[Federal Register Volume 77, Number 38 (Monday, February 27, 2012)]
[Notices]
[Pages 11560-11562]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-4376]


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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.

Model Cell Lines With and Without AKT1 Mutations Derived From Proteus 
Syndrome Patients

    Description of Technology: The Proteus syndrome is a congenital 
disorder characterized by patchy overgrowth and hyperplasia (cell 
proliferation) of multiple tissues and organs, along with 
susceptibility to developing tumors. It is a rare disorder, with 
incidence of less than one case per million, caused by a somatic 
mutation. It is also a mosaic disorder, that is one in which cells of 
the same person have different genetic content from one another. The 
NHGRI inventors have generated cell lines from patients with Proteus 
syndrome and discovered that a somatic activating mutation in the 
serine-threonine kinase AKT1 is associated with Proteus syndrome. AKT1 
is an oncogene and an enzyme known to mediate cell proliferation and 
apoptosis (programmed cell death process) and has been a target for 
anti-cancer therapies. A number of single-cell lines with the AKT1 
mutation showing increased AKT1 phosphorylation and their matched 
controls without the mutation have been generated. The cell lines can 
be used to screen therapeutic targets for AKT1, for study design, as 
models of Proteus syndrome and early stages of cancerous conditions.

Potential Commercial Applications

     Cell lines generated from patients with Proteus syndrome.
     Obtained a number of single-cell lines with the AKT1 
mutation and their matched controls without the mutation.

[[Page 11561]]

     Cell lines with the mutation showed increased AKT1 
phosphorylation for activating mutation.

Competitive Advantages

     Screening of potential therapeutics that target AKT1.
     Cell lines have well-matched controls for rigorous study 
design.
     Serves as model cell lines of Proteus syndrome and early 
stages of cancerous conditions.

Development Stage

     Prototype.
     Clinical.
     In vivo data available (human).
    Inventors: Leslie G. Biesecker and Marjorie J. Lindhurst (NHGRI).
    Publication: Lindhurst MJ, et al. A mosaic activating mutation in 
AKT1 associated with the Proteus syndrome. N Engl J Med. 2011 Aug 
18;365(7):611-619. [PMID 21793738].
    Intellectual Property: HHS Reference No. E-033-2012/0 -- Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Whitney Hastings, Ph.D.; 301-451-7337; 
[email protected]

Non-toxic Compounds That Inhibit the Formation and Spreading of Tumors

    Description of Technology: Available for licensing are novel 
pyrrolopyrimidine compounds that disrupt the assembly of the 
perinucleolar compartment (PNC), a sub-nuclear structure highly 
prevalent in metastatic tumors. These notable compounds act without 
overt cytotoxicity.
    The presence of the PNC positively correlates with metastatic 
capacity, making it a potential marker for cancer development and 
prognosis. These compounds could also serve as useful tools to 
elucidate the biology driving the formation and maintenance of the PNC, 
and unravel its association with metastasis.

Potential Commercial Applications

     Use in the therapeutic intervention of metastasis in 
cancer.
     Use as tools to elucidate the biology of the PNC.

Competitive Advantages

     No existing FDA-approved treatment for the clinical 
management of metastasis.
     Target is specific to metastatic tumors.
     Compounds are not toxic.
     Broadly acting across all metastatic cancers.

Development Stage

     Early-stage.
     In vitro data available.
    Inventors: Samarjit Patnaik et al. (NCATS).
    Intellectual Property: HHS Reference No. E-276-2011/0 -- U.S. 
Provisional Application No. 61/576,780 filed 16 Dec 2011.
    Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The National Center for 
Advancing Translational Sciences is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize this technology. For collaboration 
opportunities, please contact Lili M. Portilla, MPA at 301-217-2589 or 
[email protected].

Novel Radio-Labeled Agents for Imaging Alzheimer's Disease-Associated 
Amyloid

    Description of Technology: This technology introduces novel radio-
labeled agents for imaging amyloid deposits in the brains of 
Alzheimer's Disease patients. These are small molecule, radio-ligand 
compounds that are analogs of benzo[d]thiazole. They are highly 
specific to amyloid, have low background noise, do not undergo rapid 
defluoridation and do not produce residual radioactivity in the brain. 
In addition, the compounds are stable and may be readily synthesized 
from commercially available starting materials. These compounds may be 
used in many noninvasive imaging techniques including: magnetic 
resonance spectroscopy (MRS) or imaging (MRI), or positron emission 
tomography (PET) or single-photon emission computed tomography (SPECT) 
to measure amyloid. Non-invasive detection of Alzheimer's disease-
associated amyloid plaques in the brain would be valuable for early 
diagnosis, monitoring, and for clinical development of therapeutic 
drugs.
    Potential Commercial Applications: Imaging agents for use in 
magnetic resonance spectroscopy (MRS), or imaging (MRI), positron 
emission tomography (PET) or single-photon emission computed tomography 
(SPECT).
    Competitive Advantages: Highly specificity to amyloid, low 
background, do not undergo rapid defluoridation and do not produce 
residual radioactivity in the brain.
    Development Stage: Early-stage.
    Inventors: Lisheng Cai and Victor W. Pike (NIMH).

Publications

    1. Cai L, et al. Synthesis and structure-affinity relationships of 
new 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-dimethylbenzeneamine 
derivatives as ligands for human beta-amyloid plaques. J Med Chem. 2007 
Sep 20;50(19):4746-4758. [PMID 17722900].
    2. Cai L, et al. Synthesis and evaluation of N-methyl and S-methyl 
11C-labeled 6-methylthio-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-
a]pyridines as radioligands for imaging beta-amyloid plaques in 
Alzheimer's disease. J Med Chem. 2008 Jan 10;51(1):148-158. [PMID 
18078311].
    Intellectual Property: HHS Reference No. E-225-2011/0--U.S. 
Provisional Application No. 61/535,569 filed 16 Sep 2011.
    Related Technology: HHS Reference No. E-156-2006/0--U.S. Patent 
Application No. 12/293,340 filed 17 Sep 2008.
    Licensing Contact: Tedd Fenn, J.D.; 301-435-5031; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Mental Health (NIMH) is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate or commercialize Beta-amyloid Imaging Agents. For 
collaboration opportunities, please contact Suzanne L. Winfield, Ph.D. 
at [email protected] or 301-402-4324.

A New Class of Broad-Spectrum Antibiotics: Naturally-Occurring 
Chrysophaetins and Their Analogues

    Description of Technology: This invention, offered for licensing 
and commercial development, relates to a new class of naturally 
occurring antimicrobial compounds called Chrysophaetins, and to their 
synthetic analogues. Isolated from an alga species, the mechanism of 
action of these compounds is through the inhibition of bacterial 
cytoskeletal protein FtsZ, an enzyme necessary for the replication of 
bacteria. FtsZ is responsible for Z-ring assembly in bacteria, which 
leads to bacterial cell division. Highly conserved among all bacteria, 
FtsZ is a very attractive antimicrobial target.
    The chrysophaetin exhibits antimicrobial activity against drug 
resistant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) 
and vancomycin-resistant Enterococcus faecalis (VRE), as well as other 
drug susceptible strains. The general structure of the natural compound 
is shown below:

[[Page 11562]]

[GRAPHIC] [TIFF OMITTED] TN27FE12.009

Potential Commercial Applications

     Therapeutic potential for treating general and drug-
resistant bacterial infections in clinical and veterinary populations.
     Antiseptics in hospital settings.

Competitive Advantages

     Effective for commonly occurring drug-resistant infections 
MRSA and VRE.
     Broad spectrum of efficacy because mechanism of action is 
against the bacterial protein FtsZ, which has similar structure in all 
bacteria.
     Potential for additive efficacy when combined with other 
antibiotics due to distinct mechanism of action.
     Other drugs with similar structure and antibacterial 
properties can be synthesized using the chemical structure template 
shown above.

Development Stage

     Early-stage.
     In vitro data available.
    Inventors: Carole A Bewley, et al. (NIDDK).
    Publication: Plaza A, et al. Chrysophaentins A-H, antibacterial 
bisdiarylbutene macrocycles that inhibit the bacterial cell division 
protein FtsZ. J Am Chem Soc. 2010 Jul 7;132(26):9069-9077. [PMID 
20536175].
    Intellectual Property: HHS Reference No. E-116-2010/0--PCT 
Application No. PCT/US2011/026200 filed 25 Feb 2011, which published as 
WO 2011/106630 on 01 Sep 2011.
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic 
Chemistry, is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize the chrysophaentin antibiotics. Please contact Marguerite 
J. Miller at 301-451-3636 or [email protected] for more 
information.

    Dated: February 21, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-4376 Filed 2-24-12; 8:45 am]
BILLING CODE 4140-01-P