IP Library › Granted Patent US 12,227,745
Granted Patent B2
US 12,227,745 · App. 18/166,204 · Granted Feb 18, 2025

Compounds and compositions including phosphorothioated oligodeoxynucleotide, and methods of use thereof

Inventors: Marcin Tomasz Kortylewski (Monrovia, CA); Piotr Marek Swiderski (San Dimas, CA); Guido Marcucci (Azusa, CA); Bin Zhang (Duarte, CA); Ya-Huei Kuo (Duarte, CA)
Assignee: City of Hope
C12N15/113A61K31/506A61K31/7004A61K31/704A61K31/7125A61K45/06A61K47/549A61P35/02C12N15/111C12N2310/113C12N2310/141C12N2310/17C12N2310/315C12N2310/3519
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Quick Facts
Patent No.
US 12,227,745
App. No.
18/166,204
Granted
Feb 18, 2025
Kind
B2
Abstract

The present disclosure relates to a compound including a nucleic acid sequence conjugated to an anti-microRNA or a microRNA-mimic or a compound including a modified anti-microRNA sequence, compositions of such a compound, and method of treatment of a disease, and method of suppressing microRNA activity by the disclosed compound or composition.

Claims (20)

1. A compound comprising a phosphorothioated CpG oligodeoxynucleotide (CpG-ODN) conjugated to a nucleic acid sequence as set forth in SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, or SEQ ID NO:21.

2. The compound of claim 1 , further comprising a covalent linker between the CpG-ODN and the nucleic acid sequence.

3. The compound of claim 2 , wherein the covalent linker is substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene.

4. The compound of claim 2 , wherein the covalent linker is unsubstituted C1-C40 alkylene, unsubstituted 2 to 40 membered heteroalkylene, unsubstituted C3-C8 cycloalkylene, unsubstituted 3 to 8 membered heterocycloalkylene, unsubstituted C6-C10 arylene, or unsubstituted 5 to 10 membered heteroarylene.

5. The compound of claim 2 , wherein the covalent linker is substituted 2 to 40 membered heteroalkylene.

6. The compound of claim 1 , wherein the nucleic acid sequence is chemically modified.

7. The compound of claim 6 , wherein the nucleic acid sequence comprises a chemical modification selected for the group consisting of a 2′ O-Methyl, 2′-deoxy-2′fluoro, 2′-deoxy, a universal base, 5-C-methyl, an inverted deoxy abasic residue incorporation, and a locked nucleic acid.

8. The compound of claim 7 , wherein the modification is positioned at the terminal nucleobase of the nucleic acid sequence.

9. The compound of claim 1 , wherein the CpG-ODN is selected from the group consisting of a Class A CpG-ODN, a Class B CpG-ODN, and a Class C CpG-ODN.

10. The compound of claim 1 , wherein the CpG-ODN comprises phosphodiester derivative linkage selected from the group consisting of a phosphoramidate linkage, phosphorodiamidate linkage, phosphorodithioate linkage, phosphonocarboxylic acid linkage, phosphonocarboxylate linkage, phosphonoacetic acid linkage, phosphonoformic acid linkage, methyl phosphonate linkage, boron phosphonate linkage, and O-methylphosphoroamidite linkage.

11. The compound of claim 1 , wherein the phosphorothioated CpG oligodeoxynucleotide comprises the nucleic acid sequence of any one of SEQ ID NOS: 1-14.

12. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

13. The pharmaceutical composition of claim 12 , further comprising a second therapeutic agent.

14. A method of treating leukemia in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of claim 1 , thereby treating leukemia.

15. The method of claim 14 , further comprising administering to the subject an effective amount of a second therapeutic agent.

16. The method of claim 14 , further comprising administering to the subject an effective amount of nilotinib, cytosine arabinoside, doxorubicin, dactinomycin, bleomycin, daunorubicin, epirubicin, idarubicin, mitomycin, mitoxantrone, etoposide, docetaxel, irinotecan, paclitaxel, topotecan, vinblastine, vincristine, vinorelbine, carboplatin, cisplatin, oxaliplatin, alemtuzumab, Bacillus Calmette-Guérin, bevacizumab, cetuximab, denosumab, erlotinib, gefitinib, imatinib, interferon, ipilimumab, lapatinib, monomethyl auristatin E, mertansine, rituximab, sunitinib, sorafenib, temsirolimus, trastuzumab, or a combination of two or more thereof.

17. The compound of claim 1 , wherein the nucleic acid sequence is the nucleic acid sequence as set forth in SEQ ID NO:18.

18. The compound of claim 1 , wherein the nucleic acid sequence is the nucleic acid sequence as set forth in SEQ ID NO:19.

19. The compound of claim 1 , wherein the nucleic acid sequence is the nucleic acid sequence as set forth in SEQ ID NO:20.

20. The compound of claim 1 , wherein the nucleic acid sequence is the nucleic acid sequence as set forth in SEQ ID NO:21.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 26, 2023
From: KORTYLEWSKI, MARCIN TOMASZ; SWIDERSKI, PIOTR MAREK; MARCUCCI, GUIDO; ZHANG, BIN; KUO, YA-HUEI
To: CITY OF HOPE
Reel/Frame 065364/0105 →
Continuity (4)
Continuation 17010259 · Sep 2, 2020
Continuation 15768405
Provisional Application 62242189 · Oct 15, 2015
Related Publication 20230340479A1 · Oct 26, 2023
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