Bioerodible silicon-based devices for delivery of therapeutic agents

• US 9,808,421 B2
• Filed: 10/20/2016
• Issued: 11/07/2017
• Est. Priority Date: 11/01/2010
• Status: Active Grant

• Current Assignee: EyePoint Pharmaceuticals, Inc.
• Original Assignee: pSivida US, Inc
• Inventors: Ashton, Paul, Canham, Leigh T., Barnett, Christian
• Primary Examiner(s): DICKINSON, PAUL W
• Application Number:
  US15/299,050
• Publication Number:
  US 20170035690A1
• Time in Patent Office: 383 Days
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/143 with inorganic compounds
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 27/025 Other specific inorganic materials not covered by A61L27/04 - A61L27/12
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• 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: C12Y 302/01017 Lysozyme (3.2.1.17)

Abstract

This invention discloses bioerodible devices, such as implants for delivering therapeutic agents, particularly large molecules such as proteins and antibodies, in a controlled manner. The devices comprise a porous silicon-based carrier material impregnated with the therapeutic agent. The device 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 device may be used for treating or preventing conditions of a patient such as chronic diseases.

Claims

1. A device comprising a porous silica carrier material, wherein the carrier material comprises at least one large molecule therapeutic agent disposed in pores of the carrier material, wherein the therapeutic agent is a protein, and either:

a) the pores have an average pore size from about 15 nm to about 40 nm and the therapeutic agent has a molecular weight from about 100,000 to about 200,000 amu, or

b) the pores have an average pore size from about 25 nm to about 40 nm and the therapeutic agent has a molecular radius from about 6 nm to about 8 nm.

2. A device of claim 1, in which the therapeutic agent is distributed through a volume of the carrier material.

3. A device according to claim 2, in which the therapeutic agent is distributed through substantially the whole volume of the carrier material.

4. The device of claim 1, wherein the therapeutic agent is an antibody.

5. The device of claim 1, wherein the silica carrier material is amorphous.

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

7. The device of claim 1, wherein the surface area of the carrier material is between 20 and 1000 m²/g.

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

9. The device of claim 8, wherein the length of the carrier material measured at its longest point is between 2 and 100 microns.

10. The device of claim 1, wherein the load level of the carrier material is from about 5% to about 50% based on the combined weight of the carrier material and therapeutic agent.

11. The device of claim 1, further comprising a second therapeutic agent impregnated in pores of the carrier material.

12. A method of treating or preventing a condition in a patient comprising administering the device of claim 1 to the patient.

13. The method of claim 12, wherein the device is administered to the surface of the skin or eye of the patient.

14. The method of claim 12, wherein the device is administered subconjunctivally, intraperitoneally, intramuscularly, intravitreally, subcutaneously, or subretinally.

15. The method of claim 12, wherein the device is administered into the eye.

16. The method of claim 15, wherein the device is administered within the aqueous of the eye.

17. The method of claim 15, wherein the device is administered within the vitreous of the eye.

18. The method of claim 15, wherein the patient has a condition that affects the eye.

19. The method of claim 18, wherein the condition is selected from glaucoma, macular degeneration, diabetic macular edema, geographic atrophy and age-related macular degeneration.

20. The method of claim 15, wherein the device releases the drug into the eye over the course of 1 day to 12 months.

21. The method of claim 20, wherein the device releases the therapeutic agent over the course of 1 month to 6 months.

22. The device of claim 1, wherein the average pore size is from about 15 nm to about 40 nm and the therapeutic agent has a molecular weight from about 100,000 to about 200,000 amu.

23. The device of claim 1, wherein the average pore size is from about 25 nm to about 40 nm and the therapeutic agent has a molecular radius from about 6 nm to about 8 nm.

24. The device of claim 4, wherein the antibody is ranibizumab, bevacizumab or adalimumab.

25. The device of claim 24, wherein the antibody is bevacizumab.

26. The device of claim 25, wherein the average pore size of the carrier material is from about 25 nm to 35 nm.

27. The device of claim 25, wherein the average pore size of the carrier material is about 30 nm.