ES2642512T3 - Anticuerpos monoclonales optimizados contra el inhibidor de la ruta del factor tisular (TFPI) - Google Patents
Anticuerpos monoclonales optimizados contra el inhibidor de la ruta del factor tisular (TFPI) Download PDFInfo
- Publication number
- ES2642512T3 ES2642512T3 ES11751244.2T ES11751244T ES2642512T3 ES 2642512 T3 ES2642512 T3 ES 2642512T3 ES 11751244 T ES11751244 T ES 11751244T ES 2642512 T3 ES2642512 T3 ES 2642512T3
- Authority
- ES
- Spain
- Prior art keywords
- antibody
- tfpi
- amino acid
- seq
- antibodies
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 title description 65
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 title description 65
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 90
- 241000282414 Homo sapiens Species 0.000 claims description 54
- 102220467388 Otoancorin_Y48F_mutation Human genes 0.000 claims description 53
- 238000006467 substitution reaction Methods 0.000 claims description 47
- 102200079914 rs193302884 Human genes 0.000 claims description 36
- 230000037361 pathway Effects 0.000 claims description 20
- 239000003112 inhibitor Substances 0.000 claims description 19
- 101000635804 Homo sapiens Tissue factor Proteins 0.000 claims description 16
- 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 9
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- 102220369055 c.96C>G Human genes 0.000 description 63
- 102220594400 HLA class I histocompatibility antigen, C alpha chain_D33F_mutation Human genes 0.000 description 61
- 101000653189 Homo sapiens Tissue factor pathway inhibitor Proteins 0.000 description 45
- 235000001014 amino acid Nutrition 0.000 description 45
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 42
- 230000027455 binding Effects 0.000 description 41
- 230000004048 modification Effects 0.000 description 39
- 238000012986 modification Methods 0.000 description 39
- 210000004027 cell Anatomy 0.000 description 38
- 102220523980 Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1_D33R_mutation Human genes 0.000 description 36
- 108090000623 proteins and genes Proteins 0.000 description 36
- 230000014509 gene expression Effects 0.000 description 35
- 150000001413 amino acids Chemical class 0.000 description 31
- 229940024606 amino acid Drugs 0.000 description 30
- 230000000694 effects Effects 0.000 description 29
- 102220045277 rs587781972 Human genes 0.000 description 28
- 208000009292 Hemophilia A Diseases 0.000 description 25
- 102200135505 rs2273535 Human genes 0.000 description 25
- 230000015271 coagulation Effects 0.000 description 24
- 238000005345 coagulation Methods 0.000 description 24
- 102220057210 rs730880391 Human genes 0.000 description 24
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 23
- 239000000427 antigen Substances 0.000 description 23
- 108091007433 antigens Proteins 0.000 description 23
- 102000036639 antigens Human genes 0.000 description 23
- 238000000034 method Methods 0.000 description 23
- 102100026735 Coagulation factor VIII Human genes 0.000 description 22
- 102220523550 C-C motif chemokine 2_D91L_mutation Human genes 0.000 description 21
- 150000007523 nucleic acids Chemical class 0.000 description 20
- 201000003542 Factor VIII deficiency Diseases 0.000 description 19
- 230000035772 mutation Effects 0.000 description 18
- 108020004707 nucleic acids Proteins 0.000 description 18
- 102000039446 nucleic acids Human genes 0.000 description 18
- 239000013604 expression vector Substances 0.000 description 17
- 108010000499 Thromboplastin Proteins 0.000 description 16
- 102000002262 Thromboplastin Human genes 0.000 description 16
- 239000012634 fragment Substances 0.000 description 15
- 230000006872 improvement Effects 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 238000002965 ELISA Methods 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 101000653191 Mus musculus Tissue factor pathway inhibitor Proteins 0.000 description 11
- 102220476297 Retinaldehyde-binding protein 1_S21T_mutation Human genes 0.000 description 10
- 230000000903 blocking effect Effects 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 102220088091 rs768851540 Human genes 0.000 description 10
- 102220323550 rs940936212 Human genes 0.000 description 10
- 102100022641 Coagulation factor IX Human genes 0.000 description 9
- 208000032843 Hemorrhage Diseases 0.000 description 9
- 241001529936 Murinae Species 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 230000023555 blood coagulation Effects 0.000 description 9
- 230000035602 clotting Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 238000013169 thromboelastometry Methods 0.000 description 9
- 206010053567 Coagulopathies Diseases 0.000 description 8
- 102220614684 Ras-related protein Rab-3B_G56D_mutation Human genes 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 230000007812 deficiency Effects 0.000 description 8
- 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 8
- 210000004602 germ cell Anatomy 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 102220283790 rs1555932413 Human genes 0.000 description 8
- 102220272824 rs563079629 Human genes 0.000 description 8
- 102220475408 Acyl-coenzyme A thioesterase MBLAC2_S89A_mutation Human genes 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 229960000301 factor viii Drugs 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102200089631 rs5030808 Human genes 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 108010054265 Factor VIIa Proteins 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 208000031220 Hemophilia Diseases 0.000 description 6
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 6
- 238000012408 PCR amplification Methods 0.000 description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 description 6
- 102220501600 Putative uncharacterized protein UNQ6493/PRO21345_Y37F_mutation Human genes 0.000 description 6
- 102220572773 RNA-binding protein FUS_D91Q_mutation Human genes 0.000 description 6
- 102220614767 Ras-related protein Rab-3B_T36N_mutation Human genes 0.000 description 6
- 102220559259 Voltage-dependent L-type calcium channel subunit alpha-1C_V30L_mutation Human genes 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 208000034158 bleeding Diseases 0.000 description 6
- 230000000740 bleeding effect Effects 0.000 description 6
- 102220352372 c.148T>G Human genes 0.000 description 6
- 230000002860 competitive effect Effects 0.000 description 6
- 230000007547 defect Effects 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 230000036961 partial effect Effects 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 102220308785 rs749697322 Human genes 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 108010076282 Factor IX Proteins 0.000 description 5
- 108010054218 Factor VIII Proteins 0.000 description 5
- 102000001690 Factor VIII Human genes 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- 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 5
- 238000004458 analytical method Methods 0.000 description 5
- 208000011664 congenital factor XI deficiency Diseases 0.000 description 5
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 5
- 201000007219 factor XI deficiency Diseases 0.000 description 5
- 229960004222 factor ix Drugs 0.000 description 5
- 229940012414 factor viia Drugs 0.000 description 5
- 208000009429 hemophilia B Diseases 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 238000010606 normalization Methods 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 238000005215 recombination Methods 0.000 description 5
- 230000006798 recombination Effects 0.000 description 5
- 102220040517 rs146080119 Human genes 0.000 description 5
- 102200108151 rs17683011 Human genes 0.000 description 5
- 102220072337 rs794728990 Human genes 0.000 description 5
- 238000004904 shortening Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- 102220561506 Autophagy protein 5_K58M_mutation Human genes 0.000 description 4
- 102220600740 Calmodulin-binding transcription activator 1_Q1E_mutation Human genes 0.000 description 4
- 102220599536 Clathrin heavy chain 2_S98H_mutation Human genes 0.000 description 4
- 102100023804 Coagulation factor VII Human genes 0.000 description 4
- 108010023321 Factor VII Proteins 0.000 description 4
- 108010074860 Factor Xa Proteins 0.000 description 4
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 4
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 102220612320 Putative coiled-coil domain-containing protein 144 N-terminal-like_Y54F_mutation Human genes 0.000 description 4
- 102220465722 Serine/threonine-protein kinase ULK3_K44R_mutation Human genes 0.000 description 4
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 4
- 102220559219 Voltage-dependent L-type calcium channel subunit alpha-1C_S30R_mutation Human genes 0.000 description 4
- 102220395310 c.125T>A Human genes 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940012413 factor vii Drugs 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 238000003259 recombinant expression Methods 0.000 description 4
- 102200074432 rs104894779 Human genes 0.000 description 4
- 102220159156 rs142915569 Human genes 0.000 description 4
- 102220288745 rs1554040136 Human genes 0.000 description 4
- 102220012970 rs199742269 Human genes 0.000 description 4
- 102220036840 rs587780081 Human genes 0.000 description 4
- 102200004932 rs76764689 Human genes 0.000 description 4
- 102220250470 rs774802052 Human genes 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 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 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 3
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102220606828 Gap junction beta-1 protein_M34K_mutation Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 101710154606 Hemagglutinin Proteins 0.000 description 3
- 208000024659 Hemostatic disease Diseases 0.000 description 3
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 3
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101710176177 Protein A56 Proteins 0.000 description 3
- 108010094028 Prothrombin Proteins 0.000 description 3
- 102100027378 Prothrombin Human genes 0.000 description 3
- 102220628668 Splicing factor 3A subunit 1_K55L_mutation Human genes 0.000 description 3
- 102220600011 Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial_Q50R_mutation Human genes 0.000 description 3
- 102220600976 Syndecan-4_N26A_mutation Human genes 0.000 description 3
- 108010022394 Threonine synthase Proteins 0.000 description 3
- 102220599959 Transforming growth factor-beta-induced protein ig-h3_D62K_mutation Human genes 0.000 description 3
- 102220531786 Vacuolar protein sorting-associated protein 29_N39D_mutation Human genes 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000003114 blood coagulation factor Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000011260 co-administration Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 102000004419 dihydrofolate reductase Human genes 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000005714 functional activity Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 239000000185 hemagglutinin Substances 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 235000019799 monosodium phosphate Nutrition 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000000644 propagated effect Effects 0.000 description 3
- 229940039716 prothrombin Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 102200153431 rs1060501000 Human genes 0.000 description 3
- 102200068095 rs121913658 Human genes 0.000 description 3
- 102220340483 rs1555191854 Human genes 0.000 description 3
- 102220044529 rs587781374 Human genes 0.000 description 3
- 102220322421 rs763471932 Human genes 0.000 description 3
- 102220106607 rs773955198 Human genes 0.000 description 3
- 102220186128 rs886053020 Human genes 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000014621 translational initiation Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- PKYCWFICOKSIHZ-UHFFFAOYSA-N 1-(3,7-dihydroxyphenoxazin-10-yl)ethanone Chemical compound OC1=CC=C2N(C(=O)C)C3=CC=C(O)C=C3OC2=C1 PKYCWFICOKSIHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 102220545198 Carbohydrate sulfotransferase 6_N61T_mutation Human genes 0.000 description 2
- 102220640918 Cell division control protein 6 homolog_S54D_mutation Human genes 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102220518111 DNA-directed RNA polymerases I and III subunit RPAC2_L51R_mutation Human genes 0.000 description 2
- 102220476893 Developmental pluripotency-associated protein 3_S33G_mutation Human genes 0.000 description 2
- 102220466999 EH domain-binding protein 1-like protein 1_G33K_mutation Human genes 0.000 description 2
- 102220635184 Elongation factor G, mitochondrial_S57Y_mutation Human genes 0.000 description 2
- 108010062466 Enzyme Precursors Proteins 0.000 description 2
- 102000010911 Enzyme Precursors Human genes 0.000 description 2
- 108010014173 Factor X Proteins 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 102220476285 Retinaldehyde-binding protein 1_P54L_mutation Human genes 0.000 description 2
- 102220606700 Syndecan-1_F31H_mutation Human genes 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 102220559244 Voltage-dependent L-type calcium channel subunit alpha-1C_N32E_mutation Human genes 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000009175 antibody therapy Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000037029 cross reaction Effects 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 238000013480 data collection Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 238000002873 global sequence alignment Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229960000318 kanamycin Drugs 0.000 description 2
- 229930182823 kanamycin A Natural products 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 108010013773 recombinant FVIIa Proteins 0.000 description 2
- 229940068953 recombinant fviia Drugs 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 102220253208 rs1386720703 Human genes 0.000 description 2
- 102220209667 rs146472353 Human genes 0.000 description 2
- 102220276093 rs1555932427 Human genes 0.000 description 2
- 102200069953 rs28931601 Human genes 0.000 description 2
- 102220046415 rs587777600 Human genes 0.000 description 2
- 102220083467 rs863224774 Human genes 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 208000012908 vascular hemostatic disease Diseases 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108020004705 Codon Proteins 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
- 101150074155 DHFR gene Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101100395869 Escherichia coli sta3 gene Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 206010016077 Factor IX deficiency Diseases 0.000 description 1
- 108010074105 Factor Va Proteins 0.000 description 1
- 108010074864 Factor XI Proteins 0.000 description 1
- 108010000196 Factor XIIIa Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 108010054964 H-hexahydrotyrosyl-alanyl-arginine-4-nitroanilide Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001045988 Neogene Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000013544 Platelet disease Diseases 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101000653193 Rattus norvegicus Tissue factor pathway inhibitor Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 201000004283 Shwachman-Diamond syndrome Diseases 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
- 241000282898 Sus scrofa Species 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium 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
- 201000011510 cancer Diseases 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000004883 computer application Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid 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
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 102000057593 human F8 Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 101150091879 neo gene Proteins 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000009832 plasma treatment Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000005892 protein maturation Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- -1 sodium chloride Chemical compound 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- RPENMORRBUTCPR-UHFFFAOYSA-M sodium;1-hydroxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].ON1C(=O)CC(S([O-])(=O)=O)C1=O RPENMORRBUTCPR-UHFFFAOYSA-M 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000008733 trauma 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
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 230000003442 weekly effect Effects 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/38—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against protease inhibitors of peptide structure
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Filtering Materials (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30929010P | 2010-03-01 | 2010-03-01 | |
| US309290P | 2010-03-01 | ||
| PCT/US2011/026766 WO2011109452A1 (en) | 2010-03-01 | 2011-03-01 | Optimized Monoclonal Antibodies against Tissue Factor Pathway Inhibitor (TFPI) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2642512T3 true ES2642512T3 (es) | 2017-11-16 |
Family
ID=44542552
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11751244.2T Active ES2642512T3 (es) | 2010-03-01 | 2011-03-01 | Anticuerpos monoclonales optimizados contra el inhibidor de la ruta del factor tisular (TFPI) |
| ES17172199T Active ES2765418T3 (es) | 2010-03-01 | 2011-03-01 | Anticuerpos monoclonales optimizados contra el inhibidor de la ruta del factor tisular (TFPI) |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17172199T Active ES2765418T3 (es) | 2010-03-01 | 2011-03-01 | Anticuerpos monoclonales optimizados contra el inhibidor de la ruta del factor tisular (TFPI) |
Country Status (37)
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA112050C2 (uk) * | 2008-08-04 | 2016-07-25 | БАЄР ХЕЛСКЕР ЛЛСі | Терапевтична композиція, що містить моноклональне антитіло проти інгібітора шляху тканинного фактора (tfpi) |
| JP5714505B2 (ja) | 2008-12-22 | 2015-05-07 | ノヴォ ノルディスク アー／エス | 組織因子経路阻害因子に対する抗体 |
| CN110835373A (zh) * | 2010-03-01 | 2020-02-25 | 拜耳医药保健有限公司 | 针对组织因子途径抑制剂(tfpi)的优化的单克隆抗体 |
| JP2013533871A (ja) * | 2010-06-30 | 2013-08-29 | ノヴォ ノルディスク アー／エス | 組織因子経路インヒビターに特異的に結合することが可能な抗体 |
| EA034214B1 (ru) * | 2011-04-01 | 2020-01-17 | Байер Хелфкеа Ллк | Выделенное моноклональное антитело или его антигенсвязывающий фрагмент, который связывается с эпитопом ингибитора пути тканевого фактора человека, содержащая его фармацевтическая композиция, способ применения этой композиции и кодирующая антитело молекула нуклеиновой кислоты |
| KR20150030639A (ko) | 2012-03-30 | 2015-03-20 | 바이엘 헬스케어 엘엘씨 | 프로테아제로 조절된 항체 |
| US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
| UY35459A (es) * | 2013-03-15 | 2014-10-31 | Bayer Healthcare Llc | Anticuerpos profármaco contra el inhibidor de la vía del factor tisular |
| HRP20180078T1 (hr) * | 2013-03-15 | 2018-03-09 | Bayer Healthcare Llc | VARIJANTE ANTI-TFPI PROTUTIJELA S DIFERENCIJALNIM VEZANJEM U ŠIROKOM RASPONU pH RADI POBOLJŠANE FARMAKOKINETIKE |
| EP4279128A3 (en) * | 2015-02-25 | 2024-02-28 | Mogam Institute for Biomedical Research | Novel antibody binding to tfpi and composition comprising the same |
| KR102068915B1 (ko) | 2015-08-19 | 2020-01-22 | 화이자 인코포레이티드 | 조직 인자 경로 억제제 항체 및 그의 용도 |
| KR102337683B1 (ko) * | 2018-09-21 | 2021-12-13 | 주식회사 녹십자 | 고효율 항-tfpi 항체 조성물 |
| MX2021004120A (es) * | 2018-10-11 | 2021-09-10 | Pfizer | Regimen de dosificacion para antagonistas de tfpi. |
| KR102692277B1 (ko) * | 2019-03-11 | 2024-08-05 | 현대자동차주식회사 | 상용 전기차용 모터 마운트 |
| CN112442127A (zh) * | 2019-08-29 | 2021-03-05 | 苏州康宁杰瑞生物科技有限公司 | 针对tfpi的单克隆抗体 |
| KR20220065719A (ko) * | 2020-11-13 | 2022-05-20 | 한미약품 주식회사 | 치료학적 효소 융합단백질의 파브리병에 기인하거나 동반되는 신장질환 예방 및 치료 용도 |
| CN117285632A (zh) * | 2022-06-17 | 2023-12-26 | 安源医药科技（上海）有限公司 | 针对tfpi的单克隆抗体及其用途 |
Family Cites Families (207)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1064396A (en) | 1975-02-18 | 1979-10-16 | Myer L. Coval | Fractional precipitation of gamma globulin with polyethylene glycol |
| US4075193A (en) | 1976-11-26 | 1978-02-21 | Parke, Davis & Company | Process for producing intravenous immune globulin |
| US4374763A (en) | 1979-09-17 | 1983-02-22 | Morishita Pharmaceutical Co., Ltd. | Method for producing gamma-globulin for use in intravenous administration and method for producing a pharmaceutical preparation thereof |
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4499073A (en) | 1981-08-24 | 1985-02-12 | Cutter Laboratories, Inc. | Intravenously injectable immune serum globulin |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4597966A (en) | 1985-01-09 | 1986-07-01 | Ortho Diagnostic Systems, Inc. | Histidine stabilized immunoglobulin and method of preparation |
| US4966852A (en) | 1987-07-23 | 1990-10-30 | Monsanto Company | DNA clone of human tissue factor inhibitor |
| ATE82506T1 (de) | 1987-08-21 | 1992-12-15 | Imcera Group Inc | Stabilisierung von wachstumshormonen. |
| US4877608A (en) | 1987-11-09 | 1989-10-31 | Rorer Pharmaceutical Corporation | Pharmaceutical plasma protein formulations in low ionic strength media |
| US5096885A (en) | 1988-04-15 | 1992-03-17 | Genentech, Inc. | Human growth hormone formulation |
| WO1989011297A1 (en) | 1988-05-27 | 1989-11-30 | Centocor, Inc. | Freeze-dried formulation for antibody products |
| CA2049342A1 (en) | 1989-03-27 | 1990-09-28 | Sally Bolmer | Formulations for stabilizing of igm antibodies |
| US6969586B1 (en) | 1989-05-16 | 2005-11-29 | Scripps Research Institute | Method for tapping the immunological repertoire |
| US5217954A (en) | 1990-04-04 | 1993-06-08 | Scios Nova Inc. | Formulations for stabilizing fibroblast growth factor |
| US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| DK261490D0 (da) | 1990-10-31 | 1990-10-31 | Novo Nordisk As | New pharmaceutical compound |
| JPH0565233A (ja) | 1991-03-08 | 1993-03-19 | Mitsui Toatsu Chem Inc | モノクローナル抗体含有凍結乾燥製剤 |
| US6165467A (en) | 1991-07-20 | 2000-12-26 | Yoshihide Hagiwara | Stabilized human monoclonal antibody preparation |
| GB9122820D0 (en) | 1991-10-28 | 1991-12-11 | Wellcome Found | Stabilised antibodies |
| EP0539975A1 (en) | 1991-10-31 | 1993-05-05 | Teijin Limited | Method for immunological assay of free lipoprotein-associated coagulation inhibitor (LACI) and kit therefor |
| US5849700A (en) | 1991-12-20 | 1998-12-15 | Novo Nordisk A/S | Pharmaceutical formulation |
| DE4223132A1 (de) | 1992-07-14 | 1994-01-20 | Deutsche Aerospace | Verfahren zur Schrittakt-Regeneration bei der Demodulation von digital modulierten Signalen und Anordnung zum Ausführen des Verfahrens |
| JPH06153985A (ja) | 1992-11-16 | 1994-06-03 | Teijin Ltd | モノクローナル抗体 |
| ATE197550T1 (de) | 1993-02-23 | 2000-12-15 | Genentech Inc | Stabilisierung von mit organischen lösungsmittel behandelten polypeptiden mit einem hilfsstoff |
| US5455338A (en) | 1993-11-05 | 1995-10-03 | Zymogenetics, Inc. | DNA encoding novel human kunitz-type inhibitors and methods relating thereto |
| DE4344824C1 (de) | 1993-12-28 | 1995-08-31 | Immuno Ag | Hochkonzentriertes Immunglobulin-Präparat und Verfahren zu seiner Herstellung |
| US5580856A (en) | 1994-07-15 | 1996-12-03 | Prestrelski; Steven J. | Formulation of a reconstituted protein, and method and kit for the production thereof |
| JPH0875736A (ja) | 1994-09-06 | 1996-03-22 | Chemo Sero Therapeut Res Inst | ヒト組織因子凝固系インヒビターの定量法 |
| GB9418092D0 (en) | 1994-09-08 | 1994-10-26 | Red Cross Found Cent Lab Blood | Organic compounds |
| US6111079A (en) | 1995-06-05 | 2000-08-29 | Bionebraska, Inc. | Lead binding polypeptides and nucleotides coding therefore |
| WO1997004801A1 (en) | 1995-07-27 | 1997-02-13 | Genentech, Inc. | Stabile isotonic lyophilized protein formulation |
| US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
| US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| US5902582A (en) | 1995-09-05 | 1999-05-11 | Chiron Corporation | Use of TFPI inhibitor for treatment of cancer |
| US6686191B1 (en) | 1995-09-22 | 2004-02-03 | Bayer Healthcare Llc | Preparation of virally inactivated intravenously injectable immune serum globulin |
| US7368111B2 (en) * | 1995-10-06 | 2008-05-06 | Cambridge Antibody Technology Limited | Human antibodies specific for TGFβ2 |
| JP3681206B2 (ja) * | 1995-12-26 | 2005-08-10 | 株式会社三菱化学ヤトロン | 抗ファクターＸａ・ティシュファクターパスウェイインヒビター複合体モノクローナル抗体及びその使用 |
| DE59710863D1 (de) | 1996-01-25 | 2003-11-20 | Schering Ag | Verbesserte kontrastmittenlösungen für die intravasale anwendung |
| US5770700A (en) | 1996-01-25 | 1998-06-23 | Genetics Institute, Inc. | Liquid factor IX formulations |
| KR100236393B1 (ko) | 1996-02-02 | 1999-12-15 | 나까니시 히로유끼 | 사람성장호르몬을 함유하는 의약제제 |
| TWI240627B (en) | 1996-04-26 | 2005-10-01 | Chugai Pharmaceutical Co Ltd | Erythropoietin solution preparation |
| GB9610992D0 (en) | 1996-05-24 | 1996-07-31 | Glaxo Group Ltd | Concentrated antibody preparation |
| US20040052799A1 (en) | 1996-11-15 | 2004-03-18 | Astra Aktiebolag | Nucleic acid and amino acid sequences relating to Helicobacter pylori for diagnostics and therapeutics |
| EP0852951A1 (de) | 1996-11-19 | 1998-07-15 | Roche Diagnostics GmbH | Stabile lyophilisierte pharmazeutische Zubereitungen von mono- oder polyklonalen Antikörpern |
| US6593291B1 (en) | 1997-02-06 | 2003-07-15 | Entremed, Inc. | Compositions and methods of use of ligands that bind components of the blood coagulation/clotting pathway for the treatment of cancer and angiogenic-based disease |
| DE69833545T2 (de) | 1997-03-26 | 2006-12-14 | Imperial College Innovations Ltd. | In der zellmembran verankertes antikoagulant-fusionsprotein |
| US5994511A (en) | 1997-07-02 | 1999-11-30 | Genentech, Inc. | Anti-IgE antibodies and methods of improving polypeptides |
| US6531298B2 (en) | 1997-07-21 | 2003-03-11 | The University Of North Carolina At Chapel Hill | Factor IX antihemophilic factor with increased clotting activity |
| US6617156B1 (en) | 1997-08-15 | 2003-09-09 | Lynn A. Doucette-Stamm | Nucleic acid and amino acid sequences relating to Enterococcus faecalis for diagnostics and therapeutics |
| EP1005776B1 (de) | 1997-08-21 | 2003-01-08 | Siemens Aktiengesellschaft | Verfahren zum übertragen von nutzdaten, die unterschiedlichen anwendungen zuordenbar sind |
| US6551795B1 (en) | 1998-02-18 | 2003-04-22 | Genome Therapeutics Corporation | Nucleic acid and amino acid sequences relating to pseudomonas aeruginosa for diagnostics and therapeutics |
| AU3006799A (en) | 1998-03-12 | 1999-09-27 | Human Genome Sciences, Inc. | 31 human secreted proteins |
| GB9820525D0 (en) | 1998-09-21 | 1998-11-11 | Allergy Therapeutics Ltd | Formulation |
| US6818749B1 (en) | 1998-10-31 | 2004-11-16 | The United States Of America As Represented By The Department Of Health And Human Services | Variants of humanized anti carcinoma monoclonal antibody cc49 |
| JP2000247903A (ja) | 1999-03-01 | 2000-09-12 | Chugai Pharmaceut Co Ltd | 長期安定化製剤 |
| US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
| US20040031072A1 (en) | 1999-05-06 | 2004-02-12 | La Rosa Thomas J. | Soy nucleic acid molecules and other molecules associated with transcription plants and uses thereof for plant improvement |
| US20090087878A9 (en) | 1999-05-06 | 2009-04-02 | La Rosa Thomas J | Nucleic acid molecules associated with plants |
| US20100293669A2 (en) | 1999-05-06 | 2010-11-18 | Jingdong Liu | Nucleic Acid Molecules and Other Molecules Associated with Plants and Uses Thereof for Plant Improvement |
| WO2001024814A1 (en) | 1999-10-04 | 2001-04-12 | Chiron Corporation | Stabilized liquid polypeptide-containing pharmaceutical compositions |
| US20050208558A1 (en) | 1999-10-19 | 2005-09-22 | Applera Corporation | Detection kits, such as nucleic acid arrays, for detecting the expression or 10,000 or more Drosophila genes and uses thereof |
| JP4623825B2 (ja) | 1999-12-16 | 2011-02-02 | 協和発酵バイオ株式会社 | 新規ポリヌクレオチド |
| US20020160934A1 (en) | 2000-01-14 | 2002-10-31 | Julie Broadus | Nucleic acid sequences from Drosophila melanogaster that encode proteins essential for larval viability and uses thereof |
| US20030232054A1 (en) | 2000-01-25 | 2003-12-18 | Tang Y. Tom | Novel nucleic acids and polypeptides |
| JP4683810B2 (ja) | 2000-02-29 | 2011-05-18 | 中外製薬株式会社 | 長期安定化製剤 |
| ATE363915T1 (de) | 2000-04-07 | 2007-06-15 | Signal Coordinating Therapy In | Methoden und zusammensetzungen zur behandlung von neoplasmen |
| US20110131679A2 (en) | 2000-04-19 | 2011-06-02 | Thomas La Rosa | Rice Nucleic Acid Molecules and Other Molecules Associated with Plants and Uses Thereof for Plant Improvement |
| US7834146B2 (en) | 2000-05-08 | 2010-11-16 | Monsanto Technology Llc | Recombinant polypeptides associated with plants |
| US20040181830A1 (en) | 2001-05-07 | 2004-09-16 | Kovalic David K. | Nucleic acid molecules and other molecules associated with plants and uses thereof for plant improvement |
| US7015194B2 (en) * | 2000-05-10 | 2006-03-21 | Novo Nordisk A/S | Pharmaceutical composition comprising factor VIIa and anti-TFPI |
| US20020082206A1 (en) | 2000-05-30 | 2002-06-27 | Leach Martin D. | Novel polynucleotides from atherogenic cells and polypeptides encoded thereby |
| ES2609583T3 (es) | 2000-06-16 | 2017-04-21 | Human Genome Sciences, Inc. | Anticuerpos que se unen inmunoespecíficamente a BLyS |
| JP5490972B2 (ja) | 2000-08-04 | 2014-05-14 | 中外製薬株式会社 | タンパク質注射製剤 |
| DK1314437T3 (da) | 2000-08-11 | 2014-07-14 | Chugai Pharmaceutical Co Ltd | Stabiliserede antistofindeholdende præparater |
| WO2002017957A1 (en) | 2000-09-01 | 2002-03-07 | Chugai Seiyaku Kabushiki Kaisha | Solution preparations stabilized over long time |
| CA2423227C (en) | 2000-10-12 | 2011-11-29 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
| US6912470B2 (en) | 2001-05-21 | 2005-06-28 | Ecopia Biosciences, Inc. | Genes and proteins involved in the biosynthesis of enediyne ring structures |
| US7214786B2 (en) | 2000-12-14 | 2007-05-08 | Kovalic David K | Nucleic acid molecules and other molecules associated with plants and uses thereof for plant improvement |
| GB0101879D0 (en) | 2001-01-24 | 2001-03-07 | Enzyme Res Lab Ltd | Anticoagulants and their uses |
| CA2434323A1 (en) | 2001-02-07 | 2002-11-28 | Centre National De La Recherche Scientifique (Cnrs) | Sequence of the photorhabdus luminescens strain tt01 genome and uses |
| GB0103424D0 (en) | 2001-02-12 | 2001-03-28 | Chiron Spa | Gonococcus proteins |
| US7667004B2 (en) * | 2001-04-17 | 2010-02-23 | Abmaxis, Inc. | Humanized antibodies against vascular endothelial growth factor |
| US6891085B2 (en) | 2001-04-20 | 2005-05-10 | Pioneer Hi-Bred International, Inc. | Nucleic acid encoding the FUS6 antimicrobial polypeptide of Agrotis ipsilon and its use to enhance disease resistance in a plant |
| GB0113179D0 (en) | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
| US20030113316A1 (en) | 2001-07-25 | 2003-06-19 | Kaisheva Elizabet A. | Stable lyophilized pharmaceutical formulation of IgG antibodies |
| US20040142325A1 (en) | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
| US7262278B2 (en) | 2001-10-15 | 2007-08-28 | Kirin Beer Kabushiki Kaisha | Anti-HLA-DR antibody |
| MXPA04003640A (es) | 2001-10-16 | 2005-04-11 | Rxkinetix Inc | Formulaciones de proteina de alta concentracion y metodo de fabricacion. |
| US20040029129A1 (en) | 2001-10-25 | 2004-02-12 | Liangsu Wang | Identification of essential genes in microorganisms |
| WO2003037172A2 (en) | 2001-11-01 | 2003-05-08 | Gpc Biotech Inc. | Endothelial-cell binding peptides for diagnosis and therapy |
| JP5290489B2 (ja) | 2001-11-08 | 2013-09-18 | アッヴィ・バイオセラピューティクス・インコーポレイテッド | Ｉｇｇ抗体の安定な液体医薬製剤 |
| EP1461353A4 (en) | 2001-11-29 | 2006-05-03 | Wyeth Corp | OPEN READING FRAMES (ORF) OF BACTERIUM ALLOIOCOCCUS OTITIDIS ENCODING ANTIGENIC POLYPEPTIDES, IMUNOGENIC COMPOSITIONS, AND USES THEREOF |
| US20030138416A1 (en) | 2001-12-03 | 2003-07-24 | Jesper Lau | Use of glucokinase activator in combination with a glucagon antagonist for treating type 2 diabetes |
| US20050108791A1 (en) | 2001-12-04 | 2005-05-19 | Edgerton Michael D. | Transgenic plants with improved phenotypes |
| US7452539B2 (en) | 2001-12-19 | 2008-11-18 | Genentech, Inc. | Stabilizing polypeptides which have been exposed to urea |
| AU2003225535A1 (en) | 2002-01-31 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Methods and compositions for treating cancer |
| KR20110091822A (ko) | 2002-02-14 | 2011-08-12 | 추가이 세이야쿠 가부시키가이샤 | 항체함유 용액제제 |
| US7314974B2 (en) | 2002-02-21 | 2008-01-01 | Monsanto Technology, Llc | Expression of microbial proteins in plants for production of plants with improved properties |
| SI1946776T1 (sl) | 2002-02-27 | 2017-07-31 | Immunex Corporation | Stabiliziran tnfr-fc sestavek, ki obsega arginin |
| US20060068386A1 (en) | 2002-03-04 | 2006-03-30 | Alexei Slesarev | Complete genome and protein sequence of the hyperthermophile methanopyrus kandleri av19 and monophyly of archael methanogens and methods of use thereof |
| US7074559B2 (en) | 2002-03-06 | 2006-07-11 | Refents of the University of Minnesota | Mycobacterial diagnostics |
| IL149820A0 (en) | 2002-05-23 | 2002-11-10 | Curetech Ltd | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
| US7425618B2 (en) | 2002-06-14 | 2008-09-16 | Medimmune, Inc. | Stabilized anti-respiratory syncytial virus (RSV) antibody formulations |
| US20040022792A1 (en) | 2002-06-17 | 2004-02-05 | Ralph Klinke | Method of stabilizing proteins at low pH |
| JP2005530845A (ja) | 2002-06-21 | 2005-10-13 | アイデック ファーマシューティカルズ コーポレイション | 抗体を濃縮するための緩衝化処方物およびその使用方法 |
| AU2003256299A1 (en) | 2002-07-01 | 2004-01-19 | Human Genome Sciences, Inc. | Antibodies that specifically bind to reg iv |
| EP1539212A4 (en) | 2002-07-12 | 2007-05-02 | Medarex Inc | METHOD AND COMPOSITIONS FOR PREVENTING OXIDATIVE DEGRADATION OF PROTEINS |
| US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
| DE10239073A1 (de) | 2002-08-26 | 2004-03-11 | Basf Ag | Verfahren zur fermentativen Herstellung schwefelhaltiger Feinchemikalien |
| SI1556083T1 (sl) | 2002-10-08 | 2011-05-31 | Rinat Neuroscience Corp | Postopki za zdravljenje postoperativne bolečine z dajanjem protitelesa proti živčnemu rastnemu faktorju in sestavki, ki ga vsebujejo |
| KR100542401B1 (ko) | 2002-10-23 | 2006-01-11 | 한국전자통신연구원 | 인터넷 차별 서비스 망에서의 연결 수락 제어방법 |
| WO2004050850A2 (en) | 2002-12-02 | 2004-06-17 | Abgenix, Inc. | Antibodies directed to phospholipase a2 and uses thereof |
| WO2004055164A2 (en) | 2002-12-13 | 2004-07-01 | Abgenix, Inc. | System and method for stabilizing antibodies with histidine |
| US7569364B2 (en) | 2002-12-24 | 2009-08-04 | Pfizer Inc. | Anti-NGF antibodies and methods using same |
| AU2003299898B2 (en) | 2002-12-24 | 2010-12-16 | Rinat Neuroscience Corp. | Anti-NGF antibodies and methods using same |
| EP2853593B1 (en) | 2003-03-07 | 2017-10-04 | DSM IP Assets B.V. | Hydrolases, nucleic acids encoding them and mehods for making and using them |
| US20050158303A1 (en) | 2003-04-04 | 2005-07-21 | Genentech, Inc. | Methods of treating IgE-mediated disorders comprising the administration of high concentration anti-IgE antibody formulations |
| ZA200507757B (en) | 2003-04-04 | 2007-01-31 | Genentech Inc | High concentration antibody and protein formulations |
| CN1930187B (zh) * | 2003-06-27 | 2015-08-19 | 艾默根佛蒙特有限公司 | 针对表皮生长因子受体的缺失突变体的抗体及其使用 |
| PL1648509T3 (pl) | 2003-07-15 | 2013-02-28 | Amgen Inc | Ludzkie neutralizujące przeciwciała anty-NGF jako selektywne inhibitory szlaku NGF |
| CN103880955A (zh) | 2003-07-18 | 2014-06-25 | 安姆根有限公司 | 肝细胞生长因子的特异性结合物 |
| US7871610B2 (en) | 2003-08-12 | 2011-01-18 | Dyax Corp. | Antibodies to Tie1 ectodomain |
| US20060107345A1 (en) | 2003-09-30 | 2006-05-18 | Nickolai Alexandrov | Sequence-determined DNA fragments and corresponding polypeptides encoded thereby |
| WO2005033143A1 (ja) | 2003-10-01 | 2005-04-14 | Kyowa Hakko Kogyo Co., Ltd. | 抗体の安定化方法及び安定化された溶液状抗体製剤 |
| CA2445743A1 (en) | 2003-10-08 | 2005-04-08 | The University Of British Columbia | Methods for modulating neuronal responses |
| EP1532983A1 (en) | 2003-11-18 | 2005-05-25 | ZLB Bioplasma AG | Immunoglobulin preparations having increased stability |
| DE602004026474D1 (de) | 2003-12-03 | 2010-05-20 | Univ Rochester | Rekombinanter faktor viii mit erhöhter spezifischer aktivität |
| JPWO2005063291A1 (ja) | 2003-12-25 | 2007-07-19 | 麒麟麦酒株式会社 | 抗体を含有する安定な水性医薬製剤 |
| US7494798B2 (en) | 2004-01-09 | 2009-02-24 | Novozymes, Inc. | Bacillus licheniformis chromosome |
| US20060041961A1 (en) | 2004-03-25 | 2006-02-23 | Abad Mark S | Genes and uses for pant improvement |
| BRPI0511479C1 (pt) | 2004-05-27 | 2021-05-25 | Crucell Holland Bv | molécula de ligação tendo atividade neutralizadora do vìrus da raiva, variante funcional de uma molécula de ligação, imunoconjugado, molécula de ácido nucléico, vetor, hospedeiro, método para produzir uma molécula de ligação ou uma variante funcional, composição farmacêutica, uso de uma molécula de ligação, uma variante funcional, um imunoconjugado como, ou uma composição, kit, método para identificar uma molécula de ligação ou uma molécula de ácido nucléico, e, coleção de moléculas de ligação humanas na superfìcie de pacotes genéticos replicáveis |
| CA2564791A1 (en) | 2004-06-14 | 2005-12-29 | Medimmune Vaccines, Inc. | High pressure spray-dry of bioactive materials |
| CA2573293A1 (en) | 2004-07-10 | 2006-02-16 | Alexion Pharmaceuticals, Inc. | Methods for discovering antibodies specific to cancer cells and antibodies discovered thereby |
| US20080008719A1 (en) | 2004-07-10 | 2008-01-10 | Bowdish Katherine S | Methods and compositions for the treatment of prostate cancer |
| US20060075522A1 (en) | 2004-07-31 | 2006-04-06 | Jaclyn Cleveland | Genes and uses for plant improvement |
| US20060051347A1 (en) | 2004-09-09 | 2006-03-09 | Winter Charles M | Process for concentration of antibodies and therapeutic products thereof |
| JO3000B1 (ar) | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
| PL1838733T3 (pl) | 2004-12-21 | 2012-02-29 | Medimmune Ltd | Przeciwciała skierowane przeciwko angiopoetynie-2 i ich zastosowania |
| US20080148432A1 (en) | 2005-12-21 | 2008-06-19 | Mark Scott Abad | Transgenic plants with enhanced agronomic traits |
| US7566772B2 (en) | 2005-01-26 | 2009-07-28 | Amgen Fremont Inc. | Antibodies against interleukin-1β |
| PT1848744E (pt) | 2005-01-27 | 2012-04-24 | Novimmune Sa | Anticorpos anti-interferão gama e os seus processos de utilização |
| GT200600031A (es) | 2005-01-28 | 2006-08-29 | Formulacion anticuerpo anti a beta | |
| DOP2006000022A (es) | 2005-01-28 | 2006-08-15 | Wyeth Corp | Formulaciones líquidas estabilizadas de polipetidos |
| PT1850873T (pt) | 2005-02-08 | 2019-02-19 | Genzyme Corp | Anticorpos contra tgfbeta |
| US8088976B2 (en) | 2005-02-24 | 2012-01-03 | Monsanto Technology Llc | Methods for genetic control of plant pest infestation and compositions thereof |
| AU2006219823A1 (en) | 2005-03-02 | 2006-09-08 | Metanomics Gmbh | Process for the production of fine chemicals |
| JP2008531692A (ja) | 2005-03-04 | 2008-08-14 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・イリノイ | 凝固及び線維素溶解カスケードのモジュレーター |
| PL2620450T3 (pl) | 2005-03-08 | 2019-05-31 | Pfizer Prod Inc | Kompozycje przeciwciała anty-CTLA-4 |
| JP2006249082A (ja) | 2005-03-08 | 2006-09-21 | Pharmacia & Upjohn Co Llc | 低減レベルの内毒素を有する抗ｍ−ｃｓｆ抗体組成物 |
| US7785595B2 (en) | 2005-04-18 | 2010-08-31 | Yeda Research And Development Company Limited | Stabilized anti-hepatitis B (HBV) antibody formulations |
| US7889636B2 (en) | 2005-05-24 | 2011-02-15 | Cisco Technology, Inc. | System and method for implementing a mid-call policy in a RSVP environment |
| GB2426887B (en) | 2005-06-04 | 2009-01-07 | Ibm | Client responsibilities in messaging systems |
| ATE501248T1 (de) | 2005-07-02 | 2011-03-15 | Arecor Ltd | Stabile wässrige systeme mit proteinen |
| NZ599176A (en) | 2005-08-03 | 2014-04-30 | Immunogen Inc | Immunoconjugate formulations |
| AU2006295340B2 (en) | 2005-08-05 | 2010-11-11 | Amgen Inc. | Stable aqueous protein or antibody pharmaceutical formulations and their preparation |
| US20070086433A1 (en) | 2005-10-19 | 2007-04-19 | Cunetto Philip C | Methods and apparatus for allocating shared communication resources to outdial communication services |
| CN101360821A (zh) | 2005-11-21 | 2009-02-04 | 圣诺菲·帕斯图尔有限公司 | 重组病毒的稳定制剂 |
| CA2631327C (en) | 2005-12-02 | 2015-10-13 | Genentech, Inc. | Her2 binding polypeptides and uses thereof |
| US7669228B2 (en) | 2005-12-27 | 2010-02-23 | Cisco Technology, Inc. | System and method for changing network behavior based on presence information |
| WO2007074880A1 (ja) | 2005-12-28 | 2007-07-05 | Chugai Seiyaku Kabushiki Kaisha | 抗体含有安定化製剤 |
| KR20080098504A (ko) | 2006-02-03 | 2008-11-10 | 메디뮨 엘엘씨 | 단백질 제제 |
| DE102006005094A1 (de) | 2006-02-04 | 2007-08-09 | Degussa Gmbh | Titandioxid und Polycarboxylatether enthaltende Dispersion |
| US7790862B2 (en) | 2006-06-13 | 2010-09-07 | Zymogenetics, Inc. | IL-17 and IL-23 antagonists and methods of using the same |
| US20070224627A1 (en) | 2006-03-23 | 2007-09-27 | Lawrence Horowitz | Facilitation of translocation of molecules through the gastrointestinal tract |
| EA200870538A1 (ru) | 2006-06-14 | 2009-04-28 | Имклоун Системз Инкорпорейтед | Лиофилизированные композиции анти-egfr антител |
| ES2531933T3 (es) | 2006-06-30 | 2015-03-20 | Novo Nordisk A/S | Anticuerpos anti-NKG2A y usos de los mismos |
| US8355333B2 (en) | 2006-08-31 | 2013-01-15 | Ciena Corporation | Methods and systems for session initiation protocol control of network equipment |
| JP2010506839A (ja) | 2006-10-12 | 2010-03-04 | ワイス エルエルシー | 乳光の低減を伴う方法および組成物 |
| AU2007331712A1 (en) | 2006-12-11 | 2008-06-19 | F. Hoffmann-La Roche Ag | Abeta antibody parenteral formulation |
| US20100209434A1 (en) | 2007-03-30 | 2010-08-19 | Medimmune, Llc | Antibody formulation |
| GB0707938D0 (en) | 2007-04-25 | 2007-05-30 | Univ Strathclyde | Precipitation stabilising compositions |
| TR201820837T4 (tr) | 2007-06-14 | 2019-01-21 | Biogen Ma Inc | Natalizumab antikor formülasyonları. |
| UA107557C2 (xx) | 2007-07-06 | 2015-01-26 | Композиція антитіла офатумумабу | |
| DK3002298T3 (da) * | 2007-11-21 | 2019-10-28 | Univ Oregon Health & Science | Anti-faktor xi monoklonale antistoffer og fremgangsmåder til anvendelse deraf |
| EP2225275A4 (en) | 2007-11-28 | 2013-04-03 | Medimmune Llc | PROTEIN FORMULATION |
| DK2222706T4 (en) | 2007-12-14 | 2016-11-21 | Novo Nordisk As | Antibodies that bind to NKG2D and its use |
| AU2008340429C1 (en) | 2007-12-21 | 2016-09-08 | F. Hoffmann-La Roche Ag | Antibody formulation |
| WO2009083225A2 (en) | 2007-12-28 | 2009-07-09 | Biolnvent International Ab | Formulation |
| KR20100117120A (ko) | 2008-02-20 | 2010-11-02 | 지투 인플레메이션 피티와이 엘티디 | 인간화된 항-Ｃ5ａＲ 항체 |
| WO2009120684A1 (en) | 2008-03-25 | 2009-10-01 | Medimmune, Llc | Antibody formulation |
| JP2011526591A (ja) | 2008-06-30 | 2011-10-13 | ノボ・ノルデイスク・エー／エス | 抗ヒトインターロイキン−２０抗体 |
| UA112050C2 (uk) * | 2008-08-04 | 2016-07-25 | БАЄР ХЕЛСКЕР ЛЛСі | Терапевтична композиція, що містить моноклональне антитіло проти інгібітора шляху тканинного фактора (tfpi) |
| PL2331090T3 (pl) | 2008-09-19 | 2018-05-30 | Pfizer Inc. | Stabilny ciekły preparat przeciwciała |
| CN102301235B (zh) | 2008-11-28 | 2014-11-19 | Abbvie公司 | 稳定的抗体组合物和用于稳定其的方法 |
| EP2196476A1 (en) | 2008-12-10 | 2010-06-16 | Novartis Ag | Antibody formulation |
| US8466108B2 (en) | 2008-12-19 | 2013-06-18 | Baxter International Inc. | TFPI inhibitors and methods of use |
| US8618263B2 (en) | 2008-12-22 | 2013-12-31 | Novo Nordisk A/S | Antibodies against tissue factor pathway inhibitor (TFPI) |
| JP5714505B2 (ja) | 2008-12-22 | 2015-05-07 | ノヴォ ノルディスク アー／エス | 組織因子経路阻害因子に対する抗体 |
| AR076640A1 (es) | 2009-03-06 | 2011-06-29 | Genentech Inc | Formulacion con anticuerpo. metodo para estabilizar anticuerpo. articulo de manufactura |
| WO2010148337A1 (en) | 2009-06-18 | 2010-12-23 | Wyeth Llc | Lyophilized formulations for small modular immunopharmaceuticals |
| WO2011026945A1 (en) | 2009-09-03 | 2011-03-10 | Ablynx N.V. | Stable formulations of polypeptides and uses thereof |
| EP2332995A1 (en) | 2009-12-10 | 2011-06-15 | Bayer Schering Pharma Aktiengesellschaft | Neutralizing prolactin receptor antibodies and their therapeutic use |
| JP2013520476A (ja) | 2010-02-26 | 2013-06-06 | ノヴォ ノルディスク アー／エス | 安定な抗体含有組成物 |
| CN110835373A (zh) * | 2010-03-01 | 2020-02-25 | 拜耳医药保健有限公司 | 针对组织因子途径抑制剂(tfpi)的优化的单克隆抗体 |
| AU2011227714B2 (en) | 2010-03-19 | 2014-09-04 | Takeda Pharmaceutical Company Limited | TFPI inhibitors and methods of use |
| KR20130086144A (ko) | 2010-05-28 | 2013-07-31 | 노보 노르디스크 에이/에스 | 항체 및 보존제를 포함하는 안정한 다중-투여 조성물 |
| EP2673364A1 (en) | 2011-02-11 | 2013-12-18 | Baxter International Inc | Aptamers to tissue factor pathway inhibitor and their use as bleeding disorder therapeutics |
| EA034214B1 (ru) | 2011-04-01 | 2020-01-17 | Байер Хелфкеа Ллк | Выделенное моноклональное антитело или его антигенсвязывающий фрагмент, который связывается с эпитопом ингибитора пути тканевого фактора человека, содержащая его фармацевтическая композиция, способ применения этой композиции и кодирующая антитело молекула нуклеиновой кислоты |
| AU2013235567A1 (en) | 2012-03-22 | 2014-10-09 | Baxalta GmbH | Aptamers to tissue factor pathway inhibitor and their use as bleeding disorder therapeutics |
| US8613919B1 (en) | 2012-08-31 | 2013-12-24 | Bayer Healthcare, Llc | High concentration antibody and protein formulations |
| US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
| HRP20180078T1 (hr) | 2013-03-15 | 2018-03-09 | Bayer Healthcare Llc | VARIJANTE ANTI-TFPI PROTUTIJELA S DIFERENCIJALNIM VEZANJEM U ŠIROKOM RASPONU pH RADI POBOLJŠANE FARMAKOKINETIKE |
| EP4279128A3 (en) | 2015-02-25 | 2024-02-28 | Mogam Institute for Biomedical Research | Novel antibody binding to tfpi and composition comprising the same |
| KR102068915B1 (ko) | 2015-08-19 | 2020-01-22 | 화이자 인코포레이티드 | 조직 인자 경로 억제제 항체 및 그의 용도 |
-
2011
- 2011-03-01 CN CN201911010357.7A patent/CN110835373A/zh active Pending
- 2011-03-01 CN CN201180022078.8A patent/CN102939098B/zh not_active Expired - Fee Related
- 2011-03-01 JP JP2012556192A patent/JP6025570B2/ja not_active Expired - Fee Related
- 2011-03-01 US US13/582,401 patent/US9309324B2/en not_active Ceased
- 2011-03-01 KR KR1020197012160A patent/KR20190047135A/ko not_active Ceased
- 2011-03-01 PL PL17172199T patent/PL3345615T3/pl unknown
- 2011-03-01 DK DK17172199.6T patent/DK3345615T3/da active
- 2011-03-01 EA EA201290849A patent/EA032189B9/ru not_active IP Right Cessation
- 2011-03-01 KR KR1020127025683A patent/KR101807894B1/ko not_active Expired - Fee Related
- 2011-03-01 AU AU2011223710A patent/AU2011223710B2/en not_active Ceased
- 2011-03-01 US US15/208,498 patent/USRE47150E1/en not_active Expired - Fee Related
- 2011-03-01 CA CA2791685A patent/CA2791685C/en not_active Expired - Fee Related
- 2011-03-01 SI SI201131830T patent/SI3345615T1/sl unknown
- 2011-03-01 CA CA2976671A patent/CA2976671C/en not_active Expired - Fee Related
- 2011-03-01 WO PCT/US2011/026766 patent/WO2011109452A1/en not_active Ceased
- 2011-03-01 EP EP11751244.2A patent/EP2542257B1/en active Active
- 2011-03-01 SM SM20170454T patent/SMT201700454T1/it unknown
- 2011-03-01 PT PT171721996T patent/PT3345615T/pt unknown
- 2011-03-01 DK DK11751244.2T patent/DK2542257T3/en active
- 2011-03-01 EA EA201892184A patent/EA201892184A1/ru unknown
- 2011-03-01 LT LTEP11751244.2T patent/LT2542257T/lt unknown
- 2011-03-01 CN CN201610539997.7A patent/CN106188301A/zh active Pending
- 2011-03-01 LT LTEP17172199.6T patent/LT3345615T/lt unknown
- 2011-03-01 MY MYPI2012003902A patent/MY174760A/en unknown
- 2011-03-01 CN CN201510319455.4A patent/CN105001335B/zh not_active Expired - Fee Related
- 2011-03-01 SG SG2012062121A patent/SG183443A1/en unknown
- 2011-03-01 MX MX2012010198A patent/MX2012010198A/es active IP Right Grant
- 2011-03-01 KR KR1020187022511A patent/KR101974980B1/ko not_active Expired - Fee Related
- 2011-03-01 KR KR1020177034610A patent/KR101903931B1/ko not_active Expired - Fee Related
- 2011-03-01 ME MEP-2019-366A patent/ME03578B/me unknown
- 2011-03-01 NZ NZ702494A patent/NZ702494A/en not_active IP Right Cessation
- 2011-03-01 NZ NZ602115A patent/NZ602115A/en not_active IP Right Cessation
- 2011-03-01 HU HUE17172199A patent/HUE047173T2/hu unknown
- 2011-03-01 PT PT117512442T patent/PT2542257T/pt unknown
- 2011-03-01 SG SG10201502587SA patent/SG10201502587SA/en unknown
- 2011-03-01 ES ES11751244.2T patent/ES2642512T3/es active Active
- 2011-03-01 SI SI201131308T patent/SI2542257T1/en unknown
- 2011-03-01 EP EP17172199.6A patent/EP3345615B1/en active Active
- 2011-03-01 PH PH1/2012/501742A patent/PH12012501742A1/en unknown
- 2011-03-01 BR BR112012022258A patent/BR112012022258A2/pt active Search and Examination
- 2011-03-01 CA CA3101298A patent/CA3101298A1/en not_active Abandoned
- 2011-03-01 RS RS20191646A patent/RS59830B1/sr unknown
- 2011-03-01 CN CN201711202426.5A patent/CN107987166A/zh active Pending
- 2011-03-01 SG SG10201903166PA patent/SG10201903166PA/en unknown
- 2011-03-01 ES ES17172199T patent/ES2765418T3/es active Active
- 2011-03-01 RS RS20170978A patent/RS56409B1/sr unknown
- 2011-03-01 HR HRP20171472TT patent/HRP20171472T1/hr unknown
- 2011-03-01 PL PL11751244T patent/PL2542257T3/pl unknown
- 2011-03-01 HU HUE11751244A patent/HUE036655T2/hu unknown
- 2011-12-12 US US13/323,691 patent/US8481030B2/en not_active Expired - Fee Related
-
2012
- 2012-08-20 IL IL221551A patent/IL221551B/en active IP Right Grant
- 2012-08-30 CU CU20120126A patent/CU23982B1/es active IP Right Grant
- 2012-08-30 GT GT201200252A patent/GT201200252A/es unknown
- 2012-08-31 CL CL2012002415A patent/CL2012002415A1/es unknown
- 2012-08-31 CO CO12149294A patent/CO6620068A2/es unknown
- 2012-08-31 EC ECSP12012134 patent/ECSP12012134A/es unknown
- 2012-08-31 DO DO2012000239A patent/DOP2012000239A/es unknown
- 2012-09-03 CR CR20120453A patent/CR20120453A/es unknown
- 2012-09-03 MX MX2014010845A patent/MX354743B/es unknown
- 2012-09-18 PE PE2012001387A patent/PE20160538A1/es not_active Application Discontinuation
-
2013
- 2013-04-29 HK HK17105555.7A patent/HK1232232A1/zh unknown
-
2016
- 2016-10-11 JP JP2016199718A patent/JP6475679B2/ja not_active Expired - Fee Related
-
2017
- 2017-03-24 ME MEP-2017-78A patent/ME02894B/me unknown
- 2017-10-05 CY CY20171101040T patent/CY1119410T1/el unknown
- 2017-12-14 CL CL2017003218A patent/CL2017003218A1/es unknown
-
2018
- 2018-03-22 PH PH12018500640A patent/PH12018500640A1/en unknown
- 2018-03-22 PH PH12018500641A patent/PH12018500641A1/en unknown
- 2018-03-22 PH PH12018500639A patent/PH12018500639A1/en unknown
- 2018-10-17 IL IL262444A patent/IL262444B/en active IP Right Grant
- 2018-11-02 HK HK18114050.8A patent/HK1254947A1/zh unknown
-
2019
- 2019-02-01 JP JP2019016811A patent/JP6684369B2/ja not_active Expired - Fee Related
- 2019-04-09 EC ECSENADI201925350A patent/ECSP19025350A/es unknown
- 2019-12-20 HR HRP20192295TT patent/HRP20192295T1/hr unknown
-
2020
- 2020-01-09 CY CY20201100019T patent/CY1122476T1/el unknown
- 2020-03-27 JP JP2020057005A patent/JP2020115868A/ja not_active Withdrawn
- 2020-09-16 IL IL277391A patent/IL277391A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2642512T3 (es) | Anticuerpos monoclonales optimizados contra el inhibidor de la ruta del factor tisular (TFPI) | |
| ES2677329T3 (es) | Anticuerpos monoclonales contra el inhibidor de la ruta del factor tisular (TFPI) | |
| AU2018271420B2 (en) | Optimized monoclonal antibodies against tissue factor pathway inhibitor (TFPI) | |
| AU2013202745B2 (en) | Optimized monoclonal antibodies against tissue factor pathway inhibitor (TFPI) | |
| HK1178065A (en) | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) | |
| HK1178065B (en) | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |