METHODS OF TREATING INFLAMMATORY DISEASES BY BLOCKING GALECTIN-3
Disclosed herein are methods, antibodies, and compositions for disrupting an interaction between Galectin-3 (Gal3) and viral proteins, such as proteins of the SARS-CoV-2 virus or other coronaviruses, or viral-associated host proteins. Further disclosed herein are methods, medicaments, and compositions for the treatment of a disease or a disorder in a subject, such as the treatment of a viral infection, or treatment of a fibrosis, such as lung fibrosis, that develop as a sequela of a viral infection, or cytokine release syndrome. Further disclosed herein are methods, medicaments, and compositions for the treatment of an inflammatory disease or disorder, such as inflammation of the lungs or systemic lupus erythematosus, which may be associated with neutrophil activity, in a subject. Also disclosed herein are pharmaceutical antibody formulations for the treatment of a disease, such as a coronavirus infection.
1 . An anti-Gal3 antibody or binding fragment comprising (1) a heavy chain variable region comprising a V H -CDR1, a V H -CDR2, and a V H -CDR3; and (2) a light chain variable region comprising a V L -CDR1, a V L -CDR2, and a V L -CDR3, wherein
the V H -CDR1 comprises an amino acid sequence having at least about 90% identity to any one of SEQ ID NO: 39, 43, or 67-70;
the V H -CDR2 comprises an amino acid sequence having at least about 90% identity to any one of SEQ ID NO: 82, 103, or 109-111;
the V H -CDR3 comprises an amino acid sequence having at least about 90% identity to any one of SEQ ID NO: 138, or 165-169;
the V L -CDR1 comprises an amino acid sequence having at least about 90% identity to any one of SEQ ID NO: 192, 195, or 216-220;
the V L -CDR2 comprises an amino acid sequence having at least about 90% identity to any one of SEQ ID NO: 225, 227, 229-230, 236-237, or 247;
and the V L -CDR3 comprises an amino acid sequence having at least about 90% identity to any one of SEQ ID NO: 267, 270, or 292-296.
2 . The anti-Gal3 antibody or binding fragment thereof of claim 1 , wherein
the V H comprises an amino acid sequence having at least about 80% identity to any one of SEQ ID NO: 368-373; and
the V L comprises an amino acid sequence having at least about 80% identity to any one of SEQ ID NO: 441-447.
3 . The anti-Gal3 antibody or binding fragment thereof of claim 1 , wherein
the V H is encoded by a nucleic acid sequence having at least about 80% identity to any one of SEQ ID NO: 614-620; and
the V L is encoded by a nucleic acid sequence having at least about 80% identity to any one of SEQ ID NO: 696-702.
4 . The anti-Gal3 antibody or binding fragment thereof of claim 1 , wherein the anti-Gal3 antibody or binding fragment thereof binds to one or more peptides of SEQ ID NOs: 3-26.
5 . An anti-Gal3 antibody or binding fragment thereof comprising (1) a heavy chain variable region (V H ) and (2) a light chain variable region (V L ), wherein
the V H comprises an amino acid sequence having at least about 80% identity to any one of SEQ ID NO: 368-373; and
the V L comprises an amino acid sequence having at least about 80% identity to any one of SEQ ID NO: 441-447.
6 . The anti-Gal3 antibody or binding fragment thereof of claim 5 , wherein
the V H comprises an amino acid sequence comprising SEQ ID NO: 368 and the V L comprises an amino acid sequence comprising SEQ ID NO: 441; or
the V H comprises an amino acid sequence comprising SEQ ID NO: 369 and the V L comprises an amino acid sequence comprising SEQ ID NO: 442; or
the V H comprises an amino acid sequence comprising SEQ ID NO: 370 and the V L comprises an amino acid sequence comprising SEQ ID NO: 443; or
the V H comprises an amino acid sequence comprising SEQ ID NO: 371 and the V L comprises an amino acid sequence comprising SEQ ID NO: 444; or
the V H comprises an amino acid sequence comprising SEQ ID NO: 371 and the V L comprises an amino acid sequence comprising SEQ ID NO: 445; or
the V H comprises an amino acid sequence comprising SEQ ID NO: 372 and the V L comprises an amino acid sequence comprising SEQ ID NO: 446; or
the V H comprises an amino acid sequence comprising SEQ ID NO: 373 and the V L comprises an amino acid sequence comprising SEQ ID NO: 447.
7 . The anti-Gal3 antibody or binding fragment thereof of claim 5 , wherein the anti-Gal3 antibody or binding fragment thereof binds to one or more peptides of SEQ ID NOs: 3-26.
8 . The anti-Gal3 antibody or binding fragment thereof of claim 6 , wherein
the V H is encoded by a nucleic acid sequence having at least about 80% identity to any one of SEQ ID NO: 614-620; and
the V L is encoded by a nucleic acid sequence having at least about 80% identity to any one of SEQ ID NO: 696-702.
9 . The anti-Gal3 antibody or binding fragment thereof of claim 8 , wherein
the V H is encoded by a nucleic acid sequence comprising SEQ ID NO: 614 and the V L is encoded by a nucleic acid sequence comprising SEQ ID NO: 696; or
the V H is encoded by a nucleic acid sequence comprising SEQ ID NO: 615 and the V L is encoded by a nucleic acid sequence comprising SEQ ID NO: 697; or
the V H is encoded by a nucleic acid sequence comprising SEQ ID NO: 616 and the V L is encoded by a nucleic acid sequence comprising SEQ ID NO: 698; or
the V H is encoded by a nucleic acid sequence comprising SEQ ID NO: 617 and the V L is encoded by a nucleic acid sequence comprising SEQ ID NO: 699; or
the V H is encoded by a nucleic acid sequence comprising SEQ ID NO: 618 and the V L is encoded by a nucleic acid sequence comprising SEQ ID NO: 700; or
the V H is encoded by a nucleic acid sequence comprising SEQ ID NO: 619 and the V L is encoded by a nucleic acid sequence comprising SEQ ID NO: 701; or
the V H is encoded by a nucleic acid sequence comprising SEQ ID NO: 620 and the V L is encoded by a nucleic acid sequence comprising SEQ ID NO: 702.
10 . An anti-Gal3 antibody or binding fragment comprising (1) a heavy chain variable region comprising a V H -CDR1, a V H -CDR2, and a V H -CDR3; and (2) a light chain variable region comprising a V L -CDR1, a V L -CDR2, and a V L -CDR3, wherein
the V H -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 39, the V H -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 103, the V H -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 165; the V L -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 195, the V L -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 247, and the V L -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 292; or
the V H -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 67, the V H -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 82, the V H -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 166; the V L -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 216, the V L -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 230, and the V L -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 267; or
the V H -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 68, the V H -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 82, the V H -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 167; the V L -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 192, the V L -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 236, and the V L -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 270; or
the V H -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 69, the V H -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 109, the V H -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 168; the V L -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 217, the V L -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 229, and the V L -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 293; or
the V H -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 69, the V H -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 109, the V H -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 168; the V L -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 218, the V L -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 237, and the V L -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 294; or
the V H -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 70, the V H -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 110, the V H -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 169; the V L -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 219, the V L -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 225, and the V L -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 295; or
the V H -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 43, the V H -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 111, the V H -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 138; the V L -CDR1 comprises an amino acid sequence comprising SEQ ID NO: 220, the V L -CDR2 comprises an amino acid sequence comprising SEQ ID NO: 227, and the V L -CDR3 comprises an amino acid sequence comprising SEQ ID NO: 296.
11 . The anti-Gal3 antibody or binding fragment thereof of claim 10 , wherein
the V H comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 368 and the V L comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 441; or
the V H comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 369 and the V L comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 442; or
the V H comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 370 and the V L comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 443; or
the V H comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 371 and the V L comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 444; or
the V H comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 371 and the V L comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 445; or
the V H comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 372 and the V L comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 446; or
the V H comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 373 and the V L comprises an amino acid sequence having at least about 80% identity to SEQ ID NO: 447.
12 . The anti-Gal3 antibody or binding fragment thereof of claim 10 , wherein the anti-Gal3 antibody or binding fragment thereof binds to one or more peptides of SEQ ID NOs: 3-26.