The State University of New York

Innapharma, Inc.

Slh Innovations LLC

Other

Matthew R Pincus

Josef Michl

Joseph J Hlavka

Andrew S Kende

Henry B Abajian

Jonathan L Miller

Vicki A Lyle

John Fowler Noble

Clara N Finch

David Cunningham

Ehsan Sarafraz-Yazdi

Harry Mukerjee

Jesko Koehnke

The invention relates to novel peptides having an HDM-2 targeting sequence that target the human minute binding protein-2. The invention also relates to fusion proteins comprising a HDM-2 targeting sequence. The invention also relates to methods of using the peptides to treat cancer.

Methods for treating cancer

Peptides having a human minute binding protein-2 (HDM-2) targeting sequence that target the human minute binding protein-2, fusion proteins having a HDM-2 targeting sequence, and methods of using the peptides and proteins to treat cancer are described.

Peptides having a human minute binding protein-2 (HDM-2) targeting sequence are capable of targeting the human minute binding protein-2. Peptides having an HDM-2 targeting sequence may be used to treat cancer.

Provided are novel peptides having a human minute binding protein-2 (HDM-2) targeting sequence that target the human minute binding protein-2. Also provided are fusion proteins comprising an HDM-2 targeting sequence. Also provided are methods of using the peptides to treat cancer.

Peptides for treating cancer

A method of treating cancer in a subject, including: providing a subject having a plurality of cancer cells; and administering to the subject, a therapeutically effective amount of a composition including: an HDM-2 binding component; and a membrane resident component, the membrane resident component bound to the HDM-2 binding component. Also provided are a method of selectively necrosing cancer cells, a method of causing membranolysis in cancer cells, and a cancer treatment composition.

Small molecule cancer treatments that cause necrosis in cancer cells but do not affect normal cells

The present invention provides peptides (including analogs and derivatives thereof) corresponding to residues 96-110 and 35-47 of ras-p21, which peptides have attached thereto a membrane-penetrating leader sequence. The subject peptides, analogs and derivatives thereof are useful in treatment of cancers and have been shown to induce phenotypic reversion of pancreatic cancer cells to non-cancerous cells. Pharmaceutical compositions comprising one or more subject peptides are also provided by the present invention. The present invention further provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence and a nucleotide sequence encoding a subject peptide. Methods of treating cancer by administering one or more subject peptides, pharmaceutical compositions, and/or AdV vectors are also provided.

Phenotypic reversion of pancreatic carcinoma cells

An aspect of the invention provides a method of selectively necrosing cells, comprising: providing a plurality cells, including at least one cancer cell and at least one non-cancerous cell; and administering to the cells a compound, including an HDM-2 targeting component and a cytotoxic component attached to the HDM-2 targeting component, wherein said compound comprises a membrane-active form.

Membrane resident peptide in anti-cancer peptides causes tumor cell necrosis rather than apoptosis of cancer cells

The present invention provides peptides corresponding to all or a portion of amino acid residues 12-26 of human p53 protein, which peptides are lethal to malignant or transformed cells when fused to a membrane-penetrating leader sequence. The subject peptides are thus useful in treating neoplastic disease in an animal, preferably a human. Also provided are pharmaceutical compositions comprising the subject peptides admixed with a pharmaceutical acceptable carrier. Methods of treating neoplastic disease in a patient by administering a subject peptide fused at its carboxy terminal end to a membrane penetrating leader sequence are also provided. The present invention also provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence operably linked to a nucleotide sequence encoding a subject peptide. Methods of selectively killing cancer cells in a subject by administering a therapeutically effective amount of a subject AdV vector are also provided by the present invention.

Peptides selectively lethal to malignant and transformed mammalian cells

The present invention provides peptides corresponding to all or a portion of amino acid residues 12-26 of human p53 protein. When fused to a membrane-penetrating leader sequence, the peptides are either lethal to malignant or transformed cells or else cause reversion to the untransformed morphological phenotype. The subject peptides are thus useful in treating neoplastic disease in an animal, preferably a human. Also provided are pharmaceutical compositions comprising the subject peptides admixed with a pharmaceutical acceptable carrier. Methods of treating neoplastic disease in a patient by administering a subject peptide are also provided.

The present invention provides peptides corresponding to all or a portion of amino acid residues 12-26 of human p53 protein, which peptides are lethal to malignant or transformed cells when fused to a membrane-penetrating leader sequence. The subject peptides are thus useful in treating neoplastic disease in an animal, preferably a human. Also provided are pharmaceutical compositions comprising the subject peptides admixed with a pharmaceutical acceptable carrier. Methods of treating neoplastic disease in a patient by administering a subject peptide fused at its carboxy terminal end to a membrane-penetrating leader sequence are also provided.

This invention provides peptidomimetics which bind to T4 or CD4 cell receptors and are useful in inhibiting viral infectivity by viruses which bind to T4 cell receptors. More specifically, peptidomimetics of this invention can alleviate symptoms of AIDS by inhibiting binding of HIV, the virus associated with AIDS, to receptor sites in human cells susceptible to HIV infection. These peptidomimetics, in particular, inhibit binding of HIV to cells of brain membrane and the immune system. They also display substantially longer half-lives in vivo than peptide T. The compounds of this invention which bind to T4 or CD4 receptors and thereby inhibit binding of HIV, alone or in combination with one another, can be used to alleviate AIDS symptoms and ameliorate symptoms of HIV infection, especially neuronal dementias and Kaposi's sarcoma. The compounds of this invention, alone or in combination, can further be used to prevent development of AIDS in persons who might become exposed to HIV.

Peptidomimetics for the treatment of HIV infection

The present invention provides peptides, cyclized peptides and peptidomimetics which inhibit the oncogenic and/or transforming activity of the p21 ras protein, pharmaceutical compositions containing at least one of the ras-inhibiting peptides, cyclized peptides and peptidomimetics, and methods for inhibiting the ras-mediated oncogenic and/or transformation process in mammalian cells or tissues.

Peptidomimetics inhibiting the oncogenic action of p21 ras

The present invention provides peptides and cyclized peptides which inhibit the oncogenic and/or transforming activity of the p21 ras protein, pharmaceutical compositions containing at least one of the ras-inhibiting peptides, cyclized peptides and peptidomimetics, and methods for inhibiting the ras-mediated oncogenic and/or transformation process in mammalian cells or tissues.

Peptides inhibiting the oncogenic action of p21 ras

The subject invention provides purified polypeptides encoded by naturally-occurring wild-type platelet glycoprotein Ib alpha having a mutation which renders the polypeptide more reactive with yon Willebrand factor. Preferably, the mutation is in the hinge region of GP Ib.alpha., such as the substitution of valine for glycine at residue 233. These mutations alter the three-dimensional structure of the mutant polypeptide from a beta bend conformation to an alpha helix formation, and also create an amphipathic region within the mutant polypeptide. DNA encoding the mutant polypeptides, as well as expression systems for the production of the mutant polypeptides, are also provided. Methods and compositions using the mutant polypeptides and DNA oligomers complementary to the mutant polypeptides are further provided.

Mutations in the gene encoding the alpha chain of platelet glycoprotein

The subject invention provides purified polypeptides encoded by naturally-occurring wild-type platelet glycoprotein Ib alpha having a mutation which renders the polypeptide more reactive with von Willebrand factor. Preferably, the mutation is in the hinge region of GP Ib.alpha., such as the substitution of valine for glycine at residue 233. These mutations alter the three-dimensional structure of the mutant polypeptide from a beta bend conformation to an alpha helix formation, and also create an amphipathic region within the mutant polypeptide. DNA encoding the mutant polypeptides, as well as expression systems for the production of the mutant polypeptides, are also provided. Methods and compositions using the mutant polypeptides and DNA oligomers complementary to the mutant polypeptides are further provided.

Growing community of inventors

Brooklyn, NY, United States of America

Matthew R Pincus