Humanised antibodies

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...

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5303871, A61K 39395

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active

058592059

ABSTRACT:
CDR-grafted antibody heavy and light chains comprise acceptor framework and donor antigen binding regions, the heavy chains comprising donor residues at at least one of positions (6, 23) and/or (24, 48) and/or (49, 71) and/or (73, 75) and/or (76) and/or (78) and (88) and/or (91). The CDR-grafted light chains comprise donor residues at at least one of positions (1) and/or (3) and (46) and/or (47) or at at least one of positions (46, 48, 58) and (71). The CDR-grafted antibodies are preferably humanised antibodies, having non human, e.g. rodent, donor and human acceptor frameworks, and may be used for in vivo therapy and diagnosis. A generally applicable protocol is disclosed for obtaining CDR-grafted antibodies.

REFERENCES:
patent: 4348376 (1982-09-01), Goldenberg
Chothia, Cyrus et al (Dec. 1989) Nature, "Conformations of Immunoglobulin Hypervariable Regions", vol. 342, pp. 877-883.
Queen, C. et al (Dec. 1989) Proceedings of the National Academy of Sciences, "A Humanized Antibody That Binds to Interleukin 2 Receptor" vol. 86, pp. 10029-10033.
Riechmann et al (Mar. 1988) Nature, "Reshaping Human Antibodies for Therapy," vol. 332, pp. 323-327.
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.
Jones et al., "Replacing the complementarity-Determining Regions in a Human Antibody with those from a Mouse", Nature, 321:522-525, 1986.
Ward et al., "Binding activities of a Repertoire of Single Immunoglobulin Variable Domains Secreted from Escherichia Coli", Nature, 341:544-546, 1989.

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