Antibody molecules to lag-3 and uses thereof
AssigneesNovartis AG, Immutep S.A.S.
InventorsFrédéric Triebel, Chrystelle Brignone, Walter A. Blattler, Jennifer Marie Mataraza, Catherine Anne Sabatos-Peyton, Hwai Wen Chang, Gerhard Johann Frey
Life of this patent
Estimating the term…
Abstract
Antibody molecules that specifically bind to LAG-3 are disclosed. The anti-LAG-3 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious disorders.
Claims20
1-13. (canceled)
A bispecific antibody molecule having a first binding specificity for LAG-3 and a second binding specificity for PD-1, TIM-3, CEACAM-1, CEACAM-5, PD-L1 or PD-L2, wherein the bispecific antibody molecule comprises:
- (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.
15-31. (canceled)
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 PD-1, TIM-3, CEACAM-1, CEACAM-5, PD-L1 or PD-L2, wherein the bispecific antibody molecule comprises:
- (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.
33-40. (canceled)
A method of stimulating an immune response in a subject, comprising administering to a subject in need thereof an isolated antibody molecule in an amount effective to stimulate the immune response,
- wherein the isolated antibody is capable of binding to LAG-3 and comprises:
- (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.
A method of treating a cancer, comprising administering to a subject in need thereof an antibody molecule capable of binding to human LAG-3 in an amount effective to treat the cancer, wherein the antibody molecule comprises:
- (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.
44-47. (canceled)
A method of treating a cancer, comprising administering to a subject in need thereof a bispecific antibody molecule in an amount effective to treat the cancer, wherein the bispecific antibody molecule has a first binding specificity for LAG-3 and a second binding specificity for PD-1, TIM3-3, CEACAM-1, CEACAM-5, PD-L1 or PD-L2, and wherein the bispecific antibody molecule comprises:
- (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.
(canceled)
A method of treating an infectious disease, comprising administering to a subject in need thereof an antibody molecule in an amount effective to treat the infectious disease,
- wherein the isolated antibody is capable of binding to LAG-3 and comprises:
- (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.
A method of detecting LAG-3 in a biological sample, comprising (i) contacting the sample or the subject with an isolated antibody molecule under conditions that allow interaction of the antibody molecule and the polypeptide to occur, and (ii) detecting formation of a complex between the antibody molecule and the sample or the subject (and optionally, the reference sample or subject),
- wherein the isolated antibody is capable of binding to LAG-3 and comprises:
- (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.
Dependencies are inferred from the claim text.