[Federal Register Volume 65, Number 239 (Tuesday, December 12, 2000)]
[Notices]
[Pages 77651-77652]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-31525]


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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 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.

Antibodies and Other Ligands Directed Against KIR2DL4 Receptor for 
Production of Interferon-Gamma

Eric Long, Sumati Rajagopalan (NIAID)
    DHHS Reference No. E-255-00/0 filed 23 Oct 2000

    Interferon-gamma is a potent antiviral and antimicrobial substance 
produced by natural killer (NK) white blood cells. NK cells are 
activated during infections by viruses and by other intracellular 
pathogens, such as parasites and bacteria. Soluble substances, such as 
interleukins, produced by infected cells activate NK cells to secrete 
interferon-gamma. Injection of interleukins into patients to stimulate 
NK cells to secrete interferon-gamma has not been a successful 
therapeutic approach because of the toxicity involved. The invention is 
based on the discovery by the inventors that activation of the KIR2DL4 
receptor expressed by all NK cells stimulates them to produce 
interferon-gamma. The invention claims monoclonal antibodies and 
derivatives thereof, as well as natural and synthetic ligands of 
KIR2DL4 that can be utilized to stimulate interferon-gamma production 
by NK cells without any other stimulus. The possibility of inducing 
interferon-gamma production by NK cells without the toxic side effects 
of interleukins could be an effective therapy for various types of 
infections and of cancers. Also claimed in the invention are methods of 
treating various cancers and viral infections, methods of treating 
autoimmune disease, and methods of administration of the antibody or 
derivatives thereof.

Ixodes scapularis Tissue Factor Pathway Inhibitor

Ivo Francischetti, Jesus Valenzuela, Jose Ribeiro (NIAID)
DHHS Reference No. E-208-00/0 filed 05 Oct 2000

    Ixodes scapularis is a blood-sucking tick and the principal vector 
of Lyme disease, a spirochetal illness caused by Borrelia burgdorferi 
and now the most common vector-borne infection in the United States; 
more than 50,000 cases have been reported during the last ten years. 
The salivary gland of I. scapularis has a number of pharmacologically 
active molecules that help the tick to successfully feed on blood, such 
as inhibitors of complement system, in addition to coagulation and 
platelet aggregation inhibitors. This invention describes Ixolaris, a 
protein that inhibits the initiation of blood coagulation by inhibition 
of components of the extrinsic pathway. Accordingly, Ixolaris blocks 
Factor X activation by Factor VIIa/TissueFactor, it attenuates Factor 
Xa production by the prothrombinase, and inhibits fibrin formation in a 
diluted prothrombin time. Ixolaris is highly specific since it does not 
inhibit other serine proteases. Because Ixolaris has anticoagulant 
properties, it could be used to ameliorate a number of clinical 
conditions such as disseminated intravascular coagulation, and 
hypercoagulation states. In addition, Ixolaris may be useful as a 
vaccine candidate for Lyme disease because inactivation of Ixolaris by 
antibodies may make transmission of Borrelia burgdorferi more 
difficult. In addition to the composition of Ixolaris, the invention 
claims vaccines utilizing Ixolaris, methods of stimulating an immune 
response, and methods of treatment of restenosis, arterial thrombosis, 
and stroke.

Ixodes Salivary Anticomplement Protein

Jose Ribeiro (NIAID), Jesus Valenzuela (NIAID), Rosane Charlab (NIAID), 
Thomas Mather (EM)
DHHS Reference No. E-207-00/0 filed 28 Sep 2000

    This invention describes Isac, a novel anticomplement protein that 
can be isolated and purified from I. scapularis (tick) saliva that may 
be useful as a peptide vaccine against Lyme disease. Because 
inactivation of Isac by antibodies will make transmission of Borrelia 
burgdorferi to humans more difficult, Isac is an ideal candidate for a 
Lyme disease vaccine. Isac disrupts the alternative complement pathway 
by inhibiting factors Bb and/or C3b, preventing cell lysis and 
anaphylatoxin production. The inventors have found no similarity to any 
protein in GenBank for Isac. Isac may also be used in situations where 
alternative complement activation is implicated such as in rheumatoid 
conditions such as lupus erythematosus or juvenile arthritis. The 
invention is further described in Ribeiro et al., ``Purification, 
cloning, and expression of a novel salivary anticomplement protein from 
the tick, Ixodes scapularis,'' J Biol. Chem. 2000 Jun 23; 
275(25):18717-23.

LL-37 Is an Immunostimulant

Oleg Chertov (NCI), Joost Oppenheim (NCI), De Yang (NCI), Qian Chen 
(NCI), Ji Wang (NCI), Mark Anderson (EM), Joseph Wooters (EM)
DHHS Reference No. E-285-00/0 filed 21 Sep 2000

    This invention relates to use of an antimicrobial peptide as a 
vaccine adjuvant. LL-37 is the cleaved antimicrobial 37-residue C-
terminal peptide of hCAP18, the only identified

[[Page 77652]]

member in humans of a family of proteins called cathelicidins. LL-37/
hCAP18 is produced by neutrophils and various epithelial cells. LL-37 
is well known as an antimicrobial peptide. However, although 
antimicrobial peptides have generally been considered to contribute to 
host innate antimicrobial defense, some of them may also contribute to 
adaptive immunity against microbial infection. The inventors have shown 
that LL-37 utilizes formyl peptide receptor-like 1 (FPLR1) as a 
receptor to activate human neutrophils, monocytes, and T cells. Since 
leukocytes participate in both innate and adaptive immunity, the fact 
that LL-37 can chemoattract human leukocytes may provide one additional 
mechanism by which LL-37 can contribute to host defense against 
microbial invasion, by participating in the recruitment of leukocytes 
to sites of infection. The invention claims methods of enhancing immune 
responses through the administration of LL-37 alone, in conjunction 
with a vaccine, and methods of treating autoimmune diseases. The 
invention is further described in Chertov et al., ``LL-37, the 
neutrophil granule-and epithelial cell-derived cathelicidin, utilizes 
formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract 
human peripheral blood neutrophils, monocytes, and T cells,'' J Exp. 
Med. 2000 Oct 2;192(7):1069-74.

A Method for Bioconjugation Using Diels-Alder Cycloaddition

Vince Pozsgay (NICHD)
DHHS Reference No. E-126-00/0 filed 09 Aug 2000

    This invention relates to a new method for the synthesis of 
conjugate vaccines using the Diels-Alder cycloaddition reaction to 
covalently attach a carbohydrate antigen from a pathogen to a protein 
carrier. The Diels-Alder reaction has not been extended to conjugation 
involving biopolymers or other types of polymeric materials. Advantages 
of this method are that cross-linking during conjugation is entirely 
avoided in addition to the mild chemical conditions under which this 
synthesis method proceeds. Diels-Alder reactions commonly take place in 
high-temperature environments; the method contemplated by this 
invention takes place at much lower temperatures. In addition to 
claiming methods of synthesis for conjugate vaccines using the Diels-
Alder cycloaddition, the patent application claims vaccines produced 
utilizing the method, and methods of inducing antibodies which react 
with the polysaccharides contemplated by the invention.

5-Substituted Derivatives of Conformationally Locked Nucleoside 
Analogues

Victor Marquez, Pamela Russ (NCI)
DHHS Reference No. E-249-00/0 filed 26 Jul 2000

    This invention relates to 5-substituted derivatives of 
conformationally locked nucleoside analogues and methods of using these 
derivatives as antiviral and anticancer agents. The compounds 
contemplated by the invention are nucleoside analogues where the 5-
substituent is a halogen, alkyl, alkene, halovinyl or alkyne group, and 
the nucleotide base is cytosine or uracil. The analogues are 
particularly effective in treating viral infections, specifically 
infections of DNA viruses such as Herpes simplex virus (HSV), Varicella 
zoster virus (VSV), Epstein Barr virus (EBV), and Cytomegalovirus (CMV) 
as well as members of the Poxviridae family. The inventors have 
demonstrated in plaque reduction assays that 5-substituted uracils 
(bromo, iodo, and bromovinyl) attached to a bicyclo[3.1.0]hexane 
template are thirty times more potent than acyclovir against HSV-1 and 
HSV-2.

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

    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.

    Dated: December 4, 2000.
Jack Spiegel,
Director, Division of Technology, Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-31525 Filed 12-11-00; 8:45 am]
BILLING CODE 4140-01-P