# US 12,758,565 B2 · Methods of treating p53 mutant cancers using OGDH inhibitors

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- Number: US 12,758,565 B2
- Document ID: US12758565B2
- Status: Granted
- Kind: B2
- Application number: 17/634,775
- Filed: 2020-08-13
- Published: 2022-09-08
- Granted: 2026-10-13
- Earliest claimed: 2019-08-14
- Assignees: Memorial Sloan Kettering Cancer Center
- Applicants: Memorial Sloan Kettering Cancer Center
- Inventors: Scott Lowe; John P. Morris, IV; Scott E. Millman; Lydia Finley
- Web page: https://patentgrep.com/patent/US12758565B2

## CPC

- A61K 31/655: Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 31/282: Platinum compounds
- A61K 31/47: Quinolines; Isoquinolines
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 31/662: Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 35/00: Antineoplastic agents
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/531: Stem-loop; Hairpin
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present technology relates generally to methods and compositions for treating, preventing, and/or ameliorating p53-mutant cancers in a subject in need thereof, including acute myeloid leukemia (AML), pancreatic cancer, and liver cancer, by administration of a therapeutically effective amount of a 2-oxoglutarate dehydrogenase (OGDH) inhibitor.

## Claims

### Claim 1

A method for treating a p53 mutant cancer in a subject in need thereof comprising administering to the subject an effective amount of an OGDH inhibitor, wherein the p53 mutant cancer is acute myeloid leukemia (AML), wherein the OGDH inhibitor is an OGDH-specific inhibitory nucleic acid, succinyl phosphonate, (S)-2-[(2,6-dichlorobenzoyl) amino] succinic acid (AA6), KGD09, or KGD02, and wherein the OGDH-specific inhibitory nucleic acid is an antisense oligonucleotide, or a sgRNA.

### Claim 2 (depends on 1)

The method of claim 1, wherein the OGDH-specific inhibitory nucleic acid comprises a nucleic acid sequence of any one of SEQ ID NOs: 13, 14, 43, 44, or a complement thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the subject is human.

### Claim 4 (depends on 1)

The method of claim 1, wherein the OGDH inhibitor is administered orally, topically, intranasally, systemically, intravenously, subcutaneously intraperitoneally, intradermally, intraocularly, iontophoretically, transmucosally, or intramuscularly.

### Claim 5 (depends on 1)

The method of claim 1, further comprising separately, sequentially or simultaneously administering one or more additional therapeutic agents to the subject.

### Claim 6 (depends on 5)

The method of claim 5, wherein the one or more additional therapeutic agents are selected from the group consisting of Capecitabine, Erlotinib, Fluorouracil (5-FU), Gemcitabine, Irinotecan, Leucovorin, Nab-paclitaxel, Nanoliposomal irinotecan, Oxaliplatin, Larotrectinib, pembrolizumab, Cabozantinib-S-Malate, Ramucirumab, Lenvatinib Mesylate, Sorafenib Tosylate, Nivolumab, Ramucirumab, Regorafenib, Regorafenib, cisplatin, Doxorubicin, Mitoxantrone, Arsenic Trioxide, Daunorubicin, Cyclophosphamide, Cytarabine, Glasdegib Maleate, Dexamethasone, Doxorubicin, Enasidenib Mesylate, Gemtuzumab Ozogamicin, Gilteritinib Fumarate, Idarubicin, Ivosidenib, Midostaurin, Thioguanine, Venetoclax, and Vincristine Sulfate.