[Federal Register Volume 69, Number 163 (Tuesday, August 24, 2004)]
[Notices]
[Pages 52018-52019]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-19300]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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.

Pichia pastoris Cloning Systems for Expressing and Secreting Proteins 
of Interest

    James Hartley (NCI/SAIC-Frederick).DHHS Reference No. E-305-2004/
0--Research Tool.
    Licensing Contact: Michael Shmilovich; (301) 435-5019; 
[email protected].
    Biological materials of a Pichia pastoris cloning and expression 
system are available for licensing for internal use. The system 
provides a vector for transgenically expressing proteins that are 
secreted through signal peptide mediation (e.g., the [alpha] mating 
factor signal peptide). This expression system utilizes the 
Gateway[reg] cloning platform from Invitrogen without interference from 
the Gateway[reg] attB1 sequence. The [alpha] mating factor signal 
peptide encoding sequence includes an attB1 insertion at an XhoI site 
upstream from some gene of interest (e.g., human interferon Hyb3). The 
attB1 site does not alter the secretion or processing of the signal 
peptide.

[[Page 52019]]

Computer-Based Model for Identification and Characterization of Non-
Competitive Inhibitors of Nicotinic Acetylcholine Receptors and Related 
Ligand-Gated Ion Channel Receptors

    I. W. Wainer et al. (NIA). U.S. Patent Application No. 10/411,206 
filed 11 Apr 2003 (DHHS Reference No. E-158-2003/0-US-01); PCT 
Application No. PCT/US04/10978 filed 09 Apr 2004 (DHHS Reference No. E-
158-2003/1-PCT-01); U.S. Patent Application No. 10/820,809 filed 09 Apr 
2004 (DHHS Reference No. E-158-2003/1-US-02).
    Licensing Contact: Cristina Thalhammer-Reyero; (301) 435-4507; 
[email protected].
    This invention relates to a computer system for generating 
molecular models of ligand-gated ion channels and in particular, 
molecular models of the inner lumen of a ligand-gated ion channel and 
associated binding pockets. It further relates to a computer system 
simulating interaction of the computer-based model of the ligand-gated 
channel and non-competitive inhibitor compounds for identification and 
characterization of non-competitive inhibitors and to inhibitor 
compounds so discovered. It also includes methods for treating various 
disorders related to ligand-gated ion channel receptor function, and 
provides a way to examine compounds for ``off-target'' activity that 
may cause undesirable side effects to a desired target activity or that 
may represent a new therapeutic activity for a known compound.
    Ligand gated ion channels (LGICs) are currently very important 
targets for drug discovery in the pharmaceutical industry. The 
superfamily is separated into the nicotinic receptor superfamily 
(muscular and neuronal nicotinic, GABA-A and-C, glycine and 5-HT3 
receptors), the excitatory amino acid superfamily (glutamate, aspartate 
and kainate receptors) and the ATP purinergic ligand gated ion 
channels. These families only differ in the number of transmembrane 
domains found in each subunit (nicotinic-4 transmembrane domains, 
excitatory amino acid receptors-3 transmembrane domains, ATP purinergic 
LGICs-2 transmembrane domains). In particular, the nicotinic 
acetylcholine receptors control the fast permeation of cations through 
the postsynaptic cell membrane, and are key targets in drug discovery 
for a number of diseases, including Alzheimer's and Parkinson's 
disease.

Modulators of Nuclear Hormone Receptor Activity: Novel Compounds, 
Diverse Applications for Infectious Diseases, Including Anthrax (B. 
anthracis)

    E. M. Sternberg (NIMH), J. I. Webster (NIMH), L. H. Tonelli (NIMH), 
S. H. Leppla (NIAID), and M. Maoyeri (NIAID). U.S. Provisional 
Application No. 60/416,222 filed 04 Oct 2002 (DHHS Reference No. E-247-
2002/0-US-01); U.S. Provisional Application No. 60/419,454 filed 18 Oct 
2002 (DHHS Reference No. E-348-2003/0-US-01); PCT Application No. PCT/
US03/31406 filed 03 Oct 2003 (DHHS Reference No. E-247-2002/1-PCT-01).
    Licensing Contact: Peter Soukas; (301) 435-4646; 
[email protected].
    Technology summary and benefits: Nuclear hormones such as 
glucocorticoids dampen inflammatory responses, and thus provide 
protection to mammals against inflammatory disease and septic shock. 
The Anthrax lethal factor represses nuclear hormone receptor activity, 
and thus may contribute to the infectious agent causing even more 
damage to the host. This observation can be exploited to find new means 
of studying and interfering with the normal function of nuclear hormone 
receptors. Scientists at NIH have shown that under the appropriate 
conditions, these molecules can be used to modulate the activity of 
various nuclear hormone receptors. Identifying useful agents that 
modify these important receptors can provide relief in several human 
disorders such as inflammation, autoimmune disorders, arthritis, 
malignancies, shock and hypertension.
    Long-term potential applications: This invention provides novel 
agents that can interfere with the action of nuclear hormone receptors. 
It is well known that malfunction or overdrive of these receptors can 
lead to a number of diseases such as enhanced inflammation; worse 
sequelae of infection including shock; diabetes; hypertension and 
steroid resistance. Hence a means of controlling or fine-tuning the 
activity of these receptors can be of great benefit. Current means of 
affecting steroid receptor activity are accompanied by undesirable 
side-effects. Since the conditions for which these treatments are 
sought tend to be chronic, there is a critical need for safer drugs 
that will have manageable side-effects.
    Uniqueness or innovativeness of technology: The observation that 
the lethal factor from Anthrax has a striking effect on the activity of 
nuclear hormone receptors opens up new routes to controlling their 
activity. The means of action of this repressor is sufficiently 
different from known modulators of hormone receptors (i.e. the 
classical antagonists). For instance, the repression of receptor 
activity is non-competitive, and does not affect hormone binding or DNA 
binding. Also, the efficacy of nuclear hormone receptor repression by 
Anthrax lethal factor is sufficiently high that the pharmacological 
effect of this molecule is seen at vanishingly small concentrations. 
Taken together, these attributes may satisfy some of the golden rules 
of drug development such as the uniqueness or novelty of the agent's 
structure, a low threshold for activity, high level of sophistication 
and knowledge in the field of enquiry, and the leeway to further refine 
the molecule by rational means.
    Stage of Development: In vitro studies have been completed, and a 
limited number of animal studies have been carried out.

    Dated: August 16, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer,National Institutes of Health.
[FR Doc. 04-19300 Filed 8-23-04; 8:45 am]
BILLING CODE 4140-01-P