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AssigneeProtein Design Labs, Inc.
InventorsCary L. Queen, William P. Schneider, Harold E. Selick
Estimating the term…
Novel methods for producing, and compositions of, humanized immunoglobulins having one or more complementarity determining regions (CDR's) and possible additional amino acids from a donor immunoglobulin and a framework region from an accepting human immunoglobulin are provided. Each humanized immunoglobulin chain will usually comprise, in addition to the CDR's, amino acids from the donor immunoglobulin framework that are, e.g., capable of interacting with the CDR's to effect binding affinity, such as one or more amino acids which are immediately adjacent to a CDR in the donor immunoglobulin or those within about about 3 .ANG. as predicted by molecular modeling. The heavy and light chains may each be designed by using any one or all of various position criteria. When combined into an intact antibody, the humanized immunoglobulins of the present invention will be substantially non-immunogenic in humans and retain substantially the same affinity as the donor immunoglobulin to the antigen, such as a protein or other compound containing an epitope.
First and second polynucleotides respectively encoding heavy and light chain variable regions of a humanized immunoglobulin having complementarity determining regions (CDRs) from a donor immunoglobulin and heavy and light chain variable region frameworks from human acceptor immunoglobulin heavy and light chain frameworks, which humanized immunoglobulin specifically binds to an antigen with an affinity constant of at least about 10.sup.8 M.sup.-1 and no greater than about four-fold that of the donor immunoglobulin, wherein the sequence of the humanized immunoglobulin heavy chain variable region framework is at least 65% identical to the sequence of the donor immunoglobulin heavy chain variable region framework and comprises at least 70 amino acid residues identical to those in the acceptor human immunoglobulin heavy chain variable region framework.
First and second polynucleotides respectively encoding heavy and light chain variable regions of a humanized immunoglobulin having complementarity determining regions (CDRs) from a donor immunoglobulin and heavy and light chain variable region frameworks from acceptor immunoglobulin heavy and light chain frameworks, which humanized immunoglobulin specifically binds to an antigen with an affinity constant of at least about 10.sup.8 M.sup.-1 and no greater than about four-fold that of the donor immunoglobulin, wherein the sequence of the acceptor immunoglobulin heavy chain variable region framework is a consensus sequence of human immunoglobulin heavy chain variable region frameworks.
First and second polynucleotides respectively encoding heavy and light chain variable regions of a humanized immunoglobulin having complementarity determining regions (CDRs) from a donor immunoglobulin and heavy and light chain variable region frameworks from human acceptor immunoglobulin heavy and light chains, which humanized immunoglobulin specifically binds to an antigen with an affinity constant of at least about 10.sup.8 M.sup.-1 and no greater than about four-fold that of the donor immunoglobulin, wherein said humanized immunoglobulin heavy chain comprises one or more amino acids from the donor immunoglobulin heavy chain framework outside the Kabat and Chothia CDRs, wherein the donor amino acids substitute for corresponding amino acids in the acceptor immunoglobulin heavy chain framework, and each of these said donor amino acids:
First and second polynucleotides respectively encoding heavy and light chain variable regions of a humanized immunoglobulin having complementarity determining regions (CDRs) from a donor immunoglobulin and heavy and light chain variable region frameworks from human acceptor immunoglobulin heavy and light chains, which humanized immunoglobulin specifically binds to an antigen with an affinity constant of a least about 10.sup.8 M.sup.-1 and no greater than about four-fold that of the donor immunoglobulin, wherein said humanized immunoglobulin heavy chain comprises one or more amino acids from the donor immunoglobulin heavy chain framework outside the Kabat and Chothia CDRs that substitute for the corresponding amino acids in the acceptor immunoglobulin heavy chain framework, wherein each of these said donor amino acids:
First and second polynucleotides according to claim 20, wherein the second polynucleotide has the sequence:
Dependencies are inferred from the claim text.