National Institutes of Health, a Component of the US Dept. of Health & Human Services

Idec Pharmaceuticals Corporation

Other

The Dow Chemical Company

Smithkline Beecham Corporation

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

University of Vermont and State Agricultural College

Biogen Idec, Inc.

Cancer Research Fund of Contra Costa

Biomedics Inc.

Eduardo Agustin Padlan

Jeffrey Schlom

Syed V S Kashmiri

Nabil Hanna

Roland A Newman

Amelia Nancy Black

Ira H Pastan

Peter S Mezes

Mitchell Stuart Gross

Byungkook Lee

Daniel Robert Sylvester

Giora Zeev Feuerstein

William Robert Church

Kimberly S Johnson

Ruth A Richard

Sun-Hee Jung

Liming Shu

Andrew John Nichols

Itai Benhar

Michael Neal Blackburn

Arunbhai Haribhai Patel

Fernando Jose Rebelo Do Couto

Jerry A Peterson

Roberto L Ceriani

Tetsuo Nakamura

George E Mark, Iii

Bruce L Daugherty

Sadakazu Usuda

Syed Kashmiri

Syed Kasmiri

Rafia Mehdi Kashmiri, Legal Representative

Masanori Numazaki

Tetsuo c/o Biomedics Inc Nakamura

Masanori c/o Biomedics Inc Numazaki

The present disclosure provides humanized CC49 monoclonal antibodies that bind TAG-72 with high binding affinity and that are minimally immunogenic. In one embodiment, a humanized CC49 antibody includes a non-conservative amino acid substitution in a light chain complementarity determining region 3 of the CC49 antibody. In a further embodiment, the humanized CC49 antibody includes a non-conservative substitution of a first residue in a light chain complementarity determining region 3 and a substitution of a second residue in a complementarity determining region of the humanized CC49 antibody. In several of the embodiments, methods are disclosed for the use of a humanized CC49 antibody.

Humanized anti-tag 72 CC49 for diagnosis and therapy of human tumors

The present disclosure provides humanized COL-1 monoclonal antibodies that retain CEA binding affinity, compared to a parent antibody. Also disclosed herein are humanized COL-1 monoclonal antibodies that have reduced immunogenicity, compared to a parent antibody. The disclosed humanized COL-1 antibodies include substitution of framework residues with residues from the corresponding positions of a homologous human sequence. In several embodiments, methods are disclosed for the use of a humanized COL-1 antibody in the detection or treatment of a CEA-expressing tumor or cell in a subject. Also disclosed is a kit including the humanized COL-1 antibodies described herein.

Framework residue substituted humanized COL-1 antibodies and their use

Methods to determine immunogenicity of humanized anti-tag 72 CC49 antibodies

A murine anti-CD20 monoclonal antibody having cell growth inhibitory activities is disclosed. Cell growth inhibitory activities include apoptosis against human CD20 antigen expressing cells in culture of the CD20 antigen expressing cells without effector cells. The anti-CD20 monoclonal antibody is incorporated into chimeric anti-CD20 monoclonal antibodies in which the amino acid sequences of the variable regions of the anti-CD20 monoclonal antibody and the amino acid sequences of the constant regions of human immunoglobulin are fused. Also a humanized anti-CD20 monoclonal antibody is described which includes all of the variable region CDRs of the H chain of the anti-CD20 monoclonal antibody and all of the variable region CDRs of the L chain of the anti-CD20 monoclonal antibody and an amino acid sequence of human immunoglobulin. A nucleotide sequence encoding the amino acid sequence of the chimeric or humanized anti-CD20 monoclonal antibody can be expressed in mammalian cells.

Anti-CD20 monoclonal antibody

The invention is directed towards mouse-human chimeric variants of CC49 monoclonal antibodies with minimal murine content. A first aspect of the invention provides CDR variants of humanized monoclonal antibody (HuCC49) in which less than all six (three heavy chain and three light chain) Complementarity Determining Regions (CDRs) of CC49 are present. A second aspect of the invention provides SDR variants of humanized monoclonal antibody (HuCC49) in which only Specificity Determining Regions (SDRs) of at least one CDR from CC49 are present. The invention is also directed towards biotechnological methods of making the variants and therapeutic methods of using the variants.

Variants of humanized anti-carcinoma MAb CC49

The present disclosure provides humanized CC49 monoclonal antibodies that bind TAG-72 with high binding affinity and that are minimally immunogenic. In one embodiment, a humanized CC49 antibody includes a non-conservative amino acid substitution in a light chain complementarity determining region 3 of the CC49 antibody. In a further embodiment, the humanized CC49 antibody includes a non-conservative substitution of a first residue in a light chain complementarity determining region 3 and a substitution of a second residue in a complementarity determining region of the humanized CC49 antibody. In several of the embodiments, methods are disclosed for the use of a humanized CC49 antibody in the detection or treatment of a tumor in a subject. Also disclosed is a kit including the humanized CC49 antibody described herein.

Nucleic acids encoding humanized anti-tag 72 CC49 antbodies

Humanized anti-TAG-72 CC49 monoclonal antibodies are disclosed herein. The antibodies include a light chain Complementarity Determining Region (L-CDR)1, a L-CDR2, and a L-CDR3; and a heavy chain Complementarity Determining Region (H-CDR)1, a H-CDR2, and a H-CDR3 from humanized antibody HuCC49V10. The L-CDR1, L-CDR2, L-CDR3 are within a HuCC49V10 light chain framework region that includes the corresponding amino acid from LEN at position 5, 19, 21, and 106 in the light chain. The H-CDR1, H-CDR2, and H-CDR3 are within a heavy chain HuCC49V10 framework comprising a human 21/28' CL residue at positions 20, 38, 48, 66, 67, 69, and 80 in the heavy chain. These humanized CC49 antibodies retain binding affinity for TAG-72 and have reduced immunogenicity, as compared to a parental HuCC49V10 antibody. Methods are disclosed herein for using these antibodies in the treatment or diagnosis of a tumor, such as a carcinoma, expressing TAG-72.

Nucleic acid molecules encoding minimally immunogenic variants of SDR-grafted humanized antibody CC49

Minimally immunogenic variants of SDR-grafted humanized antibody CC49 and their use

Humanized anti-tag 72 cc49 for diagnosis and therapy of human tumors

Variants of humanized anti-carcinoma monoclonal antibody CC49

Novel composite and humanized anti-TAG-72 monoclonal antibodies, antibody fragments, and derivatives thereof using human subgroup IV kappa light chain framework regions.

Composite antibodies of humanized human subgroup IV light chain capable of binding to TAG-72

The present invention is directed to humanized antibodies which bind human gp39 and their use as therapeutic agents. These humanized antibodies are especially useful for treatment of autoimmune diseases.

Treating allergic diseases with humanized anti-CD40L antibody

Variants of humanized anti carcinoma monoclonal antibody cc49

Growing community of inventors

Kensington, MD, United States of America

Eduardo Agustin Padlan