ES2306462T3 - Analisis y separacion de proteinas del factor de crecimiento derivadas de plaquetas. - Google Patents
Analisis y separacion de proteinas del factor de crecimiento derivadas de plaquetas. Download PDFInfo
- Publication number
- ES2306462T3 ES2306462T3 ES97948629T ES97948629T ES2306462T3 ES 2306462 T3 ES2306462 T3 ES 2306462T3 ES 97948629 T ES97948629 T ES 97948629T ES 97948629 T ES97948629 T ES 97948629T ES 2306462 T3 ES2306462 T3 ES 2306462T3
- Authority
- ES
- Spain
- Prior art keywords
- rpdgf
- isoforms
- polypeptides
- pdgf
- intact
- 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.)
- Expired - Lifetime
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 68
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 66
- 239000003102 growth factor Substances 0.000 title abstract description 6
- 238000000926 separation method Methods 0.000 title description 32
- 238000004458 analytical method Methods 0.000 title description 19
- 102000001708 Protein Isoforms Human genes 0.000 claims abstract description 196
- 108010029485 Protein Isoforms Proteins 0.000 claims abstract description 196
- 108010081589 Becaplermin Proteins 0.000 claims abstract description 90
- 238000000034 method Methods 0.000 claims abstract description 86
- 239000000203 mixture Substances 0.000 claims abstract description 73
- 230000002441 reversible effect Effects 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 229920001184 polypeptide Polymers 0.000 claims description 45
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 45
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 45
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 44
- 208000027418 Wounds and injury Diseases 0.000 claims description 31
- 206010052428 Wound Diseases 0.000 claims description 30
- 210000004027 cell Anatomy 0.000 claims description 22
- 238000005515 capillary zone electrophoresis Methods 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 239000000539 dimer Substances 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 10
- -1 sulfopropyl Chemical group 0.000 claims description 7
- 241000235070 Saccharomyces Species 0.000 claims description 5
- 210000000988 bone and bone Anatomy 0.000 claims description 5
- 238000004113 cell culture Methods 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 208000025865 Ulcer Diseases 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 4
- 238000005277 cation exchange chromatography Methods 0.000 claims description 4
- 238000004811 liquid chromatography Methods 0.000 claims description 4
- 231100000397 ulcer Toxicity 0.000 claims description 4
- 208000034693 Laceration Diseases 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- 208000002847 Surgical Wound Diseases 0.000 claims description 2
- 238000004255 ion exchange chromatography Methods 0.000 claims description 2
- 238000011068 loading method Methods 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 210000005253 yeast cell Anatomy 0.000 claims 2
- 241000282412 Homo Species 0.000 claims 1
- 230000003511 endothelial effect Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 10
- 238000004587 chromatography analysis Methods 0.000 abstract description 9
- 238000000746 purification Methods 0.000 abstract description 8
- 238000011002 quantification Methods 0.000 abstract description 7
- 239000007788 liquid Substances 0.000 abstract description 4
- 230000001323 posttranslational effect Effects 0.000 abstract description 2
- 238000007693 zone electrophoresis Methods 0.000 abstract description 2
- 230000006798 recombination Effects 0.000 abstract 2
- 238000005215 recombination Methods 0.000 abstract 2
- 241001236653 Lavinia exilicauda Species 0.000 description 71
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 62
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 61
- 235000018102 proteins Nutrition 0.000 description 55
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 230000004071 biological effect Effects 0.000 description 23
- 230000000694 effects Effects 0.000 description 21
- 150000001413 amino acids Chemical group 0.000 description 20
- 235000001014 amino acid Nutrition 0.000 description 15
- 238000005251 capillar electrophoresis Methods 0.000 description 15
- 230000003241 endoproteolytic effect Effects 0.000 description 15
- 238000012545 processing Methods 0.000 description 14
- 229940088679 drug related substance Drugs 0.000 description 13
- 239000008186 active pharmaceutical agent Substances 0.000 description 12
- 230000002297 mitogenic effect Effects 0.000 description 12
- 238000004007 reversed phase HPLC Methods 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 230000004048 modification Effects 0.000 description 11
- 241000894007 species Species 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 238000010361 transduction Methods 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 210000004899 c-terminal region Anatomy 0.000 description 9
- 230000035876 healing Effects 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- RWCOTTLHDJWHRS-YUMQZZPRSA-N Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RWCOTTLHDJWHRS-YUMQZZPRSA-N 0.000 description 8
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 8
- 239000000833 heterodimer Substances 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 108010077112 prolyl-proline Proteins 0.000 description 7
- 230000029663 wound healing Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 238000001962 electrophoresis Methods 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 238000000855 fermentation Methods 0.000 description 5
- 230000004151 fermentation Effects 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 102000003670 Carboxypeptidase B Human genes 0.000 description 4
- 108090000087 Carboxypeptidase B Proteins 0.000 description 4
- 102100037596 Platelet-derived growth factor subunit A Human genes 0.000 description 4
- 239000006096 absorbing agent Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000000710 homodimer Substances 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000006317 isomerization reaction Methods 0.000 description 4
- 239000003226 mitogen Substances 0.000 description 4
- 230000002797 proteolythic effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000235649 Kluyveromyces Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 108091008606 PDGF receptors Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 210000002808 connective tissue Anatomy 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 108010000685 platelet-derived growth factor AB Proteins 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000003908 quality control method Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
- 241000235648 Pichia Species 0.000 description 2
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
- 241000235346 Schizosaccharomyces Species 0.000 description 2
- 102000013275 Somatomedins Human genes 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000012512 bulk drug substance Substances 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 230000000367 exoproteolytic effect Effects 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000013074 reference sample Substances 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000235172 Bullera Species 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 102000005367 Carboxypeptidases Human genes 0.000 description 1
- 108010006303 Carboxypeptidases Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000490729 Cryptococcaceae Species 0.000 description 1
- 241000221199 Cryptococcus <basidiomycete yeast> Species 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 208000035874 Excoriation Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 241000221207 Filobasidium Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241001138401 Kluyveromyces lactis Species 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000235087 Lachancea kluyveri Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000221479 Leucosporidium Species 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 101100494726 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pep-4 gene Proteins 0.000 description 1
- 101150029183 PEP4 gene Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 101710180012 Protease 7 Proteins 0.000 description 1
- 101100068851 Rattus norvegicus Glra1 gene Proteins 0.000 description 1
- 241000223252 Rhodotorula Species 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 244000206963 Saccharomyces cerevisiae var. diastaticus Species 0.000 description 1
- 241000204893 Saccharomyces douglasii Species 0.000 description 1
- 241001407717 Saccharomyces norbensis Species 0.000 description 1
- 241001123227 Saccharomyces pastorianus Species 0.000 description 1
- 241000235344 Saccharomycetaceae Species 0.000 description 1
- 241000235343 Saccharomycetales Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000228389 Sporidiobolus Species 0.000 description 1
- 241000222068 Sporobolomyces <Sporidiobolaceae> Species 0.000 description 1
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
- 239000007997 Tricine buffer Substances 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- IVUXTESCPZUGJC-UHFFFAOYSA-N chloroxuron Chemical compound C1=CC(NC(=O)N(C)C)=CC=C1OC1=CC=C(Cl)C=C1 IVUXTESCPZUGJC-UHFFFAOYSA-N 0.000 description 1
- 230000037319 collagen production Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000010369 molecular cloning Methods 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
- 230000007935 neutral effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 235000020077 pisco Nutrition 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
Classifications
-
- 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
- A61K38/1858—Platelet-derived growth factor [PDGF]
-
- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- C07K14/49—Platelet-derived growth factor [PDGF]
-
- 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
- C07K14/575—Hormones
- C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
- C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Toxicology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Diabetes (AREA)
- Microbiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Materials Engineering (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3272096P | 1996-12-13 | 1996-12-13 | |
| PCT/US1997/022815 WO1998025963A1 (en) | 1996-12-13 | 1997-12-12 | Analysis and separation of platelet-derived growth factor proteins |
| US32720 | 1998-02-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2306462T3 true ES2306462T3 (es) | 2008-11-01 |
Family
ID=21866458
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES97948629T Expired - Lifetime ES2306462T3 (es) | 1996-12-13 | 1997-12-12 | Analisis y separacion de proteinas del factor de crecimiento derivadas de plaquetas. |
Country Status (9)
| Country | Link |
|---|---|
| US (10) | US6017731A (https=) |
| EP (4) | EP1365028B1 (https=) |
| JP (4) | JP4341859B2 (https=) |
| AT (3) | ATE398139T1 (https=) |
| AU (2) | AU5465498A (https=) |
| DE (3) | DE69725881T2 (https=) |
| ES (1) | ES2306462T3 (https=) |
| PT (1) | PT948538E (https=) |
| WO (2) | WO1998025963A1 (https=) |
Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3486491T2 (de) | 1983-04-25 | 2003-01-16 | Chiron Corp., Emeryville | Hybrid-DNS-Synthesis von reifen insulinähnlichen Wachstumsfaktoren |
| US5811381A (en) * | 1996-10-10 | 1998-09-22 | Mark A. Emalfarb | Cellulase compositions and methods of use |
| US7883872B2 (en) * | 1996-10-10 | 2011-02-08 | Dyadic International (Usa), Inc. | Construction of highly efficient cellulase compositions for enzymatic hydrolysis of cellulose |
| DE69725881T2 (de) * | 1996-12-13 | 2004-09-09 | Chiron Corp. (N.D.Ges.D. Staates Delaware), Emeryville | Verfahren zur expression von heterologen proteinen in hefe |
| ES2237159T3 (es) * | 1998-10-06 | 2005-07-16 | Mark Aaron Emalfarb | Sistema de transformacion en el campo de los hongos micoticos filamentosos en chrysosporium. |
| US20040146918A1 (en) * | 2000-02-18 | 2004-07-29 | Weiner Michael L. | Hybrid nucleic acid assembly |
| US7166712B2 (en) * | 2000-07-12 | 2007-01-23 | Philadelphia, Health And Education Corporation | Mammalian MDM2 binding proteins and uses thereof |
| EP1596813A4 (en) * | 2003-01-31 | 2008-02-20 | Five Prime Therapeutics Inc | POLYPEPTIDES EXPRESSED IN THE LUNG |
| CN103484486B (zh) | 2003-07-02 | 2018-04-24 | 维莱尼姆公司 | 葡聚糖酶,编码它们的核酸以及制备和使用它们的方法 |
| DE10342794A1 (de) * | 2003-09-16 | 2005-04-21 | Basf Ag | Sekretion von Proteinen aus Hefen |
| EP1689348B1 (en) | 2003-12-05 | 2013-05-15 | Children's Hospital Medical Center | Oligosaccharide compositions and use thereof in the treatment of infection |
| EP2327724A3 (en) * | 2004-02-02 | 2011-07-27 | Ambrx, Inc. | Modified human growth hormone polypeptides and their uses |
| KR101699142B1 (ko) | 2004-06-18 | 2017-01-23 | 암브룩스, 인코포레이티드 | 신규 항원-결합 폴리펩티드 및 이의 용도 |
| JP2008507280A (ja) * | 2004-07-21 | 2008-03-13 | アンブレツクス・インコーポレイテツド | 非天然コードアミノ酸を用いた生合成ポリペプチド |
| US7473678B2 (en) * | 2004-10-14 | 2009-01-06 | Biomimetic Therapeutics, Inc. | Platelet-derived growth factor compositions and methods of use thereof |
| US8114841B2 (en) * | 2004-10-14 | 2012-02-14 | Biomimetic Therapeutics, Inc. | Maxillofacial bone augmentation using rhPDGF-BB and a biocompatible matrix |
| US7816320B2 (en) | 2004-12-22 | 2010-10-19 | Ambrx, Inc. | Formulations of human growth hormone comprising a non-naturally encoded amino acid at position 35 |
| CN102732588B (zh) | 2004-12-22 | 2015-01-07 | Ambrx公司 | 氨酰基-tRNA合成酶的组合物及其用途 |
| EP1828224B1 (en) | 2004-12-22 | 2016-04-06 | Ambrx, Inc. | Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides |
| GB2438760A (en) * | 2004-12-22 | 2007-12-05 | Ambrx Inc | Methods for expression and purification of recombinant human growth hormone |
| JP2008525473A (ja) | 2004-12-22 | 2008-07-17 | アンブレツクス・インコーポレイテツド | 修飾されたヒト成長ホルモン |
| WO2006133089A2 (en) * | 2005-06-03 | 2006-12-14 | Ambrx, Inc. | Improved human interferon molecules and their uses |
| JP2009501522A (ja) * | 2005-07-12 | 2009-01-22 | コドン デバイシズ インコーポレイテッド | 生体触媒工学のための組成物及び方法 |
| MX2008002149A (es) | 2005-08-18 | 2008-04-22 | Ambrx Inc | Composiciones de arnt y sus usos. |
| FR2891149B1 (fr) | 2005-09-26 | 2007-11-30 | Biodex Sarl | Composition pharmaceutique a action cicatrisante comprenant un derive de dextrane soluble et un facteur de croissance derive des plaquettes. |
| CN104710503B (zh) * | 2005-11-08 | 2023-04-25 | Ambrx 公司 | 用于修饰非天然氨基酸和非天然氨基酸多肽的促进剂 |
| EP1951890A4 (en) | 2005-11-16 | 2009-06-24 | Ambrx Inc | PROCESSES AND COMPOSITIONS WITH NON-NATURAL AMINO ACIDS |
| DK1968635T3 (en) * | 2005-12-14 | 2014-12-15 | Ambrx Inc | Compositions and Methods of, and uses of non-natural amino acids and polypeptides |
| ES2427993T3 (es) | 2006-02-09 | 2013-11-05 | Biomimetic Therapeutics, Llc | Composiciones y métodos para el tratamiento de hueso |
| US9161967B2 (en) | 2006-06-30 | 2015-10-20 | Biomimetic Therapeutics, Llc | Compositions and methods for treating the vertebral column |
| CA2656278C (en) | 2006-06-30 | 2016-02-09 | Biomimetic Therapeutics, Inc. | Compositions and methods for treating rotator cuff injuries |
| CN106008699A (zh) | 2006-09-08 | 2016-10-12 | Ambrx公司 | 经修饰的人类血浆多肽或Fc骨架和其用途 |
| MX2009002460A (es) | 2006-09-08 | 2009-03-20 | Ambrx Inc | Arnt supresor hibrido para celulas de vertebrados. |
| EP2064333B1 (en) | 2006-09-08 | 2014-02-26 | Ambrx, Inc. | Suppressor trna transcription in vertebrate cells |
| US8106008B2 (en) | 2006-11-03 | 2012-01-31 | Biomimetic Therapeutics, Inc. | Compositions and methods for arthrodetic procedures |
| US9862956B2 (en) | 2006-12-10 | 2018-01-09 | Danisco Us Inc. | Expression and high-throughput screening of complex expressed DNA libraries in filamentous fungi |
| EP2505651A3 (en) | 2006-12-10 | 2013-01-09 | Dyadic International, Inc. | Isolated fungus with reduced protease activity |
| CA2682147C (en) | 2007-03-30 | 2017-08-08 | Ambrx, Inc. | Modified fgf-21 polypeptides and their uses |
| MX2009011870A (es) | 2007-05-02 | 2009-11-12 | Ambrx Inc | Polipeptidos de interferon beta modificados y usos de los mismos. |
| CA2736661A1 (en) * | 2007-09-07 | 2009-03-12 | Dyadic International, Inc. | Novel fungal enzymes |
| MX2010005317A (es) * | 2007-11-20 | 2010-06-02 | Ambrx Inc | Polipeptidos de insulina modificados y sus usos. |
| EP2259807B1 (en) | 2008-02-07 | 2013-04-24 | Biomimetic Therapeutics, Inc. | Compositions for distraction osteogenesis |
| NZ586947A (en) | 2008-02-08 | 2012-11-30 | Ambrx Inc | Modified leptin polypeptides and their uses |
| PT2318029T (pt) | 2008-07-23 | 2018-01-10 | Ambrx Inc | Polipéptidos de g-csf bovino modificados e suas utilizações |
| KR20110067035A (ko) | 2008-09-09 | 2011-06-20 | 바이오미메틱 세라퓨틱스, 인크. | 건 및 인대 손상의 치료를 위한 혈소판-유래 성장 인자 조성물 및 방법 |
| MX2011003272A (es) | 2008-09-26 | 2011-04-28 | Ambrx Inc | Polipeptidos de eritropoyetina animal modificados y sus usos. |
| PE20110480A1 (es) | 2008-09-26 | 2011-07-01 | Ambrx Inc | Microorganismos y vacunas dependientes de replicacion de aminoacidos no naturales |
| US8183346B2 (en) * | 2008-12-05 | 2012-05-22 | Eli Lilly And Company | Anti-ferroportin 1 monoclonal antibodies and uses thereof |
| JP2013515081A (ja) | 2009-12-21 | 2013-05-02 | アンブルックス,インコーポレイテッド | 修飾されているブタのソマトトロピンポリペプチドおよびそれらの使用 |
| NZ600361A (en) | 2009-12-21 | 2014-06-27 | Ambrx Inc | Modified bovine somatotropin polypeptides and their uses |
| CN102811622A (zh) | 2010-02-22 | 2012-12-05 | 生物模拟治疗公司 | 用于治疗腱病的血小板衍生生长因子组合物和方法 |
| US9567386B2 (en) | 2010-08-17 | 2017-02-14 | Ambrx, Inc. | Therapeutic uses of modified relaxin polypeptides |
| MA34521B1 (fr) | 2010-08-17 | 2013-09-02 | Ambrx Inc | Polypeptides de relaxine modifiés et leurs utilisations |
| TWI480288B (zh) | 2010-09-23 | 2015-04-11 | Lilly Co Eli | 牛顆粒細胞群落刺激因子及其變體之調配物 |
| CN105085652B (zh) * | 2014-05-16 | 2021-06-22 | 中国人民解放军军事医学科学院生物工程研究所 | 血小板衍生生长因子b突变体、其制备方法及用途 |
| MX2017004520A (es) * | 2014-10-14 | 2018-03-15 | Lynch Samuel | Composiciones para tratar heridas. |
| SMT202100388T1 (it) | 2014-10-24 | 2021-09-14 | Bristol Myers Squibb Co | Polipeptidi fgf-21 modificati e loro usi |
| CN106496302B (zh) * | 2015-09-08 | 2021-12-10 | 三生国健药业(上海)股份有限公司 | 一种用离子交换层析纯化蛋白质的方法 |
| CN108239648B (zh) * | 2016-12-26 | 2023-04-07 | 丰益(上海)生物技术研发中心有限公司 | 高效表达米黑根毛霉脂肪酶的方法 |
| CN110637027B (zh) | 2017-02-08 | 2024-08-30 | 百时美施贵宝公司 | 包含药代动力学增强子的修饰的松弛素多肽及其用途 |
| CN110590930B (zh) * | 2018-06-13 | 2023-03-31 | 四川好医生攀西药业有限责任公司 | 美洲大蠊生长因子pdgf在制备损伤修复药物中的应用 |
| CN113015782A (zh) * | 2018-11-19 | 2021-06-22 | 巴斯夫欧洲公司 | 用于酵母的前导序列 |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2359180A (en) * | 1942-08-11 | 1944-09-26 | Gen Motors Corp | Dynamic balancer |
| NZ201918A (en) | 1981-09-18 | 1987-04-30 | Genentech Inc | N-terminal methionyl analogues of bovine growth hormone |
| US5010003A (en) * | 1983-04-25 | 1991-04-23 | Genentech, Inc. | Use of yeast homologous signals to secrete heterologous proteins |
| US4889919A (en) | 1986-08-13 | 1989-12-26 | Zymogenetics, Inc. | Biologically active PDGF derived A-chain homodimers |
| 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 |
| EP0487116B1 (en) * | 1984-10-12 | 1999-12-29 | ZymoGenetics, Inc. | Biologically active PDGF analogs in eucaryotic cells |
| US4766073A (en) * | 1985-02-25 | 1988-08-23 | Zymogenetics Inc. | Expression of biologically active PDGF analogs in eucaryotic cells |
| US4801542A (en) | 1984-10-12 | 1989-01-31 | Zymogenetics, Inc. | Expression of biologically active PDGF analogs in eucaryotic cells |
| US5516896A (en) * | 1985-02-25 | 1996-05-14 | Zymogenetics, Inc. | Biologically active B-chain homodimers |
| US5045633A (en) * | 1985-02-25 | 1991-09-03 | Zymogenetics, Inc. | Expression of biologically active PDGF analogs in eucaryotic cells |
| AU5912586A (en) * | 1985-06-20 | 1986-12-24 | Salk Institute Biotechnology/Industrial Associates, Inc., The | Alpha-factor leader peptide-facilitated secretion from transformed s cerevisiae |
| EP0259632B1 (en) * | 1986-08-13 | 1995-12-13 | Zymogenetics, Inc. | Expression of biologically active PDGF analogs in eucaryotic cells |
| US5019559A (en) | 1986-11-14 | 1991-05-28 | President And Fellows Of Harvard College | Wound healing using PDGF and IGF-II |
| IE60517B1 (en) | 1986-11-14 | 1994-07-27 | Inst Molecular Biology Inc | Wound healing and bone regeneration |
| US4873192A (en) | 1987-02-17 | 1989-10-10 | The United States Of America As Represented By The Department Of Health And Human Services | Process for site specific mutagenesis without phenotypic selection |
| US5219759A (en) * | 1987-04-22 | 1993-06-15 | Chiron Corporation | Recombinant DNA encoding PDGF A-chain polypeptide and expression vectors |
| CA1340772C (en) * | 1987-12-30 | 1999-09-28 | Patricia Tekamp-Olson | Expression and secretion of heterologous protiens in yeast employing truncated alpha-factor leader sequences |
| US5094941A (en) * | 1987-12-31 | 1992-03-10 | Zymogenetics, Inc. | Monoclonal antibodies to PDGF |
| US5422120A (en) | 1988-05-30 | 1995-06-06 | Depotech Corporation | Heterovesicular liposomes |
| DK105489D0 (da) * | 1989-03-03 | 1989-03-03 | Novo Nordisk As | Polypeptid |
| DE3900770A1 (de) * | 1989-01-12 | 1990-07-26 | Juergen Prof Dr Hoppe | Verfahren zur herstellung von pdgf-a und pdgf-aa |
| US5968778A (en) * | 1989-01-12 | 1999-10-19 | Jurgen Hoppe | PDGF-AB, preparation process and pharmaceuticals containing them |
| ZA911974B (en) | 1990-03-21 | 1994-08-22 | Res Dev Foundation | Heterovesicular liposomes |
| JPH0768139B2 (ja) | 1990-04-10 | 1995-07-26 | インスティチュート・オブ・モレキュラー・バイオロジー・インコーポレーテッド | 創傷の治癒 |
| US5962219A (en) * | 1990-06-11 | 1999-10-05 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: chemi-selex |
| DE69102651T2 (de) * | 1990-07-23 | 1994-10-06 | Zymogenetics, Inc., Seattle, Wash. | Proteaseresistenter pdgf und dessen verwendungen. |
| JP3257675B2 (ja) * | 1990-10-12 | 2002-02-18 | マックス−プランク−ゲゼルシャフト ツール フェルデルング デル ビッセンシャフテン エー.ファウ. | 修飾リボザイム |
| DK300090D0 (da) * | 1990-12-19 | 1990-12-19 | Novo Nordisk As | Fremgangsmaade til fremstilling af leadersekvenser |
| DE4216134A1 (de) * | 1991-06-20 | 1992-12-24 | Europ Lab Molekularbiolog | Synthetische katalytische oligonukleotidstrukturen |
| WO1993008825A1 (en) | 1991-11-04 | 1993-05-13 | Zymogenetics, Inc. | Pdgf gel formulation |
| EP0681482B1 (en) * | 1993-01-22 | 2005-12-07 | University Research Corporation | Localization of therapeutic agents |
| PT695169E (pt) | 1993-04-22 | 2003-04-30 | Skyepharma Inc | Lipossomas multivesiculares de ciclodextrina encapsulando compostos farmacologicos e metodos para a sua utilizacao |
| DK82893D0 (da) * | 1993-07-08 | 1993-07-08 | Novo Nordisk As | Peptid |
| US5624803A (en) * | 1993-10-14 | 1997-04-29 | The Regents Of The University Of California | In vivo oligonucleotide generator, and methods of testing the binding affinity of triplex forming oligonucleotides derived therefrom |
| PT729351E (pt) | 1993-11-16 | 2000-12-29 | Skyepharma Inc | Vesiculas com libertacao controlada de activos |
| US5902880A (en) * | 1994-08-19 | 1999-05-11 | Ribozyme Pharmaceuticals, Inc. | RNA polymerase III-based expression of therapeutic RNAs |
| US5627053A (en) * | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| CA2187626C (en) * | 1994-04-13 | 2009-11-03 | Michael G. Kaplitt | Aav-mediated delivery of dna to cells of the nervous system |
| US5639642A (en) * | 1994-06-16 | 1997-06-17 | Novo Nordisk A/S | Synthetic leader peptide sequences |
| ZA954983B (en) * | 1994-06-17 | 1996-02-14 | Novo Nordisk As | N-terminally extended proteins expressed in yeast |
| US6146886A (en) * | 1994-08-19 | 2000-11-14 | Ribozyme Pharmaceuticals, Inc. | RNA polymerase III-based expression of therapeutic RNAs |
| US5716824A (en) * | 1995-04-20 | 1998-02-10 | Ribozyme Pharmaceuticals, Inc. | 2'-O-alkylthioalkyl and 2-C-alkylthioalkyl-containing enzymatic nucleic acids (ribozymes) |
| ZA9610456B (en) * | 1995-12-20 | 1997-06-20 | Novo Nordisk As | N-terminally extended proteins expressed in yeast |
| US5998203A (en) * | 1996-04-16 | 1999-12-07 | Ribozyme Pharmaceuticals, Inc. | Enzymatic nucleic acids containing 5'-and/or 3'-cap structures |
| DE69725881T2 (de) * | 1996-12-13 | 2004-09-09 | Chiron Corp. (N.D.Ges.D. Staates Delaware), Emeryville | Verfahren zur expression von heterologen proteinen in hefe |
| US6248878B1 (en) * | 1996-12-24 | 2001-06-19 | Ribozyme Pharmaceuticals, Inc. | Nucleoside analogs |
| US6001311A (en) * | 1997-02-05 | 1999-12-14 | Protogene Laboratories, Inc. | Apparatus for diverse chemical synthesis using two-dimensional array |
| US6395713B1 (en) * | 1997-07-23 | 2002-05-28 | Ribozyme Pharmaceuticals, Inc. | Compositions for the delivery of negatively charged molecules |
-
1997
- 1997-12-12 DE DE69725881T patent/DE69725881T2/de not_active Expired - Lifetime
- 1997-12-12 AT AT97948629T patent/ATE398139T1/de active
- 1997-12-12 EP EP03012465A patent/EP1365028B1/en not_active Expired - Lifetime
- 1997-12-12 AT AT03012465T patent/ATE426030T1/de not_active IP Right Cessation
- 1997-12-12 AU AU54654/98A patent/AU5465498A/en not_active Abandoned
- 1997-12-12 JP JP52692698A patent/JP4341859B2/ja not_active Expired - Fee Related
- 1997-12-12 US US08/989,251 patent/US6017731A/en not_active Expired - Fee Related
- 1997-12-12 EP EP97948629A patent/EP0948538B1/en not_active Expired - Lifetime
- 1997-12-12 WO PCT/US1997/022815 patent/WO1998025963A1/en not_active Ceased
- 1997-12-12 US US08/989,250 patent/US6083910A/en not_active Expired - Lifetime
- 1997-12-12 JP JP52698598A patent/JP4275741B2/ja not_active Expired - Lifetime
- 1997-12-12 EP EP97954073A patent/EP0946736B1/en not_active Expired - Lifetime
- 1997-12-12 ES ES97948629T patent/ES2306462T3/es not_active Expired - Lifetime
- 1997-12-12 WO PCT/US1997/022647 patent/WO1998026080A1/en not_active Ceased
- 1997-12-12 DE DE69739319T patent/DE69739319D1/de not_active Expired - Lifetime
- 1997-12-12 AU AU57945/98A patent/AU5794598A/en not_active Abandoned
- 1997-12-12 AT AT97954073T patent/ATE253120T1/de not_active IP Right Cessation
- 1997-12-12 DE DE69738768T patent/DE69738768D1/de not_active Expired - Lifetime
- 1997-12-12 EP EP08006174A patent/EP1935901A1/en not_active Withdrawn
- 1997-12-12 PT PT97948629T patent/PT948538E/pt unknown
-
1999
- 1999-07-01 US US09/340,250 patent/US6083723A/en not_active Expired - Fee Related
-
2000
- 2000-03-17 US US09/528,108 patent/US6312923B1/en not_active Expired - Fee Related
- 2000-04-14 US US09/549,290 patent/US6448382B1/en not_active Expired - Lifetime
-
2001
- 2001-08-02 US US09/921,398 patent/US6706496B2/en not_active Expired - Fee Related
-
2002
- 2002-07-26 US US10/205,693 patent/US7084262B2/en not_active Expired - Fee Related
- 2002-10-25 US US10/280,826 patent/US6897043B2/en not_active Expired - Fee Related
-
2005
- 2005-01-28 US US11/046,099 patent/US7166446B2/en not_active Expired - Fee Related
-
2006
- 2006-07-07 US US11/483,033 patent/US20060252695A1/en not_active Abandoned
-
2007
- 2007-08-09 JP JP2007208669A patent/JP2008031173A/ja not_active Withdrawn
- 2007-12-27 JP JP2007338286A patent/JP2008119008A/ja not_active Withdrawn
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2306462T3 (es) | Analisis y separacion de proteinas del factor de crecimiento derivadas de plaquetas. | |
| US7696309B2 (en) | Protease resistant mutants of stromal cell derived factor-1 in the repair of tissue damage | |
| AU646014B2 (en) | Novel platelet-derived growth factor B chain analogs and method for homogeneous production thereof | |
| CN101121753B (zh) | 对多种皮肤细胞修复具持续作用的人血清白蛋白重组融合蛋白 | |
| MX2014009129A (es) | Polipeptidos de factor 15 de diferenciacion de crecimiento (gdf-15). | |
| EP0618227A1 (en) | Biologically active polypeptide fusion dimers | |
| ES2356360T3 (es) | Muteínas del factor de crecimiento placentario de tipo 1, método de preparación y aplicación de las mismas. | |
| CN104004097A (zh) | 重组人血清白蛋白/类胰岛素生长因子融合蛋白 | |
| JP2990162B2 (ja) | ヒト酸性線維芽細胞成長因子の組成物、その製法、dna構築物および酵母宿主細胞 | |
| Francis et al. | Carboxyl-terminal amino acid sequences of two variant forms of the gamma chain of human plasma fibrinogen. | |
| CN100535005C (zh) | 长链人胰岛素样生长因子(lr3igf-1)及其制备和应用方法 | |
| CN105777908B (zh) | 重组人血清白蛋白/角质细胞生长因子融合蛋白 | |
| KR20190025569A (ko) | Tgf-베타 슈퍼패밀리의 ab6 패밀리 디자이너 리간드 | |
| RU2607527C2 (ru) | Ковалентный моноконъюгат полиэтиленгликоля с тимозином бета 4, устойчивый к деградации в токе крови, и способ его получения | |
| Grieb et al. | Primary structure of ovine fibroblast growth factor-1 deduced by protein and cDNA analysis | |
| KR20120093870A (ko) | 호모다이머 폼의 plgf-1 | |
| MARDER | Carboxyl-terminal amino acid sequences of two variant forms of the y chain of human plasma fibrinogen | |
| KR20190005239A (ko) | Tgf-베타 슈퍼패밀리의 ab6 패밀리 디자이너 리간드를 포함하는 간질환 치료용 조성물 및 그의 이용 | |
| CN104004096A (zh) | 重组人血清白蛋白/血小板源性生长因子融合蛋白 | |
| HK1192845B (en) | Protease resistant mutants of stromal cell derived factor-1 in the repair of tissue damage | |
| HK1192845A (en) | Protease resistant mutants of stromal cell derived factor-1 in the repair of tissue damage | |
| HK1006183B (en) | Expression and secretion vectors for hirudine by way of transformed yeasts | |
| HK1006183A1 (en) | Expression and secretion vectors for hirudine by way of transformed yeasts | |
| JPH02261393A (ja) | 新規生理活性ポリペプチド |