Millennium Pharmaceuticals Limited

Other

The Brigham and Women's Hospital, Inc.

Children's Medical Center Corporation

Theodor-kocher Institute

Charles R Mackay

Shixin Qin

Paul D Ponath

Walter Newman

Craig J Gerard

Norma P Gerard

Theodore W Post

Douglas J Ringler

Charles F Schwender

Bernhard Moser

Marcel Loetscher

Julia C Pinto

Lijun Wu

The invention relates to isolated and/or recombinant nucleic acids which encode a human chemotactic cytokine designated human eotaxin, and to isolated and/or recombinant human eotaxin proteins or polypeptides, including synthetic polypeptides. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a human eotaxin, a portion thereof, or a variant; to host cells comprising such constructs, useful for the production of recombinant human eotaxin; and to antibodies reactive with human eotaxin, useful in in vitro methods, diagnosis and/or therapy. Also provided are methods of use of the eotaxin proteins, e.g., in the recruitment of eosinophils to a particular site or in the treatment of allergic conditions. Human eotaxins can be used to identify inhibitors (e.g., antagonists) or promoters (agonists) of human eotaxin, which can be used to selectively modulate leukocyte function, in inflammatory and autoimmune diseases, or in infections.

Method of diagnosis of inflammatory disease using eotaxin antibodies

Antibodies to human eotaxin

The present invention relates to proteins or polypeptides, referred to herein as isolated and/or recombinant mammalian (e.g., human) IP-10/Mig receptor proteins designated CXC Chemokine Receptor 3 (CXCR3) and variants thereof, including those characterized by selective binding of one or more chemokines (e.g., IP-10 and/or Mig), and/or the ability to induce a cellular response (e.g., chemotaxis, exocytosis). Antibodies reactive with CXCR3 receptors can be produced using the proteins or variants thereof or host cells comprising same as immunogen.

Method of inhibiting leukocytes with human CXC chemokine receptor 3 antibody

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

Human chemotactic cytokine

The present invention relates to isolated and/or recombinant nucleic acids which encode a human chemotactic cytokine designated human eotaxin, and to proteins or polypeptides referred to herein as isolated and/or recombinant human eotaxin, including synthetic polypeptides. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a human eotaxin of the present invention, a portion thereof, or a variant; to host cells comprising such constructs, useful for the production of recombinant human eotaxin; and to antibodies reactive with human eotaxin, which are useful in in vitro methods, diagnostic and/or therapeutic applications. Also provided are methods of use of the proteins of the present invention, for example in the recruitment of eosinophils to a particular site or in the treatment of allergic conditions. Human eotaxins can be used in assays to identify inhibitors (e.g., antagonists) or promoters (agonists) of human eotaxin function. Agents which inhibit or promote eotaxin function can be administered to an individual, providing 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.

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 an antibody or functional portion thereof which binds to a mammalian (e.g., human) chemokine receptor 5 protein (CKR-5 or CCR5) or portion of the receptor. The invention further relates to a method of inhibiting the interaction of a cell bearing mammalian CCR5 with a ligand thereof. Another aspect of the invention relates to a method of inhibiting HIV infection of a cell which expresses a mammalian CCR5 or portion thereof using the antibodies described herein. Also encompassed by the present invention are methods of treating or preventing HIV in a patient.

Anti-CCR5 antibodies and kits comprising same

Disclosed is a method of treating a subject with a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to the subject a therapeutically effective amount of a compound represented by the following structural formula:

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Watertown, MA, United States of America

Charles R Mackay