[Federal Register Volume 71, Number 166 (Monday, August 28, 2006)]
[Notices]
[Pages 50926-50928]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-14184]


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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 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.

Diagnostic and Therapeutic Strategies for Metastatic Hepatocellular 
Carcinoma by Targeting Osteopontin

    Description of Technology: Cancer is one of the leading causes of 
death in United States and it is estimated that there will be more than 
half a million deaths caused by cancer in 2006. For the last decade 
breast and prostate cancer survival rate has significantly decreased 
thanks to contribution of screening, early detection and novel 
therapeutics. This success needs to be translated to other cancers as 
well, where there is a need of novel diagnostic and therapeutic 
strategies for successful disease management.
    Osteopontin (OPN) is a well known serum prognostic marker for 
breast cancer. This technology identifies a 10kD residue of OPN as a 
potential prognostic marker and therapeutic target for metastatic 
hepatocellular carcinoma (HCC). Mechanistically, OPN has been shown to 
be a novel substrate for MMP-9 and the 10kD fragment is demonstrated to 
be a mediator of cell invasion and metastasis. Short synthetic peptides 
against OPN have been shown to block OPN mediated cell invasion, 
providing a novel therapeutic approach targeting OPN. Finally, 
polyclonal antibodies against the 10kD fragment of OPN have been 
developed that can be used for detection of OPN in physiological fluids 
of HCC patients. This technology provides a novel therapeutic and 
diagnostic strategy for the management of HCC patients using OPN.
    Development Status: The technology is in the pre-clinical stage, 
animal studies are under way.
    Inventors: Vivian A. Takafuji (NCI) et al.
    Relevant Publications:
    1. A manuscript relating to this invention has been submitted for 
publication and will be available once accepted.
    2. J Kim, SS Ki, SD Lee, CJ Han, YC Kim, SH Park, SY Cho, YJ Hong, 
HY Park, M Lee, HH Jung, KH Lee, SH Jeong. Elevated plasma osteopontin 
levels in patients with hepatocellular carcinoma. Am J Gastroenterol. 
2006 Jul 18; Epub ahead of print, doi: 10.1111/j.1572-0241.2006.00679.
    3. QH Ye, LX Qin, M Forgues, P He, JW Kim, AC Peng, R Simon, Y Li, 
AI Robles, Y Chen, ZC Ma, ZQ Wu, SL Ye, YK Liu, ZY Tang, XW Wang. 
Predicting hepatitis B virus-positive metastatic hepatocellular 
carcinomas using gene expression profiling and supervised machine 
learning. Nat Med. 2003 Apr; 9(4):416-423.
    Patent Status: U.S. Provisional Application No. 60/805,298 filed 20 
Jun 2006 (HHS Reference No. E-201-2006/0-US-01).
    Licensing Status: This technology is available for licensing under 
an exclusive or non-exclusive patent license.
    Licensing Contact: Michelle Booden, Ph.D.; 301/451-7337; 
[email protected].
    Collaborative Research Opportunity: The NCI Laboratory of Human 
Carcinogenesis is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize diagnostic and therapeutic strategies for 
metastatic hepatocellular carcinoma. Please contact Betty Tong at 301-
594-4263 or [email protected] for more information.

[[Page 50927]]

Hybrid T-Cell Receptors for the Development of Improved Vaccines

    Description of Technology: Cancer is one of the leading causes of 
death in United States and it is estimated that there will be more than 
half a million deaths caused by cancer in 2006. A major drawback of the 
current chemotherapy-based therapeutics is the cytotoxic side-effects 
associated with them. Thus there is a dire need to develop new 
therapeutic strategies with fewer side-effects. Immuno-therapy has 
taken a lead among the new cancer therapeutic approaches. Adoptive 
immunotherapy is one of the most promising new therapeutic approaches 
that enhance the innate immunity of an individual to fight against a 
certain disease.
    T cell receptors (TCR) are the proteins responsible for the T 
cell's ability to recognize infected or transformed cells. TCR consists 
of two domains, one variable domain that recognizes the antigen and one 
constant region that helps the TCR anchor to the membrane and transmit 
the recognition signal by interacting with other proteins.
    The present invention involves the construction of hybrid anti-
cancer TCR that is half mouse and half human. Functional analysis 
reveals that human TCR with a mouse constant region is significantly 
better than pure human TCR. This hybrid protein when put into human T 
cells makes these cells much better in recognizing cancer associated 
proteins. The hybrid protein can be used to improve the function of a T 
cell providing diagnostic and therapeutic applications in cancer and 
infectious diseases.
    Development Status: The technology is in the pre-clinical stage, 
animal studies are complete, and a clinical protocol for a Phase I 
clinical trial for stage IV refractory melanoma is currently under 
review by the NIH IRB.
    Inventors: Richard A. Morgan, Cyrille J. Cohen, Steven A. Rosenberg 
(NCI).
    Patent Status: U.S. Provisional Application No. 60/796,853 filed 03 
May 2006 (HHS Reference No. E-086-2006/0-US-01).
    Relevant Publications:
    1. CJ Cohen, Y Zhao, Z Zheng, SA Rosenberg, RA Morgan. Enhanced 
antitumor activity of murine-human hybrid T-cell receptor (TCR) in 
human lymphocytes is associated with improved pairing and TCR/CD3 
stability. Cancer Res., in press.
    2. MS Hughes, YY Yu, ME Dudley, Z Zheng, PF Robbins, Y Li, J 
Wunderlich, RG Hawley, M Moayeri, SA Rosenberg, RA Morgan. Transfer of 
a TCR gene derived from a patient with a marked antitumor response 
conveys highly active T-cell effector functions. Hum Gene Ther. 2005 
Apr;16(4):457-472.
    Licensing Status: This technology is available for licensing under 
an exclusive or non-exclusive patent license.
    Licensing Contact: Michelle Booden, Ph.D.; 301/451-7337; 
[email protected]
    Collaborative Research Opportunity: The NCI Surgery Branch is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
hybrid T-cell receptors for the development of improved vaccines. 
Please contact Betty Tong at 301-496-0477; [email protected] for more 
information.

Adoptive Immunotherapy With T Lymphocytes Engineered for Enhanced 
Survival

    Description of Technology: Available for licensing is a 
composition, comprising genetically engineered lymphocytes, transduced 
to express elevated levels of cytokine proteins. This technology is 
useful for improving cellular adoptive immunotherapies to treat a range 
of infectious diseases and cancers.
    Adoptive immunotherapy has repeatedly been shown to be useful in 
the treatment of patients with metastatic melanoma. However, clinical 
efficacy of this treatment is limited by the short-lived survival of 
the transferred, autologous, antigen-specific T cells. It would be 
desirable to genetically modify effector cells to provide not only 
enhanced effector cell survival, but also desired antigen specificity, 
and improved function, and safety. The current technology provides a 
method address this desire, by genetically modifying lymphocytes using 
retroviral vectors.
    Specifically, isolated autologous T lymphocytes can be transformed 
with polynucleotides encoding endogenous cytokines, for example IL-7 or 
IL-15. IL-15-transduced lymphocyte cultures demonstrate prolonged in 
vitro persistence. In addition, T cells can be transduced to express 
not only cytokines but also T cell receptors to confer specificity for 
certain antigens. Recent data showed that human T lymphocytes 
engineered to express a murine anti-human p53 T cell receptor can 
recognize tumor cell lines, as well as fresh human tumors, and are able 
to kill p53-expressing human tumor cells.
    Also provided in the invention are methods for treating patients 
with transformed lymphocytes as part of adoptive immunotherapy. 
Applications of this technology beyond cancer include the potential use 
of cytokine expressing cells in treating infectious and autoimmune 
diseases and vaccination.
    Inventors: Steven A. Rosenberg et al. (NCI).
    Publications:
    1. L Gattinoni, SE Finkelstein, CA Klebanoff, PA Antony, DC Palmer, 
PJ Spiess, LN Hwang, Z Yu, C Wrzesinski, DM Heimann, CD Surh, SA 
Rosenberg, NP Restifo. Removal of homeostatic cytokine sinks by 
lymphodepletion enhances the efficacy of adoptively transferred tumor-
specific CD8+ T cells. J Exp Med. 2005 Oct 3;202(7):907-912.
    2. LX Wang, R Li, G Yang, M Lim, A O'Hara, Y Chu, BA Fox, NP 
Restifo, WJ Urba, HM Hu. Interleukin-7-dependent expansion and 
persistence of melanoma-specific T cells in lymphodepleted mice lead to 
tumor regression and editing. Cancer Res. 2005 Nov 15;65(22):10569-
10577.
    3. L Gattinoni, DJ Powell Jr, SA Rosenberg, NP Restifo. Adoptive 
immunotherapy for cancer: building on success. Nat Rev Immunol. 2006 
May;6(5):383-393.
    4. CJ Cohen, et al. Recognition of fresh human tumor by human 
peripheral blood lymphocytes transduced with a bicistronic retroviral 
vector encoding a murine anti-p53 TCR. J Immunol. 2005 Nov 
1;175(9):5799-5808.
    5. C Hsu, et al. Primary human T lymphocytes engineered with a 
codon-optimized IL-15 gene resist cytokine withdrawal-induced apoptosis 
and persist long-term in the absence of exogenous cytokine. J Immunol. 
2005 Dec 1;175(11):7226-7234.
    6. SA Rosenberg and ME Dudley. Cancer regression in patients with 
metastatic melanoma after the transfer of autologous antitumor 
lymphocytes. Proc Natl Acad Sci USA 2004 Oct 5;101 Suppl 2:14639-14645.
    7. CA Klebanoff, et al. IL-15 enhances the in vivo antitumor 
activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci USA 2004 
Feb 17;101(7):1969-1974.
    8. K Liu and SA Rosenberg. Interleukin-2-independent proliferation 
of human melanoma-reactive T lymphocytes transduced with an exogenous 
IL-2 gene is stimulation dependent. J Immunother. 2003 May-
Jun;26(3):190-201.
    9. K Liu and SA Rosenberg. Transduction of an IL-2 gene into human 
melanoma-reactive lymphocytes results in their continued growth in the 
absence of exogenous IL-2 and maintenance of specific antitumor 
activity. J Immunol. 2001 Dec1;167(11):6356-6365.

[[Page 50928]]

    Patent Status: U.S. Provisional Application No. 60/617,340 filed 08 
Oct 2004 (HHS Reference No. E-340-2004/0-US-01); PCT Application No. 
PCT/US05/3640 filed 07 Oct 2005 (HHS Reference No. E-340-2004/2-PCT-01)
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Michelle A. Booden, Ph.D.; 301/451-7337; 
[email protected]
    Collaborative Research Opportunity: The NCI Surgery Branch is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
the clinical applications of T cell receptor technology. Please contact 
Steven A. Rosenberg, M.D., Ph.D. at 301-496-4164 for more information.

    Dated: August 21, 2006.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E6-14184 Filed 8-25-06; 8:45 am]
BILLING CODE 4140-01-P