JP5722927B2 - チロトロピン受容体の結合対象及びその使用 - Google Patents
チロトロピン受容体の結合対象及びその使用 Download PDFInfo
- Publication number
- JP5722927B2 JP5722927B2 JP2013007593A JP2013007593A JP5722927B2 JP 5722927 B2 JP5722927 B2 JP 5722927B2 JP 2013007593 A JP2013007593 A JP 2013007593A JP 2013007593 A JP2013007593 A JP 2013007593A JP 5722927 B2 JP5722927 B2 JP 5722927B2
- Authority
- JP
- Japan
- Prior art keywords
- binding
- tsh receptor
- tsh
- antibody
- molecule
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 230000027455 binding Effects 0.000 title claims abstract description 623
- 238000009739 binding Methods 0.000 title claims abstract description 623
- 102000015486 thyroid-stimulating hormone receptor activity proteins Human genes 0.000 title description 5
- 108040006218 thyroid-stimulating hormone receptor activity proteins Proteins 0.000 title description 5
- 102000003911 Thyrotropin Receptors Human genes 0.000 claims abstract description 599
- 108090000253 Thyrotropin Receptors Proteins 0.000 claims abstract description 599
- 239000012634 fragment Substances 0.000 claims abstract description 120
- 238000000034 method Methods 0.000 claims abstract description 88
- 230000003993 interaction Effects 0.000 claims abstract description 55
- 201000010099 disease Diseases 0.000 claims description 74
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 74
- 210000002966 serum Anatomy 0.000 claims description 70
- 230000005764 inhibitory process Effects 0.000 claims description 57
- 210000004027 cell Anatomy 0.000 claims description 53
- 230000000694 effects Effects 0.000 claims description 49
- 230000004936 stimulating effect Effects 0.000 claims description 42
- 210000001124 body fluid Anatomy 0.000 claims description 35
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 35
- 230000000638 stimulation Effects 0.000 claims description 34
- 239000010839 body fluid Substances 0.000 claims description 33
- 239000003446 ligand Substances 0.000 claims description 28
- 238000004519 manufacturing process Methods 0.000 claims description 25
- 208000023275 Autoimmune disease Diseases 0.000 claims description 24
- 230000002401 inhibitory effect Effects 0.000 claims description 24
- 238000012544 monitoring process Methods 0.000 claims description 23
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 23
- 238000012216 screening Methods 0.000 claims description 23
- 230000028993 immune response Effects 0.000 claims description 22
- 229920001184 polypeptide Polymers 0.000 claims description 20
- 230000003491 cAMP production Effects 0.000 claims description 19
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 17
- 102000005962 receptors Human genes 0.000 claims description 14
- 108020003175 receptors Proteins 0.000 claims description 14
- 238000000099 in vitro assay Methods 0.000 claims 1
- 238000003745 diagnosis Methods 0.000 abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 108010061174 Thyrotropin Proteins 0.000 description 159
- 102000011923 Thyrotropin Human genes 0.000 description 159
- 101000772267 Homo sapiens Thyrotropin receptor Proteins 0.000 description 69
- 102100029337 Thyrotropin receptor Human genes 0.000 description 67
- 125000003275 alpha amino acid group Chemical group 0.000 description 57
- 238000003556 assay Methods 0.000 description 48
- 239000002773 nucleotide Substances 0.000 description 47
- 125000003729 nucleotide group Chemical group 0.000 description 47
- 238000002360 preparation method Methods 0.000 description 44
- 239000012131 assay buffer Substances 0.000 description 40
- 210000004698 lymphocyte Anatomy 0.000 description 34
- 210000001519 tissue Anatomy 0.000 description 32
- 210000001685 thyroid gland Anatomy 0.000 description 30
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 29
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 29
- 229940095074 cyclic amp Drugs 0.000 description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- 108091022930 Glutamate decarboxylase Proteins 0.000 description 23
- 238000012360 testing method Methods 0.000 description 23
- 150000001413 amino acids Chemical class 0.000 description 18
- 102100035902 Glutamate decarboxylase 1 Human genes 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 17
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 17
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 16
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 16
- 239000013615 primer Substances 0.000 description 16
- 239000012228 culture supernatant Substances 0.000 description 15
- 238000001727 in vivo Methods 0.000 description 15
- 108091033319 polynucleotide Chemical group 0.000 description 15
- 239000002157 polynucleotide Chemical group 0.000 description 15
- 102000040430 polynucleotide Human genes 0.000 description 15
- 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 14
- 208000015023 Graves' disease Diseases 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 108010032595 Antibody Binding Sites Proteins 0.000 description 12
- 208000023328 Basedow disease Diseases 0.000 description 12
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 12
- 238000002965 ELISA Methods 0.000 description 12
- 239000005557 antagonist Substances 0.000 description 12
- 230000003302 anti-idiotype Effects 0.000 description 12
- 229960002685 biotin Drugs 0.000 description 12
- 239000011616 biotin Substances 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 241000588724 Escherichia coli Species 0.000 description 11
- 239000013078 crystal Substances 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- 239000000427 antigen Substances 0.000 description 10
- 229940098773 bovine serum albumin Drugs 0.000 description 10
- 238000010367 cloning Methods 0.000 description 10
- 108091007433 antigens Proteins 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 230000005784 autoimmunity Effects 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 238000003757 reverse transcription PCR Methods 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 230000009471 action Effects 0.000 description 8
- 239000000556 agonist Substances 0.000 description 8
- 238000010586 diagram Methods 0.000 description 8
- 230000004060 metabolic process Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 229920003023 plastic Polymers 0.000 description 8
- 239000004033 plastic Substances 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 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 7
- 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 7
- 235000020958 biotin Nutrition 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 7
- 229960000874 thyrotropin Drugs 0.000 description 7
- 230000001748 thyrotropin Effects 0.000 description 7
- 102000008214 Glutamate decarboxylase Human genes 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 208000024770 Thyroid neoplasm Diseases 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 201000002510 thyroid cancer Diseases 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 4
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 4
- 239000013504 Triton X-100 Substances 0.000 description 4
- 229920004890 Triton X-100 Polymers 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 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 4
- 229960000723 ampicillin Drugs 0.000 description 4
- 230000003466 anti-cipated effect Effects 0.000 description 4
- 239000007975 buffered saline Substances 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 230000010807 negative regulation of binding Effects 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000013391 scatchard analysis Methods 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 239000005495 thyroid hormone Substances 0.000 description 4
- 229940036555 thyroid hormone Drugs 0.000 description 4
- MZIYRTZAYQIAHW-UHFFFAOYSA-N 1-methyl-8-(2-methylpropyl)-3,7-dihydropurine-2,6-dione Chemical compound N1C(=O)N(C)C(=O)C2=C1N=C(CC(C)C)N2 MZIYRTZAYQIAHW-UHFFFAOYSA-N 0.000 description 3
- 208000026872 Addison Disease Diseases 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108010036012 Iodide peroxidase Proteins 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 102000014169 Steroid 21-Hydroxylase Human genes 0.000 description 3
- 108010011732 Steroid 21-Hydroxylase Proteins 0.000 description 3
- 102000009843 Thyroglobulin Human genes 0.000 description 3
- 108010034949 Thyroglobulin Proteins 0.000 description 3
- 102000014267 Thyroid peroxidases Human genes 0.000 description 3
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000008827 biological function Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 3
- 238000012875 competitive assay Methods 0.000 description 3
- 230000006552 constitutive activation Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 238000001114 immunoprecipitation Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 229960002175 thyroglobulin Drugs 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 206010015108 Epstein-Barr virus infection Diseases 0.000 description 2
- ARPVSMCNIDAQBO-YUMQZZPRSA-N Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(N)=O ARPVSMCNIDAQBO-YUMQZZPRSA-N 0.000 description 2
- VLDVBZICYBVQHB-IUCAKERBSA-N His-Val Chemical compound CC(C)[C@@H](C([O-])=O)NC(=O)[C@@H]([NH3+])CC1=CN=CN1 VLDVBZICYBVQHB-IUCAKERBSA-N 0.000 description 2
- 206010020850 Hyperthyroidism Diseases 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 101150008942 J gene Proteins 0.000 description 2
- JOCBASBOOFNAJA-UHFFFAOYSA-N N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Chemical compound OCC(CO)(CO)NCCS(O)(=O)=O JOCBASBOOFNAJA-UHFFFAOYSA-N 0.000 description 2
- 108010067902 Peptide Library Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000007994 TES buffer Substances 0.000 description 2
- 108010066702 Thyrotropin Alfa Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003202 long acting thyroid stimulator Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000000302 molecular modelling Methods 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- HKAVADYDPYUPRD-UHFFFAOYSA-N 1h-pyrazine-2-thione Chemical compound SC1=CN=CC=N1 HKAVADYDPYUPRD-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 238000012232 AGPC extraction Methods 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101710098119 Chaperonin GroEL 2 Proteins 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 101150097493 D gene Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 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 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 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
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 208000024799 Thyroid disease Diseases 0.000 description 1
- 102100027188 Thyroid peroxidase Human genes 0.000 description 1
- 208000026062 Tissue disease Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- -1 aliphatic amino acids Chemical class 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- YDMCWONVABEGBK-UHFFFAOYSA-N carbamimidoylazanium;phenoxide Chemical compound NC(N)=N.OC1=CC=CC=C1 YDMCWONVABEGBK-UHFFFAOYSA-N 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000000960 hypophysis hormone Substances 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000012332 laboratory investigation Methods 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 230000036473 myasthenia Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 102000004217 thyroid hormone receptors Human genes 0.000 description 1
- 108090000721 thyroid hormone receptors Proteins 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2869—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against hormone receptors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- 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
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- 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
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- G01N33/76—Human chorionic gonadotropin including luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone or their receptors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/575—Hormones
- G01N2333/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Endocrinology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Organic Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Genetics & Genomics (AREA)
- Mycology (AREA)
- Neurology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Reproductive Health (AREA)
- Rehabilitation Therapy (AREA)
- Rheumatology (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0227964.4A GB0227964D0 (en) | 2002-11-29 | 2002-11-29 | Binding partners for the thyrotropin receptor and uses thereof |
| GB0227964.4 | 2002-11-29 | ||
| GB0302140.9 | 2003-01-29 | ||
| GBGB0302140.9A GB0302140D0 (en) | 2002-11-29 | 2003-01-29 | Binding partners for the thyrotropin receptor and uses thereof |
| GB0315147.9 | 2003-06-27 | ||
| GB0315147A GB0315147D0 (en) | 2002-11-29 | 2003-06-27 | Binding partners for the thyrotropin receptor and uses thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004570698A Division JP5314234B2 (ja) | 2002-11-29 | 2003-11-28 | チロトロピン受容体の結合対象及びその使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013126987A JP2013126987A (ja) | 2013-06-27 |
| JP2013126987A5 JP2013126987A5 (enExample) | 2013-12-05 |
| JP5722927B2 true JP5722927B2 (ja) | 2015-05-27 |
Family
ID=9948838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013007593A Expired - Lifetime JP5722927B2 (ja) | 2002-11-29 | 2013-01-18 | チロトロピン受容体の結合対象及びその使用 |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JP5722927B2 (enExample) |
| AT (1) | ATE525086T1 (enExample) |
| ES (2) | ES2371244T3 (enExample) |
| GB (2) | GB0227964D0 (enExample) |
| HU (1) | HUE034370T2 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5304939B1 (ja) * | 2012-05-31 | 2013-10-02 | 大日本印刷株式会社 | 光学積層体、偏光板、偏光板の製造方法、画像表示装置、画像表示装置の製造方法及び画像表示装置の視認性改善方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9909661D0 (en) * | 1998-06-06 | 1999-06-23 | Rsr Ltd | Assays for TSH receptor autoantibodies |
| US8110664B2 (en) * | 2002-11-29 | 2012-02-07 | Rsr Limited | Binding partners for the thyrotropin receptor and uses thereof |
-
2002
- 2002-11-29 GB GBGB0227964.4A patent/GB0227964D0/en not_active Ceased
-
2003
- 2003-01-29 GB GBGB0302140.9A patent/GB0302140D0/en not_active Ceased
- 2003-11-28 ES ES03778537T patent/ES2371244T3/es not_active Expired - Lifetime
- 2003-11-28 ES ES10184462.9T patent/ES2624241T3/es not_active Expired - Lifetime
- 2003-11-28 HU HUE10184462A patent/HUE034370T2/en unknown
- 2003-11-28 AT AT03778537T patent/ATE525086T1/de active
-
2013
- 2013-01-18 JP JP2013007593A patent/JP5722927B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| GB0227964D0 (en) | 2003-01-08 |
| ES2624241T3 (es) | 2017-07-13 |
| HUE034370T2 (en) | 2018-02-28 |
| ATE525086T1 (de) | 2011-10-15 |
| GB0302140D0 (en) | 2003-03-05 |
| ES2371244T3 (es) | 2011-12-28 |
| JP2013126987A (ja) | 2013-06-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5314234B2 (ja) | チロトロピン受容体の結合対象及びその使用 | |
| JP7215759B2 (ja) | 4-1bb抗体およびその製造方法と使用 | |
| JP5982698B2 (ja) | Dll4に特異的に結合する新規モノクローナル抗体及びその用途 | |
| EP3878869A1 (en) | Nkg2a antibody, preparation method therefor and application thereof | |
| US10613099B2 (en) | Cell lines expressing surface bound anti-idiotype antibodies against anti-CD22 antibodies and uses thereof | |
| US8865871B2 (en) | Antibodies and kits for immunodetection of epitope tags | |
| US7935793B2 (en) | Treatment of inflammatory bowel diseases with anti-IP-10 antibodies | |
| US20140243265A1 (en) | Antibodies to modified human igf-1/e peptides | |
| RU2710439C2 (ru) | Новое антитело против пресепсина | |
| JP2729159B2 (ja) | ヒトグリセンチンのモノクローナル抗体、この抗体を産生するハイブリドーマおよびそれを用いるヒトグリセンチンの定量法 | |
| EP1708961B1 (en) | Anti-ip-10 antibodies | |
| JP5722927B2 (ja) | チロトロピン受容体の結合対象及びその使用 | |
| JP2011160696A (ja) | 修飾ヒトigf−1/eペプチドに対する抗体 | |
| JP2007075115A (ja) | 甲状腺機能を刺激する活性を持つ抗体 | |
| JPWO2005056597A1 (ja) | 免疫グロブリンFc受容体タンパク質 | |
| CN113999306A (zh) | 一种获得识别空间构象表位抗体的方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131018 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140624 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140919 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150224 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150326 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5722927 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |