Bristol-myers Squibb Compnay

Domantis Limited

Astrazeneca Ab

Bristol Meyers Squibb Company

Bristol-myers Squibb

Suzanne J Suchard

Steven G Nadler

Olga Ignatovich

Aaron Paul Yamniuk

Steven Grant

James William Bryson

James K Tamura

Philip Drew

Anish Suri

Steve Holmes

Robert P Rehfuss

Laura Price

Christopher Plummer

Murray McKinnon

Brendan Classon

Steve Grant

Marek Honczarenko

Steven Sheriff

Rong Shi

Diane E Shevell

Stanley Krystek

Xiaoni Liu

Chandra S Ramanathan

Liana M Lee

Mary Struthers

Joshua N Finger

Donald G Jackson

John P Throup

Nathan O Siemers

C Gordon Todderud

Dana Banas

Jenny H Xie

Vaishali Shah

Karen D Price

Xavier Valencia

Dominique Duchesne

John N Feder

Thomas C Nelson

Marc Chapdelaine

Rebecca Urbanek

Gary Steelman

Aaron Yamniuk

Wendy L Trigona

Katherine Knappenberger

Linda Sygowski

Chris Allan Veale

Lixin Lang

Urvi Aras

Christine Kratt

Nataly Manjarrez Orduño

Linda M Gustavson

Murray Mckinnon

James Tamura

Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

Compositions monovalent for CD28 binding and methods of use

Methods of treating autoimmune diseases, such as systemic lupus erythematosus using domain antibodies that specifically bind human CD28 are provided. The methods may comprise at least one administration cycle comprising one dose of the domain antibody. The method reduces symptoms of systemic lupus erythematosus compared to placebo.

Methods of treating systemic lupus erythematosus using a domain antibody directed against CD28

The present disclosure relates to the finding that the ratio of circulating (i.e., peripheral blood) central memory T cells to circulating effector T cells in a cancer patient can predict whether a tumor has an inflammatory milieu or not. In addition, since having an inflammatory milieu ('hot tumor') is a positive factor for responding to checkpoint inhibitors, e.g., PD-1 antagonists, this assay on peripheral blood can also be used to predict a response to a checkpoint inhibitor, e.g., an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity or an antibody or an antigen binding portion thereof that binds specifically to PD-1 ligand 1 (PD-L1) and inhibits PD-L1 activity.

Predictive peripheral blood biomarker for checkpoint inhibitors

The disclosure provides for antibodies that bind CD40, including a humanized antibody and a chimeric antibody with different Fc domains. The antibodies bind CD40 and do not exhibit CD40 agonist activity. The antibodies may comprise a modified IgG1 Fc domain, and exhibit minimal activation of immature dendritic cells. Compositions comprising antibodies, methods of use for treatment of diseases involving CD40 activity, and use in the preparation of a medicament for treatment of a disease involving CD40 activity are provided.

Nucleic acids encoding antagonistic CD40 monoclonal antibodies

Methods of treating autoimmune diseases, such as primary immune thrombocytopenia (ITP), solid organ transplant rejection, graft-related disease, pemphigus vulgaris, systemic sclerosis, and myasthenia gravis using antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The methods may comprise at least one administration cycle comprising one dose of the antibody polypeptide. The dose may be administered intravenously at a dose from about 75 mg to about 1500 mg. The method normalizes platelet counts in the human patient.

Methods of treating autoimmune disease using a domain antibody directed against CD40L

Antagonistic anti-CD40 antibodies and methods of antagonizing CD40 activity

Antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The antibody polypeptides are useful in the treatment of diseases involving CD40L activation, such as graft-related diseases and autoimmune diseases. The antibody polypeptides may be domain antibodies (dAbs) comprising a single Vor Vdomain. The half-life of the antibody polypeptides may be increased by modifying the antibody polypeptides to be dual specific reagents that can also bind human serum albumin (HSA) or another antigen.

Antibody polypeptides that antagonize CD40L

Antibody polypeptides that specifically bind a novel epitope of human CD40 are provided. The antibody polypeptides do not exhibit CD40 agonist activity. The antibody polypeptides are useful in the treatment of diseases involving CD40 activation, such as autoimmune diseases. The antibody polypeptides may be domain antibodies (dAbs) comprising a single Vor Vdomain. The half-life of the antibody polypeptides may be increased by modifying the antibody polypeptides to be dual specific reagents that can also bind human serum albumin (HSA).

Methods of treating immune diseases by administering antibody polypeptides that antagonize CD40

Nucleic acids encoding antibody polypeptides that antagonize CD40

A method of treating an inflammatory bowel disease is provided. The method comprises administration of an antibody polypeptide that specifically binds a novel epitope of human CD40. The antibody polypeptides do not exhibit CD40 agonist activity. The antibody polypeptides may be fusions of a domain antibody (dAb) comprising a single Vor Vdomain and an Fc domain.

Method of using antibody polypeptides that antagonize CD40 to treat IBD

Methods of treating immune diseases by administering antibody polypeptides that specifically bind CD40L

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Wilmington, DE, United States of America

Suzanne J Suchard