NO321153B1 - Preparat av MP-52-protein pa 119 aminosyrer, farmasoytisk preparat som inneholder dette, fremgangsmate for fremstilling av preparatet av MP-52-protein, fremgangsmate for fremstilling av dimert protein som er omfattet av et preparat av MP-52-protein som er homodimert, og anvendelse av det homodimere proteinet for fremstilling av medikament. - Google Patents

Preparat av MP-52-protein pa 119 aminosyrer, farmasoytisk preparat som inneholder dette, fremgangsmate for fremstilling av preparatet av MP-52-protein, fremgangsmate for fremstilling av dimert protein som er omfattet av et preparat av MP-52-protein som er homodimert, og anvendelse av det homodimere proteinet for fremstilling av medikament. Download PDF

Info

Publication number: NO321153B1
Authority: NO; Norway
Prior art keywords: protein; bone; cartilage; preparation; amino acid
Prior art date: 1995-04-19

Application number

NO19974812A

Other languages

English (en)

Norwegian (no)

Other versions

NO974812D0 (no

NO974812L (no

Inventor

Yusuke Satoh

Tomoaki Matsumoto

Fusao Makishima

Hiroyuki Takamatsu

Hideo Miki

Shinji Kawai

Michio Kimura

Mieko Katsuura

Koichi Enomoto

Original Assignee

Bioph Biotech Entw Pharm Gmbh

Hoechst Marion Roussel Ltd

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.)

1995-04-19

Filing date

1997-10-17

Publication date

2006-03-27

1997-10-17 Application filed by Bioph Biotech Entw Pharm Gmbh, Hoechst Marion Roussel Ltd filed Critical Bioph Biotech Entw Pharm Gmbh

1997-10-17 Publication of NO974812D0 publication Critical patent/NO974812D0/no

1997-12-19 Publication of NO974812L publication Critical patent/NO974812L/no

2006-03-27 Publication of NO321153B1 publication Critical patent/NO321153B1/no

Links

108090000623 proteins and genes Proteins 0.000 title claims abstract description 119
102000004169 proteins and genes Human genes 0.000 title claims abstract description 118
238000002360 preparation method Methods 0.000 title claims description 27
150000001413 amino acids Chemical class 0.000 title claims description 24
239000003814 drug Substances 0.000 title claims description 4
229940079593 drug Drugs 0.000 title claims description 4
210000000845 cartilage Anatomy 0.000 claims abstract description 38
241000588724 Escherichia coli Species 0.000 claims abstract description 26
101100472152 Trypanosoma brucei brucei (strain 927/4 GUTat10.1) REL1 gene Proteins 0.000 claims abstract description 24
239000013612 plasmid Substances 0.000 claims abstract description 18
208000020084 Bone disease Diseases 0.000 claims abstract description 15
208000015100 cartilage disease Diseases 0.000 claims abstract description 14
239000000710 homodimer Substances 0.000 claims abstract description 14
229930182817 methionine Natural products 0.000 claims abstract description 12
210000003000 inclusion body Anatomy 0.000 claims abstract description 10
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims abstract description 8
230000009466 transformation Effects 0.000 claims abstract description 6
235000018102 proteins Nutrition 0.000 claims description 107
210000000988 bone and bone Anatomy 0.000 claims description 31
230000007547 defect Effects 0.000 claims description 23
238000000034 method Methods 0.000 claims description 22
108020004414 DNA Proteins 0.000 claims description 18
238000004519 manufacturing process Methods 0.000 claims description 17
238000011282 treatment Methods 0.000 claims description 12
239000000825 pharmaceutical preparation Substances 0.000 claims description 10
235000004279 alanine Nutrition 0.000 claims description 9
235000001014 amino acid Nutrition 0.000 claims description 8
208000010392 Bone Fractures Diseases 0.000 claims description 7
238000010276 construction Methods 0.000 claims description 6
238000000746 purification Methods 0.000 claims description 6
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 5
108091028043 Nucleic acid sequence Proteins 0.000 claims description 5
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 4
208000001132 Osteoporosis Diseases 0.000 claims description 4
201000008482 osteoarthritis Diseases 0.000 claims description 4
238000004090 dissolution Methods 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 2
201000010099 disease Diseases 0.000 claims 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
239000000178 monomer Substances 0.000 abstract description 6
239000000539 dimer Substances 0.000 abstract description 4
125000003275 alpha amino acid group Chemical group 0.000 abstract 2
238000012258 culturing Methods 0.000 abstract 1
239000008194 pharmaceutical composition Substances 0.000 abstract 1
230000003381 solubilizing effect Effects 0.000 abstract 1
239000000243 solution Substances 0.000 description 18
210000000689 upper leg Anatomy 0.000 description 18
210000001519 tissue Anatomy 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
125000000539 amino acid group Chemical group 0.000 description 10
230000000694 effects Effects 0.000 description 10
238000010186 staining Methods 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
241000699666 Mus <mouse, genus> Species 0.000 description 9
241000700159 Rattus Species 0.000 description 9
238000004458 analytical method Methods 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
239000013604 expression vector Substances 0.000 description 9
210000003455 parietal bone Anatomy 0.000 description 9
108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 8
102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 8
210000001612 chondrocyte Anatomy 0.000 description 8
230000001965 increasing effect Effects 0.000 description 8
239000000203 mixture Substances 0.000 description 8
239000012634 fragment Substances 0.000 description 7
230000001002 morphogenetic effect Effects 0.000 description 7
102000012422 Collagen Type I Human genes 0.000 description 6
108010022452 Collagen Type I Proteins 0.000 description 6
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 6
239000000463 material Substances 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
239000000872 buffer Substances 0.000 description 5
229920001436 collagen Polymers 0.000 description 5
238000010353 genetic engineering Methods 0.000 description 5
230000011164 ossification Effects 0.000 description 5
238000001356 surgical procedure Methods 0.000 description 5
239000013598 vector Substances 0.000 description 5
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
102000008186 Collagen Human genes 0.000 description 4
108010035532 Collagen Proteins 0.000 description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
239000002299 complementary DNA Substances 0.000 description 4
239000008103 glucose Substances 0.000 description 4
238000002513 implantation Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000001301 oxygen Substances 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
230000008929 regeneration Effects 0.000 description 4
238000011069 regeneration method Methods 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 3
102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 3
108700039691 Genetic Promoter Regions Proteins 0.000 description 3
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 3
241000283973 Oryctolagus cuniculus Species 0.000 description 3
210000001188 articular cartilage Anatomy 0.000 description 3
210000002798 bone marrow cell Anatomy 0.000 description 3
239000004202 carbamide Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000000515 collagen sponge Substances 0.000 description 3
238000001962 electrophoresis Methods 0.000 description 3
229960003180 glutathione Drugs 0.000 description 3
230000035876 healing Effects 0.000 description 3
230000032631 intramembranous ossification Effects 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
210000000963 osteoblast Anatomy 0.000 description 3
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
108020004705 Codon Proteins 0.000 description 2
108010024636 Glutathione Proteins 0.000 description 2
108010090254 Growth Differentiation Factor 5 Proteins 0.000 description 2
102100035379 Growth/differentiation factor 5 Human genes 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
239000012506 Sephacryl® Substances 0.000 description 2
229920002684 Sepharose Polymers 0.000 description 2
108091081024 Start codon Proteins 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
230000001580 bacterial effect Effects 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000022159 cartilage development Effects 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
238000003306 harvesting Methods 0.000 description 2
229910052588 hydroxylapatite Inorganic materials 0.000 description 2
230000006698 induction Effects 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
210000000281 joint capsule Anatomy 0.000 description 2
210000004962 mammalian cell Anatomy 0.000 description 2
239000011707 mineral Substances 0.000 description 2
XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 2
239000013600 plasmid vector Substances 0.000 description 2
-1 polyethylene Polymers 0.000 description 2
229920000573 polyethylene Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
230000002265 prevention Effects 0.000 description 2
239000000047 product Substances 0.000 description 2
239000008213 purified water Substances 0.000 description 2
238000002601 radiography Methods 0.000 description 2
230000010076 replication Effects 0.000 description 2
238000004007 reversed phase HPLC Methods 0.000 description 2
FGDZQCVHDSGLHJ-UHFFFAOYSA-M rubidium chloride Chemical compound [Cl-].[Rb+] FGDZQCVHDSGLHJ-UHFFFAOYSA-M 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
210000002435 tendon Anatomy 0.000 description 2
238000012360 testing method Methods 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
238000002054 transplantation Methods 0.000 description 2
239000012137 tryptone Substances 0.000 description 2
238000011144 upstream manufacturing Methods 0.000 description 2
238000005406 washing Methods 0.000 description 2
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
229920000936 Agarose Polymers 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
229940122361 Bisphosphonate Drugs 0.000 description 1
102000055006 Calcitonin Human genes 0.000 description 1
108060001064 Calcitonin Proteins 0.000 description 1
206010007710 Cartilage injury Diseases 0.000 description 1
206010008723 Chondrodystrophy Diseases 0.000 description 1
206010061762 Chondropathy Diseases 0.000 description 1
206010009269 Cleft palate Diseases 0.000 description 1
206010010356 Congenital anomaly Diseases 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
102000012410 DNA Ligases Human genes 0.000 description 1
108010061982 DNA Ligases Proteins 0.000 description 1
108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 1
206010017076 Fracture Diseases 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
108700007698 Genetic Terminator Regions Proteins 0.000 description 1
108010053070 Glutathione Disulfide Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
108010090290 Growth Differentiation Factor 2 Proteins 0.000 description 1
108010090250 Growth Differentiation Factor 6 Proteins 0.000 description 1
102100040892 Growth/differentiation factor 2 Human genes 0.000 description 1
102100035368 Growth/differentiation factor 6 Human genes 0.000 description 1
102100035363 Growth/differentiation factor 7 Human genes 0.000 description 1
101710204283 Growth/differentiation factor 7 Proteins 0.000 description 1
241000282412 Homo Species 0.000 description 1
102000008100 Human Serum Albumin Human genes 0.000 description 1
108091006905 Human Serum Albumin Proteins 0.000 description 1
206010020649 Hyperkeratosis Diseases 0.000 description 1
108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
108010086093 Mung Bean Nuclease Proteins 0.000 description 1
241000283977 Oryctolagus Species 0.000 description 1
201000009859 Osteochondrosis Diseases 0.000 description 1
208000006735 Periostitis Diseases 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
108010006785 Taq Polymerase Proteins 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
208000005065 achondrogenesis Diseases 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000000853 adhesive Substances 0.000 description 1
230000001070 adhesive effect Effects 0.000 description 1
210000001789 adipocyte Anatomy 0.000 description 1
238000013019 agitation Methods 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
230000003698 anagen phase Effects 0.000 description 1
238000000137 annealing Methods 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
239000012237 artificial material Substances 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
150000004663 bisphosphonates Chemical class 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
229940112869 bone morphogenetic protein Drugs 0.000 description 1
230000010478 bone regeneration Effects 0.000 description 1
230000037118 bone strength Effects 0.000 description 1
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
229960004015 calcitonin Drugs 0.000 description 1
229940041514 candida albicans extract Drugs 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000003848 cartilage regeneration Effects 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000000919 ceramic Substances 0.000 description 1
208000017568 chondrodysplasia Diseases 0.000 description 1
210000001608 connective tissue cell Anatomy 0.000 description 1
229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
238000002316 cosmetic surgery Methods 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
210000003275 diaphysis Anatomy 0.000 description 1
230000029087 digestion Effects 0.000 description 1
229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
238000009547 dual-energy X-ray absorptiometry Methods 0.000 description 1
230000035194 endochondral ossification Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
229940011871 estrogen Drugs 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
210000002744 extracellular matrix Anatomy 0.000 description 1
239000000835 fiber Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
208000014674 injury Diseases 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
238000002955 isolation Methods 0.000 description 1
BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
210000003127 knee Anatomy 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000002414 leg Anatomy 0.000 description 1
230000003902 lesion Effects 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000002609 medium Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000000386 microscopy Methods 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
210000000663 muscle cell Anatomy 0.000 description 1
238000002703 mutagenesis Methods 0.000 description 1
231100000350 mutagenesis Toxicity 0.000 description 1
230000035772 mutation Effects 0.000 description 1
231100000926 not very toxic Toxicity 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000003239 periodontal effect Effects 0.000 description 1
210000003460 periosteum Anatomy 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
238000003752 polymerase chain reaction Methods 0.000 description 1
239000011148 porous material Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000013587 production medium Substances 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
238000011268 retreatment Methods 0.000 description 1
229940102127 rubidium chloride Drugs 0.000 description 1
238000007789 sealing Methods 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
238000000527 sonication Methods 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
238000007447 staining method Methods 0.000 description 1
239000010959 steel Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
229960003495 thiamine Drugs 0.000 description 1
DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
210000000515 tooth Anatomy 0.000 description 1
238000011426 transformation method Methods 0.000 description 1
QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
235000005282 vitamin D3 Nutrition 0.000 description 1
239000011647 vitamin D3 Substances 0.000 description 1
229940021056 vitamin d3 Drugs 0.000 description 1
239000003643 water by type Substances 0.000 description 1
239000012138 yeast extract Substances 0.000 description 1

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
- 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
- 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
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Medicinal Chemistry (AREA)
Biochemistry (AREA)
General Chemical & Material Sciences (AREA)
Genetics & Genomics (AREA)
Gastroenterology & Hepatology (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Zoology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Toxicology (AREA)
Chemical Kinetics & Catalysis (AREA)
Biophysics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Rheumatology (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

NO19974812A 1995-04-19 1997-10-17 Preparat av MP-52-protein pa 119 aminosyrer, farmasoytisk preparat som inneholder dette, fremgangsmate for fremstilling av preparatet av MP-52-protein, fremgangsmate for fremstilling av dimert protein som er omfattet av et preparat av MP-52-protein som er homodimert, og anvendelse av det homodimere proteinet for fremstilling av medikament. NO321153B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
JP9366495		1995-04-19
JP32240395		1995-11-17
PCT/JP1996/001062 WO1996033215A1 (en)	1995-04-19	1996-04-19	Novel protein and process for producing the same

Publications (3)

Publication Number	Publication Date
NO974812D0 NO974812D0 (no)	1997-10-17
NO974812L NO974812L (no)	1997-12-19
NO321153B1 true NO321153B1 (no)	2006-03-27

Family

ID=26434967

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19974812A NO321153B1 (no)	1995-04-19	1997-10-17	Preparat av MP-52-protein pa 119 aminosyrer, farmasoytisk preparat som inneholder dette, fremgangsmate for fremstilling av preparatet av MP-52-protein, fremgangsmate for fremstilling av dimert protein som er omfattet av et preparat av MP-52-protein som er homodimert, og anvendelse av det homodimere proteinet for fremstilling av medikament.

Country Status (18)

Country	Link
US (3)	US7235527B2 (uk)
EP (1)	EP0955313B1 (uk)
AT (1)	ATE325131T1 (uk)
AU (1)	AU704515C (uk)
BR (1)	BR9608019A (uk)
CA (1)	CA2216741C (uk)
DE (2)	DE69636728T4 (uk)
DK (1)	DK0955313T3 (uk)
EA (1)	EA000582B1 (uk)
ES (1)	ES2258774T3 (uk)
HU (1)	HU225424B1 (uk)
NO (1)	NO321153B1 (uk)
NZ (1)	NZ305472A (uk)
OA (1)	OA10528A (uk)
PL (1)	PL186518B1 (uk)
PT (1)	PT955313E (uk)
UA (1)	UA46767C2 (uk)
WO (1)	WO1996033215A1 (uk)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20070166353A1 (en) *	1988-04-08	2007-07-19	Stryker Corporation	Osteogenic proteins
US6586388B2 (en)	1988-04-08	2003-07-01	Stryker Corporation	Method of using recombinant osteogenic protein to repair bone or cartilage defects
US20080233170A1 (en) *	1992-02-21	2008-09-25	Stryker Corporation	Osteogenic Proteins
ZA9711580B (en) *	1996-12-25	1999-09-23	Hoechst Marion Roussel Ltd	Process for the production of purified dimeric bone morphogenetic factors.
RS49691B (sr) *	1997-01-30	2007-12-31	Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka Mbh.,	Liofilizovan preparat ljudskog morfogenetskog faktora mp52 kosti
DE69814352T3 (de) †	1997-02-07	2009-08-13	Stryker Corp., Kalamazoo	Matrixlose osteogene vorrichtungen und implantate und verfahren zu deren verwendung
US6727224B1 (en)	1999-02-01	2004-04-27	Genetics Institute, Llc.	Methods and compositions for healing and repair of articular cartilage
KR100775958B1 (ko)	2005-03-30	2007-11-13	김정문	조직재생 기능을 가지는 비활성 폴리펩티드 및 그 제조방법
WO2006104306A1 (en) *	2005-03-30	2006-10-05	Jung Moon Kim	Non-activated polypeptides having a function of tissue regeneration and method for preparing the same
US20060286144A1 (en) *	2005-06-17	2006-12-21	Chunlin Yang	Reinforced collagen scaffold
DK1948689T3 (da)	2005-11-18	2012-07-23	Bioph Biotech Entw Pharm Gmbh	Højaktivitetsvækstfaktormutanter
EP1880731A1 (en) *	2006-07-18	2008-01-23	BIOPHARM GESELLSCHAFT ZUR BIOTECHNOLOGISCHEN ENTWICKLUNG VON PHARMAKA mbH	Human growth and differentiation factor GDF-5
AU2007234612B2 (en)	2006-12-14	2013-06-27	Johnson & Johnson Regenerative Therapeutics, Llc	Protein stabilization formulations
US20100047299A1 (en) *	2007-01-25	2010-02-25	Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka Mbh	Use of gdf-5 for the improvement or maintenance of dermal appearance
US7678764B2 (en)	2007-06-29	2010-03-16	Johnson & Johnson Regenerative Therapeutics, Llc	Protein formulations for use at elevated temperatures
EP2019117A1 (en)	2007-07-27	2009-01-28	BIOPHARM GESELLSCHAFT ZUR BIOTECHNOLOGISCHEN ENTWICKLUNG VON PHARMAKA mbH	Optimized purification process of recombinant growth factor protein
WO2009020744A1 (en)	2007-08-07	2009-02-12	Johnson & Johnson Regenerative Therapeutics, Llc	Protein formulations comprising gdf-5 in aqueous acidic solution
JP2009106163A (ja) *	2007-10-26	2009-05-21	Kyushu Univ	核酸配列、ベクター、形質転換体、製造方法、及び、核酸配列プライマー
EP2276458A1 (en)	2008-04-14	2011-01-26	Advanced Technologies and Regenerative Medicine, LLC	Liquid buffered gdf-5 formulations
US11260110B2 (en)	2009-11-18	2022-03-01	Ptlnv, Llc, Series Four (4)	Nanoparticles for the therapeutic treatment of radiation-induced skin ulcers
US9226898B1 (en) *	2009-11-18	2016-01-05	Richard C. K. Yen	Submicron particles for the treatment of radiation damage in patients
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
US8551525B2 (en)	2010-12-23	2013-10-08	Biostructures, Llc	Bone graft materials and methods
US8455436B2 (en)	2010-12-28	2013-06-04	Depuy Mitek, Llc	Compositions and methods for treating joints
US8524662B2 (en)	2010-12-28	2013-09-03	Depuy Mitek, Llc	Compositions and methods for treating joints
US8398611B2 (en)	2010-12-28	2013-03-19	Depuy Mitek, Inc.	Compositions and methods for treating joints
EP2537538A1 (en)	2011-06-22	2012-12-26	Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka mbH	Bioresorbable Wound Dressing
US8623839B2 (en)	2011-06-30	2014-01-07	Depuy Mitek, Llc	Compositions and methods for stabilized polysaccharide formulations
EP2602264A1 (en)	2011-12-05	2013-06-12	Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka mbH	GDF-5 mutant for inducing cartilage formation
US9682099B2 (en)	2015-01-20	2017-06-20	DePuy Synthes Products, Inc.	Compositions and methods for treating joints
JP7700127B2 (ja)	2019-12-18	2025-06-30	メルクパテントゲゼルシャフトミットベシュレンクテルハフツング	疼痛及び軟骨破壊を治療するためのｇｄｆ－５変異体の使用
KR20240064367A (ko) *	2022-11-04	2024-05-13	주식회사 대웅제약	TGF-β3 단백질의 정제방법

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4725234A (en) *	1985-08-15	1988-02-16	Ethridge Edwin C	Alveolar bone grafting process with controlled surface active ceramics
US5079352A (en) *	1986-08-22	1992-01-07	Cetus Corporation	Purified thermostable enzyme
US5354557A (en) *	1988-04-08	1994-10-11	Stryker Corporation	Osteogenic devices
GB8927546D0 (en) *	1989-12-06	1990-02-07	Ciba Geigy	Process for the production of biologically active tgf-beta
US5143829A (en) *	1990-03-29	1992-09-01	California Biotechnology Inc.	High level expression of basic fibroblast growth factor having a homogeneous n-terminus
US5118667A (en) *	1991-05-03	1992-06-02	Celtrix Pharmaceuticals, Inc.	Bone growth factors and inhibitors of bone resorption for promoting bone formation
US5171579A (en) *	1991-10-11	1992-12-15	Genetics Institute, Inc.	Formulations of blood clot-polymer matrix for delivery of osteogenic proteins
ATE238417T1 (de)	1991-11-04	2003-05-15	Inst Genetics Llc	Rekombinante knochenmorphogenetische protein heterodimere, zusammensetzungen und verfahren zur verwendung
NZ249113A (en)	1992-02-12	1996-07-26	Bioph Biotech Entw Pharm Gmbh	Recombinant dna encoding tgf-b, its production and pharmaceutical compositions thereof
EP0690871A4 (en)	1993-01-12	1999-10-20	Univ Johns Hopkins Med	GROWTH DIFFERENTIATION FACTOR-5
IL110589A0 (en) *	1993-08-10	1994-11-11	Bioph Biotech Entw Pharm Gmbh	Growth/differentiation factor of the TGF- beta family
US6248554B1 (en)	1993-11-24	2001-06-19	The Procter & Gamble Company	DNA sequence coding for a BMP receptor
US5399677A (en)	1993-12-07	1995-03-21	Genetics Institute, Inc.	Mutants of bone morphogenetic proteins
ATE319823T1 (de) *	1993-12-07	2006-03-15	Inst Genetics Llc	Bmp-12, bmp-13 und diese enthaltende sehne- induzierende zusammensetzungen
US5707962A (en) *	1994-09-28	1998-01-13	Gensci Regeneration Sciences Inc.	Compositions with enhanced osteogenic potential, method for making the same and therapeutic uses thereof

1996
- 1996-04-19 EP EP96910198A patent/EP0955313B1/en not_active Expired - Lifetime
- 1996-04-19 DE DE69636728T patent/DE69636728T4/de not_active Expired - Lifetime
- 1996-04-19 PL PL96322945A patent/PL186518B1/pl not_active IP Right Cessation
- 1996-04-19 AT AT96910198T patent/ATE325131T1/de active
- 1996-04-19 AU AU53470/96A patent/AU704515C/en not_active Ceased
- 1996-04-19 PT PT96910198T patent/PT955313E/pt unknown
- 1996-04-19 BR BR9608019-1A patent/BR9608019A/pt not_active IP Right Cessation
- 1996-04-19 US US08/945,459 patent/US7235527B2/en not_active Expired - Fee Related
- 1996-04-19 HU HU9801697A patent/HU225424B1/hu not_active IP Right Cessation
- 1996-04-19 NZ NZ305472A patent/NZ305472A/en not_active IP Right Cessation
- 1996-04-19 WO PCT/JP1996/001062 patent/WO1996033215A1/ja not_active Ceased
- 1996-04-19 CA CA002216741A patent/CA2216741C/en not_active Expired - Fee Related
- 1996-04-19 DK DK96910198T patent/DK0955313T3/da active
- 1996-04-19 ES ES96910198T patent/ES2258774T3/es not_active Expired - Lifetime
- 1996-04-19 EA EA199700329A patent/EA000582B1/ru not_active IP Right Cessation
- 1996-04-19 UA UA97115563A patent/UA46767C2/uk unknown
- 1996-04-19 DE DE69636728A patent/DE69636728D1/de not_active Expired - Lifetime
1997
- 1997-10-17 OA OA70112A patent/OA10528A/en unknown
- 1997-10-17 NO NO19974812A patent/NO321153B1/no not_active IP Right Cessation
2003
- 2003-02-12 US US10/365,231 patent/US7268114B2/en not_active Expired - Fee Related
2007
- 2007-08-03 US US11/833,653 patent/US7816103B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
HUP9801697A2 (hu)	1998-10-28
CA2216741C (en)	2008-01-15
ATE325131T1 (de)	2006-06-15
PL186518B1 (pl)	2004-01-30
US7268114B2 (en)	2007-09-11
AU704515C (en)	2002-03-28
NZ305472A (en)	1999-09-29
CA2216741A1 (en)	1996-10-24
HUP9801697A3 (en)	2000-06-28
NO974812D0 (no)	1997-10-17
WO1996033215A1 (en)	1996-10-24
AU5347096A (en)	1996-11-07
EP0955313A1 (en)	1999-11-10
EP0955313A4 (en)	2001-11-07
PL322945A1 (en)	1998-03-02
ES2258774T3 (es)	2006-09-01
AU704515B2 (en)	1999-04-22
BR9608019A (pt)	1999-11-30
NO974812L (no)	1997-12-19
EP0955313B1 (en)	2006-05-03
PT955313E (pt)	2006-07-31
US20030181378A1 (en)	2003-09-25
MX9708011A (es)	1998-03-31
DE69636728T4 (de)	2007-06-28
UA46767C2 (uk)	2002-06-17
EA199700329A1 (ru)	1998-04-30
OA10528A (en)	2002-04-26
DE69636728T2 (de)	2007-02-22
US20020102633A1 (en)	2002-08-01
HU225424B1 (en)	2006-11-28
US7816103B2 (en)	2010-10-19
EA000582B1 (ru)	1999-12-29
DK0955313T3 (da)	2006-08-21
US20090325864A1 (en)	2009-12-31
US7235527B2 (en)	2007-06-26
DE69636728D1 (de)	2007-01-04

Publication	Publication Date	Title
NO321153B1 (no)	2006-03-27	Preparat av MP-52-protein pa 119 aminosyrer, farmasoytisk preparat som inneholder dette, fremgangsmate for fremstilling av preparatet av MP-52-protein, fremgangsmate for fremstilling av dimert protein som er omfattet av et preparat av MP-52-protein som er homodimert, og anvendelse av det homodimere proteinet for fremstilling av medikament.
KR100259827B1 (ko)	2000-06-15	재조합 골형태 형성 단백질 헤테로다이머, 그 조성물 및 사용방법
US6903071B2 (en)	2005-06-07	Cartilage/bone inducing materials for reparation
US9200048B2 (en)	2015-12-01	High activity growth factor mutants
EP0866125A1 (en)	1998-09-23	Novel protein hmw human mp52
AP856A (en)	2000-07-12	A novel homodimer protein used in pharmaceutical preparation for treating cartlage and bone diseases.
JP2997549B2 (ja)	2000-01-11	新規なタンパク質およびその製法
MXPA97008011A (en)	1998-10-15	New protein and process for your preparation
JP5637854B2 (ja)	2014-12-10	腱骨移行部組織または靭帯骨移行部組織の再生促進剤
JPWO1996033215A1 (ja)	1997-08-26	新規なタンパク質およびその製法

Legal Events

Date	Code	Title	Description
2013-12-02	MM1K	Lapsed by not paying the annual fees