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[Federal Register Volume 89, Number 221 (Friday, November 15, 2024)]
[Notices]
[Pages 90298-90300]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-26663]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

Government Owned Inventions Available for Licensing or 
Collaboration: Novel Kinase Inhibitory Aplithianines

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

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SUMMARY: The National Cancer Institute (NCI), an institute of the 
National Institutes of Health (NIH), Department of Health and Human 
Services (HHS), is giving notice of the licensing and/or collaboration 
opportunities for the inventions listed below, which are owned by an 
agency of the U.S. Government and are available for licensing and/or 
collaboration to achieve expeditious commercialization of results of 
federally-funded research and development.

FOR FURTHER INFORMATION CONTACT: Inquiries related to these licensing 
or collaboration opportunities should be directed to: Taryn Dick, 
Ph.D., M.B.A., Technology Transfer Manager, NCI, Technology Transfer 
Center, Email: [email protected] or Phone: 301-631-3007.

SUPPLEMENTARY INFORMATION: Researchers at the NCI seek licensing and/or 
co-development research collaborations for a class of novel 
aplithianine-derived small molecule analogs that compete with ATP for 
binding on a range of clinically relevant kinases. In 2022, the NCI 
Molecular Targets Program (MTP) completed a screen of approximately 
150,000 pre-fractionated natural products from the NCI Program for 
Natural Product Discovery (NPNPD). From this screen, a class of active 
compounds, named Aplithianines A & B (isolated from the marine organism 
Aplidium sp.), showed broad potential applicability to numerous kinases 
of importance, including but not limited to:
     Oncogenic gene fusion DNAJB1-PRKACA (PKADJ):
    [cir] Implicated in an ultra-rare adolescent liver cancer.
     Wild type protein kinase A (PKA):
    [cir] Implicated in Cushing's Disease.
     Protein kinase G (PKG):
    [cir] Potential treatment of malaria.
     Ccdc2-like kinases (CLK) 1 and 2:
    [cir] Implicated in gastric cancer.
     DYRK family of kinases:
    [cir] Implicated in gastric or colon cancer as well as infections 
caused by a protozoa or parasites.
    This technology describes the Original Family of compounds filed. 
Subsequent to this filing, two additional cohorts of related, but 
patentably distinct cohorts of compounds, have been filed. Both the 
Second and the Third Cohorts comprise the same chemical scaffold of the 
broadest generic formula of this Original Family but represent 
patentably distinct subgenus formulas.
BILLING CODE 4140-01-P

[[Page 90299]]

[GRAPHIC] [TIFF OMITTED] TN15NO24.000

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    The specificity of several of the compounds have been examined in 
kinase panels to demonstrate that while applicable to a range of 
kinases, they are

[[Page 90300]]

not promiscuous kinase inhibitors. The subject kinase inhibitors have 
broad potential commercial applicability's for cancer, immune 
suppression, preventing organ rejection, treating diabetic neuropathic 
pain, malaria, or protozoa infection. To date, there are no approved 
therapeutics targeting DNAJB1-PRKCA, an oncogenic gene fusion, which is 
ubiquitously and exclusively detected in the tumors of patients with 
ultra-rare fibrolamellar hepatocellular carcinoma FLHCC.
    This Notice is in accordance with 35 U.S.C. 209 and 37 CFR part 
404.
    NIH Reference Number: E-044-2022.
    Related Technologies: E-202-2023 and E-162-2024.
    Product Type: Therapeutic.
    Therapeutic Area(s): Oncology, Infectious Disease, Rare/Neglected 
Diseases.
    Potential Commercial Applications:
     Gastric cancer.
     Ultra-rare adolescent liver cancer.
     Solid cancers susceptible to kinase inhibitors.
     Cushing's Disease.
     Transplantation.
     Diabetic neuropathic pain.
     Malaria.
     Protozoa infection.
    Competitive Advantages:
     Applicability to numerous clinically relevant kinases, 
including:
    [cir] Oncogenic gene fusion DNAJB1-PRKACA (PKADJ).
    [cir] Wild type protein kinase A (PKA).
    [cir] Protein kinase G (PKG).
    [cir] Ccdc2-like kinases (CLK) 1 and 2.
    [cir] DYRK family of kinases.
     Applicable to a range of kinases, but are not promiscuous 
kinase inhibitors.
     Broad potential commercial applicability for several 
blockbuster indications including:
    [cir] cancer, immune suppression, transplantation, diabetic 
neuropathic pain, malaria, and protozoa infection.
     No approved therapeutics targeting DNAJB1-PRKCA.
    Publications:
     O'Keefe BR, et al. Biochemical Discovery, Intracellular 
Evaluation, and Crystallographic Characterization of Synthetic and 
Natural Product Adenosine 3',5'-Cyclic Monophosphate-Dependent Protein 
Kinase A (PKA) Inhibitors. PMID: 37082750, https://pubmed.ncbi.nlm.nih.gov/37082750/.
     O'Keefe BR, et al. Discovery and Synthesis of a Naturally 
Derived Protein Kinase Inhibitor that Selectively Inhibits Distinct 
Classes of Serine/Threonine Kinases. PMID: 37843072, https://pubmed.ncbi.nlm.nih.gov/37843072/.
    Patent Status:
     E-044-2022: PCT/US2023/070304.
     E-202-2023: PCT/US2024/038376.
     E-162-2024: 63/672,577.
    Development Stage: Pre-clinical (in vivo validation).

    Dated: November 12, 2024.
Richard U. Rodriguez,
Associate Director, Technology Transfer Center, National Cancer 
Institute.
[FR Doc. 2024-26663 Filed 11-14-24; 8:45 am]
BILLING CODE 4140-01-P
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