NKG2D decoys

Patent metadata

Field	Value
Publication number	US-10815290-B2
Application number	US-201615775298-A
Country	US
Kind code	B2
Filing date	Nov 10, 2016
Priority date	Nov 10, 2015
Publication date	Oct 27, 2020
Grant date	Oct 27, 2020

Abstract

Single chain, multimerized, and/or glycosylated NKG2D decoys are described. The NKG2D decoys have high affinity and avidity for surface bound and soluble NKG2D ligands and can be used to (i) identify NKG2D ligands; (ii) treat cancer, graft vs. host disease (GVHD), and inflammatory conditions; and (iii) potentiate an immune response against a vaccine as well as many other potential uses.

First claim

What is claimed is:

1. A single chain protein comprising the formula x-y-z, wherein x comprises a multimerization domain, y comprises a first linker derived from NKG2D, and z comprises an extracellular fragment of NKG2D comprising the formula a-b-a, wherein:
a comprises SEQ ID NO. 79, and
b comprises SEQ ID NO. 81 or SEQ ID NO. 82.

2. A single chain protein of claim 1 , wherein x comprises SEQ ID NO. 80.

3. A single chain protein of claim 1 , wherein y comprises SEQ ID NO. 81 or SEQ ID NO. 82.

4. A single chain protein of claim 1 , wherein x comprises SEQ ID NO. 80 and y comprises SEQ ID NO. 81 or SEQ ID NO. 82.

5. A single chain protein of claim 1 , wherein y comprises SEQ ID NO. 81 and b comprises SEQ ID NO. 82.

6. A single chain protein of claim 1 , wherein x consists of the multimerization domain, y consists of the first linker derived from NKG2D, and z consists of a-b-a.

7. A single chain protein of claim 1 , wherein the multimerization domain is a C4b multimerization domain.

8. A single chain protein of claim 1 , wherein the multimerization domain is selected from SEQ ID NO. 7-39 and SEQ ID NO. 80.

9. A single chain protein of claim 1 , wherein the multimerization domain is directly linked to the first linker derived from NKG2D.

10. A single chain protein of claim 1 , wherein y excludes a Gly-Ser linker.

11. A single chain protein of claim 1 , wherein the first linker is derived from human NKG2D.

12. A single chain protein of claim 1 , wherein y-z comprises SEQ ID NO. 3.

13. A single chain protein of claim 1 , wherein the two copies of SEQ ID NO: 79 form an NKG2D homodimer comprising the extracellular binding fragment of NKG2D.

14. A single chain protein of claim 1 , wherein z excludes intracellular portions of human or murine NKG2D.

15. A single chain protein of claim 1 , comprising SEQ ID NO. 78.

16. A single chain protein of claim 1 , multimerized into a heptamer.

17. A single chain protein of claim 1 , formulated as a pharmaceutical composition.

Assignees

• Hutchinson Fred Cancer Res

Inventors

• Gewe Mesfin
• Strong Roland K
• Prlic Martin
• Rupert Peter
• Spies Thomas
• Spies Veronika

Classifications

• C07K16/2833 Primary

  against MHC-molecules, e.g. HLA-molecules · CPC title

• C07K16/2851

  against the lectin superfamily, e.g. CD23, CD72 · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2319/74

  containing a fusion for binding to a cell surface receptor · CPC title