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AssigneeBiogen Idec MA Inc.
InventorsAlexey Alexandrovich Lugovskoy, Karl Hanf, You Li, Kenneth Simon, Herman Van Vlijmen
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The present invention is based, at least in part, on the discovery that strategic modifications of non-human donor antibody CDR residue(s) can be used to humanize antibodies. Such modifications modulate the 3D structural fit between donor antibody CDRs and human acceptor antibody framework regions that comprise the variable domains of a CDR-grafted antibody. Whereas prior art methods of humanization have relied on making framework substitutions (in which selected human framework residues are backmutated to the corresponding amino acid residue present in the non-human donor antibody), the instant invention is based, at least in part, on a method of humanizing antibodies in which selected CDR residues, and optionally adjacent FR residues, are changed in order to accommodate differences in FR amino acid sequences between donor and acceptor antibodies.
A method of humanizing an immunoglobulin (Ig) variable region which comprises a) variable region framework (FR) amino acid residues from a human acceptor Ig variable region and b) complementarity determining regions (CDRs) from a non-human donor Ig variable region, the method comprising . . . 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.
A method of producing a humanized Ig variable region which comprises a) variable framework regions (FRs) from a human acceptor Ig variable region and b) complementarity determining regions (CDRs) from a non-human donor Ig variable region, the method comprising,
A method of producing a humanized Ig variable region, the method comprising, i) selecting a non-human donor Ig variable region;
Dependencies are inferred from the claim text.