National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Department of Health

University of Massachusetts

St. Vincent's Institute of Medical Research

The Whittier Institute for Diabetes & Endocrinology

Whittler Institute for Diabetes and Endocrinology

The United States of America, Represented by the Secretary, U.S. Department of Commerce

Kay, Brian K.

Weisblum, Bernard

Jeffrey S Rubin

Stuart A Aaronson

Paul W Finch

Susan Cumberledge

Frieda Reichsman

Aykut Üren

Donald P Bottaro

Aykut Uren

Andrew M L Chan

Gillian M Beattie

Alberto Hayek

Nicole Joy Horwood

Matthew Todd Gillespie

Xi He

Brian K Kay

Bernard Weisblum

Vito Quaranta

Paul T Wingfield

Andrew M-l Chan

Timo P Otonkoski

Timo Pyry Otonkoski

Stephen J Stahl

Vittoria Cioce

Andrew M-L Chan

The invention stems from the discovery that sFRP and fragments thereof can bind to members of the Wnt family of proteins and cause an increase in Wnt biological activity. Furthermore, fragments of sFRP that do not contain the CRD domain are shown to bind to Wnt proteins and modulate Wnt biological activity. Accordingly, the invention provides these sFRP fragments and variants of these fragments, as well as vectors and host cells containing nucleic acid sequences encoding the sFRP fragments and variants.

Methods of use of fragments of secreted frizzled related protein, sFRP

This disclosure relates to a peptide motif and proteins containing the motif that are capable of binding to secreted Frizzled-related protein family members. Accordingly, the disclosure also includes methods of regulating the interaction of sFRP-1 with proteins containing the motif.

sFRP and peptide motifs that interact with sFRP and methods of their use

Fragments of secreted frizzled related protein

Secreted frizzled related protein, sFRP, fragments and methods of use thereof

The present invention relates to a novel truncated form of heptocyte growth factor (HGF) which specifically antagonizes the activity of HGF and to a novel truncated form of HGF that is a partial HGF agonist. In particular, the present invention relates to the purification, molecular cloning, recombinant expression of the truncated HGF variants and related pharmaceutical compositions. The present invention further relates to the utilization of the small HGF variants to either inhibit HGF mitogenesis or stimulate HGF mitogenesis in cells expressing the receptor for HGF.

Truncated hepatocyte growth factor variant protein HGF/NK2

SFRP and peptide motifs that interact with SFRP and methods of their use

Secreted frizzled related protein fragments

The invention provides a novel, secreted protein that contains a region homologous to ligand binding domain of a cytokine receptor. This protein, called Frizzled-related protein (FRP), antagonizes the signaling of the Wnt family of cytokines. Extracellular signaling molecules such as the Wnt family members have essential roles as inducers of cellular proliferation, migration, differentiation, and tissue morphogenesis. As Wnt molecules are known to participate in the aberrant growth associated with neoplasia, Wnt antagonists such as FRP are valuable tools which both for understanding oncogenesis and for the design of new cancer therapies.

Human FRP and fragments thereof including methods for using them

Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.

Epithelial cell specific growth factor, keratinocyte growth factor (KGF)

Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used sucessfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.

Method of stimulating epithelial cells using keratinocyte growth factor (KGF) and method of inhibiting KGF activity

Disccoveries are disclosed that show particular aspects of recombinant DNA technology can be used sucessfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.

DNA encoding a growth factor specific for epithelial cells

The present invention relates to a novel truncated forms of hepatocyte growth factor (HGF) which specifically antagonizes the activity of HGF and to a novel truncated form of HGF that is a partial HGF agonist. In particular, the present invention relates to the purification, molecular cloning, recombinant expression of the truncated HGF variants and related pharmaceutical compositions. The present invention further relates to the utilization of the small HGF variants to either inhibit HGF mitogenesis or stimulate HGF mitogenesis in cells expressing the receptor for HGF.

DNA encoding truncated hepatocyte growth factor variants

Polynucleotides encoding human FRP and fragments thereof

Growing community of inventors

Potomac, MD, United States of America

Jeffrey S Rubin