Patent ID: 8349324

Claim:
A polypeptide comprising the humanized Ig variable region which comprises a) variable region framework (FR) amino acid residues from a human acceptor Ig variable region and b) complementary determining regions (CDRs) from a non-human donor Ig variable region, produced by a method of humanizing an immunoglobulin (Ig) variable region, the method comprising, i) providing data which allows prediction of a 3-D conformation of at least one CDR; ii) identifying which FR amino acid residues are predicted to affect the 3-D conformation of the at least one CDR; iii) identifying at least one candidate donor CDR amino acid residue for substitution with an elected amino acid residue, wherein the elected amino acid residue conformationally accommodates a FR amino acid residue difference between the donor Ig variable region and the acceptor Ig variable region without affecting the CDR conformation; and iv) substituting the at least one candidate donor CDR amino acid residue with the elected amino acid residue, such that the immunoglobulin variable region is humanized, and v) expressing a polypeptide comprising the humanized Ig variable region, wherein the polypeptide binds to an antigen with an affinity that is greater than or not substantially changed as compared to the affinity of the donor Ig variable region for the antigen.