US 2025/0145722 A1 · ANTI-GAL3 ANTIBODIES AND METHODS OF USE

Abstract

Disclosed herein are antibodies and compositions used for binding to Gal3. Some embodiments allow for disrupting interactions between Galectin-3 (Gal3) and cell surface markers and/or proteins associated with neurological diseases and/or proteopathies, such as Alzheimer's disease. Additionally, disclosed herein are methods of treatment and uses of the antibodies or binding fragments thereof for the treatment of fibrosis, liver fibrosis, kidney fibrosis, cardiac fibrosis, pulmonary fibrosis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, sepsis, atopic dermatitis, psoriasis, cancer, brain cancer, breast cancer, colorectal cancer, kidney cancer, liver cancer, lung cancer, pancreatic cancer, bladder cancer, stomach cancer, hematological malignancy, neurological diseases and/or proteopathies. Furthermore, some embodiments provided herein can cross the blood-brain barrier and can be conjugated or otherwise associated with one or more payloads for the treatment of a neurological disease.

Claims283

Dependent claims

An anti-Gal3 antibody or binding fragment thereof comprising (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3, and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3;

wherein
the VH-CDR1 comprises an amino acid sequence selected from SEQ ID NOs:
36-44, 588-615,
the VH-CDR2 comprises an amino acid sequence selected from SEQ ID NOs:
54-60, 616-643,
the VH-CDR3 comprises an amino acid sequence selected from SEQ ID NOs:
70-81, 644-671,
the VL-CDR1 comprises an amino acid sequence selected from SEQ ID NOs:
92-101, 672-699,
the VL-CDR2 comprises an amino acid sequence selected from SEQ ID NOs:
111-116, 700-727, and
the VL-CDR3 comprises an amino acid sequence selected from SEQ ID NOs:
127-135, 728-755.

10 more elements

A method of disrupting an interaction between Gal3 and a tumor cell surface marker comprising:

contacting the tumor cell surface marker with an anti-Gal3 antibody or binding fragment thereof specific for the N-terminal domain of Gal3, N-terminus of Gal3, or the TRD of Gal3;
wherein the tumor cell surface marker is selected from the group consisting of VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR (cMet), TNF sRI, CTLA4, CD47, PD-L1, FGFR1 alpha-IIIb, FGFR1 alpha-IIIc, FGFR2 alpha-IIIc, FGFR3 IIIc, and FGFR4.

A method of treating cancer in a subject in need thereof, comprising:

administering to the subject an anti-Gal3 antibody or binding fragment thereof specific for the N-terminal domain of Gal3, N-terminus of Gal3, or the TRD of Gal3;
wherein the anti-Gal3 antibody or binding fragment thereof disrupts an interaction between Gal3 and a tumor cell surface marker;
and
wherein the tumor cell surface marker is selected from the group consisting of VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR (cMct), TNF sRI, CTLA4, CD47, PD-L1, FGFR1 alpha-IIIb, FGFR1 alpha-IIIc, FGFR2 alpha-IIIc, FGFR3 IIIc, and FGFR4.

1 more element

An anti-Gal3 antibody or binding fragment thereof comprising (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3;

and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein
the VH-CDR1 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs:
27-36, 397-399,
the VH-CDR2 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs:
45-54, 400-406,
the VH-CDR3 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs:
61-69, 71, 408-416
the VL-CDR1 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs:
82-92, 417-426,
the VL-CDR2 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs:
102-111, 427-428, and
the VL-CDR3 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs:
117-127, 429-434.

10 more elements

Use of an anti-Gal3 antibody or binding fragment thereof for the treatment of fibrosis, liver fibrosis, NAFLD, NASH, kidney fibrosis, cardiac fibrosis, arterial fibrosis, venous thrombosis, or pulmonary fibrosis.

Use of an anti-Gal3 antibody or binding fragment thereof for the treatment of cancer.

Use of an anti-Gal3 antibody or binding fragment thereof for the inhibition of tumor cell growth in vitro.

Use of an anti-Gal3 antibody or binding fragment thereof for the retardation of brain tumor growth.

A protein comprising one or more peptide sequences having at least 80%, 85%, 90%, 95%, 99%, or 100% homology to one or more of the peptide sequences of FIG. 18-27.

Dependencies are inferred from the claim text.

Anti-gal3 antibodies and methods of use

Life of this patent

Anti-gal3 antibodies and methods of use

Life of this patent

Abstract

Claims283