The Scripps Research Institute

University of California

Emd Lexigen Research Center Corp.

Leland Stanford Junior University

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

Merck Patent Gesellschaft MIT Beschrankter Haftung

Amitech Therapeutic Solutions, Inc.

The Government of the United States of America

Peter Brooks

David A. Cheresh

David A Cheresh

Peter C Brooks

Laetitia Seguin

John Hood

Stephen D Gillies

Dale L Boger

Ralph A Reisfeld

Holger N Lode

Sudarshan Anand

Mark David Bednarski

Mayra Yebra

Brian Eliceiri

Maricel Gozo

Alfred Jonczyk

Lee Daniel Arnold

Horst Kessler

Guido Melzer

Eric A Murphy

Martin Friedlander

Gunter Holzemann

Beate Diefenbach

Brunhilde Felding-Habermann

Martin A Schwartz

Sunil J Advani

William B Kiosses

Steven A Silletti

Pamela L Schwartzberg

Jacqueline Lesperance

Gerhard Muller

Marion Gurrath

Mark Bednarski

Robert Paul

Pamela L 49/4A38 Schwartzberg

In alternative embodiments, provided are compositions and methods for treating, enhancing the drug sensitivity of, and preventing the formation of cancer stems cells, including preventing or slowing the development or generation of a beta-3 (&#x3b2;3)-expressing, or integrin &#x3b2;3 (ITG-B3)-expressing cancer or tumor cells. In alternative embodiments, provided are methods using histone acetyl transferase inhibitors and/or histone methyl transferase inhibitors to determine therapeutic values in cancer cells that induce an integrin &#x3b2;3 (ITGB3) polypeptide expression. In alternative embodiments, provided are kits, blister packages, lidded blisters or a blister card or packet, clamshells, trays or shrink wraps, comprising at least one compound, composition or formulation used to practice a method as provided herein, and at least one Growth Factor Inhibitor.

Methods for inhibiting alpha-v beta-3 expression on cancer stem cells and inhibiting progression to a cancer stem cell phenotype

In alternative embodiments, provided are products of manufacture, such as assays, chimeric nucleic acids and nucleic acid constructs, recombinant cells, and methods, comprising use of beta3-integrin (ITGB3) promoters operatively linked to a reporter, for drug screening, and in particular, screening for agents that inhibit cancer cell survival and metastasis. In alternative embodiments, compositions and methods as provided herein also can be used to identifying novel pathways that lead to acquired resistance, stemness, and anchorage independent growth; and characterizing distinct populations of cancer cells within a tumor microenvironment.

Compositions and methods for identifying anti cancer, anti-metastatic and anti-stress agents

In alternative embodiments, the invention provides compositions and methods for overcoming or diminishing or preventing Growth Factor Inhibitor resistance in a cell, or, a method for increasing the growth-inhibiting effectiveness of a Growth Factor inhibitor on a cell, or, a method for re-sensitizing a cell to a Growth Factor Inhibitor, comprising for example, administration of a combination of a TBK1 inhibitor and an RTK inhibitor. In alternative embodiments, the cell is a tumor cell, a cancer cell or a dysfunctional cell. In alternative embodiments, the invention provides compositions and methods for determining: whether an individual or a patient would benefit from or respond to administration of a Growth Factor Inhibitor, or, which individuals or patients would benefit from a combinatorial approach comprising administration of a combination of: at least one growth factor and at least one compound, composition or formulation used to practice a method of the invention, such as an NFKB inhibitor, such as a lenalidomide or a REVLIMID&#x2122;, or IKK inhibitor; or an inhibitor of Galectin-3.

Assays for screening for or identifying an agent or molecule that can block or inhibit AVB3 integrin from forming a complex with KRAS

Compositions and methods for treating cancer and diseases and conditions responsive to cell growth inhibition

The present invention is directed to methods and compositions for suppressing lymphangiogenesis, angiogenesis and/or tumor growth. The methods comprise contacting the tumor with a compound that (i) stabilizes a protein kinase in the inactive state and (ii) is not an ATP competitive inhibitor of the protein kinase in the active state.

Therapeutic methods and compositions involving allosteric kinase inhibition

In alternative embodiments, the invention provides compositions and methods comprising use of microRNAs and microRNA inhibitors to modulate blood vessel growth (angiogenesis), e.g., act as anti-angiogenic agents, and modulate cell and tumor microenvironment patterning, cancer cell and tumor growth and malignant disease (metastasis). In alternative embodiments, the invention provides compositions and methods that can sensitize blood vessels, e.g., tumor blood vessels, to radiation and agents and chemotherapies that cause DNA damage.

Micro-RNAs and micro-RNA inhibitors to modulate blood vessel growth, patterning, tumor growth and malignant disease and method for making and using them

The invention provides methods for treating tumors and tumor metastases in a mammal comprising administering, to a mammal in need of treatment, a therapeutic amount of an antagonist sufficient to inhibit angiogenesis in combination with a therapeutic amount of anti-tumor immunotherapeutic agent, such as a anti-tumor antigen antibody/cytokine fusion protein having a cytokine and a recombinant immunoglobulin polypeptide chain sufficient to elicit a cytokine-specific biological response.

Methods for treatment of tumors and metastases using a combination of anti-angiogenic and immuno therapies

&#x3b1;&#x3b2;Integrin receptor targeting liposomes comprise a cationic amphiphile such as a cationic lipid, a neutral lipid, and a targeting lipid. The targeting lipid includes a non-peptidic &#x3b1;&#x3b2;integrin antagonist.

Delivery system for nucleic acids

The present invention describes methods for inhibition angiogenesis in tissues using vitronectin &#x3b1;&#x3b2;antagonists, and particularly for inhibiting angiogenesis in inflamed tissues and in tumor tissues and metastases using therapeutic compositions containing &#x3b1;&#x3b2;antagonists.

Methods of treating neovascular glaucoma, macular degeneration and capillary proliferation with alphavbeta3-specific antibodies

The present invention describes methods for modulating angiogenesis in tissues using Src protein, modified Src protein, and nucleic acids encoding for such. Particularly the invention describes methods for inhibiting angiogenesis using an inactive Src protein, or nucleic acids encoding therefor, or for potentiating angiogenesis using an active Src protein, or nucleic acids encoding therefor. The invention also describes the use of gene delivery systems for providing nucleic acids encoding for the Src protein, or modified forms thereof.

Methods and compositions useful for modulation of angiogenesis using tyrosine kinase Src

Methods of inhibiting angiogenesis to treat cancer with alphavbeta3-specific antibodies

Angiogenesis, tumor growth, and metalloproteinase 2 (MMP2) interaction with integrin-&#x3b1;&#x3b2;are inhibited by an inhibitor compound of formula: wherein Gand Gare each independently &#x2014;NH&#x2014;C(O)&#x2014;O&#x2014;(CH)&#x2014;(CH)&#x2014;X; Yand Yare each independently &#x2014;OH or C-Calkoxy; Xand Xare each independently halo or C-Calkoxy; Xis fluoro, nitro, C-Calkyl, C-Calkoxy, or C-Cperfluoroalkyl; Z is &#x2014;C&#x2261;C&#x2014;, &#x2014;CH&#x2014;, cis-CH&#x2550;CH&#x2014;, trans-CH&#x2550;CH&#x2014;, cis-CH&#x2014;CH&#x2550;CH&#x2014;CH&#x2014;, trans-CH&#x2014;CH&#x2550;CH&#x2014;CH&#x2014;, 1,4-naphthyl, cis-1,3-cyclohexyl, trans-1,3-cyclohexyl, cis-1,4-cyclohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each 1; t is an integer having a value of 0 or 1; p and r are each 2, and v is 1; with the proviso that when A is H, t is 0, and when A is a covalent bond, t is 1.

Methods for inhibiting angiogenesis and tumor growth

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La Jolla, CA, United States of America

David A Cheresh