JP7065085B2 - Cd6のリン酸化を低減させるためのイトリズマブの使用 - Google Patents
Cd6のリン酸化を低減させるためのイトリズマブの使用 Download PDFInfo
- Publication number
- JP7065085B2 JP7065085B2 JP2019520731A JP2019520731A JP7065085B2 JP 7065085 B2 JP7065085 B2 JP 7065085B2 JP 2019520731 A JP2019520731 A JP 2019520731A JP 2019520731 A JP2019520731 A JP 2019520731A JP 7065085 B2 JP7065085 B2 JP 7065085B2
- Authority
- JP
- Japan
- Prior art keywords
- alcam
- antibody
- itrizumab
- phosphorylation
- seq
- 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
- 230000026731 phosphorylation Effects 0.000 title claims description 27
- 238000006366 phosphorylation reaction Methods 0.000 title claims description 27
- 101000934376 Homo sapiens T-cell differentiation antigen CD6 Proteins 0.000 claims description 76
- 102100025131 T-cell differentiation antigen CD6 Human genes 0.000 claims description 66
- 238000000034 method Methods 0.000 claims description 31
- 210000004027 cell Anatomy 0.000 claims description 26
- 108010075348 Activated-Leukocyte Cell Adhesion Molecule Proteins 0.000 claims description 15
- 102100024210 CD166 antigen Human genes 0.000 claims description 15
- 230000014509 gene expression Effects 0.000 claims description 15
- 230000003993 interaction Effects 0.000 claims description 15
- 230000027455 binding Effects 0.000 claims description 14
- 102100034709 Lymphocyte cytosolic protein 2 Human genes 0.000 claims description 13
- 101001090688 Homo sapiens Lymphocyte cytosolic protein 2 Proteins 0.000 claims description 12
- 101000617285 Homo sapiens Tyrosine-protein phosphatase non-receptor type 6 Proteins 0.000 claims description 11
- 102100033019 Tyrosine-protein phosphatase non-receptor type 11 Human genes 0.000 claims description 11
- 101710116241 Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 claims description 11
- 102100021657 Tyrosine-protein phosphatase non-receptor type 6 Human genes 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- 108020003175 receptors Proteins 0.000 claims description 10
- 230000009467 reduction Effects 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 230000002829 reductive effect Effects 0.000 claims description 6
- 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 0.000 claims description 5
- 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 claims description 5
- 238000003032 molecular docking Methods 0.000 claims description 5
- 210000000428 immunological synapse Anatomy 0.000 claims description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 150000007523 nucleic acids Chemical class 0.000 description 12
- 230000001404 mediated effect Effects 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 230000004913 activation Effects 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 8
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 7
- 108020004707 nucleic acids Proteins 0.000 description 7
- 102000039446 nucleic acids Human genes 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- 230000006044 T cell activation Effects 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 230000010534 mechanism of action Effects 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 5
- 238000003119 immunoblot Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000003094 microcapsule Substances 0.000 description 5
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 5
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 5
- 108091005725 scavenger receptor cysteine-rich superfamily Proteins 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 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 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 3
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000005754 cellular signaling Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102000000185 SRCR domains Human genes 0.000 description 2
- 108050008568 SRCR domains Proteins 0.000 description 2
- 101000930762 Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770) Signal recognition particle receptor FtsY Proteins 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000020411 cell activation Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 210000003386 epithelial cell of thymus gland Anatomy 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- -1 m-cresol; small molecules Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 229950010203 nimotuzumab Drugs 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000287828 Gallus gallus Species 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
- 239000004471 Glycine Substances 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 101710195102 Lymphocyte cytosolic protein 2 Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000001691 Member 3 Group F Nuclear Receptor Subfamily 1 Human genes 0.000 description 1
- 108010029279 Member 3 Group F Nuclear Receptor Subfamily 1 Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 101710204410 Scaffold protein Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 210000000068 Th17 cell Anatomy 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 101150042678 VAV1 gene Proteins 0.000 description 1
- 108091005764 adaptor proteins Proteins 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000006525 intracellular process Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000007896 negative regulation of T cell activation Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940043515 other immunoglobulins in atc Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0008—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/32—Immunoglobulins specific features characterized by aspects of specificity or valency specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
-
- 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)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Microbiology (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)
- Electrically Operated Instructional Devices (AREA)
- Electrochromic Elements, Electrophoresis, Or Variable Reflection Or Absorption Elements (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
Description
本出願は、2016年10月18日にインド特許庁に出願されたインド仮特許出願第201641035602号の利益および優先権を主張するものである。2016年10月18日に出願された当該出願の内容は、全ての目的のためにその全体が参照により本明細書中に組み込まれ、これは、PCTの規則4.18の規定による、PCTの規則20.5(a)において言及された、本明細書に含まれない明細書、請求の範囲または図面のあらゆる要素または部分を包含する。
本発明は、胸腺上皮細胞、単球、活性化T細胞および種々の他の細胞種の表面に存在するCD6のスカベンジャー受容体システインリッチ(SRCR)ドメイン1(D1)に結合するヒト化IgG1アイソタイプ抗CD6モノクローナル抗体(T1h)に関する。本発明は、TヘルパーおよびTリンパ球細胞によって媒介される疾患状態の防止を包含する処置のための方法に関する。
T細胞活性化、分化および機能は、多様な発現、構造および機能を有する共刺激および共阻害受容体によって制御され、大きく状況に依存する。TCRの活性化およびその後のZAP70のリン酸化は、TCR複合体へのCD6の会合(ここでCD6は、アダプターまたはドッキングタンパク質であるLATとは独立してSLP-76およびグアニンヌクレオチド因子Vav1のリクルートを許容するスキャフォールドタンパク質のように作用する)を促進した(Roncagalli R et al, 2016)。加えて、CD6の細胞質尾部上のチロシン、セリンおよびトレオニン残基での過剰なリン酸化が、SLP-76などのアダプター分子へのCD6の結合をもたらし、これに続いて時間および用量依存的なMAPK活性化が起こる(Nair P et al, 2010)。
宿主細胞を、配列番号1および2にそれぞれ記述されたとおりの重鎖および軽鎖可変領域を含むモノクローナル抗CD6抗体と接触させることを含み、ここで、CD6上のD1受容体へのモノクローナル抗CD6抗体の結合は、活性化白血球細胞接着分子(ALCAM)とCD6のD3受容体との相互作用にとっての立体障害を引き起こし、それによってCD6-ALCAM複合体のCD6受容体のリン酸化の低減を引き起こす。好ましくは、モノクローナル抗CD6は、イトリズマブである。
宿主細胞を、配列番号1および2にそれぞれ記述されたとおりの重鎖および軽鎖可変領域を含むモノクローナル抗CD6抗体と接触させることを含み、ここで、CD6上のD1受容体へのモノクローナル抗CD6抗体の結合は、ALCAMとCD6のD3受容体との相互作用にとっての立体障害を引き起こし、それによってCD6-ALCAM複合体のCD6受容体のリン酸化の低減を引き起こす。好ましくは、モノクローナル抗CD6は、イトリズマブである。
宿主細胞を、CD6のD1に結合する抗CD6抗体と接触させることを含み、ここで、抗CD6抗体は、配列番号1および2にそれぞれ記述されたとおりの重鎖および軽鎖可変領域を含み、ここで、CD6上のD1受容体へのモノクローナル抗CD6抗体の結合は、CD6-ALCAM複合体のCD6受容体のリン酸化の低減を引き起こさせる。
宿主細胞を、配列番号1および2にそれぞれ記述されたとおりの重鎖および軽鎖可変領域を含むモノクローナル抗CD6抗体と接触させることを含み、ここで、CD6上のD1受容体へのモノクローナル抗CD6抗体の結合は、CD6-ALCAM複合体のCD6受容体のリン酸化の低減を引き起こし、それによってホスファターゼSHP1およびSHP2の発現を低減させる。
本発明は、CD6のドメイン1(D1)に結合し、ALCAMによって誘導されるCD6受容体のリン酸化を直接阻害し又は低減させ、その後の関連するZAP70(キナーゼ)とドッキングタンパク質SLP76とのドッキングを減少させることを可能とする、抗CD6モノクローナル抗体を提供する。さらに、CD6のリン酸化および関連するシグナル伝達分子の、かかる阻害および/または低減は、T細胞活性化および分化の減少をもたらす。
本明細書中において他に定義しない限り、本発明に関して使用する科学および技術用語は、当業者に普通に理解されている意味を有するものとする。さらに、別様に文脈から要求されない限り、単数形の用語は複数形を包含するものとし、複数形の用語は単数形を包含するものとする。
本発明を記載およびクレームすることにおいては、以下の専門用語を、本明細書中に定めた定義に従って使用する。
本明細書中において記載された本発明の側面は、「からなる」および「から本質的になる」という側面もまた包含することが理解される。
本発明はさらに、開示されている抗CD6抗体を生産するための方法を提供する。これらの方法は、本発明の抗体をコードする単離された核酸(単数または複数)を含有する宿主細胞を培養することを網羅する。当業者には当然認識される通り、これは、抗体の性質に応じて種々のやり方によって行うことができる。
以下に記載される使用の方法における投与のために、抗CD6モノクローナル抗体は、かかる処置を必要とするヒト対象への投与の前に、非毒性の薬学的に許容し得る担体物質(例として、生理食塩水またはリン酸緩衝生理食塩水)と混合されてもよく、あらゆる医学上適当な手順、例として、非経口投与(例として、注入)、例えば静脈内または動脈内注入などによって投与されることとなる。
今回の発明者らによる以前の研究は、イトリズマブ(配列番号3および4によってコードされている配列番号1~2)の添加が、CD6のドメイン1に結合して、活性化およびT細胞のTh17への分化を低減させ、IL-17の生産を減少させることを描いた。これらの効果は、主要な転写因子pSTAT3およびRORγTの低減と関連する。今回の例においては、阻害のメカニズムを理解するために、ALCAM-CD6に媒介されるT細胞活性化へのイトリズマブの影響を評価した。
イトリズマブに媒介されるT細胞活性化の阻害の生理学的基礎を理解するために、活性化CD6-ALCAM相互作用を阻害することにおいて、イトリズマブの役割を調査した。CD6の下流のシグナル変換を評価するために、プレートに結合されたALCAMの存在下で、PBMCをイトリズマブありおよびなしで処置した。
本明細書中において引用されているあらゆる参考文献の内容は、全ての目的のために参照により本明細書中に組み込まれる。
Claims (7)
- ホスファターゼSHP1およびSHP2の発現を阻害する方法における使用のための、配列番号1および2にそれぞれ記述されたとおりの重鎖および軽鎖可変領域を含むモノクローナル抗CD6抗体を含む組成物であって、
方法は、宿主細胞を、配列番号1および2にそれぞれ記述されたとおりの重鎖および軽鎖可変領域を含むモノクローナル抗CD6抗体と接触させることを含み、CD6上のD1受容体へのモノクローナル抗CD6抗体の結合が、CD6-ALCAM複合体のCD6受容体のリン酸化の低減を引き起こし、それによってホスファターゼSHP1およびSHP2の発現を低減させるものである、
前記組成物。 - ホスファターゼSHP1およびSHP2の発現を阻害するための、配列番号1および2にそれぞれ記述されたとおりの重鎖および軽鎖可変領域を含むモノクローナル抗CD6抗体を含む組成物。
- モノクローナル抗CD6抗体がイトリズマブである、請求項1または2に記載の組成物。
- CD6-ALCAM複合体のCD6のリン酸化の低減が、ZAP70とSLP-76とのドッキングの低減をもまた引き起こす、請求項1に記載の組成物。
- 宿主細胞がヒト対象におけるものである、請求項1~4のいずれか一項に記載の組成物。
- イトリズマブ抗体が、CD6へのD3でのALCAMの結合を阻害しないが、免疫シナプスでの立体障害に起因して、形成されたCD6-ALCAM複合体の相互作用を阻害する、請求項3に記載の組成物。
- 免疫シナプスでの立体障害に起因して、形成されたCD6-ALCAM複合体の相互作用が阻害される、請求項1~5のいずれか一項に記載の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN201641035602 | 2016-10-18 | ||
IN201641035602 | 2016-10-18 | ||
PCT/IB2017/056403 WO2018073721A1 (en) | 2016-10-18 | 2017-10-16 | Use of itolizumab to reduce phosphorylation of cd6 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2020504597A JP2020504597A (ja) | 2020-02-13 |
JP2020504597A5 JP2020504597A5 (ja) | 2020-11-26 |
JP7065085B2 true JP7065085B2 (ja) | 2022-05-11 |
Family
ID=62019244
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019520731A Active JP7065085B2 (ja) | 2016-10-18 | 2017-10-16 | Cd6のリン酸化を低減させるためのイトリズマブの使用 |
Country Status (8)
Country | Link |
---|---|
US (2) | US20190248913A1 (ja) |
EP (1) | EP3528846A4 (ja) |
JP (1) | JP7065085B2 (ja) |
KR (1) | KR102469798B1 (ja) |
AU (1) | AU2017345390A1 (ja) |
CA (1) | CA3076861A1 (ja) |
IL (1) | IL266087B2 (ja) |
WO (1) | WO2018073721A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MY159517A (en) | 2008-03-14 | 2017-01-13 | Biocon Ltd | A monoclonal antibody and a method thereof |
WO2015011658A1 (en) | 2013-07-23 | 2015-01-29 | Biocon Limited | Use of a cd6 binding partner and method based thereon |
AU2017344462A1 (en) | 2016-10-21 | 2019-05-02 | Biocon Limited | A monoclonal antibody and a method of use for the treatment of lupus |
CN112424226A (zh) * | 2018-02-27 | 2021-02-26 | 平衡生物科技股份有限公司 | 用于治疗重度哮喘的抗cd6抗体 |
EP4084808A1 (en) * | 2019-12-30 | 2022-11-09 | City of Hope | Methods of making and using regulatory t cells and effector t cells having chimeric antigen receptors targeted to cd6, cd19, and/or an il-13r for treatment of autoimmune disorders and cancers |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MY159517A (en) | 2008-03-14 | 2017-01-13 | Biocon Ltd | A monoclonal antibody and a method thereof |
WO2015011658A1 (en) * | 2013-07-23 | 2015-01-29 | Biocon Limited | Use of a cd6 binding partner and method based thereon |
-
2017
- 2017-10-16 KR KR1020197014350A patent/KR102469798B1/ko active IP Right Grant
- 2017-10-16 IL IL266087A patent/IL266087B2/en unknown
- 2017-10-16 EP EP17862860.8A patent/EP3528846A4/en active Pending
- 2017-10-16 AU AU2017345390A patent/AU2017345390A1/en active Pending
- 2017-10-16 CA CA3076861A patent/CA3076861A1/en active Pending
- 2017-10-16 WO PCT/IB2017/056403 patent/WO2018073721A1/en unknown
- 2017-10-16 JP JP2019520731A patent/JP7065085B2/ja active Active
-
2019
- 2019-04-17 US US16/387,442 patent/US20190248913A1/en not_active Abandoned
-
2023
- 2023-06-15 US US18/335,542 patent/US20240101700A1/en active Pending
Non-Patent Citations (4)
Title |
---|
Clinical and Experimental Immunology,Vol.162,2010年,p.116-130 |
mAbs,2014年,Vol.6, No.3,p.782-792 |
Molecular and Cellular Biology,2006年,Vol.26, No.17,p.6727-6738 |
Nat Immunol,2014年,15(4),P.1-32, Supplementary Information |
Also Published As
Publication number | Publication date |
---|---|
EP3528846A1 (en) | 2019-08-28 |
US20240101700A1 (en) | 2024-03-28 |
JP2020504597A (ja) | 2020-02-13 |
US20190248913A1 (en) | 2019-08-15 |
IL266087B1 (en) | 2023-10-01 |
CA3076861A1 (en) | 2018-04-26 |
AU2017345390A1 (en) | 2019-05-02 |
KR102469798B1 (ko) | 2022-11-22 |
WO2018073721A1 (en) | 2018-04-26 |
KR20190070957A (ko) | 2019-06-21 |
IL266087B2 (en) | 2024-02-01 |
EP3528846A4 (en) | 2020-06-03 |
IL266087A (en) | 2019-06-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7065085B2 (ja) | Cd6のリン酸化を低減させるためのイトリズマブの使用 | |
JP6951479B2 (ja) | IL−15及びIL−15Rαスシドメインに基づくモジュロカイン | |
US20220168395A1 (en) | Combined pharmaceutical composition | |
Lim et al. | TNF-α: a paradigm of paradox and complexity in multiple sclerosis and its animal models | |
WO2002076504A1 (fr) | Remedes contre les affections intestinales inflammatoires | |
JP2020520985A (ja) | がん療法における免疫関連有害事象の治療のための可溶性cd24の使用方法 | |
KR20020086540A (ko) | Il-18 저해물질의 용도 | |
US20120201821A1 (en) | Treatment of Gastrointestinal Inflammation and Psoriasis and Asthma | |
Bloemendaal et al. | Anti–tumor necrosis factor with a glyco-engineered Fc-region has increased efficacy in mice with colitis | |
CA2939639A1 (en) | Uti fusion proteins | |
JP2020503251A (ja) | モノクローナル抗体および狼瘡の処置のための使用の方法 | |
US20220307035A1 (en) | Composition for preventing or treating cancer | |
Genovese | and William H. Robinson |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201015 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20201015 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210917 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211217 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220216 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220311 |
|
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: 20220404 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220425 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7065085 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |