CA2662005C - Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma - Google Patents
Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma Download PDFInfo
- Publication number
- CA2662005C CA2662005C CA2662005A CA2662005A CA2662005C CA 2662005 C CA2662005 C CA 2662005C CA 2662005 A CA2662005 A CA 2662005A CA 2662005 A CA2662005 A CA 2662005A CA 2662005 C CA2662005 C CA 2662005C
- Authority
- CA
- Canada
- Prior art keywords
- antibody
- fragment
- afra
- alpha
- light chain
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 241000282414 Homo sapiens Species 0.000 title claims description 58
- 206010033128 Ovarian cancer Diseases 0.000 title claims description 56
- 102000008394 Immunoglobulin Fragments Human genes 0.000 title claims description 49
- 108010021625 Immunoglobulin Fragments Proteins 0.000 title claims description 49
- 238000011363 radioimmunotherapy Methods 0.000 title claims description 26
- 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 abstract description 162
- 102000010451 Folate receptor alpha Human genes 0.000 claims abstract description 58
- 108050001931 Folate receptor alpha Proteins 0.000 claims abstract description 58
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 44
- 210000004027 cell Anatomy 0.000 claims description 80
- 206010028980 Neoplasm Diseases 0.000 claims description 70
- 230000027455 binding Effects 0.000 claims description 58
- 239000000539 dimer Substances 0.000 claims description 57
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 36
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 36
- 108090000623 proteins and genes Proteins 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 34
- 239000013604 expression vector Substances 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 24
- 150000007523 nucleic acids Chemical class 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 229940124597 therapeutic agent Drugs 0.000 claims description 17
- 241000588724 Escherichia coli Species 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 15
- 201000011510 cancer Diseases 0.000 claims description 13
- 230000014509 gene expression Effects 0.000 claims description 13
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 11
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 11
- 229940127089 cytotoxic agent Drugs 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- 239000000178 monomer Substances 0.000 claims description 11
- 108020004707 nucleic acids Proteins 0.000 claims description 11
- 102000039446 nucleic acids Human genes 0.000 claims description 11
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 10
- 238000013518 transcription Methods 0.000 claims description 10
- 230000035897 transcription Effects 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000013598 vector Substances 0.000 claims description 9
- 230000033228 biological regulation Effects 0.000 claims description 8
- 230000002018 overexpression Effects 0.000 claims description 8
- 239000012636 effector Substances 0.000 claims description 7
- 238000003384 imaging method Methods 0.000 claims description 7
- 239000003550 marker Substances 0.000 claims 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 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 6
- 239000002254 cytotoxic agent Substances 0.000 claims description 6
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 6
- 238000003745 diagnosis Methods 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 5
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 5
- 210000005260 human cell Anatomy 0.000 claims description 5
- 241000282412 Homo Species 0.000 claims description 3
- 238000009098 adjuvant therapy Methods 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000010276 construction Methods 0.000 claims description 3
- 230000003439 radiotherapeutic effect Effects 0.000 claims description 3
- 206010027462 Metastases to ovary Diseases 0.000 claims description 2
- 238000011360 adjunctive therapy Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 230000006334 disulfide bridging Effects 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 description 37
- 229940024606 amino acid Drugs 0.000 description 35
- 150000001413 amino acids Chemical class 0.000 description 34
- 239000000427 antigen Substances 0.000 description 34
- 102000036639 antigens Human genes 0.000 description 34
- 108091007433 antigens Proteins 0.000 description 34
- 102000006815 folate receptor Human genes 0.000 description 25
- 108020005243 folate receptor Proteins 0.000 description 25
- 238000001727 in vivo Methods 0.000 description 25
- 210000001519 tissue Anatomy 0.000 description 22
- 241001465754 Metazoa Species 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 19
- 102000005962 receptors Human genes 0.000 description 18
- 108020003175 receptors Proteins 0.000 description 18
- 101001023230 Homo sapiens Folate receptor alpha Proteins 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 17
- 102000053180 human FOLR1 Human genes 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 238000007912 intraperitoneal administration Methods 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 230000000875 corresponding effect Effects 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 238000011161 development Methods 0.000 description 11
- 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
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 10
- 239000000872 buffer Substances 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 241000894007 species Species 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
- 238000006471 dimerization reaction Methods 0.000 description 9
- 210000000056 organ Anatomy 0.000 description 9
- 230000004614 tumor growth Effects 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 235000018417 cysteine Nutrition 0.000 description 8
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 8
- 235000019152 folic acid Nutrition 0.000 description 8
- 201000009030 Carcinoma Diseases 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 7
- 102000001708 Protein Isoforms Human genes 0.000 description 7
- 108010029485 Protein Isoforms Proteins 0.000 description 7
- 238000009825 accumulation Methods 0.000 description 7
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 7
- 239000011724 folic acid Substances 0.000 description 7
- 230000004807 localization Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 206010003445 Ascites Diseases 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 238000002512 chemotherapy Methods 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 238000010494 dissociation reaction Methods 0.000 description 6
- 230000005593 dissociations Effects 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 230000002285 radioactive effect Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 210000002919 epithelial cell Anatomy 0.000 description 5
- 239000000710 homodimer Substances 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-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
- 238000001574 biopsy Methods 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 229940014144 folate Drugs 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 229920003192 poly(bis maleimide) Polymers 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 4
- 210000003462 vein Anatomy 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
- 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 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 238000006664 bond formation reaction Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion 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
- 229960000304 folic acid Drugs 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
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000011221 initial treatment Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 210000003200 peritoneal cavity Anatomy 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000013391 scatchard analysis Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 238000005406 washing Methods 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
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-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
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 241001013691 Escherichia coli BW25113 Species 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000011033 desalting Methods 0.000 description 2
- 238000001514 detection method Methods 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
- 230000029142 excretion 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
- 230000012010 growth Effects 0.000 description 2
- 238000001597 immobilized metal affinity chromatography Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 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
- 230000008569 process 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
- 238000009877 rendering Methods 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
- 239000007787 solid Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012360 testing method 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
- WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 1
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 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 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 102100020871 Forkhead box protein G1 Human genes 0.000 description 1
- 102000002702 GPI-Linked Proteins Human genes 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
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 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
- 239000006142 Luria-Bertani Agar Substances 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 206010027476 Metastases 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
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 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
- 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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 101150034776 afr gene Proteins 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 101150073130 ampR gene Proteins 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
- 239000011230 binding agent Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004113 cell culture Methods 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
- 210000002987 choroid plexus Anatomy 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000356 contaminant Substances 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
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 238000011500 cytoreductive surgery Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000029087 digestion Effects 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
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 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
- 230000002349 favourable effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 1
- 108091005631 glycosylphosphatidylinositol-linked proteins Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 108010067006 heat stable toxin (E coli) Proteins 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
- 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
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 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
- 235000007635 levomefolic acid Nutrition 0.000 description 1
- 239000011578 levomefolic acid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas 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
- 210000004303 peritoneum Anatomy 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000002823 phage display Methods 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
- 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
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000004393 prognosis Methods 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
- 230000005855 radiation Effects 0.000 description 1
- 239000002534 radiation-sensitizing agent Substances 0.000 description 1
- 238000001959 radiotherapy Methods 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
- 238000009738 saturating Methods 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 238000013207 serial dilution Methods 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
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000001356 surgical procedure Methods 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
- 239000005460 tetrahydrofolate Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 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
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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 (2)
| Publication Number | Publication Date |
|---|---|
| CA2662005A1 CA2662005A1 (en) | 2008-03-20 |
| CA2662005C true CA2662005C (en) | 2018-01-02 |
Family
ID=37737768
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2662005A Active CA2662005C (en) | 2006-09-15 | 2007-09-12 | Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma |
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 |
|---|---|
| JP5513114B2 (ja) | 2014-06-04 |
| 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 |
| CA2662005A1 (en) | 2008-03-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2662005C (en) | Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma | |
| JP6077745B2 (ja) | 抗ポドプラニン抗体、及び抗ポドプラニン抗体を含む医薬組成物 | |
| CN106188305A (zh) | 具有融合至常规Fab片段的单域抗原结合片段的二价抗体 | |
| CA2682059A1 (en) | Human anti cd166 antibody binding human tumor cells | |
| CN116745317B (zh) | 抗tigit抗体及其用途 | |
| US20170158755A1 (en) | Anti-laminin4 antibodies specific for lg1-3 | |
| US20250011427A1 (en) | Anti-cd3 antibodies with cross-reactivity to human and cynomolgus proteins | |
| US20240043540A1 (en) | Anti-b7-h3 antibody and uses thereof | |
| US20240417469A1 (en) | Cd3-targeting t-cell engagers with improved therapeutic index | |
| KR20250042144A (ko) | Itga2를 표적으로 하는 항체 및 이를 포함하는 항체-약물 접합체(antibody targeting itga2 and antibody-drug conjugate comprising the same) | |
| KR20230146623A (ko) | 항-cldn18.2 항체 접합체 | |
| JP2025520692A (ja) | 抗ｓｌｃ３４ａ２モノクローナル抗体およびその使用 | |
| US10584175B2 (en) | FN14-binding proteins and uses thereof | |
| WO2025195495A1 (zh) | 一种放射性核素偶联物及其制备方法和用途 | |
| KR20250174736A (ko) | L1cam을 표적화하는 항체 및 이의 용도 | |
| AU2023274919A1 (en) | Anti-cd44v6 antibodies and their use to treat cd44v6 overexpressing cancers | |
| CN120025446A (zh) | 结合分子及抗体药物偶联物和用途 | |
| CN117402255A (zh) | 抗人pd-l1和人ox40的双特异抗体及其应用 | |
| BR112018005837B1 (pt) | Anticorpo anti-mesotelina, ácido nucleico, vetor, célula hospedeira, método de preparação do anticorpo e composição farmacêutica | |
| HK1233282B (en) | Anti-mcam antibodies and associated methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |