Bristol-myers Squibb Compnay

Domantis Limited

Bristol Meyers Squibb Company

Murray McKinnon

Steve Holmes

Suzanne J Suchard

Steven G Nadler

Olga Ignatovich

Christopher Plummer

Brendan Classon

Steve Grant

John N Feder

Chandra S Ramanathan

Gena S Whitney

Gregory Opiteck

Leah Ann Garulacan

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

The present invention describes a G-protein coupled receptor (GPCR) family member newly identified as being modified, e.g., phosphorylated, and associated with tyrosine phosphorylated activation complexes, following exposure of cells to smoke from tobacco burning substances, namely, cigarette smoke. This GPCR protein is RAI-3, which was first found to be phosphorylated in cells treated with cigarette smoke and to be associated with other proteins activated in cigarette smoke treated cells by virtue of the present invention. Because cigarette smoke is considered to be a major causative factor of chronic obstructive pulmonary disease (COPD) and disorders and conditions related thereto, the RAI-3 protein is newly provided as a cellular drug target for screening, discovering, and identifying modulators for the treatment and/or prevention of COPD and its related disorders and conditions, such as emphysema and chronic bronchitis. In accordance with the present invention RAI-3 modulators, e.g., agonists and antagonists, can be used as therapeutics in the treatment of COPD and numerous other diseases and disorders that are associated with regulation of NF-&#x3ba;B and/or its associated or interacting signaling molecules. This invention further provides SNPs of RAI-3, e.g., for determining COPD association in individuals.

Methods of diagnosing tumors using the G-protein coupled receptor (GPCR), RAI-3

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Washington Crossing, PA, United States of America

Murray McKinnon