[Federal Register Volume 67, Number 116 (Monday, June 17, 2002)]
[Notices]
[Pages 41253-41254]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-15148]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Prospective Grant of Exclusive License: Cytotoxic Treatment of 
Cancer Cells That Overexpress Matrix Metalloproteinases, Plasminogen 
Activators and/or Plasminogen Activator Receptors

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: This notice, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR 
Part 404.7(a)(1)(i), that the National Institutes of Health, Department 
of Health and Human Services is contemplating the grant of an exclusive 
patent license to practice the inventions embodied in U.S. Patent 
Application, 60/155,961 (refiled): ``Mutated anthrax toxin protective 
antigen proteins that specifically target cells containing high amounts 
of cell-surface metalloproteinase or plasminogen activator receptors' 
(DHHS Ref. E-293-99/0); PCT Patent Application, PCT/US00/26192 [WO01/
21656] (refiled): ``Mutated anthrax toxin protective antigen proteins 
that specifically target cells containing high amounts of cell-surface 
metalloproteinase or plasminogen activator receptors' (DHHS Ref. E-293-
99/1); U.S. Patent Application, S/N 10/088,952: ``Mutated anthrax toxin 
protective antigen proteins that specifically target cells containing 
high amounts of cell-surface metalloproteinase or plasminogen activator 
receptors' (DHHS Ref. E-293-99/2); U.S. Patent 5,591,631, S/N 08/
021,601, which issued on January 7, 1997 (DHHS Ref. E-064-93/0), 
entitled, ``Anthrax toxin fusion proteins, nucleic acid encoding 
same''; U.S. Patent 5,677,274, S/N 08/082,849, which issued on October 
14, 1997 (DHHS Ref. E-064-93/1), entitled, ``Anthrax toxin fusion 
proteins and related methods''; and any related foreign filed national 
stage applications claiming priority to such cases to OncoTac 
Pharmaceuticals which is located in Medicon Valley, Denmark. The patent 
rights in these inventions have been assigned to the United States of 
America.
    The prospective exclusive license territory will be worldwide and 
the field of use may be limited to human therapeutics for the treatment 
of cancer by a mechanism involving cancer-associated enzymes and/or 
receptors.

DATES: Only written comments and/or license applications that are 
received by the National Institutes of Health on or before August 16, 
2002, will be considered.

ADDRESSES: Requests for copies of the patent, inquiries, comments and 
other materials relating to the contemplated exclusive license should 
be directed to: Richard U. Rodriguez, M.B.A., Technology Licensing 
Specialist, Office of Technology Transfer, National Institutes of 
Health, 6011 Executive Boulevard, Suite 325, Rockville, MD. 20852-3804. 
Telephone: (301) 496-7056, X287; Facsimile: (301) 402-0220; and E-mail: 
[email protected].

SUPPLEMENTARY INFORMATION: The primary technology relates to an 
immunotoxin treatment system that is targeted to cancer cells via an 
anthrax-based pathway. Native anthrax toxin is a three-component toxin 
consisting of protective antigen (PrAg), lethal factor (LF), and edema 
factor (EF). PrAg binds to the recently identified cell surface anthrax 
receptor and the subsequent steps in toxin action is dependent on 
cleavage of PrAg at the sequence, 164RKKR167, by 
a cell-surface, furin-like protease. The carboxyl-terminal 63-kDa 
fragment (PrAg63) remains bound to receptor, forms a heptamer, and 
binds and internalizes LF and EF. LF kills animals and lyses mouse 
macrophages due to proteolytic cleavage of MAP kinase kinases. EF 
damages cells due to its intracellular adenylate cyclase activity. A 
potent PrAg dependent cytotoxin, FP59, created by fusing LF amino acids 
1-254 to the ADP-ribosylation domain of Pseudomonas exotoxin A can kill 
any cell having receptors for PrAg and the ability to activate PrAg by 
cleavage at amino acids 164-167.
    Activation of the native PrAg is dependent on a cell surface 
located furin-like proteolytic activity. In the current technology, the 
furin-site has been manipulated to generate mutant PrAg proteins that 
are specific for matrix metalloproteinases (MMPs) or the urokinase 
plasminogen activator (uPA). A combination of the mutated toxins PrAg 
and FP59 has been shown to be an effective cytotoxic agent that is 
strictly dependent on cell surface localized MMP and/or uPA-activity.
    The prospective exclusive license will be royalty bearing and will 
comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR part 
404.7. The prospective exclusive license may be granted unless within 
sixty (60) days from the date of this published notice, the NIH 
receives written evidence and argument that establish that the grant of 
the license would not be consistent with the requirements of 35 U.S.C. 
209 and 37 CFR part 404.7.
    Applications for a license in the field of use filed in response to 
this notice will be treated as objections to the grant of the 
contemplated exclusive license. Comments and objections submitted to 
this notice will not be made available for public inspection and, to 
the extent permitted by law, will not be released under the Freedom of 
Information Act, 5 U.S.C. 552.


[[Page 41254]]


    Dated: June 7, 2002.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 02-15148 Filed 6-14-02; 8:45 am]
BILLING CODE 4140-01-P