JP5513114B2 - 卵巣癌の放射免疫療法のためのヒト抗−葉酸受容体アルファ抗体および抗体フラグメント - Google Patents
卵巣癌の放射免疫療法のためのヒト抗−葉酸受容体アルファ抗体および抗体フラグメント Download PDFInfo
- Publication number
- JP5513114B2 JP5513114B2 JP2009527737A JP2009527737A JP5513114B2 JP 5513114 B2 JP5513114 B2 JP 5513114B2 JP 2009527737 A JP2009527737 A JP 2009527737A JP 2009527737 A JP2009527737 A JP 2009527737A JP 5513114 B2 JP5513114 B2 JP 5513114B2
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- fragment
- afra
- chain
- fab
- 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
- 241000282414 Homo sapiens Species 0.000 title claims description 59
- 206010033128 Ovarian cancer Diseases 0.000 title claims description 56
- 102000008394 Immunoglobulin Fragments Human genes 0.000 title claims description 50
- 108010021625 Immunoglobulin Fragments Proteins 0.000 title claims description 50
- 206010061535 Ovarian neoplasm Diseases 0.000 title claims description 47
- 238000011363 radioimmunotherapy Methods 0.000 title description 25
- 230000003432 anti-folate effect Effects 0.000 title description 4
- 229940127074 antifolate Drugs 0.000 title description 4
- 239000004052 folic acid antagonist Substances 0.000 title description 4
- 239000012634 fragment Substances 0.000 claims description 173
- 239000000539 dimer Substances 0.000 claims description 55
- 102000010451 Folate receptor alpha Human genes 0.000 claims description 45
- 108050001931 Folate receptor alpha Proteins 0.000 claims description 45
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 45
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 35
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 35
- 239000003814 drug Substances 0.000 claims description 29
- 102100035139 Folate receptor alpha Human genes 0.000 claims description 28
- 239000013604 expression vector Substances 0.000 claims description 27
- 150000007523 nucleic acids Chemical class 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 22
- 229940124597 therapeutic agent Drugs 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 241000588724 Escherichia coli Species 0.000 claims description 17
- 108020004707 nucleic acids Proteins 0.000 claims description 13
- 102000039446 nucleic acids Human genes 0.000 claims description 13
- 230000001105 regulatory effect Effects 0.000 claims description 11
- 230000002103 transcriptional effect Effects 0.000 claims description 11
- 229940127089 cytotoxic agent Drugs 0.000 claims description 9
- 239000012636 effector Substances 0.000 claims description 9
- 230000002018 overexpression Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 239000013598 vector Substances 0.000 claims description 9
- 239000003550 marker Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 5
- 241000282412 Homo Species 0.000 claims description 4
- 239000002254 cytotoxic agent Substances 0.000 claims description 4
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 4
- 238000001959 radiotherapy Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 description 81
- 206010028980 Neoplasm Diseases 0.000 description 68
- 230000027455 binding Effects 0.000 description 51
- 101001023230 Homo sapiens Folate receptor alpha Proteins 0.000 description 43
- 235000001014 amino acid Nutrition 0.000 description 36
- 108090000623 proteins and genes Proteins 0.000 description 35
- 229940024606 amino acid Drugs 0.000 description 34
- 238000000034 method Methods 0.000 description 34
- 150000001413 amino acids Chemical class 0.000 description 33
- 239000000427 antigen Substances 0.000 description 32
- 102000036639 antigens Human genes 0.000 description 32
- 108091007433 antigens Proteins 0.000 description 32
- 238000001727 in vivo Methods 0.000 description 25
- 102000006815 folate receptor Human genes 0.000 description 24
- 108020005243 folate receptor Proteins 0.000 description 24
- 210000001519 tissue Anatomy 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 239000000203 mixture Substances 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 102000005962 receptors Human genes 0.000 description 19
- 108020003175 receptors Proteins 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 18
- 102000053180 human FOLR1 Human genes 0.000 description 17
- 235000018102 proteins Nutrition 0.000 description 17
- 239000000126 substance Substances 0.000 description 17
- 238000006471 dimerization reaction Methods 0.000 description 16
- 201000011510 cancer Diseases 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 14
- 238000002347 injection Methods 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- 102000001708 Protein Isoforms Human genes 0.000 description 13
- 108010029485 Protein Isoforms Proteins 0.000 description 13
- 239000000178 monomer Substances 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 12
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 description 10
- 239000000872 buffer Substances 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 10
- 230000004083 survival effect Effects 0.000 description 10
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 235000018417 cysteine Nutrition 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 210000000056 organ Anatomy 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 241000894007 species Species 0.000 description 9
- 230000004614 tumor growth Effects 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 210000004899 c-terminal region Anatomy 0.000 description 8
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 235000019152 folic acid Nutrition 0.000 description 8
- 230000004807 localization Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 206010003445 Ascites Diseases 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000011724 folic acid Substances 0.000 description 7
- 238000003384 imaging method Methods 0.000 description 7
- 238000007912 intraperitoneal administration Methods 0.000 description 7
- LWGJTAZLEJHCPA-UHFFFAOYSA-N n-(2-chloroethyl)-n-nitrosomorpholine-4-carboxamide Chemical compound ClCCN(N=O)C(=O)N1CCOCC1 LWGJTAZLEJHCPA-UHFFFAOYSA-N 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000010494 dissociation reaction Methods 0.000 description 6
- 230000005593 dissociations Effects 0.000 description 6
- 210000002919 epithelial cell Anatomy 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 238000002648 combination therapy Methods 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 238000005755 formation reaction Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 4
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 229960000304 folic acid Drugs 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229920003192 poly(bis maleimide) Polymers 0.000 description 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 4
- XQUPVDVFXZDTLT-UHFFFAOYSA-N 1-[4-[[4-(2,5-dioxopyrrol-1-yl)phenyl]methyl]phenyl]pyrrole-2,5-dione Chemical group O=C1C=CC(=O)N1C(C=C1)=CC=C1CC1=CC=C(N2C(C=CC2=O)=O)C=C1 XQUPVDVFXZDTLT-UHFFFAOYSA-N 0.000 description 3
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 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 3
- 229940014144 folate Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000002523 gelfiltration Methods 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 239000000710 homodimer Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011221 initial treatment Methods 0.000 description 3
- 101150109249 lacI gene Proteins 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 238000013391 scatchard analysis Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 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 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- PBVAJRFEEOIAGW-UHFFFAOYSA-N 3-[bis(2-carboxyethyl)phosphanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCP(CCC(O)=O)CCC(O)=O PBVAJRFEEOIAGW-UHFFFAOYSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- -1 amino acids 1 Chemical class 0.000 description 2
- 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 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 238000006664 bond formation reaction Methods 0.000 description 2
- 230000009400 cancer invasion Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000001945 cysteines Chemical class 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 230000000447 dimerizing effect Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 150000002224 folic acids Chemical class 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000001597 immobilized metal affinity chromatography Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000005258 radioactive decay Effects 0.000 description 2
- 229940051022 radioimmunoconjugate Drugs 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- FJQZXCPWAGYPSD-UHFFFAOYSA-N 1,3,4,6-tetrachloro-3a,6a-diphenylimidazo[4,5-d]imidazole-2,5-dione Chemical compound ClN1C(=O)N(Cl)C2(C=3C=CC=CC=3)N(Cl)C(=O)N(Cl)C12C1=CC=CC=C1 FJQZXCPWAGYPSD-UHFFFAOYSA-N 0.000 description 1
- MSTNYGQPCMXVAQ-KIYNQFGBSA-N 5,6,7,8-tetrahydrofolic acid Chemical compound N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-KIYNQFGBSA-N 0.000 description 1
- 229940105150 5-methyltetrahydrofolic acid Drugs 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 238000012492 Biacore method Methods 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 108091000126 Dihydroorotase Proteins 0.000 description 1
- 102100034581 Dihydroorotase Human genes 0.000 description 1
- 230000010777 Disulfide Reduction Effects 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241001013691 Escherichia coli BW25113 Species 0.000 description 1
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 1
- 208000014061 Extranodal Extension Diseases 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 208000012766 Growth delay Diseases 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 206010027462 Metastases to ovary Diseases 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 208000003837 Second Primary Neoplasms Diseases 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 101000777492 Stichodactyla helianthus DELTA-stichotoxin-She4b Proteins 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 101150046213 araP gene Proteins 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000002987 choroid plexus Anatomy 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 230000002498 deadly effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 230000007412 host metabolism Effects 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- ZNOVTXRBGFNYRX-ABLWVSNPSA-N levomefolic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-ABLWVSNPSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000021121 meiosis Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 101150051230 pyrC gene Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000011191 terminal modification Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Reproductive Health (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06019399A EP1900752A1 (en) | 2006-09-15 | 2006-09-15 | Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma |
| EP06019399.2 | 2006-09-15 | ||
| PCT/EP2007/007944 WO2008031577A1 (en) | 2006-09-15 | 2007-09-12 | Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010503386A JP2010503386A (ja) | 2010-02-04 |
| JP2010503386A5 JP2010503386A5 (cg-RX-API-DMAC7.html) | 2010-10-14 |
| JP5513114B2 true JP5513114B2 (ja) | 2014-06-04 |
Family
ID=37737768
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009527737A Active JP5513114B2 (ja) | 2006-09-15 | 2007-09-12 | 卵巣癌の放射免疫療法のためのヒト抗−葉酸受容体アルファ抗体および抗体フラグメント |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US8388972B2 (cg-RX-API-DMAC7.html) |
| EP (2) | EP1900752A1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP5513114B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR101497045B1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2007296899B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0716811B8 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2662005C (cg-RX-API-DMAC7.html) |
| ES (1) | ES2644423T3 (cg-RX-API-DMAC7.html) |
| IL (1) | IL197300A (cg-RX-API-DMAC7.html) |
| MX (1) | MX2009002711A (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ575093A (cg-RX-API-DMAC7.html) |
| RU (1) | RU2464277C2 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2008031577A1 (cg-RX-API-DMAC7.html) |
| ZA (1) | ZA200901328B (cg-RX-API-DMAC7.html) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050232919A1 (en) | 2004-02-12 | 2005-10-20 | Morphotek, Inc. | Monoclonal antibodies that specifically block biological activity of a tumor antigen |
| JP2009521206A (ja) | 2005-04-22 | 2009-06-04 | モルフォテック、インク． | 免疫エフェクター活性を有する葉酸受容体アルファ陽性細胞に内部移行する抗体 |
| CN103037900B (zh) | 2010-02-24 | 2016-04-06 | 伊缪诺金公司 | 叶酸受体1抗体与免疫缀合物以及其用途 |
| EP3401333B1 (en) | 2010-09-09 | 2021-05-19 | Purdue Research Foundation | Anti-human folate receptor beta antibodies and methods of use |
| RU2630608C2 (ru) * | 2010-11-05 | 2017-09-11 | Морфотек Инк. | Рецептор фолиевой кислоты альфа в качестве диагностического и прогностического маркера злокачественных опухолей, экспрессирующих рецептор фолиевой кислоты альфа |
| US9402865B2 (en) | 2011-01-18 | 2016-08-02 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treating cancer |
| EP2687231A4 (en) | 2011-03-18 | 2014-10-22 | Univ Kagoshima | COMPOSITION FOR THE TREATMENT AND DIAGNOSIS OF PANCREATIC CANCER |
| CA2831426C (en) * | 2011-04-01 | 2023-02-21 | Immunogen, Inc. | Methods for increasing efficacy of folr1 cancer therapy |
| PL2731972T3 (pl) | 2011-07-15 | 2018-06-29 | Eisai R&D Management Co., Ltd. | Przeciwciała skierowane przeciwko receptorowi folianowemu alfa i ich zastosowania |
| MX356947B (es) | 2011-08-23 | 2018-06-20 | Roche Glycart Ag | Anticuerpos bioespecíficos específicos para antígenos que activan células t y un antígeno tumoral y métodos de uso. |
| US9629918B2 (en) | 2012-02-29 | 2017-04-25 | Purdue Research Foundation | Folate receptor alpha binding ligands |
| CN104755498B (zh) * | 2012-08-31 | 2019-06-18 | 伊缪诺金公司 | 用于检测叶酸受体1的诊断测定和试剂盒 |
| WO2014055771A1 (en) | 2012-10-05 | 2014-04-10 | The Trustees Of The University Of Pennsylvania | Human alpha-folate receptor chimeric antigen receptor |
| ES2776698T3 (es) | 2012-12-20 | 2020-07-31 | Purdue Research Foundation | Células T que expresan un receptor antigénico quimérico como terapia contra el cáncer |
| US9637547B2 (en) * | 2013-08-30 | 2017-05-02 | Immunogen, Inc. | Monoclonal antibodies for detection of folate receptor 1 |
| SG10202102555TA (en) * | 2013-10-08 | 2021-04-29 | Immunogen Inc | Anti-folr1 immunoconjugate dosing regimens |
| KR101646577B1 (ko) * | 2014-08-14 | 2016-08-09 | 원광대학교산학협력단 | 엽산수용체 표적용 화합물 또는 이의 약학적으로 허용가능한 염과, 이를 유효성분으로 포함하는 암 예방, 진단 또는 치료용 조성물 |
| LT3221357T (lt) | 2014-11-20 | 2020-08-25 | F. Hoffmann-La Roche Ag | Bendros lengvosios grandinės ir naudojimo būdai |
| HRP20201928T1 (hr) | 2014-11-20 | 2021-02-05 | F. Hoffmann - La Roche Ag | Kombinirana terapija bispecifičnom antigen vezujućom molekulom koja aktivira t-stanice, za cd3 i folatni receptor 1 (folr1), i antagonistom vezivanja osi pd-1 |
| MX2017006571A (es) | 2014-11-20 | 2017-09-29 | Hoffmann La Roche | Moleculas de union a antigeno biespecificas activadoras de celulas t. |
| IL257531B2 (en) | 2015-09-17 | 2023-04-01 | Immunogen Inc | Medicinal compositions containing anti-folr1 immunoconjugates |
| JP7282521B2 (ja) | 2016-04-08 | 2023-05-29 | パーデュー・リサーチ・ファウンデイション | Ｃａｒ ｔ細胞療法のための方法および組成物 |
| WO2018031980A1 (en) | 2016-08-12 | 2018-02-15 | L.E.A.F. Holdings Group Llc | Polyglutamated antifolates and uses thereof |
| CA3177187A1 (en) | 2016-08-12 | 2018-02-15 | L.E.A.F Holdings Group Llc | Alpha and gamma-d polyglutamated antifolates and uses thereof |
| CA3221995C (en) | 2017-02-08 | 2024-05-28 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer |
| SG11201907646YA (en) | 2017-02-20 | 2019-09-27 | Dragonfly Therapeutics Inc | Proteins binding her2, nkg2d and cd16 |
| WO2018160622A1 (en) | 2017-02-28 | 2018-09-07 | Endocyte, Inc. | Compositions and methods for car t cell therapy |
| WO2019094648A1 (en) | 2017-11-08 | 2019-05-16 | L.E.A.F. Holdings Group Llc | Platinum complexes and uses thereof |
| CN112292138A (zh) | 2018-01-22 | 2021-01-29 | 西雅图儿童医院（Dba西雅图儿童研究所） | Car t细胞的使用方法 |
| PT3749346T (pt) | 2018-02-08 | 2024-09-05 | Dragonfly Therapeutics Inc | Combinações de domínios variáveis de anticorpos dirigidas ao receptor nkg2d |
| KR20200118824A (ko) | 2018-02-08 | 2020-10-16 | 드래곤플라이 쎄라퓨틱스, 인크. | 자연 살해 세포를 활성화시키는 다중-특이성 결합 단백질을 수반하는 암의 병용 요법 |
| CA3091424A1 (en) | 2018-02-20 | 2019-08-29 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind cd33, nkg2d, and cd16, and methods of use |
| WO2019165237A1 (en) | 2018-02-23 | 2019-08-29 | Endocyte, Inc. | Sequencing method for car t cell therapy |
| MX2020009522A (es) | 2018-03-13 | 2020-10-22 | Phanes Therapeutics Inc | Anticuerpos anti-folato del receptor 1 y usos de los mismos. |
| EA202091888A1 (ru) | 2018-08-08 | 2020-10-23 | Драгонфлай Терапьютикс, Инк. | Вариабельные домены антител, нацеленные на рецептор nkg2d |
| CA3108646A1 (en) | 2018-08-08 | 2020-02-13 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and a tumor-associated antigen |
| AU2019318083A1 (en) | 2018-08-08 | 2021-02-25 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind BCMA, NKG2D and CD16, and methods of use |
| CA3138272A1 (en) | 2019-04-29 | 2020-11-05 | Immunogen, Inc. | Biparatopic fr-alpha antibodies and immunoconjugates |
| EP4010031A1 (en) | 2019-08-06 | 2022-06-15 | L.E.A.F Holdings Group LLC | Processes of preparing polyglutamated antifolates and uses of their compositions |
| CN111393528B (zh) * | 2020-01-19 | 2023-01-31 | 中国药科大学 | 一种靶向叶酸受体α的单链抗体及其应用 |
| MX2022013944A (es) | 2020-05-06 | 2022-11-30 | Dragonfly Therapeutics Inc | Proteinas que se unen al receptor activador de celulas asesinas naturales grupo 2 miembro d (nkg2d), cumulo de diferenciacion (cd16) y miembro a de la familia de dominios de lectina tipo c 12 (clec12a). |
| JP2024508894A (ja) | 2021-03-03 | 2024-02-28 | ドラゴンフライ セラピューティクス， インコーポレイテッド | Ｎｋｇ２ｄ、ｃｄ１６、及び腫瘍関連抗原に結合する多特異性結合タンパク質を使用して癌を治療する方法 |
| CN117700557B (zh) * | 2024-02-05 | 2024-04-30 | 卡秋(江苏)生物科技有限公司 | 一种特异性结合叶酸受体α的抗体或抗原结合片段 |
| CN119757601A (zh) * | 2025-01-06 | 2025-04-04 | 哈尔滨脉图精准技术有限公司 | 一种用于卵巢癌诊断的代谢标志物组合及其应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003217912A1 (en) * | 2002-03-01 | 2003-09-16 | Xencor | Antibody optimization |
| DK1517921T3 (da) * | 2002-06-28 | 2006-10-09 | Domantis Ltd | Immunglobulin-enkeltvariable antigen-bindende domæner og dobbeltspecifikke konstruktioner deraf |
| US20050232919A1 (en) * | 2004-02-12 | 2005-10-20 | Morphotek, Inc. | Monoclonal antibodies that specifically block biological activity of a tumor antigen |
| EP1945772B1 (en) * | 2005-10-06 | 2015-11-18 | Advanced Accelerator Applications S.A. | Novel selection system |
-
2006
- 2006-09-15 EP EP06019399A patent/EP1900752A1/en not_active Withdrawn
-
2007
- 2007-09-12 JP JP2009527737A patent/JP5513114B2/ja active Active
- 2007-09-12 US US12/441,207 patent/US8388972B2/en active Active
- 2007-09-12 KR KR1020097004948A patent/KR101497045B1/ko active Active
- 2007-09-12 MX MX2009002711A patent/MX2009002711A/es not_active Application Discontinuation
- 2007-09-12 WO PCT/EP2007/007944 patent/WO2008031577A1/en not_active Ceased
- 2007-09-12 NZ NZ575093A patent/NZ575093A/en unknown
- 2007-09-12 RU RU2009114161/10A patent/RU2464277C2/ru active
- 2007-09-12 ES ES07802280.3T patent/ES2644423T3/es active Active
- 2007-09-12 AU AU2007296899A patent/AU2007296899B2/en active Active
- 2007-09-12 EP EP07802280.3A patent/EP2061813B1/en active Active
- 2007-09-12 BR BRPI0716811A patent/BRPI0716811B8/pt active IP Right Grant
- 2007-09-12 CA CA2662005A patent/CA2662005C/en active Active
- 2007-09-12 ZA ZA200901328A patent/ZA200901328B/xx unknown
-
2009
- 2009-02-26 IL IL197300A patent/IL197300A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200901328B (en) | 2010-05-26 |
| RU2009114161A (ru) | 2010-10-20 |
| EP2061813B1 (en) | 2017-07-19 |
| BRPI0716811B1 (pt) | 2020-11-24 |
| EP1900752A1 (en) | 2008-03-19 |
| KR101497045B1 (ko) | 2015-02-27 |
| RU2464277C2 (ru) | 2012-10-20 |
| MX2009002711A (es) | 2009-06-18 |
| WO2008031577A8 (en) | 2009-07-02 |
| BRPI0716811A2 (pt) | 2013-11-05 |
| BRPI0716811B8 (pt) | 2021-05-25 |
| US8388972B2 (en) | 2013-03-05 |
| KR20090059114A (ko) | 2009-06-10 |
| AU2007296899B2 (en) | 2012-09-13 |
| US20100055034A1 (en) | 2010-03-04 |
| WO2008031577A1 (en) | 2008-03-20 |
| ES2644423T3 (es) | 2017-11-28 |
| NZ575093A (en) | 2012-04-27 |
| IL197300A (en) | 2016-02-29 |
| AU2007296899A1 (en) | 2008-03-20 |
| IL197300A0 (en) | 2011-08-01 |
| JP2010503386A (ja) | 2010-02-04 |
| EP2061813A1 (en) | 2009-05-27 |
| CA2662005C (en) | 2018-01-02 |
| CA2662005A1 (en) | 2008-03-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5513114B2 (ja) | 卵巣癌の放射免疫療法のためのヒト抗−葉酸受容体アルファ抗体および抗体フラグメント | |
| US10066016B2 (en) | Single chain variable fragment CD3 binding proteins | |
| JP6812551B2 (ja) | 前立腺特異的膜抗原結合タンパク質 | |
| US20240084009A1 (en) | Single chain variable fragment cd3 binding proteins | |
| MX2011004467A (es) | Moleculas de objetivo light y usos de las mismas. | |
| JP7691720B2 (ja) | 抗ヒトｃｄ７３抗体およびその適用 | |
| CN117024591A (zh) | 抗人b7-h3的单克隆抗体及其应用 | |
| CA2849705A1 (en) | Modified albumin-binding domains and uses thereof to improve pharmacokinetics | |
| CN113045659B (zh) | 抗cd73人源化抗体 | |
| KR20230146623A (ko) | 항-cldn18.2 항체 접합체 | |
| WO2025195495A1 (zh) | 一种放射性核素偶联物及其制备方法和用途 | |
| WO2025214280A1 (zh) | 一种放射性核素偶联物的制备方法 | |
| EP4532019A2 (en) | Anti-cd44v6 antibodies and their use to treat cd44v6 overexpressing cancers | |
| JP2018508193A (ja) | メディンを認識する抗体 | |
| TW202442681A (zh) | 抗ror1抗體及其藥物偶聯物 | |
| HK40006942B (en) | Single chain variable fragment cd3 binding proteins | |
| HK40006942A (en) | Single chain variable fragment cd3 binding proteins |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100820 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100820 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121031 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130131 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130207 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130228 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130307 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130401 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130516 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130812 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130819 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130917 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130925 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131008 |
|
| 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: 20140226 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140327 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5513114 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20140410 |
|
| 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 |
|
| 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 |