[Federal Register Volume 68, Number 94 (Thursday, May 15, 2003)]
[Notices]
[Pages 26313-26314]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-12102]


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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.

Triggering Receptors Expressed in Myeloid Cells (TREM) Like Transcript 
(TLT-1), A Novel Inhibitory Receptor of Platelets and Uses Therefore

Daniel W. McVicar (NCI), A. Valence Washington (NCI), Laura Quigley 
(NCI)

DHHS Reference No. E-097-2003/0 filed March 16, 2003

Licensing Contact: Jeff Walenta; 301/435-4633; [email protected].

    The human immune response involves a complex series of molecular 
interactions to produce a beneficial response to foreign invasion 
within the body. These molecular interactions orchestrate the specific 
responses of innate and adaptive immunity. When these interactions 
break down, immune related disorders such as cancer and sepsis arise.
    This invention describes an advance in understanding the regulation 
of the immune response. Triggering Receptors in Myeloid Cells (TREM) 
recently were discovered to modulate innate and adaptive immunity. 
Specifically, TREM1 amplifies the response to sepsis in innate immunity 
by activating neutrophils and other leukocytes; and TREM2 potentiates 
dendritic cell maturation in adaptive immunity. This invention 
describes a new inhibitory TREM like Transcript, TLT-1.
    TLT-1 is the first inhibitory receptor discovered to reside within 
the TREM gene locus. This discovery implies the receptor has an 
important regulatory role in both innate and adaptive immunity. 
Structurally, TLT-1 also possesses inhibitory domains that indicate 
this regulatory function. TLT-1 is highly expressed in peripheral blood 
platelets and may modulate many other types of myeloid cells. Potential 
therapeutic implications are for immune disorders, cancer, septic 
shock, infectious disease, stroke, heart disease, myocardial 
infarction, vascular disorders, and other platelet-associated 
disorders.

17-AAG Treatment of Diseases Sensitive to c-KIT Down Regulation

Gerard Fumo and Len Neckers (NCI)

DHHS Reference No. E-256-2002 filed 22 Oct 2002

Licensing Contact: George Pipia; 301/435-5560; [email protected].

    This invention describes the use of 17-allylamino-17-
demethoxygeldanamycin (17-AAG), a derivative of geldanamycin, which 
inhibits mutated KIT protein kinase activity (the product of proto-
oncogene c-KIT). This kinase has been identified as the protein 
responsible for transformation of certain human cell types into 
pathologic cells. The invention is predicated on the discovery of a new 
method of inhibiting the activity of a mutated, constitutively active 
form of the tyrosine kinase, KIT. The method involves the 
administration of 17-AAG to a cell expressing the

[[Page 26314]]

mutated KIT protein, whereby the activity level of KIT in the cell is 
reduced. The invention may prove to be useful for treating diseases 
such as mastocytosis, gastrointestinal stromal tumors (GIST), mast cell 
leukemia, myelogenenous leukemia, and testicular cancer, all of which 
are associated with mutations in the c-KIT proto-oncogene.

Recombinant Vaccinia Viruses Expressing IL-15 and Methods of Using the 
Same

Liyanage Perera et al. (NCI)

Serial No. 60/433,703 filed 16 Dec 2002
Licensing Contact: Jonathan Dixon; 301/435-5559; [email protected].

    Vaccinia-based vaccines have a proven record of being effective 
vaccines in humans as well as in animals. However, accumulating 
evidence reveals the need for technology to improve the immune 
responses such vaccines generate.
    The present invention discloses recombinant vaccinia viruses 
capable of expressing interleukin 15 (IL-15), and methods for 
modulating immune responses using such viruses. This invention shows 
that by inserting the human IL-15 gene into the vaccinia genome, more 
effective vaccines can be generated against infectious agents and 
cancer. Currently, IL-2 has been approved by the FDA for use in the 
treatment of patients with metastatic renal cell carcinoma or with 
metastatic melanoma. It has been used as a component of cancer vaccines 
and in various approaches for the treatment of AIDS. However, 
administration of IL-2 is associated with activation-induced cell death 
(AICD), and may lead to death of T-cells that recognize the antigens 
expressed in the tumor cells. Thus, IL-15 may be a superior agent in 
the treatment of cancer, or as a component of a vaccine directed 
towards cancer or infectious agents. Co-delivery of IL-15 with antigens 
during the immunization process, according to the current invention, 
leads to induction of CD8+ memory T cells that proliferate more 
effectively in vivo and persist much longer in the immunized individual 
in addition to enhancing the levels and persistence of antigen specific 
antibodies thus providing substantially longer lasting cellular and 
humoral immunity.
    This invention has the potential to be used in a variety of ways, 
including: (i) An improved, more efficacious vaccine candidate for 
smallpox, (ii) for incorporation into existing vaccinia based vaccines 
to enhance and confer superior long lasting immune response to viral 
and cancer antigens, or (iii) as a valuable source material for IL-15 
production, especially should IL-15 be proven as an alternate of more 
efficacious cytokine than IL-2.
    This research has been described, in part, in Proc. Natl. Acad. Sci 
USA 2003 Mar 18; 100(6):3392-3397.

DNA-Binding Polyamide Drug Conjugates

Zoltan Szekely, Humcha K. Hariprakasha, Marek W. Cholody, Christopher 
J. Michejda (NCI)

DHHS Reference No. E-060-2002/2-PCT-01 filed 27 Feb 2003 (PCT/US03/
06006)
Licensing Contact: George Pipia; 301/435-5560; [email protected].

    Many current anti-cancer drugs have the DNA of cancer cells as 
their principal target. However, in most instances, the drugs are not 
selective and are plagued by toxicities, which are frequently dose 
limiting. The present invention seeks to enhance anti-tumor selectivity 
and decrease unspecific toxicity. It has been known that various 
polyamides can target the minor groove of DNA, and rules have been 
devised to ascertain the sequence-reading properties of the component 
residues of the polyamide chain. The present invention utilizes 
sequence-selective polyamide technology together with groups that 
modify DNA, either by sequence-selective alkylation or strand cleavage. 
The DNA-modifying moieties that are used for this purpose are novel 
derivatives based on the cyclopropylbenzindole (CBI) core structure. 
These compounds alkylate the DNA only when bound into the minor groove, 
and they provide some DNA-sequence recognizing capability of their own. 
The DNA-modifying agents are either embedded in the polyamide chain as 
components of the chain or are located at the termini. These compounds 
are highly toxic to cancer cells that over-express a targeted DNA 
sequence (e.g. the c-Myc oncogene promoter sequence) and are much less 
toxic to non-cancerous tissue. The compounds of the present invention 
represent a novel method for targeting DNA of cancer cells.

SH2 Domain Binding Inhibitors

Terrence R. Burke, Jr., et al. (NCI)

DHHS Reference No. E-262-2000/1 filed 28 Jun 2002
Licensing Contact: George Pipia; 301/435-5560; [email protected].

    Signal transduction processes underlie the transfer of 
extracellular information to the interior of the cell and ultimately to 
the nucleus. A variety of signal transduction processes are critical 
for normal cellular homeostasis, with protein-tyrosine kinases (PTKs) 
playing central roles in many of these pathways. Examples of such PTKs 
include the PDGF receptor, the FGF receptor, the HGF receptor, members 
of the EGF receptor family, such as the EGF receptor, erb-B2, erb-B3 
and erb-B4, the src kinase family, Fak kinase and the Jak kinase 
family. Protein-tyrosine phosphorylation that results from the action 
of PTKs can modulate the activity of certain target enzymes as well as 
facilitate the formation of specific multi-protein signaling complexes 
through the actions of homologous protein modules termed Src homology 2 
(SH2) domains, which recognize specific phosphotyrosyl containging 
sequences. A malfunction in this system through tyrosine kinase 
overexpression and/or deregulation can be manifested by various 
oncogenic and hyperproliferative disorders, including cancers, 
inflammation, autoimmune disease, hyperproliferative skin disorders, 
psoriasis and allergy/asthma, etc. The disclosed compounds, e.g. 
peptides, preferably, macrocyclic peptides, are Grb2 SH2 domain 
signaling antagonists with enhanced binding affinity. The claims of the 
current application are directed to compositions of matter and methods 
of use which provide for the diagnosis, testing and treatment of the 
aforementioned disease states.

    Dated: May 7, 2003.
Steven M. Ferguson,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 03-12102 Filed 5-14-03; 8:45 am]
BILLING CODE 4140-01-P