# US 2021/0280271 A1 · Developing classifiers for stratifying patients

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- Number: US 2021/0280271 A1
- Document ID: US20210280271A1
- Status: Published application
- Kind: A1
- Application number: 17/315,580
- Filed: 2021-05-10
- Published: 2021-09-09
- Earliest claimed: 2019-06-27
- Assignees: Scipher Medicine Corporation
- Applicants: Scipher Medicine Corporation
- Inventors: Susan Dina Ghiassian; Theodore R. Mellors; Marc Santolini; Asher Ameli; Nancy Schoenbrunner; Viatcheslav R. Akmaev; Keith J. Johnson
- Web page: https://patentgrep.com/patent/US20210280271A1

## 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}
- G16B 20/20: Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
- A61K 38/1793: {for cytokines; for lymphokines; for interferons}
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 16/241: {Tumor Necrosis Factors}
- C12Q 1/6883: for diseases caused by alterations of genetic material
- G16B 40/00: ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
- G16H 10/60: for patient-specific data, e.g. for electronic patient records
- G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients
- G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems
- G16H 50/70: for mining of medical data, e.g. analysing previous cases of other patients
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/55: Fab or Fab'
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/158: Expression markers
- G01N 2333/525: Tumor necrosis factor [TNF]
- 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)
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA

## Abstract

Presented herein are systems and methods for developing classifiers useful for predicting response to particular treatments. For example, in some embodiments, the present disclosure provides a method of treating subjects suffering from an autoimmune disorder, the method comprising a step of: administering an anti-TNF therapy to subjects who have been determined to be responsive via a classifier established to distinguish between responsive and non-responsive prior subjects in a cohort who have received the anti-TNF therapy.

## Claims

### Claim at position 1

1-74. (canceled)

### Claim 75

A method of treating a subject suffering from an autoimmune disorder, comprising administering to the subject an anti-TNF therapy, wherein the subject has been determined to be responsive via a classifier determined to distinguish between responsive and non-responsive subjects who have received the anti-TNF therapy (“prior subjects”), and the classifier measures expression of one or more genes selected from: ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2.

### Claim 76 (depends on 75)

The method of claim 75, wherein the classifier further assesses at least one of:
presence of one or more single nucleotide polymorphisms (SNPs) in an expressed sequence of the one or more genes; or
at least one clinical characteristic.

### Claim 77 (depends on 75)

The method of claim 75, wherein the classifier measures expression of two or more genes selected from: ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2.

### Claim 78 (depends on 77)

The method of claim 77, wherein the classifier measures three or more genes selected from ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2.

### Claim 79 (depends on 78)

The method of claim 78, wherein the classifier measures each of the following genes: ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2

### Claim 80 (depends on 79)

The method of claim 79, wherein the classifier measures expression of each of the following genes:
ARPC1A
LOC100506083
ATAT1
MORN2
ATRAID
NGF
CD27
RHOBTB1
CHMP7
RNGTT
COMMD5
SETD9
CORO2B
SNX8
CYSLTR2
SPINT2
DNAJC7
SPON2
GOLGA1
SSNA1
HPCA
STOML2
IMPDH2
SUOX
KAT8
TMEM258
KLHDC3
UBL7-AS1

### Claim 81 (depends on 76)

The method of claim 76, wherein the at least one clinical characteristic is selected from: body-mass index (BMI), gender, age, race, previous therapy treatment, disease duration, C-reactive protein level, presence of anti-cyclic citrullinated peptide, presence of rheumatoid factor, patient global assessment, treatment response rate (e.g., ACR20, ACR50, ACR70), and combinations thereof.

### Claim 82 (depends on 75)

The method of claim 75, wherein the anti-TNF therapy comprises administration of infliximab, adalimumab, etanercept, cirtolizumab pegol, goliluma, or biosimilars thereof.

### Claim 83 (depends on 82)

The method of claim 82, wherein the anti-TNF therapy comprises administration of adalimumab, infliximab, or eternacept.

### Claim 84 (depends on 75)

The method of claim 75, wherein the autoimmune disorder is selected from rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, chronic psoriasis, hidradenitis suppurativa, multiple sclerosis, and juvenile idiopathic arthritis.

### Claim 85 (depends on 84)

The method of claim 84, wherein the autoimmune disorder is rheumatoid arthritis.

### Claim 86 (depends on 75)

The method of claim 75, wherein the classifier identifies at least 40% of subjects within a population that are non-responsive with at least 90% accuracy, wherein the population comprises at least 170 subjects.

### Claim 87 (depends on 75)

The method of claim 75, wherein the subject is determined to be responsive when the classifier determines that the subject does not express one or more of ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2.

### Claim 88

A method of treating a subject suffering from an autoimmune disorder, comprising administering to the subject an alternative to anti-TNF therapy, wherein the subject has been determined to be non-responsive via a classifier determined to distinguish between responsive and non-responsive subjects who have received the anti-TNF therapy (“prior subjects”), and the classifier measures expression of one or more genes selected from: ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2.

### Claim 89 (depends on 88)

The method of claim 88, wherein the alternative to anti-TNF therapy is selected from rituximab, sarilumab, tofacitinib citrate, lefunomide, vedolizumab, tocilizumab, anakinra, and abatacept.

### Claim 90 (depends on 88)

The method of claim 88, wherein the autoimmune disorder is selected from rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, chronic psoriasis, hidradenitis suppurativa, multiple sclerosis, and juvenile idiopathic arthritis.

### Claim 91 (depends on 90)

The method of claim 90, wherein the autoimmune disorder is rheumatoid arthritis.

### Claim 92 (depends on 88)

The method of claim 88, wherein the classifier further assesses at least one of:
presence of one or more single nucleotide polymorphisms (SNPs) in an expressed sequence of the one or more genes; or
at least one clinical characteristic.

### Claim 93 (depends on 92)

The method of claim 92, wherein the at least one clinical characteristic is selected from: body-mass index (BMI), gender, age, race, previous therapy treatment, disease duration, C-reactive protein level, presence of anti-cyclic citrullinated peptide, presence of rheumatoid factor, patient global assessment, treatment response rate (e.g., ACR20, ACR50, ACR70), and combinations thereof.

### Claim 94 (depends on 88)

The method of claim 88, wherein the subject is determined to be non-responsive when the classifier determines that the subject expresses one or more of ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2.

### Claim 95

A method of treating a subject suffering from an autoimmune disorder, the method comprising steps of:
(a) receiving, by a processor of a computing device, data corresponding to expression levels of each of one or more genes of the subject, where the genes are selected from ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2;
(b) automatically determining, by the processor, a classification of the subject as responsive or non-responsive to an anti-TNF therapy using the data received in step (a); and, optionally,
(c) administering an alternative to anti-TNF therapy to the subject for treatment of the autoimmune disorder if the subject is classified as non-responsive to the anti-TNF therapy; or administering the anti-TNF therapy if the subject is classified as responsive to the anti-TNF therapy.

### Claim 96 (depends on 95)

The method of claim 95, wherein the anti-TNF therapy comprises administration of infliximab, adalimumab, etanercept, cirtolizumab pegol, goliluma, or biosimilars thereof.

### Claim 97 (depends on 95)

The method of claim 95, wherein the alternative to anti-TNF therapy is selected from rituximab, sarilumab, tofacitinib citrate, lefunomide, vedolizumab, tocilizumab, anakinra, and abatacept.

### Claim 98 (depends on 95)

The method of claim 95, wherein the autoimmune disorder is selected from rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, chronic psoriasis, hidradenitis suppurativa, multiple sclerosis, and juvenile idiopathic arthritis.

### Claim 99 (depends on 97)

The method of claim 97, wherein the autoimmune disorder is rheumatoid arthritis.

### Claim 100

A method of classifying a subject suffering from an autoimmune disorder as likely responsive or likely non-responsive to an anti-TNF therapy prior to any administration of said anti-TNF therapy to said subject, the method comprising steps of:
(a) receiving, by a processor of a computing device, data corresponding to an expression level for the subject of each of one or more genes selected from the group consisting of ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2; and
(b) automatically determining, by the processor, a classification of the subject as responsive or non-responsive to the anti-TNF therapy using the data received in step (a).

### Claim 101 (depends on 100)

The method of claim 100, wherein the autoimmune disorder is selected from rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, chronic psoriasis, hidradenitis suppurativa, multiple sclerosis, and juvenile idiopathic arthritis.

### Claim 102 (depends on 100)

The method of claim 100, wherein the autoimmune disorder is rheumatoid arthritis.

### Claim 103 (depends on 100)

The method of claim 100, wherein the anti-TNF therapy comprises administration of infliximab, adalimumab, etanercept, cirtolizumab pegol, goliluma, or biosimilars thereof.

### Claim 104 (depends on 100)

The method of claim 100, wherein the subject is determined to be responsive subject if the subject does not express one or more of ATRAID, COMMD5, GOLGA1, IMPDH2, SPINT2, SPON2, and STOML2.