Millennium Pharmaceuticals Limited

Other

The Brigham and Women's Hospital, Inc.

Children's Medical Center Corporation

The Rockefeller University

The Beth Israel Hospital Association

Norma P Gerard

Paul D Ponath

Shixin Qin

Charles R Mackay

Craig J Gerard

Theodore W Post

Elaine I Tuomanen

Diana R Cundell

The present invention relates to isolated and/or recombinant C-C Chemokine Receptor 3 (CKR-3, CCR3) proteins or polypeptides.

C-C chemokine receptor 3 proteins

The present invention relates to isolated and/or recombinant nucleic acids which encode a mammalian (e.g., human) receptor protein designated C&#x2014;C Chemokine Receptor 3 (CKR-3) or Eos L2, and to proteins or polypeptides, referred to herein as isolated, recombinant mammalian CKR-3 receptors. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a receptor protein of the present invention or a portion thereof; to host cells comprising such constructs, useful for the production of recombinant CKR-3 receptors or polypeptides; and to antibodies reactive with the receptors, which are useful in research and diagnostic applications. Also provided are methods of use of the nucleic acids, proteins, and host cells to identify ligands, inhibitors (e.g., antagonists) or promoters (agonists) of receptor function. Administration of a compound which inhibits or promotes receptor function to an individual in need of therapy provides a new approach to selective modulation of leukocyte function, which is useful in a variety of inflammatory and autoimmune diseases, or in the treatment of infections. As a major leukocyte chemokine receptor present in leukocytes such as eosinophils and lymphocytes, the receptor provides a key target for drug screening and design.

Antibodies to C-C chemokine Receptor 3 Protein

The present invention relates to a method of identifying an inhibitor of a mammalian (e.g., human) C&#x2014;C chemokine receptor 3 (CCR3), comprising combining (a) a compound to be tested, (b) a host cell expressing a recombinant protein comprising a mammalian CCR3, and (c) a ligand of said receptor, under conditions suitable for binding of ligand to said receptor, and detecting or measuring the formation of a receptor-ligand complex. Inhibition of complex formation by the compound is indicative that the compound is an inhibitor.

Method of identifying inhibitors of C&#x2014;C chemokine receptor 3

The present invention relates to isolated and/or recombinant nucleic acids which encode a mammalian (e.g., human) receptor protein designated C-C Chemokine Receptor 3 (CKR-3) or Eos L2, and to proteins or polypeptides, referred to herein as isolated, recombinant mammalian CKR-3 receptors. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a receptor protein of the present invention or a portion thereof, and to host cells comprising such constructs, useful for the production of recombinant CKR-3 receptors or polypeptides.

G protein-coupled receptor gene and methods of use therefor

The present invention relates to a method of identifying an inhibitor of a mammalian (e.g., human) C&mdash;C chemokine receptor 3 (CCR3), comprising combining (a) a compound to be tested, (b) a host cell expressing a recombinant protein comprising a mammalian CCR3, and (c) a ligand of said receptor, under conditions suitable for binding of ligand to said receptor, and detecting or measuring the formation of a receptor-ligand complex. Inhibition of complex formation by the compound is indicative that the compound is an inhibitor.

Method of identifying inhibitors of C&mdash;C chemokine receptor 3

The present invention relates to compositions and methods for preventing pneumococcal infection. In particular, the invention relates to identification of the major reception for Streptococcus pneumoniae on activated human cells, and diagnostic and therapeutic compositions and methods based thereon. In particular, the invention relates to the discovery that platelet activating factor (PAF) receptor is an adhesive ligand for pneumococcal adherence to activated lung epithelial and venous endothelial (i.e., host) cells. Accordingly, the present invention is directed to a method for preventing or treating an infection with Streptococcus pneumoniae by administering an antagonist of platelet activating factor receptor. The invention further relates to recognition that adherence to activated cells also involves a carbohydrate ligand found on such activated cells. Thus, a method for inhibiting pneumococcal adherence may further comprise administering an amount of carbohydrate containing an N-acetyl-D-glucosamine motif. It has been found that resting lung epithelial and venous endothelial cells bear two classes of receptors containing different carbohydrate motifs. Thus, the invention further provides for administering an amount of a second carbohydrate selected from the group consisting of a carbohydrate containing a disaccharide N-acetyl-D-galactosamine .beta.1-4Gal motif, a disaccharide N-acetyl-D-galactosamine .beta.1-3Gal motif, and a mixture thereof. In addition, the invention provides pharmaceutical compositions comprising such agents that inhibit binding of pneumococci to human cells. In a specific example, platelet activating factor receptor antagonists and disaccharides are shown to inhibit binding of pneumococci to activated lung epithelial cells and venous endothelial cells, as well as cells transfected with the platelet activating factor receptor, in vitro.

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Dover, MA, United States of America

Norma P Gerard