LAG-3 and PD-1/LAG-3-antibodies
AssigneeEli Lilly and Company
InventorsYaqiong Lin, Marta Antonina Witek, Jianghuai Xu
Life of this patent
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Abstract
The present disclosure relates to antibodies that bind to and agonize human LAG-3, and to bispecific antibodies that bind to and agonize each of human PD-1 and human LAG-3.
Claims34
An antibody that comprises a human LAG-3 binding domain comprising a heavy chain variable region (VH) and a light chain variable region (VL),
- wherein the VH comprises heavy chain complementarity determining regions (HCDR):
- HCDR1 comprising SEQ ID NO:
- 1, HCDR2 comprising SEQ ID NO:
- 2, and HCDR3 comprising SEQ ID NO:
- 3;
- and
- wherein the VL comprises light chain complementarity determining regions (LCDR):
- LCDR1 comprising SEQ ID NO:
- 4, LCDR2 comprising SEQ ID NO:
- 5, and LCDR3 comprising SEQ ID NO:
- 6.
A nucleic acid comprising a sequence encoding one or both of SEQ ID NO:
- 22 and SEQ ID NO:
- 37.
A human LAG-3/human PD-1 dual agonist bispecific antibody comprising:
- (a) a first antigen binding domain that binds human LAG-3 comprising a first heavy chain variable region (VH1) and a first light chain variable region (VL1),
- wherein the VH1 comprises:
- HCDR1 comprising SEQ ID NO:
- 1, HCDR2 comprising SEQ ID NO:
- 2, and HCDR3 comprising SEQ ID NO:
- 3;
- and
- wherein the VL1 comprises:
- LCDR1 comprising SEQ ID NO:
- 4, LCDR2 comprising SEQ ID NO:
- 5, and LCDR3 comprising SEQ ID NO:
- 6;
- and
- (b) a second antigen binding domain that binds human PD-1 comprising a second heavy chain variable region (VH2) and a second light chain variable region (VL2),
- wherein the VH2 comprises:
- HCDR1 comprising SEQ ID NO:
- 7, HCDR2 comprising SEQ ID NO:
- 8, and HCDR3 comprising SEQ ID NO:
- 9;
- and
- wherein the VL2 comprises LCDR1 comprising SEQ ID NO:
- 10, LCDR2 comprising SEQ ID NO:
- 11, and LCDR3 comprising SEQ ID NO:
- 12.
A nucleic acid comprising a sequence encoding one or more of SEQ ID NOS:
- 22, 24, 37, and 38, wherein if amino acid residue 328 in SEQ ID NO:
- 37 is a lysine residue, then X at position 324 in SEQ ID NO:
- 38 is a lysine residue, and wherein if X at position 328 in SEQ ID NO:
- 37 is an alanine residue, then X at position 324 in SEQ ID NO:
- 38 is an alanine residue.
A cell comprising a nucleic acid comprising a sequence encoding one or more of the polypeptides of SEQ ID NOS:
- 22, 24, 37 and 38, wherein if X at position 328 in SEQ ID NO:
- 37 is a lysine residue, then X at position 324 in SEQ ID NO:
- 38 is a lysine residue, and wherein if X at position 328 in SEQ ID NO:
- 37 is an alanine residue, then X at position 324 in SEQ ID NO:
- 38 is an alanine residue, and wherein the cell is capable of expressing the one or more polypeptides.
Dependencies are inferred from the claim text.