IP Library › Granted Patent US 12,252,535
Granted Patent B2
US 12,252,535 · App. 16/897,238 · Granted Mar 18, 2025

Antibody molecules to LAG-3 and uses thereof

Inventors: Frédéric Triebel (Versailles, FR); Chrystelle Brignone (Chatenay-Malabry, FR); Walter A. Blattler (Brookline, MA); Jennifer Marie Mataraza (Cambridge, MA); Catherine Anne Sabatos-Peyton (Cambridge, MA); Hwai Wen Chang (San Marcos, CA); Gerhard Johann Frey (San Diego, CA)
Assignees: Novartis AG; Immutep S.A.S.
C07K16/2803A61K39/39558A61K45/06C07K2317/24C07K2317/51C07K2317/515C07K2317/56C07K2317/565C07K2317/70C07K2317/76G01N2333/70596
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Quick Facts
Patent No.
US 12,252,535
App. No.
16/897,238
Granted
Mar 18, 2025
Kind
B2
Abstract

Antibody molecules that specifically bind to LAG-3 and bispecific antibody molecules with a first binding specificity for LAG-3 and a second binding specificity for one of PD-1, TIM-3, CEACAM-1, CEACAM-5, PD-L1, or PD-L2, are disclosed. The anti-LAG-3 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious disorders.

Claims (62)

1. A bispecific antibody molecule having a first binding specificity for LAG-3 and a second binding specificity for one of the following antigens: PD-1, TIM-3, CEACAM-1, CEACAM-5, PD-L1, or PD-L2, wherein the bispecific antibody molecule comprises a LAG-3 binding domain comprising:

(a) a heavy chain variable region (VH) comprising a VHCDR1 amino acid sequence of SEQ ID NO: 4, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a light chain variable region (VL) comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 15;

(b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 1; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 12;

(c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 286, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 15; or

(d) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 286; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 12.

2. An isolated nucleic acid molecule comprising a first nucleotide sequence that encodes a VH, or a second nucleotide sequence that encodes a VL, or both, of a bispecific antibody molecule having a first binding specificity for LAG-3 and a second binding specificity for one of the following antigens: PD-1, TIM-3, CEACAM-1, CEACAM-5, PD-L1, or PD-L2, wherein the bispecific antibody molecule comprises a LAG-3 binding domain comprising:

(a) a heavy chain variable region (VH) comprising a VHCDR1 amino acid sequence of SEQ ID NO: 4, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a light chain variable region (VL) comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 15;

(b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 1; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 12;

(c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 286, a VHCDR2 amino acid sequence of SEQ ID NO: 5, and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 13, a VLCDR2 amino acid sequence of SEQ ID NO: 14, and a VLCDR3 amino acid sequence of SEQ ID NO: 15; or

(d) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 286; a VHCDR2 amino acid sequence of SEQ ID NO: 2; and a VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 10, a VLCDR2 amino acid sequence of SEQ ID NO: 11, and a VLCDR3 amino acid sequence of SEQ ID NO: 12.

3. The bispecific antibody molecule of claim 1 , wherein the LAG-3 binding domain comprises:

(a) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 32;

(b) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 36;

(c) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 40;

(d) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 44;

(e) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 48;

(f) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 52;

(g) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 56;

(h) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 60;

(i) a VH comprising the amino acid sequence of SEQ ID NO: 64 or SEQ ID NO: 104; and a VL comprising the amino acid sequence of SEQ ID NO: 36;

(j) a VH comprising the amino acid sequence of SEQ ID NO: 64 or SEQ ID NO: 104; and a VL comprising the amino acid sequence of SEQ ID NO: 40;

(k) a VH comprising the amino acid sequence of SEQ ID NO: 64 or SEQ ID NO: 104; and a VL comprising the amino acid sequence of SEQ ID NO: 56;

(1) a VH comprising the amino acid sequence of SEQ ID NO: 64 or SEQ ID NO: 104; and a VL comprising the amino acid sequence of SEQ ID NO: 60;

(m) a VH comprising the amino acid sequence of SEQ ID NO: 68 or SEQ ID NO: 108; and a VL comprising the amino acid sequence of SEQ ID NO: 36;

(n) a VH comprising the amino acid sequence of SEQ ID NO: 72 or SEQ ID NO: 8; and a VL comprising the amino acid sequence of SEQ ID NO: 40;

(o) a VH comprising the amino acid sequence of SEQ ID NO: 72 or SEQ ID NO: 8; and a VL comprising the amino acid sequence of SEQ ID NO: 60;

(p) a VH comprising the amino acid sequence of SEQ ID NO: 76 and a VL comprising the amino acid sequence of SEQ ID NO: 60;

(q) a VH comprising the amino acid sequence of SEQ ID NO: 80 and a VL comprising the amino acid sequence of SEQ ID NO: 84;

(r) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 88;

(s) a VH comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 92; or

(t) a VH comprising the amino acid sequence of SEQ ID NO: 64 or SEQ ID NO: 104; and a VL comprising the amino acid sequence of SEQ ID NO: 96.

4. The bispecific antibody molecule of claim 1 , wherein the LAG-3 binding domain comprises:

(a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 102; and a light chain comprising the amino acid sequence of SEQ ID NO: 34;

(b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 102; and a light chain comprising the amino acid sequence of SEQ ID NO: 38;

(c) a heavy chain comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 102; and a light chain comprising the amino acid sequence of SEQ ID NO: 42;

(d) a heavy chain comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 102; and a light chain comprising the amino acid sequence of SEQ ID NO: 46;

(e) a heavy chain comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 102; and a light chain comprising the amino acid sequence of SEQ ID NO: 50;

(f) a heavy chain comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 102; and a light chain comprising the amino acid sequence of SEQ ID NO: 54;

(g) a heavy chain comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 102; and a light chain comprising the amino acid sequence of SEQ ID NO: 58;

(h) a heavy chain comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 102; and a light chain comprising the amino acid sequence of SEQ ID NO: 62;

(i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 66 or SEQ ID NO: 106; and a light chain comprising the amino acid sequence of SEQ ID NO: 38;

(j) a heavy chain comprising the amino acid sequence of SEQ ID NO: 66 or SEQ ID NO: 106; and a light chain comprising the amino acid sequence of SEQ ID NO: 42;

(k) a heavy chain comprising the amino acid sequence of SEQ ID NO: 66 or SEQ ID NO: 106; and a light chain comprising the amino acid sequence of SEQ ID NO: 58;

(1) a heavy chain comprising the amino acid sequence of SEQ ID NO: 66 or SEQ ID NO: 106; and a light chain comprising the amino acid sequence of SEQ ID NO: 62;

(m) a heavy chain comprising the amino acid sequence of SEQ ID NO: 70 or SEQ ID NO: 110; and a light chain comprising the amino acid sequence of SEQ ID NO: 38;

(n) a heavy chain comprising the amino acid sequence of SEQ ID NO: 74 or SEQ ID NO: 18; and a light chain comprising the amino acid sequence of SEQ ID NO: 42;

(o) a heavy chain comprising the amino acid sequence of SEQ ID NO: 74 or SEQ ID NO: 18; and a light chain comprising the amino acid sequence of SEQ ID NO: 62;

(p) a heavy chain comprising the amino acid sequence of SEQ ID NO: 78 and a light chain comprising the amino acid sequence of SEQ ID NO: 62;

(q) a heavy chain comprising the amino acid sequence of SEQ ID NO: 82 and a light chain comprising the amino acid sequence of SEQ ID NO: 86;

(r) a heavy chain comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 102; and a light chain comprising the amino acid sequence of SEQ ID NO: 94;

(s) a heavy chain comprising the amino acid sequence of SEQ ID NO: 66 or SEQ ID NO: 106; and a light chain comprising the amino acid sequence of SEQ ID NO: 98;

(t) a heavy chain comprising the amino acid sequence of SEQ ID NO: 113 and a light chain comprising the amino acid sequence of SEQ ID NO: 34;

(u) a heavy chain comprising the amino acid sequence of SEQ ID NO: 113 and a light chain comprising the amino acid sequence of SEQ ID NO: 38;

(v) a heavy chain comprising the amino acid sequence of SEQ ID NO: 122 and a light chain comprising the amino acid sequence of SEQ ID NO: 38;

(w) a heavy chain comprising the amino acid sequence of SEQ ID NO: 122 and a light chain comprising the amino acid sequence of SEQ ID NO: 58; or

(x) a heavy chain comprising the amino acid sequence of SEQ ID NO: 134 and a light chain comprising the amino acid sequence of SEQ ID NO: 38.

5. The bispecific antibody molecule of claim 1 , wherein the LAG-3 binding domain comprises a VH comprising the amino acid sequence of SEQ ID NO: 104 and a VL comprising the amino acid sequence of SEQ ID NO: 56.

6. The bispecific antibody molecule of claim 1 , wherein the LAG-3 binding domain comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 122 and a light chain comprising the amino acid sequence of SEQ ID NO: 58.

7. An expression vector comprising the nucleic acid molecule of claim 2 .

8. An isolated host cell comprising the nucleic acid molecule of claim 2 .

9. A method of producing a bispecific antibody molecule, comprising culturing the host cell of claim 8 under conditions suitable for gene expression, wherein upon gene expression the bispecific antibody molecule is produced.

10. The method of claim 9 , further comprising isolating the bispecific antibody molecule.

Assignments (6)
CHANGE OF NAME Recorded Oct 11, 2021
From: IMMUTEP S.A.
To: IMMUTEP S.A.S.
Reel/Frame 057886/0335 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2021
From: FREY, GERHARD JOHANN; CHANG, HWAI WEN
To: BIOATLA, LLC
Reel/Frame 057478/0018 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2021
From: BIOATLA, LLC
To: COSTIM PHARMACEUTICALS INC.
Reel/Frame 057478/0096 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2021
From: BLATTLER, WALTER A.; MATARAZA, JENNIFER MARIE; SABATOS-PEYTON, CATHERINE ANNE
To: COSTIM PHARMACEUTICALS INC.
Reel/Frame 057478/0236 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2021
From: COSTIM PHARMACEUTICALS INC.
To: NOVARTIS AG
Reel/Frame 057478/0295 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2021
From: TRIEBEL, FREDERIC
To: IMMUTEP S.A.
Reel/Frame 057478/0493 →
Continuity (6)
Division 15829284 · Dec 1, 2017
Division 14657260 · Mar 13, 2015
Provisional Application 62094889 · Dec 19, 2014
Provisional Application 62059690 · Oct 3, 2014
Provisional Application 61953536 · Mar 14, 2014
Related Publication 20210009687A1 · Jan 14, 2021
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