CA2176942A1 - Bmp-12, bmp-13 and tendon-inducing compositions thereof - Google Patents

Bmp-12, bmp-13 and tendon-inducing compositions thereof

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Publication number
CA2176942A1
CA2176942A1 CA002176942A CA2176942A CA2176942A1 CA 2176942 A1 CA2176942 A1 CA 2176942A1 CA 002176942 A CA002176942 A CA 002176942A CA 2176942 A CA2176942 A CA 2176942A CA 2176942 A1 CA2176942 A1 CA 2176942A1
Authority
CA
Canada
Prior art keywords
bmp
seq
amino acid
protein
tendon
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002176942A
Other languages
French (fr)
Other versions
CA2176942C (en
Inventor
Anthony J. Celeste
John M. Wozney
Vicki A. Rosen
Neil M. Wolfman
Gerald H. Thomsen
Douglas A. Melton
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Harvard College
Genetics Institute LLC
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US08/333,576 external-priority patent/US6027919A/en
Application filed by Individual filed Critical Individual
Publication of CA2176942A1 publication Critical patent/CA2176942A1/en
Application granted granted Critical
Publication of CA2176942C publication Critical patent/CA2176942C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/51—Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1875—Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
    • A61L27/3843—Connective tissue
    • A61L27/386—Ligaments, tendons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

Abstract

Bone morphogenetic proteins BMP-12 and BMP-13 have been cloned. Compositions of these proteins with tendon/ligament-like tissue inducing activity are disclosed. The compositions are useful in the treatment of tendinitis and tendon or ligament defects and in related tissue repair.

Claims (28)

1. A DNA molecule comprising an isolated DNA sequence encoding a BMP-12 related protein.
2. A DNA molecule according to claim 1, wherein said DNA sequence is selected from the group consisting of:
(a) nucleotides #496, #571 or #577 to #882 of SEQ ID NO:1;
(b) nucleotides #605 or #659 to #964 of SEQ ID NO:25; and (c) sequences which hybridize to (a) or (b) under stringent hybridization conditions and encode a BMP-12 related protein which exhibits the ability to form tendon/ligament-like tissue.
3. A DNA molecule comprising the DNA sequence of claim 1 wherein said DNA sequence is selected from the group consisting of:
(a) nucleotides encoding for amino acids #-25, #1 or #3 to #104 of SEQ ID NO:2;
(b) in a 5' to 3' direction, nucleotides encoding a propeptide selected from the group consisting of native BMP-12 propeptide and a BMP protein propeptides; and nucleotides encoding for amino acids #-25, #1 or #3 to #104 of SEQ ID NO:2; and (c) nucleotides encoding for amino acids #1 or #19 to #120 of SEQ ID
NO:26;
(d) in a 5' to 3' direction, nucleotides encoding a propeptide selected from the group consisting of native BMP-12 propeptide and a BMP protein propeptide; and nucleotides encoding for amino acids #1 or #19 to #120 of SEQ
ID NO:26;
(e) sequences which hybridize to any of (a) through (d) under stringent hybridization conditions and encode a BMP-12 related protein which exhibits the ability to form cartilage and/or bone.
4. A host cell transformed with a DNA molecule according to claim 1.
5. A host cell transformed with the DNA molecule of claim 2.
6. A host cell transformed with the DNA molecule of claim 3.
7. An isolated DNA molecule having a sequence encoding a BMP-12 protein which is characterized by the ability to induce the formation of tendon/ligament-like tissue, said DNA molecule comprising a DNA sequence selected from the group consisting of:
(a) nucleotide #496, #571 or #577 to #882 of SEQ ID NO:1;
(b) nucleotide #605 or #659 to #964 of SEQ ID NO:25: and (c) naturally occurring allelic sequences and equivalent degenerative codon sequences of (a) or (b).
8. A host cell transformed with the DNA molecule of claim 7.
9. A vector comprising a DNA molecule of claim 7 in operative association with an expression control sequence therefor.
10. A host cell transformed with the vector of claim 9.
11. A method for producing a purified BMP-12 protein, said method comprising the steps of:
(a) culturing a host cell transformed with a DNA molecule according to claim 2, comprising a nucleotide sequence encoding a BMP-12 related protein;
and (b) recovering and purifying said BMP-12 related protein from the culture medium.
12. A method for producing a purified BMP-12 related protein said method comprising the steps of:
(a) culturing a host cell transformed with a DNA molecule according to claim 3, comprising a nucleotide sequence encoding a BMP-12 related protein;
and (b) recovering and purifying said BMP-12 related protein from the culture medium.
13. A method for producing a purified BMP-12 related protein said method comprising the steps of:
(a) culturing a host cell transformed with a DNA molecule according to claim 7, comprising a nucleotide sequence encoding a BMP-12 related protein;
and (b) recovering and purifying said BMP-12 related protein from the culture medium.
14. A purified polypeptide comprising an amino acid sequence selected from the following group:
(a) from ammo acid #-25 to amino acid #104 as set forth in SEQ ID
NO:2;
(b) from amino acid #1 to amino acid #104 as set forth in SEQ ID NO:2.
(c) from amino acid #3 to amino acid #104 as set forth in SEQ ID NO:2.
(d) from amino acid #1 to amino acid #120 as set forth in SEQ ID
NO:26; and (d) from amino acid #19 to amino acid #120 as set forth in SEQ ID
NO:26.
15. A purified polypeptide wherein said polypeptide is in the form of a dimer comprised of two subunits, each with the amino acid sequence of claim 14.
16. A purified protein produced by the steps of (a) culturing a cell transformed with a DNA molecule comprising the nucleotide sequence from nucleotide #496, #571 or #577 to #882 as shown in SEQ ID NO:1; and (b) recovering and purifying from said culture medium a protein comprising the amino acid sequence from amino acid #-25, amino acid #1 or amino acid #3 to amino acid #104 as shown in SEQ ID NO:2.
17. A purified BMP-12 related protein characterized by the ability to induce the formation of tendon/ligament-like tissue.
18. A pharmaceutical composition comprising an effective amount of the BMP-12 related protein of claim 17 in admixture with a pharmaceutically acceptable vehicle.
19. A method for inducing tendon/ligament-like tissue formation in a patient in need of same comprising administering to said patient an effective amount of the composition of claim 18.
20. A pharmaceutical composition for tendon/ligament-like tissue healing and tissue repair said composition comprising an effective amount of the proteinof a BMP-12 related protein in a pharmaceutically acceptable vehicle.
21. A method for treating tendinitis. or other tendon or ligament defect in a patient in need of same, said method comprising administering to said patient an effective amount of the composition of claim 20.
22. A chimeric DNA molecule comprising a DNA sequence encoding a propeptide from a member of the TGF-.beta. superfamily of proteins linked in correct reading frame to a DNA sequence encoding a BMP-12 related polypeptide.
23. A chimeric DNA molecule according to claim 22, wherein the propeptide is the propeptide from BMP-2.
24. A heterodimeric protein molecule comprising one monomer having the amino acid sequence of the polypeptide of claim 14, and one monomer having the amino acid sequence of a protein of the TGF-.beta. superfamily.
25. A method for inducing tendon/ligament-like tissue formation in a patient in need of same comprising administering to said patient an effective amount of a composition comprising a protein encoded by a DNA sequence selected from the group consisting of:
(a) nucleotides #496, #571 or #577 to #882 of SEQ ID NO:1;
(b) nucleotides #845 or #899 to #1204 of SEQ ID NO:3;
(c) nucleotides #605 or #659 to #964 of SEQ ID NO:25; and (d) sequences which hybridize to (a), (b) or (c) under stringent hybridization conditions and encode a protein which exhibits the ability to form tendon/ligament-like tissue.
26. A method for inducing tendon/ligament-like tissue formation in a patient in need of same comprising administering to said patient an effective amount of the composition comprising a tendon/ligament-like tissue inducing protein having an ammo acid sequence selected from the group consisting of:
(a) amino acids #-25, #1 or #3 to #104 of SEQ ID NO:2;
(b) amino acids #1 or #19 to #120 of SEQ ID NO:4;
(c) amino acids #1 or #19 to #120 of SEQ ID NO:26; and (d) mutants and/or variants of (a), (b) or (c) which exhibit the ability to form tendon and/or ligament.
27. A pharmaceutical composition for tendon/ligament-like tissue repair, said composition comprising an effective amount of a BMP-12 related protein in a pharmaceutically acceptable vehicle.
28. A method for treating tendinitis, or other tendon or ligament defect in a patient in need of same, said method comprising administering to said patient an effective amount of the composition of claim 27.
CA2176942A 1993-12-07 1994-12-06 Bmp-12, bmp-13 and tendon-inducing compositions thereof Expired - Lifetime CA2176942C (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US16410393A 1993-12-07 1993-12-07
US08/164,103 1993-12-07
US21778094A 1994-03-25 1994-03-25
US08/217,780 1994-03-25
US08/333,576 1994-11-02
US08/333,576 US6027919A (en) 1993-12-07 1994-11-02 BMP-12 and BMP-13 proteins and DNA encoding them
PCT/US1994/014030 WO1995016035A2 (en) 1993-12-07 1994-12-06 Bmp-12, bmp-13 and tendon-inducing compositions thereof

Publications (2)

Publication Number Publication Date
CA2176942A1 true CA2176942A1 (en) 1995-06-15
CA2176942C CA2176942C (en) 2011-11-01

Family

ID=27388970

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2176942A Expired - Lifetime CA2176942C (en) 1993-12-07 1994-12-06 Bmp-12, bmp-13 and tendon-inducing compositions thereof

Country Status (15)

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US (5) US5658882A (en)
EP (1) EP0733109B9 (en)
JP (3) JP3717930B2 (en)
KR (1) KR100353182B1 (en)
AT (1) ATE319823T1 (en)
AU (1) AU689184B2 (en)
CA (1) CA2176942C (en)
DE (1) DE69434651T2 (en)
DK (1) DK0733109T3 (en)
ES (1) ES2255059T3 (en)
FI (1) FI119816B (en)
NO (1) NO317801B1 (en)
OA (1) OA10582A (en)
PT (1) PT733109E (en)
WO (1) WO1995016035A2 (en)

Families Citing this family (147)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6150328A (en) * 1986-07-01 2000-11-21 Genetics Institute, Inc. BMP products
US6586388B2 (en) 1988-04-08 2003-07-01 Stryker Corporation Method of using recombinant osteogenic protein to repair bone or cartilage defects
US20070166353A1 (en) * 1988-04-08 2007-07-19 Stryker Corporation Osteogenic proteins
AU674500B2 (en) 1991-11-04 1997-01-02 Genetics Institute, Llc Recombinant bone morphogenetic protein heterodimers, compositions and methods of use
US20080070842A1 (en) * 1991-11-04 2008-03-20 David Israel Recombinant bone morphogenetic protein heterodimers, compositions and methods of use
DE19525416A1 (en) * 1995-07-12 1997-01-16 Bioph Biotech Entw Pharm Gmbh Use of MP52 for the treatment and prevention of diseases of the nervous system
US20080233170A1 (en) * 1992-02-21 2008-09-25 Stryker Corporation Osteogenic Proteins
EP0717633A4 (en) 1993-07-09 1998-05-20 Univ Johns Hopkins Med Growth differentiation factor-7
CA2165776A1 (en) * 1993-07-09 1995-01-19 Se-Jin Lee Growth differentiation factor-6
US6291206B1 (en) * 1993-09-17 2001-09-18 Genetics Institute, Inc. BMP receptor proteins
ATE319823T1 (en) * 1993-12-07 2006-03-15 Inst Genetics Llc BMP-12, BMP-13 AND TENDON-INDUCING COMPOSITIONS CONTAINING SAME
US5942496A (en) 1994-02-18 1999-08-24 The Regent Of The University Of Michigan Methods and compositions for multiple gene transfer into bone cells
US6551618B2 (en) 1994-03-15 2003-04-22 University Of Birmingham Compositions and methods for delivery of agents for neuronal regeneration and survival
US5906827A (en) * 1994-06-03 1999-05-25 Creative Biomolecules, Inc. Matrix for the manufacture of autogenous replacement body parts
WO1996014335A1 (en) * 1994-11-07 1996-05-17 The Government Of The United States Of America, Asrepresented By The Secretary, Department Of Health And Human Services Cartilage-derived morphogenetic proteins
US20010011131A1 (en) * 1997-07-28 2001-08-02 Luyten Frank P. DNA molecules encoding cartilage-derived morphogenetic proteins
US5846770A (en) * 1994-11-22 1998-12-08 Genetics Institute, Inc. DNA molecules encoding human chordin
ES2258774T3 (en) * 1995-04-19 2006-09-01 Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka Mbh A NEW PROTEIN AND PROCESS FOR PREPARATION OF THE SAME.
HU222664B1 (en) * 1995-06-05 2003-09-29 Genetics Institute, Llc Use of bone morphogenetic protein (bmp) for regeneration of functional connection of bone and tendon or ligament
US5902785A (en) * 1995-06-06 1999-05-11 Genetics Institute, Inc. Cartilage induction by bone morphogenetic proteins
ZA966489B (en) * 1995-08-03 1997-02-26 Bioph Biotech Entw Pharm Gmbh New protein human MP52 Arg.
US6048964A (en) * 1995-12-12 2000-04-11 Stryker Corporation Compositions and therapeutic methods using morphogenic proteins and stimulatory factors
US7026292B1 (en) 1995-12-12 2006-04-11 Stryker Corporation Compositions and therapeutic methods using morphogenic proteins and stimulatory factors
DE19548476A1 (en) * 1995-12-22 1997-06-26 Bioph Biotech Entw Pharm Gmbh Targeted connections with cartilage and / or bone inducing activity
US5700774A (en) * 1996-03-26 1997-12-23 Genetics Institute, Inc. Compositions comprising bone morphogenic proteins and truncated parathyroid hormone related peptide, and methods of inducing cartilage by administration of same
US5965403A (en) * 1996-09-18 1999-10-12 Genetics Institute, Inc. Nucleic acids encoding bone morphogenic protein-16 (BMP-16)
JPH11335398A (en) * 1998-05-22 1999-12-07 Hoechst Marion Roussel Kk New monomeric protein having bone-inducing activity and preventive/therapeutic agent for chondropathy/ osteopathy consisting thereof
EP1074620A1 (en) * 1999-08-06 2001-02-07 HyGene AG Monomeric protein of the TGF-beta family
AU6267798A (en) 1997-02-07 1998-08-26 Stryker Corporation Matrix-free osteogenic devices, implants and methods of use thereof
US7041641B2 (en) 1997-03-20 2006-05-09 Stryker Corporation Osteogenic devices and methods of use thereof for repair of endochondral bone and osteochondral defects
US20010016646A1 (en) 1998-03-20 2001-08-23 David C. Rueger Osteogenic devices and methods of use thereof for repair of endochondral bone, osteochondral and chondral defects
JP4394169B2 (en) 1997-04-04 2010-01-06 バーンズ − ジューウィッシュ・ホスピタル New cartilage and methods of use
CA2291514C (en) 1997-05-30 2011-07-12 Creative Biomolecules, Inc. Methods for evaluating tissue morphogenesis and activity
ATE220564T1 (en) 1997-08-14 2002-08-15 Sulzer Innotec Ag COMPOSITION AND DEVICE FOR REPAIRING CARTILAGE TISSUE IN VIVO CONSISTING OF NANOCAPSULES WITH OSTEOINDUCTIVE AND/OR CHONDROINDUCTIVE FACTORS
US6482584B1 (en) * 1998-11-13 2002-11-19 Regeneration Technologies, Inc. Cyclic implant perfusion cleaning and passivation process
US20010031254A1 (en) * 1998-11-13 2001-10-18 Bianchi John R. Assembled implant
US6281175B1 (en) 1997-09-23 2001-08-28 Scimed Life Systems, Inc. Medical emulsion for lubrication and delivery of drugs
US20020052026A1 (en) 1997-10-08 2002-05-02 Steven M. Vicik Methods of refolding proteins
CA2312009A1 (en) 1997-11-28 1999-06-10 Roche Diagnostics Gmbh An active hedgehog-protein-mutant, a process for its preparation and its use for pharmaceutical purposes
US6027917A (en) 1997-12-10 2000-02-22 Genetics Institute, Inc. Bone morphogenetic protein (BMP)-17 and BMP-18 compositions
DK1064382T3 (en) 1998-03-17 2008-12-08 Genentech Inc Homologous polypeptides for VEGF and BMP1
US6541623B1 (en) 1998-04-03 2003-04-01 Hyseq, Inc. Interleukin—1 receptor antagonist and uses thereof
US6294655B1 (en) 1998-04-03 2001-09-25 Hyseq, Inc. Anti-interleukin-1 receptor antagonist antibodies and uses thereof
US6337072B1 (en) 1998-04-03 2002-01-08 Hyseq, Inc. Interleukin-1 receptor antagonist and recombinant production thereof
US6426191B1 (en) 1998-04-03 2002-07-30 Hyseq, Inc. Assays involving an IL-1 receptor antagonist
US6958149B2 (en) 1998-10-06 2005-10-25 Stryker Corporation Repair of larynx, trachea, and other fibrocartilaginous tissues
EP1649865B1 (en) * 1998-10-06 2012-06-13 Stryker Corporation GDF-5 for use in repairing a nonarticular cartilage defect in an intervertebral disc
US7572440B2 (en) 1999-07-30 2009-08-11 Stryker Corporation Method for repairing a defect in an intervertebral disc
EP1117422B1 (en) * 1998-10-06 2005-09-28 Stryker Corporation Use of op-1 for the preparation of a pharmaceutical composition for repairing a defect locus in a non articular cartilage tissue of a mammal
US6677432B1 (en) 1998-10-07 2004-01-13 Stryker Corporation Mutations of the C-terminal portion of TGF-β superfamily proteins
US6846906B1 (en) 1998-10-07 2005-01-25 Stryker Corporation Modified proteins of the TGF-β superfamily, including morphogenic proteins
AU1103900A (en) 1998-10-07 2000-04-26 Stryker Corporation Modified tgf-beta superfamily proteins
US6727224B1 (en) * 1999-02-01 2004-04-27 Genetics Institute, Llc. Methods and compositions for healing and repair of articular cartilage
PT1148897E (en) * 1999-02-01 2004-04-30 Genetics Inst Llc METHODS AND COMPOSITIONS FOR HEALING AND REPAIR OF JOINT CARTILAGE
NZ515678A (en) 1999-04-28 2004-01-30 Genetics Inst Human GIL-19/AE289 proteins and polynucleotides encoding same
DE69940364D1 (en) 1999-05-18 2009-03-19 Dyax Corp Fab fragment libraries and methods for their use
DK1223990T3 (en) * 1999-10-15 2004-11-29 Inst Genetics Llc Formulations of hyaluronic acid for delivery of osteogenic proteins
US6368787B1 (en) 1999-12-16 2002-04-09 Stryker Corporation Methods and compositions for identifying morphogenic protein analogs using morphogenic protein responsive inhibitory elements
JP2003520830A (en) 2000-01-25 2003-07-08 エドワーズ ライフサイエンシーズ コーポレイション Delivery system for treatment of restenosis and anastomotic intimal hyperplasia
WO2001066130A1 (en) * 2000-03-09 2001-09-13 Sulzer Biologics Inc. Product and method for biological anchoring of connective tissue to bone
US20030065140A1 (en) * 2000-04-03 2003-04-03 Vernet Corine A.M. Novel proteins and nucleic acids encoding same
EP2792747A1 (en) 2000-06-23 2014-10-22 Genentech, Inc. Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis
EP2075253A1 (en) 2000-06-23 2009-07-01 Genentech, Inc. Compositions and methds for the diagnosis and treatment of disorders involving angiogensis
US7067046B2 (en) 2000-08-04 2006-06-27 Essen Instruments, Inc. System for rapid chemical activation in high-throughput electrophysiological measurements
US7270730B2 (en) * 2000-08-04 2007-09-18 Essen Instruments, Inc. High-throughput electrophysiological measurement system
US20040010118A1 (en) * 2000-08-16 2004-01-15 Zerhusen Bryan D. Novel proteins and nucleic acids encoding same
US20030082233A1 (en) * 2000-12-01 2003-05-01 Lyons Karen M. Method and composition for modulating bone growth
EP1372698A2 (en) * 2001-03-23 2004-01-02 BIOPHARM GESELLSCHAFT ZUR BIOTECHNOLOGISCHEN ENTWICKLUNG VON PHARMAKA mbH Use of cytokines of the tgf-beta superfamily for the treatment and diagnosis of skin related disorders
ES2305246T3 (en) * 2001-06-01 2008-11-01 Wyeth COMPOSITIONS FOR THE SYSTEMIC ADMINISTRATION OF SEQUENCES CODING OSEAS MORPHOGENETIC PROTEINS.
TWI267378B (en) 2001-06-08 2006-12-01 Wyeth Corp Calcium phosphate delivery vehicles for osteoinductive proteins
US20030087274A1 (en) * 2001-07-05 2003-05-08 Anderson David W. Therapeutic polypeptides, nucleic acids encoding same, and methods of use
CA2466947C (en) 2001-11-19 2012-05-22 Scil Technology Gmbh A homogeneously coated device having osteoinductive and osteoconductive properties
CH695985A5 (en) * 2002-01-21 2006-11-15 Straumann Holding Ag Surface-modified implants.
TW200638946A (en) * 2002-05-17 2006-11-16 Wyeth Corp Injectable solid hyaluronic acid carriers for delivery of osteogenic proteins
US7622562B2 (en) 2002-06-26 2009-11-24 Zimmer Orthobiologics, Inc. Rapid isolation of osteoinductive protein mixtures from mammalian bone tissue
AU2003259765B2 (en) * 2002-08-13 2009-01-22 Wyeth Peptides as solubilizing excipients for transforming growth factor Beta proteins
DK1539261T3 (en) 2002-09-10 2006-08-07 Scil Technology Gmbh Metal implant coated under reduced oxygen concentration with osteoinductive protein
WO2005012530A2 (en) 2003-07-25 2005-02-10 Amgen Inc. Antagonists and agonists of ldcam and methods of use
CN1878565B (en) 2003-09-12 2011-01-12 惠氏公司 Injectable calcium phosphate solid rods and pastes for delivery of osteogenic proteins
CA2535169A1 (en) 2003-12-31 2005-07-21 Osteotech, Inc. Improved bone matrix compositions and methods
WO2005086706A2 (en) * 2004-03-05 2005-09-22 The Trustees Of Columbia University In The City Of New York Multi-phased, biodegradable and osteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue to bone
JP4944010B2 (en) 2004-03-10 2012-05-30 サイル テクノロジー ゲーエムベーハー Coated implant, its manufacture and use
CA2563374A1 (en) 2004-04-27 2005-12-08 Research Development Foundation Antagonism of tgf-.beta.superfamily receptor signaling
EP2298335B1 (en) 2004-05-25 2014-09-03 Stryker Corporation Use of OP-1 for treating cartilage defects
WO2006026554A1 (en) * 2004-08-30 2006-03-09 Neville Alleyne Method of using an implant for treatment of ligaments and tendons
WO2006026731A1 (en) 2004-08-30 2006-03-09 Spineovations, Inc. Method of treating spinal internal disk derangement
US7473678B2 (en) 2004-10-14 2009-01-06 Biomimetic Therapeutics, Inc. Platelet-derived growth factor compositions and methods of use thereof
WO2006081379A1 (en) * 2005-01-26 2006-08-03 Wyeth Use of sfrps as markers of bmp activity
MX2007011406A (en) * 2005-03-24 2007-10-08 Wyeth Corp Use of fibrous tissue inducing proteins for hernia repair.
EP1863518A2 (en) * 2005-03-30 2007-12-12 Wyeth Methods for stimulating hair growth by administering bmps
US20060247790A1 (en) * 2005-04-30 2006-11-02 Mckay William F Shaped osteochondral grafts and methods of using same
US20060287675A1 (en) * 2005-06-15 2006-12-21 Prajapati Rita T Method of intra-operative coating therapeutic agents onto sutures composite sutures and methods of use
US20060287676A1 (en) * 2005-06-15 2006-12-21 Rita Prajapati Method of intra-operative coating therapeutic agents onto sutures, composite sutures and methods of use
US20060286289A1 (en) * 2005-06-15 2006-12-21 Rita Prajapati Method of intraoperative coating therapeutic agents onto sutures
US20060286171A1 (en) * 2005-06-17 2006-12-21 Tianhong Zhou Bone morphogenetic protein formulations
US20070056050A1 (en) * 2005-06-29 2007-03-08 Clokie Cameron M L PRODUCTION OF BONE MORPHOGENIC PROTEINS (BMPs) IN TRANSGENIC MAMMALS
CN101365499A (en) 2005-11-01 2009-02-11 骨骼技术股份有限公司 Bone matrix compositions and methods
DK1948689T3 (en) * 2005-11-18 2012-07-23 Bioph Biotech Entw Pharm Gmbh High activity growth factor mutants
US8147860B2 (en) 2005-12-06 2012-04-03 Etex Corporation Porous calcium phosphate bone material
EP2311505B1 (en) 2006-02-09 2013-11-06 BioMimetic Therapeutics, LLC Compositions and methods for treating bone
AU2007257208B2 (en) 2006-05-17 2013-05-02 Stryker Corporation Use of a soluble morphogenic protein complex for treating cartilage defects
AU2007269712B2 (en) 2006-06-30 2013-02-07 Biomimetic Therapeutics, Llc PDGF-biomatrix compositions and methods for treating rotator cuff injuries
US9161967B2 (en) 2006-06-30 2015-10-20 Biomimetic Therapeutics, Llc Compositions and methods for treating the vertebral column
US8524265B2 (en) 2006-08-17 2013-09-03 Warsaw Orthopedic, Inc. Medical implant sheets useful for tissue regeneration
US20100047309A1 (en) * 2006-12-06 2010-02-25 Lu Helen H Graft collar and scaffold apparatuses for musculoskeletal tissue engineering and related methods
AU2007234612B2 (en) 2006-12-14 2013-06-27 Johnson & Johnson Regenerative Therapeutics, Llc Protein stabilization formulations
ES2447516T3 (en) 2006-12-21 2014-03-12 Stryker Corporation Sustained release formulations comprising BMP-7 crystals
US8753391B2 (en) * 2007-02-12 2014-06-17 The Trustees Of Columbia University In The City Of New York Fully synthetic implantable multi-phased scaffold
CA2688232A1 (en) * 2007-05-25 2008-12-04 Induce Biologics Inc. A method of enhancing recombinant protein production
US20080299172A1 (en) * 2007-06-04 2008-12-04 Stuart Young Tissue repair implant
US9554920B2 (en) 2007-06-15 2017-01-31 Warsaw Orthopedic, Inc. Bone matrix compositions having nanoscale textured surfaces
WO2008157492A2 (en) 2007-06-15 2008-12-24 Osteotech, Inc. Osteoinductive demineralized cancellous bone
US8642061B2 (en) 2007-06-15 2014-02-04 Warsaw Orthopedic, Inc. Method of treating bone tissue
CA2690457C (en) 2007-06-15 2018-02-20 Osteotech, Inc. Bone matrix compositions and methods
US7678764B2 (en) 2007-06-29 2010-03-16 Johnson & Johnson Regenerative Therapeutics, Llc Protein formulations for use at elevated temperatures
US9358113B2 (en) 2007-07-10 2016-06-07 Warsaw Orthopedic, Inc. Delivery system
EP2019117A1 (en) * 2007-07-27 2009-01-28 BIOPHARM GESELLSCHAFT ZUR BIOTECHNOLOGISCHEN ENTWICKLUNG VON PHARMAKA mbH Optimized purification process of recombinant growth factor protein
CA2695697A1 (en) 2007-08-07 2009-02-12 Advanced Technologies And Regenerative Medicine, Llc Protein formulations comprising gdf-5 in aqueous acidic solution
ES2446544T3 (en) * 2007-10-19 2014-03-10 Warsaw Orthopedic, Inc. Demineralized bone matrix compositions and methods
AU2009214629A1 (en) 2008-02-13 2009-08-20 Eric T. Choi BMP-7 for use in treating vascular sclerosis
US20100010549A1 (en) * 2008-03-05 2010-01-14 Neville Alleyne device and method of minimally invasive extracapsular ligamentous augmentation for canine stifle ligament injuries
US8469961B2 (en) * 2008-03-05 2013-06-25 Neville Alleyne Methods and compositions for minimally invasive capsular augmentation of canine coxofemoral joints
US20100004700A1 (en) * 2008-03-05 2010-01-07 Neville Alleyne Method of treating tissue with a suspenson of tricalcium hydroxyapatite microspheres
AU2009236459B2 (en) 2008-04-14 2013-07-25 Advanced Technologies And Regenerative Medicine, Llc Liquid buffered GDF-5 formulations
JP2011522565A (en) * 2008-06-09 2011-08-04 ワイス・エルエルシー Novel BMP-12-related protein and method for producing the same
MX2011002555A (en) 2008-09-09 2011-08-03 Biomimetic Therapeutics Inc Platelet-derived growth factor compositions and methods for the treatment of tendon and ligament injuries.
US9101475B2 (en) 2009-02-12 2015-08-11 Warsaw Orthopedic, Inc. Segmented delivery system
CA2752160A1 (en) 2009-02-12 2010-08-19 Stryker Corporation Compositions and methods for minimally-invasive systemic delivery of proteins including tgf-.beta. superfamily members
EP2396025A2 (en) 2009-02-12 2011-12-21 Stryker Corporation Peripheral administration of proteins including tgf-beta superfamily members for systemic treatment of disorders and disease
US20120148539A1 (en) 2009-03-24 2012-06-14 Moulay Hicham Alaoui-Ismaili Methods and Compositions for Tissue Engineering
US8609127B2 (en) 2009-04-03 2013-12-17 Warsaw Orthopedic, Inc. Medical implant with bioactive material and method of making the medical implant
WO2010144696A1 (en) 2009-06-11 2010-12-16 Burnham Institute For Medical Research Directed differentiation of stem cells
US20110224138A1 (en) 2009-09-09 2011-09-15 Julie Krop Methods for treating pain induced by injuries and diseases of an articular joint
US20110224410A1 (en) 2009-09-17 2011-09-15 Hile David Buffers for Controlling the pH of Bone Morphogenetic Proteins
US8657859B2 (en) 2009-12-16 2014-02-25 Advanced Veterinary Solutions Implant for promoting stability of the canine stifle joint
EP2516456A1 (en) 2009-12-22 2012-10-31 Stryker Corporation Bmp-7 variants with reduced immunogenicity
AU2011217784B2 (en) 2010-02-22 2014-10-09 Biomimetic Therapeutics, Llc. Platelet-derived growth factor compositions and methods for the treatment of tendinopathies
AU2011284657B2 (en) 2010-07-30 2013-11-14 Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka Mbh Drug delivery devices and growth factor formulations for accelerated wound healing
EP2537538A1 (en) 2011-06-22 2012-12-26 Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka mbH Bioresorbable Wound Dressing
EP2602264A1 (en) 2011-12-05 2013-06-12 Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka mbH GDF-5 mutant for inducing cartilage formation
WO2014012101A1 (en) 2012-07-13 2014-01-16 Trustees Of Tufts College Silk powder compaction for production of constructs with high mechanical strength and stiffness
WO2014169249A1 (en) 2013-04-12 2014-10-16 The Trustees Of Columbia University In The City Of New York Methods for host cell homing and dental pulp regeneration
MX2017009241A (en) 2015-01-16 2018-03-23 Spineovations Inc Method of treating spinal disk.
EP3821880A1 (en) 2015-10-26 2021-05-19 President and Fellows of Harvard College Oxidized polysaccharides and methods of use thereof
KR101659796B1 (en) 2016-01-13 2016-10-10 주식회사 셀루메드 Mixture of bmp proteins at specific ratios
US20190328792A1 (en) * 2017-01-11 2019-10-31 Paracelsus Medizinische Privatuniversität Salzburg - Privatstiftung Mesenchymal stem cell-derived extracellular vesicles and their medical use
US20220387556A1 (en) 2019-12-18 2022-12-08 Merck Patent Gmbh Use of the gdf-5 mutant for the treatment of pain and cartilage destruction

Family Cites Families (136)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2465357A (en) 1944-08-14 1949-03-29 Upjohn Co Therapeutic sponge and method of making
CH563767A5 (en) 1973-01-30 1975-07-15 Pheulpin Jean
US4468464A (en) 1974-11-04 1984-08-28 The Board Of Trustees Of The Leland Stanford Junior University Biologically functional molecular chimeras
DE2657370C2 (en) 1976-12-17 1982-11-11 Hans Dr.med. Dr.med.dent. 8000 München Scheicher Means for covering and / or filling in bone defects
DE2732848A1 (en) 1977-07-18 1979-02-08 Schering Ag DIURETHANE, HERBICIDAL AGENTS CONTAINING THESE COMPOUNDS AND THE PROCESS FOR THEIR PRODUCTION
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4619989A (en) 1981-05-05 1986-10-28 The Regents Of The University Of Cal. Bone morphogenetic protein composition
US4789732A (en) 1980-08-04 1988-12-06 Regents Of The University Of California Bone morphogenetic protein composition
US4294753A (en) * 1980-08-04 1981-10-13 The Regents Of The University Of California Bone morphogenetic protein process
US4455256A (en) 1981-05-05 1984-06-19 The Regents Of The University Of California Bone morphogenetic protein
US4761471A (en) * 1980-08-04 1988-08-02 The Regents Of The University Of California Bone morphogenetic protein composition
US4419446A (en) 1980-12-31 1983-12-06 The United States Of America As Represented By The Department Of Health And Human Services Recombinant DNA process utilizing a papilloma virus DNA as a vector
IE52535B1 (en) 1981-02-16 1987-12-09 Ici Plc Continuous release pharmaceutical compositions
US4727028A (en) 1981-06-22 1988-02-23 Eli Lilly And Company Recombinant DNA cloning vectors and the eukaryotic and prokaryotic transformants thereof
US4472840A (en) 1981-09-21 1984-09-25 Jefferies Steven R Method of inducing osseous formation by implanting bone graft material
US4394370A (en) 1981-09-21 1983-07-19 Jefferies Steven R Bone graft material for osseous defects and method of making same
US4474181A (en) 1982-02-18 1984-10-02 Schenck Robert R Method and apparatus for anastomosing small blood vessels
US4455526A (en) * 1982-06-29 1984-06-19 The United States Of America As Represented By The Secretary Of The Air Force FET Switching regulator
DE3382562D1 (en) 1982-09-24 1992-06-25 Us Health ANIMAL TISSUE RECOVERY.
IL68218A (en) 1983-03-23 1985-12-31 Univ Ramot Compositions for cartilage repair comprising embryonal chondrocytes
US4434094A (en) * 1983-04-12 1984-02-28 Collagen Corporation Partially purified osteogenic factor and process for preparing same from demineralized bone
US4795804A (en) 1983-08-16 1989-01-03 The Regents Of The University Of California Bone morphogenetic agents
US4923805A (en) 1983-11-02 1990-05-08 Integrated Genetics, Inc. Fsh
US4703008A (en) 1983-12-13 1987-10-27 Kiren-Amgen, Inc. DNA sequences encoding erythropoietin
GB8334498D0 (en) 1983-12-24 1984-02-01 Beecham Group Plc Compounds
US4804744A (en) * 1984-01-04 1989-02-14 International Genetic Engineering, Inc. Osteogenic factors
US4608199A (en) 1984-03-20 1986-08-26 Arnold Caplan Bone protein purification process
US4662884A (en) 1984-04-25 1987-05-05 University Of Utah Research Foundation Prostheses and methods for promoting nerve regeneration
US4596574A (en) 1984-05-14 1986-06-24 The Regents Of The University Of California Biodegradable porous ceramic delivery system for bone morphogenetic protein
CA1341617C (en) 1984-06-08 2011-06-28 Henry George Burger Inhibin isolated from ovarian follicular fluid
US4868161A (en) 1984-06-29 1989-09-19 City Of Hope Method for promoting nerve regeneration
DE3588058T3 (en) * 1984-07-16 2005-04-07 Celtrix Pharmaceuticals, Inc., Palo Alto Cartilage-inducing polypeptide factors from bone
US4843063A (en) 1984-07-16 1989-06-27 Collagen Corporation Polypeptide cartilage-inducing factors found in bone
US4627982A (en) * 1984-07-16 1986-12-09 Collagen Corporation Partially purified bone-inducing factor
EP0177343B1 (en) 1984-10-05 1992-07-22 Genentech, Inc. Dna, cell cultures and methods for the secretion of heterologous proteins and periplasmic protein recovery
US5187263A (en) 1984-10-12 1993-02-16 Zymogenetics, Inc. Expression of biologically active PDGE analogs in eucaryotic cells
US4769328A (en) 1984-10-12 1988-09-06 Zymogenetics Inc. Expression of biologically active PDGF analogs in yeast
US4563350A (en) * 1984-10-24 1986-01-07 Collagen Corporation Inductive collagen based bone repair preparations
US4828990A (en) 1984-12-27 1989-05-09 Naoki Higashi Method for purifying an interferon
US4886747A (en) 1985-03-22 1989-12-12 Genentech, Inc. Nucleic acid encoding TGF-β and its uses
US4766067A (en) 1985-05-31 1988-08-23 President And Fellows Of Harvard College Gene amplification
US4681763A (en) 1985-06-11 1987-07-21 University Of Medicine And Dentistry Of New Jersey Composition for stimulating bone growth
US4851521A (en) 1985-07-08 1989-07-25 Fidia, S.P.A. Esters of hyaluronic acid
US5089396A (en) 1985-10-03 1992-02-18 Genentech, Inc. Nucleic acid encoding β chain prodomains of inhibin and method for synthesizing polypeptides using such nucleic acid
US5215893A (en) 1985-10-03 1993-06-01 Genentech, Inc. Nucleic acid encoding the ba chain prodomains of inhibin and method for synthesizing polypeptides using such nucleic acid
US4798885A (en) 1986-02-07 1989-01-17 Genentech, Inc. Compositions of hormonally active human and porcine inhibin containing an α chain and 62 chain
US4737578A (en) 1986-02-10 1988-04-12 The Salk Institute For Biological Studies Human inhibin
US4758233A (en) 1986-04-22 1988-07-19 N.J. Phillips TPY. Limited Cream applicator
NL8601328A (en) 1986-05-23 1987-12-16 Langen Research DEVICE FOR INJECTING MEAT WITH A MASS, PARTICULARLY PASTY MASS.
US5108922A (en) * 1986-07-01 1992-04-28 Genetics Institute, Inc. DNA sequences encoding BMP-1 products
US6432919B1 (en) * 1986-07-01 2002-08-13 Genetics Institute, Inc. Bone morphogenetic protein-3 and compositions
US5543394A (en) * 1986-07-01 1996-08-06 Genetics Institute, Inc. Bone morphogenetic protein 5(BMP-5) compositions
US5631142A (en) * 1986-07-01 1997-05-20 Genetics Institute, Inc. Compositions comprising bone morphogenetic protein-2 (BMP-2)
US5106748A (en) * 1986-07-01 1992-04-21 Genetics Institute, Inc. Dna sequences encoding 5 proteins
ZA874681B (en) * 1986-07-01 1988-04-27 Genetics Inst Novel osteoinductive factors
US5013649A (en) * 1986-07-01 1991-05-07 Genetics Institute, Inc. DNA sequences encoding osteoinductive products
US5187076A (en) * 1986-07-01 1993-02-16 Genetics Institute, Inc. DNA sequences encoding BMP-6 proteins
US4877864A (en) * 1987-03-26 1989-10-31 Genetics Institute, Inc. Osteoinductive factors
US5459047A (en) * 1986-07-01 1995-10-17 Genetics Institute, Inc. BMP-6 proteins
US6150328A (en) * 1986-07-01 2000-11-21 Genetics Institute, Inc. BMP products
US5019087A (en) 1986-10-06 1991-05-28 American Biomaterials Corporation Nerve regeneration conduit
US5124316A (en) 1986-11-14 1992-06-23 President And Fellows Of Harvard College Method for periodontal regeneration
US5041538A (en) 1987-08-28 1991-08-20 The Salk Institute For Biological Studies Mammalian follistatin
US5202120A (en) 1987-09-11 1993-04-13 Case Western Reserve University Methods of reducing glial scar formation and promoting axon and blood vessel growth and/or regeneration through the use of activated immature astrocytes
US5147399A (en) 1988-02-01 1992-09-15 Dellon Arnold L Method of treating nerve defects through use of a bioabsorbable surgical device
PT90216A (en) * 1988-04-06 1989-11-10 PROCESS FOR THE PREPARATION OF POLIPEPTIDES WITH OSTEOGENIC ACTIVITY
US5108753A (en) 1988-04-08 1992-04-28 Creative Biomolecules Osteogenic devices
US4968590A (en) * 1988-04-08 1990-11-06 Stryker Corporation Osteogenic proteins and polypeptides
US5266683A (en) 1988-04-08 1993-11-30 Stryker Corporation Osteogenic proteins
US5354557A (en) 1988-04-08 1994-10-11 Stryker Corporation Osteogenic devices
US6586388B2 (en) * 1988-04-08 2003-07-01 Stryker Corporation Method of using recombinant osteogenic protein to repair bone or cartilage defects
US5258494A (en) 1988-04-08 1993-11-02 Stryker Corporation Osteogenic proteins
US5011691A (en) 1988-08-15 1991-04-30 Stryker Corporation Osteogenic devices
US5024841A (en) 1988-06-30 1991-06-18 Collagen Corporation Collagen wound healing matrices and process for their production
US5071834A (en) 1988-09-16 1991-12-10 Genentech, Inc. Purified activin B composition
US5284756A (en) * 1988-10-11 1994-02-08 Lynn Grinna Heterodimeric osteogenic factor
US5106626A (en) 1988-10-11 1992-04-21 International Genetic Engineering, Inc. Osteogenic factors
US4955892A (en) 1988-10-24 1990-09-11 Louisiana State University Neural cell adhesion protein nerve prosthesis
US5457038A (en) * 1988-11-10 1995-10-10 Genetics Institute, Inc. Natural killer stimulatory factor
US5011486A (en) 1988-11-18 1991-04-30 Brown University Research Foundation Composite nerve guidance channels
US5162430A (en) 1988-11-21 1992-11-10 Collagen Corporation Collagen-polymer conjugates
US4920962A (en) 1988-11-23 1990-05-01 Claude Proulx Splint-like element for use in end-to-end nerve suture
US5217867A (en) 1988-11-30 1993-06-08 The Salk Institute For Biological Studies Receptors: their identification, characterization, preparation and use
US4963146A (en) 1989-04-20 1990-10-16 Colla-Tec Incorporated Multi-layered, semi-permeable conduit for nerve regeneration
US5026381A (en) 1989-04-20 1991-06-25 Colla-Tec, Incorporated Multi-layered, semi-permeable conduit for nerve regeneration comprised of type 1 collagen, its method of manufacture and a method of nerve regeneration using said conduit
US5166322A (en) 1989-04-21 1992-11-24 Genetics Institute Cysteine added variants of interleukin-3 and chemical modifications thereof
CA2017466A1 (en) * 1989-06-02 1990-12-02 Michael C. Kiefer Bone calcification factor
US5399346A (en) * 1989-06-14 1995-03-21 The United States Of America As Represented By The Department Of Health And Human Services Gene therapy
AU5958090A (en) 1989-06-29 1991-01-17 United States of America, as represented by the Secretary, U.S. Department of Commerce, The Method for protecting bone marrow against chemotherapeutic drugs and radiation therapy using transforming growth factor beta 1
CA2020729A1 (en) * 1989-07-19 1991-01-20 Michael C. Kiefer Bone morphogenetic protein
US5324519A (en) 1989-07-24 1994-06-28 Atrix Laboratories, Inc. Biodegradable polymer composition
US5422340A (en) * 1989-09-01 1995-06-06 Ammann; Arthur J. TGF-βformulation for inducing bone growth
CA2024629C (en) * 1989-09-06 2001-07-24 Taiheiyo Cement Corporation Xenopus laevis bone morphogenic protein, dna encoding same and use thereof
US5236456A (en) * 1989-11-09 1993-08-17 Osteotech, Inc. Osteogenic composition and implant containing same
GB8927546D0 (en) * 1989-12-06 1990-02-07 Ciba Geigy Process for the production of biologically active tgf-beta
US5166190A (en) 1990-01-08 1992-11-24 Genentech, Inc. Method for increasing fertility in males
US5256418A (en) 1990-04-06 1993-10-26 Organogenesis, Inc. Collagen constructs
US5290271A (en) 1990-05-14 1994-03-01 Jernberg Gary R Surgical implant and method for controlled release of chemotherapeutic agents
WO1991018098A1 (en) * 1990-05-16 1991-11-28 Genetics Institute, Inc. Bone and cartilage inductive proteins
US5168050A (en) * 1990-05-24 1992-12-01 Genentech, Inc. Mammalian expression of the bone morphogenetic protein-2b using bmp2a/bmp2b fusion
US5218090A (en) 1990-06-12 1993-06-08 Warner-Lambert Company EGF receptor truncates
US5206028A (en) 1991-02-11 1993-04-27 Li Shu Tung Dense collagen membrane matrices for medical uses
US5208219A (en) 1991-02-14 1993-05-04 Celtrix Pharmaceuticals Inc. Method for inducing bone growth
US5318898A (en) * 1991-04-02 1994-06-07 Genetics Institute, Inc. Production of recombinant bone-inducing proteins
US5118667A (en) 1991-05-03 1992-06-02 Celtrix Pharmaceuticals, Inc. Bone growth factors and inhibitors of bone resorption for promoting bone formation
US5229495A (en) 1991-06-18 1993-07-20 Ludwig Institute For Cancer Research Substantially pure receptor like TGF-β 1 binding molecules and uses thereof
US5216126A (en) 1991-06-19 1993-06-01 Genentech, Inc. Receptor polypeptides and their production and uses
ATE142460T1 (en) 1991-06-21 1996-09-15 Genetics Inst MEDICINAL PRODUCTS CONTAINING OSTEOGENIC PROTEINS
WO1993000432A1 (en) * 1991-06-25 1993-01-07 Genetics Institute, Inc. Bmp-9 compositions
US5306307A (en) 1991-07-22 1994-04-26 Calcitek, Inc. Spinal disk implant
US5171579A (en) 1991-10-11 1992-12-15 Genetics Institute, Inc. Formulations of blood clot-polymer matrix for delivery of osteogenic proteins
AU674500B2 (en) * 1991-11-04 1997-01-02 Genetics Institute, Llc Recombinant bone morphogenetic protein heterodimers, compositions and methods of use
UA48105C2 (en) * 1992-02-12 2002-08-15 Біофарм Гезельшафт Цур Біотехнологішен Ентвіклунг Вон Фармака Мбх DNA FRAGMENT CODING THE PROTEIN OF THE FAMILY TGF-в (VERSIONS), RECOMBINANT DNA MOLECULE (VERSIONS), CELL-HOST (VERSIONS), METHOD FOR OBTAINING THE PROTEIN OF THE FAMILY TGF-в (VERSIONS), PHARMACEUTICAL COMPOSITION (VERSIONS), ANTIBODY OR AN ANTIBODY FRAGMENT (VERSIONS), CDNA MOLECULE (VERSIONS)
ATE269371T1 (en) 1992-02-28 2004-07-15 Cohesion Tech Inc INJECTABLE CERAMIC COMPOUNDS AND METHOD FOR THEIR PRODUCTION AND USE
AU3920693A (en) * 1992-03-18 1993-10-21 General Hospital Corporation, The Four novel receptors of the TGF-beta receptor family
EP1439190A1 (en) * 1993-01-12 2004-07-21 The Johns Hopkins University School Of Medicine Growth differentiation factor-5
GB9308060D0 (en) * 1993-04-19 1993-06-02 Cancer Res Campaign Tech Stem cell inhibitor
DK0698094T3 (en) * 1993-05-12 2004-05-03 Inst Genetics Llc BMP-11 compositions
US5637480A (en) * 1993-05-12 1997-06-10 Genetics Institute, Inc. DNA molecules encoding bone morphogenetic protein-10
US5447725A (en) * 1993-06-11 1995-09-05 The Procter & Gamble Company Methods for aiding periodontal tissue regeneration
KR100294026B1 (en) * 1993-06-24 2001-09-17 야마자끼 순페이 Electro-optical device
CA2165776A1 (en) * 1993-07-09 1995-01-19 Se-Jin Lee Growth differentiation factor-6
EP0717633A4 (en) * 1993-07-09 1998-05-20 Univ Johns Hopkins Med Growth differentiation factor-7
PT716610E (en) * 1993-08-26 2006-08-31 Genetics Inst Llc MORPHOGENETIC PROTEINS OF BONES FOR HUMANS TO BE USED IN NEURAL REGENERATION
US5455041A (en) * 1993-09-13 1995-10-03 Research Foundation Of State University Of New York At Buffalo Method for inducing periodontal tissue regeneration
ATE319823T1 (en) * 1993-12-07 2006-03-15 Inst Genetics Llc BMP-12, BMP-13 AND TENDON-INDUCING COMPOSITIONS CONTAINING SAME
US5399677A (en) * 1993-12-07 1995-03-21 Genetics Institute, Inc. Mutants of bone morphogenetic proteins
US6027919A (en) * 1993-12-07 2000-02-22 Genetics Institute, Inc. BMP-12 and BMP-13 proteins and DNA encoding them
US5723331A (en) * 1994-05-05 1998-03-03 Genzyme Corporation Methods and compositions for the repair of articular cartilage defects in mammals
US5520923A (en) * 1994-09-19 1996-05-28 Genetics Institute, Inc. Formulations for delivery of osteogenic proteins
US5635372A (en) * 1995-05-18 1997-06-03 Genetics Institute, Inc. BMP-15 compositions
HU222664B1 (en) * 1995-06-05 2003-09-29 Genetics Institute, Llc Use of bone morphogenetic protein (bmp) for regeneration of functional connection of bone and tendon or ligament
US5752974A (en) * 1995-12-18 1998-05-19 Collagen Corporation Injectable or implantable biomaterials for filling or blocking lumens and voids of the body
US6034062A (en) * 1997-03-13 2000-03-07 Genetics Institute, Inc. Bone morphogenetic protein (BMP)-9 compositions and their uses
IT1302534B1 (en) * 1998-12-21 2000-09-05 Fidia Advanced Biopolymers Srl INJECTABLE, BIOCOMPATIBLE AND BIODEGRADABLE COMPOSITIONS INCLUDING AT LEAST A DERIVATIVE OF HYALURONIC ACID, CHONDROGENIC CELLS, FOR
US6420243B1 (en) * 2000-12-04 2002-07-16 Motorola, Inc. Method for producing SOI wafers by delamination

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AU1301395A (en) 1995-06-27
FI962350A0 (en) 1996-06-06
US20020160494A1 (en) 2002-10-31
WO1995016035A2 (en) 1995-06-15
EP0733109B1 (en) 2006-03-08
ATE319823T1 (en) 2006-03-15
DK0733109T3 (en) 2006-07-03
US20070004005A1 (en) 2007-01-04
AU689184B2 (en) 1998-03-26
JP2005312457A (en) 2005-11-10
US6719968B2 (en) 2004-04-13
EP0733109A1 (en) 1996-09-25
NO962304L (en) 1996-06-04
US7365052B2 (en) 2008-04-29
FI119816B (en) 2009-03-31
US6284872B1 (en) 2001-09-04
JPH09506261A (en) 1997-06-24
US20040146923A1 (en) 2004-07-29
US5658882A (en) 1997-08-19
DE69434651D1 (en) 2006-05-04
ES2255059T3 (en) 2006-06-16
CA2176942C (en) 2011-11-01
JP3717930B2 (en) 2005-11-16
JP3939729B2 (en) 2007-07-04
JP2007016037A (en) 2007-01-25
WO1995016035A3 (en) 1995-07-13
NO962304D0 (en) 1996-06-04
EP0733109B9 (en) 2006-07-05
US6984623B2 (en) 2006-01-10
PT733109E (en) 2006-07-31
FI962350A (en) 1996-07-16
DE69434651T2 (en) 2007-03-08
KR100353182B1 (en) 2002-09-28
NO317801B1 (en) 2004-12-13
OA10582A (en) 2002-08-23

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