[Federal Register Volume 72, Number 59 (Wednesday, March 28, 2007)]
[Notices]
[Pages 14591-14593]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-5675]


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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.

[[Page 14592]]

Enhanced Function of Gene Modified T-Cells: Identification of T-Cell 
Receptors (TCR) with Altered Amino Acid Sequence

    Description of Technology: A major limitation 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. Immunotherapy 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.
    This invention is directed to substitutions in gene sequences that 
code for T cell receptors, specifically the inventors found that one to 
two amino acid substitutions in the TCRs that recognize 1G4 XY-ESO-1 
and MART-1 resulted in a marked increase of these modified TCRs to 
recognize tumor cell targets. These mutated sequences are currently 
being evaluated as candidates for clinical development. The inventors 
also consider the invention as providing a ``general paradigm'' that 
will allow the generation of TCR directed against a variety of antigens 
that can enhance the function of gene modified T cells.
    Applications:
    1. Improved ability of modified TCRs to recognize tumor cell 
targets.
    2. High affinity TR can be generated that recognizes a variety of 
antigens that can be potentially used for the diagnosis and treatment 
of patients with a variety of conditions that include cancer, 
infectious diseases and autoimmunity.
    3. Mutant high affinity TR can also be used to transduce T cells in 
order to generate cells reactive with tumor antigens as well as viral 
antigens.
    Development Status: Pre-clinical work has been completed and 
clinical work is undergoing.
    Inventors: Paul F. Robbins (NCI), Steven A. Rosenberg (NCI), 
Richard A. Morgan (NCI), et al.
    Relevant Publication: A manuscript relating to this invention is 
under preparation and will be available once accepted.
    Patent Status: U.S. Provisional Application No. 60/847,447 filed 26 
Sep 2006 (HHS Reference No. E-304-2006/0-US-01).
    Licensing Status: This technology is available for licensing under 
an exclusive or non-exclusive patent license.
    Licensing Contact: Michelle Booden, PhD; 301/451-7337; 
[email protected].
    Collaborative Research Opportunity: The NIH Surgery Branch is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
adoptive immunotherapy. Please contact John D. Hewes, PhD at 301-435-
3121 or [email protected] for more information.

Novel Benzindole Based Compounds for HIV Therapy

    Description of Technology: The HIV/AIDS epidemic continues despite 
efforts from scientists, drug companies, and non-profit organizations. 
Although the existing therapy, is effective in the treatment of many 
infected individuals in developed nations, the infected individual is 
not cured and therapy must be life-long. There are problems with drug 
toxicity, the development of resistant viral strains, and with the cost 
of therapy. New anti-viral agents are needed for a more effective, and 
a more cost-effective, treatment of HIV.
    The invention describes compounds based on a benzindole moiety, 
which alkylates DNA. The compounds comprise a benzindole moiety, a 
bifunctional linker, and a fatty acid residue or dendrimer residue 
comprising at least one fatty acid. Several benzindole derivatives are 
synthesized. The compounds bind to the minor groove of DNA and can be 
useful in the inhibition of gene expression. The advantage of the 
compounds is that they remain inactive until conformational change 
induced by DNA binding makes them active. The fatty acid moiety 
immobilizes them on the cytoplasmic side of the plasma membrane. These 
anchored compounds are specifically designed to inhibit retroviral DNA 
before it translocates to the host nucleus and integrates with the host 
genome.
    Applications and Modality:
    1. Novel benzindole-based compounds for HIV therapy.
    2. Compounds are specifically designed to inhibit retroviral DNA 
before it can integrate with the host genome.
    3. Additionally, compounds might have potential anti-cancer 
activities.
    Market:
    1. More than 45 million people are living with HIV/AIDS worldwide.
    2. More than 3 million estimated deaths due to HIV/AIDS occurred 
worldwide in 2003.
    3. HIV/AIDS epidemic has caused more than 30 million deaths.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Christopher J. Michejda (NCI), Stephen H. Hughes (NCI), 
et al.
    Relevant Publication: A manuscript directly related to the above 
technology will be available as soon as it is accepted for publication.
    Patent Status: U.S. Provisional Application No. 60/850,437 filed 10 
Oct 2006 (HHS Reference No. E-126-2006/0-US-01).
    Licensing Availability: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Adaku Nwachukwu, J.D.; 301/435-5560; 
[email protected]
    Collaborative Research Opportunity: The National Cancer Institute's 
Structural Biophysics Laboratory is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize novel benzindole based compounds 
for HIV therapy. Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

Cloning and Characterization of an Avian Adeno-Associated Virus and 
Uses Thereof

    Description of Technology: Currently, adeno-associated virus (AAV) 
represents the gene therapy vehicle of choice because it has many 
advantages over current strategies for therapeutic gene insertion. AAV 
is less pathogenic than other virus types; stably integrates into 
dividing and non-dividing cells; integrates at a consistent site in the 
host genome; and shows good specificity towards various cell types for 
targeted gene delivery.
    To date, 11 AAV isolates have been isolated and characterized. New 
serotypes derived from non-human animal species have added to the 
specificity and repertoire of current AAV gene therapy techniques by 
avoiding the immunologic complications associated with human isolates.
    This invention describes vectors derived from an avian AAV. These 
vectors have innate properties related to their origin that may confer 
them with a unique cellular specificity in targeted human gene therapy 
and a unique immunologic profile that would avoid neutralization by 
pre-existing antibodies. Therefore, vectors derived

[[Page 14593]]

from this avian AAV are likely to find novel applications for gene 
therapy in humans. Furthermore because of their species of origin, this 
vector would also be useful in the engineering of avian cells.
    Inventors: Ioannis Bossis and John A. Chiorini (NIDCR).
    Publication: I Bossis, JA Chiorini. Cloning of an avian adeno-
associated virus (AAAV) and generation of recombinant AAAV particles. J 
Virol. 2003 Jun;77(12):6799-6810.
    Patent Status: U.S. Patent Application No. 10/557,662 filed 21 Dec 
2006 (HHS Reference No. E-105-2003/0-US-03).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Jesse S. Kindra, J.D.; 301/435-5559; 
[email protected]
    Collaborative Research Opportunity: The National Institute of 
Dental and Craniofacial Research, Laboratory of Dr. John Chiorini, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
gene therapy methods using AAV vectors. Please contact David W. 
Bradley, PhD at [email protected] for more information.

Serotonin-Deficient Knock-Out Mouse

    Description of Technology: Serotonin is an important modulator of 
many developmental, behavioral, and physiological processes, and it has 
been implicated in depression, anxiety, schizophrenia, obsessive 
compulsive disorders, and substance abuse. Serotonin's pharmacology is 
extremely complex and it is mediated by seven of serotonin receptor 
subtypes and it is present in several tissues. Although it has been a 
subject of a number of studies, its role has been difficult to 
ascertain. To investigate the role of serotonin in these disorders, the 
murine gene was disrupted by homologous recombination. Results indicate 
that serotonin binding sites were absent in different brain regions 
(brain stem, frontal cortex, hippocampus, and striatum), and its 
concentrations were reduced by 60-80%. These mice represent a powerful 
tool for the investigation of behavioral and neuropsychiatric 
disorders, and development of drug treatments for these disorders.
    Applications: A model to study serotonin's role in behavioral and 
neuropsychiatric disorders.
    Market:
    1. Serotonin inhibitors are most widely used treatment in 
neuropsychological disorders. Examples include Zoloft, Paxil, and 
Prozac.
    2. Depression effects approximately 18.8 million U.S. citizens and 
over 121 million people worldwide.
    3. Antidepressant market was worth $16.2 billion in 2005, and it 
has annual growth of 2% year on year.
    4. Anxiety disorders affect 40 million (18.1%) of the adult U.S. 
population.
    5. Global anxiety disorder market was $4.5 billion in 2006.
    Inventors: Dennis L. Murphy (NIMH) et al.
    Publications:
    1. RF Ren-Patterson, LW Cochran, A Holmes, S Sherrill, SJ Huang, T 
Tolliver, K-P Lesch. Loss of brain-derived neurotrophic factor gene 
allele exacerbates brain monoamine deficiencies and increases stress 
abnormalities of serotonin transporter knockout mice. J Neurosci Res. 
2005 Mar 15:79(6):756-771.
    2. DL Murphy, A Lerner, G Rudnick, K-P Lesch. Serotonin 
transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv. 
2004 April:4(2):109-123.
    3. RF Ren-Patterson, D-K Kim, X Zheng, S Sherrill, S-J Huang, T 
Tolliver, DL Murphy. Serotonergic-like progenitor cells propagated from 
neural stem cells in vitro: survival with SERT protein expression 
following implantation into brains of mice lacking SERT. FASEB J. 2005 
Sep:19(11):1537-1539.
    4. Q Li, A Holmes, L Ma, LD Van de Kar, F Garcia, DL Murphy. 
Medical hypothalamic 5-hydroxytryptamine (5HT)1A receptors regulate 
neuroendocrine responses to stress and exploratory locomotor activity 
application of recombinant adenovirus containing 5-HT1A sequences. J 
Neurosci. 2004 Dec 1:24(48):10868-10877.
    5. F Kilic, DL Murphy, G Rudnick. A human serotonin transporter 
mutation causes constitutive activation of transport activity. Mol 
Pharmacol. 2003 Aug:64(2):440-446.
    6. DL Murphy, GR Uhl, A Holmes, R Ren-Patterson, FS Hall, I Sora, S 
Detera-Wadleigh, K-P Lesch. Experimental gene interaction studies with 
SERT mutant mice as models for human polygenic and epistatic traits and 
disorders. Genes Brain Behav. 2003 Dec:2(6):350-364.
    7. N Ozaki, D Goldman, WH Kaye, K Plotnicov, BD Greenberg, J 
Lappalainen, G Rudnick, DL Murphy. Serotonin transporter missense 
mutation associated with a complex neuropsychiatric phenotype. Mol 
Psychiatry. 2003 Nov:8(11):933-936.
    Patent Status: HHS Reference No. B-019-1999/0--Research Tool.
    Licensing Status: This technology is available as a research tool 
under a Biological Materials License.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].

    Dated: March 15, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-5675 Filed 3-27-07; 8:45 am]
BILLING CODE 4140-01-P