Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-03-27
2001-06-19
Fay, Zohren (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S054000, C514S055000, C514S912000
Reexamination Certificate
active
06248734
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to the use of photodynamic therapy treatment (PDT) to prevent secondary cataracts, more particularly to the use of green porphyrins for such PDT treatment.
DESCRIPTION OF THE RELATED ART
The removal of cataracts is one of the most common surgical procedures in the United States. Secondary cataracts, more specifically posterior capsule opacification, are the most common complication of cataract extraction procedures, with or without posterior chamber intraocular lens implantation. Depending on their age, this condition affects from 15-50% of all patients, and generally is “secondary” to a proliferation and migration of residual lens epithelial cells. While ophthalmic surgeons are aware of the incidence of secondary cataracts and take care to remove as many residual lens epithelial cells as possible, e.g., prior to implantation of an artificial intraocular lens, it is difficult to identify all such cells and often difficult to reach them on the inside surface of the lens capsule.
Secondary cataracts, as a post-surgical effect, also are referred to as “after cataract.” One commentator has observed that the term “secondary cataract” is ambiguous because it also frequently is used to refer to a cataract that occurs secondary to various ocular diseases. See, e.g., Kappelhoff, J. P., et al., “The Pathology of After-Cataract. A Mini Review,”
Acta Opthamol
. Suppl. 205:13 (1992). For purposes of the present patent application, however, the term secondary cataract means the proliferation, based on histological observations, of lenticular epithelial cells, fibroblasts, macrophages and even iris-derived pigment cells on the posterior capsule following cataract removal, but not the result of unrelated changes in the remaining posterior capsule itself.
Although implanted intraocular lenses themselves are thought to inhibit capsule opacification, the mechanisms by which this results are poorly understood. It has been suggested that intraocular lenses influence secondary cataract formation by limiting the space available for lentoid formation and by maintaining a linear scaffolding for lens epithelial fibrous metaplasia. Nasisse, M. P. et al., “Lens Capsule Opacification in Aphakic and Pseudophakic Eyes,”
Graefes Arch. Clin. Exp. Opthalmol
. 233(2):63 (1995). Other commentators have suggested that intraocular lenses stimulate the development of secondary cataract. Nishi, O. et al., “Intercapsular Cataract Surgery with Lens Epithelial Cell Removal,”
J. Cataract Refract. Surg
. 17:471-477 (1991). Nonetheless, secondary cataracts occur frequently and require medical intervention.
Various techniques for reducing the opacification of secondary cataracts include, e.g., atraumatic surgery and cortical clean-up. A review of these and other techniques is presented in Apple, D. J. et al., “Posterior Capsule Opacification,”
Survey of Ophthalmology
, 37(2):73(1992). These “conventional” treatments for secondary cataracts themselves have serious side effects, including retinal detachment and damage to the implanted intraocular lens. See, e.g, Lundgren, B., et al., “Secondary Cataract: An In vivo Model for Studies on Secondary Cataract in Rabbits,”
Acta Opthalmol
. Suppl. 205:25 (1992). Thus, the technique selected for prevention of the formation of secondary cataracts is of particular importance in regard to a successful outcome of the original cataract surgery.
A variety of experimental techniques thus have been proposed or evaluated for the prevention of secondary cataracts. These include the use of heparin to inhibit migration and proliferation of fibroblasts on the posterior capsular surface. Xia, X. P., et al. “A Cytological Study of Inhibition of Secondary Cataract with Heparin,”
Chung Hua Yen Ko Tsa Chih
, 30(5):363 (1994); and Xia, X. P., et al. “A Clinical Study of Inhibition of Secondary Cataract with Heparin,”
Chung Hua Yen Ko Tsa Chih
, 30(6):405 (1994).
Other approaches to the prevention of secondary cataracts include the chemical modification of the posterior surface of the lens capsule through the covalent binding of certain compounds and their subsequent polymerization. Lindquist, B., et al., “Method for Preventing Secondary Cataract,” U.S. Pat. No. 5,375,611 (1994). An alternative approach relates to the injection of a cell-killing substance between the anterior capsule and the natural lens prior to removing the natural lens from the eye. Such a cell-killing substance preferably is a relatively strong acid or base adjusted aqueous solution and may include a viscoelastic material or a dye. Dubroff, S., “Composition for Preventing Clouding of Posterior Capsule After Extracapsular Cataract Eye Surgery and Method of Performing Cataract Surgery,” U.S. Pat. No. 5,273,751 (1993).
Somewhat related are chemical methods to prevent or reverse cataract formation involving the administration of chemical compositions that lower the phase separation temperature of a lens and prevent or inhibit the formation of opacities, high molecular weight aggregates and other physical characteristics of cataracts. See, e.g., Clark, J. I., et al., “Chemical Prevention or Reversal of Cataract by Phase Separation Inhibitors,” U.S. Pat. No. 5,401,880 (1995).
The use of monoclonal antibodies in the prevention of secondary cataracts also has been reported. For example, complement fixing monoclonal antibodies specific for lens epithelial cells can be introduced into the anterior chamber of the eye following extracapsular extraction. Following the binding of such monoclonal antibodies to any lens epithelial cells present, complement is introduced into the anterior chamber thereby effecting lysis of the remnant lens epithelial cells. Emery, J. M., et al., “Monoclonal Antibodies Against Lens Epithelial Cells and Methods for Preventing Proliferation of Remnant Lens Epithelial Cells After Extracapsular Extraction,” U.S. Pat. No. 5,202,252 (1993).
The application of electrical or thermal energy via a probe inserted between the iris and lens capsule also has been used to destroy residual lens epithelial cells within the lens capsule. Bretton, R. H., “Method and Apparatus for Preventing Posterior Capsular Opacification,” U.S. Pat. No. 5,455,637 (1995).
Photodynamic therapy for the control of lens epithelial proliferation also has been described. In photodynamic therapy, the photosensitizers used are capable of localizing in target cells, either by natural tendency or because they have been intentionally targeted to a specific type of tissue, or both. When irradiated, they may be capable of fluorescing and, thus, may be useful in diagnostic methods related to detecting target tissue. However, even more importantly, the photosensitizer has the capacity, when irradiated with light at a wavelength which the compound absorbs, of causing a cytotoxic effect against the cells in which the photosensitizer has localized. Although not yet definitively established, it is thought that this cytotoxic effect is due to the formation of singlet oxygen upon irradiation.
With respect to PDT therapy for secondary cataracts, experimental studies using Photofrin II (PII) have been reported by Parel, J. M. et al., “Endocapsular Lavage with Photofrin II as a Photodynamic Therapy for Lens Epithelial Proliferation,”
Lasers and Medical Science
5:25 (1990). These authors noted several technical difficulties with their technique, including a constant leakage of PII from the capsular bag and a minimum uptake time of less than 15 minutes after rinsing. The fluorescence from PII was still discernible after 30 hours, but provided insufficient specificity to guarantee safe photodynamic therapy treatment.
A related study by Lingua, R. et al., “Preclinical Evaluation of Photodynamic Therapy to Inhibit Lens Epithelial Proliferation,”
Lasers and Light in Ophthalmology
2(2):103 (1988) reported the earlier testing of photodynamic therapy using Photofrin II. These authors reported that their techniques did result in local epithelial cell death but also in fiber cell death and that efflux of these agents from the ca
Bussanich Marcello Nick
Hariton Claude A. A.
Huber Gustav
Levy Julia G.
Mallek David R.
Fay Zohren
Morrison & Foerster / LLP
QLT Inc.
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