[Federal Register Volume 69, Number 165 (Thursday, August 26, 2004)]
[Notices]
[Pages 52507-52508]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-19539]



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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 an agency 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.

Methylation Inhibitor Compounds

Victor Marquez et al. (NCI).
U.S. Provisional Application No. 60/547,902
Filed 25 Feb 2004
(DHHS Reference No. E-074-2004/0-US-01).
Licensing Contact: Jeff Walenta; 301/435-4633; [email protected].

    Aberrant de novo DNA methylation is commonly associated with 
cancer. Several studies have shown that de novo methylation of tumor 
suppressor genes can lead to silencing of these genes and abnormal 
growth of cancer cells. Therefore, DNA methylation inhibitors may be 
used in cancer therapy to modulate hypermethylation of genes and to 
reactivate anti-proliferative, apoptotic and differentiation-inducing 
genes in cancer cells. Although some compounds have been proposed for 
use as DNA methylation inhibitors, these compounds are chemically 
instable, have weak potency and can generate toxic metabolites, thus 
preventing them being used as therapeutic agents.
    The present invention relates to compositions and compounds that 
are useful as DNA methylation inhibitor compounds. The invention also 
relates to a method, using these compositions and compounds, of 
treating various cancers having a silenced tumor suppressor gene, and a 
method of treating a DNA-methylation-mediated disease. These compounds 
are generally chemically stable, non-toxic and may be administered 
orally or by injection. A method of making a compound is described.
    These compounds seem to have a better therapeutic profile than 
another published DNA methylation inhibitor, Zebularine.

A Combined Immunosuppressive Therapy Consisting of Glucocorticoid and 
rIL-2

Xin Chen et al. (NCI).
U.S. Provisional Application No. 60/515,217
Filed 27 Oct 2003
(DHHS Reference No. E-211-2003/0-US-01).
Licensing Contact: Mojdeh Bahar; 301/435-2950; [email protected].

    The invention is a combination immunosuppressive therapeutic 
regimen consisting of a glucocorticoid and rIL-2. The combination 
minimizes the side effects associated with glucocorticoid treatment, 
and is useful in inhibiting or treating inflammation, immune-mediated 
disorders, and transplant rejection. The treatment regimen at once 
promotes cell death of CD4+CD25- T effector cells, including cytotoxic 
T cells, and expansion of inhibitory Foxp3+CD4-CD25+ T regulatory 
(Treg) cells. This regimen involves application of both 
glucocorticoid and IL-2, and is based on the surprising observation 
that IL-2 selectively protects Treg cells from 
glucocorticoid-induced cell death. As Treg cells inhibit 
CD4+CD25- T cells, the effect of combined glucocorticoid/IL-2 therapy 
is to enhance the immunosuppressive effect of the glucocorticoids. In 
this context, glucocorticoids and IL-2 act synergistically to suppress 
cellular immune responses.

Production of Adeno-Associated Viruses in Insect Cells

Robert M. Kotin et al. (NHLBI).
U.S. Patent No. 6,723,551
Issued 20 April 2004
(DHHS Reference No. E-325-2001/1-US-01).
Licensing Contact: Jeff Walenta; 301/435-4633; [email protected].

    Adeno-associated virus (AAV) is being developed for gene therapy 
applications. This virus type presents several advantages over 
alternate vectors for therapeutic gene delivery. AAV is not considered 
pathogenic and transduces stably dividing and non-dividing cells. AAV 
also shows good serotype specificity to various cell types for targeted 
gene delivery.
    The present invention describes a highly scalable adeno-associated 
virus (AAV) vector production method in insect cells. The system for 
producing recombinant AAV (rAAV) uses the AAV Rep protein and an AAV 
ITR. This production method produces virus particles much more 
efficiently than the standard mammalian cell culture system. Yields of 
rAAV produced in Sf9 cells exceed 10e15 per liter for some constructs. 
The improvement in production efficiency translates into lower 
production costs and potential for commercial scale manufacturing. In 
addition, all serotypes of AAV can be produced, with the respective AAV 
serotype vectors available for the immediate scale up of AAV 
production.
    This technology will give a company producing large quantities of 
AAV a significant competitive advantage over traditional AAV production 
methods.

B-Homoestra-1,3,5(10)-trienes as Modulators of Tubulin Polymerization

Ernest Hamel et al. (NCI).
U.S. Patent No. 6,696,436
Issued 24 Feb 2004
(DHHS Reference No. E-230-1999/0-US-03).
Licensing Contact: Jeff Walenta; 301/435-4633; [email protected].

    This invention relates to the general field of steroid chemistry, 
particularly to estrone derivatives. Specifically, this invention 
provides B-ring expanded estra-1,3,5(10)-triene compounds of general 
formula which modulate the polymerization of tubulin and/or the 
depolymerization of microtubules. Successful cell division, as a step 
of cell mitosis, depends on the proper polymerization of tubulin and 
the proper depolymerization of microtubules. This invention also 
relates to methods of using the compounds as anti-mitotic, anti-
angiogenic and anti-tumor therapeutics for the treatment of cancer or 
other mammalian diseases characterized by undesirable angiogenesis. 
Additionally, the invention provides methods of preparing the 
compounds. The compounds of the invention are also expected to have 
utility as research tools.
    This invention was published in: Verdier-Pinard et al., ``A Steroid 
Derivative With Paclitaxel-Like Effects on Tubulin Polymerization,'' 
Mol. Pharmacol. 2000 Mar, 57(3):568-575; Wang et al., ``Synthesis of B-
ring Homologated Estradiol Analogues that Modulate Tubulin 
Polymerization and

[[Page 52508]]

Microtubule Stability,'' J. Med. Chem. 2000 Jun 15, 43(12):2419-2429.

Methods and Compositions for Transforming Dendritic Cells and 
Activating T Cells

Patrick Hwu et al. (NCI).
U.S. Patent No. 6,734,014
Issued 11 May 2004
(DHHS Reference No. E-040-1996/0-US-07).
Licensing Contact: Jeff Walenta; 301/435-4633; [email protected].

    T cells mediate most forms of cellular immunity. Typically T cells 
do not respond to free antigenic peptides, but instead T cells interact 
with a specialized set of cell surface proteins, which are the class I 
and class II major histocompatibility complexes, or MHC. Specialized 
antigen-presenting cells, such as macrophage and dendritic cells, 
present antigenic peptides on the surface cells in conjunction with the 
MHC molecules, and induce cytotoxic T cells to proliferate. T cells are 
induced by these antigen-presenting cells to recognize corresponding 
antigens expressed on MHC antigens on the surface of target cells, and 
destroy these target cells.
    This invention describes a novel method for making transformed 
dendritic cells with any recombinant nucleic acid, which have been 
difficult to transduce using existing methods. Recombinant dendritic 
cells are made by transforming a stem cell and differentiating the stem 
cell into a dendritic cell. The resulting dendritic cell is an antigen-
presenting cell that activates T cells against MHC class I-antigen 
targets. The present invention provides a valuable tool for the 
treatment of cancer, and viral and parasitic infections using the 
recombinant dendritic cells. The invention also provides therapeutic 
compositions and pharmaceutical compositions.
    This research is described in Reeves et al., ``Retroviral 
Transduction of Human Dendritic Cells with a Tumor-Associated Antigen 
Gene,'' Cancer Res. 1996 Dec15, 56(24):5672-5677.

    Dated: August 18, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-19539 Filed 8-25-04; 8:45 am]
BILLING CODE 4140-01-P