IP Library › Granted Patent US 9,988,617
Granted Patent B2
US 9,988,617 · App. 14/892,252 · Granted Jun 5, 2018

Engineered heme-binding compositions and uses thereof

Inventors: Michael Super (Lexington, MA); Alexander L. Watters (Melrose, MA); Philip T. Snell (Lexington, MA); Donald E. Ingber (Boston, MA)
Assignee: President and Fellows of Harvard College
C12N9/2474A61K38/00C07K14/805C12N9/96C12Y302/01035
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Quick Facts
Patent No.
US 9,988,617
App. No.
14/892,252
Granted
Jun 5, 2018
Kind
B2
Abstract

Described herein are heme-binding compositions and methods relating to their use, e.g. methods of treatment of, for example, sepsis and rhabdomyolysis.

Claims (28)

1. A heme-binding composition comprising:

i) an engineered heme-binding fusion protein comprising:

a. a hemopexin polypeptide domain which binds to heme, and comprises residues 27-213 of SEQ ID NO: 2;

b. a second polypeptide domain comprising a conjugation domain;

wherein the second polypeptide domain is linked to the N-terminus or C-terminus of the hemopexin domain, and

ii) a solid substrate or support to which the engineered heme-binding fusion protein is conjugated.

2. The composition of claim 1 , wherein the second polypeptide domain is an Fc domain or an Ala-Lys-Thr (AKT) tripeptide.

3. The composition of claim 1 , further comprising a detectable label.

4. The composition of claim 1 , wherein the solid substrate or support is a hollow fiber.

5. The composition of claim 1 , wherein the hemopexin polypeptide domain comprises SEQ ID NO: 2.

6. The composition of claim 1 , wherein the hemopexin polypeptide domain comprises residues 27-233 of SEQ ID NO: 2.

7. The composition of claim 1 , wherein the hemopexin polypeptide domain comprises residues 1-233 of SEQ ID NO: 2.

8. The composition of claim 1 , wherein the hemopexin polypeptide domain comprises residues 27-220 of SEQ ID NO: 2.

9. The composition of claim 1 , wherein the hemopexin polypeptide domain comprises residues 1-220 of SEQ ID NO: 2.

10. The composition of claim 1 , wherein the hemopexin polypeptide domain comprises residues 1-213 of SEQ ID NO: 2.

11. The composition of claim 5 , wherein the hemopexin polypeptide domain comprises a replacement of residues 220-226 of SEQ ID NO: 2 with a polypeptide linker of about 1-10 amino acids in length.

12. The composition of claim 5 , wherein the hemopexin polypeptide domain comprises a replacement of residues 220-226 of SEQ ID NO: 2 with the sequence of SEQ ID NO: 18.

13. The composition of claim 2 , wherein the Fc domain is a polypeptide having the sequence of SEQ ID NO: 8, SEQ ID NO: 7, or SEQ ID NO: 17.

14. The composition of claim 1 , wherein the engineered heme-binding fusion protein comprises the sequence of SEQ ID NO: 4 or SEQ ID NO: 5.

15. The composition of claim 1 , wherein the second polypeptide domain multimerizes to form a multimeric complex of the engineered heme-binding fusion protein.

16. The composition of claim 15 , wherein the multimeric complex is a dimeric complex.

17. The composition of claim 2 , wherein the second polypeptide domain is an Fc domain, wherein the Fc domain multimerizes to form a multimeric complex of the engineered heme-binding fusion protein.

18. The composition of claim 17 , wherein the multimeric complex is a dimeric complex.

19. The composition of claim 1 , wherein the second polypeptide domain is linked to the N-terminus or C-terminus of the hemopexin polypeptide domain via a linker.

20. The composition of claim 1 , wherein the second polypeptide domain is linked to the N-terminus of the hemopexin polypeptide domain.

21. The composition of claim 1 , wherein the second polypeptide domain is linked to the C-terminus of the hemopexin polypeptide domain.

22. The composition of claim 2 , wherein the second polypeptide domain is an Fc domain.

23. The composition of claim 2 , wherein the second polypeptide domain is an Ala-Lys-Thr (AKT) tripeptide.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 16, 2016
From: INGBER, DONALD E; SNELL, PHILIP T; SUPER, MICHAEL; WATTERS, ALEXANDER L
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 038933/0712 →
Continuity (2)
Provisional Application 61825707 · May 21, 2013
Related Publication 20160090583A1 · Mar 31, 2016