Bispecific antibodies

Patent Citations (211)

Non-Patent Literature (412)

• Carter P., J Immunol Methods. Feb. 1, 2001;248(1-2):7-15.Examiner
• Rudikoff et al., Proc Natl Acad Sci U S A. Mar. 1982;79(6):1979-83.Examiner
• Jain et al., “Engineering antibodies for clinical applications,” Trends Biotechnol., 25(7):307-16 (2007).Applicant
• Kufer et al., “A revival of bispecific antibodies,” Trends Biotechnol., 22(5):238-44 (2004).Applicant
• U.S. Appl. No. 14/019,117, filed Sep. 5, 2013, Igawa et al.Applicant
• U.S. Appl. No. 14/019,712, filed Sep. 5, 2013, Igawa et al.Applicant
• Fay et al., “The size of human factor VIII heterodimers and the effects produced by thrombin,” Biochim Biophys Acta., 871(3):268-78 (1986).Applicant
• Helfrich et al., “A rapid and versatile method for harnessing scFv antibody fragments with various biological effector functions,” J. Immunol. Methods, 237(1-2):131-45 (2000).Applicant
• Hoyer, L.W., “The factor VIII complex: structure and function,” Blood, 58(1):1-13 (1981).Applicant
• Kerschbaumer et al., “An antibody specific for coagulation factor IX enhances the activity of the intrinsic factor X-activating complex,” J. Biol. Chem., 279(39):40445-50 (2004).Applicant
• Miyazaki et al., “Generation of bispecific IgG, which mimics the cofactor function of blood coagulation factor VIII,” Poster sessions, (2P-B-161) (2006).Applicant
• Saito et al., “Factor VIII Mimetic Antibody: (1) Establishment and Characterization of Anti-factor IX/anti-factor X Bispecific Antibodies,” 2005 International Society of Thrombosis and Haemostatis.Applicant
• Saito et al., “Establishment of Factor VIII Mimetic Antibodies and Their In Vitro Activities in Hemophilia A,” 2006 National Hemophilia Foundation Symposia.Applicant
• Shima et al., “Factor VIII Mimetic Antibody: (2) In Vitro Assessment of Cofactor Activity in Hemophilia A,” 2005 International Society of Thrombosis and Haemostatis.Applicant
• Shima, M., “Bispecific antibodies to coagulation factors IXa and X mimic the function of factor VIII,” 2006 World Federation of Haemophilia (Haemophilia 2006:12(Suppl. 2)).Applicant
• Shirahata, Minna ni yakudatsu ketsuyubyo no kiso to rinsho. Iyaku (Medicine and Drug) Journal Co., Ltd., 280-9 (2009) (English translation).Applicant
• Vehar et al., “Structure of human factor VIII,” Nature, 312(5992):337-42 (1984).Applicant
• Wood et al., “Expression of active human factor VIII from recombinant DNA clones,” Nature, 312(5992):330-7 (1984).Applicant
• International Search Report for App. Ser. No. PCT/JP2011/076486, mailed Dec. 27, 2011, 4 pages.Applicant
• U.S. Appl. No. 10/560,098, filed Apr. 28, 2006, Miyazaki et al.Applicant
• U.S. Appl. No. 10/575,193, filed Oct. 24, 2006, Hattori et al.Applicant
• U.S. Appl. No. 10/575,905, filed Apr. 30, 2007, Hattori et al.Applicant
• U.S. Appl. No. 11/910,128, filed Oct. 7, 2008, Igawa et al.Applicant
• U.S. Appl. No. 11/910,836, filed Jan. 12, 2009, Hattori et al.Applicant
• U.S. Appl. No. 12/295,039, filed Jan. 20, 2009, Igawa et al.Applicant
• U.S. Appl. No. 12/295,075, filed Apr. 20, 2009, Igawa et al.Applicant
• U.S. Appl. No. 12/679,922, filed Oct. 1, 2010, Igawa et al.Applicant
• U.S. Appl. No. 13/434,643, filed Mar. 29, 2012, Hattori et al.Applicant
• U.S. Appl. No. 13/518,861, filed Jun. 22, 2012, Igawa et al.Applicant
• Hombach et al., “A CD16/CD30 bispecific monoclonal antibody induces lysis of Hodgkin's cells by unstimulated natural killer cells in vitro and in vivo,” Int J Cancer, 55:830-6 (1993).Applicant
• Roguska et al., “Humanization of murine monoclonal antibodies through variable domain resurfacing,” Proc Natl Acad Sci U.S.A., 91:969-73 (1994).Applicant
• Staerz et al., “Hybrid hybridoma producing a bispecific monoclonal antibody that can focus effector T-cell activity,” Proc Natl Acad Sci U.S.A., 83:1453-7 (1986).Applicant
• Dahlback, “Blood coagulation,” Lancet, 355(9215):1627-32 (2000).Applicant
• Fay et al., “Chapter 2B Nonenzymatic cofactors: factor VIII,” Comprehensive Biochemistry, 13:35-37 (1986).Applicant
• Hu et al., “Development and characterization of a novel fusion protein composed of a human lgG1 heavy chain constant region and a single-chain fragment variable antibody against Venezuelan equine encephalitis virus,” J Biochem., 133(1):59-66 (2003).Applicant
• Sampei et al., “Identification and multidimensional optimization of an asymmetric bispecific lgG antibody mimicking the function of factor VIII cofactor activity,” PLoS One, 2013; 8(2):e57479. Epub: Feb. 28, 2013.Applicant
• Zuo et al., “An efficient route to the production of an IgG-like bispecific antibody,” Protein Eng., 13(5):361-7 (2000).Applicant
• Bowie et al., “Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions,” Science, Mar. 16, 1990;247:1306-1310.Applicant
• Burgess, “Possible dissociation of the heparin-binding and mitogenic activities of heparin-binding (acidic fibroblast) growth factor-1 from its receptor-binding activities by site-directed mutagenesis of a single lysine residue,” J. Cell. Biol., 1990;111:2129-2138.Applicant
• Kabat et al., Sequence of Proteins of Immunological Interest, 5th Edition 1991, p. 690 and p. 693.Applicant
• Lazar et al., “Transforming growth factor alpha: mutation of aspartic acid 47 and leucine 48 results in different biological activities,” Mol. Cell Biol., 1988;8:1247-1252.Applicant
• Medesan et al., “Delineation of the amino acid residues involved in transcytosis and catabolism of mouse IgGl,” J Immunol., Mar. 1, 1997;158(5):2211-7.Applicant
• Pan et al., “Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth,” Cancer Cell, Jan. 2007;11(1):53-67.Applicant
• Singer et al., Genes & Genomes, 1991; 67-69.Applicant
• Singer et al., Genes & Genomes, 1998;1:63-64.Applicant
• Lindsay, “Chapter 4: Determination of the Kinetics and Mechanism of tg-FIX Activation by Factor XIa,” 49-75 (2004).Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 14/019,712, dated Nov. 18, 2013, 8 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Nov. 18, 2013 in U.S. Appl. No. 14/019,712, filed on Dec. 6, 2013, 2 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 14/019,712, dated Jan. 17, 2014, 16 pages.Applicant
• Fish & Richardson P.C., Response to Non-Final Office Action in U.S. Appl. No. 14/019,712, filed on Apr. 18, 2014, 9 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 14/019,712, dated May 27, 2014, 9 pages.Applicant
• Bowen, Haemophilia A and haemophilia B: molecular insights, Mol Pathol., Feb. 2002;55(1):1-18.Applicant
• Brandstetter et al., “X-ray structure of clotting factor IXa: active site and module structure related to Xase activity and hemophilia B,” Proc Natl Acad Sci U S A, Oct. 10, 1995;92(21):9796-800.Applicant
• De Pascalis et al., “Grafting of ‘abbreviated’ complementary-determining regions containing specificity-determining residues essential for ligand contact to engineer a less immunogenic humanized monoclonal antibody,” Journal of Immunology, Sep. 15, 2002;169(6):3076-3084.Applicant
• Fay, “Activation of factor VIII and mechanisms of cofactor action,” Blood Rev., Mar. 2004;18(1):1-15.Applicant
• Gonzales et al., “Minimizing the immunogenicity of antibodies for clinical application,” Tumour Biol., Jan.-Feb. 2005;26(1):31-43.Applicant
• Iwahashi et al., “CDR substitutions of a humanized monoclonal antibody (CC49): contributions of individual CDRs to antigen binding and immunogenicity,” Mol Immunol., Oct.-Nov. 1999;36(15-16):1079-91.Applicant
• Jirholt et al., “Exploiting sequence space: shuffling in vivo formed complementarity determining regions into a master framework,” Gene., Jul. 30, 1998;215(2):471-6.Applicant
• Schmidt et al., “Structure-function relationships in factor IX and factor IXa,” Trends Cardiovasc Med., Jan. 2003;13(1):39-45.Applicant
• Tamura et al., “Structural correlates of an anticarcinoma antibody: identification of specificity-determining residues (SDRs) and development of a minimally immunogenic antibody variant by retention of SDRs only,” J Immunol., Feb. 1, 2000;164(3):1432-41.Applicant
• Notice of Opposition against EP 1 876 236, dated May 20, 2015, in the name of Chugai Seiyaku Kabushiki Kaisha brought by Novo Nordisk A/S, 23 pages.Applicant
• Notice of Opposition against EP 1 876 236, dated May 22, 2015, in the name of Chugai Seiyaku Kabushiki Kaisha brought by Baxalta Innovations GmbH, 37 pages.Applicant
• Chugai Seiyaku Kabushiki Kaisha's letter dated Jun. 12, 2013, regarding oral proceedings scheduled on Jun. 26, 2013, in App. Ser. No. EP 06 73 0769.4-1412.Applicant
• Allard et al., “Antigen binding properties of highly purified bispecific antibodies,” Mol Immunol., Oct. 1992;29(10):1219-27.Applicant
• Haagen et al., “Unprimed CD4+ and CD8+ T cells can be rapidly activated by a CD3×CD19 bispecific antibody to proliferate and become cytotoxic,” Cancer Immunol Immunother., Dec. 1994;39(6):391-6.Applicant
• IMGT Scientific charts depicting the correspondence between Eu and Kabat numbering for the human IgG constant region, created May 17, 2001 and last updated Aug. 13, 2014.Applicant
• Lloyd et al., “The production of a bispecific anti-CEA, anti-hapten (4-amino-phthalate) hybrid-bybridoma,” J Natl Med Assoc., Oct. 1991:83(10):901-4.Applicant
• Jackman et al., “Development of a two-part strategy to identify a therapeutic human bispecific antibody that inhibits IgE receptor signaling,” J Biol Chem., Jul. 2, 2010;285(27): 20850-9. doi: 10.1074/jbc.M110.113910. Epub May 5, 2010.Applicant
• Lin et al., “Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor,” J Pharmacol Exp Ther., 288(1):371-8 (1999).Applicant
• Spiess et al., “Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies,” Nat Biotechnol., Aug. 2013; 31(8):753-8. doi: 10.1038/nbt.2621. Epub Jul. 7, 2013.Applicant
• U.S. Appl. No. 14/921,590, filed Oct. 23, 2015, Hattori et al.Applicant
• Arndt et al., “Factors influencing the dimer to monomer transition of an antibody single-chain Fv fragment,” Biochemistry, Sep. 15, 1998;37(37):12918-26.Applicant
• Chatellier et al., “Functional mapping of conserved residues located at the VL and VH domain interface of a Fab,” J. Mol. Biol., Nov. 22, 1996;264(1):1-6.Applicant
• Davies et al., “Antibody VH domains as small recognition units,” Biotechnology (N.Y.), May 1995;13(5):475-9.Applicant
• Griffin et al., “Analysis of heavy and light chain sequences of conventional camelid antibodies from Camelus dromedarius and Camelus bactrianus species,” J Immunol Methods, Mar. 2014;405:35-46. doi: 10.1016/j.jim.2014.01.003. Epub Jan. 18, 2014.Applicant
• Hamers-Casterman et al., “Naturally occurring antibodies devoid of light chains,” Nature, Jun. 3, 1993;363(6428):446-8.Applicant
• Hozumi et al., “Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions,” Proc Natl Acad Sci U S A., Oct. 1976;73(10):3628-32.Applicant
• Igawa et al., “VH/VL interface engineering to promote selective expression and inhibit conformational isomerization of thrombopoietin receptor agonist single-chain diabody,” Protein Eng Des Sel., Aug. 2010;23(8):667-77. doi: 10.1093/protein/gzq034. Epub Jun. 24, 2010.Applicant
• Jung et al., “The importance of framework residues H6, H7 and H10 in antibody heavy chains: experimental evidence for a new structural subclassification of antibody V(H) domains,” J. Mol. Biol., Jun. 8, 2001;309(3):701-16.Applicant
• Kabsch et al., “On the use of sequence homologies to predict protein structure: identical pentapeptides can have completely different conformations,” Proc Natl Acad Sci U S A., Feb. 1984;81(4):1075-8.Applicant
• Kenanova et al., “Tailoring the pharmacokinetics and positron emission tomography imaging properties of anti-carcinoembryonic antigen single-chain Fv-Fc antibody fragments,” Cancer Res., Jan. 15, 2005;65(2):622-31.Applicant
• Khalifa et al.; “Effects on interaction kinetics of mutations at the VH-VL interface of Fabs depend on the structural context,” J. Mol. Recognit., May-Jun. 2000;13(3):127-39.Applicant
• Kipriyanov et al., “Bispecific tandem diabody for tumor therapy with imprived antigen binding and pharmacokinetics,” J Mol Biol., Oct. 15, 1999;293(1):41-56.Applicant
• Kipriyanov et al., “Effect of Domain Order on the Activity of Bacterially Produced Bispecific Single-chain Fv Antibodies,” J Mol Biol., Jun. 27, 2003;330(1):99-111.Applicant
• Kontermann, R., “Recombinant bispecific antibodies for cancer therapy,” Acta Pharmacol Sin., Jan. 2005;26(1):1-9.Applicant
• Korn et al., “Recombinant bispecific antibodies for the targeting of adenoviruses to CEA-expressing tumour cells: a comparative analysis of bacterially expressed single-chain diabody and tandem scFv,” J Gene Med., Jun. 2004;6:642-51.Applicant
• Kumar et al., “The second PDZ domain of INAD is a type I domain involved in binding to eye protein kinase C. Mutational analysis and naturally occuring variants,” J. Biol. Chem., Jul. 6, 2001;276(27):24971-7. Epub May 7, 2001.Applicant
• Le Gall et al., “Effect of linker sequences between the antibody variable domains on the formation, stability and biological activity of a bispecific tandem diabody,” Protein Eng Des Sel., Apr. 2004;17(4):357-66. Epub May 4, 2004.Applicant
• Lebégue et al., “Production and characterization of hybrid monoclonal antibodies with IgG1/IgG3 double isotype,” C R Acad Sci III., 1990;310(9):377-82.Applicant
• Liu et al., “Functional interactions between arginine-133 and aspartate-88 in the human reduced folate carrier: evidence for a charge-pair association,” Biochem. J., Sep. 1, 2001;358(Pt 2):511-6.Applicant
• Maity et al., “Equilibrium unfolding of dimeric and engineered monomeric forms of Cro (F58W) repressor and the effect of added salts: evidence for the formation of folded monomer induced by sodium perchlorate,” Arch Biochem Biophys., Feb. 1, 2005;434(1):93-107.Applicant
• Male et al., “Antibodies” Immunology, 7th Edition (2006), published by Elsevier Ltd., pp. 59-86.Applicant
• Michaelsen et al., “A mutant human IgG molecule with only one Clq binding site can activate complement and induce lysis of target cells,” Eur J Immunol., Jan. 2006;36(1):129-38.Applicant
• Narhi et al., “Asn to Lys mutations at three sites which are N-glycosylated in the mammalian protein decrease the aggregation of Escherichia coli-derived erythropoietin,” Protein Eng., Feb. 2001;14(2):135-40.Applicant
• Nieba et al., “Disrupting the hydrophobic patches at the antibody variable/constant domain interface: improved in vivo folding and physical characterization of an engineered scFv fragment,” Protein Eng., Apr. 1977;10(4):435-44.Applicant
• Nohaile et al., “Altering dimerization specificity by changes in surface electrostatics,” Pro Natl Acad Sci U S A., Mar. 13, 2001;98(6):3109-14. Epub Feb. 27, 2001.Applicant
• O'Shea et al., “Peptide ‘Velcro’: design of a heterodimeric coiled coil,” Curr Biol., Oct. 1, 1993;3(10):658-67.Applicant
• Peipp et al., “Bispecific antibodies targeting cancer cells,” Biochem. Soc. Trans., Aug. 2002;30:507-511.Applicant
• Pokkuluri et al., “A domain flip as a result of a single amino-acid substitution,” Structure, Aug. 15, 1998;6(8):1067-73.Applicant
• Roitt et al., Immunology, M., Mir, 5th Edition (2000), pp. 97-113.Applicant
• Skerra, “Use of the tetracycline promoter for the tightly regulated production of a murine antibody fragment in Escherichia coli,” Gene, Dec. 30, 1994;151(1-2):131-5.Applicant
• Tan et al., “Contributions of a highly conserved VH/VL hydrogen bonding interaction to scFv folding stability and refolding efficiency,” Biophys J., Sep. 1998; 75(3):1473-82.Applicant
• Vargas-Madrazo et al., “An improved model of association for VH-VL immunoglobulin domains: asymmetries between VH and VL in the packing of some interface residues,” J. Mol. Recognit., May-Jun. 2003;16(3):113-20.Applicant
• Wang et al., “Conserved amino acid networks involved in antibody variable domain interactions,” Proteins, Jul. 2009;76(1):99-114. doi: 10.1002/prot.22319.Applicant
• Worn et al., “Stability engineering of antibody single-chain Fv fragments,” J Mol Biol., Feb. 2, 2001;305(5):989-1010.Applicant
• Wu et al., “Multimerization of a chimeric anti-CD20 single-chain Fv-Fc fusion protein is mediated through variable domain exchange,” Protein Eng., Dec. 2001;14(12):1025-33.Applicant
• Yasukawa et al., “Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene,” EMBO J, Oct. 1987;6(10):2939-45.Applicant
• Zhu et al., “Remodeling domain interfaces to enhance heterodimer formation,” Protein Sci., Apr. 1997;6(4):781-8.Applicant
• “National Haemophilia Foundation (NHF) Medical and Scientific Advisory Council (MASAC) Recommendations Concerning Prophylaxis,” MedicalBulletin, No. 193, 1 page (1994).Applicant
• Abe et al., “Purification of monoclonal antibodies with light-chain heterogeneity produced by mouse hybridomas raised with NS-1 myelomas: application of hydrophobic interaction high-performance liquid chromatography,” J. Biochem. Biophys. Methods, 27:215-227 (1993).Applicant
• Adams et al., “Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab,” Cancer Immunol. Immunother., 55:717-727 (2006).Applicant
• Algonomics—Tripole® applications [online] Retrieved from the Internet on Feb. 29, 2012: http://web.archive.org/web20090221052902/http://www.algonomics.com/proteinengineering/tripole—applications.php, 2 pages (Feb. 21, 2009).Applicant
• Almagro et al., “Humanization of antibodies,” Front Biosci., 13:1619-33 (2008).Applicant
• Amersham Biosciences, “Protein Purification Handbook, ” Edition AC, 98 pages (2001).Applicant
• Amersham Biosciences, “Affinity Chromatography: Principles and Methods,” Edition AD, pp. 16-18, 137 (2002).Applicant
• Angal et al., “A single amino acid substitution abolishes the heterogeneity of chimeric mouse/human (IgG4) antibody,” Mol. Immunol., 30:105-108 (1993).Applicant
• Armour et al., “Recombinant human IgG molecules lacking Fcgamma receptor I binding and monocyte triggering activities,” Eur. J. Immunol., 29(8):2613-24 (1999).Applicant
• Arndt et al., “Helix-stabilized Fv (hsFv) antibody fragments: substituting the constant domains of a Fab fragment for a heterodimeric coiled-coil domain,” J. Mol. Biol., 312:221-228 (2001).Applicant
• Aslan et al., “Engineering a novel, stable dimeric streptavidin with lower isoelectric point,” J. Biotechnol., 128(2):213-25 (2007).Applicant
• Asselta et al., “Factor V Deficiency,” Semin. Thromb. Hemost., 35:382-389 (2009).Applicant
• Association of Hemophilia Clinic Directors of Canada, “Hemophilia and Von Willebrand's disease: 2. Management Association of Hemophilia Clinic Directors of Canada,” Canadian Medical Association Journal, 153(2):147-157 (1995).Applicant
• Atwell et al., “Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library,” J. Mol. Biol., 270:26-35 (1997).Applicant
• Baerga-Ortiz et al., “Two different proteins that compete for binding to thrombin have opposite kinetic and thermodynamic profiles,” Protein Sci., 13(1):166-76 (2004).Applicant
• Bajaj et al., “A Monoclonal Antibody to Factor IX That Inhibits the Factor VIII:Ca Potentiation of Factor X Activation,” J. Biol. Chem., 260(21):11574-11580 (1985).Applicant
• Bartelds et al., “Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis,” Ann Rheum. Dis., 66:921-926 (2007).Applicant
• Bayry et al., “Immuno affinity purification of foot and mouth disease virus type specific antibodies using recombinant protein adsorbed to polystyrene wells,” J. Virol. Methods, 81:21-30 (1999).Applicant
• Bebbington et al., “High-Level Expression of a Recombinant Antibody from Myeloma Cells Using a Glutamine Synthetase Gene as an Amplifiable Selectable Marker,” Biotechnology (N Y), 10:169-175 (1992).Applicant
• Bender et al , “Immunogenicity, efficacy and adverse events of adalimumab in RA patients,” Rheumatol. Int., 27:269-274 (2007).Applicant
• Bessos et al., “The characterization of a panel of monoclonal antibodies to human coagulation factor IX,” Thrombosis Research, 40:863-867 (1985).Applicant
• Binz et al., “Engineering novel binding proteins from nonimmunoglobulin domains,” Nat. Biotechnol., 23:1257-68 (2005).Applicant
• Blazar, “Infusion of Anti-B7.1 (CD80) and Anti-B7.2 (CD86) Monoclonal Antibodies Inhibits Murine Graft-Versus-Host Disease Lethality in Part Via Direct Effects on CD4+ and CD8+ T Cells,” J. Immunol., 157:3250-59 (1996).Applicant
• Bolton-Maggs et al., “Haemophilias A and B,” The Lancet, 361:1801-1809 (2003).Applicant
• Bos et al., “Enhanced Transfection of a Bacterial Plasmid into Hybridoma Cells by Electroporation: Application for the Selection of Hybrid Hybridoma (Quadroma) Cell Lines,” Hybridoma, 11:41-51 (1992).Applicant
• Branden and Tooze, “Recognition of Foreign Molecules by the Immune System,” Introduction to Protein Structure, 2d Ed., Garland Publishing, pp. 299-323 (1999).Applicant
• Brennan et al., “Preparation of Bispecific Antibodies by Chemical Recombination of Monoclonal Immunoglobulin G1 Fragments,” Science, 229:81-83 (1985).Applicant
• Brinkman et al. “Phospholipid-binding domain of factor VIII is involved in endothelial cell-mediated activation of factor X by factor IXa,” Arterioscler. Thromb. Vasc. Biol., 22(3):511-516 (2002).Applicant
• Brown et al., “Tolerance of single, but not multiple, amino acid replacements in antibody VHCDR 2: a means of minimizing B cell wastage from somatic hypermutation?,” J. Immunol., 156(9):3285-91 (1996).Applicant
• Burges et al., “Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM × anti-CD3 antibody: a phase I/II study,” Clin. Cancer Res., 13(13):3899-905 (2007).Applicant
• Calbiochem® Buffers, “A guide for the preparation and use of buffers in biological systems,” by Chandra Mohan, Ph.D., Copyright© 2003 EMD Biosciences, Inc., an Affiliate of Merck KGaA, Darmstadt, Germany, 37 pages.Applicant
• Carter, “Bispecific human IgG by design,” J. Immunol. Methods, 248:7-15 (2001).Applicant
• Chamow et al., “A humanized, bispecific immunoadhesin-antibody that retargets CD3+ effectors to kill HIV-1-infected cells,” J. Immunol., 153(9):4268-80 (1994).Applicant
• Chau et al., “HuM291(Nuvion), a humanized Fc receptor-nonbinding antibody against CD3, anergizes peripheral blood T cells as partial agonist of the T cell receptor,” Transplantation., 71(7):941-50 (2001).Applicant
• Chen et al., “Generation and analysis of random point mutations in an antibody CDR2 sequence: many mutated antibodies lose their ability to bind antigen,” J. Exp. Med., 176(3):855-66 (1992).Applicant
• Chen et al., “Defective secretion of an immunoglobulin caused by mutations in the heavy chain complementarity determining region 2,” J. Exp. Med., 180(2):577-86 (1994).Applicant
• Chirino et al., “Minimizing the immunogenicity of protein therapeutics,” Drug Discov. Today., 9:82-90 (2004).Applicant
• Chu et al., “Accumulation of succinimide in a recombinant monoclonal antibody in mildly acidic buffers under elevated temperatures,” Pharm. Res., 24(6):1145-56 (2007).Applicant
• Cole et al., “Human IgG2 variants of chimeric anti-CD3 are nonmitogenic to T cells,” J. Immunol., 159(7):3613-21 (1997).Applicant
• Comper et al., “Charge selectivity in kidney ultrafiltration,” Kidney Int., 47:1242-51 (1995).Applicant
• Cordoba et al., “Non-enzymatic hinge region fragmentation of antibodies in solution,” J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci., 818(2):115-21 (2005).Applicant
• Couto et al., “Anti-BA46 Monoclonal Antibody Mc3: Humanization Using a Novel Positional Consensus and in Vivo and in Vitro Characterization,” Cancer Res., 55:1717-22 (1995).Applicant
• Dall'Acqua et al., “Antibody humanization by framework shuffling,” Methods, 36(1):43-60 (2005).Applicant
• Damschroder et al., “Framework shuffling of antibodies to reduce immunogenicity and manipulate functional and biophysical properties,” Mol. Immunol., 44(11):3049-60 (2007).Applicant
• Davie et al., “The coagulation cascade: Initiation, maintenance, and regulation,” Biochemistry, 30(43):10363-10370 (1991).Applicant
• De Groot et al., “De-immunization of therapeutic proteins by T-cell epitope modification,” Dev. Biol. (Basel), 122:171-94 (2005).Applicant
• Deen et al., “Structural determinants of glomerular permeability,” Am. J. Physiol. Renal. Physiol., 281:F579-F596 (2001).Applicant
• Del Rio et al., “An Engineered Penicillin Acylase with Altered Surface Charge Is More Stable in Alkaline pH,” Ann. NY Acad. Sci., 799:61-64 (1996).Applicant
• Deng et al., “An Agonist Murine Monoclonal Antibody to the Human c-Mpl Receptor Stimulates Megakaryocytopoiesis,” Blood, 92:1981-88 (1998).Applicant
• Dillon et al., “Structural and functional characterization of disulfide isoforms of the human IgG2 subclass,” J. Biol. Chem., 283:16206-15 (2008).Applicant
• Dumont et al., “Monomeric Fc fusions: impact on pharmacokinetic and biological activity of protein therapeutics,” BioDrugs., 20(3):151-60 (2006).Applicant
• Ewert et al., “Stability improvement of antibodies for extracellular and intracellular applications: CDR grafting to stable frameworks and structure-based framework engineering,” Methods, 34:184-199 (2004).Applicant
• Francois et al., “Construction of a Bispecific Antibody Reacting with the α- and β-Chains of the Human IL-2 Receptor,” J. Immunol., 150:4610-4619 (1993).Applicant
• Fujii, “Antibody affinity maturation by random mutagenesis,” Methods Mol. Biol., 248:345-59 (2004).Applicant
• GenPept Accession No. AAC26541, “anti BoNT/A Hc scFv antibody [synthetic construct],” 1 page (Aug. 1, 2001).Applicant
• Gelderman et al., “The inhibitory effect of CD46, CD55, and CD59 on complement activation after immunotherapeutic treatment of cervical carcinoma cells with monoclonal antibodies or bispecific monoclonal antibodies,” Lab Invest., 82(4):483-93 (2002).Applicant
• Gerstner et al., “Sequence plasticity in the antigen-binding site of a therapeutic anti-HER2 antibody,” J. Mol. Biol., 321(5):851-62 (2002).Applicant
• Gessner et al., “The IgG Fc receptor family,” Ann. Hematol., 76:231-248 (1998).Applicant
• Ghetie et al., “FcRn: the MHC class I-related receptor that is more than an IgG transporter,” Immunol. Today, 18:592-598 (1997).Applicant
• Ghetie et al., “Increasing the serum persistence of an IgG fragment by random mutagenesis,” Nat. Biotechnol., 15:637-640 (1997).Applicant
• Ghetie et al., “Multiple roles for the major histocompatibility complex class I-related receptor FcRn,” Annu. Rev. Immunol., 18:739-766 (2000).Applicant
• Gobburu et al., “Pharmacokinetics/dynamics of 5c8, a monoclonal antibody to CD154 (CD40 ligand) suppression of an immune response in monkeys,” J. Pharmacol. Exp. Ther., 286:925-930 (1998).Applicant
• Goode et al., “The glomerular basement membrane charge-selectivity barrier: an oversimplified concept?” Nephrol. Dial. Transplant., 11:1714-16 (1996).Applicant
• Graves et al., “Molecular modeling and preclinical evaluation of the humanized NR-LU-13 antibody,” Clin. Cancer Res., 5:899-908 (1999).Applicant
• Grosse-Hovest et al., “A recombinant bispecific single-chain antibody induces targeted, supra-agonistic CD28-stimulation and tumor cell killing”, European Journal of Immunology, 33(5):1334-1340 (2003).Applicant
• Gunasekaran et al., “Enhancing antibody Fc heterodimer formation through electrostatic steering effects: applications to bispecific molecules and monovalent IgG,” J. Biol. Chem., 285(25):19637-46 (2010).Applicant
• Gupta et al., “Affinity chromatography and co-chromatography of bispecific monoclonal antibody immunoconjugates,” J. Biochem. Biophys. Methods, 51:203-216 (2002).Applicant
• Guyre et al., “Increased potency of Fc-receptor-targeted antigens,” Cancer Immunol. Immunother., 45(3-4):146-8 (1997).Applicant
• Hämmerling et al., “Use of Hybrid Antibody with Anti-γG and Anti-Ferritin Specificities in Locating Cell Surface Antigens by Electron Microscopy,” J. Exp. Med., 128:1461-1473 (1968).Applicant
• Hanson et al., “Catalytic antibodies and their applications,” Curr. Opin. Biotechnol., 16:631-636 (2005).Applicant
• He et al., “Humanization and pharmacokinetics of a monoclonal antibody with specificity for both E- and P-selectin,” J. Immunol., 160:1029-35 (1998).Applicant
• Hinton et al., “An engineered human IgG1 antibody with longer serum half-life,” J. Immunol., 176:346-356 (2006).Applicant
• Hinton et al., “Engineered human IgG antibodies with longer serum half-lives in primates,” J. Biol. Chem., 279(8):6213-6 (2004).Applicant
• Hoad et al. “Characterization of monoclonal antibodies to human factor X.Xa: Initial observations with a quantitative ELISA procedure,” J. Immunol. Methods, 136(2):269-278 (1991).Applicant
• Holliger et al., “‘Diabodies’: Small bivalent and bispecific antibody fragments,” Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).Applicant
• Hsia et al., “Treatment of acquired factor X inhibitor by plasma exchange with concomitant intravenous immunoglobulin and corticosteroids,” Am. J Hematol., 83:318-320 (2008).Applicant
• Huse et al., “Generation of a Large Combinatorial Library of the Immunoglobulin Repertoire in Phage Lambda,” Science, 246:1275-1281 (1989).Applicant
• Hwang et al., “Use of human germline genes in a CDR homology-based approach to antibody humanization,” Methods, 36:35-42 (2005).Applicant
• Igawa et al., “Engineering the variable region of therapeutic IgG antibodies,” MAbs, 3(3):243-52 (2011).Applicant
• Igawa et al., “Reduced elimination of IgG antibodies by engineering the variable region,” Protein Eng. Des. Sel., 23(5):385-92 (2010).Applicant
• Igawa et al., “Antibody recycling by engineered pH-dependent antigen binding improves the duration of antigen neutralization,” Nat. Biotechnol., 28(11):1203-7 (2010).Applicant
• Ito et al., “The His-probe method: effects of histidine residues introduced into the complementarity-determining regions of antibodies on antigen-antibody interactions at different pH values,” FEBS Lett., 309:85-88 (1992).Applicant
• Janeway et al., “Structure of the Antibody Molecule and Immunoglobulin Genes,” Immunobiology, 3rd Edition, Garland Press, 3:1-3:11 (1997).Applicant
• Jendeberg et al., “Engineering of Fc(1) and Fc(3) from human immunoglobulin G to analyse subclass specificity for staphylococcal protein A,” J. Immunol. Methods., 201(1):25-34 (1997).Applicant
• Johnson et al., “Cation exchange-HPLC and mass spectrometry reveal C-terminal amidation of an IgG1 heavy chain,” Anal. Biochem., 360:75-83 (2007).Applicant
• Jones et al., “Identification and removal of a promiscuous CD4+ T cell epitope from the C1 domain of factor VIII,” Thromb. Haemost., 3:991-1000 (2005).Applicant
• Kang et al., “Linkage of recognition and replication functions by assembling combinatorial antibody Fab libraries along phage surfaces,” Proc. Natl. Acad. Sci. USA, 88:4363-4366 (1991).Applicant
• Karpovsky et al., “Production of Target-Specific Effector Cells Using Hetero—Cross-Linked Aggregates Containing Anti-Target Cell and Anti-Fcγ Receptor Antibodies,” J. Exp. Med., 160:1686-1701 (1984).Applicant
• Kashmiri et al., “Generation, characterization, and in vivo studies of humanized anticarcinoma antibody CC49,” Hybridoma, 14:461-473 (1995).Applicant
• Katayose et al., “MUC1-specific targeting immunotherapy with bispecific antibodies: inhibition of xenografted human bile duct carcinoma growth,” Cancer Res., 56(18):4205-12 (1996).Applicant
• Khawli et al., “Improved tumor localization and radioimaging with chemically modified monoclonal antibodies,” Cancer. Biother. Radiopharm., 11:203-215 (1996).Applicant
• Kim et al., “Antibody Engineering for the Development of Therapeutic Antibodies,” Mol. Cells, 20:17-29 (2005).Applicant
• Kim et al., “Chemical modification to reduce renal uptake of disulfide-bonded variable region fragment of anti-tac monoclonal antibody labeled with 99mTc,” Bioconjugate Chem., 10:447-453 (1999).Applicant
• Kim et al., “Lowering of pI by acylation improves the renal uptake of 99mTc-labeled anti-Tac dsFv: effect of different acylating reagents,” Nucl. Med. Biol., 29:795-801 (2002).Applicant
• Kim et al., “Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn,” Eur. J. Immunol., 29(9):2819-25 (1999).Applicant
• Kim et al., “Mammalian type I interferon receptors consists of two subunits: IFNaR1 and IFNaR2,” Gene, 196:279-286 (1997).Applicant
• Kobayashi et al., “A monoclonal antibody specific for a distinct region of hen egg-white lysozyme,” Mol. Immunol., 19:619-30 (1982).Applicant
• Kobayashi et al., “The pharmacokinetic characteristics of glycolated humanized anti-Tac Fabs are determined by their isoelectric points,” Cancer Res., 59:422-430 (1999).Applicant
• Komissarov et al., “Site-specific mutagenesis of a recombinant anti-single-stranded DNA Fab. Role of heavy chain complementarity-determining region 3 residues in antigen interaction,” J. Biol. Chem., 272(43):26864-70 (1997).Applicant
• Kranenborg et al., “Development and characterization of anti-renal cell carcinoma x antichelate bispecific monoclonal antibodies for two-phase targeting of renal cell carcinoma,” Cancer Res., 55:5864s-5867s (1995).Applicant
• Kreutz et al., “Efficient bispecific monoclonal antibody purification using gradient thiophilic affinity chromatography,” J. Chromatogr. B, 714:161-170 (1998).Applicant
• Kroesen et al., “Phase I study of intravenously applied bispecific antibody in renal cell cancer patients receiving subcutaneous interleukin 2,” Br. J Cancer, 70:652-661 (1994).Applicant
• Kurfis et al., “Role of Arg182 in the second extracellular loop of angiotensin II receptor AT2 in ligand binding,” Biochem. Biophys. Res. Commun., 263:816-819 (1999).Applicant
• Kurokawa et al., “Enhanced Fibrinolysis by a Bispecific Monoclonal Antibody Reactive to Fibrin and Tissue Plasminogen Activator,” Bio/Technology, 7:1163-1167 (1989).Applicant
• Lansdorp et al., “Purification and analysis of bispecific tetrameric antibody complexes,” Mol. Immunol., 27:659-666 (1990).Applicant
• Lapan et al., “Interaction of the A1 Subunit of Factor VIIIa and the Serine Protease Domain of Factor X Identified by Zero-length Cross-linking,” Thromb. Haemost., 80:418-422 (1998).Applicant
• Le Doussal et al., “Bispecific Monoclonal Antibody-Mediated Targeting of an Indium-111-Labeled DTPA Dimer to Primary Colorectal Tumors: Pharmacokinetics, Biodistribution, Scintigraphy and Immune Response,” J. Nucl. Med., 34:1662-1671 (1993).Applicant
• Lenting et al., “The life cycle of coagulation factor VIII in view of its structure and function”, Blood 92(11):3983-3996 (1998).Applicant
• Leong et al., “Adapting pharmacokinetic properties of a humanized anti-interleukin-8 antibody for therapeutic applications using site-specific pegylation,” Cytokine, 16(3):106-19 (2001).Applicant
• Life Technologies (Invitrogen: “ecdysone analogue” and pIND plasmid), Aug. 10, 2012, 2 pages.Applicant
• Lindhofer et al., “Preferential Species-Restricted Heavy/Light Chain Pairing in Rat/Mouse Quadromas,” J. Immunol., 155:219-225 (1995).Applicant
• Link et al., “Production and Characterization of a Bispecific IgG Capable of Inducing T-Cell-Mediated Lysis of Malignant B Cells,” Blood, 81:3343-3349 (1993).Applicant
• Liu et al., “Heterogeneity of monoclonal antibodies,” J. Pharm. Sci., 97(7):2426-47 (2008).Applicant
• Lobo et al., “Antibody pharmacokinetics and pharmacodynamics,” J. Pharm. Sci., 93:2645-68 (2004).Applicant
• Löfqvist et al., “Haemophilia prophylaxis in young patients—a long-term follow-up,” J. Intern. Med., 241:395-400 (1997).Applicant
• Lu et al., “Di-diabody: a novel tetravalent bispecific antibody molecule by design,” J. Immunol. Methods, 279:219-232 (2003).Applicant
• Lu et al., “Fab-scFv fusion protein: an efficient approach to production of bispecific antibody fragments,” J. Immunol. Methods, 267:213-226 (2002).Applicant
• MacCallum et al., “Antibody-antigen interactions: contact analysis and binding site topography,” J. Mol. Biol., 262:732-45 (1996).Applicant
• Maeda et al., “pH-dependent receptor/ligand dissociation as a determining factor for intracellular sorting of ligands for epidermal growth factor receptors in rat hepatocytes,” J. Control Release, 82(1):71-82 (2002).Applicant
• Maini et al., “Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate,” Arthritis Rheum., 54:2817-29 (2006).Applicant
• Manz et al., Bioanalytical Chemistry, World Scientific Publishing Co. (2003).Applicant
• Manzke et al., “Single-step purification of bispecific monoclonal antibodies for immunotherapeutic use by hydrophobic interaction chromatography,” J. Immunol. Methods, 208:6573 (1997).Applicant
• Marti et al., “Inverse electrostatic effect: electrostatic repulsion in the unfolded state stabilizes a leucine zipper,” Biochemistry, 43(39):12436-47 (2004).Applicant
• Martin et al., “Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding,” Mol. Cell, 7:867-877 (2001).Applicant
• Marvin et al., “Recombinant approaches to IgG-like bispecific antibodies,” Acta. Pharmacol. Sin., 26:649-658 (2005).Applicant
• Marvin et al., “Redesigning an antibody fragment for faster association with its antigen,” Biochemistry, 42:7077-83 (2003).Applicant
• Massino et al., “Quantitative analysis of the products of IgG chain recombination in hybrid hybridomas based on affinity chromatography and radioimmunoassay,” J. Immunol. Methods, 201:57-66 (1997).Applicant
• Maxfield et al., “Endocytic recycling,” Nat. Rev. Mol. Cell Biol., 5(2):121-32 (2004).Applicant
• McCafferty et al., “Phage antibodies: filamentous phage displaying antibody variable domains,” Nature, 348:552-554 (1990).Applicant
• Menegatti et al., “Factor X Deficiency,” Semin. Thromb. Hemost., 35:407-415 (2009).Applicant
• Merchant et al., “An efficient route to human bispecific IgG,” Nat. Biotechnol., 16:677-681 (1998).Applicant
• Mertens et al., “Factor VIII-Factor IX Interactions: Molecular Sites Involved in Enzyme-Cofactor Complex Assembly,” Thromb. Haemost., 82:209-217 (1999).Applicant
• Milstein et al., “Hybrid hybridomas and their use in immunohistochemistry,” Nature, 305:537-540 (1983).Applicant
• Morell et al., “Metabolic properties of IgG subclasses in man,” J. Clin. Invest., 49(4):673-80 (1970).Applicant
• Morimoto et al., “Single-step purification of F(ab′)2 fragments of mouse monoclonal antibodies (immunoglobulins G1) by hydrophobic interaction high performance liquid chromatography using TSKgel Phenyl-5PW,” J. Biochem. Biophys. Methods, 24:107-117 (1992).Applicant
• Murtaugh et al., “A combinatorial histidine scanning library approach to engineer highly pH-dependent protein switches,” Protein Sci., 20(9):1619-31 doi:10.1002/pro 696 (2011).Applicant
• Nesterova et al., “Glypican-3 as a novel target for an antibody-drug conjugate,” AACR Abstract No. 656, Los Angeles, CA (Apr. 4-18, 2007).Applicant
• Nilsson et al., “Induction of split tolerance and clinical cure in high-responding hemophiliacs with factor IX antibodies,” Proc. Natl. Acad. Sci. USA, 83:9169-9173 (1986).Applicant
• Nilsson et al., “Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B,” J. Intern. Med., 232:25-32 (1992).Applicant
• Nishimoto et al., “Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease,” Blood, 106:2627-32 (2005).Applicant
• Nishimoto et al., “Interleukin 6: from bench to bedside,” Nat. Clin. Pract. Rheumatol., 2:619-626 (2006).Applicant
• Nitta et al., “Preliminary trial of specific targeting therapy against malignant glioma,” Lancet, 335:368-371 (1990).Applicant
• Okubo et al. “The production and characterization of four monoclonal antibodies to human factor X,” Nara Med Assoc., 38(1):20-28 (1987).Applicant
• Onda et al., “Lowering the Isoelectric Point of the Fv Portion of Recombinant Immunotoxins Leads to Decreased Nonspecific Animal Toxicity without Affecting Antitumor Activity,” Cancer Res., 61:5070-77 (2001).Applicant
• Ono et al., “The humanized anti-HM1.24 antibody effectively kills multiple myeloma cells by human effector cell-mediated cytotoxicity,” Mol. Immunol., 36(6):387-95 (1999).Applicant
• Ozhegov et al., Tolkovyi Slovar Russkogo iazyka: 2004, p. 292 (with an English translation of the relevant passage defining “control”).Applicant
• Pakula et al., “Genetic Analysis of Protein Stability and Function,” Annu. Rev. Genet., 23:289-310 (1989).Applicant
• Panka et al., “Variable region framework differences result in decreased or increased affinity of variant anti-digoxin antibodies,” Proc. Natl. Acad. Sci. USA, 85(9):3080-84 (1988).Applicant
• Pardridge et al., “Enhanced endocytosis in cultured human breast carcinoma cells and in vivo biodistribution in rats of a humanized monoclonal antibody after cationization of the protein,” J. Pharmacol. Exp. Ther., 286(1):548-54 (1998).Applicant
• Paul, William ed., Fundamental Immunology, 3rd edition, p. 242 (1993).Applicant
• Pavlinkova et al., “Charge-modified single chain antibody constructs of monoclonal antibody CC49: Generation, characterization, pharmacokinetics, and biodistribution analysis,” Nucl. Med. Biol., 26:27-34 (1999).Applicant
• Pavlou et al., “The therapeutic antibodies market to 2008,” Eur. J. Pharm. Biopharm., 59:389-396 (2005).Applicant
• Piper et al., “Interferon therapy in primary care,” Primary Care Update for Ob/Gyns, 8(4):163-169 (2001).Applicant
• Poduslo et al., “Polyamine modification increases the permeability of proteins at the blood—nerve and blood-brain barriers,” J. Neurochem., 66:1599-1609 (1996).Applicant
• Pons et al., “Energetic analysis of an antigen/antibody interface: alanine scanning mutagenesis and double mutant cycles on the HyHEL-10/lysozyme interaction,” Protein Sci., 8(5):958-68 (1999).Applicant
• Portolano et al., “Lack of Promiscuity in Autoantigen-Specific H and L Chain Combinations as Revealed by Human H and L Chain “Roulette”,” J. Immunol., 150(3):880-887 (1993).Applicant
• Presta, “Engineering of therapeutic antibodies to minimize immunogenicity and optimize function,” Adv. Drug Deliv. Rev., 58(5-6):640-56 (2006).Applicant
• Price et al., “Tissue factor and tissue factor pathway inhibitor,” Anaesthesia, 59:483-492 (2004).Applicant
• Queen et al., “A humanized antibody that binds to the interleukin 2 receptor,” Proc. Natl. Acad. Sci. U.S.A., 86(24):10029-10033 (1989).Applicant
• Raffen et al., “Reengineering immunoglobulin domain interactions by introduction of charged residues,” Protein Eng. ,11:303-309 (1998).Applicant
• Rajpal et al., “A general method for greatly improving the affinity of antibodies by using combinatorial libraries,” Proc. Natl. Acad. Sci. USA, 102:8466-71 (2005).Applicant
• Rathanaswami et al., “Demonstration of an in vivo generated sub-picomolar affinity fully human monoclonal antibody to interleukin-8,” Biochem. Biophys. Res. Commun., 334:1004-13 (2005).Applicant
• Reddy et al., “Elimination of Fc receptor-dependent effector functions of a modified IgG4 monoclonal antibody to human CD4,” J. Immunol., 164(4):1925-33 (2000).Applicant
• Reichert et al., “Development trends for monoclonal antibody cancer therapeutics,” Nat. Rev. Drug Discov., 6(5):349-56 (2007).Applicant
• Reichert et al., “Monoclonal antibody successes in the clinic,” Nat. Biotechnol., 23:1073-78 (2005).Applicant
• Ridgway et al., “'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization,” Protein Eng., 9:617-621 (1996).Applicant
• Roitt et al., Immunology, M., Mir, (2000), pp. 110-111 (in Russian, with what is believed to be a published English equivalent of those pages taken from ROITT et al., “Antibody Structure and Function,” Immunology, Fifth Ed., (1998), pp. 80-81).Applicant
• Rothe et al., “Ribosome display for improved biotherapeutic molecules,” Expert Opin. Biol. Ther., 6:177-187 (2006).Applicant
• Rudikoff et al., “Single amino acid substitution altering antigen-binding specificity,” Proc. Natl. Acad. Sci. USA, 79:1979-1983 (1982).Applicant
• Ruef et al., “A bispecific antifibrin-antiplatelet urokinase conjugate (BAAUC) induces enhanced clot lysis and inhibits platelet aggregation,” Thromb. Haemost., 82(1):109-114 (1999).Applicant
• Ruf et al., “Pharmacokinetics and in vivo stability of intraperitoneally administered therapeutic antibody catumaxomab,” J. Clin. Oncol., 26 (May 20 suppl) (2008), abstr 14006.Applicant
• Salfeld et al., “Isotype selection in antibody engineering,” Nat. Biotechnol., 25:1369-72 (2007).Applicant
• Sal-Man et al., “Arginine mutations within a transmembrane domain of Tar, an Escherichia coli aspartate receptor, can drive homodimer dissociation and heterodimer association in vivo,” Biochem. J., 385:29-36 (2005).Applicant
• Sato et al., “Properties of Two VEGF Receptors, Flt-1 and KDR, in Signal Transduction,” Ann N.Y. Acad. Sci, 902:201-207, discussion 205-7 (May 2000).Applicant
• Sato et al., “Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth,” Cancer Res., 53:851-856 (1993).Applicant
• Schaeffer et al., “The Rat Glomerular Filtration Barrier Does Not Show Negative Charge Selectivity,” Microcirculation, 9:329-342 (2002).Applicant
• Schmidt et al., Human Physiology, Moscow, 2:431-436 (1996), and English translation: Schmidt et al., “Hemostatis and Coagulation,” Human Physiology, R.F. Schmidt, G. Thews (Eds.), Second, Completely Revised Edition, 418-423 [translated by Marguerite A. Biederman-Thorson], Springer-Verlag (1989).Applicant
• Schmidt et al., Human Physiology, Moscow, 3:764 (1996), and English translation: Schmidt et al., “Enzymes of the pancreatic juice,” Human Physiology, R.F. Schmidt, G. Thews (Eds.), Second, Completely Revised Edition, 716 [translated by Marguerite A. Biederman-Thorson], Springer-Verlag (1989).Applicant
• Schmitz et al., “Phage display: a molecular tool for the generation of antibodies—a review,” Placenta., 21 Suppl A:S106-12 (2000).Applicant
• Segal et al., “Bispecific antibodies in cancer therapy,” Curr. Opin. Immunol., 11:558-562 (1999).Applicant
• Segal et al., “Introduction: bispecific antibodies,” J. Immunol. Methods, 248:1-6 (2001).Applicant
• Shalaby et al., “Development of Humanized Bispecific Antibodies Reactive with Cytotoxic Lymphocytes and Tumor Cells Overexpressing the HER2 Protooncogene,” J. Exp. Med., 175:217-225 (1992).Applicant
• Shire et al., “Challenges in the development of high protein concentration formulations,” J. Pharm. Sci., 93:1390-1402 (2004).Applicant
• Shaul, “Exploring the charge space of protein-protein association: a proteomic study,” Proteins, 60:341-352 (2005).Applicant
• Shields et al., “High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R,”J. Biol. Chem., 276:6591-6604 (2001) (Epub Nov. 28, 2000).Applicant
• Shima et al., “Factor VIII Taitei Kotai (2), Ketsuyubyo A Kanja Katsueki ni okeru in vitro Gyoko Kassei no Kento”, Rinsho Ketsueki 46(8):777, 2005.Applicant
• Sinha et al., “Electrostatics in protein binding and function,” Curr. Protein Pept. Sci., 3(6):601-14 (2002).Applicant
• Sinha et al., “Molecular dynamics simulation of a high-affinity antibody-protein complex: the binding site is a mosaic of locally flexible and preorganized rigid regions,” Cell Biochem Biophys., 43:253-273 (2005).Applicant
• Smans et al., “Bispecific antibody-mediated lysis of primary cultures of ovarian carcinoma cells using multiple target antigens,” Int. J. Cancer, 83:270-277 (1999).Applicant
• Smith, “Creative Expression: Mammalian Expression Vectors and Systems,” The Scientist Magazine, Feb. 2, 1998, 3 pages.Applicant
• Soeda et al., “Factor VIII Taitei Kotai (1) Ko FIXa/FX bispecific Kotai no Sakusei oyobi characterization”, Rinsho Ketsueki, 46(8):728 (2005).Applicant
• Soeda et al., “Phage library-ho ni yori Sakusei shita Ko-FIXa/Ko-FX bispecific Kotai no FVIII Taitei Sayo,” Japanese Journal of Thrombosis and Hemstasis, 16(5):526 (2005).Applicant
• Stickney et al., “Bifunctional Antibody: A Binary Radiopharmaceutical Delivery System for Imaging Colorectal Carcinoma,” Cancer Res., 51:6650-6655 (1991).Applicant
• Strand et al., “Biologic therapies in rheumatology: lessons learned, future directions,” Nat. Rev. Drug Discov., 6:75-92 (2007).Applicant
• Sun et al., “Coexpression of Gas6/Axl in human ovarian cancers,” Oncology, 66(6):450-7 (2004).Applicant
• Suresh et al., “Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays,” Proc. Natl. Acad. Sci. USA, 83:7989-7993 (1986).Applicant
• Suresh et al., “Bispecific Monoclonal Antibodies from Hybrid Hybridomas,” Methods Enzymol., 121:210-228 (1986).Applicant
• Taki, The Journal of Japanese Society on Thrombosis and Hemostasis, 13:109-113 (2002) (see reference AXX for concise English explanation).Applicant
• Tan et al., “Engineering the isoelectric point of a renal cell carcinoma targeting antibody greatly enhances scFv solubility,” Immunotechnology, 4(2):107-114 (1998).Applicant
• Tarditi et al., “Selective high-performance liquid chromatographic purification of bispecific monoclonal antibodies,” J. Chromatogr., 599:13-20 (1992).Applicant
• Teeling et al., “The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20,” J. Immunol., 177(1):362-71 (2006).Applicant
• Ten Kate et al., “Effect of isoelectric point on biodistribution and inflammation: imaging with indium-111-labelled IgG,” Eur. J. Nucl. Med., 17:305-309 (1990).Applicant
• Tsuchiya, Credit Suisse Seminar, “Therapeutic Antibody,” at Fuji-Gotemba Laboratories, p. 21 (2006) (with English Translation).Applicant
• Tsurushita et al., “Design of humanized antibodies: From anti-Tac to Zenapax,” Methods, 36:69-83 (2005).Applicant
• Vaisitti et al., “Cationization of monoclonal antibodies: another step towards the “magic bullet”?,” J. Biol. Regul. Homeost. Agents., 19(3-4):105-12 (2005).Applicant
• Vajdos et al., “Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis,” J. Mol. Biol., 320(2):415-28 (2002).Applicant
• Van et al., “Immunogenicity screening in protein drug development,” Expert Opin. Biol. Ther., 7(3):405-18 (2007).Applicant
• Van Loghem et al., “Staphylococcal protein A and human IgG subclasses and allotypes,” Scand. J. Immunol., 15(3):275-8 (1982).Applicant
• Warnaar et al., “Purification of bispecific F(ab′)2 from murine trinoma OC/TR with specificity for CD3 and ovarian cancer,” Hybridoma, 13:519-526 (1994).Applicant
• Weiner et al., “A Human Tumor Xenograft Model of Therapy with a Bispecific Monoclonal Antibody Targeting c-erbB-2 and CD16,” Cancer Res., 53:94-100 (1993).Applicant
• Weiner et al., “The Role of T Cell Activation in Anti-CD3 × Antitumor Bispecific Antibody Therapy,” J. Immunol., 152:2385-2392 (1994).Applicant
• Wiens et al., “Somatic mutation in VH complementarity-determining region 2 and framework region 2: differential effects on antigen binding and Ig secretion,” J. Immunol., 159(3):1293-302 (1997).Applicant
• Wiens et al., “Mutation of a single conserved residue in VH complementarity-determining region 2 results in a severe Ig secretion defect,” J. Immunol., 167(4):2179-86 (2001).Applicant
• Wu et al., “Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract,” J. Mol. Biol., 368:652-65 (2007).Applicant
• Xiang et al., “Study of B72.3 combining sites by molecular modeling and site-directed mutagenesis,” Protein Eng., 13(5):339-44 (2000).Applicant
• Xiang et al., “Production of Murine V-Human Crl Chimeric Anti-TAG72 Antibody Using V Region cDNA Amplified by PCR,” Mol. Immunol., 27:809-817 (1990).Applicant
• Yamasaki et al., “Pharmacokinetic analysis of in vivo disposition of succinylated proteins targeted to liver nonparenchymal cells via scavenger receptors: importance of molecular size and negative charge density for in vivo recognition by receptors,” J. Pharmacol. Exp. Ther., 301:467-477 (2002).Applicant
• Yang et al., “Tailoring structure-function and pharmacokinetic properties of single-chain Fv proteins by site-specific PEGylation,” Protein Eng., 16:761-770 (2003).Applicant
• Zhu et al., “MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells,” J. Immunol., 166(5):3266-76 (2001).Applicant
• Zuckier et al., “Chimeric human-mouse IgG antibodies with shuffled constant region exons demonstrate that multiple domains contribute to in vivo half-life,” Cancer Res., 58:3905-08 (1998).Applicant
• Zwick et al., “The long third complementarity-determining region of the heavy chain is important in the activity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5,” J. Virol., 78(6):3155-61 (2004).Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 10/575,193, mailed Mar. 24, 2009, 7 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Mar. 24, 2009 in U.S. Appl. No. 10/575,193, filed Jun. 23, 2009, 1 page.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 10/575,193, mailed Sep. 24, 2009, 38 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Sep. 24, 2009 in U.S. Appl. No. 10/575,193, filed Mar. 24, 2010, 19 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 10/575,193, mailed Jun. 23, 2010, 18 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Jun. 23, 2010 in U.S. Appl. No. 10/575,193, filed Dec. 22, 2010, 13 pages.Applicant
• USPTO Notice of Allowance in U.S. Appl. No. 10/575,193, mailed Mar. 18, 2011, 11 pages.Applicant
• Fish & Richardson P.C., Amendment in U.S. Appl. No. 10/575,193, filed Jun. 17, 2011, 15 pages.Applicant
• USPTO Notice of Allowance in U.S. Appl. No. 10/575,193, mailed Jul. 13, 2011, 8 pages.Applicant
• International Search Report for App. Ser. No. PCT/JP2004/014911, mailed Jan. 25, 2005, 3 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2004/014911, dated Sep. 27, 2005, 12 pages.Applicant
• European Search Report for App. Ser. No. EP 04 79 2180, dated Jan. 17, 2008, 3 pages.Applicant
• International Search Report for App. Ser. No. PCT/JP2003/013123, mailed Nov. 25, 2003, 4 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2003/013123, dated Oct. 20, 2005, 7 pages.Applicant
• European Search Report for App. Ser. No. EP 03 75 1478, dated Jan. 11, 2008, 3 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 10/575,905, mailed Jun. 25, 2009, 10 pages.Applicant
• Fish & Richardson P.C., Amendment and Response to Restriction Requirement dated Jun. 25, 2009 in U.S. Appl. No. 10/575,905, filed Sep. 25, 2009, 14 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 10/575,905, mailed Nov. 18, 2009, 14 pages.Applicant
• Fish & Richardson P.C., Amendment and Response to Restriction Requirement dated Nov. 18, 2009 in U.S. Appl. No. 10/575,905, filed Apr. 16, 2010, 12 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 10/575,905, mailed Jun. 23, 2010, 10 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Jun. 23, 2010 in U.S. Appl. No. 10/575,905, filed Dec. 22, 2010, 10 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 10/575,905, mailed Feb. 24, 2011, 7 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 11/910,836, dated Mar. 18, 2011, 7 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Mar. 18, 2011 in U.S. Appl. No. 11/910,836, filed Sep. 6, 2011, 1 page.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 11/910,836, dated Sep. 30, 2011, 21 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. JP2006/306821, dated Oct. 9, 2007, 7 pages.Applicant
• International Search Report for App. Ser. No. JP2006/306821, mailed Jul. 11, 2006, 6 pages.Applicant
• European Search Report for App. Ser. No. 06 73 0769, dated Jun. 18, 2009 (8 pages).Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 13/434,643, dated Jul. 27, 2012, 6 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Jul. 27, 2012 and Preliminary Amendment in U.S. Appl. No. 13/434,643, filed on Jan. 24, 2013, 10 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 13/434,643, dated Feb. 12, 2013, 17 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Office Action dated Feb. 12, 2013 in U.S. Appl. No. 13/434,643, filed on May 13, 2013, 18 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 13/434,643, dated Jul. 11, 2013, 19 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2011/076486, dated Jun. 12, 2013, 9 pages.Applicant
• International Search Report for App. Ser. No. PCT/JP2009/057309, mailed Jul. 7, 2009, 8 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2009/057309, mailed Nov. 30, 2010, 7 pages.Applicant
• European Search Report for App. Ser. No. EP 09 72 9337, dated Nov. 3, 2011, 3 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 12/295,039, dated Oct. 12, 2010, 9 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Oct. 12, 2010 in U.S. Appl. No. 12/295,039, filed on Apr. 11, 2011, 9 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 12/295,039, dated Jun. 28, 2011, 9 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Jun. 28, 2011 in U.S. Appl. No. 12/295,039, filed on Dec. 27, 2011, 14 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 12/295,039, dated Apr. 12, 2012, 8 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Apr. 12, 2012 in U.S. Appl. No. 12/295,039, filed on Sep. 11, 2012, 12 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2007/057036, dated Oct. 21, 2008, 6 pages.Applicant
• International Search Report for App. Ser. No. PCT/JP2007/057036, dated May 1, 2007, 2 pages.Applicant
• European Search Report for App. Ser. No. 07 74 0494, dated Sep. 3, 2009, 3 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2007/057058, dated Oct. 21, 2008, 11 pages.Applicant
• International Search Report App. Ser. No. PCT/JP2007/057058, mailed May 7, 2001, 2 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 12/295,075, dated Feb. 22, 2011, 9 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Feb. 22, 2011 in U.S. Appl. No. 12/295,075, filed Aug. 18, 2011, 2 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 12/295,075, dated Nov. 4, 2011, 14 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Nov. 4, 2011 in U.S. Appl. No. 12/295,075, filed May 3, 2012, 12 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 12/295,075, dated Jul. 19, 2012, 12 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Jul. 19, 2012 in U.S. Appl. No. 12/295,075, filed Jan. 17, 2013, 113 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 12/295,075, dated Jun. 7, 2013, 17 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 11/910,128, dated Jun. 9, 2011, 10 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Jun. 9, 2011 in U.S. Appl. No. 11/910,128, filed Dec. 2, 2011, 1 page.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 11/910,128, dated Apr. 25, 2012, 21 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Office Action dated Apr. 25, 2012 in U.S. Appl. No. 11/910,128, filed Oct. 25, 2012, 32 pages.Applicant
• Fish & Richardson P.C., Supplemental Amendment in U.S. Appl. No. 11/910,128, filed Nov. 14, 2012, 20 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 11/910,128, dated Sep. 10, 2013, 12 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Final Office Action dated Jun. 3, 2010 in U.S. Appl. No. 10/560,098, filed Jul. 5, 2011, 17 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 10/560,098, mailed Dec. 8, 2011, 11 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Non-Final Office Action dated Dec. 8, 2011 in U.S. Appl. No. 10/560,098, filed Jun. 5, 2012, 11 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 10/560,098, dated Aug. 15, 2012, 10 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Final Office Action dated Aug. 15, 2012 in U.S. Appl. No. 10/560,098, filed Sep. 5, 2012, 8 pages.Applicant
• USPTO Interview Summary in U.S. Appl. No. 10/560,098, dated Sep. 7, 2012, 3 pages.Applicant
• USPTO Notice of Allowance in U.S. Appl. No. 10/560,098, dated Apr. 25, 2013, 12 pages.Applicant
• USPTO Notice of Allowance in U.S. Appl. No. 10/560,098, dated Jul. 9, 2013, 6 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 12/936,587, dated Dec. 6, 2011, 7 pages.Applicant
• Fish & Richardson P.C., Third Preliminary Amendment and Response to Restriction Requirement dated Dec. 6, 2011 in U.S. Appl. No. 12/936,587, filed on Jun. 5, 2012, 7 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 12/936,587, dated Jun. 25, 2012, 5 pages.Applicant
• Fish & Richardson P.C., Response to Species Election Requirement dated Jun. 25, 2012 in U.S. Appl. No. 12/936,587, filed on Jul. 25, 2012, 1 page.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 12/936,587, dated Nov. 7, 2012, 13 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 12/679,922, dated Oct. 2, 2012, 9 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Oct. 2, 2012 in U.S. Appl. No. 12/679,922, filed on Nov. 1, 2012, 2 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 12/679,922, dated Jan. 3, 2013, 25 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Jan. 3, 2013 in U.S. Appl. No. 12/679,922, filed on Jul. 2, 2013, 18 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 12/679,922, dated Aug. 2, 2013, 12 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2010/073361, dated Aug. 14, 2012, 7 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 13/595,139, dated Nov. 14, 2012, 10 pages.Applicant
• Figini et al., “In vitro assembly of repertoires of antibody chains on the surface of phage by renaturation,”. J. Mol Biol., May 27, 1994;239(1):68-78.Applicant
• Vaughan et al., “Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library,” Nat Biotechnol., Mar. 1996;14(3):309-14.Applicant