[Federal Register Volume 67, Number 26 (Thursday, February 7, 2002)]
[Notices]
[Pages 5835-5837]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-2909]


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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.

Four Chimpanzee Monoclonal Antibodies that Neutralize Hepatitis A 
Virus

Darren Schofield, Suzanne Emerson, Robert Purcell (NIAID).
DHHS Reference No. E-356-01/0 filed Nov 07 2001.
Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; 
[email protected].

    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.

N-Formyl Peptide Receptor Mediation of Platelet Chemotaxis Toward 
Injured Cells and Activation of Immune Response

Julie Lekstrom-Himes (NIAID), Allan Kirk (NIDDK), David Kleiner 
(NIAID), Meggan Czapiga (NIAID).
DHHS Reference No. E-282-01/0 filed Oct 05 2001.
Licensing Contact: Peter Soukas; 
301/496-7056 ext. 268; [email protected].

    Formyl peptides are short peptides generated by bacterial or 
mitochondrial endopepdidase cleavage of the first few amino acids 
including the N-formyl-modified methionine group of proteins. They bind 
to specific receptors on phagocytic cells and platelets, and induce 
directed migration or chemotaxis. Human phagocytes express two N-formyl 
peptide receptors, FPR 
(N-formyl peptide receptor) and FPRL-1 (FPR-like 1), both of which 
couple to pertussis toxin-sensitive G proteins. FPR binds N-formyl 
peptides at a 1000 fold higher affinity than FPRL 1 and is attributed 
with inducing chemotaxis. Based on their chemotactic actions, it has 
been hypothesized that N-formyl peptides attract phagocytes and 
platelets to sites of infection and injury and therefore play an 
important role in microbicidal and other host defense activities. In 
particular, platelets carry CD154 or CD40 ligand on their surface and 
can provide induction of dendritic cell maturation and co-stimulatory 
molecule expression, thus regulating immune versus tolerance responses.
    Claimed in the invention are compositions of N-formyl peptides and 
derivatives of N-formal peptides, use of N-formyl peptides to stimulate 
an immune or inflammatory response, and methods of using N-formal 
peptide receptor inhibitors, such as blocking antibodies or other 
receptor antagonists, for inhibiting inflammation. Also claimed in the 
invention are methods of mobilizing platelets at an injury site and 
methods of wound healing at an injury site comprising administering N-
formal peptides to the site.

Vaccination Strategies To Provide Protection Against the Ebola 
Virus

Gary Nabel et al. (VRC/NIAID).
DHHS Reference No. E-241-01/0 filed Oct 01 2001.

[[Page 5836]]

Licensing Contact: Carol Salata; 301/496-7735 ext. 232; 
[email protected].

    This invention describes a method for vaccination against Ebola 
virus. Outbreaks of hemorrhagic fever caused by the Ebola virus, 
particularly the Zaire subtype, are associated with high mortality 
rates. The virus is very contagious, and during an outbreak, presents a 
threat to anybody who comes into contact with an infected person. 
Because the virus progresses so rapidly and the mortality rate is so 
high, there is little opportunity to develop natural immunity, making 
vaccination a promising intervention. This invention relates to a 
vaccine strategy employing DNA and adenoviral vectors expressing 
proteins associated with the Ebola virus. This vaccine strategy, a DNA 
prime with an adenoviral boost, elicits a protective immune response in 
primates. A vaccine was designed to optimize expression by 
incorporating genes for two subtypes of the glycoprotein (Zaire and 
Sudan) and minimizes toxicity by eliminating the trans-membrane region. 
The specific genes identified may be used for gene-based or protein-
based vaccines that will prevent Ebola infection.

Novel Method for Rapidly Generating Mature Dendritic Cells from 
Peripheral Blood Monocytes and Myeloid Precursors

Dennis Klinman, Mayda Gursel, Daniela Verthelyi (FDA).
DHHS Reference No. E-214-01/0 filed Aug 14 2001.
Licensing Contact: Peter Soukas; 
301/496-7056 ext. 268; [email protected].

    This application claims use of CpG oligodeoxynucleotides (ODN) to 
generate mature dendritic cells (DC). Also claimed in the application 
are synergistic use of CpG ODNs with cytokines, chemokines, or other 
factors to induce the maturation of monocytes to dendritic cells. 
Dendritic cells play a critical role in the generation of adaptive 
immune responses. Dendritic cells excel at presenting antigen to naive 
T lymphocytes. Large numbers of highly active DC are necessary for 
prevention and/or treatment of cancer and infectious diseases. Current 
processes for generating mature DC from peripheral blood mononuclear 
cells (PBMC) involve incubating PBMC with GM-CSF plus IL-4 for one week 
followed by monocyte-conditioned medium for two to seven days. These 
processes are inefficient, expensive and do not uniformly generate DC 
with full functional activity. The current invention is based on the 
observation that bacterial DNA and synthetic ODNs containing 
unmethylated ``CpG motifs'' promote the maturation of murine antigen 
presenting cells (APC) in vitro. The invention is further described in 
Ishii KJ et al., ``Genomic DNA released by dying cells induces the 
maturation of APCs,'' J. Immunol. 2001 Sep 1;167(5):2602-7.

Use of Sterically Stabilized Cationic Liposomes To Efficiently 
Deliver CpG Oligonucleotides in vivo

Dennis Klinman, Ihsan Gursel (FDA).
DHHS Reference No. E-215-01/0 filed Jul 27 2001.
Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; 
[email protected].

    Immunostimulatory CpG oligonucleotides (ODN) show promise as immune 
adjuvants, anti-allergens, and immunoprotective agents. Increasing the 
bioavailability and duration of action of CpG ODN should improve their 
therapeutic utility. This invention claims use of Sterically Stabilized 
Cationic Liposomes (SSCL) to deliver CpG ODNs. In addition to use of 
SSCL to deliver CpG ODNs, SSCL-CpG compositions are also claimed in the 
patent application. The claimed SSCL comprise three distinct 
phospholipid elements, DC-CHOL (which increases liposome membrane 
stability while improving the uptake and encapsulation of DNA), DOPE (a 
pH-sensitive neutral lipid that improves the cytosolic delivery of CpG 
ODNs following internalization), and PEG-PE (which stabilizes the 
liposome and also facilitates cellular uptake). The inventors have 
conducted both in vivo and in vitro studies using the SSCL-CpG 
compositions, showing that in vitro, liposome-encapsulated CpG ODNs 
stimulated significantly more interferon-gamma (IFN-) 
production than free CpG ODNs. The in vivo testing the inventors 
completed show that SSCL encapsulation of CpG ODNs increase the 
magnitude and duration of the activity of the CpG ODNs in vivo; when 
CpG-SSCLs were administered to mice infected with L. monocytogenes 
(listeria), one hundred percent of the infected mice survived four 
weeks post-treatment. The invention is further described in Gursel I et 
al., ``Sterically stabilized cationic liposomes improve the uptake and 
immunostimulatory activity of cpg oligonucleotides,'' J. Immunol. 2001 
Sep 15; 167(6):3324-8.

Identification of DNA Sequence Motifs That Suppress the Immune 
Response to CpG DNA

Dennis Klinman, Mayda Gursel, Ihsan Gursel (FDA).
DHHS Reference No. E-218-01/0 filed Sep 24, 2001.
Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; 
[email protected].

    This invention claims compositions and methods for suppressing CpG 
oligonucleotide immunostimulatory action with suppressive motifs 
comprising mammalian DNA. The sequences of the suppressive motifs 
claimed in the application comprise multimeric repeats, which have a 
tendency to form ``G-tetrads,'' which suppress CpG induced immune 
activation. The inventors have found through in vivo and in vitro 
experimentation that these suppressive motifs inhibited CpG DNA induced 
proliferation and cytokine production. Further experimentation by the 
inventors has shown that ODNs containing the most said repeats were the 
most suppressive. There are multiple therapeutic uses for the 
suppressive oligodeoxynucleotides (ODNs) of the invention, such as use 
in the prevention or treatment of septic shock, adult respiratory 
distress syndrome (ARDS), or autoimmune disease. Furthermore, the 
inventors disclose that eliminating suppressive motifs from the plasmid 
backbone of DNA vaccines may improve vaccine immunogenicity by 
maximizing the effect of CpG motifs present in such vectors. The 
advantages associated with use of suppressive motifs is that 
therapeutics based on this technology would avoid many of the unwanted 
side effects associated with current immunosuppressive therapeutics.

Anti-Arthropod Vector Vaccines, Methods of Selecting, and Uses 
Thereof

Jesus Valenzuela, Yasmine Belkaid, Shaden Kamhawi, David Sacks, Jose 
Ribeiro (NIAID).
DHHS Reference No. E-122-01/0 filed Jun 19, 2001.
Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; 
[email protected].

    Leishmania parasites are transmitted to their vertebrate hosts by 
infected phlebotomine sand fly bites. Sand fly saliva is known to 
enhance Leishmania infection, while immunity to the saliva protects 
against infection. This invention claims nine major salivary proteins 
from the sand fly vector of Leishmania major, Phlebotomus papatasi, 
nucleic acids encoding the proteins, vaccines comprising the proteins 
and/or nucleic acids, and methods of producing an immune response to 
prevent Leshmaniasis. The inventors have shown that one of these 
salivary proteins, was able to protect vaccinated mice challenged with 
parasites plus salivary gland

[[Page 5837]]

homogenates (SGH). A DNA vaccine containing the cDNA for the same 
protein provided this same protection. Protection lasted at least 3 
months after immunization. The vaccine produced both intense humoral 
and delayed-type hypersensitivity (DTH) reactions. B cell-deficient 
mice immunized with the plasmid vaccine successfully controlled 
Leishmania infection when injected with Leishmania plus SGH. The 
invention is further described in Valenzuela JG et al., ``Toward a 
defined anti-Leishmania vaccine targeting vector antigens: 
characterization of a protective salivary protein,'' J. Exp. Med. 2001 
Aug 6; 194(3):331-42.

    Dated: January 28, 2002.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-2909 Filed 2-6-02; 8:45 am]
BILLING CODE 4140-01-P