US 12,281,166 B2
Methods of treating inflammatory diseases by blocking Galectin-3
Dongxu Sun, Los Altos, CA (US); Catherine A. Gordon, Fremont, CA (US); Ksenya Shchors, San Mateo, CA (US); Yan Wang, Concord, CA (US); Tsung-Huang Tsai, San Carlos, CA (US); and Yew Ann Leong, San Francisco, CA (US)
Assigned to TrueBinding, Inc., Foster City, CA (US)
Filed by TrueBinding, Inc., Foster City, CA (US)
Filed on May 25, 2021, as Appl. No. 17/303,268.
Claims priority of provisional application 63/030,069, filed on May 26, 2020.
Prior Publication US 2021/0371533 A1, Dec. 2, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01); A61P 19/04 (2006.01); A61P 31/14 (2006.01); A61P 37/06 (2006.01)
CPC C07K 16/2851 (2013.01) [A61K 39/395 (2013.01); A61P 19/04 (2018.01); A61P 31/14 (2018.01); A61P 37/06 (2018.01); A61K 2039/505 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01)] 9 Claims
 
1. A method of decreasing or inhibiting inflammation in a subject in need thereof, the method comprising:
administering to the subject an effective amount of an anti-Gal3 antibody or binding fragment thereof; wherein
the anti-Gal3 antibody or binding fragment thereof comprises (1) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3; and (2) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3, wherein
the VL-CDR1 comprises an amino acid that comprise SEQ ID NO: 171, the VL-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 222, the VL-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 249; the VH-CDR1 comprises an amino acid that comprise SEQ ID NO: 31, the VH-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 72, and the VH-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 113; or
the VL-CDR1 comprises an amino acid that comprise SEQ ID NO: 195, the VL-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 247, the VL-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 292; the VH-CDR1 comprises an amino acid that comprise SEQ ID NO: 39, the VH-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 103, and the VH-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 165; or
the VL-CDR1 comprises an amino acid that comprise SEQ ID NO: 216, the VL-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 230, the VL-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 267; the VH-CDR1 comprises an amino acid that comprise SEQ ID NO: 67, the VH-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 82, and the VH-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 166; or
the VL-CDR1 comprises an amino acid that comprise SEQ ID NO: 192, the VL-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 236, the VL-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 270; the VH-CDR1 comprises an amino acid that comprise SEQ ID NO: 68, the VH-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 82, and the VH-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 167; or
the VL-CDR1 comprises an amino acid that comprise SEQ ID NO: 217, the VL-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 229, the VL-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 293; the VH-CDR1 comprises an amino acid that comprise SEQ ID NO: 69, the VH-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 109, and the VH-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 168; or
the VL-CDR1 comprises an amino acid that comprise SEQ ID NO: 218, the VL-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 237, the VL-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 294; the VH-CDR1 comprises an amino acid that comprise SEQ ID NO: 69, the VH-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 109, and the VH-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 168; or
the VL-CDR1 comprises an amino acid that comprise SEQ ID NO: 219, the VL-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 225, the VL-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 295; the VH-CDR1 comprises an amino acid that comprise SEQ ID NO: 70, the VH-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 110, and the VH-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 169; or
the VL-CDR1 comprises an amino acid that comprise SEQ ID NO: 220, the VL-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 227, the VL-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 296; the VH-CDR1 comprises an amino acid that comprise SEQ ID NO: 43, the VH-CDR2 comprises an amino acid sequence that comprise SEQ ID NO: 111, and the VH-CDR3 comprises an amino acid sequence that comprise SEQ ID NO: 138; and wherein
administration of the effective amount of the anti-Gal3 antibody or binding fragment thereof decreases or inhibits neutrophil activation and/or migration in the subject, decreases or inhibits cleavage of CD62L expressed by neutrophils, decreases or inhibits IL-8 production in the subject, decreases the number of neutrophils in the subject, and/or modulates expression of myeloperoxidase (MPO), growth-related oncogene α (GROα)/keratinocytes-derived chemokine (KC), Ly6c1, INOS, IL-6, TNFα, IL-1B, Col1A1, aSMA, TGFβ, VEGFA, VEGFB, or any combination thereof, in the subject.