Self-assembling peptides comprising non-ionic polar amino acids

• US 10,682,441 B2
• Filed: 12/11/2015
• Issued: 06/16/2020
• Est. Priority Date: 12/12/2014
• Status: Active Grant

• Current Assignee: 3-D Matrix Limited
• Original Assignee: 3-D Matrix Limited
• Inventors: Gil, Eun Seok, Rioult, Marc, Nagano, Keiji, Gilbert, Karl Partick, Kiyofuji, Toshiro, Hasegawa, Yuya
• Primary Examiner(s): Alstrum-Acevedo, James H
• Assistant Examiner(s): Yang, Kaipeen E
• Application Number:
  US15/534,715
• Publication Number:
  US 20170360990A1
• Time in Patent Office: 1,649 Days
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

Compositions, peptide solutions and macroscopic scaffolds of self-assembling peptides consisting essentially of non-ionic, polar amino acids are provided. Particular peptides include those comprising or consisting essentially of serine, threonine, tyrosine, cysteine, glutamine, asparagine, methionine, tryptophan, hydroxy-proline, and combinations thereof. Methods of sterilizing the self-assembling peptides, and scaffolds comprising the peptides are also provided.

Claims

1. A peptide solution comprising a self-assembling peptide, consisting of a chemical structure (ST14) (SEQ ID NO:

2) of;

2. The peptide solution of claim 1, wherein the self-assembling peptide is capable of forming self-assembled nanofibers.

3. The peptide solution of claim 1, wherein a concentration of the self-assembling peptide in the peptide solution is between about 0.1 weight per volume (w/v) percent to about 10 weight per volume (w/v) percent.

4. The peptide solution of claim 3, wherein the concentration of the self-assembling peptide in the peptide solution is between about 0.5 weight per volume (w/v) percent and about 5 weight per volume (w/v) percent.

5. The peptide solution of claim 1, wherein a pH of the peptide solution is between about 0.5 and about 8.

6. The peptide solution of claim 5, wherein the pH of the peptide solution is between about 3 to about 7.

7. The peptide solution of claim 1, wherein a tonicity of the peptide solution is hypotonic, isotonic, or hypertonic.

8. The peptide solution of claim 7, wherein the tonicity of the peptide solution is isotonic.

9. The peptide solution of claim 7, wherein the tonicity of the peptide solution is adjusted with a tonicity agent selected from the group consisting of:

dextrose, glycerin, mannitol, potassium chloride, and sodium chloride.

10. The peptide solution of claim 7, wherein the tonicity of the peptide solution is adjusted with at least one salt selected from the group consisting of:

sodium chloride, potassium chloride, magnesium chloride, calcium chloride, and calcium sulfate.

11. The peptide solution of claim 10, wherein the at least one salt comprises one or more salt forming cations and one or more salt forming anions, wherein the one or more salt forming cations is selected from the group consisting of:

ammonium, calcium, iron, magnesium, potassium, pyridinium, quaternary ammonium, and sodium, and wherein the one or more salt forming anions is selected from the group consisting of;

acetate, carbonate, chloride, citrate, cyanide, fluoride, nitrate, nitrite, and phosphate.

12. The peptide solution of claim 1, further comprising human cells.

13. The peptide solution of claim 12, having a cell concentration of about 5 million cells per milliliter.

14. The peptide solution of claim 1, wherein the peptide solution has a storage modulus and the storage modulus increases between about 5 to about 10 times after exposure to a neutral pH.

15. The peptide solution of claim 14, wherein the storage modulus of the peptide solution increases about 7 times after exposure to a neutral pH.

16. A method for sterilizing peptides comprising:

providing a peptide solution comprising a self-assembling peptide consisting of a chemical structure (ST14) (SEQ ID NO;

     2) of;

17. The method of claim 16, further comprising measuring the molar mass of the self-assembling peptide in the peptide solution prior to treating the peptide solution.

18. The method of claim 17, further comprising measuring the molar mass of the self-assembling peptide in the peptide solution subsequent to treating the peptide solution.

19. The method of claim 18, further comprising comparing the molar mass of the self-assembling peptide in the peptide solution prior to treating the peptide solution, with the molar mass of the self-assembling peptide in the peptide solution subsequent to treating the peptide solution.

20. The method of claim 16, wherein treating the peptide solution comprises treating the peptide solution in an autoclave.

21. A peptide solution comprising a self-assembling peptide, consisting of a chemical structure (T14) (SEQ ID NO:

1) of;

22. The peptide solution of claim 21, wherein the self-assembling peptide is capable of forming self-assembled nanofibers.

23. The peptide solution of claim 21, wherein a concentration of the self-assembling peptide in the peptide solution is between about 0.1 weight per volume (w/v) percent to about 10 weight per volume (w/v) percent.

24. The peptide solution of claim 23, wherein the concentration of the self-assembling peptide in the peptide solution is between about 0.5 weight per volume (w/v) percent and about 5 weight per volume (w/v) percent.

25. The peptide solution of claim 21, wherein a pH of the peptide solution is between about 0.5 and about 8.

26. The peptide solution of claim 25, wherein the pH of the peptide solution is between about 3 to about 7.

27. The peptide solution of claim 21, wherein a tonicity of the peptide solution is hypotonic, isotonic, or hypertonic.

28. The peptide solution of claim 27, wherein the tonicity of the peptide solution is isotonic.

29. The peptide solution of claim 27, wherein the tonicity of the peptide solution is adjusted with a tonicity agent selected from the group consisting of:

dextrose, glycerin, mannitol, potassium chloride, and sodium chloride.

30. The peptide solution of claim 27, wherein the tonicity of the peptide solution is adjusted with at least one salt selected from the group consisting of:

sodium chloride, potassium chloride, magnesium chloride, calcium chloride, and calcium sulfate.

31. The peptide solution of claim 30, wherein the at least one salt comprises one or more salt forming cations and one or more salt forming anions, wherein the one or more salt forming cations is selected from the group consisting of:

ammonium, calcium, iron, magnesium, potassium, pyridinium, quaternary ammonium, and sodium, and wherein the one or more salt forming anions is selected from the group consisting of;

acetate, carbonate, chloride, citrate, cyanide, fluoride, nitrate, nitrite, and phosphate.

32. The peptide solution of claim 21, further comprising human cells.

33. The peptide solution of claim 32, having a cell concentration of about 5 million cells per milliliter.

34. The peptide solution of claim 21, wherein the peptide solution has a storage modulus and the storage modulus increases between about 5 to about 10 times after exposure to a neutral pH.

35. The peptide solution of claim 34, wherein the storage modulus of the peptide solution increases about 7 times after exposure to a neutral pH.