# US 2025/0155451 A1 · Cytokine profiling analysis

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- Number: US 2025/0155451 A1
- Document ID: US20250155451A1
- Status: Published application
- Kind: A1
- Application number: 19/025,687
- Filed: 2025-01-16
- Published: 2025-05-15
- Earliest claimed: 2016-04-05
- Assignees: Bristol-Myers Squibb Company
- Applicants: Bristol-Myers Squibb Company
- Inventors: Benedetto FARSACI
- Web page: https://patentgrep.com/patent/US20250155451A1

## CPC

- G01N 33/6863: {Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors}
- C07K 16/2803: {against the immunoglobulin superfamily}
- G01N 33/5752: of the lungs
- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- G01N 2333/52: Assays involving cytokines
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- 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

This invention relates to methods for predicting a prognosis of a patient with cancer in need of an anti-cancer treatment comprising measuring a cytokine score from a sample obtained from the patient. In some embodiments, the subject is administered an anti-cancer treatment, e.g., an anti-PD-1 antibody, following the cytokine score measurement. In some embodiments, the cancer is lung cancer.

## Claims

### Claim 1

A method of treating a patient in need of an anti-cancer treatment comprising administering to the patient an effective amount of an anti-PD-1 antibody or antigen-binding portion thereof (“anti-PD-1 antibody”) or an effective amount of an anti-PD-L1 antibody or antigen-binding portion thereof (“anti-PD-L1 antibody”);
wherein the patient has been identified as having a cytokine score that is higher than an average cytokine score;
wherein the cytokine score is the sum of a point designated to the level of at least two cytokines in a sample obtained from the patient, wherein the point is X if the sample has a high concentration of a cytokine that is positively associated with overall survival of the patient following the administration of the anti-PD-1 antibody or the anti-PD-L1 antibody or a low concentration of a cytokine that is negatively associated with overall survival of the patient following the administration of the anti-PD-1 antibody or the anti-PD-L1 antibody, wherein the point is Z if the sample has a low concentration of a cytokine that is positively associated with the overall survival of the patient following the administration of the anti-PD-1 antibody or the anti-PD-L1 antibody or a high concentration of a cytokine that is negatively associated with the overall survival of the patient following the administration of the anti-PD-1 antibody or the anti-PD-L1 antibody, and, optionally, wherein the point is Y if the sample has a medium concentration of a cytokine that is either negatively or positively associated with overall survival of the patient following the administration of the anti-PD-1 antibody or the anti-PD-L1 antibody;
wherein the at least two cytokines are selected from the group consisting of MIG, IL-1RA, MMP-3, IL-8, FRTN, ICAM, VWF, MICA, IP-10, CRP, IL-18, VDBP, IL-6, MIP1B, MCP2, ENRAGE, IL-2RA, B2M, RANTES, TNFR2, and any combination thereof.

### Claim 2 (depends on 1)

The method of claim 1, further comprising measuring the cytokine score from the sample obtained from the subject prior to administering the anti-PD-1 antibody or the anti-PD-L1 antibody is higher than an average cytokine score.

### Claim 3 (depends on 2)

The method of claim 2, wherein the cytokine score is at least about 1% higher than the average cytokine score.

### Claim 4 (depends on 1)

The method of claim 1, wherein X is any value, Z is a value that is lower than X, and, optionally, Y is a value that is between X and Z.

### Claim 5 (depends on 1)

The method of claim 1, wherein Z is 0, Y is 1, and X is 2.

### Claim 6 (depends on 1)

The method of claim 1, wherein the average cytokine score is
any integer between 1 and 100.

### Claim 7 (depends on 1)

The method of claim 1, wherein the at least two cytokines comprises three cytokines.

### Claim 8 (depends on 1)

The method of claim 1, wherein the patient has lung cancer.

### Claim 9 (depends on 8)

The method of claim 8, wherein the lung cancer is non-small cell lung cancer.

### Claim 10 (depends on 1)

The method of claim 1, wherein the at least two cytokines are selected from the group consisting of MIG, IL-1RA, MMP-3, IL-8, FRTN, ICAM, VWF, MICA, IP-10, CRP, IL-18, VDBP, IL-6, MIP1B, and any combination thereof.

### Claim 11 (depends on 1)

The method of claim 1, wherein the at least two cytokines are selected from the group consisting of FRTN, MMP-3, IL-8, MCP2, ENRAGE, IL-2RA, IL-18, VWF, B2M, RANTES, MICA, TNFR2, VDBP, and any combination thereof.

### Claim 12 (depends on 1)

The method of claim 1, wherein the positively associated cytokines are selected from the group consisting of MIG, IL-1RA, MMP-3, and any combination thereof.

### Claim 13 (depends on 1)

The method of claim 1, wherein the negatively associated cytokines are selected from the group consisting of IL-8, FRTN, ICAM, VWF, MICA, IP-10, CRP, IL-18, VDBP, IL-6, MIP1B, and any combination thereof.

### Claim 14 (depends on 1)

The method of claim 1, wherein the positively associated cytokines are B2M, VDBP, or both.

### Claim 15 (depends on 1)

The method of claim 1, wherein the negatively associated cytokines are selected from the group consisting of FRTN, MMP-3, IL-8, MCP2, ENRAGE, IL-2RA, IL-18, VWF, RANTES, MICA, TNFR2, and any combination thereof.

### Claim at position 16

16-17. (canceled)

### Claim 18 (depends on 1)

The method of claim 1, wherein the anti-PD-1 antibody is nivolumab.

### Claim 19

(canceled)

### Claim 20 (depends on 1)

The method of claim 1, wherein the anti-PD-L1 antibody is selected from BMS-936559, MPDL3280A, MEDI4736, and MSB0010718C.

### Claim 21 (depends on 1)

The method of claim 1, wherein the anti-PD-1 antibody is pembrolizumab.

### Claim 22 (depends on 1)

The method of claim 1, wherein the at least two cytokines comprise four cytokines.

### Claim 23 (depends on 1)

The method of claim 1, wherein the at least two cytokines comprise five cytokines.
