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Government-Owned Inventions; Availability for Licensing

The inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. to achieve expeditious commercialization of results of fede...

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Department of Health and Human Services

National Institutes of Health

AGENCY:

National Institutes of Health, 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. to achieve expeditious commercialization of results of federally-funded research and development.

FOR FURTHER INFORMATION CONTACT:

Licensing information may be obtained by emailing the licensing contact Michael Shmilovich, Esq, MS, CLP; 301-435-5019; michael.shmilovich@nih.gov at the National Heart, Lung, and Blood, Office of Technology Transfer and Development Office of Technology Transfer, 31 Center Drive, Room 4A25, MSC2479, Bethesda, MD 20892-2479. A signed Confidential Disclosure Agreement may be required to receive any unpublished information.

SUPPLEMENTARY INFORMATION:

This notice is in accordance with 35 U.S.C. 209 and 37 CFR part 404. Technology description follows.

Next generation MRI platform Signal Amplification by Reversible Exchange (SABRE) hyperpolarization:

Hyperpolarized magnetic resonance imaging (MRI) is an emerging molecular imaging method for metabolic imaging for detecting cancer, cardiovascular disease, stroke, and traumatic brain injury and monitoring therapy with no Gadolinium or Iron. Available for licensing and commercial development is a patent estate covering a perfluorinated single amplification by reversible exchange (SABRE) catalyst for generating MRI agents that includes a d-block element and a perfluorinated ligand hyperpolarized substrate comprising a 1/2 spin nucleus or nuclei using the perfluorinated SABRE catalysts, and isolating the resulting hyperpolarized substrate for administration. The invention also provides methods for separating a hyperpolarized substrate from the SABRE catalyst and/or hyperpolarized SABRE catalyst complex containing a ( printed page 46896) heavy metal. These changes can be observed in patients in real time with a specialized MRI approach called hyperpolarization. By transiently changing the nuclear spin of naturally occurring intermediates in cellular energy production, the metabolic fate can be observed with greater than 10,000-fold sensitivity. Current methods of hyperpolarization require expensive machines with limited throughput.

Potential Commercial Applications:

MRI imaging
Hyperpolarization
Infusion Device for imaging reagents
Cancer diagnostics
Cardiovascular disease diagnostics

Development Stage:

Early stage

Inventors: Rolf E. Swenson (NHLBI), Jessica H. Ettedgui-Benjamini (NHLBI), Carolyn Woodroofe Hitko (NCI), Murali K. Cherukuri (NCI), and Natarajan Raju (NHLBI).

Intellectual Properties:

HHS Reference No. E-035-2022-0 “Preparation Of Isotopically Labeled Ketoglutarates And Methods Of Hyperpolarization Through Signal Amplification By Reversible Exchange (SABRE)”; U.S. Provisional Patent Application No. 63/303,190 filed January 26, 2022; Patent Cooperation Treaty Application PCT/US2023/011640 filed January 26, 2023.
HHS Reference No. E-036-2022 “Sabre Catalysts Containing Fluorinated Carbon Chains For Delivery Of Metal-Free MRI Contrast Agents”; U.S. Provisional Patent Application 63/328,545 filed April 7, 2022; Patent Cooperation Treaty Application PCT/US2023/017885 filed April 7, 2023, U.S. Patent Application 18/410,773 filed January 11, 2024, Applications also pending in Japan, Canada, Israel, China, and Europe.
HHS Reference No. E-052-2022 “Infusion device for the preparation and delivery of MRI probes,” U.S. Provisional Patent Application 63/328,556 filed April 7, 2022, Patent Cooperation Treaty Application PCT/US2023/017895 filed April 7, 2023.
HHS Reference No. E-069-2020 “Real-time Monitoring Of In Vivo Free Radical Scavengers Through Hyperpolarized [1-¹³ C] N-acetyl Cysteine,” U.S. Provisional Patent Application 62/961,855 filed January 16, 2020, Patent Cooperation Treaty Application PCT/US2021/013634 filed January 15, 2021, European Patent Application 21741034.9 filed January 15, 2021, Israeli Patent Application 294365 filed January 15, 2021, European Patent Application 17/793,083 filed January 15, 2021.
HHS Reference No. E-070-2020 “Isotopes Of Alpha Ketoglutarate And Related Compounds For Hyperpolarized MRI Imaging,” U.S. Provisional Patent Application 62/962,473 filed January 17, 2020, Patent Cooperation Treaty Application PCT/US2021/013658 filed January 15, 2021, European Patent Application 21741941.5 filed January 15, 2021, Israeli Patent Application 294464 filed January 15, 2021, U.S. Patent Application 17/793,089 filed January 15, 2021.
HHS Reference No. E-039-2022 “Temperature Cycling Method for Hyperpolarization of Target Molecules and Contrast Agents using Parahydrogen,” US Provisional Patent Application 63/203591 filed July 27, 2021. Patent Cooperation Treaty Application PCT/US2022/074122 filed July 26, 2022, U.S. Application 18/291,681.

Publications:

Perfluorinated Iridium catalyst for signal amplification by reversible exchange provides metal-free aqueous hyperpolarized [1-¹³ C]-Pyruvate. J. Ettedgui, B. Blackman, N. Raju, S. Kotler, E. Chekmenev, B. Goodson, H. Merkle, C. Woodroofe, C. LeClair, K. Murali, R. Swenson J. Am. Chem. Soc. 2024, 146, 946-953.
Monitoring response to a clinically relevant IDH inhibitor in glioma—Hyperpolarized¹³ C magnetic resonance spectroscopy approaches. D. Hong, Y. Kim, C. Mushti, N. Minami, J. Wu, M. K. Cherukuri, R. E. Swenson, D. B. Vigneron, S. M. Ronen. Neuro-Oncology Advances 2023, DOI: https://academic.oup.com/noa/article/5/1/vdad143/7337326.
Catalyst-Free Aqueous Hyperpolarized¹³ C-Pyruvate Obtained by Re-Dissolution Signal Amplification by Reversible Exchange A. B. Schmidt; H. de Maissin; I. Adelabu; S. Nantogma; J. Ettedgui; P. TomHon; B. M Goodson.; T. Theis; E. Y. Chekmenev. ACS Sensors 2022, 7 (11), 3430-3439.
Rapid¹³ C Hyperpolarization of the TCA-Cycle Intermediate α-Ketoglutarate via SABRE-SHEATH. I. Adelabu, Isaiah; Ettedgui, Jessica; Joshi, Sameer; Nantogma, Shiraz; Chowdhury, Md Raduanul; McBride, Stephen; Theis, Thomas; Sabbasani, Venkata; Chandrasekhar, Mushti; Sail, Deepak; Yamamoto, Kazutoshi; Swenson, Rolf; Krishna, Murali; Goodson, Boyd; Chekmenev, Eduard. Anal. Chem. 2022, 94, 13422-13431.
Order-Unity¹³ C Nuclear Polarization of [1-¹³ C]Pyruvate in Seconds and the Interplay of Water and SABRE Enhancement. I. Adelabu, P. TomHon, M. S. H. Kabir, S Nantogma, M. Abdulmojeed, I. Mandzhieva, J. Ettedgui, R. E. Swenson, M. C. Krishna, T. Theis, B. M. Goodson, and E. Y. Chekmenev. ChemPhysChem. 2022, 23, 131-136.
Simple esterification of [1-¹³ C]-alpha-ketoglutarate enhances membrane permeability and allows for non-invasive tracing of glutamate and glutamine production. J. AbuSalim, K. Yamamoto, N. Miura, B. Blackman, J. Brender, C. Mushti, T. Seki, K. Camphausen, R. Swenson, M. Krishna, A. Kesarwala. ACS Chem. Biol. 2021, 16, 2144-2150. DOI: 10.1021/acschembio.1c00561
Synthesis of [1-¹³ C-5-12 C]-alpha-ketoglutarate enables non-invasive detection of 2-hydroxyglutarate. N. Miura, C. Mushti, D. Sail, J. E. Bingham, K. Yamamoto, J. R. Brender, T. Seki, D. I. AbuSalim, S. Matsumoto, K. A. Camphausen, M. C. Krishna, R. E. Swenson, A. H. Kesarwala. NMR in Biomedicine 2021, 34, e4588. https://doi.org/10.1002/nbm.4588.
Low-cost High-Pressure Clinical-Scale 50% Parahydrogen Generator Using Liquid Nitrogen at 77 K. B. Chapman, B. Joalland, C. Meersman, J. Ettedgui, R. E. Swenson, M. C. Krishna, P. Nikolaou, K.V. Kovtunov, O. G. Salnikov, I. V. Koptyug, M. E. Gemeinhardt, B. M. Goodson, R. V. Shchepin, and E. Y. Chekmenev. Anal. Chem. 2021, 93, 8476-8483.
Real Time Insight into In Vivo Redox Status utilizing Hyperpolarized [1-¹³ C] N-Acetyl Cysteine. K. Yamamoto, A. Opina, D. Sail, B. Blackman, K. Saeito, J. R. Brender, R. M. Malinowski, T. Seki, N. Oshima, D. R. Crooks, S. Kishimoto, Y. Saida, Y. Otowa, P. L. Choyke, J. H. Ardenkjaer-Larsen, J. B. Mitchell, W. M. Linehan, R. E. Swenson, M. C. Krishna. Sci. Reports 2021, 11, 12155.

Dated: May 23, 2024.

Michael A. Shmilovich,

Senior Licensing and Patenting Manager, National Heart, Lung, and Blood Institute, Office of Technology Transfer and Development.

[FR Doc. 2024-11796 Filed 5-29-24; 8:45 am]

BILLING CODE 4140-01-P

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89 FR 46895

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“Government-Owned Inventions; Availability for Licensing,” thefederalregister.org (May 30, 2024), https://thefederalregister.org/documents/2024-11796/government-owned-inventions-availability-for-licensing.