Controlled release microencapsulated NGF formulation

• US 7,163,701 B2
• Filed: 05/20/2003
• Issued: 01/16/2007
• Est. Priority Date: 06/13/1997
• Status: Expired due to Fees

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Cleland, Jeffrey L., Lam, Xanthe M., Duenas, Eileen T.
• Primary Examiner(s): HAYES, ROBERT CLINTON
• Application Number:
  US10/442,894
• Publication Number:
  US 20030203040A1
• Time in Patent Office: 1,337 Days
• Field of Search: 424/491, 530/399
• US Class Current: 424/491
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: C07K 14/48 Nerve growth factor [NGF]

Abstract

NGF microencapsulation compositions having controlled release characteristics, preferably with increased stability, for the NGF component, particularly human recombinant NGF (“rhNGF”) are provided that yield enhanced stability of NGF for use in promoting nerve cell growth, repair, survival, differentiation, maturation or function. Methods for making and using such compositions are also provided.

Claims

1. A polymeric microsphere device having a diameter of less than about 1000 microns for sustained controlled release of NGF and another neurotrophic factor selected from NT-3, NT-4/5, BDNF, and combinations thereof, comprising a biocompatible polymeric microsphere containing about 0.1% to about 50% NGF by weight complexed with an NGF-stabilizing metal that binds NGF, and another neurotrophic factor selected from NT-3, NT-4/5, BDNF, and combinations thereof, which device is capable of releasing NGF over a period of time in excess of about one day.

2. The polymeric microsphere device of claim 1, wherein the microspheres have a particle size of between about 0.1 microns and about 300 microns.

3. The polymeric microsphere device of claim 1, wherein the microspheres have a particle size of between about 1 micron and about 150 microns.

4. The polymeric microsphere device of claim 1, wherein the microspheres have a particle size of between about 2 microns and about 100 microns.

5. The polymeric microsphere device of claim 1, wherein the microspheres have a particle size of between about 20 microns and about 90 microns.

6. A method of making a microsphere device for controlled sustained release of neurotrophic factors, comprising:

mixing NGF in solution with an NGF-stabilizing salt of a metal that binds NGF, wherein the molar ratio of NGF to the metal is from about 1 to 4 to about 1 to 50, and

microencapsulating the NGF-metal mixture with another neurotrophic factor selected from NT-3, NT-4/5, BDNF, and combinations thereof to form a biocompatible polymeric microsphere capable of controlled sustained release of NGF containing about 0.1% to about 50% NGF by weight complexed with an NGF-stabilizing metal that binds NGF, and another neurotrophic factor selected from NT-3, NT-4/5, BDNF, and combinations thereof.

7. The method of claim 6, wherein the microspheres have a particle size of between about 1 micron to about 1000 microns.

8. The method of claim 6, wherein the microspheres have a particle size of between about 0.1 microns and about 300 microns.

9. The method of claim 6, wherein the microspheres have a particle size of between about 1 micron and about 150 microns.

10. The method of claim 6, wherein the microspheres have a particle size of between about 2 microns and about 100 microns.

11. The method of claim 6, wherein the microspheres have a particle size of between about 20 microns and about 90 microns.