ENPP3 and CD3 binders and their usage

JP2026527605APending Publication Date: 2026-08-14JANSSEN BIOTECH INC
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2024-08-06
Publication Date
2026-08-14

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Abstract

This disclosure provides an ENPP3 binder containing a bispecific ENPP3 × CD3 binding protein, as well as related compositions and methods of use.
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Claims

1. A binder containing an antigen-binding region that binds to the ENPP3 epitope.

2. The binder according to claim 1, wherein the epitope of ENPP3 is selected from the group consisting of SEQ ID NOs: 295-297, DVP, and SEQ ID NOs: 299-305.

3. The antigen-binding region is (a) The VH domain of VH shown in Sequence ID No. 22, including HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 23, (b) The VH domain of VH shown in Sequence ID No. 45, comprising HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 46, comprising LCDR1, LCDR2, and LCDR3 (c) The VH domain, which includes HCDR1, HCDR2, and HCDR3 of the VH shown in Sequence ID No. 68, and the VL domain, which includes LCDR1, LCDR2, and LCDR3 of the VL shown in Sequence ID No. 69 or Sequence ID No. 70, (d) The VH domain of VH shown in Sequence ID No. 91, which includes HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 92, which includes LCDR1, LCDR2, and LCDR3 (e) The VH domain of VH shown in Sequence ID No. 113, comprising HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 114 or Sequence ID No. 115, (f) The VH domain, which includes HCDR1, HCDR2, and HCDR3 of the VH shown in Sequence ID No. 134, and the VL domain, which includes LCDR1, LCDR2, and LCDR3 of the VL shown in Sequence ID No. 135 or Sequence ID No. 136, (g) The VH domain of VH shown in Sequence ID No. 158, which includes HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 159, and (h) The VH domain, which includes HCDR1, HCDR2, and HCDR3 of the VH shown in Sequence ID No. 177, and the VL domain, which includes LCDR1, LCDR2, and LCDR3 of the VL shown in Sequence ID No. 178 The binder according to claim 1, comprising a VH domain and a VL domain selected from the group consisting of the following.

4. The aforementioned CDR sequence is (a1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 1, the HCDR2 contains the amino acid sequence of SEQ ID NO: 2, the HCDR3 contains the amino acid sequence of SEQ ID NO: 3, the LCDR1 contains the amino acid sequence of SEQ ID NO: 4, the LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (a2) The HCDR1 contains the amino acid sequence of SEQ ID NO: 7, the HCDR2 contains the amino acid sequence of SEQ ID NO: 8, the HCDR3 contains the amino acid sequence of SEQ ID NO: 3, the LCDR1 contains the amino acid sequence of SEQ ID NO: 4, the LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (a3) The HCDR1 contains the amino acid sequence of SEQ ID NO: 9, the HCDR2 contains the amino acid sequence of SEQ ID NO: 10, the HCDR3 contains the amino acid sequence of SEQ ID NO: 3, the LCDR1 contains the amino acid sequence of SEQ ID NO: 4, the LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (a4) The HCDR1 contains the amino acid sequence of SEQ ID NO: 11, the HCDR2 contains the amino acid sequence of SEQ ID NO: 12, the HCDR3 contains the amino acid sequence of SEQ ID NO: 13, the LCDR1 contains the amino acid sequence of SEQ ID NO: 14, the LCDR2 contains the amino acid sequence of SEQ ID NO: 15, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

16. (a5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 17, the HCDR2 contains the amino acid sequence of SEQ ID NO: 18, the HCDR3 contains the amino acid sequence of SEQ ID NO: 19, the LCDR1 contains the amino acid sequence of SEQ ID NO: 20, the LCDR2 contains the amino acid sequence of GAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (b1) The HCDR1 includes the amino acid sequence of SEQ ID NO: 24, the HCDR2 includes the amino acid sequence of SEQ ID NO: 25, the HCDR3 includes the amino acid sequence of SEQ ID NO: 26, the LCDR1 includes the amino acid sequence of SEQ ID NO: 27, the LCDR2 includes the amino acid sequence of SEQ ID NO: 28, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

29. (b2) The HCDR1 includes the amino acid sequence of SEQ ID NO: 30, the HCDR2 includes the amino acid sequence of SEQ ID NO: 31, the HCDR3 includes the amino acid sequence of SEQ ID NO: 26, the LCDR1 includes the amino acid sequence of SEQ ID NO: 27, the LCDR2 includes the amino acid sequence of SEQ ID NO: 28, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

29. (b3) The HCDR1 includes the amino acid sequence of SEQ ID NO: 32, the HCDR2 includes the amino acid sequence of SEQ ID NO: 33, the HCDR3 includes the amino acid sequence of SEQ ID NO: 26, the LCDR1 includes the amino acid sequence of SEQ ID NO: 27, the LCDR2 includes the amino acid sequence of SEQ ID NO: 28, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

29. (b4) The HCDR1 includes the amino acid sequence of SEQ ID NO: 34, the HCDR2 includes the amino acid sequence of SEQ ID NO: 35, the HCDR3 includes the amino acid sequence of SEQ ID NO: 36, the LCDR1 includes the amino acid sequence of SEQ ID NO: 37, the LCDR2 includes the amino acid sequence of SEQ ID NO: 38, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

39. (b5) The HCDR1 includes the amino acid sequence of SEQ ID NO: 40, the HCDR2 includes the amino acid sequence of SEQ ID NO: 41, the HCDR3 includes the amino acid sequence of SEQ ID NO: 42, the LCDR1 includes the amino acid sequence of SEQ ID NO: 43, the LCDR2 includes the amino acid sequence of DAS, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

29. (c1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 47, the HCDR2 contains the amino acid sequence of SEQ ID NO: 48, the HCDR3 contains the amino acid sequence of SEQ ID NO: 49, the LCDR1 contains the amino acid sequence of SEQ ID NO: 50, the LCDR2 contains the amino acid sequence of SEQ ID NO: 51, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

52. (c2) The HCDR1 includes the amino acid sequence of SEQ ID NO: 53, the HCDR2 includes the amino acid sequence of SEQ ID NO: 54, the HCDR3 includes the amino acid sequence of SEQ ID NO: 49, the LCDR1 includes the amino acid sequence of SEQ ID NO: 50, the LCDR2 includes the amino acid sequence of SEQ ID NO: 51, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

52. (c3) The HCDR1 includes the amino acid sequence of SEQ ID NO: 55, the HCDR2 includes the amino acid sequence of SEQ ID NO: 56, the HCDR3 includes the amino acid sequence of SEQ ID NO: 49, the LCDR1 includes the amino acid sequence of SEQ ID NO: 50, the LCDR2 includes the amino acid sequence of SEQ ID NO: 51, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

52. (c4) The HCDR1 includes the amino acid sequence of SEQ ID NO: 57, the HCDR2 includes the amino acid sequence of SEQ ID NO: 58, the HCDR3 includes the amino acid sequence of SEQ ID NO: 59, the LCDR1 includes the amino acid sequence of SEQ ID NO: 60, the LCDR2 includes the amino acid sequence of SEQ ID NO: 61, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

62. (c5) The HCDR1 includes the amino acid sequence of SEQ ID NO: 63, the HCDR2 includes the amino acid sequence of SEQ ID NO: 64, the HCDR3 includes the amino acid sequence of SEQ ID NO: 65, the LCDR1 includes the amino acid sequence of SEQ ID NO: 66, the LCDR2 includes the amino acid sequence of QIS, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

52. (d1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 71, the HCDR2 contains the amino acid sequence of SEQ ID NO: 72, the HCDR3 contains the amino acid sequence of SEQ ID NO: 73, the LCDR1 contains the amino acid sequence of SEQ ID NO: 74, the LCDR2 contains the amino acid sequence of SEQ ID NO: 75, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (d2) The HCDR1 contains the amino acid sequence of SEQ ID NO: 77, the HCDR2 contains the amino acid sequence of SEQ ID NO: 78, the HCDR3 contains the amino acid sequence of SEQ ID NO: 73, the LCDR1 contains the amino acid sequence of SEQ ID NO: 74, the LCDR2 contains the amino acid sequence of SEQ ID NO: 75, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (d3) The HCDR1 contains the amino acid sequence of SEQ ID NO: 79, the HCDR2 contains the amino acid sequence of SEQ ID NO: 80, the HCDR3 contains the amino acid sequence of SEQ ID NO: 73, the LCDR1 contains the amino acid sequence of SEQ ID NO: 74, the LCDR2 contains the amino acid sequence of SEQ ID NO: 75, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (d4) The HCDR1 contains the amino acid sequence of SEQ ID NO: 81, the HCDR2 contains the amino acid sequence of SEQ ID NO: 82, the HCDR3 contains the amino acid sequence of SEQ ID NO: 83, the LCDR1 contains the amino acid sequence of SEQ ID NO: 84, the LCDR2 contains the amino acid sequence of SEQ ID NO: 85, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

86. (d5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 87, the HCDR2 contains the amino acid sequence of SEQ ID NO: 88, the HCDR3 contains the amino acid sequence of SEQ ID NO: 89, the LCDR1 contains the amino acid sequence of SEQ ID NO: 90, the LCDR2 contains the amino acid sequence of GAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (e1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 93, the HCDR2 contains the amino acid sequence of SEQ ID NO: 94, the HCDR3 contains the amino acid sequence of SEQ ID NO: 95, the LCDR1 contains the amino acid sequence of SEQ ID NO: 96, the LCDR2 contains the amino acid sequence of SEQ ID NO: 97, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

98. (e2) The HCDR1 includes the amino acid sequence of SEQ ID NO: 99, the HCDR2 includes the amino acid sequence of SEQ ID NO: 100, the HCDR3 includes the amino acid sequence of SEQ ID NO: 95, the LCDR1 includes the amino acid sequence of SEQ ID NO: 96, the LCDR2 includes the amino acid sequence of SEQ ID NO: 97, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

98. (e3) The HCDR1 includes the amino acid sequence of SEQ ID NO: 101, the HCDR2 includes the amino acid sequence of SEQ ID NO: 102, the HCDR3 includes the amino acid sequence of SEQ ID NO: 95, the LCDR1 includes the amino acid sequence of SEQ ID NO: 96, the LCDR2 includes the amino acid sequence of SEQ ID NO: 97, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

98. (e4) The HCDR1 contains the amino acid sequence of SEQ ID NO: 103, the HCDR2 contains the amino acid sequence of SEQ ID NO: 104, the HCDR3 contains the amino acid sequence of SEQ ID NO: 105, the LCDR1 contains the amino acid sequence of SEQ ID NO: 106, the LCDR2 contains the amino acid sequence of SEQ ID NO: 107, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

108. (e5) The HCDR1 includes the amino acid sequence of SEQ ID NO: 109, the HCDR2 includes the amino acid sequence of SEQ ID NO: 110, the HCDR3 includes the amino acid sequence of SEQ ID NO: 111, the LCDR1 includes the amino acid sequence of SEQ ID NO: 112, the LCDR2 includes the amino acid sequence of GAS, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

98. (f1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 116, the HCDR2 contains the amino acid sequence of SEQ ID NO: 117, the HCDR3 contains the amino acid sequence of SEQ ID NO: 118, the LCDR1 contains the amino acid sequence of SEQ ID NO: 119, the LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

120. (f2) The HCDR1 includes the amino acid sequence of SEQ ID NO: 121, the HCDR2 includes the amino acid sequence of SEQ ID NO: 122, the HCDR3 includes the amino acid sequence of SEQ ID NO: 118, the LCDR1 includes the amino acid sequence of SEQ ID NO: 119, the LCDR2 includes the amino acid sequence of SEQ ID NO: 5, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

120. (f3) The HCDR1 includes the amino acid sequence of SEQ ID NO: 123, the HCDR2 includes the amino acid sequence of SEQ ID NO: 124, the HCDR3 includes the amino acid sequence of SEQ ID NO: 118, the LCDR1 includes the amino acid sequence of SEQ ID NO: 119, the LCDR2 includes the amino acid sequence of SEQ ID NO: 5, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

120. (f4) The HCDR1 includes the amino acid sequence of SEQ ID NO: 125, the HCDR2 includes the amino acid sequence of SEQ ID NO: 126, the HCDR3 includes the amino acid sequence of SEQ ID NO: 127, the LCDR1 includes the amino acid sequence of SEQ ID NO: 128, the LCDR2 includes the amino acid sequence of SEQ ID NO: 15, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

129. (f5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 130, the HCDR2 contains the amino acid sequence of SEQ ID NO: 131, the HCDR3 contains the amino acid sequence of SEQ ID NO: 132, the LCDR1 contains the amino acid sequence of SEQ ID NO: 133, the LCDR2 contains the amino acid sequence of GAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

120. (g1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 137, the HCDR2 contains the amino acid sequence of SEQ ID NO: 138, the HCDR3 contains the amino acid sequence of SEQ ID NO: 139, the LCDR1 contains the amino acid sequence of SEQ ID NO: 140, the LCDR2 contains the amino acid sequence of SEQ ID NO: 141, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

142. (g2) The HCDR1 contains the amino acid sequence of SEQ ID NO: 143, the HCDR2 contains the amino acid sequence of SEQ ID NO: 144, the HCDR3 contains the amino acid sequence of SEQ ID NO: 139, the LCDR1 contains the amino acid sequence of SEQ ID NO: 140, the LCDR2 contains the amino acid sequence of SEQ ID NO: 141, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

142. (g3) The HCDR1 contains the amino acid sequence of SEQ ID NO: 145, the HCDR2 contains the amino acid sequence of SEQ ID NO: 146, the HCDR3 contains the amino acid sequence of SEQ ID NO: 139, the LCDR1 contains the amino acid sequence of SEQ ID NO: 140, the LCDR2 contains the amino acid sequence of SEQ ID NO: 141, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

142. (g4) The HCDR1 contains the amino acid sequence of SEQ ID NO: 147, the HCDR2 contains the amino acid sequence of SEQ ID NO: 148, the HCDR3 contains the amino acid sequence of SEQ ID NO: 149, the LCDR1 contains the amino acid sequence of SEQ ID NO: 150, the LCDR2 contains the amino acid sequence of SEQ ID NO: 151, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

152. (g5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 153, the HCDR2 contains the amino acid sequence of SEQ ID NO: 154, the HCDR3 contains the amino acid sequence of SEQ ID NO: 155, the LCDR1 contains the amino acid sequence of SEQ ID NO: 156, the LCDR2 contains the amino acid sequence of AAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

142. (h1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 1, the HCDR2 contains the amino acid sequence of SEQ ID NO: 160, the HCDR3 contains the amino acid sequence of SEQ ID NO: 161, the LCDR1 contains the amino acid sequence of SEQ ID NO: 162, the LCDR2 contains the amino acid sequence of SEQ ID NO: 163, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (h2) The HCDR1 contains the amino acid sequence of SEQ ID NO: 164, the HCDR2 contains the amino acid sequence of SEQ ID NO: 165, the HCDR3 contains the amino acid sequence of SEQ ID NO: 161, the LCDR1 contains the amino acid sequence of SEQ ID NO: 162, the LCDR2 contains the amino acid sequence of SEQ ID NO: 163, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (h3) The HCDR1 contains the amino acid sequence of SEQ ID NO: 166, the HCDR2 contains the amino acid sequence of SEQ ID NO: 167, the HCDR3 contains the amino acid sequence of SEQ ID NO: 161, the LCDR1 contains the amino acid sequence of SEQ ID NO: 162, the LCDR2 contains the amino acid sequence of SEQ ID NO: 163, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (h4) The HCDR1 includes the amino acid sequence of SEQ ID NO: 11, the HCDR2 includes the amino acid sequence of SEQ ID NO: 168, the HCDR3 includes the amino acid sequence of SEQ ID NO: 169, the LCDR1 includes the amino acid sequence of SEQ ID NO: 170, the LCDR2 includes the amino acid sequence of SEQ ID NO: 171, the LCDR3 includes the amino acid sequence of SEQ ID NO: 86, and (h5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 172, the HCDR2 contains the amino acid sequence of SEQ ID NO: 173, the HCDR3 contains the amino acid sequence of SEQ ID NO: 174, the LCDR1 contains the amino acid sequence of SEQ ID NO: 175, the LCDR2 contains the amino acid sequence of VAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. A binder according to claim 3, selected from the group consisting of the following.

5. The antigen-binding region is (a) A VH domain containing the amino acid sequence of SEQ ID NO: 22, and a VL domain containing the amino acid sequence of SEQ ID NO: 23, (b) A VH domain containing the amino acid sequence of SEQ ID NO: 45, and a VL domain containing the amino acid sequence of SEQ ID NO: 46, (c) A VH domain containing the amino acid sequence of SEQ ID NO: 68, and a VL domain containing the amino acid sequence of SEQ ID NO: 69, (c') VH domain containing the amino acid sequence of SEQ ID NO: 68, and VL domain containing the amino acid sequence of SEQ ID NO: 70, (d) A VH domain containing the amino acid sequence of SEQ ID NO: 91, and a VL domain containing the amino acid sequence of SEQ ID NO: 92, (e) A VH domain containing the amino acid sequence of SEQ ID NO: 113, and a VL domain containing the amino acid sequence of SEQ ID NO: 114, (e') VH domain containing the amino acid sequence of SEQ ID NO: 113, and VL domain containing the amino acid sequence of SEQ ID NO: 115, (f) A VH domain containing the amino acid sequence of SEQ ID NO: 134, and a VL domain containing the amino acid sequence of SEQ ID NO: 135, (f') A VH domain containing the amino acid sequence of SEQ ID NO: 134, and a VL domain containing the amino acid sequence of SEQ ID NO: 136, (g) A VH domain containing the amino acid sequence of SEQ ID NO: 158, and a VL domain containing the amino acid sequence of SEQ ID NO: 159, (h) VH domain containing the amino acid sequence of SEQ ID NO: 177, and VL domain containing the amino acid sequence of SEQ ID NO: 178 A binder according to any one of claims 1 to 4, comprising a VH domain and a VL domain selected from the group consisting of the above.

6. The binder according to any one of claims 1 to 5, wherein the binder is a bispecific protein or a polyspecific protein.

7. A binder according to any one of claims 1 to 6, further comprising an immunoglobulin (Ig) constant region or a fragment of the Ig constant region, wherein optionally the fragment of the Ig constant region is an Fc region or a CH3 domain.

8. The binder according to claim 7, wherein the Ig constant region, the fragment of the Ig constant region, the Fc region, or the CH3 domain contains at least one mutation.

9. The aforementioned at least one mutation is L234A / L235A / D265S, F234A / L235A, L234A / L235A, V234A / G237A / P238S / H268A / V309L / A330S / P331S, F234A / L235A, S228P / F234A / L235A, N297A, V234A / G237A, K214T / E233P / L234V / L235A / G236 deletion / A327G / P331A / D365E / L358M, H26 A binder according to claim 8, selected from the group consisting of 8Q / V309L / A330S / P331S, S267E / L328F, L234F / L235E / D265A, L234A / L235A / G237A / P238S / H268A / A330S / P331S, S228P / F234A / L235A / G237A / P238S, and S228P / F234A / L235A / G236 deletion / G237A / P238S, wherein the residue numbering follows the EU index.

10. The above at least one mutation is T366S / L368A / Y407V, T366W, T350V, L351Y, F405A, Y407V, T366Y, T366L, F405W, T394W, K392L, T394S, Y407T, Y407A, L351Y / F405A / Y407V, T366I / K392M / T394W, F405A / Y407V, T366L / K392M / T39 A binder according to claim 8, selected from the group consisting of 4W, T366L / K392L / T394W, L351Y / Y407A, L351Y / Y407V, T366A / K409F, T366V / K409F, T366A / K409F, T350V / L351Y / F405A / Y407V, and T350V / T366L / K392L / T394W, wherein the residue numbering follows the EU index.

11. The binder according to claim 8, wherein the binder comprises a knob-in-hole mutation, the knob mutation comprises T366S / L368A / Y407V, and the hole mutation comprises T366W.

12. The binder according to any one of claims 1 to 11, wherein the binder comprises a bispecific protein having an antigen-binding region that binds to a second antigen other than ENPP3.

13. The binder according to claim 12, wherein the second antigen is differentiated cluster 3ε (CD3ε).

14. A binder comprising a first antigen-binding region that binds to ENPP3 and a second antigen-binding region that binds to CD3ε, wherein the first antigen-binding region that binds to ENPP3 is (a) The VH domain of VH shown in Sequence ID No. 22, including HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 23, (b) The VH domain of VH shown in Sequence ID No. 45, comprising HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 46, comprising LCDR1, LCDR2, and LCDR3 (c) The VH domain, which includes HCDR1, HCDR2, and HCDR3 of the VH shown in Sequence ID No. 68, and the VL domain, which includes LCDR1, LCDR2, and LCDR3 of the VL shown in Sequence ID No. 69 or Sequence ID No. 70, (d) The VH domain of VH shown in Sequence ID No. 91, including HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 92, (e) The VH domain of VH shown in Sequence ID No. 113, comprising HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 114 or Sequence ID No. 115, (f) The VH domain, which includes HCDR1, HCDR2, and HCDR3 of the VH shown in Sequence ID No. 134, and the VL domain, which includes LCDR1, LCDR2, and LCDR3 of the VL shown in Sequence ID No. 135 or Sequence ID No. 136, (g) The VH domain of VH shown in Sequence ID No. 158, which includes HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 159, and (h) The VH domain, which includes HCDR1, HCDR2, and HCDR3 of the VH shown in Sequence ID No. 177, and the VL domain, which includes LCDR1, LCDR2, and LCDR3 of the VL shown in Sequence ID No. 178 A binder comprising VH and VL selected from the group consisting of the following.

15. The binder according to claim 14, wherein the second antigen-binding region that binds to CD3ε comprises a VH domain including HCDR1, HCDR2, and HCDR3 of VH as shown in SEQ ID NO: 200, and a VL domain including LCDR1, LCDR2, and LCDR3 of VL as shown in SEQ ID NO:

201.

16. The first antigen-binding region that binds to ENPP3, (a1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 1, the HCDR2 contains the amino acid sequence of SEQ ID NO: 2, the HCDR3 contains the amino acid sequence of SEQ ID NO: 3, the LCDR1 contains the amino acid sequence of SEQ ID NO: 4, the LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (a2) The HCDR1 contains the amino acid sequence of SEQ ID NO: 7, the HCDR2 contains the amino acid sequence of SEQ ID NO: 8, the HCDR3 contains the amino acid sequence of SEQ ID NO: 3, the LCDR1 contains the amino acid sequence of SEQ ID NO: 4, the LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (a3) The HCDR1 contains the amino acid sequence of SEQ ID NO: 9, the HCDR2 contains the amino acid sequence of SEQ ID NO: 10, the HCDR3 contains the amino acid sequence of SEQ ID NO: 3, the LCDR1 contains the amino acid sequence of SEQ ID NO: 4, the LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (a4) The HCDR1 contains the amino acid sequence of SEQ ID NO: 11, the HCDR2 contains the amino acid sequence of SEQ ID NO: 12, the HCDR3 contains the amino acid sequence of SEQ ID NO: 13, the LCDR1 contains the amino acid sequence of SEQ ID NO: 14, the LCDR2 contains the amino acid sequence of SEQ ID NO: 15, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

16. (a5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 17, the HCDR2 contains the amino acid sequence of SEQ ID NO: 18, the HCDR3 contains the amino acid sequence of SEQ ID NO: 19, the LCDR1 contains the amino acid sequence of SEQ ID NO: 20, the LCDR2 contains the amino acid sequence of GAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (b1) The HCDR1 includes the amino acid sequence of SEQ ID NO: 24, the HCDR2 includes the amino acid sequence of SEQ ID NO: 25, the HCDR3 includes the amino acid sequence of SEQ ID NO: 26, the LCDR1 includes the amino acid sequence of SEQ ID NO: 27, the LCDR2 includes the amino acid sequence of SEQ ID NO: 28, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

29. (b2) The HCDR1 includes the amino acid sequence of SEQ ID NO: 30, the HCDR2 includes the amino acid sequence of SEQ ID NO: 31, the HCDR3 includes the amino acid sequence of SEQ ID NO: 26, the LCDR1 includes the amino acid sequence of SEQ ID NO: 27, the LCDR2 includes the amino acid sequence of SEQ ID NO: 28, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

29. (b3) The HCDR1 includes the amino acid sequence of SEQ ID NO: 32, the HCDR2 includes the amino acid sequence of SEQ ID NO: 33, the HCDR3 includes the amino acid sequence of SEQ ID NO: 26, the LCDR1 includes the amino acid sequence of SEQ ID NO: 27, the LCDR2 includes the amino acid sequence of SEQ ID NO: 28, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

29. (b4) The HCDR1 includes the amino acid sequence of SEQ ID NO: 34, the HCDR2 includes the amino acid sequence of SEQ ID NO: 35, the HCDR3 includes the amino acid sequence of SEQ ID NO: 36, the LCDR1 includes the amino acid sequence of SEQ ID NO: 37, the LCDR2 includes the amino acid sequence of SEQ ID NO: 38, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

39. (b5) The HCDR1 includes the amino acid sequence of SEQ ID NO: 40, the HCDR2 includes the amino acid sequence of SEQ ID NO: 41, the HCDR3 includes the amino acid sequence of SEQ ID NO: 42, the LCDR1 includes the amino acid sequence of SEQ ID NO: 43, the LCDR2 includes the amino acid sequence of DAS, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

29. (c1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 47, the HCDR2 contains the amino acid sequence of SEQ ID NO: 48, the HCDR3 contains the amino acid sequence of SEQ ID NO: 49, the LCDR1 contains the amino acid sequence of SEQ ID NO: 50, the LCDR2 contains the amino acid sequence of SEQ ID NO: 51, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

52. (c2) The HCDR1 includes the amino acid sequence of SEQ ID NO: 53, the HCDR2 includes the amino acid sequence of SEQ ID NO: 54, the HCDR3 includes the amino acid sequence of SEQ ID NO: 49, the LCDR1 includes the amino acid sequence of SEQ ID NO: 50, the LCDR2 includes the amino acid sequence of SEQ ID NO: 51, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

52. (c3) The HCDR1 includes the amino acid sequence of SEQ ID NO: 55, the HCDR2 includes the amino acid sequence of SEQ ID NO: 56, the HCDR3 includes the amino acid sequence of SEQ ID NO: 49, the LCDR1 includes the amino acid sequence of SEQ ID NO: 50, the LCDR2 includes the amino acid sequence of SEQ ID NO: 51, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

52. (c4) The HCDR1 includes the amino acid sequence of SEQ ID NO: 57, the HCDR2 includes the amino acid sequence of SEQ ID NO: 58, the HCDR3 includes the amino acid sequence of SEQ ID NO: 59, the LCDR1 includes the amino acid sequence of SEQ ID NO: 60, the LCDR2 includes the amino acid sequence of SEQ ID NO: 61, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

62. (c5) The HCDR1 includes the amino acid sequence of SEQ ID NO: 63, the HCDR2 includes the amino acid sequence of SEQ ID NO: 64, the HCDR3 includes the amino acid sequence of SEQ ID NO: 65, the LCDR1 includes the amino acid sequence of SEQ ID NO: 66, the LCDR2 includes the amino acid sequence of QIS, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

52. (d1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 71, the HCDR2 contains the amino acid sequence of SEQ ID NO: 72, the HCDR3 contains the amino acid sequence of SEQ ID NO: 73, the LCDR1 contains the amino acid sequence of SEQ ID NO: 74, the LCDR2 contains the amino acid sequence of SEQ ID NO: 75, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (d2) The HCDR1 contains the amino acid sequence of SEQ ID NO: 77, the HCDR2 contains the amino acid sequence of SEQ ID NO: 78, the HCDR3 contains the amino acid sequence of SEQ ID NO: 73, the LCDR1 contains the amino acid sequence of SEQ ID NO: 74, the LCDR2 contains the amino acid sequence of SEQ ID NO: 75, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (d3) The HCDR1 contains the amino acid sequence of SEQ ID NO: 79, the HCDR2 contains the amino acid sequence of SEQ ID NO: 80, the HCDR3 contains the amino acid sequence of SEQ ID NO: 73, the LCDR1 contains the amino acid sequence of SEQ ID NO: 74, the LCDR2 contains the amino acid sequence of SEQ ID NO: 75, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (d4) The HCDR1 contains the amino acid sequence of SEQ ID NO: 81, the HCDR2 contains the amino acid sequence of SEQ ID NO: 82, the HCDR3 contains the amino acid sequence of SEQ ID NO: 83, the LCDR1 contains the amino acid sequence of SEQ ID NO: 84, the LCDR2 contains the amino acid sequence of SEQ ID NO: 85, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

86. (d5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 87, the HCDR2 contains the amino acid sequence of SEQ ID NO: 88, the HCDR3 contains the amino acid sequence of SEQ ID NO: 89, the LCDR1 contains the amino acid sequence of SEQ ID NO: 90, the LCDR2 contains the amino acid sequence of GAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (e1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 93, the HCDR2 contains the amino acid sequence of SEQ ID NO: 94, the HCDR3 contains the amino acid sequence of SEQ ID NO: 95, the LCDR1 contains the amino acid sequence of SEQ ID NO: 96, the LCDR2 contains the amino acid sequence of SEQ ID NO: 97, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

98. (e2) The HCDR1 includes the amino acid sequence of SEQ ID NO: 99, the HCDR2 includes the amino acid sequence of SEQ ID NO: 100, the HCDR3 includes the amino acid sequence of SEQ ID NO: 95, the LCDR1 includes the amino acid sequence of SEQ ID NO: 96, the LCDR2 includes the amino acid sequence of SEQ ID NO: 97, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

98. (e3) The HCDR1 includes the amino acid sequence of SEQ ID NO: 101, the HCDR2 includes the amino acid sequence of SEQ ID NO: 102, the HCDR3 includes the amino acid sequence of SEQ ID NO: 95, the LCDR1 includes the amino acid sequence of SEQ ID NO: 96, the LCDR2 includes the amino acid sequence of SEQ ID NO: 97, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

98. (e4) The HCDR1 contains the amino acid sequence of SEQ ID NO: 103, the HCDR2 contains the amino acid sequence of SEQ ID NO: 104, the HCDR3 contains the amino acid sequence of SEQ ID NO: 105, the LCDR1 contains the amino acid sequence of SEQ ID NO: 106, the LCDR2 contains the amino acid sequence of SEQ ID NO: 107, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

108. (e5) The HCDR1 includes the amino acid sequence of SEQ ID NO: 109, the HCDR2 includes the amino acid sequence of SEQ ID NO: 110, the HCDR3 includes the amino acid sequence of SEQ ID NO: 111, the LCDR1 includes the amino acid sequence of SEQ ID NO: 112, the LCDR2 includes the amino acid sequence of GAS, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

98. (f1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 116, the HCDR2 contains the amino acid sequence of SEQ ID NO: 117, the HCDR3 contains the amino acid sequence of SEQ ID NO: 118, the LCDR1 contains the amino acid sequence of SEQ ID NO: 119, the LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

120. (f2) The HCDR1 includes the amino acid sequence of SEQ ID NO: 121, the HCDR2 includes the amino acid sequence of SEQ ID NO: 122, the HCDR3 includes the amino acid sequence of SEQ ID NO: 118, the LCDR1 includes the amino acid sequence of SEQ ID NO: 119, the LCDR2 includes the amino acid sequence of SEQ ID NO: 5, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

120. (f3) The HCDR1 includes the amino acid sequence of SEQ ID NO: 123, the HCDR2 includes the amino acid sequence of SEQ ID NO: 124, the HCDR3 includes the amino acid sequence of SEQ ID NO: 118, the LCDR1 includes the amino acid sequence of SEQ ID NO: 119, the LCDR2 includes the amino acid sequence of SEQ ID NO: 5, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

120. (f4) The HCDR1 includes the amino acid sequence of SEQ ID NO: 125, the HCDR2 includes the amino acid sequence of SEQ ID NO: 126, the HCDR3 includes the amino acid sequence of SEQ ID NO: 127, the LCDR1 includes the amino acid sequence of SEQ ID NO: 128, the LCDR2 includes the amino acid sequence of SEQ ID NO: 15, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

129. (f5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 130, the HCDR2 contains the amino acid sequence of SEQ ID NO: 131, the HCDR3 contains the amino acid sequence of SEQ ID NO: 132, the LCDR1 contains the amino acid sequence of SEQ ID NO: 133, the LCDR2 contains the amino acid sequence of GAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

120. (g1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 137, the HCDR2 contains the amino acid sequence of SEQ ID NO: 138, the HCDR3 contains the amino acid sequence of SEQ ID NO: 139, the LCDR1 contains the amino acid sequence of SEQ ID NO: 140, the LCDR2 contains the amino acid sequence of SEQ ID NO: 141, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

142. (g2) The HCDR1 contains the amino acid sequence of SEQ ID NO: 143, the HCDR2 contains the amino acid sequence of SEQ ID NO: 144, the HCDR3 contains the amino acid sequence of SEQ ID NO: 139, the LCDR1 contains the amino acid sequence of SEQ ID NO: 140, the LCDR2 contains the amino acid sequence of SEQ ID NO: 141, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

142. (g3) The HCDR1 contains the amino acid sequence of SEQ ID NO: 145, the HCDR2 contains the amino acid sequence of SEQ ID NO: 146, the HCDR3 contains the amino acid sequence of SEQ ID NO: 139, the LCDR1 contains the amino acid sequence of SEQ ID NO: 140, the LCDR2 contains the amino acid sequence of SEQ ID NO: 141, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

142. (g4) The HCDR1 contains the amino acid sequence of SEQ ID NO: 147, the HCDR2 contains the amino acid sequence of SEQ ID NO: 148, the HCDR3 contains the amino acid sequence of SEQ ID NO: 149, the LCDR1 contains the amino acid sequence of SEQ ID NO: 150, the LCDR2 contains the amino acid sequence of SEQ ID NO: 151, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

152. (g5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 153, the HCDR2 contains the amino acid sequence of SEQ ID NO: 154, the HCDR3 contains the amino acid sequence of SEQ ID NO: 155, the LCDR1 contains the amino acid sequence of SEQ ID NO: 156, the LCDR2 contains the amino acid sequence of AAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

142. (h1) The HCDR1 contains the amino acid sequence of SEQ ID NO: 1, the HCDR2 contains the amino acid sequence of SEQ ID NO: 160, the HCDR3 contains the amino acid sequence of SEQ ID NO: 161, the LCDR1 contains the amino acid sequence of SEQ ID NO: 162, the LCDR2 contains the amino acid sequence of SEQ ID NO: 163, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (h2) The HCDR1 contains the amino acid sequence of SEQ ID NO: 164, the HCDR2 contains the amino acid sequence of SEQ ID NO: 165, the HCDR3 contains the amino acid sequence of SEQ ID NO: 161, the LCDR1 contains the amino acid sequence of SEQ ID NO: 162, the LCDR2 contains the amino acid sequence of SEQ ID NO: 163, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (h3) The HCDR1 contains the amino acid sequence of SEQ ID NO: 166, the HCDR2 contains the amino acid sequence of SEQ ID NO: 167, the HCDR3 contains the amino acid sequence of SEQ ID NO: 161, the LCDR1 contains the amino acid sequence of SEQ ID NO: 162, the LCDR2 contains the amino acid sequence of SEQ ID NO: 163, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. (h4) The HCDR1 contains the amino acid sequence of SEQ ID NO: 11, the HCDR2 contains the amino acid sequence of SEQ ID NO: 168, the HCDR3 contains the amino acid sequence of SEQ ID NO: 169, the LCDR1 contains the amino acid sequence of SEQ ID NO: 170, the LCDR2 contains the amino acid sequence of SEQ ID NO: 171, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

86. (h5) The HCDR1 contains the amino acid sequence of SEQ ID NO: 172, the HCDR2 contains the amino acid sequence of SEQ ID NO: 173, the HCDR3 contains the amino acid sequence of SEQ ID NO: 174, the LCDR1 contains the amino acid sequence of SEQ ID NO: 175, the LCDR2 contains the amino acid sequence of VAS, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

76. The binder according to claim 14, comprising a CDR sequence selected from the group consisting of the following.

17. The second antigen-binding region that binds to CD3ε, (a) The HCDR1 contains the amino acid sequence of SEQ ID NO: 179, the HCDR2 contains the amino acid sequence of SEQ ID NO: 180, the HCDR3 contains the amino acid sequence of SEQ ID NO: 181, the LCDR1 contains the amino acid sequence of SEQ ID NO: 182, the LCDR2 contains the amino acid sequence of SEQ ID NO: 183, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

184. (b) The HCDR1 includes the amino acid sequence of SEQ ID NO: 185, the HCDR2 includes the amino acid sequence of SEQ ID NO: 186, the HCDR3 includes the amino acid sequence of SEQ ID NO: 181, the LCDR1 includes the amino acid sequence of SEQ ID NO: 182, the LCDR2 includes the amino acid sequence of SEQ ID NO: 183, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

184. (c) The HCDR1 includes the amino acid sequence of SEQ ID NO: 187, the HCDR2 includes the amino acid sequence of SEQ ID NO: 188, the HCDR3 includes the amino acid sequence of SEQ ID NO: 181, the LCDR1 includes the amino acid sequence of SEQ ID NO: 182, the LCDR2 includes the amino acid sequence of SEQ ID NO: 183, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

184. (d) The HCDR1 includes the amino acid sequence of SEQ ID NO: 189, the HCDR2 includes the amino acid sequence of SEQ ID NO: 190, the HCDR3 includes the amino acid sequence of SEQ ID NO: 191, the LCDR1 includes the amino acid sequence of SEQ ID NO: 192, the LCDR2 includes the amino acid sequence of SEQ ID NO: 193, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

194. (e) The HCDR1 includes the amino acid sequence of SEQ ID NO: 195, the HCDR2 includes the amino acid sequence of SEQ ID NO: 196, the HCDR3 includes the amino acid sequence of SEQ ID NO: 197, the LCDR1 includes the amino acid sequence of SEQ ID NO: 198, the LCDR2 includes the amino acid sequence of DSS, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

184. The binder according to claim 15, comprising a CDR sequence selected from the group consisting of the following.

18. (i) The first binding region includes a VH domain containing the amino acid sequence of SEQ ID NO: 22 and a VL domain containing the amino acid sequence of SEQ ID NO: 23, (ii) The second binding region comprises a VH domain containing the amino acid sequence of SEQ ID NO: 200 and a VL domain containing the amino acid sequence of SEQ ID NO: 201, A binder according to any one of claims 14 to 17.

19. The binder according to any one of claims 12 to 18, wherein the first antigen-binding region comprises Fab and the second antigen-binding region comprises a stapled scFv fragment (spFv).

20. The binder according to claim 19, wherein the spFv includes at least one disulfide bond between the VH or the VL and the linker.

21. The binder according to any one of claims 12 to 20, further comprising an immunoglobulin (Ig) constant region and a fragment of the Ig constant region, wherein optionally the fragment of the Ig constant region is an Fc region or a CH3 domain.

22. (i) A first polypeptide comprising a spFv that binds to CD3ε, and comprising a CH2 domain and a CH3 domain, (ii) A second polypeptide comprising a VH domain that binds to ENPP3, and comprising a CH2 domain and a CH3 domain, (iii) A binder comprising a third polypeptide having a VL domain that binds to ENPP3, The spFv that binds to CD3ε includes a VH domain containing HCDR1, HCDR2, and HCDR3 of VH as shown in Sequence ID No. 200, and a VL domain containing LCDR1, LCDR2, and LCDR3 of VL as shown in Sequence ID No. 201, The second polypeptide and the third polypeptide each contain VH and VL that bind to ENPP3, where the VH and VL that bind to ENPP3 are (a) The VH domain of VH shown in Sequence ID No. 22, including HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 23, (b) The VH domain of VH shown in Sequence ID No. 45, comprising HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 46, comprising LCDR1, LCDR2, and LCDR3 (c) The VH domain, which includes HCDR1, HCDR2, and HCDR3 of the VH shown in Sequence ID No. 68, and the VL domain, which includes LCDR1, LCDR2, and LCDR3 of the VL shown in Sequence ID No. 69 or Sequence ID No. 70, (d) The VH domain of VH shown in Sequence ID No. 91, which includes HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 92, which includes LCDR1, LCDR2, and LCDR3 (e) The VH domain of VH shown in Sequence ID No. 113, comprising HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 114 or Sequence ID No. 115, (f) The VH domain, which includes HCDR1, HCDR2, and HCDR3 of the VH shown in Sequence ID No. 134, and the VL domain, which includes LCDR1, LCDR2, and LCDR3 of the VL shown in Sequence ID No. 135 or Sequence ID No. 136, (g) The VH domain of VH shown in Sequence ID No. 158, which includes HCDR1, HCDR2, and HCDR3, and the VL domain of VL shown in Sequence ID No. 159, and (h) The VH domain, which includes HCDR1, HCDR2, and HCDR3 of the VH shown in Sequence ID No. 177, and the VL domain, which includes LCDR1, LCDR2, and LCDR3 of the VL shown in Sequence ID No. 178 A binder selected from the group consisting of the following.

23. (i) The spFv coupled to CD3ε is (a) The HCDR1 contains the amino acid sequence of SEQ ID NO: 179, the HCDR2 contains the amino acid sequence of SEQ ID NO: 180, the HCDR3 contains the amino acid sequence of SEQ ID NO: 181, the LCDR1 contains the amino acid sequence of SEQ ID NO: 182, the LCDR2 contains the amino acid sequence of SEQ ID NO: 183, and the LCDR3 contains the amino acid sequence of SEQ ID NO:

184. (b) The HCDR1 includes the amino acid sequence of SEQ ID NO: 185, the HCDR2 includes the amino acid sequence of SEQ ID NO: 186, the HCDR3 includes the amino acid sequence of SEQ ID NO: 181, the LCDR1 includes the amino acid sequence of SEQ ID NO: 182, the LCDR2 includes the amino acid sequence of SEQ ID NO: 183, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

184. (c) The HCDR1 includes the amino acid sequence of SEQ ID NO: 187, the HCDR2 includes the amino acid sequence of SEQ ID NO: 188, the HCDR3 includes the amino acid sequence of SEQ ID NO: 181, the LCDR1 includes the amino acid sequence of SEQ ID NO: 182, the LCDR2 includes the amino acid sequence of SEQ ID NO: 183, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

184. (d) The HCDR1 includes the amino acid sequence of SEQ ID NO: 189, the HCDR2 includes the amino acid sequence of SEQ ID NO: 190, the HCDR3 includes the amino acid sequence of SEQ ID NO: 191, the LCDR1 includes the amino acid sequence of SEQ ID NO: 192, the LCDR2 includes the amino acid sequence of SEQ ID NO: 193, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

194. (e) The HCDR1 includes the amino acid sequence of SEQ ID NO: 195, the HCDR2 includes the amino acid sequence of SEQ ID NO: 196, the HCDR3 includes the amino acid sequence of SEQ ID NO: 197, the LCDR1 includes the amino acid sequence of SEQ ID NO: 198, the LCDR2 includes the amino acid sequence of DSS, and the LCDR3 includes the amino acid sequence of SEQ ID NO:

184. Includes a CDR selected from the group consisting of, (ii) The Fab that is coupled to ENPP3 (a) In the VH domain that binds to ENPP3, HCDR1 contains the amino acid sequence of SEQ ID NO: 1, HCDR2 contains the amino acid sequence of SEQ ID NO: 2, HCDR3 contains the amino acid sequence of SEQ ID NO: 3, and in the VL domain that binds to ENPP3, LCDR1 contains the amino acid sequence of SEQ ID NO: 4, LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (b) In the VH domain that binds to ENPP3, HCDR1 contains the amino acid sequence of SEQ ID NO: 7, HCDR2 contains the amino acid sequence of SEQ ID NO: 8, HCDR3 contains the amino acid sequence of SEQ ID NO: 3, and in the VL domain that binds to ENPP3, LCDR1 contains the amino acid sequence of SEQ ID NO: 4, LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (c) In the VH domain that binds to ENPP3, HCDR1 contains the amino acid sequence of SEQ ID NO: 9, HCDR2 contains the amino acid sequence of SEQ ID NO: 10, HCDR3 contains the amino acid sequence of SEQ ID NO: 3, and in the VL domain that binds to ENPP3, LCDR1 contains the amino acid sequence of SEQ ID NO: 4, LCDR2 contains the amino acid sequence of SEQ ID NO: 5, and LCDR3 contains the amino acid sequence of SEQ ID NO:

6. (d) In the VH domain that binds to ENPP3, HCDR1 contains the amino acid sequence of SEQ ID NO: 11, HCDR2 contains the amino acid sequence of SEQ ID NO: 12, HCDR3 contains the amino acid sequence of SEQ ID NO: 13, and in the VL domain that binds to ENPP3, LCDR1 contains the amino acid sequence of SEQ ID NO: 14, LCDR2 contains the amino acid sequence of SEQ ID NO: 15, and LCDR3 contains the amino acid sequence of SEQ ID NO:

16. (e) In the VH domain that binds to ENPP3, HCDR1 contains the amino acid sequence of SEQ ID NO: 17, HCDR2 contains the amino acid sequence of SEQ ID NO: 18, HCDR3 contains the amino acid sequence of SEQ ID NO: 19, and in the VL domain that binds to ENPP3, LCDR1 contains the amino acid sequence of SEQ ID NO: 20, LCDR2 contains the amino acid sequence of GAS, and LCDR3 contains the amino acid sequence of SEQ ID NO:

6. The binder according to claim 22, comprising:

24. The binder according to claim 22 or 23, wherein the spFv that binds to CD3ε comprises a VH domain containing the amino acid sequence of SEQ ID NO: 200 and a VL domain containing the amino acid sequence of SEQ ID NO: 201, the VH domain that binds to ENPP3 contains the amino acid sequence of SEQ ID NO: 22, and the VL domain that binds to ENPP3 contains the amino acid sequence of SEQ ID NO:

23.

25. The binder according to any one of claims 22 to 24, wherein the spFv that binds to CD3ε comprises the amino acid sequence of SEQ ID NO: 248, the VH domain that binds to ENPP3 comprises the amino acid sequence of SEQ ID NO: 22, and the VL domain that binds to ENPP3 comprises the amino acid sequence of SEQ ID NO:

23.

26. (i) The first polypeptide comprising spFv that binds to the CD3ε, CH2 domain and CH3 domain comprises the amino acid sequence of SEQ ID NO: 255, (ii) The second polypeptide comprising a VH domain, a CH2 domain and a CH3 domain that binds to ENPP3 comprises the amino acid sequence of SEQ ID NO: 256, (iii) The third polypeptide comprising a VL domain that binds to ENPP3 comprises the amino acid sequence of SEQ ID NO: 257, A binder according to any one of claims 22 to 25.

27. The binder according to any one of claims 22 to 26, wherein the spFv includes at least one disulfide bond between the VH or the VL and the linker.

28. A composition comprising a binder according to any one of claims 1 to 27 and a pharmaceutically acceptable carrier.

29. A polynucleotide comprising a nucleotide sequence encoding VH, VL, or both VH and VL of the binder according to any one of claims 1 to 27.

30. A vector comprising the polynucleotide described in claim 29.

31. A cell comprising the polynucleotide described in claim 29.

32. A kit comprising the binder described in any one of claims 1 to 27.

33. A method for producing a binder that binds to the epitope of ENPP3, comprising culturing the cells described in claim 31 to express the binder.

34. A method for directing T cells to target cells expressing ENPP3, comprising contacting the T cells with an effective amount of a binder according to any one of claims 12 to 27, or a composition comprising the binder and a pharmaceutically acceptable carrier, wherein the antigen-binding domain that binds to CD3ε binds to the T cells and the antigen-binding domain that binds to ENPP3 binds to the target cells.

35. A method for treating cancer or a tumor in a subject requiring treatment of cancer or a tumor, comprising administering to the subject an effective amount of a binder according to any one of claims 12 to 27 or a composition comprising the binder and a pharmaceutically acceptable carrier.

36. The method according to claim 35, wherein the cancer or tumor is selected from the group consisting of clear cell renal cell carcinoma (CCRCC), papillary renal carcinoma, endometrioid uterine carcinoma, endometrioid ovarian carcinoma, colorectal carcinoma, lung adenocarcinoma, or hepatocellular carcinoma of the liver.