[Federal Register Volume 69, Number 83 (Thursday, April 29, 2004)]
[Notices]
[Pages 23511-23512]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-9685]



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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.

Carbohydrate-Encapsulated Quantum Dots for Cell-Specific Biological 
Imaging

Joseph Barchi, Sergei Svarovsky (NCI).
U.S. Provisional Application filed 22 Mar 2004 (DHHS Reference No. E-
133-2004/0-US-01).
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    Available for licensing is intellectual property covering 
carbohydrate-encapsulated quantum dots (QD) for use in medical imaging 
and methods of making the same. Certain carbohydrates, especially those 
included on tumor glycoproteins are known to have affinity for certain 
cell types. One notable glycan used in the present invention is the 
Thomsen-Freidenreich disaccharide (Ga1[beta]1-3Ga1NA[alpha]-O-Ser/Thr) 
that is readily detectable in 90% of all primary human carcinomas and 
their metastases. These glycans can be exploited for medical imaging. 
Quantum Dots (QDs) are metallic (CdSe or CdTe) nanoparticles with 
detectable luminescent properties. Conjugating luminescent QDs with 
target specific glycans permits efficient imaging of the tissue to 
which the glycans bind with high affinity. Accurate imaging of diseased 
cells (e.g., primary and metastatic tumors) is of primary importance in 
disease management. The inventors describe the only stable synthesis of 
glycan encapsulated QDs. In one embodiment, the synthesis involves the 
preparation of hybrid QDs containing a glycan and a luminescence-
enhancing passivating agent in various ratios. Second generation QDs 
contain the glycan ligands and polyethylene glycols (PEG) of varying 
chain lengths. The PEG modifications produced QDs that maintained high 
luminescence while reducing non-specific cell binding.

MVL, an Antiviral Protein From a Cyanobacterium

Carole A. Bewley (NIDDK).
DHHS Reference No. E-068-2004/0-US-01 filed 08 Mar 2004.
Licensing Contact: Sally Hu; 301/435-5606; [email protected].

    The invention describes the discovery of the carbohydrate binding 
protein (lectin), MVL, that binds specifically to oligosaccharides 
comprising the tetrasaccharide, 
Man[alpha](1[rarr]6)(Man[beta](1[rarr]4)G1cNAc[beta](1[rarr]4)G1cNAc, 
with very high (nanomolar) affinity.
    In particular, this invention shows that the binding of MVL to the 
carbohydrate residues of the glycoprotein gp120 can block HIV fusion 
into human cells and thus inhibit HIV infection. As a consequence, 
subject invention may be used in the development of therapeutics for 
the treatment of retroviral infections, such as AIDS. In addition, MVL 
described in this invention may also have particular value when used in 
combination treatments with other antiviral therapies directed at other 
viral targets, such as protease and reverse transcriptase.

Multiplex Real-Time PCR

Enrique Zudaire Ubani, Frank Cuttitta (NCI).
U.S. Patent Application No. 10/658,602 filed 08 Sep 2003 (DHHS 
Reference No. E-215-2003/0-US-01).
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; 
[email protected].

    This invention is in the field of multiplex real-time polymerase 
chain reaction (PCR). In particular, the invention pertains to the 
quantification of multiple amplicons in a single polymerase chain 
reaction based on the different melting temperatures of amplicons. A 
utility U.S. Patent Application No. 10/658,602 was filed on September 
8, 2003.
    PCR is a primer-directed in vitro reaction for the enzymatic 
amplification of a fragment of DNA, involving repetitive cycles of DNA 
template denaturation, primer annealing to the DNA template, and primer 
extension. The result is an exponential accumulation of a specific DNA 
fragment or amplicon from an initial nominal amount of sample DNA 
templates. Multiplex PCR offers a more efficient approach to PCR, 
whereby multiple pairs of primers are used to simultaneously amplify 
multiple amplicons in a single PCR reaction. The simultaneous 
amplification of various amplicons decreases both the cost and turn-
around time of PCR analysis, minimizes experimental variations and the 
risk of cross-contamination, and increases the reliability of end 
results. Multiplex PCR has gained popularity in many areas of DNA 
testing, including prognosis, diagnostic, gene deletion analysis, 
mutation and polymorphism analysis, genotyping and DNA array analysis, 
RNA detection, farmacogenomics and identification of microorganisms.
    Real-time PCR has been developed to overcome limitations in 
quantifying amplicons during an ongoing PCR reaction, since traditional 
PCR and multiplex PCR are often limited to a qualitative analysis of 
end-product amplicons. Real-time PCR is based on the principles that 
emission of fluorescence from dyes directly or indirectly associated 
with the formation of newly synthesized amplicons or the annealing of 
primers with DNA templates can be detected and is proportional to the 
amount of amplicons in each PCR cycle. The resulting emission curve can 
then be used to calculate the initial copy number of a nucleic acid 
template at the beginning of the PCR reaction. Real-time PCR eliminates 
the need for post PCR steps and is highly recognized for its high 
sensitivity, precision and reproducibility. This invention is directed 
to methods for real-time monitoring and quantification of multiple 
amplicons in a single multiplex real-time PCR reaction based on the use 
of a double stranded DNA dye and the melting temperature discrepancy 
among the amplicons.

Methods and Compositions for the Inhibition of HIV-1 Replication

Sharon M. Wahl, Nancy Vazquez-Maldonado, Teresa Greenwell-Wild (NIDCR).
U.S. Provisional Application No. 60/516,794 filed 04 Nov 2003 (DHHS 
Reference No. E-114-2003/0-US-01).
Licensing Contact: Sally Hu; 301/435-5606; [email protected].


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    This invention relates to methods and compositions for the 
attenuation of HIV-1 replication in human cells, and especially in 
human macrophages by targeting a host cell protein. HIV-1 infected 
macrophages typically resist cell death, support viral replication, and 
facilitate HIV-1 transmission. We found that the gene encoding cyclin-
dependent kinase inhibitor 1A (CDKN1A) is consistently expressed 
following virus binding, and re-expressed at the peak of HIV-1 
replication. The protein encoded by this gene, also known as p21, is 
associated with cell cycle regulation, anti-apoptotic response and cell 
differentiation. Increased levels of p21 may enhance survival and long-
term persistence of HIV-1 infected macrophages. Treatment of cultured 
infected cells with antisense p21 oligonucleotides or p21 short 
interfering RNA (p21 siRNA) significantly reduced replication of HIV-1. 
A similar effect was observed when infected cells were exposed to the 
synthetic triterpenoid CDDO, a potent multifunctional agent that 
influences differentiation and has anti-inflammatory and anti-
proliferative properties, including inhibition of p21. Neither p21 
oligonucleotides nor CDDO were toxic to the cultured macrophages. Thus, 
p21 inhibitors could be safe and effective anti-HIV therapeutic 
candidates to be used in conjunction with current anti-retroviral 
therapy.

Cannula for Pressure Mediated Drug Delivery

Stephen Wiener, Robert Hoyt, John Deleonardis, Randal Clevenger, Robert 
Lutz, Brian Safer (NHLBI).
PCT Application No. PCT/US99/11277 filed 21 May 1999, which published 
as WO 99/59666 on 25 Nov 1999 (DHHS Reference No. E-196-1998/2-PCT-01); 
U.S., Australian, Japanese, and European rights pending.
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    Available for licensing are methods and devices for selectively 
delivering therapeutic substances to specific histological or 
microanatomical areas of organs (e.g., introduction of the therapeutic 
substance into a hollow organ space such as the hepatobiliary duct or 
the gallbladder lumen) at a controlled pressure, volume and/or rate 
which allows the substance to reach a predetermined cellular layer. The 
volume or flow rate of the substance can be controlled so that the 
intralumenal pressure reaches a predetermined threshold beyond which 
subsequent subepithehal delivery of the substance occurs. 
Alternatively, a lower pressure is selected that does not exceed the 
threshold level, so that delivery occurs substantially to the 
epithelial layer. Such site-specific delivery of therapeutic agents 
permits localized delivery in concentrations that may otherwise produce 
systemic toxicity. Occlusion of venous or lymphatic drainage from the 
organ can also help prevent systemic administration of therapeutic 
substances, and increases selective delivery to superficial epithelial 
cellular layers. Delivery of genetic vectors can also be delivered to 
target cells. The access device comprises a cannula with a wall 
piercing tracar within the lumen. Two axially spaced inflatable 
balloons engage the wall securing the cannula and sealing the puncture 
site. A catheter equipped with an occlusion balloon is guided through 
the cannula to the location where the therapeutic substance is to be 
delivered.

    Dated: April 22, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-9685 Filed 4-28-04; 8:45 am]
BILLING CODE 4140-01-P