[Federal Register Volume 67, Number 8 (Friday, January 11, 2002)]
[Notices]
[Pages 1488-1489]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-744]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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.

Expression, Purification and Efficacy Testing of Synthetic 
Plasmodium Falciparum Apical Membrane Antigen 1 Expressed in Pichia 
Pastoris

Stowers et al. (NIAID)
DHHS Reference No. E-025-02/0 filed 09 Nov 2001
Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: 
[email protected].

    A challenge facing the biotechnology industry involves finding 
robust systems for the expression of large amounts of recombinant 
protein. Extra technological hurdles are faced when these proteins are 
required for therapeutic usages.
    Malaria remains one of the leading causes of both morbidity and 
mortality in the tropical and sub-tropical world. Currently, there is 
no malaria vaccine. This invention relates to both of these issues.
    Two recombinant forms of the malaria asexual blood stage antigen 
Apical Membrane Antigen 1 (AMA1) were produced in Pichia pastoris using 
totally defined, synthetic medias and a fermentation methodology that 
has been reproducibly scaled over a 10-fold range to 60L. High levels 
of secreted recombinant protein were obtained (300mg/L secreted protein 
in the supernatant, and >50mg/L final purified bulk protein), and a 
purification strategy developed to remove Host cell-derived lipids. 
Highly purified forms of both types of AMA1 produced appear to produce 
antibodies in vivo in rabbits that block homologous parasites from 
invading red blood cells in vitro. The combination of the two allelic 
forms made appears potent at inducing antibodies capable of blocking 
the invasion of many heterologous parasite strains in vitro, suggesting 
that the combination of these two alleles of AMA1 will provide 
sufficient coverage from the diverse field populations of parasites. 
One of the two AMA1's, based on the FVO allelic variant of AMA1, was 
emulsified with complete and incomplete Freund's adjuvant.
    Vaccination of highly susceptible Aotus vociferans monkeys with 
this formulation conferred significant protection from a subsequent 
lethal challenge with the virulent FVO Plasmodium falciparum parasite. 
Five of eight animals whose primary immune response was directed 
against AMA1 were completely protected. These two recombinant form of 
AMA1 may be an effective malaria vaccine. The production and 
purification methodologies may be suitable to other therapeutic 
proteins where large-scale, inexpensive production methodologies are 
required.

Two cDNA Clones of Hepatitis E Virus (HEV) That Are Infectious for 
Primates and Encode a Virulent and an Attenuated Virus Respectively

Suzanne U. Emerson, Robert H. Purcell, Mingdong Zhang, and Xiang-Jin 
Meng (NIAID)
DHHS Reference No. E-278-01/0 filed 09 Nov 2001
Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: 
[email protected]

    Hepatitis E virus (HEV) is a human pathogen that is the most 
important cause of acute hepatitis in areas where the virus in endemic 
(Southeast and Central Asia, and parts of Africa). This invention 
relates to transcripts from the two cDNA clones that produced virus 
following intrahepatic transfection of chimpanzees. The virus encoded 
by cDNA with the consensus sequence of the wild-type Sar 55 Pakistani 
strain of HEV caused liver enzyme elevations (i.e. acute hepatitis) in 
the chimpanzee and resulted in seroconversion to anti-HEV at five weeks 
following inoculation. The second cDNA differed from the first by a two 
nucleotides, one of which was located in the coding region. The 
nucleotide at this position and the 18-20 nucleotides surrounding it 
are highly conserved in all strains sequenced thus far. Two chimpanzees 
inoculated with transcripts from this clone seroconverted to anti-HEV 
but seroconversion was delayed until week 14 and liver enzyme levels 
did not rise, indicating the virus was attenuated. Viral sequences 
could be recovered from the serum of only one chimp and at only one 
time point by reverse-transcription polymerase chain reaction, 
indicating viral replication was inefficient. An attenuated vaccine 
would be more cost effective than a recombinant protein vaccine.

Suppression of CCR5 but Not CXCR4-Tropic HIV-1 Replication in 
Lymphoid Tissue by Human Herpes Virus 6

Margolis et al. (NICHD)
DHHS Reference No. E-089-01/0 filed 28 Mar 2001
Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: 
[email protected].

    HIV-1 infects cells via a receptor complex formed by CD4 and a 
coreceptor, such as CCR5 or CXCR4. The early stages of HIV-1 infection 
are dominated by CCR5-tropic viral variants. CXCR4-tropic variants 
frequently emerge at later stages

[[Page 1489]]

followed by a rapid decline in CD4+ T cells and progression to AIDS.
    This invention describes the mechanism of the coreceptor switch 
from CCR5 to CXCR4 as HIV infection progresses. The study of the 
interaction between human herpes virus 6 (HHV-6) and HIV has shed light 
on this coreceptor switch. The inventors observed that HHV-6 affects 
HIV replication by suppressing CCR5-tropic but not CXCR4-tropic HIV-1. 
The inventors demonstrate that HHV-6 upregulates the production of 
RANTES, a CC chemokine that is known to inhibit infection by CCR5-
tropic HIV-1. RANTES interferes with the interaction of the CCR5-tropic 
HIV-1 thereby allowing the CXCR4-tropic HIV-1 variants to emerge.
    This observation may lead to new HIV-1 therapies and vaccines. For 
example, an attenuated HHV-6 or the use of other compounds to stimulate 
RANTES production could be used as an HIV vaccine while a drug 
effective against HHV-6 could be used as an HIV therapeutic. Once HHV-6 
is eradicated from the body or rendered nonfunctional the conversion 
from CCR5-tropic HIV-1 to CXCR4-tropic HIV-1 cannot take place.

Human Papilloma Virus Immunoreactive Peptides

Samir N. Khleif , David Contois, and Jay Berzofsky (NCI)
DHHS Reference No. E-126-01/0 filed 23 Mar 2001
Licensing Contact: Sally Hu; 301/496-7056 ext. 265; e-mail: 
[email protected].

    This invention provides immunogenic peptides from the HPV-18E6 
protein that comprise class I restricted T cell epitopes and discloses 
methods of administering these peptides to individuals, and a method 
for monitoring or evaluating an immune response to HPV with these 
peptides. The HPV-18E6 peptide cross-reacts immunologically with both 
HPV type 16 and HPV type 18. HPV 16 and HPV 18 are the most common HPV 
types involved in cervical cancer, which is the second most common 
cause of cancer deaths in women worldwide. This invention demonstrates 
that the HPV-18E6 peptide has a higher affinity for the most common 
human lymphocyte antigen (HLA), HLA-A2 than the homologous peptide from 
HPV 16. Thus, this invention provides a potential prophylactic or 
therapeutic vaccine against cervical cancer caused by HPV16 and 18, and 
a targeted therapy for cervical cancer and other diseases that are 
caused by HPV including other genital cancers, head and neck cancers, 
and upper digestive tract cancers. It could also be potentially used in 
the treatment of patients presenting with pre-malignant cervical 
disease, especially in underdeveloped countries with no access to 
surgical treatment or to completely avoid surgical treatment.

Parallel Measurements of Multiple Macromolecules Using a Cryoarray

Robert Star (NIDDK), Takehiko Miyaji (NIDDK), Stephen Hewitt (NCI), and 
Lance Liotta (NCI)
DHHS Reference No. E-064-01/0 filed 31 Aug 2001
Licensing Contact: Cristina Thalhammer-Reyero; 301/496-7056 ext. 263; 
e-mail: [email protected].

    Available for license is a new improved technique for the creation 
of biological arrays of 25-100 biological samples per slide, for use in 
parallel molecular screening in medical research and clinical 
diagnostics. Recent advances in genomics, including serial analysis of 
gene expression, and DNA microarrays have allowed researchers to 
perform high throughput analysis of gene expression. These experiments 
generate large amounts of information that must be validated 
independently, one gene at a time. In particular, there is an 
increasing demand for protein arrays in order to measure changes in 
protein expression or post-translational modification of proteins. 
Current techniques to create protein arrays are deficient because the 
proteins stick to the arraying pins, and array fabrication at room 
temperature may destroy the protein structure and function. The 
CryoArray technology, based on the creation of the arrays at subzero 
temperature, preserves the stability and functionality of the 
biological samples, including proteins, and is flexible with respect to 
the molecular probes it can accommodate. Wells made in a frozen block 
of embedding material are filled with biological samples, which freeze 
and bond to the surrounding block. The loaded block is cut in a 
cryostat to produce up to 800 replicate 4-10 microns thin sections. The 
samples can include DNA, RNA, and proteins such as antibodies or 
receptors. Recombinant or native tissue proteins are detected using 
antibodies; however, the system can be extended for other types of 
biological assays.
    The ability to make multiple (i.e., up to 800) cryosections from 
one cryoblock enables parallel analysis of many identical arrays. 
Unlike other proteomic techniques, cryoarrays are easy to use, 
economical, efficiently use samples with little waste, require only a 
small volume of sample, and are protein friendly because samples are 
kept frozen during production. The cryoarray method allows small 
laboratories without access to expensive arraying equipment to produce 
many identical arrays with moderate numbers of precious samples. 
Proteins can be detected in their native configuration, without SDS or 
formalin. Cryoarrays may be useful for screening small samples of 
precious biological fluids or tissues for new biomarkers or for rapid 
screening of monoclonal antibodies. It may be possible to use 
cryoarrays to also measure protein function and protein-protein 
interactions.

Method for Non-Invasive Identification of Individuals at Risk for 
Diabetes

Anthony J. Durkin, Marwood N. Ediger, Michelle V. Chenault (FDA)
DHHS Reference No. E-091-98/2 filed 17 May 2001
Licensing Contact: Dale Berkley; 301/496-7735 ext. 223; e-mail: 
[email protected]

    The invention is a non-invasive technique for the detection of 
ocular pathologies, including molecular changes associated with 
diabetes. Raman spectra emitted from an eye that is subject to a laser 
probe provides information regarding early markers of diabetes or 
diabetes-induced ocular pathologies. The invention compares spectra 
taken from the subject under study to spectra from a normal subject. 
Multivariate statistical methods are used to obtain predictive 
information based on the detected spectra, and to diagnose or predict 
the onset or stage of progression of diabetes-induced ocular pathology.

    Dated: January 4, 2002.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-744 Filed 1-10-02; 8:45 am]
BILLING CODE 4140-01-P