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US 2026/0152571 A1Published application
Anti-wt1/hla antibodies and uses thereof
AssigneeBiocytogen Pharmaceuticals (Beijing) Co., Ltd.
InventorsJun Du, Taolin Liu, Limin Zhao, Wanbo Tang, Ruixue Wang
Life of this patent
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Abstract
Provided are antibodies or antigen-binding fragments thereof that binds to a complex comprising a WT1 peptide and a MHC molecule, and the related antibody-drug conjugate (ADC) derived therefrom, chimeric antigen receptor (CAR) derived therefrom, and the uses thereof.
Claims100
An antibody or antigen-binding fragment thereof that binds to a complex comprising a WT1 peptide and a MHC molecule, comprising:
- a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3, wherein the VH CDR1 region comprises an amino acid sequence that is at least 80% identical to a selected VH CDR1 amino acid sequence, the VH CDR2 region comprises an amino acid sequence that is at least 80% identical to a selected VH CDR2 amino acid sequence, and the VH CDR3 region comprises an amino acid sequence that is at least 80% identical to a selected VH CDR3 amino acid sequence;
- and
- a light chain variable region (VL) comprising CDRs 1, 2, and 3, wherein the VL CDR1 region comprises an amino acid sequence that is at least 80% identical to a selected VL CDR1 amino acid sequence, the VL CDR2 region comprises an amino acid sequence that is at least 80% identical to a selected VL CDR2 amino acid sequence, and the VL CDR3 region comprises an amino acid sequence that is at least 80% identical to a selected VL CDR3 amino acid sequence,
- wherein the selected VH CDRs 1, 2, and 3 amino acid sequences and the selected VL CDRs, 1, 2, and 3 amino acid sequences are one of the following:
- (1) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 1-3, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 55-57, respectively;
- (2) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 4-6, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 58-60, respectively;
- (3) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 7-9, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 61-63, respectively;
- (4) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 10-12, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 64-66, respectively;
- (5) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 13-15, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 67-69, respectively;
- (6) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 16-18, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 70-72, respectively;
- (7) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 19-21, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 73-75, respectively;
- (8) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 22-24, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 76-78, respectively;
- (9) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 25-27, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 79-81, respectively;
- (10) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 28-30, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 55-57, respectively;
- (11) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 31-33, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 58-60, respectively;
- (12) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 34-36, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 61-63, respectively;
- (13) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 37-39, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 64-66, respectively;
- (14) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 40-42, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 67-69, respectively;
- (15) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 43-45, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 70-72, respectively;
- (16) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 46-48, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 73-75, respectively;
- (17) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 49-51, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 76-78, respectively;
- and
- (18) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 52-54, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 79-81, respectively.
56 more elements
A nucleic acid comprising a polynucleotide encoding a polypeptide comprising:
- (1) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 1-3, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 91 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (2) an immunoglobulin light chain or a fragment thereof comprising a VL comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 55-57, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:
- 82 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (3) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 4-6, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 92 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (4) an immunoglobulin light chain or a fragment thereof comprising a VL comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 58-60, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:
- 83 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (5) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 7-9, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 93 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (6) an immunoglobulin light chain or a fragment thereof comprising a VL comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 61-63, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:
- 84 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (7) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 10-12, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 94 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (8) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 64-66, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:
- 85 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (9) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 13-15, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 95 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (10) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 67-69, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:
- 86 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (11) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 16-18, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 96 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (12) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 70-72, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:
- 87 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (13) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 19-21, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 97 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (14) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 73-75, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:
- 88 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (15) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 22-24, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 98 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (16) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 76-78, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:
- 89 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (17) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 25-27, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 99 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (18) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 79-81, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:
- 90 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (19) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 28-30, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 91 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (20) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 31-33, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 92 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (21) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 34-36, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 93 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (22) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 37-39, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 94 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (23) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 40-42, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 95 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (24) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 43-45, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 96 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (25) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 46-48, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 97 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (26) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 49-51, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 98 binds to a complex comprising a WT1 peptide and a MHC molecule;
- (27) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs:
- 52-54, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 99 binds to a complex comprising a WT1 peptide and a MHC molecule;
- or
79 more elements
An antibody or antigen-binding fragment thereof that binds to a complex comprising a WT1 peptide and a MHC molecule, comprising
- a heavy chain variable region (VH) comprising an amino acid sequence that is at least 90% identical to a selected VH sequence, and a light chain variable region (VL) comprising an amino acid sequence that is at least 90% identical to a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following:
- (1) the selected VH sequence is SEQ ID NO:
- 82, and the selected VL sequence is SEQ ID NO:
- 91;
- (2) the selected VH sequence is SEQ ID NO:
- 83, and the selected VL sequence is SEQ ID NO:
- 92;
- (3) the selected VH sequence is SEQ ID NO:
- 84, and the selected VL sequence is SEQ ID NO:
- 93;
- (4) the selected VH sequence is SEQ ID NO:
- 85, and the selected VL sequence is SEQ ID NO:
- 94;
- (5) the selected VH sequence is SEQ ID NO:
- 86, and the selected VL sequence is SEQ ID NO:
- 95;
- (6) the selected VH sequence is SEQ ID NO:
- 87, and the selected VL sequence is SEQ ID NO:
- 96;
- (7) the selected VH sequence is SEQ ID NO:
- 88, and the selected VL sequence is SEQ ID NO:
- 97;
- (8) the selected VH sequence is SEQ ID NO:
- 89, and the selected VL sequence is SEQ ID NO:
- 98;
- and
- (9) the selected VH sequence is SEQ ID NO:
- 90, and the selected VL sequence is SEQ ID NO:
- 99.
26 more elements
An antibody or antigen-binding fragment thereof that binds to a complex comprising a WT1 peptide and a MHC molecule, comprising
- a heavy chain variable region (VH) comprising VH CDR1, VH CDR2, and VH CDR3 that are identical to VH CDR1, VH CDR2, and VH CDR3 of a selected VH sequence;
- and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3 that are identical to VL CDR1, VL CDR2, and VL CDR3 of a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following:
- (1) the selected VH sequence is SEQ ID NO:
- 82, and the selected VL sequence is SEQ ID NO:
- 91;
- (2) the selected VH sequence is SEQ ID NO:
- 83, and the selected VL sequence is SEQ ID NO:
- 92;
- (3) the selected VH sequence is SEQ ID NO:
- 84, and the selected VL sequence is SEQ ID NO:
- 93;
- (4) the selected VH sequence is SEQ ID NO:
- 85, and the selected VL sequence is SEQ ID NO:
- 94;
- (5) the selected VH sequence is SEQ ID NO:
- 86, and the selected VL sequence is SEQ ID NO:
- 95;
- (6) the selected VH sequence is SEQ ID NO:
- 87, and the selected VL sequence is SEQ ID NO:
- 96;
- (7) the selected VH sequence is SEQ ID NO:
- 88, and the selected VL sequence is SEQ ID NO:
- 97;
- (8) the selected VH sequence is SEQ ID NO:
- 89, and the selected VL sequence is SEQ ID NO:
- 98;
- and
- (9) the selected VH sequence is SEQ ID NO:
- 90, and the selected VL sequence is SEQ ID NO:
- 99.
27 more elements
An antibody or antigen-binding fragment thereof that binds to a complex comprising a WT1 peptide and a MHC molecule, wherein the antibody or antigen-binding fragment thereof binds specifically to an epitope in the WT1 peptide, wherein the epitope is one or more of the following:
- (1) an amino acid residue corresponding to R1 of SEQ ID NO:
- 100;
- (2) an amino acid residue corresponding to F3 of SEQ ID NO:
- 100;
- (3) an amino acid residue corresponding to P4 of SEQ ID NO:
- 100;
- (4) an amino acid residue corresponding to N5 of SEQ ID NO:
- 100;
- and
- (5) an amino acid residue corresponding to Y8 of SEQ ID NO:
- 100.
8 more elements
Dependencies are inferred from the claim text.