# US 11,897,958 B2 · Hybridoma clones, monoclonal antibodies to VSIG-4, and methods of making and using

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- Number: US 11,897,958 B2
- Document ID: US11897958B2
- Status: Granted
- Kind: B2
- Application number: 16/997,797
- Filed: 2020-08-19
- Published: 2021-03-25
- Granted: 2024-02-13
- Earliest claimed: 2017-06-26
- Assignees: Bio-Techne Corporation
- Applicants: Bio-Techne Corporation
- Inventors: Birte Aggeler; Christine Goetz; Jody Bonnevier; Christopher Carlin Valley; Christopher Hammerbeck; Ernesto Ruben Resnik
- Web page: https://patentgrep.com/patent/US11897958B2

## CPC

- C07K 16/2854: {against selectins, e.g. CD62}
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 16/2803: {against the immunoglobulin superfamily}
- C12N 5/163: {one of the fusion partners being a B or a T lymphocyte}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)

## Abstract

Described herein are monoclonal antibodies that bind to VSIG-4 including antibodies that block the binding of VSIG-4 to SIGLEC-7, compositions including the monoclonal antibodies, and methods of making and using those antibodies and compositions.

## Claims

### Claim 1

A method of treating a mammalian cancer comprising exposing a mammal comprising a mammalian cancer cell to a monoclonal antibody that binds to VSIG-4, wherein the monoclonal antibody comprises:
a heavy chain variable region comprising the three complementarity determining regions (CDRs) of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528902.11 (ATCC Accession No. PTA-124187), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528902.11 (ATCC Accession No. PTA-124187);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528903.111 (ATCC Accession No. PTA-124188), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528903.111 (ATCC Accession No. PTA-124188);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528905.11 (ATCC Accession No. PTA-124189), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528905.11 (ATCC Accession No. PTA-124189);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528906.11 (ATCC Accession No. PTA-124178), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528906.11 (ATCC Accession No. PTA-124178);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528908.11 (ATCC Accession No. PTA-124179), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528908.11 (ATCC Accession No. PTA-124179);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528910.111 (ATCC Accession No. PTA-124180), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528910.111 (ATCC Accession No. PTA-124180);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528912.11 (ATCC Accession No. PTA-124181), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528912.11 (ATCC Accession No. PTA-124181);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528922.111 (ATCC Accession No. PTA-124182), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528922.111 (ATCC Accession No. PTA-124182);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528927.111 (ATCC Accession No. PTA-124183), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528927.111 (ATCC Accession No. PTA-124183);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Rt x hVSIG4 489509.11 (ATCC Accession No. PTA-124184), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Rt x hVSIG4 489509.11 (ATCC Accession No. PTA-124184);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Rt x hVSIG4 489517.111 (ATCC Accession No. PTA-124185), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Rt x hVSIG4 489517.111 (ATCC Accession No. PTA-124185); or
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Rt x hVSIG4 489518.11 (ATCC Accession No. PTA-124186), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Rt x hVSIG4 489518.11 (ATCC Accession No. PTA-124186).

### Claim 2

A method of detecting cancer in a mammal comprising exposing a mammalian cancer cell to a monoclonal antibody that binds to VSIG-4, wherein the monoclonal antibody comprises:
a heavy chain variable region comprising the three complementarity determining regions (CDRs) of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528902.11 (ATCC Accession No. PTA-124187), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528902.11 (ATCC Accession No. PTA-124187);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528903.111 (ATCC Accession No. PTA-124188), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528903.111 (ATCC Accession No. PTA-124188);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528905.11 (ATCC Accession No. PTA-124189), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528905.11 (ATCC Accession No. PTA-124189);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528906.11 (ATCC Accession No. PTA-124178), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528906.11 (ATCC Accession No. PTA-124178);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528908.11 (ATCC Accession No. PTA-124179), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528908.11 (ATCC Accession No. PTA-124179);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528910.111 (ATCC Accession No. PTA-124180), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528910.111 (ATCC Accession No. PTA-124180);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528912.11 (ATCC Accession No. PTA-124181), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528912.11 (ATCC Accession No. PTA-124181);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528922.111 (ATCC Accession No. PTA-124182), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528922.111 (ATCC Accession No. PTA-124182);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528927.111 (ATCC Accession No. PTA-124183), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528927.111 (ATCC Accession No. PTA-124183);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Rt x hVSIG4 489509.11 (ATCC Accession No. PTA-124184), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Rt x hVSIG4 489509.11 (ATCC Accession No. PTA-124184);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Rt x hVSIG4 489517.111 (ATCC Accession No. PTA-124185), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Rt x hVSIG4 489517.111 (ATCC Accession No. PTA-124185); or
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Rt x hVSIG4 489518.11 (ATCC Accession No. PTA-124186), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Rt x hVSIG4 489518.11 (ATCC Accession No. PTA-124186).

### Claim 3 (depends on 2)

The method of claim 2, wherein VSIG-4 is on a cell surface.

### Claim 4 (depends on 2)

The method of claim 2, wherein the monoclonal antibody binds to an extracellular domain of VSIG-4.

### Claim 5 (depends on 2)

The method of claim 2, wherein the monoclonal antibody binds to glycosylated and unglycosylated VSIG-4.

### Claim 6 (depends on 2)

The method of claim 2, wherein the monoclonal antibody is coupled directly or indirectly to a detectable marker.

### Claim 7 (depends on 2)

The method of claim 2, wherein the monoclonal antibody comprises an IgG antibody.

### Claim 8 (depends on 2)

The method of claim 2, wherein the monoclonal antibody comprises an antigen-binding fragment comprising at least one of a Fab fragment, a Fab′ fragment, a F(ab)2 fragment, and a FIT fragment.

### Claim 9 (depends on 2)

The method of claim 2, wherein the method comprises determining a level of VSIG-4 protein in a patient sample comprising the mammalian cancer cell.

### Claim 10 (depends on 2)

The method of claim 2, wherein the method comprises identifying the presence or absence of VSIG-4 protein in a patient sample comprising the mammalian cancer cell.

### Claim 11 (depends on 9)

The method of claim 9, wherein the patient sample further comprises a macrophage.

### Claim 12 (depends on 11)

The method of claim 11, wherein VSIG-4 is on the surface of an M2c macrophage.

### Claim 13 (depends on 2)

The method of claim 2, wherein the monoclonal antibody comprises a monoclonal antibody produced by at least one of the following clones:
Ms x hVSIG4 528902.11 (ATCC Accession No. PTA-124187);
Ms x hVSIG4 528903.111 (ATCC Accession No. PTA-124188);
Ms x hVSIG4 528905.11 (ATCC Accession No. PTA-124189);
Ms x hVSIG4 528906.11 (ATCC Accession No. PTA-124178);
Ms x hVSIG4 528908.11 (ATCC Accession No. PTA-124179);
Ms x hVSIG4 528910.111 (ATCC Accession No. PTA-124180);
Ms x hVSIG4 528912.11 (ATCC Accession No. PTA-124181);
Ms x hVSIG4 528922.111 (ATCC Accession No. PTA-124182);
Ms x hVSIG4 528927.111 (ATCC Accession No. PTA-124183);
Rt x hVSIG4 489509.11 (ATCC Accession No. PTA-124184);
Rt x hVSIG4 489517.111 (ATCC Accession No. PTA-124185); and
Rt x hVSIG4 489518.11 (ATCC Accession No. PTA-124186).

### Claim 14

A method of detecting VSIG-4 in a patient sample, the method comprising contacting the patient sample with a monoclonal antibody that binds to VSIG-4, wherein the monoclonal antibody comprises:
a heavy chain variable region comprising the three complementarity determining regions (CDRs) of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528902.11 (ATCC Accession No. PTA-124187), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528902.11 (ATCC Accession No. PTA-124187);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528903.111 (ATCC Accession No. PTA-124188), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528903.111 (ATCC Accession No. PTA-124188);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528905.11 (ATCC Accession No. PTA-124189), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528905.11 (ATCC Accession No. PTA-124189);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528906.11 (ATCC Accession No. PTA-124178), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528906.11 (ATCC Accession No. PTA-124178);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528908.11 (ATCC Accession No. PTA-124179), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528908.11 (ATCC Accession No. PTA-124179);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528910.111 (ATCC Accession No. PTA-124180), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528910.111 (ATCC Accession No. PTA-124180);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528912.11 (ATCC Accession No. PTA-124181), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528912.11 (ATCC Accession No. PTA-124181);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528922.111 (ATCC Accession No. PTA-124182), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528922.111 (ATCC Accession No. PTA-124182);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Ms x hVSIG4 528927.111 (ATCC Accession No. PTA-124183), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Ms x hVSIG4 528927.111 (ATCC Accession No. PTA-124183);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Rt x hVSIG4 489509.11 (ATCC Accession No. PTA-124184), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Rt x hVSIG4 489509.11 (ATCC Accession No. PTA-124184);
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Rt x hVSIG4 489517.111 (ATCC Accession No. PTA-124185), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Rt x hVSIG4 489517.111 (ATCC Accession No. PTA-124185); or
a heavy chain variable region comprising the three CDRs of the heavy chain of a monoclonal antibody produced by Rt x hVSIG4 489518.11 (ATCC Accession No. PTA-124186), and a light chain variable region comprising the three CDRs of the light chain of a monoclonal antibody produced by Rt x hVSIG4 489518.11 (ATCC Accession No. PTA-124186).

### Claim 15 (depends on 14)

The method of claim 14, wherein the monoclonal antibody comprises a monoclonal antibody produced by at least one of the following clones:
Ms x hVSIG4 528902.11 (ATCC Accession No. PTA-124187);
Ms x hVSIG4 528903.111 (ATCC Accession No. PTA-124188);
Ms x hVSIG4 528905.11 (ATCC Accession No. PTA-124189);
Ms x hVSIG4 528906.11 (ATCC Accession No. PTA-124178);
Ms x hVSIG4 528908.11 (ATCC Accession No. PTA-124179);
Ms x hVSIG4 528910.111 (ATCC Accession No. PTA-124180);
Ms x hVSIG4 528912.11 (ATCC Accession No. PTA-124181);
Ms x hVSIG4 528922.111 (ATCC Accession No. PTA-124182);
Ms x hVSIG4 528927.111 (ATCC Accession No. PTA-124183);
Rt x hVSIG4 489509.11 (ATCC Accession No. PTA-124184);
Rt x hVSIG4 489517.111 (ATCC Accession No. PTA-124185); and
Rt x hVSIG4 489518.11 (ATCC Accession No. PTA-124186).

### Claim 16 (depends on 14)

The method of claim 14, wherein the method comprises determining a level of VSIG-4 protein in the patient sample.

### Claim 17 (depends on 14)

The method of claim 14, wherein VSIG-4 is on a cell surface.

### Claim 18 (depends on 14)

The method of claim 14, wherein VSIG-4 is on the surface of a cancer cell or a tumor cell.

### Claim 19 (depends on 14)

The method of claim 14, wherein VSIG-4 is on the surface of a macrophage.