[Federal Register Volume 75, Number 207 (Wednesday, October 27, 2010)]
[Notices]
[Pages 66104-66106]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-27179]
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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.
Immunotoxin for the Treatment of Neuroblastoma Relapse
Description of Technology: Immunotoxins are proteins which have two
distinct domains: (1) An antibody or antibody binding fragment which is
capable of recognizing a single specific cell surface protein and (2) a
toxin domain which is capable of inducing cell death. Immunotoxins are
currently being pursued as therapeutics because they specifically kill
diseased cells while leaving essential, healthy cells alone. This
increases the effectiveness of the therapy while reducing the
appearance of side-effects. A particular immunotoxin that is being
studied in clinical trials consists of an anti-CD22 antibody binding
fragment and a mutated Pseudomonas exotoxin A. Although this
immunotoxin is being explored primarily as a treatment for
hematological malignancies, it can be used to treat any condition where
CD22 is overexpressed on the cell membrane of diseased cells.
Neuroblastomas are malignant cancers that start in nerve tissue and
primarily affect infants and children. Although frontline treatments
for neuroblastoma are often effective, relapse frequently occurs in
high risk cases. The most common form of relapse in neuroblastoma
patients is caused by Neuroblastoma tumor initiating cells (NB-TIC).
Therefore, if NB-TIC could be eliminated, high risk neuroblastoma
patients could have a therapeutic option for preventing a relapse.
This invention concerns the discovery that NB-TIC expresses CD22.
As a result, NB-TIC are susceptible to treatment with an anti-CD22
immunotoxin. By combining frontline
[[Page 66105]]
neuroblastoma treatments with anti-CD22 immunotoxins, both the primary
neuroblastoma and cells capable of initiating a relapse can be
eliminated. As a result, even high risk neuroblastoma patients should
have an increased chance of surviving neuroblastoma.
Application: Treatment and prevention of neuroblastoma relapse.
Advantages:
Increased therapeutic effectiveness with decreased non-
specific killing of essential, healthy cells.
Neuroblastoma relapse commonly begins in the bone marrow,
an environment which is accessible to immunotoxins.
Combined treatment addresses both the tumor and the cause
of relapse, leading to more efficient treatments than frontline
therapeutics alone.
Development Status: Preclinical stage of development for treatment
of neuroblastoma relapse; immunotoxins have clinical data associated
with treatment of hematological malignancies.
Inventors: Thiele (NCI) et al.
Patent Status: U.S. provisional application 61/356,202 (E-204-2010/
0-US-01).
For more information, see:
U.S. Patent 7,355,012--``Mutated Anti-CD22 Antibodies with
Increased Affinity to CD22--Expressing Leukemia Cells''.
PCT Patent Application WO 2007/016150--``Mutated
Pseudomonas Exotoxins with Reduced Antigenicity''.
PCT Patent Application WO 2009/032954--``Deletions in
Domain II of Pseudomonas Exotoxin A That Reduce Non-Specific
Toxicity''.
Licensing Status: Available for licensing.
Licensing Contact: David A. Lambertson, PhD; 301-435-4632;
[email protected].
Collaborative Research Opportunity: The Center for Cancer Research,
Pediatric Oncology Branch and Laboratory of Molecular Biology, is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
recombinant anti-CD22 immunotoxins for the treatment of neuroblastoma.
Please contact John Hewes, Ph.D. at 301-435-3121 or [email protected]
for more information.
Mouse Model of Thyroid Cancer
Description of Technology: This technology describes a mouse model
of thyroid cancer where the phosphatidy-linositol 3-kinase (PI3K)-AKT/
protein kinase B-signaling pathway is overactivated. These mice have a
knock-in dominantly negative mutant thyroid hormone receptor [beta]
gene (TR[beta]PV mutant) that spontaneously develops thyroid cancer and
distant metastasis similar to human follicular thyroid cancer. The
thyroids of TR[beta]PV mice exhibit extensive hyperplasia, which
progresses to capsular invasion, vascular invasion, anaplasia, and
ultimately, metastasis to distant organs. Consequently, this mouse
model could be used as a preclinical model to understand genetic
changes during cancer development and to identify potential molecular
targets for the diagnosis, prevention, and treatment of cancer. For
example, the inventors have used the TR[beta]PV mice to show that the
peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) could
function as a tumor suppressor in vivo and that the activation of the
PI3K-AKT signaling contributes to thyroid carcinogenesis and could be a
potential therapeutic target in follicular thyroid carcinoma.
Applications:
Identifying potential molecular targets for cancer
diagnosis, prevention, and treatment.
Testing kinase inhibitors and other novel drugs being
discovered for the treatment of thyroid cancer.
Tools to understand the genetic changes during cancer
development.
Advantages: This model provides the opportunity to study the
alterations in gene regulation that occur during the progression and
metastasis of thyroid carcinogenesis, not just the genes that control
initial carcinogenesis.
Development Status: The technology is currently in the pre-clinical
stage of development.
Inventors: Sheue-yann Cheng (NCI).
Patent Status: HHS Reference No. E-208-2009/0--Research Tool.
Patent protection is not being pursued for this technology.
Publications:
1. Furuya F, Lu C, Willingham MC, Cheng SY. Inhibition of
phosphatidylinositol 3-kinase delays tumor progression and blocks
metastatic spread in a mouse model of thyroid cancer. Carcinogenesis.
2007 Dec;28(12):2451-2458. [PubMed: 17660507]
2. Kato Y, Ying H, Zhao L, Furuya F, Araki O, Willingham MC, Cheng
SY. PPARgamma insufficiency promotes follicular thyroid carcinogenesis
via activation of the nuclear factor-kappaB signaling pathway.
Oncogene. 2006 May 4;25(19):2736-2747. [PubMed: 16314832]
3. Suzuki H, Willingham MC, Cheng SY. Mice with a mutation in the
thyroid hormone receptor beta gene spontaneously develop thyroid
carcinoma: a mouse model of thyroid carcinogenesis. Thyroid. 2002
Nov;12(11):963-969. [PubMed: 12490073]
4. Kaneshige M, Kaneshige K, Zhu X, Dace A, Garrett L, Carter TA,
Kazlauskaite R, Pankratz DG, Wynshaw-Boris A, Refetoff S, Weintraub B,
Willingham MC, Barlow C, Cheng S. Mice with a targeted mutation in the
thyroid hormone beta receptor gene exhibit impaired growth and
resistance to thyroid hormone. Proc Natl Acad Sci U S A. 2000 Nov
21;97(24):13209-13214. [PubMed: 11069286]
Licensing Status: Available for licensing.
Licensing Contact: Whitney A. Hastings; 301-451-7337;
[email protected].
Chemokine-Tumor Antigen Fusion Proteins as Cancer Vaccines
Description of Technology: Available for licensing is a tumor
vaccine construct comprising a chemoattractant (such as human
chemokines CCL7 and CCL20) fused to a tumor antigen (including human
mucin-1, a transmembrane protein that is aberrantly expressed in
cancer; or single chain antibody expressed by B cell malignancy, or
melanoma antigen gp100 expressed in human melanomas). The majority of
tumor antigens are believed to be poorly immunogenic because they
represent oncogene gene products or other cellular genes which are
normally present in the host. As a result, poor immunogenicity has been
a major obstacle to successful immunotherapy with tumor vaccines.
Administration of this fusion chemokine and tumor antigen protein, or a
nucleic acid encoding this fusion protein, elicits a tumor specific
cellular and humoral immune response thereby providing a potent cancer
vaccine.
Applications: Cancer immunotherapy.
Development Status: Proof of the concept and pre-clinical
development have been successfully completed.
Market: The global cancer market is forecasted to reach US$40
billion by 2012. Cancer vaccine research is coming to fruition, with a
number of products now in Phase III trials and 15 therapeutic cancer
vaccines realistically expected to launch by 2013. The therapeutic
vaccine market has the potential to mirror the growth seen in the
monoclonal antibody market, and reach sales in excess of US$5 billion
by 2012.
Inventors: Larry Kwak (NCI) and Arya Biragyn (NIA) (both NCI at
time of invention).
Related Publications:
[[Page 66106]]
1. Coscia M, Biragyn A. Cancer immunotherapy with chemoattractant
peptides. Semin Cancer Biol. 2004 Jun;14(3):209-218. [PubMed:
15246057].
2. Biragyn A, Belyakov IM, Chow YH, Dimitrov DS, Berzofsky JA, Kwak
LW. DNA vaccines encoding human immunodeficiency virus-1 glycoprotein
120 fusions with proinflammatory chemoattractants induce systemic and
mucosal immune responses. Blood. 2002 Aug 15;100(4):1153-1159. [PubMed:
12149191].
3. Schiavo R, Baatar D, Olkhanud P, Indig FE, Restifo N, Taub D,
Biragyn A. Chemokine receptor targeting efficiently directs antigens to
MHC class I pathways and elicits antigen-specific CD8+ T-cell
responses. Blood. 2006 Jun 15;107(12):4597-4605. [PubMed: 16514063].
4. Biragyn A, Ruffini PA, Coscia M, Harvey LK, Neelapu SS, Baskar
S, Wang JM, Kwak LW. Chemokine receptor-mediated delivery directs self-
tumor antigen efficiently into the class II processing pathway in vitro
and induces protective immunity in vivo. Blood. 2004 Oct 1;104(7):1961-
1969. [PubMed: 15191951].
5. Qin H, Nehete PN, He H, Nehete B, Buchl S, Cha SC, Sastry JK,
Kwak LW. Prime-boost vaccination using chemokine-fused gp120 DNA and
HIV envelope peptides activates both immediate and long-term memory
cellular responses in rhesus macaques. J Biomed Biotechnol.
2010;2010:860160. [PubMed: 20454526].
6. Qin H, Cha SC, Neelapu SS, Lou Y, Wei J, Liu YJ, Kwak LW.
Vaccine site inflammation potentiates idiotype DNA vaccine-induced
therapeutic T cell-, and not B cell-, dependent antilymphoma immunity.
Blood. 2009 Nov 5;114(19):4142-4149. [PubMed: 19749091].
7. Singh A, Nie H, Ghosn B, Qin H, Kwak LW, Roy K. Efficient
modulation of T-cell response by dual-mode, single-carrier delivery of
cytokine-targeted siRNA and DNA vaccine to antigen-presenting cells.
Mol Ther. 2008 Dec;16(12):2011-2021. [PubMed: 18813280].
Patent Status: U.S. Patent No. 6,562,347 issued 13 May 2003 (HHS
Reference No. E-107-1998/0-US-03).
Licensing Contact: Patrick McCue, PhD; 301-435-5560;
[email protected].
Collaborative Research Opportunity: The National Institute on
Aging, Laboratory of Immunology, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize cancer vaccines that target skin
antigen-resenting cells. Please contact Nicole Guyton at 301-435-3101
or [email protected] for more information.
Dated: October 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-27179 Filed 10-26-10; 8:45 am]
BILLING CODE 4140-01-P