[Federal Register Volume 81, Number 198 (Thursday, October 13, 2016)]
[Notices]
[Pages 70690-70691]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-24693]


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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, 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. 209 and 37 CFR part 404 to achieve expeditious 
commercialization 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 National Heart, Lung and Blood 
Institute, Office of Technology Transfer and Development, National 
Institutes of Health, 31 Center Drive Room 4A29, MSC2479, Bethesda, MD 
20892-2479; telephone: 301-402-5579. A signed Confidential Disclosure 
Agreement may be required to receive copies of the patent applications.

SUPPLEMENTARY INFORMATION: Technology descriptions follow.

Enhanced Functionalization of Carbon Nanoparticles for Biomedical 
Applications

Description of Technology

    The invention pertains to methods of increasing the density of 
carboxylic acids on the surface of a carbon nanoparticle that can be 
functionalized with biologically relevant molecules, such as antibodies 
or peptides, for biomedical applications. Advantageously, the method 
could increase functionalization of a nanoparticle by at least about 
1x10\7\ functional groups/g of nanoparticle. The method includes 
contacting an oxygen-containing functional group on a surface of a 
carbon nanoparticle with a reducing agent to provide a hydroxyl group; 
reacting the hydroxyl group with a diazoacetate ester in the presence 
of a transition metal catalyst to provide an ester and then cleaving 
the ester to provide a carboxylic acid group. The carboxylic acid can 
further be secondarily functionalized to an acyl chloride, an amide, 
pegylated, a biotinylate, a folate, a thiol, a maleimide, an active 
ester, an amine, a chelated gadolinium, an azide, an alkyne, a protein 
tag, or a dendrimer. Examples of notable nanoparticles that can be 
derivatized using this method include carbon nanoparticles such as 
carbon nanotubes, fullerenes, graphenes, graphene oxides, and 
nanodiamonds; with or without fluorescent properties. Fluorescent 
nanoparticles are of particular interest for functionalization as they 
are applicable to both research and

[[Page 70691]]

diagnostic applications and can be visualized through microscopy.

Potential Commercial Applications

 Imaging
 Therapeutics

Competitive Advantages

 Higher degree of functionalization for carbon nanoparticles

Development Stage

 Early Stage

    Inventors: Keir Neuman, Rolf Swenson, Ganesh Shenoy, Chandrasekhar 
Mushti (all of NHLBI).

Publications:

1. Mochalin, V. N.; Shenderova, O.; Ho, D.; Gogotsi, Y., The 
Properties and Applications of Nanodiamonds. Nature Nanotechnology 
2012, 7 (1), 11-23.
2. Huang, J.; Deming, C. P.; Song, Y.; Kang, X.; Zhou, Z.-Y.; Chen, 
S., Chemical Analysis of Surface Oxygenated Moieties of Fluorescent 
Carbon Nanoparticles. Nanoscale 2012, 4 (3), 1010-1015.
3. Nystrom, R. F.; Brown, W. G., Reduction of Organic Compounds by 
Lithium Aluminum Hydride. I. Aldehydes, Ketones, Esters, Acid 
Chlorides and Acid Anhydrides. Journal of the American Chemical 
Society 1947, 69 (5), 1197-1199.
4. Nystrom, R. F.; Brown, W. G., Reduction of Organic Compounds by 
Lithium Aluminum Hydride. Ii. Carboxylic Acids. Journal of the 
American Chemical Society 1947, 69 (10), 2548-2549.
5. Aller, E.; Brown, D. S.; Cox, G. G.; Miller, D. J.; Moody, C. J. 
Diastereoselectivity in the O-H Insertion Reactions of Rhodium 
Carbenoids Derived from Phenyldiazoacetates of Chiral Alcohols. 
Preparation Of .Alpha.-Hydroxy And .Alpha.-Alkoxy Esters. The 
Journal of Organic Chemistry 1995, 60 (14), 4449-4460.
6. Hoehnel, S; Lutolf, M.P., Capturing Cell-Cell Interactions via 
SNAP-tag and CLIP-tag Techology. Bioconjugate Chemistry 2015, 26, 
1678-1686.
7. Moon, W. K.; Lin, Y.; O'Loughlin, T.; Tang, Y.; Kim, D.-E.; 
Weissleder, R.; and Tung, C.-H., Enhanced Tumor Detection Using a 
Folate Receptor-Targeted Near-Infrared Fluorochrome Conjugate. 
Bioconjugate Chemistry 2003, 14, 539-545.
8. Fu, C. C.,Lee, H. Y., Chen, K. C., Lim, T. S.,Wu, H. Y., Lin, P. 
K.,Wei, P. K., Tsao, P. H., Chang, H. C., Fann, W. Characterization 
and application of single fluorescent nanodiamonds as cellular 
biomarkers. Proceedings of the National Academy of Sciences of the 
United States of America, 2007, 104(3), 727-732.
9. Chang, B. M., Lin, H. H., Su, L. J., Lin, W. D., Lin, R. J., 
Tzeng, Y. K, Lee, R. T., Lee, Y. C., Yu, A. L., Chang, H. C., Highly 
Fluorescent Nanodiamonds Protein-Functionalized for Cell Labeling 
and Targeting. Advanced Functional Materials 23(46): 5737-5745.

    Intellectual Property: HHS Reference No. E-207-2016/0.
     US Provisional Patent Application No. 62/402,339 filed 30 
September 2016.
    Licensing Contact: Michael Shmilovich, Esq, CLP; 301-435-5019; 
[email protected].

    Dated: October 6, 2016.
Michael Shmilovich,
National Heart, Lung and Blood Institute, Office of Technology Transfer 
and Development, National Institutes of Health.
[FR Doc. 2016-24693 Filed 10-12-16; 8:45 am]
 BILLING CODE 4140-01-P