# US 2018/0021270 A1 · Methods for the treatment of cancer using coenzyme q10 in combination with immune checkpoint modulators

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

- Number: US 2018/0021270 A1
- Document ID: US20180021270A1
- Status: Published application
- Kind: A1
- Application number: 15/656,986
- Filed: 2017-07-21
- Published: 2018-01-25
- Earliest claimed: 2016-07-21
- Assignees: Berg LLC
- Applicants: Berg LLC
- Inventors: Maria Dorothea Nastke; Shiva Kazerounian; Anne R. Diers; Vivek K. Vishnudas; Stephane Gesta; Rangaprasad Sarangarajan; Niven Rajin Narain
- Web page: https://patentgrep.com/patent/US20180021270A1

## CPC

- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- 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 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 39/39541: {against normal tissues, cells}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 39/39575: {against materials from other living beings excluding bacteria and viruses, e.g. protozoa, fungi, plants}
- A61K 47/02: Inorganic compounds
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61P 35/02: specific for leukemia
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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)

## Abstract

Presented herein are methods for the treatment of oncological disorders by the co-administration of Coenzyme Q10 and immune checkpoint modulators. The Coenzyme Q10 formulations may be at least one of intravenous, topical, or by inhalation. Co-administration of the Coenzyme Q10 formulations may be prior to, concurrent or substantially concurrent with, intermittent with or subsequent to the administration of the chemotherapy.

## Claims

### Claim 1

A method of treating an oncological disorder in a subject in need thereof, comprising:
(a) administering coenzyme Q10 (CoQ10) to the subject; and
(b) administering at least one immune checkpoint modulator of an immune checkpoint molecule to the subject;
such that the oncological disorder is treated.

### Claim 2 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is selected from the group consisting of CD27, CD28, CD40, CD122, OX40, GITR, ICOS, 4-1BB, ADORA2A, B7-H3, B7-H4, BTLA, CTLA-4, IDO, KIR, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, and VISTA.

### Claim 3 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is selected from the group consisting of PD-1, PD-L1, PD-L2, CTLA-4, LAG-3, TIM-3 and VISTA.

### Claim 4 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is selected from the group consisting of PD-1, PD-L1 and CTLA-4.

### Claim 5 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is a stimulatory immune checkpoint molecule.

### Claim 6 (depends on 5)

The method of claim 5, wherein the immune checkpoint modulator is an agonist of the stimulatory immune checkpoint molecule.

### Claim 7 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is an inhibitory immune checkpoint molecule.

### Claim 8 (depends on 7)

The method of claim 7, wherein the immune checkpoint modulator is an antagonist of the inhibitory immune checkpoint molecule.

### Claim 9 (depends on 1)

The method of claim 1, wherein the immune checkpoint modulator is selected from the group consisting of a small molecule, an inhibitory RNA, an antisense molecule, and an immune checkpoint binding protein.

### Claim 10 (depends on 9)

The method of claim 9, wherein the immune checkpoint modulator is an immune checkpoint binding protein.

### Claim 11 (depends on 10)

The method of claim 10, wherein the immune checkpoint binding protein is selected from the group consisting of an antibody, antibody Fab fragment, divalent antibody, antibody drug conjugate, scFv, fusion protein, bivalent antibody, and tetravalant antibody.

### Claim 12 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is PD-1.

### Claim 13 (depends on 12)

The method of claim 12, wherein the immune checkpoint modulator is selected from the group consisting of pembrolizumab, novolumab, pidilizumab, SHR-1210, MEDI0680R01, BBg-A317, TSR-042, REGN2810 and PF-06801591.

### Claim 14 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is PD-L1.

### Claim 15 (depends on 14)

The method of claim 14, wherein the immune checkpoint modulator is selected from the group consisting of durvalumab, atezolizumab, avelumab, MDX-1105, AMP-224 and LY3300054.

### Claim 16 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is CTLA-4.

### Claim 17 (depends on 16)

The method of claim 16, wherein the immune checkpoint modulator is selected from the group consisting of ipilimumab, tremelimumab, JMW-3B3 and AGEN1884.

### Claim 18 (depends on 1, 2)

The method of claim 1 or 2, wherein the immune checkpoint molecule is LAG-3.

### Claim 19 (depends on 18)

The method of claim 18, wherein the immune checkpoint modulator is selected from the group consisting of pembrolizumab, nivolumab, pidilizumab, SHR-1210, MEDI0680, PDR001, BGB-A317, TSR-042, REGN2810, and PF-06801591.

### Claim 20 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is TIM-3.

### Claim 21 (depends on 20)

The method of claim 20, wherein the immune checkpoint modulator is selected from the group consisting of TSR-022 and MGB453.

### Claim 22 (depends on 1)

The method of claim 1, wherein the immune checkpoint molecule is VISTA.

### Claim 23 (depends on 22)

The method of claim 22, wherein the immune checkpoint modulator is selected from the group consisting of TSR-022 and MGB453.

### Claim 24 (depends on 1)

The method of claim 1, wherein the Coenzyme Q10 is administered before administration of the immune checkpoint modulator.

### Claim 25 (depends on 1)

The method of claim 1, wherein the Coenzyme Q10 is administered concurrently with the immune checkpoint modulator.

### Claim 26 (depends on 1)

The method of claim 1, wherein the Coenzyme Q10 is administered after administration of the immune checkpoint modulator.

### Claim 27 (depends on 1)

The method of claim 1, wherein a response of the oncological disorder to treatment is improved relative to a treatment with the at least one immune checkpoint modulator alone.

### Claim 28 (depends on 27)

The method of claim 27, wherein the response in a population of patients is improved by at least 5%, at least 10%, at least 15%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80% or more relative to treatment with the at least one immune checkpoint modulator alone.

### Claim 29 (depends on 27)

The method of claim 27, wherein the response comprises any one or more of reduction in tumor burden, reduction in tumor size, inhibition of tumor growth, achieving stable oncological disorder in a subject with a progressive oncological disorder prior to treatment, increased time to progression of the oncological disorder, and increased time of survival.

### Claim 30 (depends on 1)

The method of claim 1, wherein the Coenzyme Q10 and the immune checkpoint modulator act synergistically.

### Claim 31 (depends on 1)

The method of claim 1, wherein the CoQ10 is administered topically.

### Claim 32 (depends on 1)

The method of claim 1, wherein the CoQ10 is administered by injection or infusion.

### Claim 33 (depends on 32)

The method of claim 32, wherein the CoQ10 is administered by intravenous administration.

### Claim 34 (depends on 32)

The method of claim 32, wherein the CoQ10 is administered by continuous intravenous infusion.

### Claim 35 (depends on 34)

The method of claim 34, wherein the CoQ10 is administered by continuous infusion over between 24 and 96 hours.

### Claim 36 (depends on 1)

The method of claim 1, wherein the oncological disorder is selected from the group consisting of a carcinoma, sarcoma, lymphoma, melanoma, and leukemia.

### Claim 37 (depends on 1)

The method of claim 1, wherein the oncological disorder is selected from the group consisting of pancreatic cancer, breast cancer, liver cancer, skin cancer, lung cancer, colon cancer, prostate cancer, thyroid cancer, bladder cancer, rectal cancer, endometrial cancer, kidney cancer, bone cancer, brain cancer, cervical cancer, stomach cancer, mouth and oral cancers, neuroblastoma, testicular cancer, uterine cancer, and vulvar cancer.

### Claim 38 (depends on 37)

The method of claim 37, wherein the skin cancer is selected from the group consisting of melanoma, squamous cell carcinoma, basal cell carcinoma, and cutaneous T-cell lymphoma (CTCL).

### Claim 39 (depends on 1)

The method of claim 1, wherein the subject is human.