Methods and compositions for targeting proteins across the blood brain barrier

• US 20030072761A1
• Filed: 04/30/2002
• Published: 04/17/2003
• Est. Priority Date: 10/16/2001
• Status: Abandoned Application

• Current Assignee: Biomarin Pharmaceutical Incorporated (Amgen Inc.)
• Original Assignee: Biomarin Pharmaceutical Incorporated (Amgen Inc.)
• Inventors: LeBowitz, Jonathan
• Application Number:
  US10/136,639
• Publication Number:
  US 20030072761A1
• Time in Patent Office: Days
• US Class Current: 424/178.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C07K 2319/50 containing protease site
• CPC Class Codes: C07K 2319/74 containing a fusion for binding to a cell surface receptor

Abstract

Disclosed are methods and compositions for targeting therapeutic proteins to the brain. Methods and compositions of the invention involve associating an IGF moiety with a therapeutic protein in order to target the therapeutic protein to the brain. Soluble fusion proteins that include an IGF targeting moiety are transported to neural tissue in the brain from blood. Methods and compositions of the invention include therapeutic applications for treating lysosomal storage diseases. The invention also provides nucleic acids and cells for expressing IGF fusion proteins.

Claims

1. A method for targeting a polypeptide to the brain, the method comprising the step of providing a polypeptide in association with an IGF moiety to a mammal, thereby resulting in accumulation of the polypeptide in the brain of said mammal.

5. The method of claim 1 or 2, wherein said IGF moiety is an IGF-I targeting moiety.

2. A method for producing a CNS-targeted polypeptide, the method comprising the step of expressing a polypeptide in association with an IGF moiety, thereby to produce a polypeptide with a CNS-targeting tag.

3. A composition comprising a polypeptide in association with an IGF moiety, wherein said IGF moiety targets the composition to the brain.

4. The composition of claim 3 wherein said polypeptide and IGF moiety are expressed as a fusion protein.

6. The composition of claim 3 or 4, wherein said IGF moiety is an IGF-I targeting moiety.