National Institutes of Health, Public Health Service, HHS.
The inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected Start Printed Page 34019inventions to extend market coverage for companies and may also be available for licensing.
Licensing information and copies of the U.S. patent applications listed below may be obtained by writing to the indicated licensing contact at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.
Synthetic Macrolides Inhibit Breast Cancer Migration
Description of Technology: This technology relates to the synthesis of several novel macrocylic compounds (macrolides), built upon a quinic acid-containing scaffold, which are potent inhibitors of tumor cell migration. Specifically, the new molecules have been shown to inhibit breast cancer cell migration in vitro.
Tumor metastasis or cell migration is a multi-step process in which primary tumor cells spread or migrate by invading adjacent tissues and/or metastasizing to distance sites. Thus, one approach to cancer treatment may be the inhibition of tumor migration. The initial observation that migrastatin, a macrolide natural product first isolated from a Streptomycete, inhibits tumor cell migration gave rise to the synthesis of the analogs with increased potency and tumor cell selectivity reported here.
Applications: These compounds may be the basis for new antimetastatic and antiangiogenic drugs. Some of the novel macrolides that have been designed and synthesized, inhibit tumor cell migration with low nanomolar to sub-micromolar IC50 values via a mechanism that appears to be similar to that of migrastatin and its analogs. The synthetic protocol used is straight forward and relatively high yielding, and has the potential to be further simplified.
The new compounds and methods may be used to treat a pathologic condition that may be ameliorated by inhibiting or decreasing cell migration or metastasis, to decrease anchorage-dependent growth of tumor cells, or to treat any pathologic condition characterized by neovascularization.
Advantages: The new molecules have been shown to inhibit breast cancer cell migration in vitro. Breast cancer is the most common female cancer in the United States, the second most common cause of death in women and the main cause of death in women ages 45 to 55. Despite early diagnosis and treatment, recurrence of the cancer including distant tumor growth or metastases is common. Accordingly, there is a need for compounds, such as those described in this invention, that inhibit cell migration and angiogenesis.
Development Status: Synthesis of several analogs has been carried out; Migration of breast cancer cells has been demonstrated to be inhibited in vitro at sub-micromolar IC50 values; The lead compound has been demonstrated not to be cytotoxic at levels up to 100 micromolar; Scaled up synthesis of the most potent macrolide is presently being scaled up to unable for future testing in a mouse model of breast cancer.
Inventors: Dr. Carole Bewley (NIDDK), Dr. Belhu B. Metaferia (NIDDK).
Publication: BB Metaferia, L Chen, HL Baker, XY Huang, CA Bewley. Synthetic macrolides that inhibit breast cancer cell migration in vitro. J Am Chem Soc. 2007 Mar 7;129(9):2434-2435. Epub 2007 Feb 13, doi 10.1021/ja068538d.
Patent Status: U.S. Provisional Application No. 60/900,151 filed 07 Feb 2007 (HHS Reference No. E-098-2007/0-US-01).
Licensing Status: Available for exclusive or non-exclusive licensing.
Licensing Contact: Michelle Booden, Ph.D.; 301/451-7337; email@example.com.
Collaborative Research Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, is seeking parties interested in collaborative research to develop larger scale syntheses of the most potent macrolides and/or analogs thereof, and the conduct toxicology and other efficacy studies related to these macrolides. Please contact Dr. Carole Bewley at firstname.lastname@example.org or Rochelle S. Blaustein at Rochelle.Blaustein@nih.gov for more information.
Immunotoxin With In-Vivo T Cell Suppressant Activity
Description of Invention: The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of autoimmune diseases and T cell malignancies. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of malignant T cells and resting T cells. The transient ablation of resting T cells can “reset” the immune system by accentuating tolerizing responses. The toxin portion of the immunotoxin is genetically engineered to maintain bioactivity when recombinantly produced in Pichia pastoris. Data are available in transgenic animals expressing human CD3ε which supports the effects of the immunotoxin against T cells.
Applications: Treatment of autoimmune diseases such as multiple sclerosis, lupus, type I diabetes, aplastic anemia; Treatment of T cell leukemias and lymphomas such as cutaneous T cell leukemia/lymphoma (CTCL).
Advantages: Specificity of the immunotoxin avoids the killing of non-T cells, reducing side-effects associated with other mechanisms of treatment (e.g., radiation and cyclophosphamide) such as infection and induced malignancy; A GMP production process has already been successfully implemented, and patient doses are available; All testing required for an FDA issued IND has been completed, allowing faster evaluation of the efficacy of the invention.
Benefits: New methods and compositions with limited side-effects have the potential to revolutionize treatment of autoimmune disease; provides an opportunity to capture a significant market share for the millions of people who suffer from an autoimmune disease.
Inventors: David Neville et al. (NIMH).
Patent Status: U.S. Patent No. 5,167,956 issued 01 Dec 1992 (HHS Reference No. E-012-1991/0-US-01); U.S. Patent No. 5,725,857 issued 10 Mar 1998 (HHS Reference No. E-012-1991/2-US-01); U.S. Patent No. 6,632,928 issued 14 Oct 2003 (HHS Reference No. E-044-1997/0-US-07); U.S. Patent Application No. 10/435,567 filed 09 May 2003, which published as 2003/0185825 on 02 Oct 2003 (HHS Reference No. E-044-1997/0-US-08); U.S. Patent Application No. 10/296,085 filed 18 Nov 2002, which published as 2004/0127682 on 01 Jul 2004 (HHS Reference No. E-044-1997/1-US-06); Foreign rights are also available
Licensing Status: Available for exclusive or non-exclusive licensing.
Licensing Contact: David A. Lambertson, Ph.D.; 301/435-4632; email@example.com.
Collaborative Research Opportunity: The National Institute of Mental Health, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods of using the immunotoxins for the treatment of autoimmune diseases and T cell malignancies. Please contact David Neville at firstname.lastname@example.org for more information.Start Signature
Dated: June 13, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer,Office of Technology Transfer,National Institutes of Health.
[FR Doc. E7-11824 Filed 6-19-07; 8:45 am]
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