[Federal Register Volume 69, Number 66 (Tuesday, April 6, 2004)]
[Notices]
[Pages 18095-18097]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-7697]


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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, HHS.

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.

Reduction of HIV-1 Replication by a Mutant Apolipoprotein B mRNA 
Editing Enzyme-Catalytic Polypeptide-like 3G (APOBEC3G)

Vinay K. Pathak et al. (NCI).

[[Page 18096]]

U.S. Provisional Application filed 11 Feb 2004 (DHHS Reference No. E-
073-2004/0-US-01).
Licensing Contact: Michael Ambrose; 301/594-6565; 
[email protected].

    The invention describes a single amino acid substitution at D128K 
renders the human apolipoprotein B mRNA-editing enzyme-catalytic-like 
3G (APOBEC3G) (CEM15) capable of inhibiting HIV-1 replication in the 
presence of HIV viral infectivity factor (Vif). HIV-1 and other 
retroviruses occasionally undergo hypermutation, characterized by high 
rate of G-to-A substitution. Studies have shown that human APOBEC3G is 
packaged into the retrovirus and deaminates deoxycytidine to 
deoxyuridine in newly synthesized viral minus-strand DNA, thereby 
inducing G-to-A hypermutation and viral inactivation. This innate 
mechanism of resistance to retroviral infection is counteracted by the 
HIV-1 Vif, which protects the virus by preventing the incorporation of 
APOBEC3G into virions by rapidly inducing it ubiquitination a 
proteosomal degradation. The inventors substituted several amino acids 
in human APOBEC3G with equivalent residues in simian APOBEC3G, which 
are resistant to HIV-1 VIF and determined the effects of the mutations 
on HIV-1 replication in the presence and absence of Vif. The Vif-
resistant mutant could interact with HIV-1, but unlike the wild type of 
APOBEC3G, its intracellular steady-state levels were not reduced in the 
presence of HIV-1 Vif.
    This technology provides a potential breakthrough for the treatment 
of HIV through gene therapy. By introducing the mutant version of 
APOBEC3G into hematopoietic stem cells and transfusing into HIV/AIDS 
patients, a level of resistance can be acquired. Further, using this 
mutation in a more classical vaccine approach to gene therapy is also 
envisioned.

Mucus Shaving Apparatus for Endotracheal Tubes

Lorenzo Berra, Theodor Kolobow (NHLBI).
DHHS Reference No. E-061-2004/0-US-01 filed 05 Feb 2004.
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    DHHS seeks parties interested in manufacturing and commercializing 
an endotracheal tube cleaning apparatus for insertion into the inside 
of the endotracheal tube of a patient to shave away mucus deposits. 
This cleaning apparatus comprises a flexible central tube with an 
inflatable balloon at its distal end. Affixed to the inflatable balloon 
are one or more shaving rings, each having a squared leading edge to 
shave away mucus accumulations implicated in bacterial accumulation. In 
operation, the un-inflated cleaning apparatus is inserted into the 
endotracheal tube until its distal end is properly aligned with the 
distal end of the endotracheal tube. After proper alignment, the 
balloon is inflated by a suitable inflation device (e.g., a syringe) 
until the balloon's shaving rings are pressed against the inside 
surface of the endotracheal tube. The cleaning apparatus is then pulled 
out of the endotracheal tube and in the process the balloon's shaving 
rings shave off the mucus deposits from the inside of the endotracheal 
tube.
    Two papers have been submitted for presentations at the forthcoming 
American Thoracic Society meeting in Orlando, Florida, May 21-26, 2004. 
The abstract numbers and titles are (1) Abstract 3655, ``A Novel System 
for the Complete Removal of all Mucus fro the Endotracheal Tubes: The 
Mucus Shaver'', and (2) Abstract 3793, ``A Novel System to Maintain 
Endotracheal Tube free from Secretions and Biofilm'', which describes 
laboratory studies of its usage. The abstracts are available upon 
request.

Thermolabile Hydroxyl Protecting Groups and Methods of Use

Serge L. Beaucage, Marcin K. Chmielewski (FDA).
U.S. Provisional Application No. 60/469,312 filed 09 May 2003 (DHHS 
Reference No. E-154-2003/0-US-01).
Licensing Contact: Marlene Astor; 301/435-4426; [email protected].

    Synthetic oligonucleotides can be used in a wide variety of 
settings, which include gene therapy treatments, diagnostic and DNA 
sequencing microarray technology, and basic research. The NIH announces 
an improvement in oligonucleotide syntheses for potential application 
on glass microarrays. This improvement entails the incorporation of 
thermolytic hydroxyl protecting groups derived from 2-aminopyridine and 
its analogues into nucleosides and their phosphoramidite derivatives. 
This novel class of 2-pyridyl-substituted hydroxyl protecting groups 
can be efficiently cleaved under mild thermolytic conditions without 
the use of harsh chemicals such as strong acids or bases. As an 
example, this technology uses thermal cleavage (brief heat treatment at 
temperatures up to 90[deg]) of terminal 5'-hydroxyl protecting groups 
on a growing oligonucleotide chain without inducing the formation of 
reactive radicals, which is in contrast to the currently used 
photochemical deprotection methods. In addition, the mild neutral 
conditions employed in the thermolytic approach, will help prevent 
glass surfaces from being harmed by the harsh reagents that are still 
being used in conventional solid phase oligonucleotide synthesis. The 
thermal cleavage method also permits accurate monitoring of coupling 
efficiency after each chain elongation step by the use of fluorescent 
thermolytic groups for hydroxyl protection of nucleoside 
phosphoramidite monomers. Thus, these thermolabile groups could be 
useful in manufacturing synthetic oligonucleotides on solid supports or 
in solution. Also, thermolabile groups may be used to protect/deprotect 
drug functional groups under conditions that will not affect other 
protecting groups on the molecule.

Long Term Retrievable Venous Filter

Ziv Neeman and Bradford Wood (NIHCC).
U.S. Provisional Application No. 60/543,766 (DHHS Reference No. E-061-
2003/0-US-01).
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    Available for licensing and commercialization is a novel long-term 
or biodegradable retrievable vena cava (IVC) filter that can be 
retrieved indefinitely regardless of the time it was placed, or 
alternatively dissolves without being removed, leaving no clinically 
relevant traces of its presence. IVC Filters are underutilized due to 
the complications associated with chronic indwelling, and long term 
consequences of IVC filters (like chronic venous insufficiency and 
venous stasis) has an uncertain, but high incidence. IVC filters would 
be more widely used for short term prophylaxis against one of the most 
underdiagnosed and deadly hospital acquired diseases, namely pulmonary 
embolism. Patients with burns, trauma, or undergoing orthopedic 
procedures like hip replacement are at high risk for venous clots, that 
could then migrate to the lung, which can be lethal. This design leaves 
in only several small mm long struts that are coated with drugs that 
prevent early clot formation on the struts and legs of the filter. The 
device includes struts that, upon removal of the filter, separate from 
the filter legs mechanical or electrical means and are left behind 
permanently embedded within the venous wall. Other designs include 
filters made from biodegradable polymers that dissolve over time 
without requiring removal.

[[Page 18097]]

This biodegradable filter may suit patients with temporary needs for 
protection (patients with prolonged immobility, hip replacement, 
trauma, intensive care patients).

Triplex Hairpin Ribozyme

Joseph A. DiPaolo (NCI), Luis Alvarez-Salas (EM).
U.S. Provisional Application No. 60/500,000 filed 23 Sep 2002 (DHHS 
Reference No. E-326-2002/0-US-01); PCT Application No. PCT/US03/29893 
filed 23 Sep 2003 (DHHS Reference No. E-326-2002/0-PCT-02).
Licensing Contact: Michael Ambrose; 301/594-6565; 
[email protected].

    Much work has focused on understanding and utilizing nucleic acids 
as biological catalysts. Indeed, progress has been made in determining 
the mechanism, kinetics and conformational requirements in harnessing 
these potential biological catalysts. This technology has value in its 
potential for gene therapy applications such as gene silencing.
    The technology described is a recombinant plasmid or expression 
vector in which a DNA-encoded trans-acting hairpin ribozyme of interest 
is ligated to DNA-encoded cis-acting hairpin ribozyme. In this 
configuration, the cis-acting ribozyme serves to cleave the 5'' and 3'' 
ends of the trans-acting ribozyme of interest. The trans-acting 
ribozymes can be replaced with any user-defined sequence such as 
antisense RNA or RNAs of viruses. This unit provides several trans-
acting hairpin ribozymes that are trimmed at the ends are further 
generated. Thus several independent ribozymes can be produced from a 
single transcribed RNA.

    Dated: March 30, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-7697 Filed 4-5-04; 8:45 am]
BILLING CODE 4140-01-P