[Federal Register Volume 67, Number 85 (Thursday, May 2, 2002)]
[Notices]
[Pages 22093-22094]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-10927]


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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 agencies 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.

HIV-1 Envelope Glycoproteins Stabilized by Flexible Linkers as 
Potent Entry Inhibitors and Immunogens

    Dimitrov et al. (NCI).

[DHHS Reference No. E-039-02/0 filed 05 Mar 2002]

    Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: 
[email protected].
    The technology relates to tethered constructs where flexible 
linkers join gp120 and the ectodomain of gp41. The HIV-1 envelope 
Glycoprotein (Env) undergoes conformational changes while driving 
entry. The inventors hypothesized that some of the intermediate Env 
conformations could be stably represented in tethered constructs where 
gp120 and the ectodomain of gp41 are joined by flexible linkers. 
Tethered Envs with long (15 to 26 amino acid) linkers were stable and 
potently inhibited fusion mediated by R5, X4 and R5X4 Envs, most likely 
by exposure of gp41 structures that bind DP178 and cluster II mAbs. A 
tethered Env with a short (4 amino acid) linker, gp120 or DP178 were 
100, 20 or 10-fold less effective, respectively. The fusion proteins 
with long linkers exhibited enhanced exposure of DP178 and cluster II 
mAbs binding gp41 structures that are critical for entry. These 
findings suggest the existence of conserved structures that are 
critical for HIV-1 entry, and could be used as inhibitors and novel 
immunogens for elicitation of broadly neutralizing antibodies.

Construction of West Nile Virus and Dengue Virus Chimeras for Use 
in a Live Virus Vaccine to Prevent Disease Caused by West Nile 
Virus

    Pletnev et al. (NIAID).

[DHHS Reference No. E-357-01/0 filed 10 Jan 2002]

    Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: 
[email protected].
    A candidate live attenuated vaccine strain was constructed for West 
Nile virus (WN), a neurotrophic flavivirus that has recently emerged in 
the U.S. Considerable attenuation for mice was achieved by 
chimerization with dengue virus type 4 (DEN4). The genes for the 
structural premembrane and envelope proteins of DEN4 present in an 
infectious cDNA clone were replaced by the corresponding genes of WN 
strain NY99. Two of 18 cDNA clones of a WN/DEN4 chimera yielded full-
length RNA transcripts that were infectious when transfected into 
susceptible cells. The WN/DEN4 chimera was highly attenuated in mice 
compared with its WN parent; the chimera was at least 28,500 times less 
neurovirulent in suckling mice inoculated intracerebrally and at least 
10,000 times less virulent in adult mice inoculated intraperitoneally. 
Nonetheless, the WN/DEN4 chimera and a deletion mutant derived from it 
were immunogenic and provided complete protection against lethal WN 
challenge. These observations provide the basis for pursuing the 
development of a live attenuated WN vaccine.

MVA Expressing Modified HIV Envelope, Gag and Pol Genes

    Bernard Moss and Linda S. Wyatt (NIAID).

[DHHS Reference No. E-115-01/0 filed 08 Mar 2001]

    Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: 
[email protected].
    This technology relates to construction of a recombinant poxvirus 
using modified vaccinia Ankara (MVA). The recombinant MVA (rMVA) 
expresses HIV Gag, Pol and HIV-1 Env under the control of vaccinia 
virus early/late promoters. A related rMVA expressing SHIV genes was 
used in heterologous prime/boost regimens that raised high levels of 
immune responses. DNA priming followed by a recombinant modified 
vaccinia Ankara (rMVA) booster controlled a highly pathogenic 
immunodeficiency virus challenge in a rhesus macaque model. Both the 
DNA and rMNA components of the vaccine expressed multiple 
immunodeficiency virus proteins. Two DNA inoculations at 0 and 8 weeks 
effectively controlled an intrarectal challenge administered 7 months 
after the booster. These findings provide hope that a relatively simple 
multiprotein DNA/MVA vaccine can

[[Page 22094]]

help to control the acquired immune deficiency syndrome epidemic. This 
research is described in Science 292(5514): 69-74, April 6, 2001 
(originally published in Science Express as 10.1126/science.1058915 on 
March 8, 2001).

Specific Inhibition of Gene Expression by Small Double Stranded 
RNAs

    Caplen et al. (NHGRI).

[DHHS Reference No. E-284-01/0 filed 30 Jul 2001]

    Licensing Contact: Fatima Sayyid; 301/496-7056 ext. 243; e-mail: 
[email protected].
    Double-stranded RNA (dsRNA) has been shown to trigger sequence-
specific gene silencing in a wide variety of organisms, including 
plant, nematode and invertebrate species. Recent intense work in the 
field has shown that small dsRNAs mediate sequence specific RNA 
degradation in the process known as RNA interference (RNAi).
    This invention provides for synthetic dsRNAs (20-25 nucleotides in 
length) and methods that can inhibit gene-specific expression in 
mammalian cells. The sequence of the dsRNAs are essentially identical 
to a portion of the coding region of the target gene for which 
interference or inhibition of expression is desired. This inhibition 
has been shown to be superior to single-stranded antisense 
oligonucleotides and opens the possibility of the use of dsRNAs as 
reverse genetic and therapeutic tools in mammalian cells.

Magnetic Labeling of Cells Using Transfection Agents

    Joseph Frank and Jeff Bulte (CC).

[DHHS Reference No. E-176-01/0 filed 13 Jun 2001]

    Licensing Contact: Norbert Pontzer; 301/496-7736, ext. 284; e-mail: 
[email protected].
    Many therapeutic strategies, such as stem cell transplantation, are 
based upon introducing exogenous living cells or tissues into a patient 
or host. A problem common to all therapeutic strategies involving 
administration of exogenous cells is identifying and monitoring the 
cells in the host. It is currently difficult or impossible to monitor 
the location of such cells or tissues in the host after administration. 
It may also be difficult to establish the survival of these cells in 
the host. Currently available procedures to locate transplanted cells 
are invasive and destructive. This problem must be overcome before such 
cell therapies can achieve their full potential.
    Magnetic Resonance Imaging (MRI) is a technique that allows whole 
body in vivo imaging in three dimensions at near-cellular (microscopic) 
resolution. MR image contrast is largely determined by the nuclear 
magnetic relaxation times of tissues. To allow detection of 
transplanted cells, this technology provides compositions and methods 
for labeling cells in vitro with a contrast agent prior to 
transplantation. These contrast agents are non-toxic, biodegradable and 
are prepared by mixing commercially available magnetic responsive 
coated iron oxides and transfection agents, some of which are FDA 
approved. Magnetically labeled cells will facilitate the use or MRI to 
monitor these cells following transplantation in a clinical setting.

Anti-sera Against Arylalkylamine N-acetyltransferase (AANAT)--The 
Melatonin Rhythm Enzyme

    David C. Klein et al. (NICHD).

[DHHS Reference No. E-181-00/0]

    Licensing Contact: Pradeep Ghosh; 301/496-7736 ext. 211; e-mail: 
[email protected].
    Biological materials are important research tools that can be used 
for diagnostic purposes. In particular, antisera are of broad value in 
biomedical research and in clinical chemistry. The present invention 
comprises of unpurified and immunopurified antisera developed in 
rabbits against bovine, rat, pike-2, zebra fish, chicken, monkey, and 
human AANAT. AANAT is an important enzyme because it controls the 
production of melatonin and its rhythm in vertebrates. A daily rhythm 
of melatonin in the circulation serves as the hormonal signal of the 
daily light/dark cycle. AANAT protein is expressed at high levels in 
pineal gland and retina, and only at night. The antisera developed as 
part of this invention may serve as an important immunologic tool to 
detect and monitor the expression of AANAT protein. Expression of AANAT 
is important for the understanding of the biochemical and physiological 
role of melatonin and therefore, the antisera may have a wide use in 
research studies. In addition, antisera detecting human AANAT may be 
useful in pathological and histochemical analysis of human pineal and 
retinal tissues. Further, the use of antisera may be applicable in 
clinical testing and monitoring of the effects of drugs on AANAT 
protein and other biochemical modification procedures.
    Research articles that describe the use of the antisera include: 
Invest Opthalmol. and Visual Science 43:564-572, 2002; Proc. Natl. 
Acad. Sci U.S.A. 98:8083-8088, 2001; Endocrinology 142:1804-1813, 2001; 
J. Biol. Chem. 276:24097-24107, 2001; J. Neurochem. 75:2123-2132, 2000; 
J. Neurochem. 74:2315-2321, 1999; Science 279:1358-1360, 1998; Recent 
Progress in Hormone Research 52:307-358, 1997.

    Dated: April 24, 2002.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-10927 Filed 5-1-02; 8:45 am]
BILLING CODE 4140-01-P