Claims for Patent: 6,939,542

Summary for Patent: 6,939,542

Title:	Hyaluronidase preparation for ophthalmic administration and enzymatic methods for accelerating clearance of hemorrhagic blood from the vitreous body of the eye
Abstract:	A thimerosal-free hyaluronidase preparation wherein the preferred hyaluronidase enzyme is devoid of molecular weight fractions below 40,000 MW, between 60-70,000 MW and above 100,000 MW. Also disclosed is a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye, said method comprising the step of contacting at least one hemorrhage-clearing enzyme (e.g., a .beta.-glucuronidase, matrix metalloproteinase, chondroitinase, chondroitin sulfatase or protein kinase) with the vitreous humor in an amount which is effective to cause accelerated clearance of blood therefrom.
Inventor(s):	Karageozian; Hampar L. (San Juan Capistrano, CA), Karageozian; Vicken H. (San Juan Capistrano, CA), Kenney; Maria Cristina (Malibu, CA), Gutierrez Flores; Jose Luis (Tijuana, MX), Carpio Aragon; Gabriel Arturo (Tijuana, MX), Nesburn; Anthony B. (Malibu, CA)
Assignee:	Ista Pharmaceuticals, Inc. (Irvine, CA)
Application Number:	10/369,372
Patent Claims:	1. A method for accelerating the clearance of hemorrhagic blood from the vitreous humor of a mammalian eye, said method comprising: contacting with the vitreous humor an amount of a solution which contains hyaluronidase to provide a dose of at least 1 International Unit of hyaluronidase, said solution being free of thimerosal, and essentially devoid of hyaluronidase molecular weight fractions above 100,000, between 60,000 and 70,000, and below 40,000 as determined by 10% SDS PAGE electrophoresis and wherein said hyaluronidase is defined as causing hydrolysis of the endo-N-acetyl hexosaminic bonds of hyaluronic acid. 2. The method of claim 1, wherein the dose of hyaluronidase is 1 International Unit. 3. The method of claim 1, wherein the dose of hyaluronidase is 1-50 International Units. 4. The method of claim 1, wherein the dose of hyaluronidase is 25-75 International Units. 5. The method of claim 1, wherein the dose of hyaluronidase is 50-200 International Units. 6. The method of claim 1, wherein the dose of hyaluronidase is 25 International Units. 7. The method of claim 1, wherein the dose of hyaluronidase is 50 International Units. 8. The method of claim 1, wherein the dose of hyaluronidase is 70 International Units. 9. The method of claim 1, wherein the dose of hyaluronidase is 200 International Units. 10. The method of claim 1, wherein the dose of hyaluronidase is 10-300 International Units. 11. The method of claim 1, wherein the contacting step is performed a single time, resulting in the contacting with the vitreous humor of a single dose of at least 1 International Unit of said hyaluronidase. 12. The method of claim 1, wherein the contacting step is performed at least twice, resulting in the contacting with the vitreous humor of at least two separate doses of said hyaluronidase, each dose being at least 1 International Unit. 13. The method of claim 1, wherein the solution which contains an amount of hyaluronidase to provide said dose comprises the ingredients hyaluronidase, lactose, and phosphate. 14. The method of claim 13, wherein the ingredients are dissolved in sterile water, sterile filtered, and lyophilized to a dry composition. 15. The method of claim 14, wherein the dry composition is dissolved in a balanced salt solution. 16. The method of claim 15, wherein the solution is a solution for injection. 17. The method of claim 1, wherein the hyaluronidase is ovine testicular hyaluronidase. 18. A method for accelerating the clearance of hemorrhagic blood from the vitreous humor of a mammalian eye not as an adjunct to vitrectomy, said method comprising: contacting with the vitreous humor an amount of a solution which contains hyaluronidase to provide a dose of at least 1 International Unit of hyaluronidase, said solution being free of thimerosal, and essentially devoid of hyaluronidase molecular weight fractions above 100,000, between 60,000 and 70,000, and below 40,000 as determined by 10% SDS PAGE electrophoresis, wherein said contacting step is practiced in the absence of vitrectomy, and wherein said hyaluronidase is defined as causing hydrolysis of the endo-N-acetyl hexosaminic bonds of hyaluronic acid.

Details for Patent 6,939,542

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	05/05/2004		2015-11-22
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	12/02/2004		2015-11-22
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	10/26/2004		2015-11-22
Akorn, Inc.	HYDASE	hyaluronidase	Injection	021716	10/25/2005		2015-11-22
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2015-11-22