FI106802B - Väsentligen rent humant bisköldkörtelhormon - Google Patents
Väsentligen rent humant bisköldkörtelhormon Download PDFInfo
- Publication number
- FI106802B FI106802B FI922356A FI922356A FI106802B FI 106802 B FI106802 B FI 106802B FI 922356 A FI922356 A FI 922356A FI 922356 A FI922356 A FI 922356A FI 106802 B FI106802 B FI 106802B
- Authority
- FI
- Finland
- Prior art keywords
- pth
- parathyroid hormone
- human parathyroid
- preparation
- substantially pure
- Prior art date
Links
- 101001135770 Homo sapiens Parathyroid hormone Proteins 0.000 title claims abstract description 66
- 101001135995 Homo sapiens Probable peptidyl-tRNA hydrolase Proteins 0.000 title claims abstract description 66
- 102000058004 human PTH Human genes 0.000 title claims abstract description 66
- 238000000034 method Methods 0.000 claims abstract description 37
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 35
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 35
- 238000005251 capillar electrophoresis Methods 0.000 claims abstract description 28
- 238000004458 analytical method Methods 0.000 claims abstract description 17
- 239000000356 contaminant Substances 0.000 claims abstract description 17
- 108090000445 Parathyroid hormone Proteins 0.000 claims description 90
- 239000003795 chemical substances by application Substances 0.000 claims description 32
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 21
- 241000588724 Escherichia coli Species 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 13
- UNXNGGMLCSMSLH-UHFFFAOYSA-N dihydrogen phosphate;triethylazanium Chemical compound OP(O)(O)=O.CCN(CC)CC UNXNGGMLCSMSLH-UHFFFAOYSA-N 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 7
- 230000001580 bacterial effect Effects 0.000 claims description 6
- 125000002091 cationic group Chemical group 0.000 claims description 6
- 150000002500 ions Chemical class 0.000 claims description 6
- 230000000813 microbial effect Effects 0.000 claims description 6
- 102000030621 adenylate cyclase Human genes 0.000 claims description 4
- 108060000200 adenylate cyclase Proteins 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 102000003982 Parathyroid hormone Human genes 0.000 claims 2
- 239000000199 parathyroid hormone Substances 0.000 claims 2
- 229960001319 parathyroid hormone Drugs 0.000 claims 2
- 235000015895 biscuits Nutrition 0.000 claims 1
- -1 cationic ion Chemical class 0.000 claims 1
- 238000011210 chromatographic step Methods 0.000 claims 1
- 102100036893 Parathyroid hormone Human genes 0.000 description 88
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 36
- 235000018102 proteins Nutrition 0.000 description 33
- 238000004007 reversed phase HPLC Methods 0.000 description 31
- 239000002904 solvent Substances 0.000 description 23
- YPJUNDFVDDCYIH-UHFFFAOYSA-N perfluorobutyric acid Chemical compound OC(=O)C(F)(F)C(F)(F)C(F)(F)F YPJUNDFVDDCYIH-UHFFFAOYSA-N 0.000 description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- 238000002835 absorbance Methods 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 229920002684 Sepharose Polymers 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000005194 fractionation Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 5
- 239000005695 Ammonium acetate Substances 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 229940043376 ammonium acetate Drugs 0.000 description 5
- 235000019257 ammonium acetate Nutrition 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- 238000003556 assay Methods 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000003607 modifier Substances 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000008135 aqueous vehicle Substances 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 206010065687 Bone loss Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000010612 desalination reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000000849 parathyroid Effects 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- JSMYHXFFKXKZRN-SBMIAAHKSA-N (2s,3s,4s)-3-(carboxymethyl)-4-(2-hydroxyphenyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)C[C@@H]1[C@@H](C(O)=O)NC[C@@H]1C1=CC=CC=C1O JSMYHXFFKXKZRN-SBMIAAHKSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 101100295756 Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / JCM 6841 / CCUG 19606 / CIP 70.34 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81) omp38 gene Proteins 0.000 description 1
- 102000004400 Aminopeptidases Human genes 0.000 description 1
- 108090000915 Aminopeptidases Proteins 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 108091005598 amidated proteins Proteins 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 101150042295 arfA gene Proteins 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010884 ion-beam technique Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 101150087557 omcB gene Proteins 0.000 description 1
- 101150115693 ompA gene Proteins 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/635—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Physical Education & Sports Medicine (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Steroid Compounds (AREA)
- Pyrane Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Glass Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (12)
1. Förfarande för att rena bisköldkörtelhormon hos människa, kannetecknat av att det innefattar ett steg för att fraktionera ett delvis renat mänskligt bisköldkörtelhormon- (PTH-) preparat 5 med vätskekromatografi med hög prestationsförmäga baserad pä omvänd fas i närvaro av ett katjoniskt ämne som bildar jonpar.
2. Förfarande enligt patentkrav 1, kannetecknat av att det kat-joniska ämne som bildar jonpar är ett aminbaserat ämne som bildar jonpar. 10
3. Förfarande enligt patentkrav 2, kännetecknat av att det aminbaserade ämnet som bildar jonpar är trietylamin eller dess salt.
4. Förfarande enligt patentkrav 3, kännetecknat av att det aminbaserade ämnet som bildar jonpar är trietylaminfosfat. 15
5. Förfarande enligt patentkrav 3, kännetecknat av att det del- vis renade bisköldkörtelhormonpreparatet erhällits ur en mik-robkälla för mänskligt bisköldkörtelhormon.
6. Förfarande enligt patentkrav 5, kännetecknat av att mikrob-källan för det mänskliga bisköldkörtelhormonet är en bakterie- 20 källa för mänskligt bisköldkörtelhormon. «
7. Förfarande enligt patentkrav 6, kännetecknat av att bakte-riekällan för det mänskliga bisköldkörtelhormonet är en E.coli-källa för mänskligt bisköldkörtelhormon.
8. Förfarande enligt patentkrav 1 för framställning av väsent-25 ligen rent mänskligt bisköldkörtelhormon, kännetecknat av att • det innefattar steg för att (i) erhälla ett delvis renat preparat av mänskligt bisköldkörtelhormon producerat i E.coli, (ii) fraktionera detta delvis renade preparat med vätskekro- 30 matografi med hög prestationsförmaga baserad pä omvänd fas i närvaro av trietylamin eller dess sait; och 106802 (iii) efter kromatografisteget ta tillvara väsentligen rent mänskligt bisköldkörtelhormon.
9. Förfarande enligt patentkrav 8, käxmetecknat av att det dessutom innefattar ett steg för att lyofilisera det tillvara- 5 tagna mänskliga bisköldkörtelhormonet.
10. Förfarande enligt patentkrav 1 och 8 för framställning av ett väsentligen rent mänskligt bisköldkörtelhormon, känneteck-nat av att i kapillarelektrofores vid analys pä en 214 nm väg-längd fas endast en pik, och att EC50 definieras med adenylat- 10 cyklasanalys baserad pä högst 2 nM UMR 106.
11. Förfarande enligt patentkrav 1 eller 8 för framställning av ett väsentligen rent mänskligt bisköldkörtelhormon, känneteck-nat av att det inte finns proteinkontaminanter närvarande som kunde detekteras med kapillarelektrofores. 15
12. Förfarande enligt patentkrav 11, kännetecknat av att det väsentligen rena mänskliga bisköldkörtelhormonet är i lyofili-serad form. « .' «
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US70711491 | 1991-05-23 | ||
US07/707,114 US5208041A (en) | 1991-05-23 | 1991-05-23 | Essentially pure human parathyroid hormone |
Publications (3)
Publication Number | Publication Date |
---|---|
FI922356A0 FI922356A0 (fi) | 1992-05-22 |
FI922356A FI922356A (fi) | 1992-11-24 |
FI106802B true FI106802B (sv) | 2001-04-12 |
Family
ID=24840399
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI922356A FI106802B (sv) | 1991-05-23 | 1992-05-22 | Väsentligen rent humant bisköldkörtelhormon |
Country Status (16)
Country | Link |
---|---|
US (1) | US5208041A (sv) |
EP (1) | EP0515228B1 (sv) |
JP (1) | JP2563726B2 (sv) |
KR (1) | KR970007755B1 (sv) |
AT (1) | ATE164394T1 (sv) |
CA (1) | CA2068438C (sv) |
DE (1) | DE69224858T2 (sv) |
DK (1) | DK0515228T3 (sv) |
ES (1) | ES2115642T3 (sv) |
FI (1) | FI106802B (sv) |
HK (1) | HK1004340A1 (sv) |
IE (1) | IE921672A1 (sv) |
IL (3) | IL101829A (sv) |
NO (2) | NO304190B1 (sv) |
NZ (1) | NZ242855A (sv) |
ZA (1) | ZA923735B (sv) |
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5420242A (en) * | 1986-10-22 | 1995-05-30 | Kaare M. Gautvik | Production of human parathyroid hormone from microorganisms |
USRE37919E1 (en) | 1989-05-12 | 2002-12-03 | The General Hospital Corporation | Recombinant DNA method for production of parathyroid hormone |
TW273513B (sv) * | 1993-10-27 | 1996-04-01 | Chugai Pharmaceutical Co Ltd | |
US20020193338A1 (en) * | 1994-02-18 | 2002-12-19 | Goldstein Steven A. | In vivo gene transfer methods for wound healing |
US5962427A (en) | 1994-02-18 | 1999-10-05 | The Regent Of The University Of Michigan | In vivo gene transfer methods for wound healing |
US6074840A (en) | 1994-02-18 | 2000-06-13 | The Regents Of The University Of Michigan | Recombinant production of latent TGF-beta binding protein-3 (LTBP-3) |
US5763416A (en) | 1994-02-18 | 1998-06-09 | The Regent Of The University Of Michigan | Gene transfer into bone cells and tissues |
US5942496A (en) | 1994-02-18 | 1999-08-24 | The Regent Of The University Of Michigan | Methods and compositions for multiple gene transfer into bone cells |
US6551618B2 (en) | 1994-03-15 | 2003-04-22 | University Of Birmingham | Compositions and methods for delivery of agents for neuronal regeneration and survival |
AU745122B2 (en) | 1997-07-30 | 2002-03-14 | Emory University | Novel bone mineralization proteins, DNA, vectors, expression systems |
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US3886132A (en) * | 1972-12-21 | 1975-05-27 | Us Health | Human parathyroid hormone |
US5223407A (en) * | 1988-08-31 | 1993-06-29 | Allelix Inc. | Excretion of heterologous proteins from e. coli |
WO1991005050A1 (en) * | 1989-09-29 | 1991-04-18 | Her Majesty In Right Of Canada As Represented By The National Research Council Of Canada | Synthesis of mature human parathyroid hormone |
-
1991
- 1991-05-23 US US07/707,114 patent/US5208041A/en not_active Expired - Lifetime
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1992
- 1992-05-11 IL IL10182992A patent/IL101829A/en not_active IP Right Cessation
- 1992-05-11 IL IL11984092A patent/IL119840A/xx not_active IP Right Cessation
- 1992-05-12 CA CA002068438A patent/CA2068438C/en not_active Expired - Lifetime
- 1992-05-21 NO NO19922000A patent/NO304190B1/no not_active IP Right Cessation
- 1992-05-21 NZ NZ242855A patent/NZ242855A/xx not_active IP Right Cessation
- 1992-05-22 ES ES92304692T patent/ES2115642T3/es not_active Expired - Lifetime
- 1992-05-22 FI FI922356A patent/FI106802B/sv not_active IP Right Cessation
- 1992-05-22 DK DK92304692T patent/DK0515228T3/da active
- 1992-05-22 DE DE69224858T patent/DE69224858T2/de not_active Expired - Lifetime
- 1992-05-22 JP JP4156100A patent/JP2563726B2/ja not_active Expired - Lifetime
- 1992-05-22 EP EP92304692A patent/EP0515228B1/en not_active Expired - Lifetime
- 1992-05-22 KR KR92008730A patent/KR970007755B1/ko not_active IP Right Cessation
- 1992-05-22 AT AT92304692T patent/ATE164394T1/de active
- 1992-05-22 ZA ZA923735A patent/ZA923735B/xx unknown
- 1992-07-01 IE IE167292A patent/IE921672A1/en not_active IP Right Cessation
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1996
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1998
- 1998-04-24 HK HK98103454A patent/HK1004340A1/xx not_active IP Right Cessation
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Also Published As
Publication number | Publication date |
---|---|
AU1604992A (en) | 1993-03-11 |
JP2563726B2 (ja) | 1996-12-18 |
IL119840A0 (en) | 1997-03-18 |
HK1004340A1 (en) | 1998-11-20 |
ZA923735B (en) | 1993-01-27 |
NO2006013I2 (no) | 2009-12-07 |
NO304190B1 (no) | 1998-11-09 |
US5208041A (en) | 1993-05-04 |
KR970007755B1 (en) | 1997-05-16 |
CA2068438A1 (en) | 1992-11-24 |
AU639856B2 (en) | 1993-08-05 |
ATE164394T1 (de) | 1998-04-15 |
NZ242855A (en) | 1994-04-27 |
CA2068438C (en) | 1996-11-12 |
NO2006013I1 (no) | 2006-11-06 |
FI922356A (fi) | 1992-11-24 |
DE69224858D1 (de) | 1998-04-30 |
EP0515228A3 (sv) | 1994-05-04 |
ES2115642T3 (es) | 1998-07-01 |
NO922000L (no) | 1992-11-24 |
EP0515228A2 (en) | 1992-11-25 |
DK0515228T3 (da) | 1998-09-28 |
IL119840A (en) | 2005-08-31 |
IE921672A1 (en) | 1992-12-02 |
JPH0687897A (ja) | 1994-03-29 |
FI922356A0 (fi) | 1992-05-22 |
EP0515228B1 (en) | 1998-03-25 |
IL101829A0 (en) | 1992-12-30 |
NO922000D0 (no) | 1992-05-21 |
DE69224858T2 (de) | 1998-07-23 |
IL101829A (en) | 1999-12-31 |
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Owner name: ALLELIX BIOPHARMACEUTICALS INC. |
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