# US 10,308,714 B2 · Cancer immunotherapy by disrupting PD-1/PD-L1 signaling

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- Number: US 10,308,714 B2
- Document ID: US10308714B2
- Status: Granted
- Kind: B2
- Application number: 16/024,340
- Filed: 2018-06-29
- Published: 2018-11-08
- Granted: 2019-06-04
- Earliest claimed: 2012-05-15
- Assignees: Bristol-Myers Squibb Company
- Applicants: Bristol-Myers Squibb Company
- Inventors: John P. Cogswell; Stacie M. Goldberg; Ashok K. Gupta; Maria Jure-Kunkel; Xi-Tao Wang; Jon M. Wigginton
- Web page: https://patentgrep.com/patent/US10308714B2

## CPC

- C07K 16/2818: {against CD28 or CD152}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/18: against material from animals or humans
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- G01N 2333/70596: Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1/PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.

## Claims

### Claim 1

A method of treating a tumor in a human subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-L1 antibody; wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion; wherein the tumor is derived from a bladder cancer; and wherein the tumor is refractory to a platinum based chemotherapy.

### Claim 2 (depends on 1)

The method of claim 1, wherein the tumor is advanced.

### Claim 3 (depends on 1)

The method of claim 1, wherein the tumor is locally advanced.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of the anti-PD-L1 antibody is administered once every 3 weeks.

### Claim 6 (depends on 1)

The method of claim 1, wherein the anti-PD-L1 antibody is formulated in a pharmaceutical composition.

### Claim 7 (depends on 6)

The method of claim 6, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an anti-oxidant, an aqueous carrier, a non-aqueous carrier, or any combination thereof.

### Claim 8 (depends on 7)

The method of claim 7, wherein the salt comprises a sodium salt.

### Claim 9 (depends on 7)

The method of claim 7, wherein the salt comprises sodium chloride.

### Claim 10 (depends on 1)

The method of claim 1, wherein at least 1% of tumor cells exhibit membrane PD-L1 expression.

### Claim 11 (depends on 1)

The method of claim 1, wherein at least 5% of tumor cells exhibit membrane PD-L1 expression.

### Claim 12 (depends on 1)

The method of claim 1, further comprising administering an anti-cancer agent.

### Claim 13 (depends on 2)

The method of claim 2, further comprising administering an anti-cancer agent.

### Claim 14 (depends on 3)

The method of claim 3, further comprising administering an anti-cancer agent.

### Claim 15 (depends on 4)

The method of claim 4, further comprising administering an anti-cancer agent.

### Claim 16 (depends on 10)

The method of claim 10, further comprising administering an anti-cancer agent.

### Claim 17 (depends on 12)

The method of claim 12, wherein the anti-cancer agent is a chemotherapy.

### Claim 18 (depends on 12)

The method of claim 12, wherein the anti-cancer agent is a radiotherapy.

### Claim 19 (depends on 13)

The method of claim 13, wherein the anti-cancer agent is a chemotherapy.

### Claim 20 (depends on 13)

The method of claim 13, wherein the anti-cancer agent is a radiotherapy.

### Claim 21 (depends on 14)

The method of claim 14, wherein the anti-cancer agent is a chemotherapy.

### Claim 22 (depends on 14)

The method of claim 14, wherein the anti-cancer agent is a radiotherapy.

### Claim 23 (depends on 1)

The method of claim 1, wherein the platinum-based chemotherapy comprises cisplatin, carboplatin, or both.

### Claim 24 (depends on 1)

The method of claim 1, wherein the subject is further administered a corticosteroid.

### Claim 25

A method of treating a tumor in a human subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-L1 antibody once every 3 weeks;
wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion; wherein the tumor is derived from a bladder cancer;
wherein the tumor is advanced or metastatic; and
wherein the tumor is refractory to a platinum based chemotherapy.

### Claim 26 (depends on 1)

The method of claims 1, wherein the subject is administered an antihistamine prior to the anti-PD-L1 antibody.

### Claim 27 (depends on 25)

The method of claims 25, wherein the subject is administered an antihistamine prior to the anti-PD-L1 antibody.