Granted Patent B2

US 12,247,050 · App. 17/749,969 · Granted Mar 11, 2025

Inventors: Valerie Daggett (Seattle, WA); Dylan Shea (Seattle, WA); Alissa Bleem (Seattle, WA)

Assignee: UNIVERSITY OF WASHINGTON

C07K14/001A61K9/7007A61K38/1787A61P25/28C07K7/06C07K7/08

Abstract

Claims (49)

1. An α-sheet polypeptide multimer, comprising:

two monomeric α-sheet polypeptides that are covalently linked,

wherein each monomeric α-sheet polypeptide comprises the amino acid sequence of rGeMnLsWmneyyGwTmNmKcGr (SEQ ID NO:25) or its reverse chiral counterpart,

wherein residues in lower-case are D amino acids, residues in upper case are L amino acids, and G residues are achiral.

2. The α-sheet polypeptide multimer of claim 1 , wherein the two monomeric α-sheet polypeptides are covalently linked by 1 or more of the following:

(a) disulfide bonds;

(b) other covalent bonding between cysteine residues present in two monomers;

(c) thioether bridges between two monomers;

(d) covalent bonding between tyrosine residues present in two monomers;

(e) 1,2,3-triazole bridges between two monomers;

(f) amide bonds between two monomers;

(g) covalent bonding between histidine residues present in two monomers;

(h) conjugation to a core structure that covalently links multiple monomeric α-sheet polypeptides, including but not limited to poly-lysine, poly-ornithine, polyethylene glycol (PEG), Poly(amidoamine) (PAMAM), other polymers, and nanoparticle core structures;

(i) covalent bonding between norbrorene moieties present in two monomers;

(j) covalent bonding between a maleimide motif present in one monomer and the sulfur atom on a cysteine residue another monomer;

(k) covalent linkage of two monomers by a linking moiety including but not limited to Bis(maleimido)ethane (BMOE); 1,1′-(2,2′-oxybis(ethane-2,1-dioyl))bis(1H-pyrrole-2,5-dione) (MalPEG1);

3. A pharmaceutical composition, comprising:

(a) the α-sheet polypeptide multimer of claim 1 ; and

(b) a pharmaceutically acceptable carrier.

4. A composition, comprising:

(a) a polymer coating on a surface; and

(b) α-sheet polypeptides covalently linked to the polymer coating, wherein the α-sheet polypeptides comprise the α-sheet polypeptide multimer of claim 1 .

5. The composition of claim 4 , wherein the polymer comprises a catecholamine polymer.

6. The composition of claim 4 , wherein the polymer comprises polydopamine, poly-L-DOPA, polyepinephrine, polynoradrenaline, and any synthetic product which contains a di-hydroxyl phenol and a branched chain of any length that terminates with a primary amine, and combinations thereof.

7. The composition of claim 4 , wherein the polymer comprises polydopamine (PDA).

8. The α-sheet polypeptide multimer of claim 1 , wherein the two monomeric α-sheet polypeptides are covalently linked via a disulfide bond.

9. The α-sheet polypeptide multimer of claim 1 , wherein the two monomeric α-sheet polypeptides are covalently linked via Bis(maleimido)ethane (BMOE).

10. The α-sheet polypeptide multimer of claim 1 , wherein the two monomeric α-sheet polypeptides are covalently linked via 1,1′-(2,2′-oxybis(ethane-2,1-dioyl))bis(1H-pyrrole-2,5-dione) (MalPEG1).

11. The α-sheet polypeptide multimer of claim 1 , wherein each monomeric α-sheet polypeptide comprises the amino acid sequence: rGeMnLsWmneyyGwTmNmKcGr (SEQ ID NO:25), wherein residues in lower-case are D amino acids, residues in upper case are L amino acids, and G residues are achiral.

12. The α-sheet polypeptide multimer of claim 11 , wherein the two monomeric α-sheet polypeptides are covalently linked via a disulfide bond.

13. The α-sheet polypeptide multimer of claim 12 , wherein the N-terminus of the polypeptide is acetylated.

14. The α-sheet polypeptide multimer of claim 13 , wherein the C-terminus of the polypeptide is amidated.

15. A medical device comprising the α-sheet polypeptide multimer of claim 1 , coated on a surface of the medical device.

16. An α-sheet polypeptide comprising the amino acid sequence of

rGeMnLsWmneyyGwTmNmKcGr (SEQ ID NO:25) or its reverse chiral counterpart,

wherein residues in lower-case are D amino acids, residues in upper case are L amino acids, and G residues are achiral.

17. A composition, comprising:

(a) a polymer coating on a surface; and

(b) α-sheet polypeptides covalently linked to the polymer coating, wherein the α-sheet polypeptides comprise the α-sheet polypeptide of claim 16 .

18. The composition of claim 17 , wherein the polymer comprises a catecholamine polymer.

19. The composition of claim 17 , wherein the polymer comprises polydopamine, poly-L-DOPA, polyepinephrine, polynoradrenaline, and any synthetic product which contains a di-hydroxyl phenol and a branched chain of any length that terminates with a primary amine, and combinations thereof.

20. The composition of claim 17 , wherein the polymer comprises polydopamine (PDA).

21. The α-sheet polypeptide of claim 16 , comprising the amino acid sequence: rGeMnLsWmneyyGwTmNmKcGr (SEQ ID NO:25), wherein residues in lower-case are D amino acids, residues in upper case are L amino acids, and G residues are achiral.

22. The α-sheet polypeptide of claim 21 , wherein the N-terminus of the polypeptide is acetylated.

23. The α-sheet polypeptide of claim 22 , wherein the C-terminus of the polypeptide is amidated.

24. A pharmaceutical composition, comprising:

(a) the α-sheet polypeptide of claim 16 ; and

(b) a pharmaceutically acceptable carrier.

25. A medical device comprising the α-sheet polypeptide of claim 16 , coated on a surface of the medical device.

Assignments (3)

Continuity (2)

References Cited (197)