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US 2026/0265376 A1Published application
Multispecific antigen binding proteins and uses thereof
AssigneeItabmed Co., Ltd.
InventorsGuiyun TU, Wuzhong SHEN, Hanyang CHEN, Shengjie XUE, Zheng YANG, Bingbin XIE, Ke WANG, Zuowen DUAN, Xiaoqiang YAN
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Abstract
The invention provides novel heterodimeric proteins including heterodimeric antibodies. The present invention describes novel immunoglobulin compositions that simultaneously co-engage antigens, where both of the antigens are bound monovalently. The novel immunoglobulins described preferably utilize heterodimeric Fe regions. Methods of using the novel immunoglobulin compositions, particularly for therapeutic purposes, are also described herein.
Claims33
A multispecific antigen binding protein comprising:
- i) an anti-CD3 moiety that specifically binds to CD3;
- ii) an anti-CD8 moiety that specifically binds to CD8;
- and
- iii) an anti-target epitope moiety that specifically binds to a target epitope,
- wherein a first moiety of the three moieties is a Fab fragment, wherein the Fab fragment comprises a first polypeptide comprising a heavy chain variable region (VH) and a heavy chain constant region (CH1), and a second polypeptide comprising a light chain variable region (VL) and a light chain constant region (CL);
- wherein a second moiety of the three moieties is a first antigen binding fragment;
- wherein a third moiety of the three moieties is a second antigen binding fragment;
- and
- wherein:
- (a) the first antigen binding fragment is fused to the N-terminus of the VH of the Fab fragment, and the second antigen binding fragment is fused to the N-terminus of the VL of the Fab fragment;
- (b) the first antigen binding fragment is fused to the C-terminus of the CH1 of the Fab fragment, and the second antigen binding fragment is fused to the N-terminus of the VL of the Fab fragment;
- (c) the first antigen binding fragment is fused to the N-terminus of the VH of the Fab fragment, and the second antigen binding fragment is fused to the C-terminus of the CL of the Fab fragment;
- (d) the first antigen binding fragment is fused to the N-terminus of the VH of the Fab fragment, and the second antigen binding fragment is fused to the C-terminus of the CH1 of the Fab fragment;
- or
- (e) the first antigen binding fragment is fused to the N-terminus of the VL of the Fab fragment, and the second antigen binding fragment is fused to the C-terminus of the CL of the Fab fragment.
12 more elements
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6-7. (canceled)
9-11. (canceled)
13-26. (canceled)
(canceled)
30-38. (canceled)
41-44. (canceled)
An anti-CD8 antibody or antigen binding fragment thereof that specifically binds to CD8, wherein the anti-CD8 antibody or antigen binding fragment thereof comprises:
- i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 13, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 14, an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 15, an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 4, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 5, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 6;
- ii) 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:
- 16, an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 3, an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 4, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 5, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 6;
- iii) 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, an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 17, an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 4, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 5, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 6;
- iv) 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:
- 18, an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 19, an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 4, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 5, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 6;
- v) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 7, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 8, an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 9, an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 11, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 12;
- or
- vi) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 20, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 2, an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 22, an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 4, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 5, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 23.
40 more elements
46-50. (canceled)
An anti-CD3 antibody or antigen binding fragment thereof that specifically binds to CD3, wherein the anti-CD3 antibody or antigen binding fragment thereof comprises:
- (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 36, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 37, an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 38, an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 39, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 40, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 41;
- (b) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 36, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 157, an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 158, an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 39, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 40, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 41;
- or
- (c) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 36, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 166, an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 38, an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 39, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 40, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 41.
19 more elements
52-55. (canceled)
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Dependencies are inferred from the claim text.