Production and delivery of a stable collagen

Patent metadata

Field	Value
Publication number	US-9403895-B2
Application number	US-201514700951-A
Country	US
Kind code	B2
Filing date	Apr 30, 2015
Priority date	Apr 26, 2011
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

Improved methods are provided for the recombinant synthesis of collagen, particularly collagen VII, in host cell, and for therapeutic delivery of the same. The recombinant collagen is produced in a host cell that has increased levels of prolyl-4-hydroxylase, relative to basal cell levels. The collagen produced by the methods of the invention has increased numbers of modified proline residues, relative to a recombinant collagen produced in a host cell having basal levels of prolyl-4-hydroxylase. The increased proline modification provides for a collagen having increased stability, including increased in vivo stability.

First claim

What is claimed is:

1. A method of delivering collagen VII to the dermal layer of skin, the method comprising:
fabricating an array of biodegradable microneedles comprising collagen VII incorporated into the microneedles; and
contacting the skin of an individual with said array with a pressure sufficient to penetrate the skin to the depth of anchoring fibrils.

2. The method of claim 1 , wherein the method further comprises:
producing collagen VII for incorporation into the microneedles, by synthesizing recombinant collagen VII in a host cell that has been genetically modified to increase expression of prolyl-4-hydroxylase.

3. The method of claim 2 , wherein said individual suffers from epidermolysis bullosa.

4. An array of biodegradable microneedles, wherein said microneedles comprise collagen VII incorporated into the microneedles.

5. The array of claim 4 , wherein said collagen VII is produced by the method of synthesizing recombinant collagen VII in a host cell that has been genetically modified to increase expression of prolyl-4-hydroxylase;
wherein recombinantly produced collagen VII has increased stability relative to a collagen produced in a comparable host cell lacking said genetic modification.

6. The method of claim 1 , wherein the microneedles are comprised of alginate or chitosan mixed with Collagen VII.

7. The array of claim 4 , wherein the microneedles are comprised of alginate or chitosan mixed with Collagen VII.

Assignees

• Univ Leland Stanford Junior
• Us Veterans Affairs

Inventors

• Marinkovich M Peter
• Lane Alfred T
• Rajadas Jayakumar

Classifications

• A61M37/0015

  by using microneedles · CPC title

• C12N15/67

  General methods for enhancing the expression · CPC title

• C07K14/78 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• A61K38/39

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG] · CPC title

• A61M2037/0023

  Drug applicators using microneedles · CPC title