[Federal Register Volume 70, Number 202 (Thursday, October 20, 2005)]
[Notices]
[Pages 61142-61144]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-21010]


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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.

N- and 2-Substituted Benztropine Compounds and Use Thereof for Treating 
Mental Disorders

Amy H. Newman et al. (NIDA)

U.S. Provisional Application filed 24 Aug 2005 (HHS Reference No. E-
234-2005/0-US-01).
Licensing Contact: Marlene Shinn-Astor; 301/435-4426; 
[email protected].

    Dopamine is a neurotransmitter that exerts important effects on 
locomotor activity, motivation and reward, and cognition. The dopamine 
transporter (DAT) is expressed on the plasma membrane of dopamine 
synthesizing neurons. It is responsible for clearing dopamine released 
into the extracellular space, thereby regulating neurotransmission. The 
dopamine transporter plays a significant role in neurotoxicity and 
human diseases, such as Parkinson's disease, drug abuse (especially 
cocaine addiction), Attention Deficit Disorder/Attention Deficit 
Hyperactivity Disorder (ADD/ADHD), and a number of other CNS disorders. 
Therefore, the dopamine transporter is a strong target for research and 
the discovery of potential therapeutics for the treatment of these 
indications.
    Benztropine and its analogs bind with high affinity to the DAT and 
inhibit dopamine reuptake, but generally do not produce behavioral 
effects comparable to those produced by cocaine. Recent benztropine 
analogs have been shown to (1) reduce cocaine-induced stimulant 
effects, (2) retain long-lasting actions, and (3) lack significant 
abuse liability. These data suggest that this class of compounds may be 
useful medications for human diseases where dopamine-related behavior 
is compromised, especially in situations in which an agonist treatment 
is indicated.
    Although the benztropines bind with high affinity to the DAT 
without substitution in the 2-position of the tropane ring, only a 
substituent in the S-configuration is tolerated at DAT, in direct 
contrast to cocaine and its analogs that must have the 2-position 
substituent in the R-configuration. In this invention, substitution at 
the S-2-position of 4',4''-difluoro-or 4',4''-dichlorobenztropines with 
various functional groups such as alkyl, aryl, akyl, alcohol, ether, 
etc., as well as substitution at the tropane nitrogen were achieved and 
have demonstrated high affinity and selectivity for the DAT over the 
other monoamine transporters as well as muscarinic receptors, without a 
significant cocaine-like behavioral profile.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Novobiocin Analogues as Anticancer Agents

Leonard M. Neckers (NCI) et al.

U.S. Provisional Application No. 60/624,566 filed 03 Nov 2004 (HHS 
Reference No. E-065-2005/0-US-01).
Licensing Contact: George Pipia; 301/435-5560; [email protected].

    Functional Hsp90 requires C-terminal homodimerization of two 
molecules of Hsp90. Novobiocin competes with ATP for binding to the C-
terminus and studies demonstrated that this binding results in 
degradation of Hsp90 protein through ubiquitination and ultimately 
transportation to proteosome for proteolysis. Twenty three analogs of 
novobiocin were prepared and screened for their activity against Hsp90 
and the most active derivatives were identified. Novobiocin was 
previously identified as an inhibitor of type II topoisomerases and has 
been used clinically for more than a decade for the treatment of 
cancer. However recent studies have shown that novobiocin selectively 
inhibits the maturation of Hsp90 dependent proteins. In addition to its 
effect on Hsp90, novobiocin has been shown to reverse drug resistance 
and increase the intracellular concentration of topoisomerase II drugs 
such as Etoposide and tubulin binding drugs, such as Taxol, making 
cells more susceptible to chemotherapeutics and induction of apoptosis.
    This research is described, in part, in: Yu XM, Shen G, Neckers L, 
Blake H, Holzbeierlein J, Cronk B and Blagg BSJ. ``Hsp90 Inhibitors 
Identified from a Library of Novobiocin Analogues,'' J. Am. Chem. Soc., 
in press.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Anticancer Effects of Novel Vitamin D Receptor Antagonists

Julianna Barsony (NIDDK)

U.S. Provisional Application No. 60/300,409 filed 22 Jun 2001 (HHS 
Reference No. E-213-2001/1-US-01).
PCT Patent Application No. PCT/US02/19774 filed 20 Jun 2002 (HHS 
Reference No. E-213-2001/2-PCT-01).

[[Page 61143]]

U.S. Patent Application No. 10/481,052 filed 16 Dec 2003 (HHS Reference 
No. E-213-2001/2-US-02).
Licensing Contact: Mojdeh Bahar; 301/435-2950; [email protected].

    The present invention relates to cancer therapeutics. Specifically, 
this invention relates to novel selective vitamin D receptor modulators 
(SEDM), also known as vitamin D receptor antagonists. Methods of 
treatment resulting in inhibition of cell growth, inducement of cell 
differentiation, inhibition of breast cancer growth, and inhibition of 
parathyroid hormone secretion in mice are disclosed.
    Vitamin D does not have significant biological activity. Rather, it 
must be metabolized within the body to its hormonally active form, 
calcitriol. Calcitriol acts through the vitamin D receptor (VDR) to 
regulate important functions, such as calcium homeostasis, cell 
proliferation and differentiation, and immune functions. Many cancers 
contain VDR and, therefore respond to calcitriol. In such cancers, low 
concentrations of calcitriol stimulate growth and high concentrations 
inhibit growth. High doses of calcitriol and calcitriol analogues, 
however, cause hypercalcemia, limiting the use of this hormone for 
cancer treatment.
    The present invention relates to derivatives of calcitriol that 
have been synthesized in a manner similar to the principles developed 
to create estrogen receptor modulators (SERM). These vitamin D receptor 
modulators bind well to VDR, inhibit their ability to stimulate cancer 
cell growth and increase their ability to induce cell differentiation. 
In mice, SEDM inhibited human breast cancer growth without causing 
hypercalcemia. The technology disclosed herein may also be used for the 
prevention of breast cancer, treatment and/or prevention of other types 
of conditions or diseases, such as, but not limited to, prostate, 
colorectal, and lung cancers, leukemia, primary or metastatic melanoma, 
glyoma, and parathyroid diseases.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Zebularine, A Stable and Orally Active Inhibitor of Cytosine DNA 
Methyltransferase Capable of Reactivating Dormant Tumor Suppressor and 
Inhibiting Tumor Growth

Victor E. Marquez (NCI) et al.

U.S. Provisional Application No. 60/309,242 filed 31 Jul 2001 (HHS Ref. 
No. E-081-2001/0-US-01).
U.S. Provisional Application No. 60/311,435 filed 10 Aug 2001 (HHS Ref. 
No. E-081-2001/1-US-01).
PCT Application No. PCT/US02/24223 filed 30 Jul 2002, which published 
as WO 03/012051 on 13 Feb 2003 (HHS Ref. No. E-081-2001/2-PCT-01).
U.S. Patent Application No. 10/485,438 filed 30 Jan 2004 (HHS Ref. No. 
E-081-2001/2-US-06).
Licensing Contact: John Stansberry; 301/435-5239; 
[email protected].

    DNA methyltransferases (also referred to as DNA methylases) 
transfer methyl groups from the universal methyl donor S-adenosyl 
methionine to specific sites on a DNA molecule. When gene sequences 
contain many methylated cytosines, they are less likely to be 
expressed. Several such `silenced' genes are now known to be an 
important contributing factor in many cancers where expression of tumor 
suppressor genes has been suppressed. Preventing DNA methyltransferase 
production, or inhibiting the enzyme, may allow tumor suppressor genes 
that have been silenced by hypermethylation to be re-activated. Re-
activation of tumor suppressor genes is intended to stop or slow tumor 
growth by restoring growth control mechanisms. Thus, there exists a 
need for an effective and stable inhibitor of DNA methylation.
    The inventors have discovered a potent inhibitor of DNA methylation 
(Zebularine) that can specifically reactivate silenced tumor suppressor 
genes. This agent can be used to inhibit methylation and thereby combat 
certain cancers that have been linked to hypermethylation. This agent 
has also been shown in initial animal testing to be active orally and 
is more stable than some other agents in this same area of therapy and 
is a suitable candidate for further pre-clinical and clinical 
development as an anti-cancer agent to be used as monotherapy and/or as 
an adjunct to existing anti-cancer therapeutics.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Compositions and Methods of Specifically Targeting Tumors

Dr. Raj K. Puri (FDA) et al.

U.S. Patent No. 6,428,788 issued 06 Aug 2002 (HHS Reference No. E-266-
1994/1-US-01).
Licensing Contact: Jesse S. Kindra; 301/594-4697; [email protected].

    A chimeric molecule that binds specifically to IL-13 receptors has 
been identified. The molecule, IL13-PE38QQR, targets tumor cells with 
less binding to healthy cells. The improved specific targeting of this 
molecule is premised upon the discovery that tumor cells overexpress 
IL-13 receptors at extremely high levels and that binding of IL-13-
PE38QQR can be blocked to IL-4 receptors in normal cells. This 
phenomenon permits the use of lower dosages of chimeric molecules along 
with IL-4 receptor blocker to deliver effector molecules to targeted 
tumor cells.
    This invention may be useful in the treatment of cancer. The 
targeting method could be used in conjunction with current methods, 
e.g., chemotherapy to help maintain the healthy cells. To date, IL13-
PE38QQR has been shown to be effective against a variety of solid tumor 
cancers in animal models including adenocarcinoma, brain cancer and 
AIDS associated Kaposi's sarcoma.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

1,2-Dihydroellipticines with Activity Against CNS-Specific Cancer Cell 
Lines

Rudiger D. Haugwitz (NCI) et al.

U.S. Patent No. 5,272,146 issued 21 Dec 1993 (HHS Reference No. E-110-
1992/0-US-01).
U.S. Patent No. 5,441,941 issued 15 Aug 1995 (HHS Reference No. E-110-
1992/0-US-02).
Licensing Contact: George G. Pipia; 301/435-5560; [email protected].

    The present invention is directed, in general, to methods for 
treating human cancers and in particular to new compounds which cross 
the blood brain barrier and retain activity against CNS specific cancer 
cell lines, to pharmaceutical formulations containing such compounds, 
and to methods for the treatment of cancer.
    This research is described, in part, in Jurayj et al., ``Design and 
Synthesis of Ellipticinium Salts and 1,2-Dihydroellipticines with High 
Selectivities against Human CNS

[[Page 61144]]

Cancers in vitro,'' J. Med. Chem. 37(4):2190-2197, 1994.

    Dated: October 10, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 05-21010 Filed 10-19-05; 8:45 am]
BILLING CODE 4140-01-P