JP5410985B2 - 液体抗狂犬病抗体製剤 - Google Patents
液体抗狂犬病抗体製剤 Download PDFInfo
- Publication number
- JP5410985B2 JP5410985B2 JP2009539730A JP2009539730A JP5410985B2 JP 5410985 B2 JP5410985 B2 JP 5410985B2 JP 2009539730 A JP2009539730 A JP 2009539730A JP 2009539730 A JP2009539730 A JP 2009539730A JP 5410985 B2 JP5410985 B2 JP 5410985B2
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- formulation
- rabies virus
- months
- seq
- 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 - Fee Related
Links
- 239000000203 mixture Substances 0.000 title claims description 164
- 238000009472 formulation Methods 0.000 title claims description 153
- 206010037742 Rabies Diseases 0.000 title claims description 41
- 239000007788 liquid Substances 0.000 title description 8
- 238000003860 storage Methods 0.000 claims description 41
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 30
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 30
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 30
- 229920000053 polysorbate 80 Polymers 0.000 claims description 30
- 229940068968 polysorbate 80 Drugs 0.000 claims description 30
- 241000700605 Viruses Species 0.000 claims description 28
- 241000711798 Rabies lyssavirus Species 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 19
- 239000007979 citrate buffer Substances 0.000 claims description 17
- 230000003472 neutralizing effect Effects 0.000 claims description 16
- 239000011780 sodium chloride Substances 0.000 claims description 15
- 239000002158 endotoxin Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 239000000178 monomer Substances 0.000 claims description 9
- 238000011993 High Performance Size Exclusion Chromatography Methods 0.000 claims description 8
- 230000027455 binding Effects 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000006227 byproduct Substances 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
- 230000010530 Virus Neutralization Effects 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 3
- 239000000047 product Substances 0.000 claims description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 21
- 238000004458 analytical method Methods 0.000 description 18
- 230000015556 catabolic process Effects 0.000 description 17
- 238000006731 degradation reaction Methods 0.000 description 17
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 16
- 239000000546 pharmaceutical excipient Substances 0.000 description 14
- 125000003275 alpha amino acid group Chemical group 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 238000011109 contamination Methods 0.000 description 11
- 239000004094 surface-active agent Substances 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 10
- 239000000427 antigen Substances 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000000872 buffer Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 125000000539 amino acid group Chemical group 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 7
- 230000002265 prevention Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 6
- 239000007951 isotonicity adjuster Substances 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 5
- 239000007857 degradation product Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 238000011179 visual inspection Methods 0.000 description 5
- 238000007792 addition Methods 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000006240 deamidation Effects 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229950008882 polysorbate Drugs 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000012929 tonicity agent Substances 0.000 description 3
- 241000372837 Fumana Species 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 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 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000012502 diagnostic product Substances 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
- 239000012537 formulation buffer Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000002093 isoelectric focusing polyacrylamide gel electrophoresis Methods 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 235000004252 protein component Nutrition 0.000 description 2
- 229960003127 rabies vaccine Drugs 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- -1 sugar Chemical class 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- 206010002515 Animal bite Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 229920002642 Polysorbate 65 Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 229940124875 RabAvert Drugs 0.000 description 1
- 101000633010 Rattus norvegicus Somatostatin Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000012801 analytical assay Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 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 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 229940030156 cell vaccine Drugs 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 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
- 230000003247 decreasing effect Effects 0.000 description 1
- 210000000852 deltoid muscle Anatomy 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 210000001840 diploid cell Anatomy 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002270 exclusion chromatography Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000002977 hyperthermial effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940026063 imovax Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000010829 isocratic elution Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940099511 polysorbate 65 Drugs 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- NHXLMOGPVYXJNR-UHFFFAOYSA-N srif Chemical compound N1C(=O)C(C(C)O)NC(=O)C(CCCCN)NC(=O)C(CC=2C3=CC=CC=C3NC=2)NC(=O)C(CC=2C=CC=CC=2)NC(=O)C(CC=2C=CC=CC=2)NC(=O)C(CC(N)=O)NC(=O)C(CCCCN)NC(=O)C(NC(=O)CNC(=O)C(C)N)CSSCC(C(O)=O)NC(=O)C(CO)NC(=O)C(C(O)C)NC(=O)C1CC1=CC=CC=C1 NHXLMOGPVYXJNR-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39591—Stabilisation, fragmentation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
-
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
+2:バンドパターンはWS#に匹敵し、約43kDaのサイズを有する弱い追加の不純物バンドを含む
+3:バンドパターンはWS#に匹敵し、約10,15および43kDaのサイズを有する弱い追加の不純物バンドを含む
+4:逸脱、弱いバンドが43kDaの周りに出現
+5:バンドパターンはWS#に匹敵し、約10kDa,15kDaおよび25−50kDaのサイズを有する弱い追加の不純物バンドを含む
+6:バンドパターンはWS#で確認、8.0−8.5pI−面積にバンドのより高い汚染強度
+7:逸脱、弱いバンドがpI7.5以下に出現、8.0−8.5pI−面積に異なる汚染強度
+8:バンドパターンはWS#で確認、弱い追加バンド(pI7.2,7.3,8.6)
+9:バンドパターンはWS#で確認、弱い追加バンド(pI範囲6.3−7.4およびpI8.6)
Claims (16)
- 少なくとも12ヶ月の間2℃から8℃の間の温度で安定な二つの抗狂犬病モノクローナル抗体の製剤上の調剤物であって、
(i)配列番号1の重鎖および配列番号2の軽鎖を含む抗狂犬病ウイルスモノクロ−ナル抗体CR57、またはそれと配列で少なくとも95%同一であり、CR57により認識される標的への結合についてCR57と競合すること、および狂犬病ウイルス中和活性を有することが可能である抗体と、
(ii)配列番号3の重鎖および配列番号4の軽鎖を含む抗狂犬病ウイルスモノクロ−ナル抗体CR4098、またはそれと配列で少なくとも95%同一であり、CR4098により認識される標的への結合についてCR4098と競合すること、および狂犬病ウイルス中和活性を有することが可能である抗体と
を含み、
調剤物は、10mMの濃度のクエン酸塩緩衝剤、150mMの濃度の塩化ナトリウム、および0.01から0.03%w/vまでの量のポリソルベート80を含む、製剤上の調剤物。 - pHは5.5から6.5までに及ぶ、請求項1に記載の調剤物。
- 調剤物の重量オスモル濃度は、250mOsm/kgから350のmOsm/kgまでに及ぶ、請求項1または2に記載の調剤物。
- 二つの抗狂犬病ウイルスモノクロ−ナル抗体はそれぞれ0.1mg/mLから2.0mg/mLまでの量で存在する、請求項1〜3のいずれか一項に記載の調剤物。
- 調剤物は、250IU/mLから1500IU/mLまでに及ぶ狂犬病ウイルス中和有効性を有する、請求項1〜4のいずれか一項に記載の調剤物。
- 二つの抗体の比率は、5:1および1:5の間である、請求項1〜5のいずれか一項に記載の調剤物。
- 調剤物は滅菌されたもの(無菌)である、請求項1〜6のいずれか一項に記載の調剤物。
- 調剤物はエンドトキシンを含まない、請求項1〜7のいずれか一項に記載の調剤物。
- 調剤物は40±2℃の温度および75±5%の相対湿度で2週間貯蔵後にHPSECで求めて少なくとも95%の抗体モノマーの純度を有する、請求項1〜8のいずれか一項に記載の調剤物。
- 請求項1〜9のいずれか一項に記載の調剤物の有効量を、対象体への剤形の投与を介する対象体の曝露後の予防の処置のために含む、製剤上の単位剤形。
- 一つの調剤物での二つの抗狂犬病モノクローナル抗体の貯蔵を改善するための方法であって、請求項1〜10のいずれか一項に記載の製剤上の調剤物において抗体を調剤することを含む、方法。
- 調剤物は、2℃から40℃までの温度で貯蔵される、請求項11に記載の方法。
- 抗体の副産物形成の量を減ずる、請求項11または12に記載の方法。
- 抗体の5%またはそれ未満しか、2℃から8℃までの温度での貯蔵の12ヶ月間以内にHPSECで測定されるような凝集体を形成しない、請求項13に記載の方法。
- 配列番号1の重鎖および配列番号2の軽鎖を含む抗狂犬病ウイルスモノクロ−ナル抗体CR57、またはそれと配列で少なくとも95%同一であり、CR57により認識される標的への結合についてCR57と競合すること、および狂犬病ウイルス中和活性を有することが可能である抗体の製剤上の調剤物であって、調剤物は2℃から8℃までの間の温度および−60℃および−80℃の間の温度で少なくとも18ヶ月の間安定であり、調剤物は、10mMの濃度のクエン酸塩緩衝剤、150mMの濃度の塩化ナトリウム、および0.01から0.03%w/vまでの量のポリソルベート80を含む、調剤物。
- 配列番号3の重鎖および配列番号4の軽鎖を含む抗狂犬病ウイルスモノクロ−ナル抗体CR4098、またはそれと配列で少なくとも95%同一であり、CR4098により認識される標的への結合についてCR4098と競合すること、および狂犬病ウイルス中和活性を有することが可能である抗体の製剤上の調剤物であって、調剤物は2℃から8℃までの間の温度および−60℃および−80℃の間の温度で少なくとも18ヶ月の間安定であり、調剤物は、10mMの濃度のクエン酸塩緩衝剤、150mMの濃度の塩化ナトリウム、および0.01から0.03%w/vまでの量のポリソルベート80を含む、調剤物。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US87289206P | 2006-12-05 | 2006-12-05 | |
US60/872,892 | 2006-12-05 | ||
EP06125400 | 2006-12-05 | ||
EP06125400.9 | 2006-12-05 | ||
PCT/EP2007/063244 WO2008068246A1 (en) | 2006-12-05 | 2007-12-04 | Liquid anti-rabies antibody formulations |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2010511665A JP2010511665A (ja) | 2010-04-15 |
JP2010511665A5 JP2010511665A5 (ja) | 2011-01-20 |
JP5410985B2 true JP5410985B2 (ja) | 2014-02-05 |
Family
ID=39092188
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009539730A Expired - Fee Related JP5410985B2 (ja) | 2006-12-05 | 2007-12-04 | 液体抗狂犬病抗体製剤 |
Country Status (13)
Country | Link |
---|---|
US (1) | US7959922B2 (ja) |
EP (1) | EP2088997B1 (ja) |
JP (1) | JP5410985B2 (ja) |
KR (1) | KR101522036B1 (ja) |
CN (1) | CN101557799B (ja) |
AU (1) | AU2007328960B2 (ja) |
CA (1) | CA2668947C (ja) |
CU (1) | CU23795A3 (ja) |
EA (1) | EA017549B1 (ja) |
IL (1) | IL199004A (ja) |
MX (1) | MX2009005414A (ja) |
WO (1) | WO2008068246A1 (ja) |
ZA (1) | ZA200902772B (ja) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2526284C (en) | 2003-06-25 | 2014-11-18 | Crucell Holland B.V. | Binding molecules for the treatment of myeloid cell malignancies |
NZ550366A (en) | 2004-05-27 | 2009-11-27 | Crucell Holland Bv | Binding molecules capable of neutralizing rabies virus and uses thereof |
EP2027155B1 (en) | 2006-06-06 | 2016-01-27 | Crucell Holland B.V. | Human binding molecules having killing activity against staphylococci and uses thereof |
MX2009005414A (es) | 2006-12-05 | 2009-06-01 | Crucell Holland Bv | Formulaciones liquidas de anticuerpo antirrabico. |
JP2010085126A (ja) * | 2008-09-29 | 2010-04-15 | Adtec Kk | 狂犬病ウイルス中和抗体価判定具および狂犬病ウイルス中和抗体価の測定方法 |
US8821879B2 (en) | 2009-09-04 | 2014-09-02 | Xoma Technology Ltd. | Anti-botulism antibody coformulations |
EP4088736A1 (en) | 2011-10-25 | 2022-11-16 | Prothena Biosciences Limited | Humanized anti-amyloid antibody formulations and methods |
ME02565B (me) | 2012-03-07 | 2017-02-20 | Lilly Co Eli | Formulacija protutijela protiv il-17 |
KR20140119396A (ko) | 2013-03-29 | 2014-10-10 | 삼성전자주식회사 | 단백질 약물의 액상 제형 |
JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
RU2019138507A (ru) | 2017-05-02 | 2021-06-02 | Мерк Шарп И Доум Корп. | Составы антител против lag3 и совместные составы антител против lag3 и антител против pd-1 |
JP7159642B2 (ja) * | 2018-06-26 | 2022-10-25 | 東ソー株式会社 | カラムの抗体に対する保持力の測定方法 |
WO2021249542A1 (en) | 2020-06-12 | 2021-12-16 | Nanjing Leads Biolabs Co., Ltd. | Antibodies binding tnfr2 and uses thereof |
CN114748618B (zh) * | 2022-04-02 | 2024-07-19 | 重庆智翔金泰生物制药股份有限公司 | 包含针对狂犬病病毒g蛋白的双特异性抗体的药物制剂及其制备方法 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2062364T3 (es) | 1989-06-08 | 1994-12-16 | Wistar Inst | Un metodo de preparacion de una composicion para el tratamiento despues de la exposicion de infeccion de rabia. |
DE4006630A1 (de) | 1990-03-03 | 1991-09-12 | Behringwerke Ag | Humane monoklonale antikoerper gegen tollwutviren, ihre herstellung und verwendung |
AU4474497A (en) | 1996-10-08 | 1998-05-05 | U-Bisys B.V. | Methods and means for selecting peptides and proteins having specific affinity for a target |
US20040013672A1 (en) * | 2000-05-16 | 2004-01-22 | Thomas Jefferson University | Recombinant antibodies, and compositions and methods for making and using the same |
CA2457362C (en) | 2001-08-21 | 2012-01-17 | Thomas Jefferson University | Human monoclonal rabies virus neutralizing antibodies, and methods for making and using the same |
ATE514717T1 (de) | 2002-07-18 | 2011-07-15 | Merus B V | Rekombinante produktion von antikörpermischungen |
CA2537371A1 (en) * | 2003-09-04 | 2005-03-17 | Crucell Holland B.V. | Antigenic peptides of rabies virus and uses thereof |
ATE518888T1 (de) * | 2003-10-09 | 2011-08-15 | Chugai Pharmaceutical Co Ltd | Stabilisierte lösung mit hoher igm-konzentration |
JP4671864B2 (ja) * | 2003-10-09 | 2011-04-20 | 中外製薬株式会社 | タンパク質溶液の安定化方法 |
EP1712240B1 (en) * | 2003-12-25 | 2015-09-09 | Kyowa Hakko Kirin Co., Ltd. | Stable water-based medicinal preparation containing antibody |
NZ550366A (en) * | 2004-05-27 | 2009-11-27 | Crucell Holland Bv | Binding molecules capable of neutralizing rabies virus and uses thereof |
US7785595B2 (en) * | 2005-04-18 | 2010-08-31 | Yeda Research And Development Company Limited | Stabilized anti-hepatitis B (HBV) antibody formulations |
MX2009005414A (es) | 2006-12-05 | 2009-06-01 | Crucell Holland Bv | Formulaciones liquidas de anticuerpo antirrabico. |
-
2007
- 2007-12-04 MX MX2009005414A patent/MX2009005414A/es active IP Right Grant
- 2007-12-04 CN CN2007800448444A patent/CN101557799B/zh not_active Expired - Fee Related
- 2007-12-04 EA EA200970533A patent/EA017549B1/ru unknown
- 2007-12-04 AU AU2007328960A patent/AU2007328960B2/en not_active Ceased
- 2007-12-04 US US12/312,967 patent/US7959922B2/en not_active Expired - Fee Related
- 2007-12-04 EP EP07847749.4A patent/EP2088997B1/en active Active
- 2007-12-04 CA CA2668947A patent/CA2668947C/en active Active
- 2007-12-04 WO PCT/EP2007/063244 patent/WO2008068246A1/en active Application Filing
- 2007-12-04 JP JP2009539730A patent/JP5410985B2/ja not_active Expired - Fee Related
- 2007-12-04 KR KR1020097013012A patent/KR101522036B1/ko active IP Right Grant
-
2009
- 2009-04-21 ZA ZA2009/02772A patent/ZA200902772B/en unknown
- 2009-05-27 IL IL199004A patent/IL199004A/en active IP Right Grant
- 2009-06-04 CU CU20090099A patent/CU23795A3/es not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
AU2007328960A1 (en) | 2008-06-12 |
EA017549B1 (ru) | 2013-01-30 |
EP2088997B1 (en) | 2016-08-24 |
MX2009005414A (es) | 2009-06-01 |
CN101557799A (zh) | 2009-10-14 |
WO2008068246A1 (en) | 2008-06-12 |
JP2010511665A (ja) | 2010-04-15 |
ZA200902772B (en) | 2012-09-26 |
EA200970533A1 (ru) | 2009-10-30 |
US20100034829A1 (en) | 2010-02-11 |
CN101557799B (zh) | 2012-08-22 |
EP2088997A1 (en) | 2009-08-19 |
US7959922B2 (en) | 2011-06-14 |
IL199004A0 (en) | 2010-02-17 |
IL199004A (en) | 2015-10-29 |
KR20090089881A (ko) | 2009-08-24 |
CA2668947C (en) | 2017-02-07 |
CU23795A3 (es) | 2012-03-15 |
CA2668947A1 (en) | 2008-06-12 |
KR101522036B1 (ko) | 2015-05-20 |
AU2007328960B2 (en) | 2013-01-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5410985B2 (ja) | 液体抗狂犬病抗体製剤 | |
RU2644214C2 (ru) | СТАБИЛЬНЫЕ ПРЕПАРАТЫ СВЯЗЫВАЮЩЕГО СРЕДСТВА НА ОСНОВЕ IgG4 | |
KR20160068946A (ko) | 안정한 수성 항체 제제 | |
TWI764097B (zh) | 包含抗cd47抗體的製劑及其製備方法和用途 | |
CN111315411A (zh) | 高浓度抗c5抗体制剂 | |
KR102450280B1 (ko) | 항체 제형 | |
JP2020534255A (ja) | 治療用タンパク質の凍結乾燥医薬配合物のためのプロセス | |
US20230066762A1 (en) | Immunogenic composition | |
UA123107C2 (uk) | Стабільна рідка композиція гонадотропіну | |
JP7467438B2 (ja) | 抗rsv抗体の製剤及びその使用方法 | |
AU2020325569B2 (en) | Process for preparing a composition comprising a protein D polypeptide | |
ES2602275T3 (es) | Formulaciones líquidas de anticuerpo anti-rabia | |
RU2807524C2 (ru) | Составы антител к rsv и способы их применения |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101125 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20101125 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121002 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121228 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130219 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130520 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130723 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130814 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20131029 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131107 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5410985 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |