[Federal Register Volume 60, Number 90 (Wednesday, May 10, 1995)]
[Notices]
[Pages 24867-24870]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-11422]



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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, HHS.

ACTION: Notice.

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    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 U.S. 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 Specialist at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804 (telephone 301/496-7735; fax 301/402-0220). A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

2,5-Diamino-3,4-Disubstituted-1,6-F-Diphenyhexane Isoteres Comprising 
Benzamide, Sulfonamide and Anthranilamide Subunits and Methods Of Using 
Same

Randad, R.S., Erickson, J.W. (NCI)
Filed 20 Dec 94
Serial No. 08/359,612
Licensing Contact: Robert Benson (301/496-7056 ext 267)

    This invention concerns retroviral protease inhibitors which are 
potential drugs for the treatment of HIV infection. The compounds of 
the invention contain novel nonpeptidic and achiral substituents, 
wherein achiral benzamide, sulfonamide and anthranilamide subunits are 
introduced onto the 2,5-diamino-3,4-disubstituted-1,6-diphenylhexane 
isostere core. The compounds are more resistant to viral and mammalian 
protease degradation. The best compounds had a Ki (inhibition 
constant) of less than 100 pM for HIV protease. CEM cells chronically 
infected with HIV-1 were used to test anti-retroviral activity. The 
concentrations needed to inhibit 50% of viral activity were on the 
order of 5 nM. Therefore, these compounds compare favorably in their 
anti-viral potency to the best HIV protease inhibitors currently in 
clinical trials. [portfolio: Infectious Diseases--Therapeutics, anti-
virals, AIDS]

Conformationally Locked Nucleoside Analogs

Marquez, V.E., Rodriguez, J.B., Nicklaus, M.C., Barchi, J.J.
(NCI)
Filed 24 Sep 94
Serial No. 08/311,425 (CIP of 08/126,796)
    Licensing Contact: Carol Lavrich (301/496-7735 ext 287)
    Novel nucleoside analogues have been developed that may facilitate 
structure-function analysis of anti-HIV compounds. Recently, there has 
been intense interest in the design and use of nucleoside analogues 
that can inhibit the replication of viruses such as HIV-1. The three-
dimensional conformation of such analogues has been implicated in their 
ability to successfully inhibit viral replication; however, in the 
past, it has been difficult to conduct structure- 
[[Page 24868]] function analyses because the sugar part of the 
nucleoside is flexible and the conformation often changes. These newly 
developed nucleoside analoguess make such studies more feasible because 
they employ cyclopropane-fused di-deoxynucleosides, which lock the 
conformation of the sugar part of the molecule in place. [portfolio: 
Internal Medicine--Miscellaneous]

Mammalian Bilirubin UDP-Glucoronosyltransferase Clones, and Methods for 
Use Thereof

Owens, I., Ritter, J. (NICHD)
Filed 8 Sep 94
Serial No. 08/303,315 (CIP of 08/209,688, FWC of 07/639,453)
Licensing Contact: Carol Lavrich (301/496-7735 ext 287)

    Liver transplantation is now the only treatment for Crigler-Najjar 
Type I syndrome. Other hyperbilirubinemic syndromes are difficult and 
expensive to diagnose. This cDNA clone encodes a mammalian bilirubin 
UDP-glucoronosyltransferase. Applications include gene therapy for 
patients with Crigler-Najjar Type I syndrome, a gene-based fetal 
diagnostic probe for the syndrome, and diagnostic tools for other 
hyperbilirubinemic syndromes such as Gilbert syndrome. [portfolio: 
Internal Medicine--Miscellaneous]

Nucleotide and Deduced Amino Acid Sequences of the Envelope 1 Gene Of 
51 Isolates Of Hepatitis C Virus and the Use Of Reagents Derived from 
These Sequences in Diagnostic Methods and Vaccines

Bukh, J., Miller, R.H., Purcell, R.H. (NIAID)
Filed 15 Aug 94
Serial No. 08/290,665
Licensing Contact: Girish Barua (301/496-7735 ext 263)

    The invention is in the field of hepatitis virology and relates to 
complete nucleotide and deduced amino acid sequences of the envelope 1 
(E1) gene of hepatitis C virus (HCV) isolates from around the world and 
the grouping of these isolates into twelve distinct HCV genotypes. More 
specifically, this invention covers oligonucleotides, peptides and 
recombinant proteins derived from the envelope 1 gene sequences of the 
51 isolates of hepatitis C virus and to diagnostic methods and vaccines 
which employ these reagents. [portfolio: Infectious Diseases--Vaccines] 


Isolation of A New Murine Helicobacter Bacteria, Tentatively Classified 
as A Helicobacter Hepaticus

Ward, J.M., Fox, J.G., Collins, M.J., Gorelick, P.L., Benveniste,
R.E., Tully, J.G., Gonda, M.A. (NCI)
Filed 24 Jun 94
Serial No. 08/266,414
Licensing Contact: Girish Barua (301/496-7735 ext 263)

    An isolated bacterium of the genus Helicobacter, characterized by 
the 16S ribosomal RNA encoding nucleotide sequence is described. An 
isolated nucleic acid comprising the nucleotide sequence is also 
defined. Such a nucleic acid can be used for diagnosis of infection 
with H. hepaticus. A nucleic acid of the present invention in a vector 
suitable for expression of the nucleic acid is provided. The vector can 
be in a host suitable for expressing the nucleic acid. A purified 
antigen specific for H. hepaticus and a method of making an animal 
model for chronic Helicobacter infection is also described. [portfolio: 
Infectious Diseases--Miscellaneous]

Cloning, Expression, and Diagnosis of Human Cytochrome P450 2C19: The 
Principal Determinant of S-Mephenytoin Metabolism

Goldstein, J.A., Romkes-Sparks, M., DeMorais, S. (NIEHS)
Filed 6 May 94
Serial No. 08/238,821 (CIP of 08/201,118, CIP of 07/864,962)
Licensing Contact: Carol Lavrich (301/496-7735 ext 287)

    Two novel cytochrome P450 enzymes have been isolated and 
characterized that appear be the principal human determinant of S-
mephenytoin metabolism. This invention has particular application to 
the development of more effective anticonvulsant drugs. Mephenytoin is 
used for the control of grand mal, focal, Jacksonian, and psychomotor 
epileptic seizures that are refractory to other types of anti-
convulsant drugs. In most individuals, mephenytoin is metabolized by 4/ 
-hydroxylation of S-mephenytoin. This is accomplished by a cytochrome 
P450 enzyme in liver cells; however, some subpopulations of individuals 
have defects in this P450 enzyme, resulting in reduced levels of S-
mephenytoin 4/ -hydroxylase activity and severe side effects. The DNA 
sequence that encodes enzymes from the cytochrome P450 2C subfamily of 
enzymes has been isolated and cloned. Polymorphisms of these enzymes, 
designated 2C18 and 2C19, appear to be the principal reason that 
certain individuals cannot effectively metabolize S-mephenytoin and, 
thus, have adverse side effects with this drug. This invention provides 
purified cytochrome P450 2C19 peptides and purified cytochrome P450 
2C18 polypeptides, as well as the CDNA encoding these polypeptides. The 
invention, among other things, also provides methods for screening for 
a drug that is metabolized by S-mephenytoin 4/ -hydroxylase activity, 
for determining the metabolites activated by a xenobiotic or 
carcinogenic compound, and for diagnosing patients with a deficiency in 
S-mephenytoin 4/ -hydroxylase activity. [portfolio: Internal Medicine-- 
Miscellaneous]

Rotavirus Strain And Related Composition

Glass, R.I., Gentsch, J.R., Das, B.K., Bhan, M.K. (CDC)
Filed 15 Apr 94
Serial No. 08/231,041
Licensing Contact: Girish Barua (301/496-7735 ext 263)

    Rotavirus is the leading cause of severe diarrheal disease in 
infants in both developed and developing countries, and development of 
a vaccine for this disease is therefore a global priority. The 
availability of both cloned rotavirus genes and protein sequences of 
important rotavirus antigens should permit yet additional approaches to 
vaccine development.
    This invention covers an isolated rotavirus of strain G9P11 and an 
isolated nucleic acid encoding the rotavirus and a purified antigen 
specific for rotavirus. An isolated nucleic acid that selectively 
hybridizes under high stringency conditions with the nucleic acid 
encoding the virus is provided. A purified antibody which selectively 
binds the virus of strain G9P11 is covered. The G9P11 rotavirus in a 
pharmaceutical carrier for administration in an immunization protocol 
is disclosed. Also provided are an isolated rotavirus of strain G9P11, 
wherein the G9 gene and P11 gene are substituted. [portfolio: 
Infectious Diseases--Diagnostics, viral; Infectious Diseases--Vaccines, 
viral]

Hepatitis C Virus Core Peptide for Stimulation Of Cytotoxic T 
Lymphocytes

Berzofsky, J.A., Feinstone, S.M., Shirai, M. (NCI)
Filed 8 Apr 94
Serial No. 08/224,973
Licensing Contact: Girish Barua (301/496-7735 ext 263)

    The invention covers a series of peptide fragments of hepatitis C 
virus core protein and their use as activators of cytotoxic T 
lymphocytes. The peptides can be used as vaccines or components of 
vaccines to prevent hepatitis C. Besides the peptide 
[[Page 24869]] fragments, pharmaceutical compositions and methods of 
immunization and diagnostics are also claimed. [portfolio: Infectious 
Diseases--Therapeutics, anti-virals]

Superactive Vasoactive Intestinal Peptide Antagonist

Gozes, I., Brenneman, D.E., Fridkin, M., Moody, T.W. (NICHD)
Filed 7 Feb 94
Serial No. 08/194,591
Licensing Contact: Carol Lavrich (301/496-7735 ext 287)

    A potent antagonist of the vasoactive intestinal polypeptide (VIP) 
has been developed that may be useful in inhibiting the growth of 
certain kinds of lung cancers, among others. VIP is a widely 
distributed peptide hormone and neurotransmitter that mediates a 
variety of physiologic responses including gastrointestinal secretion; 
relaxation of gastrointestinal, vascular, and respiratory smooth 
muscle; pituitary hormone secretion; and penile erection. Receptors for 
VIP also have been detected in cells derived from small cell lung 
carcinoma and three other major types of lung cancer, and VIP has been 
shown to promote the growth of these types of lung cancers. 
Traditionally, lung cancer is treated with chemo- and/or radiation 
therapy, but survival rates for these types of therapies are quite low. 
Researchers have now developed a number of short polypeptide sequences 
that are able to bind to VIP receptors in various types of cells but do 
not display biologic activity. Thus, these polypeptides are potent 
inhibitors of VIP activity and may be effective chemotherapeutic agents 
in the treatment of certain VIP-sensitive lung cancers. These 
polypeptides, which are designed to discriminate between the various 
VIP receptors in the body, also may be useful for delineating the 
physiologic function of VIP in the CNS and other tissues. [portfolio: 
Internal Medicine--Miscellaneous]

IgE-Binding Epitopes of A Major Heat-Stable Crustacean Allergen Derived 
From Shrimp

Metcalfe, D.D., Martin, B.M., Rao, P.V.S. (NIAID)
Filed 10 Nov 93
Serial No. 08/149,809
Licensing Contact: Carol Lavrich (301/496-7735 ext 287)

    Epitopes of a major heat-stable shrimp allergen, which may be 
valuable for desensitizing individuals who are allergic to shrimp and 
other crustacea, have been developed. Crustacea are among the foods 
most frequently associated with immunoglobulin E (IgE)-mediated type I 
hypersensitive reactions in individuals with food allergies. 
Previously, there has been no method for effectively desensitizing 
individuals to crustacea-related allergic reactions. This problem has 
been overcome by isolating the IgE allergenic epitopes of the SA-I and 
SA-II heat-stable shrimp antigens. These epitopes--or their peptide 
derivatives--could potentially be given to patients in order to 
desensitize them to the antigens. The use of antigenic epitopes for 
desensitization is preferable to using the entire antigen because it 
minimizes the possibility of a severe adverse reaction. Because this 
IgE-binding antigen is highly conserved among crustacea, potential 
application includes diagnosis and treatment of a wide range of 
crustacea-induced allergies with only these two allergenic epitopes. 
[portfolio: Internal Medicine--Miscellaneous]

Nitric Oxide-Releasing Compounds for the Sensitization Of Hypoxic 
Cells in Radiation Therapy

Mitchell, J.B., Krishna, M.C., Wink, D., Liebman, J.E., Russo, A. (NCI)
Filed 8 Oct 93
Serial No. 08/133,574
Licensing Contact: Carol Lavrich (301/496-7735 ext 287)

    A novel method has been developed for sensitizing oxygen-poor, or 
hypoxic, tumor cells, which will increase the effectiveness of 
radiation treatment. It has long been known that ionizing radiation is 
more effective in killing cancer cells if the cells are in an oxygen-
rich environment; however, the farther tumor cells are away from the 
blood supply, the more hypoxic they are and the more resistant they are 
to radiation therapy. Current methods for delivering oxygen to hypoxic 
cells have limitations because they are toxic to normal tissue, require 
oxygen for their activity, or they have too short a half-life. This 
development overcomes such problems by employing a nitrous oxide (NO)-
containing compound that spontaneously releases NO under physiologic 
conditions without requiring oxygen. This compound--which has a 
relatively long half-life and is nontoxic to normals cells--has the 
dual advantages of being able to sensitize hypoxic tumor cells to 
ionizing radiation while protecting normal cells from the effects of 
radiation. [portfolio: Internal Medicine--Therapeutics, cardiology]

Transmission-Blocking Vaccine Against Malaria

Kaslow, C.K., Isaacs, S., Moss, B. (NIAID)
Filed 23 Aug 93
Serial No. 08/110,457 (CON of 07/908,765, CON of 07/658,845)
Licensing Contact: Robert Benson (301/496-7056 ext 267)

    A transmission-blocking vaccine developed against malaria contains 
a recombinant virus, which encodes a unique portion of the sexual-stage 
surface antigen of Plasmodium falciparum (referred to as Pfs25), or the 
Pfs25 protein purified from infected host cells. Mice inoculated with 
the recombinant virus developed antibodies capable of blocking 
transmission of the virus. None of the mAbs known to block transmission 
recognize the reduced Pfs25 antigen. This vaccine, which induces high, 
long-lasting titers at low cost, can be useful for controlling malaria. 
[portfolio: Infectious Diseases--Vaccines, parasite]

Rat Thyrotropin Receptor Gene, and Its Uses

Kohn, L.D., Akamizu, T., Ikuyama, S., Saji, M., Kosugi, S., Ban, T. 
(NIDDK)
Filed 29 Nov 93
Serial No. 08/064,058
Licensing Contact: Carol Lavrich (301/496-7735 ext 287)

    The rat thyrotropin receptor gene has been cloned, which will make 
it significantly easier to study this important biologic receptor and 
to develop therapies for thyroid gland disorders. Thyrotropin, or 
thyroid stimulating hormone (TSH), is a pituitary hormone that 
regulates the development and activity of the thyroid gland. Abnormal 
binding of thyrotropin to its specific thyroid cell receptor may be the 
cause of variety of syndromes such as hypothyroidism; however, the in 
situ structure of the thyrotropin receptor remains unclear because a 
number of proteins appear to bind to it. Pure sources of this receptor 
are unavailable because of the extraordinarily small numbers of 
receptors in thyroid cells. Although thyrotropin receptor genes 
previously have been cloned for two species (dog and human), a more 
desirable starting point for elucidating the structure and function of 
the thyrotropin receptor would be to study it in a more utilizable 
animal model, such as the rat. The gene product of the cloned FRTL-5 
rat thyroid cell receptor can be used in assays to look for ligands 
that bind to the receptor. Truncated forms of the protein also may be 
used for studying the structure and function of various domains of the 
receptor. Ultimately, this invention is useful for developing 
treatments for disorders arising from dysfunctions of this receptor. 
[portfolio: Internal Medicine--Miscellaneous]
[[Page 24870]]

Nucleotide-Deduced Amino Acid Sequence, Isolation, and Purification of 
Heat Shock Chlamydial Proteins

Morrison, R.B., Caldwell, H.D. (NIAID)
Filed 25 Feb 92
Serial No. 07/841,323 (DIV of 07/679,302, DIV of USPN 5,071,962)
Licensing Contact: Carol Lavrich (301/496-7735 ext 287)

    The chlamydial heat shock protein (HSP60) is an immunodominant 
genus common antigen which has been implicated in immunopathologic 
delayed type hypersensitivity reactions during chlamydial infections. 
The HypB gene which encodes the chlamydial HSP60 has been cloned and 
characterized. High levels of HSP60 expression have been obtained in 
prokaryotic vectors and methods have been developed for the 
purification of the chlamydial HSP60 protein. Availability of large 
quantities of purified recombinant chlamydial HSP60 offers novel 
approaches to preventing, treating, and diagnosing chlamydial 
infections of humans. [portfolio: Infectious Diseases--Diagnostics, 
bacterial]

Methods and Compositions for Diagnosing Cat Scratch Disease and 
Bacillary Angiomatosis

Regnery, R.L., Anderson, B.E. (CDC)
Serial No. 07/822,539
Patent Issued 21 Mar 95
U.S. Patent No. 5,399,485
Licensing Contact: Carol Lavrich (301/496-7735 ext 287)

    A previously unidentified pathogenic species of the rickettsia-like 
Bartonella, named B. henselae, sp. nov., has been identified and 
characterized. (Note: The genus designation Bartonella is now applied 
to and replaces the Rochalimaea genus designation.) This new organism 
causes two clinically related diseases: Bacillary angiomatosis and cat 
scratch disease. Currently, diagnosis of Bartonella diseases is limited 
to detection of the etiologic agent associated with ``trench fever'', 
referred to as B. quintata. Novel diagnostic tests using 
immunofluorescence assays or ELISAs can detect the newly discovered 
pathogen in sera from infected individuals and distinguish it from B. 
quintata, thus offering improved differential diagnosis for disease 
syndromes such as ``trench fever'', bacillary angiomatosis, cat scratch 
disease, and bacillary peliosis hepatitis. [portfolio: Infectious 
Diseases--Diagnostics, bacterial]

Effect of Cadmium on Human Ovarian Cancer Cells With Cisplatin 
Resistance

Bo Lee, K., Parker, R.J., Reed, E. (NCI)
Filed 3 Mar 95
Serial No. 08/398,460
Licensing Contact: Raphe Kantor (301/496-7735 ext 247)

    The present invention describes Cadmium (Cd) as a potential 
anticarcinogenic compound useful in treating ovarian cancer. The 
inventors observed strong tumor suppressive effects when applied to 
human ovarian cancer cell lines in vitro. The effects of Cd on cellular 
sensitivity, cellular drug accumulation and efflux, and Cd-DNA adduct 
formation and repair were examined. Cadmium is shown to have a 
subcellular profile that is similar, though not identical, to 
cisplatin, suggesting the possibility of future use of CD as an anti-
cancer agent. [portfolio: Cancer--Therapeutics, conventional 
chemotherapy, antimetabolites]

Trapping of Aflatoxins and Phytoestrogens

Umrigar, P.P., Kuan, S.S. (FDA)
Filed 6 Jan 93
Serial No. 08/001,573
Licensing Contact: John Fahner-Vihtelic (301/496-7735 ext 285)

    A unique process has been invented for removing aflatoxins and 
phytoestrogens from food samples that is a significant improvement over 
currently available methods. Aflatoxins are carcinogenic substances 
that are found in foods such as grains and peanuts and, thus, are a 
danger to public health. Phytoestrogens--structurally related to 
aflatoxins--are found in soy products and also are of concern to public 
health. Therefore, it is important to be able to measure concentrations 
of these compounds in foodstuffs. The current method for determining 
aflatoxin or phytoestrogen concentrations in foods requires passing a 
food sample through an affinity column containing immobilized 
antibodies specific for aflatoxins or a solid phase extraction (SPE) 
column for phytoestrogens. The bound aflatoxins or phytoestrogens are 
eluted from the affinity column and then measured using high 
performance liquid chromatography; however, such affinity columns and 
SPE columns are extremely expensive, have limited shelf life, and 
cannot be reused. These limitations have been overcome by developing 
columns packed with new derivatives of a copolymer of cyclodextrin and 
epichlorohydrin. These new copolymers, which have proven particularly 
useful in trapping aflatoxins and phyto-estrogens, are extremely stable 
and are not damaged when aflatoxins or phytoestrogens are removed by a 
suitable solvent. Thus, these materials are re-usable. [portfolio: 
Devices/Instrumentation--Miscellaneous]

    Dated: May 1, 1995.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 95-11422 Filed 5-9-95; 8:45 am]
BILLING CODE 4140-01-P