JP2019521668A - 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 - Google Patents
外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 Download PDFInfo
- Publication number
- JP2019521668A JP2019521668A JP2018563156A JP2018563156A JP2019521668A JP 2019521668 A JP2019521668 A JP 2019521668A JP 2018563156 A JP2018563156 A JP 2018563156A JP 2018563156 A JP2018563156 A JP 2018563156A JP 2019521668 A JP2019521668 A JP 2019521668A
- Authority
- JP
- Japan
- Prior art keywords
- human animal
- human
- genetically modified
- immunoglobulin
- region gene
- 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.)
- Granted
Links
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 title claims abstract description 265
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 title claims abstract description 264
- 241001465754 Metazoa Species 0.000 title claims description 35
- 241000282414 Homo sapiens Species 0.000 claims abstract description 1117
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 219
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 175
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 175
- 238000000034 method Methods 0.000 claims abstract description 72
- 210000003719 b-lymphocyte Anatomy 0.000 claims abstract description 45
- 241000894007 species Species 0.000 claims abstract description 37
- 230000011712 cell development Effects 0.000 claims abstract description 25
- 210000001948 pro-b lymphocyte Anatomy 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 108090000623 proteins and genes Proteins 0.000 claims description 346
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 314
- 108091008874 T cell receptors Proteins 0.000 claims description 313
- 238000007792 addition Methods 0.000 claims description 271
- 108091007433 antigens Proteins 0.000 claims description 114
- 102000036639 antigens Human genes 0.000 claims description 114
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 113
- 239000000427 antigen Substances 0.000 claims description 112
- 108060003951 Immunoglobulin Proteins 0.000 claims description 108
- 102000018358 immunoglobulin Human genes 0.000 claims description 108
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 98
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 80
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 80
- 210000004027 cell Anatomy 0.000 claims description 78
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 76
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 63
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 claims description 61
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 42
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 27
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 claims description 24
- 241000283984 Rodentia Species 0.000 claims description 22
- 230000014509 gene expression Effects 0.000 claims description 20
- 210000004602 germ cell Anatomy 0.000 claims description 19
- 108010029485 Protein Isoforms Proteins 0.000 claims description 14
- 102000001708 Protein Isoforms Human genes 0.000 claims description 14
- 238000012239 gene modification Methods 0.000 claims description 12
- 230000005017 genetic modification Effects 0.000 claims description 12
- 235000013617 genetically modified food Nutrition 0.000 claims description 12
- 101001061851 Homo sapiens V(D)J recombination-activating protein 2 Proteins 0.000 claims description 10
- 102000001183 RAG-1 Human genes 0.000 claims description 10
- 108060006897 RAG1 Proteins 0.000 claims description 10
- 102100029591 V(D)J recombination-activating protein 2 Human genes 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 8
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims description 7
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims description 7
- 102100029567 Immunoglobulin kappa light chain Human genes 0.000 claims description 4
- 101710189008 Immunoglobulin kappa light chain Proteins 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims 1
- 230000009261 transgenic effect Effects 0.000 claims 1
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 82
- 239000000203 mixture Substances 0.000 abstract description 80
- 241000699670 Mus sp. Species 0.000 abstract description 64
- 230000021615 conjugation Effects 0.000 description 233
- -1 HSA Proteins 0.000 description 63
- 229920001184 polypeptide Polymers 0.000 description 62
- 102000004196 processed proteins & peptides Human genes 0.000 description 62
- 102100029620 Immunoglobulin lambda constant 2 Human genes 0.000 description 54
- 108010004020 Immunoglobulin lambda-Chains Proteins 0.000 description 54
- 230000027455 binding Effects 0.000 description 54
- 102100029572 Immunoglobulin kappa constant Human genes 0.000 description 51
- 108010090227 Immunoglobulin kappa-Chains Proteins 0.000 description 51
- 241000700159 Rattus Species 0.000 description 51
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 38
- 101000800646 Homo sapiens DNA nucleotidylexotransferase Proteins 0.000 description 37
- 206010028980 Neoplasm Diseases 0.000 description 34
- 239000012634 fragment Substances 0.000 description 32
- 230000003211 malignant effect Effects 0.000 description 31
- 230000004048 modification Effects 0.000 description 25
- 238000012986 modification Methods 0.000 description 25
- 201000011510 cancer Diseases 0.000 description 23
- 210000004408 hybridoma Anatomy 0.000 description 20
- 239000000546 pharmaceutical excipient Substances 0.000 description 20
- 229940024606 amino acid Drugs 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 19
- 150000001413 amino acids Chemical class 0.000 description 19
- 102000025171 antigen binding proteins Human genes 0.000 description 18
- 108091000831 antigen binding proteins Proteins 0.000 description 18
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 18
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 17
- 150000001720 carbohydrates Chemical class 0.000 description 16
- 230000013011 mating Effects 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 16
- 239000003623 enhancer Substances 0.000 description 15
- 102000037865 fusion proteins Human genes 0.000 description 15
- 108020001507 fusion proteins Proteins 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 102000043131 MHC class II family Human genes 0.000 description 13
- 108091054438 MHC class II family Proteins 0.000 description 13
- 235000014633 carbohydrates Nutrition 0.000 description 13
- 241000700605 Viruses Species 0.000 description 12
- 125000003729 nucleotide group Chemical group 0.000 description 12
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 11
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 11
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 10
- 239000000872 buffer Substances 0.000 description 10
- 230000001086 cytosolic effect Effects 0.000 description 10
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- 230000003053 immunization Effects 0.000 description 10
- 238000002649 immunization Methods 0.000 description 10
- 108020004999 messenger RNA Proteins 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 238000012163 sequencing technique Methods 0.000 description 10
- 239000004094 surface-active agent Substances 0.000 description 10
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 9
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 9
- 239000004471 Glycine Substances 0.000 description 9
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 9
- 238000005304 joining Methods 0.000 description 9
- 239000002773 nucleotide Substances 0.000 description 9
- 244000052769 pathogen Species 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- 108700026220 vif Genes Proteins 0.000 description 9
- 102000006395 Globulins Human genes 0.000 description 8
- 108010044091 Globulins Proteins 0.000 description 8
- 102100034256 Mucin-1 Human genes 0.000 description 8
- 102000040430 polynucleotide Human genes 0.000 description 8
- 108091033319 polynucleotide Proteins 0.000 description 8
- 239000002157 polynucleotide Substances 0.000 description 8
- 239000003755 preservative agent Substances 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 7
- 102100032368 Coiled-coil domain-containing protein 110 Human genes 0.000 description 7
- 102100022430 Melanocyte protein PMEL Human genes 0.000 description 7
- 208000009956 adenocarcinoma Diseases 0.000 description 7
- 230000003321 amplification Effects 0.000 description 7
- 238000009826 distribution Methods 0.000 description 7
- 208000032839 leukemia Diseases 0.000 description 7
- 238000003199 nucleic acid amplification method Methods 0.000 description 7
- 230000001717 pathogenic effect Effects 0.000 description 7
- 230000005945 translocation Effects 0.000 description 7
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 6
- 102100039510 Cancer/testis antigen 2 Human genes 0.000 description 6
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 101000889345 Homo sapiens Cancer/testis antigen 2 Proteins 0.000 description 6
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 6
- 101000914321 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 7 Proteins 0.000 description 6
- 101000617725 Homo sapiens Pregnancy-specific beta-1-glycoprotein 2 Proteins 0.000 description 6
- 101000620554 Homo sapiens Ras-related protein Rab-38 Proteins 0.000 description 6
- 101150008942 J gene Proteins 0.000 description 6
- 102100021533 Kita-kyushu lung cancer antigen 1 Human genes 0.000 description 6
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 6
- 108060008487 Myosin Proteins 0.000 description 6
- 102000003505 Myosin Human genes 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 102100022305 Ras-related protein Rab-38 Human genes 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 101150000778 TRY gene Proteins 0.000 description 6
- 102000003425 Tyrosinase Human genes 0.000 description 6
- 108060008724 Tyrosinase Proteins 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 239000005090 green fluorescent protein Substances 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 241000701022 Cytomegalovirus Species 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 5
- 101000868824 Homo sapiens Coiled-coil domain-containing protein 110 Proteins 0.000 description 5
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 5
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 5
- 102000043129 MHC class I family Human genes 0.000 description 5
- 108091054437 MHC class I family Proteins 0.000 description 5
- 229930195725 Mannitol Natural products 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000009395 breeding Methods 0.000 description 5
- 230000001488 breeding effect Effects 0.000 description 5
- 239000006172 buffering agent Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000002779 inactivation Effects 0.000 description 5
- 239000000594 mannitol Substances 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000006798 recombination Effects 0.000 description 5
- 238000005215 recombination Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 102100023003 Ankyrin repeat domain-containing protein 30A Human genes 0.000 description 4
- 102000006306 Antigen Receptors Human genes 0.000 description 4
- 108010083359 Antigen Receptors Proteins 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 102100027314 Beta-2-microglobulin Human genes 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- 241000589874 Campylobacter fetus Species 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
- 108700024394 Exon Proteins 0.000 description 4
- 102100031546 HLA class II histocompatibility antigen, DO beta chain Human genes 0.000 description 4
- 241000711549 Hepacivirus C Species 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000757191 Homo sapiens Ankyrin repeat domain-containing protein 30A Proteins 0.000 description 4
- 101000866281 Homo sapiens HLA class II histocompatibility antigen, DO beta chain Proteins 0.000 description 4
- 101000620359 Homo sapiens Melanocyte protein PMEL Proteins 0.000 description 4
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 description 4
- 101000972282 Homo sapiens Mucin-5AC Proteins 0.000 description 4
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 4
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 4
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- 102100023123 Mucin-16 Human genes 0.000 description 4
- 102100022496 Mucin-5AC Human genes 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 4
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 4
- 206010039491 Sarcoma Diseases 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 4
- 101150117115 V gene Proteins 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000002738 chelating agent Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000006801 homologous recombination Effects 0.000 description 4
- 238000002744 homologous recombination Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000005257 nucleotidylation Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 229940068968 polysorbate 80 Drugs 0.000 description 4
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 4
- 230000000153 supplemental effect Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- SSOORFWOBGFTHL-OTEJMHTDSA-N (4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-5-oxopentanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SSOORFWOBGFTHL-OTEJMHTDSA-N 0.000 description 3
- 102100039583 116 kDa U5 small nuclear ribonucleoprotein component Human genes 0.000 description 3
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- LKKMLIBUAXYLOY-UHFFFAOYSA-N 3-Amino-1-methyl-5H-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=C(N)N=C2C LKKMLIBUAXYLOY-UHFFFAOYSA-N 0.000 description 3
- 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 description 3
- 101710163881 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 3
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 3
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 3
- 102100021222 ATP-dependent Clp protease proteolytic subunit, mitochondrial Human genes 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 102100040069 Aldehyde dehydrogenase 1A1 Human genes 0.000 description 3
- 102100032959 Alpha-actinin-4 Human genes 0.000 description 3
- 101710115256 Alpha-actinin-4 Proteins 0.000 description 3
- 102100024003 Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 Human genes 0.000 description 3
- 206010003571 Astrocytoma Diseases 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 description 3
- 102000015735 Beta-catenin Human genes 0.000 description 3
- 108060000903 Beta-catenin Proteins 0.000 description 3
- 108700012439 CA9 Proteins 0.000 description 3
- 101150108242 CDC27 gene Proteins 0.000 description 3
- 101150034344 CT83 gene Proteins 0.000 description 3
- 102100025588 Calcitonin gene-related peptide 1 Human genes 0.000 description 3
- 102000013392 Carboxylesterase Human genes 0.000 description 3
- 108010051152 Carboxylesterase Proteins 0.000 description 3
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- 102100038916 Caspase-5 Human genes 0.000 description 3
- 102100026548 Caspase-8 Human genes 0.000 description 3
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 3
- 102100039361 Chondrosarcoma-associated gene 2/3 protein Human genes 0.000 description 3
- 102000011591 Cleavage And Polyadenylation Specificity Factor Human genes 0.000 description 3
- 108010076130 Cleavage And Polyadenylation Specificity Factor Proteins 0.000 description 3
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 3
- 108010060267 Cyclin A1 Proteins 0.000 description 3
- 108010058546 Cyclin D1 Proteins 0.000 description 3
- 102100025176 Cyclin-A1 Human genes 0.000 description 3
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 3
- 108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 3
- 102100038111 Cyclin-dependent kinase 12 Human genes 0.000 description 3
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 3
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 3
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 description 3
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 3
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 3
- 102100026245 E3 ubiquitin-protein ligase RNF43 Human genes 0.000 description 3
- 102100037238 E3 ubiquitin-protein ligase UBR4 Human genes 0.000 description 3
- 102100031334 Elongation factor 2 Human genes 0.000 description 3
- 108010055191 EphA3 Receptor Proteins 0.000 description 3
- 102100030324 Ephrin type-A receptor 3 Human genes 0.000 description 3
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 3
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 description 3
- 102100037362 Fibronectin Human genes 0.000 description 3
- 201000008808 Fibrosarcoma Diseases 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 3
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000010956 Glypican Human genes 0.000 description 3
- 108050001154 Glypican Proteins 0.000 description 3
- 108050007237 Glypican-3 Proteins 0.000 description 3
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
- 102100031493 Growth arrest-specific protein 7 Human genes 0.000 description 3
- 102100039317 HAUS augmin-like complex subunit 3 Human genes 0.000 description 3
- 108010036972 HLA-A11 Antigen Proteins 0.000 description 3
- 102000004989 Hepsin Human genes 0.000 description 3
- 108090001101 Hepsin Proteins 0.000 description 3
- 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 description 3
- 101000608799 Homo sapiens 116 kDa U5 small nuclear ribonucleoprotein component Proteins 0.000 description 3
- 101000750222 Homo sapiens ATP-dependent Clp protease proteolytic subunit, mitochondrial Proteins 0.000 description 3
- 101000890570 Homo sapiens Aldehyde dehydrogenase 1A1 Proteins 0.000 description 3
- 101000741445 Homo sapiens Calcitonin Proteins 0.000 description 3
- 101000932890 Homo sapiens Calcitonin gene-related peptide 1 Proteins 0.000 description 3
- 101000741072 Homo sapiens Caspase-5 Proteins 0.000 description 3
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 3
- 101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 description 3
- 101000745414 Homo sapiens Chondrosarcoma-associated gene 2/3 protein Proteins 0.000 description 3
- 101000884345 Homo sapiens Cyclin-dependent kinase 12 Proteins 0.000 description 3
- 101000864646 Homo sapiens Dickkopf-related protein 1 Proteins 0.000 description 3
- 101000692702 Homo sapiens E3 ubiquitin-protein ligase RNF43 Proteins 0.000 description 3
- 101000807547 Homo sapiens E3 ubiquitin-protein ligase UBR4 Proteins 0.000 description 3
- 101001060267 Homo sapiens Fibroblast growth factor 5 Proteins 0.000 description 3
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 3
- 101000923044 Homo sapiens Growth arrest-specific protein 7 Proteins 0.000 description 3
- 101001035819 Homo sapiens HAUS augmin-like complex subunit 3 Proteins 0.000 description 3
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 description 3
- 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 3
- 101000614481 Homo sapiens Kidney-associated antigen 1 Proteins 0.000 description 3
- 101001027621 Homo sapiens Kinesin-like protein KIF20A Proteins 0.000 description 3
- 101000971605 Homo sapiens Kita-kyushu lung cancer antigen 1 Proteins 0.000 description 3
- 101001014223 Homo sapiens MAPK/MAK/MRK overlapping kinase Proteins 0.000 description 3
- 101001134060 Homo sapiens Melanocyte-stimulating hormone receptor Proteins 0.000 description 3
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 3
- 101001036406 Homo sapiens Melanoma-associated antigen C1 Proteins 0.000 description 3
- 101001057156 Homo sapiens Melanoma-associated antigen C2 Proteins 0.000 description 3
- 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 description 3
- 101000978949 Homo sapiens NADP-dependent malic enzyme Proteins 0.000 description 3
- 101000588345 Homo sapiens Nuclear transcription factor Y subunit gamma Proteins 0.000 description 3
- 101000601724 Homo sapiens Paired box protein Pax-5 Proteins 0.000 description 3
- 101000619805 Homo sapiens Peroxiredoxin-5, mitochondrial Proteins 0.000 description 3
- 101000829725 Homo sapiens Phospholipid hydroperoxide glutathione peroxidase Proteins 0.000 description 3
- 101000610208 Homo sapiens Poly(A) polymerase gamma Proteins 0.000 description 3
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 3
- 101000877404 Homo sapiens Protein enabled homolog Proteins 0.000 description 3
- 101001067951 Homo sapiens Protein phosphatase 1 regulatory subunit 3B Proteins 0.000 description 3
- 101000842302 Homo sapiens Protein-cysteine N-palmitoyltransferase HHAT Proteins 0.000 description 3
- 101000613391 Homo sapiens Protocadherin beta-16 Proteins 0.000 description 3
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
- 101000591201 Homo sapiens Receptor-type tyrosine-protein phosphatase kappa Proteins 0.000 description 3
- 101001073409 Homo sapiens Retrotransposon-derived protein PEG10 Proteins 0.000 description 3
- 101000821981 Homo sapiens Sarcoma antigen 1 Proteins 0.000 description 3
- 101000665150 Homo sapiens Small nuclear ribonucleoprotein Sm D1 Proteins 0.000 description 3
- 101000665250 Homo sapiens Small nuclear ribonucleoprotein Sm D2 Proteins 0.000 description 3
- 101001056234 Homo sapiens Sperm mitochondrial-associated cysteine-rich protein Proteins 0.000 description 3
- 101000824971 Homo sapiens Sperm surface protein Sp17 Proteins 0.000 description 3
- 101000664703 Homo sapiens Transcription factor SOX-10 Proteins 0.000 description 3
- 101000904724 Homo sapiens Transmembrane glycoprotein NMB Proteins 0.000 description 3
- 101000801433 Homo sapiens Trophoblast glycoprotein Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 3
- 102100034872 Kallikrein-4 Human genes 0.000 description 3
- 102100040442 Kidney-associated antigen 1 Human genes 0.000 description 3
- 102100037694 Kinesin-like protein KIF20A Human genes 0.000 description 3
- 102100031520 MAPK/MAK/MRK overlapping kinase Human genes 0.000 description 3
- 108010010995 MART-1 Antigen Proteins 0.000 description 3
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 3
- 102000005727 Mammaglobin A Human genes 0.000 description 3
- 108010031030 Mammaglobin A Proteins 0.000 description 3
- 102100030417 Matrilysin Human genes 0.000 description 3
- 108090000855 Matrilysin Proteins 0.000 description 3
- 102100034216 Melanocyte-stimulating hormone receptor Human genes 0.000 description 3
- 102100039447 Melanoma-associated antigen C1 Human genes 0.000 description 3
- 102100027252 Melanoma-associated antigen C2 Human genes 0.000 description 3
- 102100026712 Metalloreductase STEAP1 Human genes 0.000 description 3
- 108010092801 Midkine Proteins 0.000 description 3
- 102000016776 Midkine Human genes 0.000 description 3
- 108010008707 Mucin-1 Proteins 0.000 description 3
- 102000015728 Mucins Human genes 0.000 description 3
- 108010063954 Mucins Proteins 0.000 description 3
- 241000699729 Muridae Species 0.000 description 3
- 101100193635 Mus musculus Rag2 gene Proteins 0.000 description 3
- 102100022913 NAD-dependent protein deacetylase sirtuin-2 Human genes 0.000 description 3
- 102100031719 Nuclear transcription factor Y subunit gamma Human genes 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102000036673 PRAME Human genes 0.000 description 3
- 108060006580 PRAME Proteins 0.000 description 3
- 102100034640 PWWP domain-containing DNA repair factor 3A Human genes 0.000 description 3
- 108050007154 PWWP domain-containing DNA repair factor 3A Proteins 0.000 description 3
- 102100037504 Paired box protein Pax-5 Human genes 0.000 description 3
- 108010077519 Peptide Elongation Factor 2 Proteins 0.000 description 3
- 102000017794 Perilipin-2 Human genes 0.000 description 3
- 108010067163 Perilipin-2 Proteins 0.000 description 3
- 102100022078 Peroxiredoxin-5, mitochondrial Human genes 0.000 description 3
- 101710199379 Pituitary tumor-transforming gene 1 protein-interacting protein Proteins 0.000 description 3
- 102100040153 Poly(A) polymerase gamma Human genes 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 3
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 3
- 102100038358 Prostate-specific antigen Human genes 0.000 description 3
- 102100035093 Protein enabled homolog Human genes 0.000 description 3
- 102100034504 Protein phosphatase 1 regulatory subunit 3B Human genes 0.000 description 3
- 102000018471 Proto-Oncogene Proteins B-raf Human genes 0.000 description 3
- 108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 description 3
- 102100040927 Protocadherin beta-16 Human genes 0.000 description 3
- 101710104378 Putative malate oxidoreductase [NAD] Proteins 0.000 description 3
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 3
- 102100034089 Receptor-type tyrosine-protein phosphatase kappa Human genes 0.000 description 3
- 102100037421 Regulator of G-protein signaling 5 Human genes 0.000 description 3
- 101710140403 Regulator of G-protein signaling 5 Proteins 0.000 description 3
- 102100035844 Retrotransposon-derived protein PEG10 Human genes 0.000 description 3
- 108700019345 SYT-SSX fusion Proteins 0.000 description 3
- 102100021466 Sarcoma antigen 1 Human genes 0.000 description 3
- 108010041216 Sirtuin 2 Proteins 0.000 description 3
- 102100038685 Small nuclear ribonucleoprotein Sm D2 Human genes 0.000 description 3
- 102100026503 Sperm mitochondrial-associated cysteine-rich protein Human genes 0.000 description 3
- 102100022441 Sperm surface protein Sp17 Human genes 0.000 description 3
- 108010002687 Survivin Proteins 0.000 description 3
- 108700019889 TEL-AML1 fusion Proteins 0.000 description 3
- 108010017842 Telomerase Proteins 0.000 description 3
- 102100038808 Transcription factor SOX-10 Human genes 0.000 description 3
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 3
- 102000005924 Triose-Phosphate Isomerase Human genes 0.000 description 3
- 108700015934 Triose-phosphate isomerases Proteins 0.000 description 3
- 102100033579 Trophoblast glycoprotein Human genes 0.000 description 3
- LVTKHGUGBGNBPL-UHFFFAOYSA-N Trp-P-1 Chemical compound N1C2=CC=CC=C2C2=C1C(C)=C(N)N=C2C LVTKHGUGBGNBPL-UHFFFAOYSA-N 0.000 description 3
- 108010027252 Trypsinogen Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 108700020467 WT1 Proteins 0.000 description 3
- 102100040733 Zinc finger protein 395 Human genes 0.000 description 3
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 108010056708 bcr-abl Fusion Proteins Proteins 0.000 description 3
- 102000004441 bcr-abl Fusion Proteins Human genes 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 3
- 229960005091 chloramphenicol Drugs 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 210000005220 cytoplasmic tail Anatomy 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 101150007302 dntt gene Proteins 0.000 description 3
- 210000003317 double-positive, alpha-beta immature T lymphocyte Anatomy 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 108010024383 kallikrein 4 Proteins 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 229960005489 paracetamol Drugs 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 108040000983 polyphosphate:AMP phosphotransferase activity proteins Proteins 0.000 description 3
- 229950008882 polysorbate Drugs 0.000 description 3
- 229940068977 polysorbate 20 Drugs 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000002510 pyrogen Substances 0.000 description 3
- 235000002020 sage Nutrition 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 239000008181 tonicity modifier Substances 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- DIHXSRXTECMMJY-MURFETPASA-N 2-[dimethyl-[(9z,12z)-octadeca-9,12-dienyl]azaniumyl]acetate Chemical group CCCCC\C=C/C\C=C/CCCCCCCC[N+](C)(C)CC([O-])=O DIHXSRXTECMMJY-MURFETPASA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 2
- 206010069754 Acquired gene mutation Diseases 0.000 description 2
- 241000606729 Actinobacillus equuli Species 0.000 description 2
- 208000026872 Addison Disease Diseases 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 201000003076 Angiosarcoma Diseases 0.000 description 2
- 244000303258 Annona diversifolia Species 0.000 description 2
- 235000002198 Annona diversifolia Nutrition 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 241000228212 Aspergillus Species 0.000 description 2
- 241001225321 Aspergillus fumigatus Species 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
- 241000223775 Babesia caballi Species 0.000 description 2
- 241000589567 Brucella abortus Species 0.000 description 2
- 241001509299 Brucella canis Species 0.000 description 2
- 241001148106 Brucella melitensis Species 0.000 description 2
- 241000589568 Brucella ovis Species 0.000 description 2
- 241001148111 Brucella suis Species 0.000 description 2
- 241000244036 Brugia Species 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 2
- 241000222122 Candida albicans Species 0.000 description 2
- 241000222178 Candida tropicalis Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102100034357 Casein kinase I isoform alpha Human genes 0.000 description 2
- 108090000538 Caspase-8 Proteins 0.000 description 2
- 241000282994 Cervidae Species 0.000 description 2
- 241000606161 Chlamydia Species 0.000 description 2
- 241001647378 Chlamydia psittaci Species 0.000 description 2
- 208000005243 Chondrosarcoma Diseases 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- 241000193155 Clostridium botulinum Species 0.000 description 2
- 241000193449 Clostridium tetani Species 0.000 description 2
- 241000224483 Coccidia Species 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 102100024342 Contactin-2 Human genes 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 241000243990 Dirofilaria Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 102100024405 GPI-linked NAD(P)(+)-arginine ADP-ribosyltransferase 1 Human genes 0.000 description 2
- 101710144640 GPI-linked NAD(P)(+)-arginine ADP-ribosyltransferase 1 Proteins 0.000 description 2
- 101710113436 GTPase KRas Proteins 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 241000207201 Gardnerella vaginalis Species 0.000 description 2
- 241000699694 Gerbillinae Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 208000024869 Goodpasture syndrome Diseases 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 206010018691 Granuloma Diseases 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 2
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 2
- 108010050568 HLA-DM antigens Proteins 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 108010034145 Helminth Proteins Proteins 0.000 description 2
- 208000001258 Hemangiosarcoma Diseases 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 241000228402 Histoplasma Species 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- 101000994700 Homo sapiens Casein kinase I isoform alpha Proteins 0.000 description 2
- 101000909516 Homo sapiens Contactin-2 Proteins 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 2
- 101000648075 Homo sapiens Trafficking protein particle complex subunit 1 Proteins 0.000 description 2
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 2
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 description 2
- 101710112634 Interleukin-13 receptor subunit alpha-2 Proteins 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- 102100031413 L-dopachrome tautomerase Human genes 0.000 description 2
- 101710093778 L-dopachrome tautomerase Proteins 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000222722 Leishmania <genus> Species 0.000 description 2
- 102100024144 Lengsin Human genes 0.000 description 2
- 101710113750 Lengsin Proteins 0.000 description 2
- 241000589902 Leptospira Species 0.000 description 2
- 241000144128 Lichtheimia corymbifera Species 0.000 description 2
- 241000186779 Listeria monocytogenes Species 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- 206010027145 Melanocytic naevus Diseases 0.000 description 2
- 241000186359 Mycobacterium Species 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- 241000202955 Mycoplasma bovigenitalium Species 0.000 description 2
- 241000588653 Neisseria Species 0.000 description 2
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 206010061332 Paraganglion neoplasm Diseases 0.000 description 2
- 241000223785 Paramecium Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 208000031845 Pernicious anaemia Diseases 0.000 description 2
- 201000005702 Pertussis Diseases 0.000 description 2
- 241000224016 Plasmodium Species 0.000 description 2
- 241000223960 Plasmodium falciparum Species 0.000 description 2
- 241000233870 Pneumocystis Species 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001219 Polysorbate 40 Polymers 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 241000606701 Rickettsia Species 0.000 description 2
- 241000607142 Salmonella Species 0.000 description 2
- 241000607662 Salmonella enterica subsp. enterica serovar Abortusequi Species 0.000 description 2
- 241000522522 Salmonella enterica subsp. enterica serovar Abortusovis Species 0.000 description 2
- 241000607768 Shigella Species 0.000 description 2
- 101710173693 Short transient receptor potential channel 1 Proteins 0.000 description 2
- 101710173694 Short transient receptor potential channel 2 Proteins 0.000 description 2
- 241000191940 Staphylococcus Species 0.000 description 2
- 241000194017 Streptococcus Species 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 206010042742 Sympathetic ophthalmia Diseases 0.000 description 2
- 108700042076 T-Cell Receptor alpha Genes Proteins 0.000 description 2
- 241000223996 Toxoplasma Species 0.000 description 2
- 241000223997 Toxoplasma gondii Species 0.000 description 2
- 102100025256 Trafficking protein particle complex subunit 1 Human genes 0.000 description 2
- 241000589884 Treponema pallidum Species 0.000 description 2
- 241000224527 Trichomonas vaginalis Species 0.000 description 2
- 241001058196 Tritrichomonas foetus Species 0.000 description 2
- 241000186064 Trueperella pyogenes Species 0.000 description 2
- 241000223089 Trypanosoma equiperdum Species 0.000 description 2
- 102000018690 Trypsinogen Human genes 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 210000001053 ameloblast Anatomy 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 229940091771 aspergillus fumigatus Drugs 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 2
- 229960001950 benzethonium chloride Drugs 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 229940056450 brucella abortus Drugs 0.000 description 2
- 229940038698 brucella melitensis Drugs 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 229940095731 candida albicans Drugs 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 2
- 201000001981 dermatomyositis Diseases 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 244000000013 helminth Species 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 239000000710 homodimer Substances 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 230000002998 immunogenetic effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 108010024941 iodothyronine deiodinase type II Proteins 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000007834 ligase chain reaction Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 241001515942 marmosets Species 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
- 239000012457 nonaqueous media Substances 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- 210000000287 oocyte Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- 208000007312 paraganglioma Diseases 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 201000000317 pneumocystosis Diseases 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920001993 poloxamer 188 Polymers 0.000 description 2
- 201000006292 polyarteritis nodosa Diseases 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 2
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 2
- 229940101027 polysorbate 40 Drugs 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000037439 somatic mutation Effects 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000012289 standard assay Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 210000002105 tongue Anatomy 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 241000712461 unidentified influenza virus Species 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 150000005206 1,2-dihydroxybenzenes Chemical class 0.000 description 1
- 150000005207 1,3-dihydroxybenzenes Chemical class 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- TYIOVYZMKITKRO-UHFFFAOYSA-N 2-[hexadecyl(dimethyl)azaniumyl]acetate Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)CC([O-])=O TYIOVYZMKITKRO-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
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- DIROHOMJLWMERM-UHFFFAOYSA-N 3-[dimethyl(octadecyl)azaniumyl]propane-1-sulfonate Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O DIROHOMJLWMERM-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 241000699725 Acomys Species 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000016557 Acute basophilic leukemia Diseases 0.000 description 1
- 208000004804 Adenomatous Polyps Diseases 0.000 description 1
- 102100040036 Adhesion G-protein coupled receptor G4 Human genes 0.000 description 1
- 208000006468 Adrenal Cortex Neoplasms Diseases 0.000 description 1
- 206010001324 Adrenal atrophy Diseases 0.000 description 1
- 206010073360 Appendix cancer Diseases 0.000 description 1
- 101001073212 Arabidopsis thaliana Peroxidase 33 Proteins 0.000 description 1
- 208000006400 Arbovirus Encephalitis Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 208000004300 Atrophic Gastritis Diseases 0.000 description 1
- 208000031212 Autoimmune polyendocrinopathy Diseases 0.000 description 1
- 208000022106 Autoimmune polyendocrinopathy type 2 Diseases 0.000 description 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102100027522 Baculoviral IAP repeat-containing protein 7 Human genes 0.000 description 1
- 235000017166 Bambusa arundinacea Nutrition 0.000 description 1
- 235000017491 Bambusa tulda Nutrition 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 208000007690 Brenner tumor Diseases 0.000 description 1
- 206010073258 Brenner tumour Diseases 0.000 description 1
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 description 1
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 102100026094 C-type lectin domain family 12 member A Human genes 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 102100027207 CD27 antigen Human genes 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 201000002829 CREST Syndrome Diseases 0.000 description 1
- 101100426754 Caenorhabditis elegans try-5 gene Proteins 0.000 description 1
- 241000398949 Calomyscidae Species 0.000 description 1
- 241000700192 Calomyscus sp. Species 0.000 description 1
- 102100029968 Calreticulin Human genes 0.000 description 1
- 206010007275 Carcinoid tumour Diseases 0.000 description 1
- 201000000274 Carcinosarcoma Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 206010050337 Cerumen impaction Diseases 0.000 description 1
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 241000398985 Cricetidae Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- 101150097493 D gene Proteins 0.000 description 1
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- QWIZNVHXZXRPDR-UHFFFAOYSA-N D-melezitose Natural products O1C(CO)C(O)C(O)C(O)C1OC1C(O)C(CO)OC1(CO)OC1OC(CO)C(O)C(O)C1O QWIZNVHXZXRPDR-UHFFFAOYSA-N 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- 102100023226 Early growth response protein 1 Human genes 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- 241001466953 Echovirus Species 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 1
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 1
- 102100039328 Endoplasmin Human genes 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 206010014958 Eosinophilic leukaemia Diseases 0.000 description 1
- 108010055196 EphA2 Receptor Proteins 0.000 description 1
- 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 102100031512 Fc receptor-like protein 3 Human genes 0.000 description 1
- 206010053717 Fibrous histiocytoma Diseases 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- 102100035139 Folate receptor alpha Human genes 0.000 description 1
- 208000004463 Follicular Adenocarcinoma Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 102100039717 G antigen 1 Human genes 0.000 description 1
- 102100030708 GTPase KRas Human genes 0.000 description 1
- 208000036495 Gastritis atrophic Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000007465 Giant cell arteritis Diseases 0.000 description 1
- 208000000779 Gingival Neoplasms Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010018498 Goitre Diseases 0.000 description 1
- 206010018693 Granuloma inguinale Diseases 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000005234 Granulosa Cell Tumor Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 1
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 description 1
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 1
- 102100028970 HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 description 1
- 102100028966 HLA class I histocompatibility antigen, alpha chain F Human genes 0.000 description 1
- 102100033079 HLA class II histocompatibility antigen, DM alpha chain Human genes 0.000 description 1
- 102100031258 HLA class II histocompatibility antigen, DM beta chain Human genes 0.000 description 1
- 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 description 1
- 102100036243 HLA class II histocompatibility antigen, DQ alpha 1 chain Human genes 0.000 description 1
- 102100036241 HLA class II histocompatibility antigen, DQ beta 1 chain Human genes 0.000 description 1
- 102100040505 HLA class II histocompatibility antigen, DR alpha chain Human genes 0.000 description 1
- 108010075704 HLA-A Antigens Proteins 0.000 description 1
- 108010058607 HLA-B Antigens Proteins 0.000 description 1
- 108010052199 HLA-C Antigens Proteins 0.000 description 1
- 108010041384 HLA-DPA antigen Proteins 0.000 description 1
- 108010086786 HLA-DQA1 antigen Proteins 0.000 description 1
- 108010067148 HLA-DQbeta antigen Proteins 0.000 description 1
- 108010067802 HLA-DR alpha-Chains Proteins 0.000 description 1
- 101150112743 HSPA5 gene Proteins 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
- 208000006968 Helminthiasis Diseases 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 208000002291 Histiocytic Sarcoma Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 101000959604 Homo sapiens Adhesion G-protein coupled receptor G4 Proteins 0.000 description 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
- 101000936083 Homo sapiens Baculoviral IAP repeat-containing protein 7 Proteins 0.000 description 1
- 101000765923 Homo sapiens Bcl-2-like protein 1 Proteins 0.000 description 1
- 101000912622 Homo sapiens C-type lectin domain family 12 member A Proteins 0.000 description 1
- 101100059307 Homo sapiens CCDC110 gene Proteins 0.000 description 1
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 1
- 101000793651 Homo sapiens Calreticulin Proteins 0.000 description 1
- 101000910338 Homo sapiens Carbonic anhydrase 9 Proteins 0.000 description 1
- 101000954709 Homo sapiens Doublecortin domain-containing protein 2 Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101001049697 Homo sapiens Early growth response protein 1 Proteins 0.000 description 1
- 101000846910 Homo sapiens Fc receptor-like protein 3 Proteins 0.000 description 1
- 101001023230 Homo sapiens Folate receptor alpha Proteins 0.000 description 1
- 101000886137 Homo sapiens G antigen 1 Proteins 0.000 description 1
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 description 1
- 101000986085 Homo sapiens HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 description 1
- 101000986080 Homo sapiens HLA class I histocompatibility antigen, alpha chain F Proteins 0.000 description 1
- 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 description 1
- 101000985516 Homo sapiens Hermansky-Pudlak syndrome 5 protein Proteins 0.000 description 1
- 101000854886 Homo sapiens Immunoglobulin iota chain Proteins 0.000 description 1
- 101001138089 Homo sapiens Immunoglobulin kappa variable 1-39 Proteins 0.000 description 1
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 1
- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 1
- 101001063456 Homo sapiens Leucine-rich repeat-containing G-protein coupled receptor 5 Proteins 0.000 description 1
- 101000628535 Homo sapiens Metalloreductase STEAP2 Proteins 0.000 description 1
- 101001133081 Homo sapiens Mucin-2 Proteins 0.000 description 1
- 101000972284 Homo sapiens Mucin-3A Proteins 0.000 description 1
- 101000972286 Homo sapiens Mucin-4 Proteins 0.000 description 1
- 101000972276 Homo sapiens Mucin-5B Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 description 1
- 101000613490 Homo sapiens Paired box protein Pax-3 Proteins 0.000 description 1
- 101001123325 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-beta Proteins 0.000 description 1
- 101000691463 Homo sapiens Placenta-specific protein 1 Proteins 0.000 description 1
- 101000772905 Homo sapiens Polyubiquitin-B Proteins 0.000 description 1
- 101001123448 Homo sapiens Prolactin receptor Proteins 0.000 description 1
- 101001136981 Homo sapiens Proteasome subunit beta type-9 Proteins 0.000 description 1
- 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 description 1
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 description 1
- 101000873927 Homo sapiens Squamous cell carcinoma antigen recognized by T-cells 3 Proteins 0.000 description 1
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 1
- 101000638154 Homo sapiens Transmembrane protease serine 2 Proteins 0.000 description 1
- 101000801255 Homo sapiens Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000836268 Homo sapiens U4/U6.U5 tri-snRNP-associated protein 1 Proteins 0.000 description 1
- 101000808108 Homo sapiens Uroplakin-3a Proteins 0.000 description 1
- 101000955999 Homo sapiens V-set domain-containing T-cell activation inhibitor 1 Proteins 0.000 description 1
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 1
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102100020744 Immunoglobulin iota chain Human genes 0.000 description 1
- 102100020910 Immunoglobulin kappa variable 1-39 Human genes 0.000 description 1
- 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 description 1
- 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 241000701460 JC polyomavirus Species 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
- 101150028321 Lck gene Proteins 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 102100031036 Leucine-rich repeat-containing G-protein coupled receptor 5 Human genes 0.000 description 1
- 201000004462 Leydig Cell Tumor Diseases 0.000 description 1
- 208000000265 Lobular Carcinoma Diseases 0.000 description 1
- 208000000185 Localized scleroderma Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 241001482085 Meloe Species 0.000 description 1
- 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
- 201000009574 Mesenchymal Chondrosarcoma Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 102100026711 Metalloreductase STEAP2 Human genes 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 1
- 102100034263 Mucin-2 Human genes 0.000 description 1
- 102100022497 Mucin-3A Human genes 0.000 description 1
- 102100022693 Mucin-4 Human genes 0.000 description 1
- 208000013811 Mueller mixed tumour Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 241000398750 Muroidea Species 0.000 description 1
- 101001077354 Mus musculus Receptor of activated protein C kinase 1 Proteins 0.000 description 1
- 241000699669 Mus saxicola Species 0.000 description 1
- 241000282339 Mustela Species 0.000 description 1
- 241000282341 Mustela putorius furo Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N N-methylaminoacetic acid Natural products C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000232901 Nephroma Species 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 241000398990 Nesomyidae Species 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 208000007871 Odontogenic Tumors Diseases 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 102100040891 Paired box protein Pax-3 Human genes 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 241001537205 Paracoccidioides Species 0.000 description 1
- 241000526686 Paracoccidioides brasiliensis Species 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 102100028961 Peroxisome proliferator-activated receptor gamma coactivator 1-beta Human genes 0.000 description 1
- 244000082204 Phyllostachys viridis Species 0.000 description 1
- 235000015334 Phyllostachys viridis Nutrition 0.000 description 1
- 208000009077 Pigmented Nevus Diseases 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 102100026181 Placenta-specific protein 1 Human genes 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 102100030432 Polyubiquitin-B Human genes 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 102100029000 Prolactin receptor Human genes 0.000 description 1
- 102100035764 Proteasome subunit beta type-9 Human genes 0.000 description 1
- 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 208000010362 Protozoan Infections Diseases 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 108010066717 Q beta Replicase Proteins 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 241000158504 Rhodococcus hoagii Species 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 235000011449 Rosa Nutrition 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- 102100029198 SLAM family member 7 Human genes 0.000 description 1
- 108091006938 SLC39A6 Proteins 0.000 description 1
- 101100111629 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR2 gene Proteins 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 208000003252 Signet Ring Cell Carcinoma Diseases 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 239000004288 Sodium dehydroacetate Substances 0.000 description 1
- 241000398956 Spalacidae Species 0.000 description 1
- 102100035748 Squamous cell carcinoma antigen recognized by T-cells 3 Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 108700042077 T-Cell Receptor beta Genes Proteins 0.000 description 1
- 108700042074 T-Cell Receptor delta Genes Proteins 0.000 description 1
- 108700042082 T-Cell Receptor gamma Genes Proteins 0.000 description 1
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 1
- 101150006914 TRP1 gene Proteins 0.000 description 1
- 208000001106 Takayasu Arteritis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010043276 Teratoma Diseases 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 102100031989 Transmembrane protease serine 2 Human genes 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102100033726 Tumor necrosis factor receptor superfamily member 17 Human genes 0.000 description 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 1
- 102100027244 U4/U6.U5 tri-snRNP-associated protein 1 Human genes 0.000 description 1
- 102100038854 Uroplakin-3a Human genes 0.000 description 1
- 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 description 1
- 241000607626 Vibrio cholerae Species 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 102000040856 WT1 Human genes 0.000 description 1
- 101150084041 WT1 gene Proteins 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 1
- 102100023144 Zinc transporter ZIP6 Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000002517 adenoid cystic carcinoma Diseases 0.000 description 1
- 201000008395 adenosquamous carcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 201000002454 adrenal cortex cancer Diseases 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 208000010029 ameloblastoma Diseases 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 201000007436 apocrine adenocarcinoma Diseases 0.000 description 1
- 208000021780 appendiceal neoplasm Diseases 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 201000009780 autoimmune polyendocrine syndrome type 2 Diseases 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000011425 bamboo Substances 0.000 description 1
- 201000007551 basophilic adenocarcinoma Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 208000001119 benign fibrous histiocytoma Diseases 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 208000007047 blue nevus Diseases 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000003714 breast lobular carcinoma Diseases 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 210000002939 cerumen Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 201000005217 chondroblastoma Diseases 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
- 208000021668 chronic eosinophilic leukemia Diseases 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical class OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 208000002445 cystadenocarcinoma Diseases 0.000 description 1
- 201000003146 cystitis Diseases 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
- 230000001419 dependent effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 201000010877 epithelioid cell melanoma Diseases 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 201000008825 fibrosarcoma of bone Diseases 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 108091008053 gene clusters Proteins 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 235000003869 genetically modified organism Nutrition 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 108010017007 glucose-regulated proteins Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 201000003872 goiter Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000004565 granule cell Anatomy 0.000 description 1
- 101150028578 grp78 gene Proteins 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 150000004687 hexahydrates Chemical class 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 108040006861 interleukin-7 receptor activity proteins Proteins 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
- 125000003010 ionic group Chemical group 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000022013 kidney Wilms tumor Diseases 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 125000005645 linoleyl group Chemical group 0.000 description 1
- 125000003473 lipid group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 208000012804 lymphangiosarcoma Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 150000002672 m-cresols Chemical class 0.000 description 1
- 229960002337 magnesium chloride Drugs 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 201000006812 malignant histiocytosis Diseases 0.000 description 1
- 208000028676 malignant spindle cell neoplasm Diseases 0.000 description 1
- 208000025854 malignant tumor of adrenal cortex Diseases 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 201000008749 mast-cell sarcoma Diseases 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 210000005074 megakaryoblast Anatomy 0.000 description 1
- QWIZNVHXZXRPDR-WSCXOGSTSA-N melezitose Chemical compound O([C@@]1(O[C@@H]([C@H]([C@@H]1O[C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O)CO)CO)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QWIZNVHXZXRPDR-WSCXOGSTSA-N 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 201000008806 mesenchymal cell neoplasm Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 201000010225 mixed cell type cancer Diseases 0.000 description 1
- 208000029638 mixed neoplasm Diseases 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 201000010879 mucinous adenocarcinoma Diseases 0.000 description 1
- 208000010492 mucinous cystadenocarcinoma Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- NZXVYLJKFYSEPO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-16-methylheptadecanamide Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)NCCCN(C)C NZXVYLJKFYSEPO-UHFFFAOYSA-N 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 208000025351 nephroma Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- ZLGLJDGHKLKKIV-UHFFFAOYSA-M nitrosooxy(phenyl)mercury Chemical compound [O-]N=O.[Hg+]C1=CC=CC=C1 ZLGLJDGHKLKKIV-UHFFFAOYSA-M 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 208000027825 odontogenic neoplasm Diseases 0.000 description 1
- 125000001117 oleyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 201000010210 papillary cystadenocarcinoma Diseases 0.000 description 1
- 201000001494 papillary transitional carcinoma Diseases 0.000 description 1
- 208000031101 papillary transitional cell carcinoma Diseases 0.000 description 1
- 208000014837 parasitic helminthiasis infectious disease Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical class CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 1
- 102000032166 peptide antigen binding proteins Human genes 0.000 description 1
- 108091010590 peptide antigen binding proteins Proteins 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 210000004786 perivascular cell Anatomy 0.000 description 1
- 101150079312 pgk1 gene Proteins 0.000 description 1
- 208000015385 phacoanaphylactic uveitis Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000003186 pharmaceutical solution Substances 0.000 description 1
- 239000008180 pharmaceutical surfactant Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003021 phthalic acid derivatives Chemical class 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 208000031223 plasma cell leukemia Diseases 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 208000015768 polyposis Diseases 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000012175 pyrosequencing Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 108010014186 ras Proteins Proteins 0.000 description 1
- 102000016914 ras Proteins Human genes 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 208000009169 relapsing polychondritis Diseases 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 201000007416 salivary gland adenoid cystic carcinoma Diseases 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 238000007841 sequencing by ligation Methods 0.000 description 1
- 208000004548 serous cystadenocarcinoma Diseases 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 201000008123 signet ring cell adenocarcinoma Diseases 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 1
- 229940079839 sodium dehydroacetate Drugs 0.000 description 1
- 229940048109 sodium methyl cocoyl taurate Drugs 0.000 description 1
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000012409 standard PCR amplification Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 210000003699 striated muscle Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940104261 taurate Drugs 0.000 description 1
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 1
- 206010043207 temporal arteritis Diseases 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
- 208000015191 thyroid gland papillary and follicular carcinoma Diseases 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 208000029335 trabecular adenocarcinoma Diseases 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 125000000647 trehalose group Chemical group 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229940073585 tromethamine hydrochloride Drugs 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 229940118696 vibrio cholerae Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
- C07K16/462—Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
-
- 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
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- 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
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0603—Embryonic cells ; Embryoid bodies
- C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N9/1241—Nucleotidyltransferases (2.7.7)
- C12N9/1264—DNA nucleotidylexotransferase (2.7.7.31), i.e. terminal nucleotidyl transferase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/07—Nucleotidyltransferases (2.7.7)
- C12Y207/07031—DNA nucleotidylexotransferase (2.7.7.31), i.e. terminal deoxynucleotidyl transferase
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
- A01K2217/052—Animals comprising random inserted nucleic acids (transgenic) inducing gain of function
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/01—Animal expressing industrially exogenous proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- 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
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
- C12N2015/8518—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles
-
- 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
- C12N2510/00—Genetically modified cells
- C12N2510/02—Cells for production
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Environmental Sciences (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Mycology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Management, Administration, Business Operations System, And Electronic Commerce (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
本出願は、参照によりその全体が本明細書に組み込まれる、2016年6月3日に出願された米国仮特許出願第62/345,524号に対する優先権の利益を主張する。
本明細書では、それらのゲノム中にTdT(例えば、ヒト、マウス、またはラットTdT)をコードする外因性核酸を含む非ヒト動物に関連する方法および組成物が提供される。いくつかの実施形態では、遺伝子改変非ヒト動物は、齧歯類(例えば、マウスまたはラット)などの哺乳動物である。特定の実施形態では、非ヒト動物のゲノムは、それがヒト可変ドメインを有する抗原結合分子(例えば、抗体、TCR、および/またはCAR)を発現するようにさらなる改変を含む。
冠詞「a」および「an」は、本明細書では、冠詞の文法的目的語の1つまたは2つ以上(すなわち、少なくとも1つ)を指すために使用される。例として、「ある要素」は、1つの要素または2つ以上の要素を意味する。
特定の態様では、本明細書では、それらのゲノム中にTdT(例えば、ヒト、マウス、またはラットTdT)をコードする外因性核酸を含む非ヒト動物およびES細胞が提供される。特定の実施形態では、非ヒト動物およびES細胞のゲノムは、例えば、ヒト可変ドメインを有する抗原結合分子(例えば、抗体、TCR、および/またはCAR)の発現をもたらす改変を含む、さらなる改変を含む。
特定の態様では、それらの生殖系列および/またはゲノム中に外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列を含む遺伝子改変非ヒト動物およびES細胞が本明細書で提供される。デオキシヌクレオチジルトランスフェラーゼ(TdT)は、Bリンパ球およびTリンパ球における抗原−受容体多様性の増加をもたらす、V(D)J組換えにおける接合形成中の鋳型非依存性ヌクレオチド付加(NP付加)を触媒するDNAポリメラーゼである。鋳型非依存性付加、非鋳型付加、および非生殖系列付加はすべて、TdTによって触媒されるヌクレオチド付加を指し、これらの用語は本明細書では互換的に使用される。
特定の実施形態では、本明細書に記載の外因性TdTを含む遺伝子改変非ヒト動物および非ヒト動物ES細胞は、それらの生殖系列および/またはゲノム中に、未再編成ヒト免疫グロブリン可変領域遺伝子セグメントを含む免疫グロブリン可変領域と、免疫グロブリン定常領域遺伝子を含み、未再編成ヒト免疫グロブリン可変領域遺伝子セグメントが免疫グロブリン定常領域遺伝子に作動可能に連結される免疫グロブリン定常領域と、を含有する、免疫グロブリン遺伝子座(外因性または内因性)も含む。いくつかの実施形態では、非ヒト動物および非ヒトES細胞は、それらの生殖系列および/またはゲノム中に、複数のこのような免疫グロブリン遺伝子座を含む。例えば、いくつかの実施形態では、遺伝子改変非ヒト動物および非ヒト動物ES細胞は、それらの生殖系列および/またはゲノム中に、未再編成ヒト重鎖可変領域遺伝子セグメントを含む少なくとも1つの免疫グロブリン遺伝子座および未再編成ヒト軽鎖可変領域遺伝子セグメント(例えば、κ鎖遺伝子セグメントおよび/またはλ鎖遺伝子セグメント)を含む少なくとも1つの免疫グロブリン遺伝子座を含む。いくつかの実施形態では、遺伝子改変非ヒト動物および非ヒト動物ES細胞は、それらの生殖系列および/またはゲノム中に、未再編成ヒト重鎖可変領域遺伝子セグメントを含む少なくとも1つの免疫グロブリン遺伝子座、未再編成ヒトκ鎖可変領域遺伝子セグメントを含む少なくとも1つの免疫グロブリン遺伝子座、および未再編成ヒトλ鎖可変領域遺伝子セグメントを含む少なくとも1つの免疫グロブリン遺伝子座を含む。いくつかの実施形態では、遺伝子改変非ヒト動物、例えば、遺伝子改変マウスまたはラットは、それらの生殖系列および/またはゲノム中に、マウスがヒト、ヒト化、部分ヒト、逆キメラ(ヒト可変領域および非ヒト定常領域)抗体を作製するように、遺伝子改変免疫グロブリン遺伝子座(遺伝子改変された再編成または未再編成免疫グロブリン遺伝子座)を含む。
特定の実施形態では、本明細書に記載の外因性TdTを含む遺伝子改変非ヒト動物および非ヒト動物ES細胞は、それらの生殖系列および/またはゲノム中に、未再編成ヒトTCR可変領域遺伝子セグメントを含むTCR可変領域と、TCR定常領域遺伝子を含み、未再編成ヒトTCR可変領域遺伝子セグメントがTCR定常領域遺伝子に作動可能に連結されるTCR定常領域と、を含有する、TCR遺伝子座(外因性または内因性)も含む。いくつかの実施形態では、様々な遺伝子改変非ヒト動物、例えば、遺伝子改変マウスは、それらの生殖系列および/またはゲノムにおいて、マウスがヒト、ヒト化、部分ヒト、逆キメラ(ヒト可変領域および非ヒト定常領域)T細胞受容体を発現するように、遺伝子改変T細胞受容体遺伝子座(遺伝子改変TCRα、β、γ、および/またはδ遺伝子座)を含む。一実施形態では、例示的な非ヒト動物は、参照により本明細書に組み入れられる、米国特許第9,113,616号および国際特許出願公開第WO2016/164492号において提供される。
特定の態様では、キメラ抗原受容体(CAR)遺伝子座も含む、本明細書に記載の外因性TdTを含む遺伝子改変非ヒト動物および非ヒト動物ES細胞が本明細書で提供される。そのようなCAR遺伝子座は、一般に、可変領域および定常領域を含む。可変領域は、未再編成ヒトIg可変領域遺伝子セグメントを含み、定常領域遺伝子座は、TCR定常領域遺伝子を含み、Ig可変領域遺伝子セグメントは、定常領域遺伝子に作動可能に連結される。いくつかの実施形態では、TCR定常領域遺伝子は、非ヒトTCR定常領域遺伝子である。いくつかの実施形態では、TCR定常領域遺伝子は、ラット定常領域遺伝子またはマウス定常領域遺伝子などの齧歯類定常領域遺伝子である。いくつかの実施形態では、定常領域遺伝子は、内因性種由来である。いくつかの実施形態では、TCR定常領域遺伝子は、ヒト定常領域遺伝子である。
いくつかの実施形態では、外因性TdT、ヒト化TCR、またはCARを発現する本明細書に記載の遺伝子改変非ヒト動物およびES細胞は、それらのゲノムにおいて、ヒト化MHCクラスIα鎖ポリペプチドをコードする遺伝子座(例えば、ヒト化HLA−A、HLA−B、HLA−C、HLA−E、HLA−F、HLA−g、HLA−K、および/またはHLA−L)も発現する、および/または含む。いくつかの実施形態では、ヒト化MHCクラスIα鎖ポリペプチドは、完全にヒトである。いくつかの実施形態では、ヒト化MHCクラスIα鎖ポリペプチドは、ヒト細胞外ドメイン(例えば、ヒトα1、α2、およびα3ドメイン)および内因性種由来の細胞質ドメインを含む。ヒト化MHCクラスIα鎖ポリペプチド、ヒト化MHCクラスIα鎖ポリペプチドをコードする遺伝子座、およびヒト化MHCクラスIα鎖ポリペプチドを発現する非ヒト動物は、米国特許出願公開第2013/0111617号、同第2013/0185819号、および同第2014/0245467号に記載されており、これらの各々は本明細書に参照により組み込まれる。
特定の態様では、抗原結合タンパク質(例えば、抗体、CAR、TCR)、そのような抗原結合タンパク質を発現する細胞(例えば、B細胞、T細胞、B細胞ハイブリドーマ、T細胞ハイブリドーマ)、およびそのような抗原結合タンパク質またはその一部分(例えば、可変ドメイン)をコードする核酸を生成するために本明細書に記載の遺伝子改変非ヒト動物を使用する方法が本明細書で提供される。いくつかの実施形態では、より多様な抗原結合タンパク質(例えば、抗体、CAR、TCR)を作製する方法が本明細書で提供される。いくつかの実施形態では、増加した数のヌクレオチド付加を有する抗原結合タンパク質(例えば、抗体、CAR、TCR)の再編成可変領域を作製する方法が本明細書で提供される。
特定の態様では、(例えば、本明細書に記載の非ヒト動物を使用して)本明細書に記載の方法によって得ることができるおよび/または得られる抗原結合タンパク質(例えば、抗体、TCR、CAR、およびその抗原結合断片)が本明細書で提供される。
特定の実施形態では、組成物、例えば、薬学的に許容される担体と共に製剤化される本明細書に記載の少なくとも1つの薬剤(例えば、本明細書に記載の非ヒト動物から得られる、本明細書に記載の抗体、CAR、またはTCRのような、本明細書に記載の抗原結合分子)を含む、薬学的組成物が本明細書で提供される。
特定の態様において、抗原結合タンパク質(例えば、完全ヒト抗体、TCRまたはCARのような本明細書に記載の抗体、TCRおよび/またはCAR)を対象に投与することを含む疾患または障害を治療する方法を本明細書で提供する。いくつかの実施形態において、抗体、TCRおよび/またはCARは、本明細書に記載の方法から得られる、または該方法を用いて(例えば、本明細書に記載の非ヒト動物を用いて)得ることができる、抗体、TCRおよび/またはCARである。
本明細書に記載の抗体、TCRまたはCAR、および/または本明細書に記載の抗体、TCRおよびCARの一部をコードする核酸分子を本明細書で提供する。いくつかの実施形態において、核酸は、本明細書に記載の抗体、TCRまたはCARの可変ドメインをコードする。核酸分子は、例えば全細胞、細胞溶解物、または部分的に精製された、または実質的に純粋な形態に存在し得る。
例示的実施形態1において、ヒトターミナルデオキシヌクレオチジルトランスフェラーゼ(hTdT)をコードする核酸配列をゲノム中に含む、遺伝子改変非ヒト動物を本明細書で提供する。
ランダム導入遺伝子としてのまたは免疫グロブリンκ遺伝子座に標的化されたかのいずれかのヒトTdT遺伝子を含むマウスは、VELOCIGENE(登録商標)遺伝子工学技術(例えば、米国特許第6,586,251号およびValenzuela,D.M.,et al.(2003)High−throughput engineering of the mouse genome coupled with high−resolution expression analysis.Nat.Biotech.21(6):652−659参照)を用いて作製され、そこでは細菌相同組換えを用いたBACライブラリーに由来するヒト配列を用いて、ヒトTdT遺伝子座のゲノム断片を含む、TdTがIgK遺伝子座に標的化される場合には、マウスES細胞においてLTVECをIgK遺伝子座に標的化するターゲティングアームに隣接する、大きなターゲティングベクター(LTVEC)が作製される。LTVECは、Valenzuela et alに従って線状化され、マウスES細胞系に電気穿孔される。ES細胞は、TAQMAN(登録商標)によってスクリーニングされ、遺伝子コピー数(ランダムに組み込まれた導入遺伝子)またはIgK遺伝子座への正しいターゲティングのいずれかが決定される。
簡潔には、図1に詳細に示される大きなターゲティングベクター(LTVEC)は、マウスRag2遺伝子(エクソン3のATG開始コドンからエクソン3のTGA終止コドンまで)が、短いアイソフォーム、TdTS(エクソン1のATG開始コドンからエクソン13のポリAシグナルの約0.5kb 3’まで)のみをコードするヒトターミナルデオキシヌクレオチジルトランスフェラーゼ(TdTまたはDNTT)遺伝子で置換された、マウスおよびヒトBACクローンから構築した。TdTエクソン7および12のRNAスプライス部位を突然変異させて、長いアイソフォーム(TdTL1およびL2)の発現を防止した。同じLTVECにおいて、エクソン2のATG開始コドンからエクソン2のTAA終止コドンまでのマウスRag1遺伝子を、増強緑色蛍光タンパク質(EGFP)およびLacZ 3’UTR−polyAシグナルのコード配列で置換した。LTVECは、130kbのマウスRag2遺伝子の上流調節配列5’および8.8kbのマウスRag1遺伝子の上流調節配列3’、ならびに5.6kbのRag2−Rag1遺伝子間領域を含む。
(1)エクソン7のスプライスドナー部位を含む13bp(GTCGGGTCGTGGT(配列番号1))、スプライスドナー下線)を欠失させ、NotI部位(GCGGCCGC(配列番号2))で置換した。これにより重複するSacII部位(CCGCGG(配列番号3))が形成され、
(2)エクソン12の2bpスプライス受容部位を欠失させた。
マウス免疫グロブリンκ遺伝子座上のRag調節エレメントの制御下でヒトTdTを含むマウスを作製するために、ES細胞における組換えのためのマウスIgK相同性アームを、実施例1.1および図1に記載されているように作製された構築物の5’および3’末端に付加した。一般に、マウスIgKアームは、(1)I−CeuIおよびPI−SceI制限酵素部位に隣接する選択カセット(例えば、Hyg、Neoなど)を挿入する細菌相同組換えによってマウスIgK BACを改変すること、ならびに(2)I−CeuIおよびPI−SceIライゲーションによってマウスIgK BACにTdT構築物を挿入することにより付加される。最終的なLTVECを図2に示す。
実施例1.1および1.2のRag−TdTを作製するために用いたものと同じヒトTdTS遺伝子(すなわち、ATG開始コドンから約514bpのポリAシグナルの3’まで)を、689bpのマウスEμエンハンサーおよび303bpのマウスIgVH1−72プロモーターの制御下に置いた。この構築物は、マウスゲノムにランダムに組み込まれたか、または免疫グロブリンK(IgK)遺伝子座に標的化されたかのいずれかであった。標的化された組み込みについて、遺伝子は、実施例1.2のLTVECを作製するために使用されたのと同じ5’および3’マウスIgK相同性アームの間に挿入された。
あるいは、TdTS cDNAは、3682bpのDNA断片としてデノボ合成され(Blue Heron Bio)、ES細胞への導入のためのターゲティングベクターに組み込まれる。ターゲティングベクターは、5’〜3’まで、PI−SceI部位、689bpのマウスIgHイントロンエンハンサー(EcoRI−XbaI断片)、303bpのマウスVH1−72プロモーター、イントロン媒介性発現増強のためにエクソン2と3との間に保持された735bpのイントロン2を含む1530bpのヒトTdTSのCDS(NCBI RefSeq NM_004088)、340bpのヒトTdT 3’ UTR/ポリAシグナル、loxp−neo−loxpカセットでのライゲーションのためのNotIおよびSalI制限酵素部位、ならびにI−CeuI部位を含む。ベクターは、実施例1.2のLTVECを作製するために使用されたのと同じ5’および3’マウスIgK相同性アームの間に挿入され、IgK遺伝子座に標的化されたか、またはマウスゲノムにランダムに組み込まれたかのいずれかであった。
上記のように、正しく標的化されたES細胞が産生されると、それらはVELOCIMOUSE(登録商標)法により8細胞期(またはそれ以前の)マウス胚に導入され、対立遺伝子アッセイのゲインにおいてスクリーニングされ、続いてホモ接合体に繁殖させる。ヘテロ接合性またはホモ接合性動物は、ヒトTdTSと共にヒト可変軽鎖および重鎖ドメインならびにマウス定常領域を含む抗体を発現する(これらのマウスは、それぞれ内因性IgKおよびIgH遺伝子座でヒト免疫グロブリン可変軽および重遺伝子セグメントを含むため、VELOCIMMUNE(登録商標))。
実施例1に上述された様々なVELOCIMMUNE(登録商標)ヒトTdTSマウスモデルにおける免疫グロブリンレパートリー配列多様性を評価するために、IgK配列を、mIgK定常プライマーを用いて様々なマウスの脾臓から5’ RACEにより増幅し、Illumina MiSeqを用いて配列決定した。
上記実施例2に記載の次世代シーケンシングから、(VκおよびJκ遺伝子セグメントの両方の部分からなる)CDR3における非生殖系列ヌクレオチド付加の割合も決定した。
CDR3配列を、国際免疫遺伝情報システム(IMGT)境界を用いて抽出した。非鋳型ヌクレオチドを、既知の軽鎖VおよびJ配列に基づいて決定した。
図8Aおよび8Bに示すように、上記の実施例2および3に記載のマウスの2つのバージョンにおけるヒトTdTSの導入は、機能的異所性マウスAdam6遺伝子を含むVELOCIMMUNE(登録商標)マウスと比較して、Vκ遺伝子セグメントまたはJκ遺伝子セグメントのいずれかの使用を顕著に変化させなかった。
ヒト免疫グロブリンκ遺伝子座に加えて、B(λ軽鎖、重鎖)およびT(α/β)リンパ球からの他の遺伝子座における抗原−受容体多様を調査することができる。
二重軽鎖遺伝子座およびヒトTdTSを含むマウスは、機能的マウスAdam6遺伝子(米国特許第8,642,835号および同第8,697,940号参照)および外因性ヒトTdTSを含むVELOCIMMUNE(登録商標)マウスを、二重軽鎖遺伝子座(本明細書に参照により組み込まれる、米国特許出願公開第2013/0198880号)を含むマウスと繁殖させることにより作製した。
上記実施例7に記載の次世代シーケンシングから、DLC TdTマウスの免疫グロブリン配列における(VκおよびJκ遺伝子セグメントの両方の部分からなる)CDR3における非生殖系列ヌクレオチド付加の割合も決定した。
CDR3配列を、国際免疫遺伝情報システム(IMGT)境界を用いて抽出した。非鋳型ヌクレオチドを、既知の軽鎖VおよびJ配列から決定した。
図16に示すように、DLCマウスにおけるヒトTdTSの導入は、DLC対照マウス(ヒトTdTが導入されていないDLCマウス)と比較して、Vκ遺伝子セグメントまたはJκ遺伝子セグメントのいずれかの使用を顕著に変化させなかった。
本明細書中に言及されるすべての刊行物、特許、および特許出願は、各刊行物、特許、または特許出願が、具体的かつ個別に参照により組み込まれると示されるように、参照によりそれらの全体が本明細書に組み込まれる。矛盾する場合には、本明細書中の任意の定義を含む、本出願が優先される。
当業者であれば、本明細書に記載された本発明の特定の実施形態に対する多くの等価物を認識するか、または日常的な実験のみを用いて確認することができるであろう。そのような等価物は、下記の特許請求の範囲によって包含されることが意図される。
Claims (50)
- 遺伝子改変非ヒト動物であって、そのゲノム中に:
転写制御エレメントに作動可能に連結された外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列と、
免疫グロブリン定常領域遺伝子に作動可能に連結された未再編成ヒト免疫グロブリン可変領域遺伝子セグメントを含む免疫グロブリン可変領域と、を含む、遺伝子改変非ヒト動物。 - 前記転写制御エレメントが、プロB細胞および/またはプレB細胞における外因性TdTをコードする核酸配列の発現を駆動する、請求項1に記載の遺伝子改変非ヒト動物。
- 前記転写制御エレメントが、RAG1転写制御エレメント、RAG2転写制御エレメント、免疫グロブリン重鎖転写制御エレメント、免疫グロブリンκ軽鎖転写制御エレメント、および/または免疫グロブリンλ軽鎖転写制御エレメントからなる群から選択される、請求項2に記載の遺伝子改変非ヒト動物。
- 前記外因性TdTをコードする前記核酸配列が、免疫グロブリンκ軽鎖遺伝子座、免疫グロブリンλ軽鎖遺伝子座、免疫グロブリン重鎖遺伝子座、RAG1遺伝子座、RAG2遺伝子座に位置する、請求項1〜3のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記動物におけるV−J免疫グロブリン軽鎖連結の少なくとも10%が、非鋳型付加を含む、請求項1〜4のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記ヒト免疫グロブリン可変領域遺伝子セグメントが、ヒト重鎖可変領域遺伝子セグメントである、請求項1〜5のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記定常領域遺伝子が、重鎖定常領域遺伝子である、請求項6に記載の遺伝子改変非ヒト動物。
- 前記重鎖定常領域遺伝子が、内因性種由来である、請求項7に記載の遺伝子改変非ヒト動物。
- 前記免疫グロブリン可変領域および前記免疫グロブリン定常領域遺伝子が、内因性免疫グロブリン重鎖遺伝子座に位置する、請求項6〜8のいずれか1項に記載の遺伝子改変非ヒト動物。
- ゲノム中に第2の免疫グロブリン定常領域遺伝子に作動可能に連結された未再編成ヒト軽鎖可変領域遺伝子セグメントを含む免疫グロブリン可変領域をさらに含む、請求項6〜9のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記第2の免疫グロブリン定常領域遺伝子に作動可能に連結された前記免疫グロブリン可変領域が、内因性免疫グロブリン軽鎖遺伝子座に位置する、請求項10に記載の遺伝子改変非ヒト動物。
- 前記第2の免疫グロブリン定常領域遺伝子に作動可能に連結された前記ヒト免疫グロブリン可変領域遺伝子セグメントが、ヒトκ鎖可変領域遺伝子セグメントである、請求項11に記載の遺伝子改変非ヒト動物。
- 前記第2の免疫グロブリン定常領域遺伝子に作動可能に連結された前記ヒト免疫グロブリン可変領域遺伝子セグメントが、ヒトλ鎖可変領域遺伝子セグメントである、請求項11に記載の遺伝子改変非ヒト動物。
- 前記第2の定常領域遺伝子が、κ定常領域遺伝子である、請求項11〜13のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記第2の定常領域遺伝子が、λ定常領域遺伝子である、請求項11〜13のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記κ定常領域遺伝子が、内因性種由来のものである、請求項14に記載の遺伝子改変非ヒト動物。
- 前記λ定常領域遺伝子が、内因性種由来のものである、請求項15に記載の遺伝子改変非ヒト動物。
- 前記内因性免疫グロブリン軽鎖遺伝子座が、免疫グロブリンκ遺伝子座である、請求項16に記載の遺伝子改変非ヒト動物。
- 前記内因性免疫グロブリン軽鎖遺伝子座が、免疫グロブリンλ遺伝子座である、請求項17に記載の遺伝子改変非ヒト動物。
- 前記未再編成ヒト免疫グロブリン可変領域遺伝子セグメントが、B細胞発生中に再編成され、前記非ヒト動物の前記B細胞において再編成された可変領域遺伝子を生成する、請求項1〜19のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記再編成可変領域遺伝子の少なくとも10%が、非鋳型付加を含む、請求項20に記載の遺伝子改変非ヒト動物。
- 遺伝子改変非ヒト動物であって、そのゲノム中に:
転写制御エレメントに作動可能に連結された外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列と、
TCR定常領域遺伝子に作動可能に連結された未再編成ヒトTCR可変領域遺伝子セグメントを含むT細胞受容体(TCR)可変領域と、を含む、遺伝子改変非ヒト動物。 - 前記ヒトTCR可変領域遺伝子セグメントが、ヒトTCRα可変領域遺伝子セグメントである、請求項22に記載の遺伝子改変非ヒト動物。
- 前記ヒトTCR可変領域遺伝子セグメントが、ヒトTCRβ可変領域遺伝子セグメントである、請求項22に記載の遺伝子改変非ヒト動物。
- 前記未再編成ヒトTCR可変領域遺伝子セグメントが、T細胞発生中に再編成され、前記非ヒト動物の前記T細胞において再編成されたTCR可変領域遺伝子を生成する、請求項22〜24のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記再編成可変領域遺伝子の少なくとも10%が、非鋳型付加を含む、請求項25に記載の遺伝子改変非ヒト動物。
- 遺伝子改変非ヒト動物であって、そのゲノム中に:
転写制御エレメントに作動可能に連結された外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列と、
TCR定常領域遺伝子に作動可能に連結された未再編成ヒト免疫グロブリン可変領域遺伝子セグメントを含む免疫グロブリン可変領域と、を含む、遺伝子改変非ヒト動物。 - 前記ヒト免疫グロブリン可変領域遺伝子セグメントが、重鎖遺伝子セグメントである、請求項27に記載の遺伝子改変非ヒト動物。
- 前記ヒト免疫グロブリン可変領域遺伝子セグメントが、κ鎖遺伝子セグメントである、請求項27に記載の遺伝子改変非ヒト動物。
- 前記ヒト免疫グロブリン可変領域遺伝子セグメントが、λ鎖遺伝子セグメントである、請求項27に記載の遺伝子改変非ヒト動物。
- 前記TCR定常領域遺伝子が、TCRα定常領域遺伝子である、請求項28または29のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記TCR定常領域遺伝子が、TCRβ定常領域遺伝子である、請求項28に記載の遺伝子改変非ヒト動物。
- 前記転写制御エレメントが、CD4/CD8ダブルネガティブ(DN)胸腺細胞および/またはCD4/CD8ダブルポジティブ(DP)胸腺細胞における外因性TdTをコードする核酸配列の発現を駆動する、請求項22〜32のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記転写制御エレメントが、RAG1転写制御エレメント、RAG2転写制御エレメント、TCRα転写制御エレメント、TCRβ転写制御エレメント、TCRγ転写制御エレメント、および/またはTCRδ転写制御エレメントである、請求項33に記載の遺伝子改変非ヒト動物。
- 前記外因性TdTをコードする前記核酸配列が、RAG1遺伝子座、RAG2遺伝子座、TCRα鎖遺伝子座、TCRβ鎖遺伝子座、TCRγ鎖遺伝子座、および/またはTCRδ鎖遺伝子座に位置する、請求項22〜34のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記非ヒト動物が、哺乳動物である、請求項1〜35のいずれか1項に記載の遺伝子改変非ヒト動物。
- 前記哺乳動物が、齧歯類である、請求項36に記載の遺伝子改変非ヒト動物。
- 前記齧歯類が、ラットまたはマウスである、請求項37に記載の遺伝子改変非ヒト動物。
- ヒト可変ドメインを含む抗体の発現を誘導する方法であって、請求項1〜21のいずれか1項に記載の遺伝子改変非ヒト動物を抗原に曝露することであって、それにより、前記遺伝子改変非ヒト動物が前記抗原に特異的なヒト可変ドメインを含む抗体を産生する、曝露することを含む、方法。
- MHC上に提示されるペプチドに特異的なヒト可変ドメインを含むT細胞受容体(TCR)を発現するT細胞を作製する方法であって、
(a)請求項22〜26のいずれか1項に記載の遺伝子改変非ヒト動物を、ペプチドを含む抗原またはペプチドを含む抗原をコードする核酸に曝露することであって、それにより、前記ペプチドが前記非ヒト動物においてMHC上に提示される、曝露することと、
(b)(a)の前記遺伝子改変非ヒト動物から前記MHC上に提示された前記ペプチドに特異的なTCRを発現するT細胞を得ることと、を含む、方法。 - MHC上に提示されるペプチドに特異的な、ヒト免疫グロブリン可変ドメインおよび免疫グロブリン定常を含むキメラ抗原受容体(CAR)を発現するT細胞を作製する方法であって、
(a)請求項27〜32のいずれか1項に記載の遺伝子改変非ヒト動物を、ペプチドを含む抗原またはペプチドを含む抗原をコードする核酸に曝露することであって、それにより、前記ペプチドが前記非ヒト動物においてMHC上に提示される、曝露することと、
(b)(a)の前記遺伝子改変非ヒト動物から前記MHC上に提示された前記ペプチドに特異的なCARを発現するT細胞を得ることと、を含む、方法。 - 遺伝子改変非ヒト動物ES細胞であって、そのゲノム中に:
外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列と、
免疫グロブリン定常領域遺伝子に作動可能に連結された未再編成ヒト免疫グロブリン可変領域遺伝子セグメントを含む免疫グロブリン可変領域と、を含む、遺伝子改変非ヒト動物ES細胞。 - 遺伝子改変非ヒト動物ES細胞であって、そのゲノム中に:
外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列と、
TCR定常領域遺伝子に作動可能に連結された未再編成ヒトTCR可変領域遺伝子セグメントを含むT細胞受容体(TCR)可変領域と、を含む、遺伝子改変非ヒト動物ES細胞。 - 遺伝子改変非ヒト動物ES細胞であって、そのゲノム中に:
外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列と、
TCR定常領域遺伝子に作動可能に連結された未再編成ヒト免疫グロブリン可変領域遺伝子セグメントを含む免疫グロブリン可変領域と、を含む、遺伝子改変非ヒト動物ES細胞。 - 請求項42〜44のいずれか1項に記載の遺伝子改変非ヒト動物ES細胞を使用することを含む、遺伝子改変非ヒト動物を作製する方法。
- 遺伝子改変を含む非ヒト動物を作製する方法であって、前記非ヒト動物がその生殖系列中に:
外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列と、
免疫グロブリン定常領域遺伝子に作動可能に連結された未再編成ヒト免疫グロブリン可変領域遺伝子セグメントを含む免疫グロブリン可変領域と、を含むように操作することを含む、方法。 - 遺伝子改変を含む非ヒト動物を作製する方法であって、前記非ヒト動物がその生殖系列中に:
外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列と、
TCR定常領域遺伝子に作動可能に連結された未再編成ヒトTCR可変領域遺伝子セグメントを含むT細胞受容体(TCR)可変領域と、を含むように操作することを含む、方法。 - 遺伝子改変を含む非ヒト動物を作製する方法であって、前記非ヒト動物がその生殖系列中に:
外因性ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)をコードする核酸配列と、
TCR定常領域遺伝子に作動可能に連結された未再編成ヒト免疫グロブリン可変領域遺伝子セグメントを含む免疫グロブリン可変領域と、を含むように操作することを含む、方法。 - 前記ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)が、ヒトTdTである、請求項1〜48のいずれか1項に記載の遺伝子改変非ヒト動物、非ヒト動物ES細胞、または方法。
- 前記ターミナルデオキシヌクレオチジルトランスフェラーゼ(TdT)が、TdTの短いアイソフォーム(TdTS)である、請求項1〜49のいずれか1項に記載の遺伝子改変非ヒト動物、非ヒト動物ES細胞、または方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022058938A JP7274018B2 (ja) | 2016-06-03 | 2022-03-31 | 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662345524P | 2016-06-03 | 2016-06-03 | |
US62/345,524 | 2016-06-03 | ||
PCT/US2017/035731 WO2017210586A1 (en) | 2016-06-03 | 2017-06-02 | Non-human animals expressing exogenous terminal deoxynucleotidyltransferase |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022058938A Division JP7274018B2 (ja) | 2016-06-03 | 2022-03-31 | 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2019521668A true JP2019521668A (ja) | 2019-08-08 |
JP2019521668A5 JP2019521668A5 (ja) | 2020-07-09 |
JP7053499B2 JP7053499B2 (ja) | 2022-04-12 |
Family
ID=59215996
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018563156A Active JP7053499B2 (ja) | 2016-06-03 | 2017-06-02 | 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 |
JP2022058938A Active JP7274018B2 (ja) | 2016-06-03 | 2022-03-31 | 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 |
JP2023074624A Pending JP2023093729A (ja) | 2016-06-03 | 2023-04-28 | 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022058938A Active JP7274018B2 (ja) | 2016-06-03 | 2022-03-31 | 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 |
JP2023074624A Pending JP2023093729A (ja) | 2016-06-03 | 2023-04-28 | 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 |
Country Status (24)
Country | Link |
---|---|
US (2) | US10980221B2 (ja) |
EP (2) | EP3462853B1 (ja) |
JP (3) | JP7053499B2 (ja) |
KR (3) | KR102598120B1 (ja) |
CN (3) | CN116458475A (ja) |
AU (2) | AU2017272337C1 (ja) |
BR (1) | BR112018074794A2 (ja) |
CA (1) | CA3026088A1 (ja) |
CY (1) | CY1126063T1 (ja) |
DK (1) | DK3462853T3 (ja) |
ES (1) | ES2941810T3 (ja) |
FI (1) | FI3462853T3 (ja) |
HR (1) | HRP20230497T1 (ja) |
HU (1) | HUE061619T2 (ja) |
IL (2) | IL263160B2 (ja) |
LT (1) | LT3462853T (ja) |
MX (3) | MX2018014982A (ja) |
PL (1) | PL3462853T3 (ja) |
PT (1) | PT3462853T (ja) |
RS (1) | RS64216B1 (ja) |
RU (1) | RU2753585C2 (ja) |
SG (2) | SG10201914014XA (ja) |
SI (1) | SI3462853T1 (ja) |
WO (1) | WO2017210586A1 (ja) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116458475A (zh) | 2016-06-03 | 2023-07-21 | 瑞泽恩制药公司 | 表达外源末端脱氧核苷酸转移酶的非人动物 |
HUE060608T2 (hu) | 2017-12-05 | 2023-03-28 | Regeneron Pharma | Genetikailag módosított immunglobulin lambda könnyûlánccal rendelkezõ egerek és azok alkalmazása |
CN112040769B (zh) | 2018-03-24 | 2023-05-16 | 瑞泽恩制药公司 | 用于产生针对肽-mhc复合物的治疗抗体的经过基因修饰的非人动物、制造方法和用途 |
CN112566931A (zh) * | 2018-06-13 | 2021-03-26 | 儿童医疗中心有限公司 | 涉及用于抗体发现和/或优化的高通量模型的方法和组合物 |
US20190380316A1 (en) | 2018-06-14 | 2019-12-19 | Regeneron Pharmaceuticals, Inc. | Non-human animals capable of engineered dh-dh rearrangement and uses thereof |
JP2022520819A (ja) * | 2019-02-22 | 2022-04-01 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | 遺伝子改変ナトリウムチャネルを有する齧歯類およびその使用方法 |
MX2021014893A (es) | 2019-06-05 | 2022-03-11 | Regeneron Pharma | Animales no humanos que tienen un repertorio de cadena ligera lambda limitado expresado a partir del locus kappa y usos de estos. |
KR20220114026A (ko) * | 2019-12-12 | 2022-08-17 | 디엔에이 스크립트 | 폴리뉴클레오타이드의 주형-부재 효소 합성을 위한 키메라 말단 데옥시뉴클레오타이드 전달효소 |
CN111057754B (zh) * | 2019-12-27 | 2021-01-12 | 四川省医学科学院.四川省人民医院实验动物研究所 | 鉴定适用于hbv研究的动物模型的方法和应用 |
US20220090060A1 (en) | 2020-09-11 | 2022-03-24 | Regeneron Pharmaceuticals, Inc. | Identification and production of antigen-specific antibodies |
KR20230147048A (ko) | 2020-12-16 | 2023-10-20 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 Fc 알파 수용체를 발현하는 마우스 |
US20220195014A1 (en) | 2020-12-23 | 2022-06-23 | Regeneron Pharmaceuticals, Inc. | Nucleic acids encoding anchor modified antibodies and uses thereof |
CN116981357A (zh) * | 2021-03-31 | 2023-10-31 | 瑞泽恩制药公司 | 包含具有改善的tcrb组库多样性的人源化细胞免疫系统组分的基因修饰的小鼠 |
WO2024064860A1 (en) * | 2022-09-22 | 2024-03-28 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice expressing components of human cellular immune system |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013063361A1 (en) * | 2011-10-28 | 2013-05-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified t cell receptor mice |
US20150037337A1 (en) * | 2013-05-01 | 2015-02-05 | Kymab Limited | Manipulation of Immunoglobulin Gene Diversity and Multi-Antibody Therapeutics |
WO2016044745A1 (en) * | 2014-09-19 | 2016-03-24 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
Family Cites Families (101)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988007089A1 (en) | 1987-03-18 | 1988-09-22 | Medical Research Council | Altered antibodies |
US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US7041871B1 (en) | 1995-10-10 | 2006-05-09 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
GB9119338D0 (en) | 1991-09-10 | 1991-10-23 | Inst Of Animal Physiology And | Control of gene expression |
US5523226A (en) * | 1993-05-14 | 1996-06-04 | Biotechnology Research And Development Corp. | Transgenic swine compositions and methods |
US5512295A (en) | 1994-11-10 | 1996-04-30 | The Board Of Trustees Of The Leland Stanford Junior University | Synthetic liposomes for enhanced uptake and delivery |
US6001349A (en) | 1995-02-22 | 1999-12-14 | Therion Biologics Corporation | Generation of human cytotoxic T-cells specific for carcinoma self-associated antigens and uses thereof |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US7001614B2 (en) | 1996-08-19 | 2006-02-21 | The United States Of America As Represented By The Department Of Health And Human Services | Liposome complexes for increased systemic delivery |
US6770291B2 (en) | 1996-08-30 | 2004-08-03 | The United States Of America As Represented By The Department Of Health And Human Services | Liposome complexes for increased systemic delivery |
EP2314625B1 (en) | 1996-12-03 | 2014-05-07 | Amgen Fremont Inc. | Transgenic mammals having human Ig loci including plural VH and Vkappa regions and antibodies produced therefrom |
US7112338B2 (en) | 1997-03-12 | 2006-09-26 | The Regents Of The University Of California | Cationic liposome delivery of taxanes to angiogenic blood vessels |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
US6749863B1 (en) | 1997-11-19 | 2004-06-15 | Georgetown University | Targeted liposome gene delivery |
US6528624B1 (en) | 1998-04-02 | 2003-03-04 | Genentech, Inc. | Polypeptide variants |
GB9823930D0 (en) | 1998-11-03 | 1998-12-30 | Babraham Inst | Murine expression of human ig\ locus |
US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
US7183387B1 (en) | 1999-01-15 | 2007-02-27 | Genentech, Inc. | Polypeptide variants with altered effector function |
US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
MXPA03008454A (es) | 2001-03-22 | 2004-06-30 | Abbott Gmbh & Co Kg | Animales transgenicos que expresan anticuerpos especificos para genes de interes y usos de los mismos. |
US20090042291A1 (en) | 2002-03-01 | 2009-02-12 | Xencor, Inc. | Optimized Fc variants |
US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
US8093357B2 (en) | 2002-03-01 | 2012-01-10 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
US8663622B2 (en) | 2002-12-16 | 2014-03-04 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Recombinant vaccine viruses expressing IL-15 and methods using the same |
AU2004208031B2 (en) | 2003-01-28 | 2009-10-08 | Cellectis | Use of meganucleases for inducing homologous recombination ex vivo and in toto in vertebrate somatic tissues and application thereof. |
US20090010920A1 (en) | 2003-03-03 | 2009-01-08 | Xencor, Inc. | Fc Variants Having Decreased Affinity for FcyRIIb |
US8388955B2 (en) | 2003-03-03 | 2013-03-05 | Xencor, Inc. | Fc variants |
US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
US8218805B2 (en) | 2003-10-11 | 2012-07-10 | Charles Hornback | Wireless speaker system for use with ceiling fans |
WO2005063815A2 (en) | 2003-11-12 | 2005-07-14 | Biogen Idec Ma Inc. | Fcϝ receptor-binding polypeptide variants and methods related thereto |
US20060034850A1 (en) | 2004-05-27 | 2006-02-16 | Weidanz Jon A | Antibodies as T cell receptor mimics, methods of production and uses thereof |
PT1802193E (pt) | 2004-10-19 | 2014-06-23 | Regeneron Pharma | Método para gerar um murganho homozigótico para uma modificação genética |
AU2005335714B2 (en) | 2004-11-10 | 2012-07-26 | Macrogenics, Inc. | Engineering Fc antibody regions to confer effector function |
US20060222653A1 (en) | 2004-11-12 | 2006-10-05 | Xencor, Inc. | Antibodies operably linked to selected chemoattractants |
EP1858925A2 (en) | 2005-01-12 | 2007-11-28 | Xencor, Inc. | Antibodies and fc fusion proteins with altered immunogenicity |
CN103710371B (zh) * | 2005-08-03 | 2017-03-01 | 人类多克隆治疗股份有限公司 | 表达人源化免疫球蛋白的转基因动物中b细胞凋亡的抑制 |
US20070190063A1 (en) | 2005-08-19 | 2007-08-16 | Bahjat Keith S | Antibody-mediated enhancement of immune response |
ES2735531T3 (es) | 2005-08-23 | 2019-12-19 | Univ Pennsylvania | ARN que contiene nucleósidos modificados y métodos de uso del mismo |
EP2003960B1 (en) | 2006-03-31 | 2015-06-10 | E. R. Squibb & Sons, L.L.C. | Transgenic animals expressing chimeric antibodies for use in preparing human antibodies |
NZ581396A (en) | 2007-06-01 | 2012-07-27 | Omt Inc | Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies |
KR20160065985A (ko) | 2007-10-18 | 2016-06-09 | 버베리안 노딕 에이/에스 | 전립선 암 치료를 위한 mva의 용도 |
US8225343B2 (en) | 2008-01-11 | 2012-07-17 | Sony Computer Entertainment America Llc | Gesture cataloging and recognition |
SI3456190T1 (sl) | 2008-06-27 | 2022-06-30 | Merus N.V. | Transgena mišja živali, ki proizvaja protitelesa |
KR102362774B1 (ko) | 2008-09-30 | 2022-02-15 | 아블렉시스, 엘엘씨 | 키메라 항체의 제조를 위한 인간 이외의 포유동물 |
US8691502B2 (en) | 2008-10-31 | 2014-04-08 | Tremrx, Inc. | T-cell vaccination with viral vectors via mechanical epidermal disruption |
US20120204278A1 (en) | 2009-07-08 | 2012-08-09 | Kymab Limited | Animal models and therapeutic molecules |
DK3028564T5 (da) | 2009-07-08 | 2024-04-29 | Kymab Ltd | Dyremodeller og terapeutiske molekyler |
RU2425880C2 (ru) * | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
EP2509409B1 (en) | 2009-12-10 | 2016-07-27 | Regeneron Pharmaceuticals, Inc. | Mice that make heavy chain antibodies |
US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
PT2505654T (pt) | 2010-02-08 | 2016-11-18 | Regeneron Pharma | Rato de cadeia leve comum |
US20130185821A1 (en) | 2010-02-08 | 2013-07-18 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
WO2011120134A1 (en) | 2010-03-29 | 2011-10-06 | Zymeworks, Inc. | Antibodies with enhanced or suppressed effector function |
WO2011123708A2 (en) | 2010-03-31 | 2011-10-06 | Ablexis Llc | Genetic engineering of non-human animals for the production of chimeric antibodies |
PT2905338T (pt) | 2010-06-22 | 2017-11-10 | Regeneron Pharma | Ratinhos transgénicos com um locus de imunoglobulina lambda endógeno modificado |
US10881084B2 (en) | 2010-07-26 | 2021-01-05 | Trianni, Inc | Transgenic animals and methods of use |
JP6146913B2 (ja) | 2010-08-02 | 2017-06-14 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | Vlドメインを含む結合タンパク質を作製するマウス |
ES2748832T5 (es) | 2011-02-25 | 2023-06-08 | Regeneron Pharma | Ratones ADAM6 |
JP5893258B2 (ja) | 2011-03-31 | 2016-03-23 | フェリカネットワークス株式会社 | 情報処理装置および方法、並びにプログラム |
US20130018582A1 (en) | 2011-07-13 | 2013-01-17 | Miller Paul A | Inertial Navigation Common Azimuth Reference Determination System and Method |
EP3865581A1 (en) | 2011-08-05 | 2021-08-18 | Regeneron Pharmaceuticals, Inc. | Humanized universal light chain mice |
DK2757875T3 (en) | 2011-09-19 | 2018-01-08 | Kymab Ltd | MANIPULATION OF IMMUNOGLOBULIN GENE DIVERSITY AND MULTI-ANTIBODY THERAPEUTICS |
CA2791109C (en) | 2011-09-26 | 2021-02-16 | Merus B.V. | Generation of binding molecules |
EP2627773B1 (en) | 2011-10-17 | 2017-06-14 | Regeneron Pharmaceuticals, Inc. | Restricted immunoglobulin heavy chain mice |
LT3590332T (lt) | 2011-10-28 | 2022-08-10 | Regeneron Pharmaceuticals, Inc. | Genetiškai modifikuotos pelės, ekspresuojančios chimerines pagrindinio audinių dermės komplekso (mhc) ii molekules |
US9043996B2 (en) | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
JP6120451B2 (ja) | 2011-10-28 | 2017-04-26 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | ヒト化il−6および/またはil−6受容体 |
MY164836A (en) | 2011-10-28 | 2018-01-30 | Regeneron Pharma | Genetically modified major histocompatibility complex mice |
US9591835B2 (en) | 2011-10-28 | 2017-03-14 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
CN104080811B (zh) | 2011-11-04 | 2019-09-27 | 酵活有限公司 | 在Fc结构域中具有突变的稳定异源二聚的抗体设计 |
US9120662B2 (en) | 2011-11-14 | 2015-09-01 | Susan A. Thomson | Gathering and dispensing scoop with gate valve |
US9547499B2 (en) | 2011-12-09 | 2017-01-17 | Microsoft Technology Licensing, Llc | Device configuration with cached pre-assembled driver state |
US20140013456A1 (en) | 2012-03-16 | 2014-01-09 | Regeneron Pharmaceuticals, Inc. | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same |
NZ730271A (en) | 2012-03-16 | 2022-09-30 | Regeneron Pharma | Non-human animals expressing ph-sensitive immunoglobulin sequences |
WO2013138681A1 (en) * | 2012-03-16 | 2013-09-19 | Regeneron Pharmaceuticals, Inc. | Mice that produce antigen-binding proteins with ph-dependent binding characteristics |
LT2883449T (lt) | 2012-03-16 | 2018-05-10 | Regeneron Pharmaceuticals, Inc. | Histidinu modifikuoti lengvosios grandinės antikūnai ir juos gaminantys genetiškai modifikuoti graužikai |
JP5920830B2 (ja) | 2012-09-28 | 2016-05-18 | シスメックス株式会社 | 試料調製装置および細胞分析装置 |
HUE050930T2 (hu) | 2012-12-14 | 2021-01-28 | Open Monoclonal Tech Inc | Humán idiotípusos rágcsáló antitesteket kódoló polinukleotidok és azt tartalmazó állatok |
PL2958938T3 (pl) | 2013-02-20 | 2019-11-29 | Regeneron Pharma | Myszy eksprymujące humanizowane ko-receptory komórek t |
AU2014218915B2 (en) | 2013-02-20 | 2017-01-19 | Regeneron Pharmaceuticals, Inc. | Non-human animals with modified immunoglobulin heavy chain sequences |
PL2958937T3 (pl) | 2013-02-22 | 2019-01-31 | Regeneron Pharmaceuticals, Inc. | Myszy ekspresjonujące humanizowany główny układ zgodności tkankowej |
CN111500630A (zh) | 2013-04-16 | 2020-08-07 | 瑞泽恩制药公司 | 大鼠基因组的靶向修饰 |
US9546384B2 (en) | 2013-12-11 | 2017-01-17 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for the targeted modification of a mouse genome |
EP3119194B1 (en) | 2014-03-21 | 2021-04-28 | Regeneron Pharmaceuticals, Inc. | Non-human animals that make single domain binding proteins |
CA2941514A1 (en) | 2014-03-21 | 2015-09-24 | Regeneron Pharmaceuticals, Inc. | Vl antigen binding proteins exhibiting distinct binding characteristics |
CN113215196A (zh) | 2014-06-06 | 2021-08-06 | 瑞泽恩制药公司 | 用于修饰所靶向基因座的方法和组合物 |
PT3157956T (pt) * | 2014-06-19 | 2020-04-09 | Regeneron Pharma | Animais não humanos com um gene 1 de morte programada humanizada em células |
SI3354732T1 (sl) | 2014-06-23 | 2020-07-31 | Regeneron Pharmaceuticals, Inc. | Z nukleazo posredovan DNA sklop |
HUE041584T2 (hu) | 2014-06-26 | 2019-05-28 | Regeneron Pharma | Célzott genetikai módosítások és alkalmazási módszerek és készítmények |
RU2732628C2 (ru) | 2015-04-06 | 2020-09-21 | Регенерон Фармасьютикалз, Инк. | Опосредованные гуманизированными т-клетками иммунные ответы у не относящихся к человеку животных |
CN116458475A (zh) | 2016-06-03 | 2023-07-21 | 瑞泽恩制药公司 | 表达外源末端脱氧核苷酸转移酶的非人动物 |
-
2017
- 2017-06-02 CN CN202310402666.9A patent/CN116458475A/zh active Pending
- 2017-06-02 SI SI201731323T patent/SI3462853T1/sl unknown
- 2017-06-02 HU HUE17733223A patent/HUE061619T2/hu unknown
- 2017-06-02 PT PT177332236T patent/PT3462853T/pt unknown
- 2017-06-02 DK DK17733223.6T patent/DK3462853T3/da active
- 2017-06-02 SG SG10201914014XA patent/SG10201914014XA/en unknown
- 2017-06-02 KR KR1020227045806A patent/KR102598120B1/ko active IP Right Grant
- 2017-06-02 EP EP17733223.6A patent/EP3462853B1/en active Active
- 2017-06-02 KR KR1020187036917A patent/KR102483193B1/ko active IP Right Grant
- 2017-06-02 JP JP2018563156A patent/JP7053499B2/ja active Active
- 2017-06-02 IL IL263160A patent/IL263160B2/en unknown
- 2017-06-02 CA CA3026088A patent/CA3026088A1/en active Pending
- 2017-06-02 MX MX2018014982A patent/MX2018014982A/es unknown
- 2017-06-02 AU AU2017272337A patent/AU2017272337C1/en active Active
- 2017-06-02 PL PL17733223.6T patent/PL3462853T3/pl unknown
- 2017-06-02 ES ES17733223T patent/ES2941810T3/es active Active
- 2017-06-02 RU RU2018144954A patent/RU2753585C2/ru active
- 2017-06-02 RS RS20230395A patent/RS64216B1/sr unknown
- 2017-06-02 CN CN201780048900.5A patent/CN109640644B/zh active Active
- 2017-06-02 LT LTEPPCT/US2017/035731T patent/LT3462853T/lt unknown
- 2017-06-02 SG SG11201810757YA patent/SG11201810757YA/en unknown
- 2017-06-02 US US15/612,625 patent/US10980221B2/en active Active
- 2017-06-02 HR HRP20230497TT patent/HRP20230497T1/hr unknown
- 2017-06-02 WO PCT/US2017/035731 patent/WO2017210586A1/en unknown
- 2017-06-02 FI FIEP17733223.6T patent/FI3462853T3/fi active
- 2017-06-02 CN CN202111170801.9A patent/CN113907043B/zh active Active
- 2017-06-02 EP EP23151094.2A patent/EP4218408A1/en active Pending
- 2017-06-02 BR BR112018074794-7A patent/BR112018074794A2/pt unknown
- 2017-06-02 KR KR1020237037578A patent/KR20230156162A/ko not_active Application Discontinuation
-
2018
- 2018-11-30 MX MX2021010351A patent/MX2021010351A/es unknown
- 2018-11-30 MX MX2021010352A patent/MX2021010352A/es unknown
-
2021
- 2021-03-16 US US17/203,398 patent/US20210195877A1/en active Pending
-
2022
- 2022-03-31 JP JP2022058938A patent/JP7274018B2/ja active Active
-
2023
- 2023-04-28 JP JP2023074624A patent/JP2023093729A/ja active Pending
- 2023-05-31 CY CY20231100257T patent/CY1126063T1/el unknown
- 2023-07-30 IL IL304839A patent/IL304839A/en unknown
-
2024
- 2024-01-31 AU AU2024200577A patent/AU2024200577A1/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013063361A1 (en) * | 2011-10-28 | 2013-05-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified t cell receptor mice |
US20150037337A1 (en) * | 2013-05-01 | 2015-02-05 | Kymab Limited | Manipulation of Immunoglobulin Gene Diversity and Multi-Antibody Therapeutics |
WO2016044745A1 (en) * | 2014-09-19 | 2016-03-24 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
Non-Patent Citations (1)
Title |
---|
THE JOURNAL OF IMMUNOLOGY, vol. 158, no. 2, JPN5019005524, 1997, US, pages 715 - 723, ISSN: 0004721454 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7274018B2 (ja) | 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物 | |
US20160081314A1 (en) | Chimeric Antigen Receptors | |
JP2019536430A (ja) | Cd3結合抗体 | |
JP2022512882A (ja) | 抗cd33免疫細胞癌療法 | |
CN109071633A (zh) | 基于使用表达增强性基因座来制备抗体的组合物和方法 | |
KR20210004994A (ko) | 치료제를 시험하기 위한 인간화된 설치류 | |
CN109195986A (zh) | 基于使用表达增强性基因座来制备抗体的组合物和方法 | |
US11999773B2 (en) | Anti-BCMA chimeric antigen receptors | |
CN113430207A (zh) | 在免疫球蛋白重链编码序列中具有dh-dh重排能力的非人动物 | |
NZ788749A (en) | Non-human animals expressing exogenous terminal deoxynucleotidyltransferase | |
NZ788750A (en) | Non-human animals expressing exogenous terminal deoxynucleotidyltransferase |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200601 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200601 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210729 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211029 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20220308 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220331 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7053499 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |