Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
1999-08-10
2003-04-29
Witz, Jean C. (Department: 1651)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S913000, C424S427000, C424S428000, C424S429000
Reexamination Certificate
active
06555582
ABSTRACT:
TECHNICAL FIELD
This invention relates to synthetic thyroid hormones, compositions and methods for treating elevated intraocular pressure and glaucoma.
BACKGROUND
Glaucoma afflicts approximately two million people in the United States and about 15 million people worldwide. Approximately two percent of the population over 35 suffers from some form of glaucoma and it accounts for approximately 12% of all cases of blindness. Despite its easy diagnosis, therapies to lower intraocular pressure (IOP) in patients with glaucoma are frequently inadequate. Use of topical and oral medicines to lower intraocular pressure is often limited by side effects of the drugs. In other cases, use of medical therapy to treat glaucoma is not successful in lowering intraocular pressure sufficiently to prevent progressive damage to the optic nerve.
Consequently, there is a need for methods, compounds and compositions for treating glaucoma and other medical conditions of the eye or epithelium.
SUMMARY OF THE INVENTION
Before the invention described herein, changes in IOP due to systemic changes in thyroid hormone levels, were postulated to be indirect, or if direct, such thyroid hormone-induced changes in IOP were thought to be mediated through the adrenergic a or, receptors located in the eye. Aspects of the present invention now recognize for the first time an important role of thyroid hormone receptors in eye physiology. Eye thyroid receptors provide an opportunity to directly mediate thyroid hormone effects in eye cells. In particular, thyroid receptors of human trabecular meshwork (“HTM”) cells can potentially mediate the amount of extracellular hyaluronic acid (“HA”) maintained by HTM cells, which in turn can affect aqueous humor outflow.
The present invention recognizes that cells containing thyroid hormone receptors and cellular processes involved in GAG production would be useful components of in vitro or in vivo methods for identifying compounds that are useful as therapeutics, such as compounds that modulate glycosaminoglycans (“GAG”) production. The method of identifying compounds useful for therapeutics comprises: 1) contacting a compound with cells that secrete GAG, such as trabecular meshwork cells, and 2) detecting the binding of the compound to the cells, wherein the compound has concentration of 10 micromolar or less.
In addition the present invention recognizes that thyroid hormones and synthetic thyroid hormones (STHs) can directly modulate GAG production or HA secretion from cells, such as trabecular meshwork cells. Methods of the invention, consequently, are directed to modulating GAG production or HA secretion using compounds, especially STHs, that reduce the amount or activity of such substances or cellular processes in the desired cells or tissues. Preferably, such cells will be trabecular meshwork cells, ciliary cells of the eye, endothelial cells of the eye, non-eye endothelial cells, and fibroblasts of skin and internal organs. In most instances non-systemic application of a STH is preferred, although STHs can be administered systemically as well.
The present invention also provides for a method of treating glaucoma comprising administering to an eye in need thereof an ophthalmically effective amount of a synthetic thyroid hormone to the eye. Modes of administration include topical, intraocular implantation or injection, and systemic. Preferably administration of a STH to the eye is topical administration with an eye compatible pharmaceutical carrier or non-systemic administration via a surgically implantable or injectable device, which may comprise a biodegradable or non-biodegradable polymer capable of sustained release of the STH intraocularly. Ocular inserts containing STH in a sustained release polymer may also be used.
REFERENCES:
patent: 2798053 (1957-07-01), Brown
patent: 4136250 (1979-01-01), Mueller et al.
patent: 4192827 (1980-03-01), Mueller et al.
patent: 4548990 (1985-10-01), Mueller et al.
patent: 5474985 (1995-12-01), Polansky et al.
patent: 5486165 (1996-01-01), Stegmann
patent: 6221911 (2001-04-01), Lavin et al.
patent: 6380255 (2002-04-01), Lavin
patent: 253717 (1988-01-01), None
patent: WO 95/17178 (1995-06-01), None
patent: 9640048 (1996-12-01), None
patent: WO 97/21993 (1997-06-01), None
McDaniel et al., Journal of the American Optometric Association 67(2): 109-114 (Feb. 1996). Abstract.*
Wildmeister et al., Med. Welt 28(41): 1652-1655 (1977). Abstract.*
Lund et al., Acta Endocrinol. 113(1): 56-58 (1986). Abstract.*
Alekseeva, Izv. Sibirsk. Otd. Akad. Nauk SSSR, Ser. Biol-Med. Nauk (2): 108-112 (1963). Abstract.*
Schiller et al., Biochim. Biophys. Acta 58: 27-33 (1962). Abstract.*
Capechi, M. R. (1994) “Targeted Gene Replacement”Scientific American, 270(3):34-41.
Wall, R.J. (1996) “Transgenic Livestock: Progress and Prospects for the Future”Theriogenology, 45:57-68.
Yoneyama, J. (1994) “Effects of Antiglaucoma Agents on Glycosaminoglycans in Organ-Cultured Rabbit Trabecular Meshwork”Ophthalmologica, 208(5):278-283.
Alvarado et al., “Human trabecular cells II: Growth Pattern and Ultrastructural Characteristics”, Invest. Ophthalmol. Vis. Sci., vol. 23:464-478 (1982).
Apriletti J. et al., “Large Scale Purification of the Nuclear Thyroid Hormone Receptor from Rat Liver and Sequence-specific Binding of the Receptor to DNA”, J. Biol. Chem. vol. 263:9409-9417 (1988).
Apriletti J. et al., Expression of the Rat 1 Thyroid Hormone Receptor Ligand Binding Domain inEscherichia coliand the Use of a Ligand-Induced Conformation Change as a Method for Its Purification ot Homogeneity, Protein Expression and Purification, vol. 6:363-370 (1995).
Ashton, P. et al., “Review: Implants”, J. of Occ. Pharm., vol. 10:691-701 (1994).
Hallman V.L., “Effect of Thyroid Hormones on Intraocular Pressure,” Exptl. Eye Res., vol. 6:219-226 (1967).
Jorgensen, “Thyroid Hormones and Analogs”, in Hormonal Proteins and Peptides, vol. 6, Thyroid Hormones (Choh Hao Li, ed.) pp. 107-204 (1978).
Lam et al., “Hydraulic Flow Conductivity of Hyaluronic Acid Solutions: Effects on Concentration and Molecular Weight,” Biorheology, vol. 27:789-795 (1990).
Lavin T.N. “Mechanisms of Thyroid Hormone Action”, in Endocrinology (Degroot, Ed.), 2nd Edition, W.B. Saunders, pub. (1989).
Lewis et al., “Formation of Quinol Ethers using (Diacetoxyiodo)benzene”, Synthesis, vol. 1103 (1987).
Murphy, B.P. et al., “The Determination of Thyroxine by Competitive Protein-binding Analysis Employing an Anion-exchange Resin and Radiothyroxine”, J. Lab and Clin. Med., vol. 66:161-167 (1965).
Oppenheimer, J.H. et al., “Stereospecific Transport of Triiodothyronine from Plasma to Cytosol and from Cytosol to Nucleus in Rat Liver, Brain, and Heart”, J. Clin. Invest., vol. 75:147-154 (1985).
Polansky et al., “Trabecular Meshwork Cell Culture in Glaucoma Research: Evaluation of Biological Activity and Structural Properties of Human Trabecular Cell In Vitro”, Opthalmology, vol. 91:580-595 (1984).
Polansky et al., Studies on human trabecular cells propagated in vitro, Vision Res., vol. 21:155 (1981).
Polansky et al., Human trabecular cells I: Establishment in tissue culture and growth characteristics, Invest. Opthalmol. Vis. Sci. vol. 18:1043-1049 (1979).
Ribeiro et al., “Thyroid Hormone Export Regulates Cellular Hormone Content and Response,” The Journal of Biological Chemistry, vol. 271(29):17147-17151 (1996).
Samuels et al., “Depletion of L-3,5,3′-Triiodothyronine and L-Thyroxine in Euthyroid Calf Serum for Use in Cell Culture Studies of the Action of Thyroid Hormone”, J. Endocrinology, vol. 105(1):80-85 (1979).
Schwartz, H.L., et al., “Distribution and Metabolism of L- and D-Triiodothyronine (T3) in the Rat: Preferential Accumulation of L-T3 by Hepatic and Cardiac Nucleic as a Probable Explanation of the Differential Biological Potency of T3 Enantiomers”, Endocrinology, vol. 113:1236 (1983).
Schwartz, H.L. et al., “Quantitation of Rat Tissue Hormone Binding Receptor Isoforms by Immunoprecipitation of Nuclear Triiodothyronine Binding Capacity”, J. Biol. Chem., vol. 267(17):11794-11799 (1992).
Shishiba et al., Effect of Thyro
Baxter John D.
Jumper Michele D.
Scanlan Thomas S.
Schwartz Daniel M.
Hunter Tom
Quine Jonathan Alan
Quine Intellectual Property Law Group P.C.
The Regents of the University of California
Witz Jean C.
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