# US 10,765,690 B2 · TLR4 agonists and compositions thereof and their use in the treatment of cancer

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- Number: US 10,765,690 B2
- Document ID: US10765690B2
- Status: Granted
- Kind: B2
- Application number: 15/749,854
- Filed: 2016-06-03
- Published: 2018-08-09
- Granted: 2020-09-08
- Earliest claimed: 2015-08-06
- Assignees: GlaxoSmithKline Intellectual Property Development Limited
- Applicants: GlaxoSmithKline Intellectual Property Development Limited
- Inventors: Christopher W. Cluff; Hua-Xin Gao
- Web page: https://patentgrep.com/patent/US10765690B2

## CPC

- A61K 31/7032: attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
- 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 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- A61K 2039/505: {comprising antibodies}
- 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

Disclosed is a TLR4 agonist alone or in combination with an anti-cancer agent and pharmaceutical compositions thereof, uses thereof, and methods of treatment comprising administering said composition or combination, including uses in cancer.

## Claims

### Claim 1

A method of treating cancer in a human in need thereof comprising administering a composition comprising a TLR4 agonist which is CRX-601, having the formula shown below:
for treating cancer and combined with an anti-cancer agent, wherein the cancer is a solid tumor and selected from the group consisting of (1) primary and secondary metastatic forms of head and neck cancer and (2) carcinoma of the head and neck.

### Claim 2

A method of treating cancer in a human in need thereof comprising administering a pharmaceutical composition comprising a therapeutically effective amount of an anti-cancer agent and a second pharmaceutical composition comprising a therapeutically effective amount of the TLR4 agonist, which CRX-601, having the formula shown below:
wherein the cancer is wherein the cancer is a solid tumor and selected from the group consisting of (1) primary and secondary metastatic forms of head and neck cancer and (2) carcinoma of the head and neck.

### Claim 3 (depends on 2)

The method as claimed in claim 2, wherein the anti-cancer agent and the TLR4 agonist, CRX-601, are administered at the same time.

### Claim 4 (depends on 2)

The method as claimed in claim 2, wherein the anti-cancer agent and the TLR4 agonist, CRX-601, are administered sequentially, in any order.

### Claim 5 (depends on 2)

The method as claimed in claim 2, wherein the anti-cancer agent and the TLR4 agonist, CRX-601, are administered via a systemic intravenous dose.

### Claim 6 (depends on 2)

The method as claimed in claim 2, wherein the anti-cancer agent, and the TLR4 agonist, CRX-601, is administered intratumorally.

### Claim 7 (depends on 2)

The method as claimed in claim 2, wherein the anti-cancer agent is administered intratumorally, and the TLR4 agonist, CRX-601, is administered intravenously.

### Claim 8 (depends on 2)

The method as claimed in claim 2, wherein the anti-cancer agent and the TLR4 agonist, CRX-601, are both administered intratumorally.

### Claim 9 (depends on 2)

The method of claim 2, wherein anti-cancer agent is an anti PD-1 antibody.