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

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

Info

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

Links

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 US6027919A (en) 1993-12-07 1994-11-02 BMP-12 and BMP-13 proteins and DNA encoding them
US08/333,576 1994-11-02
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)

Country Link
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
DE69233022T2 (en) 1991-11-04 2004-02-12 Genetics Institute, LLC, Cambridge 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
AU688779B2 (en) * 1993-07-09 1998-03-19 Johns Hopkins University School Of Medicine, The Growth differentiation factor-7
US5770444A (en) * 1993-07-09 1998-06-23 The Johns Hopkins University School Of Medicine Growth differentiation factor-6
US6291206B1 (en) * 1993-09-17 2001-09-18 Genetics Institute, Inc. BMP receptor proteins
ES2255059T3 (en) * 1993-12-07 2006-06-16 Genetics Institute, Llc BMP-12, BMP-13 AND YOUR INDUCTION COMPOSITIONS OF TENDON.
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
NZ305472A (en) * 1995-04-19 1999-09-29 Hoechst Marion Roussel Ltd For A protein derived from human mp52 useful in treating cartilage and bone diseases
EP2289536A1 (en) * 1995-06-05 2011-03-02 Genetics Institute, LLC Use of bone morphogenetic proteins for healing and repair of connective tissue attachment
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
EP2332564A1 (en) 1997-02-07 2011-06-15 Stryker Corporation Matrix-free osteogenic devices, implants and methods 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
EP1018987B1 (en) * 1997-04-04 2014-10-29 Barnes-Jewish Hospital Neocartilage and methods of use
EP1988395A1 (en) 1997-05-30 2008-11-05 Curis, Inc. Methods for evaluating tissue morphogenesis and morphogenic activity
EP0896825B1 (en) 1997-08-14 2002-07-17 Sulzer Innotec Ag Composition and device for in vivo cartilage repair comprising nanocapsules with osteoinductive and/or chondroinductive factors
US20010031254A1 (en) * 1998-11-13 2001-10-18 Bianchi John R. Assembled implant
US6482584B1 (en) * 1998-11-13 2002-11-19 Regeneration Technologies, Inc. Cyclic implant perfusion cleaning and passivation process
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
IL136230A0 (en) 1997-11-28 2001-05-20 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
IL138488A0 (en) 1998-03-17 2001-10-31 Genentech Inc Polypeptides homologous to vegf and bmp1
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
US6294655B1 (en) 1998-04-03 2001-09-25 Hyseq, Inc. Anti-interleukin-1 receptor antagonist antibodies and uses thereof
US6541623B1 (en) 1998-04-03 2003-04-01 Hyseq, Inc. Interleukin—1 receptor antagonist and uses thereof
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
DE69933686T2 (en) * 1998-10-06 2007-08-23 Rush University Medical Center, Chicago COMPOSITION FOR USE IN CHEMONUCLEOLYSIS
US7572440B2 (en) 1999-07-30 2009-08-11 Stryker Corporation Method for repairing a defect in an intervertebral disc
JP3762222B2 (en) 1998-10-07 2006-04-05 ストライカー・コーポレーション Modified TGF-β superfamily protein
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
US6727224B1 (en) * 1999-02-01 2004-04-27 Genetics Institute, Llc. Methods and compositions for healing and repair of articular cartilage
WO2000044413A1 (en) * 1999-02-01 2000-08-03 Genetics Institute, Inc. Methods and compositions for healing and repair of articular cartilage
DK1177312T3 (en) 1999-04-28 2008-02-25 Genetics Inst Llc Therefore, human GIL-19 / AE289 proteins and polynucleotides coding
ES2549440T3 (en) 1999-05-18 2015-10-28 Dyax Corp. Fab fragment libraries and methods for use
PT1223990E (en) * 1999-10-15 2004-12-31 Fidia Advanced Biopolymers Srl HYALURONIC ACID FORMULATIONS FOR ADMINISTRATION 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
US6730313B2 (en) 2000-01-25 2004-05-04 Edwards Lifesciences Corporation Delivery systems for periadventitial delivery for treatment of restenosis and anastomotic intimal hyperplasia
EP1261365B1 (en) * 2000-03-09 2006-09-20 Zimmer Orthobiologics, Inc. Product 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
CA2648048A1 (en) 2000-06-23 2002-01-03 Genentech, Inc. Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis
EP2275549A1 (en) 2000-06-23 2011-01-19 Genentech, Inc. Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis
US7270730B2 (en) * 2000-08-04 2007-09-18 Essen Instruments, Inc. High-throughput electrophysiological measurement system
US7067046B2 (en) 2000-08-04 2006-06-27 Essen Instruments, Inc. System for rapid chemical activation in high-throughput electrophysiological measurements
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
JP2004525930A (en) * 2001-03-23 2004-08-26 バイオファーム・ゲゼルシャフト・ツア・バイオテクノロジシェン・エントヴィックルング・フォン・ファーマカ・ミット・ベシュレンクテル・ハフツング Use of TGF-β superfamily cytokines for the treatment and diagnosis of skin related diseases
WO2002099037A2 (en) * 2001-06-01 2002-12-12 Wyeth Compositions and methods for systemic administration of sequences encoding bone 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
BR0214275A (en) 2001-11-19 2004-09-21 Scil Technology Gmbh Device having osteoconductive and osteoinductive 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
WO2004014940A2 (en) 2002-08-13 2004-02-19 Wyeth PEPTIDES AS SOLUBILIZING EXCIPIENTS FOR TRANSFORMING GROWTH FACTOR ß PROTEINS
US7763270B2 (en) 2002-09-10 2010-07-27 Scil Technology Gmbh Metal implant coated under reduced oxygen concentration with osteoinductive protein
CA2533512C (en) 2003-07-25 2013-06-11 Amgen Inc. Antagonists and agonists of ldcam and methods of use
KR20060133961A (en) 2003-09-12 2006-12-27 와이어쓰 Injectable calcium phosphate solid rods and pastes for delivery of osteogenic proteins
US8328876B2 (en) * 2003-12-31 2012-12-11 Warsaw Orthopedic, Inc. Bone matrix compositions and methods
CA2557231C (en) * 2004-03-05 2013-12-31 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
WO2005089829A2 (en) 2004-03-10 2005-09-29 Scil Technology Gmbh Coated implants, their manufacturing and use thereof
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
EP1788986A1 (en) 2004-08-30 2007-05-30 Spineovations, Inc. Method of treating spinal internal disk derangement
EP1784145B1 (en) * 2004-08-30 2011-08-10 Neville Alleyne Implant for the treatment of ligaments and tendons
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
EP1863517A2 (en) * 2005-03-24 2007-12-12 Wyeth Use of fibrous tissue inducing proteins for hernia repair
BRPI0609504A2 (en) * 2005-03-30 2010-04-13 Wyeth Corp methods to stimulate hair growth by administering bone morphogenetic proteins (bmps)
US20060247790A1 (en) * 2005-04-30 2006-11-02 Mckay William F Shaped osteochondral grafts and methods of using same
US20060286289A1 (en) * 2005-06-15 2006-12-21 Rita Prajapati Method of intraoperative coating therapeutic agents onto sutures
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
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
US20060286171A1 (en) * 2005-06-17 2006-12-21 Tianhong Zhou Bone morphogenetic protein formulations
WO2007052096A2 (en) * 2005-06-29 2007-05-10 Cameron Malcolm Lang Clokie Production of bone morphogenic proteins (bmps) in transgenic mammals
WO2007053850A2 (en) 2005-11-01 2007-05-10 Osteotech, Inc. Bone matrix compositions and methods
PL1948689T3 (en) 2005-11-18 2012-09-28 Biopharm Ges Zur Biotechnologischen Entwicklung Von Pharmaka Mbh High activity growth factor mutants
US8147860B2 (en) 2005-12-06 2012-04-03 Etex Corporation Porous calcium phosphate bone material
EP1991282B1 (en) 2006-02-09 2013-06-19 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
US9161967B2 (en) 2006-06-30 2015-10-20 Biomimetic Therapeutics, Llc Compositions and methods for treating the vertebral column
JP5484047B2 (en) 2006-06-30 2014-05-07 バイオミメティック セラピューティクス， エルエルシー PDGF-biomatrix composition and method for treating rotator cuff injury
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
WO2008157492A2 (en) 2007-06-15 2008-12-24 Osteotech, Inc. Osteoinductive demineralized cancellous bone
CA2690457C (en) 2007-06-15 2018-02-20 Osteotech, Inc. Bone matrix compositions and methods
US9554920B2 (en) 2007-06-15 2017-01-31 Warsaw Orthopedic, Inc. Bone matrix compositions having nanoscale textured surfaces
WO2008157497A2 (en) 2007-06-15 2008-12-24 Osteotech, Inc. Method of treating tissue
US7678764B2 (en) 2007-06-29 2010-03-16 Johnson & Johnson Regenerative Therapeutics, Llc Protein formulations for use at elevated temperatures
US9492278B2 (en) 2007-07-10 2016-11-15 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
US8058237B2 (en) 2007-08-07 2011-11-15 Advanced Technologies & Regenerative Medicine, LLC Stable composition of GDF-5 and method of storage
WO2009052492A2 (en) 2007-10-19 2009-04-23 Osteotech, Inc. Demineralized bone matrix compositions and methods
US8741840B2 (en) 2008-02-13 2014-06-03 Washington University BMP-7 for use in treating neointimal hyperplasia
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
US20100010549A1 (en) * 2008-03-05 2010-01-14 Neville Alleyne device and method of minimally invasive extracapsular ligamentous augmentation for canine stifle ligament injuries
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
WO2010030714A2 (en) 2008-09-09 2010-03-18 Biomimetic Therapeutics, Inc. Platelet-derived growth factor compositions and methods for the treatment of tendon and ligament injuries
WO2010093955A1 (en) 2009-02-12 2010-08-19 Osteotech,Inc. Segmented delivery system
CN102369017A (en) 2009-02-12 2012-03-07 史赛克公司 Compositions and methods for minimally invasive systemic delivery of proteins comprising 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
CN102822197A (en) 2009-12-22 2012-12-12 史赛克公司 BMP-7 variants with reduced immunogenicity
NZ601559A (en) 2010-02-22 2014-10-31 Biomimetic Therapeutics Llc Platelet-derived growth factor compositions and methods for the treatment of tendinopathies
EP2598177B1 (en) 2010-07-30 2015-06-17 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
US10034945B2 (en) 2012-07-13 2018-07-31 Trustees Of Tufts College Silk powder compaction for production of constructs with high mechanical strength and stiffness
US20160296664A1 (en) 2013-04-12 2016-10-13 The Trustees Of Columbia University In The City Of New York Methods for host cell homing and dental pulp regeneration
SG10201906601TA (en) 2015-01-16 2019-09-27 Spineovations Inc Method of treating spinal disk
WO2017075055A1 (en) 2015-10-26 2017-05-04 President And Fellows Of Harvard College Reduced and 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
EP4076502A1 (en) 2019-12-18 2022-10-26 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
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
US4294753A (en) * 1980-08-04 1981-10-13 The Regents Of The University Of California Bone morphogenetic protein process
US4789732A (en) 1980-08-04 1988-12-06 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
EP0169016B2 (en) * 1984-07-16 2004-04-28 Celtrix Pharmaceuticals, Inc. Polypeptide cartilage-inducing factors found in bone
US4627982A (en) * 1984-07-16 1986-12-09 Collagen Corporation Partially purified bone-inducing factor
US4843063A (en) 1984-07-16 1989-06-27 Collagen Corporation Polypeptide cartilage-inducing factors found in bone
ATE78515T1 (en) 1984-10-05 1992-08-15 Genentech Inc DNA, CELL CULTURES AND METHODS FOR HETEROLOGOUS PROTEIN SECRETION AND PERIPLASMIC PROTEIN RECOVERY.
US4769328A (en) 1984-10-12 1988-09-06 Zymogenetics Inc. Expression of biologically active PDGF analogs in yeast
US5187263A (en) 1984-10-12 1993-02-16 Zymogenetics, Inc. Expression of biologically active PDGE analogs in eucaryotic cells
US4563350A (en) * 1984-10-24 1986-01-07 Collagen Corporation Inductive collagen based bone repair preparations
JPS63501471A (en) 1984-12-27 1988-06-09 サントリー株式会社 Method for purifying 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
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
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
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.
US5631142A (en) * 1986-07-01 1997-05-20 Genetics Institute, Inc. Compositions comprising bone morphogenetic protein-2 (BMP-2)
US5108922A (en) * 1986-07-01 1992-04-28 Genetics Institute, Inc. DNA sequences encoding BMP-1 products
ZA874681B (en) * 1986-07-01 1988-04-27 Genetics Inst Novel osteoinductive factors
US5106748A (en) * 1986-07-01 1992-04-21 Genetics Institute, Inc. Dna sequences encoding 5 proteins
US6432919B1 (en) * 1986-07-01 2002-08-13 Genetics Institute, Inc. Bone morphogenetic protein-3 and compositions
US4877864A (en) * 1987-03-26 1989-10-31 Genetics Institute, Inc. Osteoinductive factors
US5543394A (en) * 1986-07-01 1996-08-06 Genetics Institute, Inc. Bone morphogenetic protein 5(BMP-5) compositions
US6150328A (en) * 1986-07-01 2000-11-21 Genetics Institute, Inc. BMP products
US5187076A (en) * 1986-07-01 1993-02-16 Genetics Institute, Inc. DNA sequences encoding BMP-6 proteins
US5459047A (en) * 1986-07-01 1995-10-17 Genetics Institute, Inc. BMP-6 proteins
US5013649A (en) * 1986-07-01 1991-05-07 Genetics Institute, Inc. DNA sequences encoding osteoinductive 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
AU3433989A (en) * 1988-04-06 1989-11-03 Celtrix Laboratories, Inc. Bone-inducing protein
US5266683A (en) 1988-04-08 1993-11-30 Stryker Corporation Osteogenic proteins
US5354557A (en) 1988-04-08 1994-10-11 Stryker Corporation Osteogenic devices
US5108753A (en) 1988-04-08 1992-04-28 Creative Biomolecules Osteogenic devices
US5011691A (en) 1988-08-15 1991-04-30 Stryker Corporation Osteogenic devices
US4968590A (en) * 1988-04-08 1990-11-06 Stryker Corporation Osteogenic proteins and polypeptides
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
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
US5106626A (en) 1988-10-11 1992-04-21 International Genetic Engineering, Inc. Osteogenic factors
US5284756A (en) 1988-10-11 1994-02-08 Lynn Grinna Heterodimeric osteogenic factor
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
EP0416578B1 (en) * 1989-09-06 1996-07-31 Takeda Chemical Industries, Ltd. Protein, DNA 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
ATE209251T1 (en) * 1990-05-16 2001-12-15 Genetics Inst PROTEINS PRODUCING BONE AND CARTILAGE FORMATION
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
KR0145278B1 (en) 1991-06-21 1998-07-15 브루스 엠. 에이센 Pharmaceutical formulations of osteogenic proteins
EP0592562B1 (en) * 1991-06-25 1999-01-07 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
DE69233022T2 (en) * 1991-11-04 2004-02-12 Genetics Institute, LLC, Cambridge RECOMBINANT BONE MORPHOGENETIC PROTEIN HETERODIMERS, COMPOSITIONS AND METHODS OF USE
RU2208638C2 (en) * 1992-02-12 2003-07-20 Биофарм Гезельшафт Цур Биотехнологишен Энтвиклунг фон Фармака мбХ Dna (variants), method for preparing protein, protein, pharmaceutical composition
DE69331096T2 (en) 1992-02-28 2002-08-14 Cohesion Tech Inc INJECTABLE, CERAMIC COMPOUNDS AND METHOD FOR THE PRODUCTION AND USE THEREOF
AU3920693A (en) * 1992-03-18 1993-10-21 General Hospital Corporation, The Four novel receptors of the TGF-beta receptor family
JP3645258B2 (en) * 1993-01-12 2005-05-11 ジョーンズ ホプキンス ユニバーシティー スクール オブ メディシン Growth and differentiation factor-5
GB9308060D0 (en) * 1993-04-19 1993-06-02 Cancer Res Campaign Tech Stem cell inhibitor
US5637480A (en) * 1993-05-12 1997-06-10 Genetics Institute, Inc. DNA molecules encoding bone morphogenetic protein-10
EP0698094B1 (en) * 1993-05-12 2004-02-04 Genetics Institute, LLC Bmp-11 compositions
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
US5770444A (en) * 1993-07-09 1998-06-23 The Johns Hopkins University School Of Medicine Growth differentiation factor-6
AU688779B2 (en) * 1993-07-09 1998-03-19 Johns Hopkins University School Of Medicine, The Growth differentiation factor-7
JPH09501932A (en) * 1993-08-26 1997-02-25 ジェネティックス・インスティテュート・インコーポレイテッド Nerve regeneration using human and bone morphogenetic proteins
US5455041A (en) * 1993-09-13 1995-10-03 Research Foundation Of State University Of New York At Buffalo Method for inducing periodontal tissue regeneration
US6027919A (en) * 1993-12-07 2000-02-22 Genetics Institute, Inc. BMP-12 and BMP-13 proteins and DNA encoding them
US5399677A (en) * 1993-12-07 1995-03-21 Genetics Institute, Inc. Mutants of bone morphogenetic proteins
ES2255059T3 (en) * 1993-12-07 2006-06-16 Genetics Institute, Llc BMP-12, BMP-13 AND YOUR INDUCTION COMPOSITIONS OF TENDON.
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
EP2289536A1 (en) * 1995-06-05 2011-03-02 Genetics Institute, LLC Use of bone morphogenetic proteins for healing and repair of connective tissue attachment
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

Also Published As

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

Similar Documents

Publication Publication Date Title
CA2176942A1 (en) Bmp-12, bmp-13 and tendon-inducing compositions thereof
KR960706559A (en) BMP-12, BMP-13 and dry-derived compositions thereof (BMP-12, BMP-13 ANDTENDON-INDUCING COMPOSITIONS THEREOF)
KR960701997A (en) BMP-10 composition [BMP-10 COMPOSITIONS]
Hiraki et al. Molecular cloning of a new class of cartilage-specific matrix, chondromodulin-I, which stimulates growth of cultured chondrocytes
US5728679A (en) BMP-15 compositions
KR960701996A (en) BMP-11 composition [BMP-11 COMPOSITIONS]
AU682238B2 (en) Mutants of bone morphogenetic proteins
CN111944057B (en) Recombinant human collagen peptide and application thereof
EP0429570B1 (en) Osteoinductive compositions
US5932216A (en) Antibodies to bone morphogenetic protein-10 (BMP-10)
AU704515C (en) Novel protein and process for producing the same
RU2002120050A (en) NEW PROTEINS AND METHODS FOR PRODUCING SUCH PROTEINS
KR950700331A (en) DNA sequences encoding novel growth / differentiation factors (DNA SEQUENCES ENCODING NOVEL GROWTH / DIFFERENTIATION FACTORS)
CA2194172A1 (en) Neurturin and related growth factors
BR9712348B1 (en) expression vector, transformed or transfected yeast or bacterial cell, process for producing a fgf homologous polypeptide, pharmaceutical composition, and processes for stimulating ex vivo myocyte or myocyte progenitor cells
RU2001123926A (en) Polypeptide variants with increased heparin binding ability
CA2288373A1 (en) Human cerberus protein
KR900009989A (en) Endothelial growth factor
US20130190236A1 (en) BMP-7 Variants with Reduced Immunogenicity
WO2000055321B1 (en) Vertebrate protein slit, dna sequence encoding it and uses thereof
CA2574929A1 (en) Bone morphogenetic protein (bmp)-17 and bmp-18 and compositions
MXPA98008915A (en) Process to produce the bone morphogenetic protein by madurac
HUP9903484A3 (en) Fibroblast growth factor homologs

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20141208