# US 10,869,879 B2 · Combinations to treat cancer

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

- Number: US 10,869,879 B2
- Document ID: US10869879B2
- Status: Granted
- Kind: B2
- Application number: 16/295,092
- Filed: 2019-03-07
- Published: 2019-07-18
- Granted: 2020-12-22
- Earliest claimed: 2017-08-07
- Assignees: Evol Science LLC
- Applicants: Evol Science LLC
- Inventors: Vikram Bhattacharjee
- Web page: https://patentgrep.com/patent/US10869879B2

## CPC

- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- 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}
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/4375: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- 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 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- 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

## Abstract

This application describes compounds, compositions, and combinations thereof that can be used to treat cancer, such as cancers with and without BRAF and/or RAS mutations.

## Claims

### Claim 1

A method of treating a wild-type BRAF tumor in a subject comprising administering to the subject a DNA damaging agent and a pan-RAF inhibitor, wherein the tumor is a pancreatic tumor, melanoma tumor, or colon cancer tumor, wherein the pan-RAF inhibitor is 1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolamine (RAF265), 3-(2-cyanopropan-2-yl)-N-[4-methyl-3[(3-methyl-4-oxoquinazolin-6-yl)amino]phenyl]benzamide (AZ628), 1-(3,3-dimethylbutyl)-3-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]urea (LY3009120), N-[7-Cyano-6-[4-fluoro-3-[[2-[3-(trifluoromethyl)phenyl]acetyl]amino]phenoxy]-1,3-benzothiazol-2-1]cyclopropanecarboxamide (TAK632), 2-[(1R)-1-[(6-Amino-5-chloropyrimidine-4-carbonyl)amino]ethyl]-N-[5-chloro-4-(trifluoromethyl)pyridin-2-yl]-1,3-thiazole-5-carboxamide (MLN2480), N-[3-[5-[(1-Ethylpiperidin-4-yl)-methylamino]-3-pyrimidin-5-ylpyrrolo[3,2-b]pyridin-1-yl]-2,4-difluorophenyl]propane-1-sulphonamide (XP102), or a pharmaceutically acceptable salt thereof, and wherein the DNA damaging agent is gemcitabine, 5-fluorouracil, cytarabine, methotrexate, pyrimethamine, bleomycin, oxaliplatin, cisplatin, carboplatin, etoposide, doxorubicin, vinorelbin, mitoxantrone, podophyllotoxin, aphidicolin, fotemustine, carmustine, [(5S,6S)-6-Acetyloxy-11-methoxy-2,7,7-trimethyl-13-oxo-8-oxa-2-azapentacyclo[12.8.0.03,12.04,9.016,21]docosa-1(22),3,9,11,14,16,18,20-octaen-5-yl] acetate (S-23906), (19S)-10,19-diethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015.20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione(SN-38), topotecan, camptothecin, rebeccamiycin, or any pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the DNA damaging agent is gemcitabine, methotrexate, camptothecin, and/or pyrimethamine, or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the inhibitor, or a pharmaceutically acceptable salt thereof, and the DNA damaging agent is administered sequentially, simultaneously, or in an overlapping manner.

### Claim 4 (depends on 1)

The method of claim 1, wherein the DNA damaging agent is administered to the subject prior to the inhibitor being administered to the subject.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject is pre-treated with the DNA damaging agent before the inhibitor is administered to the subject.

### Claim 6 (depends on 1)

The method of claim 1, wherein the inhibitor, or a pharmaceutically acceptable salt thereof, and the DNA damaging agent is administered orally.

### Claim 7 (depends on 1)

The method of claim 1, wherein the inhibitor, or a pharmaceutically acceptable salt thereof, and the DNA damaging agent is administered intravenously.

### Claim 8 (depends on 1)

The method of claim 1, wherein the inhibitor, or a pharmaceutically acceptable salt thereof, is administered orally and the DNA damaging agent is administered intravenously.

### Claim 9 (depends on 1)

The method of claim 1, wherein the inhibitor is RAF265, or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The method of claim 1, wherein the tumor is a pancreatic tumor.

### Claim 11 (depends on 1)

The method of claim 1, wherein the tumor is a melanoma tumor.

### Claim 12 (depends on 1)

The method of claim 1, wherein the tumor is a metastatic tumor.

### Claim 13 (depends on 1)

The method of claim 1, wherein the tumor is characterized as wild-type RAS.

### Claim 14 (depends on 1)

The method of claim 1, wherein the tumor is characterized as wild-type BRAF and mutant RAS.

### Claim 15

A method of treating a wild-type BRAF melanoma tumor in a subject comprising administering to the subject a DNA damaging agent and a pan-RAF inhibitor, wherein the pan-RAF inhibitor is RAF265, wherein the DNA damaging agent is gemcitabine, 5-fluorouracil, cytarabine, methotrexate, pyrimethamine, bleomycin, oxaliplatin, cisplatin, carboplatin, etoposide, doxorubicin, vinorelbin, mitoxantrone, podophyllotoxin, aphidicolin, fotemustine, carmustine, [(5S,6S)-6-Acetyloxy-11-methoxy-2,7.7-trimethyl-13-oxo-8-oxa-2-azapentacyclo[12.8.0.03,12.04,9.016,21]docosa-1(22),3,9,11,14,16,18,20-octaen-5-yl] acetate (S-23906), (19S)-10,19-diethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione(SN-38), topotecan, camptothecin, rebeccamycin, or any pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 1)

The method of claim 1, wherein the tumor is a colon cancer tumor.