Notice: Government-Owned Inventions; Availability for Licensing

Federal Register: March 28, 2008 (Volume 73, Number 61)             
                  Page 16691-16694

AGENCY: National Institutes of Health, Public Health Service, HHS.

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

[[Page 16692]]

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.

Cell Line PE, Developed From Mouse Skin Tumors, Demonstrates Unique 
Qualities

    Description of Technology: Available for licensing is the mouse 
skin tumor cell line PE. These skin tumor cells were isolated from 
papilloma cells induced by chemical carcinogens. The PE cell lines 
differ from normal keratinocytes in their ability to maintain a 
proliferating population under conditions favoring terminal 
differentiation, their consistent proliferative response to phorbol 
esters under these same conditions, and their reduced sensitivity to 
phorbol ester-induced terminal differentiation. All of these properties 
should provide a growth advantage to these cells during tumor 
promotion. The PE cell line is one of the studied cell lines.
    Applications: The PE cell lines could be used for assays for cancer 
treatment and prevention or study of several aspects of cutaneous 
biology.
    PE cells could be used in the cosmetic industry to study response 
to cosmaceuticals or fragrances.
    PE cells also demonstrated robust expression of phase 2 
detoxification enzymes in response to a variety of inducing agents.
    Advantage: The various properties of papilloma cells (PE cell line) 
differ from keratinocytes which will provide a growth advantage to the 
PE cell lines during tumor promotion.
    Market: In the U.S., there was an estimated 59,940 new cases of 
melanoma cancer in 2007 and an estimated 8,110 melanoma deaths in 2007. 
There were nearly one million cases of non-melanoma skin cancers 
diagnosed in the U.S. in 2007.
    Cosmetics industry is a $30 billion industry with a 20% annual 
growth rate.
    Inventors: Stuart H. Yuspa and Henry Hennings (NCI).
    Publication: SH Yuspa et al. Cultivation and characterization of 
cells derived from mouse skin papillomas induced by an initiation-
promotion protocol. Carcinogenesis 1986 Jun;7(6):949-958.
    Patent Status: HHS Reference No. E-100-2008/0--Research Tool. 
Patent protection is not being sought for this technology.
    Availability: Available for non-exclusive licensing.
    Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560; 
madua@mail.nih.gov.

Mucin Binding Lectin Imaging Agents for Colonic Polyp Imaging

    Description of Technology: Available for licensing and commercial 
development is an imaging agent specific for colonic polyps that 
overexpress glycoprotein [alpha]-L-fucose containing mucins. Colon 
cancer is the second leading cause of cancer related deaths in the 
United States. The legume protein Ulex europaeus agglutinin I (UEA-1) 
has shown high specificity to [alpha]-L-fucose glycoproteins. Colonic 
mucosal neoplasia and/or polyps with high surface expression of 
[alpha]-L-fucosyl terminal residues can be specifically targeted with 
UEA-1 contrast agents. In one example, a computer tomography (CT) agent 
made from Iodine-127 (\127\I) labeled UEA-1 (I-UEA-1) and encapsulated 
into polymeric liposome nanoparticles was used to image murine colonic 
polyps. Ideally, the inventors envision a contrast agent that can be 
administered orally (e.g., liquid or pill form) and that would 
eliminate a patient's need to drink harsh enema/contrast solutions 
prior to CT imaging.
    Applications: Colon cancer; Cancer Imaging; Contrast Agents; CT 
colonography
    Inventors: Ronald M. Summers, Jianwu Xie, Celeste Roney (CC).
    Relevant Publications:
    1. J Xie et al. Oral contrast enhanced MicroCT virtual colonoscopy 
of APC knockout mouse colon polyp model. Gastroenterology. 2007 
Apr;132(4), Suppl. 1, Abstract No. M1063, pp A-353-A-354.
    2. C Roney et al. Glycoprotein expression by adenomatous polyps of 
the colon. SPIE 2008 (in press).
    3. SD O'Connor et al. Oral contrast adherence to polyps on CT 
colonography. J Comput Assist Tomogr. 2006 Jan-Feb;30(1):51-57.
    Patent Status: U.S. Provisional Application filed 15 Feb 2008 (HHS 
Ref. No. E-254-2007/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5010; 
shmilovm@mail.nih.gov.

N-Acetyl Mannosamine as a Therapeutic Agent

    Description of Technology: N-Acetyl Mannosamine is a precursor for 
the synthesis of sugar molecules known as sialic acids which play an 
important role in specific biological processes such as cellular 
adhesion, cellular communication and signal transduction. Lack of 
sialic acids also play an important role in disease processes such as 
cancer, inflammation and immunity.
    This invention relates to methods of administering N-Acetyl 
Mannosamine or its derivative (to produce sialic acid in patients who 
are deficient in the sugar molecule) to treat muscular atrophy 
including hereditary inclusion body myopathy (HIBM) and distal myopathy 
with rimmed vacuoles (Nonaka myopathy). Certain kidney conditions such 
as those arising from hyposialytion of kidney membranes may be treated 
by this method as well.
    Applications: Treatment of rare diseases such as HIBM and Nonaka 
myopathy.
    Treatment of kidney conditions involving sialic acid deficiencies 
resulting in proteinuria and hematuria.
    May be useful in treating other diseases involving sialic acid 
deficiencies.
    Publication: B Galeano et al. Mutation in the key enzyme of sialic 
acid biosynthesis causes severe glomerular proteinuria and is rescued 
by N-acetylmannosamine. J Clin Invest. 2007 Jun;117(6):1585-1594.
    Inventors: Marjan Huizing et al. (NHGRI).
    Patent Status: U.S. Provisional Application No. 60/932,451 filed 31 
May 2007 (HHS Reference No. E-217-2007/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; 
Fatima.Sayyid@nih.hhs.gov.
    Collaborative Research Opportunity: The National Human Genome 
Research Institute, Medical Genetics Branch, Cell Biology of Metabolic 
Disorders unit is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize N-acetylmannosamine as a therapeutic agent. 
Please contact Marjan Huizing at 301-402-2797or mhuizing@mail.nih.gov 
for more information.

Nitrite Adjunctive Therapy to Enhance Efficacy of Reperfusion Therapy 
for Acute Myocardial Infarction

    Description of Technology: The treatment of coronary heart disease 
is a multi-billion dollar market. In the case of acute myocardial 
infarction (MI), more commonly known as a heart attack, the patient 
receives a number of

[[Page 16693]]

diagnostic tests to determine the type and location of the heart 
damage. Most patients with ST segment elevation are treated with 
percutaneous coronary intervention (PCI) or thrombolysis. While current 
therapies, that attempt to reestablish the blood flow and limit 
ischemia, can be effective, practical delays between symptom 
presentation and intervention compromise the amount of myocardial 
salvage. Moreover, the elapsed time prior to PCI is closely related to 
the clinical outcome. This has resulted in a mortality rate of 7% after 
MI and nearly all patients suffer from some degree of myocardial 
necrosis. However, the use of adjunctive pharmacological therapies can 
improve myocardial salvage following acute percutaneous reperfusion of 
an acute MI and substantially impact cardiac function.
    This technology is a method of using nitrite as an adjunctive 
therapy to enhance efficacy of reperfusion therapy for acute MI. 
Evidence suggests that anion nitrite (NO2) is a physiological signaling 
molecule with roles in intravascular endocrine nitric oxide (NO) 
transport, hypoxic vasodilation, signaling, and cytoprotection. In 
addition, nitrite has the characteristics of an ideal adjunctive 
therapy that now appears ready for translation to human clinical 
trials. The benefits of nitrite therapy include (1) Significant 
cardioprotection after prolonged ischemia, (2) simple administration, 
(3) low dose for pharmacological action, (4) short half-life (5) 
minimal side effects, (6) low expense, (7) rapid onset of action. 
Additionally, the therapy utilizes a cardioprotective mechanism that is 
not dependent on vasodilation or pressure rate changes. The use and 
dosing protocols of nitrite, as described by this technology, could 
limit MI and apoptosis in the reperfusion phase of injury and provide a 
remarkable degree of cardioprotection.
    Applications: Treatment or amelioration of myocardial salvage 
following acute percutaneous reperfusion of an acute MI.
    Development Status: Clinical Development.
    Inventors: Mark T. Gladwin et al. (NHLBI).
    Relevant Publications:
    1. MT Gladwin, JH Shelhamer, AN Schechter, ME Pease-Fye, MA 
Waclawiw, JA Panza, FP Ognibene, RO Cannon 3rd. Role of circulating 
nitrite and S-nitrosohemoglobin in the regulation of regional blood 
flow in humans. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11482-
11487.
    2. RO Cannon 3rd, AN Schechter, JA Panza, FP Ognibene, ME Pease-
Fye, MA Waclawiw, JH Shelhamer, MT Gladwin. Effects of inhaled nitric 
oxide on regional blood flow are consistent with intravascular nitric 
oxide delivery. J Clin Invest. 2001 Jul;108(2):279-287.
    Patent Status: U.S. Provisional Application No. 60/911,026 filed 10 
Apr 2007 (HHS Reference No. E-023-2007/0-US-01)
    Licensing Status: Available for licensing.
    Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; 
Fatima.Sayyid@nih.hhs.gov.
    Collaborative Research Opportunity: The NHLBI Pulmonary and 
Vascular Medicine Branch is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize nitrite adjunctive therapy to 
enhance efficacy of reperfusion therapy for acute myocardial 
infarction. Please contact Dr. Mark Gladwin at 301-435-2310 for more 
information.

Compositions and Methods for Increasing Recombinant Protein Yields 
Through the Modification of Cellular Properties

    Description of Technology: This technology relates to compositions 
and methods for improving the growth characteristics of cells 
engineered to produce biologically active products such as antibodies 
or glycosylated proteins. Featured is a method that uses gene 
candidates (e.g., cdkl3, siat7e, or lama4), or their expressed or 
inhibited products in cell lines, such as Human Embryonic Kidney 
(including HEK-293), HeLa, or Chinese Hamster Ovary (CHO). The gene 
expression modulates growth characteristics, such as adhesion 
properties, of the cell lines thereby increasing recombinant protein 
yields and reducing product production costs.
    Applications: This technology may be used to improve production of 
therapeutic and/or diagnostic compounds, including therapeutic proteins 
or monoclonal antibodies from mammalian cells. Optimization of 
mammalian cells for use as expression systems in the production of 
biologically active products is very difficult. For certain 
applications, anchorage-independent cell lines may be preferred, 
whereas for other applications, a cell line that adheres to a surface, 
e.g., is anchorage-dependent, may be preferable. This technology 
provides a method for identifying a gene whose expression modulates 
such cellular adhesion characteristics. This method thus leads to an 
increase in the expression or yield of polypeptides, including 
therapeutic biologicals, such as antibodies, cytokines, growth factors, 
enzymes, immunomodulators, thrombolytics, glycosylated proteins, 
secreted proteins, and DNA sequences encoding such polypeptides and a 
reduction in the associated costs of such biological products.
    Advantages: This technology offers the ability to improve yields 
and reduce the cost associated with the production of recombinant 
protein products through the selection of cell lines having: Altered 
growth characteristics; altered adhesion characteristics; altered rate 
of proliferation; improvement in cell density growth; improvement in 
recombinant protein expression level.
    Market: Biopharmaceuticals, including recombinant therapeutic 
proteins and monoclonal antibody-based products used for in vivo 
medical purposes and nucleic acid based medicinal products now 
represent approximately one in every four new pharmaceuticals on the 
market. The market size has been estimated at $33 billion in 2004 and 
is projected to reach $70 billion by the end of the decade. The list of 
approved biopharmaceuticals includes recombinant hormones and growth 
factors, mAB-based products and therapeutic enzymes as well as 
recombinant vaccines and nucleic acid based products.
    Mammalian cells are widely used expression systems for the 
production of biopharmaceuticals. Human embryo kidney (including HEK-
293) and Chinese hamster ovary (CHO) are host cell of choice. The genes 
identified in this technology (e.g., cdkl3, sia7e, or lama4) can be 
used to modify these important cell based systems.
    This technology is ready for use in drug/vaccine discovery, 
production and development. The technology provides methods for 
identification of specific gene targets useful for altering the 
production properties of either existing cell lines to improve yields 
or with new cell lines for the production of therapeutic and or 
diagnostic compounds from mammalian cells.
    Companies that are actively seeking production platforms based on 
mammalian cell lines that offer high efficiency, high throughput 
systems for protein production or analysis at lower cost and ease of 
scale-up would be potential licensors of this technology.
    Development Status: Late Stage--Ready for Production.
    Inventors: Joseph Shiloach (NIDDK), Pratik Jaluria (NIDDK).
    Related Publication: P Jaluria et al. Application of microarrays to 
identify and characterize genes involved in attachment dependence in 
HeLa cells. Metab Eng. 2007 May;9(3):241-251.

[[Page 16694]]

    Patent Status: U.S. Provisional Application No. 60/840,381 filed 24 
Aug 2006 (HHS Reference No. E-149-2006/0-US-01); PCT Application No. 
PCT/US2007/018699 filed 24 Aug 2007 (HHS Reference No. E-149-2006/0-
PCT-02).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
soukasp@mail.nih.gov.
    Collaborative Research Opportunity: The National Institute of 
Diabetes and Digestive and Kidney Diseases, Biotechnology Core 
Laboratory, is seeking parties interested in collaborative research 
projects directed toward the use of this technology with cells for drug 
and vaccine production and development, including growth optimization, 
production and product recovery processes. For more information, please 
contact Dr. Joseph Shiloach, josephs@intra.niddk.nih.gov, or Rochelle 
S. Blaustein at Rochelle.Blaustein@nih.gov.

    March 20, 2008.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E8-6316 Filed 3-27-08; 8:45 am]

BILLING CODE 4140-01-P