Compounds and methods for reversible modification of biologically active molecules

• US 8,541,548 B2
• Filed: 06/17/2008
• Issued: 09/24/2013
• Est. Priority Date: 06/07/1999
• Status: Expired due to Fees

• Current Assignee: Arrowhead Madison Inc (Arrowhead Pharmaceuticals, Inc.)
• Original Assignee: Arrowhead Madison Inc (Arrowhead Pharmaceuticals, Inc.)
• Inventors: Rozema, David B.
• Primary Examiner(s): Cordero Garcia, Marcela M
• Application Number:
  US12/140,751
• Publication Number:
  US 20080281074A1
• Time in Patent Office: 1,925 Days
• Field of Search: None
• US Class Current: 530/345
• CPC Class Codes: A01K 2217/058 due to expression of inhibitory nucleic acid, e.g. siRNA, antisense
• CPC Class Codes: A01K 2267/0362 Animal model for lipid/glucose metabolism, e.g. obesity, type-2 diabetes
• CPC Class Codes: A61K 48/0041 the non-active part being polymeric
• CPC Class Codes: C07C 233/21 having the carbon atom of the carboxamide group bound to an acyclic carbon atom of an unsaturated carbon skeleton containing rings other than six-membered aromatic rings
• CPC Class Codes: C07C 233/31 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
• CPC Class Codes: C07C 233/39 having the carbon atom of the carboxamide group bound to an acyclic carbon atom of an unsaturated carbon skeleton containing rings other than six-membered aromatic rings
• CPC Class Codes: C07D 307/60 Two oxygen atoms, e.g. succinic anhydride
• CPC Class Codes: C07D 475/00 Heterocyclic compounds containing pteridine ring systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

The present invention is directed compounds for reversibly modification of biologically active molecules. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.

Claims

1. An amine-reactive modifying agent represented by the structure consisting of:

2. The amine modifying agent of claim 1 wherein said poly(ethylene glycol) contains 1-500 ethylene glycol units.

3. The amine-reactive modifying agent of claim 2 wherein the modifying agent is represented by the structure selected from the group consisting of:

4. The amine-reactive modifying agent of claim 1 wherein the modifying agent is represented by the structure consisting of:

5. The amine modifying agent of claim 1 wherein the galactose comprises a galactosamine.

6. The amine-reactive modifying agent of claim 1 wherein the modifying agent is represented by the structure selected from the group consisting of:

7. The amine modifying agent of claim 1 wherein the vitamin comprises folate.

8. The amine-reactive modifying agent of claim 7 wherein the modifying agent is represented by the structure consisting of:

9. The amine-reactive modifying agent of claim 1 wherein the modifying agent is represented by the structure consisting of:

10. A pH labile compound represented by the structure consisting of: