Claims for Patent: 10,278,920

Summary for Patent: 10,278,920

Title:	Drug delivery implant and a method using the same
Abstract:	A drug delivery implant and a method of using the same are disclosed herein. In one or more embodiments, the method includes forming a pocket in the cornea of the eye to gain access to tissue surrounding the pocket; applying a photosensitizer inside the pocket so the photosensitizer permeates at least a portion of the tissue surrounding the pocket and facilitates cross-linking of the tissue surrounding the pocket; irradiating the cornea to activate cross-linkers in the portion of the tissue surrounding the pocket, and thereby stiffen a wall of the pocket and kill cells in the portion of the tissue surrounding the pocket; and before or after the portion of the tissue surrounding the pocket has been stiffened and is devoid of cellular elements by the activation of the cross-linkers, inserting a corneal drug delivery implant into the pocket configured to release one or more medications into the eye.
Inventor(s):	Peyman; Gholam A. (Sun City, AZ)
Assignee:
Application Number:	15/816,140
Patent Claims:	1. A method of implanting a corneal drug delivery implant in an eye of a patient, said method comprising: coating an outer surface of a corneal drug delivery implant with an organic material configured to absorb a photosensitizer; forming a pocket in the cornea of the eye so as to gain access to tissue surrounding the pocket; after the pocket in the cornea has been formed, applying a photosensitizer to the pocket so that the photosensitizer permeates at least a portion of the tissue surrounding the pocket, the photosensitizer facilitating cross-linking of the tissue surrounding the pocket; inserting the corneal drug is delivery implant into the pocket, the corneal drug delivery implant configured to slowly release one or more medications into the eye of the patient without being inhibited by vascular growth around the corneal drug delivery implant; and after the corneal drug delivery implant is inserted into the pocket, irradiating the cornea so as to activate cross-linkers in the portion of the tissue surrounding the pocket, and thereby stiffen a wall of the pocket and kill cells in the portion of the tissue surrounding the pocket. 2. The method according to claim 1, wherein the step of forming a pocket in the cornea of the eye further comprises: cutting out a three-dimensional portion of stromal tissue from the cornea of the eye using a femtosecond laser; and removing the three-dimensional cut portion of the cornea using forceps so as to create a three-dimensional pocket for receiving the corneal drug delivery implant so that the corneal drug delivery implant does not exert any pressure on the stromal tissue of the cornea. 3. The method according to claim 2, wherein the three-dimensional pocket is formed in a peripheral portion of the cornea between the cornea and the anterior sclera of the eye. 4. The method according to claim 3, wherein the three-dimensional pocket formed in the peripheral portion of the cornea extends between 1 degree and 360 degrees around the corneal periphery. 5. The method according to claim 2, wherein the three-dimensional pocket has a width between approximately 0.05 millimeters and approximately 8 millimeters, inclusive. 6. The method according to claim 1, wherein the step of applying the photosensitizer to the pocket comprises injecting the photosensitizer inside the pocket using a needle such that the photosensitizer penetrates at least 20 microns beyond a wall of the pocket in the stromal tissue of the cornea, the photosensitizer comprising riboflavin. 7. The method according to claim 6, further comprising the step of: injecting 0.01 milliliters to 0.1 milliliters of a 0.02 to 2% lidocaine or bupivacaine solution alone or together with the photosensitizer so as to anesthetize the cornea for between 1 to 15 hours, thereby eliminating a pain sensation or discomfort during the surgical procedure. 8. The method according to claim 1, wherein the step of creating a pocket in the cornea of the eye further comprises forming a circular-shaped pocket, a semi-circular-shaped pocket, a C-shaped pocket, a doughnut-shaped pocket, or a rectangular-shaped pocket in the cornea of the eye, and removing the tissue inside the circular-shaped pocket, the semi-circular-shaped pocket, the C-shaped pocket, the doughnut-shaped pocket, or the rectangular-shaped pocket. 9. The method according to claim 1, wherein the step of irradiating the cornea so as to activate cross-linkers in the portion of the tissue surrounding the pocket comprises irradiating the cornea with ultraviolet light, another wavelength of light, microwaves, or combinations thereof. 10. The method according to claim 1, wherein the step of irradiating the cornea so as to activate cross-linkers in the portion of the tissue surrounding the pocket comprises inserting a fiber optic into the pocket and irradiating the cornea with light emitted from the fiber optic so as to activate the cross-linkers in the portion of the tissue surrounding the pocket. 11. The method according to claim 1, wherein the step of irradiating the cornea so as to activate cross-linkers in the portion of the tissue surrounding the pocket comprises irradiating the cornea from outside the eye. 12. The method according to claim 1, wherein the corneal drug delivery implant is formed from a biocompatible organic material, a biocompatible non-organic material, or a combination of a biocompatible organic material and a biocompatible non-organic material, and wherein the corneal drug delivery implant has a solid structure, a tubular structure, or a porous structure. 13. The method according to claim 1, wherein the corneal drug delivery implant is formed from polylactic acid, polyglycolic acid, polycaprolactone, another biodegradable polymer, silicone, acrylic, methacrylate, hydroxyethyl methacrylate (HEMA), a metallic material, a non-metallic material, or combinations thereof. 14. The method according to claim 1, wherein the corneal drug delivery implant is coated with a biocompatible material, the biocompatible material selected from the group consisting of collagen, elastin, polyethylene glycol, biotin, streptavidin, and combinations thereof. 15. The method according to claim 1, further comprising the step of: replacing the corneal drug delivery implant in the pocket with a replacement corneal drug delivery implant after the corneal drug delivery implant is no longer functional or when the medication in the corneal drug delivery implant has been exhausted. 16. A method of implanting a corneal drug delivery implant in an eye of a patient, said method comprising: forming a pocket in the cornea of the eye so as to gain access to tissue surrounding the pocket; after the pocket in the cornea has been formed, applying a photosensitizer to the pocket so that the photosensitizer permeates at least a portion of the tissue surrounding the pocket, the photosensitizer facilitating cross-linking of the tissue surrounding the pocket; irradiating the cornea so as to activate cross-linkers in the portion of the tissue surrounding the pocket, and thereby stiffen a wall of the pocket and kill cells in the portion of the tissue surrounding the pocket; and before or after the portion of the tissue surrounding the pocket has been stiffened and is devoid of cellular elements by the activation of the cross-linkers, inserting a corneal drug delivery implant into the pocket, the corneal drug delivery implant configured to release one or more medications into the eye of the patient, the corneal drug delivery implant further comprising a needle configured to fluidly couple the corneal drug delivery implant with the aqueous fluid in the anterior chamber of the eye; and wherein the method further comprises the step of: penetrating the anterior chamber of the eye using the needle, an open end of the needle opening into the anterior chamber of the eye so as to allow the medication from the corneal drug delivery implant to be delivered to the anterior chamber of the eye and/or enable an aqueous biopsy to be obtained from the aqueous fluid of the eye. 17. The method according to claim 1, further comprising the step of: after the implantation of the corneal drug delivery implant, applying the photosensitizer one or more additional times inside the space between the corneal drug delivery implant and the surrounding corneal tissue, and irradiating the cornea one or more additional times with ultraviolet radiation to cross-link the tissue surrounding the corneal drug delivery implant so as to prevent encapsulation of the corneal drug delivery implant and cellular migration towards the corneal drug delivery implant. 18. The method according to claim 17, wherein the step of applying the photosensitizer one or more additional times inside the space between the corneal drug delivery implant and the surrounding corneal tissue further comprises injecting the photosensitizer inside the space between the corneal drug delivery implant and the surrounding corneal tissue by using a 33 gauge needle. 19. The method according to claim 1, wherein the corneal drug delivery implant comprises a tubular body portion with a circular sidewall and oppositely disposed ends, the circular sidewall of the tubular body portion being solid and one of the oppositely disposed ends being open or the circular sidewall of the tubular body portion comprising a plurality of holes therein and the oppositely disposed ends being solid. 20. The method according to claim 1, further comprising the step of: prior to the implantation of the corneal drug delivery implant, constructing the corneal drug delivery implant in vitro by three-dimensionally printing the corneal drug delivery implant to a desired shape and size. 21. The method according to claim 1, further comprising the step of: prior to the implantation of the corneal drug delivery implant, forming the corneal drug delivery implant into a shape selected from the group consisting of a rod shape, a C-shape, a semi-circular shape, a doughnut shape, and a rectangular flat tube shape. 22. The method according to claim 1, wherein the medication of the corneal drug delivery implant is selected from the group consisting of an anti-inflammatory, an anti-infective, an immune-suppressant, an anti-VEGF, a biologic, an anti-PDGF, an Anti IL-6, a Rho kinase inhibitor, brimonidine, a nerve growth factor, an anti-glaucoma medication, and combinations thereof. 23. The method according to claim 1, wherein the corneal drug delivery implant is used for gene delivery with viral or non-viral antibody coated nanoparticles conjugated with DNA, RNA, or siRNA, and CRISPR/cas9 mediated homology-independent targeted integration (HITI) or homology directed repair (HDR) is used to modify the genetic components of various structures of the eye. 24. The method according to claim 1, wherein the medication of the corneal drug delivery implant comprises one or more medications selected from the group consisting of anti-inflammatory agents, Dexamethasone, NSAIDS, Anti IL-17, Anti IL-6, other Anti-ILs, antibiotics, fluoroquinolones, macrolides, cephalosporin A, vancomycin, aminoglycosides, penicillin and its derivatives, anti-virals, ganciclovir, valcyclovir, anti-fungals, amphotericine B, anti-VEGFs, Avastin, lucentis, Aflilbercept, anti-parasitics, immune-suppressants, Mycophenolic acid, cyclosporine, a Rho kinase inhibitor, a Wnt inhibitor, anti-proliferative agents, anti-metabolite agents, anti-glaucoma medications, and combinations thereof. 25. The method according to claim 1, wherein the corneal drug delivery implant comprises a plurality of stem cells, the plurality of stem cells selected from the group consisting of embryonic stem cells, ciliary hormone producing cells, neuronal stem cells, glial stem cells, Mesenchymal stem cells, trabecular meshwork stem cells, limbal stem cells, skin stem cells, and combinations thereof; and wherein the plurality of stem cells are provided in a biocompatible fluid that permits nutrition to reach the plurality of stem cells in the corneal drug delivery implant where the stem cells are immortalized to produce one or more medications or growth factors. 26. The method according to claim 25, wherein the corneal drug delivery implant comprises a tubular body portion with a circular sidewall and oppositely disposed ends, the circular sidewall of the tubular body portion comprising a plurality of holes that are sufficiently sized so as to permit the stem cells to escape from corneal drug delivery implant and to enter the tissue surrounding the tubular body portion of the corneal drug delivery implant and tissue beyond the tubular body portion of the corneal drug delivery implant. 27. The method according to claim 1, wherein the medication of the corneal drug delivery implant comprises one or more medications selected from the group consisting of immunosuppressive agents, calcineurin inhibitors, mycophenolic acid, tacrolimus, siraliums, steroids, NSAIDs, antimetabolytes, polycolonal antibodies, monocolonal antibodies, TNF inhibitors, Rho inhibitors, Wnt inhibitors, fingolimod, brimonidine, antibiotics, intraocular pressure (IOP) lowering agents, pilocarpine, prostaglandin analogues, anti-virals, anti-VEGFs, biologics, neuroprotective medications, and combinations thereof. 28. The method according to claim 1, further comprising the step of: refilling the corneal drug delivery implant in the pocket with the medication by using a needle to inject the medication into the corneal drug delivery implant. 29. The method according to claim 1, wherein the corneal drug delivery implant is formed from polymeric nanoparticles, micelles, liposomes, dendrimers, or combinations thereof. 30. The method according to claim 1, wherein, in addition to implanting the corneal drug delivery implant with the one or more medications into the pocket, the method further comprises implanting one or more additional implants in the cornea, the one or more additional implants selected from the group consisting of: (i) a biopsy implant for taking liquid biopsies from a portion of the eye, (ii) a stem cell implant for delivering therapeutic stem cells to the eye of the patient, (iii) a gene therapy implant for delivering therapeutic genes to the eye of the patient for treating degenerative or genetic diseases, (iv) a pressure sensor implant for measuring the intraocular pressure of the eye of the patient, and (v) any combination including one or all of the additional implants. 31. A method of implanting a drug delivery implant in a body portion of a patient, said method comprising: forming a pocket in the body portion of the patient so as to gain access to tissue surrounding the pocket; coating an outer surface of a drug delivery implant with an organic material configured to absorb a photosensitizer; immersing the drug delivery implant in a biocompatible solution comprising the photosensitizer so that the photosensitizer is able to diffuse out of the organic material coating of the drug delivery implant after the drug delivery implant is inserted into the pocket, the biocompatible solution comprising riboflavin nanoparticles; inserting the drug delivery implant into the pocket, the drug delivery implant configured to slowly release one or more medications into the body portion of the patient without being inhibited by vascular growth around the drug delivery implant; and after the drug delivery implant is inserted into the pocket, irradiating the body portion of the patient so as to activate cross-linkers in the portion of the tissue surrounding the pocket, and thereby stiffen a wall of the pocket and kill cells in the portion of the tissue surrounding the pocket. 32. The method according to claim 31, wherein the step of inserting the drug delivery implant into the pocket comprises implanting the drug delivery implant in one or more eye locations selected from the group consisting of under the conjunctiva, under the sclera, over the sclera in the choroid, in the retina, and in the sub-retinal space. 33. The method according to claim 31, wherein the step of inserting the drug delivery implant into the pocket comprises implanting the drug delivery implant in a wall of a vitreous cavity of an eye of the patient with one end of the drug delivery implant being open to the vitreous cavity so as to permit the release of medication into the vitreous cavity. 34. The method according to claim 31, wherein the method further comprises the step of: cross-linking the drug delivery implant before or after the step of implanting the drug delivery implant into the body portion of the patient.

Details for Patent 10,278,920

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2034-05-12
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	06/30/2006		2034-05-12
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	08/10/2012		2034-05-12
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	10/13/2016		2034-05-12
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	03/20/2018		2034-05-12