# US 10,370,455 B2 · Identification of VSIG8 as the putative VISTA receptor (V-R) and use thereof to produce VISTA/VSIG8 agonists and antagonists

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- Number: US 10,370,455 B2
- Document ID: US10370455B2
- Status: Granted
- Kind: B2
- Application number: 14/960,973
- Filed: 2015-12-07
- Published: 2016-06-09
- Granted: 2019-08-06
- Earliest claimed: 2014-12-05
- Assignees: Immunext, Inc.
- Applicants: Immunext, Inc.
- Inventors: Michael Molloy; Yalin Guo; Jay Rothstein; Michael Rosenzweig
- Web page: https://patentgrep.com/patent/US10370455B2

## CPC

- C07K 16/42: against immunoglobulins
- A61K 39/0011: {Cancer antigens}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- C07K 14/70503: {Immunoglobulin superfamily}
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C12N 15/1138: {against receptors or cell surface proteins}
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/531: Stem-loop; Hairpin
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)

## Abstract

The receptor for VISTA is identified (VSIG8) as well as the use of this receptor in the identification or synthesis of agonist or antagonist compounds, preferably antibodies, polypeptides and fusion proteins which agonize or antagonize the effects of VSIG8 and/or VISTA and/or the VSIG8/VISTA binding interaction. These antagonists may be used to suppress VISTA's suppressive effects on T cell immunity, and more particularly used in the treatment of cancer, or infectious disease. These agonist compounds may be used to potentiate or enhance VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity, such as in the treatment of autoimmunity, allergy or inflammatory conditions. Screening assays for identifying these agonists and antagonist compounds are also provided.

## Claims

### Claim 1

A method of treating cancer which method comprises the administration to a subject in need thereof a therapeutically effective amount of at least one antibody or antigen binding antibody fragment that binds to a VSIG8 polypeptide which has a sequence selected from SEQ ID NO: 1, 2, and 3, and wherein said antibody or antigen binding antibody fragment potentiates CD8+ T cell mediated anti-tumor immunity in said subject.

### Claim 2

A method of treating an infectious disease, which method comprises the administration to a subject in need thereof of a therapeutically effective amount of at least one antibody or antigen binding antibody fragment that binds to a VSIG8 polypeptide having an amino acid sequence selected from SEQ ID NO: 1, 2, and 3, and wherein said antibody or antigen binding antibody fragment potentiates CD8+ T cell mediated killing of infected cells in said subject.

### Claim 3 (depends on 1)

The method of claim 1, wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:1.

### Claim 4 (depends on 1)

The method of claim 1, wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:2.

### Claim 5 (depends on 1)

The method of claim 1, wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:3.

### Claim 6 (depends on 2)

The method of claim 2, wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:1.

### Claim 7 (depends on 2)

The method of claim 2, wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:2.

### Claim 8 (depends on 2)

The method of claim 2, wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:3.

### Claim 9 (depends on 1)

The method of claim 1, wherein said antibody or antigen binding antibody fragment comprises a human IgG1, IgG2, IgG3 or IgG4.

### Claim 10 (depends on 2)

The method of claim 2, wherein said antibody or antigen binding antibody fragment comprises a human IgG1, IgG2, IgG3 or IgG4.

### Claim 11 (depends on 1)

The method of claim 1, wherein said antibody or antigen binding antibody fragment comprises an IgG1, IgG2, IgG3 or IgG4 which is mutated to impair FcR and/or complement binding.

### Claim 12 (depends on 2)

The method of claim 2, wherein said antibody or antigen binding antibody fragment comprises an IgG1, IgG2, IgG3 or IgG4 which is mutated to impair FcR and/or complement binding.

### Claim 13 (depends on 1)

The method of claim 1, which further comprises the administration of an anti-human VISTA antibody.

### Claim 14 (depends on 2)

The method of claim 2, which further comprises the administration of an anti-human VISTA antibody.