Methods for humanizing rabbit monoclonal antibodies

Abstract

The invention provides a method for humanizing a rabbit monoclonal antibody. In general, the method involves comparing an amino acid sequences of a parent rabbit antibody to the amino acid sequences of a similar human antibody, and altering the amino acid sequence of the parent rabbit antibody such its framework regions are more similar in sequence to the equivalent framework regions of the similar human antibody. In many embodiments, amino acids in the parent rabbit antibody that are not CDR contact residues, interchain contact residues, or buried residues, are not modified. The invention further provides nucleic acids encoding the subject antibodies, as well as vectors and host cells comprising the nucleic acids and methods for producing a subject antibody. The subject antibodies, nucleic acid compositions and kits find use in a variety of applications, including diagnostics and therapeutic treatment and research of conditions and diseases.

Description

technical field

[0001] The field of the invention is antibodies, particularly methods for humanizing rabbit monoclonal antibodies. Background technique

[0002] Because monoclonal antibodies can target virtually any molecule with some specificity, monoclonal antibodies and their conjugates and derivatives will likely become a major therapeutic agent in the future. Although this possibility has long been recognized, the first attempts to realize it have failed, mainly because even the monoclonal antibodies used in the therapy are injected only once in a single low dose (Dillman, Cancer Biother 19949: 17-28), and monoclonal antibodies can also generate a strong immune response in patients (Schroff, 1985 Cancer Res 45: 879-85, Shawler. J Immunol 1985 135: 1530-5). Scientists predict that human antibodies will not produce this adverse immune response, but current hybridoma technology cannot produce human monoclonal antibodies. Since then, some other alternative techniques for ...

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