Chiron Corporation

Novartis Vaccines & Diagnostics, Gmbh

Five Prime Therapeutics, Inc.

Kyoto University

Duke University

W Michael Kavanaugh

Lewis T Williams

Cheng Liu

Kirston E Koths

Martha Jo Whitehouse

Hui Cen

Pauline Lee

David T Hung

Thomas Brennan

Judith A Abraham

Thomas Harding

Kevin P Landolfo

Siew C Schleyer

Brian H Annex

Stephen David Harrison

Li Long

Anne B Jefferson

Janine Powers

Robert Dean

Marcus D Ballinger

Denis J Gospodarowicz

David Pot

Deborah Lee Zimmerman

Kenneth Crawford

Gregory Martin Harrowe

Nobuyuki Itoh

Anke Klippel

The present invention relates to the use of Fibroblast Growth Factor Receptor I (FGFR1) extracellular domain (ECD) polypeptides for treatment of cancers characterized by ligand dependent activating mutations in Fibroblast Growth Factor Receptor 2 (FGFR2). For example, the present invention relates to the treatment of endometrial cancers and other cancers wherein tumor cells express FGFR2 mutants in the IgII-IgIII hinge region or IgIII domain of the protein, such as at amino acid positions 252 and/or 253.

Method of treatment of cancers characterized by ligand-dependent activating mutations in FGFR2 with FGFR1 ECD proteins

The present invention is directed to a method for treating a human patient for coronary artery disease, comprising administering into at least one coronary vessel of said patient a safe and angiogenically effective dose of a recombinant FGF-9 of SEQ ID NO:13, or an angiogenically active fragment or mutein thereof. The invention is also directed to a method for inducing angiogenesis in the heart of a patient, comprising administering into at least one coronary vessel of a human patient in need of coronary angiogenesis a therapeutically effective amount of a recombinant FGF-9 of SEQ ID NO:13, or an angiogenically active fragment or mutein thereof.

Method of treating coronary artery disease by administering FGF-9

The present invention relates to a method of promoting hair growth comprising administering a fibroblast growth factor receptor 3 (FGFR3) extracellular domain (ECD), including native FGFR3 ECDs, variants, fragments, and fusion molecules, to a subject in an amount sufficient to promote hair growth.

Hair growth methods using FGFR3 extracellular domains

The present invention is directed to a method for treating a human patient for coronary artery disease, comprising administering into at least one coronary vessel of a human patient in need of treatment for coronary artery disease a safe and angiogenically effective dose of a recombinant FGF-5 of SEQ ID NO:9, or an angiogenically active fragment or mutein thereof. The invention is also directed to a method for inducing angiogenesis in the heart of a patient, comprising administering into at least one coronary vessel of a human patient in need of coronary angiogenesis a therapeutically effective amount of a recombinant FGF-5 of SEQ ID NO:9, or an angiogenically active fragment or mutein thereof.

Method of treating coronary artery disease by administering FGF-5

Use of FGFR1 extra cellular domain proteins to treat cancers characterized by ligand-dependent activating mutations in FGFR2

The present invention relates to a method of promoting hair growth comprising administering a fibroblast growth factor receptor 4 (FGFR4) extracellular domain (ECD), including native FGFR4 ECDs, variants, fragments, and fusion molecules, to a subject in an amount sufficient to promote hair growth.

Method of promoting hair growth using FGFR4 extracellular domains

The present invention has multiple aspects. In one aspect, the present invention is directed to a unit dose pharmaceutical composition comprising from about 5 ng/dose to less than 135,000 ng of an angiogenic agent, typically from 5 ng to 67,500 ng. Preferably, the angiogenic agent is FGF, more preferably it is basic FGF (FGF-2). In its second aspect, the present invention is directed to a method for inducing angiogenesis, or increasing myocardial perfusion or vascular density in a patient's heart, comprising administering directly into the myocardium in an area in need, as a single injection or a series of injections, a unit dose of an angiogenic agent. It is also within the scope of the present invention that a plurality of unit dose compositions be administered directly into the myocardium at a plurality of sites in need of angiogenesis. In another aspect, the present invention is directed to a method for treating a patient for coronary artery disease, comprising administering directly into the myocardium in an area of need of angiogenesis in said patient, a unit dose (i.e., from about 5 ng to less than 135,000 ng) of an angiogenic agent. In yet another aspect, the present invention is directed to a method for treating a patient for a myocardial infarction, comprising administering directly into the myocardium in an area in need of angiogenesis in said patient, a unit dose (i.e., from about 5 ng to less than 135,000 ng) of an angiogenic agent.

Method for inducing angiogenesis in a heart of a patient

The present invention has multiple aspects. In particular, in one aspect, the present invention is directed to a unit dose comprising 0.2 &#x3bc;g/kg to 36 &#x3bc;g/kg of a recombinant FGF or an angiogenically active fragment or mutein thereof. In another aspect, the present invention is directed to a pharmaceutical composition comprising an angiogenically effective dose of an FGF or an angiogenically active fragment or mutein thereof, and a pharmaceutically acceptable carrier. Typically, the angiogenically effective dose comprises 0.2 &#x3bc;g/kg to 36 &#x3bc;g/kg of an FGF of any one of SEQ ID NOS:1-3, 5, 8-10, or 12-14 or an angiogenically active fragment or mutein thereof. In yet another aspect, the present invention is directed to a method for treating a human patient for coronary artery disease, comprising administering into at least one coronary vessel of a human patient in need of treatment for coronary artery disease a safe and angiogenically effective dose of a recombinant FGF of any one of SEQ ID NOS:1-3, 5, 8-10, or 12-14, or an angiogenically active fragment or mutein thereof.

Angiogenically effective unit dose of FGF and method of administering

This invention relates to mouse and human EGFH2, and to variants thereof and to polynucleotides encoding EGFH2. This invention also relates to therapeutic agents related to the polynucleotides and proteins.

EGFH2 genes and gene products

Method for inducing angiogenesis or vascular perfusion in the myocardium comprising administering FGF-2

Method of treating coronary artery disease by administering FGF-4

This invention relates to compositions and uses of NRG4, and to variants thereof and to polynucleotides encoding NRG4, for therapeutic and diagnostic purposes, particularly related to colon and pancreatic cancer. This invention also relates to therapeutic agents based on or derived from the polynucleotides and proteins, NRG4 inhibitors, particularly antibodies capable of specifically binding to NRG4.

Use of NRG4, or inhibitors thereof, in the treatment of colon and pancreatic cancers

Antibodies to EGFH2 polypeptides

Compositions comprising keratinocyte growth factor (KGF) polypeptides and methods of using the same are described. The KGF polypeptides of the present invention display enhanced bioactivity relative to full-length KGF. Accordingly, the KGF polypeptides of the present invention may be used in compositions in lesser amounts than would be necessary using KGF.

KGF polypeptide compositions

This invention relates to human fibroblast growth factor (hFGF-21), and to variants thereof and to polynucleotides encoding FGF-21. The invention also relates to diagnostic and therapeutic agents related to the polynucleotides and proteins, including probes and antibodies, and to methods of treating liver disease such as cirrhosis and cancer, methods of treating conditions related to thymic function, and methods of treating conditions of the testis. The invention also relates to mouse fibroblast growth factor (mFGF-21), and to variants thereof and polynucleotides encoding mFGF-21.

Human FGF-21 polypeptides

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Mill Valley, CA, United States of America

W Michael Kavanaugh