Acid alpha-glucosidase and fragments thereof

• US 7,785,856 B2
• Filed: 09/12/2007
• Issued: 08/31/2010
• Est. Priority Date: 02/10/2004
• Status: Active Grant

• Current Assignee: Biomarin Pharmaceutical Incorporated (Amgen Inc.)
• Original Assignee: ZyStor Therapeutics, Inc. (Amgen Inc.)
• Inventors: LeBowitz, Jonathan, Maga, John
• Primary Examiner(s): RAGHU, GANAPATHIRAM
• Application Number:
  US11/900,659
• Publication Number:
  US 20080299640A1
• Time in Patent Office: 1,084 Days
• Field of Search: None
• US Class Current: 435/201
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 9/2408 acting on alpha -1,4-glucosidic bonds

Abstract

Targeted acid alpha-glucosidase therapeutics that localize to the lysosome are provided. The targeted therapeutics include a therapeutic agent, GAA, and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Claims

1. A targeted therapeutic fusion protein comprising amino acid residues 70-952 of human acid alpha-glucosidase (GAA) (SEQ ID NO:

54) and a peptide tag comprising residue 1 followed by residues 8-67 of wild-type mature human insulin-like growth factor II (IGF-II) (SEQ ID NO;

70), residues 2-7 of mature human IGF-II (SEQ ID NO;

70) being deleted, wherein the peptide tag is linked to amino acid residue 70 of human GAA (SEQ ID NO;

54).

2. The targeted therapeutic fusion protein of claim 1, further comprising a spacer between the amino acid residues 70-952 of human GAA and the peptide tag.

3. The targeted therapeutic fusion protein of claim 2, wherein the spacer is a Gly-Ala-Pro (SEQ ID NO:

69) linker.