CN103739706B - 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 - Google Patents
在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 Download PDFInfo
- Publication number
- CN103739706B CN103739706B CN201410031953.4A CN201410031953A CN103739706B CN 103739706 B CN103739706 B CN 103739706B CN 201410031953 A CN201410031953 A CN 201410031953A CN 103739706 B CN103739706 B CN 103739706B
- Authority
- CN
- China
- Prior art keywords
- sequence
- mework
- single chain
- antibody
- framework
- 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
- 230000002708 enhancing effect Effects 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title description 17
- 108060003951 Immunoglobulin Proteins 0.000 title description 15
- 102000018358 immunoglobulin Human genes 0.000 title description 15
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims abstract description 26
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims abstract description 26
- 108090000623 proteins and genes Proteins 0.000 claims description 53
- 102000004169 proteins and genes Human genes 0.000 claims description 38
- 230000004927 fusion Effects 0.000 claims description 26
- 230000027455 binding Effects 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 230000004913 activation Effects 0.000 claims description 12
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 claims description 11
- 108010001515 Galectin 4 Proteins 0.000 claims description 10
- 102100039556 Galectin-4 Human genes 0.000 claims description 10
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
- 239000004471 Glycine Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000010276 construction Methods 0.000 claims description 5
- 230000002209 hydrophobic effect Effects 0.000 claims description 5
- 239000004615 ingredient Substances 0.000 claims description 5
- 108020004707 nucleic acids Proteins 0.000 claims description 5
- 102000039446 nucleic acids Human genes 0.000 claims description 5
- 150000007523 nucleic acids Chemical class 0.000 claims description 5
- 238000012797 qualification Methods 0.000 claims description 5
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 4
- 238000012790 confirmation Methods 0.000 claims description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 108091005948 blue fluorescent proteins Proteins 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 108010082025 cyan fluorescent protein Proteins 0.000 claims description 2
- 108091035707 Consensus sequence Proteins 0.000 abstract description 24
- 239000000203 mixture Substances 0.000 abstract description 10
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 abstract description 3
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 abstract description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 68
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 66
- 235000018102 proteins Nutrition 0.000 description 33
- 229940024606 amino acid Drugs 0.000 description 31
- 235000001014 amino acid Nutrition 0.000 description 31
- 150000001413 amino acids Chemical class 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 25
- 238000012216 screening Methods 0.000 description 24
- 241000894006 Bacteria Species 0.000 description 23
- 230000001580 bacterial effect Effects 0.000 description 17
- 239000002773 nucleotide Substances 0.000 description 17
- 125000003729 nucleotide group Chemical group 0.000 description 17
- 239000012634 fragment Substances 0.000 description 15
- 238000011534 incubation Methods 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 238000003908 quality control method Methods 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 230000010076 replication Effects 0.000 description 11
- 239000013612 plasmid Substances 0.000 description 10
- 239000000427 antigen Substances 0.000 description 9
- 230000015556 catabolic process Effects 0.000 description 9
- 238000006731 degradation reaction Methods 0.000 description 9
- 230000009466 transformation Effects 0.000 description 9
- 108700008625 Reporter Genes Proteins 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 210000001163 endosome Anatomy 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 8
- 102000007469 Actins Human genes 0.000 description 7
- 108010085238 Actins Proteins 0.000 description 7
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 7
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 7
- 125000000539 amino acid group Chemical group 0.000 description 7
- 230000033228 biological regulation Effects 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 7
- 210000004962 mammalian cell Anatomy 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 108060001084 Luciferase Proteins 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 6
- 125000003275 alpha amino acid group Chemical group 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 230000000968 intestinal effect Effects 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 5
- 101150098914 GAL11 gene Proteins 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 101150009006 HIS3 gene Proteins 0.000 description 5
- 238000012408 PCR amplification Methods 0.000 description 5
- 101100394989 Rhodopseudomonas palustris (strain ATCC BAA-98 / CGA009) hisI gene Proteins 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 210000005260 human cell Anatomy 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 230000001590 oxidative effect Effects 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 210000005253 yeast cell Anatomy 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000011081 inoculation Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000004445 quantitative analysis Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000005030 transcription termination Effects 0.000 description 4
- 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 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108010078532 Gal-VP16 Proteins 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000009514 concussion Effects 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 238000013016 damping Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 101150066555 lacZ gene Proteins 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 108010056274 polo-like kinase 1 Proteins 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 description 2
- 101710163881 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 2
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 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
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 2
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 101150006914 TRP1 gene Proteins 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000002457 bidirectional effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002898 library design Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229940049547 paraxin Drugs 0.000 description 2
- 210000001322 periplasm Anatomy 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012916 structural analysis Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 238000003146 transient transfection Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- 101100112372 Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1) catM gene Proteins 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 101100297347 Caenorhabditis elegans pgl-3 gene Proteins 0.000 description 1
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 244000182625 Dictamnus albus Species 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 108010001498 Galectin 1 Proteins 0.000 description 1
- 102100021736 Galectin-1 Human genes 0.000 description 1
- 102100024637 Galectin-10 Human genes 0.000 description 1
- 101001011019 Gallus gallus Gallinacin-10 Proteins 0.000 description 1
- 101001011017 Gallus gallus Gallinacin-11 Proteins 0.000 description 1
- 101001011021 Gallus gallus Gallinacin-12 Proteins 0.000 description 1
- 101001011003 Gallus gallus Gallinacin-13 Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000836351 Homo sapiens Protein SET Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 101150007280 LEU2 gene Proteins 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 241000677647 Proba Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- CWHJIJJSDGEHNS-MYLFLSLOSA-N Senegenin Chemical compound C1[C@H](O)[C@H](O)[C@@](C)(C(O)=O)[C@@H]2CC[C@@]3(C)C(CC[C@]4(CCC(C[C@H]44)(C)C)C(O)=O)=C4[C@@H](CCl)C[C@@H]3[C@]21C CWHJIJJSDGEHNS-MYLFLSLOSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 239000006035 Tryptophane Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 108010030291 alpha-Galactosidase Proteins 0.000 description 1
- 102000005840 alpha-Galactosidase Human genes 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 101150053553 catR gene Proteins 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 230000037011 constitutive activity Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000386 donor Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000000852 hydrogen donor Substances 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 101150109249 lacI gene Proteins 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 230000004879 molecular function Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- -1 polyoxyethylene Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 210000005000 reproductive tract Anatomy 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000009871 tenuigenin Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
- G01N33/6857—Antibody fragments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
-
- 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
- C07K2317/80—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/80—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies
- C07K2317/82—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies functional in the cytoplasm, the inner aspect of the cell membrane, the nucleus or the mitochondria
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38264902P | 2002-05-22 | 2002-05-22 | |
| US60/382,649 | 2002-05-22 | ||
| US43825603P | 2003-01-03 | 2003-01-03 | |
| US60/438,256 | 2003-01-03 | ||
| CN038146266A CN1662556B (zh) | 2002-05-22 | 2003-05-21 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN038146266A Division CN1662556B (zh) | 2002-05-22 | 2003-05-21 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103739706A CN103739706A (zh) | 2014-04-23 |
| CN103739706B true CN103739706B (zh) | 2015-11-18 |
Family
ID=29553590
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410031953.4A Expired - Lifetime CN103739706B (zh) | 2002-05-22 | 2003-05-21 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
| CN201010575786.1A Expired - Lifetime CN102093477B (zh) | 2002-05-22 | 2003-05-21 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
| CN201510685456.0A Pending CN105175535A (zh) | 2002-05-22 | 2003-05-21 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
| CN038146266A Expired - Lifetime CN1662556B (zh) | 2002-05-22 | 2003-05-21 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010575786.1A Expired - Lifetime CN102093477B (zh) | 2002-05-22 | 2003-05-21 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
| CN201510685456.0A Pending CN105175535A (zh) | 2002-05-22 | 2003-05-21 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
| CN038146266A Expired - Lifetime CN1662556B (zh) | 2002-05-22 | 2003-05-21 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
Country Status (14)
| Country | Link |
|---|---|
| US (5) | US8853362B2 (enExample) |
| EP (5) | EP2332989B1 (enExample) |
| JP (10) | JP2006508638A (enExample) |
| CN (4) | CN103739706B (enExample) |
| AU (2) | AU2003238370B2 (enExample) |
| CA (2) | CA2483285C (enExample) |
| CY (1) | CY1114225T1 (enExample) |
| DK (2) | DK1506236T3 (enExample) |
| ES (3) | ES2537104T3 (enExample) |
| HU (1) | HUE048922T2 (enExample) |
| NZ (1) | NZ536412A (enExample) |
| PT (2) | PT2332989E (enExample) |
| SI (2) | SI2947095T1 (enExample) |
| WO (1) | WO2003097697A2 (enExample) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0226727D0 (en) * | 2002-11-15 | 2002-12-24 | Medical Res Council | Intrabodies |
| ES2558338T3 (es) * | 2005-03-25 | 2016-02-03 | National Research Council Of Canada | Método para aislamiento de polipéptidos solubles |
| AU2016204739C1 (en) * | 2005-06-07 | 2017-10-19 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting TNFalpha |
| ES2424042T3 (es) | 2005-06-07 | 2013-09-26 | Esbatech - A Novartis Company Llc | Anticuerpos estables y solubles que inhiben TNF± |
| AU2011265593B2 (en) * | 2005-06-07 | 2013-08-15 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting TNFalpha |
| AU2013207650B2 (en) * | 2005-06-07 | 2016-04-21 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting TNFalpha |
| RU2460540C2 (ru) * | 2006-04-28 | 2012-09-10 | Деленекс Терапьютикс Аг | Антитела, связывающиеся с внеклеточным доменом тирозинкиназного рецептора (alk) |
| EP3093026B1 (en) * | 2006-07-10 | 2020-07-01 | ESBATech, an Alcon Biomedical Research Unit LLC | Scfv antibodies which pass epithelial and/or endothelial layers |
| RU2009137582A (ru) * | 2007-03-12 | 2011-04-20 | Эсбатек Аг (Ch) | Инженерия и оптимизация одноцепочечных антител на основе последовательности |
| WO2008131575A2 (en) * | 2007-04-27 | 2008-11-06 | Esbatech Ag | Anti-alk antibodies suitable for treating metastatic cancers or tumors |
| BRPI0813645A2 (pt) * | 2007-06-25 | 2014-12-30 | Esbatech Alcon Biomed Res Unit | Métodos para modificar anticorpos, e anticorpos modificados com propriedades funcionais aperfeiçoadas |
| EP2164961B1 (en) * | 2007-06-25 | 2015-01-07 | ESBATech, an Alcon Biomedical Research Unit LLC | Sequence based engineering and optimization of single chain antibodies |
| KR20100074181A (ko) | 2007-09-13 | 2010-07-01 | 델레넥스 쎄라퓨틱스 아게 | β-아밀로이드 펩티드에 대한 인간화 항체 |
| AU2013202997B2 (en) * | 2008-06-25 | 2015-01-22 | Novartis Ag | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFalpha |
| SI3628686T1 (sl) | 2008-06-25 | 2022-01-31 | Novartis Ag | Humaniziranje zajčjih protiteles z uporabo univerzalnega ogrodja protitelesa |
| MX345039B (es) * | 2008-06-25 | 2017-01-16 | Esbatech Alcon Biomed Res Unit | Anticuerpos estables y solubles que inhiben el tnfa. |
| AU2016273957C1 (en) * | 2008-06-25 | 2019-04-18 | Novartis Ag | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFa |
| CA2728829C (en) | 2008-06-25 | 2018-01-02 | Esbatech, An Alcon Biomedical Research Unit Llc | Solubility optimization of immunobinders |
| AU2015201794B2 (en) * | 2008-06-25 | 2017-01-19 | Novartis Ag | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFa |
| KR101834797B1 (ko) * | 2008-06-25 | 2018-03-07 | 에스바테크 - 어 노바티스 컴파니 엘엘씨 | 보편적 항체 프레임워크를 사용한 래빗 항체의 인간화 |
| PT2307454T (pt) * | 2008-06-25 | 2017-04-26 | Esbatech Alcon Biomed Res Unit | Anticorpos estáveis e solúveis que inibem o vegf |
| PT2752428T (pt) * | 2008-06-25 | 2020-02-14 | Novartis Ag | Humanização de anticorpos de coelho com utilização de um framework de anticorpos universal |
| JP5988580B2 (ja) | 2008-06-30 | 2016-09-07 | エスバテック − ア ノバルティス カンパニー エルエルシー | 機能性ポリペプチド |
| CN104800147A (zh) | 2008-07-10 | 2015-07-29 | 德勒尼克斯治疗股份公司 | 用于大分子的增强的递送的方法和组合物 |
| MX2011007049A (es) | 2009-02-24 | 2011-08-03 | Esbatech Alcon Biomed Res Unit | Metodos para identificar inmunoligadores de los antegenos de la superficie celular. |
| CN105116138A (zh) * | 2009-02-24 | 2015-12-02 | 艾斯巴技术-诺华有限责任公司 | 用于鉴定细胞表面抗原的免疫结合剂的方法 |
| US8399624B1 (en) * | 2009-06-25 | 2013-03-19 | Esbatech, An Alcon Biomedical Research Unit Llc | Acceptor framework for CDR grafting |
| US9597379B1 (en) | 2010-02-09 | 2017-03-21 | David Gordon Bermudes | Protease inhibitor combination with therapeutic proteins including antibodies |
| US8771669B1 (en) | 2010-02-09 | 2014-07-08 | David Gordon Bermudes | Immunization and/or treatment of parasites and infectious agents by live bacteria |
| US8524220B1 (en) | 2010-02-09 | 2013-09-03 | David Gordon Bermudes | Protease inhibitor: protease sensitivity expression system composition and methods improving the therapeutic activity and specificity of proteins delivered by bacteria |
| AR083495A1 (es) | 2010-10-22 | 2013-02-27 | Esbatech Alcon Biomed Res Unit | Anticuerpos estables y solubles |
| EP2476754A1 (en) * | 2011-01-14 | 2012-07-18 | Bundesrepublik Deutschland, Letztvertreten Durch Den Präsidenten Des Paul-Ehrlich-Instituts | Methods for the identification and repair of amino acid residues destabilizing single-chain variable fragments (scFv) |
| DK2744931T3 (en) | 2011-08-18 | 2018-08-06 | Affinity Biosciences Pty Ltd | SOLUBLE POLYPEPTIDES |
| TWI577696B (zh) | 2011-10-20 | 2017-04-11 | Ｅｓｂａ科技 諾華有限責任公司 | 穩定的多重抗原結合抗體 |
| WO2014030780A1 (en) * | 2012-08-22 | 2014-02-27 | Mogam Biotechnology Research Institute | Screening and engineering method of super-stable immunoglobulin variable domains and their uses |
| WO2014068132A1 (en) | 2012-11-05 | 2014-05-08 | Delenex Therapeutics Ag | Binding members to il-1 beta |
| EP2931750B8 (en) | 2012-12-17 | 2021-11-03 | Cell Medica Inc. | Antibodies against il-1 beta |
| AU2013378628A1 (en) * | 2013-02-15 | 2015-06-11 | Esbatech - A Novartis Company Llc | Acceptor framework for CDR grafting |
| WO2014127811A1 (en) | 2013-02-20 | 2014-08-28 | Esbatech - A Novartis Company Llc | Acceptor framework for cdr grafting |
| CA2911514A1 (en) | 2013-05-06 | 2014-11-13 | Scholar Rock, Inc. | Compositions and methods for growth factor modulation |
| US9737592B1 (en) | 2014-02-14 | 2017-08-22 | David Gordon Bermudes | Topical and orally administered protease inhibitors and bacterial vectors for the treatment of disorders and methods of treatment |
| US9879087B2 (en) | 2014-11-12 | 2018-01-30 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
| IL278574B2 (en) | 2014-11-12 | 2024-11-01 | Seagen Inc | Glycan-interacting compounds and methods of use |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| CN107531793B (zh) | 2015-10-13 | 2022-01-11 | 优瑞科生物技术公司 | 对人类cd19具有专一性的抗体药剂和其用途 |
| AU2016342041B2 (en) | 2015-10-23 | 2021-12-02 | Eureka Therapeutics, Inc. | Antibody/T-cell receptor chimeric constructs and uses thereof |
| WO2017083582A1 (en) | 2015-11-12 | 2017-05-18 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
| KR20180111870A (ko) | 2016-02-25 | 2018-10-11 | 셀 메디카 스위처란트 아게 | Pd-l1에 대한 결합 성분 |
| EP3515491A4 (en) | 2016-09-21 | 2020-09-16 | Aptevo Research and Development LLC | CD123 BINDING PROTEINS AND RELATED COMPOSITIONS AND PROCESSES |
| WO2018094143A1 (en) | 2016-11-17 | 2018-05-24 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| KR20240044544A (ko) | 2017-03-03 | 2024-04-04 | 씨젠 인크. | 글리칸-상호작용 화합물 및 사용 방법 |
| JP7416433B2 (ja) * | 2018-04-10 | 2024-01-17 | ノースウェスタン ユニバーシティ | 標的指向性親和性ドメインに基づく膜タンパク質を含む細胞外小胞 |
| WO2020069349A1 (en) * | 2018-09-27 | 2020-04-02 | Colorado State University Research Foundation | Scfv's for live cell imaging and other uses |
| US12285437B2 (en) | 2019-10-30 | 2025-04-29 | The Research Foundation For The State University Of New York | Reversing the undesirable pH-profile of doxorubicin via activation of a disubstituted maleamic acid prodrug at tumor acidity |
| PH12023550015A1 (en) | 2020-07-16 | 2024-03-11 | Novartis Ag | Anti-betacellulin antibodies, fragments thereof, and multi-specific binding molecules |
| WO2022189558A2 (en) | 2021-03-10 | 2022-09-15 | Mabylon Ag | Antibodies against tdp-43 and methods of using the same |
| US20250101089A1 (en) | 2022-01-24 | 2025-03-27 | Cambridge Enterprise Limited | Tau therapy |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001048017A1 (en) * | 1999-12-28 | 2001-07-05 | Esbatech Ag | Intrabodies with defined framework that is stable in a reducing environment and applications thereof |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1990005144A1 (en) | 1988-11-11 | 1990-05-17 | Medical Research Council | Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors |
| US5817311A (en) * | 1993-03-05 | 1998-10-06 | Universite Catholique De Louvain | Methods of inhibiting T-cell medicated immune responses with LO-CD2a-specific antibodies |
| DE4425115A1 (de) | 1994-07-15 | 1996-01-18 | Boehringer Mannheim Gmbh | Verfahren zur Modifizierung der Stabilität von Antikörpern |
| US7264963B1 (en) * | 1995-08-18 | 2007-09-04 | Morphosys Ag | Protein(poly)peptide libraries |
| CA2229043C (en) | 1995-08-18 | 2016-06-07 | Morphosys Gesellschaft Fur Proteinoptimierung Mbh | Protein/(poly)peptide libraries |
| US6262238B1 (en) | 1997-01-14 | 2001-07-17 | Roche Diagnostic, Gmbh | Process for modifying the stability of antibodies |
| WO1999028502A1 (en) | 1997-11-28 | 1999-06-10 | Invitrogen Corporation | Single chain monoclonal antibody fusion reagents that regulate transcription in vivo |
| GB2344886B (en) | 1999-03-10 | 2000-11-01 | Medical Res Council | Selection of intracellular immunoglobulins |
| GB0008419D0 (en) | 2000-04-05 | 2000-05-24 | Bioinvent Int Ab | A method for invitro molecular evolution of antibody function |
| EP1156062A1 (en) | 2000-05-12 | 2001-11-21 | GPC Biotech AG | Immunomodulatory human MHC class II antigen-binding peptides/proteins |
| US6410271B1 (en) | 2000-06-23 | 2002-06-25 | Genetastix Corporation | Generation of highly diverse library of expression vectors via homologous recombination in yeast |
| DE10039191C1 (de) | 2000-08-10 | 2002-01-17 | Infineon Technologies Ag | Hochfrequenz-Eingangsstufe |
-
2003
- 2003-05-21 CN CN201410031953.4A patent/CN103739706B/zh not_active Expired - Lifetime
- 2003-05-21 ES ES10009857.3T patent/ES2537104T3/es not_active Expired - Lifetime
- 2003-05-21 DK DK03732434.0T patent/DK1506236T3/da active
- 2003-05-21 JP JP2004506369A patent/JP2006508638A/ja not_active Withdrawn
- 2003-05-21 EP EP10009857.3A patent/EP2332989B1/en not_active Expired - Lifetime
- 2003-05-21 CN CN201010575786.1A patent/CN102093477B/zh not_active Expired - Lifetime
- 2003-05-21 CA CA2483285A patent/CA2483285C/en not_active Expired - Lifetime
- 2003-05-21 EP EP15160739.7A patent/EP2947095B1/en not_active Expired - Lifetime
- 2003-05-21 CN CN201510685456.0A patent/CN105175535A/zh active Pending
- 2003-05-21 SI SI200332610T patent/SI2947095T1/sl unknown
- 2003-05-21 SI SI200332427T patent/SI2332989T1/sl unknown
- 2003-05-21 EP EP03732434A patent/EP1506236B1/en not_active Expired - Lifetime
- 2003-05-21 PT PT100098573T patent/PT2332989E/pt unknown
- 2003-05-21 NZ NZ536412A patent/NZ536412A/en not_active IP Right Cessation
- 2003-05-21 EP EP10010455.3A patent/EP2314622B1/en not_active Expired - Lifetime
- 2003-05-21 CN CN038146266A patent/CN1662556B/zh not_active Expired - Lifetime
- 2003-05-21 ES ES03732434T patent/ES2399617T3/es not_active Expired - Lifetime
- 2003-05-21 WO PCT/EP2003/005324 patent/WO2003097697A2/en not_active Ceased
- 2003-05-21 AU AU2003238370A patent/AU2003238370B2/en not_active Expired
- 2003-05-21 EP EP19200477.8A patent/EP3656787A1/en not_active Withdrawn
- 2003-05-21 PT PT37324340T patent/PT1506236E/pt unknown
- 2003-05-21 DK DK10009857.3T patent/DK2332989T3/en active
- 2003-05-21 CA CA2867542A patent/CA2867542C/en not_active Expired - Lifetime
- 2003-05-21 ES ES10010455.3T patent/ES2656427T3/es not_active Expired - Lifetime
- 2003-05-21 HU HUE15160739A patent/HUE048922T2/hu unknown
- 2003-05-21 US US10/515,241 patent/US8853362B2/en not_active Expired - Lifetime
-
2010
- 2010-03-17 JP JP2010060713A patent/JP2010187678A/ja not_active Withdrawn
- 2010-06-24 AU AU2010202634A patent/AU2010202634B2/en not_active Expired
-
2012
- 2012-08-28 JP JP2012187518A patent/JP6075836B2/ja not_active Expired - Lifetime
-
2013
- 2013-02-04 JP JP2013019425A patent/JP6100544B2/ja not_active Expired - Lifetime
- 2013-04-08 CY CY20131100292T patent/CY1114225T1/el unknown
- 2013-09-19 JP JP2013193935A patent/JP2013256533A/ja active Pending
-
2014
- 2014-08-26 US US14/469,276 patent/US9518108B2/en not_active Expired - Fee Related
-
2015
- 2015-08-19 JP JP2015161600A patent/JP6261136B2/ja not_active Expired - Lifetime
- 2015-08-19 JP JP2015161601A patent/JP2015214583A/ja active Pending
-
2016
- 2016-11-01 US US15/340,195 patent/US10125186B2/en not_active Expired - Lifetime
-
2017
- 2017-08-24 JP JP2017161036A patent/JP2017201990A/ja active Pending
-
2018
- 2018-10-30 US US16/175,002 patent/US10570190B2/en not_active Expired - Fee Related
-
2019
- 2019-01-23 JP JP2019009288A patent/JP6918033B2/ja not_active Expired - Lifetime
- 2019-12-16 US US16/716,137 patent/US20200165322A1/en not_active Abandoned
-
2020
- 2020-05-14 JP JP2020085288A patent/JP2020171286A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001048017A1 (en) * | 1999-12-28 | 2001-07-05 | Esbatech Ag | Intrabodies with defined framework that is stable in a reducing environment and applications thereof |
Non-Patent Citations (2)
| Title |
|---|
| Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides;Knappik A.等;《Journal of Molecular Biology》;20000211;第296卷(第1期);全文 * |
| The intracellular antibody capture technology (IACT): towards a consensus sequence for intracellular antibodies;Michela V.等;《Journal of Molecular Biology》;20020315;第317卷(第1期);全文 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103739706B (zh) | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 | |
| AU2013203288B2 (en) | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same | |
| AU2012211497B2 (en) | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same | |
| HK1151804A (en) | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same | |
| HK1217712B (en) | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same | |
| HK1071378B (en) | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same | |
| HK1151804B (en) | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same | |
| HK1152320B (en) | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same | |
| AU2015202410A1 (en) | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20140423 Assignee: Delenex Therapeutics AG Assignor: ESBATECH - A NOVARTIS CO.,LLC Contract record no.: 2014990000590 Denomination of invention: Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same License type: Common License Record date: 20140724 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20191119 Address after: Basel, Switzerland Patentee after: NOVARTIS AG Address before: Swiss Shi Lilun Patentee before: ESBATECH - A NOVARTIS CO.,LLC |
|
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20151118 |