Humanized immunoglobulins
AssigneeProtein Design Labs, Inc.
InventorsCary L. Queen, Man Sung Co, William P. Schneider, Nicholas F. Landolfi, Kathleen L. Coelingh, Harold E. Selick
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AssigneeProtein Design Labs, Inc.
InventorsCary L. Queen, Man Sung Co, William P. Schneider, Nicholas F. Landolfi, Kathleen L. Coelingh, 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 Å 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.
A method of designing a humanized immunoglobulin (Ig) chain having a framework region from a human acceptor immunoglobulin and complementarity determining regions (CDR's) from a donor immunoglobulin capable of binding to an antigen, said method comprising the steps of substituting at least one human framework amino acids of the acceptor immunoglobulin with a corresponding amino acid from the donor immunoglobulin at a position in the immunoglobulins where:
A method for improving the affinity of a humanized immunoglobulin (Ig) to an antigen, by replacing amino acids of the human Ig framework with one to three or more amino acids from the donor Ig framework at positions where:
A composition comprising a substantially pure humanized immunoglobulin capable of inhibiting binding of human interleukin-2 (IL-2) to a human IL-2 receptor.
A recombinant immunoglobulin composition comprising a human framework and one or more foreign complementarity determining regions (CDRS) not naturally associated with the framework, wherein said immunoglobulin is capable of binding to a human interleukin-2 receptor.
A composition comprising a substantially pure humanized immunoglobulin specifically reactive with the p75 chain of the human IL-2 receptor.
A humanized immunoglobulin capable of binding to human interleukin-2 receptors, said immunoglobulin comprising one or more complementarity determining regions (CDR's) from mik-β1 antibody in a human framework.
A composition comprising a substantially pure humanized immunoglobulin specifically reactive with a herpes simplex virus-specific epitope.
A composition comprising a substantially pure humanized immunoglobulin capable of inhibiting binding of a herpes simplex virus (HSV) protein to a mouse monoclonal antibody specifically reactive with said protein, wherein the humanized immunoglobulin comprises at least one complementarity determining region (CDR) from the mouse monoclonal antibody.
A humanized immunoglobulin capable of binding to herpes simplex virus, said immunoglobulin comprising one or more complementarity determining regions (CDR's) from a mouse monoclonal antibody in a human framework, wherein the mouse antibody is Fd 79 or Fd 138-80.
A composition comprising a substantially pure humanized immunoglobulin specifically reactive with a CD33 antigen epitope.
A composition comprising a substantially pure humanized immunoglobulin capable of inhibiting binding of CD33 antigen to a mouse monoclonal antibody specifically reactive with said antigen, wherein the humanized immunoglobulin comprises at least one complementarity determining region (CDR) from the mouse monoclonal antibody.
A composition comprising a substantially pure humanized immunoglobulin specifically reactive with a human cytomegalovirus-specific epitope.
A composition comprising a substantially pure humanized immunoglobulin capable of inhibiting binding of a cytomegalovirus (CMV) protein to a mouse monoclonal antibody specifically reactive with said protein, wherein the humanized immunoglobulin comprises at least one complementarity determining region (CDR) from the mouse monoclonal antibody.
A recombinant immunoglobulin composition comprising a human framework and one or more foreign complementarity determining regions (CDR's) not naturally associated with the framework, wherein said immunoglobulin is capable of binding to CMV.
A humanized immunoglobulin capable of binding to cytomegalovirus, said immunoglobulin comprising one or more complementarity determining regions (CDR's) from a mouse monoclonal antibody in a human framework, wherein the mouse antibody is CMV5, CMV109 or CMV115.
A composition comprising a substantially pure humanized immunoglobulin specifically reactive with human γ-IFN.
A recombinant immunoglobulin composition comprising a human framework and one or more complementarity determining regions (CDR's) not naturally associated with the framework, wherein said immunoglobulin is capable of specifically inhibiting biniding of human γ-IFN to a human γ-IFN receptor.
Dependencies are inferred from the claim text.