CN103467598B - 一种全人源抗狂犬病毒的中和抗体 - Google Patents
一种全人源抗狂犬病毒的中和抗体 Download PDFInfo
- Publication number
- CN103467598B CN103467598B CN201310442989.7A CN201310442989A CN103467598B CN 103467598 B CN103467598 B CN 103467598B CN 201310442989 A CN201310442989 A CN 201310442989A CN 103467598 B CN103467598 B CN 103467598B
- Authority
- CN
- China
- Prior art keywords
- antibody
- seq
- cell
- monoclonal antibody
- rabies
- 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.)
- Active
Links
- 206010037742 Rabies Diseases 0.000 title claims abstract description 30
- 241000700605 Viruses Species 0.000 title abstract description 20
- 230000003472 neutralizing effect Effects 0.000 title abstract description 7
- 241000711798 Rabies lyssavirus Species 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 9
- 238000001514 detection method Methods 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 5
- 231100000614 poison Toxicity 0.000 claims description 8
- 239000002574 poison Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 239000003963 antioxidant agent Substances 0.000 claims description 4
- 230000003078 antioxidant effect Effects 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 102000040430 polynucleotide Human genes 0.000 claims description 4
- 108091033319 polynucleotide Proteins 0.000 claims description 4
- 239000002157 polynucleotide Substances 0.000 claims description 4
- 238000012360 testing method Methods 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 241000238631 Hexapoda Species 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 230000000845 anti-microbial effect Effects 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 230000002538 fungal effect Effects 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000002474 experimental method Methods 0.000 abstract description 10
- 230000035945 sensitivity Effects 0.000 abstract description 4
- 108090000790 Enzymes Proteins 0.000 abstract description 2
- 102000004190 Enzymes Human genes 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000003119 immunoblot Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 231100000957 no side effect Toxicity 0.000 abstract description 2
- 230000001900 immune effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 41
- 108090000623 proteins and genes Proteins 0.000 description 33
- 241000282414 Homo sapiens Species 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 150000001413 amino acids Chemical group 0.000 description 14
- 238000000034 method Methods 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 238000006386 neutralization reaction Methods 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 9
- 229940024606 amino acid Drugs 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 229960003127 rabies vaccine Drugs 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 235000013336 milk Nutrition 0.000 description 4
- 239000008267 milk Substances 0.000 description 4
- 210000004080 milk Anatomy 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229940125645 monoclonal antibody drug Drugs 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003259 recombinant expression Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 2
- 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 2
- 208000030507 AIDS Diseases 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000709721 Hepatovirus A Species 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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 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
- 241001597008 Nomeidae Species 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000003145 cytotoxic factor Substances 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 210000004180 plasmocyte Anatomy 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000012096 transfection reagent Substances 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- 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 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
- GACDQMDRPRGCTN-KQYNXXCUSA-N 3'-phospho-5'-adenylyl sulfate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OS(O)(=O)=O)[C@@H](OP(O)(O)=O)[C@H]1O GACDQMDRPRGCTN-KQYNXXCUSA-N 0.000 description 1
- 108010059616 Activins Proteins 0.000 description 1
- 102000005606 Activins Human genes 0.000 description 1
- 108010000239 Aequorin Proteins 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 206010002515 Animal bite Diseases 0.000 description 1
- 241000228254 Aspergillus restrictus Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100027207 CD27 antigen Human genes 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 241000724252 Cucumber mosaic virus Species 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 208000010772 Dog disease Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000150562 Hantaan orthohantavirus Species 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- 229930182816 L-glutamine Natural products 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 101710121155 Poly(A) polymerase I Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000724205 Rice stripe tenuivirus Species 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 241000192023 Sarcina Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000488 activin Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- -1 diphtherotoxin Proteins 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 108010028531 enomycin Proteins 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
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 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
- 238000005242 forging Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940118700 human rabies immune globulin Drugs 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 108010076042 phenomycin Proteins 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 150000002910 rare earth metals Chemical class 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 206010040400 serum sickness Diseases 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims (9)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310442989.7A CN103467598B (zh) | 2013-09-26 | 2013-09-26 | 一种全人源抗狂犬病毒的中和抗体 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310442989.7A CN103467598B (zh) | 2013-09-26 | 2013-09-26 | 一种全人源抗狂犬病毒的中和抗体 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103467598A CN103467598A (zh) | 2013-12-25 |
CN103467598B true CN103467598B (zh) | 2017-02-08 |
Family
ID=49792660
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201310442989.7A Active CN103467598B (zh) | 2013-09-26 | 2013-09-26 | 一种全人源抗狂犬病毒的中和抗体 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN103467598B (zh) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005002511A2 (en) * | 2003-06-13 | 2005-01-13 | Thomas Jefferson University | Recombinant antibodies and compositions and methods for making and using the same |
CN101100663A (zh) * | 2006-07-05 | 2008-01-09 | 华北制药集团新药研究开发有限责任公司 | 重组人抗狂犬病毒单克隆抗体的制备方法 |
CN101235086A (zh) * | 2007-02-02 | 2008-08-06 | 吉林圣元科技有限责任公司 | 重组人抗狂犬病毒抗体 |
CN101337990A (zh) * | 2008-06-25 | 2009-01-07 | 中国人民解放军军事医学科学院微生物流行病研究所 | 人源抗狂犬病毒中和性抗体及其制备方法与用途 |
-
2013
- 2013-09-26 CN CN201310442989.7A patent/CN103467598B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005002511A2 (en) * | 2003-06-13 | 2005-01-13 | Thomas Jefferson University | Recombinant antibodies and compositions and methods for making and using the same |
CN101100663A (zh) * | 2006-07-05 | 2008-01-09 | 华北制药集团新药研究开发有限责任公司 | 重组人抗狂犬病毒单克隆抗体的制备方法 |
CN101235086A (zh) * | 2007-02-02 | 2008-08-06 | 吉林圣元科技有限责任公司 | 重组人抗狂犬病毒抗体 |
CN101337990A (zh) * | 2008-06-25 | 2009-01-07 | 中国人民解放军军事医学科学院微生物流行病研究所 | 人源抗狂犬病毒中和性抗体及其制备方法与用途 |
Also Published As
Publication number | Publication date |
---|---|
CN103467598A (zh) | 2013-12-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105968200B (zh) | 抗人pd-l1人源化单克隆抗体及其应用 | |
CN107760690B (zh) | 一种高通量全人源抗体的制备方法及应用 | |
CN104254544B (zh) | Cdim结合蛋白及其用途 | |
CN107686520A (zh) | 抗pd‑l1纳米抗体及其应用 | |
CN109071662A (zh) | 双特异性t细胞接合抗体构建体 | |
CN104105708A (zh) | PDGF受体β结合多肽 | |
CN107206076A (zh) | 靶向b‑细胞成熟抗原的抗体及其用途 | |
CN107207609A (zh) | 共同轻链和使用方法 | |
CN102164962A (zh) | 抗gd2抗体和方法及其相关应用 | |
CN113264998A (zh) | 抗新冠病毒SARS-CoV-2表面S1蛋白的单链抗体及其应用 | |
CN104136610A (zh) | 人源化抗上皮调节蛋白抗体和含有该抗体作为有效成分的癌症治疗药 | |
CN109071637A (zh) | 结合严重发热伴血小板减少综合征病毒的包膜糖蛋白的抗体及其用途 | |
CN111718415B (zh) | 一种抗tigit纳米抗体及其应用 | |
CN105820250B (zh) | 一种抗basigin人源化抗体及其应用 | |
JP2021530207A (ja) | 二重特異性抗体及びその使用 | |
CN107614762A (zh) | 一种由噬菌体表达的单链变异片段抗体库 | |
CN107043425A (zh) | 抗pd1和cd20双特异性抗体及其应用 | |
CN107073135A (zh) | 用于将分子递送至细胞的细胞质中的构建体 | |
CN110475787A (zh) | 结合剂 | |
CN109689090A (zh) | 抗o2抗体及其用途 | |
US8344109B2 (en) | Anti-ricin antibody | |
CN107207581A (zh) | 用于制备优化的治疗分子的方法 | |
CN104045713B (zh) | 一种抗Blys的单克隆抗体及含有该抗体的药物组合物 | |
CN103467598B (zh) | 一种全人源抗狂犬病毒的中和抗体 | |
CN107827981A (zh) | 抗绿脓杆菌外毒素a的纳米抗体及其应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right |
Effective date of registration: 20171229 Address after: Zhuhai Avenue, Guangdong city of Zhuhai province Jinwan District 519000 No. 6366 Building No. 6 on the eastern side of the first to the three layer Co-patentee after: GUANGZHOU TAINUODI BIOTECHNOLOGY Co.,Ltd. Patentee after: ZHUHAI TRINOMAB BIOTECHNOLOGY Co.,Ltd. Address before: 100176 Wanyuan business, No. 10, Hongda North Road, Yizhuang Economic Development Zone, Beijing City, 615 rooms Co-patentee before: GUANGZHOU TAINUODI BIOTECHNOLOGY Co.,Ltd. Patentee before: BEIJING TAINUODI BIOTECHNOLOGY Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
DD01 | Delivery of document by public notice | ||
DD01 | Delivery of document by public notice |
Addressee: Wang Yueming Document name: Notification of Passing Examination on Formalities |
|
TR01 | Transfer of patent right |
Effective date of registration: 20220408 Address after: 519090 room 110, first floor, plant 6, No. 6366, Zhuhai Avenue, Jinwan District, Zhuhai City, Guangdong Province Patentee after: ZHUHAI TRINOMAB BIOTECHNOLOGY Co.,Ltd. Address before: 519000 the first to three floors east of 6 building, 6366 Zhuhai Avenue, Zhuhai, Guangdong. Patentee before: ZHUHAI TRINOMAB BIOTECHNOLOGY Co.,Ltd. Patentee before: GUANGZHOU TAINUODI BIOTECHNOLOGY Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A neutralizing antibody against rabies virus from human Effective date of registration: 20220509 Granted publication date: 20170208 Pledgee: Pufa Silicon Valley Bank Co.,Ltd. Shenzhen Branch Pledgor: ZHUHAI TRINOMAB BIOTECHNOLOGY Co.,Ltd. Registration number: Y2022440020054 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230316 Granted publication date: 20170208 Pledgee: Pufa Silicon Valley Bank Co.,Ltd. Shenzhen Branch Pledgor: ZHUHAI TRINOMAB BIOTECHNOLOGY Co.,Ltd. Registration number: Y2022440020054 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
CP01 | Change in the name or title of a patent holder |
Address after: 519090 room 110, first floor, plant 6, No. 6366, Zhuhai Avenue, Jinwan District, Zhuhai City, Guangdong Province Patentee after: Zhuhai Tainuo Maibo Pharmaceutical Co.,Ltd. Address before: 519090 room 110, first floor, plant 6, No. 6366, Zhuhai Avenue, Jinwan District, Zhuhai City, Guangdong Province Patentee before: ZHUHAI TRINOMAB BIOTECHNOLOGY Co.,Ltd. |
|
CP01 | Change in the name or title of a patent holder |