Claims for Patent: 4,499,065

Summary for Patent: 4,499,065

Title:	Chymopapain allergen and method
Abstract:	A chymopapain derivative having the enzymatic activity reduced by at least 95% while retaining the original allergenic activity of at least 90% is suitable for skin testing to detect allergic hypersensitivity to chymopapain and for treating patients exhibiting allergic hypersensitivity to chymopapain. The enzymatic activity can be blocked by reacting thiol groups of the enzyme with and iodoacetic acid, bromoacetic acid, or a salt, ester or amide derivative thereof, under conditions which block the undesirable enzymatic activity while retaining the desired allergenic activity.
Inventor(s):	Calenoff; Emanuel (Burlingame, CA), Jones; Ruth M. (Redwood City, CA), Tsay; Yuh-Geng (San Jose, CA), Beigler; Myron A. (Los Altos Hills, CA)
Assignee:	Axonica, Inc. (Mt. View, CA)
Application Number:	06/489,898
Patent Claims:	1. A chymopapain derivative, the enzymatic activity thereof being less than 5% of the enzymatic activity of natural chymopapain, and the allergenic activity being at least 90% of the allergenic activity of the natural chymopapain. 2. A chymopapain derivative of claim 1, sufficient thiol groups thereof having been converted to a carboxymethylthio group or a salt thereof, a carbamoylmethylthio group, or a (lower alkoxy)carbonylthio group to reduce the enzymatic activity thereof to less than 5 of the enzymatic activity of natural chymopapain while retaining at least 90% of the allergenic activity of natural chymopapain. 3. A chymopapain derivative of claim 1 wherein the thiol group thereof has been converted to a carboxymethylthio group or a salt thereof, the cation thereof being pharmaceutically acceptable. 4. A chymopapain derivative of claim 1 wherein from at least 95% of the thiol groups have been converted to carboxymethylthio groups or a salt thereof. 5. A method for reducing enzymatic activity of chymopapain comprising reacting chymopapain in an aqueous solution having a pH of from 4 to 9 at a temperature within the range of from 4.degree. to 40.degree. C. with a haloacetic acid compound selected from the group consisting of iodoacetic acid, a salt thereof, a lower alkyl ester thereof; bromoacetic acid, a salt thereof, a lower alkyl ester thereof; bromoacetamide; and iodoacetamide, the molar ratio of the haloactic acid compound to chymopapain being within the range of from 10 to 200, until the enzymatic activity of the chymopapain is reduced by 95% but before the allergenic activity of the chymopapain is reduced to less than 90%. 6. The method of claim 5 wherein the haloacetic acid compound is iodoacetic acid or a salt thereof having a pharmaceutically acceptable cation, and the reaction is carried out in an aqueous solution containing from 0.1 to 50 mg per ml of chymopapain and from 5 to 90 micrograms per liter of iodoacetic acid or a salt thereof. 7. The method of claim 6 wherein the aqueous solution has a pH of from 6 to 8, and the reaction is carried out at a temperature of from 4.degree. to 22.degree. C. 8. The product produced by the method of claim 5. 9. The product produced by the method of claim 6. 10. The product produced by the method of claim 7. 11. A method for treating a patient having hypersensitivity to chymopapain comprising administering a desensitizing amount of a pharmaceutically acceptable chymopapain derivative of claim 1 to the patient. 12. A method for treating a patient having hypersensitivity to chymopapain comprising administering a desensitizing amount of a pharmaceutically acceptable product of claim 5 to the patient. 13. A method for detecting chymopapain allergic hypersensitivity comprising carrying out a skin test with a pharmaceutically acceptable chymopapain derivative of claim 1. 14. A method for detecting chymopapain allergic hypersensitivity comprising carrying out a skin test with a product of claim 5.

Details for Patent 4,499,065

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Discure Medical, Llc	CHYMODIACTIN	chymopapain	For Injection	018663	11/10/1982		2040-04-01
Discure Medical, Llc	CHYMODIACTIN	chymopapain	For Injection	018663	08/21/1984		2040-04-01