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EP-4736952-A2 - USE OF ENCAPSULATED CELL THERAPY FOR TREATMENT OF OPHTHALMIC DISORDERS

EP4736952A2EP 4736952 A2EP4736952 A2EP 4736952A2EP-4736952-A2

Abstract

Described herein are methods and devices for the long term treatment of ophthalmic disorders. Also disclosed are encapsulated cell therapy (ECT) devices that secrete a biologically active molecule and methods for using the same for the treatment of various kinds of ophthalmic disorders, including retinitis pigmentosa, geographic atrophy (dry agerelated macular degeneration), glaucoma and/or macular telangiectasia.

Inventors

  • GOLDBERG, Jeffrey, Louis
  • MCGOVERN, Cahil
  • TAO, WENG
  • KAUPER, KONRAD

Assignees

  • Neurotech USA, Inc.

Dates

Publication Date
20260506
Application Date
20160527

Claims (15)

  1. A biocompatible device for use in a method of treating age-related macular degeneration (AMD) in a patient suffering therefrom comprising implanting the biocompatible device into an eye of the patient the biocompatible device comprising a) a core comprising: i) between 0.5 and 1.0 x 10 6 ARPE-19 cells that are genetically engineered to secrete a therapeutically effective amount of ciliary neurotrophic factor (CNTF), and ii) a matrix comprising a plurality of monofilaments twisted into a yarn or woven into a mesh or twisted into a yarn that is in non-woven strands, wherein the cells are distributed thereon, and b) a semi-permeable membrane surrounding the core, wherein the membrane has a nominal molecular weight cut off (MWCO) of about 300 kDa that permits the diffusion of the CNTF therethrough; wherein the biocompatible device produces between 0.1 and 50 ng/day of CNTF upon implantation and therapeutically effective amounts of CNTF for at least 12 months post implantation.
  2. The biocompatible device for the use of claim 1, wherein the biocompatible device produces therapeutically effective amounts of the CNTF for at least 2 years post implantation.
  3. The biocompatible device for the use of claim 1 or 2, wherein the biocompatible device is configured as a hollow fiber.
  4. The biocompatible device for the use of any one of claims 1-3, wherein the biocompatible device is implanted in the vitreous, in the aqueous humor, in the periocular space, in the anterior chamber, in the posterior chamber, or in the Subtenon's space.
  5. The biocompatible device for the use of any one of claims 1-4, wherein the monofilaments comprise polyethylene terephthalate, optionally wherein the monofilaments comprise 40-85% of the internal volume of the biocompatible device.
  6. The biocompatible device for the use of any one of claims 1-5, wherein the biocompatible device is anchored to an ocular structure following implantation.
  7. The biocompatible device for the use of any one of claims 1-6 wherein a) the semi-permeable membrane comprises a permselective, immunoprotective membrane, or b) the semi-permeable membrane is between 90 - 120 µm thick..
  8. The biocompatible device for the use of any one of claims 1-7, wherein the semi-permeable membrane has a median pore size of 100 nm.
  9. The biocompatible device for the use of any one of claims 1-8, wherein the biocompatible device is configured as a flat sheet.
  10. The biocompatible device for the use of any one of claims 1-9, wherein the length of the biocompatible device is between 4 mm-11 mm.
  11. The biocompatible device for the use of any one of claims 1-10, wherein the biocompatible device has an internal diameter of 0.9 mm and 1.2 mm.
  12. The biocompatible device for the use of any one of claims 1-11, wherein at least one additional biologically active molecule is co-delivered from the biocompatible device.
  13. The biocompatible device for the use of any one of claims 1-12, wherein the at least one additional biologically active molecule is from a non-cellular source.
  14. The biocompatible device for the use of any one of claims 1-13, wherein the at least one additional biologically active molecule is from a cellular source.
  15. The biocompatible device for the use of any one of claims 1-14 wherein the at least one additional biologically active molecule is produced by one or more genetically engineered ARPE-19 cells in the core.

Description

RELATED APPLICATIONS This application claims priority to United States Application No. 62/167,213, filed May 27, 2015, which is herein incorporated by reference in its entirety. FIELD OF THE INVENTION The present invention relates generally to the field of encapsulated cell therapy. BACKGROUND OF THE INVENTION Many clinical conditions, deficiencies, and disease states can be remedied or alleviated by supplying to the patient one or more biologically active molecules produced by living cells or by removing from the patient deleterious factors which are metabolized by living cells. In many cases, these molecules can restore or compensate for the impairment or loss of organ or tissue function. Accordingly, many investigators have attempted to reconstitute organ or tissue function by transplanting whole organs, organ tissue, and/or cells, which provide secreted products or affect metabolic functions. However, while such transplantation can provide dramatic benefits, it is limited in its application by the relatively small number of organs that are suitable and available for grafting. Moreover, in general, transplantation patients must be immunosuppressed in order to avert immunological rejection of the transplant, which results in loss of transplant function and eventual necrosis of the transplanted tissue or cells. Likewise, in many cases, the transplant must remain functional for a long period of time, even for the remainder of the patient's lifetime. It is both undesirable and expensive to maintain a patient in an immunosuppressed state for a substantial period of time. One example where additional effective therapies are still needed are vision-threatening disorders of the eye. One major problem in treatment of such diseases is the inability to deliver therapeutic agents into the eye, due to the presence of the blood-retinal barrier, as well as the inability to maintain them there at therapeutically effective concentrations. Many growth factors have shown promise in the treatment of ocular diseases. For example, BDNF and CNTF have been shown to slow degeneration of retinal ganglion cells and decrease degeneration of photoreceptors in various animal models. See, e.g., Genetic Technology News, vol. 13, no. 1 (Jan. 1993). Additionally, nerve growth factor has been shown to enhance retinal ganglion cell survival after optic nerve section and has also been shown to promote recovery of retinal neurons after ischemia. See, e.g., Siliprandi, et al., Invest. Ophthalmol. & Vis. Sci., 34, pp. 3232-3245 (1993). More recently, antibody scaffold based biologics have been designed and used for eye disorders including, for example, full antibodies (e.g., Bevacizumab) and antibody scaffold Fab fragments (e.g., Ranibizumab), and immunoglobulin Fc (e.g., Aflibercept). A desirable alternative to transplantation procedures is the implantation of cells or tissues within a physical barrier which will allow diffusion of nutrients, metabolites, and secreted products, but will block the cellular and molecular effectors of immunological rejection. A variety of devices which protect tissues or cells producing a selected product from the immune system have been explored. See, e.g., US Patent No. 5,158,881; WO92/03327; WO91/00119; and WO93/00128, each of which is incorporated herein by reference in its entirety. These devices include, for example, extravascular diffusion chambers, intravascular diffusion chambers, intravascular ultrafiltration chambers, and implantation of microencapsulated cells. See Scharp, D. W., et al., World J. Surg., 8, pp. 221-9 (1984); Lim et al., Science 210: 908-910 (1980); Sun, A. M., Methods in Enzymology 137: 575-579 (1988); WO 93/03901: and U.S. Pat. No. 5,002,661. The use of such devices would alleviate the need to maintain the patient in an immunosuppressed state. However, none of these approaches have been satisfactory for providing long-term transplant function. Thus, methods of delivering appropriate quantities of needed substances, such as, for example, neurotrophic factors, anti-angiogenic factors, anti-inflammatory factors, enzymes, hormones, and/or other factors, or of providing other needed metabolic functions, to the eye or other parts of the body for an extended period of time are needed. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. Other features and advantages of the invention will be apparent from the following detailed description