Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
1999-12-02
2001-10-02
Fay, Zohreh (Department: 1616)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
C514S178000, C514S185000, C514S912000
Reexamination Certificate
active
06297228
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to the use of angiostatic steroids in photodynamic therapy (PDT).
DESCRIPTION OF THE RELATED ART
Steroids functioning to inhibit angiogenesis in the presence of heparin or specific heparin fragments are disclosed in Crum, et al., A New Class of Steroids Inhibits Angiogenesis In The Presence of Heparin or Heparin Fragment, Science, 230:375-378, December 20, 1985. The authors refer to such steroids as “angiostatic” steroids. Included in the new class of steroids found to be angiostatic are cortisol, cortexolone, and several dihydro and tetrahydro derivatives. In a follow up study directed to testing a hypothesis as to the mechanism by which the steroids inhibit angiogenesis, it was shown that heparin/angiostatic steroid compositions caused dissolution of the basement membrane scaffolding to which anchorage dependent endothelia are attached resulting in capillary involution; see, Ingber, et al. A Possible Mechanism for Inhibition of Angiogenesis by Angiostatic Steroids. Induction of Capillary Basement Membrane Dissolution, Endocrinology 119:768-775, 1986.
A group of tetrahydrosteroids useful in inhibiting angiogenesis is disclosed in U.S. Pat. No. 4,975,537, issued to Aristoff, et al. The compounds are disclosed for use in treating head trauma, spinal trauma, septic or traumatic shock, stroke, and hemorrhage shock. In addition, the patent discusses the utility of these compounds in embryo implantation and in the treatment of cancer, arthritis, and arteriosclerosis. The compounds are not disclosed for ophthalmic use. Some of the tetrahydrosteroids disclosed in Aristoff, et al. are disclosed in U.S. Pat. No. 4,771,042 in combination with heparin or a heparin fragment for inhibiting angiogenesis in a warm blooded animal. The patent does not disclose the combination for ophthalmic use.
Compositions of hydrocortisone, “tetrahydrocortisol-S,” and U-72,745G, each in combination with a beta cyclodextrin have been shown to inhibit corneal neovascularization. Li, et al., Angiostatic Steroids Potentiated by Sulphated Cyclodextrin Inhibit Corneal Neovascularization, Investigative Ophthalmology and Visual Science, 32(11):2898-2905, October, 1991. The steroids alone reduce neovascularization somewhat but are not effective alone in providing for regression of neovascularization.
There are currently no effective therapies for the treatment of ocular neovascular diseases which do not include the destruction of healthy viable tissue. Although panretinal photocoagulation is the current medical practice for the treatment of diabetic retinopathy and is effective in inhibiting diabetic retinal neovascularization, this procedure destroys healthy peripheral retinal tissue. This destruction of healthy tissue decreases the retinal metabolic demand and thereby reduces retinal ischemia driven neovascularization. A recent new laser procedure is being tested for the inhibition of ocular neovascularization. Photodynamic therapy (PDT) is a procedure in which a photoactivatable dye is given systemically followed by laser activation of the dye in the eye at the site of new blood vessel formation (Asrani & Zeimer, Br J Ophthalmol, 79(8):776-770, August, 1995; Asrani et al, Invest Ophthalmol. Vis Sci, 38(13);2702-2710, December, 1997; Husain et al, Ophthalmology, 104(8):242-1250, August, 1997; Lin et al, Curr Eye Res, 13(7):513-522, July, 1994.) The photoactivated drug generates free oxygen radicals which seal the newly formed blood vessels. This procedure has been used in patients with the exudative form of macular degeneration and many patients show regression of their subretinal neovascular membranes. Unfortunately, it appears that the PDT induced inhibition of neovascularization is transient lasting only 6-12 weeks (Gragoudas et al, Investigative Ophthalmology & Visual Science, 38(4):S17; Mar. 15, 1997; Sickenberg et al, Investigative Ophthalmology & Visual Science, 38(4):S92, Mar. 15, 1997; Thomas et al, Investigative Ophthalmology & Visual Science, 39(4):S242, Mar. 15, 1998.)
The subject matter of the present invention involves combining the PDT induced regression of ocular neovascular tissue with agents, such as angiostatic steroids, which inhibit new blood vessel formation.
SUMMARY OF THE INVENTION
This invention is directed to methods for treating ocular neovascular diseases by combining the use of PDT with particular angiostatic steroids.
REFERENCES:
patent: 4771042 (1988-09-01), Braughler et al.
patent: 4975537 (1990-12-01), Aristoff et al.
patent: 5371078 (1994-12-01), Clark et al.
patent: WO 91/19731 (1991-12-01), None
patent: WO 95/24930 (1995-09-01), None
DeFaller, J.M.,Database Dissertation Abstracts University Microfilms International, “Mechanisms of Action and Clinical Efficacy of AL-3789, an Angiostatic Steroid (Neovascularization, Pterigium, Tumor Growth),” vol. 58/06B:2974.
Miller, et al.,Arch Ophthalmol.“Photodynamic Therapy of Experimental Choroidal Neovascularization Using Lipoprotein-Delivered Benzoporphyrin,” vol. 113:810-818, 1995.
Cowled, et al.,Cancer Letters, “Potentiation of Photodynamic Therapy with Haematoprphyrin Derivatives by Glucocorticoids,” vol. 29:107-114, 1985.
Anderson, et al.,Photochemistry and Photobiology, “Phthalocyanine Photodynamic Therapy: Disparate Effects of Pharmacolognic Inhibitors on Cutaneous Photosensitivity and on Tumor Regression,” vol. 65(5):895-901; 1997.
Clark, Abbot F.,Exp. Opin. Invest. Drugs, “Cardiovascular & Renal AL-3789: a novel ophthalmic angiostatic steroid,” vol. 6(12):1867-1877, 1997.
Nirankari, Verinder S.,Tr. AM. Ophtal. Soc., “Laser Photocoagulation for Corneal Stromal Vascularization,” vol. LXXXX, pp. 595-669, 1992.
Crum, et al.,A New Class of Steroids Inhibits Angiogenesis In the Presence of Heparin or Heparin Fragment, Science, vol. 230:1375-1378, Dec. 20, 1985.
Ingber, et al.,A Possible Mechanism for Inhibition of Angiogenesis by Angiostatic Steroids: Induction of Capillary Basement Membrane Dissolution, Endocrinology, vol. 119(4):1768-1775, 1986.
Li, et al.,Angiostatic Steroids Potentiated by Sulphated Cyclodextrin Inhibit Corneal Neovascularization, Investigative Ophthalmology and Visual Science, vol. 32(11):2898-2905, Oct., 1991.
Asrani & Zeimer,Feasibility of Laser Targeted Photo-Occlusion of Ocular Vessels, Br J Ophthalmol., vol. 79(8):776-770, Aug., 1995.
Asrani et al,Feasibility of Laser Targeted Photoocclusion of the Choriocapillary Layer in Rats, Investigative Ophthalmol. & Vis. Sci., vol. 38(13):2702-2710, Dec., 1997.
Husain et al,Photodynamic Therapy and Digital Angiography of Experimental Iris Neovascularization UsingLiposomal Benzoporphyrin Derivative; Ophthalmology, vol. 104(8):1242-1250, Aug., 1997.
Lin et al,The Photodynamic Occlusion of Choroidal Vessels Using Benzoporphyrin Derivative, Curr Eye Res, vol. 13(7):513-522, Jul., 1994.
Gragoudas et al,Results and Preliminary Dosimetry of Photodynamic Therapy for Choroidal Neovascularization . . ., Investigative Ophthalmology & Visual Science, vol. 38(4):S17, Mar. 15, 1997.
Sickenberg et al,Preliminary Results of Photodynamic Therapy for Choroidal Neovascularization in . . ., Investigative Ophthalmology & Visual Science, vol. 38(4):S92, Mar. 15, 1997.
Thomas et al,Purlytin™ (SnET2)-Photodynamic Therapy Produces Closure or Subfoveal Choroidal . . ., Investigative Ophthalmology & Visual Science, vol. 39(4):S242, Mar. 15, 1998.
Folkman, et al.,Angiogenic Factors, Science, vol. 235, pp. 442-447, 1987.
Furcht,Critical Factors Controlling Angiogenesis: Cell Products, Cell Matrix, and Growth Factors, Laboratory Investigation, vol. 55(5):505-509, 1986.
Cariou, et al.,Inhibition of Human Endothelial Cell Proliferation by Heparin and Steroids, Cell Biology International Reports, vol. 12(12):1037-1047, Dec., 1988.
Tokida, et al.,Production of Two Variant Laminin Forms by Endothelial Cells and Shift of Their Relative Levels by Angiostatic Steroids, The Journal of Biological Chemistry, vol. 265(30):18123-18129, Oct. 25, 1990.
Maragoudakis, et al.,Antiangiogenic Action of Heparin Plus Cortisone is Associated with Decreased Collagenous Protei
Alcon Manufacturing Ltd.
Fay Zohreh
Yeager Sally S.
LandOfFree
Use of angiostatic steroids in photodynamic therapy does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of angiostatic steroids in photodynamic therapy, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of angiostatic steroids in photodynamic therapy will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2583955