Albumin fusion proteins

[0001] This application is a continuation of U.S. application Ser. No. 10/775,204, filed Feb. 11, 2004, now U.S. Pat. No. 7,141,547 which is a continuation of International Application No. PCT/US02/40891, filed Dec. 23, 2002, which claims benefit under 35 USC 119(e) of U.S. Provisional Application Nos. 60/341,811, filed Dec. 21, 2001; 60/350,358, filed Jan. 24, 2002; 60/351,360, filed Jan. 28, 2002; 60/359,370, filed Feb. 26, 2002; 60/360,000, filed Feb. 28, 2002; 60/367,500, filed Mar. 27, 2002; 60/370,227, filed Apr. 8, 2002; 60/378,950, filed May 10, 2002; 60/382,617, filed May 24, 2002; 60/383,123, filed May 28, 2002; 60/385,708, filed Jun. 5, 2002; 60/394,625, filed Jul. 10, 2002; 60/398,008, filed Jul. 24, 2002; 60/402,131, filed Aug. 9, 2002; 60/402,708, filed Aug. 13, 2002; 60/411,426, filed Sep. 18, 2002; 60/411,355, filed Sep. 18, 2002; 60/414,984, filed Oct. 2, 2002; 60/417,611, filed Oct. 11, 2002; 60/420,246, filed Oct. 23, 2002; and 60/423,623, filed Nov. 5, 2002. All of the above listed applications are incorporated by reference herein.

[0002] This application refers to a “Sequence Listing” listed below, which is provided as an electronic document on three identical compact disc (CD-R), labeled “Copy 1,” “Copy 2,” and “CRF.” These compact discs each contain the file “PF564D1 SEQLIST FINAL.txt” (3,568,877 bytes, created on Apr. 19, 2006), which is incorporated by reference in its entirety. The Sequence Listing may be viewed on an IBM-PC machine running the MS-Windows operating system.

[0003] The invention relates generally to Therapeutic proteins (including, but not limited to, at least one polypeptide, antibody, peptide, or fragment and variant thereof) fused to albumin or fragments or variants of albumin. The invention encompasses polynucleotides encoding therapeutic albumin fusion proteins, therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits. Host cells transformed with the polynucleotides encoding therapeutic albumin fusion proteins are also encompassed by the invention, as are methods of making the albumin fusion proteins of the invention using these polynucleotides, and/or host cells.

[0004] Human serum albumin (HSA, or HA), a protein of 585 amino acids in its mature form (as shown in FIG. 1 (SEQ ID NO:1038)), is responsible for a significant proportion of the osmotic pressure of serum and also functions as a carrier of endogenous and exogenous ligands. At present, HA for clinical use is produced by extraction from human blood. The production of recombinant HA (rHA) in microorganisms has been disclosed in EP 330 451 and EP 361 991.

[0005] Therapeutic proteins in their native state or when recombinantly produced, such as interferons and growth hormones, are typically labile molecules exhibiting short shelf-lives, particularly when formulated in aqueous solutions. The instability in these molecules when formulated for administration dictates that many of the molecules must be lyophilized and refrigerated at all times during storage, thereby rendering the molecules difficult to transport and/or store. Storage problems are particularly acute when pharmaceutical formulations must be stored and dispensed outside of the hospital environment.

[0006] Few practical solutions to the storage problems of labile protein molecules have been proposed. Accordingly, there is a need for stabilized, long lasting formulations of proteinaceous therapeutic molecules that are easily dispensed, preferably with a simple formulation requiring minimal post-storage manipulation.

[0007] The present invention encompasses albumin fusion proteins comprising a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragment or variant thereof) fused to albumin or a fragment (portion) or variant of albumin. The present invention also encompasses polynucleotides comprising, or alternatively consisting of, nucleic acid molecules encoding a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragment or variant thereof) fused to albumin or a fragment (portion) or variant of albumin. The present invention also encompasses polynucleotides, comprising, or alternatively consisting of, nucleic acid molecules encoding proteins comprising a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragment or variant thereof) fused to albumin or a fragment (portion) or variant of albumin, that is sufficient to prolong the shelf life of the Therapeutic protein, and/or stabilize the Therapeutic protein and/or its activity in solution (or in a pharmaceutical composition) in vitro and/or in vivo. Albumin fusion proteins encoded by a polynucleotide of the invention are also encompassed by the invention, as are host cells transformed with polynucleotides of the invention, and methods of making the albumin fusion proteins of the invention and using these polynucleotides of the invention, and/or host cells.

[0008] In a preferred aspect of the invention, albumin fusion proteins include, but are not limited to, those encoded by the polynucleotides described in Table 2.

[0009] The invention also encompasses pharmaceutical formulations comprising an albumin fusion protein of the invention and a pharmaceutically acceptable diluent or carrier. Such formulations may be in a kit or container. Such kit or container may be packaged with instructions pertaining to the extended shelf life of the Therapeutic protein. Such formulations may be used in methods of treating, preventing, ameliorating or diagnosing a disease or disease symptom in a patient, preferably a mammal, most preferably a human, comprising the step of administering the pharmaceutical formulation to the patient.

[0010] In other embodiments, the present invention encompasses methods of preventing, treating, or ameliorating a disease or disorder. In preferred embodiments, the present invention encompasses a method of treating a disease or disorder listed in the “Preferred Indication: Y” column of Table 1 comprising administering to a patient in which such treatment, prevention or amelioration is desired an albumin fusion protein of the invention that comprises a Therapeutic protein or portion corresponding to a Therapeutic protein (or fragment or variant thereof) disclosed in the “Therapeutic Protein: X” column of Table 1 (in the same row as the disease or disorder to be treated is listed in the “Preferred Indication: Y” column of Table 1) in an amount effective to treat, prevent or ameliorate the disease or disorder.

[0011] In one embodiment, an albumin fusion protein described in Table 1 or 2 has extended shelf fife.

[0012] In a second embodiment, an albumin fusion protein described in Table 1 or 2 is more stable than the corresponding unfused Therapeutic molecule described in Table 1.

[0013] The present invention further includes transgenic organisms modified to contain the nucleic acid molecules of the invention (including, but not limited to, the polynucleotides described in Tables 1 and 2), preferably modified to express an albumin fusion protein of the invention.

[0034] Definitions

[0035] The following definitions are provided to facilitate understanding of certain terms used throughout this specification.

[0036] As used herein, “polynucleotide” refers to a nucleic acid molecule having a nucleotide sequence encoding a fusion protein comprising, or alternatively consisting of, at least one molecule of albumin (or a fragment or variant thereof) joined in frame to at least one Therapeutic protein X (or fragment or variant thereof); a nucleic acid molecule having a nucleotide sequence encoding a fusion protein comprising, or alternatively consisting of, the amino acid sequence of SEQ ID NO:Y (as described in column 6 of Table 2) or a fragment or variant thereof; a nucleic acid molecule having a nucleotide sequence comprising or alternatively consisting of the sequence shown in SEQ ID NO:X; a nucleic acid molecule having a nucleotide sequence encoding a fusion protein comprising, or alternatively consisting of, the amino acid sequence of SEQ ID NO:Z; a nucleic acid molecule having a nucleotide sequence encoding an albumin fusion protein of the invention generated as described in Table 2 or in the Examples; a nucleic acid molecule having a nucleotide sequence encoding a Therapeutic albumin fusion protein of the invention, a nucleic acid molecule having a nucleotide sequence contained in an albumin fusion construct described in Table 2, or a nucleic acid molecule having a nucleotide sequence contained in an albumin fusion construct deposited with the ATCC (as described in Table 3).

[0037] As used herein, “albumin fusion construct” refers to a nucleic acid molecule comprising, or alternatively consisting of, a polynucleotide encoding at least one molecule of albumin (or a fragment or variant thereof) joined in frame to at least one polynucleotide encoding at least one molecule of a Therapeutic protein (or fragment or variant thereof); a nucleic acid molecule comprising, or alternatively consisting of, a polynucleotide encoding at least one molecule of albumin (or a fragment or variant thereof) joined in frame to at least one polynucleotide encoding at least one molecule of a Therapeutic protein (or fragment or variant thereof) generated as described in Table 2 or in the Examples; or a nucleic acid molecule comprising, or alternatively consisting of, a polynucleotide encoding at least one molecule of albumin (or a fragment or variant thereof) joined in frame to at least one polynucleotide encoding at least one molecule of a Therapeutic protein (or fragment or variant thereof), further comprising, for example, one or more of the following elements: (1) a functional self-replicating vector (including but not limited to, a shuttle vector, an expression vector, an integration vector, and/or a replication system), (2) a region for initiation of transcription (e.g., a promoter region, such as for example, a regulatable or inducible promoter, a constitutive promoter), (3) a region for termination of transcription, (4) a leader sequence, and (5) a selectable marker. The polynucleotide encoding the Therapeutic protein and albumin protein, once part of the albumin fusion construct, may each be referred to as a “portion,” “region” or “moiety” of the albumin fusion construct.

[0038] The present invention relates generally to polynucleotides encoding albumin fusion proteins; albumin fusion proteins; and methods of treating, preventing, or ameliorating diseases or disorders using albumin fusion proteins or polynucleotides encoding albumin fusion proteins. As used herein, “albumin fusion protein” refers to a protein formed by the fusion of at least one molecule of albumin (or a fragment or variant thereof) to at least one molecule of a Therapeutic protein (or fragment or variant thereof). An albumin fusion protein of the invention comprises at least a fragment or variant of a Therapeutic protein and at least a fragment or variant of human serum albumin, which are associated with one another by genetic fusion (i.e., the albumin fusion protein is generated by translation of a nucleic acid in which a polynucleotide encoding all or a portion of a Therapeutic protein is joined in-frame with a polynucleotide encoding all or a portion of albumin). The Therapeutic protein and albumin protein, once part of the albumin fusion protein, may each be referred to as a “portion”, “region” or “moiety” of the albumin fusion protein (e.g., a “Therapeutic protein portion” or an “albumin protein portion”). In a highly preferred embodiment, an albumin fusion protein of the invention comprises at least one molecule of a Therapeutic protein X or fragment or variant of thereof (including, but not limited to a mature form of the Therapeutic protein X) and at least one molecule of albumin or fragment or variant thereof (including but not limited to a mature form of albumin).

[0039] In a further preferred embodiment, an albumin fusion protein of the invention is processed by a host cell and secreted into the surrounding culture medium. Processing of the nascent albumin fusion protein that occurs in the secretory pathways of the host used for expression may include, but is not limited to signal peptide cleavage; formation of disulfide bonds; proper folding; addition and processing of carbohydrates (such as for example, N- and O-linked glycosylation); specific proteolytic cleavages; and assembly into multimeric proteins. An albumin fusion protein of the invention is preferably in the processed form. In a most preferred embodiment, the “processed form of an albumin fusion protein” refers to an albumin fusion protein product which has undergone N-terminal signal peptide cleavage, herein also referred to as a “mature albumin fusion protein”.

[0040] In several instances, a representative clone containing an albumin fusion construct of the invention was deposited with the American Type Culture Collection (herein referred to as “ATCC®”). Furthermore, it is possible to retrieve a given albumin fusion construct from the deposit by techniques known in the art and described elsewhere herein. The ATCC® is located at 10801 University Boulevard, Manassas, Va. 20110-2209, USA. The ATCC® deposits were made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for the purposes of patent procedure.

[0041] In one embodiment, the invention provides a polynucleotide encoding an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein and a serum albumin protein. In a further embodiment, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein and a serum albumin protein. In a preferred embodiment, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein and a serum albumin protein encoded by a polynucleotide described in Table 2. In a further preferred embodiment, the invention provides a polynucleotide encoding an albumin fusion protein whose sequence is shown as SEQ ID NO:Y in Table 2. In other embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a biologically active and/or therapeutically active fragment of a Therapeutic protein and a serum albumin protein. In other embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a biologically active and/or therapeutically active variant of a Therapeutic protein and a serum albumin protein. In preferred embodiments, the serum albumin protein component of the albumin fusion protein is the mature portion of serum albumin. The invention further encompasses polynucleotides encoding these albumin fusion proteins.

[0042] In further embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein, and a biologically active and/or therapeutically active fragment of serum albumin. In further embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein and a biologically active and/or therapeutically active variant of serum albumin. In preferred embodiments, the Therapeutic protein portion of the albumin fusion protein is the mature portion of the Therapeutic protein. In a further preferred embodiment, the Therapeutic protein portion of the albumin fusion protein is the extracellular soluble domain of the Therapeutic protein. In an alternative embodiment, the Therapeutic protein portion of the albumin fusion protein is the active form of the Therapeutic protein. The invention further encompasses polynucleotides encoding these albumin fusion proteins.

[0043] In further embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a biologically active and/or therapeutically active fragment or variant of a Therapeutic protein and a biologically active and/or therapeutically active fragment or variant of serum albumin. In preferred embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, the mature portion of a Therapeutic protein and the mature portion of serum albumin. The invention further encompasses polynucleotides encoding these albumin fusion proteins.

[0044] Therapeutic Proteins

[0045] As stated above, a polynucleotide of the invention encodes a protein comprising or alternatively consisting of, at least a fragment or variant of a Therapeutic protein and at least a fragment or variant of human serum albumin, which are associated with one another, preferably by genetic fusion.

[0046] An additional embodiment includes a polynucleotide encoding a protein comprising or alternatively consisting of at least a fragment or variant of a Therapeutic protein and at least a fragment or variant of human serum albumin, which are linked with one another by chemical conjugation.

[0047] As used herein, “Therapeutic protein” refers to proteins, polypeptides, antibodies, peptides or fragments or variants thereof, having one or more therapeutic and/or biological activities. Therapeutic proteins encompassed by the invention include but are not limited to, proteins, polypeptides, peptides, antibodies, and biologics. (The terms peptides, proteins, and polypeptides are used interchangeably herein.) It is specifically contemplated that the term “Therapeutic protein” encompasses antibodies and fragments and variants thereof. Thus a protein of the invention may contain at least a fragment or variant of a Therapeutic protein, and/or at least a fragment or variant of an antibody. Additionally, the term “Therapeutic protein” may refer to the endogenous or naturally occurring correlate of a Therapeutic protein.

[0048] By a polypeptide displaying a “therapeutic activity” or a protein that is “therapeutically active” is meant a polypeptide that possesses one or more known biological and/or therapeutic activities associated with a therapeutic protein such as one or more of the Therapeutic proteins described herein or otherwise known in the art. As a non-limiting example, a “Therapeutic protein” is a protein that is useful to treat, prevent or ameliorate a disease, condition or disorder. As a non-limiting example, a “Therapeutic protein” may be one that binds specifically to a particular cell type (normal (e.g., lymphocytes) or abnormal e.g., (cancer cells)) and therefore may be used to target a compound (drug, or cytotoxic agent) to that cell type specifically.

[0049] For example, a non-exhaustive list of “Therapeutic protein” portions which may be comprised by an albumin fusion protein of the invention includes, but is not limited to, erythropoietin (EPO), ILM2, G-CSF, Insulin, Calcitonin, Growth Hormone, IFN-alpha, IFN-beta, PTH, TR6 (International Publication No. WO 98/30694), BLyS, BLyS single chain antibody, Resistin, Growth hormone releasing factor, VEGF-2, KGF-2, D-SLAM, KDI, and TR2, GLP-1, Extendin 4, and GM-CSF.

[0050] Interferon hybrids may also be fused to the amino or carboxy terminus of albumin to form an interferon hybrid albumin fusion protein. Interferon hybrid albumin fusion protein may have enhanced, or alternatively, suppressed interferon activity, such as antiviral responses, regulation of cell growth, and modulation of immune response (Lebleu et al., PNAS USA, 73:3107-3111 (1976); Gresser et al., Nature, 251:543-545 (1974); and Johnson, Texas Reports Biol Med, 35:357-369 (1977)). Each interferon hybrid albumin fusion protein can be used to treat, prevent, or ameliorate viral infections (e.g., hepatitis (e.g., HCV); or HIV), multiple sclerosis, or cancer.

[0051] In one embodiment, the interferon hybrid portion of the interferon hybrid albumin fusion protein comprises an interferon alpha-interferon alpha hybrid (herein referred to as an alpha-alpha hybrid). For example, the alpha-alpha hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon alpha A fused to interferon alpha D. In a further embodiment, the A/D hybrid is fused at the common BgIII restriction site to interferon alpha D, wherein the N-terminal portion of the A/D hybrid corresponds to amino acids 1-62 of interferon alpha A and the C-terminal portion corresponds to amino acids 64-166 of interferon alpha D. For example, this A/D hybrid would comprise the amino acid sequence: CDLPQTHSLGSRRTLMLLAQMRX₁ISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFTTKDSSAAWDEDLLDKFCTEL YQQLNDLEACVMQEERVGETPLMNX₂DSILAVKKYFRRITLYLTEKKYSPCAWEVVRAEIMRSLSLSTNLQERLRRKE (SEQ ID NO:1326), wherein the X₁ is R or K and the X₂ is A or V (see, for example, Construct ID #2875). In an additional embodiment, the A/D hybrid is fused at the common PvuIII restriction site, wherein the N-terminal portion of the A/D hybrid corresponds to amino acids 1-91 of interferon alpha A and the C-terminal portion corresponds to amino acids 93-166 of interferon alpha D. For example, this A/D hybrid would comprise the amino acid sequence: CDLPQTHSLGSRRTLMLLAQMRX₁ISLFSCLKDRHDFGFPQEEFGNQFQKAETPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTEL YQQLNDLEACVMQEERVGETPLMNX₂DSILAVKKYFRRITLYLTEKKYSPCAWEVVRAEIMRSLSLSTNLQERLRRKE (SEQ ID NO:1311), wherein the X₁ is R or K and the second X₂ is A or V (see, for example, Construct ID #2872). These hybrids are further described in U.S. Pat. No. 4,414,510, which is hereby incorporated by reference in its entirety.

[0052] In an additional embodiment, the alpha-alpha hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon alpha A fused to interferon alpha F. In a further embodiment, the A/F hybrid is fused at the common PvuIII restriction site, wherein the N-terminal portion of the A/F hybrid corresponds to amino acids 1-91 of interferon alpha A and the C-terminal portion corresponds to amino acids 93-166 of interferon alpha F. For example, this A/F hybrid would comprise the amino acid sequence: CDLPQTHSLGSRRTLMLLAQMRXISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELY QQLNDMEACVIQEVGVEETPLMNVDSILAVKKYFQRITLYLTEKKYSPCAWEVVRAEIMRSFSLSKIFQERLRRKE (SEQ ID NO:1321), wherein X is either R or K (see, for example, Construct ID #2874). These hybrids are further described in U.S. Pat. No. 4,414,510, which is hereby incorporated by reference in its entirety. In a further embodiment, the alpha-alpha hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon alpha A fused to interferon alpha B. In an additional embodiment, the A/B hybrid is fused at the common PvuIII restriction site, wherein the N-terminal portion of the A/B hybrid corresponds to amino acids 1-91 of interferon alpha A and the C-terminal portion corresponds to amino acids 93-166 of interferon alpha B. For example, this A/B hybrid would comprise an amino acid sequence: CDLPQTHSLGSRRTLMLLAQMRX₁ISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTEL YQQINDLEX₂X₃X₄X₅QEVGVIESPLMYEDSILAVRKYFQRITLYLTEKKYSSCAWEVVRAEIMRSFSLSINLQKRLKSKE (SEQ ID NO:1316), wherein the X₁ is R or K and X₂ through X₅ is SCVM or VLCD (see, for example, Construct ID #2873). These hybrids are further described in U.S. Pat. No. 4,414,510, which is hereby incorporated by reference in its entirety.

[0053] In another embodiment, the interferon hybrid portion of the interferon hybrid albumin fusion protein comprises an interferon beta-interferon alpha hybrid (herein referred to as a beta-alpha hybrid). For example, the beta-alpha hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon beta-1 fused to interferon alpha D (also referred to as interferon alpha-1). In a further embodiment, the beta-1/alpha D hybrid is fused wherein the N-terminal portion corresponds to amino acids 1-73 of interferon beta-1 and the C-terminal portion corresponds to amino acids 74-167 of interferon alpha D. For example, this beta-1/alpha D hybrid would comprise an amino acid sequence: MSYNLLGFLQRSSNFQCQKLLWQLNGRLEYCLKDRMNFDIPEEIKQLQQFQKEDAALTIYEMLQNIFAIFRQDSSAAWDEDLLDKFC TELYQQLNDLEACVMQEERVGETPLMNXDSILAVKKYFRRITLYLTEKKYSPCAWEVVRAEIMRSLSLSTNLQERLRRKE (SEQ ID NO:2130), wherein X is A or V. These hybrids are further described in U.S. Pat. No. 4,758,428, which is hereby incorporated by reference in its entirety.

[0054] In another embodiment, the interferon hybrid portion of the interferon hybrid albumin fusion protein comprises an interferon alpha-interferon beta hybrid (herein referred to as a alpha-beta hybrid). For example, the alpha-beta hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon alpha D (also referred to as interferon alpha-1) fused to interferon beta-1. In a further embodiment, the alpha D/beta-1 hybrid is fused wherein the N-terminal portion corresponds to amino acids 1-73 of interferon alpha D and the C-terminal portion corresponds to amino acids 74-166 of interferon beta-1. For example, this alpha D/beta-1 hybrid would have an amino acid sequence: MCDLPETHSLDNRRTLMLLAQMSRISPSSCLMDRHDFGFPQEEFDGNQFQKAPAISVLHELIQQIFNLFTTKDSSSTGWNETIVENLLA NVYHQINHLKTVLEEKLEKEDFFRGKLMSSLHLKRYYGRILHYLKAKEYSHCAWTIVRVEILRNFYFINRLTGYLRN (SEQ ID NO:2131). These hybrids are further described in U.S. Pat. No. 4,758,428, which is hereby incorporated by reference in its entirety.

[0055] In further embodiments, the interferon hybrid portion of the interferon hybrid albumin fusion proteins may comprise additional combinations of alpha-alpha interferon hybrids, alpha-beta interferon hybrids, and beta-alpha interferon hybrids. In additional embodiments, the interferon hybrid portion of the interferon hybrid albumin fusion protein may be modified to include mutations, substitutions, deletions, or additions to the amino acid sequence of the interferon hybrid. Such modifications to the interferon hybrid albumin fusion proteins may be made, for example, to improve levels of production, increase stability, increase or decrease activity, or confer new biological properties.

[0056] The above-described interferon hybrid albumin fusion proteins are encompassed by the invention, as are host cells and vectors containing polynucleotides encoding the polypeptides. In one embodiment, a interferon hybrid albumin fusion protein encoded by a polynucleotide as described above has extended shelf life. In an additional embodiment, a interferon hybrid albumin fusion protein encoded by a polynucleotide described above has a longer serum half-life and/or more stabilized activity in solution (or in a pharmaceutical composition) in vitro and/or in vivo than the corresponding unfused interferon hybrid molecule.

[0057] In another non-limiting example, a “Therapeutic protein” is a protein that has a biological activity, and in particular, a biological activity that is useful for treating, preventing or ameliorating a disease. A non-inclusive list of biological activities that may be possessed by a Therapeutic protein includes, enhancing the immune response, promoting angiogenesis, inhibiting angiogenesis, regulating endocrine function, regulating hematopoietic functions, stimulating nerve growth, enhancing an immune response, inhibiting an immune response, or any one or more of the biological activities described in the “Biological Activities” section below and/or as disclosed for a given Therapeutic protein in Table 1 (column 2).

[0058] As used herein, “therapeutic activity” or “activity” may refer to an activity whose effect is consistent with a desirable therapeutic outcome in humans, or to desired effects in non-human mammals or in other species or organisms. Therapeutic activity may be measured in vivo or in vitro. For example, a desirable effect may be assayed in cell culture. As an example, when EPO is the Therapeutic protein, the effects of EPO on cell proliferation as described in Example 8 may be used as the endpoint for which therapeutic activity is measured. Such in vitro or cell culture assays are commonly available for many Therapeutic proteins as described in the art. Examples of assays include, but are not limited to those described herein in the Examples section or in the “Exemplary Activity Assay” column (column 3) of Table 1.

[0059] Therapeutic proteins corresponding to a Therapeutic protein portion of an albumin fusion protein of the invention, such as cell surface and secretory proteins, are often modified by the attachment of one or more oligosaccharide groups. The modification, referred to as glycosylation, can dramatically affect the physical properties of proteins and can be important in protein stability, secretion, and localization. Glycosylation occurs at specific locations along the polypeptide backbone. There are usually two major types of glycosylation: glycosylation characterized by O-linked oligosaccharides, which are attached to serine or threonine residues; and glycosylation characterized by N-linked oligosaccharides, which are attached to asparagine residues in an Asn-X-Ser or Asn-X-Thr sequence, where X can be any amino acid except proline. N-acetylneuramic acid (also known as sialic acid) is usually the terminal residue of both N-linked and O-linked oligosaccharides. Variables such as protein structure and cell type influence the number and nature of the carbohydrate units within the chains at different glycosylation sites. Glycosylation isomers are also common at the same site within a given cell type.

[0060] For example, several types of human interferon are glycosylated. Natural human interferon-α2 is O-glycosylated at threonine 106, and N-glycosylation occurs at asparagine 72 in interferon-α14 (Adolf et al., J. Biochem 276:511 (1991); Nyman T A et al., J. Biochem 329:295 (1998)). The oligosaccharides at asparagine 80 in natural interferon-β1α may play an important factor in the solubility and stability of the protein, but may not be essential for its biological activity. This permits the production of an unglycosylated analog (interferon-β1b) engineered with sequence modifications to enhance stability (Hosoi et al., J. Interferon Res. 8:375 (1988; Karpusas et al., Cell Mol Life Sci 54:1203 (1998); Knight, J. Interferon Res. 2:421 (1982); Runkel et al., Pharm Res 15:641 (1998); Lin, Dev. Biol. Stand. 96:97 (1998)). Interferon-γ contains two N-linked oligosaccharide chains at positions 25 and 97, both important for the efficient formation of the bioactive recombinant protein, and having an influence on the pharmacokinetic properties of the protein (Sareneva et al., Eur. J. Biochem 242:191 (1996); Sareneva et al,. Biochem J. 303:831 (1994); Sareneva et al., J. Interferon Res. 13:267 (1993)). Mixed O-linked and N-linked glycosylation also occurs, for example in human erythropoietin, N-linked glycosylation occurs at asparagine residues located at positions 24, 38 and 83 while O-linked glycosylation occurs at a serine residue located at position 126 (Lai et al., J. Biol. Chem. 261:3116 (1986); Broudy et al., Arch. Biochem. Biophys. 265:329 (1988)).

[0061] Glycosylation of EPO albumin fusion proteins may influence the activity and/or stability of the EPO albumin fusion proteins. The EPO portion of the albumin fusion protein may contain 3 N-linked sites for glycosylation, each of which can carry one tetra-antennary structure. When the EPO albumin fusion protein is glycosylated, the half-life of the molecule may be increased. In one embodiment, the EPO albumin fusion protein is glycosylated. In another embodiment, the EPO albumin fusion protein is hyperglycosylated.

[0062] One type of sugar commonly found in oligosaccharides is sialic acid. Each tetra-antennary structure of the N-linked glycosylation sites of EPO may carry four sialic acid residues. Accordingly, in a preferred embodiment, the EPO albumin fusion protein is glycosylated with a carbohydrate group containing sialic acid. In an additional embodiment, the EPO albumin fusion protein comprises a fully sialylated EPO protein containing four sialic acid residues per tetra-antennerary structure per site with a molar ratio of sialic acid to protein 12:1 or greater. In alternative embodiments, the EPO albumin fusion protein comprises a hypersialylated EPO protein wherein one, two, or three sialic acid residues are attached at each tetra-antennerary structure per site with a molar ratio of sialic acid to protein less than 12:1.

[0063] Two types of sialic acid that may be used in the sialylation of the EPO albumin fusion protein are N-acetylneuraminic acid (Neu5Ac) or N-glycolytneuraminic acid (Neu5Gc). In a preferred embodiment, hypersialylated EPO albumin fusion proteins contain Neu5Ac. More preferably, the total sialic acid content of hypersialylated EPO albumin fusion proteins is at least 97% Neu5Ac. Most preferred are EPO albumin fusion protein structures with little or no Neu5Gc.

[0064] Preferably, the albumin EPO fusion protein has at least 4 moles of sialylation, and more preferably, at least 8-9 moles of sialylation. An additional embodiment comprises an albumin EPO fusion protein with 4 moles of sialylation, 5 moles of sialylation, 6 moles of sialylation, 7 moles of sialylation, 8-9 moles of sialylation, 8 moles of sialylation, 9 moles of sialylation, 10 moles of sialylation, 11 moles of sialylation, or 12 moles of sialylation.

[0065] The degree of sialylation of a protein changes the charge of the protein and its retention time on a chromatography column. Therefore, certain chromatography steps used in the purification process may be used to monitor or enrich for hypersialylated EPO albumin fusion proteins. In a preferred embodiment, the amount of sialylation may be monitored by HPLC chromatography. In an additional embodiment, steps in the purification process of EPO albumin fusions may be used to enrich for hypersialylated EPO albumin fusion proteins. In a preferred embodiment the purification steps that may be used to enrich for hypersialylated EPO albumin fusion proteins comprise the butyl-sepharose FF purification step to remove virus particles by high ammonium salt and the hydroxyapatite chromatography at pH 6.8 for the final purification step.

[0066] Therapeutic proteins corresponding to a Therapeutic protein portion of an albumin fusion protein of the invention, as well as analogs and variants thereof, may be modified so that glycosylation at one or more sites is altered as a result of manipulation(s) of their nucleic acid sequence, by the host cell in which they are expressed, or due to other conditions of their expression. For example, glycosylation isomers may be produced by abolishing or introducing glycosylation sites, e.g., by substitution or deletion of amino acid residues, such as substitution of glutamine for asparagine, or unglycosylated recombinant proteins may be produced by expressing the proteins in host cells that will not glycosylate them, e.g. in E. coli or glycosylation-deficient yeast. These approaches are described in more detail below and are known in the art.

[0067] Therapeutic proteins, particularly those disclosed in Table 1, and their nucleic acid and amino acid sequences are well known in the art and available in public databases such as Chemical Abstracts Services Databases (e.g., the CAS Registry), GenBank, and subscription provided databases such as GenSeq (e.g., Derwent). Exemplary nucleotide sequences of Therapeutic proteins which may be used to derive a polynucleotide of the invention are shown in column 7, “SEQ ID NO:X,” of Table 2. Sequences shown as SEQ ID NO:X may be a wild type polynucleotide sequence encoding a given Therapeutic protein (e.g., either full length or mature), or in some instances the sequence may be a variant of said wild type polynucleotide sequence (e.g., a polynucleotide which encodes the wild type Therapeutic protein, wherein the DNA sequence of said polynucleotide has been optimized, for example, for expression in a particular species; or a polynucleotide encoding a variant of the wild type Therapeutic protein (i.e., a site directed mutant; an allelic variant)). It is well within the ability of the skilled artisan to use the sequence shown as SEQ ID NO:X to derive the construct described in the same row. For example, if SEQ ID NO:X corresponds to a full length protein, but only a portion of that protein is used to generate the specific CID, it is within the skill of the art to rely on molecular biology techniques, such as PCR, to amplify the specific fragment and clone it into the appropriate vector.

[0068] Additional Therapeutic proteins corresponding to a Therapeutic protein portion of an albumin fusion protein of the invention include, but are not limited to, one or more of the Therapeutic proteins or peptides disclosed in the “Therapeutic Protein X” column of Table 1 (column 1), or fragment or variable thereof.

[0069] Table 1 provides a non-exhaustive list of Therapeutic proteins that correspond to a Therapeutic protein portion of an albumin fusion protein of the invention, or an albumin fusion protein encoded by a polynucleotide of the invention. The first column, “Therapeutic Protein X,” discloses Therapeutic protein molecules that may be followed by parentheses containing scientific and brand names of proteins that comprise, or alternatively consist of, that Therapeutic protein molecule or a fragment or variant thereof. “Therapeutic protein X” as used herein may refer either to an individual Therapeutic protein molecule, or to the entire group of Therapeutic proteins associated with a given Therapeutic protein molecule disclosed in this column. The “Biological activity” column (column 2) describes Biological activities associated with the Therapeutic protein molecule. Column 3, “Exemplary Activity Assay,” provides references that describe assays which may be used to test the therapeutic and/or biological activity of a Therapeutic protein:X or an albumin fusion protein comprising a Therapeutic protein X (or fragment thereof) portion. Each of the references cited in the “Exemplary Activity Assay” column are herein incorporated by reference in their entireties, particularly with respect to the description of the respective activity assay described in the reference (see Methods section therein, for example) for assaying the corresponding biological activity set forth in the “Biological Activity” column of Table 1. The fourth column, “Preferred Indication: Y,” describes disease, disorders, and/or conditions that may be treated, prevented, diagnosed, and/or ameliorated by Therapeutic protein X or an albumin fusion protein comprising a Therapeutic protein X (or fragment thereof) portion. The “Construct ID” column (column 5) provides a link to an exemplary albumin fusion construct disclosed in Table 2 which encodes an albumin fusion protein comprising, or alternatively consisting of the referenced Therapeutic Protein X (or fragment thereof) portion.

[0070]

TABLE 1
Therapeutic					Therapeutic
Protein: X	Biological Activity	Exemplary Activity Assay	Preferred Indication: Y	Construct ID	Protein: Z
EPO (Erythropoietin;	Stimulates cellular	Cell proliferation assay using a	Anemia; Anemia in Renal Disease; Anemia in Oncology	1772, 1774, 1781, 1783, 1793,	See Table 2, SEQ ID
Epoetin alfa; Epoetin	differentiation of bone-marrow	erythroleukemic cell line TF-1.	Patients; Bleeding Disorders; Chronic Renal Failure; Chronic	1794, 1925, 1926, 1966, 1969,	NO: Z for particular
beta; Gene-activated	stem cells at an early stage of	(Kitamura et al. 1989 J. Cell.	Renal Failure in Pre-Dialysis Patients; Renal Disease; End-	1980, 1981, 1994, 1995, 1996,	construct.
erythropoietin;	erythropoiesis; accelerates the	Physiol. 140: 323)	Stage Renal Disease; End-Stage Renal Disease in Dialysis	1997, 2047, 2102, 2283, 2284,
Darbepoetin-alpha;	proliferation and maturation of		Patients; Chemotherapy; Chemotherapy in Cancer Patients;	2287, 2289, 2294, 2298, 2310,
NESP; Epogen;	terminally differentiating cells		Anemia in zidovudine-treated HIV patients; Anemia in	2311, 2325, 2326, 2344, 2363,
Procrit; Eprex; Erypo;	into erythrocytes; and modulates		zidovudine-treated patients; Anemia in HIV patients; Anemia	2373, 2387, 2414, 2441, 2603,
Espo; Epoimmun;	the level of circulating		in premature infants; Surgical patients (pre and/or post	2604, 2605, 3194, 3195, 3196,
EPOGIN;	erythrocytes.		surgery); Surgical patients (pre and/or post surgery) who are
NEORECORMON;			anemic; Surgical patients (pre and/or post surgery) who are
HEMOLINK; Dynepo;			undergoing elective surgery; Surgical patients (pre and/or post
ARANESP)			surgery) who are undergoing elective, non-cardiac surgery;
			Surgical patients (pre and/or post surgery) who are undergoing
			elective, non-cardiac, non-vascular surgery; Surgical patients
			(pre and/or post surgery) who are undergoing elective, non-
			vascular surgery; Surgical patients (pre and/or post surgery)
			who are undergoing cardiac and/or vascular surgery; Aplastic
			anemia; Refractory anemia; Anemia in Inflammatory Bowel
			Disease; Refractory anemia in Inflammatory Bowel Disease;
			Transfusion avoidance; Transfusion avoidance for surgical
			patients; Transfusion avoidance for elective surgical patients;
			Transfusion avoidance for elective orthopedic surgical
			patients; Patients who want to Increase Red Blood Cells.
G-CSF (Granulocyte	Stimulates the proliferation and	Proliferation of murine NFS-60	Chemoprotection; Adjunct to Chemotherapy; Inflammatory	1642, 1643, 2363, 2373, 2387,	See Table 2, SEQ ID
colony-stimulating	differentiation of the progenitor	cells (Weinstein et al, Proc Natl	disorders; Cancer; Leukemia; Myelocytic leukemia;	2414, 2441, 2702, 2637, 2700,	NO: Z for particular
factor; Granulokine;	cells for granulocytes and	Acad Sci USA 1986; 83, pp5010-4)	Neutropenia, Primary neutropenias (e.g.; Kostmann	2701, 2703, 2886, 2887, 2888,	construct.
KRN 8601; Filgrastim;	monocytes-macrophages.		syndrome); Secondary neutropenia; Prevention of neutropenia;	2889, 2890,
Lenograstim;			Prevention and treatment of neutropenia in HIV-infected
Meograstim;			patients; Prevention and treatment of neutropenia associated
Nartograstim;			with chemotherapy; Infections associated with neutropenias;
Neupogen; NOPIA;			Myelopysplasia; Autoimmune disorders; Psoriasis;
Gran; GRANOCYTE;			Mobilization of hematopoietic progenitor cells; Wound
Granulokine;			Healing; Autoimmune Disease; Transplants; Bone marrow
Neutrogin; Neu-up;			transplants; Acute myelogeneous leukemia; Lymphoma, Non-
Neutromax)			Hodgkin's lymphoma; Acute lymphoblastic leukemia;
			Hodgkin's disease; Accelerated myeloid recovery; Glycogen
			storage disease.
GM-CSF	Regulates hematopoietic cell	Colony Stimulating Assay: Testa,	Bone Marrow Disorders; Bone marrow transplant;	1697, 1699, 2066, and 2067.	See Table 2, SEQ ID
(Granulocyte-	differentiation, gene expression,	N. G., et al., “Assays for	Chemoprotection; Hepatitis C; HIV Infections; Cancer; Lung		NO: Z for particular
macrophage colony-	growth, and function.	hematopoietic growth factors.”	Cancer; Melanoma; Malignant melanoma; Mycobacterium		construct.
stimulating factor;		Balkwill FR (edt) Cytokines, A	avium complex; Mycoses; Leukemia; Myeloid Leukemia;
rhuGM-CSF; BI		practical Approach, pp 229-44; IRL	Infections; Neonatal infections; Neutropenia; Mucositis; Oral
61012; Prokine;		Press Oxford 1991.	Mucositis; Prostate Cancer; Stem Cell Mobilization; Vaccine
Molgramostim;			Adjuvant; Ulcers (such as Diabetic, Venous Stasis, or Pressure
Sargramostim; GM-			Ulcers); Prevention of neutropenia; Acute myelogenous
CSF/IL 3 fusion;			leukemia; Hematopoietic progenitor cell mobilization;
Milodistim; Leuco-			Lymphoma; Non-Hodgkin's lymphoma; Acute Lymphoblastic
tropin; PROKINE;			Leukemia; Hodgkin's disease; Accelerated myeloid recovery;
LEUKOMAX;			Transplant Rejection; Xenotransplant Rejection.
Interberin; Leukine;
Leukine Liquid;
Pixykine)
Human growth	Binds to two GHR molecules	Ba/F3-hGHR proliferation assay, a	Acromegaly; Growth failure; Growth hormone replacement;	3163, 2983,	See Table 2, SEQ ID
hormone	and Induces signal transduction	novel specific bioassay for serum	Growth hormone deficiency; Pediatric Growth Hormone		NO: Z for particular
(Pegvisamont;	through receptor dimerization	human growth hormone. J Clin	Deficiency; Adult Growth Hormone Deficiency; Idiopathic		construct.
Somatrem;		Endocrinol Metab 2000	Growth Hormone Deficiency; Growth retardation; Prader-
Somatropin;		Nov.; 85(11): 4274-9 Plasma	Willi Syndrome; Prader-Willi Syndrome in children 2 years or
TROVERT;		growth hormone (GH)	older; Growth deficiencies; Growth failure associated with
PROTROPIN;		immunoassay and tibial bioassay,	chronic renal insufficiency; Osteoporosis; Postmenopausal
BIOTROPIN;		Appl Physiol 2000 Dec.; 89(6):	osteoporosis; Osteopenia, Osteoclastogenesis; burns;
HUMATROPE;		2174-8 Growth hormone (hGH)	Cachexia; Cancer Cachexia; Dwarfism; Metabolic Disorders;
NUTROPIN;		receptor mediated cell	Obesity; Renal failure; Turner's Syndrome; Fibromyalgia;
NUTROPIN AQ;		mediated proliferation, Growth	Fracture treatment; Frailty, AIDS wasting; Muscle Wasting;
NUTROPHIN;		Horm IGF Res 2000 Oct.;	Short Stature; Diagnostic Agents; Female Infertility;
NORDITROPIN;		10(5): 248-55 International standard	lipodystrophy.
GENOTROPIN;		for growth hormone, Horm Res
SAIZEN;		1999; 51 Suppl 1: 7-12
SEROSTIM)
Insulin (Human	Stimulates glucose uptake and	Insulin activity may be assayed in	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2250, 2255, 2276, 2278, 2656,	See Table 2, SEQ ID
insulin; Insulin aspart;	promotes glycogenesis and	vitro using a [3-H]-glucose uptake	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;	2668, 2669, 2671, 2821, 2822,	NO: Z for particular
Insulin Glargine;	lipogenesis.	assay. (J Biol Chem 1999 Oct. 22;	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-	2832, 2877, 2878, 2882, 2885,	construct.
Insulin lispro; Lys-B28		274(43): 30864-30873).	insulin dependent Diabetes Mellitus (NIDDM); Insulin-	2891, 2897, 2930, 2931, 2942,
Pro-B29; lyspro; LY			dependent Diabetes Mellitus (IDDM); A Condition Associated	2986, 3025, 3133, 3134, 3197,
275585;			With Diabetes Including, But Not Limited To Obesity, Heart	3198, 2726, 2727, 2784, 2789
diarginylinsulin; Des-			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
B26-B30-insulin-B25-			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
amide; Insulin detemir;			Vascular Disorders; Suppression of Body Weight;
LABI; NOVOLIN;			Suppression of Appetite; Syndrome X.
NOVORAPID;
HUMULIN;
NOVOMIX 30;
VELOSULIN;
NOVOLOG;
LANTUS; ILETIN;
HUMALOG;
MACRULIN;
EXUBRA;
INSUMAN; ORALIN;
ORALGEN;
HUMAHALE;
HUMAHALIN)
Interferon alfa	Confers a range of cellular	Anti-viral assay: Rubinstein S,	Viral infections; HIV Infections; Hepatitis; Chronic Hepatitis;	2249, 2343, 2366, 2381, 2382,	See Table 2, SEQ ID
(Interferon alfa-2b;	responses including antiviral,	Familletti PC, Pestka S. (1981)	Hepatitis B; Chronic Hepatitis B; Hepatitis C; Chronic	2410, and 3165.	NO: Z for particular
recombinant;	antiproliferative, antitumor and	Convenient assay for interferons.	Hepatitis C; Hepatitis D; Chronic Hepatitis D; Human		construct.
Interferon alfa-n1;	immunomodulatory activities;	J. Virol. 37(2): 755-8; Anti-	Papillomavirus; Herpes Simplex Virus Infection; External
Interferon alfa-n3;	stimulate production of two	proliferation assay: Gao Y, et al	Condylomata Acuminata; HIV; HIV Infection; Oncology;
Peginterferon alpha-	enzymes: a protein kinase and an	(1999) Sensitivity of an epstein-barr	Cancer; Solid Tumors; Melanoma; Malignant Melanoma;
2b; Ribavirin and	oligoadenylate synthetase.	virus-positive tumor line, Daudi, to	Renal Cancer (e.g., Renal Cell Carcinoma); Lung Cancer (e.g,.
interferon alfa-2b;		alpha interferon correlates with	Non-Small Cell Lung Cancer or Small Cell Lung Cancer)
Interferon alfacon-1;		expression of a GC-rich viral	Colon Cancer; Breast Cancer; Liver Cancer; Prostate Cancer;
interferon consensus;		transcript. Mol Cell Biol.	Bladder Cancer; Gastric Cancer; Sarcoma; AIDS-Related
YM 643; CIFN;		19(11): 7305-13.	Kaposi's Sarcoma; Lymphoma; T Cell Lymphoma; Cutaneous
interferon-alpha			T-Cell Lymphoma; Non-Hodgkin's Lymphoma; Brain Cancer;
consensus;			Glioma; Glioblastoma Multiforme; Cervical Dysplasia;
recombinant methionyl			Leukemia; Preleukemia; Bone Marrow Disorders; Bone
consensus interferon;			Disorders; Hairy Cell Leukemia; Chronic Myelogeonus
recombinant consensus			Leukemia; Hematological Malignancies; Hematological
interferon; CGP			Disorders; Multiple Myeloma; Bacterial Infections;
35269; RO 253036;			Chemoprotection; Thrombocytopenia; Multiple Sclerosis;
RO 258310; INTRON			Pulmonary Fibrosis; Age-Related Macular Degeneration;
A; PEG-INTRON;			Macular Degeneration; Crohn's Disease; Neurological
OIF; OMNIFERON;			Disorders; Arthritis; Rheumatoid Arthritis; Ulcerative Colitis;
PEG-OMNIFERON;			Osteoporosis, Osteopenia, Osteoclastogenesis; Fibromyalgia;
VELDONA; PEG-			Sjögren's Syndrome; Chronic Fatigue Syndrome; Fever;
REBETRON;			Hemmorhagic Fever; Viral Hemmorhagic Fevers;
ROFERON A;			Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes
WELLFERON;			mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;
ALFERON N/LDO;			Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-
REBETRON;			insulin dependent Diabetes Mellitus (NIDDM); Insulin-
ALTEMOL;			dependent Diabetes Mellitus (IDDM); A Condition Associated
VIRAFERONPEG;			With Diabetes Including, But Not Limited To Obesity, Heart
PEGASYS;			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
VIRAFERON;			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
VIRAFON;			Vascular Disorders; Suppression of Body Weight;
AMPLIGEN;			Suppression of Appetite; Syndrome X.
INFERGEN;
INFAREX;
ORAGEN)
Calcitonin (Salmon	Regulates levels of calcium and	Hypocalcemic Rat Bioassay, bone	Bone Disorders; Fracture prevention; Hypercalcemia;	1833, 1834, 1835, 1836, 2447,	See Table 2, SEQ ID
Calcitonin	phosphate in serum; causes a	resorbing assay and the pit assay,	Malignant hypercalcemia; Osteoporosis; Paget's disease;	2513, 2806, 2915	NO: Z for particular
(Salcatonin);	reduction in serum calcium-an	CT receptor binding assay, CAMP	Osteopenia, Osteoclastogenesis; osteolysis; osteomyelitis;		construct.
Calcitonin human-	effect opposite to that of human	stimulation assay: J Bone Miner	osteonecrosis; periodontal bone loss; osteoarthritis; rheumatoid
salmon hybrid;	parathyroid hormone.	Res 1999 Aug.; 14(8): 1425-31	arthritis; osteopetrosis; periodontal, lytic, or metastatic bone
Forcaltonin; Fortical;			disease; osteoclast differentiation inhibition; bone disorders;
Calcitonin; Calcitonina			bone healing and regeneration.
Almirall; Calcitonina
Hubber;
Calcimar; Calsynar;
Calogen; Miacalcic;
Miacalcin; SB205614;
Macritonin;
Cibacalcin;
Cibacalcina;
Cibacalcine;
Salmocalcin;
PowderJect Calcitonin)
(CAS-21215-62-3)
Interferon beta	Modulates MHC antigen	Anti-viral assay: Rubinstein S,	Multiple Sclerosis; Oncology; Cancer; Solid Tumors;	1778, 1779, 2011, 2013, 2053,	See Table 2, SEQ ID
(Interferon beta-1a;	expression, NK cell activity and	Familletti PC, Pestka S. (1981)	Melanoma; Malignant Melanoma; Renal Cancer (e.g., Renal	2054, 2492, 2580, 2795, 2796,	NO: Z for particular
Interferon beta 1b;	IFNg production and IL12	Convenient assay for interferons.	Cell Carcinoma); Lung Cancer (eg,. Non-Small Cell Lung	2797.	construct.
Interferon-beta-serine;	production in monocytes.	J. Virol. 37(2): 755-8; Anti-	Cancer or Small Cell Lung Cancer) Colon Cancer; Breast
SH 579; ZK 157046;		proliferation assay: Gao Y, et al	Cancer; Liver Cancer; Prostate Cancer; Bladder Cancer;
BCDF; beta-2 IF;		(1999) Sensitivity of an epstein-barr	Gastric Cancer; Sarcoma; AIDS-Related Kaposi's Sarcoma;
Interferon-beta-2;		virus-positive tumor line, Daudi, to	Lymphoma; T Cell Lymphoma; Cutaneous T-Cell Lymphoma;
rhIL-6; SJ0031; DL		alpha interferon correlates with	Non-Hodgkin's Lymphoma; Brain Cancer; Glioma;
8234; FERON;		expression of a GC-rich viral	Glioblastoma Multiforme; Cervical Dysplasia; Leukemia;
IFNbeta;		transcript. Mol Cell Biol.	Preleukemia; Bone Marrow Disorders; Bone Disorders; Hairy
BETASERON;		19(11): 7305-13.	Cell Leukemia; Chronic Myelogeonus Leukemia;
AVONEX; REBIF;			Hematological Malignancies; Hematological Disorders;
BETAFERON;			Multiple Myeloma; Bacterial Infections; Chemoprotection;
SIGOSIX)			Thrombocytopenia; Viral infections; HIV Infections;
			Hepatitis; Chronic Hepatitis; Hepatitis B; Chronic Hepatitis B;
			Hepatitis C; Chronic Hepatitis C; Hepatitis D; Chronic
			Hepatitis D; Human Papillomavirus; Herpes Simplex Virus
			Infection; External Condylomata Acuminata; HIV; HIV
			Infection; Pulmonary Fibrosis; Age-Related Macular
			Degeneration; Macular Degeneration; Crohn's Disease;
			Neurological Disorders; Arthritis; Rheumatoid Arthritis;
			Ulcerative Colitis; Osteoporosis, Osteopenia,
			Osteoclastogenesis; Fibromyalgia; Sjogren's Syndrome;
			Chronic Fatigue Syndrome; Fever; Hemmorhagic Fever; Viral
			Hemmorhagic Fevers; Hyperglycemia; Diabetes; Diabetes
			Insipidus; Diabetes mellitus; Type 1 diabetes; Type 2 diabetes;
			Insulin resistance; Insulin deficiency; Hyperlipidemia;
			Hyperketonemia; Non-insulin dependent Diabetes Mellitus
			(NIDDM); Insulin-dependent Diabetes Mellitus (IDDM); A
			Condition Associated With Diabetes Including, But Not
			Limited To Obesity, Heart Disease, Hyperglycemia,
			Infections, Retinopathy, And/Or Ulcers; Metabolic Disorders;
			Immune Disorders; Obesity; Vascular Disorders; Suppression
			of Body Weight; Suppression of Appetite; Syndrome X.
Growth hormone	Acts on the anterior pituitary to	Growth hormone-releasing peptides	Acromegaly; Growth failure; Growth hormone replacement;	1747 and 1748.	See Table 2, SEQ ID
releasing factor;	stimulate the production and	(GHRPs) are known to release	Growth hormone deficiency; Pediatric Growth Hormone		NO: Z for particular
Growth hormone	secretion of growth hormone and	growth hormone (GH) in vivo and	Deficiency; Adult Growth Hormone Deficiency; Idiopathic		construct.
releasing hormone	exert a trophic effect on the	in vitro by a direct action on	Growth Hormone Deficiency; Growth retardation; Prader-
(Sermorelin acetate;	gland.	receptors in anterior pituitary cells.	Willi Syndrome; Prader-Willi Syndrome in children 2 years or
Pralmorelin;		Biological activity can be measured	older; Growth deficiencies; Growth failure associated with
Somatorelin;		in cell lines expressing growth	chronic renal insufficiency; Osteoporosis; Osteopenia,
Somatoliberin; Geref;		hormone releasing factor receptor	Osteoclastogenesis; Postmenopausal osteoporosis; burns;
Gerel; Groliberin)		(Mol Endocrinol 1992	Cachexia; Cancer Cachexia; Dwarfism; Metabolic Disorders;
		Oct.; 6(10): 1734-44, Molecular	Obesity; Renal failure; Turner's Syndrome; Fibromyalgia;
		Endocrinology, Vol 7, 77-84).	Fracture treatment; Frailty, AIDS wasting; Muscle Wasting;
			Short Stature; Diagnostic Agents; Female Infertility;
			lipodystrophy.
IL-2 (Aldesleukin;	Promotes the growth of B and T	T cell proliferation assay	Cancer; Solid Tumors; Metastatic Renal Cell Carcinoma;	1757, 1758, 1812, 1813, 1952,	See Table 2, SEQ ID
interleukin-2 fusion	cells and augments NK cell and	“Biological activity of recombinant	Metastatic Melanoma; Malignant Melanoma; Melanoma;	1954, 2030, and 2031.	NO: Z for particular
toxin; T cell growth	CTL cell killing activity.	human interleukin-2 produced in	Renal Cell Carcinoma; Renal Cancer; Lung Cancer (e.g,. Non-		construct.
factor; PROLEUKIN;		Escherichia coli.” Science 223:	Small Cell Lung Cancer or Small Cell Lung Cancer); Colon
IMMUNACE;		1412-1415, 1984. natural killer	Cancer; Breast Cancer; Liver Cancer; Leukemia; Preleukemia;
CELEUK;		(NK) cell and CTL cytotoxicity	Hematological Malignancies; Hematological Disorders; Acute
ONCOLIPIN 2;		assay “Control of homeostasis of	Myeloid Leukemia; Melanoma; Malignant Melanoma; Non-
MACROLIN)		CD8+ memory T cells by opposing	Hodgkin's Lymphoma; Ovarian Cancer; Prostate Cancer;
		cytokines. Science 288: 675-678,	Brain Cancer; Glioma; Glioblastoma Multiforme; Hepatitis;
		2000; CTLL-2 Proliferation: Gillis	Hepatitis C; Lymphoma; HIV Infection (AIDS); Inflammatory
		et al (1978) J. Immunol. 120, 2027	Bowel Disorders; Kaposi's Sarcoma; Multiple Sclerosis;
			Arthritis; Rheumatoid Arthritis; Transplant Rejection;
			Diabetes; Type 1 Diabetes Mellitus; Type 2 Diabetes.
Parathyroid hormone;	Acts in conjuction with	Adenylyl cyclase stimulation in rat	Bone Disorders; Fracture prevention; Hypercalcemia;	1749, 1750, 1853, 1854, 1889,	See Table 2, SEQ ID
parathyrin (PTH;	calcitonin to control calcium and	osteosarcoma cells, ovariectomized	Malignant hypercalcemia; Osteoporosis; Paget's disease;	1906, 1907, 1914, 1932, 1938,	NO: Z for particular
Ostabolin; ALX1-11;	phosphate metabolism; elevates	rat model of osteoporosis: IUBMB	Osteopenia, Osteoclastogenesis; osteolysis; osteomyelitis;	1941, 1949, 2021, 2022, 2023,	construct.
hPTH 1-34; LY	blood calcium level; stimulates	Life 2000 Feb.; 49(2): 131-5	osteonecrosis; periodontal bone loss; osteoarthritis; rheumatoid	2428, 2714, 2791, 2965, 2966.
333334; MN 10T;	the activity of osteocytes;		arthritis; osteopetrosis; periodontal, lytic, or metastatic bone
parathyroid hormone	enhances absorption of Ca+/Pi		disease; osteoclast differentiation inhibition; bone disorders;
(1-31); FORTEO;	from small intestine into blood;		bone healing and regeneration.
PARATHAR)	promotes reabsorption of Ca+
	and inhibits Pi by kidney
	tubules.
Resistin	Mediates insulin resistance in	Ability of resistin to influence type	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2295, 2296, 2297, 2300, and	See Table 2, SEQ
	Type II diabetes; inhibits	II diabetes can be determined using	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;	2309.	ID NO: Z for
	insulin-stimulated glucose	assays known in the art: Pontoglio	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-		particular construct.
	uptake	et al., J Clin Invest 1998 May	insulin dependent Diabetes Mellitus (NIDDM); Insulin-
		15; 101(10): 2215-22.	dependent Diabetes Mellitus (IDDM); A Condition
			Associated With Diabetes Including, But Not Limited To
			Obesity, Heart Disease, Hyperglycemia, Infections,
			Retinopathy, And/Or Ulcers; Metabolic Disorders; Immune
			Disorders; Obesity; Vascular Disorders; Suppression of Body
			Weight; Suppression of Appetite; Syndrome X.
TR6 (DcR3; Decoy	Inhibits Fas Ligand and AIM-	Cellular apoptosis can be measured	Fas Ligand or LIGHT induced apoptotic disorders: hepatitis;	1520, 1537, 1545, 1546, 1568,	See Table 2, SEQ
Receptor 3; FASTR)	2 (TL5, LIGHT) mediated	by annexin staining, TUNEL	liver failure (including fulminant liver failure); graft versus	1570, 1622, 1623, 1645, 1700,	ID NO: Z for
	apoptosis.	staining, measurement of caspase	host disease; graft rejection; myelodysplastic syndrome;	1702, 1703, 1704, 1891, 1892,	particular
		levels. Inhibition of cell growth can	renal failure; insulin dependent diabetes mellitus;	1912, and 1913.	construct.
		also be directly measured, for	rheumatoid arthritis; inflammatory bowel disease;
		example by ALOMAR Blue	autoimmune disease; toxic epidermal necrolysis; multiple
		staining. Assay refs: cytotoxicity	sclerosis.
		assay on human fibrosarcoma
		(Epsevik and Nissen-Meyer, 1986,
		J. Immunol. methods).
DeCAF (D-SLAM;	Inhibits proliferation and	DeCAF activity can be determined	B cell and/or T cell mediated immune disorders;	1657.	See Table 2, SEQ
BCM-like	differentiation of B cells;	using assays known in the art, such	Immunodeficiency (e.g., Common Variable		ID NO: Z for
membrane protein;	Antagonize BLyS activity	as for example, those described in	Immunodeficiency, Selective IgA Deficiency)		particular
BLAME (B		Examples 32-33 of International			construct.
lymphocyte		Publication No. WO0111046.
activator
macrophage
expressed))
BLyS (B	Promotes proliferation,	BLyS activity can be determined	B cell and/or T cell mediated immune disorders, particularly	1680, 2095, and 2096.	See Table 2, SEQ
Lymphocyte	differentiation and survival of	using assays known in the art, such	immune system disorders associated with low B cell		ID NO: Z for
Stimulator;	B cells; Promotes	as, for example, the costimulatory	numbers or low serum immunoglobulin; Immunodeficiency		particular
Neutrokine alpha;	immunoglobulin production	proliferation assay and other assays	(e.g., Common Variable Immunodeficiency, Selective IgA		construct.
TL7; BAFF; TALL-	by B cells.	disclosed by Moore et al., 1999,	Deficiency). Radiolabeled forms: lymphoma, non-
1; THANK;		Science, 285(5425): 260-3.	Hodgkins lymphoma, chronic lymphocytic leukemia,
radiolabeled BLyS)			multiple myeloma.
Anti-BLyS single	Agonize or antagonize BlyS	BLyS agonist or antagonist activity	B cell and/or T cell mediated immune disorders;	1821, 1956, 2501, 2502, 2638.	See Table 2, SEQ
chain antibody	activity.	can be determined using assays	Autoimmune disorders, particularly autoimmune diseases		ID NO: Z for
(scFvI116A01,		known in the art, such as, for	associated with the production of autoantibodies;		particular
scFvI050B11,		example, a modified version the	Rheumatoid Arthritis, Systemic Lupus Erythmatosus;		construct.
scFvI006D08) and		costimulatory proliferation assay	Sjogren's Syndrome, cancers expressing Blys as an
others.		disclosed by Moore et al., 1999,	autocrine growth factor, e.g. certain chronic lymphocytic
		Science, 285(5425): 260-3, in	leukemias.
		which BlyS is mixed or
		preincubated with the anti-BlyS
		antibody prior to being applied to
		the responder B lymphocytes.
MPIF-1 (Myeloid	Inhibits myeloid progenitor	MPIF-1 activity can be measured	Chemoprotection; Adjunct to Chemotherapy; Inflammatory	1681, 3166, 3167, 3168,	See Table 2, SEQ
Progenitor	cells; and activates monocytes	using the myeloprotection assay	disorders; Cancer; Leukemia; Myelocytic leukemia;		ID NO: Z for
Inhibitory Factor;		and chemotaxis assay described in	Neutropenia, Primary neutropenias (e.g.; Kostmann		particular
CK beta-8;		U.S. Pat. No. 6,001,606.	syndrome); Secondary neutropenia; Prevention of		construct.
Mirostipen)			neutropenia; Prevention and treatment of neutropenia in
			HIV-infected patients; Prevention and treatment of
			neutropenia associated with chemotherapy; Infections
			associated with neutropenias; Myelopysplasia; Autoimmune
			disorders; Psoriasis; Mobilization of hematopoietic
			progenitor cells; Wound Healing; Autoimmune Disease;
			Transplants; Bone marrow transplants; Acute myelogeneous
			leukemia; Lymphoma, Non-Hodgkin's lymphoma; Acute
			lymphoblastic leukemia; Hodgkin's disease; Accelerated
			myeloid recovery; Glycogen storage disease.
KDI (Keratinocyte	Inhibits bone marrow	KDI activity can be measured using	Multiple sclerosis; Hepatitis; Cancer; Viral infections, HIV	1746.	See Table 2, SEQ
Derived Interferon;	proliferation; and shows	the antiviral and cell proliferation	infections, Leukemia.		ID NO: Z for
Interferon Kappa	antiviral activity.	assays described in Examples 57-63			particular
Precursor)		of International Publication No.			construct.
		WO0107608.
TNFR2 (p75)	Binds both TNFa and TNFb;	T-cell proliferation can be	Autoimmune disease; Rheumatoid Arthritis; Psoriatic	1777 and 1784.	See Table 2, SEQ
(ENBREL)	mediates T-cell proliferation	measured using assays known in	arthritis; Still's Disease; Ankylosing Spondylitis;		ID NO: Z for
	by TNF; reduces signs and	the art. For example,	Cardiovascular Diseases; Vasulitis; Wegener's		particular
	structural damage in patients	“Lymphocytes: a practical	granulomatosis; Amyloidosis; Systemic Lupus		construct.
	with moderately to severly	approach” edited by: SL Rowland,	Erythematosus, Insulin-Dependent Diabetes Mellitus;
	active rheumatoid arthritis	AJ McMichael - chapter 6, pages	Immunodeficiency Disorders; Infection; Inflammation;
	(RA).	138-160 Oxford University Press	Inflammatory Bowel Disease; Chrohn's Disease; Psoriasis;
		(2000); and “Current Protocols on	AIDS; Graft Rejection; Graft Versus Host Disease.
		CD-ROM” section 3.12
		Proliferation Assays for T-cell
		Function John Wiley & Soncs, Inc.
		(1999).
Keratinocyte growth	Stimulates epithelial cell	KGF-2 activity can be measured	Stimulate Epithelial Cell Proliferation; Stimulate Basal	1785, 1786, 1916, 1917, 2498,	See Table 2, SEQ
factor 2	growth.	using the wound healing assays and	Keratinocytes; Wound Healing; Stimulate Hair Follicle	2499, 2552, 2553, 2584, 2607,	ID NO: Z for
(Repifermin; KGF-		epithelial cell proliferation assays	Production; Healing Of Dermal Wounds. Wound Healing;	2608, 2606, 2630	particular
2; Fibroblast		described in U.S. Pat. No. 6,077,692.	Eye Tissue Wounds, Dental Tissue Wounds, Oral Cavity		construct.
Growth Factor-10;			Wounds, Diabetic Ulcers, Dermal Ulcers, Cubitus Ulcers,
FGF-10)			Arterial Ulcers, Venous Stasis Ulcers, Burns Resulting
			From Heat Exposure Or Chemicals, or Other Abnormal
			Wound Healing Conditions such as Uremia, Malnutrition,
			Vitamin Deficiencies or Complications Associated With
			Systemic Treatment With Steroids, Radiation Therapy or
			Antineoplastic Drugs or Antimetabolites; Promote Dermal
			Reestablishment Subsequent To Dermal Loss; Increase the
			Adherence Of Skin Grafts To A Wound Bed; Stimulate Re-
			Epithelialization from The Wound Bed; To Promote Skin
			Strength; Improve The Appearance Of Aged Skin;
			Proliferate Hepatocytes, Lung, Breast, Pancreas, Stomach,
			Bladder, Small Intestine, Large Intestine; Sebocytes, Hair
			Follicles, Type II Pneumocytes, Mucin-Producing Goblet
			Cells, or Other Epithelial Cells, Endothelial Cells,
			Keratinocytes, or Basal Keratinocytes (and Their
			Progenitors) Contained Within The Skin, Lung, Liver,
			Bladder, Eye, Salivary Glands, or Gastrointestinal Tract;
			Reduce The Side Effects Of Gut Toxicity That Result From
			Radiation, Chemotherapy Treatments Or Viral Infections;
			Cytoprotector, especially of the Small Intestine Mucosa or
			Bladder; Mucositis (Mouth Ulcers); Regeneration Of Skin;
			Full and/or Partial Thickness Skin Defects, including Burns,
			(e.g., Repopulation Of Hair Follicles, Sweat Glands, And
			Sebaceous Glands); Psoriasis; Epidermolysis Bullosa;
			Blisters; Gastric and/or Doudenal Ulcers; Reduce Scarring;
			Inflamamatory Bowel Diseases; Crohn's Disease; Ulcerative
			Colitis; Gut Toxicity; Lung Damage; Repair Of Alveoli
			And/or Brochiolar Epithelium; Acute Or Chronic Lung
			Damage; Emphysema, ARDS; Inhalation Injuries; Hyaline
			Membrane Diseases; Infant Respiratory Distress Syndrome;
			Bronchopulmonary Displasia In Premature Infants;
			Fulminant Liver Failure; Cirrhosis, Liver Damage caused by
			Viral Hepatitis and/or Toxic Substances; Diabetes Mellitus;
			Inflammation.
TR2 (and TR2sv1,	Inhibits B cell proliferation,	Co-stimulation B-cell proliferation	Herpes; immune disorders; autoimmune disease; graft	1788 and 2129.	See Table 2, SEQ
TR2SV2;	and mediates and inhibits	assay and Ig production assay	versus host disease; graft rejection; variable		ID NO: Z for
TNFRSF14;	Herpes Simplex Virus (HSV)	(Moore et al., 1999, Science,	immunodeficiency; immunodeficiency syndromes; cancer.		particular
HVEM; Herpes	infection.	285(5425): 260-3.). HSV-1 and			construct.
Virus Entry		HSV-2 Infectivity Assay:
Mediator; ATAR)		International Publication No. WO
		97/04658
Macrophage derived	Chemotactic for monocyte-	Chemokine activities can be	Inflammatory diseases; wound healing; angiogenesis; AIDS	1809, 2137, 2474, 2475, 2476,	See Table 2, SEQ
chemokine, MDC	derived dendritic cells and IL-	determined using assays known in	infection.	and 2477.	ID NO: Z for
(Ckbeta-13)	2-activated natural killer cells.	the art: Methods in Molecular			particular
		Biology, 2000, vol. 138:			construct.
		Chemokine Protocols. Edited by:
		A. E. I. Proudfoot, T. N. C. Wells,
		and C. A. Power. © Humana Press
		Inc., Totowa, NJ
HAGDG59 (Retinal	Activates MIP1a release in	Dendritic cell assays are well	Immune disorders; cancer; viral infection; inflammation;	1830 and 1831.	See Table 2, SEQ
short-chain	Dendritic Cells.	known in the art. For example, J.	sepsis; arthritis; asthma.		ID NO: Z for
dehydrogenase)		Immunol. 158: 2919-2925 (1997);			particular
		J. Leukoc. Biol. 65: 822-828			construct.
		(1999).
GnRH	Promotes release of follicle-	GnRH is known to cause the	Infertility; Kallmann's syndrome or other forms of	1862 and 1863.	See Table 2, SEQ
(Gonadotropin	stimulating hormone and	release of follicle stimulating	hypergonadotropic hypergonadism (failure to go through		ID NO: Z for
Releasing Hormone)	luteinizing hormone from	hormone (FSH) and/or luteinizing	puberty naturally).		particular
	anterior pituitary.	hormone (LH) in vivo by a direct			construct.
		action on receptors in anterior
		pituitary gonadotropes. GnRH
		activity can be determined by
		measuring FSH levels in the
		medium of cultured gonadotropes
		before and after GnRH
		supplementation. For example,
		Baker et al. Biol Reprod 2000
		Sep.; 63(3): 865-71.
Teprotide	Inhibits angiotensin	Inhibition of ACE can be	Hypertension; congestive heart failure.	1866, 1867, 2025, and 2026.	See Table 2, SEQ
	converting enzyme (ACE).	determined using assays known in			ID NO: Z for
		the art. For example,			particular
		Anzenbacherova et al., J. Pharma			construct.
		Biomed Anal 2001 Mar.; 24(5-6):
		1151-6.
Human chemokine	Involved in inflammation,	Chemokine activities can be	Autoimmune disorders; Immunity; Vascular and	1933, 1934, 1947, 1948, 1955,	See Table 2, SEQ
HCC-1 (ckBeta-1;	allergy, tissue rejection, viral	determined using assays known in	Inflammatory disorders; HIV; AIDS; infectious diseases.	1998, 2355, 2412, 2449, 2837,	ID NO: Z for
HWFBD)	infection, and tumor biology;	the art: Methods in Molecular		2838, 2839, 2840, 2841, 2842,	particular
	enhances proliferation of	Biology, 2000, vol. 138:		2843, 2844, 2845, 2849, 2947,	construct.
	CD34+ myeloid progenitor	Chemokine Protocols. Edited by:		3066, 3105, 3124, 3125, 3139,
	cells.	A. E. I. Proudfoot, T. N. C. Wells,		3152, 3153, 3154, 3155, 3156,
		and C. A. Power. © Humana Press		3169, 3170, 3202, 3203, 3204,
		Inc., Totowa, NJ		3205, 3206, 3207, 3272
ACE2 inhibitor	Inhibits production of	Inhibition of angiotensin can be	Treatment for elevated angiotensin II and/or aldosterone	1989, 2000, 2001, and 2002.	See Table 2, SEQ
(DX512)	angiotensin II which induces	determined using assays known in	levels, which can lead to vasoconstriction, impaired cardiac		ID NO: Z for
	aldosterone production,	the art. For example, in vitro using	output and/or hypertension; Cardiovascular Disease;		particular
	arteriolar smooth muscle	a proliferation assay with rat	Cardiac Failure; Diabetes; Type II Diabetes; Proteinuria;		construct.
	vasoconstriction, and	cardiac fibroblasts as described in	Renal disorders, congestive heart failure.
	proliferation of cardiac	Naunyn Schmiedebergs Arch
	fibroblasts, Induces	Pharmacol 1999 May; 359(5): 394-9.
	angiogenesis; an enzyme that
	converts angiotensin I to
	angiotensin 1-9; also cleaves
	des-Arg, bradykinin and
	neurotensin.
TR1 (OCIF;	Inhibits osteoclastogenesis and	Coculture Assay for	Osteoporosis; Paget's disease; osteopenia; osteolysis;	2016, 2017, 2085, 2086, 2529,	See Table 2, SEQ
Osteoclastogenesis	bone resorption, and induces	Osteoclastogenesis, Bone	osteomyelitis; osteonecrosis; periodontal bone loss;	2530, 2531, 2532, 2555, 2556,	ID NO: Z for
inhibitory factor;	fibroblast proliferation.	resorption assay using fetal long-	osteoarthritis; rheumatoid arthritis; osteopetrosis;	2557, and 2558.	particular
osteoprotegerin,		bone organ culture system, dentine	periodontal, lytic, or metastatic bone disease; osteoclast		construct.
OPG; tumor		resorption assay, and fibroblast	differentiation inhibition; bone disorders; bone healing and
necrosis factor		proliferation assays are each	regeneration; organ calcification; vascular calcification.
receptor superfamily		described in Kwon et al., FASEB J.
member 11B		12: 845-854 (1998).
precursor;)
Human chemokine	Chemotactic for both activated	Chemokine activities can be	Cancer; Wound healing; Inflammatory disorders;	2101, 2240, 2241, 2245, 2246,	See Table 2, SEQ
Ckbeta-7	(CD3+) T cells and	determined using assays known in	Immmunoregulatory disorders; Atherosclerosis;	2247, and 2248.	ID NO: Z for
	nonactivated (CD14−)	the art: Methods in Molecular	Parasitic Infection; Rheumatoid Arthritis; Asthma;		particular
	lymphocytes and (CD4+) and	Biology, 2000, vol. 138:	Autoimmune disorders.		construct.
	(CD8+) T lymphocytes and	Chemokine Protocols. Edited by:
	(CD45RA+) T cells	A. E. I. Proudfoot, T. N. C. Wells,
		and C. A. Power. © Humana Press
		Inc., Totowa, NJ
CKbeta4	Attracts and activates	Chemokine activities can be	Cancer; Solid Tumors; Chronic Infection; Autoimmune	2141, 2330, 2335, 2336, 2337,	See Table 2, SEQ
(HGBAN46;	microbicidal leukocytes;	determined using assays known in	Disorders; Psoriasis; Asthma; Allergy; Hematopoiesis;	2338, and 2348.	ID NO: Z for
HE9DR66)	Attracts CCR6-expressing	the art: Methods in Molecular	Wound Healing; Bone Marrow Failure; Silicosis;		particular
	immature dendritic cells and	Biology, 2000, vol. 138:	Sarcoidosis; Hyper-Eosinophilic Syndrome; Lung		construct.
	memory/effector T cells; B-	Chemokine Protocols. Edited by:	Inflammation; Fibrotic Disorders; Atherosclerosis; Periodontal
	cell chemotaxis; inhibits	A. E. I. Proudfoot, T. N. C. Wells,	diseases; Viral diseases; Hepatitis.
	proliferation of myeloid	and C. A. Power. © Humana Press
	progenitors; chemotaxis of	Inc., Totowa, NJ
	PBMC's.
Leptin	Controls obesity through	in vivo modulation of food intake,	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2146, 2184, 2186, and 2187.	See Table 2, SEQ
	regulation of appetite,	reduction in body weight, and	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin		ID NO: Z for
	reduction of body weight, and	lowering of insulin and glucose	resistance; Insulin deficiency; Hyperlipidemia;		particular
	lowering of insulin and	levels in ob/ob mice,	Hyperketonemia; Non-insulin dependent Diabetes Mellitus		construct.
	glucose level.	radioimmunoassay (RIA) and	(NIDDM); Insulin-dependent Diabetes Mellitus (IDDM); a
		activation of the leptin receptor in a	Condition Associated With Diabetes Including, But Not
		cell-based assay. Protein Expr Purif	Limited To Obesity, Heart Disease, Hyperglycemia,
		1998 Dec.; 14(3): 335-42	Infections, Retinopathy, And/Or Ulcers; Metabolic
			Disorders; Immune Disorders; Obesity; Vascular Disorders;
			Suppression of Body Weight; Suppression of Appetite;
			Syndrome X; Immunological Disorders;
			Immunosuppression.
IL-1 receptor	Binds IL1 receptor without	1) Competition for IL-1 binding to	Autoimmune Disease; Arthritis; Rheumatoid Arthritis;	2181, 2182, 2183, and 2185.	See Table 2, SEQ
antagonist	activating the target cells;	IL-1 receptors in YT-NCI or	Asthma; Diabetes; Diabetes Mellitus; GVHD; Inflammatory		ID NO: Z for
(Anakinra; soluble	inhibits the binding of IL1-	C3H/HeJ cells (Carter et al., Nature	Bowel Disorders; Chron's Disease; Ocular Inflammation;		particular
interleukin-1	alpha and IL1-beta; and	344: 633-638, 1990);	Psoriasis; Septic Shock; Transplant Rejection; Inflammatory		construct.
receptor; IRAP;	neutralizes the biologic	2) Inhibition of IL-1-induced	Disorders; Rheumatic Disorders; Osteoporosis;
KINERET;	activity of IL1-alpha and IL1-	endothelial cell-leukocyte adhesion	Postmenopausal Osteoporosis; Stroke.
ANTRIL)	beta.	(Carter et al., Nature 344: 633-638,
		1990);
		3) Proliferation assays on A375-C6
		cells, a human melanoma cell
		line highly susceptible to the
		antiproliferative action of IL-1
		(Murai T et al., J. Biol. Chem. 276:
		6797-6806, 2001).
TREM-1	Mediates activation of	Secretion of cytokines,	Inflammation; Sepsis; bacterial infection; autoimmune	2226 and 2230.	See Table 2, SEQ
(Triggering	neutrophil and monocytes;	chemokines, degranulation, and	diseases; GVHD.		ID NO: Z for
Receptor Expressed	Stimulates neutrophil and	cell surface activation markers can			particular
on Monocytes 1)	monocyte-mediated	be determined using assays			construct.
	inflammatory response;	described in Bouchon et al, J
	Promotes secretion of TNF,	Immunol 2000 May
	IL-8, and MCP-1; Induces	15; 164(10): 4991-5.
	neutrophil degranulation,
	Ca2+ mobilization and
	tyrosine phosphorylation of
	extracellular signal-related
	kinase 1 (ERK1), ERK2 and
	phospholipase C-gamma.
HCNCA73	Induces T-cell activation-	FMAT can be used to measure T-	Autoimmune disorders; Inflammation of the gastrointestinal	2244 and 2365.	See Table 2, SEQ
	expression of CD152 marker;	cell surface markers (CD69,	tract; Cancer; Colon Cancer; Allergy; Crohn's disease.		ID NO: Z for
	Stimulates release of TNF-a	CD152, CD71, HLA-DR) and T-			particular
	and MIP-1a from immature,	cell cytokine production (e.g., IFNg			construct.
	monocyte-derived dendritic	production). J. of Biomol. Screen.
	cells; Promotes maturation of	4: 193-204 (1999). Other T-cell
	dendritic cells.	proliferation assays:
		“Lymphocytes: a practical
		approach” edited by: SL Rowland,
		AJ McMichael - Chapter 6, pages
		138-160 Oxford University Press
		(2000); WO 01/21658 Examples
		11-14, 16-17 and 33.
VEGF-2 (Vascular	Promotes endothelial cell	VEGF activity can be determined	Coronary artery disease; Critical limb ischemia; Vascular	2251, 2252, 2256, and 2257.	See Table 2, SEQ
Endothelial Growth	proliferation.	using assays known in the art,	disease; proliferation of endothelial cells, both vascular and		ID NO: Z for
Factor-2; VEGF-C)		such as those disclosed in	lymphatic. Antagonists may be useful as anti-angiogenic		particular
		International Publication No.	agents; Cancer.		construct.
		WO0045835, for example.
HCHNF25	Activates MIP1a Release in	Dendritic cell assays are well	Immune disorders; cancer.	2271, 2280, and 2320.	See Table 2, SEQ
(jumping	Dendritic Cells.	known in the art. For example, J.			ID NO: Z for
translocation		Immunol. 158: 2919-2925 (1997);			particular
breakpoint)		J. Leukoc. Biol. 65: 822-828			construct.
		(1999).
HLDOU18 (Bone	Activates L6/GSK3 kinase	Assays for activation of GSK3	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2328, 2340, 2350, 2351, 22359,	See Table 2, SEQ ID
Morphogenic	assay.	kinase activity are well known in	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin	362, 2367, 2369, 22370, 2473,	NO: Z for particular
Protein 9 (BMP9);		the art. For example, Biol.	resistance; Insulin deficiency; Hyperlipidemia;	2623, 2624,	construct.
Growth		Chem. 379(8-9): (1998) 1101-1110.;	Hyperketonemia; Non-insulin dependent Diabetes Mellitus	2625, 2631,
differentiation		Biochem J. 1993 Nov.	(NIDDM); Insulin-dependent Diabetes Mellitus (IDDM); A	2632, 2633.
factor-2 precursor		15; 296 (Pt 1): 15-9.	Condition Associated With Diabetes Including, But Not
(GDF-2 precursor))			Limited To Obesity, Heart Disease, Hyperglycemia,
			Infections, Retinopathy, And/Or Ulcers; Metabolic
			Disorders; Immune Disorders; Obesity; Vascular Disorders;
			Suppression of Body Weight; Suppression of Appetite;
			Syndrome X.
Glucagon-Like-Peptide	Stimulates the synthesis and	GLP1 activity may be assayed in	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2448, 2455, 2456, 2457, 2803,	See Table 2, SEQ ID
1 (GLP1;	release of insulin; enhances the	vitro using a [3-H]-glucose uptake	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;	2804, 2900, 2904, 2945, 2964,	NO: Z for particular
Insulinotropin)	sensitivity of adipose, muscle,	assay. (J Biol Chem 1999 Oct. 22;	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-	2982, 3070, 2802, 3027, 3028,	construct.
	and liver tissues towards insulin;	274(43): 30864-30873).	insulin dependent Diabetes Mellitus (NIDDM); Insulin-	3045, 3046, 3069, 3071, 3072,
	stimulates glucose uptake; slows		dependent Diabetes Mellitus (IDDM); A Condition Associated	3085, 3086, 3087, 3140, 3309
	the digestive process; suppresses		With Diabetes Including, But Not Limited To Obesity, Heart
	appetite; blocks the secretion of		Disease, Hyperglycemia, Infections, Retinopathy, And/Or
	glucagon.		Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
Exendin-4 (AC-2993)	Stimulates the synthesis and	Exendin-4 activity may be assayed	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2469 and 2470.	See Table 2, SEQ ID
	release of insulin; enhances the	in vitro using a [3-H]-glucose	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;		NO: Z for particular
	sensitivity of adipose, muscle,	uptake assay. (J Biol Chem 1999	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-		construct.
	and liver tissues towards insulin;	Oct. 22; 274(43): 30864-30873).	insulin dependent Diabetes Mellitus (NIDDM); Insulin-
	stimulates glucose uptake; slows		dependent Diabetes Mellitus (IDDM); A Condition Associated
	the digestive process; suppresses		With Diabetes Including, But Not Limited To Obesity, Heart
	appetite; blocks the secretion of		Disease, Hyperglycemia, Infections, Retinopathy, And/Or
	glucagon.		Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
T20 (T20 HIV	a peptide from residues 643-678	Virus inhibition assays as described	HIV; AIDS; SIV (simian immunodeficiency virus) infection.	7777, 2672, 2673	See Table 2, SEQ ID
inhibitory peptide,	of the HIV gp41 transmembrane	in Zhang et al., Sep. 26, 2002,			NO: Z for particular
DP178; DP178 HIV	protein ectodomain which binds	Sciencexpress			construct.
inhibitory peptide)	to gp41 in its resting state and	(www.sciencexpress.org).
	prevents transformation to the
	fusogenic state
T1249 (T1249 HIV	a second generation HIV fusion	Virus inhibition assays as described	HIV; AIDS; SIV (simian immunodeficiency virus) infection	9999, 2667, 2670, 2946	See Table 2, SEQ ID
inhibitory peptide;	inbitor	in Zhang et al., Sep. 26, 2002,			NO: Z for particular
T1249 anti-HIV		Sciencexpress			construct.
peptide)		(www.sciencexpress.org).
Interferon Hybrids,	Confers a range of cellular	Anti-viral assay: Rubinstein S,	Viral infections; HIV Infections; Hepatitis; Chronic Hepatitis;	2875, 2872, 2876, 2874, 2873.	See Table 2, SEQ ID
specifically preferred:	responses including antiviral,	Familletti PC, Pestka S. (1981)	Hepatitis B; Chronic Hepatitis B; Hepatitis C; Chronic		NO: Z for particular
IFNalpha A/D hybrid	antiproliferative, antitumor and	Convenient assay for interferons.	Hepatitis C; Hepatitis D; Chronic Hepatitis D; Human		construct.
(BglII version)	immunomodulatory activities;	J. Virol. 37(2): 755-8; Anti-	Papillomavirus; Herpes Simplex Virus Infection; External
IFNalpha A/D hybrid	stimulate production of two	proliferation assay: Gao Y, et al	Condylomata Acuminata; HIV; HIV Infection; Oncology;
(PvuII version)	enzymes: a protein kinase and an	(1999) Sensitivity of an epstein-barr	Cancer; Solid Tumors; Melanoma; Malignant Melanoma;
IFNalpha A/F hybrid	oligoadenylate synthetase. Also,	virus-positive tumor line, Daudi, to	Renal Cancer (e.g., Renal Cell Carcinoma); Lung Cancer (e.g,.
IFNalpha A/B hybrid	modulates MHC antigen	alpha interferon correlates with	Non-Small Cell Lung Cancer or Small Cell Lung Cancer)
IFNbeta 1/alpha D	expression, NK cell activity and	expression of a GC-rich viral	Colon Cancer; Breast Cancer; Liver Cancer; Prostate Cancer;
hybrid (IFNbeta-	IFNg production and IL12	transcript. Mol Cell Biol.	Bladder Cancer; Gastric Cancer; Sarcoma; AIDS-Related
1/alpha-1 hybrid)	production in monocytes.	19(11): 7305-13.	Kaposi's Sarcoma; Lymphoma; T Cell Lymphoma; Cutaneous
IFNalpha/beta hybrid			T-Cell Lymphoma; Non-Hodgkin's Lymphoma; Brain Cancer;
			Glioma; Glioblastoma Multiforme; Cervical Dysplasia;
			Leukemia; Preleukemia; Bone Marrow Disorders; Bone
			Disorders; Hairy Cell Leukemia; Chronic Myelogeonus
			Leukemia; Hematological Malignancies; Hematological
			Disorders; Multiple Myeloma; Bacterial Infections;
			Chemoprotection; Thrombocytopenia; Multiple Sclerosis;
			Pulmonary Fibrosis; Age-Related Macular Degeneration;
			Macular Degeneration; Crohn's Disease; Neurological
			Disorders; Arthritis; Rheumatoid Arthritis; Ulcerative Colitis;
			Osteoporosis, Osteopenia, Osteoclastogenesis; Fibromyalgia;
			Sjogren's Syndrome; Chronic Fatigue Syndrome; Fever;
			Hemmorhagic Fever; Viral Hemmorhagic Fevers;
			Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes
			mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;
			Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-
			insulin dependent Diabetes Mellitus (NIDDM); Insulin-
			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
B-type natriuretic	stimulates smooth muscle	Inhibition of angiotensin can be	Congestive heart failure; cardiac volume overload; cardiac	3119, 8888.	See Table 2, SEQ ID
peptide (BNP, brain	relaxation and vasodilation,	determined using assays known in	decompensation; Cardiac Failure; Left Ventricular		NO: Z for particular
natriuretic peptide)	natriuresis, and suppression of	the art, for example using an in vitro	Dysfunction; Dyspnea		construct.
	renin-angiotensin and	proliferation assay with rat cardiac
	endothelin.	fibroblasts as described in Naunyn
		Schmiedebergs Arch Pharmacol
		1999 May; 359(5): 394-9.
		Vasodilation can be measured in
		animals by measuring the myogenic
		responses of small renal arteries in
		an isobaric arteriograph system (see
		Am J Physiol Regul Integr Comp
		Physiol 2002 Aug.;
		283(2): R349-R355).
		Natriuesis is determined by
		measuring the amount of sodium in
		the urine.
α-defensin, including	Suppression of HIV replication;	Virus inhibition assays as described	HIV, AIDS; ARC.	3208, 3209, 3210.	See Table 2, SEQ ID
alpha 1 defensin, alpha	active against bacteria, fungi,	in Zhang et al., Sep. 26, 2002,			NO: Z for particular
2 defensin, alpha 3	and enveloped viruses.	Sciencexpress			construct.
defensin (myeloid-		(www.sciencexpress.org).
related defensin;
DEFA1; neutrophil-
specific defensin;
CAF)
Phosphatonin (matrix	Regulation of phosphate	Blood phosphate levels can be	Hyperphosphatemia; Hyperphosphatemia in chronic renal	3238.	See Table 2, SEQ ID
extracellular	metabolism.	measured using methods known in	failure; hypophosphatemia; Osteomalacia; Rickets; X-linked		NO: Z for particular
phosphoglycoprotein;		the art such as the	dominant hypophosphatemic rickets/osteomalacia (XLH);		construct.
MEPE)		Hypophosphatemic Rat Bioassay.	autosomal dominant hypophosphatemic rickets/osteomalacia
		Zoolog Sci 1995 Oct.; 12(5): 607-10.	(ADHR); tumor-induced rickets/osteomalacia (TIO).
P1pal-12 (pepducin,	Regulation of protease-activated	Platelet aggregation can be	Protection against systemic platelet activation, thrombus, heart	3274.	See Table 2, SEQ ID
PAR1-based pepducin)	receptor (PAR) signal	measured using methods known in	attack, stroke, and/or coagulation disorders.		NO: Z for particular
	transduction and thrombin-	the art such as described in Nature			construct.
	mediated aggregation of human	Medicine 2002 Oct.; 8(10):
	platelets.	1161-1165.
P4pal-10 (pepducin,	Regulation of protease-activated	Platelet aggregation can be	Protection against systemic platelet activation, thrombus, heart	3275.	See Table 2, SEQ ID
PAR4-based pepducin)	receptor (PAR) signal	measured using methods known in	attack, stroke, and/or coagulation disorders.		NO: Z for particular
	transduction and thrombin-	the art such as described in Nature			construct.
	mediated aggregation of human	Medicine 2002 Oct.; 8(10):
	platelets.	1161-1165.
HRDFD27	Involved in the proliferation of T	T-cell proliferation can be measured	Chemoprotection; Adjunct to Chemotherapy; Inflammatory	2361	See Table 2, SEQ ID
	cells; Production of TNFgamma.	using assays known in the art. For	disorders; Cancer; Leukemia; Myelocytic leukemia;		NO: Z for particular
		example, “Lymphocytes: a practical	Neutropenia, Primary neutropenias (e.g.; Kostmann		construct.
		approach” edited by: SL Rowland,	syndrome); Secondary neutropenia; Prevention of neutropenia;
		AJ McMichael - chapter 6, pages	Prevention and treatment of neutropenia in HIV-infected
		138-160 Oxford University Press	patients; Prevention and treatment of neutropenia associated
		(2000); and “Current Protocols on	with chemotherapy; Infections associated with neutropenias;
		CD-ROM” section 3.12	Myelopysplasia; Autoimmune disorders; Psoriasis;
		Proliferation Assays for T-cell	Mobilization of hematopoietic progenitor cells; Wound
		Function John Wiley & Soncs, Inc.	Healing; Autoimmune Disease; Transplants; Bone marrow
		(1999).	transplants; Acute myelogeneous leukemia; Lymphoma, Non-
			Hodgkin's lymphoma; Acute lymphoblastic leukemia;
			Hodgkin's disease; Accelerated myeloid recovery; Glycogen
			storage disease
HWHGZ51 (CD59;	Stimulates an immune response	The ability to affect chondrocyte	Skeletal diseases and disorders; Musculoskeletal diseases and	2407, 2408	See Table 2, SEQ ID
Metastasis-associated	and induces inflammation by	differentiation can be measured	disorders; Bone fractures and/or breaks; Osteoporosis		NO: Z for particular
GPI-adhered protein	inducing mononuclear cell,	using methods known in the art,	(postmenopausal, senile, or idiopathic juvenile); Gout and/or		construct.
homolog)	eosinophil and PMN infiltration;	such as described in Bone (1995)	pseudogout; Paget's disease; Osteoarthritis; Tumors and/or
	Inhibits growth of breast cancer,	Sep.; 17(3): 279-86.	cancers of the bone (osteochondromas, benign chondromas,
	ovarian cancer, leukemia, and		chondroblastomas, chondromyxoid fibromas, osteoid
	melanoma; Overexpressed in		osteomas, giant cell tumors, multiple myelomas,
	colon, lung, breast and rectal		osteosarcomas, fibrosarcomas, malignant fibrous
	tumors; Regulates glucose and/		histiocytomas, chondrosarcomas, Ewing's tumors, and/or
	or FFA update by adipocytes		malignant lymphomas); Bone and joint infections
	and skeletal muscle; Induces		(osteomyelitits and/or infectious arthritis); Charcot's joints;
	redifferentiation of chondrocytes		Heel spurs; Sever's disease; Sport's injuries; Cancer; Solid
			Tumors; Melanoma; Malignant Melanoma; Renal Cancer
			(e.g., Renal Cell Carcinoma); Lung Cancer (e.g,. Non-Small
			Cell Lung Cancer or Small Cell Lung Cancer) Colon Cancer;
			Breast Cancer; Liver Cancer; Prostate Cancer; Bladder
			Cancer; Gastric Cancer; Sarcoma; AIDS-Related Kaposi's
			Sarcoma; Lymphoma; T Cell Lymphoma; Cutaneous T-Cell
			Lymphoma; Non-Hodgkin's Lymphoma; Brain Cancer;
			Glioma; Glioblastoma Multiforme; Cervical Dysplasia;
			Leukemia; Preleukemia; Bone Marrow Disorders; Bone
			Disorders; Hairy Cell Leukemia; Chronic Myelogeonus
			Leukemia; Hematological Malignancies; Hematological
			Disorders; Multiple Myeloma; Kidney diseases and disorders;
			Shonlein-Henoch purpura, Berger disease, celiac disease,
			dermatitis herpetiformis, Chron disease; Diabetes; Diabetes
			Insipidus; Diabetes mellitus; Type 1 diabetes; Type 2 diabetes;
			Insulin resistance; Insulin deficiency; Hyperlipidemia;
			Hyperketonemia; Non-insulin dependent Diabetes Mellitus
			(NIDDM); Insulin-dependent Diabetes Mellitus (IDDM); A
			Condition Associated With Diabetes Including, But Not
			Limited To Obesity, Heart Disease, Hyperglycemia,
			Infections, Retinopathy, And/Or Ulcers; Metabolic Disorders;
			Immune Disorders; Obesity; Vascular Disorders; Suppression
			of Body Weight; Suppression of Appetite; Syndrome X;
			Kidney disorders; Hyperinsulinemia; Hypoinsulinemia;
			Immunological disorders (e.g. arthritis, asthma,
			immunodeficiency diseases, AIDS, rheumatoid arthritis,
			granulomatous disease, inflammatory bowl disease, sepsis,
			acne, neutropenia, neutrophilia, psoriasis, hypersensitivities,
			T-cell mediated cytotoxicity, host-versus-graft disease,
			autoimmunity disorders, demyelination, systemic lupus
			erythematosis, drug induced hemolytic anemia, rheumatoid
			arthritis, Sjorgren's disease, scleroderma)
C17 (cytokine-like	Inhibits glucose and/or FFA	Proliferation of kidney mesangial	Kidney diseases and disorders; Shonlein-Henoch purpura,	2489, 2490	See Table 2, SEQ ID
protein C17)	uptake by adipocytes; Induces	cells can be assayed using	Berger disease, celiac disease, dermatitis herpetiformis, Chron		NO: Z for particular
	proliferation of kidney	techniques described in J. Investig.	disease; Diabetes; Diabetes Insipidus; Diabetes mellitus; Type		construct.
	mesangial cells; Regulation	Med. (1998) Aug.; 46(6): 297-302.	1 diabetes; Type 2 diabetes; Insulin resistance; Insulin
	of cytokine production		deficiency; Hyperlipidemia; Hyperketonemia; Non-insulin
	and antigen presentation		dependent Diabetes Mellitus (NIDDM); Insulin-dependent
			Diabetes Mellitus (IDDM); A Condition Associated With
			Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X; Kidney disorders;
			Hyperinsulinemia; Hypoinsulinemia; Hematopoietic disorders;
			Immunological diseases and disorders; Developmental
			diseases and disorders; Hepatic diseases and disorders; Cancer
			(particularly leukemia); Immunological disorders (e.g.
			arthritis, asthma, immunodeficiency diseases, AIDS,
			rheumatoid arthritis, granulomatous disease, inflammatory
			bowl disease, sepsis, acne, neutropenia, neutrophilia, psoriasis,
			hypersensitivities, T-cell mediated cytotoxicity, host-versus-
			graft disease, autoimmunity disorders, demyelination,
			systemic lupus erythematosis, drug induced hemolytic anemia,
			rheumatoid arthritis, Sjorgren's disease, scleroderma)
HDPBQ71	Regulates production and	Such assays that may be used or	Blood disorders and infection (e.g., viral infections,	2515, 2545	See Table 2, SEQ ID
	secretion of IFNgamma;	routinely modified to test	tuberculosis, infections associated with chronic		NO: Z for particular
	Activation of myeloid cells	immunomodulatory activity of	granulomatosus disease and malignant osteoporosis);		construct.
	and/or hematopoietic cells	polypeptides of the invention	Autoimmune disease (e.g., rheumatoid arthritis, systemic
		(including antibodies and agonists	lupus erythematosis, multiple sclerosis); Immunodeficiency,
		or antagonists of the invention)	boosting a T cell-mediated immune response, and suppressing
		include the assays disclosed in	a T cell-mediated immune response; Inflammation and
		Miraglia et al., J Biomolecular	inflammatory disorders; Idiopathic pulmonary fibrosis;
		Screening 4: 193-204 (1999);	Neoplastic diseases (e.g., leukemia, lymphoma, melanoma);
		Rowland et al., ““Lymphocytes: a	Neoplasms and cancers, such as, for example, leukemia,
		practical approach”” Chapter 6:	lymphoma, melanoma, and prostate, breast, lung, colon,
		138-160 (2000); Gonzalez et al.,	pancreatic, esophageal, stomach, brain, liver and urinary
		J Clin Lab Anal 8(5):	cancer;. Benign dysproliferative disorders and pre-neoplastic
		225-233 (1995); Billiau	conditions, such as, for example, hyperplasia, metaplasia,
		et al., Ann NY Acad Sci 856:	and/or dysplasia; Anemia; Pancytopenia; Leukopenia;
		22-32 (1998); Boehm et al.,	Thrombocytopenia; Hodgkin's disease; Acute lymphocytic
		Annu Rev Immunol 15: 749-795	anemia (ALL); Plasmacytomas; Multiple myeloma; Burkitt's
		(1997), and Rheumatology (Oxford)	lymphoma; Arthritis; AIDS; Granulomatous disease;
		38(3): 214-20 (1999)	Inflammatory bowel disease; Sepsis; Neutropenia;
			Neutrophilia; Psoriasis; Suppression of immune reactions to
			transplanted organs and tissues; Hemophilia;
			Hypercoagulation; Diabetes mellitus; Endocarditis;
			Meningitis; Lyme Disease; Asthma; Allergy
Oscar (osteoclast-	Regulator of osteoclast	Assay to detect osteoclast	Skeletal diseases and disorders; Musculoskeletal diseases and	2571, 2749	See Table 2, SEQ ID
associated receptor	differentiation; regulator of	differentiation is described in J.	disorders; Bone fractures and/or breaks; Osteoporosis		NO: Z for particular
isoform-3)	innate and adaptive immune	Exp. Med. (2002) Jan. 21;	(postmenopausal, senile, or idiopathic juvenile); Gout and/or		construct.
	responses	195(2): 201-9.	pseudogout; Paget's disease; Osteoarthritis; Tumors and/or
			cancers of the bone (osteochondromas, benign chondromas,
			chondroblastomas, chondromyxoid fibromas, osteoid
			osteomas, giant cell tumors, multiple myelomas,
			osteosarcomas, fibrosarcomas, malignant fibrous
			histiocytomas, chondrosarcomas, Ewing's tumors, and/or
			malignant lymphomas); Bone and joint infections
			(osteomyelitits and/or infectious arthritis); Charcot's joints;
			Heel spurs; Sever's disease; Sport's injuries
Tumstatin (T5, T7 or	Inhibits angiogenesis; Inhibits	A tumor cell proliferation assay is	Cancer; Solid Tumors; Melanoma; Malignant Melanoma;	2647, 2648, 2649, 2650, 2943,	See Table 2, SEQ ID
T8 peptide;	tumor growth; Inhibits protein	described in J. Biol. Chem. (1997)	Renal Cancer (e.g., Renal Cell Carcinoma); Lung Cancer (e.g,.	2944, 3047, 3048	NO: Z for particular
α3(IV)NC1)	synthesis	272: 20395-20401.	Non-Small Cell Lung Cancer or Small Cell Lung Cancer)		construct.
		Protein synthesis can be measured	Colon Cancer; Breast Cancer; Liver Cancer; Prostate Cancer;
		as described in Science (2002) Jan.	Bladder Cancer; Gastric Cancer; Sarcoma; AIDS-Related
		4; 295(5552): 140-3.	Kaposi's Sarcoma; Lymphoma; T Cell Lymphoma; Cutaneous
			T-Cell Lymphoma; Non-Hodgkin's Lymphoma; Brain Cancer;
			Glioma; Glioblastoma Multiforme; Cervical Dysplasia;
			Leukemia; Preleukemia; Bone Marrow Disorders; Bone
			Disorders; Hairy Cell Leukemia; Chronic Myelogeonus
			Leukemia; Hematological Malignancies; Hematological
			Disorders; Multiple Myeloma; Angiogenesis
CNTF (Ciliary	Enhances myelin formation;	Regulation of myelin formation	Neurological and neural diseases and disorders, particularly	2724, 2725, 3171, 3172	See Table 2, SEQ ID
neurotrophic factor)	Reduces photoreceptor	can be assayed as described	diseases and disorders associated with myelin and		NO: Z for particular
	degredation; Regulates calcium	in J. Neurosci. (2002)	demyelination, such as, for example, ALS, multiple sclerosis,		construct.
	currents	Nov. 1; 22(21): 9221-7.	Huntington's disease; Neuronal and spinal cord injuries;
			Disorders of the eye, such as, for example, retinitis
			pigmentosa, blindness, color-blindness, macular degeneration.
Somatostatin	Inhibits growth hormone,	Inhibition of growth hormone	Cancer; Metastatic carcinoid tumors; Vasoactive Intestinal	2798, 2825, 2830, 2831, 2902	See Table 2, SEQ ID
(Octreotide; octreotide	glucagons and insulin;	release in humans by somatostatin	Peptide secreting adenomas; Diarrhea and Flushing; Prostatic		NO: Z for particular
acetate; Sandostating	Suppresses LF response to	can be measured as described in J.	disorders and cancers; Breast cancer; Gastrointestinal		construct.
LAR ®)	GnRH; Decreases splanchnic	Clin. Endocrinol. Metab. (1973)	disorders and cancers; Cancers of the endocrine system; Head
	blood flow; Inhibits release of	Oct.; 37(4): 632-4.	and neck paragangliomas; Liver disorders and cancers;
	serotonin, gastrin, vasoactive	Inhibition of insulin secretion by	Nasopharyngeal cancers; Thyroid disorders and cancers;
	intestinal peptide, secretin,	somatostatin can be measured as	Acromegaly; Carcinoid Syndrome; Gallbladder disorders, such
	motilin, and pancreatic	described in the Lancet (1973) Dec..	as gallbladder contractility diseases and abnormal bile
	polypeptide.	8; 2(7841): 1299-1301.	secretion; Psoriasis; Diabetes; Diabetes Insipidus; Diabetes
			mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;
			Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-
			insulin dependent Diabetes Mellitus (NIDDM); Insulin-
			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X; Kidney disorders;
			Neurological disorders and diseases, including Alzheimers
			Disease, Parkinson's disease and dementia; Neuropsychotic
			disorders, including Bipolar affective disorder; Rheumatoid
			arthritis; Hypertension; Intracranial hypertension; Esophageal
			varices; Graves' disease; Seizures; Epilepsy; Gastritis;
			Angiogenesis;
IL-22 (IL22,	Stimulates glucose uptake in	IL-22 activity may be assayed in	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2901, 2903	See Table 2, SEQ ID
interleukin-22; IL17D,	skeletal muscle cells; increases	vitro using a [3-H]-glucose uptake	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;		NO: Z for particular
IL27)	skeletal muscle insulin	assay. (J Biol Chem 1999 Oct. 22;	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-		construct.
	sensitivity.	274(43): 30864-30873).	insulin dependent Diabetes Mellitus (NIDDM); Insulin-
			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
HCE1P80	Stimulates glucose uptake in;	HCE1P80 activity may be assayed	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2908, 3049, 3050, 3051, 3052	See Table 2, SEQ ID
	increases insulin sensitivity.	in vitro using a [3-H]-glucose	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;		NO: Z for particular
		uptake assay. (J Biol Chem 1999	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-		construct.
		Oct. 22; 274(43): 30864-30873).	insulin dependent Diabetes Mellitus (NIDDM); Insulin-
			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
HDRMI82	Stimulates glucose uptake;	HDRMI82 activity may be assayed	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2909	See Table 2, SEQ ID
	increases insulin sensitivity.	in vitro using a [3-H]-glucose	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;		NO: Z for particular
		uptake assay. (J Biol Chem 1999	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-		construct.
		Oct. 22; 274(43): 30864-30873).	insulin dependent Diabetes Mellitus (NIDDM); Insulin-
			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
HDALV07	Modulates insulin action	Insulin activity may be assayed in	Diabetes; Diabetes Insipidus; Diabetes mellitus; Type 1	3053, 3055, 3056	See Table 2, SEQ ID
(adiponectin; gelatin-		vitro using a [3-H]-glucose uptake	diabetes; Type 2 diabetes; Insulin resistance; Insulin		NO: Z for particular
binding 28k protein		assay. (J Biol Chem 1999 Oct. 22;	deficiency; Hyperlipidemia; Hyperketonemia; Non-insulin		construct.
precurson; adipose		274(43): 30864-30873).	dependent Diabetes Mellitus (NIDDM); Insulin-dependent
most abundant gene			Diabetes Mellitus (IDDM); A Condition Associated With
transcript; APM-1;			Diabetes Including, But Not Limited To Obesity, Heart
GBP28; ACRP30;			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
ADIPOQ)			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X; Hyperglycemia;
			Familial combined hyperlipidemia; Metabolic syndrome;
			Inflammatory disorders; Atherogenic disorders
C Peptide	An insulin precursor involved in	C-peptide concentrations can be	Diabetes; Diabetes Insipidus; Diabetes mellitus; Type 1	3088, 3149	See Table 2, SEQ ID
	insulin regulation	measured using assays well known	diabetes; Type 2 diabetes; Insulin resistance; Insulin		NO: Z for particular
		in the art, such as the one described	deficiency; Hyperlipidemia; Hyperketonemia; Non-insulin		construct.
		in PNAS (1970) Sep.; 67(1): 148-55	dependent Diabetes Mellitus (NIDDM); Insulin-dependent
			Diabetes Mellitus (IDDM); A Condition Associated With
			Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X; Hyperglycemia;
			Familial combined hyperlipidemia; Metabolic syndrome
HCBOG68 (enteric	Controls proliferation/	Activation of cAMP-mediated	Treatment of Obesity; treatment of Diabetes; suppression of	3106, 3270	See Table 2, SEQ ID
adipokine; Fat SID;	differentiation or metabolism/	transcription in adipocytes can be	body weight gain; suppression of appetite. Hyperglycemia;		NO: Z for particular
proline rich acidic	physiology/pathology/of	assayed using methods known in	Diabetes; Diabetes Insipidus; Diabetes mellitus; Type 1		construct.
protein)	adipocytes and adipose tissue in	the art (Berger et al., Gene 66: 1-10	diabetes; Type 2 diabetes; Insulin resistance; Insulin
	response to dietary conditions.	(1998); Cullen and Malm, Methods	deficiency; Hyperlipidemia; Hyperketonemia; Non-insulin
		in Enzymol 216: 362-368 (1992);	dependent Diabetes Mellitus (NIDDM); Insulin-dependent
		Henthorn et al., Proc Natl Acad Sci	Diabetes Mellitus (IDDM); A Condition Associated With
		USA 85: 6342-6346 (1988); Reusch	Diabetes Including, But Not Limited To Obesity, Heart
		et al., Mol Cell Biol 20(3):	Disease, Hyperglycemia, Infections, Retinopathy, And/Or
		1008-1020 (2000); and	Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
		Klemm et al., J Biol Chem 273:	Vascular Disorders; Suppression of Body Weight;
		917-923 (1998)).	Suppression of Appetite; Syndrome X.
			Other indications for antibodies and/or antagonists, include
			treatment of weight loss; treatment of AIDS wasting; appetite
			stimulant; treatment of cachexia.
PYY (Peptide YY),	Decreases appetite; increases	Appetite and food intake can be can	Most preferred: Treatment of Obesity; treatment of Diabetes;	3108, 3109, 3281, 3117, 3118,	See Table 2, SEQ ID
including PYY3-36	satiety; decreases food intake.	be measured by methods known in	suppression of body weight gain; suppression of appetite.	3282.	NO: Z for particular
(amino acid residues		the art (Batterham et al. Nature	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes		construct.
31-64 of full length		2002; 418: 650654)	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;
PYY, amino acid			Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-
residues 3-36 of			insulin dependent Diabetes Mellitus (NIDDM); Insulin-
mature PYY)			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
			Other indications for antibodies, antagonists: treatment of
			weight loss; treatment of AIDS wasting; appetite stimulant;
			treatment of cachexia.
WNT10b	Inhibits adipogenesis.	WNT10b activity can be measured	Most preferred: Treatment of Obesity; suppression of body	3141	See Table 2, SEQ ID
		using adipogenesis inhibition assays	weight gain; suppression of appetite.		NO: Z for particular
		(Ross et al., Science 2000;	Other indications: Hyperglycemia; Diabetes; Diabetes		construct.
		289(5481): 950-953	Insipidus; Diabetes mellitus; Type 1 diabetes; Type 2 diabetes;
			Insulin resistance; Insulin deficiency; Hyperlipidemia;
			Hyperketonemia; Non-insulin dependent Diabetes Mellitus
			(NIDDM); Insulin-dependent Diabetes Mellitus (IDDM).
WNT11	Promotes cardiogenesis.	WNT11 activity can be measured	Treatment of Cardiovascular disorders; Congestive Heart	3142	See Table 2, SEQ ID
		using assays known in the art,	Failure; Myocardial Infarction.		NO: Z for particular
		including cardiogenesis assays			construct.
		(Eisenberg et al., Dev Dyn 1999
		Sep.; 216(1): 45-58).
Herstatin	Inhibits cancer proliferation.	Herstatin activity can be measured	Oncology; Cancer; Solid Tumors; Melanoma; Malignant	3143	See Table 2, SEQ ID
		using cell proliferation assays	Melanoma; Renal Cancer (e.g., Renal Cell Carcinoma); Lung		NO: Z for particular
		known in the art (Doherty et al.,	Cancer (e.g,. Non-Small Cell Lung Cancer or Small Cell Lung		construct.
		PNAS 1999; 96(19): 10869-10874.	Cancer); Colon Cancer; Breast Cancer; Liver Cancer; Prostate
			Cancer; Bladder Cancer; Gastric Cancer; Sarcoma; AIDS-
			Related Kaposi's Sarcoma; Lymphoma; T Cell Lymphoma;
			Cutaneous T-Cell Lymphoma; Non-Hodgkin's Lymphoma;
			Brain Cancer; Glioma; Glioblastoma Multiforme; Cervical
			Dysplasia; Leukemia; Preleukemia; Hairy Cell Leukemia;
			Chronic Myelogeonus Leukemia; Hematological
			Malignancies; Hematological Disorders; Multiple Myeloma.
Adrenomedullin	stimulates vasodilation;	Vasodilation can be measured using	Treatment of Congestive Heart Failure; Hypertension;	3144	See Table 2, SEQ ID
	promotes bone growth.	assays known in the art (Ashton et	Myocardial Infarction; Septic Shock; Osteoporosis;		NO: Z for particular
		al. Pharmacology 2000;	Postmenopausal osteoporosis; Osteopenia.		construct.
		61(2): 101-105.
		The promotion of bone growth
		can be measured using assays
		known in the art, such as the
		osteoblast proliferation assay
		(Cornish et al. Am J Physiol 1997
		Dec.; 273(6 Pt 1): E1113-20).
Nogo Receptor	Receptor for the axon growth	The promotion of axon regeneration	Treatment of Central Nervous System Damage; Spinal Cord	3184, 3185	See Table 2, SEQ ID
	inhibitor, Nogo.	and growth can be measured using	Injury; Peripheral Nerve Damage; Neurodegenerative		NO: Z for particular
		assays known in the art (Fournier et	Diseases; Parkinson's Disease; Alzheimer's Disease;		construct.
		al. Nature 2001; 409(6818):	Huntington's Disease; Amyotrophic Lateral Sclerosis;
		341-346).	Progressive Supranuclear Palsy; Creutzfeld-Jacob Disease;
			Motor Neuron Disease.
CART (Cocaine-and	Inhibits food intact and fat	Appetite and food intake can be can	Most preferred: Treatment of Obesity; suppression of body	3232	See Table 2, SEQ ID
Amphetamine-	storage; promotes lipid	be measured by methods known in	weight gain; suppression of appetite.		NO: Z for particular
Regulated Transcript)	oxidation.	the art (Batterham et al. Nature	Other indications: Hyperglycemia; Diabetes; Diabetes		construct.
		2002; 418: 650654)	Insipidus; Diabetes mellitus; Type 1 diabetes; Type 2 diabetes;
			Insulin resistance; Insulin deficiency; Hyperlipidemia;
			Hyperketonemia; Non-insulin dependent Diabetes Mellitus
			(NIDDM); Insulin-dependent Diabetes Mellitus (IDDM).
RegIV (Colon Specific	Stimulates glucose uptake;	RegIV activity may be assayed in	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes	2910.	See Table 2, SEQ ID
Gene; Colon Specific	increases insulin sensitivity.	vitro using a [3-H]-glucose uptake	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;		NO: Z for particular
Protein)		assay. (J Biol Chem 1999 Oct. 22;	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-		construct.
		274(43): 30864-30873).	insulin dependent Diabetes Mellitus (NIDDM); Insulin-
			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
Cosyntropin	Synthetic corticotropin;	The activity of cosyntropin can be	Endocrine; Addison's disease; Cushing's syndrome; pituitary		SEQ ID: NO: 2198
(Cortrosyn)	stimulates the release of cortisol.	assessed in vivo by measuring	dysfunction; acute adrenal crisis
(CAS-16960-16-0)		serum cortisol levels. (Frank et al. J.
		Am. Vet. Med. Assoc. 1998
		212(10): 1569-71).
Pexiganan Acetate	Disrupts bacterial membranes.	Pexiganan acetate activity can be	Treatment of Infectious Diseases; Treatment of Bacterial		SEQ ID NO:
(CAS-172820-23-4)		assessed using in vitro antibacterial	Infections.		2199
		assays known in the art. (Zasloff et
		al., Antimicrobial Agents and
		Chemotherapy 1999, 43: 782-788).
Pramlintide (Amylin)	Slows gastric emptying;	Appetite and food intake can be can	Treatment of Obesity; treatment of Diabetes; suppression of		SEQ ID NO:
(CAS-151126-32-8)	decreases food intake.	be measured by methods known in	body weight gain; suppression of appetite; treatment of		2200
		the art (Batterham et al. Nature	endocrine disorders;
		2002; 418: 650654)	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes
			mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;
			Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-
			insulin dependent Diabetes Mellitus (NIDDM); Insulin-
			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
			Other indications for antibodies, antagonists: treatment of
			weight loss; treatment of AIDS wasting; appetite stimulant;
			treatment of cachexia.
Teriparatide	Acts in conjuction with	Adenylyl cyclase stimulation in rat	Bone Disorders; Fracture prevention; Hypercalcemia;		SEQ ID NO:
(CAS-52232-67-4)	calcitonin to control calcium and	osteosarcoma cells, ovariectomized	Malignant hypercalcemia; Osteoporosis; Paget's disease;		2201
	phosphate metabolism; elevates	rat model of osteoporosis: IUBMB	Osteopenia, Osteoclastogenesis; osteolysis; osteomyelitis;
	blood calcium level; stimulates	Life 2000 Feb.; 49(2): 131-5	osteonecrosis; periodontal bone loss; osteoarthritis; rheumatoid
	the activity of osteocytes;		arthritis; osteopetrosis; periodontal, lytic, or metastatic bone
	enhances absorption of Ca+/Pi		disease; osteoclast differentiation inhibition; bone disorders;
	from small intestine into blood;		bone healing and regeneration.
	promotes reabsorption of Ca+
	and inhibits Pi by kidney
	tubules.
Terlipressin	Analog of vasopressin; induces	Terlipressin activity can be	Variceal hemorrhage; cirrhosis; portal hypertension;		SEQ ID NO:
(triglycyl lycine	vasoconstriction.	measured using assays of	hepatorenal syndrome; Blood-related disorders		2202
vasopressin)		vasoconstriction, such as the
(CAS-14636-12-5)		isolated arterial ring preparation.
		(Landstrom et al., Hum Reprod
		1999 Jan.; 14(1): 151-5).
Ularitide	Stimulates natriuresis, diuresis,	Ularitide activity can be assessed by	Excretory disorders; Acute renal failure; asthma; congestive		SEQ ID NO:
(CAS-118812-69-4)	and vasodilation.	measuring cGMP accumulation in	heart failure; hypertension; pulmonary hypertension;		2203
		rat renal cells. (Valentin et al.,	cardiovascular disorders
		Hypertension 1993 Apr.;
		21(4): 432-8).
Aprotinin (Trasylol)	Serine protease inhibitor;	Inhibition of thrombin-induced	Inhibition of fibrinolysis; reduction of blood loss during		SEQ ID NO:
(CAS-9087-70-1;	attenuates Systemic	platelet aggregation can be	surgery; Treatment of Inflammation and Immune Disorders.		2204
CAS-11061-94-2;	Inflammatory Response,	measured using methods known in
CAS-12407-79-3)	fibrinolysis and thrombin-	the art. (Poullis et al., J Thorac
	induced platelet aggregation.	Cardiovasc Surg 2000
		Aug.; 120(2): 370-8).
Aspartocin	Antibacteria	Aspartocin activity can be assessed	Treatment of Infectious Diseases; treatment of bacterial		SEQ ID NO:
(CAS-4117-65-1;		using in vitro antibacterial assays	infections.		2205
CAS-1402-89-7)		known in the art. (Zasloff et al.,
		Antimicrobial Agents and
		Chemotherapy 1999, 43: 782-788).
Calcitonin (Calcimar)	Regulates levels of calcium and	Hypocalcemic Rat Bioassay, bone	Musculoskeletal; Osteroporosis; Paget's disease;		SEQ ID NO:
(CAS-21215-62-3)	phosphate in serum; causes a	resorbing assay and the pit assay,	hypercalcemia;		2206
	reduction in serum calcium-an	CT receptor binding assay, CAMP	Bone Disorders; Fracture prevention; Malignant
	effect opposite to that of human	stimulation assay: J Bone Miner	hypercalcemia; Osteopenia, Osteoclastogenesis; osteolysis;
	parathyroid hormone.	Res 1999 Aug.; 14(8): 1425-31	osteomyelitis; osteonecrosis; periodontal bone loss;
			osteoarthritis; rheumatoid arthritis; osteopetrosis; periodontal,
			lytic, or metastatic bone disease; osteoclast differentiation
			inhibition; bone disorders; bone healing and regeneration.
Carperitide (HANP;	Stimulates natriuresis, diuresis,	Carperitide activity can be assessed	Treatment of Heart Failure; Cardiovascular disorders;		SEQ ID NO:
recombinant human	and vasodilation.	in vitro by measuring cGMP	Respiratory disorders; Acute respiratory distress syndrome.		2207
atrial natriuretic		accumulation in a number of cell
peptide)		lines, including PC12 cells and
(CAS-89213-87-6)		cultured human glomerular cells.
		(Medvede et al., Life Sci 2001 Aug.
		31; 69(15): 1783-90; Green et al., J
		Am Soc Nephrol 1994
		Oct.; 5(4): 1091-8).
Desirudin	Inhibits thrombin; inhibits blood	Desirudin activity can be assessed	Blood-related disorder; Thrombosis; thrombocytopenia;		SEQ ID NO:
(recombinant hirudin;	clotting.	using blood clotting assays known	hemorrhages.		2208
Revasc)		in the art, such as in vitro platelet
(CAS-120993-53-5)		aggragation assays. (Glusa,
		Haemostasis 1991; 21 Suppl
		1: 116-20).
Emoctakin	proinflammatory cytokine		Treatment of Inflammation, Immune disorders, RSV infection.		SEQ ID NO:
(interleukin 8)					2209
(CAS-142298-00-8)
Felypressin	Derivative of Vasopressin;	Felypressin vasoconstriction activity	Treatment of pain; to induce local anesthesia.		SEQ ID NO:
(CAS-56-59-7)	Stimulates vasoconstriction;	can be measured using assays of			2210
	Induces local anesthesia.	vasoconstriction, such as the
		isolated arterial ring preparation.
		(Landstrom et al., Hum Reprod
		1999 Jan.; 14(1): 151-5).
Glucagon	Induces hyperglycemia.	Glucagon activity may be assayed in	Hypoglycemia; Diabetes; Diabetes Insipidus; Diabetes		SEQ ID NO:
(CAS-16941-32-5)		vitro using a [3-H]-glucose uptake	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;		2211
		assay. (J Biol Chem 1999 Oct. 22;	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-
		274(43): 30864-30873).	insulin dependent Diabetes Mellitus (NIDDM); Insulin-
			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X; Endocrine disorders.
Nagrestipen			Inflammation; Immune		SEQ ID NO:
(CAS-166089-33-4)					2212
Pentigetide (Pentyde)			Respiratory; Allergy; Immune		SEQ ID NO:
(CAS-62087-72-3)					2213
Proinsulin	Stimulates glucose uptake and	Insulin activity may be assayed in	Hyperglycemia; Diabetes; Diabetes Insipidus; Diabetes		SEQ ID NO:
(CAS-67422-14-4)	promotes glycogenesis and	vitro using a [3-H]-glucose uptake	mellitus; Type 1 diabetes; Type 2 diabetes; Insulin resistance;		2214
	lipogenesis.	assay. (J Biol Chem 1999 Oct. 22;	Insulin deficiency; Hyperlipidemia; Hyperketonemia; Non-
		274(43): 30864-30873).	insulin dependent Diabetes Mellitus (NIDDM); Insulin-
			dependent Diabetes Mellitus (IDDM); A Condition Associated
			With Diabetes Including, But Not Limited To Obesity, Heart
			Disease, Hyperglycemia, Infections, Retinopathy, And/Or
			Ulcers; Metabolic Disorders; Immune Disorders; Obesity;
			Vascular Disorders; Suppression of Body Weight;
			Suppression of Appetite; Syndrome X.
Becaplermin	Promotes wound healing.	Becaplermin activity can be	Stimulate Epithelial Cell Proliferation; Stimulate Basal		SEQ ID NO:
(Regranex;		assessed using animal wound	Keratinocytes; Promote Wound Healing; Stimulate Hair		2215
recombinant PDGF-		healing models known in the art.	Follicle Production; Healing Of Dermal Wounds. Wound
BB)		(Saba et al., Ann Plast Surg 2002	Healing; Eye Tissue Wounds, Dental Tissue Wounds, Oral
(CAS-165101-51-9)		Jul.; 49(1): 62-6).	Cavity Wounds, Diabetic Ulcers, Dermal Ulcers, Cubitus
			Ulcers, Arterial Ulcers, Venous Stasis Ulcers, Burns Resulting
			From Heat Exposure Or Chemicals, or Other Abnormal
			Wound Healing Conditions such as Uremia, Malnutrition,
			Vitamin Deficiencies or Complications Associated With
			Systemic Treatment With Steroids, Radiation Therapy or
			Antineoplastic Drugs or Antimetabolites; Promote Dermal
			Reestablishment Subsequent To Dermal Loss; Increase the
			Adherence Of Skin Grafts To A Wound Bed; Stimulate Re-
			Epithelialization from The Wound Bed; To Promote Skin
			Strength; Improve The Appearance Of Aged Skin; Proliferate
			Hepatocytes, Lung, Breast, Pancreas, Stomach, Bladder, Small
			Intestine, Large Intestine; Sebocytes, Hair Follicles, Type II
			Pneumocytes, Mucin-Producing Goblet Cells, or Other
			Epithelial Cells, Endothelial Cells, Keratinocytes, or Basal
			Keratinocytes (and Their Progenitors) Contained Within The
			Skin, Lung, Liver, Bladder, Eye, Salivary Glands, or
			Gastrointestinal Tract; Reduce The Side Effects Of Gut
			Toxicity That Result From Radiation, Chemotherapy
			Treatments Or Viral Infections; Cytoprotector, especially of
			the Small Intestine Mucosa or Bladder; Mucositis (Mouth
			Ulcers); Regeneration Of Skin; Full and/or Partial Thickness
			Skin Defects, including Burns, (e.g., Repopulation Of Hair
			Follicles, Sweat Glands, And Sebaceous Glands); Psoriasis;
			Epidermolysis Bullosa; Blisters; Gastric and/or Doudenal
			Ulcers; Reduce Scarring; Inflamamatory Bowel Diseases;
			Crohn's Disease; Ulcerative Colitis; Gut Toxicity; Lung
			Damage; Repair Of Alveoli And/or Brochiolar Epithelium;
			Acute Or Chronic Lung Damage; Emphysema, ARDS;
			Inhalation Injuries; Hyaline Membrane Diseases; Infant
			Respiratory Distress Syndrome; Bronchopulmonary Displasia
			In Premature Infants; Fulminant Liver Failure; Cirrhosis, Liver
			Damage caused by Viral Hepatitis and/or Toxic Substances;
			Diabetes Mellitus; Inflammation; Cancer; Digestive disorders.
Ghrelin	Stimulates release of growth	Appetite and food intake can be can	Endocrine; loss of body weight; loss of body weight associated		SEQ ID NO:
(Genbank Accession	hormone from anterior pituitary.	be measured by methods known in	with cancer or anorexia nervosa; loss of appetite; excessive		2216
No. AB029434)	Stimulates appetite and reduces	the art (Batterham et al. Nature	appetite; body weight gain; Obesity; Diabetes; Acromegaly;
	fat burning.	2002; 418: 650654)	Growth failure; Growth hormone deficiency; Growth failure
			and growth retardation Prader-Willi syndrome in children 2
			years or older; Growth deficiencies; Growth failure associated
			with chronic renal insufficiency; Postmenopausal
			osteoporosis; burns; cachexia; cancer cachexia; dwarfism;
			metabolic disorders; obesity; renal failure; Turner's Syndrome,
			pediatric and adult; fibromyalgia; fracture treatment; frailty,
			AIDS wasting
Ghrelin-binding	Inhibits growth hormone release	Appetite and food intake can be can	Endocrine; Obesity; Diabetes; body weight gain; excessive
antibody including	in response to Ghrelin; inhibits	be measured by methods known in	appetite; loss of appetite; loss of body weight.
antibody fragment, or	increase in appetite.	the art (Batterham et al. Nature
dominant-negative		2002; 418: 650654)
form of Ghrelin
receptor
NOGO-66 peptide			Neurodegenerative disorders; spinal cord injury; neuronal		SEQ ID NO:
fragment			injury; brain trauma; stroke; multiple sclerosis; demyelinating		2217
(Genbank Accession			disorders; neural activity and neurological diseases; neural cell
No. NP_008939			(e.g., neuron, glial cell, and schwann cell) regeneration and/or
(amino acids 62-101))			growth
Gastric inhibitory	Increases nutrient uptake and	Nutrient uptake and tryglyceride	Most preferred: loss of body weight, AIDS wasting, cachexia,		SEQ ID NO:
polypeptide (GIP),	tryglyceride accumulation in	accumulation can be measured by	loss of apetite. Other: Obesity; Diabetes; insulin resistance;		2218
including GIP	adipocytes, which leads to	methods desribed in Miyawaki et	body weight gain; excessive appetite.
fragments	obesity and insulin resistance.	al., Nat. Medicine, 2002, Vol
(Genbank Accession		8(7): 738-742.
No. NM_004123)
Gastric inhibitory	Increased use of fat as	Fat utilization as an energy source	Obesity; Diabetes; Insulin resistance; body weight gain.
polypeptide antibody,	predominant energy source;	can be measured as described in
or antibody fragments	decreased accumulation of fat in	Miyawaki et al., Nat. Medicine,
	adipocytes.	2002, Vol 8(7): 738-742.
Gastric inhibitory	Increased use of fat as	Fat utilization as an energy source	Most preferred: Obesity; Diabetes; body weight gain;		SEQ ID NO:
peptide receptor or	predominant energy source;	can be measured as described in	excessive appetite; insulin resistance. Other: loss of body		2219
receptor fragments or	decreased accumulation of fat in	Miyawaki et al., Nat. Medicine,	weight, AIDS wasting, loss of appetite.
variants including	adipocytes.	2002, Vol 8(7): 738-742.
soluble fragments or
variants
(Genbank Accession
Number NM_000164)
POMC	Activity of POMC-derived		Preferred: resistance to stress; anti-inflammatory activity;		SEQ ID NO:
(proopiomelanocortin),	fragments are diverse, and well-		analgesic activity; increased skin pigmentation; increased		2220
including fragments or	known in the art.		protein catabolism; increased gluconeogenesis; obesity;
variants (such as, for	See, for example, Hadley et al.,		diabetes. Other: decreased protein catabolism, decreased skin
example, alpha-	Ann N Y Acad Sci 1999 Oct.		pigmentation, Addison's disease, Cushing's syndrome
melanocyte stimulating	20; 885: 1-21; Dores, Prog Clin
hormone, αMSH,	Biol Res 1990; 342: 22-7;
gamma melanocyte	Blalock, Ann N Y Acad Sci.
stimulating hormone,	1999 Oct. 20; 885: 161-72).
γMSH, beta-
melanocyte stimulating
hormone, βMSH,
adrenocorticotropin,
ACTH, beta-
endorphin, met-
enkephalin)
(Genbank Accession
No. NM_000930)
HP 467, HP228	See U.S. Pat. No. 6,350,430	See U.S. Pat. No. 6,350,430	Resistance to stress; anti-inflammatory activity; analgesic		SEQ ID NO:
(U.S. Pat. No.			activity; increased skin pigmentation; increased protein		2221
6,350,430)			catabolism; increased gluconeogenesis.
NDP	See U.S. Pat. No. 6,350,430	See U.S. Pat. No. 6,350,430	Resistance to stress; anti-inflammatory activity; analgesic		SEQ ID NO:
(U.S. Pat. No.			activity; increased skin pigmentation; increased protein		2222
6,350,430)			catabolism; increased gluconeogenesis.
Interleukin-21	Immunomodulator; inhibits	IL-21 activity can be assessed by	Autoimmune disorders; Inflammatory disorders; Treatment of	3298	SEQ ID NO:
(IL-21)	interferon gamma production by	measuring interferon gamma	Psoriasis; Rheumatoid Arthritis; Inflammatory bowel disease.		2177
	Th1 cells.	production in Th1 cells. (Wurster et
		al., : J Exp Med 2002 Oct.
		7; 196(7): 969-77)
Interleukin-4	Immunomodulator; promotes the	IL-4 activity can be assessed by	Treatment of Psoriasis; Autoimmune disorders; Rheumatoid	3307	SEQ ID NO:
(IL-4)	differentiation of T cells into	measuring Th1/Th2 cytokine	Arthritis; Inflammatory bowel disease; Inflammatory		2178
	Th2 phenotype.	responses of isolated spleen cells in	disorders.
		vitro. (Waltz et al., Horm Metab
		Res 2002 Oct.; 34(10): 561-9).
Osteoclast Inhibitory	Inhibits osteoclast formation.	Osteoclast Inhibitory Lectin activity	Treatment of Bone Disorders; Osteoporosis; Fracture	3312	SEQ ID NO: 2181
Lectin		can be assessed using osteoclast	prevention; Hypercalcemia; Malignant hypercalcemia; Paget's
(OCIL)		formation assays known in the art.	disease; Osteopenia, Osteoclastogenesis; osteolysis;
		(Zhou et al., J Biol Chem 2002 Dec.	osteomyelitis; osteonecrosis; periodontal bone loss;
		13; 277(50): 48808-15)	osteoarthritis; rheumatoid arthritis; osteopetrosis; periodontal,
			lytic, or metastatic bone disease; osteoclast differentiation
			inhibition; bone healing and regeneration.

[0071]

TABLE 2
						SEQ		SEQ
Fusion				Expression	SEQ ID	ID	SEQ ID	ID	SEQ ID	Leader
No.	Construct ID	Construct Name	Description	Vector	NO: Y	NO: X	NO: Z	NO: A	NO: B	Sequence
1	1520	pC4:HSA/TR6.V30-H300	Amino acids V30 to H300 of TR6 (fragment shown as V1	pC4	217	1	433	649	650	HSA
			to H271 of SEQ ID NO: 433) fused downstream of HSA.
2	1537	pYPG:HSA.TR6coV30-E294	Amino acids V30 to E294 of TR6 (fragment shown as V1	pYPGaf	218	2	434	651	652	HSA
			to E265 of SEQ ID NO: 434) fused downstream of HSA.
			DNA encoding TR6 has been codon optimized.
3	1545	pYPG:HSA.TR6coV30-L288	Amino acids V30 to L288 of TR6 (fragment shown as V1	pYPGaf	219	3	435	653	654	HSA
			to L259 of SEQ ID NO: 435) fused downstream of HSA.
			DNA encoding TR6 has been codon optimized.
4	1546	pYPG:HSA.TR6coV30-R284	Amino acids V30 to R284 of TR6 (fragment shown as V1	pYPGaf	220	4	436	655	656	HSA
			to R255 of SEQ ID NO: 436) fused downstream of HSA.
			DNA encoding TR6 has been codon optimized.
5	1568	pSAC35:HSA-yTR6	TR6 fused downstream of HSA. DNA encoding TR6 has	pSAC35	221	5	437	657	658	HSA/kex2
			been codon optimized.
6	1570	pSAC35:TR6-HSA	Mature TR6 fused downstream of the HSA/kex2 leader	pSAC35	222	6	438	659	660	HSA/kex2
			and upstream of the mature HSA.
7	1622	pC4:synTR6.M1-H300.HSA	Synthetic TR6 fused upstream of mature HSA, with 2	pC4	223	7	439	661	662	Native TR6
			extra amino acids between the TR6 and HSA portions.
8	1623	pC4:HSA.synTR6.V30-H300	Synthetic mature TR6 fused downstream of FL HSA. Last	pC4	224	8	440	663	664	HSA
			amino acid HSA sequence is missing at BSU36I site.
9	1642	pSAC35:GCSF.T31-P204.HSA	Mature GCSF cloned downstream of the HSA/kex2 leader	pSAC35	225	9	441	665	666	HSA/kex2
			and upstream of the mature HSA
10	1643	pSAC35:HSA.GCSF.T31-P204	Mature GCSF cloned downstream of the mature HSA and	pSAC35	226	10	442	667	668	HSA/kex2
			HSA/kex2 leader sequence.
11	1645	pSAC35:yTR6(N173Q).HSA	Mutant mature TR6 cloned upstream of mature HSA and	pSAC35	227	11	443	669	670	HSA/kex2
			downstream of the HSA/kex2 leader sequence.
12	1657	pC4.HSA:DeCAF.A23-D233	Amino acids A23 to D233 of DeCAF fused downstream	pC4	228	12	444	671	672	HSA
			of full length HSA.
13	1680	pYPG:HSA.BLyS.A134-L285	Amino acids A134 to L285 of BLyS fused downstream of	pYPGaf	229	13	445	673	674	HSA
			FL HSA. Two extra amino acids (Leu, Glu) have been
			added between the therapeutic protein and HSA portions.
14	1681	pYPG.HSA.MPIF.D45-N120	Amino acids D45 to N120 of MPIF fused downstream of	pYPGaf	230	14	446	675	676	HSA
			FL HSA. Two additional amino acids (L and E) have been
			added between HSA and MPIF.
15	1697	pSAC35:HSA.GM-CSF.A18-E144	Amino acids A18 to E144 of GM-CSF fused downstream	pSAC35	231	15	447	677	678	HSA
			of FL HSA.
16	1699	pSAC35:GM-CSF.A18-E144:	Amino acids A18 to E144 of GM-CSF fused upstream of	pSAC35	232	16	448	679	680	HSA/kex2
		HSA	mature HSA and downstream of HSA/kex2 leader.
17	1700	pSAC35:HSA-yTR6(N173Q)	Mutant TR6 fused downstream of mature HSA with	pSAC35	233	17	449	681	682	HSA/kex2
			HSA/kex2 leader sequence.
18	1702	pYPG:HSA.ek.TR6coV30-L288	Amino acids V30 to L288 of TR6 (fragment shown as V1	pYPGaf	234	18	450	683	684	HSA
			to L259 of SEQ ID NO: 450) fused downstream of FL
			HSA with an enterokinase site in between. DNA encoding
			TR6 has been codon optimized.
19	1703	pYPG:HSA.ek.TR6coV30-R284	Amino acids V30 to R284 of TR6 (fragment shown as V1	pYPGaf	235	19	451	685	686	HSA
			to R255 of SEQ ID NO: 451) fused downstream of HSA
			with an enterokinase site in between. DNA encoding TR6
			has been codon optimized.
20	1704	pYPG:HSA.TR6.V30-E294	Amino acids V30 to E294 of TR6 fused downstream of	pYPGaf	236	20	452	687	688	HSA
			HSA. Two additional amino acids (Leu, Glu) are in
			between HSA and TR6.
21	1746	pYPG:HSA.ek.KDI.L28-K207	Amino acids L28 to K207 of KDI fused downstream of	pYPGaf	237	21	453	689	690	HSA
			HSA with an enterokinase site in between.
22	1747	pSAC35.HSA.hGHRF.Y32-L75	Amino acids Y32 to L75 of hGHRF fused downstream of	pSAC35	238	22	454	691	692	HSA
			HSA.
23	1748	pSAC35.hGHRF.Y32-L75.HSA	Amino acids Y32 to L75 of hGHRF (see also SEQ	pSAC35	239	23	455	693	694	HSA/kex2
			IDNO: 454) fused upstream of mature HSA and
			downstream of HSA/kex2 leader sequence.
24	1749	pSAC35:HSA.PTH.S1-F3	FL HSA fused upstream of amino acids S1-F34 of PTH	pSAC35	240	24	456	695	696	HSA
25	1750	pSAC35:PTH.S1-F34.HSA	Amino acids 1-34 of PTH fused upstream of mature HSA	pSAC35	241	25	457	697	698	HSA/kex2
			and downstream of HSA/kex2 leader sequence.
26	1757	pSAC35:IL2.A21-T153.	Mature human IL-2 with a single amino acid mutation (C	pSAC35	242	26	458	699	700	HSA/kex2
		145C/S.HSA	to S at position 145) cloned downstream of the
			HSA/KEX2 leader and upstream of mature HSA
27	1758	pSAC35:HSA.IL2.A21-T153.	Mature human IL-2 with a single amino acid mutation (C	pSAC35	243	27	459	701	702	HSA/kex2
		145C/S	to S at position 145) cloned downstream of HSA with
			HSA/kex2 leader sequence.
28	1772	pSAC:EPOco.A28-D192.HSA	Amino acids A28-D192 of EPO variant (where glycine at	pSAC35	244	28	460	703	704	HSA/kex2
			amino acid 140 has been replaced with an arginine) fused
			upstream of mature HSA and downstream of HSA/kex2
			leader sequence. DNA encoding EPO has been codon
			optimized.
29	1774	pSAC:HSA.EPOco.A28-D192.	Amino acids A28-D192 of EPO variant (where glycine at	pSAC35	245	29	461	705	706	HSA/kex2
			amino acid 140 has been replaced with an arginine) fused
			downstream of HSA with HSA/kex2 leader sequence.
			DNA encoding EPO has been codon optimized.
30	1777	pSAC35:TNFR2.L23-D257.HSA	Mature TNFR2 fused downstream of the HSA/kex2 signal	pSAC35	246	30	462	707	708	HSA/kex2
			and upstream of mature HSA.
31	1778	pSAC35:IFNβ.M22-N187:HSA	Residues M22-N187 of full-length IFNb (shown as M1 to	pSAC35	247	31	463	709	710	HSA/kex2
			N166 of SEQ ID NO: 463) fused upstream of mature HSA
			and downstream of HSA/kex2 leader sequence.
32	1779	pSAC35:HSA:IFNβ.M22-N187	Residues M22-N187 of full-length IFNb (shown as M1 to	pSAC35	248	32	464			HSA/kex2
			N166 of SEQ ID NO: 464) fused downstream of HSA with
			HSA/kex2 leader sequence.
33	1781	pSAC:EPOcoA28-D192.HSA	Amino acids A28-D192 of EPO variant (where glycine at	pSAC35	249	33	465	711	712	HSA/kex2
		51N/S, 65N/S, 110N/s	amino acid 140 has been replaced with an arginine) fused
			upstream of mature HSA and downstream of HSA/kex2
			leader sequence. Glycosylation sites at amino acid 51, 65,
			110 are mutated from N to S residue. DNA encoding EPO
			has been codon optimized.
34	1783	pSAC:HSA.EPOcoA28-D192.	Amino acids A28-D192 of EPO variant (where glycine at	pSAC35	250	34	466	713	714	HSA/kex2
		51N/S, 65N/S, 110N/s	amino acid 140 has been replaced with an arginine) fused
			downstream of HSA with HSA/kex2 leader sequence.
			Glycosylation sites at amino acids 51, 65, 110 are mutated
			from N to S residue. DNA encoding EPO has been codon
			optimized.
35	1784	pSAC35:HSA.TNFR2.L23-D257	Mature TNFR2 fused downstream of FL HSA.	pSAC35	251	35	467	715	716	HSA
36	1785	pSAC35:KGF2Δ28.A63-S208:	Amino acids A63 to S208 of KGF2 fused upstream of	pSAC35	252	36	468	717	718	HSA/kex2
		HSA	mature HSA and downstream of the HSA/kex2 signal
			peptide.
37	1786	pSAC35:HSA.KGF2{D}28.A63-S208	Amino acids A63 to S208 of KGF2 fused downstream of	pSAC35	253	37	469	719	720	HSA
			HSA.
38	1788	pSAC35:HSA.TR2.P37-A192	Amino acids P37 to A192 of TR2 fused downstream of	pSAC35	254	38	470	721	722	HSA/kex2
			HSA with HSA/kex2 leader sequence.
39	1793	pSAC35:HSA.EPO.A28-D192	Amino acids A28-D192 of EPO variant (where glycine at	pSAC35	255	39	471			HSA/kex2
		(N51A, N65A, N110A)	amino acid 140 has been replaced with an arginine; see,
			for example, SEQ ID NO: 499) fused downstream of HSA
			with HSA/kex2 leader sequence. Glycosylation sites at
			amino acids 51, 65, 110 are mutated from N to A residue.
40	1794	pSAC35:HSA.EPO.A28-D192	Amino acids A28-D192 of the EPO variant (where glycine	pSAC35	256	40	472			HSA/kex2
			at amino acid 140 has been replaced with an arginine; see,
			for example, SEQ ID NO: 499) fused downstream of HSA
			with HSA/kex2 leader sequence.
41	1809	pSAC35.MDC.G25-Q93.HSA	Amino acids P26 to Q93 of MDC with an N-terminal	pSAC35	257	41	473	723	724	HSA/kex2
			methionine, fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
42	1812	pSAC35:IL2.A21-T153.HSA	Amino acids A21 to T153 of IL-2 fused downstream of the	pSAC35	258	42	474	725	726	HSA/kex2
			HSA/kex2 leader and upstream of mature HSA.
43	1813	pSAC35:HSA.IL2.A21-T153	Amino acids A21 to T153 of IL-2 fused downstream of	pSAC35	259	43	475	727	728	HSA/kex2
			HSA with HSA/kex2 leader sequence.
44	1821	pSAC35:scFv116A01.HSA	BLyS antibody fused upstream of mature HSA which	pSAC35	260	44	476	729	730	Modified
			lacks the first 8 amino acids and downstream from the							HSA/kex2,
			HSA/kex2 signal sequence which lacks the last two amino							lacking the last
			acids.							two amino
										acids
45	1830	pSAC35:HSA.KEX2.HAGDG59.	Amino acids L19-Q300 of HAGDG59 fused downstream	pSAC35	261	45	477	731	732	HSA/kex2
		L19-Q300	of the HSA/kex2 signal, mature HSA and KEX2 cleavage
			site.
46	1831	pSAC35:HAGDG59.L19-Q300.	HSA/kex2 signal peptide followed by amino acids L19-Q300	pSAC35	262	46	478	733	734	HSA/kex2
		HSA	of HAGDG59 followed by mature HSA.
47	1833	pSAC35:humancalcitonin.C1-G33:	Human Calcitonin (amino acids C98-G130 of SEQ ID	pSAC35	263	47	479	735	736	HSA/kex2
		HSA	NO: 479) fused upstream of mature HSA and downstream
			of HSA/kex2 leader sequence.
48	1834	pSAC35:HSA.humancalcitonin.C1-G33	Human Calcitonin (amino acids C98-G130 of SEQ ID	pSAC35	264	48	480	737	738	HSA
			NO: 480) fused downstream of FL HSA.
49	1835	pSAC35:salmoncalcitonin.C1-G33:	Salmon Calcitonin amino acids C1-G33 fused upstream of	pSAC35	265	49	481	739	740	HSA/kex2
		HSA	mature HSA and downstream of HSA/kex2 leader
			sequence.
50	1836	pSAC35:HSA.salmoncalcitonin.C1-G33	Salmon Calcitonin amino acids C1-G33 fused downstream	pSAC35	266	50	482	741	742	HSA
			of HSA.
51	1853	pSAC35:PTH(1-34)N26.HSA	Amino acids 1 to 34 of PTH fused upstream of mature	pSAC35	267	51	483	743	744	HSA/kex2
			HSA and downstream of HSA/kex2 leader sequence.
			Amino acid K26 of PTH mutated to N26.
52	1854	pSAC35:HSA.PTH(1-34)N26	Amino acids 1 to 34 of PTH fused downstream of HSA.	pSAC35	268	52	484	745	746	HSA
			Amino acid K26 of PTH mutated to N26.
53	1862	pSAC35:HSA.GnRH.Q24-G33	Amino acids Q24-G33 of human gonadotropin releasing	pSAC35	269	53	485	747	748	HSA/kex2
			hormone fused downstream of HSA with HSA/kex2
			leader sequence.
54	1863	pSAC35:GnRHQ24-G33.HSA	Amino acids Q24-G33 of human gonadotropin releasing	pSAC35	270	54	486	749	750	HSA/kex2
			hormone fused upstream of mature HSA and downstream
			of HSA/kex2 leader sequence.
55	1866	pSAC35:teprotide.HSA	Teprotide fused upstream of mature HSA.	pSAC35	271	55	487	751	752
56	1867	pSAC35:HSA.teprotide.	Teprotide fused downstream of FL HSA.	pSAC35	272	56	488	753	754	HSA
57	1889	pC4:HSA.PTH.S1-F34	PTH(1-34) fused downstream of HSA.	pC4	273	57	489	755	756	HSA
58	1891	pEE12:HSA.sTR6	Soluble mature TR6 fused downstream of HSA.	pEE12.1	274	58	490	757	758	HSA
59	1892	pEE12:sTR6.HSA	Synthetic full length TR6 fused upstream of mature HSA.	pEE12.1	275	59	491	759	760	TR6
60	1906	pC4:PTH.S1-F34.HSA	Amino acids S1 to F34 of PTH fused upstream of mature	pC4	276	60	492	761	762	MPIF
		(junctioned)	HSA and downstream of MPIF leader sequence. There
			are two cloning junction amino acids (T, S) between PTH
			and HSA.
61	1907	pC4:HSA.PTH.S1-F34	Amino acids S1 to F34 fused downstream of FL HSA. The	pC4	277	61	493	763	764	HSA
		(junctioned)	last C-terminal amino acid (L) residue is missing for HSA
			in the cloning junction between HSA and PTH.
62	1912	pC4:sTR6.HSA	Synthetic full length TR6 fused upstream of mature HSA.	pC4	278	62	494	765	766	Native TR6
										leader
63	1913	pC4:HSA.synTR6.V30-H300	Amino acids V30 to H300 of synthetic TR6 (shown as V1	pC4	279	63	495	767	768	HSA
		(seamless)	to H271 of SEQ ID NO: 495) fused downstream of full-
			length HSA.
64	1914	pC4:PTH.S1-F34.HSA (seamless)	Amino acids S1 to F34 of PTH fused downstream of	pC4	280	64	496	769	770	MPIF
			MPIF leader sequence and upstream of mature HSA.
65	1916	pC4:HSA.KGF2D28.A63-S208	Amino acids A63 to S208 of full length KGF2 fused	pC4	281	65	497	771	772	HSA
			downstream of HSA.
66	1917	pC4:KGF2D28.A63-S208:HSA	Amino acids A63 to S208 of KGF2 fused upstream of	pC4	282	66	498	773	774	HSA/kex2
			mature HSA.
67	1925	pcDNA3.EPO M1-D192.HSA	Amino acids M1 to D192 of EPO variant (where glycine	pcDNA3	283	67	499	775	776	Native EPO
			at amino acid 140 has been replaced with an arginine)							leader peptide
			fused upstream of HSA. D192 of EPO and D1 of mature
			HSA are the same amino acids in this construct.
68	1926	pcDNA3:SPHSA.EPO A28-D192	Amino acids A28 to D192 of EPO variant (where glycine	pcDNA3	284	68	500	777	778	MPIF
			at amino acid 140 has been replaced with an arginine)
			fused upstream of mature HSA and downstream of the
			MPIF leader peptide.
69	1932	pEE12.1:HSA.PTH.S1-F34	Amino acids 1 to 34 of PTH fused downstream of full	pEE12.1	285	69	501	779	780	HSA
			length HSA.
70	1933	pSAC35:HCC-1.T20-N93:HSA	Amino acids T20 to N93 of HCC-1 fused upstream of	pSAC35	286	70	502	781	782	HSA/kex2
			mature HSA and downstream of the HSA/kex2 leader
			sequence.
71	1934	pSAC35:HCC-1C.O.T20-N93:	Amino acids T20 to N93 of HCC-1 fused upstream of	pSAC35	287	71	503	783	784	HSA/kex2
		HSA	mature HSA and downstream of the HSA/kex2 leader
			sequence. DNA sequence is codon optimized for yeast
			expression.
72	1938	pEE12.1:PTH.S1-F34.HSA	Amino acids S1 to F34 of PTH fused upstream of mature	pEE12.1	288	72	504	785	786	MPIF
			HSA and downstream of MPIF leader sequence.
73	1941	pC4:HSA/PTH84 (junctioned)	PTH fused downstream of full length HSA. The last amino	pC4	289	73	505	787	788	HSA
			acid of HSA (Leu) has been deleted.
74	1947	pSAC35:d8HCC-1.G28-N93:	Amino acids G28 to N93 of HCC-1 fused upstream of	pSAC35	290	74	506	789	790	HSA/kex2
		HSA	mature HSA and downstream of HSA/kex2 leader
			sequence.
75	1948	pSAC35:d8HCC-1C.O.G28-N93:	Amino acids G28 to N93 of HCC-1 fused upstream of	pSAC35	291	75	507	791	792	HSA/kex2
		HSA	mature HSA and downstream of HSA/kex2 leader
			sequence. DNA sequence is codon optimized for yeast
			expression.
76	1949	pC4:PTH.S1-Q84/HSA	PTH fused downstream of the MPIF leader sequence and	pC4	292	76	508	793	794	MPIF
		(junctioned)	upstream of mature HSA. There are two additional amino
			acids between PTH84 and HSA as a result of the cloning
			site.
77	1952	pcDNA3.1:IL2.HSA	Full length human IL-2, having a Cysteine to Serine	pCDNA3.1	293	77	509	795	796	Native IL-2
			mutation at amino acid 145, fused upstream of mature							leader
			HSA.
78	1954	pC4:IL2.HSA	Full length human IL-2, having a Cysteine to Serine	pC4	294	78	510	797	798	Native IL-2
			mutation at amino acid 145, fused upstream of mature							leader
			HSA.
79	1955	pSAC35:t9HCC-1.G28-N93:	Amino acids G28 to N93 of HCC-1 fused upstream of a	pSAC35	295	79	511	799	800	HSA/kex2
		spcHSA	16 amino acid spacer and mature HSA and downstream of
			HSA/kex2 leader sequence.
80	1956	pSAC35:HSA.scFv116A01	Single chain BLyS antibody fused downstream of HSA	pSAC35	296	80	512	801	802	HSA/kex2
			with HSA/kex2 leader sequence. This construct also
			contains a His tag at the 3′ end.
81	1966	pC4:EPO.M1-D192.HSA	Amino acids M1 to D192 of EPO variant (where glycine	pC4	297	81	513			Native EPO
		Construct is also named	at amino acid 140 has been replaced with an arginine)							leader peptide
		pC4:EPOM1-D192.HSA	fused upstream of mature HSA.
82	1969	pC4:MPIFsp.HSA.EPO.A28-D192	Amino acids A28 to D192 of EPO variant (where glycine	pC4	298	82	514			MPIF
			at amino acid 140 has been replaced with an arginine)
			fused downstream of MPIF leader sequence and upstream
			of mature HSA.
83	1980	pC4:EPO.A28-D192. HSA	Amino acids A28 to D192 of EPO variant (where glycine	pC4	299	83	515	803	804	HSA
			at amino acid 140 has been replaced with an arginine)
			fused downstream of the HSA leader peptide and
			upstream of mature HSA.
84	1981	pC4.HSA-EPO.A28-D192.	Amino acids A28 to D192 of EPO variant (where glycine	pC4	300	84	516	805	806	HSA
			at amino acid 140 has been replaced with an arginine)
			fused downstream of the full length HSA.
85	1989	pSAC35:activeAC2inhibitor:HSA	Active inhibitor of ACE2 (DX512) fused upstream of	pSAC35	301	85	517	807	808	HSA/kex2
			mature HSA and downstream of HSA/kex2 leader
			sequence.
86	1994	pEE12.1.HSA-EPO.A28-D192.	Amino acids A28 to D192 of EPO variant (where glycine	pEE12.1	302	86	518			HSA
			at amino acid 140 has been replaced with an arginine)
			fused downstream of full length HSA.
87	1995	pEE12.1:EPQ.A28-D192. HSA	Amino acids A28 to D192 of EPO variant (where glycine	pEE12.1	303	87	519			HSA
			at amino acid 140 has been replaced with an arginine)
			fused downstream of the HSA leader peptide and
			upstream of mature HSA.
88	1996	pEE12.1:MPIFsp.HSA.EPO.A28-D192	Amino acids A28 to D192 of EPO variant (where glycine	pEE12.1	304	88	520			MPIF
			at amino acid 140 has been replaced with an arginine)
			fused downstream of MPIF leader sequence and upstream
			of mature HSA.
89	1997	pEE12.1:EPO M1-D192.HSA	Amino acids M1 to D192 of EPO variant (where glycine	pEE12.1	305	89	521			Native EPO
			at amino acid 140 has been replaced with an arginine)							leader
			fused upstream of mature HSA.
90	1998	pC4:CKB1.G28-N93.HSA	Amino acids G28 to N93 of CkBeta1 fused upstream of	pC4	306	90	522	809	810	HSA
			mature HSA and downstream of the HSA leader sequence.
91	2000	pSAC35:HSA:activeAC2inhibitor	Active inhibitor of ACE2 (DX512) fused downstream of	pSAC35	307	91	523	811	812	HSA
			HSA.
92	2001	pSAC35:inactiveAC2inhibitor:HSA	Inactive inhibitor of ACE2 (DX510) fused upstream of	pSAC35	308	92	524	813	814	HSA/kex2
			mature HSA and downstream of HSA/kex2 leader
			sequence.
93	2002	pSAC35:HSA.inactiveAC2inhibitor	Inactive inhibitor of ACE2 (DX510) fused downstream of	pSAC35	309	93	525	815	816	HSA
			HSA.
94	2011	pC4:IFNb-HSA	Full length IFNb fused upstream of mature HSA.	pC4	310	94	526	817	818	Native IFNb
										leader
95	2013	pC4:HSA-IFNb.M22-N187	Amino acids M22 to N187 of IFNb (fragment shown as	pC4	311	95	527			HSA
			amino acids M1 to N166 of SEQ ID NO: 527) fused
			downstream of HSA.
96	2016	pC4:TR1.M1-L401.HSA	Amino acids M1 to L401 of TR1 fused upstream of	pC4	312	96	528	819	820	Native TR1
			mature HSA. Native TR1 signal sequence used. A Kozak
			sequence was added.
97	2017	pC4:HSA.TR1.E22-L401	Amino acids E22 to L401 of TR1 fused downstream of	pC4	313	97	529	821	822	HSA
			HSA.
98	2021	pC4:PTH.S1-Q84/HSA	Amino acids 1-84 of PTH fused upstream of mature HSA	pC4	314	98	530	823	824	HSA
		(seamless)	and downstream of native HSA leader sequence.
99	2022	pEE12.1:PTH.S1-Q84.HSA	Amino acids 1-84 of PTH fused upstream of mature HSA	pEE12.1	315	99	531			HSA
			and downstream of native HSA leader sequence.
100	2023	pSAC35.PTH.S1-Q84.HSA	Amino acids 1-84 of PTH fused upstream of mature HSA	pSAC35	316	100	532	825	826	HSA/kex2
			and downstream of HSA/kex2 leader sequence.
101	2025	pSAC35:teprotide.spacer.HSA	Teprotide fused upstream of a linker and mature HSA.	pSAC35	317	101	533	827	828
102	2026	pSAC35:HSA.spacer.teprotide	Teprotide fused downstream of HSA and a linker.	pSAC35	318	102	534	829	830	HSA
103	2030	pSAC35.ycoIL-2.A21-T153.HSA	Amino acids A21 to T153 of IL-2 fused upstream of	pSAC35	319	103	535	831	832	HSA/kex2
			mature HSA and downstream of HSA/kex2 leader
			sequence. DNA encoding IL-2 has been codon optimized.
104	2031	pSAC35.HSA.ycoIL-2.A21-T153	Amino acids A21 to T153 of IL-2 fused downstream of	pSAC35	320	104	536	833	834	HSA/kex2
			HSA with the HSA/kex2 leader sequence. DNA encoding
			IL-2 has been codon optimized.
105	2047	pC4HSA:SP.EPO A28-D192.	Amino acids A28 to D192 of EPO variant (where glycine	pSAC35	321	105	537	835	836	MPIF
		HSA	at amino acid 140 has been replaced with an arginine)
			fused upstream of mature HSA and downstream of MPIF
			leader peptide.
106	2053	pEE12:IFNb-HSA	Full length IFNb fused upstream of mature HSA.	pEE12.1	322	106	538			Native IFNb
		also named pEE12.1:IFNβ-HSA								leader
107	2054	pEE12:HSA-IFNb	Mature IFNb fused downstream of HSA.	pEE12.1	323	107	539			HSA
108	2066	pC4:GM-CSF.M1-E144.HSA	Amino acids M1 to E144 of GM-CSF fused upstream of	pC4	324	108	540	837	838	Native GM-
			mature HSA.							CSF
109	2067	pC4:HSA.GM-CSF.A18-E144	Amino acids A18 to E144 of GM-CSF fused downstream	pC4	325	109	541	839	840	HSA
			of HSA.
110	2085	pEE12.1:TR1.M1-L401.HSA	Amino acids M1 to L401 of TR1 fused upstream of	pEE12.1	326	110	542			Native TR-1
			mature HSA.
111	2086	pEE12.1:HSA.TR1.E22-L401	Amino acids E22 to L401 (fragment shown as amino acids	pEE12.1	327	111	543			HSA
			E1 to L380 of SEQ ID NO: 543) of TR1 fused downstream
			of HSA.
112	2095	pC4:HSA-BLyS.A134	Amino acids A134 to L285 of BLyS fused downstream of	pC4	328	112	544	841	842	HSA
			HSA.
113	2096	pC4:sp.BLyS.A134-L285.HSA	Amino acids A134 to L285 of BLyS (fragment shown as	pC4	329	113	545	843	844	Native CKβ8
			amino acids A1 to L152 of SEQ ID NO: 545) fused
			upstream of mature HSA and downstream of the CKb8
			signal peptide.
114	2101	pcDNA3:SP.Ck7 Q22-A89.HSA.	N-terminal Methionine fused to amino acids Q22 to A89	pcDNA3	330	114	546	845	846	MPIF
			of Ckβ7 fused upstream of mature HSA and downstream
			of MPIF signal peptide.
115	2102	pEE12.1:SP.EPO A28-D192.HSA	Amino acids A28 to D192 of EPO variant (where glycine	pEE12.1	331	115	547			MPIF
			at amino acid 140 has been replaced with an arginine)
			fused upstream of mature HSA and downstream of MPIF
			leader peptide.
116	2129	pC4:TR2.M1-A192.HSA	Amino acids M1-A192 of TR2 fused upstream of HSA.	pC4	332	116	548	847	848	Native TR2
117	2137	pSAC35.MDC.G25-Q93.HSA.	Amino acids G25 to Q93 of MDC fused upstream of	pSAC35	333	117	549	849	850	HSA/kex2
			mature HSA and downstream of HSA/kex2 leader
			sequence.
118	2141	HSA-CK-Beta4	Full length CK-beta4 fused downstream of HSA.	pSAC35	334	118	550	851	852	HSA
119	2146	pC4:Leptin.HSA	Full length Leptin fused upstream of mature HSA.	pC4	335	119	551	853	854	Native leptin
120	2181	pC4:HSA.IL1Ra(R8-E159)	Amino acids R8 to E159 of IL1Ra (plus an added	pC4	336	120	552	855	856	HSA
			methionine at N-terminus) fused downstream of HSA.
121	2182	pC4:MPIFsp(M1-A21).IL1Ra(R8-E159).	Amino acids R8 to E159 of IL1Ra (plus an added	pC4	337	121	553	857	858	MPIF
		HSA	methionine at N-terminus) fused downstream of the MPIF
			leader sequence and upstream of mature HSA.
122	2183	pSAC35:HSA.IL1Ra(R8-E159)	Amino acids R8 to E159 of IL1Ra (plus an added	pSAC35	338	122	554	859	860	HSA
			methionine at N-terminus) fused downstream of HSA.
123	2184	pC4:HSA.Leptin.V22-C166	Amino acids V22 to C167 of Leptin fused downstream of	pC4	339	123	555	861	862	HSA
			HSA.
124	2185	pSAC35:IL1Ra(R8-E159).HSA	Amino acids R8 to E159 of IL1Ra (plus an added	pSAC35	340	124	556	863	864	HSA/kex2
			methionine at N-terminus) fused upstream of mature HSA
			and downstream of HSA/kex2 leader sequence.
125	2186	pSAC35:Leptin.V22-C166.HSA	Amino acids V22 to C167 of Leptin fused upstream of	pSAC35	341	125	557	865	866	HSA/kex2
			mature HSA and downstream of HSA/kex2 leader
			sequence.
126	2187	pSAC35:HSA.Leptin.V22-C166	Amino acids V22 to C167 of Leptin fused downstream of	pSAC35	342	126	558	867	868	HSA/kex2
			HSA with HSA/kex2 leader sequence.
127	2226	pcDNA3(+):TREM-1(21-202)-	Amino acids A21 to P202 of TREM-1 fused upstream of	pCDNA3.1	343	127	559	869	870	MPIF
		HSA	mature HSA and downstream of the MPIF leader
			sequence.
128	2230	pC4:TREM-1.M1-P202.HSA	Amino acids M1 to P202 of TREM-1 fused upstream of	pC4	344	128	560	871	872	Native TREM-1
			mature HSA.
129	2240	pC4:SP.Ck7 Q22-A89.HSA.	N-terminal Methionine fused to amino acids Q22 to A89	pC4	345	129	561	873	874	MPIF
			of Ckβ7 fused upstream of mature HSA and downstream
			of the MPIF leader sequence. Contains a linker sequence
			between Ckβ7 and HSA.
130	2241	pC4:HSA.Ck7metQ22-A89.	N-terminal Methionine fused to amino acids Q22 to A89	pC4	346	130	562	875	876	HSA/kex2
			of Chemokine beta 7 (Ckbeta 7 or CK7) fused
			downstream of HSA with HSA/kex2 leader sequence.
			Contains a linker sequence between CkB7 and HSA.
131	2244	pC4.HCNCA73.HSA	HCNCA73 fused upstream of mature HSA.	pC4	347	131	563	877	878	HCNCA73
132	2245	pScNHSA:CK7.Q22-A89	Amino acids Q22 to A89 of Ckβ7 fused downstream of	pScNHSA	348	132	564	879	880	HSA/kex2
			HSA with HSA/kex2 leader sequence. Contains a linker
			sequence between Ckβ7 and HSA.
133	2246	pScCHSA.CK7metQ22-A89	N-terminal Methionine fused to amino acids Q22 to A89	pScCHSA	349	133	565	881	882	HSA/kex2
			of Ckβ7 fused upstream of mature HSA and downstream
			of HSA/kex2 leader sequence.
134	2247	pSAC35:CK7metQ22-A89.HSA.	N-terminal Methionine fused to amino acids Q22 to A89	pSAC35	350	134	566	883	884	HSA/kex2
			of Ckβ7 fused upstream of mature HSA and downstream
			of HSA/kex2 leader sequence.
135	2248	pSAC35:HSA.CK7metQ22-A89.	N-terminal Methionine fused to amino acids Q22 to A89	pSAC35	351	135	567	885	886	HSA/kex2
			of Ckβ7 fused downstream of HSA with HSA/kex2 leader
			sequence. Contains a linker sequence between Ckβ7 and
			HSA.
136	2249	pSAC35:IFNa2-HSA	Mature IFNa2 fused upstream of mature HSA and	pSAC35	352	136	568	887	888	HSA/kex2
		also named: pSAC23:IFNα2-HSA	downstream of HSA/kex2 leader sequence.
137	2250	pSAC35:HSA.INSULIN(GYG)	Mature Insulin wherein the C-peptide is replaced by the C-	pSAC35	353	137	569	889	890	HSA
		also named:	domain of IGF-1 fused downstream of HSA. DNA
		PSAC35.HSA.INSULING(GYG).	encoding Insulin was codon optimized.
		F1-N62
138	2251	pScCHSA:VEGF2.T103-R227.	Amino acids T103 to R227 of VEGF2 fused upstream of	pScCHSA	354	138	570	891	892	HSA/kex2
			mature HSA and downstream of HSA/kex2 leader
			sequence.
139	2252	pScNHSA:VEGF2.T103-R227.	Amino acids T103 to R227 of VEGF2 fused downstream	pScNHSA	355	139	571	893	894	HSA/kex2
			of HSA with HSA/kex2 leader sequence.
140	2255	PSAC35:INSULIN(GYG).HSA	Mature Insulin wherein the C-peptide is replaced by the C-	pSAC35	356	140	572	895	896	HSA/kex2
		also named	domain of IGF-1 fused upstream of mature HSA and
		pSAC35.INSULING(GYG).F1-N62.	downstream of HSA/kex2 leader. DNA encoding Insulin
		HSA	was codon optimized.
141	2256	pSAC35:VEGF2.T103-R227.	Amino acids T103 to R227 of VEGF2 fused upstream of	pSAC35	357	141	573	897	898	HSA/kex2
		HSA	mature HSA and downstream of HSA/kex2 leader
			sequence.
142	2257	pSAC35:HSA.VEGF2.T103-R227	Amino acids T103 to R227 of VEGF-2 fused downstream	pSAC35	358	142	574	899	900	HSA/kex2
			of HSA with HSA/kex2 leader sequence.
143	2271	pEE12.1:HCHNF25M1-R104.	Amino acids M1 to R104 of HCHNF25 fused upstream of	pEE12.1	359	143	575			Native
		HSA	mature HSA.							HCHNF25
144	2276	pSAC35:HSA.INSULIN(GGG)	Mature Insulin wherein the C-peptide is replaced by a	pSAC35	360	144	576	901	902	HSA
		also named:	synthetic linker fused downstream of HSA. DNA
		pSAC35.HSA.INSULING(GGG).	encoding Insulin was codon optimized.
		F1-N58
145	2278	pSAC35:insulin(GGG).HSA	Mature Insulin wherein the C-peptide is replaced by a	pSAC35	361	145	577	903	904	HSA/kex2
			synthetic linker fused downstream of HSA/kex2 leader
			and upstream of mature HSA. DNA encoding Insulin was
			codon optimized.
146	2280	pC4:HCHNF25.HSA	HCHNF25 fused upstream of mature HSA.	pC4	362	146	578	905	906	Native
										HCHNF25
147	2283	pScCHSA:EPOcoA28-D192.	Amino acids A28 to D192 of EPO variant (where glycine	pScCHSA	363	147	579	907	908	HSA/kex2
		51N/Q, 65N/Q, 110N/Q	at amino acid 140 has been replaced with an arginine) are
		EPO	fused upstream of mature HSA and downstream of
			HSA/kex2 leader sequence. Glycosylation sites at amino
			acids 51, 65 and 110 are mutated from N to Q residue.
			DNA encoding EPO is codon optimized.
148	2284	pScNHSA:EPOcoA28-D192.	Amino acids A28 to D192 of EPO variant (where glycine	pScNHSA	364	148	580	909	910	HSA/kex2
		51N/Q, 65N/Q, 110N/Q	at amino acid 140 has been replaced with an arginine)
		EPO	fused downstream of mature HSA and HSA/kex2 leader
			sequence. Glycosylation sites at amino acids 51, 65 and
			110 are mutated from N to Q residue. DNA encoding EPO
			is codon optimized.
149	2287	pSAC35:EPOcoA28-D192.	Amino acids A28 to D192 of EPO variant (where glycine	pSAC35	365	149	581	911	912	HSA/kex2
		51N/Q, 65N/Q, 110N/Q.HSA.	at amino acid 140 has been replaced with an arginine)
			fused upstream of mature HSA and downstream of
			HSA/kex2 leader sequence. Glycosylation sites at amino
			acid 51, 65 and 110 are mutated from N to Q residue.
			DNA encoding EPO is codon optimized.
150	2289	pSAC35:HSA.EPOcoA28-D192.	Amino acids A28 to D192 of EPO variant (where glycine	pSAC35	366	150	582	913	914	HSA/kex2
		51N/Q, 65N/Q, 110N/Q.	at amino acid 140 has been replaced with an arginine)
			fused downstream of mature HSA and HSA/kex2 leader
			sequence. Glycosylation sites at amino acid 51, 65 and 110
			are mutated from N to Q residue. DNA encoding EPO is
			codon optimized.
151	2294	pC4:EPO.R140G.HSA	Amino acids M1-D192 of EPO fused upstream of mature	pC4	367	151	587	915	916	Native EPO
		also named pC4.EPO.R1406.HSA	HSA. The EPO sequence included in construct 1997 was
			used to generate this construct, mutating arginine at EPO
			amino acid 140 to glycine. This mutated sequence
			matches the wildtype EPO sequence.
152	2295	pSAC35:humanresistin.K19-P108:	Amino acids K19 to P108 of Resistin fused upstream of	pSAC35	368	152	584	917	918	HSA/kex2
		HSA	mature HSA and downstream of HSA/kex2 leader
			sequence.
153	2296	pSAC35:HSA:humanresistin.K19-P108	Amino acids K19 to P108 of Resistin fused downstream of	pSAC35	369	153	585	919	920	HSA
			HSA.
154	2297	pSAC35:humanresistin.K19-P108.	Amino acids K19 to P108 of Resistin fused upstream of	pSAC35	370	154	586	921	922	HSA/kex2
		stop:HSA	mature HSA and downstream of HSA/kex2 leader
			sequence. Includes two stops at 3′ end for termination of
			translation before the HSA.
155	2298	pEE12.1:EPO.R140G.HSA	Amino acids M1 to D192 of EPO fused upstream of	pEE12.1	371	155	587	923	924	Native EPO
			mature HSA. The EPO sequence included in construct
			1997 was used to generate this construct, mutating
			arginine at EPO amino acid 140 to glycine. This mutated
			sequence matches the wildtype EPO sequence.
156	2300	pC4:humanresistin.M1-P108:HSA	Amino acids M1 to P108 of Resistin fused upstream of	pC4	372	156	588	925	926	Native resistin
			mature HSA.
157	2309	pEE12.1:humanresistin.M1-P108:	Amino acids M1 to P108 of Resistin fused upstream of	pEE12.1	373	157	589	927		Native resistin
		HSA	mature HSA.
158	2310	pc4:EPOco.M1-D192.HSA	Amino acids M1 to D192 of EPO variant fused upstream	pC4	374	158	590	928	929	Native EPO
			of mature HSA. DNA encoding EPO is codon optimized.
			The EPO sequence included in construct 1997 was used to
			generate this construct, mutating arginine at EPO amino
			acid 140 to glycine. This mutated sequence matches the
			wildtype EPO sequence.
159	2311	pC4:EPO.M1-G27.EPOco.A28-D192.	Amino acids M1 to D192 of EPO fused upstream of	pC4	375	159	591	930	931	Native EPO
		HSA	mature HSA. DNA encoding only EPO portion is codon
			optimized. The EPO sequence included in construct 1997
			was used to generate this construct, mutating arginine at
			EPO amino acid 140 to glycine. This mutated sequence
			matches the wildtype EPO sequence.
160	2320	pC4:HCHNF25M1-R104.HSA	Amino acids M1 to R104 of HCHNF25 fused upstream of	pC4	376	160	592	932	933	Native
			mature HSA.							HCHNF25
161	2325	pC4.EPO:M1-D192.HSA.Codon	Amino acids M1 to D192 of EPO fused upstream of	pC4	377	161	593			Native EPO
		opt.	mature HSA. DNA encoding EPO is codon optimized.
162	2326	pEE12.1.EPO:M1-D192.	Amino acids M1 to D192 of EPO fused upstream of	pEE12.1	378	162	594			Native EPO
		HSA.Codon opt.	mature HSA. DNA encoding EPO is codon optimized.
163	2328	pC4:HLDOU18.K23-R429.HSA	Amino acids K23 to R429 of HLDOU18 fused upstream	pC4	379	163	595	934	935	HSA
			of mature HSA and downstream of native HSA leader
			sequence.
164	2330	CK-Beta4-HSA	Full length Ckbeta4 fused upstream of mature HSA.	pSAC35	380	164	596	936	937	Native CKβ4
165	2335	pC4:MPIFsp.ck{b}4D31-M96.	Amino acids D31 to M96 of Ckbeta4 fused upstream of	pC4	381	165	597	938	939	MPIF
		HSA	mature HSA and downstream of MPIF leader sequence.
166	2336	pC4:MPIFsp.ck{b}4G35-M96.	Amino acids G35 to M96 of Ckbeta4 fused upstream of	pC4	382	166	598	940	941	MPIF
		HSA	mature HSA and downstream of MPIF leader sequence.
167	2337	pC4:MPIFsp.ck{b}4G48-M96.	Amino acids G48 to M96 of Ckbeta4 fused upstream of	pC4	383	167	599	942	943	MPIF
		HSA	mature HSA and downstream of MPIF leader sequence.
168	2338	pC4:MPIFsp.ck{b}4A62-M96.	Amino acids A62 to M96 of Ckbeta4 fused upstream of	pC4	384	168	600	944	945	MPIF
		HSA	mature HSA and downstream of MPIF leader sequence.
169	2340	pC4:HSA.HLDOU18.K23-R429	Amino acids K23 to R429 of HLDOU18 fused	pC4	385	169	601	946	947	HSA
			downstream of HSA.
170	2343	pSAC35.INV-IFNA2.HSA	Mature Interferon alpha2 fused upstream of mature HSA	pSAC35	386	170	602	948	949	invertase
			and downstream of invertase signal peptide.
171	2344	pC4.SpIg.EPO:A28-D192.	Amino acids A28 to D192 of EPO fused upstream of	pC4	387	171	603	950	951	Mouse Ig leader
		HSA.Codon opt.	mature HSA and downstream of mouse Ig leader
			sequence. DNA encoding EPO is codon optimized.
172	2348	pC4:MPIFsp.ck{b}4G57-M96.	Amino acids G57 to M96 of Ckbeta4 fused upstream of	pC4	388	172	604	952	953	MPIF
		HSA	mature HSA and downstream of MPIF leader sequence.
173	2350	pC4:MPIFsp.HLDOU18(S320-R429).	Amino acids S320 to R429 of HLDOU18 fused upstream	pC4	389	173	605	954	955	MPIF
		HSA	of mature HSA and downstream of MPIF leader sequence.
174	2351	pC4:HSA.HLDOU18(S320-R429)	Amino acids S320 to R429 of HLDOU18 fused	pC4	390	174	606	956	957	HSA
			downstream of HSA.
175	2355	pSAC35:MATalpha.d8ckbeta1.G28-N93:	Amino acids G28 to N93 of Ckbeta1 fused upstream of	pSAC35	391	175	607	958	959	MFα-1
		HSA	mature HSA and downstream of the yeast mating factor
			alpha leader sequence.
176	2359	pEE12:HLDOU18.K23-R429.	Amino acids K23 to R429 of HLDOU18 fused upstream	pEE12.1	392	176	608			HSA
		HSA	of mature HSA and downstream of native HSA leader
			sequence.
177	2361	pC4:HRDFD27:HSA	HRDFD27 fused upstream of mature HSA.	pC4	393	177	609	960	961	Native
										HRDFD27
178	2362	pEE12:HSA.HLDOU18.K23-R429	Amino acids K23 to R429 of HLDOU18 fused	pEE12.1	394	178	610			HSA
			downstream of HSA.
179	2363	pC4GCSF.HSA.EPO.A28-D192	Amino acids M1 to P204 of GCSF fused upstream of	pC4	395	179	611			Native GCSF
			mature HSA which is fused upstream of amino acids A28
			to D192 of EPO variant (where amino acid 140 of EPO is
			mutated from glycine to arginine.)
180	2365	pEE12.1.HCNCA73HSA	HCNCA73 is fused upstream of mature HSA.	pEE12.1	396	180	612	962	963	Native
										HCNCA73
181	2366	pSAC35.MAF-IFNa2.HSA	Mature IFNa2 fused upstream of mature HSA and	PSAC35	397	181	613	964	965	MFα-1
			downstream of yeast mating factor alpha leader sequence.
182	2367	pEE12.MPIFsp.HLDOU18.S320-R429.	Amino acids S320 to R429 of HLDOU18 fused upstream	pEE12.1	398	182	614	966	967	MPIF
		HSA	of mature HSA and downstream of MPIF leader sequence.
183	2369	pC4:HLDOU18.HSA	Amino acids M1 to R429 of HLDOU18 fused upstream of	pC4	399	183	615	968	969	Native
			mature HSA.							HLDOU18
184	2370	pEE12:HLDOU18.HSA	Amino acids M1 to R429 of HLDOU18 fused upstream of	pEE12.1	400	184	616			Native
			mature HSA.							HLDOU18
185	2373	pC4.GCSF.HSA.EPO.A28-D192.	Amino acids M1 to P204 of GCSF is fused upstream of	pC4	401	185	617			Native GCSF
		R140G	mature HSA which is fused upstream of amino acids A28
			to D192 of EPO, wherein amino acid 140 is glycine. The
			EPO sequence included in construct 1997 was used to
			generate this construct, mutating arginine at EPO amino
			acid 140 to glycine. This mutated sequence matches the
			wildtype EPO sequence.
186	2381	pC4:HSA-IFNa2(C17-E181)	Amino acids C17 to E181 of IFNa2 (fragment shown as	pC4	402	186	618	970	971	HSA
			amino acids C1 to E165 of SEQ ID NO: 618) fused
			downstream of HSA.
187	2382	pC4:IFNa2-HSA	IFNa2 fused upstream of mature HSA.	pC4	403	187	619	972	973	Native IFNα2
										leader
188	2387	pC4:EPO(G140)-HSA-	Amino acids M1-D192 of EPO fused upstream of mature	pC4	404	188	620			Native EPO
		GCSF.T31-P204	HSA which is fused upstream of amino acids T31 to P204
			of GCSF.
189	2407	pC4:HWHGZ51.M1-N323.HSA	Amino acids M1 to N323 of HWHGZ51 fused upstream	pC4	405	189	621	974	975	Native
			of mature HSA.							HWHGZ51
190	2408	pEE12.1:HWHGZ51.M1-N323.	Amino acids M1 to N323 of HWHGZ51 fused upstream	pEE12.1	406	190	622	976	977	Native
		HSA	of mature HSA.							HWHGZ51
191	2410	pSAC35INV:IFNa-HSA	Mature IFNa2 fused downstream of the invertase signal	pSAC35	407	191	623	978	979	invertase
			peptide and upstream of mature HSA.
192	2412	pSAC35:delKEX.d8ckbeta1.G28-N93:	Amino acids G28 to N93 of Ckbeta1 fused downstream of	pSAC35	408	192	624	980	981	HSA minus the
		HSA	the HSA signal sequence (with the KEX site deleted - last							KEX site
			6 amino acids of the leader) and upstream of mature HSA.
193	2414	pC4.EPO:M1-D192	Amino acids M1 to D192 of EPO fused upstream of	pC4	409	193	625	982	983	Native EPO
		copt.HSA.GCSF.T31-P204	mature HSA which is fused upstream of amino acids T31
		also named:	to P204 of GCSF. DNA encoding EPO has been codon
		pC4.EPO:M1-D192	optimized.
		copt.HAS.GCSF.T31-P204
194	2428	pN4:PTH.S1-Q84/HSA	Amino acids S1 to Q84 of PTH fused upstream of mature	pN4	410	194	626			HSA
			HSA and downstream of the native HSA leader sequence.
195	2441	pEE12.EPO:M1-D192	Amino acids M1 to D192 of EPO fused upstream of	pEE12.1	409	196	628			EPO leader
		copt.HSA.GCSF.T31-P204	mature HSA which is fused upstream of amino acids T31
		also named:	to P204 of GCSF. DNA encoding EPO has been codon
		pEE12.EPO:M1-D192	optimized.
		copt.HSA.GCSF.T31-P204
196	2447	pC4:HSA.humancalcitonin.C1-G33	Amino acids C98 to G130 of SEQ ID NO: 629 fused	pC4	413	197	629	986	987	HSA
			downstream of HSA.
197	2448	pSAC35:GLP-1(7-36).HSA	Amino acids H98 to R127 of preproglucagon (SEQ ID	pSAC35	414	198	630	988	989	HSA/kex2
			NO: 630) (hereinafter this specific domain will be referred
			to as “GLP-1(7-36)”) is fused upstream of mature HSA
			and downstream of HSA/kex2 leader sequence.
198	2449	pSAC35:INV.d8CKB1.G28-N93:	Amino acids G28 to N93 of Ckbeta1 fused downstream of	pSAC35	415	199	631	990	991	Invertase
		HSA	the invertase signal peptide and upstream of mature HSA.
199	2455	pSAC35:HSA.GLP-1(7-36)	GLP-1(7-36) is fused downstream of mature HSA and	pSAC35	416	200	632	992	993	HSA/kex2
			HSA/kex2 leader sequence.
200	2456	pSAC35:GLP-1(7-36(A8G)).HSA	Amino acids H98 to R127 of Preproglucagon (SEQ ID	pSAC35	417	201	633	994	995	HSA/kex2
			NO: 633)(also referred to as “GLP-1(7-36)”) is mutated at
			amino acid 99 of SEQ ID NO: 633 to replace the alanine
			with a glycine. This particular GLP-1 mutant will be
			hereinafter referred to as “GLP-1(7-36(A8G))” and
			corresponds to the sequence shown in SEQ ID NO: 1808.
			GLP-1(7-36(A8G)) is fused upstream of mature HSA and
			downstream of HSA/kex2 leader sequence.
201	2457	pSAC35:HSA.GLP-1(7-36(A8G))	GLP-1(7-36(A8G)) (SEQ ID NO: 1808) is fused	pSAC35	418	202	634	996	997	HSA/kex2
			downstream of mature HSA and HSA/kex2 leader
			sequence.
202	2469	pSAC35:HSA.exendin.H48-S86	Amino acids H48 to S86 of Extendin fused downstream of	pSAC35	419	203	635			HSA
			full length HSA.
203	2470	pSAC35:Exendin.H48-S86.HSA	Amino acids H48 to S86 of Extendin fused upstream of	pSAC35	420	204	636			HSA/kex2
			mature HSA and downstream of HSA/kex2 leader
			sequence.
204	2473	pC4.HLDOU18:HSA:S320-R429	M1-R319 of HLDOU18 (containing the furin site RRKR)	pC4	421	205	637	998	999	Native
			followed by residues ‘LE’ followed by mature HSA							HLDOU18
			followed by ‘LE’ and amino acids S320 through R429 of
			HLDOU18 (fragment shown as SEQ ID NO: 637).
205	2474	pSAC35.MDC.P26-Q93.HSA	Amino acids P26 to Q93 of MDC fused downstream of	pSAC35	422	206	638	1000	1001	HSA/kex2
			the HSA/kex2 leader and upstream of mature HSA.
206	2475	pSAC35.MDC.M26-Q93.HSA	Amino acids Y27 to Q93 of MDC with an N-terminal	pSAC35	423	207	639	1002	1003	HSA/kex2
			methionine, fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
207	2476	pSAC35.MDC.Y27-Q93.HSA	Amino acids Y27 to Q93 of MDC fused downstream of	pSAC35	424	208	640	1004	1005	HSA/kex2
			the HSA/kex2 leader and upstream of mature HSA.
208	2477	pSAC35.MDC.M27-Q93.HSA	Amino acids G28 to Q93 of MDC with an N-terminal	pSAC35	425	209	641	1006	1007	HSA/kex2
			methionine, fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
209	2489	pSAC35:HSA.C17.A20-R136	Amino acids A20 to R136 of C17 fused downstream of	pSAC35	426	210	642	1008	1009	HSA/kex2
			mature HSA with HSA/kex2 leader sequence.
210	2490	pSAC35:C17.A20-R136.HSA	Amino acids A20 to R136 of C17 fused downstream of	pSAC35	427	211	643	1010	1011	HSA/kex2
			the HSA/kex2 leader and upstream of mature HSA.
211	2492	pC4.IFNb(deltaM22).HSA	Mutant full length INFbeta fused upstream of mature	pC4	428	212	644			Native IFNβ
			HSA. First residue of native, mature IFNbeta (M22) has							leader
			been deleted.
212	2498	pC4:HSA.KGF2D60.G96-S208	Amino acids G96 to S208 of KGF-2 fused downstream of	pC4	429	213	645	1012	1013	HSA
			HSA.
213	2499	pC4:KGF2D60.G96-S208:HSA	Amino acids G96 to S208 of KGF2 fused upstream of	pC4	430	214	646	1014	1015	HSA
			mature HSA and downstream of the HSA signal peptide.
214	2501	pSAC35:scFvI006D08.HSA	BLyS antibody fused upstream of mature HSA and	pSAC35	431	215	647	1016	1017	HSA/kex2
			downstream of HSA/kex2 signal peptide.
215	2502	pSAC35:scFvI050B11.HSA	BLyS antibody fused upstream of mature HSA and	pSAC35	432	216	648	1018	1019	HSA/kex2
			downstream of HSA/kex2 leader sequence.
216	2513	pC4:HSA.salmoncalcitonin.C1-G33	C1 through G33 of salmon calcitonin fused downstream of	pC4	1513	1345	1681	1854	1855	HSA
			full length HSA.
217	2515	pC4:HDPBQ71.M1-N565.HSA	M1 through N565 of HDPBQ71 fused upstream of mature	pC4	1514	1346	1682	1856	1857	Native
			HSA							HDPBQ71
218	2529	pC4:TR1.M1-K194.HSA	Amino acids M1 to K194 of TR1 (including native signal	pC4	1223	1208	1238	1253	1254	Native TR1
			sequence) fused upstream of mature HSA.
219	2530	pC4:TR1.M1-Q193.HSA	Amino acids M1 to Q193 of TR1 (including native signal	pC4	1224	1209	1239	1255	1256	Native TR1
			sequence) fused upstream of mature HSA.
220	2531	pC4:TR1.M1-E203.HSA	Amino acids M1 to E203 of TR1 (including native signal	pC4	1225	1210	1240	1257	1258	Native TR1
			sequence) fused upstream of mature HSA.
221	2532	pC4:TR1.M1-Q339.HSA	Amino acids M1 to Q339 of TR1 (including native signal	pC4	1226	1211	1241	1259	1260	Native TR1
			sequence) fused upstream of mature HSA.
222	2545	pEE12.1:HDPBQ71.M1-N565.	M1 through N565 of HDPBQ71 fused upstream of mature	pEE12.1	1515	1347	1683			Native
		HSA	HSA							HDPBQ71
223	2552	pSAC35:KGF2delta33.S69-S208.	Amino acids S69 through S208 of KGF2 fused upstream	pScCHSA	1516	1348	1684	1858	1859	HSA/kex2
		HSA	of HSA.
224	2553	pSAC35:HSA.KGF2delta33.S69-S208	HSA/kex2 signal peptide followed by HSA peptide	pScNHSA	1517	1349	1685	1860	1861	HSA/kex2
			followed by amino acids S69 to S208 of KGF2.
225	2555	pEE12.1:TR1.M1-Q193.HSA	Amino acids M1 to Q193 of TR1 (including native signal	pEE12.1	1227	1212	1242			Native TR1
			sequence) fused upstream of mature HSA.
226	2556	pEE12.1:TR1.M1-K194.HSA	Amino acids M1 to K194 of TR1 (including native signal	pEE12.1	1228	1213	1243			Native TR1
			sequence) fused upstream of mature HSA.
227	2557	pEE12.1:TR1.M1-E203.HSA	Amino acids M1 to E203 of TR1 (including native signal	pEE12.1	1229	1214	1244			Native TR1
			sequence) fused upstream of mature HSA.
228	2558	pEE12.1:TR1.M1-Q339.HSA	Amino acids M1 to Q339 of TR1 (including native signal	pEE12.1	1230	1215	1245			Native TR1
			sequence) fused upstream of mature HSA.
229	2571	pC4.OSCAR.R232.HSA	M1-R232 of OSCAR fused upstream of mature HSA.	pC4	1518	1350	1686	1862	1863	Native OSCAR
										receptor leader
230	2580	pC4.IFNb(deltaM22, C38S).HSA	IFNb fused upstream of mature HSA. The IFNb used in	pC4	1519	1351	1687			Native IFNβ
			this fusion lacks the first residue of the mature form of
			IFNb, which corresponds to M22 of SEQ ID NO: 1687.
			Also amino acid 38 of SEQ ID NO: 1687 has been mutated
			from Cys to Ser.
231	2584	pC4:MPIFsp.KGF2delta28.A63-S208.	MPIF signal sequence followed by A63 through S208 of	pC4	1520	1352	1688	1864	1865	MPIF
		HSA	KGF2 followed by mature HSA.
232	2603	pC4:HSA(A14)-EPO(A28-D192.	Modified HSA A14 leader fused upstream of mature HSA	pC4	1521	1353	1689			Modified HSA
		G140)	which is fused upstream of A28 through D192 of EPO.							(A14)
			Amino acid 140 of EPO is a ‘G’.
233	2604	pC4:HSA(S14)-EPO(A28-D192.	Modified HSA S14 leader fused upstream of mature HSA	pC4	1522	1354	1690			Modified HSA
		G140)	which is fused upstream of A28 through D192 of EPO.							(S14)
			Amino acid 140 of EPO is a ‘G’.
234	2605	pC4:HSA(G14)-EPO(A28-D192.	Modified HSA G14 leader fused upstream of mature HSA	pC4	1523	1355	1691			Modified HSA
		G140)	which is fused upstream of A28 through D192 of EPO.							(G14)
			Amino acid 140 of EPO is a ‘G’.
235	2606	pC4:HSA#64.KGF2D28.A63-S208	A63 through S208 of KGF2 fused downstream of mature	pC4	1524	1356	1692	1866	1867	Modified HSA
			HSA and the modified #64 leader sequence.							#64
236	2607	pC4:HSA#65.KGF2D28.A63-S208	A63 through S208 of KGF2 downstream of mature HSA	pC4	1525	1357	1693	1868	1869	Modified HSA
			and the modified #65 leader sequence.							#65
237	2608	pC4:HSA#66.KGF2D28.A63-S208	A63 through S208 of KGF2 fused downstream of mature	pC4	1526	1358	1694	1870	1871	Modified HSA
			HSA and the modified #66 leader sequence.							#66
238	2623	pC4:(AGVSG, 14-18)	A modified HSA A14 leader followed by mature HSA and	pC4	1527	1359	1695			Modified HSA
		HSA.HLDOU18.K23-R429	amino acids K23 through R429 of HLDOU18.							(A14) leader
239	2624	pC4:(SGVSG, 14-18)	Modified HSA S14 leader followed by mature HSA and	pC4	1528	1360	1696			Modified HSA
		HSA.HLDOU18.K23-R429	amino acids K23 to R429 of HLDOU18.							(S14) leader
240	2625	pC4:(GGVSG, 14-18)	A modified HSA G14 leader sequence followed by mature	pC4	1529	1361	1697			Modified HSA
		HSA.HLDOU18.K23-R429	HSA and amino acids K23 through R429 of HLDOU18.							(G14) leader
241	2630	pC4:HSA.KGF2D28.A63-S208#2	Amino acids A63 to S208 of KGF-2 fused to the C-	pC4	1530	1362	1698	1872	1873	HSA
			terminus of HSA.
242	2631	pEE12.1:(AGVSG, 14-18)	A modified HSA A14 leader sequence followed by	pEE12.1	1531	1363	1699			Modified HSA
		HSA.HLDOU18.K23-R429	mature HSA and amino acids K23 through R429 of							(A14) leader
			HLDOU18.
243	2632	pEE12.1:(SGVSG, 14-18)	Modified HSA S14 leader followed by mature HSA and	pEE12.1	1532	1364	1700			Modified HSA
		HSA.HLDOU18.K23-R429	amino acids K23 to R429 of HLDOU18.							(S14) leader
244	2633	pEE12.1:(GGVSG, 14-18)	A modified HSA G14 leader sequence followed by	pEE12.1	1533	1365	1701			Modified HSA
		HSA.HLDOU18.K23-R429	mature HSA and amino acids K23 through R429 of							(G14) leader
			HLDOU18.
245	2637	pSAC35:HSA.GCSF.T31-P207	HSA/kex2 leader fused upstream of mature HSA	pScNHSA	1534	1366	1702	1874	1875	HSA/kex2
			followed by T31 through P207 of GCSF (SEQ ID
			NO: 1702).
246	2638	pPPC007:116A01.HSA	scFv I116A01 with C-terminal HSA fusion, where the	pPPC007	1535	1367	1703	1876	1877	scFvI006A01
			mature form of HSA lacks the first 8 amino acids.
247	2647	pSAC35:T7.HSA.	The T7 peptide (SEQ ID NO: 1704) of Tumstatin was	pScCHSA	1536	1368	1704	1878	1879	HSA/kex2
			fused with a C-terminal HSA and N terminal HSA/kex2
			leader.
248	2648	pSAC35:T8.HSA	The T8 peptide (SEQ ID NO: 1705) of Tumstatin is fused	pScCHSA	1537	1369	1705	1880	1881	HSA/kex2
			upstream to mature HSA and downstream from
			HSA/kex2.
249	2649	pSAC35:HSA.T7	The T7 peptide (SEQ ID NO: 1706) of Tumstatin was	pScNHSA	1538	1370	1706	1882	1883	HSA/kex2
			fused with a N-terminal HSA/kex2 signal sequence.
250	2650	pSAC35:HSA.T8	The T8 peptide (SEQ ID NO: 1767) of Tumstatin is fused	pScNHSA	1539	1371	1707	1884	1885	HSA/kex2
			downstream to HSA/kex2 signal sequence and mature
			HSA.
251	2656	pSac35:Insulin(KR.GGG.KR).HSA	Synthetic gene coding for a single-chain insulin with HSA	pScCHSA	1540	1372	1708	1886	1887	HSA/kex2
			at C-terminus. Contains a modified loop for processing
			resulting in correctly disulfide bonded insulin coupled to
			HSA.
252	2667	pSAC35:HSA.T1249	T1249 fused downstream of full length HSA	pSAC35	1178	1179	1180	1181	1182	HSA
253	2668	pSac35:HSA.Insulin(KR.GGG.KR)	Synthetic gene coding for insulin with FL HSA at N-	pScNHSA	1541	1373	1709	1888	1889	HSA
			terminus. Contains a modified loop for processing
			resulting in correctly disulfide bonded insulin coupled to
			HSA.
254	2669	pSac35:Insulin(GGG.KK).HSA	Synthetic gene coding for a single-chain insulin with HSA	pScCHSA	1542	1374	1710	1890	1891	HSA/kex2
			at C-terminus. Contains a modified loop.
255	2670	pSAC35:T1249.HSA	T1249 fused downstream of HSA/kex2 leader and	pSAC35	1183	1179	1180	1184	1185	HSA/kex2
			upstream of mature HSA.
256	2671	pSac35:HSA.Insulin(GGG.KK)	Synthetic gene coding for a single-chain insulin with HSA	pScNHSA	1543	1375	1711	1892	1893	HSA
			at N-terminus. Contains a modified loop for greater
			stability.
257	2672	pSAC35:HSA.T20	Amino terminus of T20 (codon optimized) fused	pSAC35	1186	1187	1188	1189	1190	HSA
			downstream of full length HSA
258	2673	pSAC35:T20.HSA	Amino terminus of T20 (codon optimized) fused	pSAC35	1191	1187	1188	1192	1193	HSA/kex2
			downstream of HSA/kex2 leader and upstream of mature
			HSA.
259	2700	pSAC35:HSA.GCSF.T31-R199	C-terminal deletion of GCSF fused downstream of mature	pSAC35	1544	1376	1712	1894	1895	HSA/kex2
			HSA.
260	2701	pSAC35:HSA.GCSF.T31-H200	C-terminal deletion of GCSF fused downstream of mature	pScNHSA	1545	1377	1713	1896	1897	HSA/kex2
			HSA.
261	2702	pSAC35:HSA.GCSF.T31-L201	HSA/kex2 leader followed by mature HSA and amino	pSAC35	1194	1195	1196	1197	1198	HSA/kex2
			acids T31-L201 of GCSF (corresponding to amino acids
			T1 to L171 of SEQ ID NO: 1196).
262	2703	pSAC35:HSA.GCSF.A36-P204	HSA/kex2 leader followed by mature HSA and amino	pScNHSA	1546	1378	1714	1898	1899	HSA/kex2
			acids A36-P204 of GCSF.
263	2714	pC4:HSASP.PTH34(2)/HSA	PTH34 double tandem repeats fused downstream of HSA	pC4	1199	1200	1201	1202	1203	HSA leader
			leader (with the KEX site deleted - last 6 amino acids of							minus Kex site
			the leader) and upstream of mature HSA.
264	2724	pSAC35.sCNTF.HSA	HSA/Kex2 fused to CNTF, and then fused to mature	pSAC35	1547	1379	1715	1900	1901	HSA/kex2
			HSA.
265	2725	pSAC35:HSA.sCNTF	HSA/Kex2 fused to mature HSA and then to CNTF	pSAC35	1548	1380	1716	1902	1903	HSA/kex2
266	2726	pSac35.INV.GYGinsulin.HSA	Synthetic gene coding for a single-chain insulin with HSA	pSAC35	1549	1381	1717	1904	1905	Invertase
			at C-terminus. The signal peptide of invertase is used for
			this construct.
267	2727	pSac35.INV.GYGinsulin(delF1).	Synthetic gene coding for a single-chain insulin with HSA	pSAC35	1550	1382	1718	1906	1907	invertase
		HSA	at C-terminus. Construct uses the invertase signal peptide
			and is lacking the first amino acid (F) of mature human
			insulin.
268	2749	pEE12.1.OSCAR.R232.HSA	Amino acids M1 through R232 of OSCAR fused upstream	pEE12.1	1551	1383	1719	1908	1909	Native OSCAR
			of mature HSA.							leader
269	2784	pSAC35:Insulin(GYG)-HSA	Synthetic gene coding for a single-chain insulin with HSA	pSAC35	1552	1384	1720	1910	1911	invertase
		codon optimized	at C-terminus.
270	2789	pSAC35:Insulin(GGG).HSA	Synthetic gene coding for a single-chain insulin with HSA	pSAC35	1553	1385	1721	1912	1913	invertase
		(codon optimized)	at C-terminus.
271	2791	pEE12.1:HSAsp.PTH34(2X).HSA	Parathyroid hormone is fused in tandem and upstream of	pEE12.1	1554	1386	1722			HSA leader
			mature HSA and downstream from HSA signal peptide							minus Kex site
			(with the KEX site deleted - last 6 amino acids of the
			leader)
272	2795	pC4:HSA(A14)-IFNb.M22-N187	The mature form of IFNb is fused to the C-terminus of	pC4	1555	1387	1723			Modified HSA
			HSA, which contains an modified signal peptide, designed							(A14)
			to improve processing and homogeneity.
273	2796	pC4:HSA(S14)-IFNb.M22-N187	The mature form of IFNb is fused to the C-terminus of	pC4	1556	1388	1724			Modified HSA
			HSA, which contains a modified signal peptide, designed							(S14)
			to improve processing and homogeneity.
274	2797	pC4:HSA(G14)-IFNb.M22-N187	The mature form of IFNb is fused to the C-terminus of	pC4	1557	1389	1725			Modified HSA
			HSA, which contains an modified signal peptide.							(G14)
275	2798	pSAC35:Somatostatin(S14).HSA	A 14 amino acid peptide of Somatostatin fused	pScCHSA	1558	1390	1726	1914	1915	HSA/kex2
			downstream of HSA/kex2 leader and upstream of mature
			HSA.
276	2802	pSAC35:GLP-1(7-	GLP-1(7-36(A8G)) (SEQ ID NO: 1808) is fused	pScNHSA	1559	1391	1727			HSA/kex2
		36(A8G)).IP2.HSA	downstream from the HSA/kex2 leader sequence and
			upstream from the intervening peptide-2 of proglucagon
			peptide and upstream from mature HSA.
277	2803	pSAC35:GLP-1(7-	GLP-1(7-36(A8G)) (SEQ ID NO: 1808) is tandemly	pScCHSA	1231	1216	1246	1261	1262	HSA/kex2
		36(A8G))x2.HSA	repeated and fused downstream of the HSA/kex2 signal
			sequence, and upstream of mature HSA.
278	2804	pSAC35:coGLP-1(7-	GLP-1(7-36(A8G)) (SEQ ID NO: 1808) is tandemly	pScCHSA	1232	1217	1247	1263	1264	HSA/kex2
		36(A8G))x2.HSA	repeated and fused downstream of the HSA/kex2 signal
			sequence, and upstream of mature HSA.
279	2806	pC4:HSA#65.salmoncalcitonin.C1-G33	Modified HSA leader #65 followed by mature HSA and	pC4	1560	1392	1728	1916	1917	Modified HSA
			C1-G33 of salmon calcitonin.							#65
280	2821	pSac35.delKex2.Insulin(GYG).HSA	Synthetic gene coding for a single-chain insulin with HSA	pScCHSA	1561	1393	1729			Modified
			at C-terminus. The kex2 site has been deleted from the							HSA/kex2,
			HSA/KEX2 signal peptide.							lacking the
										Kex2 site.
281	2822	pSac35.alphaMF.Insulin(GYG).HSA	Synthetic gene coding for a single-chain insulin with HSA	pSAC35	1562	1394	1730	1920	1921	MFα-1
			at C-terminus. The signal peptide of alpha mating factor
			(MFα-1) is used for this construct.
282	2825	pSAC35:HSA.Somatostatin(S14)	14 amino acid peptide of Somatostatin was fused	pScNHSA	1563	1395	1731	1922	1923	HSA/kex2
			downstream of HSA/kex2 leader and mature HSA.
283	2830	pSAC35:S28.HSA	28 amino acids of somatostatin fused downstream of	pScCHSA	1564	1396	1732	1924	1925	HSA/kex2
			HSA/kex2 leader and upstream of mature HSA.
284	2831	pSAC35:HSA.S28	28 amino acids of somatostatin fused downstream of	pScNHSA	1565	1397	1733	1926	1927	HSA/kex2
			HSA/kex2 leader and mature HSA.
285	2832	pSAC35:Insulin.HSA (yeast	Long-acting insulin peptide fused upstream of mature	pScCHSA	1566	1398	1734	1928	1929	invertase
		codon optimized)	HSA.
286	2837	pSAC35:CKB1.K21-N93:HSA	K21-N93 of CKB1 (fragment shown as K2 to N74 of SEQ	pScCHSA	1567	1399	1735	1930	1931	HSA/kex2
			ID NO: 1735) fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
287	2838	pSAC35:CKB1.T22-N93:HSA	T22-N93 of CKB1 (fragment shown as T3 to N74 of SEQ	pScCHSA	1568	1400	1736	1932	1933	HSA/kex2
			ID NO: 1736) fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
288	2839	pSAC35:CKB1.E23-N93:HSA	E23-N93 of CKB1 (fragment shown as E4 to N74 of SEQ	pScCHSA	1569	1401	1737	1934	1935	HSA/kex2
			ID NO: 1737) fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
289	2840	pSAC35:CKB1.S24-N93:HSA	S24-N93 of CKB1 (fragment shown as S5 to N74 of SEQ	pScCHSA	1570	1402	1738	1936	1937	HSA/kex2
			ID NO: 1738) fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
290	2841	pSAC35:CKB1.S25-N93:HSA	S25-N93 of CKB1 (fragment shown as S6 to N74 of SEQ	pScCHSA	1571	1403	1739	1938	1939	HSA/kex2
			ID NO: 1739) fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
291	2842	pSAC35:CKB1.S26-N93:HSA	S26-N93 of CKB1 (fragment shown as S7 to N74 of SEQ	pScCHSA	1572	1404	1740	1940	1941	HSA/kex2
			ID NO: 1740) fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
292	2843	pSAC35:CKB1.R27-N93:HSA	R27-N93 of CKB1 (fragment shown as R8 to N74 of SEQ	pScCHSA	1573	1405	1741	1942	1943	HSA/kex2
			ID NO: 1741) fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
293	2844	pSAC35:CKB1.P29-N93:HSA	P29-N93 of CKB1 (fragment shown as P10 to N74 of	pScCHSA	1574	1406	1742	1944	1945	HSA/kex2
			SEQ ID NO: 1742) fused downstream of the HSA/kex2
			leader and upstream of mature HSA.
294	2845	pSAC35:CKB1.Y30-N93:HSA	Y30-N93 of CKB1 (fragment shown as Y11 to N74 of	pScCHSA	1575	1407	1743	1946	1947	HSA/kex2
			SEQ ID NO: 1743) fused downstream of the HSA/kex2
			leader and upstream of mature HSA.
295	2849	pC4.MPIFsp.CKB1.G28-N93.	G28-N93 of CKB1 (fragment shown as G9 to N74 of SEQ	pC4	1576	1408	1744	1948	1949	MPIF
		HSA	ID NO: 1744) fused downstream of the MPIF signal
			peptide and upstream of mature HSA.
296	2872	pSAC35:HSA.IFNaA(C1-Q91)/	This construct contains a hybrid form of IFNaA and	pSAC35	1309	1310	1311	1312	1313	HSA/kex2
		D(L93-E166)	IFNaD fused downstream of mature HSA.
297	2873	pSAC35:HSA.IFNaA(C1-Q91)/	This construct contains a hybrid form of IFNaA and	pSAC35	1314	1315	1316	1317	1318	HSA/kex2
		B(L93-E166)	IFNaB fused downstream of mature HSA.
298	2874	pSAC35:HSA.IFNaA(C1-Q91)/	This construct contains a hybrid form of IFNaA and IFNaF	pSAC35	1319	1320	1321	1322	1323	HSA/kex2
		F(L93-E166)	fused downstream of mature HSA.
299	2875	pSAC35:HSA.IFNaA(C1Q-62)/	This construct contains a hybrid form of IFNaA and	pSAC35	1324	1325	1326	1327	1328	HSA/kex2
		D(Q64-E166)	IFNaD fused downstream of mature HSA.
300	2876	pSAC35:HSA.IFNaA(C1-Q91)/	This construct contains a hybrid form of IFNaA and	pSAC35	1329	1330	1331	1332	1333	HSA/kex2
		D(L93-E166); R23K, A113V	IFNaD fused downstream of mature HSA.
301	2877	pSAC35:KT.Insulin.HSA	Killer toxin signal peptide fused to synthetic gene coding	pScCHSA	1577	1409	1745	1950	1951	Killer toxin
			for a single-chain insulin with C-terminal HSA
302	2878	pSAC35:AP.Insulin.HSA	Acid phospatase signal peptide fused to synthetic gene	pSAC35	1578	1410	1746			Acid
			coding for a single-chain insulin with C-terminal HSA.							phosphatase
303	2882	pSac35.alphaMFprepro.Insulin(GYG).	MFα-1 prepro signal followed by GYG insulin followed	pSAC35	1579	1411	1747			MFα-1
		HSA	by mature HSA.
304	2885	pSac35.alphaMFpreproEEA.Insulin	Yeast MFα-1 prepro signal followed by GYG insulin	pSAC35	1580	1412	1748			Yeast
		(GYG).HSA	follwed by mature HSA.							MFα-1
305	2886	pSAC35:HSA.GCSF.P40-P204	HSA/kex2 signal peptide followed by mature HSA	pSAC35	1581	1413	1749	1952	1953	HSA/kex2
			followed by GCSF (P40-P204).
306	2887	pSAC35:HSA.GCSF.P40-L201	HSA/kex2 signal peptide followed by mature HSA	pSAC35	1582	1414	1750	1954	1955	HSA/kex2
			followed by GCSF (P40-L201).
307	2888	pSAC35:HSA.GCSF.Q41-L201	HSA/kex2 signal peptide followed by mature HSA	pSAC35	1583	1415	1751	1956	1957	HSA/kex2
			followed by GCSF (Q41-L201).
308	2889	pSAC35:HSA.GCSF.Q41-P204	HSA/kex2 signal peptide followed by mature HSA	pSAC35	1584	1416	1752	1958	1959	HSA/kex2
			followed by GCSF (Q41-P204).
309	2890	pC4.HSA.GCSF.T31-P204	HSA/kex2 signal peptide followed by mature HSA	pC4	1585	1417	1753	1960	1961	HSA/kex2
			followed by GCSF (T31-P204).
310	2891	pGAP.alphaMF.Insulin(GYG).HSA	Synthetic gene coding for a single-chain insulin with HSA	pYPGaf	1586	1418	1754	1962	1963	HSA/kex2
			at C-terminus. The signal peptide of HSA/kex2 is used for
			this construct.
311	2897	pGAP.Insulin(KR.GGG.KR).HSA	Long-acting insulin analog using a synthetic gene coding	pYPGaf	1587	1419	1755	1964	1965	HSA/kex2
			for a single-chain insulin with HSA at C-terminus.
			Contains a modified loop for processing resulting in
			correctly disulfide bonded insulin coupled to HSA
312	2900	pSAC:GLP-1(7-36)x2.HSA	GLP-1(7-36) is tandemly repeated and then fused	pScCHSA	1233	1218	1248	1265	1266	HSA/kex2
			downstream of the HSA/kex2 signal sequence and
			upstream of mature HSA.
313	2901	pSAC35:IL22.A18-P202.HSA	Amino acids A18-P202 of IL22 fused downstream of	pSAC35	1588	1420	1756	1966	1967	HSA/kex2
			HSA/kex2 leader and upstream of mature HSA.
314	2902	pSAC35:Somatostatin(S14(A-G)).	A 14 amino acid peptide of Somatostatin, an inhibitor of	pScCHSA	1589	1421	1757	1968	1969	HSA/kex2
		HSA	growth hormone, synthesized as a C-terminal HSA fusion.
			Somatostatin has an alanine to glycine change at amino
			acid 1 of SEQ ID NO: 1757.
315	2903	pSAC35:HSA.A18-P202.IL22	Amino acids A18-P202 of IL22 fused downstream of full	pSAC35	1590	1422	1758	1970	1971	HSA
			length HSA.
316	2904	pSAC35:GLP-1(9-36).GLP-1(7-	Amino acids E100 to R127 of preproglucagon (SEQ ID	pScCHSA	1234	1219	1249	1267	1268	HSA/kex2
		36).HSA	NO: 1249) (hereinafter, this particular mutant is referred to
			as GLP-1(9-36)) is fused downstream from the HSA/kex2
			signal sequence and upstream from GLP-1(7-36), and
			mature HSA.
317	2908	pSAC35:HSA.HCE1P80	Mature HSA fused downstream of the HSA/kex2 leader	pSAC35	1591	1423	1759	1972	1973	HSA/kex2
			and upstream of HCE1P80.
318	2909	pSAC35:HSA.HDRMI82	Mature HSA fused downstream of the HSA/kex2 leader	pSAC35	1592	1424	1760	1974	1975	HSA/kex2
			sequence and upstream of HDRMI82.
319	2910	pSAC35:HSA.RegIV	Mature HSA fused downstream of the HSA/kex2 leader	pSAC35	1593	1425	1761	1976	1977	HSA/kex2
			sequence and upstream of RegIV.
320	2915	pC4:HSA#65.humancalcitonin.C1-G33	Modified HSA leader #65 followed by mature HSA and	pC4	1594	1426	1762	1978	1979	Modified HSA
			C98 through G130 of SEQ ID NO: 1762.							#65
321	2930	pC4.MPIF.Insulin(GYG).HSA	Insulin is downstream of an MPIF signal peptide and	pC4	1595	1427	1763	1980	1981	MPIF
			upstream of mature HSA.
322	2931	pC4.HSA.Insulin(GYG)	Synthetic gene coding for a mature single-chain insulin	pC4	1596	1428	1764	1982	1983	Modified HSA
			fused downstream of the modified HSA A14 leader and							(A14) leader
			mature HSA.
323	2942	pSac35.TA57.Insulin(GYG).HSA	The TA57 Propeptide fused to a single chain insulin	pScNHSA	1597	1429	1765	1984	1985	TA57
			(GYG), and then mature HSA.							propeptide
324	2943	pSAC35:HSA.T7.T7.T74-L98	Dimer construct - HSA/kex2 leader followed by mature	pScNHSA	1598	1430	1766	1986	1987	HSA/kex2
			HSA followed by two copies of T7 peptide (SEQ ID
			NO: 1766) of Tumstatin.
325	2944	pSAC:HSA.T8.T8.K69-S95	HSA/kex2 leader followed by mature HSA followed by	pScNHSA	1599	1431	1767	1988	1989	HSA/kex2
			two copies of T8 peptide (SEQ ID NO: 1767) of
			Tumstatin
326	2945	pSAC35:GLP-1(7-36(A8S)).GLP-	Amino acids H98 to R127 of preproglucagon (SEQ ID	pScCHSA	1235	1220	1250	1269	1270	HSA/kex2
		1(7-36).HSA	NO: 1250) is mutated at position 99 from alanine to serine
			(hereinafter, this particular mutant is referred to as GLP-
			1(7-36(A8S)), which is fused downstream from the
			HSA/kex2 signal sequence and upstream from GLP-1(7-
			36), and mature HSA.
327	2946	pSAC:T1249(×2).HSA	This dimer represents the wild type sequence for T1249.	pScCHSA	1600	1432	1768	1990	1991	HSA/kex2
			Both dimers have been yeast codon optimized. The second
			dimer was optimized to be different from the first (at the
			wobble position) to ensure good amplification. Construct
			has the HSA/kex2 leader followed by T1249 dimer
			followed by mature HSA.
328	2947	pSAC:CKb-1δ8(x2).HSA	Invertase signal peptide followed by amino acids G28-N93	pSAC35	1601	1433	1769	1992	1993	invertase
			of full length CKβ1 (SEQ ID NO: 1769), tandemly
			repeated, followed by mature HSA.
329	2964	pSAC35:GLP-1(7-36)x2.HSA	GLP-1(7-36) is tandemly repeated as a dimer and fused	pSAC35	1236	1221	1251	1271	1272	HSA/kex2
			downstream from the HSA/kex2 leader sequence and
			upstream from mature HSA.
330	2965	pC4:MPIFspP.PTH(1-34).HSA	MPIF signal peptide followed by 34 amino acids of PTH	pC4	1602	1434	1770	1994	1995	MPIF
			followed by mature HSA.
331	2966	pEE12:MPIFsp.PTH(1-34).HSA	MPIF signal peptide followed by 34 amino acids of PTH	PEE12.1	1603	1435	1771	1996	1997	MPIF
			followed by mature HSA.
332	2982	pSAC35:GLP-1(7-36(A8G).GLP-	GLP-1(7-36(A8G)) (SEQ ID NO: 1808) is fused	pScCHSA	1237	1222	1252	1273	1274	HSA/kex2
		1(7-36).HSA	downstream from the HSA/kex2 signal sequence and
			upstream from GLP-1(7-36) and mature HSA.
333	2983	pC4.HSA.Growth Hormone.F27-F-217	Modified (A14) HSA leader followed by mature HSA	pC4	1604	1436	1772	1998	1999	Modified HSA
			followed by F27 through F217 of growth hormone							(A14)
			(corresponding to amino acids F1 to F191 of SEQ ID
			NO: 1772).
334	2986	pSac35.y3SP.TA57PP.Insulin(GYG).	The TA57 Propeptide fused to a single chain insulin	pScCHSA	1605	1437	1773	2000	2001	TA57
		HSA	(GYG), and then mature HSA.							propeptide
335	3025	pSAC35:INU.Insulin.HSA	Inulinase signal peptide is fused upstream of single chain	pScCHSA	1606	1438	1774	2002	2003	inulinase
			insulin (GYG) and HSA.
336	3027	pSAC35:INV.GLP-1(7-	Invertase signal peptide followed by GLP-1(7-36(A8G))	pSAC35	1607	1439	1775	2004	2005	invertase
		36A8G)x2.HSA	(SEQ ID NO: 1808) tandemly repeated as a dimer,
			followed by mature HSA.
337	3028	pSAC35:INV.GLP-1(7-	Invertase signal peptide followed by GLP-1(7-36(A8G))	pSAC35	1608	1440	1776	2006	2007	invertase
		36(A8G)).GLP-1(7-36).HSA	(SEQ ID NO: 1808), then GLP-1(7-36(A8G)), and then
			mature HSA.
338	3045	pSAC35:DeltaKex.GLP-1(7-	HSA/kex2 signal sequence, minus the last six amino acids	pSAC35	1609	1440	1776	2008	2009	HSA/kex2 last
		36A8G)x2.HSA	of the leader, is fused to GLP-1(7-36(A8G)) (SEQ ID							six amino acids
			NO: 1808) which is tandemly repeated as a dimer,
			followed by mature HSA.
339	3046	pSAC35:Delta Kex.GLP-1(7-	HSA/kex2 signal sequence, minus the last six amino acids	pSAC35	1610	1440	1776	2010	2011	HSA/kex2 last
		36A8G).GLP-1(7-36).HSA	of the leader, is fused to GLP-1(7-36(A8G)) (SEQ ID							six amino acids
			NO: 1808), GLP-1(7-36), and mature HSA.
340	3047	pSAC35:HSA.Tum5	Full length HSA fused to the Tum5 peptide (SEQ ID	pScNHSA	1611	1443	1779	2012	2013	HSA
			NO: 1779) of Tumstatin.
341	3048	pSAC35:Tum5.HSA.	The Tum5 peptide (SEQ ID NO: 1780) of Tumstatin is	pScCHSA	1612	1444	1780	2014	2015	HSA/kex2
			fused to HSA and HSA/kex2 leader.
342	3049	pC4.HSA.HCE1P80.D92-L229	Amino acids D92 to L229 of HCE1P80 are fused	pC4	1613	1445	1781	2016	2017	HSA
			downstream of the full length HSA.
343	3050	pC4.HSA.HCE1P80.A20-L229	Amino acids A20-L229 of HCE1P80 are fused	pC4	1614	1446	1782	2018	2019	HSA
			downstream of the full length human HSA
344	3051	pSAC35.HSA.HCE1P80.D92-L229	Amino acids D92 to L229 of HCE1P80, a member of the	pSAC35	1615	1447	1783	2020	2021	HSA
			C1q family of proteins, are fused downstream of the full
			length human HSA
345	3052	pSAC35.HSA.HCE1P80.A20-L229	Amino acids A20-L229 of HCE1P80 are fused	pSAC35	1616	1448	1784	2022	2023	HSA
			downstream of the full length human HSA
346	3053	pC4.HSA.HDALV07.K101-N244	The globular domain of adiponectin (amino acids K101-N244)	pC4	1617	1449	1785	2024	2025	HSA
			has been inserted downstream of full length human
			HSA
347	3055	pSAC35.HSA.HDALV07(GD)	Full length HSA followed by amino acids K101-N244 of	pSAC35	1618	1450	1786	2026	2027	HSA
			HDALV07(GD)/Adiponectin.
348	3056	pSAC35.HSA.HDALV07.Mp	Full length HSA followed by amino acids Q18 to N244 of	pSAC35	1619	1451	1787	2028	2029	HSA
			HDALV07.
349	3066	pSAC35:CKB-1d8.GLP-1(7-	Invertase signal peptide followed by amino acids G28-N93	pScCHSA	1620	1452	1788	2030	2031	invertase
		36).HSA	of full length CKβ1 (SEQ ID NO: 1788), followed by GLP-
			1(7-36), followed by mature HSA.
350	3069	pSAC35:INU.GLP-1(7-	The inulinase signal sequence is fused to GLP-1(7-	pSAC35	1621	1453	1789	2032	2033	inulinase
		36(A8G))x2.HSA	36(A8G)) (SEQ ID NO: 1808), which is tandemly repeated
			as a dimer and fused to mature HSA.
351	3070	pSAC35:KT.GLP-1(7-	GLP-1(7-36(A8G)) (SEQ ID NO: 1808) is tandemly	pSAC35	1280	1281	1282	1283	1284	Killer toxin
		36(A8G))x2.HSA	repeated as a dimer and fused upstream from mature HSA
			and downstream from the killer toxin signal sequence.
352	3071	pSAC35:MAF.GLP-1(7-	The yeast mating factor α-1 (hereinafter MFα-1) signal	pSAC35	1622	1454	1790	2034	2035	MFα-1
		36(A8G))x2.HSA	sequence is fused to tandemly repeated copies of GLP-1(7-
			36(A8G)) (SEQ ID NO: 1808), which are fused to mature
			HSA.
353	3072	pSAC35:AP.GLP-1(7-	The acid phosphatase signal sequence is fused to tandemly	pSAC35	1623	1455	1791	2036	2037	Acid
		36(A8G))x2.HSA	repeated copies of GLP-1(7-36(A8G)) (SEQ ID							phosphatase
			NO: 1808), which are fused to mature HSA.
354	3085	pSAC35:MAF.GLP-1(7-	The yeast mating factor α-1 (hereinafter MFα-1) signal	pSAC35	1624	1456	1792	2038	2039	MFα-1
		36(A8G)).GLP-1(7-36).HSA	sequence is fused to GLP-1 (7-36(A8G)) (SEQ ID
			NO: 1808), GLP-1(7-36), and mature HSA.
355	3086	pSAC35:INU.GLP-1(7-	The inulinase signal sequence is fused to GLP-1(7-	pSAC35	1625	1457	1793	2040	2041	inulinase
		36(A8G)).GLP-1(7-36).HSA	36(A8G)) (SEQ ID NO: 1808), GLP-1(7-36), and mature
			HSA.
356	3087	pSAC35:AP.GLP-1(7-	The acid phosphatase signal sequence is fused to GLP-1(7-	pSAC35	1626	1458	1794	2042	2043	Acid
		36(A8G)).GLP-1(7-36).HSA	36(A8G)) (SEQ ID NO: 1808), GLP-1(7-36), and mature							phosphatase
			HSA.
357	3088	pSAC35.HSA.C-Peptide	HSA/kex2 signal peptide, followed by HSA, followed by	pSAC35	1627	1459	1795	2044	2045	HSA/kex2
			the C-Peptide sequence.
358	3105	pSAC35:INV.t9HCC-1.G28-N93:	Invertase signal peptide followed by amino acids G28 to	pSAC35	1628	1460	1796	2046	2047	invertase
		spc.HSA	N93 of HCC-1 fused upstream of a spacer and mature
			HSA.
359	3106	pSACHSA.HCBOG68	mature HCBOG68 fused downstream of mature HSA and	pSAC35	1629	1461	1797			HSA/kex2
			the HSA/kex2 leader sequence.
360	3108	pSAC35HSA.PYY	Mature PYY fused downstream of mature HSA and the	pSAC35	1630	1462	1798			HSA/kex2
			HSA/kex2 leader.
361	3109	pSAC35HSA.PYY3-36	HSA/kex2 leader followed by mature HSA and then	pSAC35	1631	1463	1799			HSA/kex2
			PYY3-36 (SEQ ID NO: 1799).
362	3117	pC4:PYY3-36/HSA	HSA leader followed by PYY3-36 (SEQ ID NO: 1800) and	pC4	1632	1464	1800	2048	2049	HSA
			mature HSA.
363	3118	pSAC35:PYY3-36/HSA	HSA/kex2 leader followed by PYY3-36 (SEQ ID	pSAC35	1633	1465	1801	2050	2051	HSA/kex2
			NO: 1801) and mature HSA.
364	3119	pSAC35:BNP/HSA	HSA/kex2 leader followed by BNP and mature HSA.	pSAC35	1634	1466	1802	2052	2053	HSA/kex2
365	3124	pSAC35:INV.CKB1.P29-N93:	Invertase signal peptide followed by amino acids 29 to 93	pSAC35	1635	1467	1803	2054	2055	invertase
		HSA	of full length ckbeta1 fused to N-terminus of HSA.
366	3125	pSAC35:INV.CKb-1.R27-N93:	Invertase signal peptide followed by amino acids 27 to 93	pSAC35	1636	1468	1804	2056	2057	invertase
		HSA	of full length ckbeta1 fused to N-terminus of HSA.
367	3133	pSac35.ySP.TA57PP.Insulin(GYG).	Variant TA57 propeptide leader followed by single chain	pSAC35	1637	1469	1805	2058	2059	TA57 variant 1
		HSA	insulin, followed by mature HSA.
368	3134	pSac35.ySP.TA57PP+S.Insulin(GYG).	Variant TA57 propeptide leader followed by single chain	pSAC35	1638	1470	1806	2060	2061	TA57 variant 2
		HSA	insulin, followed by mature HSA.
369	3139	pSAC35:INV.CKB1.G28-N93.	Invertase signal peptide followed by amino acids G28-N93	pSAC35	1639	1471	1807	2062	2063	invertase
		DAHK.HSA	of full length CKβ1 (see, e.g, SEQ IDNO: 1788), followed
			by a 16 amino acid linker derived from the N-terminus of
			HSA, followed by mature HSA.
370	3140	pSAC35:GLP1(mut)DAHK.HSA	GLP-1(7-36(A8G)) (SEQ ID NO: 1808) is linked to mature	pSAC35	1640	1472	1808	2064	2065	HSA/kex2
			HSA by a 16 amino acid linker derived from the N-
			terminus of HSA. The HSA/kex2 signal sequence is used.
371	3141	pSAC35:Wnt10b/HSA	HSA/kex2 leader followed by amino acids N29 to K389	pSAC35	1641	1473	1809	2066	2067	HSA/kex2
			of Wnt10b followed by mature HSA.
372	3142	pSAC35:Wnt11/HSA	HSA/kex2 leader followed by mature Wnt11 followed by	pSAC35	1642	1474	1810	2068	2069	HSA/kex2
			mature HSA.
373	3143	pSAC35:herstatin/HSA	HSA/kex2 leader followed by amino acids T23 to G419	pSAC35	1643	1475	1811	2070	2071	HSA/kex2
			of herstatin followed by mature HSA.
374	3144	pSAC35:adrenomedullin(27-52)/	HSA/kex2 leader followed by amino acids 27-52 of	pSAC35	1644	1476	1812	2072	2073	HSA/kex2
		HSA	adrenomedullin followed by mature HSA.
375	3149	pSAC35.HSA.C-peptide tandem	Full length HSA fused to amino acids E7 to Q37 of SEQ	pSAC35	1645	1477	1813	2074	2075	HSA
			ID NO: 1813, tandemly repeated.
376	3152	pSAC35:INV.CKB1.Met.R27-N93.	Invertase signal peptide followed by a Met, followed by	pSAC35	1646	1478	1814	2076	2077	invertase
		HSA	amino acids R27-N93 of full length CKβ1, followed by
			mature HSA.
377	3153	pSAC35:INV.CKB1.Met.S26-N93.	Invertase signal peptide followed by a Met, followed by	pSAC35	1647	1479	1815	2078	2079	invertase
		HSA	amino acids S26-N93 of full length CKβ1, followed by
			mature HSA.
378	3154	pSAC35:INV.CKB1.Met.S25-N93.	Invertase signal peptide followed by a Met, followed by	pSAC35	1648	1480	1816	2080	2081	invertase
		HSA	amino acids S25-N93 of full length CKβ1, followed by
			mature HSA.
379	3155	pSAC35:INV.CKB1.Met.G28-N93.	Invertase signal peptide followed by a Met, followed by	pSAC35	1649	1481	1817	2082	2083	invertase
		HSA	amino acids G28-N93 of full length CKβ1, followed by
			mature HSA.
380	3156	pSAC35:INV.CKB1.Met.P29-N93.	Invertase signal peptide followed by a Met, followed by	pSAC35	1650	1482	1818	2084	2085	invertase
		HSA	amino acids P29-N93 of full length CKβ1, followed by
			mature HSA.
381	3163	pSAC35:HSA.hGH	HSA/kex2 leader fused upstream of mature HSA and 191	pSAC35	1303	1304	1305			HSA/kex2
			amino acids of hGH.
382	3165	pSAC35:HSA.IFNa	HSA fused upstream of IFNα and downstream of the	pSAC35	1300	1301	1302			HSA/kex2
		also named CID 3165,	HSA/kex2 leader.
		pSAC35:HSA.INFα
383	3166	pC4:MPIF1.A22-N93.HSA	Amino acids A49 to N120 of MPIF (SEQ ID NO: 1821) is	pC4	1651	1483	1819	2086	2087	MPIF
			fused downstream of MPIF signal peptide and upstream of
			mature HSA.
384	3167	pC4:HSA.MPIF1.D45-N120	Full length HSA followed by amino acids D45 through	pC4	1652	1484	1820	2088	2089	HSA
			N120 of MPIF.
385	3168	PC4:MPIF-1.HSA	Amino acids D45 through N120 of MPIF fused	pC4	1653	1485	1821	2090	2091	MPIF
			downstream of the MPIF signal sequence and upstream of
			mature HSA.
386	3169	pSAC35:KT.CKB1.G28-N93.	Killer toxin signal sequence fused upstream of amino	pSAC35	1654	1486	1822			Killer toxin
		HSA	acids G28 through N93 of CKB1 (fragment shown as
			amino acids G1 to N66 of SEQ ID NO: 1822) and mature
			HSA.
387	3170	pSAC35:KT.HA.CKB1.G28-N93.	Killer toxin signal sequence followed by HA dipeptide and	pSAC35	1655	1487	1823			Killer toxin
		HSA	amino acids G28 through N93 of CKB1 (fragment shown
			as amino acids G1 to N66 of SEQ ID NO: 1823) and
			mature HSA.
388	3171	pSAC35:sCNTF(M1-G185):HSA	C-terminal deletion of CNTF (amino acids M1 through	pSAC35	1656	1488	1824	2092	2093	HSA/kex2
			G185), fused upstream of mature HSA and codon
			optimized for expression in yeast. HSA/kex2 signal
			sequence is used.
389	3172	pSAC35:HSA:sCNTF(M1-G185)	HSA/kex2 signal sequence followed by mature HSA and	pSAC35	1657	1489	1825	2094	2095	HSA/kex2
			M1 through G185 of CNTF.
390	3184	pC4:HSA.NOGOR.C27-C309	Full length HSA followed by amino acids C27 to C309 of	pC4	1658	1490	1826	2096	2097	HSA
			the NOGO receptor.
391	3185	pC4.NOGOR.M1-C309.HSA	Amino acids M1-C309 of NOGO receptor fused	pC4	1659	1491	1827	2098	2099	Native NOGO
			upstream of mature HSA.							receptor
392	3194	pC4:HSA(A14)-EPO(A28-D192.	Codon optimized EPO(A28-D192.G140) fused	pC4	1660	1492	1828	2100	2101	modified HSA
		G140)codon opt	downstream of mature HSA with a modified HSA (A14)							(A14)
			signal sequence.
393	3195	pC4:HSA(S14)-EPO(A28-D192.	Codon optimized EPO(A28-D192.G140) fused	pC4	1661	1493	1829	2102	2103	modified HSA
		G140)codon opt	downstream of mature HSA and a modified HSA (S14)							(S14)
			signal sequence.
394	3196	pC4:HSA(G14)-EPO(A28-D192.	Codon optimized EPO(A28-D192.G140) fused	pC4	1662	1494	1830	2104	2105	modified (G14)
		G140)codon opt	downstream of mature HSA with a modified (G14) HSA
			signal sequence.
395	3197	pC4.MPIF.Insulin(EAE).HSA	A single-chain insulin is downstream of the MPIF signal	pC4	1663	1495	1831			MPIF
			peptide and upstream of mature human HSA.
396	3198	pSac35.INV.insulin(EAE).HSA	Single-chain insulin is downstream of the invertase signal	pSAC35	1664	1496	1832			invertase
			peptide and upstream of mature human HSA
397	3202	pSAC35:API.d8CKb1/HSA	HSA/kex2 leader followed by amino acids “API” followed	pSAC35	1665	1497	1833	2106	2107	HSA/kex2
			by d8CKb1 and mature HSA. The sequence of delta 8 for
			CKB1 is shown in SEQ ID NO: 1833.
398	3203	pSAC35:ASL.d8CKb1/HSA	HSA/kex2 leader followed by amino acids “ASL”	pSAC35	1666	1498	1834	2108	2109	HSA/kex2
			followed by d8CKb1 and mature HSA.
399	3204	pSAC35:SPY.d8CKb1/HSA	HSA/kex2 leader followed by amino acids “SPY”	pSAC35	1667	1499	1835	2110	2111	HSA/kex2
			followed by d8CKb1 and mature HSA.
400	3205	pSAC35:MSPY.d8CKb1/HSA	HSA/kex2 leader followed by amino acids “MSPY”	pSAC35	1668	1500	1836	2112	2113	HSA/kex2
			followed by d8CKb1 and mature HSA.
401	3206	pSAC35:CPYSC.d8CKb1/HSA	HSA/kex2 leader followed by a five amino acid linker	pSAC35	1669	1501	1837	2114	2115	HSA/kex2
			followed by d8CKb1 and mature HSA.
402	3207	pSAC35:GPY.d8CKb1/HSA	HSA/kex2 leader followed by amino acids “GPY”	pSAC35	1670	1502	1838	2116	2117	HSA/kex2
			followed by d8CKb1 and mature HSA.
403	3208	pSAC35:defensin alpha 1/HSA	Amino acids A65-C94 of defensin alpha 1 fused	PSAC35	1285	1286	1287	1288	1289	HSA/kex2
			downstream of the HSA/kex2 leader and upstream of
			mature HSA.
404	3209	pSAC35:defensin alpha 2/HSA	Amino acids C66-C94 of defensin alpha 2 fused	pSAC35	1290	1291	1292	1293	1294	HSA/kex2
			downstream of the HSA/kex2 leader and upstream of
			mature HSA.
405	3210	pSAC35:defensin alpha 3/HSA	Amino acids 65-94 of SEQ ID NO1297, with A65D and	pSAC35	1295	1296	1297	1298	1299	HSA/kex2
			F92I mutations, fused downstream of the HSA/kex2 leader
			and upstream of mature HSA.
406	3232	pSAC35:CART/HSA	HSA/kex2 leader followed by processed active cocaine-	pSAC35	1671	1503	1839	2118	2119	HSA/kex2
			amphetamine regulated transcript (CART) (amino acids
			V69 through L116) followed by mature HSA.
407	3238	pSAC35:phosphatonin.HSA	Phosphatonin fused upstream of HSA.	pSAC35	1306	1307	1308			Native
										phosphatonin
408	3270	pSAC35:adipokine/HSA	HSA/kex2 leader followed by adipokine followed by	pSAC35	1672	1504	1840	2120	2121	HSA/kex2
			mature HSA.
409	3272	pSAC35.INV:{D}8CK{b}1(x2)/	CKbeta-1 tandem repeat (x2) fusion to the N-termal HSA.	pSAC35	1673	1505	1841	2122	2123	invertase
		HSA	Under the invertase signal peptide.
410	3274	pSAC35:P1pal-12.HSA	P1pal-12 pepducin peptide fused upstream of mature	pSAC35	1334	1335	1336			HSA/kex2
			HSA, and downstream of the HSA/kex2 leader sequence.
411	3275	pSAC35:P4pal-10.HSA	P4pal-10 pepducin peptide fused upstream of mature	pSAC35	1337	1338	1339			HSA/kex2
			HSA, and downstream of the HSA/kex2 leader sequence.
412	3281	pSAC35.PY3-36(x2)/HSA	PYY3-36 tandem repeat (x2) fused upstream of HSA and	pSAC35	1674	1506	1842	2124	2125	HSA/kex2
			downstream of the HSA/kex2 signal peptide.
413	3282	pSAC35:HSA/PYY3-36(x2)	PYY3-36 tandem repeat (x2) fused downstream of mature	pSAC35	1675	1507	1843	2126	2127	HSA/kex2
			HSA and HSA/kex2 leader.
414	3298	pSAC35:IL21/HSA	Amino acids Q30-S162 of IL-21 fused upstream of mature	pSAC35	2167	2157	2177	2188	2189	HSA/Kex2
			HSA and downstream of HSA/kex2 leader
415	3307	pSAC35:IL4/HSA	Amino acids H25-S153 of IL-4 fused upstream of mature	pSAC35	2168	2158	2178	2190	2191	HSA/Kex2
			HSA and downstream of HSA/kex2 leader
416	3309	pSAC:KT.GLP-1(7-	Killer toxin leader sequence followed by GLP-1(7-	pSAC35	2170	2160	2180	2194	2195	Killer toxin
		36(A8G))x2.MSA.E25-A608	36(A8G) followed by mature mouse serum albumin.
417	3312	pSAC35:hOCIL/HSA	HSA/kex2 leader followed by amino acids N20 to V149	pSAC35	2171	2161	2181	2196	2197	HSA/Kex2
			of hOCIL followed by mature HSA
418	7777	T20:HSA	T20 fused downstream of full length HSA	pC4	1170	1171	1172			HSA
419	8888	pC4:BNP.HSA	Human B-type natriuretic peptide fused upstream of	pC4	1275	1276	1277	1278	1279	Native BNP
			mature HSA.
420	9999	T1249:HSA	T1249 fused downstream of full length HSA	pC4	1173	1174	1175			HSA