EA005236B1 - Композиция для лечения и/или предупреждения нарушений, приводящих к аномальному кровотечению, и способ лечения таких нарушений (варианты) - Google Patents

Композиция для лечения и/или предупреждения нарушений, приводящих к аномальному кровотечению, и способ лечения таких нарушений (варианты) Download PDF

Info

Publication number: EA005236B1
Authority: EA; Eurasian Patent Office
Prior art keywords: agent; factor; antibody; composition; factor viii
Prior art date: 1998-09-21

Application number

EA200100385A

Other languages

English (en)

Russian (ru)

Other versions

EA200100385A1 (ru

Inventor

Гэри С. Грэй

Джиахуа Киан

Мэри Коллинс

Леон У. Хойэр

Original Assignee

ДЖИНЕТИКС ИНСТИТЬЮТ, эЛэЛСи

Эмерикэн Ред Кросс

Priority date (The priority date 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 date listed.)

1998-09-21

Filing date

1999-09-21

Publication date

2004-12-30

1999-09-21 Application filed by ДЖИНЕТИКС ИНСТИТЬЮТ, эЛэЛСи, Эмерикэн Ред Кросс filed Critical ДЖИНЕТИКС ИНСТИТЬЮТ, эЛэЛСи

2001-10-22 Publication of EA200100385A1 publication Critical patent/EA200100385A1/ru

2004-12-30 Publication of EA005236B1 publication Critical patent/EA005236B1/ru

Links

238000000034 method Methods 0.000 title claims abstract description 111
239000000203 mixture Substances 0.000 title claims abstract description 81
230000023597 hemostasis Effects 0.000 title abstract description 56
230000001737 promoting effect Effects 0.000 title abstract description 5
239000003795 chemical substances by application Substances 0.000 claims abstract description 178
230000000139 costimulatory effect Effects 0.000 claims abstract description 168
108010054218 Factor VIII Proteins 0.000 claims abstract description 167
102000001690 Factor VIII Human genes 0.000 claims abstract description 165
229960000301 factor viii Drugs 0.000 claims abstract description 162
210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 106
230000028993 immune response Effects 0.000 claims abstract description 54
230000002401 inhibitory effect Effects 0.000 claims abstract description 49
101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims abstract description 45
208000009292 Hemophilia A Diseases 0.000 claims abstract description 43
102100022641 Coagulation factor IX Human genes 0.000 claims abstract description 39
230000008742 procoagulation Effects 0.000 claims abstract description 35
201000003542 Factor VIII deficiency Diseases 0.000 claims abstract description 34
102100026735 Coagulation factor VIII Human genes 0.000 claims abstract description 33
108010076282 Factor IX Proteins 0.000 claims abstract description 31
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 31
229960004222 factor ix Drugs 0.000 claims abstract description 27
210000000612 antigen-presenting cell Anatomy 0.000 claims abstract description 22
102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims abstract description 12
101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims abstract description 12
208000009429 hemophilia B Diseases 0.000 claims abstract description 11
208000027276 Von Willebrand disease Diseases 0.000 claims abstract description 9
208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 claims abstract description 9
239000003937 drug carrier Substances 0.000 claims abstract description 7
108010047303 von Willebrand Factor Proteins 0.000 claims abstract description 7
102100036537 von Willebrand factor Human genes 0.000 claims abstract description 7
229960001134 von willebrand factor Drugs 0.000 claims abstract description 7
229940125721 immunosuppressive agent Drugs 0.000 claims abstract 2
239000003018 immunosuppressive agent Substances 0.000 claims abstract 2
238000002347 injection Methods 0.000 claims description 42
239000007924 injection Substances 0.000 claims description 42
230000001225 therapeutic effect Effects 0.000 claims description 19
230000003993 interaction Effects 0.000 claims description 16
208000032843 Hemorrhage Diseases 0.000 claims description 15
230000000740 bleeding effect Effects 0.000 claims description 15
238000011282 treatment Methods 0.000 claims description 11
238000012217 deletion Methods 0.000 claims description 9
230000037430 deletion Effects 0.000 claims description 9
230000002159 abnormal effect Effects 0.000 claims description 7
230000005764 inhibitory process Effects 0.000 claims description 7
230000002265 prevention Effects 0.000 claims description 3
208000024659 Hemostatic disease Diseases 0.000 abstract 5
208000012908 vascular hemostatic disease Diseases 0.000 abstract 5
108090000623 proteins and genes Proteins 0.000 description 96
102000004169 proteins and genes Human genes 0.000 description 86
241000699670 Mus sp. Species 0.000 description 85
210000004027 cell Anatomy 0.000 description 58
239000012634 fragment Substances 0.000 description 39
230000002163 immunogen Effects 0.000 description 33
241001465754 Metazoa Species 0.000 description 32
230000000694 effects Effects 0.000 description 32
108090000765 processed proteins & peptides Proteins 0.000 description 27
210000004408 hybridoma Anatomy 0.000 description 25
208000035475 disorder Diseases 0.000 description 20
238000005516 engineering process Methods 0.000 description 19
239000003446 ligand Substances 0.000 description 18
230000004044 response Effects 0.000 description 17
108020001507 fusion proteins Proteins 0.000 description 16
102000037865 fusion proteins Human genes 0.000 description 16
241000699666 Mus <mouse, genus> Species 0.000 description 14
238000004458 analytical method Methods 0.000 description 14
239000000427 antigen Substances 0.000 description 14
108091007433 antigens Proteins 0.000 description 14
102000036639 antigens Human genes 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 14
150000007523 nucleic acids Chemical class 0.000 description 14
238000002360 preparation method Methods 0.000 description 14
108020004707 nucleic acids Proteins 0.000 description 13
102000039446 nucleic acids Human genes 0.000 description 13
108091028043 Nucleic acid sequence Proteins 0.000 description 12
150000001413 amino acids Chemical group 0.000 description 12
208000034158 bleeding Diseases 0.000 description 12
102000057593 human F8 Human genes 0.000 description 12
230000003053 immunization Effects 0.000 description 12
239000003112 inhibitor Substances 0.000 description 12
102100039496 Choline transporter-like protein 4 Human genes 0.000 description 11
101000889282 Homo sapiens Choline transporter-like protein 4 Proteins 0.000 description 11
229960000900 human factor viii Drugs 0.000 description 11
230000035755 proliferation Effects 0.000 description 11
239000000243 solution Substances 0.000 description 11
230000005867 T cell response Effects 0.000 description 10
230000000903 blocking effect Effects 0.000 description 10
230000006870 function Effects 0.000 description 10
238000002649 immunization Methods 0.000 description 10
102000004196 processed proteins & peptides Human genes 0.000 description 10
210000002966 serum Anatomy 0.000 description 10
238000010561 standard procedure Methods 0.000 description 10
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 9
241000124008 Mammalia Species 0.000 description 9
230000004913 activation Effects 0.000 description 9
210000004369 blood Anatomy 0.000 description 9
239000008280 blood Substances 0.000 description 9
150000001875 compounds Chemical class 0.000 description 9
238000009396 hybridization Methods 0.000 description 9
206010035226 Plasma cell myeloma Diseases 0.000 description 8
239000002671 adjuvant Substances 0.000 description 8
238000002474 experimental method Methods 0.000 description 8
230000004927 fusion Effects 0.000 description 8
238000010253 intravenous injection Methods 0.000 description 8
238000004519 manufacturing process Methods 0.000 description 8
201000000050 myeloid neoplasm Diseases 0.000 description 8
238000012216 screening Methods 0.000 description 8
210000004989 spleen cell Anatomy 0.000 description 8
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 8
108020004414 DNA Proteins 0.000 description 7
208000031220 Hemophilia Diseases 0.000 description 7
210000003719 b-lymphocyte Anatomy 0.000 description 7
239000000463 material Substances 0.000 description 7
210000002381 plasma Anatomy 0.000 description 7
-1 succinimidyl Chemical group 0.000 description 7
239000013598 vector Substances 0.000 description 7
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
108060003951 Immunoglobulin Proteins 0.000 description 6
239000010836 blood and blood product Substances 0.000 description 6
229940125691 blood product Drugs 0.000 description 6
238000003776 cleavage reaction Methods 0.000 description 6
238000011161 development Methods 0.000 description 6
102000018358 immunoglobulin Human genes 0.000 description 6
210000004962 mammalian cell Anatomy 0.000 description 6
239000002609 medium Substances 0.000 description 6
239000013615 primer Substances 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
102000005962 receptors Human genes 0.000 description 6
230000007017 scission Effects 0.000 description 6
238000009097 single-agent therapy Methods 0.000 description 6
230000000638 stimulation Effects 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 5
108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
108010002350 Interleukin-2 Proteins 0.000 description 5
102000000588 Interleukin-2 Human genes 0.000 description 5
241000699660 Mus musculus Species 0.000 description 5
102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 5
108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 5
108010076504 Protein Sorting Signals Proteins 0.000 description 5
230000009471 action Effects 0.000 description 5
239000013543 active substance Substances 0.000 description 5
230000005875 antibody response Effects 0.000 description 5
239000002299 complementary DNA Substances 0.000 description 5
201000010099 disease Diseases 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
239000013604 expression vector Substances 0.000 description 5
210000002865 immune cell Anatomy 0.000 description 5
244000005700 microbiome Species 0.000 description 5
230000026731 phosphorylation Effects 0.000 description 5
238000006366 phosphorylation reaction Methods 0.000 description 5
238000000746 purification Methods 0.000 description 5
230000004936 stimulating effect Effects 0.000 description 5
241000283973 Oryctolagus cuniculus Species 0.000 description 4
108091007960 PI3Ks Proteins 0.000 description 4
108010033276 Peptide Fragments Proteins 0.000 description 4
102000007079 Peptide Fragments Human genes 0.000 description 4
102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 4
108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 4
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 4
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 4
102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 4
REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 4
240000004808 Saccharomyces cerevisiae Species 0.000 description 4
230000006052 T cell proliferation Effects 0.000 description 4
239000002981 blocking agent Substances 0.000 description 4
210000001772 blood platelet Anatomy 0.000 description 4
230000016396 cytokine production Effects 0.000 description 4
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 4
239000002612 dispersion medium Substances 0.000 description 4
239000003814 drug Substances 0.000 description 4
238000013401 experimental design Methods 0.000 description 4
MCAHMSDENAOJFZ-BVXDHVRPSA-N herbimycin Chemical group N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](OC)[C@@H](OC)C[C@H](C)[C@@H](OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-BVXDHVRPSA-N 0.000 description 4
230000006058 immune tolerance Effects 0.000 description 4
230000005847 immunogenicity Effects 0.000 description 4
230000036046 immunoreaction Effects 0.000 description 4
210000004698 lymphocyte Anatomy 0.000 description 4
239000012528 membrane Substances 0.000 description 4
239000002245 particle Substances 0.000 description 4
239000002953 phosphate buffered saline Substances 0.000 description 4
150000003906 phosphoinositides Chemical class 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
229920001184 polypeptide Polymers 0.000 description 4
108020000494 protein-tyrosine phosphatase Proteins 0.000 description 4
QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
108010014172 Factor V Proteins 0.000 description 3
MCAHMSDENAOJFZ-UHFFFAOYSA-N Herbimycin A Natural products N1C(=O)C(C)=CC=CC(OC)C(OC(N)=O)C(C)=CC(C)C(OC)C(OC)CC(C)C(OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-UHFFFAOYSA-N 0.000 description 3
241001529936 Murinae Species 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
102000004140 Oncostatin M Human genes 0.000 description 3
108090000630 Oncostatin M Proteins 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
108020004511 Recombinant DNA Proteins 0.000 description 3
108010071390 Serum Albumin Proteins 0.000 description 3
102000007562 Serum Albumin Human genes 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
108091008874 T cell receptors Proteins 0.000 description 3
102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
230000003321 amplification Effects 0.000 description 3
239000003242 anti bacterial agent Substances 0.000 description 3
230000000844 anti-bacterial effect Effects 0.000 description 3
210000000628 antibody-producing cell Anatomy 0.000 description 3
229940121375 antifungal agent Drugs 0.000 description 3
239000003429 antifungal agent Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000000969 carrier Substances 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
230000036755 cellular response Effects 0.000 description 3
210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
238000000576 coating method Methods 0.000 description 3
230000004940 costimulation Effects 0.000 description 3
238000004132 cross linking Methods 0.000 description 3
239000003431 cross linking reagent Substances 0.000 description 3
230000007423 decrease Effects 0.000 description 3
230000007812 deficiency Effects 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000012530 fluid Substances 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
230000003834 intracellular effect Effects 0.000 description 3
239000007951 isotonicity adjuster Substances 0.000 description 3
150000002632 lipids Chemical class 0.000 description 3
239000002502 liposome Substances 0.000 description 3
238000002156 mixing Methods 0.000 description 3
238000003199 nucleic acid amplification method Methods 0.000 description 3
239000002773 nucleotide Substances 0.000 description 3
125000003729 nucleotide group Chemical group 0.000 description 3
238000011580 nude mouse model Methods 0.000 description 3
150000003905 phosphatidylinositols Chemical class 0.000 description 3
238000003752 polymerase chain reaction Methods 0.000 description 3
239000000843 powder Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
108020001580 protein domains Proteins 0.000 description 3
230000000284 resting effect Effects 0.000 description 3
239000007790 solid phase Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
241000894007 species Species 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
210000000952 spleen Anatomy 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000006228 supernatant Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
238000002560 therapeutic procedure Methods 0.000 description 3
239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
230000003612 virological effect Effects 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 3
206010003445 Ascites Diseases 0.000 description 2
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
108010045634 B7 Antigens Proteins 0.000 description 2
102000005738 B7 Antigens Human genes 0.000 description 2
102000015081 Blood Coagulation Factors Human genes 0.000 description 2
108010039209 Blood Coagulation Factors Proteins 0.000 description 2
102000004506 Blood Proteins Human genes 0.000 description 2
108010017384 Blood Proteins Proteins 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
241000699802 Cricetulus griseus Species 0.000 description 2
229930105110 Cyclosporin A Natural products 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
239000003155 DNA primer Substances 0.000 description 2
101100395869 Escherichia coli sta3 gene Proteins 0.000 description 2
108010048049 Factor IXa Proteins 0.000 description 2
108010014173 Factor X Proteins 0.000 description 2
102000009123 Fibrin Human genes 0.000 description 2
108010073385 Fibrin Proteins 0.000 description 2
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
102000003886 Glycoproteins Human genes 0.000 description 2
108090000288 Glycoproteins Proteins 0.000 description 2
SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 2
241000238631 Hexapoda Species 0.000 description 2
241000282412 Homo Species 0.000 description 2
101000884279 Homo sapiens CD276 antigen Proteins 0.000 description 2
206010062016 Immunosuppression Diseases 0.000 description 2
CZQHHVNHHHRRDU-UHFFFAOYSA-N LY294002 Chemical group C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1C1=CC=CC=C1 CZQHHVNHHHRRDU-UHFFFAOYSA-N 0.000 description 2
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
108010001267 Protein Subunits Proteins 0.000 description 2
102000002067 Protein Subunits Human genes 0.000 description 2
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 2
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 2
230000020385 T cell costimulation Effects 0.000 description 2
108090000190 Thrombin Proteins 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
102000014384 Type C Phospholipases Human genes 0.000 description 2
108010079194 Type C Phospholipases Proteins 0.000 description 2
241000700605 Viruses Species 0.000 description 2
239000003070 absorption delaying agent Substances 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
238000001042 affinity chromatography Methods 0.000 description 2
229940037003 alum Drugs 0.000 description 2
125000000539 amino acid group Chemical group 0.000 description 2
238000012870 ammonium sulfate precipitation Methods 0.000 description 2
239000002269 analeptic agent Substances 0.000 description 2
239000003114 blood coagulation factor Substances 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
238000001516 cell proliferation assay Methods 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
229960001265 ciclosporin Drugs 0.000 description 2
238000011260 co-administration Methods 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
230000006378 damage Effects 0.000 description 2
230000007547 defect Effects 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
238000001514 detection method Methods 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000000539 dimer Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
239000002532 enzyme inhibitor Substances 0.000 description 2
210000003527 eukaryotic cell Anatomy 0.000 description 2
229950003499 fibrin Drugs 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
108060003552 hemocyanin Proteins 0.000 description 2
230000002439 hemostatic effect Effects 0.000 description 2
230000008348 humoral response Effects 0.000 description 2
230000001900 immune effect Effects 0.000 description 2
230000001506 immunosuppresive effect Effects 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
230000006698 induction Effects 0.000 description 2
238000001802 infusion Methods 0.000 description 2
229960000367 inositol Drugs 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
238000004255 ion exchange chromatography Methods 0.000 description 2
238000002955 isolation Methods 0.000 description 2
MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000010369 molecular cloning Methods 0.000 description 2
230000035772 mutation Effects 0.000 description 2
210000005259 peripheral blood Anatomy 0.000 description 2
239000011886 peripheral blood Substances 0.000 description 2
229920001308 poly(aminoacid) Polymers 0.000 description 2
230000002062 proliferating effect Effects 0.000 description 2
230000000644 propagated effect Effects 0.000 description 2
230000006337 proteolytic cleavage Effects 0.000 description 2
150000003243 quercetin Chemical class 0.000 description 2
229960001285 quercetin Drugs 0.000 description 2
235000005875 quercetin Nutrition 0.000 description 2
CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 2
230000003248 secreting effect Effects 0.000 description 2
230000028327 secretion Effects 0.000 description 2
238000000926 separation method Methods 0.000 description 2
230000019491 signal transduction Effects 0.000 description 2
238000002741 site-directed mutagenesis Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
230000000392 somatic effect Effects 0.000 description 2
238000001179 sorption measurement Methods 0.000 description 2
238000003860 storage Methods 0.000 description 2
150000005846 sugar alcohols Polymers 0.000 description 2
230000002195 synergetic effect Effects 0.000 description 2
229960004072 thrombin Drugs 0.000 description 2
229940104230 thymidine Drugs 0.000 description 2
238000010361 transduction Methods 0.000 description 2
230000026683 transduction Effects 0.000 description 2
238000001890 transfection Methods 0.000 description 2
238000011830 transgenic mouse model Methods 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
241000701447 unidentified baculovirus Species 0.000 description 2
238000005406 washing Methods 0.000 description 2
PMJWDPGOWBRILU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(C=C1)=CC=C1N1C(=O)C=CC1=O PMJWDPGOWBRILU-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
PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
208000003950 B-cell lymphoma Diseases 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241000283707 Capra Species 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
108010078791 Carrier Proteins Proteins 0.000 description 1
108010001857 Cell Surface Receptors Proteins 0.000 description 1
102000000844 Cell Surface Receptors Human genes 0.000 description 1
102100023344 Centromere protein F Human genes 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
102100023804 Coagulation factor VII Human genes 0.000 description 1
241000699800 Cricetinae Species 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
241000701022 Cytomegalovirus 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
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
101100117236 Drosophila melanogaster speck gene Proteins 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
108010000912 Egg Proteins Proteins 0.000 description 1
102000002322 Egg Proteins Human genes 0.000 description 1
108010062466 Enzyme Precursors Proteins 0.000 description 1
102000010911 Enzyme Precursors Human genes 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
206010016077 Factor IX deficiency Diseases 0.000 description 1
108010023321 Factor VII Proteins 0.000 description 1
108010061932 Factor VIIIa Proteins 0.000 description 1
241000282324 Felis Species 0.000 description 1
108010049003 Fibrinogen Proteins 0.000 description 1
102000008946 Fibrinogen Human genes 0.000 description 1
241000724791 Filamentous phage Species 0.000 description 1
241000233866 Fungi Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
102000006395 Globulins Human genes 0.000 description 1
108010044091 Globulins 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
239000004471 Glycine Substances 0.000 description 1
241000701109 Human adenovirus 2 Species 0.000 description 1
108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
229930010555 Inosine Natural products 0.000 description 1
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
108090000978 Interleukin-4 Proteins 0.000 description 1
101150092727 KLF10 gene Proteins 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
108090001030 Lipoproteins Proteins 0.000 description 1
102000004895 Lipoproteins Human genes 0.000 description 1
241000080581 Lysmus Species 0.000 description 1
108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
101100460719 Mus musculus Noto gene Proteins 0.000 description 1
108091034117 Oligonucleotide Proteins 0.000 description 1
108010058846 Ovalbumin Proteins 0.000 description 1
238000012408 PCR amplification Methods 0.000 description 1
101710126321 Pancreatic trypsin inhibitor Proteins 0.000 description 1
102000057297 Pepsin A Human genes 0.000 description 1
108090000284 Pepsin A Proteins 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
108010039918 Polylysine Proteins 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
239000004365 Protease Substances 0.000 description 1
102000001253 Protein Kinase Human genes 0.000 description 1
108010094028 Prothrombin Proteins 0.000 description 1
102100027378 Prothrombin Human genes 0.000 description 1
241000700159 Rattus Species 0.000 description 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
230000006044 T cell activation Effects 0.000 description 1
230000024932 T cell mediated immunity Effects 0.000 description 1
108010000499 Thromboplastin Proteins 0.000 description 1
102000002262 Thromboplastin Human genes 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
102000009843 Thyroglobulin Human genes 0.000 description 1
108010034949 Thyroglobulin Proteins 0.000 description 1
241000209140 Triticum Species 0.000 description 1
235000021307 Triticum Nutrition 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
101100187345 Xenopus laevis noto gene Proteins 0.000 description 1
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
239000012190 activator Substances 0.000 description 1
230000004520 agglutination Effects 0.000 description 1
230000004931 aggregating effect Effects 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
239000000556 agonist Substances 0.000 description 1
229940064734 aminobenzoate Drugs 0.000 description 1
230000000890 antigenic effect Effects 0.000 description 1
229940030225 antihemorrhagics Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000012062 aqueous buffer Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 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
238000003556 assay Methods 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
125000005340 bisphosphate group Chemical group 0.000 description 1
230000023555 blood coagulation Effects 0.000 description 1
238000010241 blood sampling Methods 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
210000001124 body fluid Anatomy 0.000 description 1
239000010839 body fluid Substances 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
230000003185 calcium uptake Effects 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
HFNQLYDPNAZRCH-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O.OC(O)=O HFNQLYDPNAZRCH-UHFFFAOYSA-N 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
230000008859 change Effects 0.000 description 1
238000010382 chemical cross-linking Methods 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
238000010367 cloning Methods 0.000 description 1
238000000975 co-precipitation Methods 0.000 description 1
230000015271 coagulation Effects 0.000 description 1
238000005345 coagulation Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
239000003636 conditioned culture medium Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
238000010908 decantation Methods 0.000 description 1
230000001934 delay Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 1
238000006471 dimerization reaction Methods 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
230000002222 downregulating effect Effects 0.000 description 1
230000003828 downregulation Effects 0.000 description 1
239000012636 effector Substances 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
238000004520 electroporation Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
210000002889 endothelial cell Anatomy 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
229940088598 enzyme Drugs 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
229940012413 factor vii Drugs 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
229940012952 fibrinogen Drugs 0.000 description 1
229960005051 fluostigmine Drugs 0.000 description 1
238000005194 fractionation Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
108010074605 gamma-Globulins Proteins 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
238000001415 gene therapy Methods 0.000 description 1
102000034356 gene-regulatory proteins Human genes 0.000 description 1
108091006104 gene-regulatory proteins Proteins 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
238000010353 genetic engineering Methods 0.000 description 1
239000008103 glucose Substances 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
230000001279 glycosylating effect Effects 0.000 description 1
238000009499 grossing Methods 0.000 description 1
239000002874 hemostatic agent Substances 0.000 description 1
239000000833 heterodimer Substances 0.000 description 1
229960000027 human factor ix Drugs 0.000 description 1
125000001165 hydrophobic group Chemical group 0.000 description 1
230000014726 immortalization of host cell Effects 0.000 description 1
238000003018 immunoassay Methods 0.000 description 1
230000000984 immunochemical effect Effects 0.000 description 1
230000009851 immunogenic response Effects 0.000 description 1
229940072221 immunoglobulins Drugs 0.000 description 1
239000002955 immunomodulating agent Substances 0.000 description 1
230000006872 improvement Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
208000014674 injury Diseases 0.000 description 1
229960003786 inosine Drugs 0.000 description 1
CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
210000002660 insulin-secreting cell Anatomy 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
231100000518 lethal Toxicity 0.000 description 1
230000001665 lethal effect Effects 0.000 description 1
230000021633 leukocyte mediated immunity Effects 0.000 description 1
238000001638 lipofection Methods 0.000 description 1
210000001165 lymph node Anatomy 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000013507 mapping Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
210000003593 megakaryocyte Anatomy 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
239000003226 mitogen Substances 0.000 description 1
229960004857 mitomycin Drugs 0.000 description 1
238000001823 molecular biology technique Methods 0.000 description 1
150000004712 monophosphates Chemical class 0.000 description 1
238000002703 mutagenesis Methods 0.000 description 1
231100000350 mutagenesis Toxicity 0.000 description 1
210000000822 natural killer cell Anatomy 0.000 description 1
238000011330 nucleic acid test Methods 0.000 description 1
239000003921 oil Substances 0.000 description 1
238000011275 oncology therapy Methods 0.000 description 1
229940092253 ovalbumin Drugs 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
210000004681 ovum Anatomy 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
229940111202 pepsin Drugs 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
230000002688 persistence Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229960003742 phenol Drugs 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
239000013612 plasmid Substances 0.000 description 1
229920000724 poly(L-arginine) polymer Polymers 0.000 description 1
108010011110 polyarginine Proteins 0.000 description 1
229920000656 polylysine Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
210000004986 primary T-cell Anatomy 0.000 description 1
230000002947 procoagulating effect Effects 0.000 description 1
239000000047 product Substances 0.000 description 1
210000001236 prokaryotic cell Anatomy 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
108060006633 protein kinase Proteins 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
229940039716 prothrombin Drugs 0.000 description 1
150000003244 quercetin derivatives Chemical class 0.000 description 1
ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000003362 replicative effect Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
238000012552 review Methods 0.000 description 1
IKGXIBQEEMLURG-NVPNHPEKSA-N rutin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-NVPNHPEKSA-N 0.000 description 1
239000006152 selective media Substances 0.000 description 1
229960002930 sirolimus Drugs 0.000 description 1
QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
101150038846 slc46a1 gene Proteins 0.000 description 1
239000007787 solid Substances 0.000 description 1
210000001082 somatic cell Anatomy 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
210000004988 splenocyte Anatomy 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
230000008093 supporting effect Effects 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229940033663 thimerosal Drugs 0.000 description 1
229960002175 thyroglobulin Drugs 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
239000001226 triphosphate Substances 0.000 description 1
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
- A61K38/37—Factors VIII
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- 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

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Immunology (AREA)
Epidemiology (AREA)
Hematology (AREA)
Gastroenterology & Hepatology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Zoology (AREA)
General Chemical & Material Sciences (AREA)
Microbiology (AREA)
Mycology (AREA)
Diabetes (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

EA200100385A 1998-09-21 1999-09-21 Композиция для лечения и/или предупреждения нарушений, приводящих к аномальному кровотечению, и способ лечения таких нарушений (варианты) EA005236B1 (ru)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US15817898A	1998-09-21	1998-09-21
PCT/US1999/021991 WO2000016801A1 (en)	1998-09-21	1999-09-21	Methods of downmodulating the immune response to therapeutic proteins

Publications (2)

Publication Number	Publication Date
EA200100385A1 EA200100385A1 (ru)	2001-10-22
EA005236B1 true EA005236B1 (ru)	2004-12-30

Family

ID=22566971

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
EA200100385A EA005236B1 (ru)	1998-09-21	1999-09-21	Композиция для лечения и/или предупреждения нарушений, приводящих к аномальному кровотечению, и способ лечения таких нарушений (варианты)

Country Status (21)

Country	Link
EP (1)	EP1115423A1 (lt)
JP (1)	JP2002526455A (lt)
KR (1)	KR20010085830A (lt)
CN (1)	CN1331602A (lt)
AU (1)	AU761206B2 (lt)
BR (1)	BR9913991A (lt)
CA (1)	CA2343916A1 (lt)
CZ (1)	CZ20011021A3 (lt)
EA (1)	EA005236B1 (lt)
HK (1)	HK1039059A1 (lt)
HU (1)	HUP0103960A3 (lt)
IL (1)	IL142069A0 (lt)
LT (1)	LT4920B (lt)
LV (1)	LV12768B (lt)
MX (1)	MXPA01002898A (lt)
NO (1)	NO20011412L (lt)
NZ (1)	NZ511034A (lt)
PL (1)	PL346796A1 (lt)
SI (1)	SI20626A (lt)
WO (1)	WO2000016801A1 (lt)
ZA (1)	ZA200103156B (lt)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5397703A (en)	1992-07-09	1995-03-14	Cetus Oncology Corporation	Method for generation of antibodies to cell surface molecules
DE60118362T2 (de) *	2000-05-19	2007-05-24	The Center for Blood Research, Inc., Boston	VERFAHREN ZUR BEHANDLUNG VON HÄMOSTATISCHEN STÖRUNGEN DURCH LöSLICHES P-SELECTIN
EP1636579A4 (en) *	2003-06-10	2011-10-05	Smiths Detection Inc	SENSOR ASSEMBLY
GB201508024D0 (en)	2015-05-11	2015-06-24	Haemostatix Ltd	Haemostatic compositions

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5171569A (en)	1985-03-15	1992-12-15	National Research Development Corporation	Factor IX preparations uncontaminated by plasma components or pox virus
ES8801674A1 (es)	1985-04-12	1988-02-16	Genetics Inst	Un procedimiento para la preparacion de una proteina que presenta actividad procoagulante.
US5422260A (en)	1986-05-29	1995-06-06	Genetics Institute, Inc. -Legal Affairs	Human factor VIII:c muteins
US4994371A (en)	1987-08-28	1991-02-19	Davie Earl W	DNA preparation of Christmas factor and use of DNA sequences
FR2657884B1 (fr)	1990-02-05	1994-09-02	Tm Innovation	Procede pour la preparation du facteur viii humain et d'analogues du facteur viii.
US5661008A (en)	1991-03-15	1997-08-26	Kabi Pharmacia Ab	Recombinant human factor VIII derivatives
CA2580812A1 (en)	1991-06-27	1993-01-07	Bristol-Myers Squibb Company	Ctla4 receptor, fusion proteins containing it and uses thereof
US5770197A (en)	1991-06-27	1998-06-23	Bristol-Myers Squibb Company	Methods for regulating the immune response using B7 binding molecules and IL4-binding molecules
WO1993009804A1 (en)	1991-11-18	1993-05-27	The Scripps Research Institute	Serine protease derived-polypeptides and anti-peptide antibodies, systems and therapeutic methods for inhibiting coagulation
US5364771A (en)	1992-04-07	1994-11-15	Emory University	Hybrid human/porcine factor VIII
US5663060A (en)	1992-04-07	1997-09-02	Emory University	Hybrid human/animal factor VIII
US5744446A (en)	1992-04-07	1998-04-28	Emory University	Hybrid human/animal factor VIII
US5621039A (en)	1993-06-08	1997-04-15	Hallahan; Terrence W.	Factor IX- polymeric conjugates
EP0776217A1 (en) *	1994-08-19	1997-06-04	Novo Nordisk A/S	A method of treating a patient with a biologically active compound
WO1996012406A1 (en) *	1994-10-19	1996-05-02	Genetic Therapy, Inc.	Gene therapy involving concurrent and repeated administration of adenoviruses and immunosuppressive agents
US5714583A (en)	1995-06-07	1998-02-03	Genetics Institute, Inc.	Factor IX purification methods
EP0892643B2 (en) *	1996-03-20	2009-09-02	Bristol-Myers Squibb Company	Methods for inhibiting an immune response by blocking the gp39/cd40 and ctla4/cd28/b7 pathways and compositions for use therewith
PL193966B1 (pl) *	1997-01-10	2007-04-30	Biogen Idec Ma	Zastosowanie przeciwciał przeciwko CD40L lub pochodnych
CN1261285A (zh) *	1997-06-20	2000-07-26	拜奥根有限公司	治疗性蛋白抑制剂综合症的cd154阻断治疗
US8151477B2 (en)	2009-11-06	2012-04-10	Hexagon Metrology Ab	CMM with modular functionality

1999
- 1999-09-21 NZ NZ511034A patent/NZ511034A/xx unknown
- 1999-09-21 IL IL14206999A patent/IL142069A0/xx unknown
- 1999-09-21 HK HK02100157.7A patent/HK1039059A1/zh unknown
- 1999-09-21 JP JP2000573762A patent/JP2002526455A/ja not_active Withdrawn
- 1999-09-21 EA EA200100385A patent/EA005236B1/ru not_active IP Right Cessation
- 1999-09-21 KR KR1020017003611A patent/KR20010085830A/ko not_active Withdrawn
- 1999-09-21 CN CN99813510A patent/CN1331602A/zh active Pending
- 1999-09-21 PL PL99346796A patent/PL346796A1/xx not_active Application Discontinuation
- 1999-09-21 EP EP99969339A patent/EP1115423A1/en not_active Withdrawn
- 1999-09-21 HU HU0103960A patent/HUP0103960A3/hu unknown
- 1999-09-21 CA CA002343916A patent/CA2343916A1/en not_active Abandoned
- 1999-09-21 WO PCT/US1999/021991 patent/WO2000016801A1/en not_active Ceased
- 1999-09-21 MX MXPA01002898A patent/MXPA01002898A/es unknown
- 1999-09-21 AU AU60578/99A patent/AU761206B2/en not_active Ceased
- 1999-09-21 CZ CZ20011021A patent/CZ20011021A3/cs unknown
- 1999-09-21 SI SI9920084A patent/SI20626A/sl not_active IP Right Cessation
- 1999-09-21 BR BR9913991-0A patent/BR9913991A/pt not_active IP Right Cessation
2001
- 2001-03-20 NO NO20011412A patent/NO20011412L/no not_active Application Discontinuation
- 2001-04-18 ZA ZA200103156A patent/ZA200103156B/xx unknown
- 2001-04-20 LV LVP-01-62A patent/LV12768B/lv unknown
- 2001-04-20 LT LT2001045A patent/LT4920B/lt not_active IP Right Cessation

Also Published As

Publication number	Publication date
KR20010085830A (ko)	2001-09-07
NO20011412L (no)	2001-05-16
LT4920B (lt)	2002-06-25
LV12768A (en)	2001-12-20
LV12768B (lv)	2002-06-20
CN1331602A (zh)	2002-01-16
PL346796A1 (en)	2002-02-25
BR9913991A (pt)	2001-07-03
CZ20011021A3 (cs)	2001-10-17
MXPA01002898A (es)	2002-06-04
JP2002526455A (ja)	2002-08-20
NO20011412D0 (no)	2001-03-20
HK1039059A1 (zh)	2002-04-12
HUP0103960A3 (en)	2003-09-29
LT2001045A (lt)	2002-01-25
EA200100385A1 (ru)	2001-10-22
WO2000016801A1 (en)	2000-03-30
AU761206B2 (en)	2003-05-29
CA2343916A1 (en)	2000-03-30
IL142069A0 (en)	2002-03-10
EP1115423A1 (en)	2001-07-18
HUP0103960A2 (hu)	2002-02-28
SI20626A (sl)	2002-02-28
ZA200103156B (en)	2002-07-18
AU6057899A (en)	2000-04-10
WO2000016801A9 (en)	2000-10-26
NZ511034A (en)	2004-03-26

Legal Events

Date	Code	Title	Description
2003-12-25	PD1A	Registration of transfer to a eurasian application by order of succession in title
2006-06-30	MM4A	Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s)	Designated state(s): AM AZ BY KZ KG MD TJ TM RU

Publication	Publication Date	Title
JP4052524B2 (ja)	2008-02-27	Ｔ細胞における抗原特異性アポトーシスの誘導のためのリガンド
Shenoy-Scaria et al.	1992	Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1
KR100257466B1 (ko)	2000-07-01	Lag-3의 가용성 폴리펩타이드 절편 및 생산 방법 치료 조성물, 항-이디오타입 항체
Benjamin et al.	1988	Mechanisms of monoclonal antibody‐facilitated tolerance induction: a possible role for the CD4 (L3T4) and CD11a (LFA‐1) molecules in self‐non‐self discrimination
JP2003520828A (ja)	2003-07-08	Ｃｔｌａ４（ｃｄ１５２）に対する抗体、これを含む結合体、およびその使用
Qian et al.	2000	Role of CD154 in the secondary immune response: the reduction of pre‐existing splenic germinal centers and anti‐factor VIII inhibitor titer
US12319744B2 (en)	2025-06-03	Treatment and prevention of hemophilic arthropathy with an antibody against endothelial cell protein C receptor (EPCR)
EA021131B1 (ru)	2015-04-30	Антитела и способы их получения
Clarke	2009	Mechanisms of adverse drug reactions to biologics
BG107214A (bg)	2003-11-28	Пептид, модулиращ тромбопоетиновия рецептор
US20050163780A1 (en)	2005-07-28	Method for prolonged suppression of humoral immune response to a thymus-dependent antigen
CN103339149B (zh)	2016-02-03	SorLA和GDNF-家族配体受体之间的相互作用的调节
EP1755660A2 (en)	2007-02-28	Method for enhancing or inhibiting insulin-like growth factor-i
AU2004240180B2 (en)	2007-08-09	Methods of prolonged suppression of humoral immunity
Fijnvandraat et al.	2003	Immunobiology of inhibitor development in hemophilia A
EA005236B1 (ru)	2004-12-30	Композиция для лечения и/или предупреждения нарушений, приводящих к аномальному кровотечению, и способ лечения таких нарушений (варианты)
US20030161827A1 (en)	2003-08-28	Therapies that improve graft survival
US20070092506A1 (en)	2007-04-26	Use of rapamycin and agents that inhibit B7 activity in immunomodulation
Greenwood et al.	2003	Identification of T-cell epitopes in clotting factor IX and lack of tolerance in inbred mice
WO1997017360A2 (en)	1997-05-15	Methods for modulating t cell responses by manipulating a common cytokine receptor gamma chain
US20020071839A1 (en)	2002-06-13	Use of a combination of agents that modulate B7 activity in inhibiting intestinal allograft rejection
US20060073133A1 (en)	2006-04-06	Sialoadhesin factor-3 antibodies
US20050152893A1 (en)	2005-07-14	Methods and materials for the inhibition of transplant rejection
KR20070022067A (ko)	2007-02-23	에리스로포이에틴에 의해 수반되는 고혈압 방지를 위한조성물 및 방법
Cobbold	1988	Cambridge zyxwvutsrqponmlkjihgfedcb