# US 2022/0143049 A1 · A dbait molecule in combination with kinase inhibitor for the treatment of cancer

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2022/0143049 A1
- Document ID: US20220143049A1
- Status: Published application
- Kind: A1
- Application number: 17/593,474
- Filed: 2020-03-19
- Published: 2022-05-12
- Earliest claimed: 2019-03-21
- Assignees: Onxeo; Inserm (Institut National De La Sante Et De La Recherche Medicale); Universite Paul Sabatier Toulouse III; Institut Claudius Regaud
- Applicants: Onxeo; Inserm (Institut National De La Santé Et De La Recherche MéDicale); Universite Paul Sabatier Toulouse III; Institut Claudius Regaud
- Inventors: FRANÇOISE BONO; GILLES FAVRE; OLIVIER CALVAYRAC
- Web page: https://patentgrep.com/patent/US20220143049A1

## CPC

- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/6615: Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/544: {Phospholipids}
- A61K 47/554: {the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid}
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- C12N 2310/13: Decoys
- C12N 2310/315: Phosphorothioates
- C12N 2310/3515: Lipophilic moiety, e.g. cholesterol
- C12N 2320/31: Combination therapy
- 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)
- 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 invention relates to the combination of a Dbait molecule with a protein kinase inhibitor for treating cancer.

## Claims

### Claim at position 1

1-16. (canceled)

### Claim 17

A pharmaceutical composition, a combination, or a kit comprising a Dbait molecule and a protein kinase inhibitor.

### Claim 18 (depends on 17)

The pharmaceutical composition, the combination or the kit according to claim 17, wherein the kinase inhibitor is an inhibitor targeting one or several targets selected from the group consisting of EGFR family, ALK, B-Raf, MEK, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, IGF1R, c-Met, JAK family, PDGFR α and β, RET, AXL, c-KIT, TrkA, TrkB, TrkC, ROS1, BTK and Syk.

### Claim 19 (depends on 17)

The pharmaceutical composition, the combination or the kit according to claim 17, wherein the Dbait molecule has at least one free end and a DNA double stranded portion of 20-200 bp with less than 60% sequence identity to any gene in a human genome.

### Claim 20 (depends on 17)

The pharmaceutical composition, the combination or the kit according to claim 17, wherein the Dbait molecule has one of the following formulae:
wherein N is a deoxynucleotide, n is an integer from 15 to 195, the underlined N refers to a nucleotide having or not a modified phosphodiester backbone, L′ is a linker, C is the molecule facilitating endocytosis selected from a lipophilic molecule or a ligand which targets cell receptor enabling receptor mediated endocytosis, L is a linker, m and p, independently, are an integer being 0 or 1.

### Claim 21 (depends on 20)

The pharmaceutical composition, the combination or the kit according to claim 20, wherein the Dbait molecule has the following formula:

### Claim 22 (depends on 17)

The pharmaceutical composition, the combination or the kit according to claim 17, wherein the Dbait molecule has the following formula:

### Claim 23 (depends on 17)

The pharmaceutical composition or the kit according to claim 17, wherein the kinase inhibitor is selected from the group consisting of gefitinib, erlotinib, lapatinib, vandetanib, afatinib, osimertinib, neratinib, dacomitinib, brigatinib, canertinib, naquotinib, nazartinib, pelitinib, rociletinib, icotinib, AZD3759, AZ5104 (CAS No. 1421373-98-9), poziotinib, WZ4002, Crizotinib, entrectinib, ceritinib, alectinib, lorlatinib, TSR-011, CEP-37440, ensartinib, Vemurafenib, dabrafenib, regorafenib, PLX4720, Cobimetinib, Trametinib, Binimetinib, Selumetinib, PD-325901, CI-1040, PD035901, U0126, TAK-733, Lenvatinib, Debio-1347, dovitinib, BLU9931, Sorafenib, sunitinib, lestaurtinib, tandutinib, quizartinib, crenolanib, gilteritinib, ponatinib, ibrutinib, Linsitinib, NVP-AEW541, BMS-536924, AG-1024, GSK1838705A, BMS-754807, PQ 401, ZD3463, NT157, Picropodophyllin (PPP), Tivantinib, JNJ-38877605, PF-04217903, foretinib (GSK 1363089), Merestinib, Ruxolitinib, tofacitinib, oclacitinib, baricitinib, filgotinib, cerdulatinib, gandotinib, momelotinib, pacritinib, PF-04965842, upadacitinib, peficitinib, fedratinib, imatinib, pazopanib, Telatinib, bosutinib, nilotinib, cabozantinib, Bemcentinib, amuvatinib, gilteritinib (ASP2215), glesatinib (MGCD 265), SGI-7079, Larotrectinib, RXDX-102, altiratinib, LOXO-195, sitravatinib, TPX-0005, DS-6051b, fostamatinib, entospletinib and TAK-659.

### Claim 24 (depends on 17)

The pharmaceutical composition or the kit according to claim 17, wherein the kinase inhibitor is a tyrosine kinase inhibitor and is an inhibitor of a protein kinase selected from the group consisting of EGFR, ALK and B-Raf and is a tyrosine protein kinase inhibitor selected from the group consisting of gefitinib, erlotinib, lapatinib, vandetanib, afatinib, osimertinib, neratinib, dacomitinib, brigatinib, canertinib, naquotinib, nazartinib, pelitinib, rociletinib, icotinib, AZD3759, AZ5104 (CAS No. 1421373-98-9), poziotinib, WZ4002, Crizotinib, entrectinib, ceritinib, alectinib, lorlatinib, TSR-011, CEP-37440, ensartinib, Vemurafenib, dabrafenib, regorafenib and PLX4720.

### Claim 25 (depends on 17)

The pharmaceutical composition, the combination or the kit according to claim 17, wherein the protein kinase inhibitor is an EGFR inhibitor selected from the group consisting of gefitinib, erlotinib, lapatinib, vandetanib, afatinib, osimertinib, neratinib, dacomitinib, brigatinib, canertinib, naquotinib, nazartinib, pelitinib, rociletinib, icotinib, AZD3759, AZ5104 (CAS No. 1421373-98-9), poziotinib and WZ4002.

### Claim 26 (depends on 17)

The pharmaceutical composition, the combination or the kit according to claim 17, wherein the protein kinase inhibitor is an ALK inhibitor selected from the group consisting of crizotinib, entrectinib, ceritinib, alectinib, brigatinib, lorlatinib, TSR-011, CEP-37440 and ensartinib.

### Claim 27 (depends on 22)

The pharmaceutical composition or the kit according to claim 22, wherein the kinase inhibitor is selected from the group consisting of gefitinib, erlotinib, lapatinib, vandetanib, afatinib, osimertinib, neratinib, dacomitinib, brigatinib, canertinib, naquotinib, nazartinib, pelitinib, rociletinib, icotinib, AZD3759, AZ5104 (CAS No. 1421373-98-9), poziotinib, WZ4002, Crizotinib, entrectinib, ceritinib, alectinib, lorlatinib, TSR-011, CEP-37440, ensartinib, Vemurafenib, dabrafenib, regorafenib, PLX4720, Cobimetinib, Trametinib, Binimetinib, Selumetinib, PD-325901, CI-1040, PD035901, U0126, TAK-733, Lenvatinib, Debio-1347, dovitinib, BLU9931, Sorafenib, sunitinib, lestaurtinib, tandutinib, quizartinib, crenolanib, gilteritinib, ponatinib, ibrutinib, Linsitinib, NVP-AEW541, BMS-536924, AG-1024, GSK1838705A, BMS-754807, PQ 401, ZD3463, NT157, Picropodophyllin (PPP), Tivantinib, JNJ-38877605, PF-04217903, foretinib (GSK 1363089), Merestinib, Ruxolitinib, tofacitinib, oclacitinib, baricitinib, filgotinib, cerdulatinib, gandotinib, momelotinib, pacritinib, PF-04965842, upadacitinib, peficitinib, fedratinib, imatinib, pazopanib, Telatinib, bosutinib, nilotinib, cabozantinib, Bemcentinib, amuvatinib, gilteritinib (ASP2215), glesatinib (MGCD 265), SGI-7079, Larotrectinib, RXDX-102, altiratinib, LOXO-195, sitravatinib, TPX-0005, DS-6051b, fostamatinib, entospletinib and TAK-659.

### Claim 28 (depends on 22)

The pharmaceutical composition or the kit according to claim 22, wherein the kinase inhibitor is a tyrosine kinase inhibitor and is an inhibitor of a protein kinase selected from the group consisting of EGFR, ALK and B-Raf and is a tyrosine protein kinase inhibitor selected from the group consisting of gefitinib, erlotinib, lapatinib, vandetanib, afatinib, osimertinib, neratinib, dacomitinib, brigatinib, canertinib, naquotinib, nazartinib, pelitinib, rociletinib, icotinib, AZD3759, AZ5104 (CAS No. 1421373-98-9), poziotinib, WZ4002, Crizotinib, entrectinib, ceritinib, alectinib, lorlatinib, TSR-011, CEP-37440, ensartinib, Vemurafenib, dabrafenib, regorafenib and PLX4720.

### Claim 29 (depends on 22)

The pharmaceutical composition, the combination or the kit according to claim 22, wherein the protein kinase inhibitor is an EGFR inhibitor selected from the group consisting of gefitinib, erlotinib, lapatinib, vandetanib, afatinib, osimertinib, neratinib, dacomitinib, brigatinib, canertinib, naquotinib, nazartinib, pelitinib, rociletinib, icotinib, AZD3759, AZ5104 (CAS No. 1421373-98-9), poziotinib and WZ4002.

### Claim 30 (depends on 22)

The pharmaceutical composition, the combination or the kit according to claim 22, wherein the protein kinase inhibitor is an ALK inhibitor selected from the group consisting of crizotinib, entrectinib, ceritinib, alectinib, brigatinib, lorlatinib, TSR-011, CEP-37440 and ensartinib.

### Claim 31 (depends on 17)

A method of treating cancer comprising the administration of the combination or the kit according to claim 17 to a patient in need of treatment.

### Claim 32 (depends on 31)

The method according to claim 31, said method delaying and/or preventing development of a cancer resistant to a kinase inhibitor in a patient.

### Claim 33 (depends on 31)

The method according to claim 31, wherein the cancer is selected from the group consisting of leukemia, lymphoma, sarcoma, melanoma, cancers of the head and neck, kidney, ovary, pancreas, prostate, thyroid, lung, esophagus, breast, bladder, brain, colorectum, liver, and cervix.

### Claim 34 (depends on 31)

The method according to claim 31, wherein the cancer is selected from the group consisting of lung cancer, non-small cell lung cancer, leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, lymphoma, peripheral T-cell lymphoma, chronic myelogenous leukemia, squamous cell carcinoma of the head and neck, advanced melanoma with BRAF mutation, colorectal cancer, gastrointestinal stromal tumor, breast cancer, HER2+ breast cancer, thyroid cancer, advanced medullary thyroid cancer, kidney cancer, renal cell carcinoma, prostate cancer, glioma, pancreatic cancer, pancreatic neuroendocrine cancer, multiple myeloma, and liver cancer.

### Claim 35 (depends on 17)

A method of reducing the number of cancer persister cells comprising the administration of a pharmaceutical composition, a combination, or a kit comprising a Dbait molecule and a protein kinase inhibitor according to claim 17 to a patient in need of treatment.