# US 2021/0340544 A1 · Tlr9 modulators for treating cancer

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- Number: US 2021/0340544 A1
- Document ID: US20210340544A1
- Status: Published application
- Kind: A1
- Application number: 17/286,209
- Filed: 2019-10-18
- Published: 2021-11-04
- Earliest claimed: 2018-10-18
- Assignees: Idera Pharmaceuticals, Inc.
- Applicants: Idera Pharmaceuticals, Inc.
- Inventors: Cara HAYMAKER; Chantale BERNATCHEZ; Adi DIAB; Srinivas CHUNDURU
- Web page: https://patentgrep.com/patent/US20210340544A1

## CPC

- C12N 15/117: Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
- A61K 31/712: Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
- 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}
- C12N 2310/17: Immunomodulatory nucleic acids
- C12N 2310/3183: Diol linkers, e.g. glycols or propanediols
- C12N 2310/336: Modified G
- C12N 2320/31: Combination therapy
- C12N 2320/35: based on a specific dosage / administration regimen
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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

The present disclosure relates to methods for treating cancer in patients having low expression of MHC Class I genes, and in patients having increased serum levels of PD-L2 by administration of a TLR9 agonist.

## Claims

### Claim 1

A method for treating a tumor in a patient having low tumor expression of MHC Class I genes, the method comprising:
intratumoral administration of a TLR 9 agonist.

### Claim 2 (depends on 1)

The method of claim 1, wherein the TLR agonist has the structure: 5′-TCG1AACG1TTCG1-X-G1CTTG1CAAG1CT-5′ (5′ SEQ ID NO:4-X-SEQ ID NO:4 5′), wherein G1 is 2′-deoxy-7-deazaguanosine and X is a glycerol linker.

### Claim 3 (depends on 1)

The method of claim 1, further comprising administration of at least one immune checkpoint inhibitor.

### Claim at position 4

4-5. (canceled)

### Claim 6 (depends on 3)

The method of claim 3, wherein the immune checkpoint inhibitor is administered after the TLR9 agonist.

### Claim at position 6

7-8. (canceled)

### Claim 9 (depends on 1)

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

### Claim 10 (depends on 1)

The method of claim 1, wherein the tumor is selected from melanoma, lung tumor, kidney tumor, prostate tumor, cervical tumor, colorectal tumor, colon tumor, pancreatic tumor, ovarian tumor, urothelial tumor, gastric/GEJ tumor, head and neck tumor, glioblastoma, Merkel cell tumor, head and neck squamous cell carcinoma (HNSCC), non-small cell lung carcinoma (NSCLC), small cell lung tumor (SCLC), or bladder tumor.

### Claim 11 (depends on 9)

The method of claim 9, wherein the tumor is metastatic melanoma.

### Claim at position 10

12-13. (canceled)

### Claim 14 (depends on 1)

The method of claim 1, wherein the low expression of tumor MHC Class I gene expression is less than 25% of the expression in healthy tissue.

### Claim 15

(canceled)

### Claim 16 (depends on 3)

The method of claim 3, wherein the immune checkpoint inhibitor is selected from a checkpoint inhibitor that targets PD-1, PD-L1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), LAG3, B7-H3, B7-H4, KIR, OX40, IgG, IDO-2, CEACAM1, TNFRSF4, BTLA, OX40L, and TIM3.

### Claim at position 14

17-23. (canceled)

### Claim 24 (depends on 2)

The method of claim 2, wherein the TLR9 agonist is administered at a dose of from about 1 mg to about 20 mg.

### Claim at position 16

25-26. (canceled)

### Claim 27

A method for treating a tumor in a patient comprising:
(a) determining MHC Class I gene expression in a tumor sample and
(b) administering a TLR9 agonist if said gene expression is present in less than 50% of the tumor cells.

### Claim 28 (depends on 27)

The method of claim 27, wherein the TLR9 agonist has the structure: 5′-TCG1AACG1TTCG1-X-G1CTTG1CAAG1CT-5′ (5′ SEQ ID NO:4-X-SEQ ID NO:4 5′), wherein G1 is 2′-deoxy-7-deazaguanosine and X is a glycerol linker.

### Claim 29 (depends on 27)

The method of claim 27, further comprising administering at least one immune checkpoint inhibitor.

### Claim at position 20

30-52. (canceled)

### Claim 53

A method for treating a tumor in a patient having increased serum PD-L2 levels, the method comprising:
(a) determining the level of PD-L2 levels in said patient; and
(b) administering a TLR9 agonist if said PD-L2 levels in said patient are increased as compared with a control level of PD-L2.

### Claim 54 (depends on 53)

The method of claim 53, wherein the increased serum PD-L2 level is between about 750 pg/mL and 5000 pg/mL.

### Claim at position 23

55-58. (canceled)

### Claim 59 (depends on 53)

The method of claim 53, wherein the TLR9 agonist has the structure: 5′-TCG1AACG1TTCG1-X-G1CTTG1CAAG1CT-5′ (5′ SEQ ID NO:4-X-SEQ ID NO:4 5′), wherein G1 is 2′-deoxy-7-deazaguanosine and X is a glycerol linker.

### Claim 60 (depends on 53)

The method of claim 53, further comprising administering at least one immune checkpoint inhibitor.

### Claim at position 26

61-62. (canceled)

### Claim 63 (depends on 60)

The method of claim 60, wherein the immune checkpoint inhibitor is administered after the TLR9 agonist.

### Claim at position 28

64-66. (canceled)

### Claim 67 (depends on 53)

The method of claim 53, wherein the tumor is selected from melanoma, lung tumor, kidney tumor, prostate tumor, cervical tumor, colorectal tumor, colon tumor, pancreatic tumor, ovarian tumor, urothelial tumor, gastric/GEJ tumor, head and neck tumor, glioblastoma, Merkel cell tumor, head and neck squamous cell carcinoma (HNSCC), non-small cell lung carcinoma (NSCLC), small cell lung tumor (SCLC), or bladder tumor.

### Claim at position 30

68-78. (canceled)

### Claim 79 (depends on 53)

The method of claim 53, wherein the TLR9 agonist is administered at a dose of from about 1 mg to about 20 mg.

### Claim 80

(canceled)