# US 12,758,647 B2 · Anti-CSPG4 binding agents, encoding nucleic acids thereof, conjugates thereof and methods of use thereof to treat a CSPG4+ cancer

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- Number: US 12,758,647 B2
- Document ID: US12758647B2
- Status: Granted
- Kind: B2
- Application number: 18/247,628
- Filed: 2021-10-15
- Published: 2025-07-03
- Granted: 2026-10-13
- Earliest claimed: 2020-10-18
- Assignees: Ardeagen Corporation
- Applicants: Ardeagen Corporation
- Inventors: Maria Leia Smith; May Kung Sutherland
- Web page: https://patentgrep.com/patent/US12758647B2

## CPC

- A61K 47/6865: {the tumour determinant being from skin, nerves or brain cancer cell}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/68037: {the drug being a camptothecin [CPT] or derivatives}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6857: {the tumour determinant being from lung cancer cell}
- A61K 47/6889: {Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment}
- A61P 35/00: Antineoplastic agents
- 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

## Abstract

The present disclosure provides anti-CSPG4 antibodies, antigen binding portions thereof and CSPG4 conjugates thereof for use in the treatment of cancer.

## Claims

### Claim 1

A binding agent comprising:
(a) a heavy chain variable (VH) region having the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable (VL) region having the amino acid sequence set forth in SEQ ID NO:30;
(b) a heavy chain variable (VH) region having the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable (VL) region having the amino acid sequence set forth in SEQ ID NO:30; or
(c) a heavy chain variable (VH) region having the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable (VL) region having the amino acid sequence set forth in SEQ ID NO:31;
wherein the binding agent specifically binds to human CSPG4.

### Claim 2 (depends on 1)

The binding agent of claim 1, wherein the binding agent is an antibody or an antigen-binding portion thereof.

### Claim 3 (depends on 2)

The binding agent of claim 2, wherein the binding agent is a monoclonal antibody, a Fab, a Fab′, an F(ab′), an Fv, a disulfide-linked Fc, a scFv, a single-domain antibody, a diabody, a bispecific antibody, or a multispecific antibody.

### Claim 4 (depends on 1)

The binding agent of claim 1, wherein the heavy chain variable region further comprises a heavy chain constant region and the light chain variable region further comprises a light chain constant region.

### Claim 5 (depends on 4)

The binding agent of claim 4, wherein:
(a) the heavy chain constant region is of the human IgG isotype;
(b) the heavy chain constant region is an IgG1 constant region;
(c) a IgG1 heavy chain constant region has the amino acid sequence set forth in positions 113-442 of SEQ ID NO:3;
(d) the heavy chain constant region is an IgG4 constant region; or
(e) the heavy chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO: 33 or 35.

### Claim 6 (depends on 4)

The binding agent of claim 4, wherein:
(a) the light chain constant region is of the kappa isotype;
(b) a kappa light chain constant region has the amino acid sequence set forth in positions 108-214 of SEQ ID NO:4; or
(c) the light chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO:38 or 39.

### Claim 7 (depends on 1)

The binding agent of claim 1, wherein:
(a) the heavy chain variable and constant regions have the amino acid sequence set forth SEQ ID NO:33, and the light chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO:38;
(b) the heavy chain variable and constant regions have the amino acid sequence set forth SEQ ID NO:35, and the light chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO:38; or
(c) the heavy chain variable and constant regions have the amino acid sequence set forth SEQ ID NO:35, and the light chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO:39.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising the binding agent of claim 1 and a pharmaceutically acceptable carrier.

### Claim 9 (depends on 1)

A nucleic acid encoding the binding agent of claim 1.

### Claim 10 (depends on 9)

A vector comprising the nucleic acid of claim 9.

### Claim 11 (depends on 9)

A cell line comprising the nucleic acid of claim 9.

### Claim 12

A conjugate comprising:
(a) a binding agent comprising:
(i) a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:25, and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:30;
(ii) a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:30; or
(iii) a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:27, and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:31;
wherein the binding agent specifically binds to human CSPG4;
(b) at least one linker attached to the binding agent; and
(c) at least one cytotoxic agent attached to each linker.

### Claim 13 (depends on 12)

The conjugate of claim 12, wherein the binding agent is an antibody or an antigen-binding portion thereof.

### Claim 14 (depends on 13)

The conjugate of claim 13, wherein the binding agent is a monoclonal antibody, a Fab, a Fab′, an F(ab′), an Fv, a disulfide-linked Fc, a scFv, a single-domain antibody, a diabody, a bi-specific antibody, or a multi-specific antibody.

### Claim 15 (depends on 12)

The conjugate of claim 12, wherein the heavy chain variable region further comprises a heavy chain constant region and the light chain variable region further comprises a light chain constant region.

### Claim 16 (depends on 15)

The conjugate of claim 15, wherein:
(a) the heavy chain constant region is of the human IgG isotype;
(b) the heavy chain constant region is an IgG1 constant region;
(c) a IgG1 heavy chain constant region has the amino acid sequence set forth in positions 113-442 of SEQ ID NO:3;
(d) the heavy chain constant region is an IgG4 constant region; or
(e) the heavy chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO: 33 or 35.

### Claim 17 (depends on 15)

The conjugate of claim 15, wherein:
(a) the light chain constant region is of the kappa isotype;
(b) a kappa light chain constant region has the amino acid sequence set forth in positions 108-214 of SEQ ID NO:4; or
(c) the light chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO:38 or 39.

### Claim 18 (depends on 12)

The conjugate of claim 12, wherein:
(a) the heavy chain variable and constant regions have the amino acid sequence set forth SEQ ID NO:33, and the light chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO:38;
(b) the heavy chain variable and constant regions have the amino acid sequence set forth SEQ ID NO:35, and the light chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO:38; or
(c) the heavy chain variable and constant regions have the amino acid sequence set forth SEQ ID NO:35, and the light chain variable and constant regions have the amino acid sequence set forth in SEQ ID NO:39.

### Claim 19 (depends on 12)

The conjugate of claim 12, wherein the linker is attached to the binding agent via an interchain disulfide residue, an engineered cysteine, a glycan or modified glycan, an N-terminal residue of the binding agent or a polyhistidine residue attached to the binding agent.

### Claim 20 (depends on 12)

The conjugate of claim 12, wherein the average drug loading of the conjugate is from about 1 to about 8, about 2, about 4, about 6, about 8, about 10, about 12, about 14, about 16, about 3 to about 5, about 6 to about 8 or about 8 to about 16.

### Claim 21 (depends on 12)

The conjugate of claim 12, wherein the binding agent is monospecific, bivalent, or bispecific.

### Claim 22 (depends on 12)

The conjugate of claim 12, wherein the cytotoxic agent is selected from the group consisting of an auristatin, a camptothecin and a calicheamicin.

### Claim 23 (depends on 22)

The conjugate of claim 22, wherein the cytotoxic agent is monomethyl auristatin E (MMAE), exatecan, or SN-38.

### Claim 24 (depends on 12)

The conjugate of claim 12, wherein the linker is selected from the group consisting of mc-VC-PAB, CL2, CL2A, maleimide acetyl-Gly-Val-Cit-PAB, and (Succinimid-3-yl-N)—(CH2)n2—C(═O)-Gly-Gly-Phe-Gly-NH—CH2=OCH2—(C═O)—.

### Claim 25 (depends on 24)

The conjugate of claim 24, wherein:
(a) the linker is mc-VC-PAB and is attached to at least one molecule of MMAE;
(b) the linker is CL2A and is attached to at least one molecule of SN-38;
(c) the linker is CL2 and is attached to at least one molecule of SN-38; or
(d) the linker is (Succinimid-3-yl-N)—(CH2)n2—C(═O)-Gly-Gly-Phe-Gly-NH—CH2═OCH2—(C═O)— and is attached to at least one molecule of exatecan.

### Claim 26 (depends on 12)

A pharmaceutical composition comprising the conjugate of claim 12 and a pharmaceutically acceptable carrier.

### Claim 27 (depends on 8)

A method of treating a CSPG4+ cancer, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 8.

### Claim 28 (depends on 27)

The method of claim 27, wherein the CSPG4+ cancer is selected from melanoma, head and neck cancer, breast cancer, mesothelioma, renal clear cell cancer, chondrosarcoma, urothelial cancer, osteosarcoma, pancreatic cancer, thyroid cancer, and leukemia (B-ALL).

### Claim 29 (depends on 27)

The method of claim 27, further comprising administering an immunotherapy or chemotherapy to the subject.

### Claim 30 (depends on 29)

The method of claim 29, wherein the immunotherapy comprises an immune checkpoint inhibitor.

### Claim 31 (depends on 30)

The method of claim 30, wherein the immune checkpoint inhibitor is selected from an antibody that specifically binds to human PD-1, human PD-L1, or human CTLA4.

### Claim 32 (depends on 31)

The method of claim 31, wherein the immune checkpoint inhibitor is pembrolizumab, nivolumab, cemiplimab or ipilimumab.

### Claim 33 (depends on 27)

The method of claim 27, wherein the binding agent is administered intravenously.

### Claim 34 (depends on 27)

The method of claim 27, wherein the binding agent is administered in a dose of about 0.1 mg/kg to about 10 mg/kg or from about 0.1 mg/kg to about 12 mg/kg.

### Claim 35 (depends on 26)

A method of treating a CSPG4+ cancer, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 26.

### Claim 36 (depends on 35)

The method of claim 35, wherein the CSPG4+ cancer is selected from melanoma, head and neck cancer, breast cancer, mesothelioma, renal clear cell cancer, chondrosarcoma, urothelial cancer, osteosarcoma, pancreatic cancer, thyroid cancer, and leukemia (B-ALL).

### Claim 37 (depends on 35)

The method of claim 35, further comprising administering an immunotherapy or chemotherapy to the subject.

### Claim 38 (depends on 37)

The method of claim 37, wherein the immunotherapy comprises an immune checkpoint inhibitor.

### Claim 39 (depends on 38)

The method of claim 38, wherein the immune checkpoint inhibitor is selected from an antibody that specifically binds to human PD-1, human PD-L1, or human CTLA4.

### Claim 40 (depends on 35)

The method of claim 35, wherein the conjugate is administered intravenously.

### Claim 41 (depends on 35)

The method of claim 35, wherein the conjugate is administered in a dose of about 0.1 mg/kg to about 10 mg/kg or from about 0.1 mg/kg to about 12 mg/kg.