Granted Patent
B2
US 12,460,000 · App. 17/273,955 · Granted Nov 4, 2025
Anti-CD19 and anti-CD3 bispecific antigen binding proteins and uses thereof
Inventors:
Zhihua Huang (Shanghai, CN); Yiqun Rao (Shanghai, CN); Wuzhong Shen (Shanghai, CN); Yumin Cui (Shanghai, CN); Xiaoqiang Yan (Shanghai, CN)
Assignee:
ITabMed (HK) Limited
C07K16/2809A61P35/00A61K2039/505C07K2317/31C07K2317/522C07K2317/55C07K2317/56C07K2317/622C07K2317/73C07K2317/92
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Abstract
The present invention provides bispecific antigen binding proteins (BSAPs) that specifically bind to CD3 and a tumor antigen (e.g., CD19). The present invention also provides uses of the BSAPs for the preparation of pharmaceutical compositions, methods of treating cancer, and kits comprising the BSAPs.
Claims (42)
1 . A bispecific antigen binding protein (BSAP) comprising:
(I) an anti-CD19 Fab specifically recognizing CD19, wherein the anti-CD19 Fab comprises:
(a) an immunoglobulin (Ig) heavy chain variable region (VH) and an Ig heavy chain constant region 1 (CH1), and
(b) an Ig light chain variable region (VL) and an Ig light chain constant region (CL);
wherein:
(i) the VH of the anti-CD19 Fab comprises: a heavy chain hypervariable region 1 (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 the VL of the anti-CD19 Fab comprises: a light chain hypervariable region 1 (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; or
(ii) the VH of the anti-CD19 Fab 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 the VL of the anti-CD19 Fab comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 37, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 38, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 39; and
(II) an anti-CD3 scFv specifically recognizing CD3;
wherein the anti-CD3 scFv comprises a VH and a VL;
wherein the VH of the anti-CD3 scFv comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 10, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 11; and wherein the VL of the anti-CD3 scFv comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 13, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 14:
wherein:
(1) the anti-CD3 scFv is connected to the N-terminus of the VH or the VL of the anti-CD19 Fab via an optional linker; or
(2) the BSAP comprises a first anti-CD3 scFv and a second anti-CD3 scFv, wherein the first anti-CD3 scFv is connected to the N-terminus of the VH of the anti-CD19 Fab via an optional first linker, and the second anti-CD3 scFv is connected to the N-terminus of the VL of the anti-CD19 Fab via an optional second linker.
2 . The BSAP of claim 1 , wherein the anti-CD3 scFv is connected to the N-terminus of the VH of the anti-CD19 Fab.
3 . The BSAP of claim 1 , wherein the anti-CD3 scFv is connected to the N-terminus of the VL of the anti-CD19 Fab.
4 . The BSAP of claim 1 , wherein the VH of the anti-CD19 Fab comprises the amino acid sequence of SEQ ID NO: 7, and wherein the VL of the anti-CD19 Fab comprises the amino acid sequence of SEQ ID NO: 8 or 40.
5 . The BSAP of claim 1 , wherein the VH of the anti-CD3 scFv comprises the amino acid sequence of SEQ ID NO: 15, and wherein the VL of the anti-CD3 scFv comprises the amino acid sequence of SEQ ID NO: 16.
6 . The BSAP of claim 5 , wherein the anti-CD3 scFv comprises the amino acid sequence of SEQ ID NO: 17.
7 . The BSAP of claim 1 , wherein the BSAP comprises a first polypeptide and a second polypeptide, wherein the first polypeptide comprises an amino acid sequence of any of SEQ ID NOs: 23, 28, 35, 58, and 59, and wherein the second polypeptide comprises an amino acid sequence of SEQ ID NO: 24 or 27.
8 . The BSAP of claim 7 , wherein the first polypeptide comprises an amino acid sequence of any one of SEQ ID NOs: 23, 28, 35, 58, and 59, and wherein the second polypeptide comprises the amino acid sequence of SEQ ID NO: 24.
9 . The BSAP of claim 7 , wherein the first polypeptide comprises an amino acid sequence of SEQ ID NO: 28 or 58, and wherein the second polypeptide comprises the amino acid sequence of SEQ ID NO: 27.
10 . An isolated nucleic acid or vector encoding the BSAP of claim 1 .
11 . A pharmaceutical composition comprising the BSAP of claim 1 , and a pharmaceutically acceptable carrier.
12 . A method of treating a CD19-expressing cancer in an individual in need thereof, comprising administering to the individual an effective amount of the BSAP of claim 1 .
13 . The method of claim 12 , wherein the CD19-expressing cancer is selected from the group consisting of acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), mantel cell leukemia (MCL), non-Hodgkin's lymphoma (NHL), and B cell lymphoma (BCL).
14 . A method of generating the BSAP of claim 1 , comprising:
(i) culturing a host cell comprising the isolated nucleic acid or vector of claim 10 under a condition suitable for the expression of the encoded BSAP; and
(ii) recovering the expressed BSAP from the cultured host cell.
15 . A bispecific antigen binding protein (BSAP) comprising:
(I) an anti-CD19 Fab specifically recognizing CD19, wherein the anti-CD19 Fab comprises:
(a) an immunoglobulin (Ig) heavy chain variable region (VH) and an Ig heavy chain constant region 1 (CH1), and
(b) an Ig light chain variable region (VL) and an Ig light chain constant region (CL); and
(II) an anti-CD3 scFv specifically recognizing CD3;
wherein the anti-CD3 scFv is connected to the N-terminus of the VH of the anti-CD19 Fab via a linker to form a first polypeptide, and the VL and the CL of the anti-CD19 Fab form a second polypeptide; and
wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO: 23, and wherein the second polypeptide comprises the amino acid sequence of SEQ ID NO: 24.
16 . A pharmaceutical composition comprising the BSAP of claim 15 , and a pharmaceutically acceptable carrier.
17 . A method of treating a CD19-expressing cancer in an individual in need thereof, comprising administering to the individual an effective amount of the BSAP of claim 15 .
18 . The method of claim 17 , wherein the CD19-expressing cancer is selected from the group consisting of acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), mantel cell leukemia (MCL), non-Hodgkin's lymphoma (NHL), and B cell lymphoma (BCL).
19 . An isolated nucleic acid or vector encoding the BSAP of claim 15 .
20 . A method of generating the BSAP of claim 15 , comprising:
(i) culturing a host cell comprising the isolated nucleic acid or vector of claim 19 under a condition suitable for the expression of the encoded BSAP; and
(ii) recovering the expressed BSAP from the cultured host cell.
Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 6, 2026
From: ITABMED (HK) LIMITED
To: ITABMED CO., LTD.
Reel/Frame 074003/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 25, 2021
From: HUANG, ZHIHUA; RAO, YIQUN; SHEN, WUZHONG; CUI, YUMIN; YAN, XIAOQIANG
To: EVIVE BIOTECHNOLOGY (SHANGHAI) LTD
Reel/Frame 056348/0508 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 25, 2021
From: EVIVE BIOTECHNOLOGY (SHANGHAI) LTD
To: EVIVE BIOTECH LTD.
Reel/Frame 056348/0516 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 25, 2021
From: EVIVE BIOTECH LTD.
To: ITABMED (HK) LIMITED
Reel/Frame 056348/0527 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 22, 2021
From: EVIVE BIOTECH LTD.
To: ITABMED (HK) LIMITED
Reel/Frame 056003/0276 →
Priority Claims (1)
CN 201811041588.X
· Sep 7, 2018
· national
Continuity (1)
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