[Federal Register Volume 78, Number 39 (Wednesday, February 27, 2013)]
[Notices]
[Pages 13354-13357]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-04481]


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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.

FOR FURTHER INFORMATION CONTACT: 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.

Chimeric Antigen Receptors to CD22 for Treating Hematological Cancers

    Description of Technology: Chimeric antigen receptors (CARs) are 
hybrid proteins consisting of an antibody binding fragment fused to 
protein signaling domains that cause T-cells which express the CAR to 
become cytotoxic. Once activated, these cytotoxic T-cells can 
selectively eliminate the cells which they recognize via the antibody 
binding fragment of the CAR. Thus, by engineering a T-cell to express a 
CAR that is specific for a certain cell surface protein, it is possible 
to selectively target those cells for destruction. This is a promising 
new therapeutic approach known as adoptive cell therapy.
    CD22 is a cell surface protein that is expressed on a large number 
of B-cell lineage hematological cancers, such as leukemia and lymphoma. 
Several promising therapies are being developed which target CD22, 
including therapeutic antibodies and immunotoxins. This technology 
concerns the use of a high affinity antibody binding fragment to CD22 
(known as m971), as the targeting moiety of a CAR. The resulting CAR 
can be used in adoptive cell therapy treatment for cancer.
    Potential Commercial Applications:
 Treatment of diseases associated with increased or 
preferential expression of CD22
 Specific diseases include hematological cancers such as 
chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL) and 
pediatric acute lymphoblastic leukemia (ALL)
    Competitive Advantages:

 High affinity of the m971 antibody binding fragment increases 
the likelihood of successful targeting
 Targeted therapy decreases non-specific killing of healthy, 
essential cells, resulting in fewer non-specific side-effects and 
healthier patients
 Hematological cancers are susceptible to cytotoxic T-cells for 
treating because they are present in the bloodstream
 Expression of CD22 only on mature cells allows the avoidance 
of stem cell elimination during treatment

    Development Stage: Pre-clinical.
    Inventors: Rimas J. Orentas et al. (NCI).
    Intellectual Property: HHS Reference No. E-291-2012/0--US 
Provisional Application No. 61/717,960 filed 24 Oct 2012.
    Related Technology: HHS Reference No. E-080-2008/0--U.S. Patent 
Application No. 12/934,214 filed 23 Sep 2010.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected].

Modified Peptide Nucleic Acids (PNAs) for Detection of DNA or RNA and 
Identification of a Disease or Pathogen

    Description of Technology: The NIH announces a novel method for 
fast, simple, and accurate detection of nucleic acids outside the 
modern laboratory. Nucleic acid testing is highly specific and often 
provides definitive

[[Page 13355]]

identification of a disease or pathogen. Methods to detect nucleic acid 
sequences and identify a disease or pathogen are dominated by PCR, but 
applying PCR-based techniques in remote settings is challenging. 
Researchers at the NIH have developed a universal, colorimetric, 
nucleic acid-responsive diagnostic system that uses two short peptide 
nucleic acid (PNA) probes and does not rely on PCR. The design of a 
cyclopentane-modified surface probe and a biotin-containing reporter 
probe allows excellent DNA and RNA detection. NIH researchers have 
specifically demonstrated this technology's suitability for early 
detection of HIV RNA or anthrax DNA.
    Potential Commercial Applications:
 Ultra-high sensitive detection of nucleic acids
 Convenient, universal, colorimetric diagnostic tool
 Can be used to detect any kind of infectious disease by simply 
changing the PNA sequences of the specific probe
 Suitable for early detection of HIV, anthrax, tuberculosis, 
human papilloma virus (HPV), avian flu, E. coli, and more

    Competitive Advantages:

 Eliminates requirement for PCR
 Fast, simple method that can be used outside the laboratory
 Modified PNAs provide resistance to degradation by enzymes and 
a high degree of stability to any diagnostic device
    Development Stage:
 Prototype
 In vitro data available
    Inventors: Daniel Appella (NIDDK), Christopher Micklitsch (NIDDK), 
Chao Zhao (NIDDK), Bereket Oquare (ImClone Systems, Inc.).
    Publication: Micklitsch CM, et al. Cyclopentane-Peptide nucleic 
acids for qualitative, quantitative, and repetitive detection of 
nucleic acids. Anal Chem. 2013 Jan 2;85(1):251-7. [PMID 23214925].
    Intellectual Property: HHS Reference No. E-260-2012/0--US 
Application No. 61/684,354 filed 17 Aug 2012.
    Licensing Contact: Charlene Sydnor, Ph.D.; 301-435-4689; 
[email protected].
    Collaborative Research Opportunity: The NIDDK is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize Modified Peptide 
Nucleic Acids (PNAs) for Detection of DNA or RNA. For collaboration 
opportunities, please contact Cindy K. Fuchs, J.D. at 
[email protected] or 301-451-3636.

Novel Vaccine for Prevention and Treatment of Chlamydia Infection

    Description of Technology: The invention provides novel vectors, 
attenuated pathogens, compositions, methods and kits for preventing 
and/or treating chlamydia infections.
    Chlamydia trachomatis is an obligate intracellular human pathogen 
with a unique biphasic developmental growth cycle. It's the etiological 
agent of trachoma, the world's leading cause of preventable blindness 
and the most common cause of bacterial sexually transmitted disease. C. 
trachomatis isolates maintain a highly conserved plasmid and naturally 
occurring plasmidless clinical isolates are rare, implicating its 
importance in chlamydial pathogenesis. Understanding the plasmid's role 
in chlamydial pathogenesis at a molecular level is an important 
objective for the future control of chlamydial infections. The NIAID 
inventor had studied chlamydia strains in both non-human primate and 
murine infectious models providing evidence that plasmids play an 
important role in chlamydial pathogenesis. In addition, the study 
results of macaque model of trachoma supports the use of plasmid-
deficient organisms as novel live-attenuated chlamydial vaccines.
    Potential Commercial Applications: Novel live-attenuated chlamydial 
vaccines.
    Competitive Advantages:

 Virulence attenuated vectors that can be used as vaccines 
against chlamydia.
 Combination of vector with attenuated pathogenic agent 
improves the stability and replicative capacity of the pathogen.
 Features nucleic acids, attenuated pathogens, compositions, 
methods and kits to treat and prevent chlamydia infections.
    Development Stage:
 Prototype
 In vitro data available
 In vivo data available (animal)
 In vivo data available (human)

    Inventor: Harlan D Caldwell (NIAID).
    Publications:
    1. Song L, et al. The Chlamydia trachomatis plasmid-encoded Pgp4 is 
a transcriptional regulator of virulence associated genes. Infect 
Immun. 2013 Jan 14 (Epub ahead of print). [PMID 23319558]
    2. Kari L, et al. A live-attenuated chlamydial vaccine protects 
against trachoma in nonhuman primates. J Exp Med. 2011 Oct 
24;208(11):2217-23. [PMID 21987657]
    Intellectual Property: HHS Reference No. E-133-2012/0--US 
Provisional Application No. 61/753,320 filed 16 Jan 2013
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected]
    Collaborative Research Opportunity: The NIAID Laboratory of 
Intracellular Parasites is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate or commercialize chlamydia vaccine. For collaboration 
opportunities, please contact Harlan D. Caldwell, Ph.D. at 
[email protected].

A High-Throughput Assay for Detection and Monitoring of Endocrine-
Disrupting Chemicals in Water Sources

    Description of Technology: This technology describes a high-
throughput, fluorescence-based method to detect endocrine-disrupting 
chemicals (EDCs) in water sources.
    There is growing awareness that a wide variety of synthetic and 
natural compounds that may lead to adverse health effects are present 
in water sources, such as streams, wells, and ground water; however, 
these compounds are often difficult to measure and thus are not 
commonly monitored. Even low concentrations of these compounds are of 
concern, as they may have biological effects at concentrations of parts 
per billion (PPB) or less. The presence of EDCs in the environment, in 
particular, is under examination for potential adverse effects on human 
health and on wildlife, such as cancer, immune suppression, impaired 
fertility, and increased incidence of diabetes and obesity.
    Inventors at NCI have discovered a novel assay methodology for 
detecting endocrine EDCs in contaminated water. The assay utilizes 
fluorescently-labeled nuclear receptors in a high-throughput, cell-
based format, and has the capability to detect very low concentrations 
of EDCs in water or other liquid samples. The inventors have already 
demonstrated proof of concept for this technology by using this assay 
to test for the presence of glucocorticoid and androgen receptor 
disruptors in water samples from 14 U.S. states, and also plan future 
studies for other types of EDCs. A product or service based on this 
technology could fulfill an unmet need for a high-throughput, rapid 
method for screening water samples for contaminants with potential 
endocrine-disrupting effects.
    Potential Commercial Applications: Product or service for screening 
and detection of endocrine disrupting chemicals (EDCs) in samples from 
water sources and waste water.

[[Page 13356]]

    Competitive Advantages:

 Rapid results--one day or less from sample retrieval to result
 Detects very low concentrations of EDCs
 Readily adaptable for use with a variety of endocrine receptor 
targets
 High-throughput format allows testing of many samples at once, 
with multiple types of endocrine receptor targets
 Tests for activity rather than a specific chemical, therefore 
can detect many variants modified in the environment
    Development Stage:

 Prototype
 In vitro data available

    Inventors: Gordon L. Hager and Diana A. Stavreva (NCI)
    Publication: Stavreva D, et al. Prevalent Glucocorticoid and 
Androgen Activity in US Water Sources. Sci Rep. 2012;2:937. [PMID 
23226835]
    Intellectual Property: HHS Reference No. E-269-2011/0--US 
Provisional Application No. 61/656,473 filed 06 Jun 2012
    Licensing Contact: Tara Kirby, Ph.D.; 301-435-4426; 
[email protected]
    Collaborative Research Opportunity: The NCI Laboratory of Receptor 
Biology & Gene Expression is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize Detection and Monitoring of 
Endocrine-Disrupting Chemicals in Water Sources. For collaboration 
opportunities, please contact John Hewes, Ph.D. at [email protected].

Novel Diagnostic Marker for Prediction of Clearance of Hepatitis C 
Virus Infection

    Description of Technology: One of the unfortunate aspects of 
hepatitis C virus (HCV) infection is that the majority of infected 
individuals will develop a chronic HCV infection. The current treatment 
for HCV infection involves direct acting antiviral drugs, such as HCV 
protease inhibitors, with or without pegylated IFN-alpha/ribavirin. Not 
all patients respond to treatments and the treatments themselves can 
cause severe adverse effects. The subject invention (IFNL4-deltaG) is a 
novel genetic polymorphism in the newly discovered Interferon Lambda 4 
(IFNL4) gene, which is located near the IFNL3 (former IL28B) gene. The 
IFNL4-deltaG polymorphism can predict the likelihood of whether or not 
a patient will respond to treatment of HCV and, possibly, of other 
diseases treated with IFN-alpha (or other interferons). In particular, 
IFNL4-deltaG was found to be a better predictor of clinical outcome for 
IFN-alpha based treatment in people of African descent than the 
currently available diagnostic test (`IL28B' genotype, defined by 
rs12979860 located within first intron of IFNL4). The predictive value 
of the IFNL4-deltaG polymorphism for response to IFN-alpha based 
treatment in HCV-infected Caucasians and Asians is comparable to 
current diagnostics. In addition, IFNL4-deltaG can predict the 
likelihood of a whether a person who is acutely infected with HCV 
infection will spontaneously clear the infection or develop chronic 
infection. As with treatment outcome, among individuals of African 
ancestry, genotype for IFNL4-deltaG is a better predictive marker for 
spontaneous clearance of HCV than `IL28B' genotype, while providing 
similar predictive value in individuals of European or Asian descent.
    Potential Commercial Applications:

 Diagnostic for prediction of patient response to HCV treatment
 Diagnostic for prediction of patient response to treatment 
with IFN-alpha (or other interferons)
 Diagnostic tool for prediction of spontaneous clearance of HCV 
infection
    Competitive Advantages:

 Better than current `IL28B' based diagnostics for predicting 
response to IFN-alpha based HCV treatments for people of African 
descent.
 Comparable predictive capabilities to current `IL28B' based 
diagnostics for response to IFN-alpha based HCV treatments in 
Caucasians and Asians.
    Development Stage:

 Early-stage
 Pre-clinical
 In vitro data available

    Inventors: Liudmila Prokunina (NCI), Thomas R. O'Brien (NCI), Brian 
P. Muchmore (NCI), Raymond P. Donnelly (FDA)
    Publication: Prokunina-Olsson L, et al. A variant upstream of IFNL3 
(IL28B) creating novel interferon gene IFNL4 is associated with 
impaired clearance of hepatitis C virus. Nat Genet. 2013 Feb;45(2):164-
71. [PMID 23291588]
    Intellectual Property: HHS Reference No. E-217-2011/0--

 U.S. Provisional Patent Application No. 61/543,620 filed 05 
Oct 2011
 International PCT Application No. PCT/US2012/59048 filed 05 
Oct 2012

    Related Technology: HHS Reference No. E-217-2011/1--U.S. 
Provisional Patent Application No. 61/616,664 filed 28 Mar 2012
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected]
    Collaborative Research Opportunity: The NCI Division of Cancer 
Epidemiology & Genetics, Laboratory of Translational Genomics, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
development of a gene-based test to be used in the clinic. For 
collaboration opportunities, please contact John Hewes, Ph.D. at 
[email protected].

Novel Host Target for Treatment of Hepatitis C Virus Infection

    Description of Technology: The subject technology is a newly 
discovered Interferon-lambda 4 (IFNL4) protein found through analysis 
of genomic data derived from primary human hepatocytes, molecular 
cloning and functional annotation. The IFNL4 protein is related to but 
distinct from other know IFNs and its expression is inducible in 
conditions that mimic viral infection. Preliminary studies indicate 
that this protein may play a role in impaired natural and treatment 
induced clearance of HCV. These findings suggest that the protein can 
potentially be a new target for treating HCV infection.
    Potential Commercial Applications:

 Novel target for treatment of HCV infection.
 Diagnostics can be developed for detection of IFNL4 mRNA or 
protein.
 Existing biological reagents for detection of IFNL4--
expression assays, antibodies and protein.

    Competitive Advantages: IFNL4 is created by a genetic variant 
IFNL4-deltaG, which is present only in a subset of individuals, 
suggesting that IFNL4 is not an essential protein and its functional 
inactivation may be well-tolerated.
    Development Stage:

 Early-stage
 Pre-clinical
 In vitro data available

    Inventors: Liudmila Prokunina (NCI), Thomas R. O'Brien (NCI), Brian 
P. Muchmore (NCI), Raymond P. Donnelly (FDA)
    Publication: Prokunina-Olsson L, et al. A variant upstream of IFNL3 
(IL28B) creating novel interferon gene IFNL4 is associated with 
impaired clearance of hepatitis C virus. Nat Genet. 2013 Feb;45(2):164-
71. [PMID 23291588]
    Intellectual Property: HHS Reference No. E-217-2011/1--U.S. 
Provisional Patent Application No. 61/616,664 filed 28 Mar 2012
    Related Technology: HHS Reference No. E-217-2011/0--

 U.S. Provisional Patent Application No. 61/543,620 filed 05 
Oct 2011

[[Page 13357]]

 International PCT Application No. PCT/US2012/59048 filed 05 
Oct 2012
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected]
    Collaborative Research Opportunity: The NCI Division of Cancer 
Epidemiology & Genetics, Laboratory of Translational Genomics, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
development of tools for detection of IFNL4 mRNA and protein and 
modulation of its function. For collaboration opportunities, please 
contact John Hewes, Ph.D. at [email protected].

Brachyury-Directed Vaccine for the Prevention or Treatment of Cancers

    Description of Technology: Tumor invasion and metastasis are the 
primary drivers of cancer-related mortality. Therapies that have an 
ability to specifically target invasive and/or metastatic cells are 
anticipated to have a significant impact in the clinical management of 
advanced cancers.
    Researchers at the NIH have developed a vaccine technology that 
stimulates the immune system to selectively destroy metastasizing 
cells. Brachyury, a master transcription factor that governs the 
epithelial-mesenchymal transition, was shown to be significantly 
overexpressed in primary and metastasizing tumors relative to normal 
human tissues. Stimulation of T cells with the Brachyury peptide 
promoted a robust immune response and the targeted lysis of invasive 
tumor cells. Brachyury overexpression has been demonstrated in a range 
of human tumors (breast, lung, colon and prostate, among others) 
suggesting that a therapeutic vaccine derived from this technology 
would be broadly applicable for the treatment of cancer.
    Potential Commercial Applications:

 Preventative cancer vaccine for patients with precancerous 
lesions of the breast, colon or prostate.
 Therapeutic cancer vaccine for the treatment of disseminated 
and late-stage tumors.
 Vaccine component of a multi-modal cancer therapy.
    Competitive Advantages:

 Treatment targets invasive and metastatic tumor cells which 
are the primary cause of cancer-related mortality.
 Vaccine can eliminate cancer stem cells which are resistant to 
conventional therapies.
 Compatible with the clinically-proven TRICOM cancer vaccine 
platform.
 Available (Optimized) for use with non-pox, non-yeast vectors 
including: Adenovirus, lentivirus, etc., and for use with protein- or 
peptide-based vaccines.

    Development Stage:

 Pre-clinical
 In vitro data available
 In vivo data available (animal)
 In vivo data available (human)
    Inventors: Claudia Palena and Jeffrey Schlom (NCI)
    Publications:

1. Fernando RI, et al. The T-box transcription factor Brachyury 
promotes epithelial-mesenchymal transition in human tumor cells. J 
Clin Invest. 2010 Feb;120(2):533-44. [PMID 20071775]
2. Palena C, et al. The human T-box mesodermal transcription factor 
Brachyury is a candidate target for T-cell-mediated cancer 
immunotherapy. Clin Cancer Res. 2007 Apr 15;13(8):2471-8. [PMID 
17438107]

    Intellectual Property: HHS Reference No. E-055-2011/0--US 
Application No. 61/701,525 filed 14 Sep 2012
    Licensing Contact: Sabarni Chatterjee, Ph.D.; 301-435-5587; 
[email protected]
    Collaborative Research Opportunity: The National Cancer Institute 
Laboratory of Tumor Immunology and Biology is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize Brachyury-
directed cancer vaccine technology. For collaboration opportunities, 
please contact John D. Hewes, Ph.D. at [email protected].

Novel Plasmid Vectors for the Soluble Expression of Recombinant 
Proteins in Escherichia coli

    Description of Technology: A series of novel plasmid vectors for 
the soluble expression and subsequent purification of recombinant 
proteins that have historically proven to be extremely difficult to 
purify from Escherichia coli (E. coli) are provided. Because of its 
ease of growth and generally low cost to cultivate, E. coli is often 
employed as the host for vectors expressing recombinant proteins. In an 
ideal situation, the recombinant protein is expressed from a strong 
promoter, highly soluble, and recovered in high yield and activity. 
Unfortunately, it is quite common that the overproduced recombinant 
protein is either detrimental to the cell or simply compartmentalized 
into insoluble inclusion bodies. Recently, NIH investigators have 
developed plasmid vectors that enable the recovery and purification of 
recombinant proteins that have previously proven to be difficult to 
express in soluble form. These vectors have a pSC101 origin of 
replication and, therefore, are maintained in E. coli at approximately 
five (5) copies per cell (plasmid details and maps will be provided 
upon request). These vectors express the recombinant proteins at low 
basal levels and this feature facilitates higher solubility and correct 
folding of the expressed protein. The utility of these vectors is 
verified by expressing and purifying full-length human DNA polymerases 
from E. coli and showing that the purified DNA polymerases are 
catalytically active in vitro.
    Potential Commercial Applications: The expression vectors described 
here can be used to:
(a) obtain recombinant proteins that were previously hard to purify,
(b) produce recombinant proteins from a number of sources and with 
different catalytic activities, and
(c) express multimeric protein complexes.
    Competitive Advantages: The expression vectors described here:
(a) dramatically increase the proportion of soluble protein that can be 
obtained in E. coli,
(b) fully compatible with the replicons of conventional high-expression 
systems (e.g., pET vectors, EMD Biosciences, and
(c) facilitate the correct folding of the recombinant protein and 
increases its solubility.
    Development Stage:

 Prototype
 Early-stage
 In vitro data available

    Inventors: Roger Woodgate, John P. McDonald, and Karata Kiyonobu 
(NICHD)
    Publication: Frank EG, et al. A strategy for the expression of 
recombinant proteins traditionally hard to purify. Anal Biochem. 2012 
Oct 15;429(2):132-9. [PMID: 22828411]
    Intellectual Property: HHS Reference No. E-028-2010/0--Research 
Tools. Patent protection is not being pursued for this technology.
    Licensing Contact: Suryanarayana (Sury) Vepa, Ph.D., J.D.; 301-435-
5020; [email protected]

     Dated: February 21, 2013.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2013-04481 Filed 2-26-13; 8:45 am]
BILLING CODE 4140-01-P