: 35, SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, SEQ ID NO: 69, SEQ ID NO: 73, SEQ ID NO: 77, SEQ ID NO: 81, SEQ ID NO: 85, SEQ ID NO: 89, SEQ ID NO: 93, SEQ ID NO: 123, SEQ ID NO: 127, SEQ ID NO: 131, SEQ ID NO: 135, SEQ ID NO: 139, SEQ ID NO: 143, SEQ ID NO: 147, SEQ ID NO: 151, SEQ ID NO: 155, SEQ ID NO: 159, SEQ ID NO: 163, SEQ ID NO: 167, SEQ ID NO: 171 and SEQ ID NO: 175, and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group consisting of: SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 23, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 37, SEQ ID NO: 41, SEQ ID NO: 45, SEQ ID NO: 49, SEQ ID NO: 67, SEQ ID NO: 71, SEQ ID NO: 75, SEQ ID NO: 79, SEQ ID NO: 83, SEQ ID NO: 87, SEQ ID NO: 91, SEQ ID NO: 121, SEQ ID NO: 125, SEQ ID NO: 129, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ID NO: 141, SEQ ID NO: 145, SEQ ID NO: 149, SEQ ID NO: 153, SEQ ID NO: 157, SEQ ID NO: 161, SEQ ID NO: 165, SEQ ED NO: 169 and SEQ ID NO: 173.

[0029] In one embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group consisting of: SEQ ID NO: 22, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 32, SEQ ID NO: 36, SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 48, SEQ ID NO: 52, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 78, SEQ ID NO: 82, SEQ ID NO: 86, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 124, SEQ ID NO: 128, SEQ ID NO: 132, SEQ ID NO: 136, SEQ ID NO: 140, SEQ ID NO: 144, SEQ ID NO: 148, SEQ ID NO: 152, SEQ ID NO: 156, SEQ ID NO: 160, SEQ ID NO: 164, SEQ ID NO: 168, SEQ ID NO: 172 and SEQ ID NO: 176. In another embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is encoded by a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 22, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 32, SEQ ID NO: 36, SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 48, SEQ ID NO: 52, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 78, SEQ ID NO: 82, SEQ ID NO: 86, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 124, SEQ ID NO: 128, SEQ ID NO: 132, SEQ ID NO: 136, SEQ ID NO: 140, SEQ ID NO: 144, SEQ ID NO: 148, SEQ ID NO: 152, SEQ ID NO: 156, SEQ ID NO: 160, SEQ ID NO: 164, SEQ ID NO: 168, SEQ ID NO: 172 and SEQ ID NO: 176. In one embodiment, the immunoconjugate comprises a light chain variable region sequence that is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group consisting of: SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 34, SEQ ID NO: 38, SEQ ID NO: 42, SEQ ID NO: 46, SEQ ID NO: 50, SEQ ID NO: 68, SEQ ID NO: 72, SEQ ID NO: 76, SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 88, SEQ ID NO: 92, SEQ ID NO: 122, SEQ ID NO: 126, SEQ ID NO: 130, SEQ ID NO: 134, SEQ ID NO: 138, SEQ ID NO: 142, SEQ ID NO: 146, SEQ ID NO: 150, SEQ ID NO: 154, SEQ ID NO: 158, SEQ ID NO: 162, SEQ ID NO: 166, SEQ ID NO: 170 and SEQ ID NO: 174. In another embodiment, the immunoconjugate comprises a light chain variable region sequence that is encoded by a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 34, SEQ ID NO: 38, SEQ ID NO: 42, SEQ ID NO: 46, SEQ ID NO: 50, SEQ ID NO: 68, SEQ ID NO: 72, SEQ ID NO: 76, SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 88, SEQ ID NO: 92, SEQ ID NO: 122, SEQ ID NO: 126, SEQ ID NO: 130, SEQ ID NO: 134, SEQ ID NO: 138, SEQ ID NO: 142, SEQ ID NO: 146, SEQ ID NO: 150, SEQ ID NO: 154, SEQ ID NO: 158, SEQ ID NO: 162, SEQ ID NO: 166, SEQ ID NO: 170 and SEQ ID NO: 174.

[0030] In one embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 213, SEQ ID NO: 217, SEQ ID NO: 219, SEQ ID NO: 221, SEQ ID NO: 223, SEQ JD NO: 225 and SEQ ID NO: 227. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 229, SEQ ID NO: 231, SEQ ID NO: 233 and SEQ ID NO: 237. In a further embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 211, SEQ ID NO: 219, and SEQ ID NO: 221, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 231. In a further embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group of SEQ ID NO: 209, SEQ ID NO: 223, SEQ ID NO: 225 and SEQ ID NO: 227, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 229. In a further embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 213, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 233. In a further embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 217, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 237.

[0031] In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 210, SEQ ID NO: 212, SEQ ID NO: 214, SEQ ID NO: 218, SEQ ID NO: 220, SEQ ID NO: 222, SEQ ID NO: 224, SEQ ID NO: 226 and SEQ ID NO: 228. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by a polynucleotide sequence selected from the group of SEQ ID NO: 210, SEQ ID NO: 212, SEQ ID NO: 214, SEQ ID NO: 218, SEQ ID NO: 220, SEQ ID NO: 222, SEQ ID NO: 224, SEQ ID NO: 226 and SEQ ID NO: 228. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 230, SEQ ID NO: 232, SEQ ID NO: 234 and SEQ ID NO: 238. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by a polynucleotide sequence selected from the group of SEQ ID NO: 230, SEQ ID NO: 232, SEQ ID NO: 234 and SEQ ID NO: 238.

[0032] In one embodiment; the immunoconjugate comprises a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 257 or SEQ ID NO: 261. In another embodiment, the immunoconjugate comprises a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 259 or SEQ ID NO: 271. In a further embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to to the sequence of either SEQ ID NO: 257 or SEQ ID NO: 261, and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 259 or SEQ ID NO: 271.

[0033] In one embodiment, the immunoconjugate comprises a heavy chain variable region sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of either SEQ ID NO: 258 or SEQ ID NO: 262. In another embodiment, the immunoconjugate comprises a heavy chain variable region sequence that is encoded by the polynucleotide sequence of either SEQ ID NO: 258 or SEQ ID NO: 262. In one embodiment, the immunoconjugate comprises a light chain variable region sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of either SEQ ID NO: 260 or SEQ ID NO: 272. In another embodiment, the immunoconjugate comprises a light chain variable region sequence that is encoded by the polynucleotide sequence of either SEQ ID NO: 260 or SEQ ID NO: 272.

[0034] In one embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 251 or SEQ ID NO: 255. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 253 or SEQ ID NO: 265. In a further embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 251 or SEQ ID NO: 255, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of either SEQ ID NO: 253 or SEQ ID NO: 265.

[0035] In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of either SEQ ID NO: 252 or SEQ ID NO: 256. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of either SEQ ID NO: 252 or SEQ ID NO: 256. In one embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to either SEQ ID NO: 254 or SEQ ID NO: 266. In another embodiment, the immunoconjugate comprises a polypeptide sequence that is encoded by the polynucleotide sequence of either SEQ ID NO: 254 or SEQ ID NO: 266.

[0036] In another embodiment, the immunoconjugate comprises at least one effector moiety, wherein the effector moiety is a cytokine. In a specific embodiment, the effector moiety is a cytokine selected from the group consisting of: interleukin-2 (IL-2), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-α (INF-α), interleukin-12 (IL-12), interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β), and transforming growth factor-β (TGF-β). In another embodiment, at least one antigen binding moiety is specific for one of the following antigenic determinants: the Extra Domain B of fibronectin (EDB), the A1 domain of tenascin (TNC-A1), the A2 domain of tenascin (TNC-A2), the Fibroblast Activated Protein (FAP); and the Melanoma Chondroitin Sulfate Proteoglycan (MCSP).

[0037] In another embodiment, the immunoconjugate of the invention binds to an effector moiety receptor with a dissociation constant (K_D) that is at least about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 times greater than that for a control effector moiety. In another embodiment, the immunoconjugate inhibits an increase in tumor volume in vivo by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% or more at the end of an administration period. In another embodiment, the immunoconjugate prolongs the survival of mammals with malignant tumors by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% when administered to a mammal in need thereof, relative to a control effector moiety or an effector moiety in a “diabody” immunoconjugate molecule.

[0038] Another aspect of the present invention is directed to isolated polynucleotides encoding immunoconjugates of the invention or fragments thereof. Another aspect of the present invention is directed to an expression vector comprising an expression cassette comprising the polynucleotide sequences of the invention.

[0039] Another aspect of the present invention is directed to host cells that express the immunoconjugates of the invention or fragments thereof.

[0040] Another aspect of the present invention is directed to methods for producing the immunoconjugates of the invention or fragments thereof, wherein the method comprises culturing host cells transformed with expression vectors encoding for the immunoconjugates of the invention or fragments thereof under conditions suitable for the expression, of the same.

[0041] Another aspect of the present invention is directed to methods for promoting proliferation and differentiation in an activated T lymphocyte cell, comprising contacting an activated T lymphocyte cell with an effective amount of the immunoconjugates of the invention.

[0042] Another aspect of the present invention is directed to methods for promoting proliferation and differentiation in an activated B lymphocyte cell, comprising contacting an activated B lymphocyte cell with an effective amount of the immunoconjugates of the invention.

[0043] Another aspect of the present invention is directed to methods for promoting proliferation and differentiation in a natural killer (NK) cell, comprising contacting a NK cell with an effective amount of the immunoconjugates of the invention.

[0044] Another aspect of the present invention is directed to methods for promoting proliferation and differentiation in a granulocyte, a monocyte or a dendritic cell, comprising contacting a granulocyte, a monocyte or a dendritic cell with an effective amount of the immunoconjugates of the invention.

[0045] Another aspect of the present invention is directed to methods for promoting cytotoxic T lymphocyte (CTL) differentiation, comprising contacting a T lymphocyte cell with an effective amount of the immunoconjugates of the invention.

[0046] Another aspect of the present invention is directed to methods for inhibiting viral replication, comprising contacting a virus-infected cell with an effective amount of the immunoconjugates of the invention.

[0047] Another aspect of the present invention is directed to methods for upregulating the expression of major histocompatibility complex I (MHC I), comprising contacting a target cell with an effective amount of the immunoconjugates of the invention.

[0048] Another aspect of the present invention is directed to methods for inducing cell death, comprising administering to a target cell an effective amount of the immunoconjugates of the invention.

[0049] Another aspect of the present invention is directed to methods for inducing chemotaxis in a target cell, comprising administering to a target cell an effective amount of the immunoconjugate of the invention.

[0050] Another aspect of the present invention is directed to a method of treating a disease in an individual, comprising the steps of administering to an individual a therapeutically effective amount of a composition comprising the immunoconjugate of the invention and a pharmaceutical carrier.

[0104] Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art. Generally, the nomenclature used herein and the laboratory procedures in cell culture, molecular genetics, nucleic acid chemistry and hybridization described below are those well known and commonly employed in the art. Standard techniques and procedures are generally performed according to conventional methods in the art and various general references (see generally, Sambrook et al. Molecular Cloning: A Laboratory Manual, 2nd ed. (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., which is incorporated herein by reference), which are provided throughout this document.

[0105] As used herein, the term “immunoconjugate” refers to a polypeptide molecule that includes at least one effector moiety and at least one antigen binding moiety. In one embodiment, the immunoconjugate comprises at least one single-chain effector moiety, and at least two antigen binding moieties. The antigen binding molecule can be joined to the effector moiety by a variety of interactions and in a variety of configurations as described herein.

[0106] As used herein, the term “effector moiety” refers to a polypeptide, e.g., a protein or glycoprotein, that influences cellular activity, for example, through signal transduction or other cellular pathways. Accordingly, the effector moiety of the invention can be associated with receptor-mediated signaling that transmits a signal from outside the cell membrane to modulate a response in a cell bearing one or more receptors for the effector moiety. In one embodiment, an effector moiety can elicit a cytotoxic response in cells bearing one or more receptors for the effector moiety. In another embodiment, an effector moiety can elicit a proliferative response in cells bearing one or more receptors for the effector moiety. In another embodiment, an effector moiety can elicit differentiation in cells bearing receptors for the effector moiety. In another embodiment, an effector moiety can alter expression (i.e., upregulate or downregulate) of an endogenous cellular protein in cells bearing receptors for the effector moiety. Non-limiting examples of effector moieties include cytokines, growth factors, hormones, enzymes, substrates, and cofactors. The effector moiety can be associated with an antigen binding moiety in a variety of configurations to form an immunoconjugate.

[0107] As used herein, the term “cytokine” refers to a molecule that mediates and/or regulates a biological or cellular function or process (e.g., immunity, inflammation, and hematopoiesis). The term “cytokine” as used herein includes “lymphokines,” “chemokines,” “monokines,” and “interleukins.” Examples of useful cytokines include, but are not limited to, GM-CSF, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IFN-α, IFN-β, IFN-γ, MIP-1α, MIP1β, TGF-β, TNF-α, and TNF-β.

[0108] As used herein, the term “single-chain” refers to a molecule comprising amino acid monomers linearly linked by peptide bonds. In one embodiment, the effector moiety is a single-chain effector moiety. Non-limiting examples of single-chain effector moieties include cytokines, growth factors, hormones, enzymes, substrates, and cofactors. When the effector moiety is a cytokine and the cytokine of interest is normally found as a multimer in nature, each subunit of the multimeric cytokine is sequentially encoded by the single-chain of the effector moiety. Accordingly, non-limiting examples of useful single-chain effector moieties include GM-CSF, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IFN-α, IFN-β, IFN-γ, MIP1α, MIP-1β, TGF-β, TNF-α, and TNF-β.

[0109] As used herein, the term “control effector moiety” refers to an unconjugated effector moiety. For example, when comparing an IL-2 immunoconjugate of the present invention with a control effector moiety, the control effector moiety is free, unconjugated IL-2. Likewise, e.g., when comparing an IL-12 immunoconjugate of the present invention with a control effector moiety, the control effector moiety is free, unconjugated IL-12 (e.g., existing as a heterodimeric protein wherein the p40 and p35 subunits share only disulfide bond(s)).

[0110] As used herein, the term “effector moiety receptor” refers to a polypeptide molecule capable of binding specifically to an effector moiety. For example, where IL-2 is the effector moiety, the effector moiety receptor that binds to a IL-2 (e.g., an immunoconjugate comprising IL-2) is the IL-2 receptor. Similarly, e.g., where IL-12 is the effector moiety of an immunoconjugate, the effector moiety receptor is the IL-12 receptor. Where an effector moiety specifically binds to more than one receptor, all receptors that specifically bind to the effector moiety are “effector moiety receptors” for that effector moiety.

[0111] As used herein, the term “antigen binding moiety” refers to a polypeptide molecule that specifically binds to an antigenic determinant. In one embodiment, an antigen binding moiety is able to direct the entity to which it is attached (e.g., an effector moiety or a second antigen binding moiety) to a target site, for example to a specific type of tumor cell or tumor stroma bearing the antigenic determinant. Antigen binding moieties include antibodies and fragments thereof as further defined herein. By “specifically binds” is meant that the binding is selective for the antigen and can be discriminated from unwanted or non-specific interactions. In one embodiment, the immunoconjugate comprises at least one, typically two or more antigen binding moieties with constant regions as further defined herein and known in the art. Useful heavy chain constant regions include any of the five isotypes: α, δ, ε, γ, or μ. Useful light chain constant regions include any of the two isotypes: κ and λ.

[0112] As used herein, the term “antigenic determinant” is synonymous with “antigen” and “epitope,” and refers to a site (e.g., a contiguous stretch of amino acids or a conformational configuration made up of different regions of non-contiguous amino acids) on a polypeptide macromolecule to which an antigen binding moiety binds, forming an antigen binding moiety-antigen complex.

[0113] As used herein, the term “control antigen binding moiety” refers to an antigen binding moiety as it would exist free of other antigen binding moieties and effector moieties. For example, when comparing an Fab-IL2-Fab immunoconjugate of the invention with a control antigen binding moiety, the control antigen binding moiety is free Fab, wherein the Fab-IL2-Fab immunoconjugate and the free Fab molecule can both specifically bind to the same antigen determinant.

[0114] As used herein, the terms “first” and “second” with respect to antigen binding moieties, effector moieties, etc., are used for convenience of distinguishing when there is more than one of each type of moiety. Use of these terms is not intended to confer a specific order or orientation of the immunoconjugate unless explicitly so stated.

[0115] In the case where there are two or more definitions of a term which is used and/or accepted within the art, the definition of the term as used herein is intended to include all such meanings unless explicitly stated to the contrary. A specific example is the use of the term “complementarity determining region” (“CDR”) to describe the non-contiguous antigen combining sites found within the variable region of both heavy and light polypeptides. This particular region has been described by Kabat et al., U.S. Dept. of Health and Human Services, “Sequences of Proteins of Immunological Interest” (1983) and by Chothia et al., J. Mol. Biol. 196:901-917 (1987), which are incorporated herein by reference, where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or variants thereof is intended to be within the scope of the term as defined and used herein. The appropriate amino acid residues which encompass the CDRs as defined by each of the above cited references are set forth below in Table I as a comparison. The exact residue numbers which encompass a particular CDR will vary depending on the sequence and size of the CDR. Those skilled in the art can routinely determine which residues comprise a particular CDR given the variable region amino acid sequence of the antibody.

TABLE 1
CDR Definitions1
	CDR	Kabat	Chothia	AbM2
	VH CDR1	31-35	26-32	26-35
	VH CDR2	50-65	52-58	50-58
	VH CDR3	95-102	95-102	95-102
	VL CDR1	24-34	26-32	24-34
	VL CDR2	50-56	50-52	50-56
	VL CDR3	89-97	91-96	89-97
	1Numbering of all CDR definitions in Table 1 is according to the numbering conventions set forth by Kabat et al. (see below).
	2“AbM” with a lowercase “b” as used in Table 1 refers to the CDRs as defined by Oxford Molecular's “AbM” antibody modeling software.

[0116] Kabat et al. also defined a numbering system for variable domain sequences that is applicable to any antibody. One of ordinary skill in the art can unambiguously assign this system of “Kabat numbering” to any variable domain sequence, without reliance on any experimental data beyond the sequence itself. As used herein, “Kabat numbering” refers to the numbering system set forth by Kabat et al., U.S. Dept. of Health and Human Services, “Sequence of Proteins of Immunological Interest” (1983). Unless otherwise specified, references to the numbering of specific amino acid residue positions in an antigen binding moiety of the invention are according to the Kabat numbering system. The polypeptide sequences of the sequence listing (i.e., SEQ ID NOs: 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 96, 97, etc.) are not numbered according to the Kabat numbering system. However, it is well within the ordinary skill of one in the art to convert the numbering of the sequences of the Sequence Listing to Kabat numbering.

[0117] Immunoconjugates are polypeptide molecules that comprise at least one effector moiety and at least one antigen binding moiety. In one embodiment, the effector moiety is a single-chain effector moiety. In one embodiment, the immunoconjugate comprises at least two antigen binding moieties. The antigen binding moieties and effector moieties of the immunoconjugate include those that are described in detail herein above and below and in the accompanying figures. The antigen binding moiety of the immunoconjugate can be directed againt a variety of target molecules (e.g., an antigenic determinant on a protein molecule expressed on a tumor cell or tumor stroma). Non-limiting examples of antigen binding moieties are described herein. In one embodiment, the at least one antigen binding moiety is directed to an antigenic determinant of one or more of the polypeptides represented in Table 5, herein below. Immunoconjugates of the invention typically exhibit one or more of the following properties: high specificity of action, reduced toxicity and/or improved stability, particularly as compared to known immunoconjugates of different configurations targeting the same antigenic determinants and carrying the same effector moities.

[0118] In one embodiment, the immunoconjugate comprises at least a first effector moiety and at least a first and a second antigen binding moiety. In a preferred embodiment, the first effector moiety is a single chain effector moiety. In a preferred embodiment, the first and second antigen binding moeity are independently selected from the group consisting of an Fv and an Fab. In a specific embodiment, the first effector moiety shares an amino- or carboxy-terminal peptide bond with a first antigen binding moiety and a second antigen binding moiety shares an amino- or carboxy-terminal peptide bond with either i) the first effector moiety or ii) the first antigen binding moiety. In another embodiment, the immunoconjugate consists essentially of a first single-chain effector moiety and first and second antigen binding moieties.

[0119] In one embodiment, a first effector moiety, shares a carboxy-terminal peptide bond with a first antigen binding moiety and further shares an amino-terminal peptide bond with a second antigen binding moiety. In another embodiment, a first antigen binding moiety shares a carboxy-terminal peptide bond with a first effector moiety, preferably a single chain effector moiety, and further shares an amino-terminal peptide bond with a second antigen binding moiety. In another embodiment, a first antigen binding moiety shares an amino-terminal peptide bond with a first effector moiety, preferably a single chain effector moiety, and further shares a carboxy-terminal peptide with a second antigen binding moiety.

[0120] In one embodiment, an effector moiety, preferably a single chain effector moiety, shares a carboxy-terminal peptide bond with a first heavy chain variable region and further shares an amino-terminal peptide bond with a second heavy chain variable region. In another embodiment, an effector moiety, preferably a single chain effector moiety, shares a carboxy-terminal peptide bond with a first light chain variable region and further shares an amino-terminal peptide with a second light chain variable region. In another embodiment, a first heavy or light chain variable region is joined by a carboxy-terminal peptide bond to a first effector moiety, preferably a single chain effector moiety, and is further joined by an amino-terminal peptide bond to a second heavy or light chain variable region. In another embodiment, a first heavy or light chain variable region is joined by an amino-terminal peptide bond to a first effector moiety preferably a single chain effector moiety, and is further joined by a carboxy-terminal peptide bond to a second heavy or light chain variable region.

[0121] In one embodiment, an effector moiety, preferably a single chain effector moiety, shares a carboxy-terminal peptide bond with a first Fab heavy or light chain and further shares an amino-terminal peptide bond with a second Fab heavy or light chain. In another embodiment, a first Fab heavy or light chain shares a carboxy-terminal peptide bond with a first single-chain effector moiety and further shares an amino-terminal peptide bond with a second Fab heavy or light chain. In other embodiments, a first Fab heavy or light chain shares an amino-terminal peptide bond with a first single-chain effector moiety and further shares a carboxy-terminal peptide bond with a second Fab heavy or light chain.

[0122] In one embodiment, the immunoconjugate comprises at least a first effector moiety sharing an amino-terminal peptide bond to one or more scFv molecules and wherein the first effector moiety further shares a carboxy-terminal peptide bond with one or more scFv molecules. In a preferred embodiment, the effector moiety is a single chain effector moiety.

[0123] In another embodiment, the immunoconjugate comprises at least a first effector moiety, preferably a single chain effector moiety, and first and second antigen binding moieties, wherein each of the antigen binding moieties includes an scFv molecule joined at its carboxy-terminal amino acid to a constant region that includes an immunoglobulin constant domain, and wherein the first antigen binding moiety is joined at its constant region carboxy-terminal amino acid to the amino-terminal amino acid of the first effector moiety, and wherein the first and second antigen binding moieties are covalently linked through at least one disulfide bond. In a preferred embodiment, the constant region is independently selected from the group consisting of IgG CH1, IgG CH2, IgG CH3, IgG C_kappa, IgG C_lambda and IgE CH₄ domains. In one embodiment, the immunoglobulin domain of the first antigen binding moiety is covalently linked to the immunoglobulin domain of the second antigen binding moiety through a disulfide bond. In one embodiment, at least one disulfide bond is located carboxy-terminal of the immunoglobulin domains of the first and second antigen binding moieties. In another embodiment, at least one disulfide bond is located amino-terminal of the immunoglobulin domains of the first and second antigen binding moieties. In another embodiment, at least two disulfide bonds are located amino-terminal of the immunoglobulin domains of the first and second antigen binding moieties.

[0124] In a specific embodiment, the immunoconjugate comprises first and second antigen binding moieties, each comprising an scFv molecule joined at its carboxy-terminal amino acid to a constant region that comprises an IgG CH1 domain, wherein the first antigen binding moiety is joined at its constant region carboxy-terminal amino acid to the amino-terminal amino acid of the first effector moiety, preferably a single chain effector moiety, and wherein the first and second antigen binding moieties are covalently linked through at least one disulfide bond. The second antigen binding moiety of the immunoconjugate can be further joined at its carboxy-terminal amino acid to the amino-terminal amino acid of a second effector moiety. In one embodiment, the second effector moiety is a single chain effector moiety.

[0125] In a specific embodiment, the immunoconjugate comprises first and second antigen binding moieties each comprising an scFv molecule joined at its carboxy-terminal amino acid to a constant region that comprises an IgG C_kappa domain, wherein the first antigen binding moiety is joined at its constant region carboxy-terminal amino acid to the amino-terminal amino acid of the first effector moiety, preferably a single chain effector moiety, and wherein the first and second antigen binding moieties are covalently linked through at least one disulfide bond. The second antigen binding moiety of the immunoconjugate can be further joined at its carboxy-terminal amino acid to the amino-terminal amino acid of a second effector moiety. In one embodiment, the second effector moiety is a single chain effector moiety.

[0126] In another specific embodiment, the immunoconjugate comprises first and second antigen binding moieties, each comprising an scFv molecule joined at its carboxy-terminal amino acid to a constant region that comprises an IgE CH4 domain, wherein the first antigen binding moiety is joined at its constant region carboxy-terminal amino acid to the amino-terminal amino acid of the first effector moiety, preferably a single chain effector moiety, and wherein the first and second antigen binding moieties are covalently linked through at least one disulfide bond. The second antigen binding moiety of the immunoconjugate can be further joined at its carboxy-terminal amino acid to the amino-terminal amino acid of a second effector moiety. In one embodiment, the second effector moiety is a single chain effector moiety.

[0127] In another specific embodiment, the immunoconjugate comprises first and second antigen binding moieties each, comprising an scFv molecule joined at its carboxy-terminal amino acid to an IgE CH3 domain, wherein the first antigen binding moiety is joined at its carboxy-terminal amino acid to the amino-terminal amino acid of the first effector moiety, preferably a single chain effector moiety, and wherein the first and second antigen binding moieties are covalently linked through at least one disulfide bond. The second antigen binding moiety of the immunoconjugate can be further joined at its carboxy-terminal amino acid to the amino-terminal amino acid of a second effector moiety. In one embodiment, the second effector moiety is a single chain effector moiety.

[0128] In another embodiment, the immunoconjugate comprises first and second effector moieties, and first and second antigen binding moieties, wherein each of the antigen binding moieties comprises an Fab molecule joined at its heavy or light chain carboxy-terminal amino acid to an IgG1 CH3 domain, and wherein each of the IgG1 CH3 domains is joined at its respective carboxy-terminal amino acid to the amino-terminal amino acid of one of the effector moieties, and wherein the first and second antigen binding moieties are covalently linked through at least one disulfide bond. In a preferred embodiment, the first and/or second effector moiety is a single chain effector moiety. In a further embodiment, the IgG1 CH3 domains of the antigen binding moieties may be joined by disulfide bond. In another embodiment, at least one disulfide bond is located carboxy-terminal of the IgG1 CH3 domains of the first and second antigen binding moieties. In another embodiment, at least one disulfide bond is located amino-terminal of the IgG1 CH3 domains of the first and second antigen binding moieties. In another embodiment, at least two disulfide bonds are located amino-terminal of the IgG1 CH3 domains of the first and second antigen binding moieties.

[0129] In another embodiment, the immunoconjugate comprises one or more proteolytic cleavage sites located between effector moieties and antigen binding moieties.

[0130] Components of the immunoconjugate (e.g., antigen binding moieties and/or effector moieties) may be linked directly or through various linkers (e.g., peptide linkers comprising one or more amino acids, typically about 2-10 amino acids) that are described herein or are known in the art.

[0131] In a particular embodiment, the immunoconjugate has improved stability in solution, particularly compared to known immunoconjugate preparations. In one embodiment, the immunoconjugate binds to an antigenic determinant with a dissociation constant (K_D) that is at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 times lower than that for a control antigen binding moiety. In a more specific embodiment, the immunoconjugate binds to an antigenic determinant with a K_D that is about 10 times lower than that for a control antigen binding moiety. In one embodiment, the immunoconjugate binds to an antigenic determinant with a K_D that is lower than about 10 nM, lower than about 1 nM, or lower than about 0.1 nM.

[0132] In another embodiment, the immunoconjugate has a superior safety profile compared to known immunoconjugate preparations. The immunoconjugate preferably elicits fewer and less severe side effects, such as toxicity, destruction of non-tumor cells, etc. The decrease in side effects may be attributed to the reduced binding affinity of the immunoconjugates of the invention towards effector moiety receptors. In one embodiment, the immunoconjugate binds to an effector moiety receptor with a K_D that is at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 times greater than that for a control effector moiety. In a more specific embodiment, the immuonconjugate binds to an effector moiety receptor with a K_D that is about 2 times greater than that for a control effector moiety. In another embodiment, the immuonconjugate binds to an effector moiety receptor with a K_D that is about 10 times greater than that for a control effector moiety. In another embodiment, the immunoconjugate binds to an effector moiety receptor with a K_D that is at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 times greater than that for a corresponding effector moiety in a “diabody” immunoconjugate molecule. In another embodiment, the immunoconjugate binds to an effector moiety receptor with a dissociation constant K_D that is about 10 times greater than that for a corresponding effector moiety in a “diabody” immunoconjugate.

[0133] In another embodiment, the immunoconjugate has superior efficacy, particularly compared to known immunoconjugate preparations. In one embodiment, the immunoconjugate is better able to inhibit increases in tumor volume in vivo and/or better able to prolong survival in mammals with malignant tumors. In one embodiment, the immunoconjugate inhibits an increase in tumor volume in vivo by at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% by the end of an administration period of about at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days. In one embodiment, the immunoconjugate inhibits an increase in tumor volume in vivo by at least 50%, 55%, 60%, 65%, 70%, or 75% by the end of a 13 day administration period. In another embodiment, the immunoconjugate prolongs the survival of mammals with malignant tumors by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% when administered to a mammal in need thereof, relative to a control effector moiety. In another embodiment, the immunoconjugate prolongs the survival of mammals with malignant tumors by at least 30%, 32% or 35% when administered to a mammal in need thereof, relative to a control effector moiety. In another embodiment, the immunoconjugate prolongs the survival of mammals with malignant tumors by about 30% when administered to a mammal in need thereof, relative to a control effector moiety. In another embodiment, the immunoconjugate prolongs the survival of mammals with malignant tumors by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% when administered to a mammal in need thereof, relative to an effector moiety in a “diabody” immunoconjugate molecule. In another embodiment, the immunoconjugate prolongs the survival of mammals with malignant tumors by at least 30%, 32%, or 35% when administered to a mammal in need thereof, relative to an effector moiety in a “diabody” immunoconjugate molecule. In another embodiment, the immunoconjugate prolongs the survival of mammals with malignant tumors by about 30% when administered to a mammal in need thereof, relative to an effector moiety in a “diabody” immunoconjugate molecule. In another embodiment, the immunoconjugate prolongs the survival of mammals with malignant tumors by at least 5%, 10% or 15%, relative to a control effector moiety or an effector moiety in a “diabody” immunoconjugate molecule.

[0134] The antigen binding moiety of the immunoconjugate of the invention is generally a polypeptide molecule that binds to a specific antigenic determinant and is able to direct the entity to which it is attached (e.g., an effector moiety or a second antigen binding moiety) to a target site, for example to a specific type of tumor cell or tumor stroma that bears the antigenic determinant. The immunoconjugate can bind to antigenic determinants found, for example, on the surfaces of tumor cells, on the surfaces of virus-infected cells, on the surfaces of other diseased cells, free in blood serum, and/or in the extracellular matrix (ECM).

[0135] Non-limiting examples of tumor antigens include MAGE, MART-1/Melan-A, gp100, Dipeptidyl peptidase IV (DPPIV), adenosine deaminase-binding protein (ADAbp), cyclophilin b, Colorectal associated antigen (CRC)-C017-1A/GA733, Carcinoembryonic Antigen (CEA) and its immunogenic epitopes CAP-1 and CAP-2, etv6, aml1, Prostate Specific Antigen (PSA) and its immunogenic epitopes PSA-1, PSA-2, and PSA-3, prostate-specific membrane antigen (PSMA), T-cell receptor/CD3-zeta chain, MAGE-family of tumor antigens (e.g., MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A5, MAGE-A6, MAGE-A7, MAGE-A8, MAGE-A9, MAGE-A10, MAGE-A11, MAGE-A12, MAGE-Xp2 (MAGE-B2), MAGE-Xp3 (MAGE-B3), MAGE-Xp4 (MAGE-B4), MAGE-C1, MAGE-C2, MAGE-C3, MAGE-C4, MAGE-05), GAGE-family of tumor antigens (e.g., GAGE-1, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE-7, GAGE-8, GAGE-9), BAGE, RAGE, LAGE-1, NAG, GnT-V, MUM-1, CDK4, tyrosinase, p53, MUC family, HER2/neu, p21ras, RCAS1, α-fetoprotein, E-cadherin, α-catenin, β-catenin and γ-catenin, p120ctn, gp100 Pmel117, PRAME, NY-ESO-1, cdc27, adenomatous polyposis coli protein (APC), fodrin, Connexin 37, Ig-idiotype, p15, gp75, GM2 and GD2 gangliosides, viral products such as human papilloma virus proteins, Smad family of tumor antigens, lmp-1, P1A, EBV-encoded nuclear antigen (EBNA)-1, brain glycogen phosphorylase, SSX-1, SSX-2 (HOM-MEL-40), SSX-1, SSX-4, SSX-5, SCP-1 and CT-7, and c-erbB-2.

[0136] Non-limiting examples of viral antigens include influenza virus hemagglutinin, Epstein-Barr virus LMP-1, hepatitis C virus E2 glycoprotein, HIV gp160, and HIV gp120.

[0137] Non-limiting examples of ECM antigens include syndecan, heparanase, integrins, osteopontin, link, cadherins, laminin, laminin type EGF, lectin, fibronectin, notch, tenascin, and matrixin.

[0138] The immunoconjugates of the invention can bind to the following specific non-limiting examples of cell surface antigens: FAP, Her2, EGFR, CD2 (T-cell surface antigen), CD3 (heteromultimer associated with the TCR), CD22 (B-cell receptor), CD23 (low affinity IgE receptor), CD25 (IL-2 receptor a chain), CD30 (cytokine receptor), CD33 (myeloid cell surface antigen), CD40 (tumor necrosis factor receptor), IL-6R (IL6 receptor), CD20, MCSP, and PDGFβR (β platelet-derived growth factor receptor).

[0139] In one embodiment, the immunoconjugate of the invention comprises two or more antigen binding moieties, wherein each of these antigen binding moieties specifically bind to the same antigenic determinant. In another embodiment, the immunoconjugate of the invention comprises two or more antigen binding moieties, wherein each of these antigen binding moieties specifically bind to different antigenic determinants.

[0140] The antigen binding moiety can be any type of antibody or fragment thereof that retains specific binding to an antigenic determinant. Antibody fragments include, but are not limited to, V_H fragments, V_L fragments, Fab fragments, F(ab′)₂ fragments, scFv fragments, Fv fragments, minibodies, diabodies, triabodies, and tetrabodies (see, e.g., Hudson and Souriau, Nature Med. 9: 129-134 (2003)).

[0141] In one embodiment, the immunoconjugate comprises at least one, typically two or more antigen binding moieties that are specific for the Extra Domain B of fibronectin (EDB). In another embodiment, the immunoconjugate comprises at least one, typically two or more antigen binding moieties that can compete with monoclonal antibody L19 for binding to an epitope of EDB. See, e.g., PCT publication WO 2007/128563 A1 (incorporated herein by reference in its entirety). In yet another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain derived from the L19 monoclonal antibody shares a carboxy-terminal peptide bond with an IL-2 molecule which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain derived from the L19 monoclonal antibody. In yet another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain derived from the L19 monoclonal antibody shares a carboxy-terminal peptide bond with an IL-12 molecule which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain derived from the L19 monoclonal antibody. In yet another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain derived from the L19 monoclonal antibody shares a carboxy-terminal peptide bond with an IFN α molecule which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain derived from the L19 monoclonal antibody. In yet another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain derived from the L19 monoclonal antibody shares a carboxy-terminal peptide bond with a GM-CSF molecule which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain derived from the L19 monoclonal antibody. In a further embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first scFv derived from the L19 monoclonal antibody shares a carboxy-terminal peptide bond with an IL-2 molecule which in turn shares a carboxy-terminal peptide bond with a second scFv derived from the L19 monoclonal antibody. In a more specific embodiment, the immunoconjugate comprises the polypeptide sequence of SEQ ID NO: 95 or a variant thereof that retains functionality. In another embodiment, the immunoconjugate comprises an Fab light chain derived from the L19 monoclonal antibody. In a more specific embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 96 or a variant thereof that retains functionality. In yet another embodiment, the immunoconjugate comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 95 and SEQ ID NO: 96 or variants thereof that retain functionality. In a more specific embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID. NO: 104 or a variant thereof that retains functionality. In yet another embodiment, the immunoconjugate comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 104 and SEQ ID NO: 96 or variants thereof that retain functionality. In a more specific embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 105 or a variant thereof that retains functionality. In yet another embodiment, the immunoconjugate comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 105 and SEQ ID NO: 96 or variants thereof that retain functionality. In a more specific embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 106 or a variant thereof that retains functionality. In yet another embodiment, the immunoconjugate comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 106 and SEQ ID NO: 96 or variants thereof that retain functionality. In a more specific embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 107 or a variant thereof that retains functionality. In yet another embodiment, the immunoconjugate comprises a polypeptide sequences that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 107 and SEQ ID NO: 96 or variants thereof that retain functionality. In another specific embodiment, the polypeptides are covalently linked, e.g., by a disulfide bond.

[0142] In one embodiment, the immunoconjugate of the invention comprises at least one, typically two or more antigen binding moieties that are specific for the A1 domain of Tenascin (TNC-A1). In another embodiment, the immunoconjugate comprises at least one, typically two or more antigen binding moieties that can compete with monoclonal antibody F16 for binding to an epitope of TNC-A1. See, e.g., PCT Publication WO 2007/128563 A1 (incorporated herein by reference in its entirety). In one embodiment, the immunoconjugate comprises at least one, typically two or more antigen binding moieties that are specific for the A1 and/or the A4 domain of Tenascin (TNC-A1 or TNC-A4 or TNC-A1/A4). In another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain specific for the A1 domain of Tenascin shares a carboxy-terminal peptide bond with an IL-2 molecule, an IL-12 molecule, an IFN α molecule or a GM-CSF molecule, which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain specific for the A1 domain of Tenascin. In yet another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain specific for the A1 domain of Tenascin shares a carboxy-terminal peptide bond with an IL-2 molecule which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain specific for the A1 domain of Tenascin. In a further embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first scFv specific for the A1 domain of Tenascin shares a carboxy-terminal peptide bond with an IL-2 molecule which in turn shares a carboxy-terminal peptide bond with a second scFv specific for the A1 domain of Tenascin. In a specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 13 or SEQ ID NO: 15, or variants thereof that retain functionality. In another specific embodiment, the antigen binding moieties of the immunoconjugate comprise a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 9 or SEQ ID NO: 11, or variants thereof that retain functionality. In a more specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 13 or SEQ ID NO: 15 or variants thereof that retain functionality, and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 9 or SEQ ID NO: 11 or variants thereof that retain functionality. In another specific embodiment, the heavy chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to either SEQ ID NO: 14 or SEQ ID NO: 16. In yet another specific embodiment, the heavy chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by the polynucleotide sequence of either SEQ ID NO: 14 or SEQ ID NO: 16. In another specific embodiment, the light chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to either SEQ ID NO: 10 or SEQ ID NO: 12. In yet another specific embodiment, the light chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by the polynucleotide sequence of either SEQ ID NO: 10 or SEQ ID NO: 12. In a specific embodiment, the immunoconjugate comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 99 or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate of the invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 100 or SEQ ID NO: 215, or variants thereof that retain functionality. In yet another specific embodiment, the immunoconjugate of the invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 101 or SEQ ID NO: 235 or variants thereof that retain functionality. In a more specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 100 and SEQ ID NO: 101 or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 215 and SEQ ID NO: 235 or variants thereof that retain functionality. In a specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 112. In another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by the polynucleotide sequence of SEQ ID NO: 112. In another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to either SEQ ID NO: 113 or SEQ ID NO: 216. In yet another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by the polynucleotide sequence of either SEQ ID NO: 113 or SEQ ID NO: 216. In another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to either SEQ ID NO: 114 or SEQ ID NO: 236. In yet another embodiment, the immunoconjugate comprises a polypeptide sequence encoded by the polynucleotide sequence of either SEQ ID NO: 114 or SEQ ID NO: 236.

[0143] In one embodiment, the immunoconjugate comprises at least one, typically two or more antigen binding moieties that are specific for the A2 domain of Tenascin (TNC-A2). In another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain specific for the A2 domain of Tenascin shares a carboxy-terminal peptide bond with an IL-2 molecule, an IL-12 molecule, an IFN α molecule or a GM-CSF molecule, which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain specific for the A2 domain of Tenascin. In yet another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain specific for the A2 domain of Tenascin shares a carboxy-terminal peptide bond with an IL-2 molecule, which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain specific for the A2 domain of Tenascin. In a specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 7, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 187, SEQ ID NO: 191, SEQ ID NO:195, SEQ ID NO: 199, SEQ ID NO: 203 and SEQ ID NO: 207, or variants thereof that retain functionality. In another specific embodiment, the antigen binding moieties of the immunoconjugate comprise a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 3, SEQ ID NO: 5; SEQ ID NO: 177, SEQ ID NO: 181, SEQ ID NO:185, SEQ ID NO: 189, SEQ ID NO: 193, SEQ ID NO: 197, SEQ ID NO: 201 and SEQ ID NO: 205, or variants thereof that retain functionality. In a more specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 7, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 187, SEQ ID NO: 191, SEQ ID NO:195, SEQ ID NO: 199, SEQ ID NO: 203 and SEQ ID NO: 207, or variants thereof that retain functionality, and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 3, SEQ ID NO: 5; SEQ ID NO: 177, SEQ ID NO: 181, SEQ ID NO:185, SEQ ID NO: 189, SEQ ID NO: 193, SEQ ID NO: 197, SEQ ID NO: 201 and SEQ ID NO: 205, or variants thereof that retain functionality. In another specific embodiment, the heavy chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 8, SEQ ID NO: 180, SEQ ID NO: 184, SEQ ID NO: 188, SEQ ID NO: 192, SEQ ID NO: 196, SEQ ID NO: 200, SEQ ID NO: 204 and SEQ ID NO: 208. In yet another specific embodiment, the heavy chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence selected from the group of SEQ ID NO: 8, SEQ ID NO: 180, SEQ ID NO: 184, SEQ ID NO: 188, SEQ ID NO: 192, SEQ ID NO: 196, SEQ ID NO: 200, SEQ ID NO: 204 and SEQ ID NO: 208. In another specific embodiment, the light chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 178, SEQ ID NO: 182, SEQ ID NO: 186, SEQ ID NO: 190, SEQ ID NO: 194, SEQ ID NO: 198, SEQ ID NO: 202 and SEQ ID NO: 206. In yet another specific embodiment, the light chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence selected from the group of of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 178, SEQ ID NO: 182, SEQ ID NO: 186, SEQ ID NO: 190, SEQ ID NO: 194, SEQ ID NO: 198, SEQ ID NO: 202 and SEQ ID NO: 206. In a specific embodiment, the immunoconjugate of the invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 239, SEQ ID NO: 241 and SEQ ID NO: 243, or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate of the invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 245, SEQ ID NO: 247 and SEQ ID NO:249, or variants thereof that retain functionality. In a more specific embodiment, the immunoconjugate of the present invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 239, SEQ ID NO: 241, and SEQ ID NO: 243 or variants thereof that retain functionality, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 245, SEQ ID NO: 247 and SEQ ID NO:249 or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 239 and either SEQ ID NO: 247 or SEQ ID NO: 249, or variants thereof that retain functionality. In yet another specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 241 and either SEQ ID NO: 245 or SEQ ID NO: 247, or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 243 and SEQ ID NO: 245, or variants thereof that retain functionality. In a specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 240, SEQ ID NO: 242 and SEQ ID NO: 244. In another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence selected from the group of of SEQ ID NO: 240, SEQ ID NO: 242 and SEQ ID NO: 244. In another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 246, SEQ ID NO: 248 and SEQ ID NO: 250. In yet another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence selected from the group of of SEQ ID NO: 246, SEQ ID NO: 248 and SEQ ID NO: 250.

[0144] In one embodiment, the immunoconjugate comprises at least one, typically two or more antigen binding moieties that are specific for the Fibroblast Activated Protein (FAP). In another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain specific for FAP shares a carboxy-terminal peptide bond with an IL-2 molecule, an IL-12 molecule, an IFN a molecule or a GM-CSF molecule, which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain specific for FAP. In yet another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain specific for FAP shares a carboxy-terminal peptide bond with an IL-2 molecule, which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain specific for FAP. In another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain specific for FAP shares a carboxy-terminal peptide bond with an IL-12 molecule, which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain specific for FAP. In a specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 21, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 31, SEQ ID NO: 35, SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, SEQ ID NO: 69, SEQ ID NO: 73, SEQ ID NO: 77, SEQ ID NO: 81, SEQ ID NO: 85, SEQ ID NO: 89, SEQ ID NO: 93, SEQ ID NO: 123, SEQ ID NO: 127, SEQ ID NO: 131, SEQ ID NO: 135, SEQ ID NO: 139, SEQ ID NO: 143, SEQ ID NO: 147, SEQ ID NO: 151, SEQ ID NO: 155, SEQ ID NO: 159, SEQ ID NO: 163, SEQ ID NO: 167, SEQ ID NO: 171 and SEQ ID NO: 175, or variants thereof that retain functionality. In another specific embodiment, the antigen binding moieties of the immunoconjugate comprise a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group consisting of: SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 23, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 37, SEQ ID NO: 41, SEQ ID NO: 45, SEQ ID NO: 49, SEQ ID NO: 67, SEQ ID NO: 71, SEQ ID NO: 75, SEQ ID NO: 79, SEQ ID NO: 83, SEQ ID NO: 87, SEQ ID NO: 91, SEQ ID NO: 121, SEQ ID NO: 125, SEQ ID NO: 129, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ID NO: 141, SEQ ID NO: 145, SEQ ID NO: 149, SEQ ID NO: 153, SEQ ID NO: 157, SEQ ID NO: 161, SEQ ID NO: 165, SEQ ID NO: 169 and SEQ ID NO: 173, or variants thereof that retain functionality. In a more specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 21, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 31, SEQ ID NO: 35, SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, SEQ ID NO: 69, SEQ ID NO: 73, SEQ ID NO: 77, SEQ ID NO: 81, SEQ ID NO: 85, SEQ ID NO: 89, SEQ ID NO: 93, SEQ ID NO: 123, SEQ ID NO: 127, SEQ ID NO: 131, SEQ ID NO: 135, SEQ ID NO: 139, SEQ ID NO: 143, SEQ ID NO: 147, SEQ ID NO: 151, SEQ ID NO: 155, SEQ ID NO: 159, SEQ ID NO: 163, SEQ ID NO: 167, SEQ ID NO: 171, and SEQ ID NO: 175, or variants thereof that retain functionality, and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group consisting of: SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 23, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 37, SEQ ID NO: 41, SEQ ID NO: 45, SEQ ID NO: 49, SEQ ID NO: 67, SEQ ID NO: 71, SEQ ID NO: 75, SEQ ID NO: 79, SEQ ID NO: 83, SEQ ID NO: 87, SEQ ID NO: 91, SEQ ID NO: 121, SEQ ID NO: 125, SEQ ID NO: 129, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ID NO: 141, SEQ ID NO: 145, SEQ ID NO: 149, SEQ ID NO: 153, SEQ ID NO: 157, SEQ ID NO: 161, SEQ ID NO: 165, SEQ ID NO: 169, and SEQ ID NO: 173, or variants thereof that retain functionality. In another specific embodiment, the heavy chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group consisting of: SEQ ID NO: 22, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 32, SEQ ID NO: 36, SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 48, SEQ ID NO: 52, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 78, SEQ ID NO: 82, SEQ ID NO: 86, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 124, SEQ ID NO: 128, SEQ ID NO: 132, SEQ ID NO: 136, SEQ ID NO: 140, SEQ ID NO: 144, SEQ ID NO: 148, SEQ ID NO: 152, SEQ ID NO: 156, SEQ ID NO: 160, SEQ ID NO: 164, SEQ ID NO: 168, SEQ ID NO: 172, and SEQ ID NO: 176. In yet another specific embodiment, the heavy chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 22, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 32, SEQ ID NO: 36, SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 48, SEQ ID NO: 52, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 78, SEQ ID NO: 82, SEQ ID NO: 86, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 124, SEQ ID NO: 128, SEQ ID NO: 132, SEQ ID NO: 136, SEQ ID NO: 140, SEQ ID NO: 144, SEQ ID NO: 148, SEQ ID NO: 152, SEQ ID NO: 156, SEQ ID NO: 160, SEQ ID NO: 164, SEQ ID NO: 168, SEQ ID NO: 172, and SEQ ID NO: 176. In another specific embodiment, the light chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to sequence selected from the group consisting of: SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 34, SEQ ID NO: 38, SEQ ID NO: 42, SEQ ID NO: 46, SEQ ID NO: 50, SEQ ID NO: 68, SEQ ID NO: 72, SEQ ID NO: 76, SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 88, SEQ ID NO: 92, SEQ ID NO: 122, SEQ ID NO: 126, SEQ ID NO: 130, SEQ ID NO: 134, SEQ ID NO: 138, SEQ ID NO: 142, SEQ ID NO: 146, SEQ ID NO: 150, SEQ ID NO: 154, SEQ ID NO: 158, SEQ ID NO: 162, SEQ ID NO: 166, SEQ ID NO: 170, and SEQ ID NO: 174. In yet another specific embodiment, the light chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 34, SEQ ID NO: 38, SEQ ID NO: 42, SEQ ID NO: 46, SEQ ID NO: 50, SEQ ID NO: 68, SEQ ID NO: 72, SEQ ID NO: 76, SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 88, SEQ ID NO: 92, SEQ ID NO: 122, SEQ ID NO: 126, SEQ ID NO: 130, SEQ ID NO: 134, SEQ ID NO: 138, SEQ ID NO: 142, SEQ ID NO: 146, SEQ ID NO: 150, SEQ ID NO: 154, SEQ ID NO: 158, SEQ ID NO: 162, SEQ ID NO: 166, SEQ ID NO: 170, and SEQ ID NO: 174. In another specific embodiment, the immunoconjugate of the invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 213, SEQ ID NO: 217, SEQ ID NO: 219, SEQ ID NO: 221, SEQ ID NO: 223, SEQ ID NO: 225 and SEQ ID NO: 227, or variants thereof that retain functionality. In yet another specific embodiment, the immunoconjugate of the invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 229, SEQ ID NO: 231, SEQ ID NO: 233 and SEQ ID NO: 237 or variants thereof that retain functionality. In a more specific embodiment, the immunoconjugate of the present invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 211, SEQ ID NO: 219 and SEQ ID NO: 221 or variants thereof that retain functionality, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 231 or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate of the present invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence selected from the group of SEQ ID NO: 209, SEQ ID NO: 223, SEQ ID NO: 225 and SEQ ID NO: 227 or variants thereof that retain functionality, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 229 or variants thereof that retain functionality. In a further specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 213 and SEQ ID NO: 233 or variants thereof that retain functionality. In yet another specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 217 and SEQ ID NO: 237 or variants thereof that retain functionality. In yet another specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 221 and SEQ ID NO: 231 or variants thereof that retain functionality. In yet another specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 223 and SEQ ID NO: 229 or variants thereof that retain functionality. In yet another specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 225 and SEQ ID NO: 229 or variants thereof that retain functionality. In yet another specific embodiment, the immunoconjugate of the present invention comprises two polypeptide sequences that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 227 and SEQ ID NO: 229 or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 210, SEQ ID NO: 212, SEQ ID NO: 214, SEQ ID NO: 218, SEQ ID NO: 220, SEQ ID NO: 222, SEQ ID NO: 224, SEQ ID NO: 226, and SEQ ID NO: 228. In yet another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence selected from the group of SEQ ID NO: 210, SEQ ID NO: 212, SEQ ID NO: 214, SEQ ID NO: 218, SEQ ID NO: 220, SEQ ID NO: 222, SEQ ID NO: 224, SEQ ID NO: 226, and SEQ ID NO: 228. In another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a sequence selected from the group of SEQ ID NO: 230, SEQ ID NO: 232, SEQ ID NO: 234, and SEQ ID NO: 238. In yet another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence selected from the group of SEQ ID NO: 230, SEQ ID NO: 232, SEQ ID NO: 234, and SEQ ID NO: 238.

[0145] In one embodiment, the immunoconjugate comprises at least one, typically two or more antigen binding moieties that are specific for the Melanoma Chondroitin Sulfate Proteoglycan (MCSP). In another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain specific for MCSP shares a carboxy-terminal peptide bond with an IL-2 molecule, an IL-12 molecule, an IFN a molecule or a GM-CSF molecule, which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain specific for MCSP. In yet another embodiment, the immunoconjugate comprises a polypeptide sequence wherein a first Fab heavy chain specific for MCSP shares a carboxy-terminal peptide bond with an IL-2 molecule, which in turn shares a carboxy-terminal peptide bond with a second Fab heavy chain specific for MCSP. In a specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the sequence of either SEQ ID NO: 257 or SEQ ID NO: 261 or variants thereof that retain functionality. In another specific embodiment, the antigen binding moieties of the immunoconjugate comprise a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the sequence of either SEQ ID NO: 259 or SEQ ID NO: 271 or variants thereof that retain functionality. In a more specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the sequence of either SEQ ID NO: 257 or SEQ ID NO: 261, or variants thereof that retain functionality, and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the sequence of either SEQ ID NO: 259 or SEQ ID NO: 271, or variants thereof that retain functionality. In a more specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the sequence of SEQ ID NO: 257, and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the sequence of SEQ ID NO: 259. In another specific embodiment, the antigen binding moieties of the immunoconjugate comprise a heavy chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the sequence of SEQ ID NO: 261, and a light chain variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the sequence of SEQ ID NO: 259. In another specific embodiment, the heavy chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of either SEQ ID NO: 258 or SEQ ID NO: 262. In yet another specific embodiment, the heavy chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by the polynucleotide sequence of either SEQ ID NO: 258 or SEQ ID NO: 262. In another specific embodiment, the light chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of either SEQ ID NO: 260 or SEQ ID NO: 272. In yet another specific embodiment, the light chain variable region sequence of the antigen binding moieties of the immunoconjugate is encoded by the polynucleotide sequence of either SEQ ID NO: 260 or SEQ. ID NO: 272. In a specific embodiment, the immunoconjugate of the invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 251 or SEQ ID NO: 255, or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate of the invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 253 or SEQ ID NO: 265, or variants thereof that retain functionality. In a more specific embodiment, the immunoconjugate of the present invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 251 or SEQ ID NO: 255 or variants thereof that retain functionality, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to either SEQ ID NO: 253 or SEQ ID NO: 265, or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate of the present invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 251 or variants thereof that retain functionality, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 253 or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate of the present invention comprises a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 255 or variants thereof that retain functionality, and a polypeptide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 253 or variants thereof that retain functionality. In another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of either SEQ ID NO: 252 or SEQ ID NO: 256. In yet another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by the polynucleotide sequence of either SEQ ID NO: 252 or SEQ ID NO: 256. In another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by a polynucleotide sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of either SEQ ID NO: 254 or SEQ ID NO: 266. In yet another specific embodiment, the immunoconjugate comprises a polypeptide sequence encoded by the polynucleotide sequence of either SEQ ID NO: 254 or SEQ ID NO: 266.

[0146] In one embodiment the antigen binding moieties comprise at least a variable region capable of binding an antigenic determinant. Non-limiting variable regions useful in the present invention can be of murine, primate, or human origin. Human variable regions can be derived from human monoclonal antibodies made by the hybridoma method. Human myeloma and mouse-human heteromyeloma cell lines for the production of human monoclonal antibodies have been described, for example, by Kozbor et al., J Immunol. 133:3001-3005 (1984) and Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987). Human variable regions may also be produced by transgenic animals (e.g. mice) that are capable, upon immunization, of producing a repertoire of human antibodies in the absence of endogenous immunoglobulin production. For example, it has been described that the homozygous deletion of the antibody heavy chain joining region (J_H) gene in chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production. Transfer of the human germ-line immunoglobulin gene array in such germ-line mutant mice will result in the production of human antibodies upon antigenic challenge. See, e.g., Jakobovits et al., Nature 362:255-258 (1993).

[0147] Alternatively, phage display can be used to produce human antibodies and human variable regions in vitro from immunoglobulin variable (V) domain gene repertoires e.g., from unimmunized donors. (McCafferty et al., Nature 348:552-554 (1990).) In one example of this technique, antibody V domain genes are cloned in-frame into either a major or minor coat protein gene of a filamentous bacteriophage, such as M13 or fd, and displayed as functional antibody fragments on the surface of the phage particle.

[0148] Because the filamentous particle contains a single-stranded DNA copy of the phage genome, selections based on the functional properties of the antibody/antibody fragments also result in selection of the gene encoding the antibody/antibody fragments exhibiting those properties. Thus, the phage mimics some of the properties of the B-cell. Phage display can be performed in a variety of formats. For a review of phage display formats, see Hoogenboom et al., Nucleic Acids Res. 19:4133-4137 (1991). Several sources of V-gene segments can be used for phage display. Clackson et al., isolated a diverse array of anti-oxazolone antibodies from a small random combinatorial library of V genes derived from the spleens of immunized mice. See Clackson et al., Nature 352:624-628 (1991). A repertoire of V genes from unimmunized human donors can be constructed and antibodies to a diverse array of antigens (including self-antigens) can be isolated essentially following the techniques described by Marks et al., J. Mol. Bio. 222:581-597 (1991). In a natural immune response, antibody genes accumulate mutations at a high rate (somatic hypermutation). Some of the changes introduced will confer higher affinity, and B cells displaying high-affinity surface immunoglobulin are preferentially replicated and differentiated during subsequent antigen challenge. This natural process can be mimicked by employing the technique known as “chain shuffling.” See Marks et al., Biotech. 10:779-783 (1992). In this method, the affinity of “primary” human antibodies or variable regions obtained by phage display can be improved by sequentially. replacing the heavy and light chain V region genes with repertoires of naturally occurring variants (repertoires) of V domain genes obtained from unimmunized donors. This technique allows the production of antibodies and variable regions with affinities in the nM range. A strategy for making very large phage antibody repertoires has been described by Waterhouse et al., Nucl. Acids Res. 21:2265-2266 (1993), and the isolation of a high affinity human antibody directly from such large phage library is reported by Griffith et al., J. Cell. Bio. 120:885-896 (1993). Gene shuffling can also be used to derive human antibodies and variable regions from rodent antibodies, where the human antibody or variable region has similar affinities and specificities to the starting rodent antibody or variable region. According to this method, which is also referred to as “epitope imprinting,” the heavy or light chain V domain gene of rodent antibodies obtained by phage display techniques is replaced with a repertoire of human V domain genes, creating rodent-human chimeras. Selection with antigen results in the isolation of human variable regions capable of restoring a functional antigen binding site, i.e., the epitope governs (imprints) the choice of partner. When the process is repeated to replace the remaining rodent V domain, a human antibody is obtained (see PCT publication WO 93/06213). Unlike traditional humanization of rodent antibodies, the epitope imprinting technique provides completely human antibodies or variable regions, which have no framework or CDR residues of rodent origin.

[0149] Variable regions that can be used also include murine variable region sequences that have either been primatized or humanized or primate variable region sequences that have been humanized. As used herein, the term “humanized” refers to an antigen-binding moiety variable region sequence derived from a non-human antibody, for example, a murine antibody, that retains or substantially retains the antigen-binding properties of the parent molecule but which is less immunogenic in humans. This may be achieved by various methods including (a) grafting only the non-human CDRs onto human framework regions with or without retention of critical framework residues (e.g., those that are important for retaining good antigen binding affinity or antibody functions) and (b) “cloaking” the non-human variable regions with a human-like section by replacement of surface residues. Such methods are disclosed by Jones et al., Morrison et al,. Proc. Natl. Acad. Sci., 81:6851-6855 (1984); Morrison and Oi, Adv. Immunol., 44:65-92 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988); Padlan, Molec. Immun., 28:489-498 (1991); Padlan, Molec. Immun., 31(3):169-217 (1994), all of which are incorporated by reference in their entirety herein. There are generally 3 complementarity determining regions, or CDRs, (CDR1, CDR2, and CDR3) in each of the heavy and light chain variable regions of an antibody, which are flanked by four framework subregions (i.e., FR1, FR2, FR3, and FR4) in each of the heavy and light chain variable domains of an antibody: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. A discussion of antibodies with humanized variable regions can be found, inter alia, in U.S. Pat. No. 6,632,927, and in published U.S. Application No. 2003/0175269, both of which are incorporated herein by reference in their entirety.

[0150] Similarly, as used herein, the term “primatized” is used to refer to an antigen-binding moiety variable region derived from a non-primate antibody, for example, a murine antibody, that retains or substantially retains the antigen-binding properties of the parent molecule but which is less immunogenic in primates.

[0151] The choice of human variable domains, both heavy and light, in making humanized antigen binding moieties is very important to reduce antigenicity. According to the so-called “best fit” method, the sequence of the variable region of a rodent antigen binding moiety is screened against the entire library of known human variable-region sequences. The human sequence which is closest to that of the rodent is then accepted as the human framework region (FR) for the humanized antigen binding moiety (Sims et al., J. Immunol., 151:2296 (1993); Chothia et al., J. Mol. Biol., 196:901 (1987)). Another method of selecting the human framework sequence is to compare the sequence of each individual subregion of the full rodent framework (i.e., FR1, FR2, FR3, and FR4) or some combination of the individual subregions (e.g., FR1 and FR2) against a library of known human variable region sequences that correspond to that framework subregion (e.g., as determined by Kabat numbering), and choose the human sequence for each subregion or combination that is the closest to that of the rodent (U.S. Patent Application Publication No. 2003/0040606A1). Another method uses a particular framework region derived from the consensus sequence of all human antibodies of a particular subgroup of light or heavy chains. The same framework may be used for several different humanized antigen binding moieties (Carter et al., Proc. Natl. Acad. Sci. USA, 89:4285 (1992); Presta et al., J. Immunol., 151:2623 (1993)).

[0152] Generally, the antigen binding moieties of the immunoconjugate of the invention retain high affinity for specific antigenic determinants and other favorable biological properties. Accordingly, humanized variable regions are prepared by analyzing the parental sequences and various conceptual humanized products using three-dimensional models of the parental and humanized sequences. Three-dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art. Computer programs are available which illustrate and display probable three-dimensional conformation structures of selected candidate immunoglobulin variable region sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin variable region sequence, i.e., the analysis of residues that influence the ability of the candidate variable region sequence to bind its antigen. In this way, FR residues can be selected and combined from the recipient and import sequences so that the desired antigen binding moiety characteristic, such as increased affinity for the target antigen(s), is achieved. In general, the hypervariable region residues are directly and most substantially involved in influencing antigen binding.

[0153] In another embodiment, the antigen binding molecules of the present invention are engineered to have enhanced binding affinity according to, for example, the methods disclosed in U.S. Pat. Appl. Publ. No. 2004/0132066, the entire contents of which are hereby incorporated by reference. The ability of the immunoconjugate of the invention to bind to either an effector moiety receptor or to a specific antigenic determinant can be measured either through an enzyme linked immunosorbent assay (ELISA) or other techniques familiar to one of skill in the art, e.g., surface plasmon resonance technique (analyzed on a BIACORE T100 system) (Liljeblad, et al., Glyco. J. 17:323-329 (2000)), and traditional binding assays (Heeley, R. P., Endocr. Res. 28:217-229 (2002)).

[0154] The effector moieties for use in the invention are generally polypeptides that influence cellular activity, for example, through signal transduction pathways. Accordingly, the effector moiety of the immunoconjugate of the invention can be associated with receptor-mediated signaling that transmits a signal from outside the cell membrane to modulate a response within the cell. For example, an effector moiety of the immunoconjugate can be a cytokine. In a particular embodiment, the effector moiety is a single-chain effector moiety as defined herein. In one embodiment, one or more effector moieties, typically single-chain effector moieties, of the immunoconjugates of the invention are cytokines selected from the group consisting of: IL-2, GM-CSF, IFN-α, and IL-12. In another embodiment, one or more single-chain effector moieties of the immunoconjugates are cytokines selected from the group consisting of: IL-8, MIP-1α, MIP-1β, and TGF-β.

[0155] In one embodiment, the effector moiety, preferably a single-chain effector moiety, of the immunoconjugate is IL-2. In a specific embodiment, the IL-2 effector moiety can elicit one or more of the cellular responses selected from the group consisting of: proliferation in an activated T lymphocyte cell, differentiation in an activated T lymphocyte cell, cytotoxic T cell (CTL) activity, proliferation in an activated B cell, differentiation in an activated B cell, proliferation in a natural killer (NK) cell, differentiation in a NK cell, and NK/lymphocyte activated killer (LAK) antitumor cytotoxicity. In one embodiment, the effector moiety, preferably a single-chain effector moiety, of the immunoconjugate is GM-CSF. In a specific embodiment, the GM-CSF effector moiety can elicit proliferation and/or differentiation in a granulocyte, a monocyte or a dendritic cell. In one embodiment, the effector moiety, preferably a single-chain effector moiety, of the immunoconjugate is IFN-α. In a specific embodiment, the IFN-α effector moiety can elicit one or more of the cellular responses selected from the group consisting of: inhibiting viral replication in a virus-infected cell, and upregulating the expression of major histocompatibility complex I (MHC I). In another specific embodiment, the IFN α effector moiety can inhibit proliferation in a tumor cell. In one embodiment, the effector moiety, preferably a single-chain effector moiety, of the immunoconjugate is IL-12. In a specific embodiment, the IL-12 effcctor moiety can elicit one or more of the cellular responses selected from the group consisting of: proliferation in a NK cell, differentiation in a NK cell, proliferation in a T cell, and differentiation in a T cell. In one embodiment, the effector moiety, preferably a single-chain effector moiety, of the immunoconjugate is IL-8. In a specific embodiment, the IL-8 effector moiety can elicit chemotaxis in neutrophils. In one embodiment, the effector moiety, preferably a single-chain effector moiety, of the immunoconjugate, is MIP-1α. In a specific embodiment, the MIP-1α effector moiety can elicit chemotaxis in monocytes and T lymphocyte cells. In one embodiment, the effector moiety, preferably a single-chain effector moiety, of the immunoconjugate is MIP-1β. In a specific embodiment, the MIP-1β effector moiety can elicit chemotaxis in monocytes and T lymphocyte cells. In one embodiment, the effector moiety, preferably a single-chain effector moiety, of the immunoconjugate is TGF-β. In a specific embodiment, the TGF-β effector moiety can elicit one or more of the cellular responses selected from the group consisting of: chemotaxis in monocytes, chemotaxis in macrophages, upregulating the expression of IL-1 in activated macrophages, and upregulating the expression of IgA in activated B cells.

[0156] The immunoconjugates of the invention comprise polypeptides and fragments thereof. As used herein, term “polypeptide” is intended to encompass a singular “polypeptide” as well as plural “polypeptides,” and refers to a molecule composed of monomers (amino acids) linearly linked by amide bonds (also known as peptide bonds). The term “polypeptide” refers to any chain or chains of two or more amino acids, and does not refer to a specific length of the product. Thus, peptides, dipeptides, tripeptides, oligopeptides, “protein,” “amino acid chain,” or any other term used to refer to a chain or chains of two or more amino acids, are included within the definition of “polypeptide,” and the term “polypeptide” may be used instead of, or interchangeably with any of these terms. The term “polypeptide” is also intended to refer to the products of post-expression modifications of the polypeptide, including without limitation glycosylation, acetylation, phosphorylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, or modification by non-naturally occurring amino acids. A polypeptide may be derived from a natural biological source or produced by recombinant technology, but is not necessarily translated from a designated nucleic acid sequence. It may be generated in any manner, including by chemical synthesis.

[0157] A polypeptide of the invention may be of a size of about 3 or more, 5 or more, 10 or more, 20 or more, 25 or more, 50 or more, 75 or more, 100 or more, 200 or more, 500 or more, 1,000 or more, or 2,000 or more amino acids. Polypeptides may have a defined three-dimensional structure, although they do not necessarily have such structure. Polypeptides with a defined three-dimensional structure are referred to as folded, and polypeptides which do not possess a defined three-dimensional structure, but rather can adopt a large number of different conformations, and are referred to as unfolded.

[0158] By an “isolated” polypeptide or a variant, or derivative thereof is intended a polypeptide that is not in its natural milieu. No particular level of purification is required. For example, an isolated polypeptide can be removed from its native or natural environment. Recombinantly produced polypeptides and proteins expressed in host cells are considered isolated for purposed of the invention, as are native or recombinant polypeptides which have been separated, fractionated, or partially or substantially purified by any suitable technique.

[0159] Also included as polypeptides of the present invention are derivatives, analogs, or variants of the foregoing polypeptides, and any combination thereof. The terms “variant,” “derivative” and “analog” when referring to polypeptides of the present invention include any polypeptides that retain at least some of the biological, antigenic, or immunogenic properties of the corresponding native polypeptide. Variants of polypeptides of the present invention include polypeptides with altered amino acid sequences due to amino acid substitutions, deletions, or insertions. Variants may occur naturally or be non-naturally occurring. Non-naturally occurring variants may be produced using art-known mutagenesis techniques. Variant polypeptides may comprise conservative or non-conservative amino acid substitutions, deletions or additions. Derivatives of polypeptides of the present invention, are polypeptides which have been altered so as to exhibit additional features not found on the native polypeptide. Examples include fusion proteins. Variant polypeptides may also be referred to herein as “polypeptide analogs.” As used herein a “derivative” of a polypeptide refers to a subject polypeptide having one or more residues chemically derivatized by reaction of a functional side group. Also included as “derivatives” are those peptides which contain one or more naturally occurring amino acid derivatives of the twenty standard amino acids. For example, 4-hydroxyproline may be substituted for proline; 5-hydroxylysine may be substituted for lysine; 3-methylhistidine may be substituted for histidine; homoserine may be substituted for serine; and ornithine may be substituted for lysine.

[0160] Alternatively, recombinant variants encoding these same or similar polypeptides can be synthesized or selected by making use of the “redundancy” in the genetic code. Various codon substitutions, such as the silent changes which produce various restriction sites, may be introduced to optimize cloning into a plasmid or viral vector or expression in a particular prokaryotic or eukaryotic system. Mutations in the polynucleotide sequence maybe reflected in the polypeptide or domains of other peptides added to the polypeptide to modify the properties of any part of the polypeptide, to change characteristics such as ligand-binding affinities, interchain affinities, or degradation/turnover rate.

[0161] Preferably, amino acid “substitutions” are the result of replacing one amino acid with another amino acid having similar structural and/or chemical properties, i.e., conservative amino acid replacements. “Conservative” amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino, acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. “Insertions” or “deletions” are preferably in the range of about 1 to about 20 amino acids, more preferably 1 to 10 amino acids. The variation allowed may be experimentally determined by systematically making insertions, deletions, or substitutions of amino acids in a polypeptide molecule using recombinant DNA techniques and assaying the resulting recombinant variants for activity.

[0162] By a polypeptide having an amino acid sequence at least, for example, 95% “identical” to a query amino acid sequence of the present invention, it is intended that the amino acid sequence of the subject polypeptide is identical to the query sequence except that the subject polypeptide sequence may include up to five amino acid alterations per each 100 amino acids of the query amino acid sequence. In other words, to obtain a polypeptide having an amino acid sequence at least 95% identical to a query amino acid sequence, up to 5% of the amino acid residues in the subject sequence may be inserted, deleted, or substituted with another amino acid. These alterations of the reference sequence may occur at the amino or carboxy terminal positions of the reference amino acid sequence or anywhere between those terminal positions, interspersed either individually among residues in the reference sequence or in one or more contiguous groups within the references sequence.

[0163] As a practical matter, whether any particular polypeptide is at least 80%, 85%, 90%, 95%, 96,%, 97%, 98%, or 99% identical to a reference polypeptide can be determined conventionally using known computer programs. A preferred method for determining the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al., Comp. Appl. Biosci. 6:237-245 (1990). In a sequence alignment the query and subject sequences are either both nucleotide sequences or both amino acid sequences. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB amino acid alignment are: Matrix=PAM 0, k-tuple=2, Mismatch Penalty=1, Joining Penalty=20, Randomization Group Length=0, Cutoff Score=1, Window Size=sequence length, Gap Penalty=5, Gap Size Penalty-0.05, Window Size=500 or the length of the subject amino acid sequence, whichever is shorter.

[0164] If the subject sequence is shorter than the query sequence due to N- or C-terminal deletions, not because of internal deletions, a manual correction must be made to the results. This is because the FASTDB program does not account for N- and C-terminal truncations of the subject sequence when calculating global percent identity. For subject sequences truncated at the N- and C-termini; relative to the query sequence, the percent identity is corrected by calculating the number of residues of the query sequence that are N- and C-terminal of the subject sequence, which are not matched/aligned with a corresponding subject residue, as a percent of the total bases of the query sequence. Whether a residue is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This final percent identity score is what is used for the purposes of the present invention. Only residues to the N- and C-termini of the subject sequence, which are not matched/aligned with the query sequence, are considered for the purposes of manually adjusting the percent identity score. That is, only query residue positions outside the farthest N- and C-terminal residues of the subject sequence.

[0165] For example, a 90 amino acid residue subject sequence is aligned with a 100 residue query sequence to determine percent identity. The deletion occurs at the N-terminus of the subject sequence and therefore, the FASTDB alignment does not show a matching/alignment of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (number of residues at the N- and C-termini not matched/total number of residues in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 residues were perfectly matched the final percent identity would be 90%. In another example, a 90 residue subject sequence is compared with a 100 residue query sequence. This time the deletions are internal deletions so there are no residues at the N- or C-termini of the subject sequence which are not matched/aligned with the query. In this case, the percent identity calculated by FASTDB is not manually corrected. Once again, only residue positions outside the N- and C-terminal ends of the subject sequence, as displayed in the FASTDB alignment, which are not matched/aligned with the query sequence are manually corrected for: No other manual corrections are to be made for the purposes of the present invention.

[0166] Polypeptides of the invention include those that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequences set forth in Tables 3 and 4, below, including functional fragments or variants thereof. The invention also encompasses polypeptides comprising sequences of Tables 3 or 4 with conservative amino acid substitutions.

[0167] The polypeptides of the invention may be encoded by a single polynucleotide. Alternatively, the may be encoded by multiple (e.g., two or more) polynucleotides, so that the polypeptides are co-expressed. Polypeptides that are co-expressed from multiple polynucleotides may associate through, e.g., disulfide bonds or other means to form a functional immunoconjugate. For example, the heavy chain portion of an antigen binding moiety may be encoded by a separate polynucleotide from the portion of the immunoconjugate comprising the light chain portion of the antigen binding moiety and the effector moiety. When co-expressed, the heavy chain polypeptides will associate with the light chain polypeptides to form the antigen binding moiety. Alternatively, in another example, the light chain portion of the antigen binding moiety could be encoded by a separate polynucleotide from the portion of the immunoconjugate comprising the heavy chain portion of the antigen binding moiety and the effector moiety.

[0168] Immunoconjugates of the present invention and fragments thereof are generally encoded by polynucleotides. The term “polynucleotide” is intended to encompass a singular nucleic acid as well as plural nucleic acids, and refers to an isolated nucleic acid molecule or construct, e.g., messenger RNA (mRNA), virally-derived RNA, or plasmid DNA (pDNA). A polynucleotide may comprise a conventional phosphodiester bond or a non-conventional bond (e.g., an amide bond, such as found in peptide nucleic acids (PNA)). The term “nucleic acid” refers to any one or more nucleic acid segments, e.g., DNA or RNA fragments, present in a polynucleotide. By “isolated” nucleic acid or polynucleotide is intended a nucleic acid molecule, DNA or RNA, which has been removed from its native environment. For example, a recombinant polynucleotide encoding a therapeutic polypeptide contained in a vector is considered isolated for the purposes of the present invention. Further examples of an isolated polynucleotide include recombinant polynucleotides maintained in heterologous host cells or purified (partially or substantially) polynucleotides in solution. Isolated RNA molecules include in vivo or in vitro RNA transcripts of the present invention, as well as positive and negative strand forms, and double-stranded forms, of pestivirus vectors disclosed herein.

[0169] Isolated polynucleotides or nucleic acids according to the present invention further include such molecules produced synthetically. In addition, a polynucleotide or a nucleic acid may be or may include a regulatory element such as a promoter, ribosome binding site, or a transcription terminator.

[0170] As used herein, a “coding region” is a portion of nucleic acid which consists of codons translated into amino acids. Although a “stop codon” (TAG, TGA, or TAA) is not translated into an amino acid, it may be considered to be part of a coding region, if present, but any flanking sequences, for example promoters, ribosome binding sites, transcriptional terminators, introns, 5′ and 3′ non-translated regions, and the like, are not part of a coding region. Two or more coding regions of the present invention can be present in a single polynucleotide construct, e.g., on a single vector, or in separate polynucleotide constructs, e.g., on separate (different) vectors. Furthermore, any vector may contain a single coding region, or may comprise two or more coding regions, e.g., a vector of the present invention may encode one or more polyproteins, which are post- or co-translationally separated into the final proteins via proteolytic cleavage. In addition, a vector, polynucleotide, or nucleic acid of the invention may encode heterologous coding regions, either fused or unfused to a first or second nucleic acid encoding the immunoconjugate of the invention, or variant or derivative thereof. Heterologous coding regions include without limitation specialized elements or motifs, such as a secretory signal peptide or a heterologous functional domain.

[0171] In certain embodiments, the polynucleotide or nucleic acid is DNA. In the case of DNA, a polynucleotide comprising a nucleic acid, which encodes a polypeptide normally may include a promoter and/or other transcription or translation control elements operably associated with one or more coding regions. An operable association is when a coding region for a gene product, e.g., a polypeptide, is associated with one or more regulatory sequences in such a way as to place expression of the gene product under the influence or control of the regulatory sequence(s). Two DNA fragments (such as a polypeptide coding region and a promoter associated therewith) are “operably associated” if induction of promoter function results in the transcription of mRNA encoding the desired gene product and if the nature of the linkage between the two DNA fragments does not interfere with the ability of the expression regulatory sequences to direct the expression of the gene product or interfere with the ability of the DNA template to be transcribed. Thus, a promoter region would be operably associated with a nucleic acid encoding a polypeptide if the promoter was capable of effecting transcription of that nucleic acid. The promoter may be a cell-specific promoter that directs substantial transcription of the DNA only in predetermined cells. Other transcription control elements, besides a promoter, for example enhancers, operators, repressors, and transcription termination signals, can be operably associated with the polynucleotide to direct cell-specific transcription. Suitable promoters and other transcription control regions are disclosed herein.

[0172] A variety of transcription control regions are known to those skilled in the art. These include, without limitation, transcription control regions, which function in vertebrate cells, such as, but not limited to, promoter and enhancer segments from cytomegaloviruses (e.g., the immediate early promoter, in conjunction with intron-A), simian virus 40 (e.g., the early promoter), and retroviruses (such as, e.g., Rous sarcoma virus). Other transcription control regions include those derived from vertebrate genes such as actin, heat shock protein, bovine growth hormone and rabbit B-globin, as well as other sequences capable of controlling gene expression in eukaryotic cells. Additional suitable transcription control regions include tissue-specific promoters and enhancers as well as lymphokine-inducible promoters (e.g., promoters inducible by interferons or interleukins).

[0173] Similarly, a variety of translation control elements are known to those of ordinary skill in the art. These include, but are not limited to ribosome binding sites, translation initiation and termination codons, and elements derived from viral systems (particularly an internal ribosome entry site, or IRES, also referred to as a CITE sequence).

[0174] In other embodiments, a polynucleotide of the present invention is RNA, for example, in the form of messenger RNA (mRNA). RNA of the present invention may be single stranded or double stranded.

[0175] Polynucleotide and nucleic acid coding regions of the present invention may be associated with additional coding regions which encode secretory or signal peptides, which direct the secretion of a polypeptide encoded by a polynucleotide of the present invention. According to the signal hypothesis, proteins secreted by mammalian cells have a signal peptide or secretory leader sequence which is cleaved from the mature protein once export of the growing protein chain across the rough endoplasmic reticulum has been initiated. Those of ordinary skill in the art are aware that polypeptides secreted by vertebrate cells generally have a signal peptide fused to the N-terminus of the polypeptide, which is cleaved from the complete or “full length” polypeptide to produce a secreted or “mature” form of the polypeptide. In certain embodiments, the native signal peptide, e.g., an immunoglobulin heavy chain or light chain signal peptide is used, or a functional derivative of that sequence that retains the ability to direct the secretion of the polypeptide that is operably associated with it. Alternatively, a heterologous mammalian signal peptide, or a functional derivative thereof, may be used. For example, the wild-type leader sequence may be substituted with the leader sequence of human tissue plasminogen activator (TPA) or mouse β-glucuronidase.

[0176] The term “expression cassette” refers to a polynucleotide generated recombinantly or synthetically, with a series of specified nucleic acid elements that permit transcription of a particular nucleic acid in a target cell. The recombinant expression cassette can be incorporated into a plasmid, chromosome, mitochondrial DNA, plastid DNA, virus, or nucleic acid fragment. Typically, the recombinant expression cassette portion of an expression vector includes, among other sequences, a nucleic acid sequence to be transcribed and a promoter. In one embodiment, the expression cassette of the invention comprises polynucleotide sequences that encode immunoconjugates of the invention or fragments thereof.

[0177] The term “expression vector” is synonymous with “expression contsruct” and refers to a DNA molecule that is used to introduce and direct the expression of a specific gene to which it is operably associated into a target cell. The expression vector of the present invention comprises an expression cassette. Expression vectors allow transcription of large amounts of stable mRNA. Once the expression vector is inside the target cell, the ribonucleic acid molecule or protein that is encoded by the gene is produced by the cellular transcription and/or translation machinery. In one embodiment, the expression vector of the invention comprises an expression cassette comprises polynucleotide sequences that encode immunoconjugates of the invention or fragments thereof.

[0178] The term “artificial” refers to a synthetic, or non-host cell derived composition, e.g., a chemically-synthesized oligonucleotide.

[0179] By a nucleic acid or polynucleotide having a nucleotide sequence at least, for example, 95% “identical” to a reference nucleotide sequence of the present invention, it is intended that the nucleotide sequence of the polynucleotide is identical to the reference sequence except that the polynucleotide sequence may include up to five point mutations per each 100 nucleotides of the reference nucleotide sequence. In other words, to obtain a polynucleotide having a nucleotide sequence at least 95% identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence may be deleted or substituted with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence.

[0180] As a practical matter, whether any particular nucleic acid molecule or polypeptide is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a nucleotide sequence or polypeptide sequence of the present invention can be determined conventionally using known computer programs. A preferred method for determining the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al., Comp. Appl. Biosci. 6:237-245 (1990). In a sequence alignment the query and subject sequences are both DNA sequences. An RNA sequence can be compared by converting U's to T's. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB alignment of DNA sequences to calculate percent identity are: Matrix=Unitary, k-tuple=4, Mismatch Penalty=1, Joining Penalty-30, Randomization Group Length=0, Cutoff Score=1, Gap Penalty=5, Gap Size Penalty=0.05, Window Size=500 or the length of the subject nucleotide sequences, whichever is shorter.

[0181] If the subject sequence is shorter than the query sequence because of 5′ or 3′ deletions, not because of internal deletions, a manual correction must be made to the results. This is because the FASTDB program does not account for 5′ and 3′ truncations of the subject sequence when calculating percent identity. For subject sequences truncated at the 5′ or 3′ ends, relative to the query sequence, the percent identity is corrected by calculating the number of bases of the query sequence that are 5′ and 3′ of the subject sequence, which are not matched/aligned, as a percent of the total bases of the query sequence. Whether a nucleotide is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This corrected score is what is used for the purposes of the present invention. Only bases outside the 5′ and 3′ bases of the subject sequence, as displayed by the FASTDB alignment, which are not matched/aligned with the query sequence, are calculated for the purposes of manually adjusting the percent identity score.

[0182] For example, a 90 base subject sequence is aligned to a 100 base query sequence to determine percent identity. The deletions occur at the 5′ end of the subject sequence and therefore, the FASTDB alignment does not show a matched/alignment of the first 10 bases at 5′ end. The 10 unpaired bases represent 10% of the sequence (number of bases at the 5′ and 3′ ends not matched/total number of bases in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 bases were perfectly matched the final percent identity would be 90%. In another example, a 90 base subject sequence is compared with a 100 base query sequence. This time the deletions are internal deletions so that there are no bases on the 5′ or 3′ of the subject sequence which are not matached/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only bases 5′ and 3′ of the subject sequence which are not matched/aligned with the query sequence are manually corrected for. No other manual corrections are to be made for the purposes of the present invention.

[0183] Polynucleotides of the invention include those that are at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequences set forth in Tables 6 and 8, below, including functional fragments or variants thereof. The polynucleotides may be expressed as a single polynucleotide that encodes the entire immunoconjugate or as multiple (e.g., two or more) polynucleotides that are coexpressed. Polypeptides encoded by polynucleotides that are co-expressed may associate through, e.g., disulfide bonds or other means to form a functional immunoconjugate. For example, the heavy chain portion of an antigen binding moiety may be encoded by a separate polynucleotide from the portion of the immunoconjugate comprising the light chain portion of the antigen binding moiety and the effector moiety. When coexpressed, the heavy chain polypeptides will associate with the light chain polypeptides to form the antigen binding moiety. Alternatively, in another example, the light chain portion of the antigen binding moiety could be encoded by a separate polynucleotide from the portion of the immunoconjugate comprising the heavy chain portion of the antigen binding moiety and the effector moiety.

[0184] In a specific embodiment, an isolated polynucleotide of the invention encodes a fragment of an immunoconjugate comprising at least one effector moiety, preferably a single-chain effector moiety, and at least one, preferably two or more antigen binding moieties, wherein a first effector moiety shares an amino- or carboxy-terminal peptide bond with a first antigen binding moiety and a second antigen binding moiety shares an amino- or carboxy-terminal peptide bond with either the first effector moiety or the first antigen binding moiety. In a preferred embodiment, the antigen binding moieties are independently selected from the group consisting of Fv and Fab. In another specific embodiment, the polynucleotide encodes the heavy chains of two of the antigen binding moieties and one of the effector moieties. In another specific embodiment, the polynucleotide encodes the light chains of two of the antigen binding moieties and one of the effector moieties. In another specific embodiment, the polynucleotide encodes one light chain from one of the antigen binding moieties, one heavy chain from a second antigen binding moiety and one of the effector moieties.

[0185] In another specific embodiment, an isolated polynucleotide of the invention encodes a fragment of an immunoconjugate, wherein the polynucleotide encodes the heavy chains of two Fab molecules and an effector moiety, preferably a single-chain effector moiety. In another specific embodiment, an isolated polynucleotide of the invention encodes a fragment of an immunoconjugate, wherein the polynucleotide encodes the light chains of two Fab molecules and an effector moiety, preferably a single-chain effector moiety. In another specific embodiment an isolated polynucleotide of the invention encodes a fragment of an immunoconjugate, wherein the polynucleotide encodes the heavy chain of one Fab molecule, the light chain of second Fab molecule and an effector moiety, preferably a single-chain effector moiety.

[0186] In one embodiment, an isolated polynucleotide of the invention encodes an immunoconjugate comprising at least one effector moiety, preferably a single-chain effector moiety, joined at its amino- and carboxy-terminal amino acids to one or more scFv molecules.

[0187] In one embodiment, an isolated polynucleotide of the invention encodes an immunoconjugate fragment comprising at least one effector moiety, preferably a single-chain effector moiety and at least first and second antigen binding moieties, wherein each of the antigen binding moieties comprises an scFv molecule joined at its carboxy-terminal amino acid to a constant region comprising an immunoglobulin constant domain independently selected from the group consisting of IgG1 CH1, IgG C_kappa, and IgE CH4, and wherein one of the antigen binding moieties is joined at its constant region carboxy-terminal amino acid to the amino-terminal amino acid of one of the effector moieties, and wherein the first and second antigen binding moieties are covalently linked through a disulfide bond. In a further embodiment, the polynucleotide of the invention encodes one of the antigen binding moieties and an effector moiety, preferably a single-chain effector moiety.

[0188] In one embodiment, an isolated polynucleotide of the invention encodes an immunoconjugate fragment comprising first and second effector moieties and two antigen binding moieties, wherein each of the antigen binding moieties comprises an scFv molecule joined at its carboxy-terminal amino acid to a constant region comprising an immunoglobulin constant domain, and wherein one of the antigen binding moieties is joined at its constant region carboxy-terminal amino acid to the amino-terminal amino acid of one of the effector moieties, and wherein the second antigen binding moiety is joined at its constant region carboxy-terminal amino acid to the amino-terminal amino acid of the second effector moiety, and wherein the first and second antigen binding moieties are covalently linked through a disulfide bond. In a preferred embodiment, the first and/or second effector moieties are single chain effector moieties. In a preferred embodiment, the constant domain is independently selected from the group consisting of IgG1 CH1, IgG C_kappa, and IgE CH4. In a further embodiment, the polynucleotide of the invention encodes one of the antigen binding moieties and one of the effector moieties.

[0189] In one embodiment, an isolated polynucleotide of the invention encodes an immunoconjugate fragment comprising at least one effector moiety, preferably a single-chain effector moiety, and at least first and second antigen binding moieties, wherein each of the antigen binding moieties comprises an scFv molecule joined at its carboxy-terminal amino acid to an IgG CH3 domain, and wherein one of the antigen binding moieties is joined at its carboxy-terminal amino acid to the amino-terminal amino acid of one of the effector moieties, and wherein the first and second antigen binding moieties are covalently linked through a disulfide bond. In a further embodiment, the polynucleotide of the invention encodes one of the antigen binding moieties and an effector moiety, preferably a single chain effector moiety.

[0190] In one embodiment, an isolated polynucleotide of the invention encodes an immunoconjugate fragment comprising two effector moieties and two antigen binding moieties, wherein each of the antigen binding moieties comprises an scFv molecule joined at its carboxy-terminal amino acid to an IgG CH3 domain, and wherein one of the antigen binding moieties is joined at its carboxy-terminal amino acid to the amino-terminal amino acid of one of the effector moieties, and wherein the second antigen binding moiety is joined at its carboxy-terminal amino acid to the amino-terminal amino acid of the second effector moiety, and wherein the first and second antigen binding moieties are covalently linked through a disulfide bond. In a preferred embodiment, the first and/or second effector moieties are single chain effector moieties. In a further embodiment, the polynucleotide of the invention encodes one of the antigen binding moieties and one of the effector moieties, preferably a single chain effector moiety.

[0191] In one embodiment, an isolated polynucleotide of the invention encodes an immunoconugate fragment comprising two effector moieties and two antigen binding moieties, wherein each of the antigen binding moieties comprises an Fab molecule joined at its heavy or light chain carboxy-terminal amino acid to an IgG1 CH3 domain, and wherein each of the IgG1 CH3 domains is joined at its carboxy-terminal amino acid to the amino-terminal amino acid of one of the effector moieties, and wherein the first and second antigen binding moieties are covalently linked through a disulfide bond. In a preferred embodiment, the first and/or second effector moieties are single chain effector moieties. In a further embodiment, the polynucleotide of the invention comprises a sequence encoding the heavy chain variable region of one of the antigen binding moieties and one of said effector moieties, preferably a single chain moiety. In yet another embodiment, the polynucleotide of the invention comprises a sequence encoding the light chain variable region of one of the antigen binding moieties and one of the effector moieties, preferably a single chain effector moiety.

[0192] In another embodiment, the present invention is directed to an isolated polynucleotide encoding an immunoconjugate or fragment thereof, wherein the polynucleotide comprises a sequence that encodes a variable region sequence as shown in Table 3 below. In another embodiment, the present invention is directed to an isolated polynucleotide encoding an immunoconjugate or fragment thereof, wherein the polynucleotide comprises a sequence that encodes a polypeptide sequence as shown in Table 4. In another embodiment, the invention is further directed to an isolated nucleic acid encoding an immunoconjugate or fragment thereof, wherein the nucleic acid comprises a sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to a nucleotide sequence shown in Tables 6 and 8 below. In another embodiment, the invention is directed to an isolated nucleic acid encoding an immunoconjugate or fragment thereof, wherein the nucleic acid comprises a nucleic acid sequence shown in Tables 6 and 8. In another embodiment, the invention is directed to an isolated nucleic acid encoding an immunoconjugate or fragment thereof, wherein the nucleic acid comprises a sequence that encodes a variable region sequence that is at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence in Table 3. In another embodiment, the invention is directed to an isolated nucleic acid encoding an immunoconjugate or fragment thereof, wherein the nucleic acid comprises a sequence that encodes a polypeptide sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence in Table 4. The invention encompasses an isolated nucleic acid encoding an immunoconjugate or fragment thereof, wherein the nucleic acid comprises a sequence that encodes the variable region sequences of Table 3 with conservative amino acid substitutions. The invention also encompasses an isolated nucleic acid encoding an immunoconjugate of the invention or fragment thereof, wherein the nucleic acid comprises a sequence that encodes the polypeptide sequences of Table 4 with conservative amino acid substitutions.

TABLE 2
Construct	NUCLEOTIDE SEQUENCE	SEQ ID NO
Library Template	ATGAAATACCTATTGCCTACGGCAGCCGCTGGATTGTTAT	1
for DP47-3 library;	TACTCGCGGCCCAGCCGGCCATGGCCGAAATCGTGTTAAC
complete Fab	GCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGA
coding region	GCCACCCTCTCTTGCAGGGCCAGTCAGAGTGTTAGCAGCA
comprising PelB	GCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCC
leader sequence +	CAGGCTCCTCATCTATGGAGCATCCAGCAGGGCCACTGGC
Vk3_20 kappa V-	ATCCCAGACAGGTTCAGTGGCAGTGGATCCGGGACAGAC
domain + CL	TTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTG
constant domain	CAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGCTGAC
for light chain and	GTTCGGCCAGGGGACCAAAGTGGAAATCAAACGTACGGT
PelB + VH3_23	GGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAG
V-domain + CH1	CAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGA
constant domain	ATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGG
for heavy chain;	TGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG
pMS25opt	TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCA
	GCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAAC
	ACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
	GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTG
	GAGCCGCAGAACAAAAACTCATCTCAGAAGAGGATCTGA
	ATGGAGCCGCAGACTACAAGGACGACGACGACAAGGGTG
	CCGCATAATAAGGCGCGCCAATTCTATTTCAAGGAGACA
	GTCATATGAAATACCTGCTGCCGACCGCTGCTGCTGGTCT
	GCTGCTCCTCGCTGCCCAGCCGGCGATGGCCGAGGTGCA
	ATTGCTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGG
	GTCCCTGAGACTCTCCTGTGCAGCCTCCGGATTCACCTTT
	AGCAGTTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGG
	AAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGT
	GGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTC
	ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGC
	AGATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATT
	ACTGTGCGAAACCGTTTCCGTATTTTGACTACTGGGGCCA
	AGGAACCCTGGTCACCGTCTCGAGTGCTAGCACCAAAGG
	CCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGAC
	TACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCG
	CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
	GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTG
	CCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACG
	TGAATCACAAGCCCAGCAACACCAAAGTGGACAAGAAAG
	TTGAGCCCAAATCTTGTGACGCGGCCGCAAGCACTAGTGC
	CCATCACCATCACCATCACGCCGCGGCATAG
Library Template	ATGAAATACCTATTGCCTACGGCAGCCGCTGGATTGTTAT	2
for DP88-3 library;	TACTCGCGGCCCAGCCGGCCATGGCCGATATCCAGATGA
complete Fab	CCCAGTCTCCATCCTCCCTGTCTGCATCTGTCGGAGACCG
coding region	GGTCACCATCACCTGCCGGGCAAGTCAGGGCATTAGAAA
comprising PelB	TGATTTAGGCTGGTACCAGCAGAAGCCAGGGAAAGCCCC
leader sequence +	TAAGCGCCTGATCTATGCTGCATCCAGTTTGCAGAGTGGC
Vk1_17 kappa V-	GTCCCATCAAGGTTCAGCGGCAGTGGATCCGGGACAGAG
domain + CL	TTCACTCTCACCATCAGCAGCTTGCAGCCTGAAGATTTTG
constant domain	CCACCTATTACTGCTTGCAGCATAATAGTTACCCCACGTT
for light chain and	TGGCCAGGGCACCAAAGTCGAGATCAAGCGTACGGTGGC
PelB + VH1_69	TGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAG
V-domain + CH1	TTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATA
constant domain	ACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGG
for heavy chain;	ATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCA
pRJH32	CAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCA
	GCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACA
	AAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTC
	GCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTGGAGC
	CGCAGAACAAAAACTCATCTCAGAAGAGGATCTGAATGG
	AGCCGCAGACTACAAGGACGACGACGACAAGGGTGCCGC
	ATAATAAGGCGCGCCAATTCTATTTCAAGGAGACAGTCAT
	ATGAAATACCTGCTGCCGACCGCTGCTGCTGGTCTGCTGC
	TCCTCGCTGCCCAGCCGGCGATGGCCCAGGTGCAATTGGT
	GCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGT
	GAAGGTCTCCTGCAAGGCCTCCGGAGGCACATTCAGCAG
	CTACGCTATAAGCTGGGTGCGACAGGCCCCTGGACAAGG
	GCTCGAGTGGATGGGAGGGATCATCCCTATCTTTGGTACA
	GCAAACTACGCACAGAAGTTCCAGGGCAGGGTCACCATT
	ACTGCAGACAAATCCACGAGCACAGCCTACATGGAGCTG
	AGCAGCCTGAGATCTGAGGACACCGCCGTGTATTACTGTG
	CGAGACTATCCCCAGGCGGTTACTATGTTATGGATGCCTG
	GGGCCAAGGGACCACCGTGACCGTCTCCTCAGCTAGCAC
	CAAAGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAG
	AGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTC
	AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAAC
	TCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTG
	TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT
	GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATC
	TGCAACGTGAATCACAAGCCCAGCAACACCAAAGTGGAC
	AAGAAAGTTGAGCCCAAATCTTGTGACGCGGCCGCAAGC
	ACTAGTGCCCATCACCATCACCATCACGCCGCGGCATAG

TABLE 3
Construct	POLYPEPTIDE SEQUENCE	SEQ ID NO
2B10; VL	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPG	3
	KAPKRLIYAASSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFA
	TYYCLQNGLQPATFGQGTKVEIK
2B10(GS); VL	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPG	5
	KAPKRLIYAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFAT
	YYCLQNGLQPATFGQGTKVEIK
2B10; VH	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	7
	GQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSTSTAYME
	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSS
2F11; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	9
	QAPRLLIYGASSRATGVPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGQYTPPTFGQGTKVEIK
2F11(VI); VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	11
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQYTPPTFGQGTKVEIK
2F11; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	13
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDMAVYYCAKWRWMMFDYWGQGTLVTVSS
2F11(MT); VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	15
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNS$$RAEDTAVYYCAKWRWMMFDYWGQGTLVTVSS
3F2; VL	EIVLTQSPGTLSLYPGERATLSCRASQSVTSSYLAWYQQKPG	17
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
3F2(YS); VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	19
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
3F2; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	21
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAE$$TAVYYCAKGWFGGFNYWGQGTLVTVSS
3D9, VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	23
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQLIPPTFGQGTKVEIK
3D9, VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQTP	25
	GKGLEWVSAIGVSTGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGPFDYWGQGTLVTVSS
2D9(TA); VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	27
	GKGLEWVSAIGVSTGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGPFDYWGQGTLVTVSS
4G8; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSRSYLAWYQQKPG	29
	QAPRLLIIGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQVIPPTFGQGTKVEIK
4G8; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	31
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSS
4B3; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPG	33
	QAPRLLIYGAYIRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQVIPPTFGQGTKVEIK
4B3; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	35
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSS
4D6; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPG	37
	QAPRLLIQGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQVIPPTFGQGTKVEIK
4D6; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	39
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSS
2C6; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	41
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQQIPPTFGQGTKVEIK
2C6; VH	EVQLLESGGGLVQPGGSLRLSCAASGSTFSSYAMSWVRQAP	43
	GKGLEWVSAISGSAGYTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGNFDYWGQGTLVTVSS
5H5; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	45
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGNQIPPTFGQGTKVEIK
5H5; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRRSP	47
	GKGLEWVSAISGGGRTYYADSVKGRFTISRDNSKNTLYLQM
	NSLRAEDTAVYYCAKGWFTPFDYWGQGTLVTVSS
2C4; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPG	49
	QAPRLLIYGASIRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGNQIPPTFGQGTKVEIK
2C4; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	51
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFTPFDYWGQGTLVTVSS
2D9; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	67
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGNQIPPTFGQGTKVEIK
2D9; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	69
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFTPFDYWGQGTLVTVSS
4B8; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	71
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQVIPPTFGQGTKVEIK
4B8; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	73
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSS
7A1; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	75
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQQIPPTFGQGTKVEIK
7A1; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	77
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGNFDWGQGTLVTVSS
13C2; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	79
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQLIPPTFGQGTKVEIK
13C2; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	81
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGPFDYWGQGTLVTVSS
13E8; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	83
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGLNIPSTFGQGTKVEIK
13E8; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	85
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGPFDYWGQGTLVTVSS
14C10; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	87
	QAPRLL$$YGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGHIIPPTFGQGTKVEIK
14C10; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	89
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKAWMGPFDYWGQGTLVTVSS
17A11; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	91
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGLNIPSTFGQGTKVEIK
17A11; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	93
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGPFDYWGQGTLVTVSS
19G1; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	121
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
19G1; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	123
	GKGLEWVSAIISSGGLTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
20G8; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	125
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
20G8; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	127
	GKGLEWVSAIIGSGSRTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGGF$$YWGQGTLVTVSS
4B9; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	129
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
4B9; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	131
	GKGLEWVSAIIGSGASTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
5B8; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	133
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
5B8; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	135
	GKGLEWVSAIWGGGRSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
5F1; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	137
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
5F1; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	139
	GKGLEWVSAIISSGASTYYADSVKGRFTISRDNSKNTLYLQM
	NSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
14B3; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	141
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
14B3; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	143
	GKGLEWVSAILASGAITYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
16F1; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	145
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
16F1; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	147
	GKGLEWVSGIIGSGGITYYADSVKGRFTISRDNSKNTLYLQM
	NSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
16F8; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	149
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
16F8; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	151
	GKGLEWVSAILGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
O3C9; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	153
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
O3C9; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFAMSWVRQSP	155
	GKGLEWVSAIIGSGSNTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
O2D7; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	157
	QAPRLLINVGSRRATGTPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQAIMLPPTFGQGTKVEIK
O2D7; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	159
	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
28H1; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSRSYLAWYQQKPG	161
	QAPRLLIIGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQVIPPTFGQGTKVEIK
28H1; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSHAMSWVRQAP	163
	GKGLEWVSAIWASGEQYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSS
22A3; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	165
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIK
22A3; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	167
	GKGLEWVSAIIGSGSITYYADSVKGRFTISRDNSKNTLYLQM
	NSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
29B11; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	169
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVELK
29B11; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	171
	GKGLEWVSAIIGSGGITYYADSVKGRFTISRDNSKNTLYLQM
	NSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSS
23C10; VL	EIVLTQSPGTLSLSPGERATLSCRASQSVSRSYLAWYQQKPG	173
	QAPRLLIIGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQVIPPTFGQGTKVEIK
23C10; VH	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSAMSWVRQAP	175
	GKGLEWVSAISTNGNYTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSS
2B10_C3B6; VL	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPG	177
	KAPKRLIYAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFAT
	YYCLQNGLQPATFGQGTKVEIK
2B10_C3B6; VH	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	179
	GQGLEWMGAIIPILGIANYAQKFQGRVTITADKSTSTAYMEL
	SSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSS
2B10_6A12; VL	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPG	181
	KAPKRLIYAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFAT
	YYCLQNGLQPATFGQGTKVEIK
2B10_6A12; VH	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	183
	GQGLEWMGVIIPILGTANYAQKFQGRVTITADKSTSTAYME
	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSS
2B10_C3A6; VL	DIQMTQSPSSLSASVGDRVTITCRASQGIRNVLGWYQQKPG	185
	KAPKRLIYDSSSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFAT
	YYCLQNGLQPATFGQGTKVEIK
2B10_C3A6; VH	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	187
	GQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSTSTAYME
	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSS
2B10_D1A2_wt;	DIQMTQSPSSLSASVGDRVTITCRASQGIRNVLGWYQQKPG	189
VL	KAPKRLIYDAYSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFA
	TYYCLQNGLQPATFGQGTKVEIK
2B10_D1A2_wt;	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	191
VH	GQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSTSTAYME
	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSS
2B10_D1A2_VD;	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPG	193
VL	KAPKRLIYDAYSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFA
	TYYCLQNGLQPATFGQGTKVEIK
2B10_D1A2_VD;	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	195
VH	GQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSTSTAYME
	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSS
2B10_O7D8; VL	DIQMTQSPSSLSASVGDRVTITCRASQSIRNVLGWYQQKPGK	197
	APKRLIYDVSSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFAT
	YYCLQNGLQPATFGQGTKVEIK
2B10_O7D8; VH	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	199
	GQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSTSTAYME
	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSS
2B10_O1F7; VL	DIQMTQSPSSLSASVGDRVTITCRASQGIRNVLGWYQQKPG	201
	KAPKRLIYDASSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFA
	TYYCLQNGLQPATFGQGTKVEIK
2B10_O1F7; VH	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	203
	GQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSTSTAYME
	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSS
2B10_6H10; VL	DIQMTQSPSSLSASVGDRVTITCRASQGIRNVLGWYQQKPG	205
	KAPKRLIQAATSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFA
	TYYCLQNGLQPATFGQGTKVEIK
2B10_6H10; VH	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	207
	GQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSTSTAYME
	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSS
MHLG1; VH	EVQLVESGGGLVKPGGSLRLSCAASGFTFSNYWMNWVRQA	257
	PGKGLEWVAEIRLKSNNFGRYYAASVKGRFTISRDDSKNTL
	YLQMNSLKTEDTAVYYCTTYGNYVGHYFDHWGQGTTVTV
	SS
KV9; VL	DIQLTQSPSFLSASVGDRVTITCKASQNVDTNVAWYQQKPG	259
	QAPRPLIYSASYRYTGVPSRFSGSGSGTEFTLTISSLQPEDFAT
	YYCQQYNSYPLTFGGGTKVEIKRT
MHLG; VH	EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNWVRQA	261
	PGKGLEWVAEIRLKSNNFGRYYAASVKGRFTISRDDSKNTL
	YLQMNSLKTEDTAVYYCTTYGNYVGHYFDHWGQGTTVTV
	SS
KV1; VL	DIQLTQSPSFLSASVGDRVTITCRASQNVDTNLAWYQQKPGKA	269
	PKLLIYSASYRYTGVPSRFSGSGSGTEFTLTISSLQPEDFATYYC
	QQYNSYPLTFGGGTKVEIKRT
KV7; VL	DIQLTQSPSFLSASVGDRVTITCKASQNVDTNVAWYQQKPGKA	271
	PKPLIYSASYRYTGVPSRFSGSGSGTEFTLTISSLQPEDFATYYC
	QQYNSYPLTFGGGTKVEIKRT

TABLE 4
Construct	POLYPEPTIDE SEQUENCE	SEQ ID NO
Fab heavy chain	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAP	95
derived from L19	GKGLEWVSSISGSSGTTYYADSVKGRFTISRDNSKNTLYLQ
monoclonal	MNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSSASTKGP
antibody-C125A	SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS
variant of IL2-Fab	GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
heavy chain	NTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTKKTQ
derived from L19	LQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATE
monoclonal	LKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLE
antibody	LKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGGG
	SGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFSSF
	SMSWVRQAPGKGLEWVSSISGSSGTTYYADSVKGRFTISRD
	NSKNTLYLQMNSLRAEDTAVYYCAKPFPYFDYWGQGTLVT
	VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV
	SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
	ICNVNHKPSNTKVDKKVEPKSCD
Fab light chain	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	96
derived from L19	QAPRLLIYYASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
monoclonal	YYCQQTGRIPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG
antibody	TASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS
	KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
scFv derived from	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAP	97
L19 monoclonal	GKGLEWVSSISGSSGTTYYADSVKGRFTISRDNSKNTLYLQ
antibody-8 amino	MNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSSSGGSGG
acid linker-C125A	ASEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQK
variant of IL2	PGQAPRLLIYYASSRATGIPDRFSGSGSGTDFTLTISRLEPEDF
	AVYYCQQTGRIPPTFGQGTKVEISVLSSSSGSSSSGSSSSGAP
	TSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKF
	YMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLI
	SNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFAQSIIS
	TLT
F16-diabody-IL2	EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYGMSWVRQAP	98
protein	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKAHNAFDYWGQGTLVTVSSASGGSS
	ELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAP
	VLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADY
	YCNSSVYTMPPVVFGGGTKLTVLGSSSSGSSSSGSSSSGAPTS
	SSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFY
	MPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLIS
	NINVIVLELKGSETTFMCEYADETATIVEFLNRWITFAQSIIST
	LT
scFv-IL2-scFv	EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYGMSWVRQAP	99
(F16, protein)	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
	MNSLRAEDTAVYYCAKAHNAFDYWGQGTLVTVSRGGGGS
	GGGGSGGGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYA
	SWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTI
	TGAQAEDEADYYCNSSVYTMPPVVFGGGTKLTVLGSSSSGS
	SSSGSSSSGAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNP
	KLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQS
	KNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFL
	NRWITFAQSIISTLTSGGGGSGGGGSGGGGSSELTQDPAVSV
	ALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNN
	RPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSSVYTM
	PPVVFGGGTKLTVLGSGGGSGGGSGGGSGSEVQLLESGGGL
	VQPGGSLRLSCAASGFTFSRYGMSWVRQAPGKGLEWVSAIS
	GSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV
	YYCAKAHNAFDYWGQGTLVTVS
Fab-IL2-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYGMSWVRQAP	100
(F16, heavy chain	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
cytokine fusion	MNSLRAEDTAVYYCAKAHNAFDYWGQGTLVTVSSASTKG
construct, protein)	PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
	SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP
	SNTKVDKKVEPKSCDSSSSGSSSSGSSSSGAPTSSSTKKTQLQ
	LEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELK
	HLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELK
	GSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGGGSG
	GGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFSRYG
	MSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDN
	SKNTLYLQMNSLRAEDTAVYYCAKAHNAFDYWGQGTLVT
	VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV
	SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
	ICNVNHKPSNTKVDKKVEPKSCD
F16, light chain,	SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQ	101
protein	APVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEAD
	YYCNSSVYTMPPVVFGGGTKLTVLGQPKAAPSVTLFPPSSEE
	LQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPS
	KQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
IL2R-beta-	MDMRVPAQLLGLLLLWFPGARCAVNGTSQFTCFYNSRANIS	102
Fc(hole) fusion	CVWSQDGALQDTSCQVHAWPDRRRWNQTCELLPVSQASW
protein, protein	ACNLILGAPDSQKLTTVDIVTLRVLCREGVRWRVMAIQDFK
	PFENLRLMAPISLQVVHVETHRCNISWEISQASHYFERHLEFE
	ARTLSPGHTWEEAPLLTLKQKQEWICLETLTPDTQYEFQVR
	VKPLQGEFTTWSPWSQPLAFRTKPAALGKDTGAQDKTHTCP
	PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
	DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL
	HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCT
	LPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNY
	KTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEAL
	HNHYTQKSLSLSPGK
IL2R-gamma-	MLKPSLPFTSLLFLQLPLLGVGLNTTILTPNGNEDTTADFFLT	103
Fc(knob), protein	TMPTDSLSVSTLPLPEVQCFVFNVEYMNCTWNSSSEPQPTNL
	TLHYWYKNSDNDKVQKCSHYLFSEEITSGCQLQKKEIHLYQ
	TFVVQLQDPREPRRQATQMLKLQNLVIPWAPENLTLHKLSE
	SQLELNWNNRFLNHCLEHLVQYRTDWDHSWTEQSVDYRH
	KFSLPSVDGQKRYTFRVRSRFNPLCGSAQHWSEWSHPIHWG
	SNTSKENPFLFALEAGAQDKTHTCPPCPAPELLGGPSVFLFPP
	KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH
	NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN
	KALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWC
	LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
	LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Fab-IL12-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAP	104
L19 antibody,	GKGLEWVSSISGSSGTTYYADSVKGRFTISRDNSKNTLYLQ
murine scIL 12,	MNSLRAEDTAVYYCAKPFPYFDYVVGQGTLVTVSSASTKGP
protein	SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS
	GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
	NTKVDKKVEPKSCDSGGGGSGGGGSGGGGAMWELEKDVY
	VVEVDWTPDAPGETVNLTCDTPEEDDITWTSDQRHGVIGSG
	KTLTITVKEFLDAGQYTCHKGGETLSHSHLLLHKKENGIWS
	TEILKNFKNKTFLKCEAPNYSGRFTCSWLVQRNMDLKFNIK
	SSSSPPDSRAVTCGMASLSAEKVTLDQRDYEKYSVSCQEDV
	TCPTAEETLPIELALEARQQNKYENYSTSFFIRDIIKPDPPKNL
	QMKPLKNSQVEVSWEYPDSWSTPRSYFSLKFFVRIQRKKEK
	MKETEEGCNQKGAFFVEKTSTEVQCKGGNVCVQAQDRYY
	NSSCSKWACVPCRVRSGGDGSGGGGSGGGGSRVIPVSGPAR
	CLSQSRNLLKTTDDMVKTAREKLKHYSCTAEDIDHEDITRD
	QTSTLKTCLPLELHKNESCLATRETSSTTRGSCLPPQKTSLM
	MTLCLGSIYEDLKMYQTEFQAINAALQNHNHQQIILDKGML
	VAIDELMQSLNHNGETLRQKPPVGEADPYRVKMKLCILLHA
	FSTRVVTINRVMGYLSSAGGGGSGGGGSGGGGEVQLLESGG
	GLVQPGGSLRLSCAASGFTFSSFSMSWVRQAPGKGLEWVSS
	ISGSSGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
	VYYCAKPFPYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKST
	SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
	SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPK
	SCD
Fab-IL12-Fab L19	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAP	105
antibody, human	GKGLEWVSSIRGSSGTTYYADSVKGRFTISRDNSKNTLYLQ
scIL12, protein	MNSLRAEDTAVYYCAKPFPYFDWGQGTLVTVSSASTKGP
	SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS
	GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
	NTKVDKKVEPKSCDSGGGGSGGGGSGGGGIWELKKDVYV
	VELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSGK
	TLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWST
	DILKDQKEPKNKTFLRCEAKNYSGRFTCWWLITISTDLTFSV
	KSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDS
	ACPAAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKN
	LQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQVQGKS
	KREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEW
	ASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQ
	NLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEA
	CLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSI
	YEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELM
	QALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTID
	RVMSYLNASGGGGSGGGGSGGGGEVQLLESGGGLVQPGGS
	LRLSCAASGFTFSSFSMSWVRQAPGKGLEWVSSIRGSSGTTY
	YADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKPF
	PYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
	CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
	VTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD
Fab-GMCSF-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAP	106
L19 antibody,	GKGLEWVSSIRGSSGTTYYADSVKGRFTISRDNSKNTLYLQ
human GM-CSF,	MNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSSASTKGP
protein	SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS
	GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
	NTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPARSPSPSTQP
	WEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPT
	CLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPET
	SCATQIITFESFKENLKDFLLVIPFDCWEPVQESGGGGSGGGG
	SGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSW
	VRQAPGKGLEWVSSIRGSSGTTYYADSVKGRFTISRDNSKN
	TLYLQMNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSSA
	STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS
	GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
	NHKPSNTKVDKKVEPKSCD
Fab-IFNα2-Fab,	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAP	107
L19 antibody,	GKGLEWVSSIRGSSGTTYYADSVKGRFTISRDNSKNTLYLQ
protein	MNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSSASTKGP
	SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS
	GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
	NTKVDKKVEPKSCDSGGGGSGGGGSGGGGCDLPQTHSLGN
	RRALILLAQMRRISPFSCLKDRHDFGFPQEEFDGNQFQKAQA
	ISVLHEMIQQTFNLFSTKDSSAAWDESLLEKFYTELYQQLND
	LEACVIQEVGVEETPLMNVDSILAVKKYFQRITLYLTEKKYS
	PCAWEVVRAEIMRSFSLSTNLQERLRRKESGGGGSGGGGSG
	GGGEVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVR
	QAPGKGLEWVSSIRGSSGTTYYADSVKGRFTISRDNSKNTLY
	LQMNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSSASTK
	GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL
	TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
	PSNTKVDKKVEPKSCD
3F2 Fab-IL2-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	209
(heavy chain	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
cytokine fusion	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSSASTK
construct)	GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL
	TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
	PSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTKKT
	QLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKAT
	ELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVL
	ELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGG
	GSGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFS
	SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTIS
	RDNSKNTLYLQMNSLRAEDTAVYYCAKGWFGGFNYWGQG
	TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE
	PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
	TQTYICNVNHKPSNTKVDKKVEPKSCD
4G8 Fab-IL2-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	211
(heavy chain	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
cytokine fusion	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSSASTK
construct)	GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL
	TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
	PSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTKKT
	QLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKAT
	ELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVL
	ELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGG
	GSGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFS
	SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTIS
	RDNSKNTLYLQMNSLRAEDTAVYYCAKGWLGNFDYWGQG
	TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE
	PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
	TQTYICNVNHKPSNTKVDKKVEPKSCD
3D9 Fab-IL2-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQTP	213
(heavy chain	GKGLEWVSAIGVSTGSTYYADSVKGRFTISRDNSKNTLYLQ
cytokine fusion	MNSLRAEDTAVYYCAKGWLGPFDYWGQGTLVTVSSASTK
construct)	GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL
	TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
	PSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTKKT
	QLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKAT
	ELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVL
	ELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGG
	GSGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFS
	SYAMSWVRQTPGKGLEWVSAIGVSTGSTYYADSVKGRFTIS
	RDNSKNTLYLQMNSLRAEDTAVYYCAKGWLGPFDYWGQG
	TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE
	PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
	TQTYICNVNHKPSNTKVDKKVEPKSCD
2F11 Fab-IL2-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	215
(heavy chain	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
cytokine fusion	MNSLRAEDTAVYYCAKWRWMMFDYWGQGTLVTVSSAST
construct)	KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG
	ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
	HKPSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTK
	KTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKK
	ATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVI
	VLELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSG
	GGGSGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFT
	FSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRF
	TISRDNSKNTLYLQMNSLRAEDTAVYYCAKWRWMMFDYW
	GQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY
	FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
	SLGTQTYICNVNHKPSNTKVDKKVEPKSCD
4B3 Fab-IL2-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	217
(heavy chain	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
cytokine fusion	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSSASTK
construct)	GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL
	TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
	PSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTKKT
	QLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKAT
	ELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVL
	ELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGG
	GSGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFS
	SYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTIS
	RDNSKNTLYLQMNSLRAEDTAVYYCAKGWLGNFDYWGQG
	TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE
	PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
	TQTYICNVNHKPSNTKVDKKVEPKSCD
4G8 Fab-IL12-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	219
(murine IL-12;	GKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQ
heavy chain	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSSASTK
cytokine fusion	GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL
construct)	TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
	PSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAMWELEKD
	VYVVEVDWTPDAPGETVNLTCDTPEEDDITWTSDQRHGVIG
	SGKTLTITVKEFLDAGQYTCHKGGETLSHSHLLLHKKENG$$
	WSTEILKNFKNKTFLKCEAPNYSGRFTCSWLVQRNMDLKFN
	IKSSSSPPDSRAVTCGMASLSAEKVTLDQRDYEKYSVSCQED
	VTCPTAEETLPIELALEARQQNKYENYSTSFFIRDIIKPDPPKN
	LQMKPLKNSQVEVSWEYPDSWSTPRSYFSLKFFVRIQRKKE
	KMKETEEGCNQKGAFFVEKTSTEVQCKGGNVCVQAQDRY
	YNSSCSKWACVPCRVRSGGDGSGGGGSGGGGSRVIPVSGPA
	RCLSQSRNLLKTTDDMVKTAREKLKHYSCTAEDIDHEDITR
	DQTSTLKTCLPLELHKNESCLATRETSSTTRGSCLPPQKTSL
	MMTLCLGSIYEDLKMYQTEFQAINAALQNHNHQQIILDKGM
	LVAIDELMQSLNHNGETLRQKPPVGEADPYRVKMKLCILLH
	AFSTRVVTINRVMGYLSSAGGGGSGGGGSGGGGEVQLLESG
	GGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWV
	SAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
	TAVYYCAKGWLGNFDYWGQGTLVTVSSASTKGPSVFPLAP
	SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP
	AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDK
	KVEPKSCD
28H1 Fab-IL2-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSHAMSWVRQAP	221
(heavy chain	GKGLEWVSAIWASGEQYYADSVKGRFTISRDNSKNTLYLQ
cytokine fusion	MNSLRAEDTAVYYCAKGWLGNFDYWGQGTLVTVSSASTK
construct)	GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL
	TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
	PSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTKKT
	QLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKAT
	ELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVL
	ELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGG
	GSGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFS
	SHAMSWVRQAPGKGLEWVSAIWASGEQYYADSVKGRFTIS
	RDNSKNTLYLQMNSLRAEDTAVYYCAKGWLGNFDYWGQG
	TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE
	PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
	TQTYICNVNHKPSNTKVDKKVEPKSCD
29B11 Fab-IL2-	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	223
Fab	GKGLEWVSAIIGSGGITYYADSVKGRFTISRDNSKNTLYLQM
(heavy chain	NSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSSASTKGP
cytokine fusion	SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS
construct)	GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
	NTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTKKTQ
	LQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATE
	LKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLE
	LKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGGG
	SGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFSS
	YAMSWVRQAPGKGLEWVSAIIGSGGITYYADSVKGRFTISR
	DNSKNTLYLQMNSLRAEDTAVYYCAKGWFGGFNYWGQGT
	LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP
	VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT
	QTYICNVNHKPSNTKVDKKVEPKSCD
19G1 Fab-IL2-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	225
(heavy chain	GKGLEWVSAIISSGGLTYYADSVKGRFTISRDNSKNTLYLQ
cytokine fusion	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSSASTK
construct)	GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL
	TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
	PSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTKKT
	QLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKAT
	ELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVL
	ELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGG
	GSGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFS
	SYAMSWVRQAPGKGLEWVSAIISSGGLTYYADSVKGRFTIS
	RDNSKNTLYLQMNSLRAEDTAVYYCAKGWFGGFNYWGQG
	TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE
	PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
	TQTYICNVNHKPSNTKVDKKVEPKSCD
20G8 Fab-IL2-Fab	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	227
(heavy chain	GKGLEWVSAIIGSGSRTYYADSVKGRFTISRDNSKNTLYLQ
cytokine fusion	MNSLRAEDTAVYYCAKGWFGGFNYWGQGTLVTVSSASTK
construct)	GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL
	TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
	PSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTKKT
	QLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKAT
	ELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVL
	ELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSGGG
	GSGGGGSGGGGEVQLLESGGGLVQPGGSLRLSCAASGFTFS
	SYAMSWVRQAPGKGLEWVSAIIGSGSRTYYADSVKGRFTIS
	RDNSKNTLYLQMNSLRAEDTAVYYCAKGWFGGFNYWGQG
	TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE
	PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
	TQTYICNVNHKPSNTKVDKKVEPKSCD
3F2 light chain	EIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQKPG	229
	QAPRLLINVGSRRATGIPDRFSGSGSGTDFTLTISRLEPEDFA
	VYYCQQGIMLPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKS
	GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
	SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
4G8 light chain	EIVLTQSPGTLSLSPGERATLSCRASQSVSRSYLAWYQQKPG	231
	QAPRLLIIGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQVIPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG
	TASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS
	KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
3D9 light chain	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	233
	QAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQLIPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG
	TASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS
	KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
2F11 light chain	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPG	235
	QAPRLLIYGASSRATGIP$$RFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQYTPPTFGQGTKVEIKRTVAAPSVF$$PPSDEQLKS
	GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
	SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
4B3 light chain	EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPG	237
	QAPRLLIYGAYIRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	YYCQQGQVIPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG
	TASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS
	KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
2B10 Fab-IL2-Fab	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	239
(heavy chain	GQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSTSTAYME
cytokine fusion	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSSA
construct)	STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS
	GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
	NHKPSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSST
	KKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPK
	KATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNIN
	VIVLELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTS
	GGGGSGGGGSGGGGQVQLVQSGAEVKKPGSSVKVSCKASG
	GTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGR
	VTITADKSTSTAYMELSSLRSEDTAVYYCARLYGYAYYGAF
	DYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL
	VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV
	TVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD
C3B6 Fab-IL2-	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	241
Fab	GQGLEWMGAIIPILGIANYAQKFQGRVTITADKSTSTAYMEL
(heavy chain	SSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSSAS
cytokine fusion	TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG
construct)	ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
	HKPSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSSTK
	KTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKK
	ATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVI
	VLELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTSG
	GGGSGGGGSGGGGQVQLVQSGAEVKKPGSSVKVSCKASGG
	TFSSYAISWVRQAPGQGLEWMGAIIPILGIANYAQKFQGRVT
	ITADKSTSTAYMELSSLRSEDTAVYYCARLYGYAYYGAFDY
	WGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
	DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
	SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD
6A12 Fab-IL2-Fab	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAP	243
(heavy chain	GQGLEWMGVIIPILGTANYAQKFQGRVTITADKSTSTAYME
cytokine fusion	LSSLRSEDTAVYYCARLYGYAYYGAFDYWGQGTTVTVSSA
construct)	STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS
	GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
	NHKPSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPTSSST
	KKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPK
	KATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNIN
	VIVLELKGSETTFMCEYADETATIVEFLNRWITFAQSIISTLTS
	GGGGSGGGGSGGGGQVQLVQSGAEVKKPGSSVKVSCKASG
	GTFSSYAISWVRQAPGQGLEWMGVIIPILGTANYAQKFQGR
	VTITADKSTSTAYMELSSLRSEDTAVYYCARLYGYAYYGAF
	DYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL
	VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV
	TVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD
2B10 light chain	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPG	245
	KAPKRLIYAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFAT
	YYCLQNGLQPATFGQGTKVEIKRTVAAPSVFIFPPSDEQLKS
	GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
	SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
D1A2 light chain	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPG	247
	KAPKRLIYDAYSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFA
	TYYCLQNGLQPATFGQGTKVEIKRTVAAPSVFIFPPSDEQLK
	SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ
	DSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
	SFNRGEC
O7D8 light chain	DIQMTQSPSSLSASVGDRVTITCRASQSIRNVLGWYQQKPGK	249
	APKRLIYDVSSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFAT
	YYCLQNGLQPATFGQGTKVEIKRTVAAPSVFIFPPSDEQLKS
	GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
	SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
MHLG1 Fab-IL2-	EVQLVESGGGLVKPGGSLRLSCAASGFTFSNYWMNWVRQA	251
Fab	PGKGLEWVAEIRLKSNNFGRYYAASVKGRFTISRDDSKNTL
(heavy chain	YLQMNSLKTEDTAVYYCTTYGNYVGHYFDHWGQGTTVTV
cytokine fusion	SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
construct)	WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI
	CNVNHKPSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPT
	SSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFY
	MPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLIS
	NINVIVLELKGSETTFMCEYADETATIVEFLNRWITFAQSIIST
	LTSGGGGSGGGGSGGGGEVQLVESGGGLVKPGGSLRLSCA
	ASGFTFSNYWMNWVRQAPGKGLEWVAEIRLKSNNFGRYY
	AASVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTYGN
	YVGHYFDHWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGT
	AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
	SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD
KV9 light chain	DIQLTQSPSFLSASVGDRVTITCKASQNVDTNVAWYQQKPG	253
	QAPRPLIYSASYRYTGVPSRFSGSGSGTEFTLTISSLQPEDFAT
	YYCQQYNSYPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS
	GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
	SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
MHLG Fab-IL2-	EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNWVRQA	255
Fab	PGKGLEWVAEIRLKSNNFGRYYAASVKGRFTISRDDSKNTL
(heavy chain	YLQMNSLKTEDTAVYYCTTYGNYVGHYFDHWGQGTTVTV
cytokine fusion	SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
construct)	WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI
	CNVNHKPSNTKVDKKVEPKSCDSGGGGSGGGGSGGGGAPT
	SSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFY
	MPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLIS
	NINVIVLELKGSETTFMCEYADETATIVEFLNRWITFAQSIIST
	LTSGGGGSGGGGSGGGGEVQLVESGGGLVQPGGSLRLSCA
	ASGFTFSNYWMNWVRQAPGKGLEWVAEIRLKSNNFGRYY
	AASVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTYGN
	YVGHYFDHWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGT
	AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
	SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD
KV1 light chain	DIQLTQSPSFLSASVGDRVTITCRASQNVDTNLAWYQQKPGKA	263
	PKLLIYSASYRYTGVPSRFSGSGSGTEFTLTISSLQPEDFATYYC
	QQYNSYPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV
	VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
KV7 light chain	DIQLTQSPSFLSASVGDRVTITCKASQNVDTNVAWYQQKPGKA	265
	PKPLIYSASYRYTGVPSRFSGSGSGTEFTLTISSLQPEDFATYYC
	QQYNSYPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV
	VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

TABLE 5
Construct	POLYPEPTIDE SEQUENCE	SEQ ID NO
Human FAP	RPSRVHNSEENTMRALTLKDILNGTFSYKTFFPNWISGQEYL	53
ectodomain + poly-	HQSADNNIVLYNIETGQSYTILSNRTMKSVNASNYGLSPDRQ
lys-tag + his6-tag	FVYLESDYSKLWRYSYTATYYIYDLSNGEFVRGNELPRPIQY
	LCWSPVGSKLAYVYQNNIYLKQRPGDPPFQITFNGRENKIFN
	GIPDWVYEEEMLATKYALWWSPNGKFLAYAEFNDTDIPVIA
	YSYYGDEQYPRTINIPYPKAGAKNPVVRIFIIDTTYPAYVGPQ
	EVPVPAMIASSDYYFSWLTWVTDERVCLQWLKRVQNVSVL
	SICDFREDWQTWDCPKTQEHIEESRTGWAGGFFVSTPVFSY
	DAISYYKIFSDKDGYKHIHYIKDTVENAIQITSGKWEAINIFR
	VTQDSLFYSSNEFEEYPGRRNIYRISIGSYPPSKKCVTCHLRK
	ERCQYYTASFSDYAKYYALVCYGPGIPISTLHDGRTDQEIKI
	LEENKELENALKNIQLPKEEIKKLEVDEITLWYKMILPPQFD
	RSKKYPLLIQVYGGPCSQSVRSVFAVNWISYLASKEGMVIAL
	VDGRGTAFQGDKLLYAVYRKLGVYEVEDQITAVRKFIEMG
	FIDEKRIAIWGWSYGGYVSSLALASGTGLFKCGIAVAPVSSW
	EYYASVYTERFMGLPTKDDNLEHYKNSTVMARAEYFRNVD
	YLLIHGTADDNVHFQNSAQIAKALVNAQVDFQAMWYSDQ
	NHGLSGLSTNHLYTHMTHFLKQCFSLSDGKKKKKKGHHHH
	HH
Murine FAP	RPSRVYKPEGNTKRALTLKDILNGTFSYKTYFPNWISEQEYL	55
ectodomain + poly-	HQSEDDNIVFYNIETRESYIILSNSTMKSVNATDYGLSPDRQF
lys-tag + his6-tag	VYLESDYSKLWRYSYTATYYIYDLQNGEFVRGYELPRPIQY
	LCWSPVGSKLAYVYQNNIYLKQRPGDPPFQITYTGRENRIFN
	GIPDWVYEEEMLATKYALWWSPDGKFLAYVEFNDSDIPIIA
	YSYYGDGQYPRTINIPYPKAGAKNPVVRVFIVDTTYPHHVG
	PMEVPVPEMIASSDYYFSWLTWVSSERVCLQWLKRVQNVS
	VLSICDFREDWHAWECPKNQEHVEESRTGWAGGFFVSTPAF
	SQDATSYYKIFSDKDGYKHIHYIKDTVENAIQITSGKWEAIYI
	FRVTQDSLFYSSNEFEGYPGRRNIYRISIGNSPPSKKCVTCHL
	RKERCQYYTASFSYKAKYYALVCYGPGLPISTLHDGRTDQE
	IQVLEENKELENSLRNIQLPKVEIKKLKDGGLTFWYKMILPP
	QFDRSKKYPLLIQVYGGPCSQSVKSVFAVNWITYLASKEGIV
	IALVDGRGTAFQGDKFLHAVYRKLGVYEVEDQLTAVRKFIE
	MGFIDEERIAIWGWSYGGYVSSLALASGTGLFKCGIAVAPVS
	SWEYYASIYSERFMGLPTKDDNLEHYKNSTVMARAEYFRN
	VDYLLIHGTADDNVHFQNSAQIAKALVNAQVDFQAMWYS
	DQNHGILSGRSQNHLYTHMTHFLKQCFSLSDGKKKKKKGH
	HHHHH
Human TNC-	ASTGETPNLGEVVVAEVGWDALKLNWTAPEGAYEYFFIQV	57
A2 + avi-tag + his6-	QEADTVEAAQNLTVPGGLRSTDLPGLKAATHYTITIRGVTQ
tag	DFSTTPLSVEVLTASGLNDIFEAQKIEWHEGTHHHHHH
Human TNC-	EQAPELENLTVTEVGWDGLRLNWTAADQAYEHFIIQVQEA	59
A1 + avi-tag + his6-	NKVEAARNLTVPGSLRAVDIPGLKAATPYTVSIYGVIQGYRT
tag	PVLSAEASTASGLNDIFEAQKIEWHEGTHHHHHH
Murine TNC-	ISEFGSSTEEVPSLENLTVTEAGWDGLRLNWTADDLAYEYF	61
A1 + avi-tag + his6-	VIQVQEANNVETAHNFTVPGNLRAADIPGLKVATSYRVSIY
tag	GVARGYRTPVLSAETSTASGLNDIFEAQKIEWHEGTHHHHHH
Human TNC-A4 +	EDLPQLGDLAVSEVGWDGLRLNWTAADNAYEHFVIQVQEV	63
avi-tag + his6-tag	NKVEAAQNLTLPGSLRAVDIPGLEAATPYRVSIYGVIRGYRT
	PVLSAEASTASGLNDIFEAQKIEWHEGTHHHHHH
Murine TNC-A4 +	ISEFGSLTEDLPQLGGLSVTEVSWDGLTLNWTTDDLAYKHF	65
avi-tag + his6-tag	VVQVQEANNVEAAQNLTVPGSLRAVDIPGLKADTPYRVSIY
	GVIQGYRTPMLSTDVSTASGLNDIFEAQKIEWHEGTHHHHHH

TABLE 6
Construct	POLYNUCLEOTIDE SEQUENCE	SEQ ID NO
2B10; VL	GATATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	4
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGCATTAGAAATGATTTAGGCTGGTACCAGCAGAAGC
	CAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCA
	GTTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCGGTG
	GATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCA
	GCCTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGT
	CTGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAG
	ATCAAG
2B10(GS); VL	GATATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	6
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGCATTAGAAATGATTTAGGCTGGTACCAGCAGAAGC
	CAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCA
	GTTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCAGTG
	GATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCA
	GCCTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGT
	CTGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAG
	ATCAAG
2B10; VH	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	8
	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
	CCCCTGGACAAGGGCTCGAGTGGATGGGAGGGATCATCC
	CTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCA
2F11; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	10
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCGTCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGTATACTCCCCCCACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
2F11(VI); VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	12
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGTATACTCCCCCCACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
2F11; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	14
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACATGGCC
	GTATATTACTGTGCGAAATGGAGATGGATGATGTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
2F11(MT); VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	16
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACCGCC
	GTATATTACTGTGCGAAATGGAGATGGATGATGTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
3F2; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	18
	ATCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
3F2(YS); VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	20
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
3F2; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	22
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
3D9, VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	24
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGCTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
3D9, VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	26
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCTATGAGCTGGGTCCGCCAGAC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTGGTGTT
	AGTACTGGTAGCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGTTGGCTGGGTCCTTTTGACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
2D9(TA); VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	28
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTGGTGTT
	AGTACTGGTAGCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGTTGGCTGGGTCCTTTTGACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
4G8; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	30
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCCGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCATTGGGGCCTC
	CACCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACGGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGGTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
4G8; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	32
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGCTGGGTAATTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
4B3; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	34
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAATTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGCGCCTA
	CATCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGGTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
4B3; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	36
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGCTGGGTAATTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
4D6; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	38
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAACTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCCAGGGCGCCTC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGGTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
4D6; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	40
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGCTGGGTAATTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
2C6; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	42
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGGCTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGCAGATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
2C6; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	44
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	CCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	GAGTGCTGGTTATACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGTTGGTTTGGGAATTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
5H5; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	46
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	ATCAGATTCCCCCTACGTTCGGTCAGGGGACCAAAGTGG
	AAATCAAA
5H5; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	48
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATACCATGAGCTGGGTCCGCCGGTC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TGGTGGTAGGACATACTACGCAGACTCCGTGAAGGGCCG
	GTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
	CTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCGTA
	TATTACTGTGCGAAAGGTTGGTTTACGCCTTTTGACTACT
	GGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
2C4; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	50
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGTAACTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCCTC
	CATTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	ATCAGATTCCCCCTACGTTCGGTCAGGGGACCAAAGTGG
	AAATCAAA
2C4; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	52
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGCGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGTTGGTTTACGCCTTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
2D9; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	68
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	ATCAGATTCCCCCTACGTTCGGTCAGGGGACCAAAGTGG
	AAATCAAA
2D9; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	70
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGCGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGTTGGTTTACGCCTTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
4B8; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	72
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGGTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
4B8; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	74
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGCTGGGTAATTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
7A1; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	76
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGCAGATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
7A1; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	78
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGTTGGTTTGGGAATTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
13C2; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	80
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGCTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
13C2; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	82
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGTTGGCTGGGTCCTTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
13E8; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	84
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	TGAATATTCCCTCGACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
13E8; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	86
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGTTGGTTGGGTCCGTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
14C10; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	88
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	ATATTATTCCCCCGACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
14C10; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	90
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGCTTGGATGGGGCCTTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
17A11; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	92
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	TGAATATTCCCTCGACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
17A11; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	94
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGTTGGTTGGGTCCGTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
19G1; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	122
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
19G1; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	124
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCGATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCGATTATTAG
	TAGTGGTGGTCTCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
20G8; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	126
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
20G8; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	128
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCAATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTATTGG
	GAGTGGTAGTCGTACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
4B9; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	130
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
4B9; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	132
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTATTGGT
	AGTGGTGCTAGCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
5B8; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	134
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
5B8; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	136
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTTGGGG
	TGGTGGTCGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
5F1; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	138
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
5F1; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	140
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTATTAGT
	AGTGGGGCTAGCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
14B3; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	142
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
14B3; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	144
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTTTGGCT
	AGTGGTGCGATCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
16F1; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	146
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
16F1; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	148
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTATTATTGG
	TAGTGGTGGTATCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
16F8; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	150
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
16F8; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	152
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTCTTGGT
	AGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
O3C9; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	154
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
O3C9; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	156
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTTTGCCATGAGCTGGGTCCGTCAGTC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTATTGGT
	AGTGGTAGTAACACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
O2D7; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	158
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCACCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGCTA
	TTATGCTTCCTCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
O2D7; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	160
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGTCC
28H1; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	162
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCCGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCATTGGGGCCTC
	CACCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGGTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
28H1; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	164
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTCATGCTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTTGGGC
	TAGTGGGGAGCAATACTACGCAGACTCCGTGAAGGGCCG
	GTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
	CTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCGTA
	TATTACTGTGCGAAAGGGTGGCTGGGTAATTTTGACTACT
	GGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
22A3; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	166
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
22A3; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	168
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTATTGGT
	AGTGGTAGTATCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
29B11; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	170
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTACCAGTAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCAATGTGGGCTC
	CCGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTA
	TTATGCTTCCCCCGACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAA
29B11; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	172
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTATGCTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTATTGGT
	AGTGGTGGTATCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
23C10; VL	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	174
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCCGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCATTGGGGCCTC
	CACCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGGTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAA
23C10; VH	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	176
	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
	TCACCTTTAGCAGTTCTGCCATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTAC
	TAATGGTAATTATACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGGTGGCTGGGTAATTTTGACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT
2B10_C3B6; VL	GATATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	178
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGCATTAGAAATGATTTAGGCTGGTACCAGCAGAAGC
	CAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCA
	GTTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCAGTG
	GATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCA
	GCCTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGT
	CTGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAG
	ATCAAG
2B10_C3B6; VH	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	180
	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
	CCCCTGGACAAGGGCTCGAGTGGATGGGAGCTATCATCC
	CGATCCTTGGTATCGCAAACTACGCACAGAAGTTCCAGG
	GCAGGGTCACCATTACTGCAGACAAATCCACGAGCACAG
	CCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCG
	CCGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTA
	CGGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCA
2B10_6A12; VL	GATATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	182
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGCATTAGAAATGATTTAGGCTGGTACCAGCAGAAGC
	CAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCA
	GTTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCAGTG
	GATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCA
	GCCTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGT
	CTGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAG
	ATCAAG
2B10_6A12; VH	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	184
	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
	GCACATTCAGCAGCTATGCTATAAGCTGGGTGCGACAGG
	CCCCTGGACAAGGGCTCGAGTGGATGGGAGTGATCATCC
	CTATCCTTGGTACCGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCA
2B10_C3A6; VL	GACATCCAGATGACCCAGTCTCCTTCCTCCCTGTCTGCAT	186
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGCATTCGTAATGTTTTAGGCTGGTACCAGCAGAAGCC
	AGGGAAAGCCCCTAAGCGCCTGATCTATGATTCGTCCAGT
	TTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCGGTGGA
	TCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCAGC
	CTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGTCT
	GCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAGAT
	CAAG
2B10_C3A6; VH	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	188
	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
	CCCCTGGACAAGGGCTCGAGTGGATGGGAGGGATCATCC
	CTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCA
2B10_D1A2_wt;	GATATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	190
VL	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGGATTCGTAATGTTTTAGGCTGGTACCAGCAGAAGC
	CAGGGAAAGCCCCTAAGCGCCTGATCTATGATGCTTACA
	GCTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCGGTG
	GATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCA
	GCCTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGT
	CTGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAG
	ATCAAG
2B10_D1A2_wt;	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	192
VH	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
	CCCCTGGACAAGGGCTCGAGTGGATGGGAGGGATCATCC
	CTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCA
2B10_D1A2_VD;	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	194
VL	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGGATTCGTAATGATTTAGGCTGGTACCAGCAGAAGC
	CAGGGAAAGCCCCTAAGCGCCTGATCTATGATGCTTACA
	GCTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCGGTG
	GATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCA
	GCCTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGT
	CTGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAG
	ATCAAG
2B10_D1A2_VD;	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	196
VH	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
	CCCCTGGACAAGGGCTCGAGTGGATGGGAGGGATCATCC
	CTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCA
2B10_O7D8; VL	GATATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	198
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGAGCATTCGTAATGTTTTAGGCTGGTACCAGCAGAAGCC
	AGGGAAAGCCCCTAAGCGCCTGATCTATGATGTGTCCAGT
	TTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCGGTGGA
	TCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCAGC
	CTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGTCT
	GCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAGAT
	CAAG
2B10_O7D8; VH	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	200
	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
	CCCCTGGACAAGGGCTCGAGTGGATGGGAGGGATCATCC
	CTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCA
2B10_O1F7; VL	GATATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	202
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGCATTCGTAATGTTTTAGGCTGGTACCAGCAGAAGCC
	AGGGAAAGCCCCTAAGCGCCTGATCGTATGATGCGTCCAG
	TTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCGGTGG
	ATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCAG
	CCTGAAGATTTTGCCACCTATTACTGCCTGCAGAATGGTC
	TGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAGA
	TCAAG
2B10_O1F7; VH	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	204
	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
	CCCCTGGACAAGGGCTCGAGTGGATGGGAGGGATCATCC
	CTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCA
2B10_6H10; VL	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	206
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGCATTCGTAATGTTTTAGGCTGGTACCAGCAGAAGCC
	AGGGAAAGCCCCTAAGCGCCTGATCCAGGCTGCTACCAG
	TTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCGGTGG
	ATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCAG
	CCTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGTC
	TGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAGA
	TCAAG
2B10_6H10; VH	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	208
	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
	CCCCTGGACAAGGGCTCGAGTGGATGGGAGGGATCATCC
	CTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCA
MHLG1; VH	GAAGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGGTCAAG	258
	CCTGGCGGGTCCCTGCGGCTCTCCTGTGCAGCCTCCGGAT
	TCACATTTAGCAACTATTGGATGAACTGGGTGCGGCAGGC
	TCCTGGAAAGGGCCTCGAGTGGGTGGCCGAGATCAGATT
	GAAATCCAATAACTTCGGAAGATATTACGCTGCAAGCGT
	GAAGGGCCGGTTCACCATCAGCAGAGATGATTCCAAGAA
	CACGCTGTACCTGCAGATGAACAGCCTGAAGACCGAGGA
	TACGGCCGTGTATTACTGTACCACATACGGCAACTACGTT
	GGGCACTACTTCGACCACTGGGGCCAAGGGACCACCGTC
	ACCGTCTCCAGT
KV9; VL	GATATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATC	260
	TGTGGGCGACCGGGTCACCATCACCTGCAAGGCCAGTCA
	GAATGTGGATACTAACGTGGCTTGGTACCAGCAGAAGCC
	AGGGCAGGCACCTAGGCCTCTGATCTATTCGGCATCCTAC
	CGGTACACTGGCGTCCCATCAAGGTTCAGCGGCAGTGGA
	TCCGGGACAGAGTTCACTCTCACAATCTCAAGCCTGCAAC
	CTGAAGATTTCGCAACTTACTACTGTCAACAGTACAATAG
	TTACCCTCTGACGTTCGGCGGAGGTACCAAGGTGGAGATC
	AAGCGTACG
MHLG; VH	GAAGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGGTCCAG	262
	CCTGGCGGGTCCCTGCGGCTCTCCTGTGCAGCCTCCGGAT
	TCACATTTAGCAACTATTGGATGAACTGGGTGCGGCAGGC
	TCCTGGAAAGGGCCTCGAGTGGGTGGCCGAGATCAGATT
	GAAATCCAATAACTTCGGAAGATATTACGCTGCAAGCGT
	GAAGGGCCGGTTCACCATCAGCAGAGATGATTCCAAGAA
	CACGCTGTACCTGCAGATGAACAGCCTGAAGACCGAGGA
	TACGGCCGTGTATTACTGTACCACATACGGCAACTACGTT
	GGGCACTACTTCGACCACTGGGGCCAAGGGACCACCGTC
	ACCGTCTCCAGT
KV1; VL	GATATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATCT	270
	GTGGGCGACCGGGTCACCATCACCTGCAGGGCCAGTCAGAA
	TGTGGATACTAACTTAGCTTGGTACCAGCAGAAGCCAGGGA
	AAGCACCTAAGCTCCTGATCTATTCGGCATCCTACCGTTACA
	CTGGCGTCCCATCAAGGTTCAGCGGCAGTGGATCCGGGACA
	GAGTTCACTCTCACAATCTCAAGCCTGCAACCTGAAGATTTC
	GCAACTTACTACTGTCAACAGTACAATAGTTACCCTCTGACG
	TTCGGCGGAGGTACCAAGGTGGAGATCAAGCGTACGGTG
KV7; VL	GATATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATC	272
	TGTGGGCGACCGGGTCACCATCACCTGCAAGGCCAGTCA
	GAATGTGGATACTAACGTGGCTTGGTACCAGCAGAAGCC
	AGGGAAAGCACCTAAGCCTCTGATCTATTCGGCATCCTAC
	CGGTACACTGGCGTCCCATCAAGGTTCAGCGGCAGTGGA
	TCCGGGACAGAGTTCACTCTCACAATCTCAAGCCTGCAAC
	CTGAAGATTTCGCAACTTACTACTGTCAACAGTACAATAG
	TTACCCTCTGACGTTCGGCGGAGGTACCAAGGTGGAGATC
	AAGCGTACGGTG

TABLE 7
Construct	POLYNUCLEOTIDE SEQUENCE	SEQ ID NO
Human FAP	CGCCCTTCAAGAGTTCATAACTCTGAAGAAAATACAATG	54
ectodomain + poly-	AGAGCACTCACACTGAAGGATATTTTAAATGGAACATTTT
lys-tag + his6-tag	CTTATAAAACATTTTTTCCAAACTGGATTTCAGGACAAGA
	ATATCTTCATCAATCTGCAGATAACAATATAGTACTTTAT
	AATATTGAAACAGGACAATCATATACCATTTTGAGTAATA
	GAACCATGAAAAGTGTGAATGCTTCAAATTACGGCTTATC
	ACCTGATCGGCAATTTGTATATCTAGAAAGTGATTATTCA
	AAGCTTTGGAGATACTCTTACACAGCAACATATTACATCT
	ATGACCTTAGCAATGGAGAATTTGTAAGAGGAAATGAGC
	TTCCTCGTCCAATTCAGTATTTATGCTGGTCGCCTGTTGGG
	AGTAAATTAGCATATGTCTATCAAAACAATATCTATTTGA
	AACAAAGACCAGGAGATCCACCTTTTCAAATAACATTTA
	ATGGAAGAGAAAATAAAATATTTAATGGAATCCCAGACT
	GGGTTTATGAAGAGGAAATGCTTGCTACAAAATATGCTCT
	CTGGTGGTCTCCTAATGGAAAATTTTTGGCATATGCGGAA
	TTTAATGATACGGATATACCAGTTATTGCCTATTCCTATTA
	TGGCGATGAACAATATCCTAGAACAATAAATATTCCATAC
	CCAAAGGCTGGAGCTAAGAATCCCGTTGTTCGGATATTTA
	TTATCGATACCACTTACCCTGCGTATGTAGGTCCCCAGGA
	AGTGCCTGTTCCAGCAATGATAGCCTCAAGTGATTATTAT
	TTCAGTTGGCTCACGTGGGTTACTGATGAACGAGTATGTT
	TGCAGTGGCTAAAAAGAGTCCAGAATGTTTCGGTCCTGTC
	TATATGTGACTTCAGGGAAGACTGGCAGACATGGGATTG
	TCCAAAGACCCAGGAGCATATAGAAGAAAGCAGAACTGG
	ATGGGCTGGTGGATTCTTTGTTTCAACACCAGTTTTCAGC
	TATGATGCCATTTCGTACTACAAAATATTTAGTGACAAGG
	ATGGCTACAAACATATTCACTATATCAAAGACACTGTGGA
	AAATGCTATTCAAATTACAAGTGGCAAGTGGGAGGCCAT
	AAATATATTCAGAGTAACACAGGATTCACTGTTTTATTCT
	AGCAATGAATTTGAAGAATACCCTGGAAGAAGAAACATC
	TACAGAATTAGCATTGGAAGCTATCCTCCAAGCAAGAAG
	TGTGTTACTTGCCATCTAAGGAAAGAAAGGTGCCAATATT
	ACACAGCAAGTTTCAGCGACTACGCCAAGTACTATGCACT
	TGTCTGCTACGGCCCAGGCATCCCCATTTCCACCCTTCAT
	GATGGACGCACTGATCAAGAAATTAAAATCCTGGAAGAA
	AACAAGGAATTGGAAAATGCTTTGAAAAATATCCAGCTG
	CCTAAAGAGGAAATTAAGAAACTTGAAGTAGATGAAATT
	ACTTTATGGTACAAGATGATTCTTCCTCCTCAATTTGACA
	GATCAAAGAAGTATCCCTTGCTAATTCAAGTGTATGGTGG
	TCCCTGCAGTCAGAGTGTAAGGTCTGTATTTGCTGTTAAT
	TGGATATCTTATCTTGCAAGTAAGGAAGGGATGGTCATTG
	CCTTGGTGGATGGTCGAGGAACAGCTTTCCAAGGTGACA
	AACTCCTCTATGCAGTGTATCGAAAGCTGGGTGTTTATGA
	AGTTGAAGACCAGATTACAGCTGTCAGAAAATTCATAGA
	AATGGGTTTCATTGATGAAAAAAGAATAGCCATATGGGG
	CTGGTCCTATGGAGGATACGTTTCATCACTGCCCTTGCA
	TCTGGAACTGGTCTTTTCAAATGTGGTATAGCAGTGGCTC
	CAGTCTCCAGCTGGGAATATTACGCGTCTGTCTACACAGA
	GAGATTCATGGGTCTCCCAACAAAGGATGATAATCTTGA
	GCACTATAAGAATTCAACTGTGATGGCAAGAGCAGAATA
	TTTCAGAAATGTAGACTATCTTCTCATCCACGGAACAGCA
	GATGATAATGTGCACTTTCAAAACTCAGCACAGATTGCTA
	AAGCTCTGGTTAATGCACAAGTGGATTTCCAGGCAATGTG
	GTACTCTGACCAGAACCACGGCTTATCCGGCCTGTCCACG
	AACCACTTATACACCCACATGACCCACTTCCTAAAGCAGT
	GTTTCTCTTTGTCAGACGGCAAAAAGAAAAAGAAAAAGG
	GCCACCACCATCACCATCAC
Murine FAP	CGTCCCTCAAGAGTTTACAAACCTGAAGGAAACACAAAG	56
ectodomain + poly-	AGAGCTCTTACCTTGAAGGATATTTTAAATGGAACATTCT
lys-tag + his6-tag	CATATAAAACATATTTTCCCAACTGGATTTCAGAACAAGA
	ATATCTTCATCAATCTGAGGATGATAACATAGTATTTTAT
	AATATTGAAACAAGAGAATCATATATCATTTTGAGTAATA
	GCACCATGAAAAGTGTGAATGCTACAGATTATGGTTTGTC
	ACCTGATCGGCAATTTGTGTATCTAGAAAGTGATTATTCA
	AAGCTCTGGCGATATTCATACACAGCGACATACTACATCT
	ACGACCTTCAGAATGGGGAATTTGTAAGAGGATACGAGC
	TCCCTCGTCCAATTCAGTATCTATGCTGGTCGCCTGTTGG
	GAGTAAATTAGCATATGTATATCAAAACAATATTTATTTG
	AAACAAAGACCAGGAGATCCACCTTTTCAAATAACTTAT
	ACTGGAAGAGAAAATAGAATATTTAATGGAATACCAGAC
	TGGGTTTATGAAGAGGAAATGCTTGCCACAAAATATGCTC
	TTTGGTGGTCTCCAGATGGAAAATTTTTGGCATATGTAGA
	ATTTAATGATTCAGATATACCAATTATTGCCTATTCTTATT
	ATGGTGATGGACAGTATCCTAGAACTATAAATATTCCATA
	TCCAAAGGCTGGGGCTAAGAATCCGGTTGTTCGTGTTTTT
	ATTGTTGACACCACCTACCCTCACCACGTGGGCCCAATGG
	AAGTGCCAGTTCCAGAAATGATAGCCTCAAGTGACTATTA
	TTTCAGCTGGCTCACATGGGTGTCCAGTGAACGAGTATGC
	TTGCAGTGGCTAAAAAGAGTGCAGAATGTCTCAGTCCTGT
	CTATATGTGATTTCAGGGAAGACTGGCATGCATGGGAAT
	GTCCAAAGAACCAGGAGCATGTAGAAGAAAGCAGAACA
	GGATGGGCTGGTGGATTCTTTGTTTCGACACCAGCTTTTA
	GCCAGGATGCCACTTCTTACTACAAAATATTTAGCGACAA
	GGATGGTTACAAACATATTCACTACATCAAAGACACTGTG
	GAAAATGCTATTCAAATTACAAGTGGCAAGTGGGAGGCC
	ATATATATATTCCGCGTAACACAGGATTCACTGTTTTATT
	CTAGCAATGAATTTGAAGGTTACCCTGGAAGAAGAAACA
	TCTACAGAATTAGCATTGGAAACTCTCCTCCGAGCAAGAA
	GTGTGTTACTTGCCATCTAAGGAAAGAAAGGTGCCAATAT
	TACACAGCAAGTTTCAGCTACAAAGCCAAGTACTATGCA
	CTCGTCTGCTATGGCCCTGGCCTCCCCATTTCCACCCTCCA
	TGATGGCCGCACAGACCAAGAAATACAAGTATTAGAAGA
	AAACAAAGAACTGGAAAATTCTCTGAGAAATATCCAGCT
	GCCTAAAGTGGAGATTAAGAAGCTCAAAGACGGGGGACT
	GACTTTCTGGTACAAGATGATTCTGCCTCCTCAGTTTGAC
	AGATCAAAGAAGTACCCTTTGCTAATTCAAGTGTATGGTG
	GTCCTTGTAGCCAGAGTGTTAAGTCTGTGTTTGCTGTTAA
	TTGGATAACTTATCTCGCAAGTAAGGAGGGGATAGTCATT
	GCCCTGGTAGATGGTCGGGGCACTGCTTTCCAAGGTGACA
	AATTCCTGCATGCCGTGTATCGAAAACTGGGTGTATATGA
	AGTTGAGGACCAGCTCACAGCTGTCAGAAAATTCATAGA
	AATGGGTTTCATTGATGAAGAAAGAATAGCCATATGGGG
	CTGGTCCTACGGAGGTTATGTTTCATCCCTGGCCCTTGCA
	TCTGGAACTGGTCTTTTCAAATGTGGCATAGCAGTGGCTC
	CAGTCTCCAGCTGGGAATATTACGCATCTATCTACTCAGA
	GAGATTCATGGGCCTCCCAACAAAGGACGACAATCTCGA
	ACACTATAAAAATTCAACTGTGATGGCAAGAGCAGAATA
	TTTCAGAAATGTAGACTATCTTCTCATCCACGGAACAGCA
	GATGATAATGTGCACTTTCAGAACTCAGCACAGATTGCTA
	AAGCTTTGGTTAATGCACAAGTGGATTTCCAGGCGATGTG
	GTACTCTGACCAGAACCATGGTATATTATCTGGGCGCTCC
	CAGAATCATTTATATACCCACATGACGCACTTCCTCAAGC
	AATGCTTTTCTTTATCAGACGGCAAAAAGAAAAAGAAAA
	AGGGCCACCACCATCACCATCAC
Human TNC-	GCGTCCACCGGGGAAACCCCGAACCTGGGCGAAGTGGTG	58
A2 + avi-tag + his6-	GTGGCGGAAGTGGGTTGGGATGCGCTGAAACTGAACTGG
tag	ACCGCGCCGGAAGGCGCGTATGAATATTTTTTCATCCAGG
	TGCAGGAAGCGGATACCGTTGAAGCGGCGCAGAACCTGA
	CCGTTCCGGGCGGTCTGCGTAGCACCGATCTGCCGGGCCT
	GAAAGCGGCGACCCATTATACCATTACCATCCGTGGGGT
	GACCCAGGATTTTAGCACCACCCCGCTGTCTGTGGAAGTG
	CTGACCGCTAGCGGCCTGAACGACATCTTCGAGGCTCAG
	AAAATCGAATGGCACGAAGGTACCCATCACCATCACCAC
	CAC
Human TNC-	GAACAAGCCCCTGAGCTGGAAAACCTCACCGTGACTGAG	60
A1 + avi-tag + his6-	GTTGGCTGGGATGGCCTCAGACTCAACTGGACCGCGGCT
tag	GACCAGGCCTATGAGCACTTTATCATTCAGGTGCAGGAG
	GCCAACAAGGTGGAGGCAGCTCGGAACCTCACCGTGCCT
	GGCAGCCTTCGGGCTGTGGACATACCGGGCCTCAAGGCT
	GCTACGCCTTATACAGTCTCCATCTATGGGGTGATCCAGG
	GCTATAGAACACCAGTGCTCTCTGCTGAGGCCTCCACAGC
	TAGCGGCCTGAACGACATCTTCGAGGCTCAGAAAATCGA
	ATGGCACGAAGGTACCCATCACCATCACCACCAC
Murine TNC-	ATTTCAGAATTCGGATCCAGCACCGAAGAAGTGCCGAGC	62
A1 + avi-tag + his6-	CTGGAAAACCTGACCGTGACCGAAGCGGGCTGGGATGGC
tag	CTGCGTCTGAACTGGACCGCGGATGATCTGGCCTATGAAT
	ATTTTGTGATCCAGGTGCAGGAAGCGAACAACGTTGAAA
	CCGCGCATAACTTTACCGTGCCGGGCAATCTGCGTGCGGC
	GGATATTCCGGGCCTGAAAGTGGCGACCAGCTATCGTGT
	GAGCATTTATGGCGTGGCGCGTGGCTATCGTACCCCGGTT
	CTGAGCGCGGAAACCAGCACCGCTAGCGGCCTGAACGAC
	ATCTTCGAGGCTCAGAAAATCGAATGGCACGAAGGTACC
	CATCACCATCACCACCAC
Human TNC-A4 +	GAAGATCTGCCGCAGCTGGGCGATCTGGCCGTGAGCGAA	64
avi-tag + his6-tag	GTGGGCTGGGATGGCCTGCGTCTGAACTGGACCGCGGCG
	GATAACGCGTATGAACATTTTGTGATTCAGGTGCAGGAA
	GTGAACAAAGTTGAAGCGGCGCAGAACCTGACCCTGCCG
	GGCAGCCTGCGTGCGGTGGATATTCCGGGCCTGGAAGCG
	GCGACCCCGTATCGTGTGAGCATCTATGGCGTGATTCGTG
	GCTATCGTACCCCGGTTCTGAGCGCGGAAGCGAGCACCG
	CTAGCGGCCTGAACGACATCTTCGAGGCTCAGAAAATCG
	AATGGCACGAAGGTACCCATCACCATCACCACCAC
Murine TNC-A4 +	ATTTCAGAATTCGGATCCCTGACCGAAGATCTGCCGCAGC	66
avi-tag + his6-tag	TGGGCGGTCTGAGCGTGACCGAAGTGAGCTGGGATGGCC
	TGACCCTGAACTGGACCACCGATGATCTGGCCTATAAACA
	TTTTGTGGTGCAGGTGCAGGAAGCGAACAACGTTGAAGC
	GGCGCAGAACCTGACCGTTCCGGGTAGCCTGCGTGCGGT
	GGATATTCCGGGCCTGAAAGCGGATACCCCGTATCGTGTG
	AGCATTTATGGCGTGATTCAGGGCTATCGTACCCCGATGC
	TGTCTACCGATGTGAGCACCGCTAGCGGCCTGAACGACAT
	CTTCGAGGCTCAGAAAATCGAATGGCACGAAGGTACCCA
	TCACCATCACCACCAC

TABLE 8
Construct	POLYNUCLEOTIDE SEQUENCE	SEQ ID NO
Fab heavy chain	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAG	108
derived from L19	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAT
monoclonal	TCACCTTTAGCAGTTTTTCGATGAGCTGGGTCCGCCAGGC
antibody-C125A	TCCAGGGAAGGGGCTGGAGTGGGTCTCATCTATTTCCGGT
variant of IL2-Fab	AGTTCGGGTACCACATACTACGCAGACTCCGTGAAGGGC
heavy chain	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
derived from L19	ATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCG
monoclonal	TATATTACTGTGCGAAACCGTTTCCGTATTTTGACTACTG
antibody	GGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCTAGCAC
	CAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAG
	AGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTC
	AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAAC
	TCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTG
	TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT
	GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATC
	TGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGAT
	AAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCGGAGGA
	GGGAGCGGCGGAGGTGGCTCCGGAGGTGGCGGAGCACCT
	ACTTCAAGTTCTACAAAGAAAACACAGCTACAACTGGAG
	CATTTACTGCTGGATTTACAGATGATTTTGAATGGAATTA
	ATAATTACAAGAATCCCAAACTCACCAGGATGCTCACATT
	TAAGTTTTACATGCCCAAGAAGGCCACAGAACTGAAACA
	TCTTCAGTGTCTAGAAGAAGAACTCAAACCTCTGGAGGA
	AGTGCTAAATTTAGCTCAAAGCAAAAACTTTCACTTAAGA
	CCCAGGGACTTAATCAGCAATATCAACGTAATAGTTCTGG
	AACTAAAGGGATCTGAAACAACATTCATGTGTGAATATG
	CTGATGAGACAGCAACCATTGTAGAATTTCTGAACAGAT
	GGATTACCTTTGCCCAAAGCATCATCTCAACACTGACTTC
	CGGCGGAGGAGGATCCGGCGGAGGTGGCTCTGGCGGTGG
	CGGAGAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGT
	ACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT
	GGATTCACCTTTAGCAGTTTTTCGATGAGCTGGGTCCGCC
	AGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCATCTATTTC
	CGGTAGTTCGGGTACCACATACTACGCAGACTCCGTGAA
	GGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACAC
	GCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACAC
	GGCCGTATATTACTGTGCGAAACCGTTTCCGTATTTTGAC
	TACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCTA
	GCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
	CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCT
	GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG
	GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
	GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
	GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
	ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG
	TGGATAAGAAAGTTGAGCCCAAATCTTGTGACTGA
Fab light chain	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGT	109
derived from L19	CTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTC
monoclonal	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
antibody	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATTATGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGACGG
	GTCGTATTCCTCCGACGTTCGGCCAAGGGACCAAGGTGG
	AAATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTT
	CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCT
	GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCA
	AAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTA
	ACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACA
	GCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAG
	CAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCA
	CCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCA
	ACAGGGGAGAGTGTTAG
scFv derived from	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAG	110
L19 monoclonal	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAT
antibody-8 amino	TCACCTTTAGCAGTTTTTCGATGAGCTGGGTCCGCCAGGC
acid linker-C125A	TCCAGGGAAGGGGCTGGAGTGGGTCTCATCTATTTCCGGT
variant of IL2	AGTTCGGGTACCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAACCGTTTCCGTATTTTGACTACTG
	GGGCCAGGGAACCCTGGTCACCGTCTCGAGTAGCGGCGG
	GAGCGGCGGGGCTAGCGAAATTGTGTTGACGCAGTCTCC
	AGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTC
	TCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAG
	CCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCT
	CATCTATTATGCATCCAGCAGGGCCACTGGCATCCCAGAC
	AGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCA
	CCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTA
	CTGTCAGCAGACGGGTCGTATTCCTCCGACGTTCGGCCAA
	GGGACCAAGGTGGAAATCTCCGTGCTGTCTTCCTCATCGG
	GTAGTAGCTCTTCCGGCTCATCGTCCTCCGGAGCACCTAC
	TTCAAGTTCTACAAAGAAAACACAGCTACAACTGGAGCA
	TTTACTGCTGGATTTACAGATGATTTTGAATGGAATTAAT
	AATTACAAGAATCCCAAACTCACCAGGATGCTCACATTTA
	AGTTTTACATGCCCAAGAAGGCCACAGAACTGAAACATC
	TTCAGTGTCTAGAAGAAGAACTCAAACCTCTGGAGGAAG
	TGCTAAATTTAGCTCAAAGCAAAAACTTTCACTTAAGACC
	CAGGGACTTAATCAGCAATATCAACGTAATAGTTCTGGA
	ACTAAAGGGATCTGAAACAACATTCATGTGTGAATATGCT
	GATGAGACAGCAACCATTGTAGAATTTCTGAACAGATGG
	ATTACCTTTGCCCAAAGCATCATCTCAACACTGACTTGA
F16-diabody-IL2	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAG	111
DNA	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAT
	TCACCTTTAGCCGGTATGGTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGCGCATAATGCTTTTGACTACT
	GGGGCCAGGGAACCCTGGTCACCGTGTCGAGTGCTAGCG
	GCGGATCGTCTGAGCTGACTCAGGACCCTGCTGTGTCTGT
	GGCCTTGGGACAGACAGTCAGGATCACATGCCAAGGAGA
	CAGCCTCAGAAGCTATTATGCAAGCTGGTACCAGCAGAA
	GCCAGGACAGGCCCCTGTACTTGTCATCTATGGTAAAAAC
	AACCGGCCCTCAGGGATCCCAGACCGATTCTCTGGCTCCA
	GCTCAGGAAACACAGCTTCCTTGACCATCACTGGGGCTCA
	GGCGGAAGATGAGGCTGACTATTACTGTAACTCCTCTGTT
	TATACTATGCCGCCCGTGGTATTCGGCGGAGGGACCAAG
	CTGACCGTCCTAGGCTCTTCCTCATCGGGTAGTAGCTCTT
	CCGGCTCATCGTCCTCCGGAGCACCTACTTCAAGTTCTAC
	AAAGAAAACACAGCTACAACTGGAGCATTTACTGCTGGA
	TTTACAGATGATTTTGAATGGAATTAATAATTACAAGAAT
	CCCAAACTCACCAGGATGCTCACATTTAAGTTTTACATGC
	CCAAGAAGGCCACAGAACTGAAACATCTTCAGTGTCTAG
	AAGAAGAACTCAAACCTCTGGAGGAAGTGCTAAATTTAG
	CTCAAAGCAAAAACTTTCACTTAAGACCCAGGGACTTAAT
	CAGCAATATCAACGTAATAGTTCTGGAACTAAAGGGATC
	TGAAACAACATTCATGTGTGAATATGCTGATGAGACAGC
	AACCATTGTAGAATTTCTGAACAGATGGATTACCTTTGCC
	CAAAGCATCATCTCAACACTGACTTGA
scFv-IL2-scFv	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAG	112
(F16, DNA)	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAT
	TCACCTTTAGCCGGTATGGTATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGCGCATAATGCTTTTGACTACT
	GGGGCCAGGGAACCCTGGTCACCGTGTCGAGAGGTGGAG
	GCGGTTCAGGCGGAGGTGGCTCTGGCGGTGGCGGATCGT
	CTGAGCTGACTCAGGACCCTGCTGTGTCTGTGGCCTTGGG
	ACAGACAGTCAGGATCACATGCCAAGGAGACAGCCTCAG
	AAGCTATTATGCAAGCTGGTACCAGCAGAAGCCAGGACA
	GGCCCCTGTACTTGTCATCTATGGTAAAAACAACCGGCCC
	TCAGGGATCCCAGACCGATTCTCTGGCTCCAGCTCAGGAA
	ACACAGCTTCCTTGACCATCACTGGGGCTCAGGCGGAAG
	ATGAGGCTGACTATTACTGTAACTCCTCTGTTTATACTAT
	GCCGCCCGTGGTATTCGGCGGAGGGACCAAGCTGACCGT
	CCTAGGCTCTTCCTCATCGGGTAGTAGCTCTTCCGGCTCA
	TCGTCCTCCGGAGCACCTACTTCAAGTTCTACAAAGAAAA
	CACAGCTACAACTGGAGCATTTACTGCTGGATTTACAGAT
	GATTTTGAATGGAATTAATAATTACAAGAATCCCAAACTC
	ACCAGGATGCTCACATTTAAGTTTTACATGCCCAAGAAGG
	CCACAGAACTGAAACATCTTCAGTGTCTAGAAGAAGAAC
	TCAAACCTCTGGAGGAAGTGCTAAATTTAGCTCAAAGCA
	AAAACTTTCACTTAAGACCCAGGGACTTAATCAGCAATAT
	CAACGTAATAGTTCTGGAACTAAAGGGATCTGAAACAAC
	ATTCATGTGTGAATATGCTGATGAGACAGCAACCATTGTA
	GAATTTCTGAACAGATGGATTACCTTTGCCCAAAGCATCA
	TCTCAACACTGACTTCCGGCGGAGGAGGGAGCGGCGGAG
	GTGGCTCTGGCGGTGGCGGATCGTCTGAGCTCACTCAGGA
	CCCTGCTGTGTCTGTGGCCTTGGGACAGACAGTCAGGATC
	ACATGCCAAGGAGACAGCCTCAGAAGCTATTATGCAAGC
	TGGTACCAGCAGAAGCCAGGACAGGCCCCTGTACTTGTC
	ATCTATGGTAAAAACAACCGGCCCTCAGGGATCCCAGAC
	CGATTCTCTGGCTCCAGCTCAGGAAACACAGCTTCCTTGA
	CCATCACTGGGGCTCAGGCGGAAGATGAGGCTGACTATT
	ACTGTAACTCCTCTGTTTATACTATGCCGCCCGTGGTATTC
	GGCGGAGGGACCAAGCTTACCGTACTAGGCTCAGGAGGC
	GGTTCAGGCGGAGGTTCTGGCGGCGGTAGCGGATCGGAG
	GTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCT
	GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCA
	CCTTTAGCCGGTATGGTATGAGCTGGGTCCGCCAGGCTCC
	AGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAG
	TGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCG
	GTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
	CTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTA
	TATTACTGTGCGAAAGCGCATAATGCTTTTGACTACTGGG
	GCCAGGGAACCCTGGTCACCGTGTCGTGA
Fab-IL2-Fab	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAG	113
(F16, heavy chain	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAT
cytokine fusion	TCACCTTTAGCCGGTATGGTATGAGCTGGGTCCGCCAGGC
construct, DNA)	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGCGCATAATGCTTTTGACTACT
	GGGGCCAGGGAACCCTGGTCACCGTGTCGAGTGCTAGCA
	CCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAA
	GAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGT
	CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA
	CTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT
	GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGG
	TGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACAT
	CTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGA
	TAAGAAAGTTGAGCCCAAATCTTGTGACTCTTCCTCATCG
	GGTAGTAGCTCTTCCGGCTCATCGTCCTCCGGAGCACCTA
	CTTCAAGTTCTACAAAGAAAACACAGCTACAACTGGAGC
	ATTTACTGCTGGATTTACAGATGATTTTGAATGGAATTAA
	TAATTACAAGAATCCCAAACTCACCAGGATGCTCACATTT
	AAGTTTTACATGCCCAAGAAGGCCACAGAACTGAAACAT
	CTTCAGTGTCTAGAAGAAGAACTCAAACCTCTGGAGGAA
	GTGCTAAATTTAGCTCAAAGCAAAAACTTTCACTTAAGAC
	CCAGGGACTTAATCAGCAATATCAACGTAATAGTTCTGGA
	ACTAAAGGGATCTGAAACAACATTCATGTGTGAATATGCT
	GATGAGACAGCAACCATTGTAGAATTTCTGAACAGATGG
	ATTACCTTTGCCCAAAGCATCATCTCAACACTGACTTCCG
	GCGGAGGAGGGAGCGGCGGAGGTGGCTCTGGCGGTGGCG
	GAGAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTAC
	AGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGG
	ATTCACCTTTAGCCGGTATGGTATGAGCTGGGTCCGCCAG
	GCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGT
	GGTAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAG
	GGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACG
	CTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACG
	GCCGTATATTACTGTGCGAAAGCGCATAATGCTTTTGACT
	ACTGGGGCCAGGGAACCCTGGTCACCGTGTCGAGTGCTA
	GCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
	CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCT
	GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG
	GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
	GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
	GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
	ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG
	TGGACAAGAAAGTTGAGCCCAAATCTTGTGACTGA
F16, light chain,	TCTTCTGAGCTGACTCAGGACCCTGCTGTGTCTGTGGCCT	114
DNA	TGGGACAGACAGTCAGGATCACATGCCAAGGAGACAGCC
	TCAGAAGCTATTATGCAAGCTGGTACCAGCAGAAGCCAG
	GACAGGCCCCTGTACTTGTCATCTATGGTAAAAACAACCG
	GCCCTCAGGGATCCCAGACCGATTCTCTGGCTCCAGCTCA
	GGAAACACAGCTTCCTTGACCATCACTGGGGCTCAGGCG
	GAAGATGAGGCTGACTATTACTGTAACTCCTCTGTTTATA
	CTATGCCGCCCGTGGTATTCGGCGGAGGGACCAAGCTGA
	CCGTCCTAGGTCAACCCAAGGCTGCCCCCAGCGTGACCCT
	GTTCCCCCCCAGCAGCGAGGAACTGCAGGCCAACAAGGC
	CACCCTGGTCTGCCTGATCAGCGACTTCTACCCAGGCGCC
	GTGACCGTGGCCTGGAAGGCCGACAGCAGCCCCGTGAAG
	GCCGGCGTGGAGACCACCACCCCCAGCAAGCAGAGCAAC
	AACAAGTACGCCGCCAGCAGCTACCTGAGCCTGACCCCC
	GAGCAGTGGAAGAGCCACAGGTCCTACAGCTGCCAGGTG
	ACCCACGAGGGCAGCACCGTGGAGAAAACCGTGGCCCCC
	ACCGAGTGCAGCTGA
IL2R-beta-	ATGGACATGAGGGTCCCCGCTCAGCTCCTGGGCCTCCTGC	115
Fc(hole) fusion	TGCTCTGGTTCCCAGGTGCCAGGTGTGCGGTGAATGGCAC
protein, DNA	TTCCCAGTTCACATGCTTCTACAACTCGAGAGCCAACATC
	TCCTGTGTCTGGAGCCAAGATGGGGCTCTGCAGGACACTT
	CCTGCCAAGTCCATGCCTGGCCGGACAGACGGCGGTGGA
	ACCAAACCTGTGAGCTGCTCCCCGTGAGTCAAGCATCCTG
	GGCCTGCAACCTGATCCTCGGAGCCCCAGATTCTCAGAAA
	CTGACCACAGTTGACATCGTCACCCTGAGGGTGCTGTGCC
	GTGAGGGGGTGCGATGGAGGGTGATGGCCATCCAGGACT
	TCAAGCCCTTTGAGAACCTTCGCCTGATGGCCCCCATCTC
	CCTCCAAGTTGTCCACGTGGAGACCCACAGATGCAACAT
	AAGCTGGGAAATCTCCCAAGCCTCCCACTACTTTGAAAGA
	CACCTGGAGTTCGAGGCCCGGACGCTGTCCCCAGGCCAC
	ACCTGGGAGGAGGCCCCCCTGCTGACTCTCAAGCAGAAG
	CAGGAATGGATCTGCCTGGAGACGCTCACCCCAGACACC
	CAGTATGAGTTTCAGGTGCGGGTCAAGCCTCTGCAAGGC
	GAGTTCACGACCTGGAGCCCCTGGAGCCAGCCCCTGGCCT
	TCAGAACAAAGCCTGCAGCCCTTGGGAAGGACACCGGAG
	CTCAGGACAAAACTCACACATGCCCACCGTGCCCAGCAC
	CTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCC
	AAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGA
	GGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCC
	TGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGT
	GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAA
	CAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCAC
	CAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTC
	TCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCT
	CCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTGCA
	CCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGG
	TCAGCCTCTCGTGCGCAGTCAAAGGCTTCTATCCCAGCGA
	CATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAA
	CAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
	CTCCTTCTTCCTCGTGAGCAAGCTCACCGTGGACAAGAGC
	AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGC
	ATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCT
	CCCTGTCTCCGGGTAAATGA
IL2R-gamma-	ATGTTGAAGCCATCATTACCATTCACATCCCTCTTATTCCT	116
Fc(knob), DNA	GCAGCTGCCCCTGCTGGGAGTGGGGCTGAACACGACAAT
	TCTGACGCCCAATGGGAATGAAGACACCACAGCTGATTT
	CTTCCTGACCACTATGCCCACTGACTCCCTCAGTGTTTCCA
	CTCTGCCCCTCCCAGAGGTTCAGTGTTTTGTGTTCAATGTC
	GAGTACATGAATTGCACTTGGAACAGCAGCTCTGAGCCC
	CAGCCTACCAACCTCACTCTGCATTATTGGTACAAGAACT
	CGGATAATGATAAAGTCCAGAAGTGCAGCCACTATCTATT
	CTCTGAAGAAATCACTTCTGGCTGTCAGTTGCAAAAAAAG
	GAGATCCACCTCTACCAAACATTTGTTGTTCAGCTCCAGG
	ACCCACGGGAACCCAGGAGACAGGCCACACAGATGCTAA
	AACTGCAGAATCTGGTGATCCCCTGGGCTCCAGAGAACCT
	AACACTTCACAAACTGAGTGAATCCCAGCTAGAACTGAA
	CTGGAACAACAGATTCTTGAACCACTGTTTGGAGCACTTG
	GTGCAGTACCGGACTGACTGGGACCACAGCTGGACTGAA
	CAATCAGTGGATTATAGACATAAGTTCTCCTTGCCTAGTG
	TGGATGGGCAGAAACGCTACACGTTTCGTGTTCGGAGCC
	GCTTTAACCCACTCTGTGGAAGTGCTCAGCATTGGAGTGA
	ATGGAGCCACCCAATCCACTGGGGGAGCAATACTTCAAA
	AGAGAATCCTTTCCTGTTTGCATTGGAAGCCGGAGCTCAG
	GACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAA
	CTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAAC
	CCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCAC
	ATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGT
	CAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAA
	TGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCAC
	GTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGAC
	TGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAAC
	AAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA
	GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTG
	CCCCCATGCCGGGATGAGCTGACCAAGAACCAGGTCAGC
	CTGTGGTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCG
	CCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACT
	ACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTT
	CTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTG
	GCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG
	GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGT
	CTCCGGGTAAATGA
Fab-IL12-Fab	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAG	117
L19 antibody,	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAT
murine scIL12,	TCACCTTTAGCAGTTTTTCGATGAGCTGGGTCCGCCAGGC
DNA	TCCAGGGAAGGGGCTGGAGTGGGTCTCATCTATTTCCGGT
	AGTTCGGGTACCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAACCGTTTCCGTATTTTGACTACTG
	GGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCTAGCAC
	CAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAG
	AGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTC
	AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAAC
	TCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTG
	TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT
	GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATC
	TGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGAT
	AAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCGGAGGA
	GGGAGCGGCGGAGGTGGCTCCGGAGGGGGCGGAGCCAT
	GTGGGAGCTGGAAAAGGACGTGTACGTGGTGGAGGTGGA
	CTGGACCCCCGACGCCCCTGGCGAGACAGTGAACCTGAC
	CTGCGACACCCCCGAAGAGGACGACATCACCTGGACCAG
	CGACCAGCGGCACGGCGTGATCGGCAGCGGCAAGACCCT
	GACCATCACCGTGAAAGAGTTTCTGGACGCCGGCCAGTA
	CACCTGCCACAAGGGCGGCGAGACACTGAGCCACAGCCA
	CCTGCTGCTGCACAAGAAAGAGAACGGCATCTGGTCCAC
	CGAGATCCTGAAGAACTTCAAGAACAAGACCTTCCTGAA
	GTGCGAGGCCCCCAACTACAGCGGCCGGTTCACCTGCAG
	CTGGCTGGTGCAGCGGAACATGGACCTGAAGTTCAACAT
	CAAGAGCAGCAGCAGCCCCCCTGACAGCAGGGCCGTGAC
	CTGCGGCATGGCCAGCCTGAGCGCCGAGAAGGTGACCCT
	GGACCAGAGGGACTACGAGAAGTACAGCGTGAGCTGCCA
	GGAAGATGTCACCTGCCCCACCGCCGAGGAAACCCTGCC
	CATCGAGCTGGCCCTGGAAGCCCGGCAGCAGAACAAGTA
	CGAGAACTACTCTACCAGCTTCTTCATCCGGGACATCATC
	AAGCCCGACCCCCCCAAGAACCTGCAGATGAAGCCCCTG
	AAGAACAGCCAGGTGGAGGTGTCCTGGGAGTACCCTGAC
	AGCTGGTCCACCCCCAGAAGCTACTTCAGCCTGAAGTTCT
	TCGTGAGAATCCAGCGGAAGAAAGAAAAGATGAAAGAG
	ACAGAGGAAGGCTGCAACCAGAAGGGCGCCTTCTTCGTC
	GAGAAAACCAGCACCGAGGTGCAGTGCAAGGGCGGCAA
	CGTGTGCGTGCAGGCCCAGGACCGGTACTACAACAGCAG
	CTGCAGCAAGTGGGCCTGCGTGCCCTGCAGAGTGCGGTCT
	GGCGGCGACGGCTCTGGCGGCGGAGGAAGCGGCGGAGG
	GGGCAGCAGAGTGATCCCCGTGAGCGGCCCTGCCCGGTG
	CCTGAGCCAGAGCCGGAACCTGCTGAAAACCACCGACGA
	CATGGTGAAAACCGCCAGAGAGAAGCTGAAGCACTACAG
	CTGCACAGCCGAGGACATCGACCACGAGGACATCACCCG
	GGACCAGACCAGCACCCTGAAAACCTGCCTGCCCCTGGA
	ACTGCACAAAAACGAGAGCTGCCTGGCCACCCGGGAGAC
	AAGCAGCACCACCCGGGGCAGCTGCCTGCCTCCCCAGAA
	AACCTCCCTGATGATGACCCTGTGCCTGGGCAGCATCTAC
	GAGGACCTGAAGATGTACCAGACCGAGTTCCAGGCCATC
	AACGCCGCCCTGCAGAACCACAATCACCAGCAGATCATC
	CTGGACAAGGGCATGCTGGTCGCCATCGACGAGCTGATG
	CAGAGCCTGAACCACAACGGCGAAACCCTGCGGCAGAAA
	CCCCCCGTGGGCGAGGCCGACCCCTACCGGGTGAAGATG
	AAGCTGTGCATCCTGCTGCACGCCTTCAGCACCCGGGTGG
	TGACCATCAACCGGGTGATGGGCTACCTGTCCTCTGCCGG
	GGGAGGGGGATCCGGCGGAGGTGGCTCTGGCGGTGGCGG
	AGAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACA
	GCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGA
	TTCACCTTTAGCAGTTTTTCGATGAGCTGGGTCCGCCAGG
	CTCCAGGGAAGGGGCTGGAGTGGGTCTCATCTATTTCCGG
	TAGTTCGGGTACCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAACCGTTTCCGTATTTTGACTACT
	GGGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCTAGCA
	CCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAA
	GAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGT
	CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA
	CTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT
	GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGG
	TGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACAT
	CTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGA
	TAAGAAAGTTGAGCCCAAATCTTGTGACTGA
Fab-IL12-FabL19	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAG	118
antibody, human	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAT
scIL12, DNA	TCACCTTTAGCAGTTTTTCGATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCATCTATTAGAGG
	TAGTTCGGGTACCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAACCGTTTCCGTATTTTGACTACT
	GGGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCTAGCA
	CCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAA
	GAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGT
	CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA
	CTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT
	GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGG
	TGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACAT
	CTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGA
	TAAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCGGAGG
	AGGGAGCGGCGGAGGTGGCTCCGGAGGGGGCGGAATCTG
	GGAGCTGAAGAAAGACGTGTACGTGGTGGAGCTGGACTG
	GTATCCCGACGCCCCTGGCGAGATGGTGGTGCTGACCTGC
	GACACCCCCGAAGAGGACGGCATCACCTGGACCCTGGAC
	CAGAGCAGCGAGGTGCTGGGCAGCGGCAAGACCCTGACC
	ATCCAGGTGAAAGAGTTCGGCGACGCCGGCCAGTACACC
	TGCCACAAGGGCGGCGAAGTGCTGTCCCACAGCCTGCTG
	CTGCTGCACAAGAAAGAGGATGGCATCTGGTCCACCGAC
	ATCCTGAAGGACCAGAAAGAGCCCAAGAACAAGACCTTC
	CTGCGGTGCGAGGCCAAGAACTACAGCGGCCGGTTCACC
	TGTTGGTGGCTGACCACCATCAGCACCGACCTGACCTTCA
	GCGTGAAGAGCAGCCGGGGCAGCAGCGACCCTCAGGGCG
	TGACCTGCGGAGCCGCCACCCTGAGCGCCGAGAGAGTGC
	GGGGCGACAACAAAGAGTACGAGTACAGCGTCGAGTGCC
	AGGAAGATAGCGCCTGCCCTGCCGCCGAGGAAAGCCTGC
	CCATCGAGGTGATGGTGGACGCCGTGCACAAGCTGAAGT
	ACGAGAACTACACCAGCAGCTTTTTCATCCGGGACATCAT
	CAAGCCCGACCCCCCCAAGAACCTGCAGCTGAAGCCCCT
	GAAGAACAGCCGGCAGGTGGAGGTGTCCTGGGAGTACCC
	TGACACCTGGTCCACCCCCCACAGCTACTTCAGCCTGACA
	TTCTGTGTGCAGGTGCAGGGCAAGAGCAAGCGGGAGAAG
	AAAGACCGGGTGTTCACCGACAAGACCAGCGCCACCGTG
	ATCTGCCGGAAGAACGCCAGCATCAGCGTGCGGGCCCAG
	GACCGGTACTACAGCAGCTCCTGGTCCGAGTGGGCCAGC
	GTGCCTTGCAGCGGCGGAGGGGGCTCTGGCGGCGGAGGA
	TCTGGGGGAGGGGGCAGCCGGAACCTGCCCGTGGCCACC
	CCCGACCCCGGCATGTTCCCCTGCCTGCACCACAGCCAGA
	ACCTGCTGCGGGCCGTGAGCAACATGCTGCAGAAGGCCC
	GGCAGACCCTGGAATTCTACCCCTGCACCAGCGAGGAAA
	TCGACCACGAGGACATCACCAAGGATAAGACCAGCACCG
	TGGAGGCCTGCCTGCCCCTGGAACTGACCAAGAACGAGA
	GCTGCCTGAACAGCCGGGAGACAAGCTTCATCACCAACG
	GCAGCTGCCTGGCCAGCAGAAAGACCAGCTTCATGATGG
	CCCTGTGCCTGAGCAGCATCTACGAGGACCTGAAGATGT
	ACCAGGTGGAGTTCAAGACCATGAACGCCAAGCTGCTGA
	TGGACCCCAAGCGGCAGATCTTCCTGGATCAGAACATGCT
	GGCCGTGATCGACGAGCTGATGCAGGCCCTGAACTTCAA
	CAGCGAGACAGTGCCCCAGAAGTCCAGCCTGGAAGAGCC
	CGACTTCTACAAGACCAAGATCAAGCTGTGCATCCTGCTG
	CACGCCTTCAGAATCCGGGCCGTGACCATCGACCGGGTG
	ATGAGCTACCTGAACGCCAGCGGAGGGGGGGGATCCGGC
	GGAGGTGGCTCTGGCGGTGGCGGAGAGGTGCAGCTGTTG
	GAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTG
	AGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGTT
	TTTCGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGC
	TGGAGTGGGTCTCATCTATTAGAGGTAGTTCGGGTACCAC
	ATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCC
	AGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAAC
	AGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCG
	AAACCGTTTCCGTATTTTGACTACTGGGGCCAGGGAACCC
	TGGTCACCGTCTCGAGTGCTAGCACCAAGGGCCCATCGGT
	CTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGC
	ACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCG
	AACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCA
	GCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGG
	ACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGC
	AGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCAC
	AAGCCCAGCAACACCAAGGTGGATAAGAAAGTTGAGCCC
	AAATCTTGTGACTGA
Fab-GMCSF-Fab	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAG	119
L19 antibody,	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAT
human GM-CSF,	TCACCTTTAGCAGTTTTTCGATGAGCTGGGTCCGCCAGGC
DNA	TCCAGGGAAGGGGCTGGAGTGGGTCTCATCTATTAGAGG
	TAGTTCGGGTACCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAACCGTTTCCGTATTTTGACTACT
	GGGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCTAGCA
	CCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAA
	GAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGT
	CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA
	CTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT
	GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGG
	TGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACAT
	CTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGA
	TAAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCGGAGG
	AGGGAGCGGCGGAGGTGGCTCCGGAGGTGGCGGAGCACC
	CGCCCGCTCGCCCAGCCCCAGCACGCAGCCCTGGGAGCA
	TGTGAATGCCATCCAGGAGGCCCGGCGTCTCCTGAACCTG
	AGTAGAGACACTGCTGCTGAGATGAATGAAACAGTAGAA
	GTCATCTCAGAAATGTTTGACCTCCAGGAGCCGACCTGCC
	TACAGACCCGCCTGGAGCTGTACAAGCAGGGCCTGCGGG
	GCAGCCTCACCAAGCTCAAGGGCCCCTTGACCATGATGG
	CCAGCCACTACAAGCAGCACTGCCCTCCAACCCCGGAAA
	CTTCCTGTGCAACCCAGATTATCACCTTTGAAAGTTTCAA
	AGAGAACCTGAAGGACTTTCTGCTTGTCATCCCCTTTGAC
	TGCTGGGAGCCAGTCCAGGAGTCCGGCGGAGGAGGATCC
	GGCGGAGGTGGCTCTGGCGGTGGCGGAGAGGTGCAGCTG
	TTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCC
	CTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCA
	GTTTTTCGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGG
	GGCTGGAGTGGGTCTCATCTATTAGAGGTAGTTCGGGTAC
	CACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC
	TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATG
	AACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGT
	GCGAAACCGTTTCCGTATTTTGACTACTGGGGCCAGGGAA
	CCCTGGTCACCGTCTCGAGTGCTAGCACCAAGGGCCCATC
	GGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGG
	GGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCC
	CCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGA
	CCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTC
	AGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCC
	AGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAAT
	CACAAGCCCAGCAACACCAAGGTGGATAAGAAAGTTGAG
	CCCAAATCTTGTGACTGA
Fab-IFNα2-Fab,	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAG	120
L19 antibody,	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGAT
DNA	TCACCTTTAGCAGTTTTTCGATGAGCTGGGTCCGCCAGGC
	TCCAGGGAAGGGGCTGGAGTGGGTCTCATCTATTAGAGG
	TAGTTCGGGTACCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAACCGTTTCCGTATTTTGACTACT
	GGGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCTAGCA
	CCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAA
	GAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGT
	CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA
	CTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT
	GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGG
	TGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACAT
	CTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGA
	TAAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCGGAGG
	AGGGAGCGGCGGAGGTGGCTCCGGAGGGGGCGGATGCG
	ACCTGCCCCAGACCCACAGCCTGGGCAACAGACGGGCCC
	TGATCCTGCTGGCCCAGATGCGGCGGATCAGCCCCTTCAG
	CTGCCTGAAGGACCGGCACGACTTCGGCTTCCCCCAGGA
	AGAGTTCGACGGCAACCAGTTCCAGAAGGCCCAGGCCAT
	CAGCGTGCTGCACGAGATGATCCAGCAGACCTTCAACCT
	GTTCAGCACCAAGGACAGCAGCGCCGCCTGGGACGAGAG
	CCTGCTGGAAAAGTTCTACACCGAGCTGTACCAGCAGCTG
	AACGACCTGGAAGCCTGCGTGATCCAGGAAGTGGGCGTC
	GAGGAAACCCCCCTGATGAACGTGGACAGCATCCTGGCC
	GTGAAGAAGTACTTCCAGCGGATCACCCTGTACCTGACCG
	AGAAGAAGTATAGCCCCTGCGCCTGGGAGGTGGTGCGGG
	CCGAGATCATGCGGAGCTTCAGCCTGAGCACCAACCTGC
	AGGAACGGCTGCGGCGGAAAGAGAGCGGCGGAGGGGGA
	TCCGGCGGAGGTGGCTCTGGCGGTGGCGGAGAGGTGCAG
	CTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGG
	TCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTA
	GCAGTTTTTCGATGAGCTGGGTCCGCCAGGCTCCAGGGAA
	GGGGCTGGAGTGGGTCTCATCTATTAGAGGTAGTTCGGGT
	ACCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACC
	ATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAA
	ATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTAC
	TGTGCGAAACCGTTTCCGTATTTTGACTACTGGGGCCAGG
	GAACCCTGGTCACCGTCTCGAGTGCTAGCACCAAGGGCC
	CATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTC
	TGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTA
	CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCC
	CTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGT
	CCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC
	CTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG
	AATCACAAGCCCAGCAACACCAAGGTGGATAAGAAAGTT
	GAGCCCAAATCTTGTGACTGA
3F2 Fab-IL2-Fab	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	210
(heavy chain	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
cytokine fusion	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
construct)	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGTTTGGTGGTTTTAACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGTGCTA
	GCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
	CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCT
	GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG
	GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
	GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
	GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
	ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG
	TGGATAAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCG
	GAGGAGGGAGCGGCGGAGGTGGCTCCGGAGGTGGCGGA
	GCACCTACTTCAAGTTCTACAAAGAAAACACAGCTACAA
	CTGGAGCATTTACTGCTGGATTTACAGATGATTTTGAATG
	GAATTAATAATTACAAGAATCCCAAACTCACCAGGATGC
	TCACATTTAAGTTTTACATGCCCAAGAAGGCCACAGAACT
	GAAACATCTTCAGTGTCTAGAAGAAGAACTCAAACCTCT
	GGAGGAAGTGCTAAATTTAGCTCAAAGCAAAAACTTTCA
	CTTAAGACCCAGGGACTTAATCAGCAATATCAACGTAAT
	AGTTCTGGAACTAAAGGGATCTGAAACAACATTCATGTGT
	GAATATGCTGATGAGACAGCAACCATTGTAGAATTTCTGA
	ACAGATGGATTACCTTTGCCCAAAGCATCATCTCAACACT
	GACTTCCGGCGGAGGAGGATCCGGCGGAGGTGGCTCTGG
	CGGTGGCGGAGAGGTGCAATTGTTGGAGTCTGGGGGAGG
	CTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCA
	GCCTCCGGATTCACCTTTAGCAGTTATGCCATGAGCTGGG
	TCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAG
	CTATTAGTGGTAGTGGTGGTAGCACATACTACGCAGACTC
	CGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAA
	GAACACGCTGTATCTGCAGATGAACAGCCTGAGAGCCGA
	GGACACGGCCGTATATTACTGTGCGAAAGGGTGGTTTGGT
	GGTTTTAACTACTGGGGCCAAGGAACCCTGGTCACCGTCT
	CGAGTGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGC
	ACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCT
	GGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGAC
	GGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA
	CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
	CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCA
	CCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCA
	ACACCAAGGTGGATAAGAAAGTTGAGCCCAAATCTTGTG
	ACTGA
4G8 Fab-IL2-Fab	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	212
(heavy chain	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
cytokine fusion	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
construct)	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGCTGGGTAATTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGTGCTA
	GCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
	CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCT
	GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG
	GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
	GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
	GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
	ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG
	TGGATAAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCG
	GAGGAGGGAGCGGCGGAGGTGGCTCCGGAGGTGGCGGA
	GCACCTACTTCAAGTTCTACAAAGAAAACACAGCTACAA
	CTGGAGCATTTACTGCTGGATTTACAGATGATTTTGAATG
	GAATTAATAATTACAAGAATCCCAAACTCACCAGGATGC
	TCACATTTAAGTTTTACATGCCCAAGAAGGCCACAGAACT
	GAAACATCTTCAGTGTCTAGAAGAAGAACTCAAACCTCT
	GGAGGAAGTGCTAAATTTAGCTCAAAGCAAAAACTTTCA
	CTTAAGACCCAGGGACTTAATCAGCAATATCAACGTAAT
	AGTTCTGGAACTAAAGGGATCTGAAACAACATTCATGTGT
	GAATATGCTGATGAGACAGCAACCATTGTAGAATTTCTGA
	ACAGATGGATTACCTTTGCCCAAAGCATCATCTCAACACT
	GACTTCCGGCGGAGGAGGATCCGGCGGAGGTGGCTCTGG
	CGGTGGCGGAGAGGTGCAATTGTTGGAGTCTGGGGGAGG
	CTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCA
	GCCTCCGGATTCACCTTTAGCAGTTATGCCATGAGCTGGG
	TCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAG
	CTATTAGTGGTAGTGGTGGTAGCACATACTACGCAGACTC
	CGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAA
	GAACACGCTGTATCTGCAGATGAACAGCCTGAGAGCCGA
	GGACACGGCCGTATATTACTGTGCGAAAGGGTGGCTGGG
	TAATTTTTGACTACTGGGGCCAAGGAACCCTGGTCACCGTC
	TCGAGTGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGG
	CACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCT
	GGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGAC
	GGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA
	CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
	CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCA
	CCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCA
	ACACCAAGGTGGATAAGAAAGTTGAGCCCAAATCTTGTG
	ACTGA
3D9 Fab-IL2-Fab	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	214
(heavy chain	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
cytokine fusion	TCACCTTTAGCAGTTATGCTATGAGCTGGGTCCGCCAGAC
construct)	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTGGTGTT
	AGTACTGGTAGCACATACTACGCAGACTCCGTGAAGGGC
	CGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGT
	ATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCCG
	TATATTACTGTGCGAAAGGTTGGCTGGGTCCTTTTGACTA
	CTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGTGCTAG
	CACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC
	AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTG
	GTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGG
	AACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCG
	GCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCG
	TGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTA
	CATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGT
	GGATAAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCGG
	AGGAGGGAGCGGCGGAGGTGGCTCCGGAGGTGGCGGAG
	CACCTACTTCAAGTTCTACAAAGAAAACACAGCTACAACT
	GGAGCATTTACTGCTGGATTTACAGATGATTTTGAATGGA
	ATTAATAATTACAAGAATCCCAAACTCACCAGGATGCTCA
	CATTTAAGTTTTACATGCCCAAGAAGGCCACAGAACTGA
	AACATCTTCAGTGTCTAGAAGAAGAACTCAAACCTCTGG
	AGGAAGTGCTAAATTTAGCTCAAAGCAAAAACTTTCACTT
	AAGACCCAGGGACTTAATCAGCAATATCAACGTAATAGT
	TCTGGAACTAAAGGGATCTGAAACAACATTCATGTGTGA
	ATATGCTGATGAGACAGCAACCATTGTAGAATTTCTGAAC
	AGATGGATTACCTTTGCCCAAAGCATCATCTCAACACTGA
	CTTCCGGCGGAGGAGGATCCGGCGGAGGTGGCTCTGGCG
	GTGGCGGAGAGGTGCAATTGTTGGAGTCTGGGGGAGGCT
	TGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGC
	CTCCGGATTCACCTTTAGCAGTTATGCTATGAGCTGGGTC
	CGCCAGACTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCT
	ATTGGTGTTAGTACTGGTAGCACATACTACGCAGACTCCG
	TGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA
	ACACGCTGTATCTGCAGATGAACAGCCTGAGAGCCGAGG
	ACACGGCCGTATATTACTGTGCGAAAGGTTGGCTGGGTCC
	TTTTGACTACTGGGGCCAAGGAACCCTGGTCACCGTCTCG
	AGTGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCAC
	CCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGG
	GCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGT
	GTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACAC
	CTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC
	AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC
	CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAAC
	ACCAAGGTGGATAAGAAAGTTGAGCCCAAATCTTGTGAC
	TGA
2F11 Fab-IL2-Fab	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	216
(heavy chain	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
cytokine fusion	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
construct)	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACCGCC
	GTATATTACTGTGCGAAATGGAGATGGATGATGTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGTGCTA
	GCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
	CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCT
	GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG
	GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
	GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
	GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
	ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG
	TGGATAAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCG
	GAGGAGGGAGCGGCGGAGGTGGCTCCGGAGGTGGCGGA
	GCACCTACTTCAAGTTCTACAAAGAAAACACAGCTACAA
	CTGGAGCATTTACTGCTGGATTTACAGATGATTTTGAATG
	GAATTAATAATTACAAGAATCCCAAACTCACCAGGATGC
	TCACATTTAAGTTTTACATGCCCAAGAAGGCCACAGAACT
	GAAACATCTTCAGTGTCTAGAAGAAGAACTCAAACCTCT
	GGAGGAAGTGCTAAATTTAGCTCAAAGCAAAAACTTTCA
	CTTAAGACCCAGGGACTTAATCAGCAATATCAACGTAAT
	AGTTCTGGAACTAAAGGGATCTGAAACAACATTCATGTGT
	GAATATGCTGATGAGACAGCAACCATTGTAGAATTTCTGA
	ACAGATGGATTACCTTTGCCCAAAGCATCATCTCAACACT
	GACTTCCGGCGGAGGAGGATCCGGCGGAGGTGGCTCTGG
	CGGTGGCGGAGAGGTGCAATTGTTGGAGTCTGGGGGAGG
	CTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCA
	GCCTCCGGATTCACCTTTAGCAGTTATGCCATGAGCTGGG
	TCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAG
	CTATTAGTGGTAGTGGTGGTAGCACATACTACGCAGACTC
	CGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAA
	GAACACGCTGTATCTGCAGATGAACAGCCTGAGAGCCGA
	GGACACCGCCGTATATTACTGTGCGAAATGGAGATGGAT
	GATGTTTGACTACTGGGGCCAAGGAACCCTGGTCACCGTC
	TCGAGTGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGG
	CACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCT
	GGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGAC
	GGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA
	CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
	CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCA
	CCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCA
	ACACCAAGGTGGATAAGAAAGTTGAGCCCAAATCTTGTG
	ACTGA
4B3 Fab-IL2-Fab	GAGGTGCAATTGTTGGAGTCTGGGGGAGGCTTGGTACAG	218
(heavy chain	CCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCCGGAT
cytokine fusion	TCACCTTTAGCAGTTATGCCATGAGCTGGGTCCGCCAGGC
construct)	TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGG
	TAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGG
	CCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
	TATCTGCAGATGAACAGCCTGAGAGCCGAGGACACGGCC
	GTATATTACTGTGCGAAAGGGTGGCTGGGTAATTTTGACT
	ACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGTGCTA
	GCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
	CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCT
	GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG
	GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
	GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
	GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
	ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG
	TGGATAAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCG
	GAGGAGGGAGCGGCGGAGGTGGCTCCGGAGGTGGCGGA
	GCACCTACTTCAAGTTCTACAAAGAAAACACAGCTACAA
	CTGGAGCATTTACTGCTGGATTTACAGATGATTTTGAATG
	GAATTAATAATTACAAGAATCCCAAACTCACCAGGATGC
	TCACATTTAAGTTTTACATGCCCAAGAAGGCCACAGAACT
	GAAACATCTTCAGTGTCTAGAAGAAGAACTCAAACCTCT
	GGAGGAAGTGCTAAATTTAGCTCAAAGCAAAAACTTTCA
	CTTAAGACCCAGGGACTTAATCAGCAATATCAACGTAAT
	AGTTCTGGAACTAAAGGGATCTGAAACAACATTCATGTGT
	GAATATGCTGATGAGACAGCAACCATTGTAGAATTTCTGA
	ACAGATGGATTACCTTTGCCCAAAGCATCATCTCAACACT
	GACTTCCGGCGGAGGAGGATCCGGCGGAGGTGGCTCTGG
	CGGTGGCGGAGAGGTGCAATTGTTGGAGTCTGGGGGAGG
	CTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCA
	GCCTCCGGATTCACCTTTAGCAGTTATGCCATGAGCTGGG
	TCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAG
	CTATTAGTGGTAGTGGTGGTAGCACATACTACGCAGACTC
	CGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAA
	GAACACGCTGTATCTGCAGATGAACAGCCTGAGAGCCGA
	GGACACGGCCGTATATTACTGTGCGAAAGGGTGGCTGGG
	TAATTTTGACTACTGGGGCCAAGGAACCCTGGTCACCGTC
	TCGAGTGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGG
	CACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCT
	GGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGAC
	GGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA
	CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC
	CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCA
	CCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCA
	ACACCAAGGTGGATAAGAAAGTTGAGCCCAAATCTTGTG
	ACTGA
4G8 Fab-IL12-Fab	GAGGTGCAATTGCTGGAAAGCGGCGGAGGACTGGTGCAG	220
(murine IL-12;	CCTGGCGGCAGCCTGAGACTGAGCTGCGCCGCCAGCGGC
heavy chain	TTCACCTTCAGCAGCTACGCCATGTCTTGGGTCCGCCAGG
cytokine fusion	CCCCTGGAAAGGGCCTGGAATGGGTGTCCGCCATCAGCG
construct)	GCAGCGGCGGCAGCACCTACTACGCCGACAGCGTGAAGG
	GCCGGTTCACCATCAGCCGGGACAACAGCAAGAACACCC
	TGTACCTGCAGATGAACAGCCTGAGAGCCGAGGACACCG
	CCGTGTACTACTGCGCCAAGGGCTGGCTGGGCAACTTCGA
	CTACTGGGGCCAGGGCACTCTGGTCACAGTGTCTAGCGCT
	AGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCT
	CCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCC
	TGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG
	GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
	GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
	GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
	ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG
	TGGATAAGAAAGTTGAGCCCAAATCTTGTGACTCCGGCG
	GAGGAGGGAGCGGCGGAGGTGGCTCCGGAGGGGGCGGA
	GCCATGTGGGAGCTGGAAAAGGACGTGTACGTGGTGGAG
	GTGGACTGGACCCCCGACGCCCCTGGCGAGACAGTGAAC
	CTGACCTGCGACACCCCCGAAGAGGACGACATCACCTGG
	ACCAGCGACCAGCGGCACGGCGTGATCGGCAGCGGCAAG
	ACCCTGACCATCACCGTGAAAGAGTTTCTGGACGCCGGCC
	AGTACACCTGCCACAAGGGCGGCGAGACACTGAGCCACA
	GCCACCTGCTGCTGCACAAGAAAGAGAACGGCATCTGGT
	CCACCGAGATCCTGAAGAACTTCAAGAACAAGACCTTCC
	TGAAGTGCGAGGCCCCCAACTACAGCGGCCGGTTCACCT
	GCAGCTGGCTGGTGCAGCGGAACATGGACCTGAAGTTCA
	ACATCAAGAGCAGCAGCAGCCCCCCTGACAGCAGGGCCG
	TGACCTGCGGCATGGCCAGCCTGAGCGCCGAGAAGGTGA
	CCCTGGACCAGAGGGACTACGAGAAGTACAGCGTGAGCT
	GCCAGGAAGATGTCACCTGCCCCACCGCCGAGGAAACCC
	TGCCCATCGAGCTGGCCCTGGAAGCCCGGCAGCAGAACA
	AGTACGAGAACTACTCTACCAGCTTCTTCATCCGGGACAT
	CATCAAGCCCGACCCCCCCAAGAACCTGCAGATGAAGCC
	CCTGAAGAACAGCCAGGTGGAGGTGTCCTGGGAGTACCC
	TGACAGCTGGTCCACCCCCAGAAGCTACTTCAGCCTGAAG
	TTCTTCGTGAGAATCCAGCGGAAGAAAGAAAAGATGAAA
	GAGACAGAGGAAGGCTGCAACCAGAAGGGCGCCTTCTTC
	GTCGAGAAAACCAGCACCGAGGTGCAGTGCAAGGGCGGC
	AACGTGTGCGTGCAGGCCCAGGACCGGTACTACAACAGC
	AGCTGCAGCAAGTGGGCCTGCGTGCCCTGCAGAGTGCGG
	TCTGGCGGCGACGGCTCTGGCGGCGGAGGAAGCGGCGGA
	GGGGGCAGCAGAGTGATCCCCGTGAGCGGCCCTGCCCGG
	TGCCTGAGCCAGAGCCGGAACCTGCTGAAAACCACCGAC
	GACATGGTGAAAACCGCCAGAGAGAAGCTGAAGCACTAC
	AGCTGCACAGCCGAGGACATCGACCACGAGGACATCACC
	CGGGACCAGACCAGCACCCTGAAAACCTGCCTGCCCCTG
	GAACTGCACAAAAACGAGAGCTGCCTGGCCACCCGGGAG
	ACAAGCAGCACCACCCGGGGCAGCTGCCTGCCTCCCCAG
	AAAACCTCCCTGATGATGACCCTGTGCCTGGGCAGCATCT
	ACGAGGACCTGAAGATGTACCAGACCGAGTTCCAGGCCA
	TCAACGCCGCCCTGCAGAACCACAATCACCAGCAGATCA
	TCCTGGACAAGGGCATGCTGGTCGCCATCGACGAGCTGA
	TGCAGAGCCTGAACCACAACGGCGAAACCCTGCGGCAGA
	AACCCCCCGTGGGCGAGGCCGACCCCTACCGGGTGAAGA
	TGAAGCTGTGCATCCTGCTGCACGCCTTCAGCACCCGGGT
	GGTGACCATCAACCGGGTGATGGGCTACCTGTCCTCTGCC
	GGGGGAGGGGGATCCGGCGGAGGTGGCTCTGGCGGTGGC
	GGAGAGGTGCAATTGCTGGAAAGCGGCGGAGGACTGGTG
	CAGCCTGGCGGCAGCCTGAGACTGAGCTGCGCCGCCAGC
	GGCTTCACCTTCAGCAGCTACGCCATGTCTTGGGTCCGCC
	AGGCCCCTGGAAAGGGCCTGGAATGGGTGTCCGCCATCA
	GCGGCAGCGGCGGCAGCACCTACTACGCCGACAGCGTGA
	AGGGCCGGTTCACCATCAGCCGGGACAACAGCAAGAACA
	CCCTGTACCTGCAGATGAACAGCCTGAGAGCCGAGGACA
	CCGCCGTGTACTACTGCGCCAAGGGCTGGCTGGGCAACTT
	CGACTACTGGGGCCAGGGCACTCTGGTCACAGTGTCTAGC
	GCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCT
	CCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCT
	GCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTC
	GTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT
	CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGC
	AGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG
	ACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC
	AAGGTGGATAAGAAAGTTGAGCCCAAATCTTGTGACTGA
28H1 Fab-IL2-Fab	GAAGTGCAGCTGCTGGAATCCGGCGGAGGCCTGGTGCAG	222
(heavy chain	CCTGGCGGATCTCTGAGACTGTCCTGCGCCGCCTCCGGCT
cytokine fusion	TCACCTTCTCCTCCCACGCCATGTCCTGGGTCCGACAGGC
construct)	TCCTGGCAAAGGCCTGGAATGGGTGTCCGCCATCTGGGCC
	TCCGGCGAGCAGTACTACGCCGACTCTGTGAAGGGCCGG
	TTCACCATCTCCCGGGACAACTCCAAGAACACCCTGTACC
	TGCAGATGAACTCCCTGCGGGCCGAGGACACCGCCGTGT
	ACTACTGTGCCAAGGGCTGGCTGGGCAACTTCGACTACTG
	GGGACAGGGCACCCTGGTCACCGTGTCCAGCGCTAGCAC
	CAAGGGACCCTCCGTGTTCCCCCTGGCCCCCTCCAGCAAG
	TCTACCTCTGGCGGCACCGCCGCTCTGGGCTGCCTGGTCA
	AGGACTACTTCCCCGAGCCCGTGACCGTGTCCTGGAACTC
	TGGCGCCCTGACCAGCGGCGTCCACACCTTTCCAGCCGTG
	CTGCAGTCCTCCGGCCTGTACTCCCTGTCCTCCGTCGTGA
	CCGTGCCCTCCAGCTCTCTGGGCACCCAGACCTACATCTG
	CAACGTGAACCACAAGCCCTCCAACACCAAGGTGGACAA
	GAAGGTGGAACCCAAGTCCTGCGACAGTGGTGGGGGAGG
	ATCTGGTGGCGGAGGTTCTGGCGGAGGTGGCGCTCCTAC
	ATCCTCCAGCACCAAGAAAACCCAGCTCCAGCTGGAACA
	TCTCCTGCTGGATCTGCAGATGATCCTGAACGGCATCAAC
	AACTACAAGAACCCCAAGCTGACCCGGATGCTGACCTTC
	AAGTTCTACATGCCCAAGAAGGCCACCGAGCTGAAACAT
	CTGCAGTGCCTGGAAGAGGAACTGAAGCCTCTGGAAGAG
	GTGCTGAACCTGGCCCAGTCCAAGAACTTCCACCTGAGGC
	CTCGGGACCTGATCTCCAACATCAACGTGATCGTGCTGGA
	ACTGAAGGGCTCCGAGACAACCTTCATGTGCGAGTACGC
	CGACGAGACAGCTACCATCGTGGAATTTCTGAACCGGTG
	GATCACCTTCGCCCAGTCCATCATCTCCACCCTGACCTCC
	GGTGGTGGCGGATCCGGGGGAGGGGGTTCTGGCGGAGGC
	GGAGAAGTGCAGCTGCTGGAATCCGGCGGAGGCCTGGTG
	CAGCCTGGCGGATCTCTGAGACTGTCCTGCGCCGCCTCCG
	GCTTCACCTTCTCCTCCCACGCCATGTCCTGGGTCCGACA
	GGCTCCAGGCAAGGGCCTGGAATGGGTGTCCGCCATCTG
	GGCCTCCGGCGAGCAGTACTACGCCGACTCTGTGAAGGG
	CCGGTTCACCATCTCCCGGGACAACTCCAAGAACACCCTG
	TACCTGCAGATGAACTCCCTGCGGGCCGAGGACACCGCC
	GTGTACTACTGTGCCAAGGGCTGGCTGGGCAACTTCGACT
	ACTGGGGCCAGGGCACCCTGGTCACCGTGTCCTCCGCCTC
	TACCAAGGGCCCCTCCGTGTTCCCTCTGGCCCCCTCCAGC
	AAGTCTACCTCTGGCGGCACCGCCGCTCTGGGCTGCCTGG
	TCAAGGACTACTTCCCCGAGCCCGTGACCGTGTCCTGGAA
	CTCTGGCGCCCTGACCAGCGGCGTGCACACCTTTCCAGCC
	GTGCTGCAGTCCTCCGGCCTGTACTCCCTGTCCTCCGTCGT
	GACCGTGCCCTCCAGCTCTCTGGGCACCCAGACCTACATC
	TGCAACGTGAACCACAAGCCCTCCAACACCAAGGTGGAC
	AAGAAGGTGGAACCCAAGTCCTGCGACTGA
29B11 Fab-IL2-	GAAGTGCAGCTGCTGGAATCCGGCGGAGGCCTGGTGCAG	224
Fab	CCTGGCGGATCTCTGAGACTGTCCTGCGCCGCCTCCGGCT
(heavy chain	TCACCTTCTCCTCCTACGCCATGTCCTGGGTCCGACAGGC
cytokine fusion	TCCTGGCAAAGGCCTGGAATGGGTGTCCGCCATCATCGGC
construct)	TCCGGCGGCATCACCTACTACGCCGACTCTGTGAAGGGCC
	GGTTCACCATCTCCCGGGACAACTCCAAGAACACCCTGTA
	CCTGCAGATGAACTCCCTGCGGGCCGAGGACACCGCCGT
	GTACTACTGTGCCAAGGGCTGGTTCGGAGGCTTCAACTAC
	TGGGGACAGGGCACCCTGGTCACCGTGTCCAGCGCTAGC
	ACCAAGGGACCCTCCGTGTTCCCCCTGGCCCCCTCCAGCA
	AGTCTACCTCTGGCGGCACCGCCGCTCTGGGCTGCCTGGT
	CAAGGACTACTTCCCCGAGCCCGTGACCGTGTCCTGGAAC
	TCTGGCGCCCTGACCAGCGGCGTCCACACCTTTCCAGCCG
	TGCTGCAGTCCTCCGGCCTGTACTCCCTGTCCTCCGTCGTG
	ACCGTGCCCTCCAGCTCTCTGGGCACCCAGACCTACATCT
	GCAACGTGAACCACAAGCCCTCCAACACCAAGGTGGACA
	AGAAGGTGGAACCCAAGTCCTGCGACAGTGGTGGGGGAG
	GATCTGGTGGCGGAGGTTCTGGCGGAGGTGGCGCTCCTA
	CATCCTCCAGCACCAAGAAAACCCAGCTCCAGCTGGAAC
	ATCTCCTGCTGGATCTGCAGATGATCCTGAACGGCATCAA
	CAACTACAAGAACCCCAAGCTGACCCGGATGCTGACCTT
	CAAGTTCTACATGCCCAAGAAGGCCACCGAGCTGAAACA
	TCTGCAGTGCCTGGAAGAGGAACTGAAGCCTCTGGAAGA
	GGTGCTGAACCTGGCCCAGTCCAAGAACTTCCACCTGAG
	GCCTCGGGACCTGATCTCCAACATCAACGTGATCGTGCTG
	GAACTGAAGGGCTCCGAGACAACCTTCATGTGCGAGTAC
	GCCGACGAGACAGCTACCATCGTGGAATTTCTGAACCGG
	TGGATCACCTTCGCCCAGTCCATCATCTCCACCCTGACCT
	CCGGTGGTGGCGGATCCGGGGGAGGGGGTTCTGGCGGAG
	GCGGAGAAGTGCAGCTGCTGGAATCCGGCGGAGGCCTGG
	TGCAGCCTGGCGGATCTCTGAGACTGTCCTGCGCCGCCTC
	CGGCTTCACCTTCTCCTCCTATGCCATGTCCTGGGTCCGAC
	AGGCTCCAGGCAAGGGCCTGGAATGGGTGTCCGCCATCA
	TCGGCTCCGGCGGCATCACCTACTACGCCGACTCTGTGAA
	GGGCCGGTTCACCATCTCCCGGGACAACTCCAAGAACAC
	CCTGTACCTGCAGATGAACTCCCTGCGGGCCGAGGACAC
	CGCCGTGTACTACTGTGCCAAGGGCTGGTTCGGAGGCTTC
	AACTACTGGGGCCAGGGCACCCTGGTCACCGTGTCCTCCG
	CCTCTACCAAGGGCCCCTCCGTGTTCCCTCTGGCCCCCTC
	CAGCAAGTCTACCTCTGGCGGCACCGCCGCTCTGGGCTGC
	CTGGTCAAGGACTACTTCCCCGAGCCCGTGACCGTGTCCT
	GGAACTCTGGCGCCCTGACCAGCGGCGTGCACACCTTTCC
	AGCCGTGCTGCAGTCCTCCGGCCTGTACTCCCTGTCCTCC
	GTCGTGACCGTGCCCTCCAGCTCTCTGGGCACCCAGACCT
	ACATCTGCAACGTGAACCACAAGCCCTCCAACACCAAGG
	TGGACAAGAAGGTGGAACCCAAGTCCTGCGACTGA
19G1 Fab-IL2-Fab	GAGGTGCAGCTGCTCGAAAGCGGCGGAGGACTGGTGCAG	226
(heavy chain	CCTGGCGGCAGCCTGAGACTGTCTTGCGCCGCCAGCGGCT
cytokine fusion	TCACCTTCAGCAGCTACGCCATGAGCTGGGTCCGCCAGGC
construct)	CCCTGGCAAGGGACTGGAATGGGTGTCCGCCATCATCAG
	CTCTGGCGGCCTGACCTACTACGCCGACAGCGTGAAGGG
	CCGGTTCACCATCAGCCGGGACAACAGCAAGAACACCCT
	GTACCTGCAGATGAACAGCCTGCGGGCCGAGGACACCGC
	CGTGTACTACTGCGCCAAGGGATGGTTCGGCGGCTTCAAC
	TACTGGGGACAGGGCACCCTGGTCACAGTGTCCAGCGCT
	AGCACCAAGGGACCCAGCGTGTTCCCCCTGGCCCCCAGC
	AGCAAGAGCACATCTGGCGGAACAGCCGCCCTGGGCTGC
	CTGGTCAAAGACTACTTCCCCGAGCCCGTGACCGTGTCCT
	GGAACAGCGGAGCCCTGACCAGCGGCGTGCACACCTTTC
	CAGCCGTGCTGCAGAGCAGCGGCCTGTACAGCCTGAGCA
	GCGTGGTCACCGTGCCTAGCTCTAGCCTGGGCACCCAGAC
	CTACATCTGCAACGTGAACCACAAGCCCAGCAACACCAA
	GGTGGACAAGAAGGTGGAACCCAAGAGCTGCGACTCCGG
	CGGAGGCGGATCTGGCGGTGGAGGCTCCGGAGGCGGAGG
	CGCTCCTACTAGCAGCTCCACCAAGAAAACCCAGCTCCA
	GCTGGAACATCTGCTGCTGGATCTGCAGATGATCCTGAAC
	GGCATCAACAACTACAAGAACCCCAAGCTGACCCGGATG
	CTGACCTTCAAGTTCTACATGCCCAAGAAGGCCACCGAAC
	TGAAACATCTGCAGTGCCTGGAAGAGGAACTGAAGCCTC
	TGGAAGAGGTGCTGAACCTGGCCCAGAGCAAGAACTTCC
	ACCTGAGGCCCAGGGACCTGATCAGCAACATCAACGTGA
	TCGTGCTGGAACTGAAGGGCAGCGAGACAACCTTCATGT
	GCGAGTACGCCGACGAGACAGCCACCATCGTGGAATTTC
	TGAACCGGTGGATCACCTTCGCCCAGAGCATCATCAGCAC
	CCTGACAAGCGGAGGCGGCGGATCCGGCGGAGGCGGATC
	TGGCGGAGGAGGCGAGGTCCAGCTGCTCGAAAGCGGCGG
	AGGACTGGTGCAGCCTGGCGGCAGCCTGAGACTGTCTTG
	CGCCGCCAGCGGCTTCACCTTCAGCAGCTACGCCATGAGC
	TGGGTCCGCCAGGCCCCTGGCAAGGGACTGGAATGGGTG
	TCCGCCATCATCAGCTCTGGCGGCCTGACCTACTACGCCG
	ACAGCGTGAAGGGCCGGTTCACCATCAGCCGGGACAACA
	GCAAGAACACCCTGTACCTGCAGATGAACAGCCTGCGGG
	CCGAGGACACCGCCGTGTACTACTGCGCCAAGGGATGGT
	TCGGCGGCTTCAACTACTGGGGACAGGGCACCCTGGTCA
	CAGTGTCCAGCGCCAGCACCAAGGGCCCCAGCGTGTTCC
	CCCTGGCCCCCAGCAGCAAGAGCACATCTGGCGGAACAG
	CCGCCCTGGGCTGCCTGGTCAAAGACTACTTCCCCGAGCC
	CGTGACCGTGTCCTGGAACAGCGGAGCCCTGACCAGCGG
	CGTGCACACCTTTCCAGCCGTGCTGCAGAGCAGCGGCCTG
	TACAGCCTGAGCAGCGTGGTCACCGTGCCTAGCTCTAGCC
	TGGGCACCCAGACCTACATCTGCAACGTGAACCACAAGC
	CCAGCAACACCAAGGTGGACAAGAAGGTGGAACCCAAG
	AGCTGCGACTGA
20G8 Fab-IL2-Fab	GAGGTGCAGCTGCTCGAAAGCGGCGGAGGACTGGTGCAG	228
(heavy chain	CCTGGCGGCAGCCTGAGACTGTCTTGCGCCGCCAGCGGCT
cytokine fusion	TCACCTTCAGCAGCTACGCCATGAGCTGGGTCCGCCAGGC
construct)	CCCTGGCAAGGGACTGGAATGGGTGTCCGCCATCATCGG
	CTCTGGCAGCCGGACCTACTACGCCGACAGCGTGAAGGG
	CCGGTTCACCATCAGCCGGGACAACAGCAAGAACACCCT
	GTACCTGCAGATGAACAGCCTGCGGGCCGAGGACACCGC
	CGTGTACTACTGCGCCAAGGGATGGTTCGGCGGCTTCAAC
	TACTGGGGACAGGGCACCCTGGTCACAGTGTCCAGCGCT
	AGCACCAAGGGACCCAGCGTGTTCCCCCTGGCCCCCAGC
	AGCAAGAGCACATCTGGCGGAACAGCCGCCCTGGGCTGC
	CTGGTCAAAGACTACTTCCCCGAGCCCGTGACCGTGTCCT
	GGAACAGCGGAGCCCTGACCAGCGGCGTGCACACCTTTC
	CAGCCGTGCTGCAGAGCAGCGGCCTGTACAGCCTGAGCA
	GCGTGGTCACCGTGCCTAGCTCTAGCCTGGGCACCCAGAC
	CTACATCTGCAACGTGAACCACAAGCCCAGCAACACCAA
	GGTGGACAAGAAGGTGGAACCCAAGAGCTGCGACTCCGG
	CGGAGGCGGATCTGGCGGTGGAGGCTCCGGAGGCGGAGG
	CGCTCCTACTAGCAGCTCCACCAAGAAAACCCAGCTCCA
	GCTGGAACATCTGCTGCTGGATCTGCAGATGATCCTGAAC
	GGCATCAACAACTACAAGAACCCCAAGCTGACCCGGATG
	CTGACCTTCAAGTTCTACATGCCCAAGAAGGCCACCGAAC
	TGAAACATCTGCAGTGCCTGGAAGAGGAACTGAAGCCTC
	TGGAAGAGGTGCTGAACCTGGCCCAGAGCAAGAACTTCC
	ACCTGAGGCCCAGGGACCTGATCAGCAACATCAACGTGA
	TCGTGCTGGAACTGAAGGGCAGCGAGACAACCTTCATGT
	GCGAGTACGCCGACGAGACAGCCACCATCGTGGAATTTC
	TGAACCGGTGGATCACCTTCGCCCAGAGCATCATCAGCAC
	CCTGACAAGCGGAGGCGGCGGATCCGGCGGAGGCGGATC
	TGGCGGAGGAGGCGAGGTCCAGCTGCTCGAAAGCGGCGG
	AGGACTGGTGCAGCCTGGCGGCAGCCTGAGACTGTCTTG
	CGCCGCCAGCGGCTTCACCTTCAGCAGCTACGCCATGAGC
	TGGGTCCGCCAGGCCCCTGGCAAGGGACTGGAATGGGTG
	TCCGCCATCATCGGCTCTGGCAGCCGGACCTACTACGCCG
	ACAGCGTGAAGGGCCGGTTCACCATCAGCCGGGACAACA
	GCAAGAACACCCTGTACCTGCAGATGAACAGCCTGCGGG
	CCGAGGACACCGCCGTGTACTACTGCGCCAAGGGATGGT
	TCGGCGGCTTCAACTACTGGGGACAGGGCACCCTGGTCA
	CAGTGTCCAGCGCCAGCACCAAGGGCCCCAGCGTGTTCC
	CCCTGGCCCCCAGCAGCAAGAGCACATCTGGCGGAACAG
	CCGCCCTGGGCTGCCTGGTCAAAGACTACTTCCCCGAGCC
	CGTGACCGTGTCCTGGAACAGCGGAGCCCTGACCAGCGG
	CGTGCACACCTTTCCAGCCGTGCTGCAGAGCAGCGGCCTG
	TACAGCCTGAGCAGCGTGGTCACCGTGCCTAGCTCTAGCC
	TGGGCACCCAGACCTACATCTGCAACGTGAACCACAAGC
	CCAGCAACACCAAGGTGGACAAGAAGGTGGAACCCAAG
	AGCTGCGACTGA
3F2 light chain	GAGATCGTGCTGACCCAGTCCCCCGGCACCCTGTCTCTGA	230
	GCCCTGGCGAGAGAGCCACCCTGTCCTGCAGAGCCTCCC
	AGTCCGTGACCTCCTCCTACCTCGCCTGGTATCAGCAGAA
	GCCCGGCCAGGCCCCTCGGCTGCTGATCAACGTGGGCAG
	TCGGAGAGCCACCGGCATCCCTGACCGGTTCTCCGGCTCT
	GGCTCCGGCACCGACTTCACCCTGACCATCTCCCGGCTGG
	AACCCGAGGACTTCGCCGTGTACTACTGCCAGCAGGGCA
	TCATGCTGCCCCCCACCTTTGGCCAGGGCACCAAGGTGGA
	AATCAAGCGTACGGTGGCCGCTCCCTCCGTGTTCATCTTC
	CCACCCTCCGACGAGCAGCTGAAGTCCGGCACCGCCTCC
	GTCGTGTGCCTGCTGAACAACTTCTACCCCCGCGAGGCCA
	AGGTGCAGTGGAAGGTGGACAACGCCCTGCAGTCCGGCA
	ACTCCCAGGAATCCGTCACCGAGCAGGACTCCAAGGACA
	GCACCTACTCCCTGTCCTCCACCCTGACCCTGTCCAAGGC
	CGACTACGAGAAGCACAAGGTGTACGCCTGCGAAGTGAC
	CCACCAGGGCCTGTCCAGCCCCGTGACCAAGTCCTTCAAC
	CGGGGCGAGTGCTGATGA
4G8 light chain	GAGATCGTGCTGACCCAGTCCCCCGGCACCCTGTCTCTGA	232
	GCCCTGGCGAGAGAGCCACCCTGTCCTGCAGAGCCTCCC
	AGTCCGTGTCCCGGTCCTACCTCGCCTGGTATCAGCAGAA
	GCCCGGCCAGGCCCCTCGGCTGCTGATCATCGGCGCCTCT
	ACCAGAGCCACCGGCATCCCTGACCGGTTCTCCGGCTCTG
	GCTCCGGCACCGACTTCACCCTGACCATCTCCCGGCTGGA
	ACCCGAGGACTTCGCCGTGTACTACTGCCAGCAGGGCCA
	GGTCATCCCTCCCACCTTTGGCCAGGGCACCAAGGTGGAA
	ATCAAGCGTACGGTGGCCGCTCCCTCCGTGTTCATCTTCC
	CACCCTCCGACGAGCAGCTGAAGTCCGGCACCGCCTCCGT
	CGTGTGCCTGCTGAACAACTTCTACCCCCGCGAGGCCAAG
	GTGCAGTGGAAGGTGGACAACGCCCTGCAGTCCGGCAAC
	TCCCAGGAATCCGTCACCGAGCAGGACTCCAAGGACAGC
	ACCTACTCCCTGTCCTCCACCCTGACCCTGTCCAAGGCCG
	ACTACGAGAAGCACAAGGTGTACGCCTGCGAAGTGACCC
	ACCAGGGCCTGTCCAGCCCCGTGACCAAGTCCTTCAACCG
	GGGCGAGTGCTGATGA
3D9 light chain	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	234
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGCTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGGA
	AATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTC
	CCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTG
	TTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAA
	AGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAA
	CTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAG
	CACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGC
	AGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCAC
	CCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAA
	CAGGGGAGAGTGTTAG
2F11 light chain	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	236
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATC
	CAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGTATACTCCCCCCACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTT
	CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCT
	GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCA
	AAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTA
	ACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACA
	GCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAG
	CAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCA
	CCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCA
	ACAGGGGAGAGTGTTAG
4B3 light chain	GAAATCGTGTTAACGCAGTCTCCAGGCACCCTGTCTTTGT	238
	CTCCAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTC
	AGAGTGTTAGCAGCAATTACTTAGCCTGGTACCAGCAGA
	AACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGCGCCTA
	CATCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
	TGGATCCGGGACAGACTTCACTCTCACCATCAGCAGACTG
	GAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGGGTC
	AGGTTATTCCCCCTACGTTCGGCCAGGGGACCAAAGTGG
	AAATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTT
	CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCT
	GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCA
	AAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTA
	ACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACA
	GCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAG
	CAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCA
	CCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCA
	ACAGGGGAGAGTGTTAG
2B10 Fab-IL2-Fab	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	240
(heavy chain	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
cytokine fusion	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
construct)	CCCCTGGACAAGGGCTCGAGTGGATGGGAGGGATCATCC
	CTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCC
	TGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGG
	CCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT
	GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGT
	GCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTAC
	TCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG
	GCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCA
	GCAACACCAAGGTGGATAAGAAAGTTGAGCCCAAATCTT
	GTGACTCCGGCGGAGGAGGGAGCGGCGGAGGTGGCTCCG
	GAGGTGGCGGAGCACCTACTTCAAGTTCTACAAAGAAAA
	CACAGCTACAACTGGAGCATTTACTGCTGGATTTACAGAT
	GATTTTGAATGGAATTAATAATTACAAGAATCCCAAACTC
	ACCAGGATGCTCACATTTAAGTTTTACATGCCCAAGAAGG
	CCACAGAACTGAAACATCTTCAGTGTCTAGAAGAAGAAC
	TCAAACCTCTGGAGGAAGTGCTAAATTTAGCTCAAAGCA
	AAAACTTTCACTTAAGACCCAGGGACTTAATCAGCAATAT
	CAACGTAATAGTTCTGGAACTAAAGGGATCTGAAACAAC
	ATTCATGTGTGAATATGCTGATGAGACAGCAACCATTGTA
	GAATTTCTGAACAGATGGATTACCTTTGCCCAAAGCATCA
	TCTCAACACTGACTTCCGGCGGAGGAGGATCCGGCGGAG
	GTGGCTCTGGCGGTGGCGGACAGGTGCAATTGGTGCAGT
	CTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGG
	TCTCCTGCAAGGCCTCCGGAGGCACATTCAGCAGCTACGC
	TATAAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTCGA
	GTGGATGGGAGGGATCATCCCTATCTTTGGTACAGCAAAC
	TACGCACAGAAGTTCCAGGGCAGGGTCACCATTACTGCA
	GACAAATCCACGAGCACAGCCTACATGGAGCTGAGCAGC
	CTGAGATCTGAGGACACCGCCGTGTATTACTGTGCGAGAC
	TGTACGGTTACGCTTACTACGGTGCTTTTGACTACTGGGG
	CCAAGGGACCACCGTGACCGTCTCCTCAGCTAGCACCAA
	GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
	ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAG
	GACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG
	GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCT
	ACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACC
	GTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCA
	ACGTGAATCACAAGCCCAGCAACACCAAGGTGGATAAGA
	AAGTTGAGCCCAAATCTTGTGACTGA
C3B6 Fab-IL2-	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	242
Fab	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
(heavy chain	GCACATTCAGCAGCTACGCTATAAGCTGGGTGCGACAGG
cytokine fusion	CCCCTGGACAAGGGCTCGAGTGGATGGGAGCTATCATCC
construct)	CGATCCTTGGTATCGCAAACTACGCACAGAAGTTCCAGG
	GCAGGGTCACCATTACTGCAGACAAATCCACGAGCACAG
	CCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCG
	CCGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTA
	CGGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCC
	TGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGG
	CCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT
	GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGT
	GCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTAC
	TCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG
	GCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCA
	GCAACACCAAGGTGGATAAGAAAGTTGAGCCCAAATCTT
	GTGACTCCGGCGGAGGAGGGAGCGGCGGAGGTGGCTCCG
	GAGGTGGCGGAGCACCTACTTCAAGTTCTACAAAGAAAA
	CACAGCTACAACTGGAGCATTTACTGCTGGATTTACAGAT
	GATTTTGAATGGAATTAATAATTACAAGAATCCCAAACTC
	ACCAGGATGCTCACATTTAAGTTTTACATGCCCAAGAAGG
	CCACAGAACTGAAACATCTTCAGTGTCTAGAAGAAGAAC
	TCAAACCTCTGGAGGAAGTGCTAAATTTAGCTCAAAGCA
	AAAACTTTCACTTAAGACCCAGGGACTTAATCAGCAATAT
	CAACGTAATAGTTCTGGAACTAAAGGGATCTGAAACAAC
	ATTCATGTGTGAATATGCTGATGAGACAGCAACCATTGTA
	GAATTTCTGAACAGATGGATTACCTTTGCCCAAAGCATCA
	TCTCAACACTGACTTCCGGCGGAGGAGGATCCGGCGGAG
	GTGGCTCTGGCGGTGGCGGACAGGTGCAATTGGTGCAGT
	CTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGG
	TCTCCTGCAAGGCCTCCGGAGGCACATTCAGCAGCTACGC
	TATAAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTCGA
	GTGGATGGGAGCTATCATCCCGATCCTTGGTATCGCAAAC
	TACGCACAGAAGTTCCAGGGCAGGGTCACCATTACTGCA
	GACAAATCCACGAGCACAGCCTACATGGAGCTGAGCAGC
	CTGAGATCTGAGGACACCGCCGTGTATTACTGTGCGAGAC
	TGTACGGTTACGCTTACTACGGTGCTTTTGACTACTGGGG
	CCAAGGGACCACCGTGACCGTCTCCTCAGCTAGCACCAA
	GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
	ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAG
	GACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG
	GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCT
	ACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACC
	GTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCA
	ACGTGAATCACAAGCCCAGCAACACCAAGGTGGATAAGA
	AAGTTGAGCCCAAATCTTGTGACTGA
6A12 Fab-IL2-Fab	CAGGTGCAATTGGTGCAGTCTGGGGCTGAGGTGAAGAAG	244
(heavy chain	CCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCCTCCGGAG
cytokine fusion	GCACATTCAGCAGCTATGCTATAAGCTGGGTGCGACAGG
construct)	CCCCTGGACAAGGGCTCGAGTGGATGGGAGTGATCATCC
	CTATCCTTGGTACCGCAAACTACGCACAGAAGTTCCAGGG
	CAGGGTCACCATTACTGCAGACAAATCCACGAGCACAGC
	CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACCGC
	CGTGTATTACTGTGCGAGACTGTACGGTTACGCTTACTAC
	GGTGCTTTTGACTACTGGGGCCAAGGGACCACCGTGACC
	GTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCC
	TGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGG
	CCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT
	GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGT
	GCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTAC
	TCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG
	GCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCA
	GCAACACCAAGGTGGATAAGAAAGTTGAGCCCAAATCTT
	GTGACTCCGGCGGAGGAGGGAGCGGCGGAGGTGGCTCCG
	GAGGTGGCGGAGCACCTACTTCAAGTTCTACAAAGAAAA
	CACAGCTACAACTGGAGCATTTACTGCTGGATTTACAGAT
	GATTTTGAATGGAATTAATAATTACAAGAATCCCAAACTC
	ACCAGGATGCTCACATTTAAGTTTTACATGCCCAAGAAGG
	CCACAGAACTGAAACATCTTCAGTGTCTAGAAGAAGAAC
	TCAAACCTCTGGAGGAAGTGCTAAATTTAGCTCAAAGCA
	AAAACTTTCACTTAAGACCCAGGGACTTAATCAGCAATAT
	CAACGTAATAGTTCTGGAACTAAAGGGATCTGAAACAAC
	ATTCATGTGTGAATATGCTGATGAGACAGCAACCATTGTA
	GAATTTCTGAACAGATGGATTACCTTTGCCCAAAGCATCA
	TCTCAACACTGACTTCCGGCGGAGGAGGATCCGGCGGAG
	GTGGCTCTGGCGGTGGCGGACAGGTGCAATTGGTGCAGT
	CTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGG
	TCTCCTGCAAGGCCTCCGGAGGCACATTCAGCAGCTATGC
	TATAAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTCGA
	GTGGATGGGAGTGATCATCCCTATCCTTGGTACCGCAAAC
	TACGCACAGAAGTTCCAGGGCAGGGTCACCATTACTGCA
	GACAAATCCACGAGCACAGCCTACATGGAGCTGAGCAGC
	CTGAGATCTGAGGACACCGCCGTGTATTACTGTGCGAGAC
	TGTACGGTTACGCTTACTACGGTGCTTTTGACTACTGGGG
	CCAAGGGACCACCGTGACCGTCTCCTCAGCTAGCACCAA
	GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGC
	ACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAG
	GACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG
	GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCT
	ACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACC
	GTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCA
	ACGTGAATCACAAGCCCAGCAACACCAAGGTGGATAAGA
	AAGTTGAGCCCAAATCTTGTGACTGA
2B10 light chain	GATATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	246
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGCATTAGAAATGATTTAGGCTGGTACCAGCAGAAGC
	CAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCA
	GTTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCAGTG
	GATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCA
	GCCTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGT
	CTGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAG
	ATCAAGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCC
	CGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGT
	TGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAA
	GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAAC
	TCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGC
	ACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCA
	GACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC
	CATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAAC
	AGGGGAGAGTGTTAG
D1A2 light chain	GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	248
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGGGGATTCGTAATGATTTAGGCTGGTACCAGCAGAAGC
	CAGGGAAAGCCCCTAAGCGCCTGATCTATGATGCTTACA
	GCTTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCGGTG
	GATCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCA
	GCCTGAAGATTTTGCCACCTATTACTGCTGCAGAATGGT
	CTGCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAG
	ATCAAGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCC
	CGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGT
	TGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAA
	GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAAC
	TCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGC
	ACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCA
	GACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC
	CATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAAC
	AGGGGAGAGTGTTAG
O7D8 light chain	GATATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT	250
	CTGTCGGAGACCGGGTCACCATCACCTGCCGGGCAAGTC
	AGAGCATTCGTAATGTTTTAGGCTGGTACCAGCAGAAGCC
	AGGGAAAGCCCCTAAGCGCCTGATCTATGATGTGTCCAGT
	TTGCAGAGTGGCGTCCCATCAAGGTTCAGCGGCGGTGGA
	TCCGGGACAGAGTTCACTCTCACCATCAGCAGCTTGCAGC
	CTGAAGATTTTGCCACCTATTACTGCTTGCAGAATGGTCT
	GCAGCCCGCGACGTTTGGCCAGGGCACCAAAGTCGAGAT
	CAAGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCG
	CCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTG
	TGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGT
	ACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTC
	CCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCA
	CCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAG
	ACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCC
	ATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACA
	GGGGAGAGTGTTAG
MHLG1 Fab-IL2-	GAAGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGGTCAAG	252
Fab	CCTGGCGGGTCCCTGCGGCTCTCCTGTGCAGCCTCCGGAT
(heavy chain	TCACATTTAGCAACTATTGGATGAACTGGGTGCGGCAGGC
cytokine fusion	TCCTGGAAAGGGCCTCGAGTGGGTGGCCGAGATCAGATT
construct)	GAAATCCAATAACTTCGGAAGATATTACGCTGCAAGCGT
	GAAGGGCCGGTTCACCATCAGCAGAGATGATTCCAAGAA
	CACGCTGTACCTGCAGATGAACAGCCTGAAGACCGAGGA
	TACGGCCGTGTATTACTGTACCACATACGGCAACTACGTT
	GGGCACTACTTCGACCACTGGGGCCAAGGGACCACCGTC
	ACCGTCTCCAGTGCTAGCACCAAGGGCCCATCGGTCTTCC
	CCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
	GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCG
	GTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGC
	GTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCT
	ACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTT
	GGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCC
	CAGCAACACCAAGGTGGATAAGAAAGTTGAGCCCAAATC
	TTGTGACTCCGGCGGAGGAGGGAGCGGCGGAGGTGGCTC
	CGGAGGTGGCGGAGCACCTACTTCAAGTTCTACAAAGAA
	AACACAGCTACAACTGGAGCATTTACTGCTGGATTTACAG
	ATGATTTTGAATGGAATTAATAATTACAAGAATCCCAAAC
	TCACCAGGATGCTCACATTTAAGTTTTACATGCCCAAGAA
	GGCCACAGAACTGAAACATCTTCAGTGTCTAGAAGAAGA
	ACTCAAACCTCTGGAGGAAGTGCTAAATTTAGCTCAAAG
	CAAAAACTTTCACTTAAGACCCAGGGACTTAATCAGCAAT
	ATCAACGTAATAGTTCTGGAACTAAAGGGATCTGAAACA
	ACATTCATGTGTGAATATGCTGATGAGACAGCAACCATTG
	TAGAATTTCTGAACAGATGGATTACCTTTGCCCAAAGCAT
	CATCTCAACACTGACTTCCGGCGGAGGAGGATCCGGCGG
	AGGTGGCTCTGGCGGTGGCGGAGAAGTGCAGCTGGTGGA
	GTCTGGAGGAGGCTTGGTCAAGCCTGGCGGGTCCCTGCG
	GCTCTCCTGTGCAGCCTCCGGATTCACATTTAGCAACTAT
	TGGATGAACTGGGTGCGGCAGGCTCCTGGAAAGGGCCTC
	GAGTGGGTGGCCGAGATCAGATTGAAATCCAATAACTTC
	GGAAGATATTACGCTGCAAGCGTGAAGGGCCGGTTCACC
	ATCAGCAGAGATGATTCCAAGAACACGCTGTACCTGCAG
	ATGAACAGCCTGAAGACCGAGGATACGGCCGTGTATTAC
	TGTACCACATACGGCAACTACGTTGGGCACTACTTCGACC
	ACTGGGGCCAAGGGACCACCGTCACCGTCTCCAGTGCTA
	GCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
	CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCT
	GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG
	GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
	GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
	GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
	ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG
	TGGATAAGAAAGTTGAGCCCAAATCTTGTGACTGA
KV9 light chain	GATATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATC	254
	TGTGGGCGACCGGGTCACCATCACCTGCAAGGCCAGTCA
	GAATGTGGATACTAACGTGGCTTGGTACCAGCAGAAGCC
	AGGGCAGGCACCTAGGCCTCTGATCTATTCGGCATCCTAC
	CGGTACACTGGCGTCCCATCAAGGTTCAGCGGCAGTGGA
	TCCGGGACAGAGTTCACTCTCACAATCTCAAGCCTGCAAC
	CTGAAGATTTCGCAACTTACTACTGTCAACAGTACAATAG
	TTACCCTCTGACGTTCGGCGGAGGTACCAAGGTGGAGATC
	AAGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGC
	CATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGT
	GTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTA
	CAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCC
	CAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCAC
	CTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGA
	CTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCA
	TCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAG
	GGGAGAGTGTTAG
MHLG Fab-IL2-	GAAGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGGTCCAG	256
Fab (heavy chain	CCTGGCGGGTCCCTGCGGCTCTCCTGTGCAGCCTCCGGAT
cytokine fusion	TCACATTTAGCAACTATTGGATGAACTGGGTGCGGCAGGC
construct)	TCCTGGAAAGGGCCTCGAGTGGGTGGCCGAGATCAGATT
	GAAATCCAATAACTTCGGAAGATATTACGCTGCAAGCGT
	GAAGGGCCGGTTCACCATCAGCAGAGATGATTCCAAGAA
	CACGCTGTACCTGCAGATGAACAGCCTGAAGACCGAGGA
	TACGGCCGTGTATTACTGTACCACATACGGCAACTACGTT
	GGGCACTACTTCGACCACTGGGGCCAAGGGACCACCGTC
	ACCGTCTCCAGTGCTAGCACCAAGGGCCCATCGGTCTTCC
	CCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGC
	GGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCG
	GTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGC
	GTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCT
	ACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTT
	GGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCC
	CAGCAACACCAAGGTGGATAAGAAAGTTGAGCCCAAATC
	TTGTGACTCCGGCGGAGGAGGGAGCGGCGGAGGTGGCTC
	CGGAGGTGGCGGAGCACCTACTTCAAGTTCTACAAAGAA
	AACACAGCTACAACTGGAGCATTTACTGCTGGATTTACAG
	ATGATTTTGAATGGAATTAATAATTACAAGAATCCCAAAC
	TCACCAGGATGCTCACATTTAAGTTTTACATGCCCAAGAA
	GGCCACAGAACTGAAACATCTTCAGTGTCTAGAAGAAGA
	ACTCAAACCTCTGGAGGAAGTGCTAAATTTAGCTCAAAG
	CAAAAACTTTCACTTAAGACCCAGGGACTTAATCAGCAAT
	ATCAACGTAATAGTTCTGGAACTAAAGGGATCTGAAACA
	ACATTCATGTGTGAATATGCTGATGAGACAGCAACCATTG
	TAGAATTTCTGAACAGATGGATTACCTTTGCCCAAAGCAT
	CATCTCAACACTGACTTCCGGCGGAGGAGGATCCGGCGG
	AGGTGGCTCTGGCGGTGGCGGAGAAGTGCAGCTGGTGGA
	GTCTGGAGGAGGCTTGGTCCAGCCTGGCGGGTCCCTGCG
	GCTCTCCTGTGCAGCCTCCGGATTCACATTTAGCAACTAT
	TGGATGAACTGGGTGCGGCAGGCTCCTGGAAAGGGCCTC
	GAGTGGGTGGCCGAGATCAGATTGAAATCCAATAACTTC
	GGAAGATATTACGCTGCAAGCGTGAAGGGCCGGTTCACC
	ATCAGCAGAGATGATTCCAAGAACACGCTGTACCTGCAG
	ATGAACAGCCTGAAGACCGAGGATACGGCCGTGTATTAC
	TGTACCACATACGGCAACTACGTTGGGCACTACTTCGACC
	ACTGGGGCCAAGGGACCACCGTCACCGTCTCCAGTGCTA
	GCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
	CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCT
	GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG
	GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
	GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
	GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
	ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG
	TGGATAAGAAAGTTGAGCCCAAATCTTGTGACTGA
KV1 light chain	GATATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATCT	264
	GTGGGCGACCGGGTCACCATCACCTGCAGGGCCAGTCAGAA
	TGTGGATACTAACTTAGCTTGGTACCAGCAGAAGCCAGGGA
	AAGCACCTAAGCTCCTGATCTATTCGGCATCCTACCGTTACA
	CTGGCGTCCCATCAAGGTTCAGCGGCAGTGGATCCGGGACA
	GAGTTCACTCTCACAATCTCAAGCCTGCAACCTGAAGATTTC
	GCAACTTACTACTGTCAACAGTACAATAGTTACCCTCTGACG
	TTCGGCGGAGGTACCAAGGTGGAGATCAAGCGTACGGTGGC
	TGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTT
	GAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTT
	CTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACG
	CCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAG
	GACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGAC
	GCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT
	GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAG
	AGCTTCAACAGGGGAGAGTGTTAG
KV7 light chain	GATATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATCT	266
	GTGGGCGACCGGGTCACCATCACCTGCAAGGCCAGTCAGAA
	TGTGGATACTAACGTGGCTTGGTACCAGCAGAAGCCAGGGA
	AAGCACCTAAGCCTCTGATCTATTCGGCATCCTACCGGTACA
	CTGGCGTCCCATCAAGGTTCAGCGGCAGTGGATCCGGGACA
	GAGTTCACTCTCACAATCTCAAGCCTGCAACCTGAAGATTTC
	GCAACTTACTACTGTCAACAGTACAATAGTTACCCTCTGACG
	TTCGGCGGAGGTACCAAGGTGGAGATCAAGCGTACGGTGGC
	TGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTT
	GAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTT
	CTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACG
	CCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAG
	GACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGAC
	GCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT
	GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAG
	AGCTTCAACAGGGGAGAGTGTTAG