SUSTAINED RELEASE INTRAOCULAR DRUG DELIVERY SYSTEMS COMPRISING A WATER SOLUBLE THERAPEUTIC AGENT AND A RELEASE MODIFIER

• US 20080107694A1
• Filed: 11/03/2006
• Published: 05/08/2008
• Est. Priority Date: 11/03/2006
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Trogden, John T., Lyons, Robert T.
• Granted Patent: US 8,039,010 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 31/711 Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 48/0008 characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• 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: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators

Abstract

A biocompatible, sustained release intraocular drug delivery system comprising a protein or polynucleotide therapeutic agent, a polymeric carrier for the therapeutic agent and a long chain fatty alcohol release modifier. The biocompatible, sustained release intraocular drug delivery system can be used to treat an ocular condition.

Claims

1. A sustained release drug delivery system comprising:

(a) a water soluble therapeutic agent;

(b) a polymeric carrier for the therapeutic agent, and;

(c) a release modifier for modifying a release rate of the therapeutic agent from the polymeric carrier

wherein said therapeutic agent is an inhibitor of vascular endothelial growth factor (VEGF), and wherein the release modifier is an aliphatic alcohol, and the sustained release drug delivery system can release a therapeutic amount of the therapeutic agent over a period of time of at least about one week.

2. The sustained release drug delivery system of claim 1, wherein the water soluble therapeutic agent is a protein.

3. The sustained release drug delivery system of claim 1, wherein the water soluble therapeutic agent is a polynucleotide.

4. The sustained release drug delivery system of claim 1, wherein the polymeric carrier is a biodegradable polymer.

5. The sustained release drug delivery system of claim 1, wherein the polymeric carrier is a poly-lactide-co-glycolide (PLGA) polymer.

6. The sustained release drug delivery system of claim 1, wherein the aliphatic alcohol release modifier is a long chain fatty alcohol.

7. The sustained release drug delivery system of claim 6, wherein the long chain fatty alcohol comprises from 10 to 40 carbon atoms.

8. The sustained release drug delivery system of claim 1, wherein the sustained release drug delivery system exhibits a substantially linear release of the therapeutic agent in vivo over a period of about 50 days.

9. The sustained release drug delivery system of claim 1, wherein the sustained release drug delivery system releases less that about 30% of the therapeutic agent after about 5 days in vivo and the sustained release drug delivery system releases less that about 80% of the therapeutic agent after about 50 days in vivo.

12. The sustained release drug delivery system of claim 1, wherein the release modifier is selected from the group consisting of capryl alcohol, pelargonic alcohol, capric alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, palmitoleyl alcohol, stearyl alcohol, isostearyl alcohol, elaidyl alcohol, oleyl alcohol, linoleyl alcohol, polyunsaturated elaidolinoleyl alcohol, polyunsaturated linolenyl alcohol, elaidolinolenyl alcohol, polyunsaturated ricinoleyl alcohol, arachidyl alcohol, behenyl alcohol, erucyl alcohol, lignoceryl alcohol, ceryl alcohol, montanyl alcohol, cluytyl alcohol, myricyl alcohol, melissyl alcohol, and geddyl alcohol.

15. The system of claim 1, wherein the polymeric carrier comprises a polymer selected from the group consisting of poly-lactic acid (PLA), poly-glycolic acid (PGA), poly-lactide-co-glycolide (PLGA), polyesters, poly (ortho ester), poly(phosphazine), poly (phosphate ester), polycaprolactones, gelatin, collagen, derivatives thereof, and combinations thereof.

10. A sustained release drug delivery system comprising:

(a) a water soluble therapeutic agent, wherein the water soluble therapeutic agent is a protein or a polynucleotide;

(b) a biodegradable polymeric carrier associated with the therapeutic agent; and

(c) a release modifier,

wherein said therareutic acient is an inhibitor of VEGF, and wherein the release modifier has the formula R—

(CH2)_n—

OH, where n is an integer between 8 and 40 and R is selected from the group consisting of CH3—

, a cyclic compound, a polycyclic compound and an aromatic compound, wherein the sustained release drug delivery system can release a therapeutic amount of the therapeutic agent over a period of time of at least about one week.

11. The sustained release drug delivery system of claim 10, wherein the biodegradable polymeric carrier is a PLGA.

19. The sustained release drug delivery system of claim 10, wherein the water soluble therapeutic agent is a protein.

20. The sustained release drug delivery system of claim 2 or 19, wherein said protein is an antibody.

21. The sustained release drug delivery system of claim 20, wherein said protein is ranibizumab, bevacizumab or both.

22. The sustained release drug delivery system of claim 10, wherein the water soluble therapeutic agent is a polynucleotide.

23. The sustained release drug delivery system of claim 3 or 22, wherein said polynucleotide is an siRNA molecule.u

13. The sustained release drug delivery system wherein the polymeric carrier is a viscous aqueous carrier.

14. The sustained release drug delivery system of claim 13, wherein the polymeric carrier is a hyaluronic acid.

16. A method for treating an ocular condition, the method comprising the step of intraocular placement of a sustained release drug delivery system comprising:

(a) a water soluble therapeutic agent;

(b) a polymeric carrier for the therapeutic agent, and;

(c) a release modifier for modifying a release rate of the therapeutic agent from the polymeric carrier, wherein said therapeutic agent is an inhibitor of VEGF, and wherein the release modifier is an aliphatic alcohol, and the sustained release drug delivery system can release a therapeutic amount of the therapeutic agent over a period of time of at least about one week.

17. The method of claim 16, wherein the step of intraocular placement is carrier out using an intraocular injector.

18. The method of claim 16, wherein the ocular condition is selected from the group consisting of uveitis, macular edema, macular degeneration, proliferative retinopathy, diabetic retinopathy, retinitis pigmentosa and glaucoma.