Method for making humanized antibodies

6719971
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Inventors

Carter, Paul J.
Presta, Leonard G.

Application #

705392

Filed

Nov-2-2000

Published

Apr-13-2004

Current US Class

424/130.1
424/133.1
424/136.1
424/141.1
424/155.1
435/7.1
530/387.1
530/388.1
530/388.8
530/388.85

International Classes

A61K 039/395

Field of Search

435/7.1 424/130.1 424/133.1 424/136.1 424/155.1 424/141.1 530/387.1 530/388.1 530/388.8 530/388.85

Assignee

Genentech, Inc. (South San Francisco, CA)

Examiners

Ungar; Susan

Attorney, Agent or Firm

Lee; Wendy M.

US Patent References

4753894   Monoclonal anti-hu...
4816567   Recombinant imm...
4845198   Hybridoma antibo...
4968603   Determination of st...
5132405   Biosynthetic antibo...
5169774   Monoclonal anti-hu...
5225539   Recombinant alter...
5530101   Humanized immu...
5545403   Method for treating...
5545404   Method for treating...
5545405   Method for treating...
5558864   Humanized and c...
5585089   Humanized immu...
5677171   Monoclonal antibo...
5693761   Polynucleotides en...
5693762   Humanized immu...
5714350   Increasing antibod...
5720937   In vivo tumor detect...
5720954   Monoclonal antibo...
5725856   Monoclonal antibo...
5770195   Monoclonal antibo...
5772997   Monoclonal antibo...
5821337   Immunoglobulin v...
5834598   Human growth hor...
5859205   Humanised antibo...
5877293   CDR grafted anti-C...
5929212   CD3 specific recom...
5994510   Recombinant antib...
6054297   Humanized antibo...
6054561   Antigen-binding sit...
6180370   Humanized immu...
6350861   Antibodies with incr...
6407213   Method for making...
 

Referenced by:

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Other References

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Abstract
Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.
 
Claims
We claim:

1. A method of treating cancer overexpressing p185.sup.HER2 in a patient comprising administering to the patient a therapeutically effective amount of a humanized antibody that specifically binds p185.sup.HER2, wherein the antibody comprises the V.sub.L and V.sub.H domains of an antibody selected from the group consisting of huMAb4D5-3 (SEQ ID NOS. 27 and 28, respectively), huMAb4D5-4 (SEQ ID NOS. 29 and 30, respectively), huMAb4D5-5 (SEQ ID NOS. 1 and 2, respectively), huMAb4D5-6 (SEQ ID NOS. 31 and 32, respectively), huMAb4D5-7 (SEQ ID NOS. 33 and 34, respectively), and huMAb4D5-8 (SEQ ID NOS. 35 and 36, respectively).

2. A method of treating cancer overexpressing p185.sup.HER2 in a patient comprising administering to the patient a therapeutically effective amount of a humanized antibody that specifically binds p185.sup.HER2, wherein he antibody comprises the V.sub.L and V.sub.H domains of huMAb4D5-8 (SEQ ID NOS. 35 and 36, respectively).



Description
FIELD OF THE INVENTION

This invention relates to methods for the preparation and use of variant antibodies and finds application particularly in the fields of immunology and cancer diagnosis and therapy.

BACKGROUND OF THE INVENTION

Naturally occurring antibodies (immunoglobulins) comprise two heavy chains linked together by disulfide bonds and two light chains, one light chain being linked to each of the heavy chains by disulfide bonds. Each heavy chain has at one end a variable domain (V.sub.H) followed by a number of constant domains. Each light chain has a variable domain (V.sub.L) at one end and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light chain variable domain is aligned with the variable domain of the heavy chain. Particular amino acid residues are believed to form an interface between the light and heavy chain variable domains, see e.g. Chothia et al., J. Mol. Biol. 186:651-663 (1985); Novotny and Haber, Proc. Natl. Acad. Sci. USA 82:4592-4596 (1985).