Matrix-free osteogenic devices, implants and methods of use thereof

• US 6,426,332 B1
• Filed: 06/22/2001
• Issued: 07/30/2002
• Est. Priority Date: 02/07/1997
• Status: Expired due to Term

• Current Assignee: Mariel Therapeutics, Inc.
• Original Assignee: Stryker Corporation
• Inventors: Rueger, David C., Tucker, Marjorie M.
• Primary Examiner(s): Russel, Jeffrey E.
• Application Number:
  US09/887,901
• Publication Number:
  US 20020091077A1
• Time in Patent Office: 403 Days
• Field of Search: 424/422, 424/423, 424/426, 514/8, 514/12, 514/21, 604/500, 604/506, 604/518, 604/522
• US Class Current: 514/8.8
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease

Abstract

Provided herein are methods for inducing bone formation in a mammal sufficient to fill a defect defining a void, wherein osteogenic protein is provided alone or dispersed in a biocompatible non-rigid, amorphous carrier having no defined surfaces. The methods and devices provide injectable formulations for filling critical size defects, as well as for accelerating the rate and enhancing the quality of bone formation in non-critical size defects.

Claims

1. A device for inducing bone formation sufficient to fill a defect locus defining a void, the device comprising:

an osteogenic protein dispersed in a biocompatible, nonrigid amorphous carrier having no defined surfaces, wherein said carrier is selected from the group consisting of poloxamers;

gelatins;

polyethylene glycols (PEG);

dextrins; and

vegetable oils;

with the proviso that said osteogenic protein is not TGF-β

.

2. The device of claim 1 wherein said carrier comprises a gel.

3. The device of claim 1 wherein said carrier comprises an aqueous solution.

4. The device of claim 1 wherein said carrier is selected from the group consisting of:

mannitol;

PEG 3350;

poloxamer 407; and

sesame oil.

5. The device of claim 1 wherein said osteogenic protein is selected from the group consisting of OP1;

OP2, OP3, BMP2;

BMP3;

BMP4;

BMP5;

BMP6;

BMP-10, BMP-11, BMP-12, BMP-15, BMP-3b, BMP9;

DPP;

Vg1;

Vgr;

60A protein;

GDF-1;

GDF-3, GDF-5, GDF-6, GDF-7, GDF-8, GDF-9, GDF-10, GDF-11; and

amino acid sequence variants thereof.

6. The device of claim 1 wherein said osteogenic protein is selected from the group consisting of OP1;

OP2, BMP2;

BMP4;

BMP5;

BMP6; and

amino acid sequence variants thereof.

7. The device of claim 1 wherein said osteogenic protein is a morphogen, said morphogen comprising an amino acid sequence having at least 70% homology within the C-terminal 102-106 amino acids, including the conserved seven cysteine domain, of human OP-1.

8. The device of claim 1 wherein said osteogenic protein is OP1.

9. The device of claim 1 wherein said osteogenic protein is mature OP1 solubilized in a saline solution.