[Federal Register Volume 89, Number 105 (Thursday, May 30, 2024)]
[Notices]
[Pages 46895-46896]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-11796]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

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; [email protected] 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to receive any unpublished information.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

[[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-
13C]-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--Hyperpolarized 13C 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 Hyperpolarized \13\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.
     Rapid 13C Hyperpolarization of the TCA-Cycle 
Intermediate [alpha]-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-Unity 13C Nuclear Polarization of [1-
13C]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 [1-13C]-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