EA036483B1 - Пептиды, способные индуцировать толерантность к рекомбинантному fviii, содержащая их композиция, их применение и способ лечения гемофилии - Google Patents
Пептиды, способные индуцировать толерантность к рекомбинантному fviii, содержащая их композиция, их применение и способ лечения гемофилии Download PDFInfo
- Publication number
- EA036483B1 EA036483B1 EA201590927A EA201590927A EA036483B1 EA 036483 B1 EA036483 B1 EA 036483B1 EA 201590927 A EA201590927 A EA 201590927A EA 201590927 A EA201590927 A EA 201590927A EA 036483 B1 EA036483 B1 EA 036483B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- seq
- peptide
- fviii
- glu
- gly
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 240
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 83
- 208000009292 Hemophilia A Diseases 0.000 title claims abstract description 46
- 239000000203 mixture Substances 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 title claims abstract description 20
- 230000001939 inductive effect Effects 0.000 title claims abstract description 12
- 208000031220 Hemophilia Diseases 0.000 title abstract description 26
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 47
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims abstract description 39
- 102100026735 Coagulation factor VIII Human genes 0.000 claims abstract description 31
- 238000004519 manufacturing process Methods 0.000 claims abstract description 18
- 238000001727 in vivo Methods 0.000 claims abstract description 17
- 102000043129 MHC class I family Human genes 0.000 claims abstract description 13
- 108091054437 MHC class I family Proteins 0.000 claims abstract description 13
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 claims abstract description 11
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 claims abstract description 11
- 238000012545 processing Methods 0.000 claims abstract description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 25
- 208000013633 acquired hemophilia Diseases 0.000 claims description 19
- 201000003542 Factor VIII deficiency Diseases 0.000 claims description 18
- 108010051539 HLA-DR2 Antigen Proteins 0.000 claims description 12
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical compound NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 11
- 238000009256 replacement therapy Methods 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 6
- 239000004472 Lysine Substances 0.000 claims description 6
- 235000013922 glutamic acid Nutrition 0.000 claims description 6
- 239000004220 glutamic acid Substances 0.000 claims description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 2
- 229940124135 Factor VIII inhibitor Drugs 0.000 abstract description 3
- 230000002265 prevention Effects 0.000 abstract description 2
- 230000001629 suppression Effects 0.000 abstract description 2
- 108010054218 Factor VIII Proteins 0.000 description 125
- 229960000301 factor viii Drugs 0.000 description 125
- 102000001690 Factor VIII Human genes 0.000 description 123
- 238000011282 treatment Methods 0.000 description 28
- 239000003112 inhibitor Substances 0.000 description 23
- 230000004044 response Effects 0.000 description 21
- 208000032843 Hemorrhage Diseases 0.000 description 15
- 208000034158 bleeding Diseases 0.000 description 15
- 230000000740 bleeding effect Effects 0.000 description 15
- 230000003472 neutralizing effect Effects 0.000 description 15
- 210000000612 antigen-presenting cell Anatomy 0.000 description 14
- 230000028993 immune response Effects 0.000 description 14
- 230000003053 immunization Effects 0.000 description 14
- 238000002649 immunization Methods 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 230000005867 T cell response Effects 0.000 description 13
- 108091007433 antigens Proteins 0.000 description 13
- 102000036639 antigens Human genes 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 12
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 12
- 239000000427 antigen Substances 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 239000003114 blood coagulation factor Substances 0.000 description 12
- 230000007423 decrease Effects 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 12
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 12
- 150000001413 amino acids Chemical group 0.000 description 11
- 201000010099 disease Diseases 0.000 description 10
- 108091005601 modified peptides Proteins 0.000 description 10
- 241000699660 Mus musculus Species 0.000 description 9
- 230000015271 coagulation Effects 0.000 description 9
- 238000005345 coagulation Methods 0.000 description 9
- 238000011830 transgenic mouse model Methods 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 8
- 102000057593 human F8 Human genes 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 208000023275 Autoimmune disease Diseases 0.000 description 6
- 210000003719 b-lymphocyte Anatomy 0.000 description 6
- 208000009429 hemophilia B Diseases 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 210000001503 joint Anatomy 0.000 description 6
- 230000007774 longterm Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 102100022641 Coagulation factor IX Human genes 0.000 description 5
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 230000016784 immunoglobulin production Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 230000003614 tolerogenic effect Effects 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000043131 MHC class II family Human genes 0.000 description 4
- 108091054438 MHC class II family Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 102100035703 Prostatic acid phosphatase Human genes 0.000 description 4
- 108091008874 T cell receptors Proteins 0.000 description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 4
- 230000000890 antigenic effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 238000001415 gene therapy Methods 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 230000001112 coagulating effect Effects 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 229960000900 human factor viii Drugs 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 230000035935 pregnancy Effects 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 229960004641 rituximab Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 206010053567 Coagulopathies Diseases 0.000 description 2
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 208000026552 Severe hemophilia A Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000033289 adaptive immune response Effects 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 238000007820 coagulation assay Methods 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 102000054766 genetic haplotypes Human genes 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229940047434 kogenate Drugs 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 230000036581 peripheral resistance Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 description 2
- 210000001519 tissue Anatomy 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000699800 Cricetinae Species 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
- 108020004414 DNA Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 108010048049 Factor IXa Proteins 0.000 description 1
- 108010014173 Factor X 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
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 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
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 241000702619 Porcine parvovirus Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 206010037379 Pulmonary embolism and thrombosis Diseases 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 230000006044 T cell activation Effects 0.000 description 1
- 230000017274 T cell anergy Effects 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 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
- 208000027276 Von Willebrand disease Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 210000001766 X chromosome Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 230000002411 adverse 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
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 108010018823 anti-inhibitor coagulant complex Proteins 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000006470 autoimmune attack Effects 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 239000003659 bee venom Substances 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 238000003339 best practice Methods 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
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 235000019846 buffering salt Nutrition 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 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
- 208000035475 disorder Diseases 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 229940105776 factor viii inhibitor bypassing activity Drugs 0.000 description 1
- 238000009093 first-line therapy Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000004073 interleukin-2 production Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000001589 lymphoproliferative effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000003039 myelosuppressive effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000007479 persistent immune response Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000002616 plasmapheresis Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 208000012113 pregnancy disease Diseases 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002947 procoagulating effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229940047431 recombinate Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 206010040400 serum sickness Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 239000006200 vaporizer Substances 0.000 description 1
- 208000034280 venom allergy Diseases 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
- 230000003253 viricidal effect Effects 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
-
- 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
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
- A61K2039/577—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 tolerising response
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1220328.7A GB201220328D0 (en) | 2012-11-12 | 2012-11-12 | Peptides |
| GBGB1316660.8A GB201316660D0 (en) | 2013-09-19 | 2013-09-19 | Peptides |
| PCT/IB2013/060060 WO2014072958A1 (en) | 2012-11-12 | 2013-11-11 | Peptides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201590927A1 EA201590927A1 (ru) | 2015-10-30 |
| EA036483B1 true EA036483B1 (ru) | 2020-11-16 |
Family
ID=49627013
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201590927A EA036483B1 (ru) | 2012-11-12 | 2013-11-11 | Пептиды, способные индуцировать толерантность к рекомбинантному fviii, содержащая их композиция, их применение и способ лечения гемофилии |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US20150306192A1 (enExample) |
| EP (1) | EP2917232B1 (enExample) |
| JP (1) | JP6247696B2 (enExample) |
| KR (1) | KR102165486B1 (enExample) |
| CN (1) | CN104903347B (enExample) |
| AU (1) | AU2013343024B2 (enExample) |
| BR (1) | BR112015010625B1 (enExample) |
| CA (1) | CA2890835C (enExample) |
| CY (1) | CY1119164T1 (enExample) |
| DK (1) | DK2917232T3 (enExample) |
| EA (1) | EA036483B1 (enExample) |
| ES (1) | ES2626881T3 (enExample) |
| HR (1) | HRP20170794T1 (enExample) |
| HU (1) | HUE033586T2 (enExample) |
| IL (1) | IL238627B (enExample) |
| IN (1) | IN2015DN03814A (enExample) |
| LT (1) | LT2917232T (enExample) |
| MX (1) | MX350777B (enExample) |
| MY (1) | MY176708A (enExample) |
| NZ (1) | NZ708812A (enExample) |
| PH (1) | PH12015501033B1 (enExample) |
| PL (1) | PL2917232T3 (enExample) |
| PT (1) | PT2917232T (enExample) |
| RS (1) | RS56069B1 (enExample) |
| SG (1) | SG11201503657UA (enExample) |
| SI (1) | SI2917232T1 (enExample) |
| WO (1) | WO2014072958A1 (enExample) |
| ZA (1) | ZA201503127B (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2018206358B2 (en) | 2017-01-04 | 2021-05-27 | Worg Pharmaceuticals (Zhejiang) Co., Ltd. | S-Arrestin peptides and therapeutic uses thereof |
| EP3715374A1 (en) | 2019-03-23 | 2020-09-30 | Ablevia biotech GmbH | Compound for the sequestration of undesirable antibodies in a patient |
| US11986536B2 (en) | 2019-03-23 | 2024-05-21 | Ablevia Biotech Gmbh | Compound for the sequestration of undesirable antibodies in a patient |
| GB201909774D0 (en) | 2019-07-08 | 2019-08-21 | Apitope Tech Bristol Limited | Method |
| WO2022063887A1 (en) | 2020-09-23 | 2022-03-31 | Ablevia Biotech Gmbh | Compound for increasing the efficacy of factor viii replacement therapy |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2842812A1 (fr) * | 2002-07-26 | 2004-01-30 | Pf Medicament | Procede de solubilisation de peptides hydrophobes et leur utilisation pour generer une reponse de type ctl antitumorale ou anti-infectueuse |
| WO2009071886A1 (en) * | 2007-12-04 | 2009-06-11 | Apitope Technology (Bristol) Limited | Fviii peptides and their use in tolerising haemophiliacs |
| WO2009095646A2 (en) * | 2008-01-28 | 2009-08-06 | Circassia Limited | Peptides from factor viii |
| WO2010133834A2 (en) * | 2009-05-18 | 2010-11-25 | Apitope Technology (Bristol) Limited | Peptide |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030062321A (ko) | 2000-08-21 | 2003-07-23 | 아피토프 테크놀러지 (브리스톨) 리미티드 | 펩티드 선별 방법 |
| US20040096456A1 (en) * | 2000-12-01 | 2004-05-20 | Conti-Fine Bianca M | Method to treat hemophilia |
| JP2006188507A (ja) * | 2004-12-10 | 2006-07-20 | Tokyo Univ Of Agriculture & Technology | 蛋白質の溶解度向上方法 |
| EP1945797B1 (en) * | 2005-10-28 | 2012-05-30 | Boehringer Ingelheim International GmbH | Hepatitis c virus ns2/3 activity assay |
| CA2780763A1 (en) * | 2009-11-13 | 2011-05-19 | Puget Sound Blood Center | Factor viii b cell epitope variants having reduced immunogenicity |
| PL3260132T3 (pl) * | 2010-10-27 | 2022-08-08 | Takeda Pharmaceutical Company Limited | Peptydy fviii do wywoływania tolerancji immunologicznej oraz immunodiagnostyki |
-
2013
- 2013-11-11 CN CN201380069078.2A patent/CN104903347B/zh not_active Expired - Fee Related
- 2013-11-11 LT LTEP13795002.8T patent/LT2917232T/lt unknown
- 2013-11-11 MX MX2015005973A patent/MX350777B/es active IP Right Grant
- 2013-11-11 BR BR112015010625-0A patent/BR112015010625B1/pt not_active IP Right Cessation
- 2013-11-11 DK DK13795002.8T patent/DK2917232T3/en active
- 2013-11-11 MY MYPI2015001224A patent/MY176708A/en unknown
- 2013-11-11 KR KR1020157012787A patent/KR102165486B1/ko not_active Expired - Fee Related
- 2013-11-11 RS RS20170542A patent/RS56069B1/sr unknown
- 2013-11-11 PL PL13795002T patent/PL2917232T3/pl unknown
- 2013-11-11 AU AU2013343024A patent/AU2013343024B2/en not_active Ceased
- 2013-11-11 JP JP2015541291A patent/JP6247696B2/ja not_active Expired - Fee Related
- 2013-11-11 EP EP13795002.8A patent/EP2917232B1/en active Active
- 2013-11-11 EA EA201590927A patent/EA036483B1/ru unknown
- 2013-11-11 PT PT137950028T patent/PT2917232T/pt unknown
- 2013-11-11 IN IN3814DEN2015 patent/IN2015DN03814A/en unknown
- 2013-11-11 SI SI201330663A patent/SI2917232T1/sl unknown
- 2013-11-11 HU HUE13795002A patent/HUE033586T2/hu unknown
- 2013-11-11 ES ES13795002.8T patent/ES2626881T3/es active Active
- 2013-11-11 HR HRP20170794TT patent/HRP20170794T1/hr unknown
- 2013-11-11 SG SG11201503657UA patent/SG11201503657UA/en unknown
- 2013-11-11 US US14/441,923 patent/US20150306192A1/en not_active Abandoned
- 2013-11-11 WO PCT/IB2013/060060 patent/WO2014072958A1/en not_active Ceased
- 2013-11-11 CA CA2890835A patent/CA2890835C/en active Active
- 2013-11-11 NZ NZ708812A patent/NZ708812A/en not_active IP Right Cessation
-
2015
- 2015-05-04 IL IL238627A patent/IL238627B/en active IP Right Grant
- 2015-05-07 ZA ZA2015/03127A patent/ZA201503127B/en unknown
- 2015-05-08 PH PH12015501033A patent/PH12015501033B1/en unknown
-
2017
- 2017-05-31 CY CY20171100568T patent/CY1119164T1/el unknown
-
2021
- 2021-04-23 US US17/239,251 patent/US20210346476A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2842812A1 (fr) * | 2002-07-26 | 2004-01-30 | Pf Medicament | Procede de solubilisation de peptides hydrophobes et leur utilisation pour generer une reponse de type ctl antitumorale ou anti-infectueuse |
| WO2009071886A1 (en) * | 2007-12-04 | 2009-06-11 | Apitope Technology (Bristol) Limited | Fviii peptides and their use in tolerising haemophiliacs |
| WO2009095646A2 (en) * | 2008-01-28 | 2009-08-06 | Circassia Limited | Peptides from factor viii |
| WO2010133834A2 (en) * | 2009-05-18 | 2010-11-25 | Apitope Technology (Bristol) Limited | Peptide |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2227488B3 (en) | Fviii peptides and their use in tolerising haemophiliacs | |
| US20210346476A1 (en) | Modified FVIII Apitope Peptides | |
| EP2465523B1 (en) | FVIII-derived peptides and their use in tolerising haemophiliacs | |
| HK1209138B (en) | Factor viii-derived peptides for use in the treatment of haemophilia a | |
| HK1144292B (en) | Fviii peptides and their use in tolerising haemophiliacs | |
| HK1172240B (en) | Fviii-derived peptides and their use in tolerising haemophiliacs | |
| HK1172240A (en) | Fviii-derived peptides and their use in tolerising haemophiliacs | |
| HK1173358B (en) | Fviii-derived peptides |