[Federal Register Volume 71, Number 124 (Wednesday, June 28, 2006)]
[Notices]
[Pages 36814-36816]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-5867]


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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.

Agonist Epitopes for Renal Cell Carcinoma

    Description of Technology: Approximately 30,000 patients are 
diagnosed with renal cell carcinoma (RCC) each year in the United 
States, and an estimated 12,000 patients die of this disease. Most 
patients are diagnosed with advanced local disease or metastatic 
disease. Metastatic RCC carries a poor prognosis with median survivals 
in the range of 10-12 months. Drugs that inhibit VEGF receptor tyrosine 
kinases such as Sorafenib and Sunitinib have recently been approved by 
the FDA to treat metastatic RCC. Although a significant percentage of 
patients will achieve a partial response or disease stabilization with 
these agents, complete responses are rare and disease progression 
eventually ensues. RCC is unusual among solid tumors as it appears to 
be susceptible to immunotherapy. Cytokines such as IL-2 and IFN-alpha 
nonspecifically stimulate the immune system resulting in disease 
regression. Unfortunately, these drugs achieve success in only a 
minority (15-20%) of the metastatic RCC patient population. Therefore, 
new methods are needed to improve on immune-based therapies and expand 
the curative potential of therapies for patients with RCC.
    The present invention discloses peptides and antigen epitopes 
specific for RCC for use in the diagnosis, vaccination, or adoptive 
infusion of antigen specific T cells to treat patients with metastatic 
RCC. The immunogenic peptide, which binds to the HLA-A11 epitope, was 
identified in a patient with metastatic RCC that under went an 
investigational allogeneic hematopoietic stem cell transplant. Cancer 
regression occurred post-transplant consistent with a graft-vs-tumor 
effect. A T-cell line, expanded from the patient's blood cells at the 
time of tumor regression, was isolated and subsequently shown to kill 
the patients RCC cells in vitro. Expression and sequencing studies 
revealed that the patient's T-cells recognize an antigen epitope 
derived from a human endogenous retrovirus (HERV). Further, pre-
clinical studies using quantitative real-time PCR found that this HERV 
was expressed in eight of 14 RCC tumor cell lines with no HERV 
expression in patient fibroblasts, hematopoietic cells or in c-DNAs 
analyzed from 48 different normal tissues. Plans are underway to 
investigate the immunogenic potential of this peptide to induce 
expansion of T-cells that are cytotoxic to RCC cells in vitro and in 
pre-clinical animal models.
    Inventors: Richard W. Childs, et al. (NHLBI).
    Publications: Details of the invention are published in:
    1. I. Delgado-Espinoza, et al., ``Nonmyeloablative transplantation 
for solid tumors: A new frontier for allogeneic immunotherapy,'' Expert 
Rev Anticancer Ther. 2004 Oct;4(5):865-75.

[[Page 36815]]

    2. Y. Takahashi, et al., ``Nonmyeloablative transplantation: An 
allogeneic-based immunotherapy for renal cell carcinoma,'' Clin Cancer 
Res. 2004 Sep 15;10(18 Pt 2):6353S-9S.
    3. R.W. Childs, et al., ``Regression of Metastatic Renal-Cell 
Carcinoma after Nonmyeloablative Allogeneic Peripheral-Blood Stem-Cell 
Transplantation,'' N Engl J Med. 2000 Sep 14;343:750-758.
    4. Marco Bregni, Naoto T. Ueno, and Richard Childs. Meeting Report: 
The Second International Meeting on Allogeneic Transplantation in Solid 
Tumors (ATST). Bone Marrow Transplantation (Submitted 2006).
    Patent Status: U.S. Provisional Application No. 60/783,350 filed 17 
Mar 2005 (HHS Reference No. E-122-2006/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Michelle A. Booden, PhD; 301/451-7337; 
[email protected].
    Collaborative Research Opportunity: The Hematology Branch of the 
NHLBI is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize therapeutic treatment approaches targeting this novel RCC 
antigen. Please contact Dr. Richard Childs at 301/594-8008 or 
[email protected] for more information.

Immunogenic Peptides and Methods of Use for Treating Prostrate and 
Uterine Cancers

    Description of Technology: Cancer of the prostate is the most 
commonly diagnosed cancer in men and the second leading cause of cancer 
death in men. Despite the use of standard therapy, including surgery, 
radiotherapy, chemotherapy, and/or hormonal therapy more than 30,000 
men will die from prostate cancer. Moreover, current therapy has 
limited success against metastatic androgen insensitive prostate 
cancer. A potential systemic treatment for all subclasses of prostate 
cancer is immunotherapy, either alone or in combination with standard 
radiation or chemotherapy.
    Prostate Antigen Gene-4 (PAGE4) is an X chromosome-linked cancer-
testis antigen that is highly expressed in prostate and uterine 
cancers. To this end, Drs. Jeffery Schlom, Kwong Tsang, and Ira Pastan 
have identified and characterized novel PAGE4 cytotoxic T-cell 
lymphocyte (CTL) epitopes and enhanced agonist epitopes. Preclinical 
studies performed by Dr. Schlom and colleagues indicate that the PAGE4 
agonist epitopes bound HLA-A2 molecules at lower peptide 
concentrations, form more stable peptide HLA-A2 complexes, induce 
higher levels of production of INF[gamma], Granzyme B, TNF[alpha], IL-
2, and lymphotactin by PAGE4 specific T-cell lines, and T-cell lines 
generated against the agonist peptide were more efficient at lysing 
human tumor cells expressing native PAGE4. Thus, these agonist epitopes 
of PAGE4 could be incorporated into immunotherapy protocols, and may 
constitute an alternative and/or additional approach for the treatment 
of PAGE4 expressing prostate and uterine cancers.
    Development Status: The Laboratory of Tumor Immunobiology plans to 
initiate clinical studies utilizing this technology and collaborative 
opportunities may be available.
    Inventors: Jeffrey Schlom, Kwong-Yok Tsang, Ira Pastan (NCI).
    Publications: Publications which may provide background information 
for this technology include:
    1. C. Iavarone, et al., ``PAGE4 is a cytoplasmic protein that is 
expressed in normal prostate and in prostate cancers,'' Mol Cancer 
Ther. 2002 Mar;1(5):329-335.
    2. L. Prikler, et al., ``Adaptive immunotherapy of the advanced 
prostate cancer--cancer testis antigen (CTA) as possible target 
antigens,'' Aktuelle Urol. 2004 Aug;35(4):326-330. [article in German].
    Patent Status: U.S. Provisional Application No. 60/776,506 filed 24 
Feb 2006 (HHS Reference No. E-104-2006/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Michelle A. Booden, PhD; 301/451-7337; 
[email protected].
    Collaborative Research Opportunity: The NCI Laboratory of Tumor 
Immunobiology is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize cancer vaccine technology encompassing 
PAGE4. Please contact Denise M. Crooks, PhD, at 301/451-3943 and/or 
[email protected] for more information.

Novel Human IGF-1 Specific IGF-I and IGF-II Cross-Reactive Human 
Monoclonal Antibodies as Potential Anti-Tumor Agents

    Description of Technology: Cancer is one of the leading causes of 
death in United States and it is estimated that there will be 
approximately 600,000 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. Monoclonal antibody-
based therapies have taken a lead among the new cancer therapeutic 
approaches.
    The type 1 insulin-like growth factor (IGF) receptor (IGF1R) is 
over-expressed by many tumors and mediates proliferation, motility, and 
protection from apoptosis. Agents that inhibit IGF1R expression or 
function can potentially block tumor growth and metastasis. Its major 
ligands, IGF-I, and IGF-II are over-expressed by multiple tumor types. 
Previous studies indicate that inhibition of IGF-I, and/or IGF-II 
binding to its cognizant receptor negatively modulates signal 
transduction through the IGF pathway and concomitant cell proliferation 
and growth. Therefore, use of humanized or fully human antibodies 
against IGFs represents a valid approach to inhibit tumor growth.
    The present invention discloses the identification and 
characterization of three (3) novel fully human monoclonal antibodies 
designated m705, m706, and m708, which are specific for insulin-like 
growth factor (IGF)-I. Two (2) of the three (3) antibodies, m705 and 
m706 are specific for IGF-I and do not cross react with IGF-II and 
insulin while, m708 cross reacts with IGF-II. These antibodies can be 
used to prevent binding of IGF-I to its concomitant receptor IGFIR, 
consequently, modulating diseases such as cancer. Additional 
embodiments describe methods for treating various human diseases 
associated with aberrant cell growth and motility including breast, 
prostate, and leukemia carcinomas. Thus, these novel IGF-I antibodies 
may provide a therapeutic intervention for multiple carcinomas.
    Development Status: The technology is in the pre-clinical stage; 
animal studies are currently under way.
    Inventors: Dimiter S. Dimitrov and Zhongyu Zhu (NCI).
    Publications:
    1. A manuscript from the IGF-I work is in preparation (Copy can be 
provided with Confidential Disclosure Agreement).
    2. Y. Feng, Z. Zhu, X. Xiao, V. Choudhry, J.C. Barrett, D.S. 
Dimitrov, ``Novel human monoclonal antibodies to insulin-like growth 
factor (IGF)-II that potently inhibit the IGF receptor type I signal 
transduction function,'' Mol Cancer Ther. 2006 Jan; 5 (1):114-120.

[[Page 36816]]

    Patent Status: U.S. Provisional Patent Application filed 07 Apr 
2006 (HHS Reference No. E-336-2005/0-US-01).
    Licensing Status: This technology is available for licensing under 
an exclusive or non-exclusive patent license.
    Licensing Contact: Michelle A. Booden, PhD; 301/451-7337; 
[email protected].
    Collaborative Research Opportunity: The NCI Center for Cancer 
Research Nanobiology Program is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize monoclonal antibodies to treat 
human diseases. Please contact Melissa Maderia at [email protected] 
or by phone at (301) 846-5465 for more information.

Immortal Human Prostate Epithelial Cell Cultures as a Prostate Cancer 
Model

    Description of Technology: The National Institutes of Health has 
multiple immortalized, malignant, human, adult prostate epithelial cell 
lines available for license. They are useful as models in epithelial 
cell oncogenesis studies and in the diagnosis and treatment of prostate 
cancer.
    The cell lines were generated from primary adenocarcinomas of the 
prostate. Long-term cultures were established by immortalizing cells 
with human papillomavirus (HPV) transforming proteins. The cultures 
were characterized and single-cell clones with unique genetic 
characteristics were selected based on allelic loss of heterozygosity 
(LOH). Tissue-matched normal cell lines are available also, useful for 
the appropriate controls.
    The invention also encompasses polyclonal and monoclonal antibodies 
directed to the cell lines, which may be useful as immunotherapeutics.
    Applications: (1) Screening tool to identify novel genes unique to 
or overexpressed in prostate cancer; (2) Raising of prostate cancer-
reactive antibodies, useful as immunotherapeutics or diagnostics; (3) 
Screen for compounds that kill tumor cells and represent potential 
therapeutic agents; (4) Identification of prostate cancer antigens to 
develop recombinant prostate cancer vaccines.
    Inventors: Susan L. Topalian, W. Marston Linehan, Robert K. Bright, 
Cathy D. Vocke (NCI).
    Publication: R.K. Bright, et al., ``Generation and genetic 
characterization of immortal human prostate epithelial cell lines 
derived from primary cancer specimens,'' Cancer Res. 1997 Mar 
5;57(5):995-1002.
    Patent Status: U.S. Patent 6,982,168 issued on 07 May 2003 (HHS 
Reference No. E-053-1996/0-US-03).
    Licensing Status: Available for non-exclusive internal use and 
biological material license.
    Licensing Contact: Michelle A. Booden, PhD; 301/451-7337; 
[email protected].
    Collaborative Research Opportunity: The NCI Center for Cancer 
Research, Surgery Branch, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize this technology. Please contact 
Brian W. Bailey, PhD, at 301/451-2158 or [email protected] for more 
information.

    Dated: June 21, 2006.
David R. Sadowski,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 06-5867 Filed 6-27-06; 8:45 am]
BILLING CODE 4140-01-P