CN115279785A - SARS-CoV-2和SARS-CoV交叉中和抗体的制备及应用 - Google Patents
SARS-CoV-2和SARS-CoV交叉中和抗体的制备及应用 Download PDFInfo
- Publication number
- CN115279785A CN115279785A CN202180020022.2A CN202180020022A CN115279785A CN 115279785 A CN115279785 A CN 115279785A CN 202180020022 A CN202180020022 A CN 202180020022A CN 115279785 A CN115279785 A CN 115279785A
- Authority
- CN
- China
- Prior art keywords
- sars
- antibody
- cov
- seq
- light chain
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 241001678559 COVID-19 virus Species 0.000 title claims abstract description 85
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 241000315672 SARS coronavirus Species 0.000 title claims abstract 10
- 230000003472 neutralizing effect Effects 0.000 title description 18
- 239000003814 drug Substances 0.000 claims abstract description 31
- 150000007523 nucleic acids Chemical group 0.000 claims abstract description 30
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 claims abstract description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 229940096437 Protein S Drugs 0.000 claims abstract description 13
- 101710198474 Spike protein Proteins 0.000 claims abstract description 13
- 102000053723 Angiotensin-converting enzyme 2 Human genes 0.000 claims abstract description 8
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 claims description 252
- 230000027455 binding Effects 0.000 claims description 164
- 210000004027 cell Anatomy 0.000 claims description 104
- 108091007433 antigens Proteins 0.000 claims description 63
- 102000036639 antigens Human genes 0.000 claims description 63
- 239000012634 fragment Substances 0.000 claims description 63
- 239000000427 antigen Substances 0.000 claims description 62
- 108090000623 proteins and genes Proteins 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 39
- 102000004169 proteins and genes Human genes 0.000 claims description 39
- 239000013604 expression vector Substances 0.000 claims description 34
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 31
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 claims description 28
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims description 27
- 239000002773 nucleotide Substances 0.000 claims description 26
- 125000003729 nucleotide group Chemical group 0.000 claims description 26
- 108020004707 nucleic acids Proteins 0.000 claims description 24
- 102000039446 nucleic acids Human genes 0.000 claims description 24
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 claims description 23
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 claims description 22
- 102000005962 receptors Human genes 0.000 claims description 22
- 108020003175 receptors Proteins 0.000 claims description 22
- 238000010253 intravenous injection Methods 0.000 claims description 18
- 101000629318 Severe acute respiratory syndrome coronavirus 2 Spike glycoprotein Proteins 0.000 claims description 15
- 239000000611 antibody drug conjugate Substances 0.000 claims description 15
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 15
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 claims description 14
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 claims description 14
- 230000014509 gene expression Effects 0.000 claims description 14
- 238000001727 in vivo Methods 0.000 claims description 14
- 102000014447 Complement C1q Human genes 0.000 claims description 13
- 108010078043 Complement C1q Proteins 0.000 claims description 13
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 13
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 claims description 13
- 108091005609 SARS-CoV-2 Spike Subunit S1 Proteins 0.000 claims description 13
- 208000025721 COVID-19 Diseases 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 229940124597 therapeutic agent Drugs 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 230000000903 blocking effect Effects 0.000 claims description 8
- 230000008859 change Effects 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 208000037847 SARS-CoV-2-infection Diseases 0.000 claims description 7
- 238000012258 culturing Methods 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 101150023212 fut8 gene Proteins 0.000 claims description 6
- 210000004962 mammalian cell Anatomy 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 4
- 108010087819 Fc receptors Proteins 0.000 claims description 3
- 102000009109 Fc receptors Human genes 0.000 claims description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims description 3
- -1 antibodies Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 108020004999 messenger RNA Proteins 0.000 claims description 3
- 239000013043 chemical agent Substances 0.000 claims description 2
- 239000001963 growth medium Substances 0.000 claims description 2
- 239000003443 antiviral agent Substances 0.000 claims 3
- 108060004795 Methyltransferase Proteins 0.000 claims 2
- 239000003112 inhibitor Substances 0.000 claims 2
- 102000002227 Interferon Type I Human genes 0.000 claims 1
- 108010014726 Interferon Type I Proteins 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims 1
- 230000013595 glycosylation Effects 0.000 claims 1
- 238000006206 glycosylation reaction Methods 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 230000007246 mechanism Effects 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims 1
- 150000003384 small molecules Chemical class 0.000 claims 1
- 239000013598 vector Substances 0.000 abstract description 15
- 208000035473 Communicable disease Diseases 0.000 abstract description 6
- 230000000241 respiratory effect Effects 0.000 abstract description 6
- 102100031673 Corneodesmosin Human genes 0.000 abstract description 4
- 101710139375 Corneodesmosin Proteins 0.000 abstract description 4
- 230000001154 acute effect Effects 0.000 abstract description 3
- 235000018102 proteins Nutrition 0.000 description 38
- 241001529936 Murinae Species 0.000 description 37
- 230000006870 function Effects 0.000 description 37
- 108091005634 SARS-CoV-2 receptor-binding domains Proteins 0.000 description 32
- 239000000523 sample Substances 0.000 description 31
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 24
- 239000012636 effector Substances 0.000 description 21
- 238000005406 washing Methods 0.000 description 21
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 description 20
- 230000000694 effects Effects 0.000 description 17
- 230000001404 mediated effect Effects 0.000 description 17
- 108091028043 Nucleic acid sequence Proteins 0.000 description 16
- 101001028244 Onchocerca volvulus Fatty-acid and retinol-binding protein 1 Proteins 0.000 description 16
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 16
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 15
- 241000700605 Viruses Species 0.000 description 15
- 238000001514 detection method Methods 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 14
- 241001112090 Pseudovirus Species 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- 238000002296 dynamic light scattering Methods 0.000 description 12
- 239000013642 negative control Substances 0.000 description 12
- 239000002245 particle Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000002965 ELISA Methods 0.000 description 11
- 108010076504 Protein Sorting Signals Proteins 0.000 description 11
- 238000012216 screening Methods 0.000 description 11
- 101000629313 Severe acute respiratory syndrome coronavirus Spike glycoprotein Proteins 0.000 description 10
- 238000010494 dissociation reaction Methods 0.000 description 10
- 230000005593 dissociations Effects 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 238000002156 mixing Methods 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 230000035772 mutation Effects 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 239000000872 buffer Substances 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000007500 overflow downdraw method Methods 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 241000711573 Coronaviridae Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000000533 capillary isoelectric focusing Methods 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 210000004602 germ cell Anatomy 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 241000283707 Capra Species 0.000 description 4
- 101000913079 Homo sapiens IgG receptor FcRn large subunit p51 Proteins 0.000 description 4
- 108010073807 IgG Receptors Proteins 0.000 description 4
- 102000009490 IgG Receptors Human genes 0.000 description 4
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 4
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 230000001133 acceleration Effects 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 238000006386 neutralization reaction Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000009792 yinqiao Substances 0.000 description 4
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 3
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 230000009514 concussion Effects 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000036737 immune function Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 210000000822 natural killer cell Anatomy 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 238000002732 pharmacokinetic assay Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 238000003259 recombinant expression Methods 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 description 2
- 208000001528 Coronaviridae Infections Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000218033 Hibiscus Species 0.000 description 2
- 235000005206 Hibiscus Nutrition 0.000 description 2
- 235000007185 Hibiscus lunariifolius Nutrition 0.000 description 2
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 2
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 2
- 208000025370 Middle East respiratory syndrome Diseases 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000029918 bioluminescence Effects 0.000 description 2
- 238000005415 bioluminescence Methods 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 238000005277 cation exchange chromatography Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000003209 gene knockout Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 108010068617 neonatal Fc receptor Proteins 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000003030 reporter gene method Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- VSIVTUIKYVGDCX-UHFFFAOYSA-M sodium;4-[2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].COC1=CC([N+]([O-])=O)=CC=C1[N+]1=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=NN1C1=CC=C([N+]([O-])=O)C=C1 VSIVTUIKYVGDCX-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101100013695 Caenorhabditis elegans fut-8 gene Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 101100364969 Dictyostelium discoideum scai gene Proteins 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 238000011993 High Performance Size Exclusion Chromatography Methods 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 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
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 102100029205 Low affinity immunoglobulin gamma Fc region receptor II-b Human genes 0.000 description 1
- 206010027417 Metabolic acidosis Diseases 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100364971 Mus musculus Scai gene Proteins 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000029301 Protein S Human genes 0.000 description 1
- 231100000645 Reed–Muench method Toxicity 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102100035559 Transcriptional activator GLI3 Human genes 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000005887 cellular phagocytosis Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000006240 deamidation Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000001094 effect on targets Effects 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 230000036252 glycation Effects 0.000 description 1
- 125000003712 glycosamine group Chemical group 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 208000018875 hypoxemia Diseases 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000012482 interaction analysis Methods 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003125 jurkat cell Anatomy 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000006655 lysosomal degradation pathway Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 108010087904 neutravidin Proteins 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000003921 particle size analysis Methods 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000009832 plasma treatment Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 102220262830 rs143843875 Human genes 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000012409 standard PCR amplification Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000001370 static light scattering Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1002—Coronaviridae
- C07K16/1003—Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2 or Covid-19]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1002—Coronaviridae
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Physics & Mathematics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pathology (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Pulmonology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
涉及多个交叉中和人源化单克隆抗体的制备。该抗体可交叉封闭SARS‑CoV‑2和SARS‑CoV刺突蛋白(S蛋白)同ACE2受体的结合，高效中和SARS‑CoV‑2和SARS‑CoV病毒侵染细胞。编码所述抗体的核酸序列(包括重/轻链可变区)、含有所述核酸序列的载体、药物组合物和试剂盒。制备的人源化交叉中和抗体可作为特异性抗体药物用于同时预防和治疗SARS‑CoV‑2和SARS‑CoV病毒引起的急性呼吸道传染病。所述交叉中和抗体还具有诊断等用途。
Description
PCT国内申请，说明书已公开。
Claims (30)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2020102198671 | 2020-03-25 | ||
| CN202010219867 | 2020-03-25 | ||
| PCT/CN2021/082374 WO2021190500A1 (zh) | 2020-03-25 | 2021-03-23 | SARS-CoV-2和SARS-CoV交叉中和抗体的制备及应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115279785A true CN115279785A (zh) | 2022-11-01 |
Family
ID=77890960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202180020022.2A Pending CN115279785A (zh) | 2020-03-25 | 2021-03-23 | SARS-CoV-2和SARS-CoV交叉中和抗体的制备及应用 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN115279785A (zh) |
| WO (1) | WO2021190500A1 (zh) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1566342B (zh) * | 2003-06-16 | 2010-09-08 | 中国人民解放军军事医学科学院毒物药物研究所 | Sars冠状病毒的s蛋白的抗原表位、其抗体、编码核酸以及含有它们的组合物 |
| WO2005060520A2 (en) * | 2003-11-25 | 2005-07-07 | Dana-Farber Cancer Institute, Inc. | ANTIBODIES AGAINST SARS-CoV AND METHODS OF USE THEREOF |
| CN100588430C (zh) * | 2004-02-20 | 2010-02-10 | 复旦大学 | 基于表位的SARS-Cov基因疫苗及其构建 |
| CN107033250B (zh) * | 2017-05-23 | 2020-01-21 | 山东省农业科学院奶牛研究中心 | 牛冠状病毒重组多表位抗原及其应用 |
| KR102076917B1 (ko) * | 2018-10-25 | 2020-02-13 | 연세대학교 산학협력단 | 자가조립 나노 입자를 제조하기 위한 유전자 재조합 발현 벡터 시스템 및 이를 이용하는 방법 |
-
2021
- 2021-03-23 WO PCT/CN2021/082374 patent/WO2021190500A1/zh active Application Filing
- 2021-03-23 CN CN202180020022.2A patent/CN115279785A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021190500A1 (zh) | 2021-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI830774B (zh) | 抗cd47抗體及其應用 | |
| CN108779179B (zh) | Cd47抗体、其抗原结合片段及其医药用途 | |
| CN112625136B (zh) | 针对冠状病毒具有中和活性的双特异性抗体及其用途 | |
| CN107849136B (zh) | 抗TfR抗体及其在治疗增殖性和炎性疾病中的用途 | |
| CN115380046A (zh) | SARS-CoV-2中和抗体及其制备和应用 | |
| WO2022105772A1 (zh) | 针对冠状病毒具有中和活性的双特异性抗体及其用途 | |
| US20230120270A1 (en) | New polypeptide complex | |
| JP7328324B2 (ja) | Ｔｉｍ－３に対する抗体およびその使用 | |
| US20140286957A1 (en) | ANTIBODIES TO CD1d | |
| AU2014233503A1 (en) | Anti-CD25 antibodies and their uses | |
| EP3178931B1 (en) | Anti-orai1 antibody | |
| US20230212306A1 (en) | Anti-human tlr7 antibody | |
| CN114286827A (zh) | 人源化抗il17a抗体及其应用 | |
| JP2022540859A (ja) | 新規ｂｓｓｌ抗体 | |
| WO2020221451A1 (en) | Antibodies binding to plasmodium circumsporozoite protein and uses thereof | |
| WO2022068844A1 (en) | Neutralizing antibody against sars-cov-2 | |
| US20230399385A1 (en) | Neutralizing antibodies against sars-cov-2 | |
| CN115279785A (zh) | SARS-CoV-2和SARS-CoV交叉中和抗体的制备及应用 | |
| CN117480179A (zh) | 一种呼吸道合胞病毒的抗体及其应用 | |
| CN113056480A (zh) | 人源化抗N截短淀粉样β单克隆抗体 | |
| WO2022156739A1 (zh) | 特异性结合bcma和cd3的抗原结合分子及其医药用途 | |
| WO2022052968A1 (zh) | 针对冠状病毒刺突蛋白的单克隆抗体及其用途 | |
| WO2024022478A1 (zh) | 结合大麻素受体cb1的抗体及其用途 | |
| WO2023093899A1 (zh) | 经修饰的蛋白或多肽 | |
| US20240034772A1 (en) | Antibodies binding to f-protein of metapneumovirus and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |