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CHAPTER 6. PATENTS ON MACULAR DEGENERATION
Overview
Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents.
In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “macular degeneration” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on macular degeneration, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Macular Degeneration
By performing a patent search focusing on macular degeneration, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter.
9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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The following is an example of the type of information that you can expect to obtain from a patent search on macular degeneration:
•.alpha.V integrin receptor antagonists
Inventor(s): Duggan; Mark E. (Schwenksville, PA), Halczenko; Wasyl (Lansdale, PA), Hutchinson; John H. (Philadelphia, PA), Li; Aiwen (Audubon, PA), Meissner; Robert S. (Schwenksville, PA), Patane; Michael A. (Billerica, MA), Perkins; James J. (Churchville, PA), Steele; Thomas G. (Schwenksville, PA), Wang; Jiabing (Chalfont, PA)
Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,472,403
Date filed: January 19, 2001
Abstract: The present invention relates to novel imidazolidinone derivatives thereof, their synthesis, and their use as.alpha.v integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors.alpha.v.beta.3 and/or.alpha.v.beta.5 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, inflammatory arthritis, viral disease, cancer, and metastatic tumor growth.
Excerpt(s): The present invention relates to imidazolidinone derivatives, their synthesis, and their use as.alpha.v integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors.alpha.v.beta.3,.alpha.v.beta.5, and.alpha.v integrin receptors associated with other.beta.-subunits, and are useful for inhibiting bone resorption, treating and/or preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth. It is believed that a wide variety of disease states and conditions can be mediated by acting on integrin receptors and that integrin receptor antagonists represent a useful class of drugs. Integrin receptors are heterodimeric transmembrane receptors through which cells attach and communicate with extracellular matrices and other cells. (See S. B. Rodan and G. A. Rodan, "Integrin Function In Osteoclasts," Journal of Endocrinology, 154: S47-S56 (1997), which is incorporated by reference herein in its entirety). In one aspect of the present invention, the compounds herein are useful for inhibiting bone resorption. Bone resorption is mediated by the action of cells known as osteoclasts. Osteoclasts are large multinucleated cells of up to about 400 mm in diameter that resorb mineralized tissue, chiefly calcium carbonate and calcium phosphate, in vertebrates. Osteoclasts are actively motile cells that migrate along the surface of bone, and can bind to bone, secrete necessary acids and proteases, thereby causing the actual resorption of mineralized tissue from the bone. More specifically, osteoclasts are believed to exist in at least two physiological states, namely, the secretory state and the migratory or motile state. In the secretory state, osteoclasts are flat, attach to the bone matrix via a tight attachment zone (sealing zone), become highly polarized, form a ruffled border, and secrete lysosomal enzymes and protons to resorb bone. The adhesion of osteoclasts to bone surfaces is an important initial step in bone resorption. In the migratory or motile state, the osteoclasts migrate across bone matrix and do not take part in resorption until they again attach to bone.
Web site: http://www.delphion.com/details?pn=US06472403__
Patents 149
•Amine salts of an integrin receptor antagonist
Inventor(s): Humphrey; Guy R. (Hillsborough, NJ), Waters; Marjorie See (Cranbury, NJ), Xu; Wei (North Wales, PA)
Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,444,680
Date filed: November 29, 2001
Abstract: Amine salts of 3-(2-methyl-pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]- naphthyridin-2-yl) -nonanoic acid are potent antagonists of the integrin.alpha.v.beta.3 receptor and are useful for the prevention and/or treatment of osteoporosis and vascular restenosis, as well as conditions associated with excessive angiogenesis, such as macular degeneration, diabetic retinopathy, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth. The invention also relates to a process for the preparation of the novel salts as well as pharmaceutical compositions containing the salts and methods of using the salts. Also disclosed are 3(R)- and 3(S)-(2- methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl )-nonanoic acid in the form of a zwitterion trihydrate.
Excerpt(s): The present invention relates to particular salts of an integrin receptor antagonist. More particularly, the invention relates to amine salts of 3-(2-methyl- pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl) -nonanoic acid, which are potent integrin.alpha.sub.v.beta.sub.3 receptor antagonists. These novel salts are therefore useful for the treatment and prevention of diseases and conditions for which an antagonist of the integrin.alpha.sub.v.beta.sub.3 receptor is indicated. Integrin.alpha.sub.v.beta.sub.3 receptor antagonists have been described as being of use for the prevention and/or treatment of osteoporosis, vascular restenosis, macular degeneration, diabetic retinopathy, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth [see, for example, M. E. Duggan, et al., "Ligands to the integrin receptor.alpha.sub.v.beta.sub.3, Exp. Opin. Ther. Patents, 10: 1367-1383 (2000); M. Gowen, et al., "Emerging therapies for osteoporosis," Emerging Drugs, 5: 1-43 (2000); J. S. Kerr, et al., "Small molecule.alpha.sub.v integrin antagonists: novel anticancer agents," Exp. Opin. Invest. Drugs, 9: 1271-1291 (2000); and W. H. Miller, et al., "Identification and in vivo efficacy of small-molecule antagonists of integrin.alpha.sub.v.beta.sub.3 (the vitronectin receptor)," Drug Discovery Today, 5: 397-408 (2000)]. U.S. Pat. No. 6,048,861, assigned to Merck & Co., describes a class of 9-substituted-3-aryl-nonanoic acid derivatives, which are potent integrin.alpha.sub.v.beta.sub.3 receptor antagonists and therefore useful for inhibiting bone resorption, vascular restenosis, treating and/or preventing osteoporosis, and inhibiting diseases and conditions associated with excessive and undesirable angiogenesis. Specifically disclosed in U.S. Pat. No. 6,048,861 is 3-(2-methyl-pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1, 8]-naphthyridin-2-yl)-nonanoic acid. Pharmaceutically acceptable salts of this compound are generically encompassed within the scope of U.S. Pat. No. 6,048,861.
Web site: http://www.delphion.com/details?pn=US06444680__
150 Macular Degeneration
•Device for the treatment of macular degeneration and other eye disorders
Inventor(s): Schachar; Ronald A. (Dallas, TX) Assignee(s): RAS Holding Corp (Dallas, TX) Patent Number: 6,589,217
Date filed: November 26, 2001
Abstract: Introduced is a device that may be used to treat the effects of macular degeneration and other eye disorders by increasing the optical effect of the retinal surface of the eye. This may be accomplished using a device whose body has a shape prescribed to increase the depth of the fovea and, in the process, make the sides of the clivus more convex, thereby utilizing the varying optical properties of the retinal area. A suitable association of this device with the eye will cause an image beam traveling from the lens through the vitreous humor to magnify and impinge an image perception area encompassing the macula. According to one advantageous embodiment, the device includes a body adapted for association with the eye to manipulate the retina of the eye to effectively augment the photoreceptor cells proximate the macula of the eye. The body of the device may be that of a band, a segment, a partial band, a plate, or, for that matter, any shape suitably adapted to perform the functions described herein to treat the effects of macular degeneration as well as other eye disorders.
Excerpt(s): which are commonly owned by the assignee of the present invention. The disclosures of these related United States patent applications and issued United States patents (collectively referred to hereafter as the "Presbyopia and Related Eye Disorder Patent Documents") are incorporated herein by reference for all purposes as if fully set forth herein. The present invention is generally related to the treatment of eye disorders and, more particularly, to device for the treatment of macular degeneration. Macular degeneration is a degenerative (age related) process that involves a highly specialized central part of the retina of the eye known as the macula, which is responsible for detailed central vision tasks such as reading, television viewing, sewing, etc. The various risk factors that may play a role in the cause of macular degeneration are being acutely studied--heredity, nutritional deficiencies, arteriosclerosis and hypertension, smoking, exposure to ultraviolet light, etc., are all suspect but further research is necessary to clearly identify the most significant factors.
Web site: http://www.delphion.com/details?pn=US06589217__
•Eyeglasses and method of making same for the treatment of low-vision
Inventor(s): Alberts; Davida Charlene (1124 Reedsport Pl., DeSoto, TX 75115) Assignee(s): none reported
Patent Number: 6,488,374 Date filed: February 12, 2002
Abstract: Eyeglasses for the treatment of low-vision and macular degeneration include a frame for supporting lenses on an occipital dexter side and an occipital sinister side. An occipital dexter lens has a near portion and a distance portion. The near portion has a dioptric power for near vision in a right eye, and the distance portion has a dioptric power for distance vision in the right eye. The optical center of the near portion of the occipital dexter lens is below and on the temporal side of the optical center of the distance portion. An occipital sinister lens similarly has a near portion and a distance
Patents 151
portion. The near portion has a dioptric power for near vision in a left eye, and the distance portion has a dioptric power for distance vision in the left eye. The optical center of the near portion of the occipital sinister lens is below and on the temporal side of the optical center of the distance portion.
Excerpt(s): The present invention is directed to an ophthalmic apparatus, and in particular to bifocal eyeglasses for the treatment of patients with low-vision, and more particularly macular degeneration. The macula is the small center portion of the light sensitive retina, which is the lining at the back of the eye. Light rays from objects come to a focus in the eye on the retina and are converted to electrical impulses that are interpreted by the brain. The macula is responsible for sharp, straight-ahead vision, which is necessary for functions such as reading, driving, and recognizing faces. Macular degeneration is a disorder that affects the macula causing decreased visual acuity and possible loss of central vision. The degeneration results from a partial breakdown of the retinal pigment epithelium (RPE). Breakdown of the RPE interferes with the metabolism of the retina, causing thinning of the retina (the "dry" phase of macular degeneration] and may allow these harmful elements from the blood to damage and scar the retina [the "wet" phase of macular degeneration].
Web site: http://www.delphion.com/details?pn=US06488374__
•Eyesight enhanced maintenance composition
Inventor(s): Gorsek; Wayne F. (Boynton Beach, FL) Assignee(s): Vitacost.com, Inc. (Boynton Beach, FL) Patent Number: 6,649,195
Date filed: July 11, 2002
Abstract: A powerful formulation for preventing and treating macular degeneration, cataracts, glaucoma and other eye diseases, and contains over thirty naturally effective vitamins, minerals, phytonutrients and amino acids, which have all been found to demonstrate a powerful protective effect on the health of the eye.
Excerpt(s): The invention relates to a composition for maintaining healthy eyesight. The composition provides over thirty naturally effective vitamins, minerals, phytonutrients and amino acids, which have all been found to demonstrate a powerful protective effect on the health of the eye. Vision loss is often related to damage caused by free radicals. A free radical is a highly reactive molecule that binds to and destroys body components. Free radicals are found in every thing from air pollution and chemicals in the water we drink, to preservatives in the foods we eat and cigarette smoke. As a result of their dependence on light to function properly, the eyes are especially vulnerable to free radical attacks. Paradoxically, while this light enables a person to see, it also creates additional free radicals that lead to cell and membrane damage.
Web site: http://www.delphion.com/details?pn=US06649195__
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•Gene therapy for inhibition of angiogenesis
Inventor(s): Bett; Andrew J. (Lansdale, PA), Goldman; Corey K. (Birmingham, AL), Huckle; William R. (Lansdale, PA), Kendall; Richard L. (Doylestown, PA), Thomas, Jr.; Kenneth A. (Chatham Borough, NJ)
Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,375,929
Date filed: October 26, 1999
Abstract: The present invention relates to methods of gene therapy for inhibiting angiogenesis associated with solid tumor growth, tumor metastasis, inflammation, psoriasis, rheumatoid arthritis, hemangiomas, diabetic retinopathy, angiofibromas, and macular degeneration Gene therapy methodology is disclosed for inhibition of primary tumor growth and metastasis by gene transfer of a nucleotide sequence encoding a soluble form of a VEGF tyrosine kinase receptor to a mammalian host. The transferred nucleotide sequence transcribes mRNA and a soluble receptor protein which binds to VEGF in extracellular regions adjacent to the primary tumor and vascular endothelial cells. Formation of a sVEGF-R/VEGF complex will prevent binding of VEGF to the KDR and FLT-1 tyrosine kinase receptors, antagonizing transduction of the normal intracellular signals associated with vascular endothelial cell-induced tumor angiogenesis. In addition, expression of a soluble receptor tyrosine kinase may also impart a therapeutic effect by binding either with or without VEGFs to form nonfunctional heterodimers with full-length VEGF-specific tyrosine kinase receptors and thereby inhibiting the mitogenic and angiogenic activities of VEGFs.
Excerpt(s): The present invention relates to methods of gene therapy for inhibiting angiogenesis associated with tumor growth, inflammation, psoriasis, rheumatoid arthritis, hemangiomas, diabetic retinopathy, angiofibromas, and macular degeneration. This invention also relates to animal models useful in the investigation of gene therapymediated inhibition of angiogenesis. The invention also relates to recombinant vectors which are useful in the disclosed gene therapy methods. Vascular endothelial cells form a luminal non-thrombogenic monolayer throughout the vascular system. Mitogens promote embryonic vascular development, growth, repair and angiogenesis in these cells. Angiogenesis involves the proteolytic degradation of the basement membrane on which endothelial cells reside followed by the subsequent chemotactic migration and mitosis of these cells to support sustained growth of a new capillary shoot. One class of mitogens selective for vascular endothelial cells include vascular endothelial growth factor (referred to as VEGF or VEGF-A) and the homologues placenta growth factor (PlGF), VEGF-B and VEGF-C.
Web site: http://www.delphion.com/details?pn=US06375929__
•Integrin antagonists
Inventor(s): Jadhav; Prabhakar K. (Wilmington, DE), Pitts; William J. (Newtown, PA) Assignee(s): Bristol - Meyers Squibb Pharma Company (Princeton, NJ)
Patent Number: 6,489,333 Date filed: April 9, 2001
Abstract: This invention relates to novel heterocycles which are useful as antagonists of the.alpha.sub.v.beta.sub.3 integrin, the.alpha.sub.2b.beta.sub.3 integrin, and related cell
Patents 153
surface adhesive protein receptors, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of cell adhesion, the treatment of angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, thrombosis, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.
Excerpt(s): Angiogenesis or neovascularization is critical for normal physiological processes such as embryonic development and wound repair (Folkman and Shing, J. Biol. Chem. 1992, 267:10931-10934; D'Amore and Thompson, Ann. Rev. Physiol. 1987, 49:453-464). However, angiogenesis also occurs pathologically, for example, in ocular neovascularization (leading to diabetic retinopathy, neovascular glaucoma, retinal vein occlusion and blindness), in rheumatoid arthritis and in solid tumors (Folkman and Shing, J. Biol. Chem., 1992, 267:10931-10934; Blood and Zetter, Biochim. Biophys. Acta., 1990, 1032:118-128). Tumor dissemination, or metastasis, involves several distinct and complementary components, including the penetration and transversion of tumor cells through basement membranes and the establishment of self-sustaining tumor foci in diverse organ systems. To this end, the development and proliferation of new blood vessels, or angiogenesis, is critical to tumor survival. Without neovascularization, tumor cells lack the nourishment to divide and will not be able to leave the primary tumor site (Folkman and Shing, J. Biol. Chem., 1992, 267:10931-10934).
Web site: http://www.delphion.com/details?pn=US06489333__
•Mesozeaxanthin formulations for treatment of retinal disorders
Inventor(s): Bone; Richard A. (Miami, FL), Howard; Alan Norman (Cambridge, GB), Landrum; John T. (Miami, FL)
Assignee(s): The Howard Foundation (Cambridge, GB) Patent Number: 6,329,432
Date filed: March 2, 2001
Abstract: Meso-zeaxanthin compositions for pharmaceutical use and use of mesozeaxanthin to increase the deposition of macular pigment in the human eye, and for the therapeutic treatment or prophylaxis of diseases and disorders of the macula, in particular age-related macular degeneration (AMD).
Excerpt(s): The invention relates to the use of meso-zeaxanthin to increase the deposition of macular pigment in the human eye, and for the therapeutic treatment or prophylaxis of diseases and disorders of the macula, and in particular age-related macular degeneration (AMD). The macula is the anatomical region of the retina which in man is responsible for central vision. Centered on the fovea, where the visual axis meets the retina, it extends radially outwards to a distance of about 2.75 mm (Davson, 1990). The macula is divided into the inner macula and the outer macula. The inner macula extends radially out to a distance of 1.5 mm while the outer macula is defined by the surrounding annular ring. The central portion of the macula is easily recognizable because of its yellow coloration which results from the presence of macular pigment. Despite its small size, the macula is endowed with the highest degree of visual acuity. It is therefore not surprising that considerable effort is devoted to understanding and, when possible, treating diseases which disrupt the nominal functioning of the macula. One such disease is age-related macular degeneration (AMD) which occurs in about
154Macular Degeneration
20% of the population above the age of 65 and is the leading cause of visual impairment in the USA and UK. AMD has up to the present time been an irreversible condition.
Web site: http://www.delphion.com/details?pn=US06329432__
•Method and compositions for treatment of the aging eye
Inventor(s): Petrus; Edward J. (Austin, TX)
Assignee(s): Advanced Medical Instruments (Austin, TX) Patent Number: 6,573,299
Date filed: September 20, 1999
Abstract: This invention relates to a method for the prevention and treatment of orbital disorders associated with the aging eye in mammals by the application of a topical composition comprising a permeation enhancing amount of one or more penetration enhancers, and one or more bio-affecting agents which penetrate into the underlying tissues and into the vascular network of the orbit. Another object of this invention is the improvement of age-related changes to the eyelids such as dry skin, wrinkles, keratoses, age spots and pigmented skin lesions. It is a further object of this invention to prevent and treat cataract formation, glaucoma, diabetic retinopathy and macular degeneration.
Excerpt(s): A method and compositions for the prevention and treatment of orbital disorders associated with the aging eye. The eyes, usually the very first aspect noticed of a person's face, often show the earliest signs of the aging process. The aging process is ordinary first demonstrated by wrinkles of the eyelids, the need for glasses to correct for presbyopia, or visual loss associated with cataracts, glaucoma, diabetic retinopathy or macular degeneration. Eyelids show age-related changes such as dry skin, wrinkles, keratoses, age spots and pigmented skin lesions. Dry eyelid skin appears dull and loses its radiance and is usually caused by low humidity, cold weather, contact pressure, detergents, solvents and some chemicals. A moisturizing topical lotion, cream or ointment usually restores the dry skin condition of the eyelids.
Web site: http://www.delphion.com/details?pn=US06573299__
•Method for increasing intestinal absorption of fat soluble vitamins in postmenopausal women and lower animals
Inventor(s): Gross; Kathy Lynn (Topeka, KS), Koo; Sung I. (Manhattan, KS), Owen; Kevin (Manhattan, KS)
Assignee(s): Hill's Pet Nutrition (Topeka, KS), Kansas State Research Foundation (Manhattan, KS), Lonza Ltd. (Basel, CH)
Patent Number: 6,476,010 Date filed: March 1, 2001
Abstract: The present invention provides a method for increasing the intestinal (lymphatic) absorption, cellular concentration, biliary secretion, hepatic storage, and/or liver concentration of a fat soluble vitamin in a post-menopausal woman. The method comprises orally administering to a post-menopausal woman in need thereof, a fat soluble vitamin and a fat soluble vitamin absorption increasing effective amount of L- carnitine. The L-carnitine enhances the antioxidant defense mechanism and lowers the risk of certain degenerative diseases, such as coronary heart disease, age-related
Patents 155
macular degeneration, osteoporosis, cancer, and Alzheimer's, in post-menopausal women. The invention also provides a method for increasing the intestinal absorption of a fat soluble vitamin in an animal. The method comprises orally administering to the animal in need thereof, a fat soluble vitamin and a fat soluble vitamin absorption increasing effective amount of L-carnitine.
Excerpt(s): This invention relates to a method for increasing the intestinal absorption, cellular concentration, biliary secretion, hepatic storage, and/or liver concentration of a fat soluble vitamin in a post-menopausal woman or a lower animal by orally administering L-carnitine and a fat soluble vitamin. L-carnitine plays a crucial role in the energy supply of tissues by modulating the entry of long-chain fatty acids into the mitochondrial matrix and their subsequent oxidation. Consistent with such a metabolic role, L-carnitine has been shown to be effective in lowering the serum levels of cholesterol, triglyceride, and free fatty acids, while increasing high density lipoprotein (HDL) cholesterol which is antiatherogenic. See Pola, P. et al., "Carnitine in the theraphy of dyslipemic patients", Curr Ther Res 27:208-16 (1980); Lacour, B. et al., "Carnitine improves lipid abnormalies in haemodialysis patients", Lancet 12:763-4 (1980); Avogaro, P., "Acute effect of L-carnitine on FFA and beta-hydroxy-butyrate in man", Pharmacol Res Commun 13:433-50 (1981); and Vacha, G. M. et al. "Favourable effects of L-carnitine treatment on hypertriglyceridemia in hemodialysis patients: Decisive role of low levels of high density lipoprotein cholesterol", Am J Clin Nutr 38:532-40 (1983). Existing evidence indicates that L-carnitine and its esters enhance the stability and integrity of erythrocyte membranes by participating in the reacylation (repair) of membrane phospholipids subjected to oxidative damage. See Arduini, A. et al., "Effect of propionyl-L-carnitine treatment on membrane phospholipid fatty acid turnover in diabetic rat erythrocytes", Mol Cell Biochem 152:31-7 (1995); Arduini, A. et al., "Carnitine palmitoyltransferase and acyl-CoA binding protein: two more players in the membrane phospholipid fatty acid turnover of human red cells?", Biochem J 325:811-4 (1997); and Arduini, A. et al., "Addition of L-carnitine to additive solution-suspended red cells stored at 4.degree. C. reduces in vitro hemolysis and improves in vivo viability", Trandfusion 37:166-74 (1997). It is of interest to note that such an action of L-carnitine and its esters is shown in the erythrocyte devoid of mitochondrial. L-carnitine supplementation to old rats has been shown to reverse the age-related decline in mitochondrial function, which may be linked to the membrane-stabilizing effect of L- carnitine. See Hagen, T. M. et al., "Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity", Proc Natl Acad Sci USA 95:9562-6 (1998). This finding is of particular significance in that oxidative damage to mitochondrial DNA increases markedly with age, leading to impaired cellular metabolism and function. See Hagen, T. M. et al., "Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase", Proc Natl Acad Sci USA 94:3064-9 (1997). Postmenopausal women make up over 15% of the total population in industrialized countries. By 2030, the proportion of postmenopausal women is predicted to increase to 23% of the total population. See Hill, K., "The demography of menopause", Maturitas 23:113-127 (1996). In addition, numerous epidemiological studies have shown that depletion of estrogen at the menopause influences cause-specific morbidity and mortality in later life. From the nutritional standpoint, the menopause is the time when the body's ability to absorb, assimilate, and metabolize nutrients begins to deteriorate. Consequently, the body status of nutrients is compromised at and after menopause, with the manifestations of specific nutrient deficiency symptoms with time.
Web site: http://www.delphion.com/details?pn=US06476010__
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•Method of ocular treatment
Inventor(s): Grinstead; Robert (206 Hector Ave., Metairie, LA 70005), Khoobehi; Bahram (5024 Cleveland Pl., Metairie, LA 70003), Peyman; Gholam (8654 Pontchartrain Blvd., Unit #1, New Orleans, LA 70124)
Assignee(s): none reported Patent Number: 6,524,330 Date filed: October 27, 2000
Abstract: A method for treating abnormal blood vessel growth and proliferation is disclosed. Members of the hypocrellin class of compounds such as hypocrellin A, hypocrellin B, and/or amino-substituted derivatives of hypocrellin B are administered and photoactivated with photodynamic therapy. The method may be used, for example, to treat ocular blood vessel proliferation as occurs with macular degeneration.
Excerpt(s): This invention relates to a composition and method to treat abnormal blood vessel proliferation in the eye. Many therapeutic treatments of pathological conditions involve selective targeting of specific tissues or cells for destruction. For example, a goal in cancer therapy is to destroy only malignant cells while leaving normal cells undisturbed. As another example, a goal in ophthalmology is to destroy new abnormal blood vessels in the eye that can result in visual impairment if allowed to proliferate, while leaving normal existing blood vessels intact. In the mammalian eye, macular degeneration (also called age related macula degeneration, AMD) is a pathological condition that results in proliferation of new blood vessels in the subretinal area. The new blood vessels proliferate from the choriocapillaris through defects in Bruch's membrane beneath or on top of retinal pigment epithelium (RPE), and form vascular membranes. While the presence of the new vessels themselves is not problematic, new vessels leak blood and other serous fluid which accumulate in surrounding spaces. It is this fluid accumulation that leads to visual impairment. For example, in the retina, both the large vessels and the capillaries normally have intact vessel walls. In the choroid, the large vessels normally have intact vessel walls, but the capillary walls or membranes contain fenestrations or openings. Any endogenous or exogenous fluid present in these capillaries, for example, blood, serous fluid, solubilized drug, etc. will leak outside the vessels and into the surrounding area. The accumulation of fluid can result in serous and hemorrhagic detachment of the RPE and neurosensory retina, and can lead to loss of vision due to fibrous deform scarring. More than 90% of cases having significant loss of central vision in AMD are attributed to choroidal neovascularization and the resulting exudation and scarring. Choroidal neovascularization occurs in about 8-10% of all patients with AMD, and is also seen in patient with pathologic myopia and presumed ocular histoplasmosis syndrome, as well as other idiopathic conditions.
Web site: http://www.delphion.com/details?pn=US06524330__
Patents 157
•Method of preventing proliferation of retinal pigment epithelium by retinoic acid receptor agonists
Inventor(s): Campochiaro; Peter A. (Baltimore, MD), Chandraratna; Roshantha A. (Laguna Hills, CA), De Juan, Jr.; Eugene (Phoenix, MD), Nagpal; Sunil (Lake Forest, CA), Wheeler; Larry A. (Irvine, CA)
Assignee(s): Allergan (Irvine, CA), The Johns Hopkins University School of Medicine (Baltimore, MD)
Patent Number: 6,372,753 Date filed: March 27, 2000
Abstract: Proliferation of retinal pigment epithelium following surgery or trauma or resulting in ocular diseases associated with choroidal neovascularization, such as age related macular degeneration and histoplasmosis syndrome, is prevented by contacting retinal pigment epithelium cells with a therapeutic amount of a retinoic acid receptor (RAR agonist, preferably one with specific activity for retinoic acid receptors. Preferably the RAR agonist is also a potent antagonist of AP1-dependent gene expression. Alternatively, the proliferation of retinal pigment epithelium is ameliorated with a therapeutic amount of an AP-1 antagonist, alone or in combination with an RAR agonist. The drug can be administered by bolus injection into the vitreous cavity using a dosage from about 50 to 150.mu.g. Or by slow release from liposomes or an oil tamponade injected into the vitreous cavity. Formulations for preventing proliferation of retinal pigment epithelium are also provided.
Excerpt(s): This invention relates to pharmacological uses of retinoids. More particularly, this invention relates to use of retinoids in treatment of ocular disorders. The retinal pigment epithelium (RPE) forms a monolayer of cells beneath the sensory retina that is normally mitotically inactive except when it is participating in retinal wound repair, in which it plays a central role. When wound repair is complete, the RPE usually stops proliferating; failure to do so can result in blinding disorders such as proliferative vitreoretinopathy (PVR) and disciform scarring. For instance, after detachment of the sensory retina, the RPE changes in morphology and begins to proliferate. Multilayered colonies of dedifferentiated RPE cells are formed. Cells then begin to migrate into the subretinal space where they engulf rod outer segments. In some instances cells migrate onto the surface of the retina and form epiretinal membranes. These events have been implicated in the pathogenesis of proliferative vitreoretinopathy, severe scarring occurring in association with macular degeneration, and poor or delayed recovery of vision after retinal reattachment. Age-related macular degeneration (AMD) is the major cause of blindness in patients over the age of 60 in the United States. Severe loss of vision in patients with AMD is usually due to the development of choroidal neovascularization (CNV). Laser treatment can ablate CNV and help to preserve vision in selected cases not involving the center of the retina; however, the treatment benefit is often transient due to the high rate of recurrent CNV (50% over 3 years and approximately 60% at 5 years) (Macular Photocoagulation Study Group, Arch. Ophthalmol. 204: 694-701, 1986). In addition, many patients who develop CNV are not good candidates for laser therapy because the CNV is too large for laser treatment, or the location cannot be determined so that the physician cannot accurately aim the laser.
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•Methods for treating acromegaly and giantism with growth hormone antagonists
Inventor(s): Chen; Wen Y. (Athens, OH), Kopchick; John J. (Athens, OH) Assignee(s): Ohio University/Edison Biotechnology Institute (Athens, OH) Patent Number: 6,583,115
Date filed: June 7, 1995
Abstract: The present invention relates to antagonists of vertebrate growth hormones obtained by mutation of the third alpha helix of such proteins (especially bovine or human GHs). These mutants-have growth-inhibitory or other GH-antagonizing effects. These novel hormones may be administered exogenously to animals, or transgenic animals may be made that express the antagonist. Animals have been made which exhibited a reduced growth phenotype. The invention also describes methods of treating acromegaly, gigantism, cancer, diabetes, vascular eye diseases (diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, retinopathy of sickle-cell anemia, etc.) as well as nephropathy and other diseases, by administering an effective amount of a growth hormone antagonist. The invention also provides pharmaceutical formulations comprising one or more growth hormone antagonists.
Excerpt(s): This invention relates to novel muteins of growth hormone ("GH"), especially human growth hormone ("hGH"), which diminish, decrease or inhibit the growth of animals or otherwise diminish, decrease or inhibit the effects of endogenous GH by acting as an antagonist to growth hormone receptors ("GHRs"). This invention also relates to DNAs encoding such muteins as well as methods for the treatment of diseases and disorders that are wholly or partially mediated by GHRs using a GH antagonist. Several forms of mature bGH have been found in nature. The amino-terminus can vary (due to variation in the site of cleavage during secretion) so that the mature protein begins with either NH.sub.2 -Ala-Phe-Pro or NH.sub.2 -Phe-Pro, the latter referred to as "(des Ala) bGH". Additionally, the amino acid at bGH position 126 may be either Leu or Val, apparently as a result of allelic variation in the bovine population. Exogenous administration of bGH to cattle increases milk production, feed efficiency, growth rate, and the lean-to-fat ratio, and decreases fattening time.
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•Methods for treating conditions and illnesses associated with abnormal vasculature
Inventor(s): Alam; Abu (Lake Forest, IL), Flower; Robert W. (Hunt Valley, MD) Assignee(s): Akorn, Inc. (Buffalo Grove, IL)
Patent Number: 6,443,976 Date filed: November 30, 1999
Abstract: Use of radiation-absorbing dyes (e.g., indocyanine green (ICG), fluorescein, rose bengal) and photodynamic dyes (e.g., hematoporphyrins, aminolevulinic acids, porphyrins, merocyanines, porphycenes, porfimer sodium, verteporfin, Photofrin II, PH-10, chlorins, zinc phthalocyanine, purpurins, pheophorbides, monoclonal antibodydye conjugates of any of the foregoing dyes) for the treatment of conditions associated with abnormal vasculature, including, generally, lesions, and, more specifically, tumors (cancerous and benign) and choroidal neovascularization (CNV) associated with agerelated macular degeneration (ARMD).
Patents 159
Excerpt(s): The present invention relates generally to methods for treating harmful conditions and illnesses associated with abnormal vasculature. Abnormal vasculature in a body is typically associated with a lesion. Lesions are generally defined as an abnormal tissue structure located in an organ or other body part, and are often a manifestation of a harmful condition, disease or illness. Lesions may take many specific forms, e.g., choroidal neovascularization (CNV) found in the eye, and tumors, both benign and malignant, located in organs and other parts of the body. Common methods of treating abnormal vasculature use laser technology. One example of such methods, used in the treatment of CNV, is photodynamic therapy (PDT). The object of PDT is to permit selective destruction of undesirable tissue without damaging surrounding healthy tissue. This is possible because the photodynamic dyes used in PDT are selectively retained in the area to be treated. For example, in the case of CNV, the photodynamic dye selectively binds to the proliferating endothelium in the CNV. Similarly, in the case of tumors, the photodynamic dye remains in cancer cells for a longer period of time than in normal, healthy cells. Thus, only a general identification of the tissue to be treated need be obtained before administering PDT.
Web site: http://www.delphion.com/details?pn=US06443976__
•Methods of ophthalmic administration
Inventor(s): Bowman; Lyle M. (Pleasanton, CA), Clark; Leslie A. (Alameda, CA), Hecker; Karl L. (Keene, NH), Pfeiffer; James F. (Oakland, CA)
Assignee(s): InSite Vision, Incorporated (Alameda, CA) Patent Number: 6,378,526
Date filed: August 3, 1998
Abstract: Intrascleral injection of a therapeutic or diagnostic material at a location overlying the retina provides a minimally invasive technique for delivering the agent to the posterior segment of the eye. The procedure also allows for close proximity of the material to the targeted site and can be effectively used to treat conditions associated with the posterior segment of the eye, including macular degeneration, vein occlusion, and diabetic retinopathy.
Excerpt(s): The present invention relates to methods of ophthalmic administration. Specifically, the methods relate to intrascleral injection of therapeutic or diagnostic materials. Delivering therapeutic or diagnostic agents to the posterior segment of the eye, especially to the retina, macula, etc., poses several challenges. Topical instillation of an agent to the front of the eye such as by eye drops, generally provides low amounts of the agent (including none) to the posterior portion of the eye, due in part to poor diffusion through the various layers as well as the natural clearing processes encountered. Providing effective amounts of an agent to, for example, the retina via topical instillation is generally not possible given the distance and number of layers between the deposit site of the agent and the site to be treated. Another potential shortcoming with topical instillation is that the composition tends to be quickly removed from the eye by tears and other natural clearing processes. The resulting short duration of contact can further limit the likelihood of an appreciable amount of the agent reaching the posterior segment. Conversely, systemic delivery of an agent to the posterior segment of the eye such as by oral administration, is limited by the bloodretinal barrier. The barrier limits the size and amount of agents that can reach the choroid and retina. Moreover, because the agent is systemically delivered, the dosage is limited so as not to provide a toxic dose of the agent to other parts of the body. This is
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especially a concern in treating chronic disorders where a long term dosing regimen is typically required. For this reason, overcoming the barrier by administering higher doses of the agent is usually not a practical alternative. Likewise, the risk of side effects is increased with systemic delivery.
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•Mouse model for ocular neovascularization
Inventor(s): Campochiaro; Peter A. (Baltimore, MD), Zack; Donald J. (Lutherville, MD) Assignee(s): The Johns Hopkins University (Baltimore, MD)
Patent Number: 6,479,729 Date filed: June 5, 2000
Abstract: Transgenic mammals are provided which develop neovascularization of the retina, similar to that found in a variety of disease states, including diabetes, age related macular degeneration, retinopathy of prematurity, sickle cell retinopathy. These mammals can be used as test systems to evaluate potential prophylactic and therapeutic regimens. The effect of a regimen on the neovascularization is indicative of its beneficial effect in a disease state which is associated with neovascularization.
Excerpt(s): This invention is related to the field of retinopathies, particularly those caused by neovascularization. New blood vessel formation or neovascularization (NV) is essential for normal eye development, but it can also cause severe ocular disease. In the retina, NV is associated with a number of disease processes, the most common of which is diabetic retinopathy, a major cause of new blindness in developed nations.sup.1. Occlusion of retinal vessels leading to retinal ischemia is a feature shared by most diseases in which retinal NV occurs. This observation led to the hypothesis that the development of retinal NV is stimulated by one or more angiogenesis factors released by ischemic retina.sup.2, 3. Substantial effort has been devoted to identifying the factor or factors involved. The demonstration that vascular endothelial cell growth factor (VEGF) is upregulated by hypoxia.sup.4, 5 and that levels of VEGF are increased in the retina and vitreous of patients.sup.6-9 or laboratory animals.sup.10, 11 with ischemic retinopathies has focused attention on VEGF as a potential mediator of retinal angiogenesis. This is supported by studies showing that VEGF antagonists partially inhibit retinal or iris NV in animal models.sup.12-14. There is also ample-data indicating that VEGF can stimulate NV in other tissues.sup.15-18.
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•Neural retinal cells and retinal pigment epithelium cells and their use in treatment of retinal disorders
Inventor(s): Edge; Albert (Cambridge, MA) Assignee(s): Diacrin, Inc. (Charlestown, MA) Patent Number: 6,517,833
Date filed: June 12, 2001
Abstract: Compositions comprising porcine retinal cells and methods for using the compositions to treat retinal disorders are described. The porcine retinal cells are preferably fetal neural retina cells or retinal pigment epithelial cells. The porcine retinal
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cells can be modified to be suitable for transplantation into a xenogeneic subject, such as a human. For example, the porcine retinal cells can be modified such that an antigen (e.g., an MHC class I antigen) on the cell surface which is capable of stimulating an immune response against the cell in a xenogeneic subject is altered (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cell when introduced into the subject. In one embodiment, the porcine retinal cells are obtained from a pig predetermined to be free from organisms which originate in pig and which are capable of transmitting infection or disease to the recipient subject. The porcine retinal cells of the present invention can be used to treat a xenogeneic subject having a retinal disorder (e.g., a human with retinis pigmentosa, light damaged retina and macular degeneration by introducing the cells into the retina of the subject.
Excerpt(s): Macular degeneration is a disease of the retina which affects over thirteen million people in the United States and is characterized by loss of central vision due to the loss of photoreceptors in the central part of the retina, the macula lutea. D'Amico et al. (1994) New England J. Med. 331:95-106 and Kliffen et al. (1997) Microscopy Res. & Techniq. 36:106-122. The macula is the most important part of the eye for high resolution vision because there is a greater concentration of cone type photoreceptors which are responsible for color vision and visual acuity. Photoreceptor cells, especially rod cells, renew their outer segments at a high rate. Thus, as new lamellae discs are formed and added to the photoreceptor cells, the older lamellae discs at the tip are discarded. Retinal pigment epithelial (RPE) cells function to provide support for the retinal photoreceptors and are responsible for the metabolic digestion of the discarded outer segments of the neural retina. Thus, RPE cells are responsible for the phagocytosis and digestion of the discarded discs at a turn over rate of approximately 30-100 discs each day. Underlying the RPE cells is the choriocapillaris which contains the vasculature to provide nutrients and remove metabolic by-products from the retina. In macular degeneration, the RPE cells are dysfunctional, thereby leading to a build up of metabolic by-products, including discarded discs in the retina. The presence of metabolic debris and excess fluid in the retina damage photoreceptor cells, thereby compromising visual acuity. Cingle et al. (1996) Curr. Eye. Res. 15:433-438 and Curcio et al. (1996) Invest. Ophthal. & Vis. Sci. 37:1236-1249. In addition, the degeneration of the RPE layer is also reflected by ensuing atrophy of the choriocapillaris.
Web site: http://www.delphion.com/details?pn=US06517833__
•Ophthalmic brachytherapy device
Inventor(s): Finger; Paul T. (1 Gracie Ter., Apt. 12A, New York, NY 10028) Assignee(s): none reported
Patent Number: 6,443,881 Date filed: June 6, 2000
Abstract: A method and apparatus are provided for use in ocular brachytherapy. The device comprises a handle, an applicator coupled with said handle, and adapted to receive a source of radiation. The applicator is movable between a radiation shielding position and a position wherein radiation is allowed to reach the diseased area. A plurality of light-emitting diodes are located so as to define the area to be treated. A shield receives the applicator so as to shield the radiation source during insertion and positioning proximal the treatment site. An actuator moves the applicator between the shielded position and the treatment position. The method of treating macular degeneration employs the device according to the invention.
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Excerpt(s): The present invention relates generally to a device and method for the treatment of ocular diseases with radiation. Particularly, the device and method will be utilized to deliver a dose of radiation to a portion of the eye globe to treat subretinal neovascularization associated with age-related macular degeneration. Macular degeneration is a pathologic process associated with subretinal neovascularization. The subretinal neovascularization allows fluid, blood, and lipids to leak beneath the surface of the retina. This leakage has detrimental effects on the health of the globe. For example, this leakage may cause hypoxia, retinal detachment or other eye condition problems. These conditions can cause scarring that will destroy the macular retina. The effect of the scarring on the macular retina can be severe. Specifically, it may cause irreversible loss of central vision. There are currently two methods for treatment of macular degeneration. These methods utilize lasers to effect closure of subretinal neovascularization. While laser/photocoagulation is effective in closing subretinal neovascularization and preserving visual acuity, laser treatment is only effective in a small subset of patients, and can cause destruction of the overlying retina. The. other laser-assisted treatment utilizes light-activated dyes to close the subretinal neovascular vessels.
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•Regulated angiogenesis genes and polypeptides
Inventor(s): Jay; Gilbert (North Bethesda, MD), Li; Xuan (Silver Spring, MD), Sun; Zairen (Rockville, MD)
Assignee(s): Origene Technologies, Inc. (Rockville, MD) Patent Number: 6,657,054
Date filed: June 10, 2002
Excerpt(s): The present invention relates to all facets of novel polynucleotides, the polypeptides they encode, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides are expressed in angiogenesis and are therefore useful in variety of ways, including, but not limited to, as molecular markers for blood vessels and blood vessel formation, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing, treating, and/or determining predisposition to diseases and conditions of the vascular system. The identification of specific genes, and groups of genes, expressed in pathways physiologically relevant to angiogenesis permits the definition of functional and disease pathways, and the delineation of targets in these pathways which are useful in diagnostic, therapeutic, and clinical applications. The present invention also relates to methods of using the polynucleotides and related products (proteins, antibodies, etc.) in business and computer-related methods, e.g., advertising, displaying, offering, selling, etc., such products for sale, commercial use, licensing, etc. Angiogenesis, the process of blood vessel formation, is a key event in many physiological processes that underlie normal and diseased tissue function. During ontogeny, angiogenesis is necessary to establish to the network of blood vessels required for normal cell, tissue and organ development and maintenance. In the adult organism, the production of new blood vessels is needed for organ homeostasis, e.g., in the cycling of the female endometrium, for blood vessel maturation during wound healing, and other processes involved in the maintenance of organism integrity. It also is important in regenerative medicine, including, e.g., in promoting tissue repair, tissue engineering, and the growth of new
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tissues, inside and outside the body. Not all angiogenesis is beneficial. Inappropriate and ectopic expression of angiogenesis can be deleterious to an organism. A number of pathological conditions are associated with the growth of extraneous blood vessels. These include, e.g., diabetic retinopathy, neovascular glaucoma, psoriasis, retrolental fibroplasias, angiofibroma, inflammation, etc. In addition, the increased blood supply associated with cancerous and neoplastic tissue, encourages growth, leading to rapid tumor enlargement and metastasis.
Web site: http://www.delphion.com/details?pn=US06657054__
•Synthesis and clinical uses of D,.alpha.-tocopherol nicotinate compounds
Inventor(s): Pearson; Don C. (Lakewood, WA), Richardson; Kenneth T. (Anchorage, AK) Assignee(s): Chronorx, LLC (Anchorage, AK)
Patent Number: 6,423,847 Date filed: March 20, 2000
Abstract: A process of synthesis of D,.alpha.-tocopherol nicotinate compounds is presented. Therapeutic uses for this compound are described. The active agents are demonstrated to be complementary in their physiological functions especially as these relate to cellular and endothelial biochemistry and physiology and, ultimately to vascular health. The active components of the invention are selected for inclusion in a unique combination that clinically reduces risks of vasculopathy, DNA strand breakage and neuronal excitotoxicity in various diseases. In addition to the systemic vascular benefits acquired, improvement of the vascular health of the eye reduces the risk of glaucomatous optic nerve atrophy with its accompanying visual field loss and potential blindness and reduces conditions of risk for macular degeneration.
Excerpt(s): The fields of the invention reside in biochemistry and in pharmacology. This invention relates to the synthesis and the therapeutic uses of various dosage forms comprised of D,.alpha.-tocopherol nicotinate and their uses as nutritional supplements and therapeutic agents. Dextro and levo stereoisomeric forms of a-tocopherol exist, but the dextro form is the most physiologically active and the most nutritionally useful. 1. Vascular oxidative stress brought about by superoxide radicals and oxidized lowdensity lipoproteins (oxLDL) are major factors contributing to decreased NO-dependent vasodilator functions in hypercholesterolemia and atherosclerosis. DAT antagonizes the oxLDL-related events in atherogenesis. DAT is generally regarded as the most important lipid-soluble, chain-breaking antioxidant in human plasma.
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•Treatment of chronic hypertension and related conditions with thiol complexes
Inventor(s): Pearson; Don C. (Lakewood, WA), Richardson; Kenneth T. (Anchorage, AK) Assignee(s): Chronorx, LLC (Anchorage, AK)
Patent Number: 6,429,219 Date filed: May 3, 2000
Abstract: This invention relates to the synthesis of certain complexes of cysteine, N- acetylcysteine, N-(2-mercaptopropionyl)glycine, and L-2-oxothiazolidine-4-carboxylate and to the nutritional use of these and other related individual or complexed thiol-
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contributing glutathione predecessors. Clinical uses for these molecules and complexes in the beneficial modification of various physiological conditions and functions associated with aging, chronic glaucoma, diabetes mellitus, insulin resistance, macular degeneration, neurodegenerative diseases and vasoconstriction are described in particular.
Excerpt(s): This invention is in the fields of pharmacology and biochemistry. It relates to the synthesis of certain complexes of L-cysteine, N-acetyl L-cysteine, N-(2-mercapto- propionyl)glycine, L-2-oxothiazolidine-4-carboxylate and the nutritional or clinical use of these and other related individual or complexed thiol contributing, glutathione predecessors. The use of these molecules and complexes in clinical presentations of chronic glaucoma, diabetes mellitus, macular degeneration, neurodegenerative diseases and vasoconstriction are described in particular. The eye is maintained in a homeostatic shape by a relatively stable intraocular pressure (IOP) that varies within a reasonably narrow range so long as the intraocular production of aqueous fluid remains equal to its exit from the eye. The optic nerve head can tolerate relatively high levels of IOP if the availability of oxygen from posterior ciliary arteries and optic nerve head arterioles remains adequate. However, if the global intraocular pressure is higher than the perfusion pressure driving oxygen through the arteriole into the surrounding tissues, decreasing amounts of oxygen will reach the optic nerve head and nerve disability will result.
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•Use of green porphyrins to treat neovasculature in the eye
Inventor(s): Gragoudas; Evangelos S. (Lexington, MA), Miller; Joan W. (Winchester, MA)
Assignee(s): Massachusetts Eye and Ear Infirmary (Boston, MA) Patent Number: 6,610,679
Date filed: April 2, 2001
Abstract: Photodynamic therapy of conditions of the eye characterized by unwanted neovasculature, such as age-related macular degeneration, is effective using green porphyrins as photoactive agents, preferably as liposomal compositions.
Excerpt(s): The invention is in the field of photodynamic therapy, specifically related to ocular conditions. More particularly, the invention concerns the use of green porphyrins in photodynamic therapeutic treatment of conditions characterized by unwanted neovasculature in the eye. Choroidal neovascularization leads to hemorrhage and fibrosis, with resultant visual loss in a number of eye diseases, including macular degeneration, ocular histoplasmosis syndrome, myopia, and inflammatory diseases. Age-related macular degeneration (AMD) is the leading cause of new blindness in the elderly, and choroidal neovascularization is responsible for 80% of the severe visual loss in patients with this diseases. Although the natural history of the disease is eventual quiescence and regression of the neovascularization process, this usually occurs at the cost of sub-retinal fibrosis and vision loss. Current treatment of AMD relies on occlusion of the blood vessels using laser photocoagulation. However, such treatment requires thermal destruction of the neovascular tissue, and is accompanied by full-thickness retinal damage, as well as damage to medium and-large choroidal vessels. Further, the subject is left with an atrophic scar and visual scotoma. Moreover, recurrences are common, and visual prognosis is poor.