IL23R binding molecules and methods of use
The present disclosure relates to biologically active molecules comprising a single domain antibody (sdAb) that specifically binds to the extracellular domain of human IL23R, compositions comprising such antibodies, and methods of use thereof. Further disclosed are sequences of complementarity determining regions (CDR1, CDR2 and CDR3) and polypeptide sequences of human and mouse sdAbs.
1. A 1IL23R binding molecule that specifically binds to the extracellular domain of IL23R, wherein the IL23R binding molecule comprises a single domain antibody (sdAb), wherein the sdAb comprises a complementary determining region 1 (CDR1), a CDR2, and a CDR3 as shown in a row of the table below:
CDR1
CDR2
CDR3
YTYCSYDMS
AFNSDGTTSYADSVKG
DPHVQSSGGYCPPY
(SEQ ID NO: 21)
(SEQ ID NO: 22)
(SEQ ID NO: 23)
YTYCSYDMS
SFNSDGSTSYADSVKG
DPHADWGAPCGGDY
(SEQ ID NO: 24)
(SEQ ID NO: 25)
(SEQ ID NO: 26)
YTYCSYDMS
AIASDGSTSYADSLKG
DPHVQSSGGYCPPY
(SEQ ID NO: 33)
(SEQ ID NO: 34)
(SEQ ID NO: 35)
YTYCSYDMG
SINSDGTTSYADSVKG
DPQTRPGKPCADY
(SEQ ID NO: 36)
(SEQ ID NO: 37)
(SEQ ID NO: 38)
YTYCSYDMK
GIDSDGSISYADSVKG
EGTIPVGACPNY
(SEQ ID NO: 42)
(SEQ ID NO: 43)
(SEQ ID NO: 44)
YTYCSYDMS
SINSDGTTSYADSVKG
DPQTRPGKPCADY
(SEQ ID NO: 45)
(SEQ ID NO: 46)
(SEQ ID NO: 47)
YTYCSYDMT
AIDSDGSTSYADSVKG
DPIATISRRCDSY
(SEQ ID NO: 51)
(SEQ ID NO: 52)
(SEQ ID NO: 53)
YTYCSYDMK
AIDSDGSTSYADSVKG
EGTIPVGVCPNY
(SEQ ID NO: 57)
(SEQ ID NO: 58)
(SEQ ID NO: 59)
YTYCSYDMK
AIDSDGSTSYADSVKG
EGTVPVGVCPNY
(SEQ ID NO: 60)
(SEQ ID NO: 61)
(SEQ ID NO: 62)
YTSCSYDMS
AIHSDGTTSYADSMKG
DPNYSDHVCPPY
(SEQ ID NO: 75)
(SEQ ID NO: 76)
(SEQ ID NO: 77).
2. The IL23R binding molecule of claim 1 , wherein the sdAb has at least 95% identity to a polypeptide sequence of any one of SEQ ID NOS: 2, 3, 6, 7, 9, 10, 12, 14, 15, and 20.
3. The IL23R binding molecule of claim 1 , wherein the sdAb is humanized or otherwise comprises CDRs grafted onto a heterologous framework.
4. The IL23R binding molecule of claim 1 , further comprising a labeling agent, an imaging agent, and/or a therapeutic agent.
5. A method for isolating, depleting, or enriching IL23R+ cells in a biological sample, comprising contacting the biological sample with the IL23R binding molecule of claim 1 .
6. A pharmaceutical preparation comprising the IL23R binding molecule of claim 1 .
7. A kit comprising the IL23R binding molecule of claim 1 .
8. The IL23R binding molecule of claim 1 , wherein the sdAb is linked to a second binding molecule that specifically binds to the extracellular domain of a second cell surface molecule.
9. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:21, 22, and 23, respectively.
10. The IL23R binding molecule of claim 9 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:2.
11. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:24, 25, and 26, respectively.
12. The IL23R binding molecule of claim 11 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:3.
13. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:33, 34, and 35, respectively.
14. The IL23R binding molecule of claim 13 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:6.
15. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:36, 37, and 38, respectively.
16. The IL23R binding molecule of claim 15 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:7.
17. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:42, 43, and 44, respectively.
18. The IL23R binding molecule of claim 17 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:9.
19. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:45, 46, and 47, respectively.
20. The IL23R binding molecule of claim 19 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:10.
21. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:51, 52, and 53, respectively.
22. The IL23R binding molecule of claim 21 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:12.
23. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:57, 58, and 59, respectively.
24. The IL23R binding molecule of claim 23 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:14.
25. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:60, 61, and 62, respectively.
26. The IL23R binding molecule of claim 25 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:15.
27. The IL23R binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:75, 76, and 77, respectively.
28. The IL23R binding molecule of claim 27 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:20.
29. The IL23R binding molecule of claim 1 , wherein the sdAb is a VHH.
30. A nucleic acid sequence encoding the IL23R binding molecule of claim 1 .
31. A recombinant viral or non-viral vector comprising a nucleic acid of claim 30 .
32. A host cell comprising a nucleic acid of claim 30 .
33. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:21, 22, and 23, respectively.
34. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:24, 25, and 26, respectively.
35. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:33, 34, and 35, respectively.
36. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:36, 37, and 38, respectively.
37. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:42, 43, and 44, respectively.
38. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:45, 46, and 47, respectively.
39. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:51, 52, and 53, respectively.
40. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:57, 58, and 59, respectively.
41. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:60, 61, and 62, respectively.
42. The nucleic acid sequence of claim 30 , encoding the IL23R binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:75, 76, and 77, respectively.