# US 2021/0330742 A1 · PHARMACEUTICAL COMPOSITION COMPRISING RUNX3 PROTEIN AND CDK4 INHIBITOR OR mTOR INHIBITOR COTREATMENT FOR PREVENTION OR 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 2021/0330742 A1 - Document ID: US20210330742A1 - Status: Published application - Kind: A1 - Application number: 17/239,433 - Filed: 2021-04-23 - Published: 2021-10-28 - Earliest claimed: 2020-04-23 - Assignees: Run-x Corporation - Applicants: Run-x Corporation - Inventors: Suk Chul Bae; Jung Won Lee; You Soub Lee - Web page: https://patentgrep.com/patent/US20210330742A1 ## CPC - A61K 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)} - A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 38/1709: {from mammals} - A61K 47/46: Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts - A61P 35/00: Antineoplastic agents - C07K 14/4702: {Regulators; Modulating activity} - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - C12N 2710/10343: viral genome or elements thereof as genetic vector - C12N 2750/14143: viral genome or elements thereof as genetic vector - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - 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 - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The present invention relates to a pharmaceutical composition for prevention or treatment of cancer, comprising a Runx3 (Runt-related transcription factor 3) protein, a polynucleotide encoding thereof, a vector carrying the polynucleotide or a virus or cell transformed with the vector; and a CDK4 inhibitor or an mTOR inhibitor as an active ingredient. It was confirmed that the binding of Runx3 and BRD2 was maintained for up to 8 hours when the CDK4 inhibitor (PD0332991) was present at the concentration of 11 nM known to be non-toxic to normal cells. It was also confirmed that the binding of Runx3 and BRD2 was maintained for up to 8 hours when the mTOR inhibitor (rapamycin) was present at the concentration of 100 nM known to be non-cytotoxic to normal cells. In addition, it was confirmed that the cancer apoptotic effect was significantly increased when the CDK4 inhibitor or mTOR inhibitor was administered simultaneously with Runx3 than when Runx3 was administered alone to Runx3 deficient cancer cells. Therefore, the CDK4 inhibitor or mTOR inhibitor can be effectively used for preventing or treating various cancers by administering the same in combination with Runx3. ## Claims ### Claim 1 A method for treating cancer, comprising administering a Runx3 (Runt-related transcription factor 3) protein, a polynucleotide encoding thereof, a vector carrying the polynucleotide or a virus or cell transformed with the vector; and a CDK4 inhibitor in a pharmaceutically effective amount to a subject in need thereof. ### Claim 2 A method for treating cancer, comprising administering a Runx3 (Runt-related transcription factor 3) protein, a polynucleotide encoding thereof, a vector carrying the polynucleotide or a virus or cell transformed with the vector; and an mTOR inhibitor in a pharmaceutically effective amount to a subject in need thereof. ### Claim 3 (depends on 1) The method for treating cancer according to claim 1, wherein the CDK4 inhibitor is any one selected from the group consisting of Abemaciclib, Palbociclib and Ribociclib ### Claim 4 (depends on 1) The method for treating cancer according to claim 1, wherein the CDK4 inhibitor is Palbociclib represented by the following formula 1. ### Claim 5 (depends on 2) The method for treating cancer according to claim 2, wherein the mTOR inhibitor is any one selected from the group consisting of rapamycin, Ridaforolimus, Everolimus and Temsirolimus. ### Claim 6 (depends on 2) The method for treating cancer according to claim 2, wherein the mTOR inhibitor is rapamycin represented by the following formula 2. ### Claim 7 (depends on 1) The method for treating cancer according to claim 1, wherein the cancer is solid cancer. ### Claim 8 (depends on 7) The method for treating cancer according to claim 7, wherein the solid cancer is one or more selected from the group consisting of lung cancer, pancreatic cancer, liver cancer and stomach cancer. ### Claim 9 (depends on 1) The method for treating cancer according to claim 1, wherein the Runx3 forms a complex with Brd2. ### Claim 10 (depends on 1) The method for treating cancer according to claim 1, wherein the CDK4 inhibitor increases the time for maintaining the Runx3-Brd2 complex. ### Claim 11 (depends on 2) The method for treating cancer according to claim 2, wherein the mTOR inhibitor increases the time for maintaining the Runx3-Brd2 complex. ### Claim 12 (depends on 9) The method for treating cancer according to claim 9, wherein the BRD2 binds to the acetylated Runx3. ### Claim 13 (depends on 9) The method for treating cancer according to claim 9, wherein the complex is formed by mitogenic stimulation. ### Claim 14 (depends on 9) The method for treating cancer according to claim 9, wherein the complex contributes to the determination of restriction point (R-point). ### Claim 15 (depends on 1) The method for treating cancer according to claim 1, wherein the Runx3 protein is composed of the amino acid sequence represented by SEQ. ID. NO: 11 or SEQ. ID. NO: 12. ### Claim 16 (depends on 1) The method for treating cancer according to claim 1, wherein the polynucleotide encoding the Runx3 protein is composed of the nucleotide sequence represented by SEQ. ID. NO: 13 or SEQ. ID. NO: 14. ### Claim 17 (depends on 1) The method for treating cancer according to claim 1, wherein the vector is linear DNA or plasmid DNA. ### Claim 18 (depends on 1) The method for treating cancer according to claim 1, wherein the virus is any one selected from the group consisting of retrovirus, adenovirus, herpes simplex virus and lentivirus. ### Claim 19 (depends on 1) The method for treating cancer according to claim 1, wherein the cell is bacterium. ### Claim 20 (depends on 19) The method for treating cancer according to claim 19, wherein the bacterium is Listeria, Shigella, Salmonella or E. coli.