# US 2019/0375847 A1 · Combination treatment for cancer

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- Number: US 2019/0375847 A1
- Document ID: US20190375847A1
- Status: Published application
- Kind: A1
- Application number: 16/485,270
- Filed: 2018-02-13
- Published: 2019-12-12
- Earliest claimed: 2017-02-15
- Assignees: GlaxoSmithKline Intellectual Property Development Limited; Board of Regents, The University of Texas System
- Applicants: Glaxosmithkline Intellectual Property Development Limited; Board of Regents, the University of Texas System
- Inventors: Maria Angelica CORTEZ; Sharareh NIKNAM; Jonathan E. SCHOENHALS; James W. WELSH; Niranjan YANAMANDRA
- Web page: https://patentgrep.com/patent/US20190375847A1

## CPC

- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- A61K 39/39541: {against normal tissues, cells}
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- C07K 16/2818: {against CD28 or CD152}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 2039/505: {comprising antibodies}
- A61N 2005/1098: {Enhancing the effect of the particle by an injected agent or implanted device}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/75: Agonist effect on antigen
- 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)
- 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
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)

## Abstract

Disclosed herein is a method of treatment involving the combination of an anti-OX40 antigen binding protein (e.g., an anti-OX40 agonist antibody) and/or radiotherapy, for use in treating a cancer. The cancer may include anti-PD-1 resistance.

## Claims

### Claim at position 1

-95. (canceled)

### Claim 96

A method of treating human cancer, the method comprising:
(i) administering an anti-human OX40 antigen binding protein comprising: (a) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1; (b) a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2; (c) a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3; (d) a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:7; (e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:8; and (f) a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:9; and,
(ii) administering radiotherapy;
wherein a therapeutically effective amount of the anti-human OX40 antigen binding protein and the radiotherapy is administered.

### Claim 97 (depends on 96)

The method of claim 96, wherein the radiotherapy is selected from the group consisting of systemic radiation therapy, external beam radiation therapy, image-guided radiation therapy, tomotherapy, stereotactic radio surgery, stereotactic body radiation therapy, and proton therapy.

### Claim 98 (depends on 96)

The method of claim 96, wherein the cancer is a solid tumor.

### Claim 99 (depends on 98)

The method of claim 98, wherein the solid tumor is selected from the group consisting of: melanoma, lung cancer, kidney cancer, breast cancer, head and neck cancer, colon cancer, ovarian cancer, pancreatic cancer, liver cancer, prostate cancer, bladder cancer, and gastric cancer.

### Claim 100 (depends on 96)

The method of claim 96, wherein the anti-human OX40 antigen binding protein is a monoclonal antibody.

### Claim 101 (depends on 100)

The method according to claim 100, wherein the anti-human OX40 monoclonal antibody is a human monoclonal antibody or a humanized monoclonal antibody.

### Claim 102 (depends on 100)

The method according to claim 100, wherein the anti-human OX40 monoclonal antibody is an IgG1 antibody isotype, an IgG4 antibody isotype, or a variant thereof.

### Claim 103 (depends on 96)

The method of claim 96, wherein the human cancer is anti-PD-1 resistant.

### Claim 104 (depends on 96)

The method of claim 96, wherein the anti-human OX40 antigen binding protein is administered systemically or intratumorally.

### Claim 105 (depends on 96)

The method of claim 96, wherein the anti-human OX40 antigen binding protein comprises:
(i) a light chain variable region comprising an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 11; and
(ii) a heavy chain variable region comprising an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 5.

### Claim 106 (depends on 105)

The method of claim 105, wherein the anti-human OX40 antigen binding protein comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:5 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:11.

### Claim 107 (depends on 96)

The method of claim 96, wherein the anti-human OX40 antigen binding protein comprises a heavy chain comprising an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as set forth in SEQ ID NO:48 and a light chain comprising an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as set forth in SEQ ID NO:49.

### Claim 108

A method of treating a human solid tumor, the method comprising:
(i) administering an anti-human OX40 monoclonal antibody, the antibody comprising: (a) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1; (b) a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2; (c) a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3; (d) a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:7; (e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:8; and, (f) a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:9;
(ii) administering radiotherapy; and,
(iii) administering an anti-PD-1 monoclonal antibody;
wherein a therapeutically effective amount of the anti-human OX40 monoclonal antibody, the radiotherapy, and the anti-PD-1 monoclonal antibody is administered.

### Claim 109 (depends on 108)

The method of claim 108, wherein the anti-PD-1 monoclonal antibody is pembrolizumab, or an antibody comprising 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to each of heavy chain SEQ ID NO:50 and light chain SEQ ID NO:51.

### Claim 110 (depends on 108)

The method of claim 108, wherein the anti-PD-1 monoclonal antibody is nivolumab, or an antibody having 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to each of heavy chain SEQ ID NO:98 and light chain SEQ ID NO:99.

### Claim 111 (depends on 108)

The method of claim 108, the method further comprising the administration of at least one additional anti-neoplastic agent.

### Claim 112 (depends on 108)

The method of claim 108, wherein the human solid tumor is selected from the group consisting of melanoma, lung cancer, kidney cancer, breast cancer, head and neck cancer, colon cancer, ovarian cancer, pancreatic cancer, liver cancer, prostate cancer, bladder cancer, and gastric cancer.

### Claim 113 (depends on 108)

The method of claim 108, wherein the human solid tumor is anti-PD-1 resistant.

### Claim 114

A method for reducing tumor size in a human in need thereof, the method comprising: (i) administering an anti-human OX40 monoclonal antibody; (ii) administering radiotherapy; and, (iii) administering an anti-PD-1 monoclonal antibody.

### Claim 115 (depends on 114)

The method of claim 114, wherein the anti-human OX40 monoclonal antibody comprises: (a) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1; (b) a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2; (c) a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3; (d) a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:7; (e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:8; and, (f) a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:9.

### Claim 116 (depends on 115)

The method of claim 115, wherein the tumor is a solid tumor selected from the group consisting of melanoma, lung cancer, kidney cancer, breast cancer, head and neck cancer, colon cancer, ovarian cancer, pancreatic cancer, liver cancer, prostate cancer, bladder cancer, and gastric cancer.

### Claim 117 (depends on 116)

The method of claim 116, wherein the anti-PD-1 monoclonal antibody is selected from the group consisting of: pembrolizumab; an antibody comprising 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to each of heavy chain SEQ ID NO:50 and light chain SEQ ID NO:51; nivolumab; and, an antibody having 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to each of heavy chain SEQ ID NO:98 and light chain SEQ ID NO:99.