[Federal Register Volume 63, Number 138 (Monday, July 20, 1998)]
[Notices]
[Pages 38840-38842]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-19146]


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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.

Murine Intracisternal a Particle Constitutive Transport Elements 
and Uses Thereof

BK Felber, C Tabernero, AS Zolotukhin (NCI)
Serial No. 60/070,204 filed 31 Dec 97
Licensing Contact: Robert Benson, 301/496-7056 ext. 267

    This invention concerns recombinant attenuated HIV strains useful 
as vaccines. HIV regulates its expression by controlling the nuclear 
transport of unspliced mRNA encoding structural proteins. HIV utilizes 
the Rev/RRE system. RRE (Rev. Responsive Element) is an HIV encoded 
nucleo-cytoplasmic transport element (NCTE), which is part of every HIV 
RNA encoding the structural genes (gas/pol and env). Rev is an HIV 
encoded protein which binds to the RRE. This interaction is essential 
for the nucleo-cytoplasmic transport of the RRE-containing viral mRNAs 
and the expression of Gap/Pol and Env proteins. The inventors have 
produced an attenuated HIV by disabling rev/RRE, by point mutations, 
and inserting in its place a novel murine NCTE, isolated form an 
intracisternal A-type particle (IAP). The resultant HIV is attenuated 
between 50 and 200 fold compared to wild-type HIV. Claimed are the 
novel murine NCTE, recombinant retroviruses comprising the NCTE, and 
vaccines. The use of another NCTE is described in Zolotukhin et al., 
(1994) J. Virology 68:7944-7952.

Design and Construction of Non-Infectious Human Retroviral Mutants 
Deficient in Genomic RNA

RJ Gorelick, LO Arthur, A Rein, LE Henderson, S Oroszlan (NCI)
U.S. Patent No. 5,674,720 issued 07 Oct 97
Licensing Contract: Robert Benson, 301/496-7056 ext. 267

    This invention describes methods for generating non-replicating 
(i.e. non-infectious) virus-like particles that mimic HIV-1, SIV and 
other retroviruses, which are capable of generating a protective immune 
response. In addition to being replication defective, these virus like 
particles are deficient in packaged genomic RNA but have the added 
benefit of a normal compliment of viral and cellular proteins that 
remain in their native conformations. Also claimed are methods of 
making the mutant retroviruses which may potentially be used as 
immunogens for vaccines, particularly against HIV-1. The basis of the 
method and the mutant viruses of the claims is the finding that a 
conserved amino acid sequence motif, found in the nucleocapsid domain 
of

[[Page 38841]]

the Gag precursor polyprotein of all retroviruses, when mutated 
resulted in virions with much lower or zero infectivity. This concept 
has been tested in the primate lentivirus, SIV, which is related to 
HIV-1. Mutations were introduced into the gene coding for the conserved 
sequence motif found in the nucleocapsid domain of the Gag precursor 
polyprotein of SIV. The viruses obtained upon transfection were 
defective in replication. Plasmid DNA containing the mutated provirus 
was injected into five pig tailed macques and the vector without the 
provirus was injected into four control animals. The vaccinated animals 
were either partially or fully protected when challenged with 
infectious SIV(Mne) whereas three of the four control animals became 
persistently infected and developed AIDS as indicated by a marked 
decline in CD4 cell numbers. The invention has been filed in foreign 
countries and has been granted in Europe (No. 91900636.1) and Japan 
(No. Hei 7-16420).

The Application of Induction Tolerance by Oral Feeding of Myelin 
Basic Protein to the Generation of Increased Resistance to Stroke

KJ Becker, JM Hallenbeck, RM McCarron (NINDS)
Serial No. 08/994,293 filed 19 Dec 97
Licensing Contact: Stephen Finley, 301/496-7735 ext. 215

    In vivo experiments have shown that immunosuppression in the brain 
can be achieved through oral tolerance to myelin basic protein (MBP). 
Following exposure to MBP again which has the effect of suppressing the 
inflammatory reaction associated with stroke. This possible new means 
of minimizing the severity of damage from stroke, the number three 
killer of Americans and leading cause of disability, does not result in 
detrimental systemic side effects as other immunosuppressive agents do. 
This treatment could be administered to those considered at 
significantly increased risk for a stroke including those with a 
previous stroke, diabetes mellitus, hypertension, hypercholesteremia, 
or a history of smoking as well as those undergoing a medical or 
surgical treatment which increases the possibility of an ischemic 
event.

Salivary Prolactin Test for Serotonergic Activity

JD Higley (NIAAA), S Lindell (NICHD)
Serial No. 60.082,126 filed 16 April 98
Licensing Contact: Stephen Finley, 301/496-7735 ext. 215

    A noninvasive diagnostic assay improves on previous methods for 
determining central serotonin functioning, an indicator of 
susceptibility to aggression, alcohol abuse, obsessive-compulsive 
disorder and eating disorders. Levels of salivary prolactin can be 
assayed to determine susceptibility to the set of pysychiatric 
disorders related to central serotonin functioning. Levels of salivary 
prolactin were found to be positively correlated with levels of 
cerebrospinal fluid (CSF) 5-hydroxyindol acetic acid (5-HIAA), the 
current measurement of central serotonin functioning. Elevated CSF 
levels of 5-HIAA are associated with obsessive-compulsive disorders, 
and reduced levels are associated with violent behavior, alcohol abuse 
and bulimia. There are an estimated 9 million alcoholics in the United 
States and currently 0.5% of women 10 to 30 years old have anorexia 
nervosa while 5% of college-age women have bulimia. The user-
friendliness and reduced costs of the saliva assay suggest possible 
candidacy for mass screenings to determine susceptibility to various 
psychiatric disorders.

Conjugate Vaccine for Salmonella Paratyphi A

E Konadu and S Szu (NICHD)
Serial No. PCT/US96/19978 filed 18 Dec 96
Licensing Contact: Robert Benson, 301/496-7056 ext. 267

    This invention concerns a conjugate vaccine against Salmonella 
paratyphi A comprising the o-specific polysaccharide bound to a carrier 
protein. Salmonella paratyphi A infection causes enteritis and enteric 
fever. The emergence of multidrug resistant strains has raised alarms. 
The present invention offers a method of preventing the disease. The 
conjugate is made by isolating lipopolysaccharide, detoxifying by 
removing the lipid A, while retaining substantially all the O-acetyl 
groups, and conjugating by known means to a carrier protein such as 
tetanus toxoid or detoxified exoprotein A. In a Phase I clinical trial 
the vaccine has been given to healthy adults and elicited anti-LPS IgG 
levels at least 4-fold higher compared to preimmune serum in 85% of 
volunteers. The invention is also described in Konadu et al., Infection 
and Immunity 64(7), 2709-2715, 1996.

Cloning of GMEB 1 and 2: Two Proteins Involved in the Modulation of 
Glucocorticoid Regulated Gene Transcription

S. Stoney Simons, Jr., et al. (NIDDK)
DDH Reference No. E-070-97/0 filed 25 Jul 97
Licensing Contact: Charles Maynard, 301/496-7735 ext. 243

    This technology relates to a previously identified DNA element from 
a naturally occurring gene that has the properties of causing 
glucocorticoid induction at lower steroid concentrations than for other 
glucocorticoid inducible genes in the same cell. This DNA element, also 
called a glucocorticoid modulatory element, or GME, has been found to 
involve two proteins of 88 and 67 kDa.
    This technology has succeeded in cloning and characterizing both 
the 67 kDa protein and the 88 kDa protein which together offer a unique 
and not previously described method of using genetic engineering to 
achieve selective regulation of glucocorticoid responsive genes. This 
group of proteins appears to be members of a larger class of related 
proteins which may have similar roles in modifying the activity of RNA 
polymerase II transcriptional complex.

Gated RF Preamplifier for Use in Pulsed Radiofrequency Electron 
Paramagnetic Resonance and MRI

RG Tschudin (NIDDK), R Murugesan (NCI), MK Cherukuri (NCI), JB Mitchell 
(NCI), S Subramanian (NCI)
Serial No. 08/699,383 filed 19 Aug 96
Licensing Contact: John Fahner-Vihtelic, 201/496-7735 ext. 270

    The present application describes a radiofrequency preamplifier 
featuring very fast recovery after the transmit cycle to allow for 
ultrafast data acquisition, intended for use in pulsed EPR, MRI and 
related computed imaging applications. One advantage of this device is 
that it allows the use of low frequency EPR, which offers better tissue 
penetration during in vivo diagnostic studies. The invention permits 
the use of a pulsed EPR method, which offers improved speed and 
sensitivity over existing methods. A prototype device has been made and 
the design has proven to work in an EPR system.

Lipopolysaccharide Carriers for Use in Vaccines

B Golding (FDA)
Serial No. 08/369,565 filed 06 Jan 95 (allowed)
Licensing Contact: Robert Benson, 301/496-7056 ext. 267

    This invention is a new carrier for conjugate vaccines. The carrier 
is lipopolysaccharide (LPS) isolated from Brucella abortus (BA). The 
claims of the patent cover all conjugates comprising BA-LPS and an 
antigen from an infectious agent or tumor. BA-LPS, like other LPSs from 
gram-negative bacteria,

[[Page 38842]]

raises antibody responses in a T-independent fashion, which allows 
antibodies to be raised in the absence of T cell help. BA-LPS is much 
less toxic than LPS from other bacteria, and is much less potent than 
other bacterial LPS in including inflammatory cytokines. Thus, BA-LPS 
is much less likely to cause endotoxic shock. There are no foreign 
patent rights. The invention is further described in Infection & 
Immunity 61(5), pp. 1722-1729, 1993.

    Dated: July 6, 1998.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 98-19146 Filed 7-17-98; 8:45 am]
BILLING CODE 4140-01-M