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US 2023/0399408 A1Published application
Multispecific antibodies and uses thereof
AssigneeTherapeutics, Inc.
InventorsMohd Saif Zaman, Yue Liu
Life of this patent
Estimating the term…
Abstract
This disclosure relates to multi specific antibodies (e.g., bi specific antibodies) or antigen binding fragments thereof. In one aspect, the multispecific antibodies or antigen-binding fragments thereof binds to cMET and/or EGFR, or a combination thereof. An antibody or antigen-binding fragment thereof that binds to cMET (tyrosine-protein kinase Met), comprising: a heavy-chain antibody variable domain (VHH) comprising complementarity determining regions (CDRs) 1, 2, and 3.
Claims106
An antibody or antigen-binding fragment thereof that binds to cMET (tyrosine-protein kinase Met), comprising:
- a heavy-chain antibody variable domain (VHH) comprising complementarity determining regions (CDRs) 1, 2, and 3, wherein the VHH CDR1 region comprises an amino acid sequence that is at least 80% identical to a selected VHH CDR1 amino acid sequence, the VHH CDR2 region comprises an amino acid sequence that is at least 80% identical to a selected VHH CDR2 amino acid sequence, and the VHH CDR3 region comprises an amino acid sequence that is at least 80% identical to a selected VHH CDR3 amino acid sequence;
- wherein the selected VHH CDRs 1, 2, and 3 amino acid sequences are one of the following:
- (1) the selected VHH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 1, 2, and 3, respectively;
- (2) the selected VHH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 4, 5, and 6, respectively;
- (3) the selected VHH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 7, 8, and 9, respectively;
- and
- (4) the selected VHH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs:
- 10, 11, and 12, respectively.
8 more elements
An antibody or antigen-binding fragment thereof that binds to cMET comprising a heavy-chain antibody variable domain (VHH) comprising an amino acid sequence that is at least 80% identical to a selected VHH sequence, wherein the selected VHH sequence is selected from the group consisting of SEQ ID NOs:
- 19-22 and 77-84.
A multi-specific antibody or antigen-binding fragment thereof, comprising a first antigen-binding site that specifically binds to EGFR, and a second antigen-binding site that specifically binds to cMET.
A polypeptide complex, comprising
- (a) a first polypeptide comprising from N-terminus to C-terminus:
- a first heavy-chain antibody variable domain (VHH), a first hinge region, a first Fc region;
- (b) a second polypeptide comprising from N-terminus to C-terminus:
- a heavy chain variable region (VH), a second hinge region, and a second Fc region;
- and
- (c) a third polypeptide comprising a light chain variable region (VL);
- wherein the first VHH specifically binds to cMET, wherein the VH and the VL associate with each other and specifically bind to EGFR.
4 more elements
A polypeptide complex, comprising
- (a) a first polypeptide comprising from N-terminus to C-terminus:
- a first heavy-chain antibody variable domain (VHH), a first hinge region, a first Fc region;
- and
- (b) a second polypeptide comprising from N-terminus to C-terminus:
- a single-chain variable fragment (scFv), a second hinge region, and a second Fc region;
- wherein the first VHH specifically binds to cMET;
- wherein the scFv comprises a heavy chain variable region (VH), a first linker peptide sequence, and a light chain variable region (VL);
- wherein the VH and the VL associate with each other and specifically bind to EGFR.
5 more elements
A polypeptide complex, comprising
- (a) a first polypeptide comprising from N-terminus to C-terminus:
- a first heavy-chain antibody variable domain (VHH1), a first linker peptide sequence, a first heavy chain variable region (VH1), a first hinge region, and a first Fc region;
- (b) a second polypeptide comprising a first light chain variable region (VL1);
- (c) a third polypeptide comprising from N-terminus to C-terminus:
- a second heavy-chain antibody variable domain (VHH2), a second linker peptide sequence, a second heavy chain variable region (VH2), a second hinge region, and a second Fc region;
- and
- (d) a fourth polypeptide comprising a second light chain variable region (VL2);
- wherein the VHH1 and the VHH2 specifically bind to cMET;
- wherein the VH1 and the VL1 associate with each other and specifically bind to EGFR;
- wherein the VH2 and the VL2 associate with each other and specifically bind to EGFR.
7 more elements
A polypeptide complex, comprising
- (a) a first polypeptide comprising from N-terminus to C-terminus:
- a first heavy chain variable region (VH1), a first hinge region, a first Fc region;
- a first linker peptide sequence, and a first heavy-chain antibody variable domain (VHH1);
- (b) a second polypeptide comprising a first light chain variable region (VL1);
- (c) a third polypeptide comprising from N-terminus to C-terminus:
- a second heavy chain variable region (VH2), a second hinge region, a second Fc region, a second linker peptide sequence, and a second heavy-chain antibody variable domain (VHH2);
- and
- (d) a fourth polypeptide comprising a second light chain variable region (VL2);
- wherein the VHH1 and/or the VHH2 specifically bind to cMET;
- wherein the VH1 and the VL1 associate with each other and specifically bind to EGFR;
- wherein the VH2 and the VL2 associate with each other and specifically bind to EGFR.
8 more elements
A polypeptide complex, comprising
- (a) a first polypeptide comprising from N-terminus to C-terminus:
- a first heavy-chain antibody variable domain (VHH), a first hinge region, a first Fc region;
- (b) a second polypeptide comprising from N-terminus to C-terminus:
- a heavy chain variable region (VH), a second hinge region, and a second Fc region;
- and
- (c) a third polypeptide comprising a light chain variable region (VL);
- wherein the first VHH specifically binds to cMET, wherein the VH and the VL associate with each other and specifically bind to EGFR;
- wherein the first polypeptide further comprises a second VHH that specifically binds to cMET, wherein the second VHH is linked to the N-terminus of the first VHH via a linker peptide sequence.
5 more elements
A polypeptide complex, comprising
- (a) a first polypeptide comprising from N-terminus to C-terminus:
- a first heavy-chain antibody variable domain (VHH), a first hinge region, a first Fc region;
- and
- (b) a second polypeptide comprising from N-terminus to C-terminus:
- a single-chain variable fragment (scFv), a second hinge region, and a second Fc region;
- wherein the first VHH specifically binds to cMET;
- wherein the scFv comprises a heavy chain variable region (VH), a first linker peptide sequence, and a light chain variable region (VL);
- wherein the VH and the VL associate with each other and specifically bind to EGFR;
- wherein the first polypeptide further comprises a second VHH that specifically binds to cMET, wherein the second VHH is linked to the N-terminus of the first VHH via a second linker peptide sequence.
6 more elements
A polypeptide complex, comprising
- (a) a first polypeptide comprising from N-terminus to C-terminus:
- a first heavy-chain antibody variable domain (VHH1), a first linker peptide sequence, a first heavy chain variable region (VH1), a first hinge region, and a first Fc region;
- (b) a second polypeptide comprising a first light chain variable region (VL1);
- (c) a third polypeptide comprising from N-terminus to C-terminus:
- a second heavy-chain antibody variable domain (VHH2), a second linker peptide sequence, a second heavy chain variable region (VH2), a second hinge region, and a second Fc region;
- and
- (d) a fourth polypeptide comprising a second light chain variable region (VL2);
- wherein the VHH1 and the VHH2 specifically bind to cMET;
- wherein the VH1 and the VL1 associate with each other and specifically bind to EGFR;
- wherein the VH2 and the VL2 associate with each other and specifically bind to EGFR;
- wherein sequences of the VHH1 and the VHH2 are different.
8 more elements
A polypeptide complex, comprising
- (a) a first polypeptide comprising from N-terminus to C-terminus:
- a first heavy chain variable region (VH1), a first hinge region, a first Fc region;
- a first linker peptide sequence, and a first heavy-chain antibody variable domain (VHH1);
- (b) a second polypeptide comprising a first light chain variable region (VL1);
- (c) a third polypeptide comprising from N-terminus to C-terminus:
- a second heavy chain variable region (VH2), a second hinge region, a second Fc region, a second linker peptide sequence, and a second heavy-chain antibody variable domain (VHH2);
- and
- (d) a fourth polypeptide comprising a second light chain variable region (VL2);
- wherein the VHH1 and/or the VHH2 specifically bind to cMET;
- wherein the VH1 and the VL1 associate with each other and specifically bind to EGFR;
- wherein the VH2 and the VL2 associate with each other and specifically bind to EGFR;
- wherein sequences of the VHH1 and the VHH2 are different.
9 more elements
Dependencies are inferred from the claim text.