[Federal Register Volume 72, Number 46 (Friday, March 9, 2007)]
[Notices]
[Pages 10769-10770]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-4182]


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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.

Methods of Treating Conditions Characterized by Unwanted or Excessive 
Presynaptic Neuronal Activity or Secretion

    Description of Technology: Botulinum toxins are highly potent 
neurotoxins produced by the spore-forming bacterium, Clostridium 
botulinum. Poisoning by any of the seven known botulinum toxin 
serotypes, designated A to G, results in impaired communication between 
nerve and muscle that causes paralysis in patients and possible death 
by respiratory failure. Injections of botulinum toxins A and B have 
been approved for treating disorders associated with uncontrollable 
muscle contractions. However, the use of approved botulinum toxins is 
limited by their temporary duration of action, the development of 
neutralizing antibodies after repeated injections, and cross-reactivity 
with autonomic neurons. Thus, an interest exists in finding new ways to 
achieve longer-lasting effects using botulinum toxins.
    This technology describes a novel method for treating diseases by 
combining two botulinum toxins, botulinum toxin A and B. Researchers at 
the FDA have shown that the combination of the A and B toxins is 
synergistic, improves muscle paralysis characteristics compared to 
individually administered serotypes, and produces a longer duration of 
action and a faster onset of paralysis. The synergistic effect allows 
lower doses compared to single use of either toxin and should help 
reduce resistance after repeated use. This technology is beneficial for 
the treatment of diseases already known to be treatable with botulinum 
toxins, such as facial wrinkles, headaches, muscle spasms, and cervical 
dystonia. This technology is also suitable to treat other diseases, 
such as strabismus, hemifacial spasms, facial nerve damage, and 
hyperhidrosis (excessive sweating).
    Available for licensing are methods and pharmaceutical compositions 
for administering a combination of botulinum toxin A and B to treat 
unwanted or excessive presynaptic neuronal activity or secretion.
    Application: Alternative therapy for diseases treatable with 
individual botulinum toxins; such therapies include Botox[supreg], 
Botox Cosmetic[supreg], and Myobloc[supreg].
    Market: Patients who are currently prescribed individual toxins for 
treatment of diseases such as strabismus, blepharospasm, cervical 
dystonia, and cosmetic wrinkle reduction.
    Development Status: Pre-clinical data is available.
    Inventors: James E. Keller (CBER/FDA).
    Publications: JE Keller. Recovery from botulinum neurotoxin 
poisoning in vivo. Neuroscience 2006 May 12;139(2):629-637.
    Patent Status: U.S. Provisional Application No. 60/773,412 filed 15 
Feb 2006 (HHS Reference No. E-172-2005/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Norbert Pontzer, PhD, J.D.; 301/435-5502; 
[email protected].
    Collaborative Research Opportunity: The FDA Center for Biologics 
Evaluation and Research, Laboratory of Respiratory and Special 
Pathogens, is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize this technology. Please contact James E. Keller, PhD, at 
301/ for more information.

Synergistic Effect of TGF-Beta Blockade and Immunogenic Agents on 
Tumors

    Description of Technology: Overcoming immune suppression in cancer 
patients is a major challenge for the success of cancer immunotherapy. 
TGF-[beta] and its receptors are expressed in essentially all tissues, 
and they have been found to be important in many cellular processes 
including cell growth inhibition. The inhibition of TGF-[beta] 
signaling has been shown to have an inhibitory effect on tumor growth. 
However, TGF-[beta] also has immunosuppressive properties.
    Cancer vaccines are one of many therapies available for treatment 
and prevention. In particular, vaccines that elicit immune responses 
have been used to treat or control tumor growth that has evaded 
immunosurveillance. However, these vaccines have demonstrated limited 
success.
    Available for licensing is a method for synergistically affecting 
tumor growth involving the administration of an agent that blocks the 
TGF-[beta] signaling pathway, in combination with an immunogenic agent. 
The agent that blocks the TGF-[beta] signaling pathway may inhibit the 
immunosuppressive effects of TGF-[beta], while the immunogenic agent is 
believed to enhance an immune response. Surprisingly, the combination 
of such elements produces a synergistic effect. The administration of 
the 1D11.16 anti-TGF-[beta] antibody in combination with the human 
papilloma virus E7(49-57) peptide enhances tumor regression in an 
animal model. The administration of the 1D11.16 anti-TGF-[beta] 
antibody in

[[Page 10770]]

combination with irradiated CT26 cells enhances tumor regression in 
another mouse model. The investigators found that administering the 
combination of agents is more effective than the sum of their 
individual effects.
    Applications: A method of cancer combination therapy based on 
immunotherapeutics.
    Development Status: The invention is in the clinical stages of 
development.
    Inventors: Masaki Terabe (NCI) et al.
    Publications:
    1. PCT patent publication WO 2006/089251, August 24, 2006.
    2. M Terabe et al. Transforming growth factor-beta production and 
myeloid cells are an effector mechanism through which CD1d-restricted T 
cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: 
abrogation prevents tumor recurrence. J Exp Med. 2003 Dec 
1;198(11):1741-1752.
    Patent Status: U.S. Provisional Application No. 60/654,329 filed 17 
Feb 2005 (HHS Reference No. E-019-2005/0-US-01); PCT Application No. 
PCT/US2006/005888 filed 16 Feb 2006 (HHS Reference No. E-019-2005/0-
PCT-02).
    Licensing Availability: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; [email protected]

Arylthioindole Tubulin Polymerization Inhibitors and Methods of 
Treating or Preventing Cancer Using Same

    Description of Technology: Microtubules are involved in a variety 
of cellular functions including motility, division, shape maintenance, 
and intracellular transport. Tubulin is the major protein component in 
microtubules, and interference with microtubule assembly leads to an 
increase of cells in metaphase arrest. Inhibition of microtubule 
function using tubulin targeted agents are widely used in the treatment 
of cancer.
    This invention describes novel arylthioindole derivatives, 3-
arylthioindole-2-carboxylic acid esters derivatives, having excellent 
affinity for tubulin and excellent efficacy as inhibitors of the growth 
of MCF-7 breast cancer cells. These new chemical compounds have the 
potential to result in more effective therapeutics for the treatment of 
neoplastic diseases.
    Applications: Therapeutic for proliferative diseases such as 
cancer.
    Market: 600,000 deaths from cancer related diseases estimated in 
2006.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Ernest Hamel (NCI) et al.
    Publications:
    1. G De Martino, MC Edler, G La Regina, A Coluccia, MC Barbera, D 
Barrow, RI Nicholson, G Chiosis, A Brancale, E Hamel, M Artico, R 
Silvestri. New arylthioindoles: potent inhibitors of tubulin 
polymerization. 2. Structure-activity relationship and molecular 
modeling studies. J Med Chem. 2006 Feb 9;49(3):947-954.
    2. G De Martino, G La Regina, A Coluccia, MC Edler, MC Barbera, A 
Brancale, E Wilcox, E Hamel, M Artico, R Silvestri. Arylthioindoles, 
potent inhibitors of tubulin polymerization. J Med Chem. 2004 Dec 
2;47(25):6120-6123.
    Patent Status: PCT Application No. PCT/US2005/035896 filed 05 Oct 
2005 (HHS Reference No. E-323-2004/0-PCT-02).
    Licensing Availability: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].

    Dated: March 2, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-4182 Filed 3-8-07; 8:45 am]
BILLING CODE 4140-01-P