[Federal Register Volume 67, Number 200 (Wednesday, October 16, 2002)]
[Notices]
[Pages 63935-63938]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-26211]


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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 and issued patents listed below may be obtained by 
contacting Peter A. Soukas, J.D., at the Office of Technology Transfer, 
National Institutes of Health, 6011 Executive Boulevard, Suite 325, 
Rockville, Maryland 20852-3804; telephone: 301/496-7056 ext. 268; fax: 
301/402-0220; e-mail: [email protected]. A signed Confidential 
Disclosure Agreement will be required to receive copies of the patent 
applications.

Novel Spore Wall Proteins and Genes From Microsporidia

J. Russell Hayman, John T. Conrad, Theodore Nash (NIAID)
DHHS Reference No. E-125-01/0
Filed 04 Dec 2001
    Microsporidia are obligate intracellular organisms that infect a 
wide variety of animals ranging from insects and fish to mammals, 
including humans. Of over 1,000 microsporidial species identified, at 
least 13 are known to infect humans. The species most commonly 
identified in humans are members of the families Encephalitozoonidae 
and Enterocytozoonidae. In humans, microsporidiosis is most often found 
in HIV/AIDS patients and commonly results in severe diarrhea and 
wasting. However, microsporidiosis also occurs in immunocompetent 
individuals and common farm animals. The disease is transmitted via 
environmentally resistant spores.
    This invention claims two spore wall constituents (SWP1 and SWP2) 
from the microsporidian Encephalitozoon intestinalis and the genes from 
which these two proteins are derived. Further claimed are methods of 
diagnosing and treating microsporidiosis in a subject. Also claimed are 
methods for producing an immunoprotective response in a subject. SWP1 
is expressed on the surfaces of developing sporonts and SWP2 is 
expressed on the surfaces of fully formed sporonts. Therefore, they 
should be exposed to the host cell environment. Based on this theory, 
antibody responses to SWP1 and SWP2 were addressed in an in vivo mouse 
model. Immunoprecipitation and Western blot analyses indicated that 
SWP1 and SWP2 are immunogenic in mouse infections.
    This invention is further described in Hayman et al., 
``Developmental expression of two spore wall proteins during maturation 
of the microsporidian Encephalitozoon intestinalis,'' Infect. Immun. 
2001 Nov;69(11):7057-66.

Method for Determining Sensitivity to a Bacteriophage

Carl R. Merril (NIMH), Sankar Adhya (NCI), Dean M. Scholl (NIMH)
DHHS Reference No. E-318-00/0
Filed 23 Jan 2002

[[Page 63936]]

    Traditionally, chemical antibiotics have been used to treat a 
variety of bacterial infections. However, bacterial resistance to 
current antibiotics is an increasingly serious problem in human and 
veterinary health as well as agriculture. Many experts believe that 
strains of disease-causing bacteria resistant to all common antibiotics 
will arise in the next ten to twenty years. Bacteriophages offer a 
promising therapeutic alternative to antibiotics for these antibiotic 
resistant bacteria. There are also situations in which bacteriophage 
may be more suitable than antibiotics to treat infections caused by 
against antibiotic-sensitive bacteria. Bacteriophages are highly host-
specific, thus determining whether a phage would be therapeutically 
useful against a particular bacterium or strain of bacteria is very 
important but can be a time-consuming and labor-intensive process.
    The current invention claims a method for selecting a therapeutic 
bacteriophage that would be effective against a particular disease-
causing bacteria, comprising a number of bacteriophages containing 
reporter nucleic acids capable of being expressed when the 
bacteriophage infects a bacterial cell. These bacteriophages are 
separately contacted with a sample contaminated by a bacterium. 
Expression of the reporter is then detected, indicating which 
bacteriophage has infected a bacterial cell and is thus a potential 
therapeutic phage against the particular bacteria. Also claimed in the 
application are kits allowing for the rapid identification of 
potentially therapeutic bacteriophages.

Four Chimpanzee Monoclonal Antibodies That Neutralize Hepatitis A Virus

Darren Schofield, Suzanne Emerson, Robert Purcell (NIAID)
DHHS Reference No. E-356-01/0
Filed 07 Nov 2001

    This invention claims antibodies and/or fragments thereof specific 
for hepatitis A virus (HAV) and the use of the antibodies in the 
diagnosis, prevention, and treatment of hepatitis A. Hepatitis A is the 
most common type of hepatitis reported in the United States, which 
reports an estimated 134,000 cases annually, and infects at least 1.4 
million people worldwide each year. HAV is a positive sense RNA virus 
that is transmitted via the fecal-oral route, mainly through 
contaminated water supplies and food sources. HAV is thought to 
replicate in the oropharynx and epithelial lining of the intestines, 
where it initiates a transient viremia and subsequently infects the 
liver. Humoral immunity has been shown to provide an effective defense 
against Hepatitis A. Prior to the availability of the current 
inactivated virus vaccines, pooled human immune globulin preparations 
were routinely used to protect individuals traveling to areas of the 
world where HAV is endemic. Chimpanzees are susceptible to infection 
with HAV and can produce antibodies that neutralize the virus. 
Chimpanzee immunoglobulins are virtually identical to those of humans; 
thus, they have the same potential as human antibodies for clinical 
applications. The inventors have shown that the four chimpanzee 
monoclonal antibodies described in the patent application neutralized 
HAV strains HM-175, AGM-27, and the HM-175 VP3-070 mutant. Since only a 
single serotype of HAV has been identified, these antibodies are 
predicted to neutralize most, if not all, isolates of HAV.

Efficient Inhibition of HIV-1 Viral Entry Through a Novel Fusion 
Protein Including CD4

James Arthos, Claudia Cicala, Anthony Fauci (NIAID)
DHHS Reference No. E-337-01/0
Filed 25 Oct 2001
    This invention relates to CD4 fusion proteins for use in the 
treatment of an immunodeficiency virus infection such as human 
immunodeficiency virus (HIV). These polypeptides have been shown by the 
inventors to inhibit the entry of primary isolates of HIV-1 into CD4+ T 
cells by targeting the gp120 subunit of the HIV-1 envelope. The 
invention claims recombinant polypeptides comprising a CD4 polypeptide 
ligated at its C-terminus with a portion of a human immunoglobulin 
comprising a hinge region and two constant domains of an immunoglobulin 
heavy chain. The portion of the IgG is fused at its C-terminus with a 
polypeptide comprising a tailpiece from the C terminus of the heavy 
chain of an IgA antibody. This protein is very large (greater than 800 
kilodaltons), which may contribute to its ability to inhibit entry of 
primary isolates of HIV-1 into T cells. It presents twelve gp120 
binding domains (D1D2) and can bind at least ten gp120s simultaneously. 
The inventors have shown that the construct efficiently neutralizes 
primary isolates from different HIV subgroups. Also claimed are use of 
the construct as a component of a vaccine and as a diagnostic.

Novel Antimalarial Compounds, Methods of Synthesis Thereof, 
Pharmaceutical Compositions Comprising Same, and Methods of Using Same 
for Treatment and Prevention of Malaria

Michael R. Boyd (NCI), Gerhard Bringmann (EM), Sven Harmsen (EM) Roland 
Gotz (EM), T. Ross Kelly (EM), Matthias Wenzel (EM), Guido Francois 
(EM), J. D. Phillipson (EM), Laurent A. Assi (EM), Christopher 
Schneider (EM)
DHHS Reference No. E-090-94/0, Issued as U.S. Patent 5,639,761 on 17 
Jun 1997
DHHS Reference No. E-090-94/1,
Filed 16 Apr 1997
DHHS Reference No. E-200-94/0, Issued as U.S. Patent 5,552,550 on 03 
Sep 1996
DHHS Reference No. E-200-94/1, Issued as U.S. Patent 5,763,613 on 09 
Jun 1998
DHHS Reference No. E-200-94/2, Issued as U.S. Patent 6,140,339 on 31 
Oct 2000
DHHS Reference No. E-200-94/4, Filed 16 Mar 2000
DHHS Reference No. E-201-94/0, Issued as U.S. Patent 5,571,919 on 05 
Nov 1996
DHHS Reference No. E-201-94/2, Issued as U.S. Patent 5,578,729 on 26 
Nov 1996
DHHS Reference No. E-201-94/3, Issued as U.S. Patent 5,789,594 on 04 
Aug 1998
DHHS Reference No. E-201-94/4, Issued as U.S. Patent 5,786,482 on 28 
Jul 1998
    According to data recently reported by the World Health 
Organization (WHO), the death rate from malaria exceeds one million 
individuals per year. The Public Health Service seeks exclusive or non-
exclusive licensee(s) to develop and commercialize the technology 
claimed within the portfolio of U.S. patents issued and pending, and 
corresponding international patents issued and pending. These patents 
and pending applications claim an exceptionally broad universe of novel 
naphthylisoquinoline alkaloid compounds, and methods of total synthesis 
thereof. Representative examples of these compounds have been shown to 
have potent in vitro activity against malaria parasites, including 
parasites that are highly resistant to available antimalarial drugs. 
Representative examples have also been shown to have potent in vivo 
activity against malaria parasites in animal models. Pharmaceutical 
compositions comprising these compounds, as well as methods of using 
the compounds to

[[Page 63937]]

treat or prevent a malarial infection of a host, are claimed. The 
relative structural simplicity of this class of compounds, and the 
ready synthetic access thereto, provide unprecedented opportunities for 
structure-activity relationship (SAR), lead-optimization and 
antimalarial drug development. The technology is further described in 
the following publications: J. Nat Prod. 1997 Jul.;60(7):677-83 and 
Bioorg. Med. Chem. Lett. 1998 Jul.;8(13): 1729-34.

A Novel Chimeric Protein for Prevention and Treatment of HIV Infection

Edward A. Berger (NIAID), Christie M. Del Castillo
DHHS Reference No. E-039-99/0 Filed 16 Mar 1999; PCT/US00/06946 Filed 
16 Mar 2000
DHHS Reference No. E-039-99/2 Filed 13 Sep 2001

    This invention relates to bispecific fusion proteins effective in 
viral neutralization. Specifically, the invention is a genetically 
engineered chimeric protein containing a soluble extracellular region 
of human CD4 attached via a flexible polypeptide linker to a single 
chain human monoclonal antibody directed against a CD4-induced, highly 
conserved HIV gp120 determinant involved in coreceptor interaction. 
Binding of the sCD4 moiety to gp120 induces a conformational change 
that enables the antibody moiety to bind, thereby blocking Env function 
and virus entry. This novel bispecific protein displays neutralizing 
activity against genetically diverse primary HIV-1 isolates, with 
potency at least 10-fold greater than the best described HIV-1 
neutralizing monoclonal antibodies. The agent has considerable 
potential for prevention of HIV-1 infection, both as a topical 
microbicide and as a systemic agent to protect during and after acute 
exposure (e.g. vertical transmission, post-exposure prophylaxis). It 
also has potential utility for treatment of chronic infection. Such 
proteins, nucleic acid molecules encoding them, and their production 
and use in preventing or treating viral infections are claimed.

Bacteriophage Having Multiple Host Range

Carl Merril (NIMH), Sankar Adhya (NCI), Dean Scholl (NIMH)
DHHS Reference No. E-257-00/0 Filed 25 Jul 2000; PCT/US01/22390
Filed 25 Jul 2001

    Recently, there has been a renewed interest in the use of phages to 
treat bacterial infections. The inventors have discovered FK1-5, a 
highly lytic, non-lysogenic, stable bacteriophage with the ability to 
kill bacteria rapidly, making it a good candidate for phage therapy. 
The designation FK1-5 denotes the phage's ability to infect E. coli 
strains that contain the K1 polysaccharide in their outer capsule as 
well as E. coli strains that contain the K5 polysaccharide in their 
outer capsule. Sequence analysis of the tail proteins of phage FK1-5 by 
the inventors has shown that they are arranged in a cassette structure, 
suggesting that the host range of phages can be broadened to other K 
antigens, and even possibly other species of bacteria by recombinant 
techniques. FK1-5 has a particular advantage because it recognizes and 
attaches to the structures that confer virulence to bacteria. The 
inventors' demonstration that a phage can contain multiple tail 
proteins that expand its host range is useful for generating phage with 
broad-spectrum antibacterial properties for the treatment of infectious 
diseases. The inventors have completed in vitro studies on this phage. 
Furthermore, because of the possibility of engineering the expression 
of recombinant tail proteins, gene transfer to organisms that are not 
normally infected by phages is also contemplated by the invention.

Vaccine for Protection Against Shigella sonnei Disease

Dennis J. Kopecko, De-Qi Xu, John O. Cisar (FDA)
DHHS Reference No. E-210-01/0
Filed 16 Jan 2002

    Shigellosis is a global human health problem. Transmission usually 
occurs by contaminated food and water or through person-to-person 
contact. The bacterium is highly infectious by the oral route, and 
ingestion of as few as 10 organisms can cause an infection in 
volunteers. An estimated 200 million people worldwide suffer from 
shigellosis, with more than 650,000 associated deaths annually. A 
recent CDC estimate indicates the occurrence of over 440,000 annual 
shigellosis cases in the United States alone, approximately eighty 
percent (80%) of which are caused by Shigella sonnei. Shigella sonnei 
is more active in developed countries. Shigella infections are 
typically treated with a course of antibiotics. However, due to the 
emergence of multidrug resistant Shigella strains, a safe and effective 
vaccine is highly desirable. No vaccines against Shigella infection 
currently exist. Immunity to Shigellae is mediated largely by immune 
responses directed against the serotype specific O-polysaccharide. 
Claimed in the invention are compositions and methods for inducing an 
immunoprotective response against S. sonnei. Specifically, an 
attenuated bacteria capable of expressing an S. sonnei antigen 
comprised of the S. sonnei form I O-polysaccharide expressed from the 
S. sonnei rfb/rfc gene cluster is claimed. The inventors have shown 
that the claimed vaccine compositions showed 100 percent protection 
against parenteral challenge with virulent S. sonnei in mice.

Vaccine Against Eschericha coli 0157 Infection, Composed of Detoxified 
LPS Conjugated to Proteins

Shousun C. Szu, Edward Konadu, and John B. Robbins (NICHD)
DHHS Reference No. E-158-98/0 Filed 20 July 1998 (PCT/US98/14976)
DHHS Reference No. E-158-98/1
Filed 22 Jan 2001

    This invention is a conjugate vaccine to prevent infection, in 
particular in young children under 5 years of age, by E. coli 0157:H7, 
an emerging human pathogen which causes a spectrum of illnesses with 
high morbidity and mortality, ranging from diarrhea to hemorrhagic 
colitis and hemolytic-uremic syndrome (HUS). Infection is due to the 
consumption of water or meat contaminated by feces from infected 
animals, such as cattle. The conjugate is composed of the O-specific 
polysaccharide isolated from E. coli 0157, or other Shiga-toxin 
producing bacteria, conjugated to carrier proteins, such as non-toxic 
P. aeruginosa exotoxin A or Shiga toxin 1. A Phase I clinical trial, 
involving adult humans, showed the vaccine is safe and highly 
immunogenic. Adults, after one injection containing 25 [mu]g of 
antigen, responded with high titers of bactericidal antibodies. Thus 
the conjugates of the invention are promising vaccines, especially for 
children and the elderly, who are most likely to suffer serious 
consequences from infection. The clinical study is described in J. 
Infectious Diseases 177, 383-387, 1998.

Murine Monoclonal Antibodies Effective To Treat Respiratory Syncytial 
Virus

Robert Chanock, Brian Murphy, Judy Beeler, and Kathleen van Wyke 
Coelingh (NIAID)
DHHS Reference No. B-056-94/1

    Available for licensing through a Biological Materials License 
Agreement are the murine MAbs described in Beeler, J.A. et al, 
``Neutralization Epitopes of the F Glycoprotein of Respiratory 
Syncytial Virus: Effect of Mutation Upon Fusion Function,'' J. Virology 
63:2941-2950 (1989). The

[[Page 63938]]

MAbs that are available for licensing are the following: 1129, 1153, 
1142, 1200, 1214, 1237, 1121, 1112, 1269, and 1243. One of these MAbs, 
1129, is the basis for a humanized murine MAb (see U.S. Patent Number 
5,824,307 to humanized 1129 owned by MedImmune, Inc.), recently 
approved for marketing in the United States. MAbs in the panel reported 
by Beeler, et al. have been shown to be effective therapeutically when 
administered into the lungs of cotton rats by small-particle aerosol. 
Among these MAbs several exhibited a high affinity (approximately 
109-1) for the RSV F glycoprotein and are directed at 
epitopes encompassing amino acid 262, 272, 275, 276 or 389. These 
epitopes are separate, nonoverlapping and distinct from the epitope 
recognized by the human Fab of U.S. Patent 5,762,905 owned by The 
Scripps Research Institute.

Cloned Genomes of Infectious Hepatitis C Virus and Uses Thereof

Masayuki Yanagi, Jens Bukh, Suzanne U. Emerson, Robert H. Purcell 
(NIAID)
DHHS Reference No. E-050-98/0, Issued as U.S. Patent 6,153,421 on 28 
Nov 2000
DHHS Reference No. E-050-98/2 Filed 14 Sep 2000; Canadian Application 
2295552; Australian Application 84889/98; European Application 
98935702.5

    The current invention provides nucleic acid sequences comprising 
the genomes of infectious hepatitis C viruses (HCV) of genotype 1a and 
1b. It covers the use of these sequences, and polypeptides encoded by 
all or part of the sequences, in the development of vaccines and 
diagnostic assays for HCV and the development of screening assays for 
the identification of antiviral agents for HCV. Additional information 
can be found in Yanagi et al., (1997) Proc. Natl. Acad. Sci., USA 94, 
8738-8743 and Yanagi et al., (1998) Virology 244, 151-172.

Infectious cDNA Clone of GB Virus B and Uses Thereof

Jens Bukh, Masayuki Yanagi, Robert H. Purcell, Suzanne U. Emerson 
(NIAID)
DHHS Reference No. E-173-99/0
Filed 04 Jun 1999; PCT/US00/15293 Filed 02 Jun 2000
DHHS Reference No. E-173-99/2 Filed 03 Dec 2001

    The current invention provides nucleic acid sequences comprising 
the genomes of infectious GB virus B, the most closely related member 
of the Flaviviridae to hepatitis C virus (HCV). It also covers chimeric 
GBVB-HCV sequences and polypeptides for use in the development of 
vaccines and diagnostic assays for HCV and the development of screening 
assays for the identification of antiviral agents for HCV. Additional 
information can be found in Bukh et al. (1999), Virology 262, 470-478.

HCV/BVDV Chimeric Genomes and Uses Thereof

Jae-Hwan Nam, Jens Bukh, Robert H. Purcell, Suzanne U. Emerson (NIAID)
DHHS Reference No. E-102-99/0
Filed 04 June 1999
PCT/US00/15527 Filed 02 Jun 2000
DHHS Reference No. E-102-99/2
Filed 04 Dec 2001
    The current invention provides nucleic acid sequences comprising 
chimeric viral genome of hepatitis C Virus (HCV) and bovine viral 
diarrhea viruses (BVDV). The chimeric viruses are produced by replacing 
the structural region or a structural gene of an infectious BVDV clone 
with the corresponding region or gene of an infectious HCV. It covers 
the use of these sequences and polypeptides encoded by all or part of 
the sequences in the development of vaccines and diagnostic assays for 
HCV and the development of screening assays for the identification of 
antiviral agents for HCV.

Cloned Genome of Infectious Hepatitis C Virus of Genotype 2a and Uses 
Thereof

Jens Bukh, Masayuki Yanagi, Robert H. Purcell, Suzanne U. Emerson 
(NIAID)
DHHS Reference No. E-100-99/0 Filed 04 Jun 1999
PCT/US00/15466
Filed 02 Jun 2000
DHHS Reference No. E-100-99/2
Filed 03 Dec 2001
    The current invention provides a nucleic acid sequence comprising 
the genome of infectious hepatitis C viruses (HCV) of genotype 2a. The 
encoded polyprotein differs from those of the infectious clones of 
genotypes 1a and 1b (U.S. Patent 6,153,421) by approximately 30 
percent. It covers the use of this sequence and polypeptides encoded by 
all or part of the sequence, in the development of vaccines and 
diagnostic assays for HCV and the development of screening assays for 
the identification of antiviral agents for HCV. Additional information 
can be found in Yanagi et al. (1999), Virology 262, 250-263.

    Dated: September 30, 2002.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-26211 Filed 10-15-02; 8:45 am]
BILLING CODE 4140-01-P