[Federal Register Volume 68, Number 244 (Friday, December 19, 2003)]
[Notices]
[Pages 70823-70824]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-31328]


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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, HHS.

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.

Thalidomide Analogs

Nigel Greig (NIA),
U.S. Provisional Patent Application filed 17 Sep 2003 (DHHS Reference 
No. E-189-2003/0-US-01),
Licensing Contact: Matthew Kiser; 301/435-5236; [email protected].

    Inflammatory processes associated with the over-production of 
cytokines, particularly of tumor necrosis factor-alpha (TNF-a), 
accompany numerous neurodegenerative diseases, such as Alzheimer's 
disease and ALS, in addition to numerous common systemic conditions, 
such as rheumatoid arthritis, septic shock, graft-versus-host disease, 
Crohn's disease and erythema nodosum leprosum (ENL). TNF-a has been 
validated as a drug target with the development of the inhibitors 
Enbril (Amgen, Thousand Oaks, CA/Wyeth, Princeton, NJ) and Remicade 
(Centocor, Malvern, PA/Schering-Plough, Orange, NJ) as prescription 
medications for rheumatoid arthritis. Both, however, are large 
macromolecules and hence are expensive to produce, require direct 
intravenous or subcutaneous injection, and have negligible brain 
access. The classical orally active drug, thalidomide (N-a-
phthalimidoglutarimide), a glutamic acid derivative, is being 
increasingly used in the clinical management of a wide spectrum of 
immunologically-mediated and infectious diseases, and cancers. Its 
clinical value in treating ENL derives from its TNF-a inhibitory 
activity. Specifically, it inhibits TNF-a protein expression at the 
post-transcriptional level by facilitating turnover of the mRNA 
(Sampaio et al., 1991 & 1993; Moreira et al., 1993). More recent 
research has shown similar inhibitory action of COX2 protein expression 
(Fujita et al., 2001). These actions are mediated post-
transcriptionally via AU-rich elements found in the 3' untranslated 
regions (3'-UTRs) of each mRNA (Kruys et al., 1994; Chen et al., 1995). 
Thalidomide's anti-angiogenesis activity derives from its inhibitory 
actions on basic fibroblast growth factor (bFGF) and vascular 
endothelial growth factor (VEGF) (D'Amato et al., 1994; Figg et al., 
2002). The agent, additionally, acts as an inhibitor of the 
transcription factor, NFkB and a co-stimulator of both CD8+ and CD4+ T 
cells (Haslett et al., 1998). However, the action of thalidomide to 
lower TNF-a levels and inhibit angiogenesis is not particularly potent 
and it therefore represents an interesting lead compound for medicinal 
chemistry.
    Novel structural modification of thalidomide was achieved towards 
the discovery of original and potent isosteric analogues. The present 
invention relates to thalidomide analogues and, in particular, 
thiothalidomides (sulfur-containing thalidomide analogues), methods of 
synthesizing the analogues, and methods for using the analogues to 
modulate TNF-[alpha] and angiogenesis activities in a subject. 
Disclosed analogues potently inhibited TNF-[alpha] secretion, compared 
to thalidomide, via post-transcriptional mechanisms that decreased TNF-
[alpha] mRNA stability via its 3'-UTR (Zhu et al., 2003). Actions to 
inhibit angiogenesis were determined in widely accepted ex vivo assays.

Methods and Compositions for Treating Diseases and Disorders Associated 
With Natural Killer T-Cells

John R. Ortaldo, Robert H. Wiltrout (NCI)
U.S. Provisional Application No. 60/488,339 filed 17 Jul 2003 (DHHS 
Reference No. E-282-2002/0-US-01)
Licensing Contact: Catherine Joyce; 301/435-5031; [email protected].

    The invention relates to the discovery that C12 beta-D-galactosyl 
ceramide may be used to deplete or inactivate NKT cell populations. 
These findings suggest methods for using C12 beta-D-galactosyl ceramide 
to treat conditions that would benefit from depletion of NKT cells, 
such as certain auto-immune diseases (e.g. lupus, MS) and AIDs.
    The presence of NKT cells can be associated with either beneficial 
effects or pathology. Deficiencies in NKT cells are associated with at 
least some types of autoimmune disease, including type 1 diabetes and 
autoimmune gastritis in mice. In contrast, NKT cells augment 
autoantibody secretion and lupus development in lupus-prone mouse 
models and therefore lupus patients may benefit from the depletion of 
NKT cells. The remission state of multiple sclerosis (MS) is also 
associated with decreased levels of NKT cells, suggesting NKT cell 
depletion as a method of treatment for MS.
    The above-mentioned invention is available for licensing on an 
exclusive or a non-exclusive basis.

Leu574 of HIF-1alpha as a Molecular Basis for Therapeutic Application

L. E. Huang (NCI)
U.S. Provisional Application No. 60/465,565 filed 25 Apr 2003 (DHHS 
Reference No. E-281-2002/0-US-01)
Licensing Contact: Catherine Joyce; 301/435-5031; [email protected].

    The hypoxia-inducible factor 1 (HIF-1) is a transcription factor 
that plays a pivotal role in cellular adaptation to oxygen 
availability. HIF-1alpha protein is a subunit of HIF-1. Although the 
gene for HIF-1alpha is constitutively expressed, it is an extremely 
short-lived protein under normoxic conditions and is targeted for 
destruction via the proteosome pathway by an E3 ubiquitin ligase (the 
VHL protein).
    The invention relates to the discovery that mutations or deletions 
of Leu574 result in a more stable form of HIF-1alpha. Therefore, the 
invention relates

[[Page 70824]]

to methods and compositions for modulating oxygen homeostasis for 
therapeutic application. In one aspect, the inventors contemplate the 
use of a more stable form of HIF-1alpha protein for therapeutic 
angiogenesis purposes such as may be useful in ischemic vascular 
disease. In another aspect, the inventors contemplate the use of this 
particular site in a screen for targeted drugs that modulates HIF-
1alpha activity. The inventors also suggest that Leu574 could be used 
for developing drugs targeted to HIF hydroxylase binding, thereby 
altering HIF-1alpha stability.
    This technology is available for licensing on an exclusive or a 
non-exclusive basis.

Vasostatin as Marrow Protectant

Giovanna Tosato et al. (NCI)
U.S. Patent No. 6,596,690 B2 issued 22 Jul 2003 (DHHS Reference No. E-
230-2000/0-US-01); U.S. Patent Application No. 10/405,588 filed 01 Apr 
2003 (DHHS Reference No. E-230-2000/0-US-02)
Licensing Contact: Matthew Kiser; 301/435-5236; [email protected].

    This patent relates to the stimulation of hematopoiesis, more 
specifically to the protection of hematopoietic stem cells from toxic 
agents, including chemotherapeutic agents and/or irradiation. The 
subject patent discloses specific fragments of vasostatin, and their 
application as stimulants of hematopoiesis in vitro and in vivo. Also 
disclosed is a method for stimulating the proliferation/survival of 
hematopoietic cells exposed to a chemotherapeutic agent or irradiation 
using these fragments. In one embodiment, a method is disclosed for 
stimulating the growth or survival of hematopoietic stem cells with a 
fragment of vasostatin, in the presence of a growth factor.

    Dated: December 11, 2003.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 03-31328 Filed 12-18-03; 8:45 am]
BILLING CODE 4140-01-P