[Federal Register Volume 72, Number 118 (Wednesday, June 20, 2007)]
[Notices]
[Pages 34018-34020]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-11824]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: 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

[[Page 34019]]

inventions to extend market coverage for companies and may also be 
available for licensing.

ADDRESSES: 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 protected].
    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 
[email protected] or Rochelle S. Blaustein at 
[email protected] 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 CD3[epsi] 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 protected].
    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 [email protected] 
for more information.


[[Page 34020]]


    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]
BILLING CODE 4140-01-P