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US 12,577,305 B2Granted
Multispecific antigen binding proteins capable of binding CD19 and CD3, and use thereof
AssigneeITabMed (HK) Limited
InventorsZhihua Huang, Wuzhong Shen, Yiqun Rao, Yumin Cui, Xiaoqiang Yan
Life of this patent
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Abstract
Provided are multispecific antigen binding proteins (MSAPs) that specifically bind to CD3 and CD19. Further provided are uses of the MSAPs for the preparation of pharmaceutical compositions, methods of treating cancer, and kits comprising the MSAPs.
Claims26
A multispecific antigen binding protein comprising:
- (I) an anti-CD3 Fab fragment that specifically binds to CD3, wherein the anti-CD3 Fab fragment comprises:
- (a) an immunoglobulin (Ig) heavy chain variable region (VH) and an Ig heavy chain constant region (CH1);
- and
- (b) an Ig light chain variable region (VL) and an Ig light chain constant region (CL);
- (II) an anti-CD19 single chain variable fragment (scFv) that specifically binds to CD19,
- wherein the anti-CD19 scFv comprises a VH, wherein the VH of the anti-CD19 scFv comprises an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 1, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 2, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 3;
- and
- wherein the anti-CD19 scFv comprises a VL, wherein the VL of the anti-CD19 scFv comprises an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 47, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 48, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 49;
- and
- (III) an optional linker connecting the anti-CD3 Fab fragment and the anti-CD19 scFv;
- and
- wherein:
- (i) the anti-CD19 scFv is connected to the N-terminus of the VH or the VL of the anti-CD3 Fab fragment;
- or
- (ii) the multispecific antigen binding protein comprises a first anti-CD19 scFv and a second anti-CD19 scFv, wherein the first anti-CD19 scFv is fused to the N-terminus of the VH of the anti-CD3 Fab fragment, and wherein the second anti-CD19 scFv is fused to the N-terminus of the VL of the anti-CD3 Fab fragment.
18 more elements
A multispecific antigen binding protein comprising:
- (I) an anti-CD3 Fab fragment that specifically binds to CD3, wherein the anti-CD3 Fab fragment comprises:
- (a) a VH and a CH1;
- and
- (b) a VL and a CL;
- (II) a first anti-CD19 scFv and a second anti-CD19 scFv;
- and
- (III) a first linker and a second linker;
- wherein the first anti-CD19 scFv is fused to the N-terminus of the VH of the anti-CD3 Fab fragment via the first linker to form a first polypeptide of the multispecific antigen binding protein, and the second anti-CD19 scFv is fused to the N-terminus of the VL of the anti-CD3 Fab fragment via the second linker to form a second polypeptide of the multispecific antigen binding protein;
- wherein the first polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 53, and wherein the second polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 54.
8 more elements
A multispecific antigen binding protein comprising:
- (I) an anti-CD3 Fab fragment that specifically binds to CD3, wherein the anti-CD3 Fab fragment comprises:
- (a) a VH and a CH1;
- and
- (b) a VL and a CL;
- (II) a first anti-CD19 scFv and a second anti-CD19 scFv;
- and
- (III) a first linker and a second linker;
- wherein the first anti-CD19 scFv is fused to the N-terminus of the VH of the anti-CD3 Fab fragment via the first linker to form a first polypeptide of the multispecific antigen binding protein, and the second anti-CD19 scFv is fused to the N-terminus of the VL of the anti-CD3 Fab fragment via the second linker to form a second polypeptide of the multispecific antigen binding protein;
- wherein the first polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 60, and wherein the second polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 61.
8 more elements
A multispecific antigen binding protein, wherein:
- i) the multispecific antigen binding protein comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO:
- 57, wherein the multispecific antigen binding protein comprises an anti-CD19 scFv connected to the N-terminus of the VL of an anti-CD3 Fab fragment via a linker to form a second polypeptide of the multispecific antigen binding protein, wherein the second polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 61;
- ii) the multispecific antigen binding protein comprises an anti-CD19 scFv connected to the N-terminus of the VH of an anti-CD3 Fab fragment via a linker to form a first polypeptide of the multispecific antigen binding protein, wherein the first polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 60, and wherein the multispecific antigen binding protein comprises a second polypeptide comprising the amino acid sequence of SEQ ID NO:
- 58;
- iii) the multispecific antigen binding protein comprises a first anti-CD19 scFv connected to the N-terminus of the VH of an anti-CD3 Fab fragment via a first linker to form a first polypeptide of the multispecific antigen binding protein, wherein the first polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 53, wherein the multispecific antigen binding protein comprises a second anti-CD19 scFv connected to the N-terminus of the VL of the anti-CD3 Fab fragment via a second linker to form a second polypeptide of the multispecific antigen binding protein, and wherein the second polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 61;
- or
- iv) the multispecific antigen binding protein comprises an anti-CD19 scFv connected to the N-terminus of the VH of an anti-CD3 Fab fragment via a first linker to form a first polypeptide of the multispecific antigen binding protein, wherein the first polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 60, wherein the multispecific antigen binding protein comprises a second anti-CD19 scFv connected to the N-terminus of the VL of the anti-CD3 Fab fragment via a second linker to form a second polypeptide of the multispecific antigen binding protein, and wherein the second polypeptide of the multispecific antigen binding protein comprises the amino acid sequence of SEQ ID NO:
- 54.
10 more elements
Dependencies are inferred from the claim text.