IP Library › Granted Patent US 12,649,794
Granted Patent B2
US 12,649,794 · App. 17/789,961 · Granted Jun 9, 2026

Anti-galectin-9 antibody and uses thereof

Inventors: Germain Margall Ducos (Saint Maurice, FR); Rachel Pacherie (Sceaux, FR); Nicola Arturo Aldo Beltraminelli (Villeurbanne, FR); Francisco Adrian (Belmont, MA); Liang Schweizer (Cambridge, MA); Muriel David (Cambridge, MA); Yun-Yueh Lu (Cambridge, MA)
Assignee: HIFIBIO, INC.
C07K16/2851A61P35/00C07K16/2818A61K2039/505A61K2039/507C07K2317/24C07K2317/55C07K2317/565C07K2317/622C07K2317/92
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Quick Facts
Patent No.
US 12,649,794
App. No.
17/789,961
Granted
Jun 9, 2026
Kind
B2
Abstract

The invention provides humanized monoclonal antibodies against Gal9, and method of using the antibodies to treat cancer, including combination therapy with antagonists of the PD-1/PD-L1 immune checkpoint.

Claims (68)

1 . An isolated monoclonal antibody, or an antigen-binding fragment thereof, wherein said monoclonal antibody or antigen-binding fragment thereof is specific for Galectin-9, and wherein said monoclonal antibody comprises:

(1a) a heavy chain variable region (HCVR), comprising the HCVR CDR1 sequence of SEQ ID NO: 2, the HCVR CDR2 sequence of SEQ ID NO: 4, and the HCVR CDR3 sequence of SEQ ID NO: 6; and,

(1b) a light chain variable region (LCVR), comprising the LCVR CDR1 sequence of SEQ ID NO: 10, the LCVR CDR2 sequence of SEQ ID NO: 12, and the LCVR CDR3 sequence of SEQ ID NO: 14; or

(2a) a heavy chain variable region (HCVR), comprising the HCVR CDR1 sequence of SEQ ID NO: 18, the HCVR CDR2 sequence of SEQ ID NO: 20, and the HCVR CDR3 sequence of SEQ ID NO: 22; and,

(2b) a light chain variable region (LCVR), comprising the LCVR CDR1 sequence of SEQ ID NO: 26, the LCVR CDR2 sequence of SEQ ID NO: 28, and the LCVR CDR3 sequence of SEQ ID NO: 30; or

(3a) a heavy chain variable region (HCVR), comprising the HCVR CDR1 sequence of SEQ ID NO: 34, the HCVR CDR2 sequence of SEQ ID NO: 36, and the HCVR CDR3 sequence of SEQ ID NO: 38; and,

(3b) a light chain variable region (LCVR), comprising the LCVR CDR1 sequence of SEQ ID NO: 42, the LCVR CDR2 sequence of SEQ ID NO: 44, and the LCVR CDR3 sequence of SEQ ID NO: 46; or

(4a) a heavy chain variable region (HCVR), comprising the HCVR CDR1 sequence of SEQ ID NO: 50, the HCVR CDR2 sequence of SEQ ID NO: 52, and the HCVR CDR3 sequence of SEQ ID NO: 54; and,

(4b) a light chain variable region (LCVR), comprising the LCVR CDR1 sequence of SEQ ID NO: 58, the LCVR CDR2 sequence of SEQ ID NO: 60, and the LCVR CDR3 sequence of SEQ ID NO: 62; or

(5a) a heavy chain variable region (HCVR), comprising the HCVR CDR1 sequence of SEQ ID NO: 66, the HCVR CDR2 sequence of SEQ ID NO: 68, and the HCVR CDR3 sequence of SEQ ID NO: 70; and,

(5b) a light chain variable region (LCVR), comprising the LCVR CDR1 sequence of SEQ ID NO: 74, the LCVR CDR2 sequence of SEQ ID NO: 76, and the LCVR CDR3 sequence of SEQ ID NO: 78; or

(6a) a heavy chain variable region (HCVR), comprising the HCVR CDR1 sequence of SEQ ID NO: 82, the HCVR CDR2 sequence of SEQ ID NO: 84, and the HCVR CDR3 sequence of SEQ ID NO: 86; and,

(6b) a light chain variable region (LCVR), comprising the LCVR CDR1 sequence of SEQ ID NO: 90, the LCVR CDR2 sequence of SEQ ID NO: 92, and the LCVR CDR3 sequence of SEQ ID NO: 94; or

(7a) a heavy chain variable region (HCVR), comprising the HCVR CDR1 sequence of SEQ ID NO: 98, the HCVR CDR2 sequence of SEQ ID NO: 100, and the HCVR CDR3 sequence of SEQ ID NO: 102; and,

(7b) a light chain variable region (LCVR), comprising the LCVR CDR1 sequence of SEQ ID NO: 106, the LCVR CDR2 sequence of SEQ ID NO: 108, and the LCVR CDR3 sequence of SEQ ID NO: 110; or

(8a) a heavy chain variable region (HCVR), comprising the HCVR CDR1 sequence of SEQ ID NO: 114, the HCVR CDR2 sequence of SEQ ID NO: 116, and the HCVR CDR3 sequence of SEQ ID NO: 118; and,

(8b) a light chain variable region (LCVR), comprising the LCVR CDR1 sequence of SEQ ID NO: 122, the LCVR CDR2 sequence of SEQ ID NO: 124, and the LCVR CDR3 sequence of SEQ ID NO: 126.

2 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein:

(1c) the antibody or antigen-binding fragment thereof of (1a) and (1b) further comprises the heavy chain framework region 3 (HFR3) sequence of SEQ ID NO: 5, and optionally further comprises the HFR1 sequence of SEQ ID NO: 1; or

(2c) the antibody or antigen-binding fragment thereof of (2a) and (2b) further comprises the HFR3 sequence of SEQ ID NO: 21, and optionally further comprises the HFR1 sequence of SEQ ID NO: 17; or

(3c) the antibody or antigen-binding fragment thereof of (3a) and (3b) further comprises the HFR3 sequence of SEQ ID NO: 37, and optionally further comprises the HFR1 sequence of SEQ ID NO: 33; or

(4c) the antibody or antigen-binding fragment thereof of (4a) and (4b) further comprises the HFR3 sequence of SEQ ID NO: 53, and optionally further comprises the HFR1 sequence of SEQ ID NO: 49; or

(5c) the antibody or antigen-binding fragment thereof of (5a) and (5b) further comprises the HFR3 sequence of SEQ ID NO: 69, and optionally further comprises the HFR1 sequence of SEQ ID NO: 65; or

(6c) the antibody or antigen-binding fragment thereof of (6a) and (6b) further comprises the HFR3 sequence of SEQ ID NO: 85, and optionally further comprises the HFR1 sequence of SEQ ID NO: 81; or

(7c) the antibody or antigen-binding fragment thereof of (7a) and (7b) further comprises the HFR3 sequence of SEQ ID NO: 101, and optionally further comprises the HFR1 sequence of SEQ ID NO: 97; or

(8c) the antibody or antigen-binding fragment thereof of (8a) and (8b) further comprises the HFR3 sequence of SEQ ID NO: 117, and optionally further comprises the HFR1 sequence of SEQ ID NO: 113.

3 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein:

(1A) the HCVR sequence is SEQ ID NO: 8; and/or,

(1B) the LCVR sequence is SEQ ID NO: 16, or,

(2A) the HCVR sequence is SEQ ID NO: 24; and/or,

(2B) the LCVR sequence is SEQ ID NO: 32, or,

(3A) the HCVR sequence is SEQ ID NO: 40; and/or,

(3B) the LCVR sequence is SEQ ID NO: 48, or,

(4A) the HCVR sequence is SEQ ID NO: 56; and/or,

(4B) the LCVR sequence is SEQ ID NO: 64, or,

(5A) the HCVR sequence is SEQ ID NO: 72; and/or,

(5B) the LCVR sequence is SEQ ID NO: 80, or,

(6A) the HCVR sequence is SEQ ID NO: 88; and/or,

(6B) the LCVR sequence is SEQ ID NO: 96, or

(7A) the HCVR sequence is SEQ ID NO: 104; and/or,

(7B) the LCVR sequence is SEQ ID NO: 112, or

(8A) the HCVR sequence is SEQ ID NO: 120; and/or,

(8B) the LCVR sequence is SEQ ID NO: 128.

4 . The isolated monoclonal antibody or antigen-binding fragment thereof according to claim 1 , which is a humanized antibody, and comprises:

(1) the HCVR sequence of SEQ ID NO: 8 and the LCVR sequence of SEQ ID NO: 16; or,

(2) the HCVR sequence of SEQ ID NO: 72 and the LCVR sequence of SEQ ID NO: 80.

5 . The isolated monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein said antigen-binding fragment thereof is an Fab, Fab′, F(ab′) 2 , F d , single chain Fv or scFv, disulfide linked Fv, intrabody, IgGΔCH 2 , minibody, F(ab′) 3 , tetrabody, triabody, diabody, single-domain antibody, DVD-Ig, Fcab, mAb 2 , (scFv) 2 , or scFv-Fc.

6 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein said monoclonal antibody or antigen-binding fragment thereof cross-reacts with mouse Gal9.

7 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein said monoclonal antibody or antigen-binding fragment thereof binds to human Gal9 with an EC50 of about 0.1-0.2 nM, and/or binds to mouse Gal9 with an EC50 of about 0.5-1.0 nM.

8 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein said monoclonal antibody or antigen-binding fragment thereof binds human Gal9 with a K d of less than about 25 nM, 20 nM, 15 nM, 10 nM, 5 nM, 2 nM, or 1 nM.

9 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , which binds to Gal9 and inhibits Gal9 binding to a Gal9 receptor.

10 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , which neutralizes Gal-9-induced Th1 apoptosis of T cells.

11 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , which suppresses Gal9-induced Treg expansion.

12 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , which synergistically inhibits tumor growth in vivo and/or prolongs survival in a mouse with a xenograph tumor with an antagonist of an immune checkpoint.

13 . The isolated monoclonal antibody or antigen-binding fragment thereof of claim 12 , wherein the antagonist of the immune checkpoint is an antibody or antigen-binding fragment thereof specific for PD-1 or PD-L1.

14 . A method of treating cancer in a patient in need thereof, the method comprising administering to the patient an effective amount of the isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , and an antagonist of an immune checkpoint.

15 . The method of claim 14 , wherein the immune checkpoint is PD-1/PD-L1 immune checkpoint, wherein the antagonist of the immune checkpoint is an antibody or antigen-binding fragment thereof specific for PD-1 or PD-L1.

16 . The method of claim 14 , wherein the cancer is a hematological cancer, or a solid tumor.

17 . The method of claim 14 , further comprising administering to the patient a chemotherapeutic agent, an anti-angiogenesis agent, a growth inhibitory agent, an immune-oncology agent, and/or an anti-neoplastic composition.

18 . A method of rescuing or promoting effector T cells proliferation and/or enhancing effector T cell activity in a patient diagnosed with cancer, in risk of developing cancer or having cancer relapse, or a method of identifying and treating a patient having cancer, the method comprising: administering to the patient an effective amount of the isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 and an antagonist of an immune checkpoint, upon identifying the patient as having a level of Galectin-9 in a sample from the patient higher than a reference level of Galectin-9 in a healthy or a control individual.

19 . The method of claim 18 , further comprising identifying the patient as having the level of Galectin-9 in the sample higher than the reference level, by comparing the level of Galectin-9 in the sample to the reference level.

20 . The method of claim 18 , wherein the immune checkpoint is PD-1/PD-L1 immune checkpoint.

21 . The method of claim 20 , wherein the antagonist of the immune checkpoint is an antibody or antigen-binding fragment thereof specific for PD-1 or PD-L1.

22 . The method of claim 18 , wherein the cancer is a hematological cancer or a solid tumor.

23 . The method of claim 22 , wherein the patient is a French-American-British (FAB) M0, M1, M4 or M5 AML patient, or wherein the patient is not an FAB M2 or M3 AML patient.

24 . The method of claim 18 , wherein the sample is a blood sample, a plasma sample, or a serum sample.

25 . A method of rescuing or promoting effector T cells proliferation and/or enhancing effector T cell activity in a patient diagnosed with AML, in risk of developing AML or having AML relapse, or a method of identifying and treating a patient having AML, the method comprising: administering to the patient an effective amount of the isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 and an antagonist of an immune checkpoint, upon identifying the patient as having a level of Galectin-9-encoding mRNA in a bone-marrow (BM)-derived mononuclear cell (MNC) sample from the patient statistically significantly higher or lower than a reference level in BM-derived MNC or CD34 + cells in a healthy or a control individual.

26 . The method of claim 25 , wherein (1) the level of Galectin-9-encoding mRNA in the BM-derived MNC sample from the patient is significantly higher than the reference level when the patient is an FAB M0, M1, M2, M4, or M5 AML patient, or (2) the level of Galectin-9-encoding mRNA in the BM-derived MNC sample from the patient is significantly lower than the reference level when the patient is an FAB M3 AML patient.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 5, 2024
From: HIFIBIO (HK) LIMITED
To: HIFIBIO, INC.
Reel/Frame 066347/0278 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 29, 2022
From: MARGALL DUCOS, GERMAIN; PACHERIE, RACHEL; BELTRAMINELLI, NICOLA ARTURO ALDO; ADRIAN, FRANCISCO; SCHWEIZER, LIANG; DAVID, MURIEL; LU, YUN-YUEH
To: HIFIBIO (HK) LIMITED
Reel/Frame 060358/0279 →
Continuity (2)
Provisional Application 62957910 · Jan 7, 2020
Related Publication 20230054718A1 · Feb 23, 2023
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