JP5091476B2 - 均質な抗体溶液の生成のための疎水性相互作用クロマトグラフィーまたはヒンジ領域改変の使用 - Google Patents
均質な抗体溶液の生成のための疎水性相互作用クロマトグラフィーまたはヒンジ領域改変の使用 Download PDFInfo
- Publication number
- JP5091476B2 JP5091476B2 JP2006517784A JP2006517784A JP5091476B2 JP 5091476 B2 JP5091476 B2 JP 5091476B2 JP 2006517784 A JP2006517784 A JP 2006517784A JP 2006517784 A JP2006517784 A JP 2006517784A JP 5091476 B2 JP5091476 B2 JP 5091476B2
- Authority
- JP
- Japan
- Prior art keywords
- polypeptide
- seq
- antibody
- domain
- amino acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000004191 hydrophobic interaction chromatography Methods 0.000 title description 45
- 230000004048 modification Effects 0.000 title description 13
- 238000012986 modification Methods 0.000 title description 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 591
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 466
- 229920001184 polypeptide Polymers 0.000 claims description 448
- 230000027455 binding Effects 0.000 claims description 262
- 238000000034 method Methods 0.000 claims description 122
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 120
- 239000000427 antigen Substances 0.000 claims description 103
- 108091007433 antigens Proteins 0.000 claims description 102
- 102000036639 antigens Human genes 0.000 claims description 102
- 239000000539 dimer Substances 0.000 claims description 95
- 206010028980 Neoplasm Diseases 0.000 claims description 82
- 239000000203 mixture Substances 0.000 claims description 76
- 108010075254 C-Peptide Proteins 0.000 claims description 71
- 239000003446 ligand Substances 0.000 claims description 56
- 102000005962 receptors Human genes 0.000 claims description 49
- 108020003175 receptors Proteins 0.000 claims description 49
- 238000011282 treatment Methods 0.000 claims description 44
- 239000003814 drug Substances 0.000 claims description 40
- 150000007523 nucleic acids Chemical class 0.000 claims description 39
- 108020004707 nucleic acids Proteins 0.000 claims description 37
- 102000039446 nucleic acids Human genes 0.000 claims description 37
- 239000002773 nucleotide Substances 0.000 claims description 33
- 125000003729 nucleotide group Chemical group 0.000 claims description 33
- 230000001965 increasing effect Effects 0.000 claims description 28
- 238000004519 manufacturing process Methods 0.000 claims description 25
- 230000015572 biosynthetic process Effects 0.000 claims description 22
- 201000011510 cancer Diseases 0.000 claims description 21
- 208000027866 inflammatory disease Diseases 0.000 claims description 17
- 230000008901 benefit Effects 0.000 claims description 14
- 238000003786 synthesis reaction Methods 0.000 claims description 12
- 208000023275 Autoimmune disease Diseases 0.000 claims description 11
- 206010025323 Lymphomas Diseases 0.000 claims description 11
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 10
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 10
- 108010008212 Integrin alpha4beta1 Proteins 0.000 claims description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 277
- 210000004027 cell Anatomy 0.000 description 115
- 108090000623 proteins and genes Proteins 0.000 description 80
- 108010029485 Protein Isoforms Proteins 0.000 description 64
- 102000001708 Protein Isoforms Human genes 0.000 description 64
- 235000001014 amino acid Nutrition 0.000 description 63
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 53
- 102000004169 proteins and genes Human genes 0.000 description 52
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 47
- 235000018102 proteins Nutrition 0.000 description 47
- 108060003951 Immunoglobulin Proteins 0.000 description 44
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 44
- 102000018358 immunoglobulin Human genes 0.000 description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 42
- 239000000243 solution Substances 0.000 description 40
- 229940024606 amino acid Drugs 0.000 description 37
- 150000001413 amino acids Chemical class 0.000 description 36
- 238000000746 purification Methods 0.000 description 36
- 108020001507 fusion proteins Proteins 0.000 description 33
- 102000037865 fusion proteins Human genes 0.000 description 33
- 238000006467 substitution reaction Methods 0.000 description 33
- 108020004414 DNA Proteins 0.000 description 30
- 239000012634 fragment Substances 0.000 description 28
- 229940079593 drug Drugs 0.000 description 27
- 241000699666 Mus <mouse, genus> Species 0.000 description 26
- 239000000463 material Substances 0.000 description 24
- 239000000523 sample Substances 0.000 description 24
- 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 23
- 230000002829 reductive effect Effects 0.000 description 23
- 229940127089 cytotoxic agent Drugs 0.000 description 22
- 208000035475 disorder Diseases 0.000 description 22
- 230000003993 interaction Effects 0.000 description 22
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 22
- 201000010099 disease Diseases 0.000 description 20
- 239000000178 monomer Substances 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 20
- 210000001519 tissue Anatomy 0.000 description 20
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 19
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 19
- 235000011130 ammonium sulphate Nutrition 0.000 description 19
- 231100000599 cytotoxic agent Toxicity 0.000 description 19
- 238000012217 deletion Methods 0.000 description 19
- 230000037430 deletion Effects 0.000 description 19
- 239000002246 antineoplastic agent Substances 0.000 description 18
- 239000000872 buffer Substances 0.000 description 18
- 239000000651 prodrug Substances 0.000 description 18
- 229940002612 prodrug Drugs 0.000 description 18
- 230000001225 therapeutic effect Effects 0.000 description 18
- 239000013598 vector Substances 0.000 description 18
- 239000000499 gel Substances 0.000 description 17
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 17
- 150000003839 salts Chemical class 0.000 description 17
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 16
- 125000000539 amino acid group Chemical group 0.000 description 16
- 239000002738 chelating agent Substances 0.000 description 16
- 239000002619 cytotoxin Substances 0.000 description 16
- 230000002209 hydrophobic effect Effects 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 238000007792 addition Methods 0.000 description 15
- 238000000926 separation method Methods 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 108091028043 Nucleic acid sequence Proteins 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 210000004881 tumor cell Anatomy 0.000 description 13
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 230000001154 acute effect Effects 0.000 description 12
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 12
- 210000004408 hybridoma Anatomy 0.000 description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 230000004927 fusion Effects 0.000 description 11
- 238000002372 labelling Methods 0.000 description 11
- 239000013612 plasmid Substances 0.000 description 11
- 229920000642 polymer Polymers 0.000 description 11
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 11
- 229960004618 prednisone Drugs 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 238000001542 size-exclusion chromatography Methods 0.000 description 11
- 239000001488 sodium phosphate Substances 0.000 description 11
- 229910000162 sodium phosphate Inorganic materials 0.000 description 11
- 238000003860 storage Methods 0.000 description 11
- -1 sulfoethyl Chemical group 0.000 description 11
- 208000011580 syndromic disease Diseases 0.000 description 11
- 231100000765 toxin Toxicity 0.000 description 11
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000002512 chemotherapy Methods 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 101150047061 tag-72 gene Proteins 0.000 description 10
- 108010006654 Bleomycin Proteins 0.000 description 9
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 9
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 9
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 9
- 101710120037 Toxin CcdB Proteins 0.000 description 9
- 229960001561 bleomycin Drugs 0.000 description 9
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 9
- 210000001185 bone marrow Anatomy 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 230000000295 complement effect Effects 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 235000018417 cysteine Nutrition 0.000 description 9
- 231100000433 cytotoxic Toxicity 0.000 description 9
- 230000001472 cytotoxic effect Effects 0.000 description 9
- 229960005420 etoposide Drugs 0.000 description 9
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 210000004698 lymphocyte Anatomy 0.000 description 9
- 229960000485 methotrexate Drugs 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 8
- 101710112752 Cytotoxin Proteins 0.000 description 8
- 108010087819 Fc receptors Proteins 0.000 description 8
- 102000009109 Fc receptors Human genes 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 241001529936 Murinae Species 0.000 description 8
- 230000001363 autoimmune Effects 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 8
- 238000010828 elution Methods 0.000 description 8
- 229960003180 glutathione Drugs 0.000 description 8
- 230000002163 immunogen Effects 0.000 description 8
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 8
- 229960000624 procarbazine Drugs 0.000 description 8
- 230000000069 prophylactic effect Effects 0.000 description 8
- 230000005855 radiation Effects 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 239000003053 toxin Substances 0.000 description 8
- 108700012359 toxins Proteins 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 101001018085 Lysobacter enzymogenes Lysyl endopeptidase Proteins 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 238000003384 imaging method Methods 0.000 description 7
- 229940072221 immunoglobulins Drugs 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 230000003211 malignant effect Effects 0.000 description 7
- 230000001613 neoplastic effect Effects 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 7
- 230000036961 partial effect Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 241000699670 Mus sp. Species 0.000 description 6
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical group OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 6
- 229920002684 Sepharose Polymers 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 6
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- 229960004679 doxorubicin Drugs 0.000 description 6
- 239000012636 effector Substances 0.000 description 6
- 238000001962 electrophoresis Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000005847 immunogenicity Effects 0.000 description 6
- 230000016784 immunoglobulin production Effects 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 230000004807 localization Effects 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000000813 microbial effect Effects 0.000 description 6
- 210000005170 neoplastic cell Anatomy 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 238000001959 radiotherapy Methods 0.000 description 6
- 229960004641 rituximab Drugs 0.000 description 6
- 102200106299 rs1057519982 Human genes 0.000 description 6
- 239000002002 slurry Substances 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 229960003048 vinblastine Drugs 0.000 description 6
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 6
- 229960004528 vincristine Drugs 0.000 description 6
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 6
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 6
- 229920000936 Agarose Polymers 0.000 description 5
- 206010065553 Bone marrow failure Diseases 0.000 description 5
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 5
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 230000005526 G1 to G0 transition Effects 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
- 102100029268 Neurotrophin-3 Human genes 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 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
- 108090000631 Trypsin Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 238000002648 combination therapy Methods 0.000 description 5
- 239000010949 copper Substances 0.000 description 5
- 229960004397 cyclophosphamide Drugs 0.000 description 5
- 229960000684 cytarabine Drugs 0.000 description 5
- 239000000824 cytostatic agent Substances 0.000 description 5
- 239000002254 cytotoxic agent Substances 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- 230000029087 digestion Effects 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 239000000710 homodimer Substances 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 238000004255 ion exchange chromatography Methods 0.000 description 5
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 5
- 229960000310 isoleucine Drugs 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- 125000006850 spacer group Chemical group 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- 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 4
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 102000006395 Globulins Human genes 0.000 description 4
- 108010044091 Globulins Proteins 0.000 description 4
- 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 4
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
- 108010025020 Nerve Growth Factor Proteins 0.000 description 4
- 108090000099 Neurotrophin-4 Proteins 0.000 description 4
- 241000721454 Pemphigus Species 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- 108020004682 Single-Stranded DNA Proteins 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 238000009098 adjuvant therapy Methods 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 230000001588 bifunctional effect Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000003196 chaotropic effect Effects 0.000 description 4
- 108010057085 cytokine receptors Proteins 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000006471 dimerization reaction Methods 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 239000003797 essential amino acid Substances 0.000 description 4
- 235000020776 essential amino acid Nutrition 0.000 description 4
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 4
- 235000008191 folinic acid Nutrition 0.000 description 4
- 239000011672 folinic acid Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 4
- 229960001101 ifosfamide Drugs 0.000 description 4
- 208000026278 immune system disease Diseases 0.000 description 4
- 238000003018 immunoassay Methods 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 229960001691 leucovorin Drugs 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- 238000003127 radioimmunoassay Methods 0.000 description 4
- 230000000306 recurrent effect Effects 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000003950 B-cell lymphoma Diseases 0.000 description 3
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 3
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 3
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- 102000019034 Chemokines Human genes 0.000 description 3
- 241000699802 Cricetulus griseus Species 0.000 description 3
- 238000001712 DNA sequencing Methods 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 3
- 108010024636 Glutathione Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000009465 Growth Factor Receptors Human genes 0.000 description 3
- 108010009202 Growth Factor Receptors Proteins 0.000 description 3
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 3
- 108010000521 Human Growth Hormone Proteins 0.000 description 3
- 102000002265 Human Growth Hormone Human genes 0.000 description 3
- 239000000854 Human Growth Hormone Substances 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 208000011200 Kawasaki disease Diseases 0.000 description 3
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 3
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 3
- 108090000742 Neurotrophin 3 Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 108010030544 Peptidyl-Lys metalloendopeptidase Proteins 0.000 description 3
- 229920005654 Sephadex Polymers 0.000 description 3
- 239000012507 Sephadex™ Substances 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000003114 blood coagulation factor Substances 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 239000004327 boric acid Substances 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 3
- 229960004630 chlorambucil Drugs 0.000 description 3
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 3
- 238000011210 chromatographic step Methods 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000012875 competitive assay Methods 0.000 description 3
- 230000009137 competitive binding Effects 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000011109 contamination Methods 0.000 description 3
- 239000005289 controlled pore glass Substances 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 102000003675 cytokine receptors Human genes 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 108010033706 glycylserine Proteins 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 229940127121 immunoconjugate Drugs 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 229940047122 interleukins Drugs 0.000 description 3
- 238000001361 intraarterial administration Methods 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 230000005865 ionizing radiation Effects 0.000 description 3
- 238000010829 isocratic elution Methods 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 229960002247 lomustine Drugs 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 3
- 229960004961 mechlorethamine Drugs 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 230000009826 neoplastic cell growth Effects 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 229960003330 pentetic acid Drugs 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 239000002534 radiation-sensitizing agent Substances 0.000 description 3
- 238000011363 radioimmunotherapy Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical class NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-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
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 2
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 2
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 2
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 229940124292 CD20 monoclonal antibody Drugs 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 206010010741 Conjunctivitis Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000016607 Diphtheria Toxin Human genes 0.000 description 2
- 108010053187 Diphtheria Toxin Proteins 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 101150029707 ERBB2 gene Proteins 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 102000003951 Erythropoietin Human genes 0.000 description 2
- 108090000394 Erythropoietin Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 229930189413 Esperamicin Natural products 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 208000005577 Gastroenteritis Diseases 0.000 description 2
- 208000007465 Giant cell arteritis Diseases 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 208000015023 Graves' disease Diseases 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 2
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 2
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- 208000003456 Juvenile Arthritis Diseases 0.000 description 2
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 108010092694 L-Selectin Proteins 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 102100033467 L-selectin Human genes 0.000 description 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 2
- 102000016267 Leptin Human genes 0.000 description 2
- 108010092277 Leptin Proteins 0.000 description 2
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 102000003683 Neurotrophin-4 Human genes 0.000 description 2
- 102100033857 Neurotrophin-4 Human genes 0.000 description 2
- 108091093105 Nuclear DNA Proteins 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 102000003982 Parathyroid hormone Human genes 0.000 description 2
- 108090000445 Parathyroid hormone Proteins 0.000 description 2
- 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 description 2
- 201000011152 Pemphigus Diseases 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108010001014 Plasminogen Activators Proteins 0.000 description 2
- 102000001938 Plasminogen Activators Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 206010037549 Purpura Diseases 0.000 description 2
- 241001672981 Purpura Species 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 108010039491 Ricin Proteins 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- 108090000184 Selectins Proteins 0.000 description 2
- 102000003800 Selectins Human genes 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 description 2
- 101150006914 TRP1 gene Proteins 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 102000011923 Thyrotropin Human genes 0.000 description 2
- 108010061174 Thyrotropin Proteins 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000011360 adjunctive therapy Methods 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229940009456 adriamycin Drugs 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 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
- 208000006673 asthma Diseases 0.000 description 2
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 2
- 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 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 108010006025 bovine growth hormone Proteins 0.000 description 2
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 2
- 229930195731 calicheamicin Natural products 0.000 description 2
- 150000001720 carbohydrates Chemical group 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229960005243 carmustine Drugs 0.000 description 2
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000001085 cytostatic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 201000001981 dermatomyositis Diseases 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- GNGACRATGGDKBX-UHFFFAOYSA-N dihydroxyacetone phosphate Chemical compound OCC(=O)COP(O)(O)=O GNGACRATGGDKBX-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 150000002019 disulfides Chemical class 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 229940105423 erythropoietin Drugs 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002710 external beam radiation therapy Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229940028334 follicle stimulating hormone Drugs 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 210000002837 heart atrium Anatomy 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 239000003667 hormone antagonist Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 239000000367 immunologic factor Substances 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 210000003000 inclusion body Anatomy 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000007917 intracranial administration Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 2
- 206010023332 keratitis Diseases 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- 108020001756 ligand binding domains Proteins 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 229960001156 mitoxantrone Drugs 0.000 description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 2
- 201000005962 mycosis fungoides Diseases 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 239000003900 neurotrophic factor Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 239000000199 parathyroid hormone Substances 0.000 description 2
- 229960001319 parathyroid hormone Drugs 0.000 description 2
- 201000001976 pemphigus vulgaris Diseases 0.000 description 2
- 238000012510 peptide mapping method Methods 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 229940127126 plasminogen activator Drugs 0.000 description 2
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 2
- 208000005987 polymyositis Diseases 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 239000012521 purified sample Substances 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000000637 radiosensitizating effect Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 238000009118 salvage therapy Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- PVYJZLYGTZKPJE-UHFFFAOYSA-N streptonigrin Chemical compound C=1C=C2C(=O)C(OC)=C(N)C(=O)C2=NC=1C(C=1N)=NC(C(O)=O)=C(C)C=1C1=CC=C(OC)C(OC)=C1O PVYJZLYGTZKPJE-UHFFFAOYSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 206010043207 temporal arteritis Diseases 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- PXSOHRWMIRDKMP-UHFFFAOYSA-N triaziquone Chemical compound O=C1C(N2CC2)=C(N2CC2)C(=O)C=C1N1CC1 PXSOHRWMIRDKMP-UHFFFAOYSA-N 0.000 description 2
- 229960004560 triaziquone Drugs 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- YMXHPSHLTSZXKH-RVBZMBCESA-N (2,5-dioxopyrrolidin-1-yl) 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)ON1C(=O)CCC1=O YMXHPSHLTSZXKH-RVBZMBCESA-N 0.000 description 1
- MCEHFIXEKNKSRW-LBPRGKRZSA-N (2s)-2-[[3,5-dichloro-4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=C(Cl)C=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1Cl MCEHFIXEKNKSRW-LBPRGKRZSA-N 0.000 description 1
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- WLKSPGHQGFFKGE-UHFFFAOYSA-N 1-chloropropan-2-yl n-(3-chlorophenyl)carbamate Chemical compound ClCC(C)OC(=O)NC1=CC=CC(Cl)=C1 WLKSPGHQGFFKGE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- DBPWSSGDRRHUNT-CEGNMAFCSA-N 17α-hydroxyprogesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DBPWSSGDRRHUNT-CEGNMAFCSA-N 0.000 description 1
- OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 description 1
- FZDFGHZZPBUTGP-UHFFFAOYSA-N 2-[[2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical class OC(=O)CN(CC(O)=O)C(C)CN(CC(O)=O)CC(N(CC(O)=O)CC(O)=O)CC1=CC=C(N=C=S)C=C1 FZDFGHZZPBUTGP-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- AOPRXJXHLWYPQR-UHFFFAOYSA-N 2-phenoxyacetamide Chemical class NC(=O)COC1=CC=CC=C1 AOPRXJXHLWYPQR-UHFFFAOYSA-N 0.000 description 1
- 208000010543 22q11.2 deletion syndrome Diseases 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- GUPXYSSGJWIURR-UHFFFAOYSA-N 3-octoxypropane-1,2-diol Chemical compound CCCCCCCCOCC(O)CO GUPXYSSGJWIURR-UHFFFAOYSA-N 0.000 description 1
- XNPKNHHFCKSMRV-UHFFFAOYSA-N 4-(cyclohexylamino)butane-1-sulfonic acid Chemical compound OS(=O)(=O)CCCCNC1CCCCC1 XNPKNHHFCKSMRV-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010001881 Alveolar proteinosis Diseases 0.000 description 1
- 206010001935 American trypanosomiasis Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 244000303258 Annona diversifolia Species 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000033241 Autosomal dominant hyper-IgE syndrome Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 241001112741 Bacillaceae Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 101100222854 Bacillus subtilis (strain 168) czcO gene Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 102000013585 Bombesin Human genes 0.000 description 1
- 108010051479 Bombesin Proteins 0.000 description 1
- 206010051779 Bone marrow toxicity Diseases 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010006474 Bronchopulmonary aspergillosis allergic Diseases 0.000 description 1
- 208000033386 Buerger disease Diseases 0.000 description 1
- 208000023611 Burkitt leukaemia Diseases 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 239000012619 Butyl Sepharose® Substances 0.000 description 1
- 102100031092 C-C motif chemokine 3 Human genes 0.000 description 1
- 101710155856 C-C motif chemokine 3 Proteins 0.000 description 1
- 102100031102 C-C motif chemokine 4 Human genes 0.000 description 1
- 101710155855 C-C motif chemokine 4 Proteins 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 201000002829 CREST Syndrome Diseases 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- FVLVBPDQNARYJU-XAHDHGMMSA-N C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O Chemical compound C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O FVLVBPDQNARYJU-XAHDHGMMSA-N 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000024699 Chagas disease Diseases 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 102100021809 Chorionic somatomammotropin hormone 1 Human genes 0.000 description 1
- 208000008818 Chronic Mucocutaneous Candidiasis Diseases 0.000 description 1
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 description 1
- 229910020366 ClO 4 Inorganic materials 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 241000272201 Columbiformes Species 0.000 description 1
- 102000016917 Complement C1 Human genes 0.000 description 1
- 108010028774 Complement C1 Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010063057 Cystitis noninfective Diseases 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 208000000398 DiGeorge Syndrome Diseases 0.000 description 1
- 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000021866 Dressler syndrome Diseases 0.000 description 1
- 229930193152 Dynemicin Natural products 0.000 description 1
- 108010024212 E-Selectin Proteins 0.000 description 1
- 102100023471 E-selectin Human genes 0.000 description 1
- 201000004315 EAST syndrome Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- MBYXEBXZARTUSS-QLWBXOBMSA-N Emetamine Natural products O(C)c1c(OC)cc2c(c(C[C@@H]3[C@H](CC)CN4[C@H](c5c(cc(OC)c(OC)c5)CC4)C3)ncc2)c1 MBYXEBXZARTUSS-QLWBXOBMSA-N 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 206010053776 Eosinophilic cellulitis Diseases 0.000 description 1
- 206010014954 Eosinophilic fasciitis Diseases 0.000 description 1
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010015218 Erythema multiforme Diseases 0.000 description 1
- 101100127166 Escherichia coli (strain K12) kefB gene Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108050001049 Extracellular proteins Proteins 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 108010074864 Factor XI Proteins 0.000 description 1
- 108010080865 Factor XII Proteins 0.000 description 1
- 102000000429 Factor XII Human genes 0.000 description 1
- 108010071289 Factor XIII Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 101150048336 Flt1 gene Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- 206010018690 Granulocytosis Diseases 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 1
- 108091008603 HGF receptors Proteins 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 101000691214 Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809) 50S ribosomal protein L44e Proteins 0.000 description 1
- 101100028493 Haloferax volcanii (strain ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 / VKM B-1768 / DS2) pan2 gene Proteins 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 1
- 206010019860 Hereditary angioedema Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 description 1
- 101100495232 Homo sapiens MS4A1 gene Proteins 0.000 description 1
- 101000642195 Homo sapiens Protein turtle homolog A Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 101000835745 Homo sapiens Teratocarcinoma-derived growth factor 1 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 206010073257 Idiopathic angioedema Diseases 0.000 description 1
- 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
- 108010073816 IgE Receptors Proteins 0.000 description 1
- 102000009438 IgE Receptors Human genes 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 102100025323 Integrin alpha-1 Human genes 0.000 description 1
- 102100022339 Integrin alpha-L Human genes 0.000 description 1
- 108010041341 Integrin alpha1 Proteins 0.000 description 1
- 108010055795 Integrin alpha1beta1 Proteins 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 102100037872 Intercellular adhesion molecule 2 Human genes 0.000 description 1
- 101710148794 Intercellular adhesion molecule 2 Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 208000009388 Job Syndrome Diseases 0.000 description 1
- 208000012528 Juvenile dermatomyositis Diseases 0.000 description 1
- 108010025815 Kanamycin Kinase Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 101150088608 Kdr gene Proteins 0.000 description 1
- 102100038609 Lactoperoxidase Human genes 0.000 description 1
- 108010023244 Lactoperoxidase Proteins 0.000 description 1
- 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 1
- 108010091221 Lymphotoxin beta Receptor Proteins 0.000 description 1
- 102000018170 Lymphotoxin beta Receptor Human genes 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 1
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010059282 Metastases to central nervous system Diseases 0.000 description 1
- 101100537961 Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88) trkA2 gene Proteins 0.000 description 1
- 102100026632 Mimecan Human genes 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 1
- 206010027910 Mononeuritis Diseases 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 108010008707 Mucin-1 Proteins 0.000 description 1
- 102100034256 Mucin-1 Human genes 0.000 description 1
- 108010063954 Mucins Proteins 0.000 description 1
- 206010028080 Mucocutaneous candidiasis Diseases 0.000 description 1
- 102100028793 Mucosal addressin cell adhesion molecule 1 Human genes 0.000 description 1
- 101710139349 Mucosal addressin cell adhesion molecule 1 Proteins 0.000 description 1
- 101100425758 Mus musculus Tnfrsf1b gene Proteins 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- WTBIAPVQQBCLFP-UHFFFAOYSA-N N.N.N.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O Chemical compound N.N.N.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O WTBIAPVQQBCLFP-UHFFFAOYSA-N 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 108090000095 Neurotrophin-6 Proteins 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 101800002327 Osteoinductive factor Proteins 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010068786 Overlap syndrome Diseases 0.000 description 1
- 108010035766 P-Selectin Proteins 0.000 description 1
- 102100023472 P-selectin Human genes 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 108700034306 PROMACE-CytaBOM protocol Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 206010034498 Pericarditis uraemic Diseases 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 description 1
- 108010003044 Placental Lactogen Proteins 0.000 description 1
- 239000000381 Placental Lactogen Substances 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Porfiromycine Chemical compound O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
- 206010036303 Post streptococcal glomerulonephritis Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102100033219 Protein turtle homolog A Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 108090000103 Relaxin Proteins 0.000 description 1
- 102000003743 Relaxin Human genes 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
- 241000235343 Saccharomycetales Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010039705 Scleritis Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 206010058556 Serositis Diseases 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 102100022831 Somatoliberin Human genes 0.000 description 1
- 101710142969 Somatoliberin Proteins 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010042742 Sympathetic ophthalmia Diseases 0.000 description 1
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 208000001106 Takayasu Arteritis Diseases 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 206010043255 Tendonitis Diseases 0.000 description 1
- 102100026404 Teratocarcinoma-derived growth factor 1 Human genes 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 206010043540 Thromboangiitis obliterans Diseases 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 102000036693 Thrombopoietin Human genes 0.000 description 1
- 108010041111 Thrombopoietin Proteins 0.000 description 1
- 101150009046 Tnfrsf1a gene Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- FYAMXEPQQLNQDM-UHFFFAOYSA-N Tris(1-aziridinyl)phosphine oxide Chemical compound C1CN1P(N1CC1)(=O)N1CC1 FYAMXEPQQLNQDM-UHFFFAOYSA-N 0.000 description 1
- 241000223109 Trypanosoma cruzi Species 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 206010052568 Urticaria chronic Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046914 Vaginal infection Diseases 0.000 description 1
- 201000008100 Vaginitis Diseases 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 206010047124 Vasculitis necrotising Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 208000008526 Wells syndrome Diseases 0.000 description 1
- 208000016807 X-linked intellectual disability-macrocephaly-macroorchidism syndrome Diseases 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- ZMPZNCDIFIQVJZ-UHFFFAOYSA-N acetic acid;n'-[2-(cyclohexylamino)ethyl]ethane-1,2-diamine Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.NCCNCCNC1CCCCC1 ZMPZNCDIFIQVJZ-UHFFFAOYSA-N 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 201000004484 acute conjunctivitis Diseases 0.000 description 1
- 201000005661 acute cystitis Diseases 0.000 description 1
- 208000012873 acute gastroenteritis Diseases 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 201000005638 acute proliferative glomerulonephritis Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 108010035879 albumin-bilirubin complex Proteins 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 208000006778 allergic bronchopulmonary aspergillosis Diseases 0.000 description 1
- 208000002029 allergic contact dermatitis Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000000961 alloantigen Effects 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 229960003437 aminoglutethimide Drugs 0.000 description 1
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 229940045696 antineoplastic drug podophyllotoxin derivative Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 201000004995 autoimmune glomerulonephritis Diseases 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 230000001651 autotrophic effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 238000010364 biochemical engineering Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003139 biocide Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 229940019700 blood coagulation factors Drugs 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 description 1
- 231100000366 bone marrow toxicity Toxicity 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- 229940112129 campath Drugs 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 1
- 229930188550 carminomycin Natural products 0.000 description 1
- XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 description 1
- 229950001725 carubicin Drugs 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 238000012832 cell culture technique Methods 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000002032 cellular defenses Effects 0.000 description 1
- 208000025997 central nervous system neoplasm Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 201000010415 childhood type dermatomyositis Diseases 0.000 description 1
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 201000001352 cholecystitis Diseases 0.000 description 1
- 238000011098 chromatofocusing Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 208000019069 chronic childhood arthritis Diseases 0.000 description 1
- 201000005547 chronic conjunctivitis Diseases 0.000 description 1
- 201000003139 chronic cystitis Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 201000006778 chronic monocytic leukemia Diseases 0.000 description 1
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 208000024376 chronic urticaria Diseases 0.000 description 1
- VYVRIXWNTVOIRD-UHFFFAOYSA-N ciguatoxin Natural products O1C(C(C(C)C2OC3CC(C)CC4OC5(C)C(O)CC6OC7C=CC8OC9CC%10C(C(C%11OC(C=CCC%11O%10)C=CC(O)CO)O)OC9C=CC8OC7CC=CCC6OC5CC4OC3CC2O2)O)C2C(C)C(C)C21CC(O)CO2 VYVRIXWNTVOIRD-UHFFFAOYSA-N 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 229920006026 co-polymeric resin Polymers 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 206010009869 cold urticaria Diseases 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 201000003278 cryoglobulinemia Diseases 0.000 description 1
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
- IMBXRZKCLVBLBH-OGYJWPHRSA-N cvp protocol Chemical compound ClCCN(CCCl)P1(=O)NCCCO1.O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1.C([C@H](C[C@]1(C(=O)OC)C=2C(=C3C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)=CC=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 IMBXRZKCLVBLBH-OGYJWPHRSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000005695 dehalogenation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 229960000452 diethylstilbestrol Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- HQWKKEIVHQXCPI-UHFFFAOYSA-L disodium;phthalate Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C([O-])=O HQWKKEIVHQXCPI-UHFFFAOYSA-L 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000011143 downstream manufacturing Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- AUVVAXYIELKVAI-CKBKHPSWSA-N emetine Chemical compound N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC AUVVAXYIELKVAI-CKBKHPSWSA-N 0.000 description 1
- 229960002694 emetine Drugs 0.000 description 1
- AUVVAXYIELKVAI-UWBTVBNJSA-N emetine Natural products N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@H]1CC AUVVAXYIELKVAI-UWBTVBNJSA-N 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
- 108010002591 epsilon receptor Proteins 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- LJQQFQHBKUKHIS-WJHRIEJJSA-N esperamicin Chemical compound O1CC(NC(C)C)C(OC)CC1OC1C(O)C(NOC2OC(C)C(SC)C(O)C2)C(C)OC1OC1C(\C2=C/CSSSC)=C(NC(=O)OC)C(=O)C(OC3OC(C)C(O)C(OC(=O)C=4C(=CC(OC)=C(OC)C=4)NC(=O)C(=C)OC)C3)C2(O)C#C\C=C/C#C1 LJQQFQHBKUKHIS-WJHRIEJJSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 231100000776 exotoxin Toxicity 0.000 description 1
- 239000002095 exotoxin Substances 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 229940012426 factor x Drugs 0.000 description 1
- 229940012444 factor xiii Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 229960004413 flucytosine Drugs 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000003500 gene array Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 201000008326 granulomatous myositis Diseases 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 229960004198 guanidine Drugs 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 229960002899 hydroxyprogesterone Drugs 0.000 description 1
- 208000014796 hyper-IgE recurrent infection syndrome 1 Diseases 0.000 description 1
- 206010051040 hyper-IgE syndrome Diseases 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
- 230000005931 immune cell recruitment Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 208000015446 immunoglobulin a vasculitis Diseases 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000012432 intermediate storage Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 201000010666 keratoconjunctivitis Diseases 0.000 description 1
- 201000000062 kidney sarcoma Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940057428 lactoperoxidase Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000015073 liquid stocks Nutrition 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 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 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 201000008350 membranous glomerulonephritis Diseases 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- PIDANAQULIKBQS-RNUIGHNZSA-N meprednisone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)CC2=O PIDANAQULIKBQS-RNUIGHNZSA-N 0.000 description 1
- 229960001810 meprednisone Drugs 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 150000002739 metals 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
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- FBOZXECLQNJBKD-UHFFFAOYSA-N methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-UHFFFAOYSA-N 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- MXWHMTNPTTVWDM-NXOFHUPFSA-N mitoguazone Chemical compound NC(N)=N\N=C(/C)\C=N\N=C(N)N MXWHMTNPTTVWDM-NXOFHUPFSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000013734 mononeuritis simplex Diseases 0.000 description 1
- 201000005518 mononeuropathy Diseases 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 102000051367 mu Opioid Receptors Human genes 0.000 description 1
- 201000011201 multicentric reticulohistiocytosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- UGAHKAYVILJXGK-UHFFFAOYSA-N n-(2-aminoethyl)-n'-[2-(propylamino)ethyl]propane-1,3-diamine Chemical compound CCCNCCNCCCNCCN UGAHKAYVILJXGK-UHFFFAOYSA-N 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 229940032018 neurotrophin 3 Drugs 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical class NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000014207 opsonization Effects 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 229940043515 other immunoglobulins in atc Drugs 0.000 description 1
- 208000014734 ovarian Wilms tumor Diseases 0.000 description 1
- 201000003018 ovarian papillary cystadenoma Diseases 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- KLAKIAVEMQMVBT-UHFFFAOYSA-N p-hydroxy-phenacyl alcohol Natural products OCC(=O)C1=CC=C(O)C=C1 KLAKIAVEMQMVBT-UHFFFAOYSA-N 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 101150081585 panB gene Proteins 0.000 description 1
- 101150012634 panT gene Proteins 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008010 parenteral excipient Substances 0.000 description 1
- 208000017262 paroxysmal cold hemoglobinuria Diseases 0.000 description 1
- 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 239000007981 phosphate-citrate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 208000008423 pleurisy Diseases 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229960001237 podophyllotoxin Drugs 0.000 description 1
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 1
- 239000003600 podophyllotoxin derivative Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 208000019629 polyneuritis Diseases 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- WINGFJQHCRYKRB-UHFFFAOYSA-L potassium;sodium;diiodide Chemical compound [Na+].[K+].[I-].[I-] WINGFJQHCRYKRB-UHFFFAOYSA-L 0.000 description 1
- 201000011461 pre-eclampsia Diseases 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 108010087851 prorelaxin Proteins 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 231100000654 protein toxin Toxicity 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229940051022 radioimmunoconjugate Drugs 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 208000009169 relapsing polychondritis Diseases 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 238000002702 ribosome display Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- RPQXVSUAYFXFJA-HGRQIUPRSA-N saxitoxin Chemical compound NC(=O)OC[C@@H]1N=C(N)N2CCC(O)(O)[C@@]22N=C(N)N[C@@H]12 RPQXVSUAYFXFJA-HGRQIUPRSA-N 0.000 description 1
- RPQXVSUAYFXFJA-UHFFFAOYSA-N saxitoxin hydrate Natural products NC(=O)OCC1N=C(N)N2CCC(O)(O)C22NC(N)=NC12 RPQXVSUAYFXFJA-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 208000037921 secondary disease Diseases 0.000 description 1
- 208000011571 secondary malignant neoplasm Diseases 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 229960003440 semustine Drugs 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 1
- 229960004532 somatropin Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- 229940056501 technetium 99m Drugs 0.000 description 1
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 1
- 229960001674 tegafur Drugs 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- UDEJEOLNSNYQSX-UHFFFAOYSA-J tetrasodium;2,4,6,8-tetraoxido-1,3,5,7,2$l^{5},4$l^{5},6$l^{5},8$l^{5}-tetraoxatetraphosphocane 2,4,6,8-tetraoxide Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)O1 UDEJEOLNSNYQSX-UHFFFAOYSA-J 0.000 description 1
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 1
- 229950010357 tetrodotoxin Drugs 0.000 description 1
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical compound [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000001296 transplacental effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 101150025395 trkA gene Proteins 0.000 description 1
- 101150113435 trkA1 gene Proteins 0.000 description 1
- 102000047459 trkC Receptor Human genes 0.000 description 1
- 108010064892 trkC Receptor Proteins 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 208000000143 urethritis Diseases 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
- 108020001612 μ-opioid receptors Proteins 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- A61P31/10—Antimycotics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2851—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the lectin superfamily, e.g. CD23, CD72
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/624—Disulfide-stabilized antibody (dsFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Communicable Diseases (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
Description
本出願は、2003年6月27日提出の発明の名称が「ポリペプチドの精製および優先的合成」であるUSSN60/483877号および2003年10月3日提出の発明の名称が「抗原結合ポリペプチドの精製および優先的合成」であるUSSN60/508,810号の優先権を主張する。本出願はまた、2003年10月28日提出の発明の名称が「連結ペプチドを含む修飾抗体分子」であるUSSN60/515,351号および2003年10月30日提出の発明の名称が「抗原結合ポリペプチドの精製および優先的合成」であるUSSN60/516,030号の優先権を主張する。本出願はまた、2004年6月28日提出の発明の名称が「連結ペプチドを含む改変された結合分子」であるUSSNXX/XXXXXX号に関連する。これらの出願の内容は、その全体が本明細書中で参考として援用される。
抗体は二量体分子であり、二量体を構成する各単量体は1つの軽鎖および1つの重鎖を含む。抗体分子溶液は、ヒンジ不均一性に関連する2つの形態で存在する。精製Mab(MAb)のSDS−PAGE分析を使用して、典型的には、2つの形態は、2つのタンパク質バンド(主要なバンド(分子量約150〜160kDa)および主要でないバンド(分子量約75〜80kDa))として認められる。この後者の形態は、典型的には、精製IgG4調製物のSDS−PAGE分析後に認められるが、全てのIgGアイソタイプ(精製組換えMAbが含まれる)においてはるかに低頻度で同定することができる(非特許文献1;非特許文献2)。A型と呼ばれるより高い分子量のアイソタイプは、239位および242位(Kabatナンバリングシステム)(EUナンバリングシステムでは226位および229位)に対応する位置に共有結合性鎖間ジスルフィド結合を含む(非特許文献3)。非還元SDS−PAGE電気泳動で認められた75〜80kDaによって証明されるように、第2のアイソフォームであるB型は、2つの重鎖間に共有結合を含まず、かつ2つの隣接システイン残基間に鎖間ジスルフィド結合を含まないと考えられる。B型の2つの重鎖は、おそらく分子のCH3ドメインと会合した強固な非共有(例えば、イオン)相互作用によって連結している。これらのA型とB型との混合物は、インタクトなヒンジを含むがCH3ドメインを欠くMAbフラグメント(例えば、F(ab)2フラグメントなど)の溶液中に存在しない。典型的には、遺伝子操作されたか酵素消化されたF(ab)2MAb調製物は、分子が非共有相互作用(例えば、水素結合)の維持に必要なドメインを欠くため、B型を欠く。しかし、これらはCH3ドメインを含むMAb調製物(例えば、IgG4)、CH2ドメイン欠失MAbフラグメント(特許文献1などに記載)、およびミニボディ(minibody)(非特許文献4など)ならびにIgG4分子中に存在する。
本発明は、少なくとも一部が、異なるアイソフォーム(分子画分が少なくとも1つの鎖間ジスルフィド結合を介して結合した2つの重鎖部分(A型)を含み、分子の一部が少なくとも1つの鎖間ジスルフィド結合を介して結合しない2つの重鎖部分(B型)を含む、2つの重鎖部分を含む分子)を含む二量体ポリペプチド分子の混合物を含む組成物において、例えば、疎水性相互作用クロマトグラフィを使用した分離またはA型もしくはB型が優先的に生合成される合成連結ペプチドの封入によって一方の形態または他方の形態を優先的に得ることができるという所見に基づく。本発明の連結ペプチドは、A型およびB型の両方を形成する傾向がある任意の二量体分子(例えば、抗体分子、ドメイン欠失抗体分子(例えば、CH2ドメインの全部または一部を欠く)、ミニボディ、二重特異性抗体、融合タンパク質など)に含まれ得る。好ましい実施形態では、A型の形成が増強される。A型ポリペプチド二量体は、インビトロでの強化された安定性およびインビボでの強化された体内分布を示す。
i)その第一のポリペプチド二量体および第二のポリペプチド二量体を含む混合物を、媒体に接触させ、その媒体は、そのポリペプチド二量体をその媒体に結合させる条件下での疎水性相互作用に基づいてそのポリペプチド鎖を分離する媒体である、工程;ならびに
ii)その第一のポリペプチド二量体を収集し、それによりその第一のポリペプチド二量体を分離する工程であって、そしてその収集工程は、その媒体を、ほぼ中性のpHで約120mS/cmの伝導率を有する溶液と接触させる工程を包含する工程、を包含する。
i)その第一の抗体分子および第二の抗体分子を含む混合物を、抗体分子を疎水性相互作用に基づいて分離する媒体と接触させる工程、
ii)その媒体を、ほぼ中性のpHで約120mS/cmの伝導率を有する溶液と接触させ、その結果、その第一の抗体分子はその媒体に結合されず、かつその第二の抗体分子はその媒体に結合され、それによりその第一の抗体分子と第二の抗体分子とを分離する工程、を包含する。
1つの局面において、本発明は、少なくとも2つの結合部位および少なくとも2本のポリペプチド鎖を有するポリペプチド二量体を含む組成物に関し、その少なくとも2本のポリペプチド鎖は、少なくとも1つの重鎖部分を含み、かつCH2ドメインの全てまたは一部分を欠損し、50%を超えるこのポリペプチド二量体が、少なくとも1つの鎖間ジスルフィド結合を介して結合されているポリペプチド鎖を含む。
ヒト免疫グロブリン(Ig)(モノクローナル抗体(MAb)が含まれる)は、ヒンジの異種性に関連する2つの形態で存在し得る。天然の溶液では、これらの両形態は二量体タンパク質(各単量体は1つの重鎖および1つの軽鎖を含む)として存在する。一方の免疫グロブリン分子は、二量体が鎖間重鎖ジスルフィド結合によってつなぎ合わされた約150〜160kDaの安定な四鎖構築体を含み(A型)、他方は二量体が鎖間ジスルフィド結合を介して結合していない形態を含む(B型)。B型はまた天然条件下で安定な二量体を形成するが、変性非還元条件下で同定することができ、重鎖の解離によって75〜80kDaの分子が得られる。これらの形態は、MAbアフィニティ精製後でさえも分離が極めて困難である。
本発明のポリペプチドは、標的分子(抗原または結合パートナー)と特異的に結合する結合部位を含む少なくとも1つの結合ドメインを含む結合分子(すなわち、ポリペプチド(polypepdide)分子またはこれらをコードする核酸分子)である。例えば、1つの実施形態では、本発明の結合分子は、免疫グロブリン抗原結合部位またはリガンド結合を担うレセプター分子の一部、またはレセプター結合を担うリガンド分子の一部を含む。本発明の結合分子は、ポリペプチドまたはこれらをコードする核酸分子である。
本発明の二量体の少なくとも1つのポリペプチド鎖は、本発明の合成連結ペプチドを含み得る。1つの実施形態では、本発明の二量体の少なくとも2つの鎖は連結ペプチドを含む。好ましい実施形態では、本発明の二量体の2つの鎖は連結ペプチドを含む。
(A.抗体またはその一部)
1つの実施形態では、本発明の結合分子は抗体分子である。当該分野で認識されたプロトコールを使用して、例えば、関連抗原(例えば、精製腫瘍関連抗原またはこのような抗原を含む細胞もしくは細胞抽出物)およびアジュバントの複数回の皮下注射または腹腔内注射によって哺乳動物中に抗体を惹起することが好ましい。この免疫化により、典型的には、活性化脾臓細胞またはリンパ球由来の抗原反応性抗体の産生を含む免疫応答が誘発される。ポリクローナル調製物を得るために得られた抗体を動物の血清から回収することができる一方で、モノクローナル抗体(MAb)の均一な調製物を得るために脾臓、リンパ節、または末梢血から各リンパ球を単離することがしばしば望ましい。好ましくは、脾臓からリンパ球を得る。
et al.2002.Nat.Med.8:801;Huie et al.2001.Proc.Natl.Acad.Sci.USA 98:2682;Lui et al.2002.J:Mol.Biol.315:1063(それぞれ本明細書中で参考として援用される)に記載されている。いくつかの刊行物(例えば、Marks et al.Bio/Technology 10:779−783(1992))は、鎖シャフリングならびに巨大ファージライブラリーの構築のためのストラテジーとしての組み合わせ感染およびin vivo組換えによる高親和性ヒト抗体の産生を記載している。別の実施形態では、ディスプレプラットフォームとしてリボゾームディスプレイを使用して、バクテリオファージを置換することができる(例えば、Hanes et al.2000.Nat.Biotechnol.18:1287;Wilson et al.2001.Proc.Natl.Acad.Sci.USA 98:3750;またはIrving et al.2001 J.Immunol.Methods 248:31を参照のこと)。さらに別の実施形態では、抗体について細胞表面ライブラリーをスクリーニングすることができる(Boder et al.2000.Proc.Natl.Acad.Sci.USA 97:10701;Daugherty et al.2000 J.Immunol.Methods 243:211)。このような手順は、モノクローナル抗体の単離およびその後のクローニングのための従来のハイブリドーマ技術の代替法を提供する。
る。このような生殖系列変異マウスへのヒト免疫グロブリン遺伝子アレイの導入により、抗原の抗原誘発時にヒト抗体が産生される。SCIDマウスを使用した別の好ましいヒト抗体の作製手段は、米国特許第5,811,524号(本明細書中で参考として援用される)に開示されている。これらのヒト抗体に関連する遺伝物質を本明細書中に記載のように単離および操作することもできることが認識される。
1つの実施形態において、本発明の結合分子または抗原結合分子は、1つ以上のドメインが部分的にかまたは全体的に欠失(「ドメイン欠失抗体」)している合成定常領域を含む。特に好ましい実施形態において、適合性の改変された抗体は、CH2ドメインの全体が取り除かれているドメイン欠失構築体または改変体(ΔCH2構築体)を含む。他の好ましい実施形態について、短い連結ペプチドがその欠失されたドメインに対して置換され、可変領域の運動の可動性および自由度を提供し得る。当業者は、その抗体の異化速度におけるCH2ドメインの調節特性のために、このような構築体が特に好まれることを理解する。
)を残すこと、またはそのヒンジ領域が屈曲性を残すことを保証するために、付加され得る。例えば、そのCH2ドメインについて置換された短いアミノ酸スペーサーGGSSGGGGSG(配列番号1)および下流(lower)ヒンジ領域(CC49.ΔCH2[
gly/ser])を有するドメイン欠失CC49構築体が、使用され得る。他の例示的
連結ペプチドが、表2に示される。これらの連結ペプチドは、任意の本発明のポリペプチドと一緒に使用され得る。好ましくは、その連結ペプチドは、CH2重鎖ドメインを欠くポリペプチドと一緒に使用される。好ましくは、本発明に適合する任意のリンカーは、相対的に非免疫原性であり、かつ本発明のポリペプチドの非共有結合を阻害しない。
本発明はまた、1つまたは複数の免疫グロブリンドメインを含む結合分子に関する。本発明の融合タンパク質は、結合ドメイン(少なくとも1つの結合部位を含む)および二量体化ドメイン(少なくとも1つの重鎖部分を含む)を含む。本発明の融合タンパク質は二重特異性(第1の標的に対する1つの結合部位および第2の標的に対する第2の結合部位を含む)であり得るか、多特異性(同一標的に対する2つの結合部位を含む)であり得る。
サイトカインは、リンパ球の増殖、分化、および機能的活性化に多面的効果を有する。種々のサイトカインまたはそのレセプター結合部分を、本発明の融合タンパク質で使用することができる。例示的サイトカインには、インターロイキン(例えば、IL−1、IL−2、IL−3、IL−4、IL−5、IL−6、IL−7、IL−8、IL−10、IL−11、IL−12、IL−13、およびIL−18)、コロニー刺激因子(CSF)(例えば、顆粒球CSF(G−CSF)、顆粒球−マクロファージCSF(GM−CSF)、および単球−マクロファージCSF(M−CSF))、腫瘍壊死因子(TNF)αおよびβ、ならびにインターフェロンα、β、またはγなどのインターフェロン(米国特許第4,925,793号および同第4,929,554号)が含まれる。
接着分子は、細胞を互いに相互作用させる膜結合タンパク質である。そのレセプター結合部分の種々の接着タンパク質(白血球ホーミングレセプターおよび細胞接着分子が含まれる)を、本発明の融合タンパク質に組み込むことができる。白血球ホーミングレセプターは、炎症時に白血球細胞表面で発現し、細胞外マトリクス成分への結合を媒介するβ−1インテグリン(例えば、VLA−1、2、3、4、5、および6)および血管内皮上の細胞接着分子(CAM)に結合するβ2−インテグリン(例えば、LFA−1、LPAM−1、CR3、およびCR4)が含まれる。例示的CAMには、ICAM−1、ICAM−2、VCAM−1、およびMAdCAM−1が含まれる。他のCAMには、セレクチンファミリー(E−セレクチン、L−セレクチン、およびP−セレクチンが含まれる)のセレクチンが含まれる。
ケモカイン(感染部位への白血球の移動を刺激する走化性タンパク質)を、本発明の融合タンパク質に組み込むこともできる。例示的ケモカインには、マクロファージ炎症性タンパク質(MIP−1−αおよびMIP−1−β)、好中球走化性因子、およびRANTES(通常はT細胞を発現および分泌する活性化に対して調節される)が含まれる。
成長因子またはそのレセプター(またはそのレセプター結合部分もしくはリガンド結合部分)を、本発明の融合タンパク質に組み込むことができる。例示的成長因子には、血管内皮成長因子(VEGF)およびそのアイソタイプ(米国特許第5,194,596号;線維芽細胞成長因子(FGF)(aFGFおよびbFGFが含まれる);心房性ナトリウム利尿因子(ANF);肝臓成長因子(HGF;米国特許第5,227,158号および同第6,099,841号)、神経栄養因子(骨由来神経栄養因子(BDNF)、ニューロトロフィン−3、−4、−5、または−6(NT−3、NT−4、NT−5、またはNT−6)など)または神経成長因子(NGF−β血小板由来成長因子(PDGF)(米国特許第4,889,919号、同第4,845,075号、同第5,910,574号、および同第5,877,016号)など);形質転換成長因子(TGF)(TGF−αおよびTGF−β(WO90/14359)、骨誘導因子(osteoinductive factor)(形態形成タンパク質(BMP)などが含まれる);インスリン様成長因子IおよびII(IGF−IおよびIGF−II;米国特許第6,403,764号および同第6,506,874号);エリスロポイエチン(EPO);幹細胞因子(SCF)、トロンボポイエチン(c−Mplリガンド)、およびWntポリペプチド(米国特許第6,159,462)が含まれる。本発明のターゲティングレセプタードメインとして使用することができる例示的な成長因子レセプターには、EGFレセプター;VEGFレセプター(例えば、Flt1またはFlk1/KDR)、PDGF受容体(WO90/14425);HGFレセプター(米国特許第5,648,273号および同第5,686,292号)、およびNGF、BDNF、およびNT−3に結合する神経栄養レセプター(p75NTRまたはp75とも呼ばれる低親和性レセプター(LNGFR))、レセプターチロシンキナーゼのtrkファミリーのメンバーである高親和性レセプター(例えば、trkA、trkB(欧州特許第455,460号)、trkC(欧州特許第522,530号))が含まれる。
本発明の融合タンパク質におけるターゲティング因子として使用するための例示的成長ホルモンには、レニン、ヒト成長ホルモン(HGH;米国特許第5,834,598号)、N−メチオニルヒト成長ホルモン;ウシ成長ホルモン;成長ホルモン放出因子;副甲状腺ホルモン(PTH);甲状腺刺激ホルモン(TSH);チロキシン;プロインスリンおよびインスリン(米国特許第5,157,021号および同第6,576,608号);卵胞刺激ホルモン(FSH)、カルシトニン、黄体形成ホルモン(LH)、レプチン、グルカゴン;ボンベシン;ソマトロピン;ミューラー阻害物質;レラキシンおよびプロレラキシン;ゴナドトロピン関連ペプチド;プロラクチン;胎盤性ラクトゲン;OBタンパク質;またはミューラー阻害物質が含まれる。
本発明の融合タンパク質におけるターゲティング因子として使用するための例示的血液凝固因子には、凝固因子(例えば、第V因子、第VII因子、第VIII因子、第X因子、第IX因子、第XI因子、第XII因子、および第XIII因子、フォンウィルブランド因子);組織因子(米国特許第5,346,991号、同第5,349,991号、同第5,726,147号、および同第6,596,84号);トロンビンおよびプロトロンビン;フィブリンおよびフィブリノゲン;プラスミンおよびプラスミノゲン;プラスミノゲンアクチベーター(ウロキナーゼまたはヒト尿または組織特異的プラスミノゲンアクチベーター(t−PA)など)が含まれる。
上記の本発明のポリペプチドを得るための単離遺伝物質の操作後、典型的には、上記遺伝子は、所望される量のポリペプチドを産生するために使用され得る宿主細胞への導入のための発現ベクターへ挿入され、これが次に特許請求の範囲に記載のポリペプチドを与える。
1つの局面では、本発明は、ある分子画分は2つの重鎖部分が少なくとも1つの鎖間ジスルフィド結合を介して結合している形態で存在し、ある分子画分は少なくとも1つのジスルフィド結合を介して結合していない重鎖部分を含む混合物からの、疎水性相互作用クロマトグラフィによる、2つの重鎖部分を有する分子の分離に関する。
本発明のポリペプチド分子を、非結合体化形態で使用することができるか、例えば、標的の検出を容易にするためか患者の画像化もしくは治療のために種々の分子のうちの少なくとも1つに結合体化(conjugate)することができる。本発明のポリペプチドを、精製を行う場合、精製前または精製後のいずれかで標識または結合体化することができる。特に、本発明のポリペプチドを、細胞毒素(放射性同位体、細胞毒性薬、または毒素など)、治療薬、細胞増殖抑制薬、生物毒素、プロドラッグ、ペプチド、タンパク質、酵素、ウイルス、脂質、生物反応修飾物質、薬物、免疫学的に活性なリガンド(例えば、得られた分子が新生物細胞とT細胞などのエフェクター細胞との両方に結合する、リンホカインまたは他の抗体)、またはPEGに結合体化することができる。別の実施形態では、本発明のポリペプチドを、腫瘍の血管新生を減少させる分子に結合体化することができる。他の実施形態では、開示の組成物は、薬物またはプロドラッグに結合した本発明のポリペプチドを含み得る。本発明のさらに他の実施形態は、リシン、ゲロニン、緑膿菌外毒素、またはジフテリア毒素などの特定の生物毒素またはその細胞毒性フラグメントに結合体化した本発明のポリペプチドの使用を含む。使用する結合体化または非結合体化ポリペプチドの選択は、癌の型および進行度、補助療法(例えば、化学療法または外部照射)の使用、および患者の健康状態に依存する。当業者は、本明細書中の教示を考慮して、このような選択を容易に行うことができると認識する。
本発明のポリペプチドの調製方法および被験体への投与方法は周知であるか、または当業者によって容易に決定される。本発明のポリペプチドの投与経路は、経口、非経口、吸入、または局所であり得る。本明細書中で使用される、用語「非経口」には、静脈内、動脈内、腹腔内、筋肉内、皮下、直腸、または膣への投与が含まれる。非経口投与の静脈内、動脈内、皮下、および筋肉内形態が一般に好ましい。これらの全投与形態は、本発明の範囲内であることが明らかに意図される一方で、投与形態は、注射、特に、静脈内もしくは動脈内の注射または滴注のための溶液である。通常、注射に適切な薬学的組成物は、緩衝液(例えば、酢酸緩衝液、リン酸緩衝液、またはクエン酸緩衝液)、界面活性剤(例えば、ポリソルベート)、任意選択的に、安定剤(例えば、ヒトアルブミン)などを含み得る。しかし、本明細書中の教示に適合可能な他の方法では、ポリペプチドを直接有害な細胞集団部位に送達させ、それによって治療薬への罹患組織の曝露を増加させることができる。
上記病態の治療のための本発明の組成物の有効用量は、多数の異なる要因(投与手段、標的部位、患者の身体の状態、患者がヒトであるかまたは動物であるか、他の投与される薬物、および治療が予防であるかまたは治療であるのかが含まれる)に依存して変化する。通常、患者はヒトであるが、トランスジェニック哺乳動物を含む非ヒト哺乳動物も治療することができる。安全性および有効性を至適化するために当業者に公知の日常的方法を使用して、治療用量を漸増(titrate)することができる。抗体を使用した受動免疫法のために、投薬量は、例えば、約0.0001〜100mg/kg宿主体重、より通常には約0.01〜5mg/kg宿主体重(例えば、0.02mg/kg宿主体重、0.25mg/kg宿主体重、0.5mg/kg宿主体重、0.75mg/kg宿主体重、1mg/kg宿主体重、2mg/kg宿主体重など)の範囲であり得る。例えば、投薬量は、1mg/kg体重または10mg/kg体重または1〜10mg/kg体重の範囲内、好ましくは少なくとも1mg/kg体重であり得る。上記範囲の中間値も本発明の範囲内に含まれることが意図される。被験体にこのような用量を毎日、隔日、毎週、または経験的分析によって決定した任意の他のスケジュールにしたがって投与することができる。例示的治療は、(例えば、少なくとも6ヶ月の)長期間にわたる複数回投薬量での投与を必要とする。さらなる例示的治療投与計画は、2週間毎に1回または1ヶ月毎に1回または3ヶ月〜6ヶ月毎に1回の投与を必要とする。例示的投薬計画には、1〜10mg/kgまたは15mg/kgを毎日、30mg/kgを隔日、または60mg/kgを毎週が含まれる。いくつかの方法では、異なる結合特異性を有する2つまたはそれより多くのモノクローナル抗体を同時に投与し、その場合、投与される各抗体の投薬量は表示される範囲内に入る。
本発明の分子を、診断または治療目的で使用することができる。本発明の好ましい実施形態は、このような治療を必要とする哺乳動物被験体の障害(例えば、新生物障害)の診断および/または治療のための化合物、組成物、キット、および方法を提供する。被験体はヒトであるのが好ましい。
「処置」は、治療上の処置および予防的または防止手段の両方をいう。処置を必要とする者には、既に疾患または障害を有する者および疾患または障害を防止すべき者が含まれる。したがって、哺乳動物を、疾患または障害を有するか、疾患にかかりやすいか感受性を示し得ると診断することができる。
抗体分子溶液は、2つの異なるアイソフォームを含む。一方の形態であるA型は、少なくとも1つのジスルフィド結合を介して結合した重鎖分子を含む。他方の形態であるB型は、少なくとも1つのジスルフィド結合を介して結合していない重鎖分子を含む。Rituxan(登録商標)などのインタクトなγ1MAbを使用した場合、B型は出現しないか非常に低い頻度で出現する。しかし、類似のヒンジを有するドメイン欠失(dd)構造を使用すると、B型の頻度ははるかに高くなる。変性非還元SDSpageを使用して、これらの形態を区別することができる。ドメイン欠失抗体調製物では、A型は120kDaの二量体として出現し、B型は60kDaの単量体として出現する(図1)。図2Aおよび図2Bは、それぞれddCC49(CH2)およびddCC49(Gly/Ser)に対する非還元SDS−PAGEの濃度計プロットを示す。
ヒンジドメインを、上部、中央、および下部ヒンジ領域の3つの異なる領域に細分することができる(Roux et al.J.Immunol.1998 161:4083)。IgG1およびIgG3ヒンジについてのこれらの領域を含むポリペプチド配列を、表1に示す。IgG3ヒンジ中央領域は、2つの保存システイン残基に加えて、3回反復した15アミノ酸モチーフを含む。これらの領域由来のアミノ酸配列を使用して、合成IgG1/IgG3連結ペプチドをデザインした。これらは、226位〜238位に対応するIgG1上部ヒンジ残基、239位〜241位に対応するIgG1中央ヒンジ、および243位にプロリンを付加するか、243位、244位、および245位(Kabatナンバリングシステム)にそれぞれプロリン、アラニン、プロリンを付加し、その後に可動性Gly/Serスペーサーを付加した、241EE位〜242位に対応する1つのIgG3中央ヒンジ反復モチーフからなる(表2)。さらに、243位にプロリンを付加するか、243位、244位、および245位(Kabatナンバリングシステム)にそれぞれプロリン、アラニン、プロリンを付加した、239位または242位のシステインがセリンアミノ酸残基に置換された新規の連結ペプチドをデザインした。Pro243Ala244Pro245およびPro 243連結ペプチドも作製した。IgG1ヒンジの最初の残基(226位、Kabatナンバリングシステム)から始まり、ヒンジ/GlySer連結ペプチドの最後の残基で終わる親CH2ドメイン欠失ヒト化CC49連結ペプチドのアミノ酸配列を表2に示す。Kabatナンバリングシステムで示したシステイン残基の位置を使用したCC49とのアラインメントによる種々の連結ペプチドデザインも示す。
重複伸長スプライシング(SOE)法を使用して、表2に示すヒンジ領域連結ペプチドをコードする核酸配列を、CH2ドメイン欠失huCC49遺伝子配列に移入した(Horton,R.M.1993 Methods in Molecular Biology,Vol 15:PCR Protocols:Current Methods and applications.Ed.B.A.White)。ヒンジ領域の正確な修飾を、DNA配列分析によって確認した。抗体タンパク質の安定な産生のために、プラスミドDNAを使用して、CHO DG44細胞を形質転換した。
Pro230Ala231Pro232 A型物質およびHuCC49 V2 Pro230Ala231Pro232 A型物質の精製を達成した。HuCC49 G1/G3/Pro243Ala244Pro245 A型物質およびHuCC49 V2 G1/G3/Pro243Ala244Pro245 A型物質を、プロテインGカラムのみを使用して精製し、さらなるHIC精製なしでどちらも96%を越える純度で単一ピークとして溶出した(図5および図6)。全ての抗体をサイズ排除クロマトグラフィー(size exclusion chromatography)により試験し、そして抗体の有意な凝集または分解が存在しないことを示す単一ピークとして溶出することを見出した。
研究は、CH2ドメイン欠失抗体のA型アイソフォームの合成における242位(Kabatナンバリングシステム)でのシステイン残基の重要性も示す。従って、1つの実施形態において、本発明の連結ペプチドは、239位または242位の少なくとも1つに、システインを含む。239位または242位のいずれかのシステインのセリンへの置換(例えば、配列番号10、11、12、または13に示す連結ペプチドを使用)により、CH2ドメイン欠失抗体生合成がB型アイソフォームにシフトされる。A型の産生比率が増加する連結ペプチドの使用により、プロセス、収率、および/または安定性が有利に改善される。これらの合成ヒンジ領域の連結ペプチドは、4つ全てのヒトアイソタイプのCH3ドメインの間での非常に高い相同性に基づいて、任意の抗体アイソタイプ(例えば、IgG1、IgG2、IgG3、またはIgG4)のCH2ドメイン欠失抗体A型アイソフォームの優先的合成に有用である。同一および保存されたアミノ酸残基を含むことにより、IgG1のCH3ドメインはIgG2のCH3と98.13%相同であり、IgG3のCH3と97.20%相同であり、IgG4のCH3と96.26%相同である。
10mLのddCC49上清を、1M Tris(pH9.0)で最終pH7.5まで漸増(titrate)した。この物質を、一連のSol−Vac0.8μおよび0.4μメンブレンで濾過した。100mLのXK50プロテインGカラムを、流速80mL/分にて1×PBSで予備平衡化した。漸増し、濾過した上清を、80mL/分でカラムにロードした。結合したタンパク質を、2カラム体積の平衡緩衝液で洗浄し、その後pH3.0で100mMグリシンにて溶離した。ddCC49ピークを含む画分を回収し、その直後に1M Tris(pH9.0)で最終pH7.0に漸増した。
A型およびB型の生物活性(例えば、直接結合または競合研究を使用した予備実験での測定)により、A型およびB型が類似の生物活性を有することが明らかとなった。
サイズ排除クロマトグラフィ(SEC)はインタクトな分子および分解生成物(フラグメントおよび可溶性凝集体の両方)の比率の解明のための強力な方法であり、再現性が高い。表5A〜5Cでは、異なる温度でのAアイソフォーム、Bアイソフォーム、および混合物のインタクトな単量体の比率を列挙する。2〜8℃で保存したサンプルについては、A型はB型と比較して単量体の比率が高く、A型とB型との混合物はその間であることが明らかである。この保存温度では、両型は、pH3、5、および7で約3ヶ月間比較的安定であった(pH5が最も安定な条件である)。しかし、pH9では、B型では単量体の比率が有意に減少するが、A型ではわずかしか減少しなかった。
IDEC−159(ddCC49)は、腫瘍表面上に発現する、TAG−72抗原に指向するCH2ドメイン欠失モノクローナル抗体である。IDEC−159は、A型およびB型と呼ばれる抗体の2つのアイソフォームを含む。IDEC−159のための現在の細胞培養プロセスにより、A型:B型が約50:50の比で産生される。Aアイソフォームは、重鎖のFc部分のCH2領域が欠失した抗体である。CH2領域の欠失に加えて、B型はFc領域を横切るジスルフィド結合も欠き、疎水性相互作用および塩橋のみでつなぎ合わされている。
・150cm以下/時間で3CV以上の0.5N NaOHを使用してカラムを浄化した。
・150cm以下/時間で5CV以上の0.73M硫酸アンモニウム/20mMリン酸ナトリウム(pH4.0)を使用してカラムを平衡化した。
・5mg/mL樹脂で0.43倍体積の2.5M硫酸アンモニウム/20mMリン酸ナトリウム(pH4.0)液体ストック溶液を含むように調整した室温のTMAE Flowthroughをカラムにロードした。
・pH4.0で100cm以下/時間にて抗体をカラムにロードした。
・280nmでの排出O.D.が10mAUに到達した時に抗体を回収し始めた。
・100cm以下/時間で15CVの0.73M硫酸アンモニウム/20mMリン酸ナトリウム(pH4.0)を使用してカラムを洗浄した。
・15CV洗浄の間中抗体を回収し続け、その後排出液を廃液に戻した。
・100cm以下/時間で5CV以上の20mMリン酸ナトリウム(pH4.0)を使用してカラムから剥離した。6.150cm以下/時間で3CV以上の0.5N NaOHを使用してカラムを洗浄した。
・150cm以下/時間で3CV以上の0.73M硫酸アンモニウム/20mMリン酸ナトリウム(pH4.0)を使用してカラムを平衡化した。
・150cm以下/時間で3CV以上の20%エタノール中にカラムを保存した。
CC49抗体に対していくつもの変化をさせ、ヒト化CC49バージョン2(huCC49 V2)を作製した。図19は、マウスCC49、LENまたは21/28’CL、ヒト化CC49、およびヒト化CC49 V2(これはヒト化CC49と比較して、軽鎖において1つのアミノ酸置換、重鎖において2つのアミノ酸置換を含有する)の軽鎖可変領域のアライメント(図19A)および重鎖可変領域のアライメント(図19B)を示す。このヒト化CC49 MAbの免疫原性をさらに減少させるために、その抗体に存在するマウス残基を、軽鎖の置換に対してはヒトアクセプター配列LEN由来の、重鎖の置換に対しては21/28’CL由来のヒトフレームワーク残基での置換について、試験および考察した。(Singer IIら、1993.Optimal Humanization of 1B4,an Anti−CD18 Murin Monoclonal
Antibody,is Achieved by Correct Choice of Human V−Region Framework Sequence.J.Immunol.150:2844−2857.Padlan E A,1991.Possible Procedure For Reducing the Immunogenicity of Antibody Variable Domeins While Preserving Their Ligand−Binding Properties.Molecular Immunol.28:489−498)。結合部位の特異性および親和性を保存するために重要だと考えられるフレームワーク残基は、わずかに少数の差異であることを明らかにした。その重鎖配列において、69位(ロイシン)および93位(トレオニン)の予測された埋め込まれた残基を、いずれもヒト残基のイソロイシンおよびアラニンにそれぞれ置換した。軽鎖配列において、43位(セリン)に主に埋め込まれていると予測された1つの残基を、ヒト残基のプロリンと置換した。
種々の形態のドメイン欠失抗体(連結ペプチドを有するまたは有さない)を、Wallac 1420 Multilabel Counter Victor V(PerkinElmer)を使用する時間分解蛍光定量イムノアッセイにより、それらのウシ下顎ムチン(mucine)(TAG−72抗原の供給源)への結合能について、競合結合アッセイにおいて試験した。競合結合曲線を、図20に示す。HuCC49 PAP(配列番号14に示される連結ペプチドを含む)、HuCC49 PAP(配列番号14に示される連結ペプチドを含む)、HuCC49 G1/G3:PAP(配列番号9に示される連結ペプチドを含む)、HuCC49 V2 G1/G3/PAP(配列番号9に示される連結ペプチドを含む)およびコントロールの親HuCC49抗体を評価した。3つ全てのヒンジが操作された抗体についての相対的結合活性は、コントロールの親CC49抗体と区別不能または2〜3倍以内である。
定)、逆に腎臓において低かった(p<0.01)。これらの抗体についての腫瘍組織比を比較した場合、そのHuCC49 V2 PAPは、血液を除く全ての組織に対して、より高い腫瘍組織比という結果になった。
この実施例は、実施例9において提示された結果を確認および拡張する。上記ヒトCC49 V2 G1/G3/Pro243Ala244Pro245+[Gly/Ser](配列番号9)およびHuCC49(gly/ser)の抗体を、ダイアフィルトレーションし、そして前もってリンスされたAmicon Centricon 30を使用して低金属(low metal)5mM酢酸ナトリウム緩衝液(pH5.0)(LMB)内に濃縮した。そのcentriconの遠心分離を、温度を2〜8℃に維持しつつ、5000×gの固定されたアングルローターにおいて行った。50μlのLMBをそのサンプルレザバーに加え、簡単にボルテックスし、1000×gにて10分間バックスピン(back−spinning)することにより、各抗体を回収した。1.48の吸光係数を用いる280nmのUV Spec分析を使用して、そのタンパク質濃度を決定した。次いで各抗体を、LMBを使用して10.5mg/mlに至るまで調整した。
この実施例は、ドメイン欠失CC49 G1/G3/Pro243Ala244Pro245+[Gly/Ser](配列番号9)が、Gly−Serリンカーを有するドメイン欠失CC49よりも、親CC49のように、グルタチオン(GSH)還元に対してより安定であるようであることを示す。
G1/G3/Pro243Ala244Pro245をさらに保護した。還元剤に対する減少した感受性のこの予期しなかった知見は、その抗体の物理的強度を維持しながら、そのG1/G3/Pro243Ala244Pro245+[Gly/Ser](配列番号9)ヒンジの設計が、還元剤を使用する化学(例えば、薬物結合体(例えば、SPDPリンカー)調製に使用されるものまたは抗体への放射性同位体(例えば、99MTc)付加のための技術)の使用を可能にすることを示唆する。還元剤感受性に関するこの利点は、CH2−ドメイン欠失構築体の薬物動態学的な利点(実施例10におけるマウスの生体分布データを参照のこと)を変化させないようである。還元剤に対するこの感受性の減少はまた、インビボでの安定性の増加を予測させ得る。
上記ヒンジ領域連結ペプチドG1/G3/Pro243Ala244Pro245+[Gly/Ser](配列番号9)を、実施例3に記載されたように、CH2ドメイン欠失C2B8抗体に導入した。C2B8は、それぞれヒト重鎖および軽鎖定常領域に融合されたマウス重鎖および軽鎖可変ドメインからなるキメラ抗−CD20モノクローナル抗体である。そのヒンジ領域への正確な改変を、DNA配列決定分析により確認した。プラスミドDNAを、抗体タンパク質の一過性産生のためにCHO DG44細胞を形質転換するために使用した。
上記ヒンジ領域連結ペプチドG1/G3/Pro243Ala244Pro245+[Gly/Ser](配列番号9)を使用して、基本的には実施例3に記載されるようにCH2ドメイン欠失5E8(5E8ΔCH2)抗体を構築した。5E8は、それぞれヒト重鎖および軽鎖定常領域に融合されたマウス重鎖および軽鎖可変ドメインからなるキメラ抗−CD23モノクローナル抗体である。そのヒンジ領域への正確な改変を、DNA配列決定分析により確認した。5E8軽鎖および重鎖の核酸配列およびアミノ酸配列を、それぞれ図28および図29に示す。プラスミドDNAを使用し、抗体タンパク質産生のためのCHO DG44細胞を形質転換した。
上記ヒンジ領域連結ペプチドG1/G3/Pro243Ala244Pro245+[Gly/Ser](配列番号9)を使用して、基本的には実施例3に記載されるようにCH2ドメイン欠失5E8(chB3F6ΔCH2)抗体を構築した。chB3F6は、それぞれヒト重鎖および軽鎖定常領域に融合されたマウス重鎖および軽鎖可変ドメインからなるキメラ抗−CRIPTOモノクローナル抗体である。そのヒンジ領域への正確な改変を、DNA配列決定分析により確認した。chB3F6軽鎖および重鎖の核酸配列およびアミノ酸配列を、それぞれ図32および図33に示す。プラスミドDNAを使用し、抗体タンパク質産生のためのCHO DG44細胞を形質転換した。
当業者は、日常的な実験しか使用せずに本明細書中に記載の本発明の特定の実施形態に対する多数の等価物を認識するか確認することができる。このような等価物は、以下の特許請求の範囲に含まれることが意図される。
Claims (33)
- 少なくとも2つの結合部位および少なくとも2本のポリペプチド鎖を有するポリペプチド二量体を含む組成物であって、該少なくとも2本のポリペプチド鎖が、少なくとも1つの免疫グロブリン重鎖部分と、合成連結ペプチドとを含み、該合成連結ペプチドは、配列番号9のアミノ酸配列および配列番号14のアミノ酸配列からなる群より選択され、90%を超える該ポリペプチド二量体が、少なくとも1つの鎖間ジスルフィド結合を介して結合されているポリペプチド鎖を含む、組成物。
- 少なくとも2つの結合部位および少なくとも2本のポリペプチド鎖を有するポリペプチド二量体を含む組成物であって、該少なくとも2本のポリペプチド鎖が、IgG1抗体アイソタイプに由来する少なくとも1つの免疫グロブリン重鎖部分と、合成連結ペプチドとを含み、該合成連結ペプチドが、配列番号9のアミノ酸配列および配列番号14のアミノ酸配列からなる群より選択され、90%を超える該ポリペプチド二量体が、少なくとも1つの鎖間ジスルフィド結合を介して結合されているポリペプチド鎖を含む、組成物。
- 前記ポリペプチド鎖のうちの少なくとも1本が、前記連結ペプチドを介してVL、VHまたはCH1ドメインに直接遺伝的に融合されたCH3ドメインを含む、請求項1または2に記載の組成物。
- 前記ポリペプチド鎖が、CH2ドメインの全てまたは部分を欠損している、請求項1または2に記載の組成物。
- 前記ポリペプチド二量体が、2つ以上の鎖間ジスルフィド結合を介して結合されているポリペプチド鎖を含む、請求項1または2に記載の組成物。
- 前記免疫グロブリン重鎖部分が、IgG1、IgG2、IgG3およびIgG4からなる群より選択されるアイソタイプの抗体に由来する、請求項1に記載の組成物。
- 前記結合部位が、個々に、抗原結合部位、レセプターのリガンド結合部分、およびリガンドのレセプター結合部分、からなる群より選択される、請求項1または2に記載の組成物。
- 前記ポリペプチド二量体が、4本のポリペプチド鎖を含み、そして該ポリペプチド鎖のうち2本が、少なくとも1つの重鎖部分および合成連結ペプチドを含む、請求項1または2に記載の組成物。
- 少なくとも2つの結合部位および少なくとも2本のポリペプチド鎖を有するポリペプチド二量体を含む組成物であって、該少なくとも2本のポリペプチド鎖が、少なくとも1つの免疫グロブリン重鎖部分と、合成連結ペプチドとを含み、該合成連結ペプチドは、配列番号9のアミノ酸配列および配列番号14のアミノ酸配列からなる群より選択され、90%を超える該ポリペプチド二量体が、少なくとも1つの鎖間ジスルフィド結合を介して結合されているポリペプチド鎖を含む、組成物。
- 少なくとも2つの結合部位および少なくとも2本のポリペプチド鎖を有するポリペプチド二量体を含む組成物であって、該少なくとも2本のポリペプチド鎖が、IgG1抗体アイソタイプに由来する少なくとも1つの免疫グロブリン重鎖部分と、合成連結ペプチドとを含み、該合成連結ペプチドは、配列番号9のアミノ酸配列および配列番号14のアミノ酸配列からなる群より選択され、90%を超える該ポリペプチド二量体が、少なくとも1つの鎖間ジスルフィド結合を介して結合されているポリペプチド鎖を含む、組成物。
- 少なくとも1本の前記ポリペプチド鎖が、前記連結ペプチドを介してVL、VHまたはCH1ドメインに直接結合されているCH3ドメインを含む、請求項9または10に記載の組成物。
- 前記結合部位が、個々に、抗原結合部位、レセプターのリガンド結合部分、およびリガンドのレセプター結合部分からなる群より選択される、請求項9または10に記載の組成物。
- 医薬としての使用のための、請求項1〜12のいずれか1項に記載の組成物。
- 結合分子での処置から恩恵を受ける被験体を処置するための医薬の製造における、請求項1〜12のいずれか1項に記載の組成物の使用。
- 前記被験体が、癌を罹患している、請求項14に記載の使用。
- 前記被験体が、リンパ腫を罹患している、請求項14に記載の使用。
- 前記被験体が、自己免疫疾患または自己免疫障害を罹患している、請求項14に記載の使用。
- 前記被験体が、炎症性疾患または炎症性障害を罹患している、請求項14に記載の使用。
- 請求項1、2、9または10のいずれか1項に記載のポリペプチド鎖をコードするヌクレオチド配列を含む、核酸分子であって、該ポリペプチド鎖は、免疫グロブリン重鎖部分と、合成連結ペプチドとを含み、該合成連結ペプチドは、配列番号9のアミノ酸配列および配列番号14のアミノ酸配列からなる群より選択される、核酸分子。
- 請求項19に記載の核酸分子を含む、宿主細胞。
- 配列番号9および14からなる群より選択されるアミノ酸配列を含む、連結ペプチド。
- 配列番号9および14からなる群より選択されるアミノ酸配列からなる、連結ペプチド。
- ポリペプチド鎖をコードする核酸分子であって、該核酸分子が、配列番号16、配列番号21、配列番号38、配列番号42、および配列番号46からなる群より選択されるヌクレオチド配列を含む、核酸分子。
- ポリペプチド鎖をコードする核酸分子であって、該核酸分子が、配列番号24のヌクレオチド配列を含む、核酸分子。
- 配列番号18、配列番号23、配列番号40、配列番号44、および配列番号47からなる群より選択されるアミノ酸配列を含む、ドメイン欠失抗体分子。
- 配列番号26のアミノ酸配列を含む、ドメイン欠失抗体分子。
- 少なくとも2つのポリペプチド鎖が少なくとも1つのジスルフィド結合によって結合されていないポリペプチド二量体の量に対して、該ポリペプチド鎖が少なくとも1つのジスルフィド結合によって結合されている該ポリペプチド二量体の量を増加させるための方法であって、該方法は、該ポリペプチド鎖が合成連結ペプチドを含むように該ポリペプチド二量体を操作する工程を包含し、該合成連結ペプチドは、配列番号9のアミノ酸配列および配列番号14のアミノ酸配列からなる群より選択され、該ポリペプチド二量体は少なくとも2つの結合部位を含み、該二量体の組成物中の90%を超える該ポリペプチド二量体が、少なくとも1つの鎖間ジスルフィド結合を介して結合されているポリペプチド鎖を含む、方法。
- 請求項27に記載の方法により作製される、組成物。
- 前記ポリペプチド二量体が、4本のポリペプチド鎖を含み、そして該ポリペプチド鎖のうちの2本が、少なくとも1つの重鎖部分および合成連結ペプチドを含む、請求項28に記載の組成物。
- 合成連結ペプチドを含むポリペプチドであって、該合成連結ペプチドは、配列番号9のアミノ酸配列および配列番号14のアミノ酸配列からなる群より選択され、該ポリペプチドは天然に生じるIgG3分子ではない、ポリペプチド。
- 前記ポリペプチドが、IgG4分子である、請求項30に記載のポリペプチド。
- 前記ポリペプチドが、VLA−4に結合する、請求項31に記載のポリペプチド。
- 細胞により産生されるIgG4分子の集団において、少なくとも1つのジスルフィド結合を介して結合されているポリペプチド鎖を含む二量体の量を増加させるための方法であって、該方法は、IgG4分子の集団において少なくとも1つのジスルフィド結合を介して結合されているポリペプチドを含む二量体の量が増加されるように、該細胞に合成連結ペプチドを含むIgG4分子を発現させる工程を包含し、該合成連結ペプチドは、配列番号9のアミノ酸配列および配列番号14のアミノ酸配列からなる群より選択される、方法。
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US48387703P | 2003-06-27 | 2003-06-27 | |
US60/483,877 | 2003-06-27 | ||
US50881003P | 2003-10-03 | 2003-10-03 | |
US60/508,810 | 2003-10-03 | ||
US51535103P | 2003-10-28 | 2003-10-28 | |
US60/515,351 | 2003-10-28 | ||
US51603003P | 2003-10-30 | 2003-10-30 | |
US60/516,030 | 2003-10-30 | ||
PCT/US2004/020944 WO2005000898A2 (en) | 2003-06-27 | 2004-06-28 | Use of hydrophobic-interaction-chromatography or hinge-region modifications for the production of homogeneous antibody-solutions |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010167646A Division JP2010273686A (ja) | 2003-06-27 | 2010-07-26 | 均質な抗体溶液の生成のための疎水性相互作用クロマトグラフィーまたはヒンジ領域改変の使用 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2007535296A JP2007535296A (ja) | 2007-12-06 |
JP2007535296A5 JP2007535296A5 (ja) | 2010-09-24 |
JP5091476B2 true JP5091476B2 (ja) | 2012-12-05 |
Family
ID=33556653
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006517784A Expired - Lifetime JP5091476B2 (ja) | 2003-06-27 | 2004-06-28 | 均質な抗体溶液の生成のための疎水性相互作用クロマトグラフィーまたはヒンジ領域改変の使用 |
JP2006517785A Expired - Fee Related JP5068072B2 (ja) | 2003-06-27 | 2004-06-28 | 連結ペプチドを含む改変された結合分子 |
JP2010167646A Withdrawn JP2010273686A (ja) | 2003-06-27 | 2010-07-26 | 均質な抗体溶液の生成のための疎水性相互作用クロマトグラフィーまたはヒンジ領域改変の使用 |
JP2010167609A Withdrawn JP2010280683A (ja) | 2003-06-27 | 2010-07-26 | 連結ペプチドを含む改変された結合分子 |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006517785A Expired - Fee Related JP5068072B2 (ja) | 2003-06-27 | 2004-06-28 | 連結ペプチドを含む改変された結合分子 |
JP2010167646A Withdrawn JP2010273686A (ja) | 2003-06-27 | 2010-07-26 | 均質な抗体溶液の生成のための疎水性相互作用クロマトグラフィーまたはヒンジ領域改変の使用 |
JP2010167609A Withdrawn JP2010280683A (ja) | 2003-06-27 | 2010-07-26 | 連結ペプチドを含む改変された結合分子 |
Country Status (7)
Country | Link |
---|---|
US (3) | US20050163782A1 (ja) |
EP (2) | EP1641826A2 (ja) |
JP (4) | JP5091476B2 (ja) |
AU (3) | AU2004252170B2 (ja) |
CA (2) | CA2529945A1 (ja) |
NZ (2) | NZ544924A (ja) |
WO (2) | WO2005000899A2 (ja) |
Families Citing this family (236)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6136311A (en) | 1996-05-06 | 2000-10-24 | Cornell Research Foundation, Inc. | Treatment and diagnosis of cancer |
US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
US8093357B2 (en) | 2002-03-01 | 2012-01-10 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
US8188231B2 (en) | 2002-09-27 | 2012-05-29 | Xencor, Inc. | Optimized FC variants |
US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
US20090010920A1 (en) | 2003-03-03 | 2009-01-08 | Xencor, Inc. | Fc Variants Having Decreased Affinity for FcyRIIb |
US8388955B2 (en) | 2003-03-03 | 2013-03-05 | Xencor, Inc. | Fc variants |
US8084582B2 (en) | 2003-03-03 | 2011-12-27 | Xencor, Inc. | Optimized anti-CD20 monoclonal antibodies having Fc variants |
US9051373B2 (en) | 2003-05-02 | 2015-06-09 | Xencor, Inc. | Optimized Fc variants |
EP1641826A2 (en) * | 2003-06-27 | 2006-04-05 | Biogen Idec MA Inc. | Use of hydrophobic-interaction-chromatography or hinge-region modifications for the production of homogeneous antibody-solutions |
US8101720B2 (en) | 2004-10-21 | 2012-01-24 | Xencor, Inc. | Immunoglobulin insertions, deletions and substitutions |
US9714282B2 (en) | 2003-09-26 | 2017-07-25 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
US20150010550A1 (en) | 2004-07-15 | 2015-01-08 | Xencor, Inc. | OPTIMIZED Fc VARIANTS |
US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8802820B2 (en) | 2004-11-12 | 2014-08-12 | Xencor, Inc. | Fc variants with altered binding to FcRn |
KR101027427B1 (ko) | 2004-11-12 | 2011-04-11 | 젠코어 인코포레이티드 | FcRn에 대하여 증가된 결합력을 갖는 Fc 변이체 |
US8546543B2 (en) | 2004-11-12 | 2013-10-01 | Xencor, Inc. | Fc variants that extend antibody half-life |
WO2006074397A2 (en) | 2005-01-05 | 2006-07-13 | Biogen Idec Ma Inc. | Cripto binding molecules |
WO2006074399A2 (en) * | 2005-01-05 | 2006-07-13 | Biogen Idec Ma Inc. | Multispecific binding molecules comprising connecting peptides |
WO2006116260A2 (en) | 2005-04-26 | 2006-11-02 | Medimmune, Inc. | Modulation of antibody effector function by hinge domain engineering |
EP1874821B1 (de) | 2005-04-26 | 2013-04-17 | Trion Pharma Gmbh | Kombination von antikörpern mit glukokortikoiden zur behandlung von krebs |
US8309690B2 (en) | 2005-07-01 | 2012-11-13 | Medimmune, Llc | Integrated approach for generating multidomain protein therapeutics |
UA97469C2 (uk) | 2005-07-25 | 2012-02-27 | Емерджент Продакт Дівелопмент Сіетл, Елелсі | Гуманізована специфічна до cd37 зв'язувальна молекула імуноглобуліну |
WO2007041635A2 (en) | 2005-10-03 | 2007-04-12 | Xencor, Inc. | Fc variants with optimized fc receptor binding properties |
JP4860703B2 (ja) | 2005-10-06 | 2012-01-25 | ゼンコー・インコーポレイテッド | 最適化された抗cd30抗体 |
AU2006304387A1 (en) | 2005-10-14 | 2007-04-26 | Medimmune, Llc | Cell display of antibody libraries |
AR056142A1 (es) * | 2005-10-21 | 2007-09-19 | Amgen Inc | Metodos para generar el anticuerpo igg monovalente |
NZ591252A (en) | 2006-03-17 | 2012-06-29 | Biogen Idec Inc | Methods of designing antibody or antigen binding fragments thereof with substituted non-covarying amino acids |
CA2646329C (en) | 2006-03-20 | 2018-07-03 | The Regents Of The University Of California | Engineered anti-prostate stem cell antigen (psca) antibodies for cancer targeting |
US20100278821A1 (en) | 2006-03-21 | 2010-11-04 | The Regents Of The University Of California | N-cadherin: target for cancer diagnosis and therapy |
AU2014200661B2 (en) * | 2006-06-12 | 2016-06-30 | Aptevo Research And Development Llc | Single-chain multivalent binding proteins with effector function |
NZ573646A (en) * | 2006-06-12 | 2012-04-27 | Wyeth Llc | Single-chain multivalent binding proteins with effector function |
PT2059536E (pt) | 2006-08-14 | 2014-04-14 | Xencor Inc | Anticorpos otimizados que visam cd19 |
US8497246B2 (en) | 2006-08-18 | 2013-07-30 | Armagen Technologies, Inc. | Methods for diagnosing and treating CNS disorders by trans-blood-brain barrier delivery of protein compositions |
WO2008036688A2 (en) | 2006-09-18 | 2008-03-27 | Xencor, Inc. | Optimized antibodies that target hm1.24 |
AU2008234248C1 (en) * | 2007-03-29 | 2015-01-22 | Genmab A/S | Bispecific antibodies and methods for production thereof |
JP5901877B2 (ja) | 2007-07-27 | 2016-04-13 | アーメイゲン・テクノロジーズ・インコーポレイテッドArmagen Technologies, Inc. | 中枢神経系のα−L−イデュロニダーゼ活性を増加させるための方法および組成物 |
US8940298B2 (en) | 2007-09-04 | 2015-01-27 | The Regents Of The University Of California | High affinity anti-prostate stem cell antigen (PSCA) antibodies for cancer targeting and detection |
JP5963341B2 (ja) * | 2007-09-14 | 2016-08-10 | アムジエン・インコーポレーテツド | 均質な抗体集団 |
EP2535349A1 (en) | 2007-09-26 | 2012-12-19 | UCB Pharma S.A. | Dual specificity antibody fusions |
WO2009043051A2 (en) * | 2007-09-27 | 2009-04-02 | Biogen Idec Ma Inc. | Cd23 binding molecules and methods of use thereof |
EP2209498A2 (en) * | 2007-10-03 | 2010-07-28 | Cornell University | Treatment of proliferative disorders using antibodies to psma |
US9464135B2 (en) | 2007-10-08 | 2016-10-11 | The Regents Of The University Of California | Epithelial membrane protein-2 (EMP2) and proliferative vitroretinopathy (PVR) |
US9266967B2 (en) | 2007-12-21 | 2016-02-23 | Hoffmann-La Roche, Inc. | Bivalent, bispecific antibodies |
US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
SI2235059T1 (sl) | 2007-12-26 | 2015-06-30 | Xencor, Inc. | Fc variante s spremenjeno vezjo na fcrn |
NZ603059A (en) | 2008-04-11 | 2014-07-25 | Emergent Product Dev Seattle | Cd37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
US20100069616A1 (en) * | 2008-08-06 | 2010-03-18 | The Regents Of The University Of California | Engineered antibody-nanoparticle conjugates |
US10407513B2 (en) | 2008-09-26 | 2019-09-10 | Ucb Biopharma Sprl | Biological products |
US8268314B2 (en) | 2008-10-08 | 2012-09-18 | Hoffmann-La Roche Inc. | Bispecific anti-VEGF/anti-ANG-2 antibodies |
WO2010079149A1 (de) * | 2009-01-09 | 2010-07-15 | Ipk Gatersleben | Fusionsantikörper |
JP2012515556A (ja) * | 2009-01-23 | 2012-07-12 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | 低下したエフェクタ機能を有する安定化Fcポリペプチドおよび使用方法 |
WO2010096394A2 (en) | 2009-02-17 | 2010-08-26 | Redwood Biosciences, Inc. | Aldehyde-tagged protein-based drug carriers and methods of use |
ES2712732T3 (es) * | 2009-02-17 | 2019-05-14 | Cornell Res Foundation Inc | Métodos y kits para el diagnóstico de cáncer y la predicción de valor terapéutico |
WO2010112194A1 (en) | 2009-04-02 | 2010-10-07 | F. Hoffmann-La Roche Ag | Antigen-binding polypeptides and multispecific antibodies comprising them |
BRPI1014089A2 (pt) | 2009-04-02 | 2016-04-19 | Roche Glycart Ag | anticorpos multiespecíficos que compreendem anticorpos de comprimento completo e fragmentos fab de cadeia simples |
JP5616428B2 (ja) | 2009-04-07 | 2014-10-29 | ロシュ グリクアート アクチェンゲゼルシャフト | 三価の二重特異性抗体 |
EP2417159A1 (en) | 2009-04-07 | 2012-02-15 | Roche Glycart AG | Bispecific anti-erbb-3/anti-c-met antibodies |
AU2010233995A1 (en) | 2009-04-07 | 2011-09-08 | Roche Glycart Ag | Bispecific anti-ErbB-2/anti-c-Met antibodies |
US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
WO2011028952A1 (en) | 2009-09-02 | 2011-03-10 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
NZ598962A (en) | 2009-09-16 | 2014-12-24 | Genentech Inc | Coiled coil and/or tether containing protein complexes and uses thereof |
EP2485761B1 (en) | 2009-10-09 | 2019-02-27 | Armagen, Inc. | Methods and compositions for increasing iduronate 2-sulfatase activity in the cns |
TW201120210A (en) * | 2009-11-05 | 2011-06-16 | Hoffmann La Roche | Glycosylated repeat-motif-molecule conjugates |
CA2782333C (en) | 2009-12-02 | 2019-06-04 | Imaginab, Inc. | J591 minibodies and cys-diabodies for targeting human prostate specific membrane antigen (psma) and methods for their use |
WO2011091078A2 (en) | 2010-01-19 | 2011-07-28 | Xencor, Inc. | Antibody fc variants with enhanced complement activity |
GB201005064D0 (en) | 2010-03-25 | 2010-05-12 | Ucb Pharma Sa | Biological products |
TWI426920B (zh) | 2010-03-26 | 2014-02-21 | Hoffmann La Roche | 雙專一性、雙價抗-vegf/抗-ang-2抗體 |
AR080793A1 (es) | 2010-03-26 | 2012-05-09 | Roche Glycart Ag | Anticuerpos biespecificos |
MX353144B (es) | 2010-04-20 | 2017-12-20 | Genmab As | Proteinas que contienen fc de anticuerpos heterodimericos y metodos para produccion de las mismas. |
EP2588631A4 (en) | 2010-07-01 | 2013-11-20 | Univ California | GENETIC MUTATION OF CK2 PROTEIN KINASE, AMPLIFICATIONS AND POLYMORPHISMS IN HUMAN CANCER, AND METHODS OF USE |
CA2807278A1 (en) | 2010-08-24 | 2012-03-01 | F. Hoffmann - La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
US9518132B2 (en) | 2010-11-09 | 2016-12-13 | Altimab Therapeutics, Inc. | Protein complexes for antigen binding and methods of use |
WO2012085111A1 (en) | 2010-12-23 | 2012-06-28 | F. Hoffmann-La Roche Ag | Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery |
RU2606016C2 (ru) | 2011-01-14 | 2017-01-10 | Редвуд Байосайнс, Инк. | Меченые альдегидом полипептиды иммуноглобулина и способы их применения |
MX341921B (es) | 2011-02-28 | 2016-09-07 | Hoffmann La Roche | Proteinas de union a antigeno. |
CA2824824A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Monovalent antigen binding proteins |
CN112028985A (zh) * | 2011-05-09 | 2020-12-04 | 米纳瓦生物技术公司 | 基因工程生长因子变异体 |
AU2012328322A1 (en) | 2011-10-27 | 2014-06-12 | Genmab A/S | Production of heterodimeric proteins |
WO2013119966A2 (en) | 2012-02-10 | 2013-08-15 | Genentech, Inc. | Single-chain antibodies and other heteromultimers |
AU2013244999A1 (en) | 2012-04-05 | 2014-09-25 | F. Hoffmann-La Roche Ag | Bispecific antibodies against human TWEAK and human IL17 and uses thereof |
US9745381B2 (en) * | 2012-05-18 | 2017-08-29 | Scott & White Healthcare (Swh) | Bispecific scFv immunofusion (BIf) |
EP2867253B1 (en) | 2012-06-27 | 2016-09-14 | F. Hoffmann-La Roche AG | Method for selection and production of tailor-made highly selective and multi-specific targeting entities containing at least two different binding entities and uses thereof |
WO2014001326A1 (en) | 2012-06-27 | 2014-01-03 | F. Hoffmann-La Roche Ag | Method for the selection and production of tailor-made, selective and multi-specific therapeutic molecules comprising at least two different targeting entities and uses thereof |
BR112014028368A2 (pt) | 2012-06-27 | 2017-11-14 | Hoffmann La Roche | método de produção de conjugado de região fc de anticorpo, conjugado de região fc de anticorpo e formulação farmacêutica |
CN104394886B (zh) | 2012-07-04 | 2017-05-24 | 弗·哈夫曼-拉罗切有限公司 | 抗茶碱抗体及使用方法 |
EP3339328A1 (en) | 2012-07-04 | 2018-06-27 | F. Hoffmann-La Roche AG | Anti-biotin antibodies and methods of use |
EP2869848B1 (en) | 2012-07-04 | 2016-09-21 | F. Hoffmann-La Roche AG | Covalently linked antigen-antibody conjugates |
EP2905290B1 (en) | 2012-10-05 | 2019-12-04 | Kyowa Kirin Co., Ltd. | Heterodimeric protein composition |
TWI682941B (zh) | 2013-02-01 | 2020-01-21 | 美商再生元醫藥公司 | 含嵌合恆定區之抗體 |
BR112015024926A2 (pt) * | 2013-04-16 | 2017-10-10 | Genentech Inc | composições, artigo de fabricação, métodos para tratar um paciente com câncer, para avaliar uma composição, para avaliar a atividade biológica, para produzir uma composição e para avaliar a fragmentação de uma composição e variante de pertuzumabe |
AR096713A1 (es) | 2013-06-25 | 2016-01-27 | Cadila Healthcare Ltd | Proceso de purificación para anticuerpos monoclonales |
CN104341504B (zh) | 2013-08-06 | 2017-10-24 | 百奥泰生物科技(广州)有限公司 | 双特异性抗体 |
BR112016006929A2 (pt) | 2013-10-11 | 2017-09-19 | Hoffmann La Roche | Anticorpo, ácido nucleico, vetor de expressão, célula hospedeira, métodos de preparação de anticorpo, de tratamento de pacientes e de geração de um anticorpo, composição farmacêutica e uso do anticorpo |
GB2519786A (en) * | 2013-10-30 | 2015-05-06 | Sergej Michailovic Kiprijanov | Multivalent antigen-binding protein molecules |
WO2015079977A1 (ja) * | 2013-11-26 | 2015-06-04 | シャープ株式会社 | 抗体分離方法、抗体評価方法、医薬の評価方法、及び、抗体の2次元電気泳動用キット |
CN105899533B (zh) | 2013-12-20 | 2019-10-11 | 豪夫迈·罗氏有限公司 | 人源化的抗-Tau(pS422)抗体和使用方法 |
JP6476194B2 (ja) | 2014-01-03 | 2019-02-27 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 二重特異性抗ハプテン/抗血液脳関門受容体抗体、それらの複合体、及び血液脳関門シャトルとしてのそれらの使用 |
MX2016008191A (es) | 2014-01-03 | 2017-11-16 | Hoffmann La Roche | Conjugados de toxina polipeptidica-anticuerpo unidos covalentemente. |
BR112016012666A2 (pt) | 2014-01-03 | 2017-09-26 | Hoffmann La Roche | conjugado, anticorpos, formulação farmacêutica e usos de conjugado |
JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
EP3116909B1 (en) | 2014-03-14 | 2019-11-13 | Novartis Ag | Antibody molecules to lag-3 and uses thereof |
EP3593812A3 (en) | 2014-03-15 | 2020-05-27 | Novartis AG | Treatment of cancer using chimeric antigen receptor |
TWI701042B (zh) | 2014-03-19 | 2020-08-11 | 美商再生元醫藥公司 | 用於腫瘤治療之方法及抗體組成物 |
AR100978A1 (es) | 2014-06-26 | 2016-11-16 | Hoffmann La Roche | LANZADERAS CEREBRALES DE ANTICUERPO HUMANIZADO ANTI-Tau(pS422) Y USOS DE LAS MISMAS |
DK3160513T3 (da) | 2014-06-30 | 2020-04-06 | Glykos Finland Oy | Saccharidderivat af en toksisk payload og antistofkonjugater deraf |
AU2015283704A1 (en) | 2014-07-01 | 2016-12-15 | Pfizer Inc. | Bispecific heterodimeric diabodies and uses thereof |
JP2017528433A (ja) | 2014-07-21 | 2017-09-28 | ノバルティス アーゲー | 低い免疫増強用量のmTOR阻害剤とCARの組み合わせ |
US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
TWI750110B (zh) | 2014-07-21 | 2021-12-21 | 瑞士商諾華公司 | 使用人類化抗-bcma嵌合抗原受體治療癌症 |
CN112481283A (zh) | 2014-07-21 | 2021-03-12 | 诺华股份有限公司 | 使用cd33嵌合抗原受体治疗癌症 |
EP3174546B1 (en) | 2014-07-31 | 2019-10-30 | Novartis AG | Subset-optimized chimeric antigen receptor-containing t-cells |
JP6919118B2 (ja) | 2014-08-14 | 2021-08-18 | ノバルティス アーゲー | GFRα−4キメラ抗原受容体を用いる癌の治療 |
MY189028A (en) | 2014-08-19 | 2022-01-20 | Novartis Ag | Anti-cd123 chimeric antigen receptor (car) for use in cancer treatment |
AU2015317608B2 (en) | 2014-09-17 | 2021-03-11 | Novartis Ag | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
EP4245376A3 (en) | 2014-10-14 | 2023-12-13 | Novartis AG | Antibody molecules to pd-l1 and uses thereof |
PL3221359T3 (pl) | 2014-11-17 | 2020-11-16 | Regeneron Pharmaceuticals, Inc. | Sposoby leczenia nowotworów przy użyciu dwuswoistego przeciwciała CD3XCD20 |
WO2016090034A2 (en) | 2014-12-03 | 2016-06-09 | Novartis Ag | Methods for b cell preconditioning in car therapy |
WO2016087416A1 (en) | 2014-12-03 | 2016-06-09 | F. Hoffmann-La Roche Ag | Multispecific antibodies |
US10865253B2 (en) | 2014-12-19 | 2020-12-15 | Genmab A/S | Rodent bispecific heterodimeric proteins |
US10538589B2 (en) * | 2015-01-14 | 2020-01-21 | Armagen Inc. | Methods and compositions for increasing N-acetylglucosaminidase (NAGLU) activity in the CNS using a fusion antibody comprising an anti-human insulin receptor antibody and NAGLU |
AU2016215205B2 (en) | 2015-02-05 | 2021-10-21 | Molecular Templates, Inc. | Multivalent CD20-binding molecules comprising shiga toxin a subunit effector regions and enriched compositions thereof |
AU2016242866B2 (en) | 2015-03-30 | 2021-06-03 | Regeneron Pharmaceuticals, Inc. | Heavy chain constant regions with reduced binding to FC gamma receptors |
SI3280729T1 (sl) | 2015-04-08 | 2022-09-30 | Novartis Ag | Terapije CD20, terapije CD22 in kombinacija terapij s celico, ki izraža himerni antigenski receptor CD19 (CAR) |
WO2016172583A1 (en) | 2015-04-23 | 2016-10-27 | Novartis Ag | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
WO2016207245A1 (en) | 2015-06-24 | 2016-12-29 | F. Hoffmann-La Roche Ag | Humanized anti-tau(ps422) antibodies and methods of use |
EP3313871A1 (en) | 2015-06-26 | 2018-05-02 | Institute for Research in Biomedicine | Proteins comprising a mutated lair-1 fragment and uses thereof |
LT3317301T (lt) | 2015-07-29 | 2021-07-26 | Novartis Ag | Kombinuotos terapijos, apimančios antikūno molekules prieš lag-3 |
US20180207273A1 (en) | 2015-07-29 | 2018-07-26 | Novartis Ag | Combination therapies comprising antibody molecules to tim-3 |
EP3328418A1 (en) | 2015-07-29 | 2018-06-06 | Novartis AG | Combination therapies comprising antibody molecules to pd-1 |
AU2016304764C1 (en) | 2015-08-07 | 2023-06-01 | Imaginab, Inc. | Antigen binding constructs to target molecules |
US11352426B2 (en) | 2015-09-21 | 2022-06-07 | Aptevo Research And Development Llc | CD3 binding polypeptides |
IL299114A (en) * | 2015-10-06 | 2023-02-01 | Hope City | Chimeric antigen receptors targeting PSCA |
WO2017059878A1 (en) | 2015-10-07 | 2017-04-13 | Humabs Biomed Sa | Antibodies that potently neutralize hepatitis b virus and uses thereof |
EP3819310A1 (en) | 2015-10-25 | 2021-05-12 | Sanofi | Trispecific and/or trivalent binding proteins for prevention or treatment of hiv infection |
MX2018007423A (es) | 2015-12-17 | 2018-11-09 | Novartis Ag | Moleculas de anticuerpo que se unen a pd-1 y usos de las mismas. |
US20200261573A1 (en) | 2015-12-17 | 2020-08-20 | Novartis Ag | Combination of c-met inhibitor with antibody molecule to pd-1 and uses thereof |
EP3851457A1 (en) | 2016-01-21 | 2021-07-21 | Novartis AG | Multispecific molecules targeting cll-1 |
WO2017149515A1 (en) | 2016-03-04 | 2017-09-08 | Novartis Ag | Cells expressing multiple chimeric antigen receptor (car) molecules and uses therefore |
EP3432924A1 (en) | 2016-03-23 | 2019-01-30 | Novartis AG | Cell secreted minibodies and uses thereof |
MY192090A (en) | 2016-04-13 | 2022-07-26 | Sanofi Sa | Trispecific and/or trivalent binding proteins |
BR112018071096A2 (pt) | 2016-04-15 | 2019-02-26 | Novartis Ag | composições e métodos para a expressão da proteína seletiva |
CN109071634A (zh) | 2016-04-26 | 2018-12-21 | R.P.谢勒技术有限责任公司 | 抗体偶联物及其制备和使用方法 |
US20210177896A1 (en) | 2016-06-02 | 2021-06-17 | Novartis Ag | Therapeutic regimens for chimeric antigen receptor (car)- expressing cells |
WO2018010789A1 (en) * | 2016-07-13 | 2018-01-18 | Humabs Biomed Sa | Novel antibodies specifically binding to zika virus epitopes and uses thereof |
US20190336504A1 (en) | 2016-07-15 | 2019-11-07 | Novartis Ag | Treatment and prevention of cytokine release syndrome using a chimeric antigen receptor in combination with a kinase inhibitor |
KR20230100748A (ko) | 2016-07-28 | 2023-07-05 | 노파르티스 아게 | 키메라 항원 수용체 및 pd-1 억제제의 조합 요법 |
MX2019001469A (es) | 2016-08-01 | 2019-10-02 | Novartis Ag | Tratamiento del cáncer usando un receptor de antígeno quimérico en combinación con un inhibidor de una molécula de macrófago pro- m2. |
MY196321A (en) | 2016-08-16 | 2023-03-24 | Regeneron Pharma | Methods for Quantitating Individual Antibodies From a Mixture |
BR112019005333A2 (pt) | 2016-09-21 | 2019-06-11 | Aptevo Research And Development Llc | proteínas de ligação a cd123 e composições e métodos relacionados |
TW202340473A (zh) | 2016-10-07 | 2023-10-16 | 瑞士商諾華公司 | 利用嵌合抗原受體之癌症治療 |
WO2018081203A1 (en) | 2016-10-25 | 2018-05-03 | Regeneron Pharmaceuticals, Inc. | Methods and systems for chromatography data analysis |
AU2018213194B2 (en) | 2017-01-25 | 2023-01-12 | Molecular Templates, Inc. | Cell-targeting molecules comprising de-immunized, Shiga toxin A Subunit effectors and CD8+ T-cell epitopes |
WO2018140725A1 (en) | 2017-01-26 | 2018-08-02 | Novartis Ag | Cd28 compositions and methods for chimeric antigen receptor therapy |
WO2018147960A1 (en) | 2017-02-08 | 2018-08-16 | Imaginab, Inc. | Extension sequences for diabodies |
US20200048359A1 (en) | 2017-02-28 | 2020-02-13 | Novartis Ag | Shp inhibitor compositions and uses for chimeric antigen receptor therapy |
EA201892312A1 (ru) | 2017-03-17 | 2019-04-30 | Санофи | Триспецифические и/или тривалентные связывающие белки |
US20200093909A1 (en) | 2017-04-19 | 2020-03-26 | Institute For Research In Biomedicine | Plasmodium sporozoite npdp peptides as vaccine and target novel malaria vaccines and antibodies binding to |
WO2018201056A1 (en) | 2017-04-28 | 2018-11-01 | Novartis Ag | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
WO2018201051A1 (en) | 2017-04-28 | 2018-11-01 | Novartis Ag | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
PE20200717A1 (es) | 2017-06-22 | 2020-07-21 | Novartis Ag | Moleculas de anticuerpo que se unen a cd73 y usos de las mismas |
EP3645037A1 (en) | 2017-06-27 | 2020-05-06 | Novartis AG | Dosage regimens for anti-tim-3 antibodies and uses thereof |
KR20200035966A (ko) | 2017-07-11 | 2020-04-06 | 콤파스 테라퓨틱스 엘엘씨 | 인간 cd137에 결합하는 작동자 항체 및 이의 용도 |
US20200172617A1 (en) | 2017-07-20 | 2020-06-04 | Novartis Ag | Dosage regimens of anti-lag-3 antibodies and uses thereof |
WO2019024979A1 (en) | 2017-07-31 | 2019-02-07 | Institute For Research In Biomedicine | FUNCTIONAL DOMAIN ANTIBODIES IN THE ELBOW REGION |
WO2019042555A1 (en) | 2017-08-31 | 2019-03-07 | Humabs Biomed Sa | MULTISPECIFIC ANTIBODIES SPECIFICALLY BINDING TO ZIKA VIRUS EPITOPES AND USES THEREOF |
EP4249068A3 (en) | 2017-10-10 | 2023-11-22 | Sanofi | Anti-cd38 antibodies and combinations with anti-cd3 and anti-cd28 antibodies |
EP3697441B1 (en) | 2017-10-20 | 2023-06-07 | F. Hoffmann-La Roche AG | Method for generating multispecific antibodies from monospecific antibodies |
BR112020007736A2 (pt) | 2017-10-30 | 2020-10-20 | F. Hoffmann-La Roche Ag | composição e método de tratamento |
WO2019089798A1 (en) | 2017-10-31 | 2019-05-09 | Novartis Ag | Anti-car compositions and methods |
WO2019089753A2 (en) | 2017-10-31 | 2019-05-09 | Compass Therapeutics Llc | Cd137 antibodies and pd-1 antagonists and uses thereof |
MX2020004756A (es) | 2017-11-16 | 2020-08-20 | Novartis Ag | Terapias de combinacion. |
EP3713961A2 (en) | 2017-11-20 | 2020-09-30 | Compass Therapeutics LLC | Cd137 antibodies and tumor antigen-targeting antibodies and uses thereof |
AU2019215031A1 (en) | 2018-01-31 | 2020-08-20 | Novartis Ag | Combination therapy using a chimeric antigen receptor |
US20210147547A1 (en) | 2018-04-13 | 2021-05-20 | Novartis Ag | Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof |
EP3784351A1 (en) | 2018-04-27 | 2021-03-03 | Novartis AG | Car t cell therapies with enhanced efficacy |
CA3099308A1 (en) | 2018-05-21 | 2019-11-28 | Compass Therapeutics Llc | Compositions and methods for enhancing the killing of target cells by nk cells |
WO2019226658A1 (en) | 2018-05-21 | 2019-11-28 | Compass Therapeutics Llc | Multispecific antigen-binding compositions and methods of use |
US20210213063A1 (en) | 2018-05-25 | 2021-07-15 | Novartis Ag | Combination therapy with chimeric antigen receptor (car) therapies |
US20210214459A1 (en) | 2018-05-31 | 2021-07-15 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
KR20210020932A (ko) | 2018-06-13 | 2021-02-24 | 노파르티스 아게 | Bcma 키메라 항원 수용체 및 이의 용도 |
PE20210418A1 (es) | 2018-06-19 | 2021-03-08 | Atarga Llc | Moleculas de anticuerpo de componente de complemento 5 y sus usos |
TW202005694A (zh) | 2018-07-02 | 2020-02-01 | 美商里珍納龍藥品有限公司 | 自混合物製備多肽之系統及方法 |
AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
WO2020021465A1 (en) | 2018-07-25 | 2020-01-30 | Advanced Accelerator Applications (Italy) S.R.L. | Method of treatment of neuroendocrine tumors |
US20210308184A1 (en) * | 2018-08-01 | 2021-10-07 | City Of Hope | Tag72 targeted chimeric antigen receptor modified t cells for treatment of tag72-positive tumors |
CA3110513A1 (en) | 2018-08-31 | 2020-03-05 | Regeneron Pharmaceuticals, Inc. | Dosing strategy that mitigates cytokine release syndrome for cd3/c20 bispecific antibodies |
JP7462621B2 (ja) | 2018-10-09 | 2024-04-05 | サノフイ | 三重特異性抗cd38、抗cd28、および抗cd3結合タンパク質ならびにウイルス感染を処置するための使用方法 |
WO2020078568A1 (en) | 2018-10-19 | 2020-04-23 | Humabs Biomed Sa | Antibodies and methods for treatment of lyssavirus infection |
AU2019379576A1 (en) | 2018-11-13 | 2021-06-03 | Compass Therapeutics Llc | Multispecific binding constructs against checkpoint molecules and uses thereof |
PT3898668T (pt) | 2018-12-19 | 2023-12-06 | Humabs Biomed Sa | Anticorpos que neutralizam o vírus da hepatite b e suas utilizações |
WO2020128892A1 (en) | 2018-12-20 | 2020-06-25 | Novartis Ag | Extended low dose regimens for mdm2 inhibitors |
LT3897672T (lt) | 2018-12-20 | 2023-11-10 | Vir Biotechnology, Inc. | Kombinuota hbv terapija |
KR20210106437A (ko) | 2018-12-20 | 2021-08-30 | 노파르티스 아게 | 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체를 포함하는 투약 요법 및 약학적 조합물 |
KR20210118945A (ko) | 2019-02-15 | 2021-10-01 | 유니버시티 오브 써던 캘리포니아 | Lym-1 및 lym-2 항체 조성물 및 개선된 car 구성물 |
US20220144807A1 (en) | 2019-02-15 | 2022-05-12 | Novartis Ag | 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
EP3924055B1 (en) | 2019-02-15 | 2024-04-03 | Novartis AG | Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
US10871640B2 (en) | 2019-02-15 | 2020-12-22 | Perkinelmer Cellular Technologies Germany Gmbh | Methods and systems for automated imaging of three-dimensional objects |
WO2020172553A1 (en) | 2019-02-22 | 2020-08-27 | Novartis Ag | Combination therapies of egfrviii chimeric antigen receptors and pd-1 inhibitors |
AU2020253833A1 (en) | 2019-03-29 | 2021-10-28 | Atarga, Llc | Anti FGF23 antibody |
US11613576B2 (en) | 2019-04-09 | 2023-03-28 | Sanofi | Trispecific binding proteins, methods, and uses thereof |
WO2020221451A1 (en) | 2019-04-30 | 2020-11-05 | Humabs Biomed Sa | Antibodies binding to plasmodium circumsporozoite protein and uses thereof |
EP3757127A1 (en) | 2019-06-28 | 2020-12-30 | Institute for Research in Biomedicine | Deimmunized antibodies binding to alpha-4 integrin and uses thereof |
CA3152511A1 (en) | 2019-08-29 | 2021-03-04 | Vir Biotechnology, Inc. | Antibody compositions and methods for treating hepatitis b virus infection |
WO2021079195A1 (en) | 2019-10-21 | 2021-04-29 | Novartis Ag | Tim-3 inhibitors and uses thereof |
BR112022007376A2 (pt) | 2019-10-21 | 2022-07-05 | Novartis Ag | Terapias de combinação com venetoclax e inibidores de tim-3 |
US20210155671A1 (en) | 2019-11-24 | 2021-05-27 | Molecular Templates, Inc. | Uses of cd20-binding molecules and additional therapeutic agents |
EP4065158A2 (en) | 2019-11-26 | 2022-10-05 | Novartis AG | Chimeric antigen receptors binding bcma and cd19 and uses thereof |
WO2021123996A1 (en) | 2019-12-20 | 2021-06-24 | Novartis Ag | Uses of anti-tgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases |
EP4090762A1 (en) | 2020-01-17 | 2022-11-23 | Becton, Dickinson and Company | Methods and compositions for single cell secretomics |
JP2023510393A (ja) | 2020-01-17 | 2023-03-13 | ノバルティス アーゲー | 骨髄異形成症候群または慢性骨髄単球性白血病の処置に使用するためのtim-3阻害剤と低メチル化剤とを含む組合せ |
EP4110377A2 (en) | 2020-02-27 | 2023-01-04 | Novartis AG | Methods of making chimeric antigen receptor-expressing cells |
GB202007842D0 (en) | 2020-05-26 | 2020-07-08 | Quell Therapeutics Ltd | Polypeptide useful in adoptive cell therapy |
CN115916199A (zh) | 2020-06-23 | 2023-04-04 | 诺华股份有限公司 | 包含3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物的给药方案 |
BR112022026316A2 (pt) | 2020-06-24 | 2023-03-07 | Vir Biotechnology Inc | Anticorpos neutralizantes do vírus da hepatite b engenheirados e usos dos mesmos |
IL299586A (en) | 2020-07-16 | 2023-03-01 | Novartis Ag | Anti-betacellulin antibodies, their fragments, and multispecific binding molecules |
WO2022026592A2 (en) | 2020-07-28 | 2022-02-03 | Celltas Bio, Inc. | Antibody molecules to coronavirus and uses thereof |
US20230271940A1 (en) | 2020-08-03 | 2023-08-31 | Novartis Ag | Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
GB202013477D0 (en) | 2020-08-27 | 2020-10-14 | Quell Therapeutics Ltd | Nucleic acid constructs for expressing polypeptides in cells |
US20230338587A1 (en) | 2020-08-31 | 2023-10-26 | Advanced Accelerator Applications International Sa | Method of treating psma-expressing cancers |
WO2022043557A1 (en) | 2020-08-31 | 2022-03-03 | Advanced Accelerator Applications International Sa | Method of treating psma-expressing cancers |
JP2023547499A (ja) | 2020-11-06 | 2023-11-10 | ノバルティス アーゲー | 抗体Fc変異体 |
CA3198447A1 (en) | 2020-11-13 | 2022-05-19 | Novartis Ag | Combination therapies with chimeric antigen receptor (car)-expressing cells |
US20240034772A1 (en) | 2020-12-08 | 2024-02-01 | Humabs Biomed Sa | Antibodies binding to f-protein of metapneumovirus and uses thereof |
US20240092872A1 (en) | 2021-01-26 | 2024-03-21 | Vir Biotechnology, Inc. | Compositions and methods for treating hepatitis b virus infection |
JP2024505049A (ja) | 2021-01-29 | 2024-02-02 | ノバルティス アーゲー | 抗cd73及び抗entpd2抗体のための投与方式並びにその使用 |
TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途 |
AR125874A1 (es) | 2021-05-18 | 2023-08-23 | Novartis Ag | Terapias de combinación |
WO2023036774A1 (en) | 2021-09-07 | 2023-03-16 | Institute For Research In Biomedicine | Antibodies binding to tetanus toxin and uses thereof |
WO2023044483A2 (en) | 2021-09-20 | 2023-03-23 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of her2 positive cancer |
WO2023092004A1 (en) | 2021-11-17 | 2023-05-25 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of tau-related disorders |
US20230383010A1 (en) | 2022-02-07 | 2023-11-30 | Visterra, Inc. | Anti-idiotype antibody molecules and uses thereof |
WO2023220695A2 (en) | 2022-05-13 | 2023-11-16 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of her2 positive cancer |
WO2024030976A2 (en) | 2022-08-03 | 2024-02-08 | Voyager Therapeutics, Inc. | Compositions and methods for crossing the blood brain barrier |
Family Cites Families (117)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4485045A (en) * | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
US4816567A (en) * | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4544545A (en) * | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
NZ212207A (en) | 1984-05-31 | 1991-07-26 | Genentech Inc | Recombinant lymphotoxin |
US5206344A (en) * | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
US5618920A (en) * | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
GB8529014D0 (en) * | 1985-11-25 | 1986-01-02 | Biogen Nv | Enhanced secretion of heterologous proteins |
EP0307434B2 (en) * | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
EP0284898A3 (de) * | 1987-04-02 | 1990-06-27 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Hinge-Peptid, Verfahren zu seiner Herstellung und seine Verwendung zur Herstellung synthetischer Immunogene |
US5892019A (en) * | 1987-07-15 | 1999-04-06 | The United States Of America, As Represented By The Department Of Health And Human Services | Production of a single-gene-encoded immunoglobulin |
US5677425A (en) * | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
GB8720833D0 (en) * | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
JP3095168B2 (ja) | 1988-02-05 | 2000-10-03 | エル. モリソン,シェリー | ドメイン‐変性不変部を有する抗体 |
DE68928427T2 (de) * | 1988-09-15 | 1998-06-04 | Univ Columbia | Antikörper mit modifiziertem Kohlenhydratgehalt und Verfahren zur Herstellung und Verwendung |
US6051225A (en) * | 1988-10-19 | 2000-04-18 | The Dow Chemical Company | Family of high affinity, modified antibodies for cancer treatment |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5714149A (en) * | 1989-02-10 | 1998-02-03 | Celltech Therapeutics Limited | Crosslinked antibodies and processes for their preparation |
US5225538A (en) * | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
US5166322A (en) * | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
GB8916400D0 (en) * | 1989-07-18 | 1989-09-06 | Dynal As | Modified igg3 |
US5208020A (en) * | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5859205A (en) * | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
US6552170B1 (en) * | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
US6495137B1 (en) * | 1990-04-19 | 2002-12-17 | The Dow Chemical Company | Humanized anti-tag-72 monoclonal antibodies using human subgroup 4 kappa light chains |
US5976531A (en) * | 1990-04-19 | 1999-11-02 | The Dow Chemical Company | Composite antibodies of human subgroup IV light chain capable of binding to tag-72 |
GB9009106D0 (en) * | 1990-04-23 | 1990-06-20 | 3I Res Expl Ltd | Processes and intermediates for synthetic antibody derivatives |
US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
US7030080B2 (en) * | 1990-06-27 | 2006-04-18 | Biogen, Inc. | Lymphotoxin-β, lymphotoxin-β complexes, pharmaceutical preparations and therapeutic uses thereof |
US5795964A (en) * | 1990-06-27 | 1998-08-18 | Biogen, Inc. | Lymphotoxin-beta and lymphotoxin-beta complexes |
WO1992000329A1 (en) * | 1990-06-27 | 1992-01-09 | Biogen, Inc. | Surface complexed lymphotoxin |
DE4111283A1 (de) * | 1991-04-08 | 1992-10-15 | Basf Ag | Strahlungsempfindliches gemisch, enthaltend saeurelabile gruppierungen und verfahren zur herstellung von reliefmustern und reliefbildern |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
DE4118120A1 (de) * | 1991-06-03 | 1992-12-10 | Behringwerke Ag | Tetravalente bispezifische rezeptoren, ihre herstellung und verwendung |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
US20020037558A1 (en) * | 1991-10-23 | 2002-03-28 | Kin-Ming Lo | E.coli produced immunoglobulin constructs |
US6329507B1 (en) * | 1992-08-21 | 2001-12-11 | The Dow Chemical Company | Dimer and multimer forms of single chain polypeptides |
DE69232604T2 (de) | 1992-11-04 | 2002-11-07 | City Of Hope Duarte | Antikörperkonstrukte |
CA2150249A1 (en) | 1992-12-04 | 1994-06-23 | Jeffrey Browning | Lymphotoxin-.beta., lymphotoxin-.beta. complexes, pharmaceutical preparations and therapeutic uses thereof |
SG55079A1 (en) * | 1992-12-11 | 1998-12-21 | Dow Chemical Co | Multivalent single chain antibodies |
IL108776A (en) | 1993-03-11 | 1999-11-30 | Genentech Inc | A method of dissolving a cell or inhibiting cell growth, a bispecific molecule that binds FNT-1R and an SAF antibody, a medical preparation that contains it and its use |
JPH08511420A (ja) | 1993-06-16 | 1996-12-03 | セルテック・セラピューテイクス・リミテッド | 抗 体 |
WO1995009917A1 (en) | 1993-10-07 | 1995-04-13 | The Regents Of The University Of California | Genetically engineered bispecific tetravalent antibodies |
US5429746A (en) | 1994-02-22 | 1995-07-04 | Smith Kline Beecham Corporation | Antibody purification |
US6312691B1 (en) * | 1996-01-26 | 2001-11-06 | Jeffrey L. Browning | Lymphotoxin-α/β complexes and anti-lympotoxin-β receptor antibodies as anti-tumor agents |
SK286497B6 (sk) | 1995-01-26 | 2008-11-06 | Biogen Idec Ma, Inc. | Zmes LT-alfa/beta heteromérneho komplexu a/alebo najmenej jedného LT-beta-R aktivujúceho činidla, farmaceutický prostriedok, LT-beta-R aktivujúce činidlo a spôsob jeho výberu |
US5731168A (en) * | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US5641870A (en) * | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
US5925351A (en) * | 1995-07-21 | 1999-07-20 | Biogen, Inc. | Soluble lymphotoxin-β receptors and anti-lymphotoxin receptor and ligand antibodies as therapeutic agents for the treatment of immunological disease |
EP0861440A1 (en) * | 1995-09-22 | 1998-09-02 | Immunomedics, Inc. | Recombinant proteins having multiple disulfide bonds and thiol-substituted conjugates thereof |
US5834597A (en) * | 1996-05-20 | 1998-11-10 | Protein Design Labs, Inc. | Mutated nonactivating IgG2 domains and anti CD3 antibodies incorporating the same |
CA2262405A1 (en) | 1996-08-02 | 1998-02-12 | Bristol-Myers Squibb Company | A method for inhibiting immunoglobulin-induced toxicity resulting from the use of immunoglobulins in therapy and in vivo diagnosis |
US7247302B1 (en) * | 1996-08-02 | 2007-07-24 | Bristol-Myers Squibb Company | Method for inhibiting immunoglobulin-induced toxicity resulting from the use of immunoglobulins in therapy and in vivo diagnosis |
US7255854B1 (en) * | 1996-10-25 | 2007-08-14 | Biogen, Inc. | Use of lymphotoxin-β receptor blocking agents for the treatment of antibody mediated immunological diseases |
US6348581B1 (en) * | 1996-10-31 | 2002-02-19 | The Dow Chemical Company | High affinity humanized anti-TAG-72 monoclonalantibodies |
WO1998023289A1 (en) | 1996-11-27 | 1998-06-04 | The General Hospital Corporation | MODULATION OF IgG BINDING TO FcRn |
US6063905A (en) * | 1997-01-07 | 2000-05-16 | Board Of Regents, The University Of Texas System | Recombinant human IGA-J. chain dimer |
US6011138A (en) | 1997-02-20 | 2000-01-04 | Idec Pharmaceuticals Corporation | Gamma-1 anti-human CD23 monoclonal antibodies |
JP4128227B2 (ja) * | 1997-03-14 | 2008-07-30 | バイオジェン・アイデック・インコーポレイテッド | 哺乳類細胞内の特定部位に相同組換えによって遺伝子を組み込む方法とそれを実施するためのベクター |
US20020062010A1 (en) * | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
US20030207346A1 (en) * | 1997-05-02 | 2003-11-06 | William R. Arathoon | Method for making multispecific antibodies having heteromultimeric and common components |
ES2258817T3 (es) | 1997-05-21 | 2006-09-01 | Biovation Limited | Metodo para la produccion de proteinas no inmunogenas. |
US20030060444A1 (en) * | 1997-06-25 | 2003-03-27 | Celltech Therapeutics, Ltd. | Cell activation process and reagents therefor |
US6165476A (en) * | 1997-07-10 | 2000-12-26 | Beth Israel Deaconess Medical Center | Fusion proteins with an immunoglobulin hinge region linker |
GB9720054D0 (en) * | 1997-09-19 | 1997-11-19 | Celltech Therapeutics Ltd | Biological products |
AUPO930697A0 (en) | 1997-09-19 | 1997-10-09 | Walter And Eliza Hall Institute Of Medical Research, The | Catalytic antibodies and a method of producing same |
CA2315944A1 (en) * | 1997-12-24 | 1999-07-08 | Diatech Pty. Ltd. | Bifunctional molecules |
BR9908214A (pt) | 1998-01-30 | 2000-11-28 | Biogen Inc | Tratamento para linfomas foliculares utilizando inibidores da via da linfotoxina (lt) |
US7060667B1 (en) * | 1998-01-30 | 2006-06-13 | Biogen Idec Ma, Inc. | Treatment of follicular lymphomas using inhibitors of the LT pathway |
HUP9900956A2 (hu) * | 1998-04-09 | 2002-04-29 | Aventis Pharma Deutschland Gmbh. | Egyláncú, több antigéntkötőhely kialakítására képes molekulák, előállításuk és alkalmazásuk |
US6284536B1 (en) * | 1998-04-20 | 2001-09-04 | The Regents Of The University Of California | Modified immunoglobin molecules and methods for use thereof |
GB9809951D0 (en) | 1998-05-08 | 1998-07-08 | Univ Cambridge Tech | Binding molecules |
GB9809839D0 (en) | 1998-05-09 | 1998-07-08 | Glaxo Group Ltd | Antibody |
HUP0103563A3 (en) * | 1998-08-31 | 2004-04-28 | Biogen Idec Ma Inc Cambridge | Method of modulating memory effector t-cells and compositions |
DE69931944T2 (de) * | 1998-10-09 | 2007-02-08 | Biogen Idec Ma Inc., Cambridge | Umkehr des viral-induzierten systemischen schocks und des atemnotsyndroms durch blockierung des lymphotoxin-beta- aktivierungsweges |
US6576746B2 (en) * | 1998-10-13 | 2003-06-10 | Immunomedics, Inc. | Site-specific labeling of disulfide-containing targeting vectors |
EP1051432B1 (en) | 1998-12-08 | 2007-01-24 | Biovation Limited | Method for reducing immunogenicity of proteins |
US6737056B1 (en) * | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
WO2000052204A2 (en) * | 1999-02-22 | 2000-09-08 | Orntoft Torben F | Gene expression in bladder tumors |
CN1413220A (zh) | 1999-10-29 | 2003-04-23 | 杰南技术公司 | 抗前列腺干细胞抗原(psca)抗体组合物及其应用方法 |
CN100455599C (zh) | 2000-03-03 | 2009-01-28 | 协和发酵工业株式会社 | 基因重组抗体及其抗体片段 |
CA2410551A1 (en) | 2000-06-30 | 2002-01-10 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw (Vib) | Heterodimeric fusion proteins |
GB0020953D0 (en) | 2000-08-24 | 2000-10-11 | Smithkline Beecham Biolog | Vaccine |
DE10045591A1 (de) * | 2000-09-15 | 2002-04-04 | Klaus Pfizenmaier | Ortsspezifische, antikörpervermittelte Aktivierung proapoptotischer Zytokine - AMAIZe (Antibody-Mediated Apoptosis Inducing Zytokine) |
WO2002030986A2 (en) | 2000-10-13 | 2002-04-18 | Biogen, Inc. | HUMANIZED ANTI-LT-β-R ANTIBODIES |
GB0029407D0 (en) * | 2000-12-01 | 2001-01-17 | Affitech As | Product |
WO2002096948A2 (en) | 2001-01-29 | 2002-12-05 | Idec Pharmaceuticals Corporation | Engineered tetravalent antibodies and methods of use |
BR0206985A (pt) | 2001-01-29 | 2005-04-19 | Idec Pharma Corp | Anticorpos modificados e métodos de uso |
JP2004533997A (ja) | 2001-02-20 | 2004-11-11 | ザイモジェネティクス,インコーポレイティド | Bcma及びtaciの両者を結合する抗体 |
AUPR395801A0 (en) * | 2001-03-26 | 2001-04-26 | Austin Research Institute, The | Antibodies against cancer |
US20020155109A1 (en) | 2001-04-20 | 2002-10-24 | Lynch David H. | Bispecific antibodies that bind TRAIL-R1 and TRAIL-R2 |
AU2002334799B2 (en) | 2001-04-26 | 2009-05-07 | Biogen Ma Inc. | Cripto-specific antibodies |
CA2715570A1 (en) | 2001-04-26 | 2002-11-07 | Biogen Idec Ma Inc. | Cripto blocking antibodies and uses thereof |
KR101008758B1 (ko) | 2001-09-18 | 2011-01-14 | 제넨테크, 인크. | 종양의 진단 및 치료를 위한 방법 및 이를 위한 조성물 |
US20040014690A1 (en) * | 2002-02-13 | 2004-01-22 | Zhenkun Ma | Macrolides with activity against methicillin-resistant staphylococcus aureus |
US7317091B2 (en) * | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
MY139983A (en) * | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
ATE328906T1 (de) | 2002-06-28 | 2006-06-15 | Domantis Ltd | Dual-specifische liganden mit erhöhter halbwertszeit |
NZ537965A (en) * | 2002-07-01 | 2008-04-30 | Biogen Idec Inc | Humanized anti-lymphotoxin beta receptor antibodies |
WO2004026427A2 (en) | 2002-09-17 | 2004-04-01 | Gtc Biotherapeutics, Inc. | Isolation of immunoglobulin molecules that lack inter-heavy chain disulfide bonds |
DK2345671T3 (en) | 2002-09-27 | 2016-02-15 | Xencor Inc | Optimized Fc variants and methods for their formation |
MXPA05004677A (es) | 2002-10-31 | 2005-11-17 | Genentech Inc | Metodos y composiciones para aumentar la produccion de anticuerpos. |
US20050097625A1 (en) * | 2002-11-27 | 2005-05-05 | Meade Harry M. | Modified antibodies stably produced in milk and methods of producing same |
BR0317573A (pt) * | 2002-12-20 | 2005-11-22 | Biogen Idec Inc | Agentes de receptores de linfotoxina beta em combinação com agentes quimioterapêuticos |
AU2003299984A1 (en) * | 2002-12-20 | 2004-07-22 | Biogen Idec Ma Inc. | Multivalent lymphotoxin beta receptor agonists and therapeutic uses thereof |
MXPA05008222A (es) | 2003-01-31 | 2005-10-05 | Immunomedics Inc | Metodos y composiciones para administrar agentes terapeuticos y de diagnostico. |
WO2005007809A2 (en) | 2003-05-30 | 2005-01-27 | Alexion Pharmaceuticals, Inc. | Antibodies and fusion proteins that include engineered constant regions |
EP1641826A2 (en) | 2003-06-27 | 2006-04-05 | Biogen Idec MA Inc. | Use of hydrophobic-interaction-chromatography or hinge-region modifications for the production of homogeneous antibody-solutions |
AU2004273791A1 (en) | 2003-09-05 | 2005-03-31 | Genentech, Inc. | Antibodies with altered effector functions |
US7820620B2 (en) * | 2003-09-15 | 2010-10-26 | Research Development Foundation | Cripto antagonism of activin and TGF-b signaling |
EP1756162A1 (en) | 2004-03-23 | 2007-02-28 | Biogen Idec MA Inc. | Receptor coupling agents and therapeutic uses thereof |
EP1737890A2 (en) * | 2004-03-24 | 2007-01-03 | Xencor, Inc. | Immunoglobulin variants outside the fc region |
WO2006074397A2 (en) | 2005-01-05 | 2006-07-13 | Biogen Idec Ma Inc. | Cripto binding molecules |
WO2006074399A2 (en) * | 2005-01-05 | 2006-07-13 | Biogen Idec Ma Inc. | Multispecific binding molecules comprising connecting peptides |
GB0514779D0 (en) | 2005-07-19 | 2005-08-24 | Celltech R&D Ltd | Biological products |
WO2007127461A2 (en) | 2006-04-28 | 2007-11-08 | Biogen Idec Ma Inc. | Composition and methods for the detection of cripto-3 |
-
2004
- 2004-06-28 EP EP04777278A patent/EP1641826A2/en not_active Withdrawn
- 2004-06-28 NZ NZ544924A patent/NZ544924A/en unknown
- 2004-06-28 CA CA002529945A patent/CA2529945A1/en not_active Abandoned
- 2004-06-28 JP JP2006517784A patent/JP5091476B2/ja not_active Expired - Lifetime
- 2004-06-28 WO PCT/US2004/020945 patent/WO2005000899A2/en active Search and Examination
- 2004-06-28 US US10/880,028 patent/US20050163782A1/en not_active Abandoned
- 2004-06-28 JP JP2006517785A patent/JP5068072B2/ja not_active Expired - Fee Related
- 2004-06-28 WO PCT/US2004/020944 patent/WO2005000898A2/en active Search and Examination
- 2004-06-28 AU AU2004252170A patent/AU2004252170B2/en not_active Expired
- 2004-06-28 US US10/880,320 patent/US7700097B2/en active Active
- 2004-06-28 CA CA002530388A patent/CA2530388A1/en not_active Abandoned
- 2004-06-28 AU AU2004252171A patent/AU2004252171B2/en not_active Expired
- 2004-06-28 NZ NZ544923A patent/NZ544923A/en unknown
- 2004-06-28 EP EP04777279A patent/EP1641827A2/en not_active Withdrawn
-
2008
- 2008-04-09 US US12/100,375 patent/US8603473B2/en active Active
-
2010
- 2010-07-26 JP JP2010167646A patent/JP2010273686A/ja not_active Withdrawn
- 2010-07-26 JP JP2010167609A patent/JP2010280683A/ja not_active Withdrawn
-
2011
- 2011-04-27 AU AU2011201880A patent/AU2011201880A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
AU2004252170A1 (en) | 2005-01-06 |
NZ544923A (en) | 2009-02-28 |
JP2007535297A (ja) | 2007-12-06 |
CA2530388A1 (en) | 2005-01-06 |
JP2007535296A (ja) | 2007-12-06 |
AU2004252171B2 (en) | 2011-04-21 |
AU2004252171A1 (en) | 2005-01-06 |
US20090041758A1 (en) | 2009-02-12 |
CA2529945A1 (en) | 2005-01-06 |
EP1641826A2 (en) | 2006-04-05 |
US8603473B2 (en) | 2013-12-10 |
WO2005000898A2 (en) | 2005-01-06 |
WO2005000898A3 (en) | 2005-09-09 |
JP2010280683A (ja) | 2010-12-16 |
JP5068072B2 (ja) | 2012-11-07 |
NZ544924A (en) | 2009-03-31 |
AU2004252170B2 (en) | 2011-01-27 |
EP1641827A2 (en) | 2006-04-05 |
US20050163782A1 (en) | 2005-07-28 |
US7700097B2 (en) | 2010-04-20 |
AU2011201880A1 (en) | 2011-05-19 |
JP2010273686A (ja) | 2010-12-09 |
WO2005000899A3 (en) | 2005-08-11 |
WO2005000899A2 (en) | 2005-01-06 |
US20050163783A1 (en) | 2005-07-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5091476B2 (ja) | 均質な抗体溶液の生成のための疎水性相互作用クロマトグラフィーまたはヒンジ領域改変の使用 | |
JP2007535296A5 (ja) | ||
EP1838736B1 (en) | Cripto binding molecules | |
JP2007535297A5 (ja) | ||
US7319139B2 (en) | TAG-72 specific CH2 domain deleted antibodies | |
JP6588422B2 (ja) | 糖類工学による部位特異的抗体−薬物コンジュゲーション | |
JP2015533490A (ja) | 変更されたグリコシル化および低減されたエフェクター機能を有するFc含有ポリペプチド | |
CA2688563A1 (en) | Cripto binding molecules | |
CN100497390C (zh) | 疏水-相互作用-层析或铰链区修饰对于均质抗体溶液的制备的用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100326 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100625 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100702 |
|
A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20100726 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110601 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110831 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110907 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110929 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20111006 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111025 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120105 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120404 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120411 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120704 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120726 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120731 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120821 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120914 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150921 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5091476 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |