New York University

Sugen Incorporated

Yale University

Celldex Therapeutics Limited

Other

Duke University

Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Kolltan Pharmaceuticals, Inc.

Rhone-poulenc Rorer International (holdings), Inc.

Max Planck Gesellschaft Forgerung Der Wissenschaften

Max Planck Gessellschaft

Joseph Schlessinger

Jan M Sap

Benjamin L Margolis

Edward Y Skolnik

Irit Lax

Axel Ullrich

Yaron R Hadari

Sima Lev

Susanne Radke

Yoshihisa Suzuki

Moosa Mohammadi

Mikhail L Gishizky

Wolfgang Vogel

Stevan R Hubbard

Miriam Fuchs

Gregory D Plowman

Ann Marie Pendergast

Elizabeth M Mandel-Bausch

Gilad Barnea

Mark A Lemmon

Kathryn M Ferguson

Paul B Sigler

Hai Yan

Haruhiko Kouhara

Taly Spivak-Kroizman

Sangwon Lee

Peng Cho Tang

William L Jorgensen

Harald App

Victoria J South

Reiner Lammers

Richard M Kris

Richard U Margolis

Xiang-peng Kong

Yan Yang

George A Ricca

Christopher Cheadle

Diego Alvarado

Mitsuhiko Okigaki

Francoise Bellot

Veraragavan Palani Eswarakumar

David Givol

Martin Hyman Grumet

Ben Lewis Margolis

Vijay Yajnik

John E Ladbury

Alexei Igorevich Kharitonenkov

Alexander Plotnikov

Satoru Yuzawa

Zhongtao Zhang

Yarden Opatowsky

The compounds of Formula I described herein regulate activity of JAK2 by specifically binding to the JAK2 pseudokinase domain, JH2, and are useful as therapeutic agents in the treatment or amelioration of myeloproliferative disorders. Also provided herein are methods of treating myeloproliferative disorders, and methods of making compounds of Formula I.

Selective JAK2 pseudokinase ligands and methods of use

Provided herein, in one aspect, are antibodies that immunospecifically bind to a human KIT antigen comprising the fourth and/or fifth extracellular Ig-like domains (that is, D4 and/or D5 domains), polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. The antibodies can inhibit KIT activity, such as ligand-induced receptor phosphorylation. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to a KIT antigen, as well as methods of treating or managing a KIT-mediated disorder or disease and methods of diagnosing a KIT-mediated disorder or disease using the antibodies described herein.

Anti-KIT antibodies and uses thereof

The present invention relates, in one aspect, to certain mutant FGF21 polypeptide constructs. In certain non-limiting embodiments, the construct binds to &#x3b2;-Klotho more tightly than wild-type FGF21. In certain non-limiting embodiments, the construct has a mutation in at least one residue of SEQ ID NO:3 selected from the group consisting of V188, R203, and L194. In certain non-limiting embodiments, the construct further comprises a stability enhancing domain.

Mutant FGF21 polypeptide compositions

Methods of treating by administering anti-kit antibodies

Provided herein are compositions, methods and uses involving antibodies that bind to ErbB, a receptor tyrosine kinase, and modulate the activity of ErbB. Also provided are uses and methods for treating disorders, such as cancer, by administering to subject an antibody that binds to ErbB.

Anti-ErbB antibodies and methods of use thereof

Polynucleotides encoding anti-KIT antibodies

Anti-kit antibodies

The present invention provides moieties that bind to an Ig-like domain, e.g., D4 or D5, of a human receptor tyrosine kinase, e.g., the human Kit RTK or the PDGFR RTK, or the D7 domain of a type V receptor tyrosine kinase wherein the moieties lock the ectodomain of the receptor tyrosine kinase in an inactive state thereby antagonizing the activity of the receptor tyrosine kinase.

Inhibitors of receptor tyrosine kinases and methods of use thereof

The invention provides materials, reagents, systems, and methods for identifying agents useful for treating diseases resulting from abnormal (e.g., excessive) FGF receptor signaling. The invention also provides (therapeutic) agents thus identified, and methods of using such agents in treating such diseases. In certain embodiments, the invention relates to the treatment of various craniofacial disorders, or Craniosynostosis, that result from FGFR (e.g. FGFR2) malfunction, such as Crouzon, Apert, Jackson-Weiss, Pfeiffer Syndromes, Crouzon+acanthosis nigricans, Beare-Stevenson cutis gyrata, and non-syndromic craniosynostosis (NS). The methods comprise administering to the individuals a therapeutically effective amount of an inhibitor of the FGFR2c-FRS2 signaling. The inhibitor inhibits signaling by antagonizing FGFR2c-FRS2 interaction, inhibiting the expression and/or subcellular localization of wild-type or mutant FGFR2c and/or FRS2, inhibiting the kinase activity of FGFR2c (e.g. for autophosphorylation and/or phosphorylation of FRS2), and/or inhibiting downstream signaling of FRS2 (such as Sos-Ras-MAPK, Shp2, and/or Gab 1-PI3K pathways).

Method for treating skeletal disorders resulting from FGFR malfunction

Methods for treatment, diagnosis, and screening are provided for diseases or conditions characterized by an abnormality in a signal transduction disorder. The signal transduction pathway involves an interaction between a PH domain and a PH domain binding partner.

Methods for diagnosis and treatment of PH domain signal transduction disorders

The present invention relates generally to a newly identified adaptor protein FRS2 and related products and methods. FRS2 links protein kinases to activating partners in cells. The invention also relates to nucleic acid molecules encoding portions of FRS2, nucleic acid vectors containing FRS2 related nucleic acid molecules, recombinant cells containing such nucleic acid vectors, polypeptides purified from such recombinant cells, antibodies to such polypeptides, and methods of identifying compounds that enhance or block FRS2 interactions with natural binding partners. Also disclosed are methods for diagnosing abnormal conditions in an organism with FRS2 related molecules or compounds.

Adaptor protein FRS2 and related products and methods

The determination and use of three dimensional structures of receptor protein tyrosine kinases and/or their ligands are described. One particular group of such structures includes three dimensional structures of the extracellular domain of RPTKs. The three dimensional structures of RPTKs can faciliate the design and identification of modulators of RPTK function. Other such structures can include of RPTK ligands, such as stem cell factor or a fragment thereof. Modulators of RPTK function can be used to treat diseases that are mediated by inappropriate RPTK activity.

Crystal of fibroblast growth factor receptor 1 in complex with fibroblast growth factor

A novel receptor-type protein tyrosine phosphatase (RPTP) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. Included in this family of proteins are human RPTP&#x3b1;, human RPTP&#x3b2; and human RPTP&#x3b3;. The RPTP protein or glycoprotein may be produced by recombinant means. Antibodies to the proteins, methods for measuring the quantity of the proteins, methods for screening compounds, such as drugs, which can bind to the proteins and inhibit or stimulate their activity, are provided.

Receptor-type phosphotyrosine phosphatase-alpha

A novel receptor-type protein tyrosine phosphatase-&#x3ba; (RPTP&#x3ba;) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. The RPTP&#x3ba; protein or glycoprotein may be produced by recombinant means. Antibodies to the protein, methods for measuring the quantity of the protein, methods for screening compounds, such as drugs, which can bind to the protein and inhibit or stimulate their enzymatic activity, are provided. Further, methods for inhibiting homophilic binding of Type II RPTP, especially RPTP&#x3ba; molecules are provided.

Receptor-type phosphotyrosine phosphatase-kappa antibodies

The present invention relates generally to the fields of immunology and medicine, and more specifically to the field of cellular signal transduction. The present invention relates, inter alia, to methods for diagnosis, treatment, and identification of therapeutics for particular inflammation-related diseases or disorders characterized by an interaction between a PYK2 polypeptide and a natural binding partner.

PYK2 and inflammation

Growing community of inventors

New York, NY, United States of America

Joseph Schlessinger