De novo design of potent and selective interleukin mimetics

Patent metadata

Field	Value
Publication number	US-11117944-B2
Application number	US-202016905669-A
Country	US
Kind code	B2
Filing date	Jun 18, 2020
Priority date	Jun 25, 2018
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

De novo designed polypeptides that bind to IL-2 receptor βγ c heterodimer (IL-2Rβγ c ), IL-4 receptor αγ c heterodimer (IL-4Rαγ c ), 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 that binds to IL-2 receptor βγc heterodimer (IL-2Rβγc) and comprises an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO:181, wherein the polypeptide further comprises a targeting domain.

2. The polypeptide of claim 1 wherein the targeting domain binds to a cell surface protein marker on the surface of a tumor cell, a tumor vascular component cell, or a tumor microenvironment cell.

3. The polypeptide of claim 1 wherein the targeting domain binds to an immune cell surface protein marker.

4. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in SEQ ID NO:181.

5. The polypeptide of claim 4 wherein the targeting domain binds to a cell surface protein marker on the surface of a tumor cell, a tumor vascular component cell, or a tumor microenvironment cell.

6. The polypeptide of claim 4 wherein the targeting domain binds to an immune cell surface protein marker.

7. The polypeptide of claim 4 wherein the targeting domain is an antibody.

8. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:181.

9. The polypeptide of claim 8 wherein the targeting domain binds to a cell surface protein marker on the surface of a tumor cell, a tumor vascular component cell, or a tumor microenvironment cell.

10. The polypeptide of claim 8 wherein the targeting domain binds to an immune cell surface protein marker.

11. The polypeptide of claim 8 wherein the targeting domain is an antibody.

12. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence at least 93% identical to the amino acid sequence set forth in SEQ ID NO:181.

13. The polypeptide of claim 12 wherein the targeting domain binds to a cell surface protein marker on the surface of a tumor cell, a tumor vascular component cell, or a tumor microenvironment cell.

14. The polypeptide of claim 12 wherein the targeting domain binds to an immune cell surface protein marker.

15. The polypeptide of claim 12 wherein the targeting domain is an antibody.

16. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence set forth in SEQ ID NO:181.

17. The polypeptide of claim 16 wherein the targeting domain binds to a cell surface protein marker on the surface of a tumor cell, a tumor vascular component cell, or a tumor microenvironment cell.

18. The polypeptide of claim 16 wherein the targeting domain binds to an immune cell surface protein marker.

19. The polypeptide of claim 16 wherein the targeting domain is an antibody.

20. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence at least 97% identical to the amino acid sequence set forth in SEQ ID NO:181.

21. The polypeptide of claim 20 wherein the targeting domain binds to a cell surface protein marker on the surface of a tumor cell, a tumor vascular component cell, or a tumor microenvironment cell.

22. The polypeptide of claim 20 wherein the targeting domain binds to an immune cell surface protein marker.

23. The polypeptide of claim 20 wherein the targeting domain is an antibody.

24. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO:181.

25. The polypeptide of claim 24 wherein the targeting domain binds to a cell surface protein marker on the surface of a tumor cell, a tumor vascular component cell, or a tumor microenvironment cell.

26. The polypeptide of claim 24 wherein the targeting domain binds to an immune cell surface protein marker.

27. A non-naturally occurring polypeptide that binds to IL-2 receptor βγc heterodimer (IL-2Rβγc) and comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:181, wherein the polypeptide is linked to a stabilization compound selected from polyethylene glycol or albumin.

28. A non-naturally occurring polypeptide that binds to IL-2 receptor βγc heterodimer (IL-2Rβγc) and comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in SEQ ID NO:181.

29. The polypeptide of claim 28 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO:181.

30. The polypeptide of claim 28 , wherein (i) the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 181, except that the N-terminal proline and the C-terminal serine of SEQ ID NO:181 are absent and the amino acid sequence CNSN (SEQ ID NO:260) is present at the N-terminus of SEQ ID NO: 181 and the amino acid sequence NFQC (SEQ ID NO:261) is present at the C terminus of SEQ ID NO:181; (ii) the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 181, except for a tyrosine at position 8 and a glutamic acid at position 33 of SEQ ID NO:181; or (iii) the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 181, except for a cysteine at position 50, 53, or 82 of SEQ ID NO:181.

Assignees

• Univ Washington
• Univ Leland Stanford Junior

Inventors

• Manzano Daniel Adriano Silva
• Yu Shawn
• Ulge Umut
• Baker David
• Garcia Kenan Christopher
• Spangler Jamie
• Walkey Carl
• Rubio Alfredo Quijano
• Weitzner Brian

Classifications

• G01N2333/55

  IL-2 · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• G16B15/30

  Drug targeting using structural data; Docking or binding prediction · CPC title

• G16B50/30

  Data warehousing; Computing architectures · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title