Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Structurally-modified antibody – immunoglobulin – or fragment...
Patent
1996-02-09
2000-07-18
Saunders, David
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Structurally-modified antibody, immunoglobulin, or fragment...
4241351, 4241421, 4241451, 5303873, 53038815, 53038823, A61K 39395, C07K 1624
Patent
active
060903821
ABSTRACT:
Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor .alpha. (hTNF.alpha.) are disclosed. These antibodies have high affinity for hTNF.alpha. (e.g., K.sub.d =10.sup.-8 M or less), a slow off rate for hTNF.alpha. dissociation (e.g., K.sub.off =10.sup.-3 sec.sup.-1 or less) and neutralize hTNF.alpha. activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF.alpha. and for inhibiting hTNF.alpha. activity, e.g., in a human subject suffering from a disorder in which hTNF.alpha. activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.
REFERENCES:
patent: 5231024 (1993-07-01), Moeller et al.
patent: 5654407 (1997-08-01), Boyle et al.
patent: 5795967 (1998-08-01), Aggarwal et al.
Barbuto, J.A.M., et al. "Production of Neutralizing Antibodies to Tumor Necrosis Factor by Human Tumor-Infiltrating B Lymphocytes", Abstract 2904, Proc. Am. Assoc. Cancer Res., vol. 34, p. 487, Mar. 1993.
Bendtzen, K. et al. "Auto-Antibodies to IL-1.alpha. and TNF.alpha. in Nornal Individuals and in Infectious and Immunoinflammatory Disorders", in The Physiological and Pathological Effects of Cytokines, pp. 447-452, Wiley-Liss, Inc., 1990.
Boyle, P. et al. "A Novel Monoclonal Human IgM Autoantibody which Binds Recombinant Human and Mouse Tumor Necrosis Factor-.alpha.", Cell. Immunol., vol. 152, pp. 556-568, (1993).
Boyle, P. et al. "The B5 Monoclonal Human Autoanitibody Binds to Cell Surface TNF.alpha. on Human Lymphoid Cells and Cell Lines and Aappears to Recognize a Novel Epitope", Cell. Immunol., vol. 152, pp. 569-581, (1993).
Cox, J.P.L. et al., "A directory of human germ-line V.sub.x segments reveals a strong bias in their usage", Eur. J. Immunol., vol. 24, pp. 827-836 (1994).
Elliot, M.J. et al., "Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor .alpha.", Arthritis & Rheumatism, vol. 36, No. 12, pp. 1681-1690 (1993).
Fomsgaard, A. et al. "Auto-antibodies to Tumor Necrosis Factor .alpha. in Healthy Humans and Patients with Inflammatory Diseases and Gram-Negative Bacterial Infections", Scand. J. Immunol., vol. 30, pp. 219-223, (1989).
Huse, W.D. et al., "Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda", Science, vol. 246, pp. 1275-1281 (1989).
Lerner, R.A. et al., "Antibodies without immunization", Science, vol. 258, pp. 1313-1314 (1992).
Leusch, H-G. et al. "Failure to demonstrate TNF.alpha.-specific autoantibodies in human sera by ELISA and Western blot", J. Immunol. Methods, vol. 139, pp. 145-147, (1991).
Marks, J.D. et al., "By-passing immunization: Human antibodies from V-gene libraries displayed on phage", J. Mol. Biol., vol. 222, pp. 581-597 (1991).
Moller, et al., "Monoclonal antibodies to human tumor necrosis factor .alpha.: in vitro and in vivo application", Cytokine, vol. 2, No. 3, pp. 162-169 (1990).
Tomlinson, I.M. et al., "The structural repertoire of the human V.sub.k domain", EMBO, vol. 14, No. 18, pp. 4628-4638 (1995).
Tomlinson, I.M. et al., "The repertoire of human germline V.sub.H sequences reveals about fifty groups of V.sub.H segments with different hypervariable loops", J. Mol. Biol., vol. 227, pp. 776-698 (1992).
Tracey, K.J. et al., "Tumor necrosis factor: A pleiotropic cytokine and therapuetic target", Annu. Rev. Med., vol. 45, pp. 491-503 (1994).
Winter, G. et al., "Humanized antibodies", Immunology Today, vol. 14, No. 6, pp. 243-246 (1993).
Griffiths et al., The EMBO J. 12(2):725, 1993.
Lewis et al., J. Cell. Biochem., 18D:215, 1994.
Allen Deborah J.
Hoogenboom Hendricus R. J. M.
Kaymakcalan Zehra
Labkovsky Boris
Mankovich John A.
BASF - Aktiengesellschaft
Hanley, Esq. Elizabeth A.
Kara Catherine J.
Saunders David
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