Claims for Patent: 6,991,788

Summary for Patent: 6,991,788

Title:	Utilization of wolinella succinogenes asparaginase to treat diseases associated with asparagine dependence
Abstract:	Described herein are methods for producing recombinant forms of asparaginase derived from Wolinella succinogenes. In addition, methods for covalent modification of proteins, including asparaginases, by acylation are also provided. Certain embodiments provide for epitopic-labeling of the amino terminus of W. succinogenes asparaginase. Additional embodiments concern methods for the therapeutic utilization of the native, homotetrameric form of W. succinogenes asparaginase, as well as the use of epitopically-labeled or non-epitopically-labeled recombinant W. succinogenes asparaginase (or a covalently modified analog thereof) in the therapeutic treatment of malignant and non-malignant hematological disease and other diseases where asparagine depletion or deprivation would be efficacious or which respond to asparagine depletion or deprivation, as well as their potential utilization in the therapeutic treatment of autoimmune diseases such as rheumatoid arthritis, AIDS, and SLE.
Inventor(s):	Durden; Donald L. (Glendale, CA)
Assignee:	Childrens Hospital Los Angeles (Los Angeles, CA)
Application Number:	10/349,374
Patent Claims:	1. A method of producing a recombinant Wolinella succinogenes asparaginase analog containing a N-terminal tag, the method comprising the steps of: (a) obtaining a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 3; (b) cloning the nucleic acid sequence into an expression vector; (c) introducing the expression vector into a suitable host cell or cells; (d) culturing the host cell(s) under conditions that allow expression of the asparaginase from the expression vector in biologically active form or in a form from which biological activity can be reconstituted; and (e) subjecting the asparaginase to modification by acylation with one or more acyl halides, wherein the modified asparaginase has asparaginase enzyme activity. 2. The method of claim 1, further comprising the step of isolating said asparaginase. 3. The method of claim 1, wherein said method is performed in vivo. 4. The method of claim 1, wherein said expression vector is carried in a gene delivery vehicle. 5. The method of claim 4 wherein said gene delivery vehicle is selected from the group consisting of a recombinant virus and a non-viral gene delivery system. 6. The method of claim 2, wherein said polypeptide is an analog Wolinella succinogenes asparaginase. 7. The method of claim 2, wherein said polypeptide is covalently modified by a process selected from the group consisting of acylation and pegylation. 8. The method of claim 7, wherein said acylation is accomplished by using one or more acyl halides. 9. A composition comprising a purified recombinant Wolinella succinogenes asparaginase analog, obtained by the method of claim 1. 10. The composition of claim 9, further comprising a pharmaceutically acceptable carrier.

Details for Patent 6,991,788

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2017-06-09