CA2085744A1 - Interleukin-6 compositions, and a production process thereof - Google Patents

Interleukin-6 compositions, and a production process thereof

Info

Publication number: CA2085744A1
Authority: CA; Canada
Prior art keywords: pro; human interleukin; carrier; chromatography; compositions
Prior art date: 1991-04-18
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.): Abandoned

Application number

CA002085744A

Other languages

English (en)

French (fr)

Inventor

Shingou Sakurai

Masanobu Naruto

Makoto Kihara

Keizo Hanada

Emiko Sano

Shigeru Ichikura

Jun Utsumi

Kazuo Hosoi

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Toray Industries Inc

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1991-04-18

Filing date

1992-04-17

Publication date

1992-10-19

1992-04-17 Application filed by Individual filed Critical Individual

1992-10-19 Publication of CA2085744A1 publication Critical patent/CA2085744A1/en

Status Abandoned legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims abstract description 25
238000004519 manufacturing process Methods 0.000 title claims abstract description 24
102000004889 Interleukin-6 Human genes 0.000 title description 87
108090001005 Interleukin-6 Proteins 0.000 title description 87
229940100601 interleukin-6 Drugs 0.000 title description 5
101001076408 Homo sapiens Interleukin-6 Proteins 0.000 claims abstract description 42
229960002897 heparin Drugs 0.000 claims abstract description 25
229920000669 heparin Polymers 0.000 claims abstract description 25
235000000346 sugar Nutrition 0.000 claims abstract description 24
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 23
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 21
238000004587 chromatography analysis Methods 0.000 claims abstract description 14
239000011668 ascorbic acid Substances 0.000 claims abstract description 10
235000010323 ascorbic acid Nutrition 0.000 claims abstract description 10
229960005070 ascorbic acid Drugs 0.000 claims abstract description 10
238000012258 culturing Methods 0.000 claims abstract description 9
229940116886 human interleukin-6 Drugs 0.000 claims abstract 23
210000004027 cell Anatomy 0.000 claims description 49
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 25
239000000377 silicon dioxide Substances 0.000 claims description 11
210000002950 fibroblast Anatomy 0.000 claims description 10
150000008163 sugars Chemical class 0.000 claims description 7
SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims description 5
PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 claims description 5
SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 claims description 5
239000003463 adsorbent Substances 0.000 claims description 5
125000001165 hydrophobic group Chemical group 0.000 claims description 5
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 4
SQVRNKJHWKZAKO-PFQGKNLYSA-N N-acetyl-beta-neuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-PFQGKNLYSA-N 0.000 claims description 4
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 4
SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 claims description 4
229930182830 galactose Natural products 0.000 claims description 4
OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims description 3
MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims description 3
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims description 3
CLNJSLSHKJECME-BQBZGAKWSA-N Pro-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]1CCCN1 CLNJSLSHKJECME-BQBZGAKWSA-N 0.000 claims description 3
125000003275 alpha amino acid group Chemical group 0.000 claims description 2
OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 claims 2
OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims 2
MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 claims 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims 2
229950006780 n-acetylglucosamine Drugs 0.000 claims 2
238000002264 polyacrylamide gel electrophoresis Methods 0.000 claims 2
229940083575 sodium dodecyl sulfate Drugs 0.000 claims 2
235000019333 sodium laurylsulphate Nutrition 0.000 claims 2
238000000034 method Methods 0.000 abstract description 12
239000003814 drug Substances 0.000 abstract description 5
229940079593 drug Drugs 0.000 abstract description 3
239000002609 medium Substances 0.000 description 33
239000000243 solution Substances 0.000 description 23
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
102000052611 human IL6 Human genes 0.000 description 19
235000002639 sodium chloride Nutrition 0.000 description 18
239000012064 sodium phosphate buffer Substances 0.000 description 16
239000000047 product Substances 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
108090000623 proteins and genes Proteins 0.000 description 12
102000004169 proteins and genes Human genes 0.000 description 11
239000000411 inducer Substances 0.000 description 10
239000011780 sodium chloride Substances 0.000 description 10
-1 IL- I Proteins 0.000 description 9
238000001179 sorption measurement Methods 0.000 description 9
239000012051 hydrophobic carrier Substances 0.000 description 8
150000003839 salts Chemical class 0.000 description 8
238000002965 ELISA Methods 0.000 description 7
150000002926 oxygen Chemical class 0.000 description 7
238000004007 reversed phase HPLC Methods 0.000 description 7
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 6
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 6
230000001419 dependent effect Effects 0.000 description 6
239000008103 glucose Substances 0.000 description 6
238000011534 incubation Methods 0.000 description 6
DBSABEYSGXPBTA-RXSVEWSESA-N (2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one;phosphoric acid Chemical class OP(O)(O)=O.OC[C@H](O)[C@H]1OC(=O)C(O)=C1O DBSABEYSGXPBTA-RXSVEWSESA-N 0.000 description 5
102000008186 Collagen Human genes 0.000 description 5
108010035532 Collagen Proteins 0.000 description 5
229920002307 Dextran Polymers 0.000 description 5
239000002253 acid Substances 0.000 description 5
239000001913 cellulose Substances 0.000 description 5
229920002678 cellulose Polymers 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
229920001436 collagen Polymers 0.000 description 5
239000005289 controlled pore glass Substances 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
239000002028 Biomass Substances 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 4
229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
241000588724 Escherichia coli Species 0.000 description 4
210000001744 T-lymphocyte Anatomy 0.000 description 4
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
210000003719 b-lymphocyte Anatomy 0.000 description 4
239000000872 buffer Substances 0.000 description 4
239000001768 carboxy methyl cellulose Substances 0.000 description 4
235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
239000008112 carboxymethyl-cellulose Substances 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
238000000746 purification Methods 0.000 description 4
239000012264 purified product Substances 0.000 description 4
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
230000004936 stimulating effect Effects 0.000 description 4
239000011534 wash buffer Substances 0.000 description 4
229920000936 Agarose Polymers 0.000 description 3
102000004127 Cytokines Human genes 0.000 description 3
108090000695 Cytokines Proteins 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000002158 endotoxin Substances 0.000 description 3
239000012510 hollow fiber Substances 0.000 description 3
239000003094 microcapsule Substances 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
238000003756 stirring Methods 0.000 description 3
229920001059 synthetic polymer Polymers 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 2
102000009016 Cholera Toxin Human genes 0.000 description 2
108010049048 Cholera Toxin Proteins 0.000 description 2
108010092160 Dactinomycin Proteins 0.000 description 2
241001131785 Escherichia coli HB101 Species 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
102000014150 Interferons Human genes 0.000 description 2
108010050904 Interferons Proteins 0.000 description 2
150000000996 L-ascorbic acids Chemical class 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
235000010724 Wisteria floribunda Nutrition 0.000 description 2
RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
230000001464 adherent effect Effects 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
229910052921 ammonium sulfate Inorganic materials 0.000 description 2
235000011130 ammonium sulphate Nutrition 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
229940098773 bovine serum albumin Drugs 0.000 description 2
150000001768 cations Chemical class 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
229960000640 dactinomycin Drugs 0.000 description 2
238000000502 dialysis Methods 0.000 description 2
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
239000013604 expression vector Substances 0.000 description 2
239000012091 fetal bovine serum Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000000499 gel Substances 0.000 description 2
238000001641 gel filtration chromatography Methods 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
150000004676 glycans Chemical class 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
210000004408 hybridoma Anatomy 0.000 description 2
230000001965 increasing effect Effects 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
229940079322 interferon Drugs 0.000 description 2
238000004255 ion exchange chromatography Methods 0.000 description 2
229920006008 lipopolysaccharide Polymers 0.000 description 2
210000002540 macrophage Anatomy 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
239000011325 microbead Substances 0.000 description 2
150000002772 monosaccharides Chemical class 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
229920001282 polysaccharide Polymers 0.000 description 2
239000005017 polysaccharide Substances 0.000 description 2
238000011084 recovery Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000010414 supernatant solution Substances 0.000 description 2
238000011282 treatment Methods 0.000 description 2
210000003556 vascular endothelial cell Anatomy 0.000 description 2
229960001722 verapamil Drugs 0.000 description 2
SXOUIMVOMIGLHO-AATRIKPKSA-N (E)-3-(indol-2-yl)acrylic acid Chemical compound C1=CC=C2NC(/C=C/C(=O)O)=CC2=C1 SXOUIMVOMIGLHO-AATRIKPKSA-N 0.000 description 1
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 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
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 1
MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
241000283707 Capra Species 0.000 description 1
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 1
241000588722 Escherichia Species 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
108091006905 Human Serum Albumin Proteins 0.000 description 1
102000008100 Human Serum Albumin Human genes 0.000 description 1
102000000588 Interleukin-2 Human genes 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
108010002386 Interleukin-3 Proteins 0.000 description 1
238000012375 Ion exchange chromatography - high performance liquid chromatography Methods 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
ACFGRWJEQJVZTM-LEJBHHMKSA-L Magnesium L-ascorbic acid-2-phosphate Chemical compound [Mg+2].OC[C@H](O)[C@H]1OC(=O)C(OP([O-])([O-])=O)=C1O ACFGRWJEQJVZTM-LEJBHHMKSA-L 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
241001529936 Murinae Species 0.000 description 1
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
102000036693 Thrombopoietin Human genes 0.000 description 1
108010041111 Thrombopoietin Proteins 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
229960000723 ampicillin Drugs 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
239000011324 bead Substances 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000003995 blood forming stem cell Anatomy 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
238000010322 bone marrow transplantation Methods 0.000 description 1
244000309466 calf Species 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
239000007979 citrate buffer Substances 0.000 description 1
238000005352 clarification Methods 0.000 description 1
238000004040 coloring Methods 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
239000012045 crude solution Substances 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
238000009826 distribution Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
239000013613 expression plasmid Substances 0.000 description 1
235000003891 ferrous sulphate Nutrition 0.000 description 1
239000011790 ferrous sulphate Substances 0.000 description 1
239000012634 fragment Substances 0.000 description 1
238000005227 gel permeation chromatography Methods 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
208000005017 glioblastoma Diseases 0.000 description 1
229960002442 glucosamine Drugs 0.000 description 1
229930182478 glucoside Natural products 0.000 description 1
239000011544 gradient gel Substances 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
PLVPPLCLBIEYEA-UHFFFAOYSA-N indoleacrylic acid Natural products C1=CC=C2C(C=CC(=O)O)=CNC2=C1 PLVPPLCLBIEYEA-UHFFFAOYSA-N 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
238000009776 industrial production Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910017053 inorganic salt Inorganic materials 0.000 description 1
BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
239000007788 liquid Substances 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000003226 mitogen Substances 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002674 ointment Substances 0.000 description 1
201000008968 osteosarcoma Diseases 0.000 description 1
238000012856 packing Methods 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
229910052939 potassium sulfate Inorganic materials 0.000 description 1
235000011151 potassium sulphates Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
230000037452 priming Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000000926 separation method Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
YFGAFXCSLUUJRG-WCCKRBBISA-M sodium;(2s)-2-amino-5-(diaminomethylideneamino)pentanoate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCCN=C(N)N YFGAFXCSLUUJRG-WCCKRBBISA-M 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000012086 standard solution Substances 0.000 description 1
125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
229920003002 synthetic resin Polymers 0.000 description 1
239000000057 synthetic resin Substances 0.000 description 1
239000003826 tablet Substances 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
206010043554 thrombocytopenia Diseases 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
229910000406 trisodium phosphate Inorganic materials 0.000 description 1
235000019801 trisodium phosphate Nutrition 0.000 description 1
238000005406 washing Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/204—IL-6
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5412—IL-6
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/18—Ion-exchange chromatography
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/20—Partition-, reverse-phase or hydrophobic interaction chromatography
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- 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
- C12N2510/00—Genetically modified cells
- C12N2510/02—Cells for production
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0656—Adult fibroblasts

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Genetics & Genomics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biophysics (AREA)
Zoology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Epidemiology (AREA)
Gastroenterology & Hepatology (AREA)
Veterinary Medicine (AREA)
Analytical Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Wood Science & Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
Toxicology (AREA)
Microbiology (AREA)
Inorganic Chemistry (AREA)
General Engineering & Computer Science (AREA)
Biotechnology (AREA)
Oil, Petroleum & Natural Gas (AREA)
Immunology (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Peptides Or Proteins (AREA)

CA002085744A 1991-04-18 1992-04-17 Interleukin-6 compositions, and a production process thereof Abandoned CA2085744A1 (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
JP86602/91		1991-04-18
JP8660291		1991-04-18
JP8828491		1991-04-19
JP88284/91		1991-04-19

Publications (1)

Publication Number	Publication Date
CA2085744A1 true CA2085744A1 (en)	1992-10-19

Family

ID=26427716

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002085744A Abandoned CA2085744A1 (en)	1991-04-18	1992-04-17	Interleukin-6 compositions, and a production process thereof

Country Status (10)

Country	Link
EP (1)	EP0550756B1 (2)
KR (1)	KR930700550A (2)
AT (1)	ATE210150T1 (2)
AU (1)	AU1554592A (2)
CA (1)	CA2085744A1 (2)
DE (1)	DE69232259T2 (2)
ES (1)	ES2164050T3 (2)
FI (1)	FI925745A7 (2)
TW (1)	TW221379B (2)
WO (1)	WO1992018537A1 (2)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5338834A (en) *	1993-01-26	1994-08-16	Allelix Biopharmaceuticals Inc.	Ultrapure human interleukin-6
DK1036179T4 (da)	1997-12-03	2014-03-31	Roche Diagnostics Gmbh	Fremgangsmåde til fremstilling af polypeptider med egnet glycosilering
DK1137789T3 (da)	1998-12-09	2010-11-08	Phyton Holdings Llc	Fremgangsmåde til fremstilling af et glycoprotein med glycosylering af human type
DE60044858D1 (de)	1999-10-26	2010-09-30	Stichting Dienst Landbouwkundi	Säugetierartige Glykosylierung in Pflanzen
DK1356068T3 (en)	2001-01-19	2015-02-16	Phyton Holdings Llc	PROCESS FOR THE PRODUCTION OF secretory glycoprotein with HUMAN TYPE SUGAR CHAIN FOR USING A PLANT CELL
CN101613705A (zh)	2002-03-19	2009-12-30	国际植物研究所	在植物中优化聚糖生成
CN1665934B (zh)	2002-03-19	2010-05-26	国际植物研究所	GNTIII(UDP-N乙酰葡萄糖胺:β-D-甘露糖苷β(1,4)-N-乙酰葡萄糖胺基-转移酶III)在植物中的表达
CL2003002461A1 (es)	2002-11-27	2005-01-07	Dow Chemical Company Agroscien	Inmunoglobulina que comprende al menos un glicano afucosilado, composicion que la contiene, secuencia nucleotidica y vector que la comprende, procedimiento para producir dicha inmunoglobulina en plantas.
WO2008125972A2 (en)	2007-04-17	2008-10-23	Plant Research International B.V.	Mammalian-type glycosylation in plants by expression of non-mammalian glycosyltransferases

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS6062997A (ja) *	1983-09-17	1985-04-11	Mochida Pharmaceut Co Ltd	インタ−フエロンの生産方法
DE3519011A1 (de) *	1985-05-25	1986-11-27	Behringwerke Ag, 3550 Marburg	Verfahren zur herstellung eines materials zur affinitaetschromatographie
JPS62153755A (ja) *	1985-12-27	1987-07-08	Showa Denko Kk	クロマトグラフイ−用吸着担体
JP2648860B2 (ja) *	1986-05-08	1997-09-03	イエダリサーチアンドデベロップメントコンパニーリミテッド	ヒトインターフエロン−β２Ａ及びヒトインターフエロン−β２Ｂ、該インターフエロンをコードする遺伝子を含むベクター、該インターフエロンを産生するセルライン及び該インターフエロンの医薬品としての用途
IE67035B1 (en) *	1986-07-08	1996-02-21	Genetics Inst	Production and use of non-glycosylated IL-6
JP2676336B2 (ja) *	1986-08-06	1997-11-12	忠三岸本	ヒトｂ細胞分化因子の遺伝子
JPS63150297A (ja) *	1986-12-12	1988-06-22	Ajinomoto Co Inc	新規ｂ細胞分化因子蛋白標品
DE3851685D1 (de) *	1987-10-13	1994-11-03	Thomae Gmbh Dr K	Verfahren zur Herstellung von Proteinen.
JPH03133935A (ja) *	1989-10-19	1991-06-07	Toray Ind Inc	ヒト天然型インターロイキン６組成物

1992
- 1992-04-17 AT AT92908258T patent/ATE210150T1/de not_active IP Right Cessation
- 1992-04-17 ES ES92908258T patent/ES2164050T3/es not_active Expired - Lifetime
- 1992-04-17 WO PCT/JP1992/000487 patent/WO1992018537A1/ja not_active Ceased
- 1992-04-17 DE DE69232259T patent/DE69232259T2/de not_active Expired - Fee Related
- 1992-04-17 FI FI925745A patent/FI925745A7/fi not_active Application Discontinuation
- 1992-04-17 CA CA002085744A patent/CA2085744A1/en not_active Abandoned
- 1992-04-17 EP EP92908258A patent/EP0550756B1/en not_active Expired - Lifetime
- 1992-04-17 AU AU15545/92A patent/AU1554592A/en not_active Abandoned
- 1992-04-30 TW TW081103408A patent/TW221379B/zh active
- 1992-12-16 KR KR1019920703255A patent/KR930700550A/ko not_active Withdrawn

Also Published As

Publication number	Publication date
WO1992018537A1 (en)	1992-10-29
FI925745A0 (fi)	1992-12-17
EP0550756B1 (en)	2001-12-05
DE69232259T2 (de)	2002-06-13
AU1554592A (en)	1992-11-17
ES2164050T3 (es)	2002-02-16
FI925745L (fi)	1992-12-17
ATE210150T1 (de)	2001-12-15
EP0550756A1 (en)	1993-07-14
KR930700550A (ko)	1993-03-15
DE69232259D1 (de)	2002-01-17
FI925745A7 (fi)	1992-12-17
EP0550756A4 (2)	1994-04-27
TW221379B (2)	1994-03-01

Legal Events

Date	Code	Title	Description
1998-04-17	FZDE	Discontinued

Publication	Publication Date	Title
US5362490A (en)	1994-11-08	Human myelomonocyte interferon-gamma, and process for preparation and use thereof
EP0344796B1 (en)	1994-09-21	Crystalline human granulocyte colony stimulating factor and process for preparing the same
EP0550756B1 (en)	2001-12-05	Preparation of interleukin-6 compositions
EP0260708A2 (en)	1988-03-23	Tumor egress factor and processes for producing the same
EP0240348A2 (en)	1987-10-07	Agent for the removal of nucleic acids and/or endotoxin and method for the removal thereof
EP0291728A2 (en)	1988-11-23	Production of immune interferon and its mRNA
FI72143C (fi)	1987-04-13	Foerfarande foer framstaellning av maenniskointerferon.
EP0861663B1 (en)	2003-07-23	Osteoclastgenic inhibitory agent comprising interleukin-18
JPH0112760B2 (2)	1989-03-02
Guan et al.	1996	Use of aqueous two-phase systems in the purification of human interferon-α1 from recombinant Escherichia coli
US4777241A (en)	1988-10-11	Proteinaceous substance showing antitumorous action and its preparing method
US5417970A (en)	1995-05-23	Drugs containing a glycosylated interleukin-2
JPH0550273B2 (2)	1993-07-28
EP0550769B1 (en)	2000-04-05	Use of hepatocyte growth factors for the manufacture of a hemopoietic stem cell augmenting agent
US5641868A (en)	1997-06-24	Interlekin-6 compositions, and a production process thereof
RU2129878C1 (ru)	1999-05-10	Иммуномодулирующий препарат с противовирусной активностью "неоферон"
WO1989010133A1 (en)	1989-11-02	Stem cell inhibitors
AU601168B2 (en)	1990-09-06	Novel cell growth regulatory factor
Weil et al.	2018	Interferon structure: facts and speculation
JPH05255106A (ja)	1993-10-05	血小板減少症治療剤
TW385313B (en)	2000-03-21	Method for the production of rDSPA alpha 1
EP0672684A1 (en)	1995-09-20	Novel megakaryocyte colony stimulating factor and production thereof
KR20050054005A (ko)	2005-06-10	인체 인터페론 알파의 제조방법
AU618382B2 (en)	1991-12-19	Human interferon-gamma, process to prepare said human interferon-gamma, and its use
JPWO1992018537A1 (ja)	1993-05-13	インターロイキン６組成物およびその製造法