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CN-122003438-A - ENPP3 and CD3 binding agents and methods of use thereof

CN122003438ACN 122003438 ACN122003438 ACN 122003438ACN-122003438-A

Abstract

The present disclosure provides ENPP3 binding agents, including bispecific ENPP3xCD3 binding proteins, and related compositions and methods of use.

Inventors

  • S. Vijayaragawan
  • E. R. lacy
  • Y. Hamro
  • P. K. Seth
  • N. R. Shah

Assignees

  • 詹森生物科技公司

Dates

Publication Date
20260508
Application Date
20240806
Priority Date
20230807

Claims (20)

  1. 1. A binding agent comprising an antigen binding region that binds to an epitope of ENPP 3.
  2. 2. The binding agent of claim 1, wherein the epitope of ENPP3 is selected from the group consisting of SEQ ID NO 295-297, DVP and SEQ ID NO 299-305.
  3. 3. The binding agent of claim 1, wherein the antigen binding region comprises a VH domain and a VL domain selected from the group consisting of: (a) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 22, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 23; (b) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as set forth in SEQ ID No. 45, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as set forth in SEQ ID No. 46; (c) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 68, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 69 or SEQ ID No. 70; (d) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as set forth in SEQ ID No. 91, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as set forth in SEQ ID No. 92; (e) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 113, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 114 or SEQ ID No. 115; (f) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 134, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 135 or SEQ ID No. 136; (g) VH domains comprising HCDR1, HCDR2 and HCDR3 of the VH set forth in SEQ ID NO 158, and VL domains comprising LCDR1, LCDR2 and LCDR3 of the VL set forth in SEQ ID NO 159, and (H) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 177, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 178.
  4. 4. A binding agent according to claim 3, wherein the CDR sequences are selected from the group consisting of: (a1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 1, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 2, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 3, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 4, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 6; (a2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 7, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 8, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 3, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 4, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 6; (a3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 9, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 10, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 3, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 4, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 6; (a4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 13, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 14, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 15, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 16; (a5) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 17, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 18, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 19, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 20, the LCDR2 comprises the amino acid sequence of GAS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 6; (b1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 24, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 25, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 26, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 27, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 28, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 29; (b2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 30, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 31, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 26, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 27, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 28, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 29; (b3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 32, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 33, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 26, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 27, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 28, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 29; (b4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 34, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 35, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 36, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 37, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 38, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 39; (b5) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 40, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 41, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 42, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 43, the LCDR2 comprises the amino acid sequence of DAS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 29; (c1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 47, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 48, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 49, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 50, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 51, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 52; (c2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 53, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 54, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 49, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 50, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 51, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 52; (c3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 55, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 56, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 49, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 50, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 51, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 52; (c4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 57, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 58, the HCDR3 comprises the amino acid sequence of SEQ ID NO.59, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 60, the LCDR2 comprises the amino acid sequence of SEQ ID NO.61, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 62; (c5) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 63, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 64, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 65, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 66, the LCDR2 comprises the amino acid sequence of QIS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 52; (d1) The HCDR1 comprises the amino acid sequence of SEQ ID NO: 71, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 72, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 73, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 74, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 75, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 76; (d2) The HCDR1 comprises the amino acid sequence of SEQ ID No. 77, the HCDR2 comprises the amino acid sequence of SEQ ID No. 78, the HCDR3 comprises the amino acid sequence of SEQ ID No. 73, the LCDR1 comprises the amino acid sequence of SEQ ID No. 74, the LCDR2 comprises the amino acid sequence of SEQ ID No. 75, and the LCDR3 comprises the amino acid sequence of SEQ ID No. 76; (d3) The HCDR1 comprises an amino acid sequence of SEQ ID No. 79, the HCDR2 comprises an amino acid sequence of SEQ ID No. 80, the HCDR3 comprises an amino acid sequence of SEQ ID No. 73, the LCDR1 comprises an amino acid sequence of SEQ ID No. 74, the LCDR2 comprises an amino acid sequence of SEQ ID No. 75, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 76; (d4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 81, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 82, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 83, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 84, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 85, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 86; (d5) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 87, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 88, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 89, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 90, the LCDR2 comprises the amino acid sequence of GAS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 76; (e1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 93, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 94, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 95, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 96, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 97, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 98; (e2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 99, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 100, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 95, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 96, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 97, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 98; (e3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 101, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 102, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 95, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 96, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 97, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 98; (e4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 103, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 104, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 105, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 106, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 107, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 108; (e5) The HCDR1 comprises the amino acid sequence of SEQ ID No. 109, the HCDR2 comprises the amino acid sequence of SEQ ID No. 110, the HCDR3 comprises the amino acid sequence of SEQ ID No. 111, the LCDR1 comprises the amino acid sequence of SEQ ID No. 112, the LCDR2 comprises the amino acid sequence of GAS, and the LCDR3 comprises the amino acid sequence of SEQ ID No. 98; (f1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 116, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 117, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 118, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 119, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 120; (f2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 121, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 122, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 118, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 119, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 120; (f3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 123, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 124, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 118, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 119, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 120; (f4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 125, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 126, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 127, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 128, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 15, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 129; (f5) The HCDR1 comprises an amino acid sequence of SEQ ID No. 130, the HCDR2 comprises an amino acid sequence of SEQ ID No. 131, the HCDR3 comprises an amino acid sequence of SEQ ID No. 132, the LCDR1 comprises an amino acid sequence of SEQ ID No. 133, the LCDR2 comprises an amino acid sequence of GAS, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 120; (g1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 138, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 139, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 140, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 141, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 142; (g2) The HCDR1 comprises an amino acid sequence of SEQ ID No. 143, the HCDR2 comprises an amino acid sequence of SEQ ID No. 144, the HCDR3 comprises an amino acid sequence of SEQ ID No. 139, the LCDR1 comprises an amino acid sequence of SEQ ID No. 140, the LCDR2 comprises an amino acid sequence of SEQ ID No. 141, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 142; (g3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 145, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 146, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 139, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 140, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 141, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 142; (g4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 147, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 148, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 149, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 150, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 151, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 152; (g5) The HCDR1 comprises an amino acid sequence of SEQ ID No. 153, the HCDR2 comprises an amino acid sequence of SEQ ID No. 154, the HCDR3 comprises an amino acid sequence of SEQ ID No. 155, the LCDR1 comprises an amino acid sequence of SEQ ID No. 156, the LCDR2 comprises an amino acid sequence of AAS, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 142; (h1) The HCDR1 comprises the amino acid sequence of SEQ ID No. 1, the HCDR2 comprises the amino acid sequence of SEQ ID No. 160, the HCDR3 comprises the amino acid sequence of SEQ ID No. 161, the LCDR1 comprises the amino acid sequence of SEQ ID No. 162, the LCDR2 comprises the amino acid sequence of SEQ ID No. 163, and the LCDR3 comprises the amino acid sequence of SEQ ID No. 76; (h2) The HCDR1 comprises an amino acid sequence of SEQ ID No. 164, the HCDR2 comprises an amino acid sequence of SEQ ID No. 165, the HCDR3 comprises an amino acid sequence of SEQ ID No. 161, the LCDR1 comprises an amino acid sequence of SEQ ID No. 162, the LCDR2 comprises an amino acid sequence of SEQ ID No. 163, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 76; (h3) The HCDR1 comprises the amino acid sequence of SEQ ID No. 166, the HCDR2 comprises the amino acid sequence of SEQ ID No. 167, the HCDR3 comprises the amino acid sequence of SEQ ID No. 161, the LCDR1 comprises the amino acid sequence of SEQ ID No. 162, the LCDR2 comprises the amino acid sequence of SEQ ID No. 163, and the LCDR3 comprises the amino acid sequence of SEQ ID No. 76; (h4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 168, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 169, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 170, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 171, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 86, and (H5) The HCDR1 comprises the amino acid sequence of SEQ ID NO: 172, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 173, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 174, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 175, the LCDR2 comprises the amino acid sequence of VAS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 76.
  5. 5. The binding agent of any one of claims 1 to 4, wherein the antigen binding region comprises a VH domain and a VL domain selected from the group consisting of: (a) A VH domain comprising the amino acid sequence of SEQ ID No. 22 and a VL domain comprising the amino acid sequence of SEQ ID No. 23; (b) A VH domain comprising the amino acid sequence of SEQ ID No. 45 and a VL domain comprising the amino acid sequence of SEQ ID No. 46; (c) A VH domain comprising the amino acid sequence of SEQ ID No. 68 and a VL domain comprising the amino acid sequence of SEQ ID No. 69; (c') a VH domain comprising the amino acid sequence of SEQ ID NO. 68 and a VL domain comprising the amino acid sequence of SEQ ID NO. 70; (d) A VH domain comprising the amino acid sequence of SEQ ID No. 91 and a VL domain comprising the amino acid sequence of SEQ ID No. 92; (e) A VH domain comprising the amino acid sequence of SEQ ID No. 113 and a VL domain comprising the amino acid sequence of SEQ ID No. 114; (e') a VH domain comprising the amino acid sequence of SEQ ID NO. 113 and a VL domain comprising the amino acid sequence of SEQ ID NO. 115; (f) A VH domain comprising the amino acid sequence of SEQ ID No. 134 and a VL domain comprising the amino acid sequence of SEQ ID No. 135; (f') a VH domain comprising the amino acid sequence of SEQ ID NO. 134 and a VL domain comprising the amino acid sequence of SEQ ID NO. 136; (g) A VH domain comprising the amino acid sequence of SEQ ID NO. 158 and a VL domain comprising the amino acid sequence of SEQ ID NO. 159, and (H) A VH domain comprising the amino acid sequence of SEQ ID NO. 177 and a VL domain comprising the amino acid sequence of SEQ ID NO. 178.
  6. 6. The binding agent of any one of claims 1 to 5, wherein the binding agent is a bispecific protein or a multispecific protein.
  7. 7. The binding agent of 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. 8. The binding agent of claim 7, wherein the Ig constant region, the fragment of the Ig constant region, the Fc region, or the CH3 domain comprises at least one mutation.
  9. 9. The binding agent of claim 8, wherein the at least one mutation is selected from the group consisting of ：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、H268Q/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 residue numbering is according to the EU index.
  10. 10. The binding agent of claim 8, wherein the at least one mutation is selected from the group consisting of ：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/T394W、T366L/K392L/T394W、L351Y/Y407A、L351Y/Y407V、T366A/K409F、T366V/K409F、T366A/K409F、T350V/L351Y/F405A/Y407V and T350V/T366L/K392L/T394W, wherein the residues are numbered according to the EU index.
  11. 11. The binding agent of claim 8, wherein the binding agent comprises a knob-to-hole structural mutation, wherein the knob mutation comprises T366S/L368A/Y407V and the knob mutation comprises T366W.
  12. 12. The binding agent of any one of claims 1 to 11, wherein the binding agent comprises a bispecific protein comprising an antigen binding region that binds a second antigen other than ENPP 3.
  13. 13. The binding agent of claim 12, wherein the second antigen is cluster of differentiation 3 epsilon (CD 3 epsilon).
  14. 14. A binding agent comprising a first antigen-binding region that binds ENPP3 and a second antigen-binding region that binds CD3 epsilon, wherein said first antigen-binding region that binds ENPP3 comprises VH and VL selected from the group consisting of: (a) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 22, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 23; (b) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as set forth in SEQ ID No. 45, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as set forth in SEQ ID No. 46; (c) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 68, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 69 or SEQ ID No. 70; (d) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as set forth in SEQ ID No. 91, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as set forth in SEQ ID No. 92; (e) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 113, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 114 or SEQ ID No. 115; (f) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 134, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 135 or SEQ ID No. 136; (g) VH domains comprising HCDR1, HCDR2 and HCDR3 of the VH set forth in SEQ ID NO 158, and VL domains comprising LCDR1, LCDR2 and LCDR3 of the VL set forth in SEQ ID NO 159, and (H) VH domains comprising HCDR1, HCDR2 and HCDR3 of VH as shown in SEQ ID No. 177, and VL domains comprising LCDR1, LCDR2 and LCDR3 of VL as shown in SEQ ID No. 178.
  15. 15. The binding agent of claim 14, wherein in the second antigen binding region that binds CD3 epsilon comprises a VH domain comprising the VH of HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NO: 200, and a VL domain comprising the LCDR1, LCDR2, and LCDR3 of the VL as set forth in SEQ ID NO: 201.
  16. 16. The binding agent of claim 14, wherein the first antigen binding region that binds ENPP3 comprises a CDR sequence selected from the group consisting of: (a1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 1, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 2, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 3, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 4, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 6; (a2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 7, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 8, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 3, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 4, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 6; (a3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 9, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 10, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 3, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 4, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 6; (a4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 12, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 13, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 14, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 15, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 16; (a5) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 17, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 18, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 19, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 20, the LCDR2 comprises the amino acid sequence of GAS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 6; (b1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 24, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 25, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 26, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 27, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 28, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 29; (b2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 30, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 31, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 26, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 27, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 28, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 29; (b3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 32, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 33, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 26, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 27, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 28, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 29; (b4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 34, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 35, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 36, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 37, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 38, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 39; (b5) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 40, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 41, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 42, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 43, the LCDR2 comprises the amino acid sequence of DAS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 29; (c1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 47, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 48, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 49, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 50, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 51, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 52; (c2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 53, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 54, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 49, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 50, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 51, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 52; (c3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 55, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 56, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 49, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 50, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 51, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 52; (c4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 57, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 58, the HCDR3 comprises the amino acid sequence of SEQ ID NO.59, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 60, the LCDR2 comprises the amino acid sequence of SEQ ID NO.61, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 62; (c5) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 63, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 64, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 65, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 66, the LCDR2 comprises the amino acid sequence of QIS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 52; (d1) The HCDR1 comprises the amino acid sequence of SEQ ID NO: 71, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 72, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 73, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 74, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 75, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 76; (d2) The HCDR1 comprises the amino acid sequence of SEQ ID No. 77, the HCDR2 comprises the amino acid sequence of SEQ ID No. 78, the HCDR3 comprises the amino acid sequence of SEQ ID No. 73, the LCDR1 comprises the amino acid sequence of SEQ ID No. 74, the LCDR2 comprises the amino acid sequence of SEQ ID No. 75, and the LCDR3 comprises the amino acid sequence of SEQ ID No. 76; (d3) The HCDR1 comprises an amino acid sequence of SEQ ID No. 79, the HCDR2 comprises an amino acid sequence of SEQ ID No. 80, the HCDR3 comprises an amino acid sequence of SEQ ID No. 73, the LCDR1 comprises an amino acid sequence of SEQ ID No. 74, the LCDR2 comprises an amino acid sequence of SEQ ID No. 75, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 76; (d4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 81, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 82, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 83, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 84, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 85, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 86; (d5) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 87, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 88, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 89, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 90, the LCDR2 comprises the amino acid sequence of GAS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 76; (e1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 93, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 94, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 95, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 96, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 97, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 98; (e2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 99, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 100, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 95, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 96, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 97, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 98; (e3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 101, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 102, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 95, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 96, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 97, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 98; (e4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 103, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 104, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 105, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 106, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 107, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 108; (e5) The HCDR1 comprises the amino acid sequence of SEQ ID No. 109, the HCDR2 comprises the amino acid sequence of SEQ ID No. 110, the HCDR3 comprises the amino acid sequence of SEQ ID No. 111, the LCDR1 comprises the amino acid sequence of SEQ ID No. 112, the LCDR2 comprises the amino acid sequence of GAS, and the LCDR3 comprises the amino acid sequence of SEQ ID No. 98; (f1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 116, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 117, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 118, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 119, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 120; (f2) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 121, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 122, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 118, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 119, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 120; (f3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 123, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 124, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 118, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 119, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 120; (f4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 125, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 126, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 127, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 128, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 15, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 129; (f5) The HCDR1 comprises an amino acid sequence of SEQ ID No. 130, the HCDR2 comprises an amino acid sequence of SEQ ID No. 131, the HCDR3 comprises an amino acid sequence of SEQ ID No. 132, the LCDR1 comprises an amino acid sequence of SEQ ID No. 133, the LCDR2 comprises an amino acid sequence of GAS, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 120; (g1) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 137, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 138, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 139, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 140, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 141, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 142; (g2) The HCDR1 comprises an amino acid sequence of SEQ ID No. 143, the HCDR2 comprises an amino acid sequence of SEQ ID No. 144, the HCDR3 comprises an amino acid sequence of SEQ ID No. 139, the LCDR1 comprises an amino acid sequence of SEQ ID No. 140, the LCDR2 comprises an amino acid sequence of SEQ ID No. 141, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 142; (g3) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 145, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 146, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 139, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 140, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 141, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 142; (g4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 147, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 148, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 149, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 150, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 151, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 152; (g5) The HCDR1 comprises an amino acid sequence of SEQ ID No. 153, the HCDR2 comprises an amino acid sequence of SEQ ID No. 154, the HCDR3 comprises an amino acid sequence of SEQ ID No. 155, the LCDR1 comprises an amino acid sequence of SEQ ID No. 156, the LCDR2 comprises an amino acid sequence of AAS, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 142; (h1) The HCDR1 comprises the amino acid sequence of SEQ ID No. 1, the HCDR2 comprises the amino acid sequence of SEQ ID No. 160, the HCDR3 comprises the amino acid sequence of SEQ ID No. 161, the LCDR1 comprises the amino acid sequence of SEQ ID No. 162, the LCDR2 comprises the amino acid sequence of SEQ ID No. 163, and the LCDR3 comprises the amino acid sequence of SEQ ID No. 76; (h2) The HCDR1 comprises an amino acid sequence of SEQ ID No. 164, the HCDR2 comprises an amino acid sequence of SEQ ID No. 165, the HCDR3 comprises an amino acid sequence of SEQ ID No. 161, the LCDR1 comprises an amino acid sequence of SEQ ID No. 162, the LCDR2 comprises an amino acid sequence of SEQ ID No. 163, and the LCDR3 comprises an amino acid sequence of SEQ ID No. 76; (h3) The HCDR1 comprises the amino acid sequence of SEQ ID No. 166, the HCDR2 comprises the amino acid sequence of SEQ ID No. 167, the HCDR3 comprises the amino acid sequence of SEQ ID No. 161, the LCDR1 comprises the amino acid sequence of SEQ ID No. 162, the LCDR2 comprises the amino acid sequence of SEQ ID No. 163, and the LCDR3 comprises the amino acid sequence of SEQ ID No. 76; (h4) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 168, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 169, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 170, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 171, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 86, and (H5) The HCDR1 comprises the amino acid sequence of SEQ ID NO: 172, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 173, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 174, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 175, the LCDR2 comprises the amino acid sequence of VAS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 76.
  17. 17. The binding agent of claim 15, wherein the second antigen binding region that binds CD3 epsilon comprises a CDR sequence selected from the group consisting of: (a) The HCDR1 comprises the amino acid sequence of SEQ ID NO: 179, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 180, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 181, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 182, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 183, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 184; (b) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 185, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 186, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 181, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 182, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 183, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 184; (c) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 187, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 188, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 181, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 182, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 183, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 184; (d) The HCDR1 comprises the amino acid sequence of SEQ ID NO. 189, the HCDR2 comprises the amino acid sequence of SEQ ID NO. 190, the HCDR3 comprises the amino acid sequence of SEQ ID NO. 191, the LCDR1 comprises the amino acid sequence of SEQ ID NO. 192, the LCDR2 comprises the amino acid sequence of SEQ ID NO. 193, and the LCDR3 comprises the amino acid sequence of SEQ ID NO. 194, and (E) The HCDR1 comprises the amino acid sequence of SEQ ID NO: 195, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 196, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 197, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 198, the LCDR2 comprises the amino acid sequence of DSS, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 184.
  18. 18. The binding agent of any one of claims 14 to 17, wherein: (i) The first binding region comprising a VH domain comprising the amino acid sequence of SEQ ID NO. 22 and a VL domain comprising the amino acid sequence of SEQ ID NO. 23, and (Ii) The second binding region comprises a VH domain comprising the amino acid sequence of SEQ ID NO. 200 and a VL domain comprising the amino acid sequence of SEQ ID NO. 201.
  19. 19. The binding agent of any one of claims 12 to 18, wherein the first antigen binding region comprises a Fab and the second antigen binding region comprises a stapled scFv fragment (spFv).
  20. 20. The binding agent of claim 19, wherein the spFv comprises at least one disulfide bond between the VH or the VL and a linker.

Description

ENPP3 and CD3 binding agents and methods of use thereof Cross Reference to Related Applications The present application claims priority from U.S. provisional patent application No. 63/531,157 filed on 7, 8, 2023, the disclosure of which is incorporated herein by reference in its entirety. Sequence listing The present application encompasses a sequence table that has been electronically submitted in XML format and is hereby incorporated by reference in its entirety. The XML copy was created at 2024, 7, 29, named JBI6827WOPCT1_SL.xml and was 290 kilobytes in size. Technical Field The present disclosure relates generally to T cell adaptors that bind anti-ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP 3) and cluster of differentiation 3 (CD 3), compositions comprising such adaptors, and methods of use thereof. Background Solid tumors have been a challenge for antibody-mediated T cell redirection therapies, and to date, the U.S. Food and Drug Administration (FDA) approved drugs, if any, have been very limited. Limitations of this approach may be related to lack of cancer specificity of the target, resulting in toxicity when an effective dose is not reached. There remains an unmet need in extending and improving the prognosis of solid tumors and overall treatment duration. Innovative approaches are needed to achieve effective targeting of solid tumors and minimize therapeutic toxicity. This disclosure meets this and other needs. Disclosure of Invention In one aspect, provided herein is a binding agent comprising an antigen binding region that binds to an epitope of ENPP 3. In some embodiments, the epitope of ENPP3 is selected from the group consisting of SEQ ID NO 295 through SEQ ID NO 297, DVP and SEQ ID NO 299 through SEQ ID NO 305. In some embodiments, the antigen binding region comprises a VH domain selected from the group consisting of (a) a VH domain comprising HCDR1, HCDR2 and HCDR3 of a VH as set forth in SEQ ID NO. 22, and a VL domain comprising LCDR1, LCDR2 and LCDR3 of a VL as set forth in SEQ ID NO. 23; (b) a VH domain comprising the VH of HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 45, and a VL domain comprising the VL of LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 46, (c) a VH domain comprising the VH of HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 68, and a VL domain comprising the VL of LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 69 or 70, (d) a VH domain comprising the VH of HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 91, and a VL domain comprising the VL of LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 92, (e) a VL domain comprising the VL of HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 68, and a VL domain comprising the VL of LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 114 or SEQ ID NO: 115, and a VL domain comprising the VL of LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 115, (158) a VL domain comprising the VL of LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 92, and a VL domain comprising the VL of LCDR2 and LCDR3 as shown in SEQ ID NO: 134, and VL domain comprising the VL of LCDR2 and LCDR3 as shown in SEQ ID NO: 31 VH domains of HCDR2 and HCDR3, and VL domains of LCDR1, LCDR2, and LCDR3 comprising a VL as set forth in SEQ ID NO: 178. In some embodiments, the CDR sequence is selected from the group consisting of (a 1) HCDR1 comprises the amino acid sequence of SEQ ID NO 1, HCDR2 comprises the amino acid sequence of SEQ ID NO 2, HCDR3 comprises the amino acid sequence of SEQ ID NO 3, LCDR1 comprises the amino acid sequence of SEQ ID NO 4, LCDR2 comprises the amino acid sequence of SEQ ID NO 5, and LCDR3 comprises the amino acid sequence of SEQ ID NO 6, (a 2) HCDR1 comprises the amino acid sequence of SEQ ID NO 7, HCDR2 comprises the amino acid sequence of SEQ ID NO 8, HCDR3 comprises the amino acid sequence of SEQ ID NO 3, LCDR1 comprises the amino acid sequence of SEQ ID NO 4, LCDR2 comprises the amino acid sequence of SEQ ID NO 5, and LCDR3 comprises the amino acid sequence of SEQ ID NO 6, (a 3) HCDR1 comprises the amino acid sequence of SEQ ID NO 9, HCDR2 comprises the amino acid sequence of SEQ ID NO 10, HCDR3 comprises the amino acid sequence of SEQ ID NO 3, LCDR3 comprises the amino acid sequence of SEQ ID NO 3, and LCDR1 comprises the amino acid sequence of SEQ ID NO 11, and LCDR1 comprises the amino acid sequence of SEQ ID NO 3, LCDR1 comprises the amino acid sequence of SEQ ID NO 5, and LCDR1 comprises the amino acid sequence of SEQ ID NO 1 and LCDR1 comprises the amino acid sequence of SEQ ID NO 2 comprises the amino acid sequence of NO 5, LCDR1 comprises the amino acid sequence of SEQ ID NO 6 and LCDR1 comprises the amino acid sequence of SEQ ID NO 6 comprises the amino acid sequence of SEQ ID NO 1 and SEQ ID NO 2 comprises the amino acid sequence of 1, HCDR2 comprises the amino acid sequence of SEQ ID NO. 18, HCDR3 comprises the amino acid sequence of SEQ ID NO. 19, LCDR1 comprises the amino acid sequence of SEQ ID NO. 20, LCDR2 comprises the a