[Federal Register Volume 61, Number 201 (Wednesday, October 16, 1996)]
[Notices]
[Page 53931]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-26411]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

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.

ADDRESSES: Licensing information and a copy of the U.S. patent 
applications referenced below may be obtained by contacting Larry 
Tiffany, J.D., at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804 (telephone 301/496-7056 ext 206; fax 301/402-0220). 
A signed Confidential Disclosure Agreement will be required to receive 
a copy of the patent application.

Recombinant Pseudomonas Exotoxin With Increased Activity

IH Pastan, DJ Fitzgerald (NCI)
Serial Nos. 07/901,709 filed 18 Jun 92 and 08/405,615 filed 15 Mar 
95 (FWC of 07/901,709); also 08/463,480 and 08/461,234 filed on 05 
Jun 95 (DIVs of 08/405,615)

    Development of novel recombinant Pseudomonas exotoxin molecules 
with higher target cell toxicity and less nonspecific cell toxicity 
offers to significantly improve the effectiveness of immunotherapies 
against virally infected and cancer cells. Toxins attached to growth 
factors, antibodies, and other cell-targeting molecules can be used to 
kill harmful cells bearing specific surface receptors or antigens. One 
promising source of an effective therapeutic toxin is Pseudomonas 
exotoxin (PE) A, an extremely active monomeric protein that is excreted 
by the bacteria Pseudomonas aeruginosa. PE, which causes cell death by 
inhibiting protein synthesis in eukaryotic cells, contains three 
structural domains that act in concert to cause cytotoxicity: domain Ia 
mediates cell binding, domain II is responsible for translocation into 
the cytosol, and domain III leads indirectly to inhibition of protein 
synthesis. Unfortunately, immunotoxins made with native PE also attack 
the liver and--when given in large doses--may produce death due to 
liver toxicity. This problem has been overcome by cleaving parts of the 
native endotoxin molecule including all of domain Ia and part of domain 
II. Such ``pre-cleaved'' PE molecules are smaller in size and, thus, 
less likely to be immunogenic. They also are better able to penetrate 
tumors. These new PE molecules are at least 20 times more cytotoxic to 
target cells and less cytotoxic to normal cells than previously 
developed PE immunotoxins.

    Dated: October 2, 1996.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 96-26411 Filed 10-15-96; 8:45 am]
BILLING CODE 4140-01-M