[Federal Register Volume 69, Number 2 (Monday, January 5, 2004)]
[Notices]
[Page 372]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-99]


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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.

Combinatorial Therapy for Protein Signaling Diseases

Arpita Mehta (NCI), Lance Liotta (NCI), Emmanuel Petricoin (FDA)
U.S. Provisional Application No. 60/453,629 filed 10 Mar 2003 (DHHS 
Reference No. E-039-2003/0-US-01)
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    Available for licensing are methods for individualizing therapy 
based on information obtained concerning deranged signaling pathways 
that cause disease. The invention includes the use of protein 
microarrays to detect the deranged signaling pathways that are specific 
for the subject's disease. The invention covers the use of combination 
therapy targeting multiple points in the protein network. The invention 
is based, in part, on the unexpected discovery that treatment of 
interconnected nodes in a protein signaling pathway can provide a 
synergistic improvement in therapeutic efficacy at reduced toxicity. 
For example, a protein signaling network of a diseased cell (e.g., 
colon cancer) is analyzed and the information obtained from the 
analysis is used to select at least two drugs whose targets are 
interconnected within the protein signaling network.

Fluorescent Pteridine Nucleoside Analogs

Mary Hawkins, Wolfgang Pfleiderer, Frank Balis, Michael Davis (NCI)
    U.S. Patent 5,525,711 issued 11 Jun 1996 (DHHS Reference No. E-181-
1993/0-US-01);
    U.S. Patent 5,612,468 issued 18 Mar 1997 (DHHS Reference No. E-181-
1993/0-US-23);
    U.S. Patent 6,451, 530 issued 17 Sep 2002 (DHHS Reference No. E-
155-1996/0-US-03);
    U.S. Patent Application No. 09/786,666 filed 07 Mar 2001, allowed 
(DHHS Reference No. E-035-1998/0-US-0).
Worldwide IP coverage.
Licensing Contact: Susan Carson; 301/435-5020; [email protected].

    Pteridines are naturally occurring, highly fluorescent compounds 
(Quantum yields 0.88-0.40) that are structurally similar to purines and 
that were first isolated from butterfly wings in 1889. The pteridine 
nucleoside analogs developed by NCI scientist Hawkins and co-workers 
are structurally similar to guanosine (3-MI and 6-MI) or adenosine (6-
MAP). These analogs are stable, can be formulated as phosphoramidites 
and are incorporated into oligonucleotides as a direct substitute for a 
purine base using automated DNA synthesis. The fluorescence properties 
of these probes are directly impacted by the chemistry of neighboring 
bases and reflect changes in tertiary structure due to interactions 
with proteins, RNA or DNA. Even subtle changes in base stacking or base 
pairing can be observed through changes in fluorescence intensity, 
lifetimes, energy transfer or anisotropy, making these pteridines 
ideally suited for the study of DNA/DNA and DNA/protein interactions.
    Several applications have been further developed using this 
technology and one such application causes the pteridine probe to 
``bulge'' out of the base stacking environment as it anneals to a 
target sequence which does not contain a base pairing partner for the 
pteridine. Prior to binding to the bulge-forming target strand the 
fluorescence of the probe is very quiet, only ``lighting up'' when 
bound to a specific sequence. This highly specific technique results in 
a dramatic increase in fluorescence intensity of up to 27 fold, is very 
rapid, does not require separation of oligonucleotides in a mixture and 
has been used in the development of a PCR product detection system. The 
specific nature of the ``bulge hybridization'' technique may be used to 
overcome some of the issues caused by non-specific probe binding in 
standard chip technology. (For a review see: Hawkins, M. (2003) 
Fluorescent Nucleoside Analogues as DNA Probes, in DNA Technology. J. 
R. Lakowicz. New York, Kluwer Academic/Plenum Publishers Vol 7 151-
175.) More recent applications have shown that the stability and 
brightness of the guanosine analogy 3-MI are suitable for studies 
requiring probe detection at the single molecule level and studies 
using 6-MAP and 2-photon counting excitation demonstrate the adenosine 
analog's usefulness as a UV probe.
    The pteridine nucleoside analogs provide a unique opportunity to 
use native-like, stable and highly fluorescent probes in the 
development of further refined, quantitative approaches to the study of 
DNA/DNA and DNA/protein interactions. The pteridine nucleoside patent 
portfolio is available for licensing and provides composition and 
methods of use claims for these versatile fluorophores.

    Dated: December 22, 2003.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-99 Filed 1-2-04; 8:45 am]
BILLING CODE 4140-01-P