2024-26663. Government Owned Inventions Available for Licensing or Collaboration: Novel Kinase Inhibitory Aplithianines

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Department of Health and Human Services

National Institutes of Health

AGENCY:

National Institutes of Health, HHS.

ACTION:

Notice.

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: [e-mail] or Phone: [phone].

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):

○ Implicated in an ultra-rare adolescent liver cancer.

• Wild type protein kinase A (PKA):

○ Implicated in Cushing's Disease.

• Protein kinase G (PKG):

○ Potential treatment of malaria.

• Ccdc2-like kinases (CLK) 1 and 2:

○ Implicated in gastric cancer.

• DYRK family of kinases:

○ 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.

( print page 90299)

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 ( print 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:

○ Oncogenic gene fusion DNAJB1-PRKACA (PKADJ).

○ Wild type protein kinase A (PKA).

○ Protein kinase G (PKG).

○ Ccdc2-like kinases (CLK) 1 and 2.

○ 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:

○ 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.