CA2853836C - Methods of inhibiting tumor growth by antagonizing il-6 receptor - Google Patents
Methods of inhibiting tumor growth by antagonizing il-6 receptor Download PDFInfo
- Publication number
- CA2853836C CA2853836C CA2853836A CA2853836A CA2853836C CA 2853836 C CA2853836 C CA 2853836C CA 2853836 A CA2853836 A CA 2853836A CA 2853836 A CA2853836 A CA 2853836A CA 2853836 C CA2853836 C CA 2853836C
- Authority
- CA
- Canada
- Prior art keywords
- tumor
- vegf
- antibody
- stat3
- antagonist
- 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
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title description 46
- 230000004614 tumor growth Effects 0.000 title description 35
- 108010038501 Interleukin-6 Receptors Proteins 0.000 title description 17
- 102000010781 Interleukin-6 Receptors Human genes 0.000 title description 16
- 230000003042 antagnostic effect Effects 0.000 title description 2
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 128
- 239000005557 antagonist Substances 0.000 claims abstract description 92
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract description 64
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract description 64
- 239000000427 antigen Substances 0.000 claims abstract description 62
- 102000036639 antigens Human genes 0.000 claims abstract description 62
- 108091007433 antigens Proteins 0.000 claims abstract description 62
- 230000027455 binding Effects 0.000 claims abstract description 36
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 239000012634 fragment Substances 0.000 claims abstract description 29
- 230000012010 growth Effects 0.000 claims abstract description 21
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims abstract description 11
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 claims abstract description 10
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 claims abstract description 10
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims abstract description 9
- 108020001507 fusion proteins Proteins 0.000 claims abstract 3
- 102000037865 fusion proteins Human genes 0.000 claims abstract 3
- 150000001413 amino acids Chemical class 0.000 claims description 19
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 8
- 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 2
- 102000004889 Interleukin-6 Human genes 0.000 description 45
- 108090001005 Interleukin-6 Proteins 0.000 description 45
- 229940100601 interleukin-6 Drugs 0.000 description 45
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 42
- 108010081667 aflibercept Proteins 0.000 description 31
- 210000004027 cell Anatomy 0.000 description 29
- 241000699670 Mus sp. Species 0.000 description 27
- 238000011282 treatment Methods 0.000 description 27
- 230000009870 specific binding Effects 0.000 description 26
- 102000014914 Carrier Proteins Human genes 0.000 description 24
- 108091008324 binding proteins Proteins 0.000 description 24
- 108090000623 proteins and genes Proteins 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 239000008194 pharmaceutical composition Substances 0.000 description 18
- 230000007423 decrease Effects 0.000 description 16
- 230000011664 signaling Effects 0.000 description 16
- 102000001301 EGF receptor Human genes 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 13
- 101100476210 Caenorhabditis elegans rnt-1 gene Proteins 0.000 description 12
- 108060006698 EGF receptor Proteins 0.000 description 12
- 108091008605 VEGF receptors Proteins 0.000 description 12
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 229940122558 EGFR antagonist Drugs 0.000 description 10
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 10
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 229940124597 therapeutic agent Drugs 0.000 description 9
- 101100075829 Caenorhabditis elegans mab-3 gene Proteins 0.000 description 8
- 238000011579 SCID mouse model Methods 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- 238000001574 biopsy Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 210000004602 germ cell Anatomy 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- -1 peptibodies) Proteins 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 238000010254 subcutaneous injection Methods 0.000 description 5
- 239000007929 subcutaneous injection Substances 0.000 description 5
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000011284 combination treatment Methods 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000002513 implantation Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 3
- 102000003952 Caspase 3 Human genes 0.000 description 3
- 108090000397 Caspase 3 Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- ORMNNUPLFAPCFD-DVLYDCSHSA-M phenethicillin potassium Chemical compound [K+].N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C([O-])=O)=O)C(=O)C(C)OC1=CC=CC=C1 ORMNNUPLFAPCFD-DVLYDCSHSA-M 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000009131 signaling function Effects 0.000 description 3
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 2
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 229940090047 auto-injector Drugs 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101150039808 Egfr gene Proteins 0.000 description 1
- 108010008177 Fd immunoglobulins Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 229940015979 epipen Drugs 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000005002 female reproductive tract Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 229940062714 humalog mix Drugs 0.000 description 1
- 102000045108 human EGFR Human genes 0.000 description 1
- 102000052611 human IL6 Human genes 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005001 male reproductive tract Anatomy 0.000 description 1
- 208000006178 malignant mesothelioma Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000006712 oncogenic signaling pathway Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000003300 oropharynx Anatomy 0.000 description 1
- 201000003733 ovarian melanoma Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940090048 pen injector Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- QHGVXILFMXYDRS-UHFFFAOYSA-N pyraclofos Chemical compound C1=C(OP(=O)(OCC)SCCC)C=NN1C1=CC=C(Cl)C=C1 QHGVXILFMXYDRS-UHFFFAOYSA-N 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 210000002268 wool 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
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- 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
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- 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
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Endocrinology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161557939P | 2011-11-10 | 2011-11-10 | |
| US61/557,939 | 2011-11-10 | ||
| US201261609968P | 2012-03-13 | 2012-03-13 | |
| US61/609,968 | 2012-03-13 | ||
| US201261613538P | 2012-03-21 | 2012-03-21 | |
| US61/613,538 | 2012-03-21 | ||
| PCT/US2012/064311 WO2013071016A2 (en) | 2011-11-10 | 2012-11-09 | Methods of inhibiting tumor growth by antagonizing il-6 receptor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2853836A1 CA2853836A1 (en) | 2013-05-16 |
| CA2853836C true CA2853836C (en) | 2019-07-23 |
Family
ID=47179020
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2853836A Active CA2853836C (en) | 2011-11-10 | 2012-11-09 | Methods of inhibiting tumor growth by antagonizing il-6 receptor |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US20130122003A1 (enExample) |
| EP (1) | EP2776468B1 (enExample) |
| JP (3) | JP6144689B2 (enExample) |
| KR (1) | KR101718748B1 (enExample) |
| CN (1) | CN103930443B (enExample) |
| AR (1) | AR088671A1 (enExample) |
| AU (2) | AU2012335596B2 (enExample) |
| BR (1) | BR112014011211A2 (enExample) |
| CA (1) | CA2853836C (enExample) |
| IL (2) | IL231854A (enExample) |
| IN (1) | IN2014CN02923A (enExample) |
| JO (1) | JO3370B1 (enExample) |
| MX (1) | MX357837B (enExample) |
| MY (1) | MY163953A (enExample) |
| RU (1) | RU2648150C2 (enExample) |
| SG (1) | SG11201401286QA (enExample) |
| TW (3) | TW201806620A (enExample) |
| UY (1) | UY34444A (enExample) |
| WO (1) | WO2013071016A2 (enExample) |
| ZA (1) | ZA201402414B (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JO3370B1 (ar) * | 2011-11-10 | 2019-03-13 | Regeneron Pharma | طريقة لتثبيط نمو الورم عن طريق تثبيط مستقبل انترلوكين 6 |
| WO2015000181A1 (zh) * | 2013-07-05 | 2015-01-08 | 华博生物医药技术（上海）有限公司 | 新型重组融合蛋白及其制法和用途 |
| US9017678B1 (en) | 2014-07-15 | 2015-04-28 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
| DE202014010499U1 (de) | 2013-12-17 | 2015-10-20 | Kymab Limited | Targeting von humaner PCSK9 zur Cholesterinbehandlung |
| EP3161000A4 (en) * | 2014-06-28 | 2018-05-02 | Kodiak Sciences Inc. | Dual pdgf/vegf antagonists |
| US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
| WO2016196377A1 (en) * | 2015-05-29 | 2016-12-08 | Merrimack Pharmaceuticals, Inc. | Combination cancer therapies |
| AU2016381964B2 (en) | 2015-12-30 | 2024-02-15 | Kodiak Sciences Inc. | Antibodies and conjugates thereof |
| US10610104B2 (en) | 2016-12-07 | 2020-04-07 | Progenity, Inc. | Gastrointestinal tract detection methods, devices and systems |
| WO2018112237A1 (en) | 2016-12-14 | 2018-06-21 | Progenity Inc. | Treatment of a disease of the gastrointestinal tract with an il-6r inhibitor |
| CN112203679A (zh) * | 2018-03-02 | 2021-01-08 | 科达制药股份有限公司 | Il-6抗体及其融合构建体和缀合物 |
| AU2019235782A1 (en) | 2018-03-14 | 2020-10-08 | Celledit Llc | Modification of immune cells for reducing toxicity and uses thereof in adoptive cell therapy |
| CN108567981A (zh) * | 2018-07-17 | 2018-09-25 | 漯河医学高等专科学校 | 白细胞介素-6的拮抗剂在制备抑制Notch-1蛋白表达、治疗胰腺癌的药物中的应用 |
| WO2020106757A1 (en) | 2018-11-19 | 2020-05-28 | Progenity, Inc. | Ingestible device for delivery of therapeutic agent to the gastrointestinal tract |
| CN113677356A (zh) * | 2019-01-07 | 2021-11-19 | 湖南思为康医药有限公司 | 用于降低毒性的共表达嵌合抗原受体和il-6拮抗剂的修饰免疫细胞及其在过继细胞疗法中的用途 |
| CA3157509A1 (en) | 2019-10-10 | 2021-04-15 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
| CN115666704B (zh) | 2019-12-13 | 2025-09-26 | 比特比德科有限责任公司 | 用于将治疗剂递送至胃肠道的可摄取装置 |
| EP4298127A4 (en) * | 2021-02-27 | 2025-04-23 | Eluminex Biosciences (Suzhou) Limited | Antibody fusion proteins targeting il-6 receptor and angiogenic factors |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5670373A (en) | 1988-01-22 | 1997-09-23 | Kishimoto; Tadamitsu | Antibody to human interleukin-6 receptor |
| CA1341152C (en) | 1988-01-22 | 2000-12-12 | Tadamitsu Kishimoto | Receptor protein for human b cell stimulatory factor-2 |
| US5795965A (en) | 1991-04-25 | 1998-08-18 | Chugai Seiyaku Kabushiki Kaisha | Reshaped human to human interleukin-6 receptor |
| US5888510A (en) | 1993-07-21 | 1999-03-30 | Chugai Seiyaku Kabushiki Kaisha | Chronic rheumatoid arthritis therapy containing IL-6 antagonist as effective component |
| ATE214602T1 (de) | 1994-12-29 | 2002-04-15 | Chugai Pharmaceutical Co Ltd | Verstärker eines anti-tumoragens beinhaltend einen il-6 antagonisten |
| US5795695A (en) | 1996-09-30 | 1998-08-18 | Xerox Corporation | Recording and backing sheets containing linear and cross-linked polyester resins |
| BRPI0011407B8 (pt) * | 1999-06-08 | 2021-05-25 | Regeneron Pharma | molécula de ácido nucléico quimérica, polipeptídeo de fusão, vetor de expressão, sistema de vetor hospedeiro, e, métodos de produzir um polipeptídeo de fusão |
| US7087411B2 (en) * | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
| US7396664B2 (en) * | 1999-06-08 | 2008-07-08 | Regeneron Pharmaceuticals, Inc. | VEGF-binding fusion proteins and nucleic acids encoding the same |
| ATE316531T1 (de) | 1999-10-07 | 2006-02-15 | Lilly Co Eli | Kondensierte dihydrochinolinon-derivate zur hemmung von mrp1 |
| AU2000279624A1 (en) | 2000-10-27 | 2002-05-15 | Chugai Seiyaku Kabushiki Kaisha | Blooe vegf level-lowering agent containing il-6 antagonist as the active ingredient |
| US7595378B2 (en) * | 2001-06-13 | 2009-09-29 | Genmab A/S | Human monoclonal antibodies to epidermal growth factor receptor (EGFR) |
| KR20060079180A (ko) * | 2003-07-02 | 2006-07-05 | 노보 노르디스크 에이/에스 | Ｎｋ 세포 활성을 조절하기 위한 조성물 및 방법 |
| BRPI0415505A (pt) | 2003-10-17 | 2006-12-12 | Chugai Pharmaceutical Co Ltd | agente terapêutico para mesotelioma |
| US20090269335A1 (en) | 2005-11-25 | 2009-10-29 | Keio University | Therapeutic agent for prostate cancer |
| US8080248B2 (en) | 2006-06-02 | 2011-12-20 | Regeneron Pharmaceuticals, Inc. | Method of treating rheumatoid arthritis with an IL-6R antibody |
| PL2374818T3 (pl) | 2006-06-02 | 2013-05-31 | Regeneron Pharma | Przeciwciała o wysokim powinowactwie przeciw ludzkiemu receptorowi IL 6 |
| WO2008154927A1 (en) * | 2007-06-21 | 2008-12-24 | Genmab A/S | Novel methods for treating egfr-associated tumors |
| US8323649B2 (en) * | 2008-11-25 | 2012-12-04 | Alderbio Holdings Llc | Antibodies to IL-6 and use thereof |
| CN102292449B (zh) * | 2008-11-25 | 2016-03-30 | 奥尔德生物制药公司 | 预防或治疗血栓形成的il-6拮抗剂 |
| JO3417B1 (ar) * | 2010-01-08 | 2019-10-20 | Regeneron Pharma | الصيغ المستقرة التي تحتوي على الأجسام المضادة لمضاد مستقبل( interleukin-6 (il-6r |
| JO3370B1 (ar) * | 2011-11-10 | 2019-03-13 | Regeneron Pharma | طريقة لتثبيط نمو الورم عن طريق تثبيط مستقبل انترلوكين 6 |
-
2012
- 2012-11-04 JO JOP/2012/0332A patent/JO3370B1/ar active
- 2012-11-06 AR ARP120104169A patent/AR088671A1/es not_active Application Discontinuation
- 2012-11-09 RU RU2014118739A patent/RU2648150C2/ru active
- 2012-11-09 TW TW106138384A patent/TW201806620A/zh unknown
- 2012-11-09 JP JP2014541298A patent/JP6144689B2/ja active Active
- 2012-11-09 KR KR1020147012146A patent/KR101718748B1/ko active Active
- 2012-11-09 AU AU2012335596A patent/AU2012335596B2/en active Active
- 2012-11-09 UY UY0001034444A patent/UY34444A/es unknown
- 2012-11-09 MX MX2014004886A patent/MX357837B/es active IP Right Grant
- 2012-11-09 EP EP12787338.8A patent/EP2776468B1/en active Active
- 2012-11-09 US US13/672,923 patent/US20130122003A1/en not_active Abandoned
- 2012-11-09 TW TW101141702A patent/TWI604852B/zh active
- 2012-11-09 CN CN201280055109.4A patent/CN103930443B/zh active Active
- 2012-11-09 CA CA2853836A patent/CA2853836C/en active Active
- 2012-11-09 TW TW105142150A patent/TW201716776A/zh unknown
- 2012-11-09 WO PCT/US2012/064311 patent/WO2013071016A2/en not_active Ceased
- 2012-11-09 MY MYPI2014000968A patent/MY163953A/en unknown
- 2012-11-09 BR BR112014011211A patent/BR112014011211A2/pt not_active Application Discontinuation
- 2012-11-09 SG SG11201401286QA patent/SG11201401286QA/en unknown
-
2014
- 2014-04-01 IL IL231854A patent/IL231854A/en active IP Right Grant
- 2014-04-02 ZA ZA2014/02414A patent/ZA201402414B/en unknown
- 2014-04-17 IN IN2923CHN2014 patent/IN2014CN02923A/en unknown
- 2014-07-11 US US14/329,565 patent/US9409990B2/en active Active
-
2016
- 2016-07-07 US US15/204,639 patent/US20170022279A1/en not_active Abandoned
- 2016-10-30 IL IL248620A patent/IL248620A0/en unknown
-
2017
- 2017-01-06 JP JP2017000818A patent/JP6283754B2/ja active Active
-
2018
- 2018-01-26 JP JP2018011135A patent/JP2018083841A/ja not_active Withdrawn
- 2018-05-24 AU AU2018203666A patent/AU2018203666A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2853836C (en) | Methods of inhibiting tumor growth by antagonizing il-6 receptor | |
| US11655291B2 (en) | Compositions and methods for increasing muscle mass and muscle strength by specifically antagonizing GDF8 and or activin A | |
| JP6486268B2 (ja) | 抗ｅｇｆｒ抗体及びその使用 | |
| CA2926853C (en) | Methods and compositions comprising a combination of a vegf antagonist and an anti-ctla-4 antibody | |
| HK1197681B (en) | Methods of inhibiting tumor growth by antagonizing il-6 receptor | |
| HK1197681A (en) | Methods of inhibiting tumor growth by antagonizing il-6 receptor | |
| HK1202559B (en) | Compositions and methods for increasing muscle mass and muscle strength by specifically antagonizing gdf8 and/or activin a |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20171031 |