Protein Design Labs, Inc.

The United States of America As Represented by the Department of Health

Other

The United States of America As Represented by the Secretary of

Memorial Sloan Kettering Cancer Center

Pdl Biopharma, Inc.

Sloan-kettering Cancer Center

Facet Biotech Corporation

Cary L Queen

Harold E Selick

Man Sung Co

Ira H Pastan

Maximiliano Vasquez

David A Scheinberg

Nicholas F Landolfi

Thomas Alexander Waldmann

William P Schneider

Naoya Tsurushita

David J FitzGerald

Vijay K Chaudhary

J Yun Tso

David J Fitzgerald

Kathleen L Coelingh

Vijay Kumar Chaudhary

Kenneth Hong

Rolf Ehrhardt

Susan Light

Harold Edwin Selick

The invention provides humanized immunoglobulins that bind to and neutralize &#x3b3;-interferon. The antibodies are useful for treatment of diseases of the immune system, particularly autoimmune diseases.

Humanized antibodies to gamma-interferon

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&#x212b; 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.

Humanized immunoglobulins

The present invention provides methods for producing mutationally-altered immunoglobulins and compositions containing such mutationally-altered immunoglobulins, wherein the mutationally-altered immunoglobulins have at least one mutation that alters the pattern of glycosylation in a variable region and thereby modifies the affinity of the immunoglobulin for a preselected antigen. The methods and compositions of the invention provide immunoglobulins that possess increased affinity for antigen. Such glycosylation-altered immunoglobulins are suitable for diagnostic and therapeutic applications.

Increasing antibody affinity by altering glycosylation of immunoglobulin variable region

Methods and compositions are provided for the creation and screening of non-human animal models having many of the histologic characteristics of human psoriasis. Immunocompromised host animals are injected with a purified population of CD45Rb positive cells, which are tolerant of the host major histocompatibility antigens, but are mismatched at one or more minor antigens. The injected cells are stimulated with a pro-inflammatory cytokine, e.g. IL-12, and a polyclonal activating agent. The injected animals develop a chronic skin disorder that includes histological features observed in human psoriasis, e.g. rete pegs, severe acanthosis and infiltration of Th1 cells into the dermis.

Animal model for psoriasis for the prevention and treatment of psoriasis in humans

Antibodies with increased binding affinity

The invention provides humanized immunoglobulins that bind to and neutralize &ggr;-interferon. The antibodies are useful for treatment of diseases of the immune system, particularly autoimmune diseases.

Humanized antibodies to &ggr;-interferon

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 &angst; 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.

Humanized immunoglobulins and methods of making the same

The present invention describes constructs encoding recombinant scFv-toxin fusion proteins which selectively kill cells bearing appropriate antigens or receptors.

Constructs encoding recombinant antibody-toxin fusion proteins

Fas ligand fusion proteins comprising a polypeptide capable of specifically binding an antigen or a cell surface marker are prepared employing recombinant DNA technology for use in, e.g., treatment of autoimmune disorders.

FAS ligand fusion proteins and their uses

The invention provides methods of preventing acute rejection following renal or other solid organ transplantation. The methods entail administering, e.g., intravenously, to a transplant patient a monoclonal antibody which binds to the p55 subunit of the human interleukin-2 (IL-2) receptor of human T lymphocytes. The monoclonal antibody is preferably a chimeric or humanized antibody that blocks binding of IL-2 to the IL-2 receptor. In some methods, a single dose of about 1 mg/kg of antibody is administered about every other week, commencing immediately prior to transplantation and continuing until 8 weeks after transplantation.

Method of preventing acute rejection following solid organ

The present invention describes recombinant antibody toxin fusion proteins which selectively kill cells bearing appropriate antigens or receptors.

Recombinant antibody-toxin fusion protein

Increasing antibody affinity by altering glycosylation in the

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.

Growing community of inventors

Los Altos, CA, United States of America

Cary L Queen