Osi Pharmaceuticals, Inc.

Oncogene Science, Inc.

John R Stephenson

J Gordon Foulkes

Christian Pieler

Franz E Leichtfried

Robert Franco

Kenneth K Iwata

Casey C Case

Leslie I Gold

Franz E Liechtfried

Ron Zeheb

Frederick H Reynolds, Jr

John M Sorvillo

Peter Ten Dijke

The present invention provides a method of transcriptionally modulating the expression of a gene of interest, the expression of which is associated with a defined physiological or pathological effect within a multicellular organism. The method comprises contacting a cell which is capable of expressing the gene with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell. Molecules useful in the practice of the invention are characterized as follows (a) do not naturally occur in the cell, (b) specifically transcriptionally modulate expression of the gene of interest, and (c) bind to DNA or RNA or bind to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell, the binding of a ligand to which ligand binding domain is normally associated with the defined physiological or pathological effect.

Methods of preparing compositions comprising chemicals capable of transcriptional modulators

This invention is directed to a chromatographically recovered polypeptide having the N-terminal amino acid sequence Ala-Leu-Asp-Thr-Asn-Tyr-Cys-Phe-Arg-Asn-Leu-Glu-Clu-Asn-Cys-Cys-Val. This polypeptide is known as TGI, TGI-1 and TGI-2. It is also referred to as TGF-&bgr;3. The invention is also directed to a compositions which comprises the chromatographically recovered polypeptide. The invention also provides a pharmaceutical compositions to inhibit the growth of epithelial cells or heal a wound or treat a burn consisting of the chromatographically recovered polypeptide. The invention is also directed to methods which comprise administering to a subject an effective amount of the chromatographically recovered so as to thereby inhibit the growth of epithelial cells, or heal the wound or treat the burn.

Tissue-derived tumor growth inhibitor

This invention is directed to a method of treating a burn or healing a wound in a mammal by administering a chromatographically recovered polypeptide having the N-terminal amino acid sequence Ala-Leu-Asp-Thr-Asn-Tyr-Cys-Phe-Arg-Asn-Leu-Glu-Glu-Asn-Cys-Cys-Val. This polypeptide is known as TGI, TGI-1 and TGI-2. It is also referred to as TGF-&bgr;3. The invention is also directed to a compositions which comprises the chromatographically recovered polypeptide. The invention also provides a pharmaceutical compositions to inhibit the growth of epithelial cells or heal a wound or treat a burn consisting of the chromatographically recovered polypeptide.

Tissue-derived tumor growth inhibitors, methods of preparation and uses thereof

The invention provides a recombinant nucleic acid vector comprising a nucleic acid encoding a polypeptide of 112 amino acids having the amino acid sequence shown in FIG. beginning with alanine at position 1 and ending with serine at position 112. The sequence of FIG. represents a member of the TGF-&bgr; family of tumor growth factors. The invention also provides a method for producing a protein which comprises culturing the host cell under conditions suitable to express the protein in the host cell and recovering the protein so produced.

The present invention provides a method of transcriptionally modulating the expression of a gene-of-interest. The method comprises contacting a cell which is capable of expressing the gene with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell. Molecules useful in the practice of the invention are characterized as follows (a) do not naturally occur in the cell, (b) bind to DNA or RNA or bind to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell. Additionally, this invention provides a method for determining whether a molecule known to be a modulator of protein biosynthesis is capable of transcriptionally modulating expression of a gene-of-interest.

Methods of discovering chemicals capable of functioning as gene expression modulators

The present invention provides a method of transcriptionally modulating the expression of a gene encoding a protein of interest, the expression of which gene is associated with the production in cell culture of a protein encoded by the gene, which comprises contacting a cell, which is capable of expressing the gene, with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell in culture, which molecule (a) does not naturally occur in the cell and (b) directly transcriptionally modulates expression of the gene.

Methods of preparing compositions comprising chemicals capable of transcriptional modulation

The present invention provides a method of transcriptionally modulating the expression of a gene encoding a protein of interest, the expression of which gene is associated with the production in cell culture of a protein encoded by the gene, which comprises contacting a cell, which is capable of expressing the gene, with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell in culture, which molecule (a) directly transcriptionally modulates expression of the gene.

Methods of transcriptionally modulating expression of viral genes and

Methods of specifically transcriptionally modulating the expression of

Immunoassay for detection of mutant P53 polypeptide in serum

Methods of transcriptionally modulating gene expression and of

The invention provided for a method of transcriptionally modulating the expression of a gene encoding a protein of interest associated with treatment of one or more symptoms of a cardiovascular disease. Further provided is a method of determining whether a molecule not previously known to be a modulator of protein biosynthesis is capable of directly and specifically transcriptionally modulating the expression of a gene encoding a protein of interest associated with treatment of one or more symptoms of a cardiovascular disease. Screening methods, including methods of essentially simultaneously screening molecules to determine whether the molecules are capable of directly and specifically transcriptionally modulating one or more genes encoding proteins of interest associated with treatment of one or more symptoms of a cardiovascular disease, are also provided.

Methods of determining chemicals that modulate expression of genes

Methods of transcriptionally modulating gene expression

Method of discovering chemicals capable of functioning as gene

The invention provided for a method of directly and specifically transcriptionally modulating the expression of a gene encoding a protein of interest associated with treatment of one or more symptoms of a cardiovascular disease such as atherosclerosis, restenosis or hypertension. Further provided is a method of determining whether a molecule not previously known to be a modulator of protein biosynthesis is capable of directly and specifically transcriptionally modulating the expression of a gene encoding a protein of interest associated with treatment of one or more symptoms of a cardiovascular disease. Lastly, the invention provides a method of directly and specifically transcriptionally modulating in a human being the expression of a gene encoding a protein of interest associated with treatment of one or more symptoms of a cardiovascular disease, thus ameliorating the disease.

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Rockville Centre, NY, United States of America

John R Stephenson