POSH inhibitor complex biomolecules and amphiphile micelles

Patent metadata

Field	Value
Publication number	US-11286489-B2
Application number	US-201716076521-A
Country	US
Kind code	B2
Filing date	Feb 13, 2017
Priority date	Feb 11, 2016
Publication date	Mar 29, 2022
Grant date	Mar 29, 2022

Abstract

The present invention is directed to a composition that includes an amphiphile, its use in a method of preventing and/or treating cancer, and its use in a method of producing a pharmaceutical composition. In certain embodiments, the amphiphile includes a hydrophilic peptide that binds to a Plenty of SH3 domain (POSH) and inhibits or disrupts a POSH scaffold network, a hydrophobic moiety, and an aptamer. The present invention is also directed to other POSH inhibitor complex biomolecules that do not contain a hydrophobic moiety.

First claim

We claim:

1. A composition comprising:
a plurality of amphiphiles comprising:
a hydrophilic therapeutic peptide that inhibits or disrupts a scaffold network of POSH by targeting an SH3 domain of POSH selected from the group consisting of POSH SH3.1, POSH SH3.2, POSH SH3.3, and POSH SH3.4; and
a hydrophobic moiety; and

a medium in which at least a portion of the hydrophobic moieties of the amphiphiles is insoluble, such that at least a portion of the plurality of said amphiphiles are arranged as micelles in the medium.

2. The composition of claim 1 , wherein the amphiphile further comprises an aptamer.

3. The composition of claim 2 , wherein the aptamer has a specific binding affinity for a specific cell surface marker.

4. The composition of claim 3 , wherein the aptamer has a specific binding affinity for a specific cell surface marker selected from the group consisting of CD4, CD19, Transferrin Receptor, CD7, CD20, CD33, and CD13.

5. The composition of claim 1 , wherein the hydrophobic moiety comprises an aliphatic compound.

6. The composition of claim 5 , wherein the hydrophobic moiety comprises a lipid comprising a saturated or unsaturated fatty acid.

7. The composition of claim 6 , where the hydrophobic moiety is selected from the group consisting of palmitic acid, oleic acid, eicosapentaenoic acid, n-decylamine, oleylamine, and combinations thereof.

8. The composition of any of claim 1 , wherein the amphiphile comprises two hydrophobic moieties.

9. The composition of claim 2 , wherein the hydrophobic moiety and aptamer are attached to opposite ends of the hydrophilic peptide, and each of the hydrophobic moiety and aptamer are independently attached via a compound selected from the group consisting of cysteine, lysine, glutamic acid, aspartic acid, serine, threonine, tyrosine, maleimide, a modified cysteine, a modified lysine, a modified glutamic acid, a modified aspartic acid, a modified serine, a modified threonine, a modified tyrosine, or a modified maleimide.

10. The composition of claim 7 , wherein the hydrophobic moiety is selected from the group consisting of dipalmitoyllysyllysine (KKP2) and dipalmitoylglutamylsuccinate lysine (diC16 lysine-K(diC16)).

11. The composition of claim 1 , wherein the medium is an aqueous medium.

12. The composition of claim 11 , wherein the composition further comprises a biomolecule comprising:
a second hydrophilic peptide that inhibits or disrupts a scaffold network of POSH by targeting an SH3 domain of POSH selected from the group consisting of POSH SH3.1, POSH SH3.2, POSH SH3.3, and POSH SH3.4; and
a second aptamer;
wherein the biomolecule does not comprise a hydrophobic moiety.

13. The composition of claim 1 , wherein the micelles are spherical.

14. The composition of claim 2 , wherein the aptamer is selected from the group consisting of human CD4 (hCD4) and human CD19 (hCD19).

15. The composition of any of claim 1 or 14 , wherein the hydrophilic peptide comprises a sequence selected from the group consisting of: SEQ. ID. NO: 1 (EGKEPGDLKFSKGDIIILRR), SEQ. ID. NO: 2 (KEADKDCLPFAKDDVLTVIR), SEQ. ID. NO: 3 (RKEDELELRKGEMFLVFER), SEQ. ID. NO: 4 (PQSEAELELKEGDIVFVHKK) and an amino acid sequence having over it total length at least 50% sequence identity with any one of SEQ. ID. NO: 1 to SEQ. ID. NO: 4.

16. A composition comprising:
a plurality of amphiphiles, each amphiphile independently comprising:
a hydrophobic moiety; and
(a) hydrophilic peptide that and inhibits or disrupts a scaffold network of POSH by targeting an SH3 domain of POSH selected from the group consisting of POSH SH3.1, POSH SH3.2, POSH SH3.3, and POSH SH3.4, (b) an aptamer, or (c) combinations thereof;

wherein at least a portion of said amphiphiles comprise said hydrophilic peptide; and
a medium in which at least a portion of the hydrophobic moieties of the amphiphiles is insoluble, such that at least a portion of the plurality of said amphiphiles are arranged as micelles in the medium.

17. The composition of claim 16 , wherein at least a portion of said micelles are heterogeneous.

18. The composition of claim 16 , wherein the composition is heterogeneous.

19. The composition of claim 16 , wherein the micelles are spherical.

Assignees

• Daniels Mark
• Ulery Bret
• Porciani David
• Tawiah Kwaku
• Smith Josiah
• Cardwell Leah
• Burke Donald
• Newcomer Erin
• Univ Missouri

Inventors

• Daniels Mark
• Ulery Bret
• Porciani David
• Tawiah Kwaku
• Smith Josiah
• Cardwell Leah
• Burke Donald
• Newcomer Erin

Classifications

• A61K38/10 Primary

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K9/1075

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• C12N9/93

  Ligases (6) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K38/16

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)} · CPC title