[Federal Register Volume 75, Number 185 (Friday, September 24, 2010)]
[Notices]
[Pages 58401-58404]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-23977]



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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.

Phantasmidine, a Nicotinic Receptor Agonist for the Treatment of 
Addiction and Neurological Disorders

    Description of Invention: The inventors have isolated and 
characterized an alkaloid, phantasmidine, from the skin of the 
Ecuadoran poison frog E. anthonyi. Phantasmidine is selective for 
[beta]4-containing receptor subtypes, unlike many nicotinic receptor 
agonists currently in development, which target [beta]2-containing 
receptor subtypes. This selectivity makes phantasmidine a unique 
pharmacological probe, as well as a promising lead compound for the 
development of selective therapeutics targeting [beta]4-containing 
receptor subtypes, which appear to play any important role in nicotine 
addiction and other substance dependencies.
    Nicotinic acetylcholine receptors (nAChRs) are broadly distributed 
in both the peripheral and central nervous systems; activation of brain 
nAChRs results in enhanced release of various key neurotransmitters. 
Dysfunction of these receptors is associated with a variety of 
neurological diseases, including nicotine addiction. Nicotinic 
agonists, which enhance action at nicotinic acetylcholine receptors, 
have been shown to possess potential clinical utility in many of these 
diseases, although development is hindered by the existence of a large 
number of nAChR subtypes with highly variable properties.
    Alkaloids, such as epibatidine found in skin from the frog species 
E. tricolor, have been shown to activate nicotinic acetylcholine 
receptors. However, while epibatidine has been shown to be a powerful 
analgesic, it is also extremely toxic, so research has focused on the 
identification and development of less toxic analogs.

Applications

     Development of therapies for the treatment of addiction, 
including nicotine and alcohol addictions.
     Development of therapies for neurological diseases such as 
Alzheimer's disease, attention deficit hyperactivity disorder (ADHD), 
and schizophrenia.
     Development of selective pharmacological probes for 
bioimaging, binding assays, and functional assays of nicotinic 
receptors.
    Inventors: Richard W. Fitch et al. (NIDDK)
    Related Publication: R Fitch et al. Phantasmidine: An epibatidine 
congener from the Ecuadorian poison frog Epipedobates anthonyi. J Nat 
Prod. 2010 Mar 26;73(3):331-337. [PubMed: 20337496]
    Patent Status: U.S. Provisional Application No. 61/315,674 filed 19 
March 2010 (HHS Reference No. E-125-2010/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Tara Kirby, PhD; 301-435-4426; 
[email protected].

Transplant and Autoimmune Therapy Using T-Cells Expressing Programmed 
Death Ligand-1 (PD-L1)

    Description of Invention: Transplant complications (graft rejection 
and graft-versus-host disease) and autoimmune diseases are primarily 
caused by T cell immune responses against normal host tissue or 
transplanted tissues. These disorders can lead to serious complications 
and may be chronic, debilitating, and fatal. Current treatment for 
these disorders is oftentimes not effective, and is typically 
associated with significant side effects, including global immune 
suppression, which increases the rate of infection and cancer. Hence, 
there is a need for new technologies to more specifically suppress the 
immune system for treatment of these diseases.
    Programmed death (PD) ligand 1 (PD-L1) is an immune molecule 
present on regulatory T cells (Tregs), other suppressor cell 
populations, and tumor cells; the function of PD-L1 is to suppress the 
function of pathogenic T cells that express the PD1 receptor. 
Therefore, it has been hypothesized that the transfer of T cells that 
are enriched for PD-L1 expression might represent an effective method 
to suppress autoimmunity or transplant complications. Adoptive T cell 
therapy using Tregs is one such approach; however, this approach is 
limited due to the relative rarity of Tregs and their tendency to 
possess differentiation plasticity towards pathogenic T cell subsets 
such as the Th17 subset. Ex vivo co-stimulated and expanded effector T 
cells can be generated in sufficient numbers for cell therapy; however, 
such cells are not enriched for PD-L1 expression.
    The current technology overcomes these limitations through 
transduction of co-stimulated T cells with a lentiviral expression 
vector that dictates T cell expression of PD-L1. In this method, the 
co-stimulated T cells acquire the immunosuppressant characteristics of 
Treg cells. The PD-L1 gene expression construct co-expresses a cell 
surface molecule (i.e., CD19 or CD34) that allows enrichment of the 
gene-modified T cells to high purity. Also the construct co-expresses 
another gene, TMPK, which acts as a safety cell fate switch because the 
TMPK can specifically activate the cytotoxic prodrug, AZT. By 
incorporation of this TMPK/AZT cell fate safety switch, the current 
technology will allow for PD-L1 therapeutic delivery, with subsequent 
elimination of the therapeutic cells in the event of toxicity.
    Applications: Co-stimulated T cells expressing the PD-L1, CD19-TMPK 
construct can be adoptively transferred into patients to: (1) Treat 
autoimmune diseases; (2) prevent graft-versus-host disease (GVHD), 
which remains the primary lethal complication after hematopoietic cell 
transplantation (HCT); and (3) prevent solid organ or HCT transplant 
rejection.

Advantages

    (1) Relative to other proposed cell therapies such as Treg therapy, 
co-stimulated T cells expressing the gene construct can be manufactured 
in clinically relevant numbers, possess a defined mechanism of action, 
and can be specifically modulated (eliminated) in vivo.
    (2) The proposed immuno-gene therapy would prove advantageous to 
current immune suppressive therapies, which cause many side effects.

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Market

    (1) Many diseases have been identified to represent autoimmune 
disorders, including but not limited to: inflammatory bowel disease 
(IBD; including Crohn's disease); multiple sclerosis (MS); systemic 
lupus erythematosis (SLE); rheumatoid arthritis; and immune-mediated 
(type-1) diabetes mellitus. Approximately 1 in every 31 people in the 
U.S. suffers from an autoimmune disease; women suffer 
disproportionately from autoimmune diseases as they represent about 75% 
of cases.
    (2) Graft rejection can occur in the setting of solid organ 
transplantation (for example, pancreatic, renal, cardiac, and liver 
transplantation) and also occurs after hematopoietic stem cell or bone 
marrow transplantation (including matched sibling, unrelated donor, and 
cord blood transplantation). More than 19,000 transplants are performed 
each year in the United States and the prevalence of graft rejection is 
considerable in these transplant recipients. In addition to graft 
rejection, graft-versus-host disease (GVHD) represents a significant 
transplant complication. Acute GVHD can occur in all types of 
hematopoietic stem cell or bone marrow transplantation (matched 
related, unrelated, or cord blood) and ranges in incidence from 30-80%. 
Chronic disease can also occur in approximately 54-70% of hematopoietic 
stem cell transplant recipients.
    Development Status: Early-stage development.
    Inventors: Daniel H. Fowler and Shoba Amarnath (NCI).
    Publication: Amarnath S, Costanzo CM, Mariotti J, Ullman JL, 
Telford WG, Kapoor V, Riley JL, Levine BL, June CH, Fong T, Warner NL, 
Fowler DH. Regulatory T cells and human myeloid dendritic cells promote 
tolerance via programmed death ligand-1. PLoS Biol. 2010 Feb 
2;8(2):e1000302. [PubMed: 20126379].
    Patent Status: U.S. Patent Application No. 61/261,081 filed 13 Nov 
2009 (HHS Reference No. E-022-2010/0-US-01).
    Related Technologies: HHS Reference No. E-058-2006.
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Experimental Transplantation and Immunology Branch, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology. Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

A New ``Destination'' for Protein Expression: A Lentiviral Gateway[reg] 
Destination Vector for High-Level Protein Expression (pDEST-673)

    Description of Invention: A laboratory at the Science Applications 
International Corporation in Frederick, MD (SAIC-Frederick) has 
developed a lentiviral vector, pDEST-673, for high protein expression 
yields in cells. The pDEST-673 vector combines three features that make 
it optimal for protein expression in lentiviruses: the pFUGW backbone, 
a Gateway[reg] vector conversion cassette, and a neomycin antibiotic 
resistance marker. The pFUGW portion contains a highly potent 
polypurine tract (PPT) that allows for the production of higher viral 
titers within transfected cells and a woodchuck regulatory element 
(WRE) to enhance protein expression. The addition of the Gateway[reg] 
conversion cassette converts the vector into a Destination vector and 
the neomycin resistance marker allows for researchers to select for 
stable transfectants using antibiotic selection (a feature not 
possessed by many lentiviral vectors). This lentiviral Destination 
vector should be useful for researchers desiring to utilize neomycin 
resistance to select for proteins expressed in cells stably transfected 
with lentiviruses.

Applications

     Research tool for high quantity production of a protein(s) 
of interest for studying the role of the protein(s) in a variety of 
biological processes, including pathologies such as cancers, infectious 
diseases, autoimmune diseases, and many other disorders.
     Research tool for selecting stable lentiviral 
transfectants following the insertion of the vector into tumor cells.
     Potential tool for enhancing production of proteins that 
are normally difficult to express in other types of bacterial, insect, 
or mammalian expression systems.

Advantages

     The pFUGW backbone provides the pDEST-673 vector with 
optimal protein expression properties: The polypurine tract (PPT) 
region in the vector allows for efficient viral transcription leading 
to increased lentiviral production in cells. The woodchuck regulatory 
element acts as a posttranscriptional enhancer to promote the 
conversion of more mRNA transcripts into protein to yield high-levels 
of the protein of interest. These elements are not found in most 
commercially available lentiviral vectors.
     The incorporation of the neomycin resistance marker 
facilitates selection of the transfectants of interest: Many 
laboratories rely on neomycin selection as a key selectable marker in 
their protein expression experiments. Few commercially available 
lentiviral vectors contain a neomycin resistance marker.
    Inventors: Dominic Esposito (SAIC).

Selected Publications

    1. A Ventura, et al. Cre-lox-regulated conditional RNA interference 
from transgenes. Proc. Natl. Acad. Sci. USA. 2004 Jul 13;101(28):10380-
10385. [PubMed: 15240889].
    2. C Lois, et al. Germline transmission and tissue-specific 
expression of transgenes delivered by lentiviral vectors. Science 2002 
Feb 1;295(5556):868-872. [PubMed: 11786607].
    Patent Status: HHS Reference No. E-119-2009/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing under a Biological 
Materials License Agreement.
    Licensing Contact: Samuel E. Bish, PhD; 301-435-5282; 
[email protected].

A Hand Held Portable Device Based on Light Emitting Diodes (LEDs) as a 
Light Source for Use in the Detection of Counterfeit Pharmaceutical 
Drugs and Packaging

    Purpose: The FDA is seeking a device company to commercialize its 
patent pending hand held portable device for the detection of 
counterfeited pharmaceuticals. The device will be based on the 
technology described below. The invention was further described and 
claimed in provisional patent application 61/165,395 filed March 31, 
2009. The FDA scientists have built highly reliable prototypes of two 
different models of the device and demonstrated the validity of the 
device for multiple applications.
    Description of Technology: A hand held portable device was designed 
and developed for use in the detection of counterfeit pharmaceutical 
products and packaging. The light source of the device emits different 
wavelengths of light onto a sample. The device incorporates the use of 
single wavelength light emitting diodes (LEDs) which generate intense 
single wavelengths of light. Two models of the device have been 
developed and

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manufactured. The first model incorporates only LEDs at specific 
wavelengths and the second model incorporates a camera and display 
along with the LEDs at specific wavelengths. The different LED 
wavelengths of light interact with the sample by either being absorbed, 
reflected or by generating an apparent color change in the sample. The 
absorption, reflection or apparent color change by the sample may be 
observed using different colored goggles (yellow, orange, red). The 
fluorescence profiles of suspect pills can be compared with the 
authentic article to determine legitimacy. The device can be used for 
field examination of suspect counterfeit pharmaceutical products, 
packaging and diverted pharmaceutical products. Due to its size, and 
the simplicity in design and use, the hand held portable LED light 
source can be used by health safety officials (e.g. FDA investigators), 
by law enforcement authorities, or by the pharmaceutical companies 
themselves, to rapidly screen samples for suspect counterfeit products 
improving the safety of that the U.S. drug distribution chain.

Applications

     Testing for authenticity of pharmaceutical products.
     Combating the ever growing problem of counterfeiting in 
pharmaceutical products to protect public safety.
     Traditional law enforcement activities.
    Advantages: Current methods of detecting counterfeit 
pharmaceuticals include vibrational spectroscopy, x-ray diffraction, 
gas chromatography, liquid chromatography, and mass spectrometry. These 
methods although often effective, require expensive and bulky 
instrumentation, and are generally performed in a laboratory by highly 
trained operators. The LED devices based on the subject technology thus 
offer the following advantages:
     Small size, light and portable.
     Tests can be performed at desired location outside of lab 
setting.
     Simple to use and does not require special technical 
skills.
     Low cost and simple to manufacture.
     Reliable and provides reproducible results.
     Image capture and storage capabilities.
    Development Status: Fully developed and ready for manufacturing.
    Market: The volume of counterfeit pharmaceuticals entering the 
United States and other countries continues to increase. Counterfeit 
pharmaceuticals are illegally imported and are commonly available over 
the Internet. It is often difficult to determine the authenticity of a 
pharmaceutical, since the genuine and counterfeit products often have 
nearly identical appearance and markings (shape, color, size, packing, 
labeling etc.), even when viewed by professionals. Detection of 
counterfeit pharmaceuticals is of extreme importance since the efficacy 
of a counterfeit product is often lower than the actual product. In 
addition, the counterfeit product may contain toxic components, and 
result in side effects which are not associated with the authentic 
product. Such counterfeit products also result in monetary loss to 
pharmaceutical companies and retailers. It is for these reasons, i.e. 
health safety and economic loss, that the commercial potential of 
devices that detect such counterfeit products is large. Due to the 
advantages offered by the subject invention as outlined above, it is 
predicted that both models of subject device will enjoy commercial 
success. The ease of use allows for examination of products anywhere an 
investigator or inspector can travel and gives a preliminary result 
that would allow action to be taken. The device has the potential to be 
expanded to uses related to product tampering, counterterrorism and 
other traditional law enforcement applications.
    Inventors: Nicola Ranieri (FDA) et al.

Patent Status

     U.S. Provisional Application No. 61/165,395 filed 31 Mar 
2009, entitled ``Device and Method for Detection of Counterfeit 
Pharmaceuticals'' (HHS Reference No. E-206-2008/0-US-01).
     PCT Application No. PCT/US2010/029502 filed 31 Mar 2010 
(HHS Reference No. E-206-2008/0-PCT-03).
    Licensing Status: Available for licensing.

Licensing Contacts

     Uri Reichman, PhD, MBA; 301-435-4616; [email protected].
     Michael Shmilovich, Esq.; 301-435-5019; 
[email protected].

Methods for Treatment and Diagnosis of Psychiatric Disorders

    Description of Invention: Current drugs used to treat schizophrenia 
block dopamine receptors. These drugs can effectively suppress the 
``positive'' symptoms of schizophrenia but have little impact on the 
debilitating or ``negative'' symptoms of the disease which include 
social withdrawal, emotional unresponsiveness, difficulty with 
attention and memory, and apathy. There is thus a therapeutic need for 
improved antipsychotics that can improve both positive and negative 
symptoms. This technology describes novel interactions between 
neuregulins (NRGs), ErbB receptors, and dopamine signaling pathways 
that may influence the expression of schizophrenia. Researchers at the 
NIH demonstrated that NRGs reverse long term potentiation (LTP) when 
given shortly after LTP is established without affecting basal 
transmission. Blockade of ErbB receptors with antagonists prevented 
depotentiation by NRG, and NRG showed no effect in an ErbB-4 knockout 
mouse model. Thus NRG regulation of LTP occurs through the ErbB-4 
receptor. Data also showed that dopamine antagonists block the effects 
of NRGs on LTP. These findings could be useful in the development of 
antipsychotic drugs that block NRG actions, and in doing so, provide 
better therapies for schizophrenia.
    This technology describes methods of treating schizophrenia with an 
antagonist that blocks neuregulin-1 activation of the ErbB-4 receptor 
signaling pathway, methods of identifying schizophrenia in affected 
patients, as well as methods of identifying modulators of ErbB-4 
receptor signaling. This technology may also be applicable for treating 
or preventing other psychiatric disorders such as bipolar disorder, 
attention deficit disorder (ADD), and autism.

Applications

     Method of diagnosis and treatment for schizophrenia, 
bipolar disease, ADD and autism.
     Methods of finding modulators of ErbB-4 receptor 
signaling.

Market

     The U.S. schizophrenia market averages 10 billion dollars 
a year.
     Schizophrenia affects approximately 1% of the population.
    Inventors: Andres Buonanno (NICHD).

Publications

    1. Kwon OB, Longart M, Vullhorst D, Hoffman DA, Buonanno A. 
Neuregulin-1 reverses long-term potentiation at CA1 hippocampal 
synapses. J Neurosci. 2005 Oct 12;25(41):9378-9383. [PubMed: 16221846].
    2. Kwon OB, Paredes D, Gonzalez CM, Neddens J, Hernandez L, 
Vullhorst D, Buonanno A. Neuregulin-1 regulates LTP at CA1 hippocampal 
synapses through activation of dopamine D4 receptors. Proc Natl Acad 
Sci USA. 2008 Oct 7;105(40):15587-15592. [PubMed: 18832154].
    3. Vullhorst D, Neddens J, Karavanova I, Tricoire L, Petralia RS, 
McBain CJ, Buonanno A. Selective expression of

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ErbB4 in interneurons, but not pyramidal cells, of the rodent 
hippocampus. 2009 J Neurosci. Sep 30;29(39):12255-12264. [PubMed: 
19793984].
    4. Buonanno, A. The neuregulin signaling pathway and schizophrenia: 
From genes to synapses and neural circuits. Brain Res Bull. 2010 Aug 3; 
Epub ahead of print. [PubMed: 20688137].

Patent Status

     U.S. Provisional Application No. 60/837,449 filed 11 Aug 
2006 (HHS Reference No. E-304-2005/0-US-01).
     International Application No. PCT/US07/75724 filed 10 Aug 
2007, which published as WO 2008/019394 on 14 Feb 2008 (HHS Reference 
No. E-304-2005/0-PCT-02).
     U.S. Patent Application No. 12/377,025 filed 10 Feb 2009 
(HHS Reference No. E-304-2005/0-US-03).
    Licensing Status: Available for licensing.
    Licensing Contact: Jeffrey Clark Klein, PhD; 301-594-4697; 
[email protected].
    Collaborative Research Opportunity: The National Institutes of 
Child Health and Human Development, Section on Molecular Neurobiology, 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize this technology. Please contact John D. Hewes, PhD at 
301-435-3121 or [email protected] for more information.

    Dated: September 20, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-23977 Filed 9-23-10; 8:45 am]
BILLING CODE 4140-01-P