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Methods for antibody engineering

  • US 7,462,697 B2
  • Filed: 11/08/2004
  • Issued: 12/09/2008
  • Est. Priority Date: 11/08/2004
  • Status: Active Grant
First Claim
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1. A method for humanizing a rabbit antibody, comprising:

  • a) identifying a variation tolerant position in a parent rabbit antibody by comparing its amino acid sequence to the amino acid sequences of a plurality of related antibodies that are obtained from the same rabbit as said parent rabbit antibody, wherein said parent antibody and said related antibodies;

    i. bind to the same antigen;

    ii. each comprise heavy chain variable domains that have an overall amino acid sequence identity of at least 90% relative to one another;

    iii. each comprise light chain variable domains that have an overall amino acid sequence identity of at least 90% relative to one another;

    iv. have H3 CDRs that are identical in length and identical in sequence except for 0, 1 or 2 amino acid substitutions relative to one another;

    v. have L3 CDRs that are identical in length and identical in sequence except for 0, 1 or 2 amino acid substitutions relative to one another;

    b) aligning the amino acid sequence of said parent rabbit antibody with the amino acid sequence of a human antibody, wherein said human antibody is one of ten human antibodies that are most homologous to said parent rabbit antibody; and

    c) substituting the amino acid present at said variation tolerant position with the corresponding amino acid of said human antibody to produce a humanized antibody.

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