De novo design of potent and selective interleukin mimetics

Patent metadata

Field	Value
Publication number	US-10844105-B2
Application number	US-202016909185-A
Country	US
Kind code	B2
Filing date	Jun 23, 2020
Priority date	Jun 25, 2018
Publication date	Nov 24, 2020
Grant date	Nov 24, 2020

Abstract

De novo designed polypeptides that bind to IL-2 receptor βc heterodimer (IL-2Rβc), IL-4 receptor αc heterodimer (IL-4Rαc), or IL-13 receptor α subunit (IL-13Rα) are disclosed, as are methods for using and designing the polypeptides.

First claim

We claim:

1. A non-naturally occurring polypeptide comprising an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO:181 provided that a cysteine residue is at amino acid position 62, 69 or 73 of SEQ ID NO:181, wherein the polypeptide binds to IL-2 receptor β c heterodimer (IL-2Rβ c ).

2. The non-naturally occurring polypeptide of claim 1 comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:181 provided that a cysteine residue is at amino acid position 62, 69 or 73 of SEQ ID NO:181.

3. The non-naturally occurring polypeptide of claim 2 comprising an amino acid sequence at least 95% identical to the amino acid sequence set forth in SEQ ID NO:181 provided that a cysteine residue is at amino acid position 62, 69 or 73 of SEQ ID NO:181.

4. The non-naturally occurring polypeptide of claim 1 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.

5. The non-naturally occurring polypeptide of claim 4 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.

6. The non-naturally occurring polypeptide of claim 2 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.

7. The non-naturally occurring polypeptide of claim 6 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.

8. The non-naturally occurring polypeptide of claim 3 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.

9. The non-naturally occurring polypeptide of claim 8 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.

10. The non-naturally occurring polypeptide of claim 1 wherein the cysteine residue is at amino acid position 62 of SEQ ID NO: 181.

11. The non-naturally occurring polypeptide of claim 2 wherein the cysteine residue is at amino acid position 62 of SEQ ID NO: 181.

12. The non-naturally occurring polypeptide of claim 3 wherein the cysteine residue is at amino acid position 62 of SEQ ID NO: 181.

13. The non-naturally occurring polypeptide of claim 3 comprising the amino acid sequence as set forth in SEQ ID NO: 195.

14. The non-naturally occurring polypeptide of claim 10 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.

15. The non-naturally occurring polypeptide of claim 14 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.

16. The non-naturally occurring polypeptide of claim 11 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.

17. The non-naturally occurring polypeptide of claim 16 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.

18. The non-naturally occurring polypeptide of claim 12 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.

19. The non-naturally occurring polypeptide of claim 18 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.

20. The non-naturally occurring polypeptide of claim 13 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.

21. The non-naturally occurring polypeptide of claim 20 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.

22. The non-naturally occurring polypeptide of claim 1 wherein the cysteine residue is at amino acid position 69 of SEQ ID NO: 181.

23. The non-naturally occurring polypeptide of claim 3 wherein the cysteine residue is at amino acid position 69 of SEQ ID NO: 181.

24. The non-naturally occurring polypeptide of claim 22 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.

25. The non-naturally occurring polypeptide of claim 24 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.

26. The non-naturally occurring polypeptide of claim 1 wherein the cysteine residue is at amino acid position 73 of SEQ ID NO: 181.

27. The non-naturally occurring polypeptide of claim 3 wherein the cysteine residue is at amino acid position 73 of SEQ ID NO: 181.

28. The non-naturally occurring polypeptide of claim 26 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.

29. The non-naturally occurring polypeptide of claim 28 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.

30. A pharmaceutical composition comprising the polypeptide of claim 1 , and a pharmaceutically acceptable carrier.

Assignees

• Univ Washington
• Univ Leland Stanford Junior

Inventors

• Silva Manzano Daniel Adriano
• Yu Shawn
• Ulge Umut
• Baker David
• Garcia Kenan Christopher
• Spangler Jamie
• Walkey Carl

Classifications

• G16B15/20

  Protein or domain folding · CPC title

• G01N2333/55

  IL-2 · CPC title

• G01N2333/5406

  IL-4 · CPC title

• G01N33/6869

  Interleukin · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title