DE69903666T2 - Hilfsstoffe zur verwendung in adeno-assoziiertes virus enthaltenden pharmazeutischen zubereitungen und damit hergestellte pharmazeutische zubereitungen - Google Patents
Hilfsstoffe zur verwendung in adeno-assoziiertes virus enthaltenden pharmazeutischen zubereitungen und damit hergestellte pharmazeutische zubereitungenInfo
- Publication number
- DE69903666T2 DE69903666T2 DE69903666T DE69903666T DE69903666T2 DE 69903666 T2 DE69903666 T2 DE 69903666T2 DE 69903666 T DE69903666 T DE 69903666T DE 69903666 T DE69903666 T DE 69903666T DE 69903666 T2 DE69903666 T2 DE 69903666T2
- Authority
- DE
- Germany
- Prior art keywords
- tween
- polyoxyethylene sorbitan
- virion
- sorbitol
- detergent
- 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
- 241000702421 Dependoparvovirus Species 0.000 title claims abstract description 6
- 239000000126 substance Substances 0.000 title description 2
- 239000000825 pharmaceutical preparation Substances 0.000 title 2
- 210000002845 virion Anatomy 0.000 claims abstract description 70
- 239000000203 mixture Substances 0.000 claims abstract description 61
- -1 polypropylene Polymers 0.000 claims abstract description 61
- 239000011521 glass Substances 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 47
- 239000003599 detergent Substances 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 238000003860 storage Methods 0.000 claims abstract description 15
- 150000005846 sugar alcohols Polymers 0.000 claims abstract description 13
- 238000007710 freezing Methods 0.000 claims abstract description 9
- 230000008014 freezing Effects 0.000 claims abstract description 9
- 238000010257 thawing Methods 0.000 claims abstract description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 103
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 58
- 239000000600 sorbitol Substances 0.000 claims description 58
- 230000000694 effects Effects 0.000 claims description 57
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 49
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 46
- 229920000053 polysorbate 80 Polymers 0.000 claims description 46
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 30
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 30
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 30
- 150000001298 alcohols Chemical class 0.000 claims description 16
- 229920001223 polyethylene glycol Polymers 0.000 claims description 16
- 239000002202 Polyethylene glycol Substances 0.000 claims description 11
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 10
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 7
- 230000000087 stabilizing effect Effects 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 5
- 239000004147 Sorbitan trioleate Substances 0.000 claims description 4
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 claims description 4
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 claims description 4
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 claims description 4
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 claims description 4
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 claims description 4
- 235000019337 sorbitan trioleate Nutrition 0.000 claims description 4
- 229960000391 sorbitan trioleate Drugs 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 3
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 2
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims 1
- 229950011392 sorbitan stearate Drugs 0.000 claims 1
- 239000004743 Polypropylene Substances 0.000 abstract description 42
- 229920001155 polypropylene Polymers 0.000 abstract description 42
- 239000013607 AAV vector Substances 0.000 abstract description 18
- 238000002474 experimental method Methods 0.000 description 93
- 239000003085 diluting agent Substances 0.000 description 50
- 239000013598 vector Substances 0.000 description 49
- 210000004027 cell Anatomy 0.000 description 48
- 238000009472 formulation Methods 0.000 description 35
- 239000000546 pharmaceutical excipient Substances 0.000 description 28
- 108090000623 proteins and genes Proteins 0.000 description 22
- 108020004414 DNA Proteins 0.000 description 21
- 238000003556 assay Methods 0.000 description 17
- 241000700605 Viruses Species 0.000 description 16
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- 238000010790 dilution Methods 0.000 description 13
- 239000012895 dilution Substances 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 12
- 108091026890 Coding region Proteins 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 235000013772 propylene glycol Nutrition 0.000 description 11
- 108020004707 nucleic acids Proteins 0.000 description 9
- 102000039446 nucleic acids Human genes 0.000 description 9
- 150000007523 nucleic acids Chemical class 0.000 description 9
- 238000010361 transduction Methods 0.000 description 9
- 230000026683 transduction Effects 0.000 description 9
- 239000004471 Glycine Substances 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 230000001681 protective effect Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 102000053602 DNA Human genes 0.000 description 5
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 5
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 5
- 229940098773 bovine serum albumin Drugs 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000008177 pharmaceutical agent Substances 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 229960000027 human factor ix Drugs 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 239000013608 rAAV vector Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 230000002463 transducing effect Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 239000010981 turquoise Substances 0.000 description 3
- 229930024421 Adenine Natural products 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 108091029865 Exogenous DNA Proteins 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- 244000178870 Lavandula angustifolia Species 0.000 description 2
- 235000010663 Lavandula angustifolia Nutrition 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000001102 lavandula vera Substances 0.000 description 2
- 235000018219 lavender Nutrition 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 210000004777 protein coat Anatomy 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 229940113082 thymine Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000005030 transcription termination Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 1
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 1
- 244000056139 Brassica cretica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002534 Polyethylene Glycol 1450 Polymers 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 1
- 241000083869 Polyommatus dorylas Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000013022 formulation composition Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 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
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- YXZRCLVVNRLPTP-UHFFFAOYSA-J turquoise blue Chemical compound [Na+].[Na+].[Na+].[Na+].[Cu+2].NC1=NC(Cl)=NC(NC=2C=C(NS(=O)(=O)C3=CC=4C(=C5NC=4NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)NC=4NC(=C6C=C(C=CC6=4)S([O-])(=O)=O)NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)N5)C=C3)C(=CC=2)S([O-])(=O)=O)=N1 YXZRCLVVNRLPTP-UHFFFAOYSA-J 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- 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
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14151—Methods of production or purification of viral material
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11068998P | 1998-12-03 | 1998-12-03 | |
| PCT/US1999/028460 WO2000032233A2 (en) | 1998-12-03 | 1999-12-02 | Excipients for use in adeno-associated virus pharmaceutical formulations, and pharmaceutical formulations made therewith |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69903666D1 DE69903666D1 (de) | 2002-11-28 |
| DE69903666T2 true DE69903666T2 (de) | 2003-07-03 |
Family
ID=22334360
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69903666T Expired - Lifetime DE69903666T2 (de) | 1998-12-03 | 1999-12-02 | Hilfsstoffe zur verwendung in adeno-assoziiertes virus enthaltenden pharmazeutischen zubereitungen und damit hergestellte pharmazeutische zubereitungen |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1144009B1 (enExample) |
| JP (5) | JP2002531418A (enExample) |
| AT (1) | ATE226449T1 (enExample) |
| AU (2) | AU773834B2 (enExample) |
| CA (1) | CA2353417C (enExample) |
| DE (1) | DE69903666T2 (enExample) |
| ES (1) | ES2185417T3 (enExample) |
| PT (1) | PT1144009E (enExample) |
| WO (1) | WO2000032233A2 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002229823B2 (en) * | 2001-04-04 | 2007-02-15 | Delsitech Oy | Biodegradable carrier and method for preparation thereof |
| WO2003049763A1 (en) | 2001-12-12 | 2003-06-19 | Fh Faulding & Co Limited | Composition for the preservation of viruses |
| US7261882B2 (en) | 2003-06-23 | 2007-08-28 | Reagents Of The University Of Colorado | Methods for treating neuropathic pain by administering IL-10 polypeptides |
| LT2816118T (lt) | 2005-05-31 | 2018-12-10 | The Regents Of The University Of Colorado, A Body Corporate | Genų pristatymo būdai |
| US8980610B2 (en) * | 2008-11-20 | 2015-03-17 | Biogen Idec Ma Inc. | Arginine inactivation of viruses |
| JP6348064B2 (ja) | 2011-11-22 | 2018-06-27 | ザ チルドレンズ ホスピタル オブ フィラデルフィア | 効率の高いトランスジーン送達のためのウイルスベクター |
| EP4008356A1 (en) | 2016-03-31 | 2022-06-08 | University of Cincinnati | Methods and compositions for the treatment of als |
| EP3510161A4 (en) | 2016-08-23 | 2020-04-22 | Akouos, Inc. | COMPOSITIONS AND METHODS FOR TREATING NON-AGE-ASSOCIATED HEARING DEFICIENCY IN A HUMAN SUBJECT |
| WO2018212271A1 (ja) | 2017-05-18 | 2018-11-22 | 国立大学法人京都大学 | 脊髄小脳変性症36型の予防又は治療用組成物 |
| CA3084802A1 (en) * | 2017-12-05 | 2019-06-13 | Applied Genetic Technologies Corporation | Formulation optimization for viral particles |
| JP7630443B2 (ja) * | 2019-04-19 | 2025-02-17 | レジェンクスバイオ インコーポレーテッド | アデノ随伴ウイルスベクター製剤及び方法 |
| US20220325250A1 (en) | 2019-08-14 | 2022-10-13 | Leukocare Ag | Method for obtaining efficient compositions comprising viral vectors for vaccination or gene therapy |
| WO2021168362A1 (en) | 2020-02-21 | 2021-08-26 | Akouos, Inc. | Compositions and methods for treating non-age-associated hearing impairment in a human subject |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5616487A (en) * | 1994-09-15 | 1997-04-01 | Aastrom Biosciences, Inc. | Stabilized retrovirus compositions |
| FR2751343B1 (fr) * | 1996-07-16 | 1998-12-18 | Transgene Sa | Procede de conservation de virus recombinants infectieux, suspension aqueuse virale et utilisation comme medicament |
| EP0933997A4 (en) * | 1996-09-06 | 2000-08-16 | Chiron Corp | METHODS AND COMPOSITIONS FOR LIVER-SPECIFIC ADMINISTRATION OF THERAPEUTIC MOLECULES USING RECOMBINANT AAV VECTORS |
-
1999
- 1999-12-02 JP JP2000584922A patent/JP2002531418A/ja active Pending
- 1999-12-02 AT AT99964038T patent/ATE226449T1/de not_active IP Right Cessation
- 1999-12-02 CA CA002353417A patent/CA2353417C/en not_active Expired - Lifetime
- 1999-12-02 WO PCT/US1999/028460 patent/WO2000032233A2/en not_active Ceased
- 1999-12-02 EP EP99964038A patent/EP1144009B1/en not_active Expired - Lifetime
- 1999-12-02 PT PT99964038T patent/PT1144009E/pt unknown
- 1999-12-02 AU AU20361/00A patent/AU773834B2/en not_active Expired
- 1999-12-02 DE DE69903666T patent/DE69903666T2/de not_active Expired - Lifetime
- 1999-12-02 ES ES99964038T patent/ES2185417T3/es not_active Expired - Lifetime
-
2004
- 2004-08-27 AU AU2004205308A patent/AU2004205308A1/en not_active Abandoned
-
2010
- 2010-12-08 JP JP2010274133A patent/JP5663285B2/ja not_active Expired - Lifetime
-
2014
- 2014-01-06 JP JP2014000095A patent/JP2014058578A/ja not_active Withdrawn
-
2015
- 2015-12-11 JP JP2015241786A patent/JP2016040330A/ja not_active Withdrawn
-
2017
- 2017-08-18 JP JP2017157878A patent/JP2017206556A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| PT1144009E (pt) | 2003-01-31 |
| AU2036100A (en) | 2000-06-19 |
| JP2002531418A (ja) | 2002-09-24 |
| CA2353417C (en) | 2008-04-22 |
| ES2185417T3 (es) | 2003-04-16 |
| JP2011046748A (ja) | 2011-03-10 |
| JP2016040330A (ja) | 2016-03-24 |
| JP5663285B2 (ja) | 2015-02-04 |
| AU2004205308A1 (en) | 2004-09-23 |
| EP1144009B1 (en) | 2002-10-23 |
| ATE226449T1 (de) | 2002-11-15 |
| CA2353417A1 (en) | 2000-06-08 |
| EP1144009A3 (en) | 2002-02-06 |
| DE69903666D1 (de) | 2002-11-28 |
| AU773834B2 (en) | 2004-06-10 |
| EP1144009A2 (en) | 2001-10-17 |
| JP2014058578A (ja) | 2014-04-03 |
| WO2000032233A2 (en) | 2000-06-08 |
| WO2000032233A3 (en) | 2001-10-18 |
| JP2017206556A (ja) | 2017-11-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8852607B2 (en) | Excipients for use in adeno-associated virus pharmaceutical formulations, and pharmaceutical formulations made therewith | |
| DE60117550T2 (de) | Doppelsträngige parvovirus-vektoren | |
| JP5663285B2 (ja) | アデノ随伴ウイルスの薬学処方物における使用のための賦形剤、およびそれにより構成される薬学処方物 | |
| EP4005603B1 (en) | Adeno-associated virus virions with variant capsid and methods of use thereof | |
| DE69232983T2 (de) | Adeno-assozierter virus 2 basalvektoren | |
| EP1088075B1 (de) | Strukturprotein von aav, seine herstellung und verwendung | |
| EP1198580B1 (de) | Strukturprotein von adeno-assoziiertem virus mit veränderten chromatographischen eigenschaften | |
| DE69936104T2 (de) | Nukleinsäuresequenzen des adeno-assoziierten virus des serotyps i, und vektoren und wirtszellen, die diese enthalten | |
| DE69738351T2 (de) | Verfaheren zur durch rekombinante adeno-assoziierte virus-gerichtete gentherapie | |
| DE19933288A1 (de) | Strukturprotein von Adeno-assoziiertem Virus mit veränderter Antigenität, seine Herstellung und Verwendung | |
| DE10066104A1 (de) | Wirtszellen zur Verpackung von rekombinantem Adeno-assoziiertem Virus (rAAV), Verfahren zu ihrer Herstellung und deren Verwendung | |
| DE69631480T2 (de) | Helfersystem zur wirkungssteigerung der aav-vektorproduktion | |
| EP4100539B1 (en) | Adeno-associated variants, formulations and methods for pulmonary delivery | |
| DE4003826C2 (de) | Peptide der Kapsidproteine VP1 oder VP2 des Parvovirus B19 | |
| EP1448782A1 (de) | Optimierte herstellung von viralen, von parvoviren abgeleiteten vektoren in verpackungs- und produktionszellen durch hsv-infektion oder behandlung mit inhibitoren der dna-methylierung | |
| DE10056210A1 (de) | Virales Expressionssystem | |
| DE69636456T2 (de) | In-vitro verpackung von adeno-assoziierten virus dns | |
| Lin et al. | An Evolved AAV Variant with Enhanced Brain and Spinal Cord Tropism and Translation across Primate Species | |
| WO2000065075A1 (de) | Verwendung von coxsackieviren zur verbesserung der transfektion von zellen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |