[Federal Register Volume 69, Number 44 (Friday, March 5, 2004)]
[Notices]
[Pages 10459-10460]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-4915]


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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, DHHS.

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.

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

Ioannis Bossis (NIDCR).
U.S. Provisional Application No. 60/472,066 filed 19 May 2003 (DHHS 
Reference No. E-105-2003/0-US-01).
Licensing Contact: Jesse S. Kindra; 301/435-5559; [email protected].

    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, eight AAV isolates have been isolated and characterized, 
but new serotypes derived from other animal species may add to the 
specificity and repertoire of current AAV gene therapy techniques.
    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. 
Therefore, vectors derived from this avian AAV are likely to find novel 
applications for gene therapy in humans and fowl.
    This research has been described, in part, in Bossis and Chiorini 
(2003) J. Virol. 12:6799-6810.

Activation of Recombinant Diphtheria Toxin Fusion Proteins by Specific 
Proteases Highly Expressed on the Surface of Tumor Cells

Stephen Leppla, Shi-Hui Liu, Manuel Osorio, and Jennifer Avallone 
(NIDCR).
DHHS Reference No. E-331-2002/0-US-01 filed 06 May 2003.
Licensing Contact: Brenda Hefti; 301/435-4632; [email protected].

    This invention relates to diphtheria toxin fusion proteins 
comprising a diphtheria toxin (DT) cell-killing component and a cell-
binding component such as granulocyte macrophage colony-stimulating 
factor (GM-CSF), interleukin 2 (IL-2), or epidermal growth factor 
(EGF). Receptors for the latter three materials are present on many 
types of cancer cells; therefore, these fusion proteins bind 
preferentially to these cancer cells. A key feature is that these 
toxins are altered so as to require activation by a cell-surface 
protease that is overexpressed on many types of cancers. Examples of 
such proteases include matrix metalloproteinases and urokinase 
plasminogen activator. Consequently, these novel cytotoxins kill tumors 
expressing receptors for either GM-CSF, IL-2, or EGF along with the 
cell-surface protease. Because killing requires the presence of both a 
receptor and a cancer-cell enriched protease, and few normal tissues 
contain both, there is less toxicity to normal cells. Thus, a larger 
amount of the agent may be used for cancer therapy without inducing 
side effects. In other words, these cytotoxins have a higher 
therapeutic index than toxins that are targeted to cells using a single 
strategy.

Dominant Negative Deletion Mutants of C-Jun and Their Use in the 
Prevention and Treatment of Cancer

NH Colburn, Z Dong, PH Brown, MJ Birrer (NCI).
U.S. Patent Application No. 08/213,433 filed 10 Mar 94 (DHHS Reference 
No. E-240-1993/0-US-01).
Licensing Contact: Jesse Kindra; 301/435-5559; [email protected].

    A number of mutants of the c-jun oncogene have been developed, 
which may be particularly useful in the prevention and treatment of 
cancer. Numerous studies have shown that tumor promotion is a long-term 
process that is partially reversible and that requires chronic exposure 
to a tumor promoter, and that subsequent progression of tumors through 
invasive and metastatic stages is also a long term process. In recent 
years, numerous cellular oncogenes have been implicated in the 
transactivation of genes associated with cellular growth and 
differentiation. One such cellular oncogene, c-jun, encodes a 
phosphoprotein that is a component of the dimeric transcriptional 
activator AP-1 along with c-Fos or other Jun or Fos family proto-
oncoproteins. Several genes that may be involved in tumor promotion or 
progression have been shown to be dependent on AP-1 transactivation, 
including collagenase and stromelysin (transin). AP-1 inhibiting 
dominant negative deletion mutants of the c-jun gene have been 
developed that, when given to a mammal, may prevent or reverse 
carcinogenesis during early or late stages. For the treatment of 
cancer, a deletion mutant of the c-jun gene or the protein product may 
inhibit the elevated AP-1 transactivation that frequently characterizes 
tumor progression and may consequently prevent or reverse the 
development or further progression of

[[Page 10460]]

tumors. This invention also includes a method for determining whether a 
tumor promoter induces transformation via a pathway that depends on 
induction or elevation of AP-1 transcriptional activity and AP-1 target 
gene expression.

Deazaflavin Compounds and Methods of Use Thereof

Alan Weissman et al. (NCI).
U.S. Provisional Application No. 60/447,610 filed 13 Feb 2003 (DHHS 
Reference No. E-231-2002/0-US-01).
Licensing Contact: Jeffrey Walenta; 301/435-4633; 
[email protected].

    Recently, a new strategy for the treatment of cancer was validated 
by the FDA approval of a small molecule proteasome inhibitor. This 
treatment strategy, while being efficacious, achieved this result by 
generally inhibiting all proteasome activity. However, the ubiquitin-
mediated process that instructs the proteasome to degrade specific 
proteins is exquisitely specific to the type of protein degraded. The 
exact mechanism of how the individual components of the ubiquitin-
mediated process regulate the amount of a specific protein present in a 
cell is just beginning to be elucidated with certainty. Drugs specific 
to these components can regulate cellular level of important proteins.
    This invention is a family of 7-nitro-5-deazaflavin compounds that 
inhibit MDM2 protein activity in a cell. The MDM2 protein is an E3 
ubiquitin ligase that mediates the transfer of ubiquitin to the 
important tumor suppressor protein p53: p53 will initiate apoptosis in 
cancer cells. By minimizing ubiquitin transfer to p53--and its 
subsequent degradation--the 7-nitro-5-deazaflavin compounds can 
potentially increase the tumor suppressor properties of p53 by 
maintaining a higher concentration of the important tumor suppressor 
protein within the cell.
    This invention could be an important next generation proteasome 
inhibitor as it can potentially inhibit the degradation of specific 
proteasome substrates.

    Dated: February 27, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-4915 Filed 3-4-04; 8:45 am]
BILLING CODE 4140-01-P