National Institutes of Health, Public Health Service, DHHS.
This notice, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR part 404.7(a)(1)(i), announces that the Department of Health and Human Services is contemplating the grant of an exclusive license to practice the inventions embodied in U.S. Patent Application No. 60/504,724 filed September 17, 2003, entitled “Thalidomide Analogs” (DHHS Reference E-189-2003/0-US-01) and PCT Application No. PCT/US2004/030506 filed September 17, 2004, entitled “Thalidomide Analogs” (DHHS Ref. E-189-2003/0-PCT-02) to Phase 2 Discovery, Inc. The patent rights in these inventions have been assigned to the United States of America.
The prospective exclusive license territory may be United States, Denmark, Italy, Ireland, United Kingdom, Germany, France, Sweden, Switzerland, Spain, Czech Republic, Greece, Russia, Australia, Japan, Taiwan, Singapore, China, Argentina and Brazil, and the field of use may be limited to development and sale of a pharmaceutical product useful in treating Amyotrophic Lateral Sclerosis (ALS) and Attention Deficit Hyperactivity Disorder (ADHD).
Only written comments and/or license applications which are received by the National Institutes of Health on or before May 9, 2005 will be considered.
Requests for copies of the patent and/or patent applications, inquiries, comments and other materials relating to the contemplated exclusive license should be directed to: Mojdeh Bahar, J.D., Technology Licensing Specialist, Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, MD 20852-3804. Telephone: (301) 435-2950; Facsimile: (301) 402-0220; E-mail: firstname.lastname@example.org.End Preamble Start Supplemental Information
Inflammatory processes associated with the over-production of cytokines, particularly of tumor necrosis factor-alpha (TNF-α), 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-α has been validated as a drug target with the development of the inhibitors Enbril and Remicade as prescription medications for rheumatoid arthritis. Both, however, are large macromolecules that are expensive to produce, require direct intravenous or subcutaneous injection, and have negligible brain access. The classical orally active drug, thalidomide (N-α-phthalimidoglutarimide), a glutamic acid derivative, is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated, infectious diseases, and cancers. Its clinical value in treating ENL derives from its TNF-α inhibitory activity. Specifically, it inhibits TNF-α protein expression at the post-transcriptional level by facilitating turnover of the mRNA. More recent research has shown similar inhibitory action of COX2 protein expression. These actions are mediated post-transcriptionally via AU-rich elements found in the 3′ untranslated regions (3′-UTRs) of each mRNA. Thalidomide's anti-angiogenesis activity derives from its inhibitory actions on basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The agent, additionally, acts as an inhibitor of the transcription factor, NFkB and a co-stimulator of both CD8+ and CD4+ T cells. However, the action of thalidomide to lower TNF-α levels and inhibit angiogenesis is not particularly potent, and it therefore represents an interesting lead compound for medicinal chemistry.
Novel structural modification of thalidomide led to 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-α and angiogenesis activities in a subject. Disclosed analogues potently inhibited TNF-α secretion, compared to thalidomide, via post-transcriptional mechanisms that decreased TNF-α mRNA stability via its 3′-UTR. Actions to inhibit angiogenesis were determined in widely accepted ex vivo assays.
The prospective exclusive license will be royalty-bearing and will comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR part 404.7. The prospective exclusive license may be granted unless within sixty (60) days Start Printed Page 11254from the date of this published notice, the NIH receives written evidence and argument that establish that the grant of the license would not be consistent with the requirements of 35 U.S.C. 209 and 37 CFR part 404.7.
Applications for a license in the field of use filed in response to this notice will be treated as objections to the grant of the contemplated exclusive license. Comments and objections submitted to this notice will not be made available for public inspection and, to the extent permitted by law, will not be released under the Freedom of Information Act, 5 U.S.C. 552.Start Signature
Dated: February 28, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. 05-4488 Filed 3-7-05; 8:45 am]
BILLING CODE 4140-01-P