CA1213229A - Antibodies having dual specificities, their preparation and uses therefor - Google Patents
Antibodies having dual specificities, their preparation and uses thereforInfo
- Publication number
- CA1213229A CA1213229A CA000425558A CA425558A CA1213229A CA 1213229 A CA1213229 A CA 1213229A CA 000425558 A CA000425558 A CA 000425558A CA 425558 A CA425558 A CA 425558A CA 1213229 A CA1213229 A CA 1213229A
- Authority
- CA
- Canada
- Prior art keywords
- process according
- antibody
- hybrid
- hybridoma
- monoclonal antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 230000009977 dual effect Effects 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 174
- 230000008569 process Effects 0.000 claims abstract description 152
- 239000000427 antigen Substances 0.000 claims abstract description 132
- 102000036639 antigens Human genes 0.000 claims abstract description 132
- 108091007433 antigens Proteins 0.000 claims abstract description 132
- 210000004408 hybridoma Anatomy 0.000 claims abstract description 116
- 230000004927 fusion Effects 0.000 claims abstract description 34
- 230000000890 antigenic effect Effects 0.000 claims abstract description 22
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 19
- 210000003719 b-lymphocyte Anatomy 0.000 claims abstract description 17
- 231100000518 lethal Toxicity 0.000 claims abstract description 12
- 230000001665 lethal effect Effects 0.000 claims abstract description 12
- 238000003745 diagnosis Methods 0.000 claims abstract description 10
- 210000004027 cell Anatomy 0.000 claims description 72
- 108090000790 Enzymes Proteins 0.000 claims description 64
- 102000004190 Enzymes Human genes 0.000 claims description 64
- 239000002609 medium Substances 0.000 claims description 45
- 239000000523 sample Substances 0.000 claims description 35
- 229960003343 ouabain Drugs 0.000 claims description 28
- LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 claims description 27
- LPMXVESGRSUGHW-GHYGWZAOSA-N Ouabain Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1)[C@H]1C[C@@H](O)[C@@]2(CO)[C@@](O)(C1)CC[C@H]1[C@]3(O)[C@@](C)([C@H](C4=CC(=O)OC4)CC3)C[C@@H](O)[C@H]21 LPMXVESGRSUGHW-GHYGWZAOSA-N 0.000 claims description 27
- 244000166550 Strophanthus gratus Species 0.000 claims description 27
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 claims description 27
- 239000000126 substance Substances 0.000 claims description 25
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 20
- 210000001519 tissue Anatomy 0.000 claims description 19
- 229940097325 prolactin Drugs 0.000 claims description 18
- 102000003946 Prolactin Human genes 0.000 claims description 17
- 108010057464 Prolactin Proteins 0.000 claims description 17
- 239000003112 inhibitor Substances 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 230000015572 biosynthetic process Effects 0.000 claims description 15
- 238000011534 incubation Methods 0.000 claims description 12
- 230000005764 inhibitory process Effects 0.000 claims description 12
- 230000027455 binding Effects 0.000 claims description 11
- 238000003018 immunoassay Methods 0.000 claims description 11
- 241000894007 species Species 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 10
- 229960003087 tioguanine Drugs 0.000 claims description 10
- LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 claims description 9
- 229960005508 8-azaguanine Drugs 0.000 claims description 9
- 230000002427 irreversible effect Effects 0.000 claims description 8
- 210000004989 spleen cell Anatomy 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 7
- 239000002738 chelating agent Substances 0.000 claims description 7
- 238000012258 culturing Methods 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 239000013068 control sample Substances 0.000 claims description 6
- 239000001963 growth medium Substances 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 6
- 238000010791 quenching Methods 0.000 claims description 6
- 230000000171 quenching effect Effects 0.000 claims description 6
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims description 5
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims description 5
- 230000002503 metabolic effect Effects 0.000 claims description 5
- 229940104230 thymidine Drugs 0.000 claims description 5
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 claims description 4
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 claims description 4
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 claims description 4
- XEQLGWAGMYUVTR-UHFFFAOYSA-N O=C1NC=NC2=C1NC=N2.C1=CN=C2C(=O)NC(NN)=NC2=N1 Chemical compound O=C1NC=NC2=C1NC=N2.C1=CN=C2C(=O)NC(NN)=NC2=N1 XEQLGWAGMYUVTR-UHFFFAOYSA-N 0.000 claims description 4
- 210000000805 cytoplasm Anatomy 0.000 claims description 4
- 239000003053 toxin Substances 0.000 claims description 4
- 231100000765 toxin Toxicity 0.000 claims description 4
- AGNGYMCLFWQVGX-AGFFZDDWSA-N (e)-1-[(2s)-2-amino-2-carboxyethoxy]-2-diazonioethenolate Chemical group OC(=O)[C@@H](N)CO\C([O-])=C\[N+]#N AGNGYMCLFWQVGX-AGFFZDDWSA-N 0.000 claims description 3
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 claims description 3
- 229950011321 azaserine Drugs 0.000 claims description 3
- 238000003776 cleavage reaction Methods 0.000 claims description 3
- 208000002672 hepatitis B Diseases 0.000 claims description 3
- 238000004255 ion exchange chromatography Methods 0.000 claims description 3
- 230000001737 promoting effect Effects 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- 108060003951 Immunoglobulin Proteins 0.000 claims description 2
- 238000001042 affinity chromatography Methods 0.000 claims description 2
- RXFMBIALQLOPAW-UHFFFAOYSA-N arsoric acid Chemical class O[As](O)(O)=O.O[As](O)(O)=O RXFMBIALQLOPAW-UHFFFAOYSA-N 0.000 claims description 2
- 102000018358 immunoglobulin Human genes 0.000 claims description 2
- 238000004020 luminiscence type Methods 0.000 claims description 2
- 238000011580 nude mouse model Methods 0.000 claims description 2
- 238000003375 selectivity assay Methods 0.000 claims 4
- 102100035703 Prostatic acid phosphatase Human genes 0.000 claims 2
- 108010043671 prostatic acid phosphatase Proteins 0.000 claims 2
- 241001529936 Murinae Species 0.000 claims 1
- 108010039491 Ricin Proteins 0.000 claims 1
- 238000001962 electrophoresis Methods 0.000 claims 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical group O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 238000000163 radioactive labelling Methods 0.000 claims 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical group [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 claims 1
- 230000001024 immunotherapeutic effect Effects 0.000 abstract description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 67
- 229910052763 palladium Inorganic materials 0.000 description 35
- 238000003556 assay Methods 0.000 description 21
- 239000011324 bead Substances 0.000 description 13
- 239000000758 substrate Substances 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 11
- 229910019142 PO4 Inorganic materials 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000001263 anti-prolactin effect Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 229960004927 neomycin Drugs 0.000 description 7
- 235000021317 phosphate Nutrition 0.000 description 7
- 230000003248 secreting effect Effects 0.000 description 7
- 229930193140 Neomycin Natural products 0.000 description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 6
- 201000000050 myeloid neoplasm Diseases 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 230000005855 radiation Effects 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 5
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 102000005548 Hexokinase Human genes 0.000 description 4
- 108700040460 Hexokinases Proteins 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 108010032595 Antibody Binding Sites Proteins 0.000 description 3
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- 229940000489 arsenate Drugs 0.000 description 3
- 230000001588 bifunctional effect Effects 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 238000004925 denaturation Methods 0.000 description 3
- 230000036425 denaturation Effects 0.000 description 3
- 229940064790 dilantin Drugs 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000006911 enzymatic reaction Methods 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000000760 immunoelectrophoresis Methods 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- DJHGAFSJWGLOIV-UHFFFAOYSA-K Arsenate3- Chemical compound [O-][As]([O-])([O-])=O DJHGAFSJWGLOIV-UHFFFAOYSA-K 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
- 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
- 241000699670 Mus sp. Species 0.000 description 2
- -1 PAP Proteins 0.000 description 2
- 208000037062 Polyps Diseases 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000007910 cell fusion Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000013198 immunometric assay Methods 0.000 description 2
- 210000001785 incus Anatomy 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 1
- SNMOMUYLFLGQQS-UHFFFAOYSA-N 8-bromooct-1-ene Chemical compound BrCCCCCCC=C SNMOMUYLFLGQQS-UHFFFAOYSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 241000234435 Lilium Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 241000604739 Phoebe Species 0.000 description 1
- 241001310793 Podium Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241001274197 Scatophagus argus Species 0.000 description 1
- 238000010266 Sephadex chromatography Methods 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241001504505 Troglodytes troglodytes Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 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 1
- 238000010170 biological method Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000007499 fusion processing Methods 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- PPTXFSQSISUDAU-UHFFFAOYSA-M hydrogen sulfate;2-methyl-4-[(2-methylphenyl)diazenyl]benzenediazonium Chemical compound OS([O-])(=O)=O.CC1=CC=CC=C1N=NC1=CC=C([N+]#N)C(C)=C1 PPTXFSQSISUDAU-UHFFFAOYSA-M 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229950006238 nadide Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 239000011824 nuclear material Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- WFLQAMUOBIONDG-UHFFFAOYSA-N phenoxyarsonic acid Chemical compound O[As](O)(=O)OC1=CC=CC=C1 WFLQAMUOBIONDG-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 235000019633 pungent taste Nutrition 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000004153 renaturation Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003544 thiamines Chemical class 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1084—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody the antibody being a hybrid immunoglobulin
- A61K51/109—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody the antibody being a hybrid immunoglobulin immunoglobulins having two or more different antigen-binding sites or multifunctional antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
Landscapes
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36778482A | 1982-04-12 | 1982-04-12 | |
| US367,784 | 1982-04-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1213229A true CA1213229A (en) | 1986-10-28 |
Family
ID=23448582
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000425558A Expired CA1213229A (en) | 1982-04-12 | 1983-04-11 | Antibodies having dual specificities, their preparation and uses therefor |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0105360A4 (es) |
| JP (2) | JPH0753119B2 (es) |
| AT (1) | AT394577B (es) |
| AU (1) | AU550486B2 (es) |
| CA (1) | CA1213229A (es) |
| CH (1) | CH672796A5 (es) |
| ES (7) | ES8504461A1 (es) |
| FI (1) | FI834529A0 (es) |
| GB (4) | GB2128631B (es) |
| IT (1) | IT1219778B (es) |
| WO (1) | WO1983003679A1 (es) |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3177776B2 (ja) * | 1988-09-27 | 2001-06-18 | 武田薬品工業株式会社 | ハイブリッドモノクローナル抗体，抗体産生ポリドーマおよび抗体含有薬剤 |
| US5292668A (en) * | 1981-12-21 | 1994-03-08 | Boston Biomedical Research Institute, Inc. | Bispecific antibody determinants |
| CA1214123A (en) * | 1983-01-20 | 1986-11-18 | Masashi Matsui | Cell lines for use in the preparation of hybridoma cells |
| EP0467416A1 (en) * | 1983-09-01 | 1992-01-22 | Hybritech Incorporated | Antibody compositions of therapeutic agents having an extended serum half-life |
| GB2148299B (en) * | 1983-09-01 | 1988-01-06 | Hybritech Inc | Antibody compositions of therapeutic agents having an extended serum half-life |
| ATE64622T1 (de) * | 1984-04-23 | 1991-07-15 | Boston Biomed Res Inst | Doppelspezifische antikoerper-determinanten. |
| NL8501219A (nl) * | 1985-04-29 | 1986-11-17 | Stichting Vrienden Van De Stic | Immunologisch complex, de bereiding en toepassing daarvan. |
| US5453269A (en) * | 1986-04-14 | 1995-09-26 | The General Hospital Corporation | Heterobifunctional antibodies having dual specificity for fibrin and thrombolylic agents and methods of use |
| JP2635343B2 (ja) | 1986-04-14 | 1997-07-30 | ザ・ジェネラル・ホスピタル・コーポレーション | ヘテロ二官能性抗体および利用方法 |
| FR2604092B1 (fr) * | 1986-09-19 | 1990-04-13 | Immunotech Sa | Immunoreactifs destines a cibler les cellules animales pour leur visualisation ou leur destruction in vivo |
| GB8626412D0 (en) * | 1986-11-05 | 1986-12-03 | Clark M R | Antibodies |
| GB8626413D0 (en) * | 1986-11-05 | 1986-12-03 | Gilliland L K | Antibodies |
| US5053226A (en) * | 1987-07-15 | 1991-10-01 | Board Of Regents, The University Of Texas System | Monoclonal antibodies binding platinum complexes |
| ES2058199T3 (es) * | 1987-09-23 | 1994-11-01 | Bristol Myers Squibb Co | Heteroconjugados de anticuerpos para la eliminacion de celulas infectadas por el vih. |
| GB2218100A (en) * | 1988-03-02 | 1989-11-08 | Erling Sundrehagen | Conjugates for the detection and/or quantification of antigenic substances in body fluids |
| US4892824A (en) * | 1988-03-15 | 1990-01-09 | Synbiotics Corporation | Fast track method for producing monoclonal bi-specific immunoglobulins |
| US5372812A (en) * | 1988-04-04 | 1994-12-13 | The General Hospital Corporation | Composition and method for acceleration of clot lysis |
| US5582862A (en) | 1988-04-04 | 1996-12-10 | General Hospital Corporation | Antibodies that bind to α2-antiplasmin crosslinked to fibrin which do not inhibit plasma α2-antiplasmin |
| JPH02196799A (ja) * | 1988-04-08 | 1990-08-03 | Agency Of Ind Science & Technol | 抗ヒト癌蛋白複合体 |
| US5851527A (en) * | 1988-04-18 | 1998-12-22 | Immunomedics, Inc. | Method for antibody targeting of therapeutic agents |
| IT1235349B (it) * | 1988-12-23 | 1992-06-30 | Biodata Spa | Saggio immunologico per determinazioni in fase omogenea |
| US5217713A (en) * | 1988-12-27 | 1993-06-08 | Takeda Chemical Industries, Ltd. | Cytotoxic bispecific monoclonal antibody, its production and use |
| CA2006408A1 (en) * | 1988-12-27 | 1990-06-27 | Susumu Iwasa | Bispecific monoclonal antibody, its production and use |
| WO1990012109A1 (en) * | 1989-03-30 | 1990-10-18 | Board Of Regents, The University Of Texas System | Monoclonal antibodies binding platinum complexes |
| FR2652004B1 (fr) * | 1989-09-21 | 1994-10-28 | Immunotech Partners | Nouveaux derives hydrophiles, application au diagnostic et a la therapeutique, kits diagnostiques ou therapeutiques et reactifs immunologiques. |
| CA2075927A1 (en) * | 1990-02-16 | 1991-08-17 | Victor A. Raso | Hybrid reagents capable of selectively releasing molecules into cells |
| TW212184B (es) * | 1990-04-02 | 1993-09-01 | Takeda Pharm Industry Co Ltd | |
| JP3431140B2 (ja) * | 1991-04-26 | 2003-07-28 | サーフィス・アクティブ・リミテッド | 抗体およびその使用方法 |
| GB9316369D0 (en) * | 1993-08-06 | 1993-09-22 | Surface Active Ltd | Diagnostic method |
| US5541110A (en) | 1994-05-17 | 1996-07-30 | Bristol-Myers Squibb | Cloning and expression of a gene encoding bryodin 1 from Bryonia dioica |
| GB9421468D0 (en) * | 1994-10-18 | 1994-12-07 | Surface Active Ltd | Biosensor |
| AU741338B2 (en) * | 1996-09-20 | 2001-11-29 | Bristol-Myers Squibb Company | Chimeric, humanized and single chain antibodies to alpha-2-antiplasmin |
| US20020132274A1 (en) | 2001-01-17 | 2002-09-19 | Nevalainen Marja T. | Diagnostic and monitorings methods for cancer |
| WO2004010957A2 (en) | 2002-07-31 | 2004-02-05 | Seattle Genetics, Inc. | Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease |
| AU2004316290C1 (en) | 2003-11-06 | 2012-02-02 | Seagen Inc. | Monomethylvaline compounds capable of conjugation to ligands |
| EP3138832A1 (en) | 2004-03-16 | 2017-03-08 | Temple University - Of The Commonwealth System of Higher Education | Substituted phenoxy- and phenylthio- derivatives for treating proliferative disorders |
| AU2005332660A1 (en) | 2004-11-12 | 2006-12-14 | Seattle Genetics, Inc. | Auristatins having an aminobenzoic acid unit at the N terminus |
| EP1871418B1 (en) | 2005-04-19 | 2014-03-19 | Seattle Genetics, Inc. | Humanized anti-cd70 binding agents and uses thereof |
| PL1912671T3 (pl) | 2005-07-18 | 2018-02-28 | Seattle Genetics, Inc. | Koniugaty beta-glukuronid-linker-lek |
| WO2008070593A2 (en) | 2006-12-01 | 2008-06-12 | Seattle Genetics, Inc. | Variant target binding agents and uses thereof |
| ES2374330T3 (es) | 2007-01-22 | 2012-02-15 | Genentech, Inc. | Precipitación con polielectrolito y purificación de anticuerpos. |
| WO2009135181A2 (en) | 2008-05-02 | 2009-11-05 | Seattle Genetics, Inc. | Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation |
| WO2011133658A1 (en) | 2010-04-22 | 2011-10-27 | Boston Medical Center Corporation | Compositions and methods for targeting and delivering therapeutics into cells |
| US9353150B2 (en) | 2012-12-04 | 2016-05-31 | Massachusetts Institute Of Technology | Substituted pyrazino[1′,2′:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment |
| PL2968440T3 (pl) | 2013-03-15 | 2019-12-31 | Zymeworks Inc. | Związki cytotoksyczne i antymitotyczne oraz sposoby ich stosowania |
| US10227407B2 (en) | 2013-10-10 | 2019-03-12 | Yukinari Kato | Anti-podoplanin antibody |
| CA2935077C (en) | 2013-12-27 | 2022-03-15 | Geoffrey C. Winters | Sulfonamide-containing linkage systems for drug conjugates |
| CA2960899C (en) | 2014-09-17 | 2021-08-17 | Zymeworks Inc. | Cytotoxic and anti-mitotic compounds, and methods of using the same |
| CN107029242A (zh) | 2015-11-03 | 2017-08-11 | 财团法人工业技术研究院 | 抗体药物复合物及其制造方法 |
| US11844839B2 (en) | 2016-03-25 | 2023-12-19 | Seagen Inc. | Process for the preparation of pegylated drug-linkers and intermediates thereof |
| US10918627B2 (en) | 2016-05-11 | 2021-02-16 | Massachusetts Institute Of Technology | Convergent and enantioselective total synthesis of Communesin analogs |
| EP3600443A1 (en) | 2017-03-24 | 2020-02-05 | Seattle Genetics, Inc. | Process for the preparation of glucuronide drug-linkers and intermediates thereof |
| US11932650B2 (en) | 2017-05-11 | 2024-03-19 | Massachusetts Institute Of Technology | Potent agelastatin derivatives as modulators for cancer invasion and metastasis |
| US10640508B2 (en) | 2017-10-13 | 2020-05-05 | Massachusetts Institute Of Technology | Diazene directed modular synthesis of compounds with quaternary carbon centers |
| US10869888B2 (en) | 2018-04-17 | 2020-12-22 | Innovative Cellular Therapeutics CO., LTD. | Modified cell expansion and uses thereof |
| CA3110096A1 (en) * | 2018-08-30 | 2020-03-05 | Innovative Cellular Therapeutics CO., LTD. | Chimeric antigen receptor cells for treating solid tumor |
| US20220409734A1 (en) | 2019-05-10 | 2022-12-29 | Yutaka Nishimoto | Antibody drug conjugates |
| TW202138388A (zh) | 2019-12-30 | 2021-10-16 | 美商西根公司 | 以非海藻糖苷化抗－ｃｄ７０抗體治療癌症之方法 |
| US12076343B2 (en) | 2020-02-19 | 2024-09-03 | Innovative Cellular Therapeutics Holdings, Ltd. | Engineered safety in cell therapy |
| US12043654B2 (en) | 2020-06-02 | 2024-07-23 | Innovative Cellular Therapeutics Holdings, Ltd. | Anti-GCC antibody and CAR thereof for treating digestive system cancer |
| US20220168330A1 (en) | 2020-11-09 | 2022-06-02 | Takeda Pharmaceutical Company Limited | Antibody drug conjugates |
| US12030888B2 (en) | 2021-02-24 | 2024-07-09 | Massachusetts Institute Of Technology | Himastatin derivatives, and processes of preparation thereof, and uses thereof |
| WO2023278377A1 (en) | 2021-06-29 | 2023-01-05 | Seagen Inc. | Methods of treating cancer with a combination of a nonfucosylated anti-cd70 antibody and a cd47 antagonist |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4130634A (en) * | 1974-03-15 | 1978-12-19 | University Of Illinois Foundation | Method for detecting and quantifying antigens |
| US4331647A (en) * | 1980-03-03 | 1982-05-25 | Goldenberg Milton David | Tumor localization and therapy with labeled antibody fragments specific to tumor-associated markers |
| US4376110A (en) * | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
| US4474893A (en) * | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
-
1983
- 1983-04-11 ES ES521370A patent/ES8504461A1/es not_active Expired
- 1983-04-11 CA CA000425558A patent/CA1213229A/en not_active Expired
- 1983-04-12 GB GB08332646A patent/GB2128631B/en not_active Expired
- 1983-04-12 EP EP19830901672 patent/EP0105360A4/en not_active Ceased
- 1983-04-12 WO PCT/US1983/000525 patent/WO1983003679A1/en not_active Application Discontinuation
- 1983-04-12 AU AU15559/83A patent/AU550486B2/en not_active Expired
- 1983-04-12 AT AT0901883A patent/AT394577B/de not_active IP Right Cessation
- 1983-04-12 CH CH6700/83A patent/CH672796A5/de not_active IP Right Cessation
- 1983-04-12 IT IT20548/83A patent/IT1219778B/it active
- 1983-12-09 FI FI834529A patent/FI834529A0/fi not_active Application Discontinuation
- 1983-12-12 ES ES527963A patent/ES8503441A1/es not_active Expired
-
1984
- 1984-07-02 ES ES533931A patent/ES8506091A1/es not_active Expired
- 1984-07-02 ES ES533930A patent/ES533930A0/es active Granted
- 1984-10-31 ES ES537257A patent/ES8606655A1/es not_active Expired
- 1984-12-18 ES ES538727A patent/ES8604424A1/es not_active Expired
-
1985
- 1985-07-16 ES ES545247A patent/ES8607386A1/es not_active Expired
- 1985-12-09 GB GB08530308A patent/GB2168998B/en not_active Expired
- 1985-12-09 GB GB08530309A patent/GB2169921B/en not_active Expired
- 1985-12-09 GB GB08530310A patent/GB2167086B/en not_active Expired
-
1987
- 1987-01-05 JP JP62000342A patent/JPH0753119B2/ja not_active Expired - Lifetime
-
1994
- 1994-02-10 JP JP6016728A patent/JP2562002B2/ja not_active Expired - Lifetime
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1213229A (en) | Antibodies having dual specificities, their preparation and uses therefor | |
| EP0068763B2 (en) | Recombinant monoclonal antibodies | |
| US4714681A (en) | Quadroma cells and trioma cells and methods for the production of same | |
| JP2865645B2 (ja) | キメラ抗体の産生方法 | |
| JP2793587B2 (ja) | 免疫複合体レセプター | |
| US4471058A (en) | Method for the detection and/or determination of a polyvalent antigen using at least two different monoclonal antibodies | |
| CA1253816A (en) | Monoclonal antibodies against alveolar surfactant protein | |
| US6808901B1 (en) | Production of chimeric antibodies | |
| JPH03501440A (ja) | 免疫反応性ヘテロ鎖抗体 | |
| Segal et al. | Production of bispecific antibodies | |
| EA007494B1 (ru) | Моноклональные антитела к растворимому рецептору лпнп человека, способы их получения и применения и гибридомы, продуцирующие указанные антитела | |
| Schmitz et al. | Production of monoclonal antibodies with preselected submolecular binding specificities to protein antigenic sites: antibodies to sperm whale myoglobin sites | |
| JPH0467959B2 (es) | ||
| EP1142995B1 (en) | Antiuracil monoclonal antibody | |
| US7067314B2 (en) | Monoclonal antibody, its immunoreactive fragment and hybridoma | |
| NO171643B (no) | Antistoffer med dobbelte spesifisiteter, deres fremstilling og anvendelse | |
| JPH05252986A (ja) | 異種二機能抗体およびその利用法 | |
| CA1329545C (en) | Immunological complex, its preparation and its use | |
| Liu | Development of bispecific monoclonal antibodies and their applications in ultrasensitive virus ELISA: phage display technology and viral purification | |
| Liu | Development of bispecific monoclonal antibodies and their applications in ultrasensitive virus ELISA; phage display technology and viral purification. | |
| Xu | Development of bispecific monoclonal antibodies and their applications in ultrasensitive immunoassays. | |
| JPS6239772A (ja) | ヒト血中のヒトプロリルヒドロキシラーゼの放射性免疫学的測定法による定量法 | |
| JPH01500722A (ja) | 膵臓α‐アミラーゼに対する抗体の産生及び診断への使用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |