US5854207A
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Compositions and therapeutic methods using morphogenic proteins and stimulatory factors
Assignee: MARIEL THERAPEUTICS Inc
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Filing: 1998-02-23
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Granted: 1998-12-29
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Expires: 2018-02-23
Abstract
Abstract The present invention provides pharmaceutical compositions comprising a morphogenic protein stimulatory factor (MPSF) for improving the tissue inductive activity of morphogenic proteins, particularly those belonging to the BMP protein family. Methods for improving the tissue inductive activity of a morphogenic protein in a mammal using those compositions are provided. This invention also provides implantable morphogenic devices comprising a morphogenic protein and a MPSF disposed within a carrier, that are capable of inducing tissue formation in allogeneic and xenogeneic implants. Methods for inducing local tissue formation from a progenitor cell in a mammal using those devices are also provided. A method for accelerating allograft repair in a mammal using morphogenic devices is provided. This invention also provides a prosthetic device comprising a prosthesis coated with a morphogenic protein and a MPSF, and a method for promoting in vivo integration of an implantable prosthetic device to enhance the bond strength between the prosthesis and the existing target tissue at the joining site. Methods of treating tissue degenerative conditions in a mammal using the pharmaceutical compositions are also provided.
Inventors
- 👤 John C. Lee
- 👤 Lee-Chuan C. Yeh
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:23
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/227; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/1875; A61K38/22; A61K38/30; A61L24/00; A61L24/04; A61L24/10; A61L24/108; A61P; A61P19/00; A61P43/00
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
168 words
A pharmaceutical composition for inducing tissue formation in a mammal, comprising: a) a morphogenic protein capable of inducing tissue formation when accessible to a progenitor cell in the mammal; b) a morphogenic protein stimulatory factor selected from the group consisting of hormones, cytokines, peptides and growth factors, said factor capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell; and c) a pharmaceutically acceptable carrier; with the proviso that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer, TGF-β or activin, the MPSF may not be estrogen or calcitonin; when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer or TGF-β, the MPSF may not be FGF, IGF-II, PDGF or vitamin D; and when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone.
Claim 2
Dependent Claim
168 words
A pharmaceutical composition for inducing tissue formation in a mammal, comprising: a) a morphogenic protein capable of inducing tissue formation when accessible to a progenitor cell in the mammal; b) a morphogenic protein stimulatory factor selected from the group consisting of hormones, cytokines, peptides and growth factors, said factor capable of stimulating the ability of the morphogenic protein to induce tissue formation from the progenitor cell; and c) a pharmaceutically acceptable carrier; with the proviso that when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer, TGF-β or activin, the MPSF may not be estrogen or calcitonin; when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a BMP homodimer or TGF-β, the MPSF may not be FGF, IGF-II, PDGF or vitamin D; and when the progenitor cell is an osteoblast stimulated to form bone and the morphogenic protein is a homodimer of BMP-2 or BMP-3, the MPSF may not be parathyroid hormone.
Claim 3
Dependent Claim
39 words
The composition according to claim 1, wherein the morphogenic protein comprises a pair of subunits disulfide bonded to produce a dimeric species and wherein at least one of the subunits comprises a polypeptide belonging to the BMP protein family.
Claim 4
Dependent Claim
14 words
The composition according to claim 1, wherein the morphogenic protein is an osteogenic protein.
Claim 5
Dependent Claim
21 words
The composition according to claim 3 osteogenic protein is capable of inducing the progenitor cell to form endochondral or intramembranous bone.
Claim 6
Dependent Claim
20 words
The composition according to claim 3, wherein the osteogenic protein is capable of inducing the progenitor cell to form cartilage.
Claim 7
Dependent Claim
27 words
The composition according to any one of claims 1-3, wherein the morphogenic protein is capable of inducing the progenitor cell to form tissue tendon/ligament-like or neural-like tissue.
Claim 8
Dependent Claim
37 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises a polypeptide selected from the group consisting of: BMP-2, BMP-4, BMP-5, BMP-6, BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, and BMP-13, COP-5, COP-7.
Claim 9
Dependent Claim
27 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises a polypeptide selected from the group consisting of OP-1, BMP-2, BMP-4 and BMP-6.
Claim 10
Dependent Claim
15 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1.
Claim 11
Dependent Claim
24 words
The composition according to claim 2, wherein the dimer is a homo- or a heterodimer comprising at least one BMP-2 or OP-1 (BMP-7) subunit.
Claim 12
Dependent Claim
57 words
The composition according to any one of claims 1-3, wherein the morphogenic protein stimulatory factor comprises at least one compound selected from the group consisting of: insulin-like growth factor I (IGF-I), estradiol, fibroblast growth factor (FGF), growth hormone (GH), growth and differentiation factor (GDF), hydrocortisone (HC), insulin, progesterone, parathyroid hormone (PTH), vitamin D, retinoic acid and IL-6.
Claim 13
Dependent Claim
25 words
The composition according to any one of claims 1-3, wherein the morphogenic protein stimulatory factor comprises an agent that increases IGF-I bioactivity in the mammal.
Claim 14
Dependent Claim
37 words
The composition according to any one of claims 1-3, wherein the morphogenic protein stimulatory factor is present in an amount capable of synergistically stimulating the ability of the morphogenic protein to induce tissue formation in the mammal.
Claim 15
Dependent Claim
41 words
The composition according to any one of claims 1-3, wherein the morphogenic protein is present at a concentration of at least about 1 ng/ml, and the morphogenic protein stimulatory factor is present at a concentration of at least about 0.01 ng/ml.
Claim 16
Dependent Claim
46 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises IGF-I at a concentration from about 0.1 ng/ml to about 50 ng/ml.
Claim 17
Dependent Claim
16 words
The composition according to claim 15, comprising 200 ng/ml of OP-1 and 25 ng/ml of IGF-I.
Claim 18
Dependent Claim
47 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises estradiol at a concentration of from about 0.05 nM to about 1000 nM.
Claim 19
Dependent Claim
17 words
The composition according to claim 17, comprising about 200 ng/ml of OP-1 and about 5 nM estradiol.
Claim 20
Dependent Claim
48 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises growth hormone at a concentration of from about 5 ng/ml to about 1000 ng/ml.
Claim 21
Dependent Claim
18 words
The composition according to claim 19, comprising about 200 ng/ml of OP-1 and about 500-1000 ng/ml growth hormone.
Claim 22
Dependent Claim
47 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises hydrocortisone at a concentration of from about 0.05 nM to about 5.0 nM.
Claim 23
Dependent Claim
16 words
The composition according to claim 21, comprising about 200 ng/ml OP-1 and about 0.5-5.0 nM hydrocortisone.
Claim 24
Dependent Claim
47 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises insulin at a concentration of from about 0.01 nM to about 1000 nM.
Claim 25
Dependent Claim
16 words
The composition according to claim 23, comprising about 200 ng/ml OP-1 and about 0.05 nM insulin.
Claim 26
Dependent Claim
48 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises parathyroid hormone at a concentration of from about 10 nM to about 1000 nM.
Claim 27
Dependent Claim
17 words
The composition according to claim 25, comprising about 200 ng/ml OP-1 and about 25-200 nM parathyroid hormone.
Claim 28
Dependent Claim
47 words
The composition according to any one of claims 1-3, wherein the morphogenic protein comprises OP-1 at a concentration of from about 1 ng/ml to about 500 ng/ml and the morphogenic protein stimulatory factor comprises progesterone at a concentration of from about 0.05 nM to about 1000 nM.
Claim 29
Dependent Claim
16 words
The composition according to claim 27, comprising about 200 ng/ml OP-1 and about 0.05-5 nM progesterone.
References Cited (Backward Citations)
US5459047A
Cited
US5258494A
Cited
US5354557A
Cited
US5108753A
Cited
US5344654A
Cited
US5324819A
Cited
US5011691A
Cited
US5461034A
Cited
US5171574A
Cited
US5162114A
Cited
EP0436469A1
Cited
WO1993005823A1
Cited
WO1992009697A1
Cited
EP0514720A2
Cited
WO1992021365A1
Cited
WO1995005846A1
Cited
WO1995016034A1
Cited
WO1995016035A2
Cited
WO1995024210A1
Cited
JPH0948738A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-12-28 | 2002-06-29 | 2002-12-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-12-28 | 2006-06-29 | 2006-12-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-12-28 | 2010-06-29 | 2010-12-29 | $7700.00 | Window Closed / Lapsed |