Schering Corporation

Pharmacopeia Inc.

Paul J Zavodny

Barbara Dalie

Jimmy C Tan

Daniel Lundell

Charles A Lunn

Chung-Her Jenh

Xuedong Fan

Nicholas J Murgolo

Stephen Tindall

Satwant K Narula

Chuan-Chu Chou

Hung V Le

William T Windsor

Jan E De Vries

John S Abrams

Kenneth Miller

Mary E Petro

Jon E Silver

Hanh Nguyen

Neng-Yang Shih

Joseph A Kozlowski

Stuart B Rosenblum

Douglas Walsh Hobbs

Brian F McGuinness

Seong Heon Kim

Gopinadhan N Anilkumar

Guizhen Dong

Yuefei Shao

Lisa Guise Zawacki

Herinder K Lonial

Cangmeng Yang

Carolyn Dilanni Carroll

Changmeng Yang

The present application discloses a compound, or enantiomers, stereoisomers, rotamers, tautomers, racemates or prodrug of said compound, or pharmaceutically acceptable salts, solvates or esters of said compound, or of said prodrug, said compound having the general structure shown in Formula 1: and the pharmaceutically acceptable salts, solvates and esters thereof. Also disclosed is a method of treating chemokine mediated diseases, such as, palliative therapy, curative therapy, prophylactic therapy of certain diseases and conditions such as inflammatory diseases (non-limiting example(s) include, psoriasis), autoimmune diseases (non-limiting example(s) include, rheumatoid arthritis, multiple sclerosis), graft rejection (non-limiting example(s) include, allograft rejection, xenograft rejection), infectious diseases (e.g, tuberculoid leprosy), fixed drug eruptions, cutaneous delayed-type hypersensitivity responses, ophthalmic inflammation, type I diabetes, viral meningitis and tumors using a compound of Formula 1.

Pyridyl and phenyl substituted piperazine-piperidines with CXCR3 antagonist activity

The present invention provides isolated human and bovine TNF-&#x3b1; convertases, nucleic acids and; recombinant vectors encoding the same, host cells comprising the nucleic acids and vectors, and methods for making the convertases using the host cells. This invention further provides antibodies and antigen binding fragments thereof which specifically bind to the convertases and are useful for treating medical conditions caused or mediated by TNF-&#x3b1;. Also provided are screening methods for identifying specific inhibitors of mammalian TNF-&#x3b1; convertases, and for identifying nucleic acids encoding such convertases.

Nucleic acids encoding human TNF-&#x3b1; convertase

The present invention provides isolated human and bovine TNF-&#x3b1; convertases, nucleic acids and recombinant vectors encoding the same, host cells comprising the nucleic acids and vectors, and methods for making the convertases using the host cells. This invention further provides antibodies and antigen binding fragments thereof which specifically bind to the convertases and are useful for treating medical conditions caused or mediated by TNF-&#x3b1;. Also provided are screening methods for identifying specific inhibitors of mammalian TNF-&#x3b1; convertases, and for identifying nucleic acids encoding such convertases.

Mammalian TNF-&#x3b1; convertases

The present invention provides isolated human and bovine TNF-&agr; convertases, nucleic acids and recombinant vectors encoding the same, host cells comprising the nucleic acids and vectors, and methods for making the convertases using the host cells. This invention further provides antibodies and antigen binding fragments thereof which specifically bind to the convertases and are useful for treating medical conditions caused or mediated by TNF-&agr;. Also provided are screening methods for identifying specific inhibitors of mammalian TNF-&agr; convertases, and for identifying nucleic acids encoding such convertases.

Mammalian TNF- &agr; convertase

A monoclonal antibody is provided which specifically binds to human interleukin-5. Also provided are a hybridoma which produces the monoclonal antibody; complementary DNAs which encode the heavy and light chain variable regions of the monoclonal antibody and CDRs therefrom; humanized monoclonal antibodies; and pharmaceutical compositions comprising the monoclonal antibody or anti-idiotypic antibodies directed against it, humanized monoclonal antibodies, binding fragments, binding compositions or single-chain binding proteins derived from the antibody and a physiologically acceptable carrier.

Design, cloning and expression of humanized monoclonal antibodies against human interleukin-5

Mammalian TNF-&agr; convertases

Stably-transformed human cell lines containing a reporter gene operatively linked to an IL-4-responsive element are provided. In some embodiments a human Fc,RII IL-4-responsive element is used. In other embodiments a human germline &egr; transcript promoter is used as the responsive element. Also provided are methods for using such transformed cell lines to screen for agonists and/or antagonists of human interleukin-4.

Materials and methods for screening human interleukin-4 antagonists/agonists

Humanized monoclonal antibodies against human interleukin-5

Stably-transformed human cell lines containing a human gamma interferon-responsive human HLA-DR.alpha. promoter operatively linked to a reporter gene are provided. Also provided are methods for using such transformed cell lines to screen for agonists and/or antagonists of human gamma interferon.

Human gamma interferon antagonist/agonist screen

Stably-transformed human cell lines containing a reporter gene operatively linked to an IL-4-responsive element are provided. In some embodiments a human Fc.sub..epsilon. RII IL-4-responsive element is used. In other embodiments a human germline .epsilon. transcript promoter is used as the responsive element. Also provided are methods for using such transformed cell lines to screen for agonists and/or antagonists of human interleukin-4.

Human interleukin-4 antagonist/agonist screens

Humanized monoclonal antibodies against human interleukin-4

The present invention provides isolated human and bovine TNF-.alpha. convertases, nucleic acids and recombinant vectors encoding the same, host cells comprising the nucleic acids and vectors, and methods for making the convertases using the host cells. This invention further provides antibodies and antigen binding fragments thereof which specifically bind to the convertases and are useful for treating medical conditions caused or mediated by TNF-.alpha.. Also provided are screening methods for identifying specific inhibitors of mammalian TNF-.alpha. convertases, and for identifying nucleic acids encoding such convertases.

Mammalian TNF-.alpha. convertases

Monoclonal antibodies are provided which are specific for human interleukin-4. Also provided are complementary DNAs which encode the heavy and light chain variable regions of such monoclonal antibodies and complementarity determining regions from such DNAs; and kits and methods for detecting, measuring and immunopurifying human interleukin-4, and for blocking the biological activity of human interleukin-4.

Cloning and exprssion of humanized monoclonal antibodies against human

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Mountainside, NJ, United States of America

Paul J Zavodny