RU2688349C2 - In vitro прогнозирование времени полужизни антител in vivo - Google Patents
In vitro прогнозирование времени полужизни антител in vivo Download PDFInfo
- Publication number
- RU2688349C2 RU2688349C2 RU2016137932A RU2016137932A RU2688349C2 RU 2688349 C2 RU2688349 C2 RU 2688349C2 RU 2016137932 A RU2016137932 A RU 2016137932A RU 2016137932 A RU2016137932 A RU 2016137932A RU 2688349 C2 RU2688349 C2 RU 2688349C2
- Authority
- RU
- Russia
- Prior art keywords
- antibody
- fcrn
- retention time
- region
- life
- Prior art date
Links
- 238000001727 in vivo Methods 0.000 title claims abstract description 133
- 238000000338 in vitro Methods 0.000 title description 14
- 230000014759 maintenance of location Effects 0.000 claims abstract description 425
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 claims abstract description 390
- 238000000034 method Methods 0.000 claims abstract description 133
- 238000001042 affinity chromatography Methods 0.000 claims abstract description 100
- 238000010828 elution Methods 0.000 claims abstract description 92
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 88
- 239000011780 sodium chloride Substances 0.000 claims abstract description 44
- 230000002829 reductive effect Effects 0.000 claims abstract description 33
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 claims abstract 4
- 150000003839 salts Chemical class 0.000 claims description 145
- 230000035772 mutation Effects 0.000 claims description 56
- 230000003247 decreasing effect Effects 0.000 claims description 4
- 230000000694 effects Effects 0.000 abstract description 22
- 239000000126 substance Substances 0.000 abstract description 15
- 238000002789 length control Methods 0.000 abstract 1
- 235000002639 sodium chloride Nutrition 0.000 description 177
- 230000003993 interaction Effects 0.000 description 139
- 230000027455 binding Effects 0.000 description 131
- 238000009739 binding Methods 0.000 description 130
- 229960002874 briakinumab Drugs 0.000 description 114
- MJZJYWCQPMNPRM-UHFFFAOYSA-N 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1OCCCOC1=CC(Cl)=C(Cl)C=C1Cl MJZJYWCQPMNPRM-UHFFFAOYSA-N 0.000 description 102
- 229960003824 ustekinumab Drugs 0.000 description 101
- 229920001184 polypeptide Polymers 0.000 description 89
- 102000004196 processed proteins & peptides Human genes 0.000 description 89
- 108090000765 processed proteins & peptides Proteins 0.000 description 89
- 125000003275 alpha amino acid group Chemical group 0.000 description 69
- 108010068617 neonatal Fc receptor Proteins 0.000 description 63
- 210000004027 cell Anatomy 0.000 description 46
- 125000000539 amino acid group Chemical group 0.000 description 43
- 238000010494 dissociation reaction Methods 0.000 description 40
- 230000005593 dissociations Effects 0.000 description 40
- 210000002966 serum Anatomy 0.000 description 37
- 108090000623 proteins and genes Proteins 0.000 description 35
- 239000012071 phase Substances 0.000 description 34
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 34
- 238000013456 study Methods 0.000 description 31
- 102000004169 proteins and genes Human genes 0.000 description 29
- 102000013462 Interleukin-12 Human genes 0.000 description 25
- 108010065805 Interleukin-12 Proteins 0.000 description 25
- 239000000427 antigen Substances 0.000 description 25
- 108091007433 antigens Proteins 0.000 description 25
- 102000036639 antigens Human genes 0.000 description 25
- 229940117681 interleukin-12 Drugs 0.000 description 25
- 235000018102 proteins Nutrition 0.000 description 25
- 239000000243 solution Substances 0.000 description 24
- 235000001014 amino acid Nutrition 0.000 description 22
- 241001465754 Metazoa Species 0.000 description 20
- 229940024606 amino acid Drugs 0.000 description 20
- 150000001413 amino acids Chemical class 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 20
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 19
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 19
- 238000000329 molecular dynamics simulation Methods 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- 230000000875 corresponding effect Effects 0.000 description 16
- 230000007423 decrease Effects 0.000 description 16
- 238000009826 distribution Methods 0.000 description 16
- 239000003814 drug Substances 0.000 description 16
- 230000001404 mediated effect Effects 0.000 description 16
- 150000007523 nucleic acids Chemical class 0.000 description 16
- 239000013612 plasmid Substances 0.000 description 16
- 241000699660 Mus musculus Species 0.000 description 15
- 239000000872 buffer Substances 0.000 description 15
- 230000001419 dependent effect Effects 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 239000012149 elution buffer Substances 0.000 description 15
- 230000004927 fusion Effects 0.000 description 15
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 15
- 238000002347 injection Methods 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 108020004707 nucleic acids Proteins 0.000 description 14
- 102000039446 nucleic acids Human genes 0.000 description 14
- 238000011830 transgenic mouse model Methods 0.000 description 14
- 229960000397 bevacizumab Drugs 0.000 description 13
- 239000007790 solid phase Substances 0.000 description 13
- 229920002684 Sepharose Polymers 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 239000012634 fragment Substances 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 238000003776 cleavage reaction Methods 0.000 description 11
- 230000007017 scission Effects 0.000 description 11
- 238000004088 simulation Methods 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 10
- 239000006172 buffering agent Substances 0.000 description 10
- 230000007935 neutral effect Effects 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 9
- 241000282553 Macaca Species 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 8
- 238000004364 calculation method Methods 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 238000002523 gelfiltration Methods 0.000 description 8
- 238000011813 knockout mouse model Methods 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 239000011159 matrix material Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 230000009261 transgenic effect Effects 0.000 description 8
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 7
- 108010090804 Streptavidin Proteins 0.000 description 7
- 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 7
- 239000006167 equilibration buffer Substances 0.000 description 7
- 230000002209 hydrophobic effect Effects 0.000 description 7
- 238000010253 intravenous injection Methods 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 159000000000 sodium salts Chemical class 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- 239000003490 Thiodipropionic acid Substances 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 235000018977 lysine Nutrition 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000004064 recycling Methods 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 5
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 5
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 5
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 5
- 102000013264 Interleukin-23 Human genes 0.000 description 5
- 108010065637 Interleukin-23 Proteins 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- 239000012505 Superdex™ Substances 0.000 description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
- 239000004473 Threonine Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000008030 elimination Effects 0.000 description 5
- 238000003379 elimination reaction Methods 0.000 description 5
- 239000013613 expression plasmid Substances 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 229940124829 interleukin-23 Drugs 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 230000008520 organization Effects 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 239000001103 potassium chloride Substances 0.000 description 5
- 235000011164 potassium chloride Nutrition 0.000 description 5
- 238000005070 sampling Methods 0.000 description 5
- 238000002741 site-directed mutagenesis Methods 0.000 description 5
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 101100022187 Caenorhabditis elegans mab-10 gene Proteins 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 101000913100 Rattus norvegicus IgG receptor FcRn large subunit p51 Proteins 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 210000001163 endosome Anatomy 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
- 239000010931 gold Substances 0.000 description 4
- 229910052737 gold Inorganic materials 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 230000001771 impaired effect Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000006674 lysosomal degradation Effects 0.000 description 4
- 239000011859 microparticle Substances 0.000 description 4
- 230000004962 physiological condition Effects 0.000 description 4
- 239000004331 potassium propionate Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- 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 4
- 235000011083 sodium citrates Nutrition 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 102000009109 Fc receptors Human genes 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000009490 IgG Receptors Human genes 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 3
- 239000012124 Opti-MEM Substances 0.000 description 3
- 108090000526 Papain Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 3
- 235000011130 ammonium sulphate Nutrition 0.000 description 3
- 239000012491 analyte Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000007413 biotinylation Methods 0.000 description 3
- 230000006287 biotinylation Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 239000001201 calcium disodium ethylene diamine tetra-acetate Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000000919 ceramic Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 229940055729 papain Drugs 0.000 description 3
- 235000019834 papain Nutrition 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000008884 pinocytosis Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000001508 potassium citrate Substances 0.000 description 3
- 229960002635 potassium citrate Drugs 0.000 description 3
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 3
- 235000011082 potassium citrates Nutrition 0.000 description 3
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 3
- 229910052939 potassium sulfate Inorganic materials 0.000 description 3
- 235000011151 potassium sulphates Nutrition 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 239000012619 Butyl Sepharose® Substances 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 2
- 108700025474 F 372 Proteins 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 239000001825 Polyoxyethene (8) stearate Substances 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 239000004268 Sodium erythorbin Substances 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 229940120638 avastin Drugs 0.000 description 2
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000005251 capillar electrophoresis Methods 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000012832 cell culture technique Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 2
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000013024 dilution buffer Substances 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000009881 electrostatic interaction Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000028023 exocytosis Effects 0.000 description 2
- 238000013230 female C57BL/6J mice Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 229940065638 intron a Drugs 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
- 210000003734 kidney Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000013227 male C57BL/6J mice Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 2
- 235000019799 monosodium phosphate Nutrition 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 102200067302 rs281865268 Human genes 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 229940071598 stelara Drugs 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000010474 transient expression Effects 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
- 230000002792 vascular Effects 0.000 description 2
- 210000003462 vein Anatomy 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
- XSYUPRQVAHJETO-WPMUBMLPSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidaz Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 XSYUPRQVAHJETO-WPMUBMLPSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 1
- IITIZHOBOIBGBW-UHFFFAOYSA-N 3-ethyl-2h-1,3-benzothiazole Chemical compound C1=CC=C2N(CC)CSC2=C1 IITIZHOBOIBGBW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 239000010755 BS 2869 Class G Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 101100075830 Caenorhabditis elegans mab-5 gene Proteins 0.000 description 1
- 101100313161 Caenorhabditis elegans mab-9 gene Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 description 1
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 1
- 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 1
- 101000913079 Homo sapiens IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 208000029422 Hypernatremia Diseases 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-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
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 240000006240 Linum usitatissimum Species 0.000 description 1
- 235000004431 Linum usitatissimum Nutrition 0.000 description 1
- 239000007987 MES buffer Substances 0.000 description 1
- 239000012515 MabSelect SuRe Substances 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 101000913073 Mus musculus High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- -1 V289 Substances 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 108010004388 beta 2 microglobulin receptor Proteins 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
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000012928 buffer substance Substances 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 238000004422 calculation algorithm Methods 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000005421 electrostatic potential Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000005294 ferromagnetic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 102000047279 human B2M Human genes 0.000 description 1
- 102000055647 human CSF2RB Human genes 0.000 description 1
- 238000011577 humanized mouse model Methods 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000010039 intracellular degradation Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 150000002669 lysines Chemical class 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 102220308874 rs747070258 Human genes 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 125000004436 sodium atom Chemical group 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000000954 titration curve Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 239000001393 triammonium citrate Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/16—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
- B01D15/166—Fluid composition conditioning, e.g. gradient
- B01D15/168—Fluid composition conditioning, e.g. gradient pH gradient or chromatofocusing, i.e. separation according to the isoelectric point pI
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 and B01D15/30 - B01D15/36, e.g. affinity, ligand exchange or chiral chromatography
- B01D15/3804—Affinity chromatography
- B01D15/3809—Affinity chromatography of the antigen-antibody type, e.g. protein A, G or L chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14161103.8 | 2014-03-21 | ||
| EP14161103 | 2014-03-21 | ||
| EP14165987.0 | 2014-04-25 | ||
| EP14165987 | 2014-04-25 | ||
| PCT/EP2015/055482 WO2015140126A1 (en) | 2014-03-21 | 2015-03-17 | In vitro prediction of in vivo half-life of antibodies |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2016137932A RU2016137932A (ru) | 2018-04-23 |
| RU2016137932A3 RU2016137932A3 (enExample) | 2018-10-29 |
| RU2688349C2 true RU2688349C2 (ru) | 2019-05-21 |
Family
ID=52684232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2016137932A RU2688349C2 (ru) | 2014-03-21 | 2015-03-17 | In vitro прогнозирование времени полужизни антител in vivo |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US20170227547A1 (enExample) |
| EP (1) | EP3119490B1 (enExample) |
| JP (2) | JP6744855B2 (enExample) |
| KR (1) | KR20160134687A (enExample) |
| CN (1) | CN106103478B (enExample) |
| BR (1) | BR112016023417A2 (enExample) |
| CA (1) | CA2938722A1 (enExample) |
| MX (1) | MX377315B (enExample) |
| RU (1) | RU2688349C2 (enExample) |
| WO (1) | WO2015140126A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2814587T1 (en) | 2012-02-15 | 2018-08-31 | F. Hoffmann-La Roche Ag | Affinity chromatography based on the Fc receptor |
| DK3042205T3 (da) * | 2013-09-06 | 2020-03-02 | Hoffmann La Roche | Fremgangsmåde til forbedring af antistofstabilitet |
| WO2015140126A1 (en) | 2014-03-21 | 2015-09-24 | F. Hoffmann-La Roche Ag | In vitro prediction of in vivo half-life of antibodies |
| RU2714116C2 (ru) | 2014-11-06 | 2020-02-11 | Ф. Хоффманн-Ля Рош Аг | ВАРИАНТЫ Fc-ОБЛАСТИ С МОДИФИЦИРОВАННЫМ СВЯЗЫВАНИЕМ FcRn И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| CN106957364B (zh) * | 2016-01-11 | 2021-03-16 | 上海交通大学 | 一种单克隆抗体FnAb12及其应用 |
| CN106957365B (zh) * | 2016-01-11 | 2021-03-16 | 上海交通大学 | 一种单克隆抗体FnAb8及其应用 |
| EP3615678B1 (en) | 2017-04-28 | 2024-07-31 | F. Hoffmann-La Roche AG | Antibody selection method |
| US12172106B2 (en) | 2018-08-09 | 2024-12-24 | Regeneron Pharmaceuticals, Inc. | Methods for assessing binding affinity of an antibody variant to the neonatal Fc receptor |
| CN112955468B (zh) | 2018-10-01 | 2024-08-09 | 豪夫迈·罗氏有限公司 | 包含抗fap克隆212的双特异性抗原结合分子 |
| JP2022511396A (ja) | 2018-10-01 | 2022-01-31 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | Cd40への三価結合を伴う二重特異性抗原結合分子 |
| WO2020084032A1 (en) | 2018-10-25 | 2020-04-30 | F. Hoffmann-La Roche Ag | Modification of antibody fcrn binding |
| CN113227134A (zh) * | 2018-12-05 | 2021-08-06 | 株式会社梅花治疗 | 抗体的Fc区变体 |
| EP3903102B1 (en) | 2018-12-30 | 2023-04-12 | F. Hoffmann-La Roche AG | Ph-gradient spr-based binding assay |
| AR121706A1 (es) | 2020-04-01 | 2022-06-29 | Hoffmann La Roche | Moléculas de unión a antígeno biespecíficas dirigidas a ox40 y fap |
| JP2023521371A (ja) * | 2020-04-08 | 2023-05-24 | エフ. ホフマン-ラ ロシュ アーゲー | 高分子の非特異的クリアランスアッセイ方法 |
| JP7322858B2 (ja) * | 2020-11-02 | 2023-08-08 | 株式会社三洋物産 | 遊技機 |
| JP7322857B2 (ja) * | 2020-11-02 | 2023-08-08 | 株式会社三洋物産 | 遊技機 |
| CN113308476B (zh) * | 2021-05-12 | 2022-06-28 | 广东药康生物科技有限公司 | 一种FcRn基因人源化动物模型的构建方法 |
| WO2022244838A1 (ja) * | 2021-05-19 | 2022-11-24 | 中外製薬株式会社 | 分子のin vivo薬物動態を予測する方法 |
| WO2025090910A2 (en) * | 2023-10-25 | 2025-05-01 | Multiverse Pharma Inc. | Antigen binding molecules targeting il-12 and il-23 |
| US20250332526A1 (en) * | 2024-04-26 | 2025-10-30 | Waters Technologies Corporation | Direct affinity to size-exclusion chromatography methods and systems thereof |
Family Cites Families (126)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4737456A (en) | 1985-05-09 | 1988-04-12 | Syntex (U.S.A.) Inc. | Reducing interference in ligand-receptor binding assays |
| US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
| US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
| IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| US5770701A (en) | 1987-10-30 | 1998-06-23 | American Cyanamid Company | Process for preparing targeted forms of methyltrithio antitumor agents |
| US5606040A (en) | 1987-10-30 | 1997-02-25 | American Cyanamid Company | Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group |
| DE68913658T3 (de) | 1988-11-11 | 2005-07-21 | Stratagene, La Jolla | Klonierung von Immunglobulin Sequenzen aus den variablen Domänen |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| CA2026147C (en) | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| US5959177A (en) | 1989-10-27 | 1999-09-28 | The Scripps Research Institute | Transgenic plants expressing assembled secretory antibodies |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| ATE164395T1 (de) | 1990-12-03 | 1998-04-15 | Genentech Inc | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
| US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
| WO1992022653A1 (en) | 1991-06-14 | 1992-12-23 | Genentech, Inc. | Method for making humanized antibodies |
| GB9114948D0 (en) | 1991-07-11 | 1991-08-28 | Pfizer Ltd | Process for preparing sertraline intermediates |
| IE922437A1 (en) | 1991-07-25 | 1993-01-27 | Idec Pharma Corp | Recombinant antibodies for human therapy |
| JP3951062B2 (ja) | 1991-09-19 | 2007-08-01 | ジェネンテック・インコーポレーテッド | 少なくとも遊離のチオールとして存在するシステインを有する抗体フラグメントの大腸菌での発現、2官能性F(ab’)2抗体の産生のための使用 |
| FI941572A7 (fi) | 1991-10-07 | 1994-05-27 | Oncologix Inc | Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenete lmä |
| WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
| ATE503496T1 (de) | 1992-02-06 | 2011-04-15 | Novartis Vaccines & Diagnostic | Biosynthetisches bindeprotein für tumormarker |
| NZ258392A (en) | 1992-11-13 | 1997-09-22 | Idec Pharma Corp | Chimeric and radiolabelled antibodies to the b lymphocyte cellsurface antigen bp35 (cd-20) and their use in the treatment of b cell lymphona |
| US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
| US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
| WO1994029351A2 (en) | 1993-06-16 | 1994-12-22 | Celltech Limited | Antibodies |
| US5429746A (en) | 1994-02-22 | 1995-07-04 | Smith Kline Beecham Corporation | Antibody purification |
| US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
| US5610285A (en) | 1994-08-24 | 1997-03-11 | Bayer Corporation | Purification of α-1 proteinase inhibitor using novel chromatographic separation conditions |
| US5789199A (en) | 1994-11-03 | 1998-08-04 | Genentech, Inc. | Process for bacterial production of polypeptides |
| US5840523A (en) | 1995-03-01 | 1998-11-24 | Genetech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| IL118069A (en) | 1995-05-02 | 2000-06-01 | Japan Tobacco Inc | Monoclonal antibody reactive to human CETP and assay method for human CETP |
| US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
| US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
| US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| GB9603256D0 (en) | 1996-02-16 | 1996-04-17 | Wellcome Found | Antibodies |
| US6451308B1 (en) | 1996-04-26 | 2002-09-17 | Beth Israel Deaconess Medical Center | Antagonists of interleukin-15 |
| US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
| PT994903E (pt) | 1997-06-24 | 2005-10-31 | Genentech Inc | Metodos e composicoes para glicoproteinas galactosiladas |
| US6040498A (en) | 1998-08-11 | 2000-03-21 | North Caroline State University | Genetically engineered duckweed |
| WO1999022764A1 (en) | 1997-10-31 | 1999-05-14 | Genentech, Inc. | Methods and compositions comprising glycoprotein glycoforms |
| US6610833B1 (en) | 1997-11-24 | 2003-08-26 | The Institute For Human Genetics And Biochemistry | Monoclonal human natural antibodies |
| BR9813365A (pt) | 1997-12-05 | 2004-06-15 | Scripps Research Inst | Método para produção e humanização de um anticorpo monoclonal de rato |
| ES2292236T3 (es) | 1998-04-02 | 2008-03-01 | Genentech, Inc. | Variantes de anticuerpos y sus fragmentos. |
| US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| US20030175884A1 (en) | 2001-08-03 | 2003-09-18 | Pablo Umana | Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity |
| DE69942021D1 (de) | 1998-04-20 | 2010-04-01 | Glycart Biotechnology Ag | Glykosylierungs-engineering von antikörpern zur verbesserung der antikörperabhängigen zellvermittelten zytotoxizität |
| JP4469933B2 (ja) | 1998-05-06 | 2010-06-02 | ジェネンテック, インコーポレイテッド | イオン交換クロマトグラフィによるタンパク質精製 |
| US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| PT1914244E (pt) | 1999-04-09 | 2013-07-26 | Kyowa Hakko Kirin Co Ltd | Processo para regular a actividade de moléculas funcionais sob o ponto de vista imunológico |
| AU782626B2 (en) | 1999-10-04 | 2005-08-18 | Medicago Inc. | Method for regulating transcription of foreign genes |
| US7125978B1 (en) | 1999-10-04 | 2006-10-24 | Medicago Inc. | Promoter for regulating expression of foreign genes |
| EP1229125A4 (en) | 1999-10-19 | 2005-06-01 | Kyowa Hakko Kogyo Kk | PROCESS FOR PREPARING A POLYPEPTIDE |
| EP1240319A1 (en) | 1999-12-15 | 2002-09-18 | Genentech, Inc. | Shotgun scanning, a combinatorial method for mapping functional protein epitopes |
| WO2001049698A1 (en) | 1999-12-29 | 2001-07-12 | Immunogen, Inc. | Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use |
| HUP0300369A2 (hu) | 2000-04-11 | 2003-06-28 | Genentech, Inc. | Többértékű antitestek és alkalmazásuk |
| US7064191B2 (en) | 2000-10-06 | 2006-06-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for purifying antibody |
| US6946292B2 (en) | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
| AU1344102A (en) | 2000-10-12 | 2002-04-22 | Genentech Inc | Reduced-viscosity concentrated protein formulations |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| DE60131456T2 (de) | 2000-11-30 | 2008-07-10 | Medarex, Inc., Milpitas | Transchromosomale transgen-nagetiere zur herstellung von humanen antikörpern |
| ES2184594B1 (es) | 2001-01-17 | 2004-01-01 | Probitas Pharma Sa | Procedimiento para la produccion de gammaglobulina g humana inactivada de virus. |
| CN1294148C (zh) | 2001-04-11 | 2007-01-10 | 中国科学院遗传与发育生物学研究所 | 环状单链三特异抗体 |
| BR0213761A (pt) | 2001-10-25 | 2005-04-12 | Genentech Inc | Composições, preparação farmacêutica, artigo industrializado, método de tratamento de mamìferos, célula hospedeira, método para a produção de uma glicoproteìna e uso da composição |
| US20040093621A1 (en) | 2001-12-25 | 2004-05-13 | Kyowa Hakko Kogyo Co., Ltd | Antibody composition which specifically binds to CD20 |
| JPWO2003084569A1 (ja) | 2002-04-09 | 2005-08-11 | 協和醗酵工業株式会社 | 抗体組成物含有医薬 |
| US20050031613A1 (en) | 2002-04-09 | 2005-02-10 | Kazuyasu Nakamura | Therapeutic agent for patients having human FcgammaRIIIa |
| WO2003085102A1 (en) | 2002-04-09 | 2003-10-16 | Kyowa Hakko Kogyo Co., Ltd. | Cell with depression or deletion of the activity of protein participating in gdp-fucose transport |
| WO2003085107A1 (en) | 2002-04-09 | 2003-10-16 | Kyowa Hakko Kogyo Co., Ltd. | Cells with modified genome |
| AU2003236018A1 (en) | 2002-04-09 | 2003-10-20 | Kyowa Hakko Kirin Co., Ltd. | METHOD OF ENHANCING ACTIVITY OF ANTIBODY COMPOSITION OF BINDING TO FcGamma RECEPTOR IIIa |
| US20040132140A1 (en) | 2002-04-09 | 2004-07-08 | Kyowa Hakko Kogyo Co., Ltd. | Production process for antibody composition |
| JP4753578B2 (ja) | 2002-06-03 | 2011-08-24 | ジェネンテック, インコーポレイテッド | 合成抗体ファージライブラリー |
| US7361740B2 (en) | 2002-10-15 | 2008-04-22 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
| BRPI0316779B1 (pt) | 2002-12-16 | 2020-04-28 | Genentech Inc | anticorpo humanizado que liga cd20 humano, composição, artigo manufaturado, método de indução da apoptose, método de tratamento de câncer cd20 positivo, métodos de tratamento de doenças autoimunes, ácidos nucléicos isolados, vetores de expressão, células hospedeiras, método para a produção de um anticorpo 2h7 humanizado, polipeptídeo isolado, formulação líquida, método de tratamento de artrite reumatóide (ra) e anticorpos de ligação de cd20 humanizados |
| WO2004065416A2 (en) | 2003-01-16 | 2004-08-05 | Genentech, Inc. | Synthetic antibody phage libraries |
| US20060104968A1 (en) | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
| US7871607B2 (en) | 2003-03-05 | 2011-01-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases |
| JPWO2005035586A1 (ja) | 2003-10-08 | 2007-11-22 | 協和醗酵工業株式会社 | 融合蛋白質組成物 |
| US20070134759A1 (en) | 2003-10-09 | 2007-06-14 | Harue Nishiya | Process for producing antibody composition by using rna inhibiting the function of alpha1,6-fucosyltransferase |
| DE602004026470D1 (de) | 2003-11-05 | 2010-05-20 | Roche Glycart Ag | Fc-rezeptor und effektorfunktion |
| CN103394083B (zh) | 2003-11-06 | 2017-07-18 | 西雅图基因公司 | 能够与配体偶联的单甲基缬氨酸化合物 |
| EP2385069A3 (en) * | 2003-11-12 | 2012-05-30 | Biogen Idec MA Inc. | Neonatal Fc rReceptor (FcRn)- binding polypeptide variants, dimeric Fc binding proteins and methods related thereto |
| WO2005053742A1 (ja) | 2003-12-04 | 2005-06-16 | Kyowa Hakko Kogyo Co., Ltd. | 抗体組成物を含有する医薬 |
| SE0400501D0 (sv) | 2004-02-27 | 2004-02-27 | Amersham Biosciences Ab | Antibody purification |
| ZA200608130B (en) | 2004-03-31 | 2008-12-31 | Genentech Inc | Humanized anti-TGF-beta antibodies |
| US7785903B2 (en) | 2004-04-09 | 2010-08-31 | Genentech, Inc. | Variable domain library and uses |
| TWI380996B (zh) | 2004-09-17 | 2013-01-01 | Hoffmann La Roche | 抗ox40l抗體 |
| SI1791565T1 (sl) | 2004-09-23 | 2016-08-31 | Genentech, Inc. | Cisteinsko konstruirana protitelesa in konjugati |
| JO3000B1 (ar) | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
| TWI320788B (en) | 2005-05-25 | 2010-02-21 | Hoffmann La Roche | Method for the purification of antibodies |
| US8679490B2 (en) | 2005-11-07 | 2014-03-25 | Genentech, Inc. | Binding polypeptides with diversified and consensus VH/VL hypervariable sequences |
| US20070237764A1 (en) | 2005-12-02 | 2007-10-11 | Genentech, Inc. | Binding polypeptides with restricted diversity sequences |
| US7662930B2 (en) | 2005-12-06 | 2010-02-16 | Amgen Inc. | Polishing steps used in multi-step protein purification processes |
| CA2651567A1 (en) | 2006-05-09 | 2007-11-22 | Genentech, Inc. | Binding polypeptides with optimized scaffolds |
| PL2059533T3 (pl) | 2006-08-30 | 2013-04-30 | Genentech Inc | Przeciwciała wieloswoiste |
| US20080226635A1 (en) | 2006-12-22 | 2008-09-18 | Hans Koll | Antibodies against insulin-like growth factor I receptor and uses thereof |
| US20080167450A1 (en) | 2007-01-05 | 2008-07-10 | Hai Pan | Methods of purifying proteins |
| US7691980B2 (en) | 2007-01-09 | 2010-04-06 | Bio-Rad Laboratories, Inc. | Enhanced capacity and purification of antibodies by mixed mode chromatography in the presence of aqueous-soluble nonionic organic polymers |
| JP5522723B2 (ja) | 2007-05-21 | 2014-06-18 | ノマディックバイオサイエンス株式会社 | 新規ポリペプチド,アフィニティークロマトグラフィー用材,及びイムノグロブリンの分離及び/又は精製方法 |
| CN100592373C (zh) | 2007-05-25 | 2010-02-24 | 群康科技(深圳)有限公司 | 液晶显示面板驱动装置及其驱动方法 |
| CN101679509A (zh) | 2007-06-01 | 2010-03-24 | 弗·哈夫曼-拉罗切有限公司 | 免疫球蛋白纯化 |
| BRPI0817294A2 (pt) | 2007-09-26 | 2015-03-17 | Chugai Pharmaceutical Co Ltd | Método de modificação do ponto isoelétrico de anticorpo via substituição de aminoácido em cdr. |
| US8227577B2 (en) | 2007-12-21 | 2012-07-24 | Hoffman-La Roche Inc. | Bivalent, bispecific antibodies |
| US8242247B2 (en) | 2007-12-21 | 2012-08-14 | Hoffmann-La Roche Inc. | Bivalent, bispecific antibodies |
| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| US20100069617A1 (en) | 2008-09-12 | 2010-03-18 | Ge Healthcare Bio-Sciences Ab | Enhanced protein aggregate removal by mixed mode chromatography on hydrophobic interaction media in the presence of protein-excluded zwitterions |
| JP5913980B2 (ja) | 2008-10-14 | 2016-05-11 | ジェネンテック, インコーポレイテッド | 免疫グロブリン変異体及びその用途 |
| SG175004A1 (en) | 2009-04-02 | 2011-11-28 | Roche Glycart Ag | Multispecific antibodies comprising full length antibodies and single chain fab fragments |
| DK2417156T3 (en) | 2009-04-07 | 2015-03-02 | Roche Glycart Ag | Trivalent, bispecific antibodies |
| AU2010252284A1 (en) | 2009-05-27 | 2011-11-17 | F. Hoffmann-La Roche Ag | Tri- or tetraspecific antibodies |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| US8703132B2 (en) | 2009-06-18 | 2014-04-22 | Hoffmann-La Roche, Inc. | Bispecific, tetravalent antigen binding proteins |
| BR112012020964B8 (pt) | 2010-03-10 | 2021-08-24 | Hoffmann La Roche | método para produzir uma imunoglobulina da subclasse igg1 ou igg4 |
| TWI667346B (zh) | 2010-03-30 | 2019-08-01 | 中外製藥股份有限公司 | 促進抗原消失之具有經修飾的FcRn親和力之抗體 |
| SG10201605397PA (en) | 2011-07-01 | 2016-08-30 | Hoffmann La Roche | Method For Separation Of Monomeric Polypeptides From Aggregated Polypeptides |
| KR101862402B1 (ko) * | 2011-12-06 | 2018-05-30 | 삼성전기주식회사 | 도체 패턴 및 이를 포함하는 코일 부품 |
| SI2814587T1 (en) * | 2012-02-15 | 2018-08-31 | F. Hoffmann-La Roche Ag | Affinity chromatography based on the Fc receptor |
| RS62509B1 (sr) | 2012-07-13 | 2021-11-30 | Roche Glycart Ag | Bispecifična anti-vegf/anti-ang-2 antitela i njihova upotreba u lečenju očnih vaskularnih bolesti |
| WO2015140126A1 (en) | 2014-03-21 | 2015-09-24 | F. Hoffmann-La Roche Ag | In vitro prediction of in vivo half-life of antibodies |
| JP6832709B2 (ja) | 2014-05-16 | 2021-02-24 | メディミューン,エルエルシー | 新生児Fc受容体結合が改変されて治療および診断特性が強化された分子 |
| RU2714116C2 (ru) | 2014-11-06 | 2020-02-11 | Ф. Хоффманн-Ля Рош Аг | ВАРИАНТЫ Fc-ОБЛАСТИ С МОДИФИЦИРОВАННЫМ СВЯЗЫВАНИЕМ FcRn И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
-
2015
- 2015-03-17 WO PCT/EP2015/055482 patent/WO2015140126A1/en not_active Ceased
- 2015-03-17 JP JP2017500408A patent/JP6744855B2/ja active Active
- 2015-03-17 RU RU2016137932A patent/RU2688349C2/ru active
- 2015-03-17 KR KR1020167025760A patent/KR20160134687A/ko not_active Ceased
- 2015-03-17 BR BR112016023417-0A patent/BR112016023417A2/pt not_active Application Discontinuation
- 2015-03-17 MX MX2016011982A patent/MX377315B/es active IP Right Grant
- 2015-03-17 CN CN201580015172.9A patent/CN106103478B/zh active Active
- 2015-03-17 EP EP15710178.3A patent/EP3119490B1/en active Active
- 2015-03-17 CA CA2938722A patent/CA2938722A1/en not_active Abandoned
-
2016
- 2016-09-20 US US15/271,091 patent/US20170227547A1/en not_active Abandoned
-
2020
- 2020-07-31 JP JP2020129979A patent/JP7032490B2/ja active Active
-
2021
- 2021-01-26 US US17/158,431 patent/US12461109B2/en active Active
Non-Patent Citations (2)
| Title |
|---|
| WO 2013/120929 Al от 22.08.2013 (F. HOFFMANN-LA ROCHE AG). Козлов И. Г. Моноклональные антитела новая эра в фармакологии и терапии //Лечебное дело. - 2006. - n. 1. * |
| Козлов И. Г. Моноклональные антитела новая эра в фармакологии и терапии //Лечебное дело. - 2006. - n. 1. * |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2016137932A (ru) | 2018-04-23 |
| EP3119490A1 (en) | 2017-01-25 |
| WO2015140126A1 (en) | 2015-09-24 |
| MX377315B (es) | 2025-03-07 |
| US12461109B2 (en) | 2025-11-04 |
| JP2020183967A (ja) | 2020-11-12 |
| JP2017517745A (ja) | 2017-06-29 |
| KR20160134687A (ko) | 2016-11-23 |
| JP6744855B2 (ja) | 2020-08-19 |
| US20210190795A1 (en) | 2021-06-24 |
| BR112016023417A2 (pt) | 2019-04-16 |
| MX2016011982A (es) | 2016-12-09 |
| US20170227547A1 (en) | 2017-08-10 |
| CN106103478A (zh) | 2016-11-09 |
| CA2938722A1 (en) | 2015-09-24 |
| CN106103478B (zh) | 2020-04-03 |
| JP7032490B2 (ja) | 2022-03-08 |
| RU2016137932A3 (enExample) | 2018-10-29 |
| EP3119490B1 (en) | 2021-09-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2688349C2 (ru) | In vitro прогнозирование времени полужизни антител in vivo | |
| US12487245B2 (en) | Antibody selection method | |
| ES2676031T3 (es) | Cromatografía de afinidad basada en el receptor Fc | |
| KR102636726B1 (ko) | 향상된 il-6 항체 | |
| JP2025098167A (ja) | Fcrnアンタゴニストで抗体媒介性障害を処置する方法 | |
| US20230194547A1 (en) | Large molecule unspecific clearance assay | |
| JP7622134B2 (ja) | 抗体FcRn結合の改変 | |
| HK1230632B (zh) | 抗体体内半寿期的体外预测 | |
| HK1230632A1 (zh) | 抗体体内半寿期的体外预测 | |
| HK40055912B (en) | Modification of antibody fcrn binding | |
| HK40055912A (en) | Modification of antibody fcrn binding | |
| HK40017956B (zh) | 抗体选择方法 | |
| HK40017956A (en) | Antibody selection method | |
| HK40031063B (zh) | 具有降低的生物活性的抗体变体和同种型 |