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Patent
Temple University and Onconova Therapeutics, Inc. | Date: 2017-03-08

Substituted phenol derivatives of Formula I:


Patent
Onconova Therapeutics, Inc. | Date: 2015-05-15

An aqueous pharmaceutical solution composition comprising between about 20 mg/ml to about 100 mg/ml of a radioprotective ,-unsaturated aryl sulfone, a cosolvent comprising polyethylene glycol (PEG), polypropylene glycol, polyglycerol, DMA, propylene glycol, glycerol, ethanol, sorbitol, isopropyl alcohol, or a combination thereof in an amount between about 25% and about 90% w/v, and a water soluble Vitamin E derivative, wherein the composition has a pH within the range of about 7.0 to about 9.5.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 275.86K | Year: 2011

DESCRIPTION (provided by applicant): The recent success of imatinib for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia has made tyrosine and serine/threonine kinases as major targets for cancer therapy. Currently, since only a small fraction of the human kinome has been targeted by reasonably selective and potent inhibitors, there is an urgent need to develop strategies for efficient discovery and optimization of new inhibitors. Towards this goal, we have recently developeda compound library of candidate ATP-competitive kinase inhibitors. We screened our collection of novel small molecules (approximately 2,000) against a panel of 16 cultured tumor cell lines for the ability to induce cell death. This search revealed one compound, ON 1231320, with remarkable cytotoxicity against the entire panel of 16 tumor cell lines. Kinase inhibition assays against a panel of 285 kinases revealed that this compound had a remarkable specificity towards Polo-like kinase 2 (Plk2 or Snk), a kinase involved in centrosome duplication and mitotic progression. As expected, tumor cells treated with ON 1231320 arrest in mitosis due to abnormal microtubule spindle development. Plk2 has recently been implicated as one of the kinases that links cellularmetabolism to the cell cycle. Mitochondrial dysfunction, with resulting increased dependence on glycolysis, is frequently observed in cancer cells (known as the Warburg effect). Identification of pathways that promote cell survival under conditions of mitochondrial dysfunction has therapeutic implications. In a recent study, it has been shown that targeted ablation of the SCO2 gene in HCT116 human colon cancer cell line results in the ablation of mitochondrial respiration and that PLK2 is the most highly expressed gene in SCO2-/-cells. Furthermore, even a modest reduction in Plk2 levels in human cancer cells with defects in mitochondrial respiration results in the elimination of their ability to form xenografts in mice. In this proposal, we plan to furtherexamine this potent and selective Plk2 inhibitor in order to determine important chemical characteristics and biological activity necessary for advanced pre-clinical development. We propose to study the effects of this compound on tumor growth in vitro andin vivo to determine how ON 1231320 will serve as a novel cancer chemotherapeutic. The aims of this proposal are to: (1) Prepare an optimal formulation of ON 1231320 for stability and parenteral delivery; (2) Characterize the pharmacokinetic and pharmacodynamic properties of ON 1231320 in non-tumor and tumor-bearing mice; and (3) Evaluate anti-tumor efficacy of ON 01231320, determine the degree of inhibition of Plk2 required for inhibition of human tumor growth in xenograft models, and assess how ON 1231320 doses and schedules are related to the anti-tumor activity of the compound. PUBLIC HEALTH RELEVANCE: This application describes the discovery of a novel cancer therapeutic, ON 1231320, which could find a wide application in the treatment of someof the most difficult-to-treat cancers that are traditionally resistant to chemotherapy. ON 1231320 has a unique and targeted anti-cancer mechanism of action. In this application, we propose to develop optimal formulation, preclinical pharmacology, and anti-cancer efficacy profiles for ON 1231320 in preparation for a Phase I study in cancer patients.


The invention discloses a diagnostic method for predicting the therapeutic efficacy of a broad specificity kinase inhibitor in a subject with refractory cancer comprising determining the locus-specific DNA methylation profile of the subject, wherein the locus-specific DNA methylation profile predicts the therapeutic efficacy of a broad specificity kinase inhibitor for treatment of a subject with refractory cancer.


Patent
Onconova Therapeutics, Inc. | Date: 2011-03-24

The present invention provides compositions and methods for promoting rapid healing and/or regeneration of damaged tissue resulting from a wound comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound of (E)-4-carboxystyryl-4-chlorobenzylsulfone, or a functional derivative thereof, and a pharmaceutically acceptable excipient.


Patent
Onconova Therapeutics, Inc. | Date: 2011-03-24

An aqueous pharmaceutical solution composition comprising between about 20 mg/ml to about 100 mg/ml of a radioprotective ,-unsaturated aryl sulfone, a cosolvent comprising polyethylene glycol (PEG), polypropylene glycol, polyglycerol, DMA, propylene glycol, glycerol, ethanol, sorbitol, isopropyl alcohol, or a combination thereof in an amount between about 25% and about 90% w/v, and a water soluble Vitamin E derivative, wherein the composition has a pH within the range of about 7.0 to about 9.5.


Patent
Onconova Therapeutics, Inc. | Date: 2015-04-29

Solution and suspension formulations are provided for administration prior to or after exposure to ionizing radiation for reducing toxic effects of the radiation in a subject which comprises an effective amount of at least one radioprotective , unsaturated aryl sulfone wherein the composition has a pH within the range of about 8 to about 9.


Patent
Onconova Therapeutics, Inc. | Date: 2014-08-27

Solution and suspension formulations are provided for administration prior to or after exposure to ionizing radiation for reducing toxic effects of the radiation in a subject which comprises an effective amount of at least one radioprotective , unsaturated aryl sulfone wherein the composition has a pH within the range of about 8 to about 9.


Patent
Onconova Therapeutics, Inc. and Columbia University | Date: 2013-12-06

The invention discloses a method of treating cancer refractory to an anticancer agent comprising administering to a cancer patient a pharmaceutical composition comprising at least one compound of Formula 1 Where R_(1 )is selected from the group consisting of NH_(2), NHCH_(2)COOH, NHCH(CH_(3))COOH, NHC(CH_(3))_(2)COOH, NHCH_(2)CH_(2)OH and N(CH_(2)CH_(2)OH)_(2 )or a pharmaceutically acceptable salt of such a compound, and an anticancer agent.


News Article | March 1, 2017
Site: globenewswire.com

HAMPTON, N.J., March 01, 2017 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (NASDAQ:CLDX) today announced the appointment of James J. Marino, J.D., to the Company’s Board of Directors. Mr. Marino was with the global law firm of Dechert LLP for 28 years, where he served as Managing Partner of the Princeton, N.J. office. His practice focused on the representation of leading life sciences companies, both privately- and publicly-held, in a broad range of corporate, transactional and finance matters. He will serve as the Chairman of the Compensation Committee. “Jim’s wealth of experience advising numerous life science companies provides us additional perspective on the current healthcare business environment,” said Larry Ellberger, Chairman of the Board of Directors at Celldex Therapeutics. “His knowledge and guidance will be important to Celldex as we advance our pipeline through clinical development and explore multi-drug combinations to address unmet patient needs.” Mr. Marino currently serves on the Board of Trustees of Wake Forest University and Wake Forest University Baptist Medical Center and on the Board of Directors of Onconova Therapeutics, Inc. He previously served on the Board of Directors of Pharmacopeia, Inc. He has also worked in advisory capacities and on the boards of multiple non-profit organizations, including Robert Wood Johnson University Hospital. Additionally, Mr. Marino is a co-founder of BioNJ, the trade association of biotechnology companies based in New Jersey, which he represented from its inception. Mr. Marino received his B.A., his M.B.A. and his J.D. from Rutgers University. About Celldex Therapeutics, Inc. Celldex is developing targeted therapeutics to address devastating diseases for which available treatments are inadequate. Our pipeline is built from a proprietary portfolio of antibodies and immunomodulators used alone and in strategic combinations to create novel, disease-specific therapies that induce, enhance or suppress the body's immune response. Visit www.celldex.com. Forward Looking Statements This release contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including those related to the Company's strategic focus and the future development and commercialization of our drug candidates and our future goals. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct or that those goals will be achieved, and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, our ability to successfully complete research and further development and commercialization of our drug candidates; our ability to obtain additional capital to meet our long-term liquidity needs on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials that we have initiated or plan to initiate; our ability to successfully integrate our and the recently acquired business of Kolltan Pharmaceuticals, and to operate the combined businesses efficiently; our ability to realize the anticipated benefits from the acquisition of Kolltan; the uncertainties inherent in clinical testing and accruing patients for clinical trials; our limited experience in bringing programs through Phase 3 clinical trials; our ability to manage and successfully complete multiple clinical trials and the research and development efforts for our multiple products at varying stages of development; the availability, cost, delivery and quality of clinical and commercial grade materials produced by our own manufacturing facility or supplied by contract manufacturers, who may be our sole source of supply; the timing, cost and uncertainty of obtaining regulatory approvals; the failure of the market for the Company's programs to continue to develop; our ability to protect the Company's intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company's products; and other factors listed under "Risk Factors" in our annual report on Form 10-K and quarterly reports on Form 10-Q. All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. We have no obligation, and expressly disclaim any obligation, to update, revise or correct any of the forward-looking statements, whether as a result of new information, future events or otherwise.

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