Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Patent
1995-06-01
1999-11-30
Johnson, Nancy A
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
5303871, 53038822, 5303892, C07K 1624
Patent
active
059945109
ABSTRACT:
Recombinant, in particular humanised, e.g. humanised chimeric and CDR-grafted humanised, antibody molecules having specificity for human TNF.alpha., are provided for use in diagnosis and therapy. In particular, the antibody molecules have antigen binding sites derived from murine monoclonal antibodies CB0006, CB0010, hTNF3 or 101.4. Preferred CDR-grafted humanised anti-hTNF.alpha. antibodies comprise variable region domains comprising human acceptor framework and donor antigen binding regions and wherein the frameworks comprise donor residues at specific positions. The antibody molecules may be used for therapeutic treatment of human patients suffering from or at risk of disorders associated with undesirably high levels of TNF, in particular for treatment of immunoregulatory and inflammatory disorders or of septic, endotoxic or cardiovascular shock.
REFERENCES:
Opal, Steven M., et al., "Efficacy of a Monoclonal Antibody Directed Against Tumor Necrosis Factor in Protecting Neutropenic Rats from Lethal Infection with Pseudomonas aeruginosa," Journal of Infectious Diseases, vol. 161, No. 6, Jun. 1990, pp. 1148-1152.
Queen, Cary, et al., "A Humanized Antibody That Binds to the Interleukin 2 Receptor," Proceedings of the National Academy of Sciences, USA, vol. 86, No. 24, Dec. 1989, pp. 10029-10033.
Roberts et al, "Generation of Antibody with Enhanced Affinity and Specificity for its Antigen by Protein Engineering" Nature, 328(20):731-734, Aug., 1987.
Verhoeyen et al, "Reshaping Human Antibodies: Grafting an Antilysozyme Activity", Science, 239:1534-36 Mar. 25, 1988.
Levitt, J. of Molec Biol. 168: 595-657 (1983) "Molecular Dynamics of Native Protein".
Whittle et al, J. of Cellular Biochemistry, Suppl. 13A, p. 96 1989, "Construction and Expression of a CDR-grafted anti--TNF antibody".
Stevens et al, Transplantation, 50: 856-861 (Nov. 1990).
Leevwenberg et al, Eur. J. Imm., 18: 1469-1472 (1988).
Adair John Robert
Athwal Diljeet Singh
Bodmer Mark William
Emtage John Spencer
Celltech Therapeutics Limited
Johnson Nancy A
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