ES2370225T3 - Anticuerpos superhumanizados. - Google Patents
Anticuerpos superhumanizados. Download PDFInfo
- Publication number
- ES2370225T3 ES2370225T3 ES02752269T ES02752269T ES2370225T3 ES 2370225 T3 ES2370225 T3 ES 2370225T3 ES 02752269 T ES02752269 T ES 02752269T ES 02752269 T ES02752269 T ES 02752269T ES 2370225 T3 ES2370225 T3 ES 2370225T3
- Authority
- ES
- Spain
- Prior art keywords
- cdr
- antibody
- subject
- variable region
- human
- 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
- 238000000034 method Methods 0.000 claims abstract description 94
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 31
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 241000282414 Homo sapiens Species 0.000 claims description 274
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 claims description 126
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 claims description 90
- 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 claims description 53
- 108090000623 proteins and genes Proteins 0.000 claims description 53
- 239000000427 antigen Substances 0.000 claims description 52
- 108091007433 antigens Proteins 0.000 claims description 51
- 102000036639 antigens Human genes 0.000 claims description 51
- 210000004602 germ cell Anatomy 0.000 claims description 30
- 150000001413 amino acids Chemical class 0.000 claims description 24
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 23
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 23
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- 238000010494 dissociation reaction Methods 0.000 claims description 7
- 230000005593 dissociations Effects 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 5
- 210000004027 cell Anatomy 0.000 claims description 5
- 102000039446 nucleic acids Human genes 0.000 claims description 4
- 108020004707 nucleic acids Proteins 0.000 claims description 4
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 39
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 28
- 241001529936 Murinae Species 0.000 description 26
- 235000001014 amino acid Nutrition 0.000 description 22
- 108090000765 processed proteins & peptides Proteins 0.000 description 21
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 19
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 19
- 102000054751 human RUNX1T1 Human genes 0.000 description 19
- 241000894007 species Species 0.000 description 15
- 238000010276 construction Methods 0.000 description 12
- 125000003275 alpha amino acid group Chemical group 0.000 description 11
- 230000005847 immunogenicity Effects 0.000 description 11
- 241000282412 Homo Species 0.000 description 10
- 102000008214 Glutamate decarboxylase Human genes 0.000 description 8
- 108091022930 Glutamate decarboxylase Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 238000013459 approach Methods 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 210000004408 hybridoma Anatomy 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 7
- 108060003951 Immunoglobulin Proteins 0.000 description 7
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 7
- 102000018358 immunoglobulin Human genes 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 235000010335 lysozyme Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 239000002795 scorpion venom Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 102000016943 Muramidase Human genes 0.000 description 5
- 108010014251 Muramidase Proteins 0.000 description 5
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 101150117115 V gene Proteins 0.000 description 5
- 210000000628 antibody-producing cell Anatomy 0.000 description 5
- 229960000274 lysozyme Drugs 0.000 description 5
- 239000004325 lysozyme Substances 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 3
- 101150008942 J gene Proteins 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 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 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229960000598 infliximab Drugs 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 101150040566 B3 gene Proteins 0.000 description 1
- 208000031872 Body Remains Diseases 0.000 description 1
- 102000004031 Carboxy-Lyases Human genes 0.000 description 1
- 108090000489 Carboxy-Lyases Proteins 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 101100166600 Homo sapiens CD28 gene Proteins 0.000 description 1
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
- 108010070875 Human Immunodeficiency Virus tat Gene Products Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 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
- 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
- 241000124008 Mammalia Species 0.000 description 1
- 101100332755 Mus musculus Edar gene Proteins 0.000 description 1
- 101100370002 Mus musculus Tnfsf14 gene Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 101710149951 Protein Tat Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009933 burial Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000011268 retreatment Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
Landscapes
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2002/022011 WO2004006955A1 (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2370225T3 true ES2370225T3 (es) | 2011-12-13 |
Family
ID=43969199
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02752269T Expired - Lifetime ES2370225T3 (es) | 2002-07-12 | 2002-07-12 | Anticuerpos superhumanizados. |
Country Status (4)
| Country | Link |
|---|---|
| AT (1) | ATE506966T1 (de) |
| DE (1) | DE60239895D1 (de) |
| DK (1) | DK1539233T3 (de) |
| ES (1) | ES2370225T3 (de) |
-
2002
- 2002-07-12 AT AT02752269T patent/ATE506966T1/de active
- 2002-07-12 ES ES02752269T patent/ES2370225T3/es not_active Expired - Lifetime
- 2002-07-12 DK DK02752269.7T patent/DK1539233T3/da active
- 2002-07-12 DE DE60239895T patent/DE60239895D1/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ATE506966T1 (de) | 2011-05-15 |
| DE60239895D1 (de) | 2011-06-09 |
| DK1539233T3 (da) | 2011-08-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1671416B (zh) | 超人源化抗体 | |
| US20050288491A1 (en) | Super-humanized antibodies against respiratory syncytial virus | |
| US7456260B2 (en) | Humanized antibody | |
| TWI351407B (en) | Method of humanizing immune system molecules | |
| JP6744856B2 (ja) | α−シヌクレインを認識する抗体を含む血液脳関門シャトル | |
| US20190031770A1 (en) | Intercalated single-chain variable fragments | |
| US9550986B2 (en) | High-throughput antibody humanization | |
| KR20140125409A (ko) | 알파-시누클레인을 인식하는 인간화된 항체 | |
| JP2023518952A (ja) | 獣医用抗il4受容体抗体 | |
| TW201134489A (en) | Basigin binding proteins | |
| WO2018235247A1 (ja) | 抗cd10抗体 | |
| WO2019079762A1 (en) | METHODS OF DISCOVERING ANTIBODIES USING TRANSCRIPTOMES AND COMPOSITIONS DERIVED THEREFROM | |
| CN101962408A (zh) | 超人源化抗体 | |
| JP7607289B2 (ja) | 新規の抗b型肝炎ウイルス抗体及びその使用 | |
| ES2370225T3 (es) | Anticuerpos superhumanizados. | |
| JP2023508366A (ja) | 二重特異性fcyriii×cd30抗体構築体の製造方法 | |
| Mader et al. | Humanization strategies for an anti-idiotypic antibody mimicking HIV-1 gp41 | |
| WO2024006975A1 (en) | Methods for antibody humanization | |
| JP2011115175A (ja) | スーパーヒト化抗体 | |
| JP2012152223A (ja) | スーパーヒト化抗体 | |
| JT George et al. | Section Review Biologicals & Immunologicals: Advances in antibody engineering | |
| Marks | Selection of Human Antibody Fragments which Bind Novel Breast Tumor Antigens | |
| Holm | Single-chain antibody construction and functional mapping of the monoclonal antibody TS1: Its interaction with the antigen and the anti-idiotype |