[Federal Register Volume 66, Number 164 (Thursday, August 23, 2001)]
[Notices]
[Pages 44363-44364]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-21265]


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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 agencies 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.

Single-Chain Antibody Fragment Protein Binding to HIV-1 Integrase

Eugene Barsov and Stephen Hughes (NCI), DHHS Reference No. E-193-01/0

    Licensing Contact: Sally Hu; 301/496-7056 ext. 265; e-mail: 
[email protected]
    Integration of the viral DNA into the host genome is a prerequisite 
for efficient viral transcription and establishment of productive HIV-1 
infection in humans. This function is mediated by the viral protein 
integrase. The invention discloses a single-chain Fab fragment of a 
murine monoclonal antibody (scFv35) that is able to inhibit the viral 
integrase. The antibody fragment can be recombinantly expressed. The 
Fab fragment is further described in the Journal of Virology 70 (7), pp 
4484-4495, 1996. It is available for licensing through a Biological 
Materials License Agreement as no patent application has been filed.

Plasmid Based Assay for the in vitro Repair of Oxidatively Induced 
DNA Double Strand Breaks

Thomas A. Winters, Elzbeitz Pastwa, and Ronald D. Neumann (CC), DHHS 
Reference No. E-319-00/0 filed 06 Oct 2000

    Licensing Contact: Wendy Sanhai; 301/496-7736 ext. 244; e-mail: 
[email protected]
    We describe a new non-radioactive, high throughput in vitro assay 
for the repair of oxidatively induced DNA double-strand breaks by HeLa 
cell nuclear extracts. The assay measures non-homologous end joining 
(NHEJ) repair by employing linear plasmid DNA containing DNA double-
strand breaks (DSBs) produced by either the radiomimetic drug bleomycin 
or StuI restriction endonuclease. The complex structure of the 
bleomycin-induced DSB more closely models naturally occurring DSBs than 
restriction enzyme induced DSBs. Although initial optimization 
reactions were conducted with these DNA molecules, any double-strand-
break-inducing agent may be employed to create the linear DNA 
substrates used in the assay.
    Cellular extraction and initial end-joining reaction conditions 
were optimized with restriction enzyme cleaved DNA to maximize ligation 
activity. Several parameters affecting ligation were examined including

[[Page 44364]]

extract protein concentration, substrate concentration, ATP 
utilization, reaction time, temperature, and effect of ionic strength. 
Similar reactions were performed with the bleomycin-linearized 
substrate. In all cases, end-joined molecules ranging from dimers to 
higher molecular weight forms were produced and observed directly in 
agarose gels stained with Vistra Green and imaged with a FluorImager 
595. This method permits detection of less than or equal to 0.25 ng 
double-stranded DNA per band directly in post-electrophoretically 
stained agarose gels. Therefore, the optimized end joining reactions 
required only 100 ng or less of substrate DNA, and up to 50% conversion 
of substrate to product was achieved.
    The DSB end structure was shown to directly affect repair of the 
strand break. Bleomycin-induced DSBs were repaired at a 6-fold lower 
rate than blunt-ended DNA, and initiation of the reaction lagged behind 
that of the blunt-end rejoining reaction. Recent experiments have shown 
repair of DSBs produced by -rays to be 15-fold less efficient 
than for DSBs produced by restriction enzyme. While repair of the high-
LET-like DSB produced by 125I was near the lower limit of detection. 
Thus, as the cytotoxicity of the DNA damaging agent increases, the DSB 
created by the agent is less efficiently repaired.
    Repair efficiency is also dependent upon the repair capacity of the 
cellular extract employed as a source of repair enzymes. These repair 
activities are known to vary from tissue to tissue, and person to 
person.
    Therefore, by using patient samples as a source of enzyme 
activities, our method might be employed clinically as a predictive 
assay for patient sensitivity to DNA damaging agents. Knowledge of a 
patient's sensitivity to DNA damaging agents may permit more effective 
choices to be made when selecting treatment options in cases of cancer, 
and other diseases where DNA damaging agents are commonly used.

Sensitization of Cancer Cells to Immunoconjugate-Induced Cell Death 
by Transfection With Interleukin-13 Receptor Alpha-Chain

R. Puri (FDA), DHHS Reference No. E-032-00/1 filed 31 August 2000

    Licensing Contact: Richard Rodriguez; 301/496-7056 ext. 287; e-
mail: [email protected]
    The claimed technology relates to the use of gene transfer 
techniques to sensitize cancer cells to IL-13 Receptor-mediated 
immunotoxin induced cell death. Specifically, the inventor has shown 
that stable gene transfer of the IL-13R2 chain, of the IL-13 
receptor, significantly sensitizes cancer cells to the effects of IL-13 
toxin by approximately 520-1000-fold. Since many cancers, e.g., brain, 
breast, lung, head and neck, pancreatic, prostate or liver, can be 
inoperable, direct intratumoral administration of treatment-agents may 
become necessary. As such, the claimed invention shows that a 
combination approach, utilizing both gene transfer and systemic or 
locoregional cytotoxin therapy, may be available as a new potent 
treatment regimen for intractable or refractory cancers.

    Dated: August 13, 2001.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 01-21265 Filed 8-22-01; 8:45 am]
BILLING CODE 4140-01-P