Methods of modifying antibodies for purification of bispecific antibodies

Patent Citations (431)

Non-Patent Literature (641)

• Smans et al. (Int. J. Cancer, 83:270:277, 1999).Examiner
• Onda et al. (Cancer Res., 61:5070:5077, 2001).Examiner
• Manz et al. (Bioanalytical Chemistry, World Scientific Publishing Co., 2003).Examiner
• Roguska et al. (PNAS, 91: 969-973, 1994).Examiner
• Hombach et al. (Int. J. Cancer, 55: 830-836, 1993).Examiner
• Staerz and Bevan (PNAS, 83: 1453-1457).Examiner
• Manzke et al. (Journal of Immunological Methods, 208: 65-73, 1997).Examiner
• Haagen et al. (Cancer Immunol Immunother, 39: 391-396, 1994).Examiner
• Exhibit A (IMGT Scientific charts depicting the correspondence between Eu and Kabat numberings for the human IgG constant region, created May 17, 2001 and last updated Aug. 13, 2014).Examiner
• Exhibit B (IMGT Scientific charts depicting the correspondence between Eu and Kabat numberings for the human IgG constant region, created May 17, 2001 and last updated Aug. 13, 2014).Examiner
• Suresh et al. (Methods in Enzymology, 121: 210-228, 1986).Examiner
• Branden and Tooze, “Recognition of Foreign Molecules by the Immune System,” Introduction to Protein Structure, 2d Ed., Garland Publishing, pp. 299-323 (1999).Applicant
• Carter, “Bispecific human IgG by design,” J. Immunol Methods, 248:7-15 (2001).Applicant
• Gupta and Suresh, “Affinity chromatography and co-chromatography of bispecific monoclonal antibody immunoconjugates,” J. Biochem. Biophys. Methods, 51:203-216 (2002).Applicant
• Kreutz et al., “Efficient bispecific monoclonal antibody purification using gradient thiophilic affinity chromatography,” J. Chromatogr. B, 714:161-170 (1998).Applicant
• Lindhofer et al., “Preferential Species-Restricted Heavy/Light Chain Pairing in Rat/Mouse Quadromas,” J. Immunol , 155:219-225 (1995).Applicant
• Manzke et al., “Single-step purification of bispecific monoclonal antibodies for immunotherapeutic use by hydrophobic interaction chromatography,” J. Immunol Methods, 208:65-73 (1997).Applicant
• Marvin and Zhu, “Recombinant approaches to IgG-like bispecific antibodies,” Acta. Pharmacol. Sin., 26(6):649-658 (2005).Applicant
• Merchant et al., “An efficient route to human bispecific IgG,” Nat. Biotechnol., 16:677-681 (1998).Applicant
• Segal et al., “Bispecific antibodies in cancer therapy,” Curr. Opin. Immunol., 11:558-562 (1999).Applicant
• Tarditi et al., “Selective high-performance liquid chromatographic purification of bispecific monoclonal antibodies,” J. Chromatogr., 599:13-20 (1992).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
• 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
• Panka et al., “Variable region framework differences result in decreased or increased affinity of variant anti-digoxin antibodies,” Proc. Natl. Acad. Sci. U.S.A., 85(9):3080-4 (1988).Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Oct. 12, 2010 in U.S. Appl. No. 12/295,039, filed Apr. 11, 2011, 9 pages.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
• Binz et al., “Engineering novel binding proteins from nonimmunoglobulin domains,” Nature Biotechnol., 23:1257-68 (2005).Applicant
• Comper and Glasgow, “Charge selectivity in kidney ultrafiltration,” Kidney Int., 47:1242-51 (1995).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
• 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
• 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
• Ghetie and Ward, “FcRn: the MHC class I-related receptor that is more than an IgG transporter,” Immunol. Today, 18(12):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
• U.S. Appl. No. 12/295,039, filed Sep. 29, 2008, Igawa et al.Applicant
• He et al., “Humanization and Pharmacokinetics of a Monoclonal Antibody with Specificity for Both E- and P-Selectin,” J. Immunol., 1029-35 (1998).Applicant
• Hinton et al., “An Engineered Human IgG1 Antibody with Longer Serum Half-Life,” J. Immunol., 346-356 (2006).Applicant
• Kashmiri et al., “Generation, Characterization, and in Vivo Studies of Humanized Anticarcinoma Antibody CC49,” Hybridoma, 14:461-473 (1995).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
• 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
• Lobo et al., “Antibody Pharmacokinetics and Pharmacodynamics,” J. Pharm. Sci., 93:2645-68 (2004).Applicant
• Martin et al., “Crystal structure at 2.8 Å of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding,” Mol. Cell, 7:867-877 (2001).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
• 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 and Belsey, “The therapeutic antibodies market to 2008,” Eur. J. Pharm. Biopharm., 59:389-396 (2005).Applicant
• Poduslo and Curran, “Polyamine Modification Increases the Permeability of Proteins at the Blood-Nerve and Blood-Brain Barriers,” J. Neurochem., 1599-1609 (1996).Applicant
• Rajpal et al., “A general method for greatly improving the affinity of antibodies by using combinational libraries,” Proc. Natl. Acad. Sci. USA, 102:8466-71 (2005).Applicant
• Reichert et al., “Monoclonal antibody successes in the clinic,” Nat. Biotechnol., 23:1073-78 (2005).Applicant
• Schaeffer et al., “The Rat Glomerular Filtration Barrier Does Not Show Negative Charge Selectivity,” Microcirculation, 9:329-342 (2002).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 (2000).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
• Tsurushita et al., “Design of humanized antibodies: From anti-Tac to Zenapax,” Methods, 36:69-83 (2005).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 Engineering, 16:761-770 (2003).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
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2007/057036, dated Oct. 21, 2008, 6 pages.Applicant
• Japanese Patent Office, International Search Report for App. Ser. No. PCT/JP2007/057036, dated May 1, 2007, 2 pages.Applicant
• European Search Report for Application No. EP 07 74 0474, dated Mar. 16, 2009, 5 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2007/057058, dated Oct. 21, 2008, 11 pages.Applicant
• Japanese Patent Office, International Search Report App. Ser. No. PCT/JP2007/057058, mailed May 7, 2001, 2 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
• 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 Final Office Action dated Jun. 3, 2010 in U.S. Appl. No. 10/560,098, filed Jul. 5, 2011, 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 Mar. 18, 2011 in U.S. Appl. No. 11/910,836, filed Sep. 6, 2011, 1 page.Applicant
• European Search Report for App. Ser. No. 07 74 0494, dated Sep. 3, 2009, 3 pages.Applicant
• Marvin et al., “Redesigning an antibody fragment for faster association with its antigen,” Biochemistry, 42:7077-83 (2003).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
• Shaul, “Exploring the charge space of protein-protein association: a proteomic study,” Proteins, 60:341-352 (2005).Applicant
• USPTO Final Office Action in U.S. Appl. No. 10/575,905, mailed Feb. 24, 2011, 7 pages.Applicant
• Abe et al., “Surrogate thrombopoietin,” Immunology Letters, 61:73-78 (1998).Applicant
• Andris-Widhopf et al., “Methods for the generation of chicken monoclonal antibody fragments by phage display,” Journal of Immunological Methods, 242:159-181 (2000).Applicant
• Arndt et al., “Factors influencing the dimer to monomer transition of an antibody single-chain Fv fragment,” Biochemistry, 37(37):12918-26 (1998).Applicant
• Arndt et al., “Generation of a highly stable, internalizing anti-DC22 single-chain Fv fragment for targeting non-Hodgkin's lymphoma,” Int. J. Cancer, 107(5):822-829 (2003).Applicant
• Ballmaier et al., “c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia,” Blood, 97:139-146 (2001).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
• Bowie et al., “Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions,” Science, 247:1306-1310 (1990).Applicant
• Brinkmann et al., “FTY720: targeting G-protein-coupled receptors for sphingosine 1-phosphate in transplantation and autoimmunity,” Curr. Opin. Immunol., 14:569-575 (2002).Applicant
• Bruenke et al., “A recombinant bispecific single-chain Fv antibody against HLA class II and FcγRIII (CD16) triggers effective lysis of lymphoma cells,” Br. J. Haematol., 125:167-179 (2004).Applicant
• Casset et al., “A peptide mimetic of an anti-CD4 monoclonal antibody by rational design,” Biochemical and Biophysical Research Communications, 307:198-205 (2003).Applicant
• Cekaite et al., “Protein Arrays: A versatile toolbox for target identification and monitoring of immune mmune responses,” Methods Mol. Biol., 360:335-348 (2007).Applicant
• Chatellier et al., “Functional mapping of conserved residues located at the VL and VH domain interface of a Fab,” J. Mol. Biol., 264(1):1-6 (1996).Applicant
• Chen et al., “Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen,” Journal of Molecular Biology, 293:865-881 (1999).Applicant
• Chowdhury et al., “Engineering scFvs for improved stability,” Methods Mol. Biol., 207:237-54 (2003).Applicant
• Clackson et al., “Making antibody fragments using phage display libraries,” Nature, 352:624- 628 (1991).Applicant
• Clark, “CD22, a B Cell-Specific Receptor, Mediates Adhesion and Signal Transduction,” J. Immunol., 150:4715-4718 (1993).Applicant
• Co et al., “A Humanized Antibody Specific for the Platelet Integrin gpIIb/IIIa,” J. Immunol., 152:2968-2976 (1994).Applicant
• Cochlovius et al., “Treatment of human B cell lymphoma xenografts with a CD3 x CD19 diabody and T cells,” The Journal of Immunology, 165:888-895 (2000).Applicant
• Creighton, T., “Protein folding,” Biochem. J., 270(1):1-16 (1990).Applicant
• Daniel et al., “Induction of Apoptosis in Human Lymphocytes by Human Anti-HLA Class I Antibodies,” Transplantation, 75:1380-1386 (2003).Applicant
• Davies et al., “Antibody VH domains as small recognition units,” Biotechnology (N.Y.), 13(5):475-9 (1995).Applicant
• De Felice et al., “Differential regulatory role of monomorphic and polymorphic determinants of histocompatibility leukocyte antigen class I antigens in monoclonal antibody OKT3-induced T cell proliferation,” J. Immunol., 139:2683-2689 (1987).Applicant
• De Jonge et al., “Production and Characterization of Bispecific Single-Chain Antibody Fragments,” Mol. Immunol., 32:1405-1412 (1995).Applicant
• Dejonge et al., “In vivo retargeting of T cell effector function by recombinant bispecific single chain Fv (anti-DC3 x anti-idiottype) induces long term survival of the murine BCL1 lymphoma model,” J. Immunol., 161(3):1454-1461 (1998).Applicant
• Denardo et al., “Anti-HLA-DR/anti-DOTA Diabody Construction in a Modular Gene Design Platform: Bispecific Antibodies for Pretargeted Radioimmunotherapy,” Cancer Biother. Radiopharm., 16:525-535 (2001).Applicant
• Deng et al., “An Agonist Murine Monoclonal Antibody to the Human c-Mpl Receptor Stimulates Megakaryocytopoiesis,” Blood, 92:1981-1988 (1998).Applicant
• Desplancq et al., “Multimerization behaviour of single chain Fv variants for the tumour-binding antibody B72.3,” Protein Engineering, 7(8):1027-1033 (1994).Applicant
• Dillon et al., “Structural and functional characterization of disulfide isoforms of the human IgG2 subclass,” J. Biol. Chem., 283(23):16206-15 (2008).Applicant
• Ebert et al., “Expression of Metallothionein II in Intestinal Metaplasia, Dysplasia, and Gastric Cancer,” Cancer Res., 60:1995-2001 (2000).Applicant
• Eijsink et al., “Rational engineering of enzyme stability,” Journal of Biotechnology, 113:105-120 (2004).Applicant
• Elliott et al., “Activation of the Erythropoietin (EPO) Receptor by Bivalent Anti-EPO Receptor Antibodies,” J. Biol. Chem., 271:24691-24697 (1996).Applicant
• Ewert et al., “Biophysical properties of human antibody variable domains,” J. Mol. Biol., 325:531-553 (2003).Applicant
• Ewert et al., “Structure-based improvement of the biophysical properties of immunoglobulin VH domains with a generalizable approach,” Biochemistry, 42:1517-1528 (2003).Applicant
• Fayen et al., “Negative signaling by anti-HLA class I antibodies is dependent upon two triggering events,” Int. Immunol., 10:1347-1358 (1998).Applicant
• Funaro et al., “Monoclonal antibodies and therapy of human cancers,” Biotechnol. Adv., 18:385-401 (2000).Applicant
• Genestier et al., “Caspase-dependent Ceramide Production in Fas- and HLA Class I-mediated Peripheral T Cell Apoptosis,” J. Biol. Chem., 273:5060-5066 (1998).Applicant
• Genestier et al., “Antibodies to HLA Class 1 α1 Domain Trigger Apoptosis of CD40-Activated Human B Lymphocytes,” Blood, 90:726-735 (1997).Applicant
• Genestier et al., “Fas-Independent Apoptosis of Activated T Cells Induced by Antibodies to the HLA Class I α1 Domain,” Blood, 90:3629-3639 (1997).Applicant
• Genestier et al., “T cell sensitivity to HLA class I-mediated apoptosis is dependent on interleukin-2 and interleukin-4,” Eur. J. Immunol., 27:495-499 (1997).Applicant
• Ghetie et al., “Homodimerization of tumor-reactive monoclonal antibodies markedly increases their ability to induce growth arrest or apoptosis of tumor cells,” Proc. Natl. Acad. Sci. USA, 94:7509-7514 (1997).Applicant
• Goding, “Monoclonal Antibodies: Principles and Practice,” Academic Press, second Ed., 125:129 (1986).Applicant
• Goel et al., “99mTc-Labeled Divalent and Tetravalent CC49 Single-Chain Fv's: Novel Imaging Agents for Rapid In Vivo Localization of Human Colon Carcinoma,” J. Nucl. Med., 42:1519-1527 (2001).Applicant
• Goel et al., “Genetically Engineered Tetravalent Single-Chain Fv of the Pancarcinoma Monoclonal Antibody CC49: Improved Biodistribution and Potential for Therapeutic Application,” Cancer Res., 60:6964-6971 (2000).Applicant
• Goldstein et al., “Cytolytic and Cytostatic Properties of an Anti-Human FcγRI (CD64) x Epidermal Growth Factor Bispecific Fusion Protein,” J. Immunol., 158:872-879 (1997).Applicant
• Goto et al., “A Novel Membrane Antigen Selectively Expressed on Terminally Differentiated Human B Cells,” Blood, 84:1922-1930 (1994).Applicant
• Gruber et al., “Efficient tumor cell lysis mediated by a bispecific single chain antibody expressed in Escherichia coli,” Journal of Immunology, 152:5368-5374 (1994).Applicant
• Hanson et al., “Catalytic antibodies and their applications,” Curr. Opin. Biotechnol., 16:631-636 (2005).Applicant
• Holliger et al., “‘Diabodies’: Small bivalent and bispecific antibody fragments,” Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).Applicant
• Hoogenboom et al., “Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains,” Nucleic Acids Res., 19:4133-4137 (1991).Applicant
• Hozumi and Tonegawa, “Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions,” Proc. Natl. Acad. Sci. USA, 73(10):3628-3632 (1976).Applicant
• Hu et al., “Minibody: A Novel Engineered Anti-Carcinoembryonic Antigen Antibody Fragment (Single-Chain Fv-CH3) Which Exhibits Rapid, High-Level Targeting of Xenografts,” Cancer Res., 56:3055-3061 (1996).Applicant
• Hudson et al., “High avidity scFv multimers; diabodies and triabodies,” J. Immunol. Methods, 231:177-189 (1999).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
• Jäger et al., “Folding and assembly of an antibody Fv fragment, a heterodimer stabilized by antigen,” Journal of Molecular Biology, 285:2005-2019 (1999).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., 309(3):701-16 (2001).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., 13(3):127-39 (2000).Applicant
• Kikuchi et al., “A bivalent single-chain Fv fragment against CD47 induces apoptosis for leukemic cells,” Biochem. Biophys. Res. Commun., 315:912-918 (2004).Applicant
• Kimura et al., “2D7 diabody bound to the α2 domain of HLA class I efficiently induces caspase-independent cell death against malignant and activated lymphoid cells,” Biochem. Biophys. Res. Commun., 325:1201-1209 (2004).Applicant
• Kipriyanov and Little, “Generation of Recombinant Antibodies,” Molecular Biotechnology, 12:173-201 (1999).Applicant
• Kipriyanov et al., “Bispecific CD3 x CD19 diabody for T cell-mediated lysis of malignant human B cells,” In. J. Cancer, 77:763-772 (1998).Applicant
• Kipriyanov et al., “Bispecific tandem diabody for tumor therapy with imprived antigen binding and pharmacokinetics,” Journal of Molecular Biology, 293:41-56 (1999).Applicant
• Kipriyanov et al., “Effect of Domain Order on the Activity of Bacterially Produced Bispecific Single-chain Fv Antibodies,” J. Mol. Biol., 330:99-111 (2003).Applicant
• Kong et al., “A Single Residue, Aspartic Acid 95, in the δ Opioid Receptor Specifies Selective High Affinity Agonist Binding,” The Journal of Biological Chemistry, 268(31):23056-23058 (1993).Applicant
• Kontermann, R., “Recombinant bispecific antibodies for cancer therapy,” Acta Pharmacol. Sin., 26(1):1-9 (2005).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,” The Journal of Gene Medicine, 6:642-651 (2004).Applicant
• Kortt et al., “Dimeric and trimeric antibodies: high avidity scFvs for cancer targeting,” Biomol. Eng., 18:95-108 (2001).Applicant
• Krebber et al., “Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system,” J. Immunol. Methods, 201:35-55 (1997).Applicant
• Kreitman et al., “Cytotoxic Activity of Disulfide-stabilized Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) toward Fresh Malignant Cells from Patients with B-Cell Leukemias,” Clin. Cancer Res., 6:1476-1487 (2000).Applicant
• Kriangkum et al., “Bispecific and bifunctional single chain recombinant antibodies,” Biomol. Eng., 18(2):31-40 (2001).Applicant
• Kulkarni et al., “Construction of a Single-Chain Antibody Derived From 5H7, A Monoclonal Antibody Specific for a Death Signaling Domain of Human Class I Major Histocompatibility Complex,” Transplant. Proc., 30:1081 (1998).Applicant
• Kulkarni et al., “Programmed Cell Death Signaling Via Cell-Surface Expression of a Single-Chain Antibody Transgene,” Transplantation, 69:1209-1217 (2000).Applicant
• Kumar et al., “Molecular cloning and expression of the fabs of human autoantibodies in Escherichia coli,” The Journal of Biological Chemistry, 275(41):35129-35136 (2000).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., 276(27):24971-24977 (2001).Applicant
• Kurucz et al., “Retargeting of CTL by an efficiently refolded bispecific single-chain Fv dimer produced in bacteria,” The Journal of Immunology, 154:4576-4582 (1995).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 Engineering Design & Selection, 17(4):357-366 (2004).Applicant
• Lebrun et al., “Antibodies to the Extracellular Receptor Domain Restore the Hormone-insensitive Kinase and Conformation of the Mutant Insulin Receptor Valine 382,” J. Biol. Chem., 268:11272-11277 (1993).Applicant
• Ledbetter et al., “Agonistic Activity of a CD40-Specific Single-Chain Fv Constructed from the Variable Regions of mAb G28-5,” Critical Reviews in Immunology, 17:427-435 (1997).Applicant
• Li et al., “The Epitope Specificity and Tissue Reactivity of Four Murine Monoclonal Anti-CD22 Antibodies,” Cell. Immunol., 118:85-99 (1989).Applicant
• Little et al., “Of mice and men: hybridoma and recombinant antibodies,” Immunol. Today, 21:364-370 (2000).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., 358:511-516 (2001).Applicant
• Lund et al., “Expression and characterization of truncated forms of humanized L243 IgG1. Architectural features can influence synthesis of its oligosaccharide chains and affect superoxide production triggered through human Fcgamma receptor I,” Eur. J. Biochem., 267(24):7246-57 (2000).Applicant
• Mack et al., “A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity,” Proc. Natl. Acad. Sci. USA, 92(15):7021-7025 (1995).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,” Archives of Biochemistry and Biophysics, 434:93-107 (2005).Applicant
• Mallender et al., “Construction, expression and activity of a bivalent bispecific single-chain antibody,” J. Biol. Chem., 269(1):199-206 (1994).Applicant
• Matsuoka et al., “A Monoclonal Antibody to the α2 Domain of Murine Major Histocompatibility Complex Class I that Specifically Kills Activated Lymphocytes and Blocks Liver Damage in the Concanavalin A Hepatitis Model,” J. Exp. Med., 198:497-503 (2003).Applicant
• Matsuoka et al., “A Novel Type of Cell Death of Lymphocytes Induced by a Monoclonal Antibody without Participation of Complement,” J. Exp. Med., 181:2007-2015 (1995).Applicant
• McGuinness et al., “Phage diabody repertoires for selection of large number of bispecific antibody fragments,” Nature Biotechnology, 14(9):1149-1154 (1996).Applicant
• Medline Plus Drug Information: Dexamethasone Oral www.nlm.nih.gov/medlineplus/druginfo/meddmaster/a682792.html, downloaded Jul. 19, 2007; last revised Apr. 1, 2003 (see p. 3) (4 pages).Applicant
• Meng et al., “The evaluation of recombinant, chimeric, tetravalent antihuman CD22 antibodies,” Clinical Cancer Research, 10:1274-1281 (2004).Applicant
• Moore et al., “Kinetics and thermodynamics of dimer formation and dissociation for a recombinant humanized monoclonal antibody to vascular endothelial growth factor,” Biochemistry, 38:13960-13967 (1999).Applicant
• Ngo et al., “Computational Complexity, Protein Structure Prediction, and the Levinthal Paradox ,” The Protein Folding Problem and Tertiary Structure Prediction, Merz, Jr. et al. Editors, Birkhauser Boston, 433-506 (1994).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 Engineering, 10(4):435-444 (1997).Applicant
• Nishii, “CD22 antibody therapy,” Current Therapy, 20:47-50 (2001) (English translation included).Applicant
• Nohaile et al., “Altering dimerization specificity by changes in surface electrostatics,” PNAS 98(6):3109-3114 (2001).Applicant
• Ohtomo et al., “Molecular Cloning and Characterization of a Surface Antigen Preferentially Overexpressed on Multiple Myeloma Cells,” Biochem. Biophys. Res. Commun., 258:583-591 (1999).Applicant
• Oka, “Development of Novel Immunotoxin Using Recombinant Alpha-Sarcin and Its Application Treatment of Hematopoietic Tumor,” Sankyo Seimei Kagaku Kenkyu Shinko Zaidan Kenkyu Hokokushu, 12:46-56 (1998) (English translation included).Applicant
• Ono et al., “The humanized anti-HM1.24 antibody effectively kills multiple myeloma cells by human effector cell-mediated cyto-toxicity,” Mol. Immunol., 36:387-395 (1999).Applicant
• Orita et al., “A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor,” Blood, 105:562-566 (2005).Applicant
• Ozaki et al., “A Recombinant HLA Class I-Specific Single Chain Fv Diabody Induces Cell Death in Human Lymphoid Malignancies,” Blood, 102:933a, Abstract No. 3474 (2003).Applicant
• Ozaki et al., “Humanized Anti-HM1.24 Antibody Mediates Myeloma Cell Cytotoxicity That Is Enhanced by Cytokine Stimulation of Effector Cells,” Blood, 93:3922-3930 (1999).Applicant
• Ozaki et al., “Immunotherapy of Multiple Myeloma With a Monoclonal Antibody Directed Against a Plasma Cell-Specific Antigen, HM1.24,” Blood, 90:3179-3186 (1997).Applicant
• Palacios et al., “IL-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocutes in vivo,” Cell, 41:727-734 (1985).Applicant
• Peipp et al., “Bispecific antibodies targeting cancer cells,” Biochem. Soc. Trans., 30:507-511 (2002).Applicant
• Pettersen et al., “The TCR-Binding Region of the HLA Class I α2 Domain Signals Rapid Fas-Independent Cell Death: A Direct Pathway for T Cell-Mediated Killing of Target Cells?” J. Immunol., 160:4343-4352 (1998).Applicant
• Piétri-Rouxel et al., “The biochemical effect of the naturally occurring Trp64→Arg mutation on human β3-adrenoceptor activity,” Eur. J. Biochem., 247:1174-1179 (1997).Applicant
• Plückthun et al., “New protein engineering approaches to multivalent and bispecific antibody fragments,” Immunotechnology, 3:83-105 (1997).Applicant
• Rajagopal et al., “A form of anti-Tac (Fv) which is both single-chain and disulfide stabilized: comparison with its single-chain and disulfide-stabilized homologs,” Protein Engineering, 10(12):1453-1459 (1997).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
• Ridgway et al., “‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization,” Protein Eng., 9:617-621 (1996).Applicant
• Rossi et al., “Development of New Multivalent-bispecific Agents for Pretargeting Tumor Localization and Therapy,” Clin. Cancer Res., 9:3886s-3896s (2003).Applicant
• Rousch et al., “Somatostatin displayed on filamentous phage as a receptor-specific agonist,” Br. J. Pharmacol., 125:5-16 (1998).Applicant
• Sal-Man et al., “Arginine mutations within a transmembrane domain of Tar, an Escherichia coli aspartate receptor, can drive monodimer dissociation and heterodimer association n vivo,” Biochem. J., 385(1):29-36 (2005).Applicant
• Sato et al., “CD22 Is Both a Positive and Negative Regulator of B Lymphocyte Antigen Receptor Signal Transduction: Altered Signaling in CD22-Deficient Mice,” Immunity, 5:551-562 (1996).Applicant
• Scheurle et al., “Cancer Gene Discovery Using Digital Differential Display,” Cancer Res., 60:4037-4043 (2000).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
• 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
• Shimba et al., “Comparative thermodynamic analyses of the Fv, Fab* and Fab fragments of anti-dansyl mouse monoclonal antibody,” FEBS Letters, 360:247-250 (1995).Applicant
• Shire et al., “Challenges in the development of high protein concentration formulations,” Journal of Pharmaceutical Sciences, 93(6):1390-1402 (2004).Applicant
• Skerra, “Use of the tetracycline promoter for the tightly regulated production of a murine antibody fragment in Escherichia coli,” Gene, 151:131-135 (1994).Applicant
• Smith et al , “Inhibition of T Cell Activation by a Monoclonal Antibody Reactive Against the α3 Domain of Human MHC Class I Molecules,” J. Immunol., 153:1054-1067 (1994).Applicant
• Smith-Gill et al., “Contributions of immunoglobulin heavy and light chains to antibody specificity for lysozyme and two haptens,” The Journal of Immunology, 139:4135-4144 (1987).Applicant
• Song et al., “Light chain of natural antibody plays a dominant role in protein antigen binding,” Biochemical and Biophysical Research Communications, 268:390-394 (2000).Applicant
• Souyri, M., “Mpl: from an acute myeloproliferative virus to the isolation of the long sought thrombopoietin,” Seminars in Hematology, 35(3):222-231 (1998).Applicant
• Tahtis et al., “Biodistribution Properties of 111Indium-labeled C-Functionalized trans-Cyclohexyl Diethylenetriaminepentaacetic Acid Humanized 3S193 Diabody and F(ab′)2 Constructs in a Breast Carcinoma Xenograft Model,” Clin. Cancer Res., 7:1061-1072 (2001).Applicant
• Tan et al., “Contributions of a highly conserved VH/VL hydrogen bonding interaction to scFv folding stability and refolding efficiency,” Biophysical Journal, 75:1473-1482 (1998).Applicant
• Tang et al., “Selection of linkers for a catalytic single-chain antibody using phage display technology”, The Journal of Biological Chemistry, 271(26):15682-15686 (1996).Applicant
• Tedder et al., “CD22, a B Lymphocyte-Specific Adhesion Molecule That Regulates Antigen Receptor Signaling,” Annu. Rev. Immunol., 15:481-504 (1997).Applicant
• Thilenius et al., “Agonist antibody and Fas ligand mediate different sensitivity to death in the signaling pathways of Fas and cytoplasmic mutants,” Eur. J. Immunol., 27:1108-1114 (1997).Applicant
• Turner et al., “Importance of the linker in expression of single-chain Fv antibody fragments: optimization of peptide sequence using phage display technology,” Journal of Immunological Methods, 205:43-54 (1997).Applicant
• Van Den Burg et al., “Selection of mutations for increased protein stability,” Curr. Opin. Biotechnol., 13(4):333-337 (2002).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., 16(3):113-20 (2003).Applicant
• Vieille et al., “Hyperthermophilic enzymes: sources, uses, and molecular mechanisms for thermostability,” Microbiology and Molecular Biology Reviews, 65(1):1-43 (2001).Applicant
• Volkel et al., “Optimized linker sequences for the expression of monomeric and dimeric bispecific single-chain diabodies,” Protein Engineering, 14(10):815-823 (2001).Applicant
• Wells, “Perspectives in Biochemistry,” Biochemistry, 29(37):8509-8517 (1990).Applicant
• Whitlow et al., “An improved linker for single-chain Fv with reduced aggregation and enhanced proteolytic stability,” Protein Engineering, 6(8):989-995 (1993).Applicant
• Woodle et al., “Anti-Human Class I MHC Antibodies Induce Apoptosis by a Pathway That Is Distinct from the Fas Antigen-Mediated Pathway,” J. Immunol., 158:2156-2164 (1997).Applicant
• Woodle et al., “Anti-Human Class I α3 Domain-Specific Monoclonal Antibody Induces Programmed Cell Death in Murine Cells Expressing Human Class I MHC Transgenes,” Transplant. Proc., 30:1059-1060 (1998).Applicant
• Woodle et al., “Class I MHC Mediates Programmed Cell Death in Human Lymphoid Cells,” Transplantation, 64:140-146 (1997).Applicant
• Worn et al., “Stability engineering of antibody single-chain Fv fragments,” J. Mol. Biol., 305:989-1010 (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(3):652-65 (2007).Applicant
• Wu et al., “Multimerization of a chimeric anti-CD20 single-chain Fv-Fc fusion protein is mediated through variable domain exchange,” Protein Eng., 14(12):1025-33 (2001).Applicant
• Wu et al., “Tumor localization of anti-CEA single-chain Fvs: improved targeting by non-covalent dimers,” Immunotechnology, 2:21-36 (1996).Applicant
• Xiong et al., “Efficient inhibition of human B-cell lymphoma xenografts with an anti-CD20 X anti-CD3 bispecific diabody,” Cancer Lett., 177:29-39 (2002).Applicant
• Xu et al., “Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver,” Proc. Natl. Acad. Sci. USA, 98:15089-15094 (2001).Applicant
• Zhu et al., “An efficient route to the production of an IgG-like bispecific antibody”, Protein Eng., 13:361-367 (2000).Applicant
• Zhu et al., “Remodeling domain interfaces to enhance heterodimer formation,” Protein Science, 6:781-788 (1997).Applicant
• International Search Report for App. Ser. No. PCT/US2006/306803, mailed Jul. 11, 2006, 4 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/US2006/306803, dated Oct. 3, 2007, 6 pages.Applicant
• International Search Report for App. Ser. No. PCT/JP2008/067534, mailed Oct. 21, 2008, 4 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2008/067534, dated Apr. 7, 2010, 7 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
• USPTO Restriction Requirement in U.S. Appl. No. 12/295,039, dated Oct. 12, 2010, 9 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
• 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
• 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
• USPTO Restriction Requirement in U.S. Appl. No. 11/910,836, dated Mar. 18, 2011, 7 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 11/910,836, dated Sep. 30, 2011, 21 pages.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
• 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
• Maxfield et al., “Endocytic recycling,” Nat. Rev. Mol. Cell Biol., 5(2):121-32 (2004).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
• European Search Report for App. Ser. No. EP 09 72 9337, dated Nov. 3, 2011, 3 pages.Applicant
• Algonomics—Tripole® applications [online] [retrieved on Feb. 29, 2012]. Retrieved from the Internet: 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
• 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
• 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
• 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
• Bender et al., “Immunogenicity, efficacy and adverse events of adalimumab in RA patients,” Rheumatol. Int., 27:269-274 (2007).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
• 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
• 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
• De Groot et al., “De-immunization of therapeutic proteins by T-cell epitope modification,” Dev. Biol. (Basel), 122:171-94 (2005).Applicant
• Fujii, “Antibody affinity maturation by random mutagenesis,” Methods Mol. Biol., 248:345-59 (2004).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
• Guyre et al., “Increased potency of Fc-receptor-targeted antigens,” Cancer Immunol. Immunother., 45(3-4):146-8 (1997).Applicant
• Hinton et al., “Engineered human IgG antibodies with longer serum half-lives in primates,” J. Biol. Chem., 279(8):6213-6 (2004).Applicant
• Hwang et al., “Use of human germline genes in a CDR homology-based approach to antibody humanization,” Methods, 36:35-42 (2005).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
• 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
• 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
• 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
• 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
• Liu et al., “Heterogeneity of monoclonal antibodies,” J. Pharm. Sci., 97(7):2426-47 (2008).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
• Martinez et al., “Disulfide connectivity of human immunoglobulin G2 structural isoforms,” Biochemistry, 47(28):7496-7508 (2008).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
• 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
• 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
• 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
• Presta, “Engineering of therapeutic antibodies to minimize immunogenicity and optimize function,” Adv. Drug Deliv. Rev., 58(5-6):640-56 (2006).Applicant
• Raffen et al., “Reengineering immunoglobulin domain interactions by introduction of charged residues,” Protein Eng. ,11:303-309 (1998).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
• Rothe et al., “Ribosome display for improved biotherapeutic molecules,” Expert Opin. Biol. Ther., 6:177-187 (2006).Applicant
• Salfeld et al., “Isotype selection in antibody engineering,” Nat. Biotechnol., 25:1369-72 (2007).Applicant
• Sato et al., “Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth,” Cancer Res., 53:851-856 (1993).Applicant
• Schmitz et al., “Phage display: a molecular tool for the generation of antibodies—a review,” Placenta., 21 Suppl A:S106-12 (2000).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
• Strand et al., “Biologic therapies in rheumatology: lessons learned, future directions,” Nat. Rev. Drug Discov., 6:75-92 (2007).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
• 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
• Tsuchiya, Credit Suisse Seminar, “Therapeutic Antibody,” at Fuji-Gotemba Laboratories, p. 21 (2006) [English translation].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 Walle et al., “Immunogenicity screening in protein drug development,” Expert Opin. Biol. Ther., 7(3):405-18 (2007).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
• Wypych et al., “Human IgG2 antibodies display disulfide-mediated structural isoforms,” J. Biol. Chem., 283(23):16194-16205 (2008).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
• 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
• 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 Restriction Requirement in U.S. Appl. No. 10/560,098, mailed Jul. 13, 2007, 9 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Jul. 13, 2007 in U.S. Appl. No. 10/560,098, filed Aug. 10, 2007, 6 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 10/560,098, mailed Oct. 23, 2007, 17 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 10/560,098, mailed Sep. 11, 2008, 20 pages.Applicant
• USPTO Interview Summary for U.S. Appl. No. 10/560,098, mailed Jun. 5, 2009, 8 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Office Action dated Sep. 11, 2008 in U.S. Appl. No. 10/560,098, filed Jun. 10, 2009, 12 pages.Applicant
• USPTO Office Action in U.S. Appl. No. 10/560,098, mailed Aug. 13, 2009, 21 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Office Action dated Aug. 13, 2009 in U.S. Appl. No. 10/560,098, filed Feb. 16, 2010, 14 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 10/560,098, mailed Jun. 3, 2010, 16 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 10/560,098, mailed Dec. 8, 2011, 11 pages.Applicant
• International Search Report for App. Ser. No. PCT/JP2004/008585, mailed Sep. 7, 2004, 4 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2004/008585, dated Apr. 15, 2005, 16 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Office Action dated Jun. 28, 2011 in U.S. Appl. No. 12/295,039, filed 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
• USPTO Restriction Requirement in U.S. Appl. No. 12/936,587, dated Dec. 6, 2011, 7 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 11/910,128, dated Apr. 25, 2012, 21 pages.Applicant
• Wang et al., “Polyethylene Glycol-modified Chimeric Toxin Composed of Transforming Growth Factor alpha and Pseudomonas Exotoxin,” Cancer. Res., 53:4588-4594 (1993).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
• 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 Jun. 5, 2012, 7 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 12/936,587, dated Jun. 25, 2012, 5 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 12/680,082, dated Jun. 6, 2012, 12 pages.Applicant
• Fish & Richardson P.C., Fourth Preliminary Amendment and Response to Restriction Requirement dated Jun. 6, 2012 in U.S. Appl. No. 12/680,082, filed Jun. 29, 2012, 13 pages.Applicant
• International Search Report for App. Ser. No. PCT/JP2010/066490, mailed Nov. 9, 2010, 5 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2010/066490, dated Apr. 11, 2012, 6 pages.Applicant
• Amersham Biosciences, “Affinity Chromatography: Principles and Methods,” Edition AD, pp. 16-18, 137 (2002).Applicant
• Presta et al., “Molecular engineering and design of therapeutic antibodies,” Curr. Opin. Immunol., 20(4):460-70. doi: 10.1016/j.coi.2008.06.012 (2008).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
• USPTO Non-Final Office Action U.S. Appl. No. 12/680,082, dated Feb. 14, 2013, 12 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 Jan. 24, 2013, 12 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 13/434,643, dated Feb. 12, 2013, 17 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 13/257,145, dated Mar. 20, 2013, 11 pages.Applicant
• Allen et al., “Interchain disulfide bonding in human IgG2 antibodies probed by site-directed mutagenesis,” Biochemistry, 48(17):3755-66 (2009).Applicant
• USPTO Notice of Allowance in U.S. Appl. No. 10/560,098, dated Apr. 25, 2013, 12 pages.Applicant
• Fish & Richardson P.C., Response to Restriction Requirement dated Dec. 6, 2012 in U.S. Appl. No. 13/497,269, filed May 1, 2013, 2 pages.Applicant
• Fish & Richardson P.C., Preliminary Amendment and Response to Restriction Requirement dated Mar. 20, 2013 in U.S. Appl. No. 13/257,145, filed Apr. 22, 2013, 7 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 May 13, 2013, 18 pages.Applicant
• U.S. Appl. No. 13/518,861, Igawa et al.Applicant
• U.S. Appl. No. 13/582,073, Kuramochi et al.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
• Amersham Biosciences, “Protein Purification Handbook,” Edition AC, 98 pages (2001).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
• 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
• 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
• Brown et al., “Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR2: 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 x anti-CD3 antibody: a phase I/II study,” Clin. Cancer Res., 13(13):3899-905 (2007).Applicant
• Dall'Acqua et al., “Modulation of the effector functions of a human IgG1 through engineering of its hinge region,” J. Immunol., 177(2):1129-38 (2006).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
• Jefferis et al., “Recognition sites on human IgG for Fc gamma receptors: the role of glycosylation,” Immunol. Lett., 44(2-3):111-7 (1995).Applicant
• Kai et al., “Switching constant domains enhances agonist activities of antibodies to a thrombopoietin receptor,” Nat. Biotechnol., 26(2):209-11 (2008).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
• Kobayashi et al., “A monoclonal antibody specific for a distinct region of hen egg-white lysozyme,” Mol. Immunol., 19:619-30 (1982).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
• Lansdorp et al., “Purification and analysis of bispecific tetrameric antibody complexes,” Mol. Immunol., 27:659-666 (1990).Applicant
• Life Technologies (Invitrogen: “ecdysone analogue” and pIND plasmid), Aug. 10, 2012, 2 pages.Applicant
• MacCallum et al., “Antibody-antigen interactions: contact analysis and binding site topography,” J. Mol. Biol., 262:732-45 (1996).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 Gl) by hydrophobic interaction high performance liquid chromatography using TSKgel Phenyl-5PW,” J. Biochem. Biophys. Methods, 24:107-117 (1992).Applicant
• Ozhegov et al., Tolkovyi Slovar Russkogo iazyka: 2004, p. 292 (with an English translation of the relevant passage defining “control”).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
• Rudikoff et al., “Single amino acid substitution altering antigen-binding specificity,” Proc. Natl. Acad. Sci. U.S.A., 79(6):1979-83 (1982).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
• Sarmay et al., “Mapping and comparison of the interaction sites on the Fc region of IgG responsible for triggering antibody dependent cellular cytotoxicity (ADCC) through different types of human Fc gamma receptor,” Mol. Immunol., 29(5):633-9 (1992).Applicant
• Smith, “Creative Expression: Mammalian Expression Vectors and Systems,” The Scientist Magazine, Feb. 2, 1998, 3 pages.Applicant
• Sun et al., “Coexpression of Gas6/Ax1 in human ovarian cancers,” Oncology, 66(6):450-7 (2004).Applicant
• Suresh et al., “Bispecific monoclonal antibodies from hybrid hybridomas,” Methods Enzymol., 121:210-228 (1986).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
• USPTO Final Office Action in U.S. Appl. No. 10/560,098, mailed 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, mailed Sep. 7, 2012, 3 pages.Applicant
• Fish & Richardson P.C., Response to Species Election Requirement dated Jun. 25, 2012 in U.S. Appl. No. 12/936,587, filed Jul. 25, 2012, 1 page.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 13/434,643, dated Jul. 27, 2012, 6 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Apr. 12, 2012 in U.S. Appl. No. 12/295,039, filed Sep. 11, 2012, 12 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 Nov. 1, 2012, 2 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
• 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. 12/936,587, dated Nov. 7, 2012, 13 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 12/680,082, dated Sep. 14, 2012, 6 pages.Applicant
• Fish & Richardson P.C., Amendment and Response to Election Requirement dated Sep. 14, 2012 in U.S. Appl. No. 12/680,082, filed Nov. 8, 2012, 14 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 13/595,139, dated Nov. 14, 2012, 10 pages.Applicant
• International Search Report for App. Ser. No. PCT/JP2011/055101, mailed May 10, 2011, 4 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 12/679,922, dated Jan. 3, 2013, 25 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 13/497,269, dated Dec. 6, 2012, 9 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2011/055101, dated Oct. 2, 2012, 6 pages.Applicant
• U.S. Appl. No. 13/885,421, filed Aug. 30, 2013, Igawa et al.Applicant
• U.S. Appl. No. 13/990,088, filed May 29, 2013, Nezu et al.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. 6, 2013, Igawa et al.Applicant
• Aslan et al., “Engineering a novel, stable dimeric streptavidin with lower isoelectric point,” J. Biotechnol., 128(2):213-25 (2007).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
• Baker et al., “Conversion of a T cell antagonist into an agonist by repairing a defect in the TCR/peptide/MHC interface: implications for TCR signaling,” Immunity, 13:475-484 (2000).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., 111:2129-2138 (1990).Applicant
• Dumont et al., “Monomeric Fc fusions: impact on pharmacokinetic and biological activity of protein therapeutics,” BioDrugs., 20(3):151-60 (2006).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
• 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
• Ju et al., “Conversion of the interleukin 1 receptor antagonist into an agonist by site-specific mutagenesis,” Proc. Natl. Acad. Sci. U.S.A., 88:2658-2662 (1991).Applicant
• Lazar et al., “Transforming growth factor alpha: mutation of aspartic acid 47 and leucine 48 results in different biological activities,” Mol. Cell Biol., 8:1247-1252 (1988).Applicant
• Marti et al., “Inverse electrostatic effect: electrostatic repulsion in the unfolded state stabilizes a leucine zipper,” Biochemistry, 43(39):12436-47 (2004).Applicant
• Pakula et al., “Genetic Analysis of Protein Stability and Function,” Annu. Rev. Genet., 23:289-310 (1989).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
• Van Loghem et al., “Staphylococcal protein A and human IgG subclasses and allotypes,” Scand. J. Immunol., 15(3):275-8 (1982).Applicant
• USPTO Final Office Action in U.S. Appl. No. 11/910,128, dated Sep. 10, 2013, 12 pages.Applicant
• USPTO Notice of Allowance in U.S. Appl. No. 10/560,098, dated Jul. 9, 2013, 6 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Non-Final Office Action dated Feb. 14, 2013 in U.S. Appl. No. 12/680,082, filed Aug. 12, 2013, 17 pages.Applicant
• USPTO Final Office Action U.S. Appl. No. 12/680,082, dated Oct. 22, 2013, 12 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 13/434,643, dated Jul. 11, 2013, 19 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Jan. 3, 2013 in U.S. Appl. No. 12/679,922, filed 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
• USPTO Non-Final Office Action in U.S. Appl. No. 13/497,269, dated Aug. 15, 2013, 13 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 13/257,145, dated Jul. 2, 2013, 20 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2011/077603, dated Jun. 4, 2013, 10 pages.Applicant
• International Preliminary Report on Patentability for App. Ser. No. PCT/JP2011/076486, dated Jun. 12, 2013, 9 pages.Applicant
• USPTO Restriction Requirement in U.S. Appl. No. 13/257,112, dated Oct. 15, 2013, 10 pages.Applicant
• Kabat et al., Sequence of Proteins of Immunological Interest, 5th Edition 1991, p. 690 and p. 693.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
• Wally et al., “Identification of a novel substitution in the constant region of a gene coding for an amyloidogenic kappal light chain,” Biochim Biophys Acta., May 31, 1999;1454(1):49-56.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Jul. 28, 2014 in U.S. Appl. No. 12/679,922, filed Nov. 29, 2014, 23 pages.Applicant
• Amann et al., “Therapeutic window of an EpCAM/CD3-specific BiTE antibody in mice is determined by a subpopulation of EpCAM-expressing lymphocytes that is absent in humans,” Cancer Immunol Immunother., Jan. 2009; 58(1):95-109. Epub Jul. 2, 2008.Applicant
• Bargou et al., “Tumor regression in cancer patients by very low doses of a T cell-engaging antibody,” Science, 321(5891):974-7 (2008).Applicant
• Bokemeyer, “Catumaxomab—trifunctional anti-EpCAM antibody used to treat malignant ascites,” Expert Opin Biol Ther., 10(8):1259-69 (2010).Applicant
• Campoli et al., “Immunotherapy of malignant disease with tumor antigen-specific monoclonal antibodies,” Clin Cancer Res., Jan. 1, 2010;16(1):11-20. Epub Dec. 22, 2009.Applicant
• Dahlback, “Blood coagulation,” Lancet, 355(9215):1627-32 (2000).Applicant
• Datta-Mannan et al., “Monoclonal antibody clearance. Impact of modulating the interaction of IgG with the neonatal Fc receptor,” J Biol Chem., 282(3):1709-17 (2007).Applicant
• Fay et al., “Chapter 2B Nonenzymatic cofactors: factor VIII,” Comprehensive Biochemistry, 13:35-37 (1986).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
• Hu et al., “Development and characterization of a novel fusion protein composed of a human 1gG1 heavy chain constant region and a single-chain fragment variable antibody against Venezuelan equine encephalitis virus,” J Biochem., 133(1):59-66 (2003).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., 285(27): 20850-9. doi: 10.1074/jbc.M110.113910. Epub May 5, 2010.Applicant
• Jain et al., “Engineering antibodies for clinical applications,” Trends Biotechnol., 25(7):307-16 (2007).Applicant
• Janeway et al., “Structure of the Antibody Molecule and Immunoglobulin Genes,” Immunobiology, 3rd Edition, Garland Press, 3:1-3:11 (1997).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
• Klein et al., “Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies,” MAbs., Nov.-Dec. 2012;4(6):653-63. doi: 10.4161/mabs.21379. Epub Aug. 27, 2012.Applicant
• Kufer et al., “A revival of bispecific antibodies,” Trends Biotechnol., 22(5):238-44 (2004).Applicant
• Kumagai et al., “Humanized bispecific antibodies that recognize lymphocytes and cancer cells,” Drug Delivery System, 23(5):518-25 (2008) (English translation).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
• Lindsay, “Chapter 4: Determination of the Kinetics and Mechanism of tg-FIX Activation by Factor XIa,” 49-75 (2004).Applicant
• McEarchern et al., “Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities,” Blood, Feb. 1, 2007;109(3):1185-92. Epub Oct. 12, 2006.Applicant
• Mezzanzanica et al., “Human ovarian carcinoma lysis by cytotoxic T cells targeted by bispecific monoclonal antibodies: analysis of the antibody components,” Int J Cancer, 41(4):609-15 (1988).Applicant
• Miyazaki et al., “Generation of bispecific IgG, which mimics the cofactor function of blood coagulation factor VIII,” Seikagaku, Poster sessions (2P-B-161) (2006).Applicant
• Molhoj et al., “CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected tumor cell lysis,” Mol Immunol., 44(8):1935-43 (2007).Applicant
• Nakano et al., “Anti-glypican 3 antibodies cause ADCC against human hepatocellular carcinoma cells,” Biochem Biophys Res Commun., Jan. 9, 2009;378(2):279-84. doi: 10.1016/j.bbrc.2008.11.033. Epub Nov. 18, 2008.Applicant
• Natsume et al., “Improving effector functions of antibodies for cancer treatment: Enhancing ADCC and CDC,” Drug Des Devel Ther., 3:7-16 (2009).Applicant
• Paul, William ed., Fundamental Immunology, 3rd edition, p. 242 (1993).Applicant
• Paul, “Structure and function of immunoglobulins,” Fundamental Immunology, Third Edition, 292-295 (1993).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
• 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 Haemostasis, vol. 3, Issue Supplement s1, p. #OR160.Applicant
• Saito et al., “Establishment of Factor VIII Mimetic Antibodies and Their In Vitro Activities in Hemophilia A,” 2006 National Hemophilia Foundation Symposia.Applicant
• Sampei et al., “Identification and multidimensional optimization of an asymmetric bispecific 1gG antibody mimicking the function of factor VIII cofactor activity,” PLoS One, 2013;8(2):e57479. doi: 10.1371/journal.pone.0057479. Epub Feb. 28, 2013.Applicant
• Schlereth et al., “T-cell activation and B-cell depletion in chimpanzees treated with a bispecific anti-CD19/anti-CD3 single-chain antibody construct,” Cancer Immunol Immunother., May 2006;55(5):503-14. Epub Jul. 20, 2005.Applicant
• Sebastian et al., “Treatment of non-small cell lung cancer patients with the trifunctional monoclonal antibody catumaxomab (anti-EpCAM x anti-CD3): a phase I study,” Cancer Immunol Immunother., 56(10):1637-44 (2007).Applicant
• Seimetz et al., “Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy,” Cancer Treat Rev., 36(6):458-67 (2010).Applicant
• Shima et al., “Factor VIII Mimetic Antibody: (2) In Vitro Assessment of Cofactor Activity in Hemophilia A,” 2005 International Society of Thrombosis and Haemostasis, vol. 3, Issue Supplement s1, p. #P0038.Applicant
• Shima, M., “Bispecific antibodies to coagulation factors IXa and X mimic the function of factor VIII,” 2006 World Federation of Haemophilia (Haemophilia, 12(Suppl. 2):98 (2006)).Applicant
• Shirahata, Minna ni yakudatsu ketsuyubyo no kiso to rinsho. Iyaku (Medicine and Drug) Journal Co., Ltd., 280-9 (2009) (including English translation).Applicant
• Soeda et al., “Factor VIII Taitei Kotai (1) Ko FIXa/FX bispecific Kotai no Sakusei oyobi characterization,” Rinsho Ketsueki, 46(8):728 (2005) (including English translation).Applicant
• Soeda et al., “Phage library-ho ni yori Sakusei shita Ko-FIXa/Ko-FX bispecific Kotai no FVIII Taitei Sayo,” Jpn J Thromb Hemost., 16(5):526 (2005) (including English translation).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
• Staerz et al., “Hybrid antibodies can target sites for attack by T cells,” Nature, 314(6012):628-31 (1985).Applicant
• Stroehlein et al., “Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis,” J Exp Clin Cancer Res., Feb. 14, 2009;28:18. doi: 10.1186/1756-9966-28-18.Applicant
• Suzuki, “Research and Development of Antibody Pharmaceuticals,” NIBS Letter, 56(4):45-51 (2010) (English translation).Applicant
• Teerinen et al., “Structure-based stability engineering of the mouse IgG1 Fab fragment by modifying constant domains,” J Mol Biol., 361(4):687-97 (2006).Applicant
• Thakur et al., “Cancer therapy with bispecific antibodies: Clinical experience,” Curr Opin Mol Ther., 12(3):340-9 (2010).Applicant
• Tsubaki et al., “C-terminal modification of monoclonal antibody drugs: amidated species as a general product-related substance,” Int J Biol Macromol., 52:139-47. doi: 10.1016/j.ijbiomac.2012.09.016. Epub Sep. 25, 2012.Applicant
• Vehar et al., “Structure of human factor VIII,” Nature, 312(5992):337-42 (1984).Applicant
• Wolf et al., “BiTEs: bispecific antibody constructs with unique anti-tumor activity,” Drug Discov Today, 10(18):1237-44 (2005).Applicant
• Wood et al., “Expression of active human factor VIII from recombinant DNA clones,” Nature, 312(5992):330-7 (1984).Applicant
• Zuo et al., “An efficient route to the production of an IgG-like bispecific antibody,” Protein Eng., 13(5):361-7 (2000).Applicant
• International Search Report for App. Ser. No. PCT/JP2011/076486, mailed Dec. 27, 2011, 4 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Aug. 2, 2013 in U.S. Appl. No. 12/679,922, filed Jan. 29, 2014, 24 pages.Applicant
• USPTO Non-Final Office Action in U.S. Appl. No. 12/679,922, dated Mar. 18, 2014, 11 pages.Applicant
• Fish & Richardson P.C., Amendment in Reply to Action dated Mar. 18, 2014 in U.S. Appl. No. 12/679,922, filed Jun. 18, 2014, 13 pages.Applicant
• USPTO Final Office Action in U.S. Appl. No. 12/679,922, dated Jul. 28, 2014, 12 pages.Applicant
• International Search Report for App. Ser. No. PCT/JP2011/077603, mailed Mar. 13, 2012, 8 pages.Applicant
• Chappel et al., “Identification of a secondary Fc gamma RI binding site within a genetically engineered human IgG antibody,” J Biol Chem., Nov. 25, 1993;268(33):25124-31.Applicant
• Chappel et al., “Identification of the Fc gamma receptor class I binding site in human IgG through the use of recombinant IgG1/IgG2 hybrid and point-mutated antibodies,” Proc Natl Acad Sci U S A., Oct. 15, 1991;88(20):9036-40.Applicant
• Reist et al., “Human IgG2 constant region enhances in vivo stability of anti-tenascin antibody 81C6 compared with its murine parent,” Clin Cancer Res., Oct. 1998;4(10):2495-502.Applicant
• USPTO Notice of Allowance in U.S. Appl. No. 12/679,922, dated Mar. 30, 2015, 12 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
• Medesan et al., “Delineation of the amino acid residues involved in transcytosis and catabolism of mouse IgG1,” 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
• Ruf et al., “Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody,” Blood, Oct. 15, 2001;98(8):2526-34.Applicant
• Allard et al., “Antigen binding properties of highly purified bispecific antibodies,” Mol Immunol., Oct. 1992;29(10):1219-27.Applicant
• Batra et al., “Pharmacokinetics and biodistribution of genetically engineered antibodies,” Curr Opin Biotechnol., Dec. 2002;13(6):603-8.Applicant
• Borrebaeck et al., “Antibody evolution beyond Nature,” Nat Biotechnol., Dec. 2002;20(12):1189-90.Applicant
• Greenwood et al., “Structural motifs involved in human IgG antibody effector functions,” Eur J Immunol., May 1993;23(5):1098-104.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
• 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
• 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
• 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
• Lloyd et al., “The production of a bispecific anti-CEA, anti-hapten (4-amino-phthalate) hybrid-hybridoma,” J Natl Med Assoc., Oct. 1991;83(10):901-4.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 C1q binding site can activate complement and induce lysis of target cells,” Eur J Immunol., Jan. 2006;36(1):129-38.Applicant
• O'Shea et al., “Peptide ‘Velcro’: design of a heterodimeric coiled coil,” Curr Biol., Oct. 1, 1993;3(10):658-67.Applicant
• Roitt et al., Immunology, M., Mir, 5th Edition (2000), pp. 97-113.Applicant
• Smolen et al., “Interleukin-6: a new therapeutic target,” Arthritis Res Ther., 2006;8 Suppl 2:S5. Epub Jul. 28, 2006.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
• U.S. Appl. No. 10/575,905, Hattori et al., filed Apr. 30, 2007.Applicant
• U.S. Appl. No. 11/910,128, Igawa et al., filed Oct. 7, 2008.Applicant
• U.S. Appl. No. 11/910,836, Hattori et al., filed Jan. 12, 2009.Applicant
• U.S. Appl. No. 13/434,643, Hattori et al., filed Mar. 29, 2012.Applicant
• U.S. Appl. No. 14/921,590, Hattori et al., filed Oct. 23, 2015.Applicant
• U.S. Appl. No. 15/172,727, Hattori et al., filed Jun. 3, 2016.Applicant
• U.S. Appl. No. 12/295,039, Igawa et al., filed Jan. 20, 2009.Applicant
• U.S. Appl. No. 14/741,786, Igawa et al., filed Jun. 17, 2015.Applicant
• U.S. Appl. No. 12/680,082, Igawa et al., filed Jun. 25, 2010.Applicant
• U.S. Appl. No. 14/962,293, Igawa et al., filed Dec. 8, 2015.Applicant
• U.S. Appl. No. 13/257,145, Igawa et al., filed Nov. 22, 2011.Applicant
• U.S. Appl. No. 14/680,250, Igawa et al., filed Apr. 7, 2015.Applicant
• U.S. Appl. No. 13/497,269, Kuramochi et al., filed Jun. 1, 2012.Applicant
• U.S. Appl. No. 13/518,861, Igawa et al., filed Oct. 4, 2012.Applicant
• U.S. Appl. No. 13/582,073, Kuramochi et al., filed Dec. 20, 2012.Applicant
• U.S. Appl. No. 14/019,117, Igawa et al., filed Sep. 5, 2013.Applicant
• U.S. Appl. No. 14/019,712, Igawa et al., filed Sep. 6, 2013.Applicant
• U.S. Appl. No. 15/132,996, Igawa et al., filed Apr. 19, 2016.Applicant
• U.S. Appl. No. 15/288,965, Igawa et al., filed Oct. 7, 2016.Applicant
• U.S. Appl. No. 13/990,088, Nezu et al., filed Dec. 19, 2013.Applicant
• U.S. Appl. No. 15/024,063, Igawa et al., filed Mar. 23, 2016.Applicant
• U.S. Pat. No. 8,597,911, Miyazaki et al., issued Dec. 3, 2013.Applicant
• U.S. Pat. No. 8,062,635, Hattori et al., issued Nov. 22, 2001.Applicant
• U.S. Pat. No. 9,096,651, Igawa et al., issued Aug. 4, 2015.Applicant
• U.S. Pat. No. 9,228,017, Igawa et al., issued Jan. 5, 2016.Applicant
• U.S. Pat. No. 9,334,331, Igawa et al., issued May 10, 2016.Applicant
• U.S. Appl. No. 15/024,063, filed Mar. 23, 2016, Igawa et al.Applicant
• U.S. Appl. No. 15/132,996, filed Apr. 19, 2016, Igawa et al.Applicant
• Asano et al., “Highly effective recombinant format of a humanized IgG-like bispecific antibody for cancer immunotherapy with retargeting of lymphocytes to tumor cells,” JBiol Chem., Sep. 21, 2007;282(38):27659-65. Epub Jul. 19, 2007.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
• Gramer et al., “Production of stable bispecific IgG1 by controlled Fab-arm exchange: scalability from bench to large-scale manufacturing by application of standard approaches,” MAbs., Nov.-Dec. 2013;5(6):962-73. doi: 10.4161/mabs 26233. Epub Aug. 22, 2013.Applicant
• Johnson et al., “Kabat database and its applications: 30 years after the first variability plot,” Nucleic Acids Res., Jan. 1, 2000;28(1):214-8.Applicant
• Labrijn et al., “Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange,” Pro Natl Acad Sci U S A., Mar. 26, 2013;110(13):5145-50. doi: 10.1073/pnas.1220145110. Epub Mar. 11, 2013.Applicant
• Labrijn et al., “Species-specific determinants in the IgG CH3 domain enable Fab-arm exchange by affecting the noncovalent CH3-CH3 interaction strength,” J Immunol., Sep. 15, 2011;187(6):323846. doi: 10.4049/jimmuno1.1003336. Epub Aug. 12, 2011.Applicant
• Rispens et al., “Dynamics of inter-heavy chain interactions in human immunoglobulin G (IgG) subclasses studied by kinetic Fab arm exchange,” J Biol Chem., Feb. 28, 2014;289(9):6098-109. doi: 10.1074/jbc.M113.541813. Epub Jan. 14, 2014.Applicant
• Schaefer et al., “Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies,” Proc Natl Acad Sci U S A., Jul. 5, 2011;108(27):11187-92. doi: 10.1073/pnas.1019002108. Epub Jun. 20, 2011.Applicant
• Schuurman et al., “Normal human immunoglobulin G4 is bispecific: it has two different antigen-combining sites,” Immunology, Aug. 1999;97(4):693-8.Applicant
• Schuurman et al., “The inter-heavy chain disulfide bonds of IgG4 are in equilibrium with intra-chain disulfide bonds,” Mol Immunol., Jan. 2001;38(1):1-8.Applicant
• Van Der Neut Kolfschoten et al., “Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange,” Science, Sep. 14, 2007;317(5844):1554-7.Applicant
• Ward et al., “Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli,” Nature, Oct. 12, 1989;341(6242):544-6.Applicant
• Mcphee et al., “Engineering human immunodeficiency virus 1 protease heterodimers as macromolecular inhibitors of viral maturation,” Proc Natl Acad Sci U S A., Oct. 15, 1996; 93(21):11477-81.Applicant
• Ward et al., “Effects of engineering complementary charged residues into the hydrophobic subunit interface of tyrosyl-tRNA synthetase. Appendix: Kinetic analysis of dimeric enzymes that reversibly dissociate into inactive subunits,” Biochemistry, Jun. 30, 1987;26(13):4131-8.Applicant
• U.S. Appl. No. 15/172,727, filed Jun. 3, 2016, Hattori et al.Applicant
• U.S. Appl. No. 15/288,965, filed Oct. 7, 2016, Igawa et al.Applicant
• Dall'Acqua et al., “Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences,” J. Immunol., Nov. 1, 2002;169(9):5171-80.Applicant
• U.S. Appl. No. 13/990,088, filed Dec. 19, 2013.Applicant
• U.S. Pat. No. 8,597,911, issued Dec. 3, 2013.Applicant
• U.S. Appl. No. 14/921,590, filed Oct. 23, 2015, Hattori et al.Applicant
• U.S. Appl. No. 14/962,293, filed Dec. 8, 2015, Igawa et al.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
• 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
• Bebbington et al., “High-Level Expression of a Recombinant Antibody from Myeloma Cells Using a Glutamine Synthetase Gene as an Amplifiable Selectable Marker,” Biotechnology (NY), 10:169-175 (1992).Applicant
• Bessos et al., “The characterization of a panel of monoclonal antibodies to human coagulation factor IX,” Thrombosis Research, 40:863-867 (1985).Applicant
• Bian et al., “Discovery of promiscuous HLA-II-restricted T cell epitopes with TEPITOPE,” Methods, Dec. 2004;34(4):468-75.Applicant
• Bolton-Maggs et al., “Haemophilias A and B,” The Lancet, May 24, 2003;361:1801-9.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, Feb. 1992;11:41-51.Applicant
• Brennan et al., “Preparation of Bispecific Antibodies by Chemical Recombination of Monoclonal Immunoglobulin G1 Fragments,” Science, Jul. 5, 1985;229:81-3.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., Mar. 1, 2002;22(3):511-6.Applicant
• Davie et al., “The coagulation cascade: Initiation, maintenance, and regulation,” Biochemistry, Oct. 29, 1991;30(43):10363-70.Applicant
• Dhiman et al., “Gene expression microarrays: a 21st century tool for directed vaccine design,” Vaccine, Oct. 12, 2001;20(1-2):22-30.Applicant
• Francois et al., “Construction of a Bispecific Antibody Reacting with the α- and β-Chains of the Human IL-2 Receptor,” J. Immunol., May 15, 1993;150:4610-9.Applicant
• GenPept Accession No. AAC26541, “anti BoNT/A Hc scFv antibody [synthetic construct],” 1 page (Aug. 1, 2001).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, May 2003; 33(5):1334-40.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., Dec. 1, 1968;128:1461-73.Applicant
• Hoad et al. “Characterization of monoclonal antibodies to human factor X/Xa: Initial observations with a quantitative ELISA procedure,” J. Immunol. Methods, Feb. 15, 1991;136(2):269-78.Applicant
• Hsia et al., “Treatment of acquired factor X inhibitor by plasma exchange with concomitant intravenous immunoglobulin and corticosteroids,” Am. J. Hematol., Apr. 2008;83:318-20.Applicant
• Huse et al., “Generation of a Large Combinatorial Library of the Immunoglobulin Repertoire in Phage Lambda,” Science, Dec. 8, 1989;246:1275-81.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 USA., Feb. 1984;81(4):1075-8.Applicant
• Kang et al., “Linkage of recognition and replication functions by assembling combinatorial antibody Fab libraries along phage surfaces,” Proc. Natl. Acad. Sci. USA, May 15, 1991;88:4363-6.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., Dec. 1, 1984;160:1686-701.Applicant
• Kim et al., “Mammalian type I interferon receptors consists of two subunits: IFNaR1 and IFNaR2,” Gene, Sep. 1, 1977;196:279-86.Applicant
• Kroesen et al., “Phase I study of intravenously applied bispecific antibody in renal cell cancer patients receiving subcutaneous interleukin 2,” Br. J. Cancer, Oct. 1994;70:652-61.Applicant
• Kurokawa et al., “Enhanced Fibrinolysis by a Bispecific Monoclonal Antibody Reactive to Fibrin and Tissue Plasminogen Activator,” Bio/Technology, Nov. 1989; 7:1163-7.Applicant
• Lapan et al., “Interaction of the Al Subunit of Factor VIIIa and the Serine Protease Domain of Factor X Identified by Zero-length Cross-linking,” Thromb. Haemost., Sep. 1998;80:418-22.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., Oct. 1993; 34:1662-71.Applicant
• Lenting et al., “The life cycle of coagulation factor VIII in view of its structure and function”, Blood, Dec. 1, 1998;92(11):3983-96.Applicant
• Link et al., “Production and Characterization of a Bispecific IgG Capable of Inducing T-Cell-Mediated Lysis of Malignant B Cells,” Blood, Jun. 15, 1993;81:3343-9.Applicant
• Löfqvist et al., “Haemophilia prophylaxis in young patients —a long-term follow-up,” J. Intern. Med., May 1997;241:395-400.Applicant
• Lu et al., “Fab-scFv fusion protein: an efficient approach to production of bispecific antibody fragments,” J. Immunol. Methods, Sep. 15, 2002;267:213-26.Applicant
• Lu et al., “Di-diabody: a novel tetravalent bispecific antibody molecule by design,” J. Immunol. Methods, Aug. 2003;279:219-32.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, Feb. 14, 1997;201:57-66.Applicant
• Mccafferty et al., “Phage antibodies: filamentous phage displaying antibody variable domains,” Nature, Dec. 6, 1990;348:552-4.Applicant
• Menegatti et al., “Factor X Deficiency,” Semin Thromb. Hemost., Jun. 2009;35:407-15.Applicant
• Mertens et al., “Factor VIII-Factor IX Interactions: Molecular Sites Involved in Enzyme-Cofactor Complex Assembly,” Thromb. Haemost., Aug. 1999;82:209-17.Applicant
• Milstein et al., “Hybrid hybridomas and their use in immunohistochemistry,” Nature, Oct. 6-12, 1983;305:537-40.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
• “National Haemophilia Foundation (NHF) Medical and Scientific Advisory Council (MASAC) Recommendations Concerning Prophylaxis,” Medical Bulletin, No. 193, 1 page (1994).Applicant
• Nilsson et al., “Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B,” J. Intern. Med., Jul. 1992;232:25-32.Applicant
• Nilsson et al., “Induction of split tolerance and clinical cure in high-responding hemophiliacs with factor IX antibodies,” Proc. Natl. Acad. Sci. U S A., Dec. 1986;83:9169-73.Applicant
• Nitta et al., “Preliminary trial of specific targeting therapy against malignant glioma,” Lancet, Feb. 17, 1990;335:368-371.Applicant
• Okubo et al. “The production and characterization of four monoclonal antibodies to human factor X,” Nara Med Assoc., 1987;38(1):20-28.Applicant
• Piper et al., “Interferon therapy in primary care,” Primary Care Update for Ob/Gyns, Jul. 2001;8(4):163-69.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
• Price et al., “Tissue factor and tissue factor pathway inhibitor,” Anaesthesia, May 2004;59:483-92.Applicant
• Ruef et al., “A bispecific antifibrin-antiplatelet urokinase conjugate (BAAUC) induces enhanced clot lysis and inhibits platelet aggregation,” Thromb. Haemost., Jul. 1999;82(1):109-14.Applicant
• Sato et al., “Properties of Two VEGF Receptors, Flt-1 and KDR, in Signal Transduction,” Ann n. Y. Acad. Sci, May 2000;902:201-207, discussion 205-7.Applicant
• Segal et al., “Introduction: bispecific antibodies,” J. Immunol. Methods, Feb. 1, 2001;248:1-6.Applicant
• Shima et al., “Factor VIII Taitei Kotai (2), Ketsuyubyo a Kanja Katsueki ni okeru in vitro Gyoko Kassei no Kento”, Rinsho Ketsueki, Aug. 30, 2005;46(8):777 (#WS-36-5) (with English translation).Applicant
• Stickney et al., “Bifunctional Antibody: A Binary Radiopharmaceutical Delivery System for Imaging Colorectal Carcinoma,” Cancer Res., Dec. 15, 1991;51:6650-5.Applicant
• Suresh et al., “Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays,” Proc. Natl. Acad. Sci. U S A., Oct. 1986;83:7989-93.Applicant
• Taki, The Journal of Japanese Society on Thrombosis and Hemostasis, Feb. 2, 2002;13:109-113.Applicant
• Thies et al., “The alternatively folded state of the antibody C(H)3 domain,” J Mol Biol., Jun. 22, 2001;309(5):1077-85.Applicant
• Weiner et al., “A Human Tumor Xenograft Model of Therapy with a Bispecific Monoclonal Antibody Targeting c-erbB-2 and CD16,” Cancer Res., Jan. 1, 1993;53:94-100.Applicant
• Weiner et al., “The Role of T Cell Activation in Anti-CD3 x Antitumor Bispecific Antibody Therapy,” J. Immunol., Mar. 1, 1994;152:2385-92.Applicant
• Xiang et al., “Production of Murine V-Human Crl Chimeric Anti-TAG72 Antibody Using V Region cDNA Amplified by PCR,” Mol. Immunol., Aug. 1990;27:809-17.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
• Coloma et al., “Position effects of variable region carbohydrate on the affinity and in vivo behavior of an anti-(1-->6) dextran antibody,” J Immunol., Feb. 15, 1999;162(4):2162-70.Applicant
• Dufner et al., “Harnessing phage and ribosome display for antibody optimization,” Trends Biotechnol., Nov. 2006;24(11):523-9. Epub Sep. 26, 2006.Applicant
• Hird et al., “Tumour localisation with a radioactively labelled reshaped human monoclonal antibody,” Br J Cancer, Nov. 1991;64(5):911-4.Applicant
• Hong et al., “Enhanced cellular uptake and transport of polyclonal immunoglobulin G and fab after their cationization,” J Drug Target., 2000;8(2):67-77.Applicant
• Li et al., “Construction and characterization of a humanized anti-human CD3 monoclonal antibody 12F6 with effective immunoregulation functions,” Immunology, Dec. 2005;116(4):487-98.Applicant
• Marshall et al., “Rational design and engineering of therapeutic proteins,” Drug Discov Today, Mar. 1, 2003;8(5):212-21.Applicant
• Padlan, “X-ray crystallography of antibodies,” Adv Protein Chem., 1996;49:57-133.Applicant
• Pardridge et al., “Enhanced cellular uptake and in vivo biodistribution of a monoclonal antibody following cationization,” J Pharm Sci., Aug. 1995;84(8):943-8.Applicant
• Reimann et al., “A humanized form of a CD4-specific monoclonal antibody exhibits decreased antigenicity and prolonged plasma half-life in rhesus monkeys while retaining its unique biological and antiviral properties,” AIDS Res Hum Retroviruses, Jul. 20, 1997;13(11):933-43.Applicant
• Sarkar et al., “Rational cytokine design for increased lifetime and enhanced potency using pH-activated 'histidine switching',” Nat Biotechnol., Sep. 2002;20(9):908-13. Epub Aug. 5, 2002.Applicant
• Sharifi et al., “Improving monoclonal antibody pharmacokinetics via chemical modification,” Q J Nucl Med., Dec. 1998;42(4):242-9.Applicant
• Strohl, “Optimization of Fc-mediated effector functions of monoclonal antibodies,” Curr Opin Biotechnol., Dec. 2009;20(6):685-91. doi: 10.1016/j.copbio.2009.10.011. Epub Nov. 4, 2009.Applicant
• Tabrizi et al , “Elimination mechanisms of therapeutic monoclonal antibodies,” Drug Discov Today, Jan. 2006;11(1-2):81-8.Applicant
• Verhoeyen et al., “Construction of a reshaped HMFG1 antibody and comparison of its fine specificity with that of the parent mouse antibody,” Immunology, Mar. 1993;78(3):364-70.Applicant
• Verhoeyen et al., “Monoclonal Antibodies in Clinical Oncology,” 1991, Edited by AA Epenetos, Chapter 5, pp. 37-43, Chapman and Hall.Applicant
• Choi et al., “Engineering of Immunoglobulin Fc Heterodimers Using Yeast Surface-Displayed Combinatorial Fc Library Screening,” PLoS One, Dec. 16, 2015;10(12):e0145349. doi: 10.1371/journal.pone.0145349. eCollection 2015.Applicant
• Roopenian et al., “FcRn: the neonatal Fc receptor comes of age,” Nat Rev Immunol., Sep. 2007;7(9):715-25. Epub Aug. 17, 2007.Applicant
• Yang et al., “CDR walking mutagenesis for the affinity maturation of a potent human anti-HIV-1 antibody into the picomolar range,” J Mol Biol., Dec. 1, 1995;254(3):392-403.Applicant