Bioerodible silicon-based compositions for delivery of therapeutic agents

• US 9,980,911 B2
• Filed: 04/29/2016
• Issued: 05/29/2018
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: EyePoint Pharmaceuticals, Inc.
• Original Assignee: pSivida US, Inc
• Inventors: Barnett, Christian, Ashton, Paul, Canham, Leigh T.
• Primary Examiner(s): Justice, Gina C
• Application Number:
  US15/143,283
• Publication Number:
  US 20170049703A1
• Time in Patent Office: 760 Days
• CPC Class Codes: A61K 38/42 Haemoglobins; Myoglobins
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/143 with inorganic compounds
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered

Abstract

The invention comprises a composition comprising a bioerodible porous silicon-based carrier material wherein the carrier material carries at least one large molecule therapeutic agent and at least one amorphous sugar, optionally further comprising a crystallization inhibitor. The composition may be used in vitro or in vivo to deliver the therapeutic agent, preferably in a controlled fashion over an intended period of time such as over multiple days, weeks or months. The composition may be used for treating or preventing conditions of a patient such as chronic diseases.

Claims

1. A method of treating or preventing a condition in a patient comprising administering to the patient a composition comprising a bioerodible porous silicon-based carrier material, wherein at least one large-molecule therapeutic agent and an amorphous sugar are disposed in pores of the carrier material.

2. The method of claim 1, wherein the composition is administered to the surface or the skin or eye of a patient.

3. The method of claim 1, wherein the composition is administered intravitreally, subcutaneously, subconjunctivally, intraperitoneally, intramuscularly or subretinally.

4. The method of claim 1, wherein the composition is administered into the eye.

5. The method of claim 4, wherein the composition is administered within the aqueous of the eye.

6. The method of claim 4, wherein the composition is administered within the vitreous of the eye.

7. The method of claim 1, wherein the condition is selected from conditions of the eye.

8. The method of claim 7, wherein the condition is selected from glaucoma, macular degeneration, diabetic macular edema, geographic atrophy and age-related macular degeneration.

9. The method of claim 1, wherein the composition releases the therapeutic agent into the eye over the course of 1 day to 6 months.

10. The method of claim 9, wherein the composition releases the therapeutic agent over the course of 1 week to 3 months.

11. The method of claim 1, wherein the porous silicon-based carrier material is contacted with a solution comprising the therapeutic agent.

12. The method of claim 1, wherein the carrier material is resorbable.

13. The method of claim 1, wherein the therapeutic agent is selected from proteins, peptides, antibodies, carbohydrates, polymers and polynucleotides.

14. The method of claim 13, wherein the therapeutic agent is an antibody.

15. The method of claim 1, wherein the amorphous sugar is selected from trehalose, trehalose dihydrate, sucrose, mannitol, sorbitol, xylitol and glycerol, or a combination thereof.

16. The method of claim 1, wherein the carrier material has a porosity in the range of about 40% to about 80%.

17. The method of claim 1, wherein the average pore size is in the range 2-50 nm.

18. The method of claim 1, wherein the average width of the walls in the carrier material which separate the pores is less than 5 nm.

19. The method of claim 1, wherein a length of the carrier material measured at its longest point is between 1 and 500 microns.

20. The method of claim 1, wherein the load level of the carrier material is less than 80% by weight based on the combined weight of the carrier material and therapeutic agent.