IP Library › Granted Patent US 12,611,462
Granted Patent B2
US 12,611,462 · App. 17/812,607 · Granted Apr 28, 2026

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

Inventors: Marcin Tomasz Kortylewski (Monrovia, CA); Piotr Marek Swiderski (San Dimas, CA); Dayson Friaca Moreira (Duarte, CA)
Assignee: CITY OF HOPE
A61K47/549A61K31/713A61K45/06A61P35/00A61P35/02A61P37/00C12N15/113C12N15/1135A61K48/00C12N2310/11C12N2310/315C12N2310/3519C12N2320/30C12N2320/31C12N2320/35C12N2320/51
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,611,462
App. No.
17/812,607
Granted
Apr 28, 2026
Kind
B2
Abstract

The present disclosure relates to an isolated compound including a phosphorothioated oligodeoxynucleotide (ODN) sequence conjugated to a short-activating RNA (saRNA) or an antisense oligonucleotide sequence (ASO), compositions of such a compound, and method of treatment of cancer and autoimmune diseases (with or without stimulating an immune response), method of immune stimulation, method of activating CEBPA, and method of reducing activity of STAT transcription factor, by one of the disclosed compounds or compositions.

Claims (23)

1 . An isolated compound comprising a phosphorothioated oligodeoxynucleotide conjugated to an antisense oligonucleotide of Signal Transducer and Activator of Transcription 3 (STAT3).

2 . The compound of claim 1 , wherein the phosphorothioated oligodeoxynucleotide comprises the sequence of any one of SEQ ID NOS: 7-18 and 98-101.

3 . The compound of claim 1 , wherein the phosphorothioated oligodeoxynucleotide comprises the sequence of SEQ ID NO:7.

4 . The compound of claim 1 , wherein the antisense oligonucleotide of STAT3 comprises the sequence of any one of SEQ ID NOS: 31-42 and 110-113.

5 . The compound of claim 1 , wherein the antisense oligonucleotide of STAT3 comprises the sequence of SEQ ID NO:111.

6 . The compound of claim 1 , wherein the antisense oligonucleotide of STAT3 comprises the sequence of SEQ ID NO:31, SEQ ID NO:32, or SEQ ID NO: 110.

7 . The compound of claim 1 , wherein the phosphorothioated oligodeoxynucleotide comprises the sequence of SEQ ID NO:7 and the antisense oligonucleotide of STAT3 comprises the sequence of SEQ ID NO:111.

8 . The compound of claim 1 , wherein the compound comprises the sequence of any one of SEQ ID NOS: 19, 21, 43-60, and 78-86.

9 . The compound of claim 1 , wherein the compound comprises the sequence of SEQ ID NO: 19, SEQ ID NO:20, or SEQ ID NO:44.

10 . The compound of claim 1 , wherein the compound comprises the sequence of SEQ ID NO:44.

11 . The compound of claim 1 , wherein the antisense oligonucleotide of STAT3 comprises a chemical modification, wherein the chemical modification is 2′ O-Methyl, 2′-deoxy-2′fluoro, 2′-deoxy, a universal base, 5-C-methyl, an inverted deoxy abasic residue incorporation, a locked nucleic acid, or a combination of two or more thereof.

12 . The compound of claim 1 , wherein the antisense oligonucleotide of STAT3 comprises a single-stranded DNA substituent.

13 . The compound of claim 1 , wherein the phosphorothioated oligodeoxynucleotide is conjugated to the antisense oligonucleotide of STAT3 via a linker.

14 . The compound of claim 12 , wherein the linker is a substituted 2 to 40 membered heteroalkylene.

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

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

17 . A method of treating prostate cancer, bladder cancer, or kidney cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of claim 1 .

18 . The method of claim 15 , wherein the cancer is breast cancer, glioblastoma, ovarian cancer, lung cancer, head and neck cancer, esophageal cancer, melanoma, brain cancer, colorectal cancer, leukemia, lymphoma, or myeloma.

19 . The compound of claim 1 , wherein the phosphorothioated oligodeoxynucleotide comprises a CpG nucleic acid sequence.

20 . The compound of claim 1 , wherein the phosphorothioated oligodeoxynucleotide comprises a GpC nucleic acid sequence.

21 . The compound of claim 1 , wherein the phosphorothioated oligodeoxynucleotide comprises the sequence of SEQ ID NO:29 or SEQ ID NO:30.

22 . The compound of claim 1 , wherein the compound comprises the sequence of any one of SEQ ID NOS: 61-77 and 87-95.

23 . The compound of claim 1 , wherein the phosphorothioated oligodeoxynucleotide comprises the sequence of SEQ ID NO:7 and the antisense oligonucleotide of STAT3 comprises the sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO: 110, or SEQ ID NO:111.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 30, 2025
From: KORTYLEWSKI, MARCIN TOMASZ; SWIDERSKI, PIOTR MAREK; MOREIRA, DAYSON FRIACA
To: CITY OF HOPE
Reel/Frame 072429/0161 →
Continuity (5)
Continuation 16938169 · Jul 24, 2020
Continuation 15740914
Provisional Application 62264026 · Dec 7, 2015
Provisional Application 62187878 · Jul 2, 2015
Related Publication 20220401563A1 · Dec 22, 2022
References Cited (49)
US 4861760A · Mazuel et al. · 1989 [cited by applicant]
US 4911920A · Jani et al. · 1990 [cited by applicant]
US 5212162A · Missel et al. · 1993 [cited by applicant]
US 5403841A · Lang et al. · 1995 [cited by applicant]
US 8816056B2 · Swayze et al. · 2014 [cited by applicant]
US 10758624B2 · Kortylewski et al. · 2020 [cited by applicant]
US 20030027184A1 · Gorenstein et al. · 2003 [cited by applicant]
US 20060046259A1 · Baird et al. · 2006 [cited by applicant]
US 20100210707A1 · Li et al. · 2010 [cited by applicant]
US 20110250138A1 · Fan et al. · 2011 [cited by applicant]
US 20120065125A1 · Yu et al. · 2012 [cited by applicant]
US 20140287987A1 · Yu et al. · 2014 [cited by applicant]
US 20150190525A1 · Tatro et al. · 2015 [cited by applicant]
US 20160298113A1 · Saetrom · 2016 [cited by applicant]
US 20210038733A1 · Kortylewski et al. · 2021 [cited by applicant]
CN 101848923A · 2010 [cited by applicant]
CN 102361985A · 2012 [cited by applicant]
WO WO0061602A1 · 2000 [cited by applicant]
WO WO2004087920A1 · 2004 [cited by applicant]
WO WO2008094254A2 · 2008 [cited by applicant]
WO WO2008094254A3 · 2008 [cited by applicant]
WO WO2008136902A1 · 2008 [cited by applicant]
WO WO2010065787A2 · 2010 [cited by applicant]
WO WO2010065787A3 · 2010 [cited by applicant]
WO WO2012128785A1 · 2012 [cited by applicant]
WO WO2012135736A2 · 2012 [cited by applicant]
WO WO2012135736A3 · 2012 [cited by applicant]
WO WO2014070868A1 · 2014 [cited by applicant]
WO WO2014153023A1 · 2014 [cited by applicant]
WO WO2015075557A2 · 2015 [cited by applicant]
WO WO2015075557A3 · 2015 [cited by applicant]
WO WO2015077657A2 · 2015 [cited by applicant]
WO WO2015077657A3 · 2015 [cited by applicant]
Dhir, R. et al. (Jun. 2002). “Stat3 activation in prostatic carcinomas,” [cited by applicant]
Donner, A. et al. (2014). “RNA is for activation,” [cited by applicant]
European Search Report mailed Jan. 28, 2019, for EP Patent Application No. 16818778.9, 6 pages. [cited by applicant]
Extended European Search Report mailed on May 21, 2019, for EP Patent Application No. 16818778.9, 11 pages. [cited by applicant]
Hedvat, M. et al. (Dec. 8, 2009). “The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors,” [cited by applicant]
Huang, V. et al. (Jan. 22, 2010). “RNAa is conserved in mammalian cells,” [cited by applicant]
International Search Report mailed on Dec. 1, 2016, for PCT Application No. PCT/US2016/040361, filed Jun. 30, 2016, 6 pages. [cited by applicant]
Kortylewski, M. et al. (Oct. 2009, e-published Sep. 133, 2009). “In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses,” [cited by applicant]
Lee, S.O. et al. (Sep. 2004). “RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells,” [cited by applicant]
Li, L.C. et al. (Nov. 14, 2006, e-published Nov. 3, 2006). “Small dsRNAs induce transcriptional activation in human cells,” [cited by applicant]
Mora, L.B. et al. (Nov. 15, 2002). “Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells,” [cited by applicant]
Reebye, V. et al. (Jan. 2014, e-published Dec. 9, 2013). “A novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo,” [cited by applicant]
Written Opinion mailed on Dec. 1, 2016, for PCT Application No. PCT/US2016/040361, filed Jun. 30, 2016, 11 pages. [cited by applicant]
Takeshita, F. et al. (Jan. 2000). “Positive and negative regulatory elements contribute to CpG oligonucleotide-mediated regulation of human IL-6 gene expression,” [cited by applicant]
Takeshita, F. et al. (Jul. 2000). “CpG ODN-mediated regulation of IL-12 p40 transcription,” [cited by applicant]
Wang Chengxing et al. (Mar. 31, 2002). “Secretion of EB virus LMP1 in nasopharyngeal carcinoma cell line by promoting IL-8 with NF-κB, AP-1,” [cited by applicant]