# US 12,180,285 B2 · Antibodies to galectin-3 and methods of use thereof

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- Number: US 12,180,285 B2
- Document ID: US12180285B2
- Status: Granted
- Kind: B2
- Application number: 16/966,438
- Filed: 2019-02-01
- Published: 2021-02-04
- Granted: 2024-12-31
- Earliest claimed: 2018-02-01
- Assignees: Memorial Sloan Kettering Cancer Center
- Applicants: Memorial Sloan Kettering Cancer Center
- Inventors: David Spriggs; Dharmarao Thapi; Marina Stasenko
- Web page: https://patentgrep.com/patent/US12180285B2

## CPC

- C07K 16/2851: {against the lectin superfamily, e.g. CD23, CD72}
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61P 35/04: specific for metastasis
- C07K 14/7056: {Lectin superfamily, e.g. CD23, CD72}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- 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 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- 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

## Abstract

Provided herein are compositions, methods, and uses involving antibodies that immunospecifically bind the Galactin-3 (LGALS3) carbohydrate binding domain (CBD). Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer.

## Claims

### Claim 1

An antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH), wherein the antibody or antigen-binding fragment comprises:
(a) a VH complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 5, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 7, a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 10; or
(b) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 13, a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 14, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 16; or
(c) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 17, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 19, a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 20, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 22; and
wherein the antibody or an antigen-binding fragment thereof immunospecifically binds to a Galectin-3 (LGALS3) carbohydrate binding domain (CBD), wherein the LGALS3 CBD comprises SEQ ID NO: 27.

### Claim 2 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof
inhibits in vitro invasion of tumor cells in a Matrigel invasion assay;
inhibits binding of LGALS3 to a glycosylated cell surface protein, a glycosylated cell surface receptor, or a glycosylated growth factor receptor,
inhibits binding of LGALS3 to glycosylated mucin-1 (MUC1), glycosylated mucin-4 (MUC4), glycosylated mucin-16 (MUC16), a disialoganglioside, GD2, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), insulin-like growth factor receptor (IGFR), an integrin and CTLA4, or
inhibits growth of a tumor that expresses a glycosylated form of MUC16.

### Claim 3 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody is a monoclonal antibody or a humanized antibody.

### Claim 4 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 26 and/or
a VH comprising the amino acid sequence of SEQ ID NO: 24.

### Claim 5 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody comprises human-derived heavy and light chain constant regions, wherein the heavy chain constant region has an isotype selected from the group consisting of gamma 1, gamma 2, gamma 3, and gamma 4 or wherein the light chain constant region has an isotype selected from the group consisting of kappa and lambda.

### Claim 6 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody comprises an immunoglobulin comprising two identical heavy chains and two identical light chains, or comprises an IgG.

### Claim 7 (depends on 1)

An antibody conjugate comprising the antibody or antigen-binding fragment thereof of claim 1 conjugated to an agent.

### Claim 8 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof is a bispecific antibody.

### Claim 9 (depends on 8)

The bispecific antibody of claim 8, wherein the bispecific antibody immunospecifically binds CD3.

### Claim 10 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antigen-binding fragment thereof is a scFv.

### Claim 11 (depends on 4)

A polynucleotide comprising nucleic acid sequences encoding the antibody or antigen binding fragment of claim 4.

### Claim 12 (depends on 11)

An isolated cell or vector comprising the polynucleotide of claim 11 operably linked to a promoter.

### Claim 13 (depends on 12)

An isolated cell comprising the vector of claim 12.

### Claim 14 (depends on 1)

A pharmaceutical composition comprising: a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 14)

A method of treating cancer in a patient in need thereof, comprising administering to said patient the pharmaceutical composition of claim 14, wherein the cancer expresses glycosylated MUC16.

### Claim 16 (depends on 15)

The method of claim 15, wherein the cancer is a metastatic cancer or a cancer of the ovary, lung, pancreas, breast, uterine, fallopian tube, or primary peritoneum.

### Claim 17 (depends on 2)

The antibody or antigen-binding fragment thereof of claim 2, wherein the glycosylated MUC16 is N-glycosylated at Asn1800 or Asn1806.

### Claim 18 (depends on 6)

The antibody of claim 6, wherein the immunoglobulin immunospecifically binds LGALS3, wherein the antibody is a bispecific antibody, and wherein each light chain of the immunoglobulin is conjugated via a peptide linker to a single chain variable fragment (scFv) that immunospecifically binds to CD3.

### Claim 19 (depends on 8)

The bispecific antibody of claim 8, wherein the bispecific antibody is conjugated to an imaging agent or a cytotoxic agent.

### Claim 20 (depends on 10)

The antigen-binding fragment thereof of claim 10, wherein the scFv is conjugated to an agent.