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

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Icahn School of Medicine at Mount Sinai

The United States of America As Represented by the Secretary of

The United States of America

Stuart A Aaronson

Jeffrey S Rubin

Paul W Finch

Matthias H Kraus

Jacalyn H Pierce

Donald P Bottaro

William J Larochelle

Toshimitsu Matsui

C Richter King

Roy A Jensen

Andrew M L Chan

Toru Miki

Xi He

Andrew M-l Chan

Albino Troilo

George F Vande Woude

Paul T Wingfield

Donna Faletto

Olaf Dirsch

Davide Esposito

Anna Bafico

Stephen J Stahl

John F Beeler

Toshio Ishibashi

Gary D Kruh

Vittoria Cioce

Jeffery S Rubin

Erica K Benson

Andrew Chan

Juan C Lacal

The present invention relates to methods of treating a tumor or treating cancer in a subject having a p53 DNA contact mutation that involve administering, to the subject, a ROCK inhibitor. Also disclosed is a method of identifying a subject as a candidate for such treatment.

Methods of treating tumors and cancer, and identifying candidate subjects for such treatment

The present invention relates to a method of treating a tumor in a subject. This method involves administering to a subject having a Hippo pathway mutant tumor a tankyrase inhibitor, where the tumor is susceptible to treatment with the tankyrase inhibitor, and said administering is carried out to treat the tumor. The present invention also relates to a method of treating cancer in a subject, and a method of identifying a subject as a candidate for treatment.

Treatment of hippo pathway mutant tumors and methods of identifying subjects as candidates for treatment

The present invention relates to compounds and methods for treating cancers in which the autocrine Wnt canonical signaling pathway is activated. In particular, there is provided a method for inhibiting growth of a tumor cell or sensitizing a cancer cell to treatment by contacting such a tumor cell with a compound that alters Wnt signaling. The compound that alters Wnt signaling can be a Wnt antagonist, a Wnt receptor antagonist, or a combination thereof.

Compositions and methods for altering Wnt autocrine signaling

The isolation, cloning and characterization of a human gene related to but distinct from EGF receptor gene has been described. Nucleotide sequence of the gene and amino acid sequence of the polypeptide encoded by the gene have been determined. The use of the nucleic acid probes and antibodies having specific binding affinity with said polypeptide for diagnostic and therapeutic purposes have also been described.

Human gene related to but distinct from EGF receptor gene

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

A DNA sequence which encodes a human type &#x3b1; platelet derived growth factor receptor protein which preferentially binds to the AA homodimer and AB heterodimer forms of platelet derived growth factor and also binds the BB homodimer at high affinity, is described. Substantially pure human a platelet derived growth factor receptor protein and methods for recombinantly producing human &#x3b1; platelet derived growth factor receptor protein are also described.

Compositions of alpha platelet derived growth factor receptor nucleic acid and protein and method of making

Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce a hitherto unknown type of human Platelet-Derived Growth Factor (PDGF) receptor protein free of other PDGF receptors. These proteins can be produced from DNA segments in cells in various functional forms. These forms variously enable biochemical and functional studies of these novel receptors as well as production of antibodies. Means are described for determining the level of expression of genes for specific types of PDGF receptor proteins, for example, by measuring mRNA in cells with PDGF receptor type-specific DNA probes or by measuring antigen in biological samples with type-specific antibodies.

Methods for identifying alpha PDGFR agonists and antagonists

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

Antibodies for the alpha platelet-derived growth factor receptor

The isolation, cloning and characterization of a human gene related to but distinct from the EGF receptor gene has been described. Nucleotide sequence of the gene and amino acid sequence of the polypeptide encoded by the gene have been determined. The use of the nucleic acid probes and antibodies having specific binding affinity with said polypeptide for diagnostic and therapeutic purposes has also been described.

Anti-erbB-2 antibodies to human receptor related to but distinct from EGF receptor

A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest homology of 64% and 67% to a contiguous region within the tyrosine kinase domains of the EGFR and erbB-2 proteins, respectively. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was mapped to human chromosome 12q11-13 and was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180 .

erbB-3 nucleic acids

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.

Growing community of inventors

Great Falls, VA, United States of America

Stuart A Aaronson