[Federal Register Volume 69, Number 95 (Monday, May 17, 2004)]
[Notices]
[Page 27939]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-11088]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Prospective Grant of Exclusive License: 1,8-Naphthalimide Imidazo 
[4,5,1-de] Acridones With Anti-Tumor Activity

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

ACTION: Notice.

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SUMMARY: This is 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 6,664,263 issued December 16, 2003, entitled ``1,8-Naphthalimide 
Imidazo [4,5,1-de] Acridones with Anti-Tumor Activity'' (DHHS Reference 
No. E-289-1999/0), and all related foreign patents/patent applications, 
to Reata Discovery, Inc., which is located in Richardson, TX. 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 pharmaceutical uses of 1,8-
naphthalimide imidazo [4,5,1-de] acridones as anti-cancer agents.

DATES: Only written comments and/or applications for a license which 
are received by the NIH Office of Technology Transfer on or before July 
16, 2004 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: George G. Pipia, Ph.D., Technology Licensing 
Specialist, Office of Technology Transfer, National Institutes of 
Health, 6011 Executive Boulevard, Suite 325, Rockville, MD 20852-3804; 
Telephone: (301) 435-5560; Facsimile: (301) 402-0220; and e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION: The present invention relates to novel 
bifunctional molecules with anti-tumor activity. These agents are 
composed of an imidazoacridone moiety linked by a nitrogen containing 
aliphatic chain of various length and rigidity to another aromatic ring 
system capable of intercalation to DNA.
    Previous studies on related symmetrical bis-imidazoacridones 
revealed that only one planar imidazoacridone moiety intercalates into 
DNA. The second aromatic moiety, which is crucial for biological 
activity, resides in a DNA groove, and is believed to interact with 
DNA-binding proteins. It is hypothesized that the action of bis-
imidazoacridone constitutes a new paradigm of how small molecules can 
interfere with the gene transcription.
    To enhance the biological activity, the inventors have developed 
asymmetrical compounds in which one imidazoacridone system, with 
relatively poor DNA-intercalating properties, was replaced with much 
stronger intercalators, such as 3-chloro-7-methoxyacridine or 
naphthalimide moieties. These new compounds, especially those 
containing a naphthalimide moiety, are extremely cytotoxic in vitro 
against variety of tumor cells (IC50 at low nanomolar range) and kill 
tumor cells by inducing apoptosis. In vivo, in nude mice xenografted 
with human tumors, the compounds significantly inhibited growth of such 
tumors as colon tumor HCT116 and Colo205 as well as pancreatic tumors.
    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.

    Dated: May 7, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-11088 Filed 5-14-04; 8:45 am]
BILLING CODE 4140-01-P