[Federal Register Volume 72, Number 167 (Wednesday, August 29, 2007)]
[Notices]
[Pages 49724-49726]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-16929]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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 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.

Collagen-Induced Platelet Aggregation Inhibitor From Mosquito Salivary 
Glands

    Description of Technology: Exposed collagen in injured blood 
vessels provides a substrate for platelets to adhere and aggregate 
initiating the first step in thrombosis, the formation of blood clots 
inside a blood vessel. Despite the essential role of platelets in 
vascular injury, excessive platelet aggregation may also result in 
thrombotic diseases such as stroke and heart attack.
    Available for licensing is a collagen binding protein, named 
aegyptin, which selectively inhibits collagen-platelet aggregation, but 
not platelet aggregation induced by other agonists. Collagen initiates 
recruitment of circulating platelets and triggers platelet activation. 
Collagen also plays a critical role in angiogenesis. Aegyptin blocks 
the interaction of collagen with its major ligands, von Willebrand 
factor, glycoprotein VI (GPVI), and integrin [alpha]2[beta]1. These 
three ligands are of particular importance because von Willebrand 
factor plays a critical role in tethering platelets to collagen, GPVI 
is the major signaling platelet receptor, and integrin [alpha]2[beta]1 
mediates platelet adhesion and contributes to activation. Since these 
ligands play a critical role in the early stages of thrombus formation, 
aegyptin represents a potentially highly effective therapeutic that can 
prevent and treat patients with thrombotic disease. Alternatively, 
aegyptin is potentially useful in conditions where collagen plays a 
critical role in angiogenesis or in conditions where excessive 
deposition of collagen plays a pathological role (e.g. pancreatic 
carcinoma).
    Applications:
    Adjuvant to ``Clot busting'' therapeutics.
    Method to prevent and/or treat cardiovascular/thrombotic disease.
    Method to treat patients undergoing invasive cardiovascular 
procedures ( e.g. angioplasty).
    Model to study collagen-dependent platelet aggregation or collagen-
mediated angiogenesis.
    Advantages:
    Highly effective therapeutics can negatively modulate thrombosis in 
its early stages by preventing collagen interaction with three major 
ligands involved in thrombus/clot formation.
    Aegyptin's potential use as a prototype for drug delivery as an 
oral therapeutic, which can reduce the need for invasive surgeries that 
dilate blood vessels such as stents or catheters.
    Market:
    Thrombolytic/antithrombotic therapies are worth billions of 
dollars, common therapeutics include heparin, warfarin, and plasminogen 
activators.
    Anticancer and antiangiogenic therapies.

[[Page 49725]]

    Cardiac disease is the number one cause of death in the U.S.
    Pancreatic cancer is one of the most lethal cancers, where only 23% 
patients will survive after one year of diagnosis, and 4% survive after 
five years of diagnosis.
    An estimated 37,170 Americans will be newly diagnosed with 
pancreatic cancer in 2007.
    An estimated 33,370 deaths from pancreatic cancer in the U.S. in 
2007.
    Pancreatic cancer is the fourth leading cause of cancer death in 
the U.S.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Eric Calvo et al. (NIAID).
    Related Publications:
    1. A manuscript directly related to this technology will be 
available as soon as it is accepted for publication.
    2. E Calvo. Collagen-platelet aggregation inhibitor from mosquito 
salivary glands. Biacore T100 seminar series, November 2006, St. Louis, 
Missouri.
    3. S Yoshida and H Watanabe. Robust salivary gland-specific 
transgene expression in Anopheles stephensi mosquito. Insect Mol Biol. 
2006 Aug;15(4):403-410.
    4. D Sun et al. Expression of functional recombinant mosquito 
salivary apyrase: A potential therapeutic platelet aggregation 
inhibitor. Platelets. 2006 May;17(3):178-184.
    Patent Status: U.S. Provisional Application No. 60/198,629 filed 09 
Jul 2007 (HHS Reference No. E-172-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; [email protected]
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases, Laboratory of Malaria and Vector 
Research, is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize the platelet aggregation inhibitor Aegyptin. Please 
contact Dr. Jose Ribeiro, Head, Vector Biology Section, at 301-496-9389 
or [email protected] for more information.

Bifunctional Compounds That Bind to Hormone Receptors

    Description of Technology: The development and progression of 
prostate cancer is dependent on the androgen receptor (AR), a ligand-
dependent transcription factor. In the inactive form AR resides in the 
cytosolic region of the cell and when activated, AR is imported into 
the nucleus. Initial hormonal therapy for prostate cancer involves 
lowering serum levels of testosterone to shut down AR activity. Despite 
initial patient responses to testosterone-depleting therapies, prostate 
cancer becomes refractory to hormonal therapy. Notably, AR is 
reactivated in hormone-refractory prostate cancer and reinstates its 
proliferative and survival activity.
    Available for licensing is a novel chemical compound which is 
bifunctional and binds to AR. This compound is comprised of tubulin-
binding and steroid receptor-binding moieties. This compound is 
designed to antagonize AR function in a nonclassical manner by several 
mechanisms and kills hormone-refractory prostate cells better than both 
functional moieties. This compound is a first-in-class of bifunctional 
steroid receptor binding agents that can antagonize steroid receptors 
in a variety of hormone-dependent diseases, such as breast and prostate 
cancer.
    Applications:
    Therapeutic compounds that selectively target steroid receptor-
expressing cancer cells resulting in decreased toxicity.
    Method to treat hormone resistant prostate cancer and potentially 
other steroid receptor dependent diseases such as breast cancer.
    Market:
    Prostate cancer is the second most common type of cancer among men, 
wherein one in six men will be diagnosed with prostate cancer.
    An estimated 218,890 new cases of prostate cancer and 27,050 deaths 
due to prostate cancer in the U.S. in 2007.
    An estimated 180,510 new cases of breast cancer and 40,060 deaths 
due to breast cancer in the U.S. in 2007.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Nima Sharifi et al. (NCI).
    Patent Status: U.S. Provisional Application No. 60/958,351 filed 03 
Jul 2007 (HHS Reference No. E-163-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301 435-4633; [email protected]
    Collaborative Research Opportunity: The Medical Oncology Branch, 
National Cancer Institute is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize treatments of resistant prostate 
cancer. Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

Specific Binding Agents for KSHV vIL-6 That Neutralize a Biological 
Activity

    Description of Technology: Kaposi's sarcoma-associated herpes virus 
(KSHV) is an oncogenic herpes virus originally identified in AIDS 
associated Kaposi's sarcoma (KS) lesions, the most common tumor 
associated with HIV infection. KSHV encodes various proteins that have 
characteristics associated with cellular growth and transformation, 
including viral (v) IL-6 (KSHV vIL-6). These viral proteins display 
structural homology to their cellular counterparts, and human and vIL-6 
are multifunctional cytokines that have been shown to induce vascular 
endothelial growth factor and other factors.
    Available for licensing are binding agents that neutralize vIL-6 
biological activities, methods of diagnosing and treating KSHV 
disorders, and methods to monitor KSHV patient response to treatment. 
Deregulation of cellular IL-6 expression is known to contribute to 
tumor development, suggesting that KSHV-derived vIL-6 could be part of 
a viral strategy to promote malignant transformation. Neutralizing 
activity of anti-vIL-6 antibodies may provide a potential therapeutic 
for KSHV disorders such as HIV, Castleman's disease, and primary 
effusion lymphoma.
    Applications:
    Therapeutic compositions to treat KSHV disorders such as KS, 
Castleman's disease, and primary effusion lymphoma.
    Method to diagnose and treat KSHV disorders.
    Method to monitor patient response to KSHV treatment.
    Market:
    Approximately 476,095 persons currently living with HIV/AIDS in the 
United States.
    Estimated annual incidence rate for KS is 5 cases per 100,000/year 
in the U.S.; KS contributes to approximately 30% of AIDS related 
deaths.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Giovanna Tosato (NCI) et al.
    Publications:
    1. Y Aoki and G Tosato. Therapeutic options for human herpesvirus-
8/Kaposi's sarcoma-associated herpesvirus-related disorders. Expert Rev 
Anti Ther. 2004 Apr;2(2):213-225.
    2. Y Aoki et al. Detection of viral interleukin-6 in Kaposi 
sarcoma-associated herpesvirus-linked disorders. Blood. 2001 Apr 
1;97(7):2173-2176.

[[Page 49726]]

    3. Y Aoki et al. Kaposi's sarcoma-associated herpesvirus-encoded 
interleukin-6. J Hemathother Stem Cell Res. 2000;9(2):137-145.
    Patent Status:
    U.S. Patent No. 6,939,547 issued 06 Sep 2005 (HHS Reference No. E-
180-2000/0-US-03).
    U.S. Patent No. 7,108,981 issued 19 Sep 2006 (HHS Reference No. E-
180-2000/0-US-04).
    U.S. Patent No. 7,235,365 issued 26 Jun 2007 (HHS Reference No. E-
180-2000/0-US-05).
    U.S. Patent Application No. 11/803,732 filed 14 May 2007 (HHS 
Reference No. E-180-2000/0-US-06).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Laboratory of Cellular Oncology is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize therapeutics for Kaposi's sarcoma-
associated herpes virus (KSHV). Please contact John D. Hewes, Ph.D. at 
301-435-3121 or [email protected] for more information.

Interferon Alpha Hybrids

    Description of Technology: Available for licensing are hybrid 
interferon alpha (INF-[alpha]) polypeptides constructed by combinations 
of INF[alpha]21b and INF[alpha]2c, and mutants of these hybrids. These 
hybrid constructs have resulted in novel IFNs that either combine 
different biological properties from the parent proteins or have 
significantly different biological activity from both the parents in 
anti-proliferative, anti-viral, or competitive binding properties. For 
instance, the hybrid designated HY-3 has higher anti-proliferative 
activity in Daudi, WISH, and primary human lymphocyte cells exhibiting 
approximately 6 times higher anti-proliferative activity than either 
parent IFN. These IFN hybrids provide a powerful tool for studying the 
structure-function relationship of these molecules. The engineered IFN-
[alpha] proteins may have important new therapeutic applications and 
may provide greater insights into understanding of the clinical 
activities of existing IFN-[alpha]s.
    Also available for licensing are hybrid INF-[alpha] nucleic acids 
encoding the hybrid polypeptides as well as cells, vectors, 
pharmaceutical compositions with these nucleic acid sequences.
    Applications:
    Anti-viral and cancer therapeutics.
    Research tool to study IFN-[alpha] functions.
    Market:
    Interferon alpha market was worth $2.1 billion in 2005.
    Industry focus is novel subtype or interferon alpha variants with 
improved pharmacodynamic and safety properties.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Kathryn C. Zoon et al. (FDA).
    Publications:
    1. R Hu et al. Protein engineering of interferon alphas. Methods 
Mol Med. 2005;116:69-80.
    2. R Hu et al. Human IFN-alpha protein engineering: The amino acid 
residues at positions 86 and 90 are important for antiproliferative 
activity. J Immunol. 2001 Aug 1;167(3):1482-1489.
    3. Hu et al. Divergence of binding, signaling, and biological 
responses to recombinant human hybrid IFN. J Immunol. 1999 Jul 
15;163(2):854-860.
    Patent Status:
    U.S. Patent No. 7,235,232 issued 26 Jun 2007 (HHS Reference No. E-
068-1998/0-US-04)
    U.S. Patent No. 6,685,933 issued 03 Feb 2004 (HHS Reference No. E-
068-1998/0-US-03).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].

    Dated: August 20, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-16929 Filed 8-28-07; 8:45 am]
BILLING CODE 4140-01-P