CA2668947C - Liquid anti-rabies antibody formulations - Google Patents
Liquid anti-rabies antibody formulations Download PDFInfo
- Publication number
- CA2668947C CA2668947C CA2668947A CA2668947A CA2668947C CA 2668947 C CA2668947 C CA 2668947C CA 2668947 A CA2668947 A CA 2668947A CA 2668947 A CA2668947 A CA 2668947A CA 2668947 C CA2668947 C CA 2668947C
- Authority
- CA
- Canada
- Prior art keywords
- formulation
- antibody
- polysorbate
- antibodies
- formulations
- 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.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 204
- 238000009472 formulation Methods 0.000 title claims abstract description 191
- 206010037742 Rabies Diseases 0.000 title claims abstract description 43
- 239000007788 liquid Substances 0.000 title description 12
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims abstract description 44
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 44
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 44
- 229940068968 polysorbate 80 Drugs 0.000 claims abstract description 44
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 32
- 241000700605 Viruses Species 0.000 claims abstract description 31
- 239000004094 surface-active agent Substances 0.000 claims abstract description 20
- 239000007979 citrate buffer Substances 0.000 claims abstract description 19
- 239000011780 sodium chloride Substances 0.000 claims abstract description 16
- 230000002064 post-exposure prophylaxis Effects 0.000 claims abstract description 8
- 238000003860 storage Methods 0.000 claims description 43
- 238000011993 High Performance Size Exclusion Chromatography Methods 0.000 claims description 32
- 241000711798 Rabies lyssavirus Species 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 20
- 230000003472 neutralizing effect Effects 0.000 claims description 20
- 239000002158 endotoxin Substances 0.000 claims description 11
- 239000000178 monomer Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 239000002552 dosage form Substances 0.000 claims description 7
- 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 5
- 238000011282 treatment Methods 0.000 claims description 5
- 239000012929 tonicity agent Substances 0.000 abstract description 10
- 230000002035 prolonged effect Effects 0.000 abstract description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 29
- 238000004458 analytical method Methods 0.000 description 21
- 235000018102 proteins Nutrition 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 18
- 230000015556 catabolic process Effects 0.000 description 15
- 238000006731 degradation reaction Methods 0.000 description 15
- 239000000546 pharmaceutical excipient Substances 0.000 description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 13
- 239000012535 impurity Substances 0.000 description 13
- 238000003556 assay Methods 0.000 description 12
- 125000003275 alpha amino acid group Chemical group 0.000 description 11
- 239000002245 particle Substances 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 9
- 239000000427 antigen Substances 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 230000006240 deamidation Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 229960005486 vaccine Drugs 0.000 description 6
- 230000002776 aggregation Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 239000007857 degradation product Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000007792 addition Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 229940088679 drug related substance Drugs 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
- 238000011179 visual inspection Methods 0.000 description 4
- 230000004075 alteration Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 229960003127 rabies vaccine Drugs 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000012430 stability testing Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 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
- 229910019142 PO4 Inorganic materials 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
- 206010052428 Wound Diseases 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
- 238000012512 characterization method Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000012502 diagnostic product Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
- 238000005516 engineering process Methods 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
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 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
- 238000011005 laboratory method Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 2
- 238000010369 molecular cloning 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 229950008882 polysorbate Drugs 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 235000004252 protein component Nutrition 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars 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
- 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
- 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
- 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
- 241000282412 Homo Species 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
- 241000239218 Limulus Species 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
- 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
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 230000010530 Virus Neutralization Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 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
- 239000004411 aluminium Substances 0.000 description 1
- 238000012801 analytical assay Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution 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
- 238000000149 argon plasma sintering Methods 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
- 238000007068 beta-elimination reaction Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007853 buffer solution 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
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000003837 chick embryo Anatomy 0.000 description 1
- 229960002303 citric acid monohydrate Drugs 0.000 description 1
- 238000010367 cloning Methods 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
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 210000000852 deltoid muscle Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 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
- 238000011143 downstream manufacturing Methods 0.000 description 1
- 238000012444 downstream purification process Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 108010072542 endotoxin binding proteins Proteins 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
- 238000007710 freezing 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
- 230000001900 immune effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 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
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 238000006386 neutralization reaction 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
- 239000006174 pH buffer Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035515 penetration 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
- -1 polypropylene Polymers 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000523 sample Substances 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
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
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)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87289206P | 2006-12-05 | 2006-12-05 | |
| EP06125400.9 | 2006-12-05 | ||
| US60/872,892 | 2006-12-05 | ||
| EP06125400 | 2006-12-05 | ||
| PCT/EP2007/063244 WO2008068246A1 (en) | 2006-12-05 | 2007-12-04 | Liquid anti-rabies antibody formulations |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2668947A1 CA2668947A1 (en) | 2008-06-12 |
| CA2668947C true CA2668947C (en) | 2017-02-07 |
Family
ID=39092188
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2668947A Active CA2668947C (en) | 2006-12-05 | 2007-12-04 | Liquid anti-rabies antibody formulations |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US7959922B2 (enExample) |
| EP (1) | EP2088997B1 (enExample) |
| JP (1) | JP5410985B2 (enExample) |
| KR (1) | KR101522036B1 (enExample) |
| CN (1) | CN101557799B (enExample) |
| AU (1) | AU2007328960B2 (enExample) |
| CA (1) | CA2668947C (enExample) |
| CU (1) | CU23795A3 (enExample) |
| EA (1) | EA017549B1 (enExample) |
| IL (1) | IL199004A (enExample) |
| MX (1) | MX2009005414A (enExample) |
| WO (1) | WO2008068246A1 (enExample) |
| ZA (1) | ZA200902772B (enExample) |
Families Citing this family (17)
| 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 |
| PL2314621T3 (pl) * | 2004-05-27 | 2014-08-29 | Crucell Holland Bv | Cząsteczki wiążące zdolne do neutralizowania wirusa wścieklizny i ich zastosowania |
| CA2881717C (en) | 2006-06-06 | 2018-06-12 | Cecilia Anna Wilhelmina Geuijen | Human binding molecules having killing activity against staphylococci and uses thereof |
| CN101557799B (zh) | 2006-12-05 | 2012-08-22 | 克鲁塞尔荷兰公司 | 液体抗狂犬病抗体制剂 |
| 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 |
| WO2011028961A2 (en) | 2009-09-04 | 2011-03-10 | Xoma Technology Ltd. | Anti-botulism antibody coformulations |
| US9089529B2 (en) | 2011-10-25 | 2015-07-28 | Prothena Therapeutics Limited | Antibody formulations and methods |
| US9376491B2 (en) * | 2012-03-07 | 2016-06-28 | Eli Lilly And Company | IL-17 antibody formulation and method of treatment using same |
| UA117466C2 (uk) | 2012-12-13 | 2018-08-10 | Мерк Шарп Енд Доме Корп. | СТАБІЛЬНИЙ СКЛАД У ВИГЛЯДІ РОЗЧИНУ АНТИТІЛА ДО IL-23p19 |
| 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 |
| BR112019022873A8 (pt) | 2017-05-02 | 2023-04-11 | Merck Sharp & Dohme | Formulação, e, vaso ou dispositivo de injeção. |
| 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 |
| CN113316458B (zh) | 2018-11-07 | 2024-08-02 | 默沙东有限责任公司 | 抗lag3抗体和抗pd-1抗体的共制剂 |
| WO2021249542A1 (en) | 2020-06-12 | 2021-12-16 | Nanjing Leads Biolabs Co., Ltd. | Antibodies binding tnfr2 and uses thereof |
| CN119405798A (zh) * | 2022-04-02 | 2025-02-11 | 重庆智翔金泰生物制药股份有限公司 | 一种治疗狂犬病的抗体药物组合物及其制备方法 |
| CN117771365B (zh) * | 2023-12-07 | 2025-07-04 | 兰州生物制品研究所有限责任公司 | 一种抗狂犬病病毒组合单克隆抗体制剂 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE99958T1 (de) | 1989-06-08 | 1994-01-15 | Wistar Inst | Monoklonale antikoerper zur behandlung nach einem kontakt mit tollwutvirus. |
| DE4006630A1 (de) | 1990-03-03 | 1991-09-12 | Behringwerke Ag | Humane monoklonale antikoerper gegen tollwutviren, ihre herstellung und verwendung |
| CA2267139A1 (en) | 1996-10-08 | 1998-04-16 | Ton Logtenberg | 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 |
| NZ531291A (en) | 2001-08-21 | 2006-02-24 | Univ Jefferson | Recombinant anti rabies antibodies MAb JB.1 and Mab 57 and compositions and methods for making and using the same |
| PT2314629E (pt) | 2002-07-18 | 2014-01-22 | Merus B V | Produção recombinante de misturas de anticorpos |
| WO2005023849A2 (en) | 2003-09-04 | 2005-03-17 | Crucell Holland B.V. | Antigenic peptides of rabies virus and uses thereof |
| EP1686137A4 (en) * | 2003-10-09 | 2009-10-28 | Chugai Pharmaceutical Co Ltd | PROCESS FOR STABILIZING PROTEIN SOLUTIONS |
| US20070212346A1 (en) * | 2003-10-09 | 2007-09-13 | Tomoyuki Igawa | Highly Concentrated Stabilized Igm Solution |
| JPWO2005063291A1 (ja) * | 2003-12-25 | 2007-07-19 | 麒麟麦酒株式会社 | 抗体を含有する安定な水性医薬製剤 |
| PL2314621T3 (pl) * | 2004-05-27 | 2014-08-29 | Crucell Holland Bv | Cząsteczki wiążące zdolne do neutralizowania wirusa wścieklizny i ich zastosowania |
| CA2604840A1 (en) * | 2005-04-18 | 2006-10-26 | Xtl Biopharmaceuticals Ltd. | Stabilized anti-hepatitis b (hbv) antibody formulations |
| CN101557799B (zh) | 2006-12-05 | 2012-08-22 | 克鲁塞尔荷兰公司 | 液体抗狂犬病抗体制剂 |
-
2007
- 2007-12-04 CN CN2007800448444A patent/CN101557799B/zh not_active Expired - Fee Related
- 2007-12-04 JP JP2009539730A patent/JP5410985B2/ja not_active Expired - Fee Related
- 2007-12-04 WO PCT/EP2007/063244 patent/WO2008068246A1/en not_active Ceased
- 2007-12-04 AU AU2007328960A patent/AU2007328960B2/en not_active Ceased
- 2007-12-04 EA EA200970533A patent/EA017549B1/ru unknown
- 2007-12-04 CA CA2668947A patent/CA2668947C/en active Active
- 2007-12-04 EP EP07847749.4A patent/EP2088997B1/en active Active
- 2007-12-04 KR KR1020097013012A patent/KR101522036B1/ko not_active Expired - Fee Related
- 2007-12-04 MX MX2009005414A patent/MX2009005414A/es active IP Right Grant
- 2007-12-04 US US12/312,967 patent/US7959922B2/en not_active Expired - Fee Related
-
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 |
|---|---|
| CN101557799B (zh) | 2012-08-22 |
| JP5410985B2 (ja) | 2014-02-05 |
| MX2009005414A (es) | 2009-06-01 |
| CA2668947A1 (en) | 2008-06-12 |
| JP2010511665A (ja) | 2010-04-15 |
| EP2088997B1 (en) | 2016-08-24 |
| EP2088997A1 (en) | 2009-08-19 |
| AU2007328960A1 (en) | 2008-06-12 |
| KR20090089881A (ko) | 2009-08-24 |
| IL199004A0 (en) | 2010-02-17 |
| ZA200902772B (en) | 2012-09-26 |
| CN101557799A (zh) | 2009-10-14 |
| EA200970533A1 (ru) | 2009-10-30 |
| KR101522036B1 (ko) | 2015-05-20 |
| US20100034829A1 (en) | 2010-02-11 |
| CU23795A3 (es) | 2012-03-15 |
| WO2008068246A1 (en) | 2008-06-12 |
| AU2007328960B2 (en) | 2013-01-17 |
| EA017549B1 (ru) | 2013-01-30 |
| US7959922B2 (en) | 2011-06-14 |
| IL199004A (en) | 2015-10-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2668947C (en) | Liquid anti-rabies antibody formulations | |
| AU2022291595B2 (en) | Stable, aqueous antibody formulations | |
| RU2644214C2 (ru) | СТАБИЛЬНЫЕ ПРЕПАРАТЫ СВЯЗЫВАЮЩЕГО СРЕДСТВА НА ОСНОВЕ IgG4 | |
| AU2013334740A1 (en) | Stable, low viscosity antibody formulation | |
| KR102885113B1 (ko) | 항-rsv 항체의 제제 및 그의 사용 방법 | |
| 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 | |
| CN116077646B (zh) | 一种抗冠状病毒s蛋白的抗体制剂及其制备方法和用途 | |
| AU2020325569B2 (en) | Process for preparing a composition comprising a protein D polypeptide | |
| ES2602275T3 (es) | Formulaciones líquidas de anticuerpo anti-rabia | |
| CA3115708C (en) | Formulations of anti-rsv antibodies and methods of use thereof | |
| RU2807524C2 (ru) | Составы антител к rsv и способы их применения | |
| EA043419B1 (ru) | Способ получения лиофилизированного фармацевтического состава на основе терапевтического белка |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |