Posterior segment drug delivery

• US 8,277,830 B2
• Filed: 10/04/2011
• Issued: 10/02/2012
• Est. Priority Date: 01/29/2009
• Status: Active Grant

• Current Assignee: Forsight Vision4, Inc. (Roche Holding AG)
• Original Assignee: Forsight Vision4, Inc. (Roche Holding AG)
• Inventors: de Juan, Eugene Jr., Alster, Yair, Farinas, Kathleen Cogan, Gifford, Hanson S. III, MacFarlane, K. Angela, Reich, Cary J., Barrett, Michael, Campbell, Randolph E., Sutton, Douglas
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): EBRAHIM, NABILA G
• Application Number:
  US13/252,998
• Publication Number:
  US 20120029445A1
• Time in Patent Office: 364 Days
• Field of Search: None
• US Class Current: 424/422
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 38/385 Serum albumin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

A therapeutic device to release a therapeutic agent comprises a porous structure coupled to a container comprising a reservoir. The reservoir comprises a volume sized to release therapeutic amounts of the therapeutic agent for an extended time when coupled to the porous structure and implanted in the patient. The porous structure may comprise a first side coupled to the reservoir and a second side to couple to the patient to release the therapeutic agent. A plurality of interconnecting channels can extend from the first side to the second side so as to connect a first a plurality of openings on the first side with a second plurality of openings on the second side.

Claims

1. An implantable therapeutic device to treat an eye of a patient having a posterior chamber and a sclera, the therapeutic device comprising:

a rigid, hollow, refillable body for implantation within the posterior chamber of the eye through a penetration in the sclera, the body formed of a substantially rigid, impermeable wall of biocompatible material, the body having a proximal cap portion adapted to be positioned outside the sclera, an intermediate neck portion, and a distal reservoir portion adapted to reside in the posterior chamber such that the sclera is positioned about the neck portion when the device is positioned in the eye, wherein the neck portion has a smaller transverse outer dimension than at least one transverse outer dimension of the cap portion and at least one transverse outer dimension of the reservoir portion;

the cap portion adapted to receive an injection of a therapeutic agent into the reservoir and to remain external to the posterior chamber; and

a rigid porous structure having a plurality of interconnecting, irregularly shaped channels, said rigid porous structure coupled to a discrete, distal portion of the reservoir and tuned to release therapeutic amounts of a therapeutic agent from the reservoir through said plurality of channels and into said posterior chamber for an extended time, wherein the therapeutic device has a substantially fixed volume during implantation and use.

2. The therapeutic device of claim 1, wherein the channels of the rigid porous structure comprise interconnected, substantially fixed channels.

3. The therapeutic device of claim 2, wherein a volume of the refillable reservoir remains substantially unchanged, the rigid porous structure remains rigid and the channels remain substantially fixed when the reservoir is pressurized with injection of therapeutic agent into the reservoir.

4. The therapeutic device of claim 1, wherein the reservoir extends along an axis so as to extend through the sclera and choroid and wherein the penetrable barrier is located on a proximal end of the reservoir so as to allow refill of the reservoir with advancement of an injection needle through the conjunctiva and penetrable barrier without the needle penetrating the sclera or choroid.

5. The therapeutic device of claim 1, wherein at least some of the plurality of interconnecting channels intersect at a plurality of locations.

6. The therapeutic device of claim 1, wherein the rigid, porous structure comprises a sintered material.

7. The therapeutic device of claim 1, wherein the rigid, porous structure comprises a sintered metallic disc.

8. The therapeutic device of claim 1, wherein the rigid, porous structure comprises at least one of a metal, a ceramic, and a glass.

9. The therapeutic device of claim 1, wherein the rigid, porous structure comprises a thickness and a surface area corresponding to a rate of release of the therapeutic agent over the extended time.

10. The therapeutic device of claim 9, wherein the thickness extends between a first side and a second side of the structure, and wherein the plurality of interconnecting channels extends between the first side and the second side and wherein the plurality of interconnecting channels of the rigid porous structure comprises interconnected, substantially fixed, tortuous channels having an effective length extending from the first side of the porous structure to the second side of the porous structure, the effective length greater than the thickness of said structure.

11. The therapeutic device of claim 1, wherein the interconnecting channels of the rigid, porous structure are configured to permit the therapeutic agent to pass among the interconnecting channels.

12. The therapeutic device of claim 1, wherein the rigid, porous structure comprises rigid sintered grains of material and wherein the interconnecting channels extend at least partially around the rigid sintered grains of material to pass the therapeutic agent through the porous structure.

13. The therapeutic device of claim 1 wherein the therapeutic device comprises a retention structure and a penetrable barrier, the retention structure comprising an extension coupled to the reservoir and extending outward from the reservoir, said retention structure adapted to extend between the sclera and the conjunctiva to retain the therapeutic device in its implanted position, without the need for sutures.

14. The therapeutic device of claim 1, wherein the therapeutic agent comprises a half-life within the reservoir of at least about 20 days when the device is implanted, and wherein the device is adapted to remain implanted in the eye and to treat the eye with the therapeutic agent for at least about 90 days.

15. The therapeutic device of claim 1, wherein the therapeutic agent comprises a half-life within the reservoir of at least about 30 days when implanted, and wherein the device is adapted to remain implanted in the eye and to treat the eye with the therapeutic agent for at least about 120 days.

16. The therapeutic device of claim 1, wherein the reservoir comprises a volume and the rigid porous structure comprises a release rate adapted to provide the therapeutic agent with a half-life within the reservoir when implanted into the eye, the half-life within the reservoir substantially greater than a corresponding half-life of the therapeutic agent when injected directly into the vitreous and the half-life within the reservoir corresponding to release of therapeutic amounts for at least about 120 days.

17. The therapeutic device of claim 1, wherein the porous structure comprises a porosity, a thickness, a channel parameter and a surface area configured to release therapeutic amounts for the extended period.

18. The therapeutic device of claim 17, wherein the channel parameter comprises a fit parameter corresponding to an effective length of interconnecting channels extending from a first side of the porous structure to a second side of the porous structure.

19. The therapeutic device of claim 18, wherein the rate of release of the at least one therapeutic agent through the porous structure corresponds to a ratio of the porosity to the channel parameter and wherein the ratio of the porosity to the channel parameter is less than about 0.5 such that the porous structure is capable of releasing the at least one therapeutic agent for the extended period.

20. The therapeutic device of claim 1, wherein the porous structure comprises a release rate index of no more than about 5.0 mm.

21. The therapeutic device of claim 1, wherein the reservoir comprises a volume sized to contain the quantity of the therapeutic agent for release over a predetermined extended time and wherein the rigid, porous structure comprises a thickness and a surface area corresponding to a rate of release of the therapeutic agent and wherein the volume and the rate of release correspond a half-life of the therapeutic agent in the reservoir.

22. The therapeutic device of claim 21, wherein the half-life corresponds substantially to a maximum rate at the predetermined extended time so as to provide therapeutic concentrations of the therapeutic agent.

23. The device of claim 1, further comprising an initial quantity of therapeutic agent within the reservoir prior to implantation into the eye.

24. The device of claim 1, wherein the rigid porous structure comprises a first side having a first area, a second side having a second area corresponding substantially to the first area, a thickness extending between the first side and the second side, a porosity, and a channel parameter corresponding to a release of release of the therapeutic agent from the reservoir to the posterior chamber of the eye.

25. A therapeutic device to treat an eye of a patient, the eye having a posterior chamber and a sclera, the therapeutic device comprising:

a rigid-walled reservoir having a volume, the reservoir adapted to reside in the posterior chamber when the device is implanted in the eye;

a rigid, porous structure having a plurality of intersecting, irregularly shaped channels, the porous structure located at a distal region of the reservoir, said porous structure and rigid-walled reservoir tuned to release a predetermined rate profile of a particular therapeutic agent from the reservoir through said plurality of channels and into the posterior chamber to treat the eye for an extended period of time;

a proximal cap portion adapted to be positioned outside the sclera when the device is implanted in the eye, the cap portion comprising a retention structure and a penetrable, non-permeable barrier to introduce said therapeutic agent into said device without any need to explant the device during introduction of the therapeutic agent into the reservoir chamber; and

a neck portion positioned between the cap portion and the reservoir portion, wherein the sclera is positioned about the neck portion when the device is positioned in the eye, and wherein the cap portion has a cross-sectional shape that is different than a cross-sectional shape of the reservoir.

26. The therapeutic device of claim 25, wherein the porous structure and reservoir chamber are tuned to release an additional quantity of the particular therapeutic agent through the porous structure over a second extended period of time with the predetermined release rate profile after the additional quantity of the therapeutic agent has been introduced into the reservoir after the extended period of time.

27. The therapeutic device of claim 25, further comprising an initial quantity of the particular therapeutic agent within the reservoir prior to implantation into the eye.

28. The therapeutic device of claim 25, wherein the particular therapeutic agent comprises a molecular weight within a range from 100 Daltons to about 1,000,000 Daltons and wherein the molecular weight corresponds to the predetermined release rate profile.

29. The therapeutic device of claim 25, wherein the particular therapeutic agent comprises one or more compounds of 2-Methoxyestradiol analogs, 3-aminothalidomide, 13-cis retinoic acid, A0003, A5b1 integrin inhibitor, Abarelix, Abatacept, Abciximab, ABT-578, Acetonide, Adalimumab, Aldesleukin, Alefacept, Alemtuzumab, Alpha-1-proteinase inhibitor, Alteplase, AMG-1470, Anakinra, Anecortave acetate, Angiostatin, Anistreplase, Anti-angiogenesis peptides, Anti-angiogenesis antibodies, TRC093, TRC105, Anti-angiogeric bifunctional protein, Anti-endothelial growth factor, Antihemophilic Factor, Antithymocyte globulin, Anti-hypertensive MC1101, Anti-platelet devired growth factor, Anti-VEGF, AP23841, Aprotinin, Arcitumomab, Asparaginase, Axitinib, Basiliximab, Becaplermin, Bevacizumab, Bivalirudin, Bortezomib, Bosutinib, Botulinum Toxin Type A, Botulinum Toxin Type B, C5 inhibitor, Canstatin, Capromab, Captopril, CCI-779, Cediranib, Celecoxib, Cetrorelix, Cetuximab, Choriogonadotropin alfa, Cilary neurotrophic factor, Coagulation Factor IX, Coagulation factor VIIa, Colchicines, Collagenase, Complement factor H recombinant, Compstatin derivative peptide, POT-4, Corticotropin, Cosyntropin, Cyclophilins, Cyclosporine, Daclizumab, Darbepoetin alfa, Dasatinib, Defibrotide, Denileukin diftitox, Desmopressin, Dexamethasone, Diclofenac, Dithiocarbamate, Dornase Alfa, Drotrecogin alfa, Eculizumab, Efalizumab, Endostatin, Enfuvirtide, Epoetin alfa, Eptifibatide, Erlotinib, Etanercept, Everolimus, Exenatide, Felypressin, Fenretinide, Filgrastim, FK605-binding proteins, FKBPs, Fluocinolone Acetonide, Follitropin beta, Fumagillin, Galsulfase, Gefitinib, Gemtuzumab ozogamicin, Glatiramer Acetate, Glucagon recombinant, Goserelin, Human Serum Albumin, Hyaluronidase, Ibritumomab, Idursulfase, Imatinib, Immune globulin, Infliximab, Insulin Glargine recombinant, Insulin Lyspro recombinant, Insulin recombinant, Insulin, porcine, Interferon, Interferon Alfa-2a, Recombinant, Interferon Alfa-2b, Recombinant, Interferon alfacon-1, Interferon alfa-n1, Interferon alfa-n3, Interferon beta-1b, Interferon gamma-1b, Lapatinib, Lepirudin, Lestaurtinib, Leuprolide, Lutropin alfa, Mecasermin, Menotropins, mTOR inhibitors, Muromonab, Natalizumab, Nepafenac, Nesiritide, Nilotinib, NS398, Octreotide, Omalizumab, Oprelvekin, OspA lipoprotein, OT-551, Oxytocin, Palifermin, Palivizumab, Panitumumab, PDGF inhibitor, PEDF (pigment epithelium derived factor), Pegademase bovine, Pegaptanib, Pegaspargase, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pegvisomant, Pentoxifylline, Perindozril, Pimecrolimus, PKC (protein kinase C) inhibitors, Pramlintide, Proteosome inhibitors, Pyrrolidine, Quinopril, Ranibizumab, Rapamycin (siroliums), Rasburicase, Reteplase, Retinal stimulant, Retinoid(s), Rituximab, RNAI (RNA interference of angiogenic factors), Rofecoxib, Rosiglitazone, Ruboxistaurin, Salmon Calcitonin, Sargramostim, SDZ-RAD, Secretin, Selective inhibitor of the factor 3 complement cascade, Selective inhibitor of the factor 5 complement cascade, Semaxanib, Sermorelin, Serum albumin iodinated, Siroliums reformulation (rapamycin), siRNAi molecule synthetic, FTP-801i-14, Somatropin recombinant, Squalamine, Streptokinase, Sunitinib, Tacrolimus, Tenecteplase, Teriparatide, Tetrathiomolybdate, Thyrotropin Alfa, Tie-1 and Tie-2 kinase inhibitors, Toceranib, Tositumomab, TPN 470 analogue, Trastuzumab, Triamcinolone acetonide, Troglitazone, Tumistatin, Urofollitropin, Urokinase, Vandetanib, Vasopressin, Vatalanib, VEGF receptor kinase inhibitor, VEGF Trap, Visual Cycle Modulator ACU-4229, Vitamin(s), Vitronectin receptor antagonists, or Volociximabe.