JP2004532038A - 新規抗原結合分子の治療、診断、予防、酵素、産業ならびに農業各分野への応用とそのための新規抗原結合分子の作製とスクリーニングの方法 - Google Patents
新規抗原結合分子の治療、診断、予防、酵素、産業ならびに農業各分野への応用とそのための新規抗原結合分子の作製とスクリーニングの方法 Download PDFInfo
- Publication number
- JP2004532038A JP2004532038A JP2002589648A JP2002589648A JP2004532038A JP 2004532038 A JP2004532038 A JP 2004532038A JP 2002589648 A JP2002589648 A JP 2002589648A JP 2002589648 A JP2002589648 A JP 2002589648A JP 2004532038 A JP2004532038 A JP 2004532038A
- Authority
- JP
- Japan
- Prior art keywords
- antigen binding
- binding site
- amino acid
- nucleic acid
- sequence
- 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.)
- Pending
Links
- 239000000427 antigen Substances 0.000 title claims abstract description 398
- 108091007433 antigens Proteins 0.000 title claims abstract description 398
- 102000036639 antigens Human genes 0.000 title claims abstract description 398
- 238000000034 method Methods 0.000 title claims abstract description 398
- 230000027455 binding Effects 0.000 title claims abstract description 353
- 238000009739 binding Methods 0.000 title claims abstract description 352
- 238000012216 screening Methods 0.000 title claims description 63
- 230000002255 enzymatic effect Effects 0.000 title description 5
- 230000001225 therapeutic effect Effects 0.000 title description 4
- 230000000069 prophylactic effect Effects 0.000 title 1
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 368
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 344
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 344
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 276
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 253
- 229920001184 polypeptide Polymers 0.000 claims abstract description 242
- 108091008874 T cell receptors Proteins 0.000 claims abstract description 112
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims abstract description 112
- 239000012634 fragment Substances 0.000 claims abstract description 111
- 108700018351 Major Histocompatibility Complex Proteins 0.000 claims abstract description 98
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 claims abstract description 98
- 241000282414 Homo sapiens Species 0.000 claims abstract description 49
- 238000004519 manufacturing process Methods 0.000 claims abstract description 48
- 230000014509 gene expression Effects 0.000 claims abstract description 23
- 150000001413 amino acids Chemical class 0.000 claims description 205
- 108091034117 Oligonucleotide Proteins 0.000 claims description 174
- 102000040430 polynucleotide Human genes 0.000 claims description 172
- 108091033319 polynucleotide Proteins 0.000 claims description 172
- 239000002157 polynucleotide Substances 0.000 claims description 172
- 230000035772 mutation Effects 0.000 claims description 131
- 108020004705 Codon Proteins 0.000 claims description 113
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 106
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 51
- 238000003752 polymerase chain reaction Methods 0.000 claims description 39
- 238000006467 substitution reaction Methods 0.000 claims description 38
- 238000006243 chemical reaction Methods 0.000 claims description 37
- 230000003321 amplification Effects 0.000 claims description 34
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 34
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 31
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 21
- 230000001965 increasing effect Effects 0.000 claims description 19
- 125000000539 amino acid group Chemical group 0.000 claims description 18
- 238000000338 in vitro Methods 0.000 claims description 18
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 12
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 12
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 11
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 11
- 230000035897 transcription Effects 0.000 claims description 11
- 238000013518 transcription Methods 0.000 claims description 11
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims description 10
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 8
- 238000002823 phage display Methods 0.000 claims description 7
- 238000002965 ELISA Methods 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 6
- 239000007791 liquid phase Substances 0.000 claims description 5
- 238000002702 ribosome display Methods 0.000 claims description 5
- 238000013519 translation Methods 0.000 claims description 5
- 230000002829 reductive effect Effects 0.000 claims description 4
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 claims description 3
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 claims description 3
- 230000009471 action Effects 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 230000009261 transgenic effect Effects 0.000 claims 2
- 231100000350 mutagenesis Toxicity 0.000 abstract description 82
- 238000002703 mutagenesis Methods 0.000 abstract description 81
- 102000004190 Enzymes Human genes 0.000 abstract description 69
- 108090000790 Enzymes Proteins 0.000 abstract description 69
- 230000000694 effects Effects 0.000 abstract description 26
- 102000008394 Immunoglobulin Fragments Human genes 0.000 abstract description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 abstract description 3
- 230000001900 immune effect Effects 0.000 abstract description 3
- 230000004807 localization Effects 0.000 abstract 1
- 230000002688 persistence Effects 0.000 abstract 1
- 238000012036 ultra high throughput screening Methods 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 171
- 229940024606 amino acid Drugs 0.000 description 147
- 108090000623 proteins and genes Proteins 0.000 description 142
- 102000004169 proteins and genes Human genes 0.000 description 72
- 235000018102 proteins Nutrition 0.000 description 70
- 229940088598 enzyme Drugs 0.000 description 68
- 210000004027 cell Anatomy 0.000 description 62
- 108020004414 DNA Proteins 0.000 description 56
- 229910052757 nitrogen Inorganic materials 0.000 description 39
- 230000000295 complement effect Effects 0.000 description 36
- 230000006798 recombination Effects 0.000 description 34
- 238000005215 recombination Methods 0.000 description 34
- 239000002773 nucleotide Substances 0.000 description 27
- 125000003729 nucleotide group Chemical group 0.000 description 27
- 239000000523 sample Substances 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 25
- 230000008569 process Effects 0.000 description 23
- 102000005962 receptors Human genes 0.000 description 23
- 108020003175 receptors Proteins 0.000 description 23
- 238000012217 deletion Methods 0.000 description 22
- 230000037430 deletion Effects 0.000 description 22
- 230000004048 modification Effects 0.000 description 22
- 238000012986 modification Methods 0.000 description 22
- 239000000306 component Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 238000013537 high throughput screening Methods 0.000 description 19
- 230000008901 benefit Effects 0.000 description 18
- 238000009396 hybridization Methods 0.000 description 18
- 241000894007 species Species 0.000 description 18
- 230000006870 function Effects 0.000 description 17
- 210000003719 b-lymphocyte Anatomy 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- 238000004422 calculation algorithm Methods 0.000 description 16
- 230000028993 immune response Effects 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- 239000002299 complementary DNA Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 230000000670 limiting effect Effects 0.000 description 14
- 239000013598 vector Substances 0.000 description 14
- 108091026890 Coding region Proteins 0.000 description 12
- 238000007792 addition Methods 0.000 description 12
- -1 i.e. Proteins 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 11
- 230000002068 genetic effect Effects 0.000 description 11
- 239000003446 ligand Substances 0.000 description 11
- 230000000890 antigenic effect Effects 0.000 description 10
- 230000009870 specific binding Effects 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 9
- 230000008859 change Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 229960005486 vaccine Drugs 0.000 description 9
- 108060003951 Immunoglobulin Proteins 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000004132 cross linking Methods 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 102000018358 immunoglobulin Human genes 0.000 description 8
- 108091008146 restriction endonucleases Proteins 0.000 description 8
- 108010011619 6-Phytase Proteins 0.000 description 7
- 108010032595 Antibody Binding Sites Proteins 0.000 description 7
- 239000004475 Arginine Substances 0.000 description 7
- 102000053602 DNA Human genes 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
- 238000003491 array Methods 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 238000013461 design Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000003780 insertion Methods 0.000 description 7
- 230000037431 insertion Effects 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 229940085127 phytase Drugs 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 238000002741 site-directed mutagenesis Methods 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 230000009897 systematic effect Effects 0.000 description 7
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
- 108091005461 Nucleic proteins Proteins 0.000 description 6
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 239000013615 primer Substances 0.000 description 6
- 230000008707 rearrangement Effects 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 206010068051 Chimerism Diseases 0.000 description 5
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 5
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 5
- 108060002716 Exonuclease Proteins 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000012219 cassette mutagenesis Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 102000013165 exonuclease Human genes 0.000 description 5
- 229960000310 isoleucine Drugs 0.000 description 5
- 229920002521 macromolecule Polymers 0.000 description 5
- 229930182817 methionine Natural products 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 210000004940 nucleus Anatomy 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 239000007790 solid phase Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 239000004474 valine Substances 0.000 description 5
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-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
- 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
- 239000004472 Lysine Substances 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 235000009582 asparagine Nutrition 0.000 description 4
- 229960001230 asparagine Drugs 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 238000009940 knitting Methods 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 235000018977 lysine Nutrition 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000033607 mismatch repair Effects 0.000 description 4
- 230000004962 physiological condition Effects 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 230000001568 sexual effect Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 239000013076 target substance Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 241000557626 Corvus corax Species 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
- 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 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 3
- 108091093037 Peptide nucleic acid Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 108700005078 Synthetic Genes Proteins 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 235000008206 alpha-amino acids Nutrition 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 238000007845 assembly PCR Methods 0.000 description 3
- 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 3
- 230000000903 blocking effect Effects 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 239000013599 cloning vector Substances 0.000 description 3
- 230000009918 complex formation Effects 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 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 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 125000001165 hydrophobic group Chemical group 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 239000002853 nucleic acid probe Substances 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 125000005642 phosphothioate group Chemical group 0.000 description 3
- 210000004180 plasmocyte Anatomy 0.000 description 3
- 230000003334 potential effect Effects 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000002708 random mutagenesis Methods 0.000 description 3
- 238000003259 recombinant expression Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 229940035893 uracil Drugs 0.000 description 3
- 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 2
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 102000000989 Complement System Proteins Human genes 0.000 description 2
- 108010069112 Complement System Proteins Proteins 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 102000012410 DNA Ligases Human genes 0.000 description 2
- 108010061982 DNA Ligases Proteins 0.000 description 2
- 238000000018 DNA microarray Methods 0.000 description 2
- 239000003155 DNA primer Substances 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 2
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 2
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 2
- 102000003960 Ligases Human genes 0.000 description 2
- 108090000364 Ligases Proteins 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 102100023715 Poly(A)-specific ribonuclease PARN Human genes 0.000 description 2
- 108010066717 Q beta Replicase Proteins 0.000 description 2
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 150000001371 alpha-amino acids Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 238000011005 laboratory method Methods 0.000 description 2
- 238000007834 ligase chain reaction Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 239000003471 mutagenic agent Substances 0.000 description 2
- 238000007899 nucleic acid hybridization Methods 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 210000002729 polyribosome Anatomy 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000012857 radioactive material Substances 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 230000014639 sexual reproduction Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 230000005030 transcription termination Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 241001515965 unidentified phage Species 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 1
- BEJKOYIMCGMNRB-GRHHLOCNSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-amino-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BEJKOYIMCGMNRB-GRHHLOCNSA-N 0.000 description 1
- PIINGYXNCHTJTF-UHFFFAOYSA-N 2-(2-azaniumylethylamino)acetate Chemical group NCCNCC(O)=O PIINGYXNCHTJTF-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 108020005065 3' Flanking Region Proteins 0.000 description 1
- 108020005029 5' Flanking Region Proteins 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
- 108010002156 Depsipeptides Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000702191 Escherichia virus P1 Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins 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
- 101710182312 High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 1
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 101710122625 Low affinity immunoglobulin gamma Fc region receptor II Proteins 0.000 description 1
- 101710177649 Low affinity immunoglobulin gamma Fc region receptor III Proteins 0.000 description 1
- 101710099301 Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 241000907681 Morpho Species 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710149086 Nuclease S1 Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 101710086015 RNA ligase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 101800001707 Spacer peptide Proteins 0.000 description 1
- 206010042602 Supraventricular extrasystoles Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000024932 T cell mediated immunity Effects 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
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 102000025171 antigen binding proteins Human genes 0.000 description 1
- 108091000831 antigen binding proteins Proteins 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 101150010487 are gene Proteins 0.000 description 1
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- OGBVRMYSNSKIEF-UHFFFAOYSA-L benzyl-dioxido-oxo-$l^{5}-phosphane Chemical compound [O-]P([O-])(=O)CC1=CC=CC=C1 OGBVRMYSNSKIEF-UHFFFAOYSA-L 0.000 description 1
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 1
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229940126587 biotherapeutics Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 101150039352 can gene Proteins 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000009614 chemical analysis method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000010960 commercial process Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000022811 deglycosylation Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 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
- 239000012636 effector Substances 0.000 description 1
- 239000012645 endogenous antigen Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000000284 extract Substances 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
- 230000004907 flux Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000012224 gene deletion Methods 0.000 description 1
- 150000002337 glycosamines Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 210000000688 human artificial chromosome Anatomy 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000005931 immune cell recruitment Effects 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000002919 insect venom Substances 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000005061 intracellular organelle Anatomy 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 210000000723 mammalian artificial chromosome Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000021121 meiosis Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- ZTLGJPIZUOVDMT-UHFFFAOYSA-N n,n-dichlorotriazin-4-amine Chemical compound ClN(Cl)C1=CC=NN=N1 ZTLGJPIZUOVDMT-UHFFFAOYSA-N 0.000 description 1
- 230000009707 neogenesis Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 238000003499 nucleic acid array Methods 0.000 description 1
- 102000044158 nucleic acid binding protein Human genes 0.000 description 1
- 108700020942 nucleic acid binding protein Proteins 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000005426 pharmaceutical component Substances 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000013492 plasmid preparation Methods 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 210000004896 polypeptide structure Anatomy 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 239000012521 purified sample Substances 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000033458 reproduction Effects 0.000 description 1
- 230000032537 response to toxin Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000002955 secretory cell Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000005309 stochastic process Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1093—General methods of preparing gene libraries, not provided for in other subgroups
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
- C12N15/1027—Mutagenizing nucleic acids by DNA shuffling, e.g. RSR, STEP, RPR
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/66—General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
Landscapes
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Computational Biology (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30038101P | 2001-05-17 | 2001-05-17 | |
| US30090701P | 2001-06-25 | 2001-06-25 | |
| PCT/US2002/015767 WO2002092780A2 (en) | 2001-05-17 | 2002-05-17 | Novel antigen binding molecules for therapeutic, diagnostic, prophylactic, enzymatic, industrial, and agricultural applications, and methods for generating and screening thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004532038A true JP2004532038A (ja) | 2004-10-21 |
| JP2004532038A5 JP2004532038A5 (OSRAM) | 2006-01-05 |
Family
ID=26971759
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002589648A Pending JP2004532038A (ja) | 2001-05-17 | 2002-05-17 | 新規抗原結合分子の治療、診断、予防、酵素、産業ならびに農業各分野への応用とそのための新規抗原結合分子の作製とスクリーニングの方法 |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1421203A4 (OSRAM) |
| JP (1) | JP2004532038A (OSRAM) |
| WO (1) | WO2002092780A2 (OSRAM) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010008391A (ja) * | 2008-05-27 | 2010-01-14 | Toray Ind Inc | 分析用チップ |
Families Citing this family (133)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003276403B2 (en) | 2002-11-09 | 2010-04-15 | Adaptimmune Limited | T cell receptor display |
| KR101374514B1 (ko) | 2003-12-10 | 2014-03-13 | 메다렉스, 인코포레이티드 | Ｉｐ―１０ 항체 및 그의 용도 |
| ES2399050T3 (es) | 2003-12-10 | 2013-03-25 | Medarex, Inc. | Anticuerpos contra interferón alfa y sus usos |
| KR20150041193A (ko) | 2004-06-21 | 2015-04-15 | 메다렉스, 엘.엘.시. | 인터페론 알파 수용체 1 항체 및 그의 용도 |
| PL2161336T5 (pl) | 2005-05-09 | 2017-10-31 | Ono Pharmaceutical Co | Ludzkie przeciwciała monoklonalne przeciwko białku Programmed Death 1 (PD-1) oraz sposoby leczenia raka z zastosowaniem samych przeciwciał anty-PD-1 lub w połączeniu z innymi środkami immunoterapeutycznymi |
| EP1899379B1 (en) | 2005-06-20 | 2018-04-11 | E. R. Squibb & Sons, L.L.C. | Cd19 antibodies and their uses |
| CA2612241C (en) | 2005-07-01 | 2018-11-06 | Medarex, Inc. | Human monoclonal antibodies to programmed death ligand 1 (pd-l1) |
| US7910708B2 (en) | 2005-10-21 | 2011-03-22 | Novartis Ag | Anti-IL13 human antibodies |
| EP1960434B1 (en) | 2005-12-08 | 2012-07-11 | Medarex, Inc. | Human monoclonal antibodies to fucosyl-gm1 and methods for using anti-fucosyl-gm1 |
| EP2010569A4 (en) | 2006-03-20 | 2009-09-09 | Xoma Technology Ltd | HUMAN ANTIBODIES SPECIFIC TO GASTRINE MATERIALS AND METHODS |
| JP5406027B2 (ja) | 2006-08-04 | 2014-02-05 | ノバルティス アーゲー | ＥｐｈＢ３特異的抗体およびその使用 |
| EP2046834B9 (en) | 2006-08-11 | 2013-04-10 | Ono Pharmaceutical Co., Ltd. | Monoclonal antibodies against stromal derived factor-1 (sdf-1) |
| EP3018144A1 (en) | 2006-08-18 | 2016-05-11 | XOMA Technology Ltd. | Prlr-specific antibody and uses thereof |
| KR20090088852A (ko) | 2006-09-05 | 2009-08-20 | 메다렉스, 인코포레이티드 | 골형성 단백질의 항체와 이의 수용체 및 이의 사용방법 |
| ES2625798T3 (es) | 2006-10-02 | 2017-07-20 | E. R. Squibb & Sons, L.L.C. | Anticuerpos humanos que se unen a CXCR4 y usos de los mismos |
| DK2068922T3 (da) | 2006-10-19 | 2012-10-08 | Csl Ltd | Anti-IL-13Ralfa1-antistoffer samt deres anvendelser |
| US8618248B2 (en) | 2006-10-31 | 2013-12-31 | President And Fellows Of Harvard College | Phosphopeptide compositions and anti-phosphopeptide antibody compositions and methods of detecting phosphorylated peptides |
| AU2007334264A1 (en) | 2006-11-15 | 2008-06-26 | Medarex, Inc. | Human monoclonal antibodies to BTLA and methods of use |
| EP2097097B1 (en) | 2006-12-01 | 2018-05-30 | E. R. Squibb & Sons, L.L.C. | Antibodies, in particular human antibodies, that bind cd22 and uses thereof |
| KR20140119831A (ko) | 2006-12-07 | 2014-10-10 | 노파르티스 아게 | Ｅｐｈｂ３에 대한 길항제 항체 |
| CL2007003622A1 (es) | 2006-12-13 | 2009-08-07 | Medarex Inc | Anticuerpo monoclonal humano anti-cd19; composicion que lo comprende; y metodo de inhibicion del crecimiento de celulas tumorales. |
| AU2007333098A1 (en) | 2006-12-14 | 2008-06-19 | Medarex, Inc. | Human antibodies that bind CD70 and uses thereof |
| EP2190469B1 (en) | 2007-09-04 | 2015-02-25 | Compugen Ltd. | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
| TWI489993B (zh) | 2007-10-12 | 2015-07-01 | Novartis Ag | 骨硬化素（ｓｃｌｅｒｏｓｔｉｎ）抗體組合物及使用方法 |
| CN101951954A (zh) | 2007-11-02 | 2011-01-19 | 诺瓦提斯公司 | 调节低密度脂蛋白受体相关蛋白6(lrp6)的分子和方法 |
| DK2222706T4 (en) | 2007-12-14 | 2016-11-21 | Novo Nordisk As | Antibodies that bind to NKG2D and its use |
| AU2009212442C1 (en) | 2008-02-05 | 2014-07-17 | Bristol-Myers Squibb Company | Alpha 5 - beta 1 antibodies and their uses |
| PY09026846A (es) | 2008-08-05 | 2015-09-01 | Novartis Ag | Composiciones y métodos para anticuerpos que se dirigen a la proteína de complemento c5 |
| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| EP2865689A1 (en) | 2008-12-08 | 2015-04-29 | Compugen Ltd. | FAM26F polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
| PT2403878T (pt) | 2009-03-05 | 2017-09-01 | Squibb & Sons Llc | Anticorpos completamente humanos específicos a cadm1 |
| EP3009454A3 (en) | 2009-04-20 | 2016-10-19 | Oxford Bio Therapeutics Limited | Antibodies specific to cadherin-17 |
| US8715657B2 (en) | 2009-04-27 | 2014-05-06 | Novartis Ag | Therapeutic antibodies binding IL12Rβ1 |
| CA2993053A1 (en) | 2009-04-27 | 2010-11-04 | Novartis Ag | Antagonistic activin receptor iib (actriib) antibodies for increasing muscle growth |
| AU2010273974B2 (en) | 2009-07-17 | 2016-01-14 | Bioatla, Llc | Simultaneous, integrated selection and evolution of antibody/protein performance and expression in production hosts |
| WO2011021146A1 (en) | 2009-08-20 | 2011-02-24 | Pfizer Inc. | Osteopontin antibodies |
| US8926976B2 (en) | 2009-09-25 | 2015-01-06 | Xoma Technology Ltd. | Modulators |
| WO2011038301A2 (en) | 2009-09-25 | 2011-03-31 | Xoma Technology Ltd. | Screening methods |
| EP2470569A1 (en) | 2009-10-13 | 2012-07-04 | Oxford Biotherapeutics Ltd. | Antibodies against epha10 |
| US9428586B2 (en) | 2009-12-01 | 2016-08-30 | Compugen Ltd | Heparanase splice variant |
| US20150231215A1 (en) | 2012-06-22 | 2015-08-20 | Randolph J. Noelle | VISTA Antagonist and Methods of Use |
| MX342017B (es) | 2010-03-26 | 2016-09-09 | Dartmouth College | Proteina mediadora de celula t regulatoria vista, agentes de enlace de vista y uso de los mismos. |
| US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
| EA201291181A1 (ru) | 2010-05-06 | 2013-05-30 | Новартис Аг | Композиции и способы применения терапевтических поливалентных антител против белка, родственного рецептору липопротеинов низкой плотности 6 (lrp6) |
| CA2798432A1 (en) | 2010-05-06 | 2011-11-10 | Novartis Ag | Compositions and methods of use for therapeutic low density lipoprotein -related protein 6 (lrp6) antibodies |
| CA2803391C (en) | 2010-06-22 | 2021-11-09 | Neogenix Oncology, Inc. | Npc1 antibodies that bind a muc5ac epitope |
| ES2966088T3 (es) * | 2010-07-16 | 2024-04-18 | Bioatla Inc | Nuevos métodos de evolución de proteínas |
| KR20130100267A (ko) | 2010-08-09 | 2013-09-10 | 시박스, 인크. | 질환을 예방하기 위한 방법 및 조성물 |
| SG187908A1 (en) | 2010-08-20 | 2013-03-28 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) |
| WO2012035518A1 (en) | 2010-09-17 | 2012-03-22 | Compugen Ltd. | Compositions and methods for treatment of drug resistant multiple myeloma |
| WO2012040617A2 (en) | 2010-09-23 | 2012-03-29 | Neogenix Oncology, Inc. | Colon and pancreas cancer peptidomimetics |
| JP2013543384A (ja) | 2010-10-05 | 2013-12-05 | ノバルティス アーゲー | 抗−ｉｌ１２ｒベータ１抗体ならびに自己免疫性および炎症性疾患の処置おけるその使用 |
| JP2014504503A (ja) | 2010-12-28 | 2014-02-24 | ゾーマ テクノロジー リミテッド | Ｐｄｚドメインを用いた細胞表面提示 |
| US9409987B2 (en) | 2011-04-15 | 2016-08-09 | Compugen Ltd | Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer |
| PH12013502489B1 (en) | 2011-06-03 | 2019-04-24 | Xoma Technology Ltd | Antibodies specific for tgf-beta |
| WO2012172495A1 (en) | 2011-06-14 | 2012-12-20 | Novartis Ag | Compositions and methods for antibodies targeting tem8 |
| CN103649121B (zh) | 2011-06-28 | 2016-10-19 | 牛津生物疗法有限公司 | 针对adp-核糖基环化酶2的抗体 |
| WO2013001517A1 (en) | 2011-06-30 | 2013-01-03 | Compugen Ltd. | Polypeptides and uses thereof for treatment of autoimmune disorders and infection |
| DK2726099T3 (en) | 2011-07-01 | 2018-11-05 | Novartis Ag | Method of treating metabolic disorders |
| KR102083957B1 (ko) | 2011-12-05 | 2020-03-04 | 노파르티스 아게 | 표피 성장 인자 수용체 3 (her3)에 대한 항체 |
| JP2015500829A (ja) | 2011-12-05 | 2015-01-08 | ノバルティス アーゲー | 上皮細胞増殖因子受容体３（ｈｅｒ３）のドメインｉｉに対するｈｅｒ３の抗体 |
| ES2728278T3 (es) | 2011-12-21 | 2019-10-23 | Novartis Ag | Composiciones que comprenden anticuerpos dirigidos al factor P y C5 |
| SG2014008304A (en) | 2012-02-01 | 2014-06-27 | Compugen Ltd | C10rf32 antibodies, and uses thereof for treatment of cancer |
| US9890215B2 (en) | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and treatment of cancer |
| CN104619722B (zh) | 2012-06-22 | 2022-10-04 | 达特茅斯大学理事会 | 新型vista-ig构建体和vista-ig用于治疗自身免疫性、过敏性和炎性疾病的用途 |
| CA2884704C (en) | 2012-09-07 | 2023-04-04 | Randolph J. Noelle | Vista modulators for diagnosis and treatment of cancer |
| WO2014089111A1 (en) | 2012-12-05 | 2014-06-12 | Novartis Ag | Compositions and methods for antibodies targeting epo |
| CA2891686A1 (en) | 2012-12-18 | 2014-06-26 | Novartis Ag | Compositions and methods that utilize a peptide tag that binds to hyaluronan |
| AU2013370171B2 (en) | 2012-12-28 | 2018-09-13 | Precision Biologics, Inc. | Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer |
| MX371052B (es) | 2013-02-08 | 2020-01-14 | Novartis Ag | Anticuerpos anti-il-17a y su uso en el tratamiento de trastornos autoinmunes e inflamatorios. |
| JP2016514130A (ja) | 2013-03-14 | 2016-05-19 | ノバルティス アーゲー | Ｎｏｔｃｈ３に対する抗体 |
| UY35620A (es) | 2013-06-21 | 2015-01-30 | Novartis Ag | Anticuerpos del receptor 1 de ldl oxidado similar a lectina y métodos de uso |
| AR096601A1 (es) | 2013-06-21 | 2016-01-20 | Novartis Ag | Anticuerpos del receptor 1 de ldl oxidado similar a lectina y métodos de uso |
| CA2918300A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Methods of treating sporadic inclusion body myositis |
| EP4043493A1 (en) | 2013-12-24 | 2022-08-17 | Janssen Pharmaceutica NV | Anti-vista antibodies and fragments |
| US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
| TW201622746A (zh) | 2014-04-24 | 2016-07-01 | 諾華公司 | 改善或加速髖部骨折術後身體復原之方法 |
| AU2015271709B2 (en) | 2014-06-06 | 2020-11-26 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (GITR) and uses thereof |
| EP3154585B1 (en) | 2014-06-11 | 2022-02-23 | Kathy A. Green | Use of vista agonists and antagonists to suppress or enhance humoral immunity |
| EP3160990A2 (en) | 2014-06-25 | 2017-05-03 | Novartis AG | Compositions and methods for long acting proteins |
| US20170327553A1 (en) | 2014-06-25 | 2017-11-16 | Novartis Ag | Compositions and methods for long acting proteins |
| US20170291939A1 (en) | 2014-06-25 | 2017-10-12 | Novartis Ag | Antibodies specific for il-17a fused to hyaluronan binding peptide tags |
| SG10201805646WA (en) | 2014-08-07 | 2018-08-30 | Novartis Ag | Angiopoietin-like 4 antibodies and methods of use |
| WO2016020882A2 (en) | 2014-08-07 | 2016-02-11 | Novartis Ag | Angiopoetin-like 4 (angptl4) antibodies and methods of use |
| TWI711630B (zh) | 2014-11-21 | 2020-12-01 | 美商必治妥美雅史谷比公司 | 抗ｃｄ７３抗體及其用途 |
| JP2018505911A (ja) | 2014-12-05 | 2018-03-01 | イミュネクスト，インコーポレーテッド | 推定上のｖｉｓｔａ受容体としてのｖｓｉｇ８の同定と、ｖｉｓｔａ／ｖｓｉｇ８調節剤を産生するためのその使用 |
| UY36449A (es) | 2014-12-19 | 2016-07-29 | Novartis Ag | Composiciones y métodos para anticuerpos dirigidos a bmp6 |
| EA035412B1 (ru) | 2015-05-29 | 2020-06-10 | Бристол-Майерс Сквибб Компани | Антитела к ox40 и их применение |
| EA201792561A1 (ru) | 2015-06-05 | 2018-04-30 | Новартис Аг | Антитела, нацеленные на морфогенетический белок кости 9 (bmp9), и способы их применения |
| EP3722314A1 (en) | 2015-06-24 | 2020-10-14 | Janssen Pharmaceutica NV | Anti-vista antibodies and fragments |
| UY36751A (es) | 2015-06-26 | 2017-01-31 | Novartis Ag | Anticuerpos de factor xi y métodos de uso |
| WO2017021893A1 (en) | 2015-08-03 | 2017-02-09 | Novartis Ag | Methods of treating fgf21-associated disorders |
| US10000561B2 (en) | 2015-09-09 | 2018-06-19 | Novartis Ag | Thymic stromal lymphopoietin (TSLP)-binding molecules and methods of using the molecules |
| KR20180042433A (ko) | 2015-09-09 | 2018-04-25 | 노파르티스 아게 | 흉선 기질 림포포이에틴 (tslp)-결합 항체 및 항체의 사용 방법 |
| CA3005855A1 (en) | 2015-11-19 | 2017-05-26 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
| CA3008102A1 (en) | 2015-12-18 | 2017-06-22 | Novartis Ag | Antibodies targeting cd32b and methods of use thereof |
| TW202216201A (zh) | 2016-02-12 | 2022-05-01 | 比利時商楊森製藥公司 | 抗vista抗體及片段、其用途及鑑定其之方法 |
| CA3016187A1 (en) | 2016-03-04 | 2017-09-08 | Bristol-Myers Squibb Company | Combination therapy with anti-cd73 antibodies |
| JP7184751B2 (ja) | 2016-04-15 | 2022-12-06 | イミュネクスト インコーポレイテッド | 抗ヒトｖｉｓｔａ抗体およびその使用 |
| CN109071647B (zh) | 2016-04-27 | 2022-11-22 | 诺华股份有限公司 | 抗生长分化因子15的抗体及其用途 |
| TW201802121A (zh) | 2016-05-25 | 2018-01-16 | 諾華公司 | 抗因子XI/XIa抗體之逆轉結合劑及其用途 |
| CA3027651A1 (en) | 2016-06-15 | 2017-12-21 | Novartis Ag | Methods for treating disease using inhibitors of bone morphogenetic protein 6 (bmp6) |
| SG11201900026TA (en) | 2016-07-14 | 2019-01-30 | Bristol Myers Squibb Co | Antibodies against tim3 and uses thereof |
| CA3032146A1 (en) | 2016-08-03 | 2018-02-08 | Bio-Techne Corporation | Identification of vsig3/vista as a novel immune checkpoint and use thereof for immunotherapy |
| KR102431830B1 (ko) | 2016-11-07 | 2022-08-16 | 주식회사 뉴라클사이언스 | 서열 유사성을 가진 항-패밀리 19, 멤버 a5 항체 및 그것의 사용 방법 |
| EP3538546B1 (en) | 2016-11-14 | 2025-01-08 | Novartis AG | Compositions, methods, and therapeutic uses related to fusogenic protein minion |
| BR112019012667A2 (pt) | 2016-12-23 | 2020-02-11 | Novartis Ag | Anticorpos do fator xi e métodos de uso |
| JP2020515283A (ja) | 2016-12-28 | 2020-05-28 | インブバックス，インコーポレーテッド | インフルエンザワクチン |
| EP3580237B1 (en) | 2017-02-08 | 2025-05-14 | Novartis AG | Fgf21 mimetic antibodies and uses thereof |
| SI3600415T1 (sl) | 2017-03-24 | 2026-01-30 | Novartis Ag | Protitelo proti aktivinskemu receptorju tipa ii za uporabo pri zdravljenju srčnega popuščanja |
| WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
| JP7076059B2 (ja) | 2017-06-27 | 2022-05-27 | ニューラクル サイエンス カンパニー リミテッド | 抗ｆａｍ１９ａ５抗体及びその用途 |
| EP3645564A1 (en) | 2017-06-28 | 2020-05-06 | Novartis AG | Methods for preventing and treating urinary incontinence |
| WO2019081983A1 (en) | 2017-10-25 | 2019-05-02 | Novartis Ag | CD32B TARGETING ANTIBODIES AND METHODS OF USE |
| EP3713965A1 (en) | 2017-11-22 | 2020-09-30 | Novartis AG | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
| JP7358361B2 (ja) | 2018-01-12 | 2023-10-10 | ブリストル－マイヤーズ スクイブ カンパニー | Ｔｉｍ３に対する抗体およびその使用 |
| EP3746477A1 (en) | 2018-02-02 | 2020-12-09 | Bio-Techne Corporation | Compounds that modulate the interaction of vista and vsig3 and methods of making and using |
| CA3093407A1 (en) | 2018-03-23 | 2019-09-26 | Bristol-Myers Squibb Company | Antibodies against mica and/or micb and uses thereof |
| KR102824112B1 (ko) | 2018-03-28 | 2025-06-24 | 브리스톨-마이어스 스큅 컴퍼니 | 인터루킨-2/인터루킨-2 수용체 알파 융합 단백질 및 사용 방법 |
| KR20240056644A (ko) | 2018-05-10 | 2024-04-30 | 주식회사 뉴라클사이언스 | 서열 유사성 19, 멤버 a5 항체를 갖는 항-패밀리 및 그의 사용 방법 |
| UY38247A (es) | 2018-05-30 | 2019-12-31 | Novartis Ag | Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación |
| UY38407A (es) | 2018-10-15 | 2020-05-29 | Novartis Ag | Anticuerpos estabilizadores de trem2 |
| EP3898700A1 (en) | 2018-12-18 | 2021-10-27 | Novartis AG | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
| CN113412281B (zh) | 2018-12-26 | 2024-07-23 | 感应检查疗法公司 | Btn3a结合蛋白及其用途 |
| CN113195533B (zh) | 2019-01-02 | 2024-04-26 | 纽洛可科学有限公司 | 抗序列相似家族19成员a5的抗体及其使用方法 |
| EP3914622A1 (en) | 2019-01-22 | 2021-12-01 | Bristol-Myers Squibb Company | Antibodies against il-7r alpha subunit and uses thereof |
| JP2022548881A (ja) | 2019-09-18 | 2022-11-22 | ノバルティス アーゲー | Ｅｎｔｐｄ２抗体、組合せ療法並びに抗体及び組合せ療法を使用する方法 |
| TW202124446A (zh) | 2019-09-18 | 2021-07-01 | 瑞士商諾華公司 | 與ｅｎｔｐｄ２抗體之組合療法 |
| US11524998B2 (en) | 2020-07-16 | 2022-12-13 | Novartis Ag | Anti-betacellulin antibodies, fragments thereof, and multi-specific binding molecules |
| US12018254B2 (en) * | 2020-07-27 | 2024-06-25 | Wisconsin Alumni Research Foundation | Methods of making unbiased phage libraries |
| EP4314068A1 (en) | 2021-04-02 | 2024-02-07 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
| US20250353909A1 (en) | 2022-05-10 | 2025-11-20 | Imcheck Therapeutics | Anti-btn3a antibodies for use in methods of treating gastro-intestinal inflammatory disorders |
| WO2025155877A2 (en) | 2024-01-18 | 2025-07-24 | The Regents Of The University Of California | Antibodies binding to pad4 and uses thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0527809B1 (en) * | 1990-04-05 | 1995-08-16 | CREA, Roberto | Walk-through mutagenesis |
| US6335160B1 (en) * | 1995-02-17 | 2002-01-01 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
| US6238884B1 (en) * | 1995-12-07 | 2001-05-29 | Diversa Corporation | End selection in directed evolution |
| WO2000053744A2 (en) * | 1999-03-09 | 2000-09-14 | Diversa Corporation | End selection in directed evolution |
| IL140441A0 (en) * | 1998-09-29 | 2002-02-10 | Maxygen Inc | Shuffling of codon altered genes |
-
2002
- 2002-05-17 WO PCT/US2002/015767 patent/WO2002092780A2/en not_active Ceased
- 2002-05-17 JP JP2002589648A patent/JP2004532038A/ja active Pending
- 2002-05-17 EP EP02747843A patent/EP1421203A4/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010008391A (ja) * | 2008-05-27 | 2010-01-14 | Toray Ind Inc | 分析用チップ |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1421203A4 (en) | 2005-06-01 |
| WO2002092780A3 (en) | 2004-03-25 |
| EP1421203A2 (en) | 2004-05-26 |
| WO2002092780A2 (en) | 2002-11-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4699662B2 (ja) | 定方向進化における合成ライゲーション再集合 | |
| US5965408A (en) | Method of DNA reassembly by interrupting synthesis | |
| US6740506B2 (en) | End selection in directed evolution | |
| US6635449B2 (en) | Exonuclease-mediated nucleic acid reassembly in directed evolution | |
| US6713282B2 (en) | End selection in directed evolution | |
| US6696275B2 (en) | End selection in directed evolution | |
| JP2002537836A (ja) | 定方向進化におけるエンドセレクション | |
| US20030219752A1 (en) | Novel antigen binding molecules for therapeutic, diagnostic, prophylactic, enzymatic, industrial, and agricultural applications, and methods for generating and screening thereof | |
| WO2002092780A2 (en) | Novel antigen binding molecules for therapeutic, diagnostic, prophylactic, enzymatic, industrial, and agricultural applications, and methods for generating and screening thereof | |
| US20050130156A1 (en) | Methods for making polynucleotides and purifying double-stranded polynucleotides | |
| JP2002505845A (ja) | Ｄｎａシャッフリング方法 | |
| JP2004500019A (ja) | 定方向進化におけるエキソヌクレアーゼ仲介核酸再集合 | |
| JP2003515150A (ja) | キャピラリーアレイに基づくサンプルスクリーニング | |
| US6939689B2 (en) | Exonuclease-mediated nucleic acid reassembly in directed evolution | |
| US20080248464A1 (en) | Method of DNA Shuffling with Polynucleotides Produced by Blocking or Interrupting a Synthesis or Amplification Process | |
| AU2009212959B2 (en) | Synthetic ligation reassembly in directed evolution | |
| Class et al. | Patent application title: SYNTHETIC LIGATION REASSEMBLY IN DIRECTED EVOLUTION Inventors: Jay M. Short (Del Mar, CA, US) | |
| AU2002318140A1 (en) | Novel antigen binding molecules for therapeutic, diagnostic, prophylactic, enzymatic, industrial, and agricultural applications, and methods for generating and screening thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050517 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050517 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080630 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20081208 |