CA3101298A1 - Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) - Google Patents
Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi)Info
- Publication number
- CA3101298A1 CA3101298A1 CA3101298A CA3101298A CA3101298A1 CA 3101298 A1 CA3101298 A1 CA 3101298A1 CA 3101298 A CA3101298 A CA 3101298A CA 3101298 A CA3101298 A CA 3101298A CA 3101298 A1 CA3101298 A1 CA 3101298A1
- Authority
- CA
- Canada
- Prior art keywords
- antibody
- tfpi
- antibodies
- amino acid
- light chain
- 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.)
- Abandoned
Links
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 title abstract description 61
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 title abstract description 61
- 101150070659 tfpI gene Proteins 0.000 title 1
- 101000653189 Homo sapiens Tissue factor pathway inhibitor Proteins 0.000 claims abstract description 68
- 238000006467 substitution reaction Methods 0.000 claims description 74
- 102220467388 Otoancorin_Y48F_mutation Human genes 0.000 claims description 62
- 241000282414 Homo sapiens Species 0.000 claims description 50
- 230000027455 binding Effects 0.000 claims description 43
- 102200079914 rs193302884 Human genes 0.000 claims description 36
- 102220523550 C-C motif chemokine 2_D91L_mutation Human genes 0.000 claims description 29
- 208000009292 Hemophilia A Diseases 0.000 claims description 28
- 102100026735 Coagulation factor VIII Human genes 0.000 claims description 24
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims description 24
- 239000000427 antigen Substances 0.000 claims description 23
- 108091007433 antigens Proteins 0.000 claims description 23
- 102000036639 antigens Human genes 0.000 claims description 23
- 201000003542 Factor VIII deficiency Diseases 0.000 claims description 21
- 239000012634 fragment Substances 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 14
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 12
- 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 10
- 208000009429 hemophilia B Diseases 0.000 claims description 7
- 102200108151 rs17683011 Human genes 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 102220004991 rs121912517 Human genes 0.000 claims 1
- 102200129367 rs1805044 Human genes 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 22
- 150000007523 nucleic acids Chemical class 0.000 abstract description 21
- 108020004707 nucleic acids Proteins 0.000 abstract description 19
- 102000039446 nucleic acids Human genes 0.000 abstract description 19
- 230000015271 coagulation Effects 0.000 abstract description 12
- 238000005345 coagulation Methods 0.000 abstract description 12
- 230000007547 defect Effects 0.000 abstract description 9
- 230000007812 deficiency Effects 0.000 abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 7
- 125000003275 alpha amino acid group Chemical group 0.000 description 86
- 102220594400 HLA class I histocompatibility antigen, C alpha chain_D33F_mutation Human genes 0.000 description 62
- 102220369055 c.96C>G Human genes 0.000 description 60
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 45
- 235000001014 amino acid Nutrition 0.000 description 44
- 230000004048 modification Effects 0.000 description 42
- 238000012986 modification Methods 0.000 description 42
- 210000004027 cell Anatomy 0.000 description 37
- 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 35
- 230000014509 gene expression Effects 0.000 description 31
- 150000001413 amino acids Chemical class 0.000 description 29
- 230000000694 effects Effects 0.000 description 29
- 229940024606 amino acid Drugs 0.000 description 28
- 102220045277 rs587781972 Human genes 0.000 description 28
- 230000035602 clotting Effects 0.000 description 25
- 206010053567 Coagulopathies Diseases 0.000 description 24
- 102220057210 rs730880391 Human genes 0.000 description 23
- 108010000499 Thromboplastin Proteins 0.000 description 18
- 102000002262 Thromboplastin Human genes 0.000 description 18
- 239000013604 expression vector Substances 0.000 description 17
- 230000035772 mutation Effects 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 238000003556 assay Methods 0.000 description 12
- 230000037361 pathway Effects 0.000 description 12
- 102200135505 rs2273535 Human genes 0.000 description 12
- 238000004904 shortening Methods 0.000 description 12
- 238000002965 ELISA Methods 0.000 description 11
- 101000653191 Mus musculus Tissue factor pathway inhibitor Proteins 0.000 description 11
- 230000000903 blocking effect Effects 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 102220088091 rs768851540 Human genes 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 230000006872 improvement Effects 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 241001529936 Murinae Species 0.000 description 9
- 102220614684 Ras-related protein Rab-3B_G56D_mutation Human genes 0.000 description 9
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 238000013169 thromboelastometry Methods 0.000 description 9
- 208000032843 Hemorrhage Diseases 0.000 description 8
- 239000000872 buffer Substances 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
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000002953 phosphate buffered saline Substances 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
- 208000031220 Hemophilia Diseases 0.000 description 7
- 102220501600 Putative uncharacterized protein UNQ6493/PRO21345_Y37F_mutation Human genes 0.000 description 7
- 102220476297 Retinaldehyde-binding protein 1_S21T_mutation Human genes 0.000 description 7
- 208000034158 bleeding Diseases 0.000 description 7
- 230000000740 bleeding effect Effects 0.000 description 7
- 230000023555 blood coagulation Effects 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 210000004602 germ cell Anatomy 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 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
- 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
- 125000000539 amino acid group Chemical group 0.000 description 6
- 102220352372 c.148T>G Human genes 0.000 description 6
- 230000002860 competitive effect Effects 0.000 description 6
- 229960000301 factor viii Drugs 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
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 238000011002 quantification Methods 0.000 description 6
- 102200089631 rs5030808 Human genes 0.000 description 6
- 102220308785 rs749697322 Human genes 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 108010076282 Factor IX Proteins 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000002950 deficient Effects 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
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 229960004222 factor ix Drugs 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 238000010606 normalization Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102220288745 rs1554040136 Human genes 0.000 description 5
- 102220072337 rs794728990 Human genes 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 102220561506 Autophagy protein 5_K58M_mutation Human genes 0.000 description 4
- 102220599536 Clathrin heavy chain 2_S98H_mutation Human genes 0.000 description 4
- 108010054218 Factor VIII Proteins 0.000 description 4
- 102000001690 Factor VIII Human genes 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
- 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
- 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 4
- 102220395310 c.125T>A Human genes 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 208000011664 congenital factor XI deficiency Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 201000007219 factor XI deficiency Diseases 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000003259 recombinant expression Methods 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
- 102220323550 rs940936212 Human genes 0.000 description 4
- 239000000758 substrate Substances 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
- 102100023804 Coagulation factor VII Human genes 0.000 description 3
- 102220466999 EH domain-binding protein 1-like protein 1_G33K_mutation Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010023321 Factor VII Proteins 0.000 description 3
- 108010054265 Factor VIIa Proteins 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
- 208000024659 Hemostatic disease Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010094028 Prothrombin Proteins 0.000 description 3
- 102100027378 Prothrombin Human genes 0.000 description 3
- 102220476285 Retinaldehyde-binding protein 1_P54L_mutation 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
- 102220559259 Voltage-dependent L-type calcium channel subunit alpha-1C_V30L_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
- 238000012258 culturing Methods 0.000 description 3
- 238000013480 data collection Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000001514 detection method Methods 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
- 229940012413 factor vii Drugs 0.000 description 3
- 230000005714 functional activity Effects 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
- 230000000977 initiatory effect 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
- 235000019799 monosodium phosphate Nutrition 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- -1 phenylaIanine Chemical compound 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 229940039716 prothrombin Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 102200074432 rs104894779 Human genes 0.000 description 3
- 102200068095 rs121913658 Human genes 0.000 description 3
- 102220253208 rs1386720703 Human genes 0.000 description 3
- 102220040517 rs146080119 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
- 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
- 238000010561 standard procedure 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
- 230000014621 translational initiation Effects 0.000 description 3
- 208000012908 vascular hemostatic disease Diseases 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
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 102220600740 Calmodulin-binding transcription activator 1_Q1E_mutation Human genes 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
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102220476893 Developmental pluripotency-associated protein 3_S33G_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
- 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
- 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
- 102220559219 Voltage-dependent L-type calcium channel subunit alpha-1C_S30R_mutation Human genes 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000008186 active pharmaceutical agent 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
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000000969 carrier Substances 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
- 230000009260 cross reactivity Effects 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
- 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
- 229940012414 factor viia Drugs 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
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory 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
- 238000005304 joining Methods 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
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 102200153431 rs1060501000 Human genes 0.000 description 2
- 102220159156 rs142915569 Human genes 0.000 description 2
- 102220276093 rs1555932427 Human genes 0.000 description 2
- 102200069953 rs28931601 Human genes 0.000 description 2
- 102220083467 rs863224774 Human genes 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
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000009870 specific binding Effects 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
- 229960004072 thrombin Drugs 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000013519 translation Methods 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
- 210000003462 vein Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000003442 weekly effect Effects 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
- 241000283690 Bos taurus 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
- 101150023426 Ccin gene Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 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
- 238000001712 DNA sequencing Methods 0.000 description 1
- 102220518111 DNA-directed RNA polymerases I and III subunit RPAC2_L51R_mutation Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 231100000491 EC50 Toxicity 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
- 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
- 108010054964 H-hexahydrotyrosyl-alanyl-arginine-4-nitroanilide Proteins 0.000 description 1
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000016988 Hemorrhagic Stroke Diseases 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
- 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
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-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
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 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
- 239000013543 active substance 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
- 230000005875 antibody response Effects 0.000 description 1
- 230000000890 antigenic effect 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
- 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
- 229960005069 calcium 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
- 229960001714 calcium phosphate Drugs 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
- 230000011748 cell maturation Effects 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
- 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
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000004883 computer application Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 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
- 108010082025 cyan fluorescent protein Proteins 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
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process 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
- 239000012636 effector Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000006624 extrinsic pathway Effects 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
- 238000010353 genetic engineering Methods 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
- 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
- 230000006623 intrinsic pathway Effects 0.000 description 1
- 238000004255 ion exchange chromatography 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
- 229930182817 methionine Natural products 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
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 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
- 229920000136 polysorbate Polymers 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000009117 preventive therapy Methods 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
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010188 recombinant method Methods 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
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 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
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection 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
- 239000003981 vehicle Substances 0.000 description 1
- 230000003612 virological 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)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (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)
- Epidemiology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (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 | |
| US61/309,290 | 2010-03-01 | ||
| CA2976671A CA2976671C (en) | 2010-03-01 | 2011-03-01 | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2976671A Division CA2976671C (en) | 2010-03-01 | 2011-03-01 | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3101298A1 true CA3101298A1 (en) | 2011-09-09 |
Family
ID=44542552
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3101298A Abandoned CA3101298A1 (en) | 2010-03-01 | 2011-03-01 | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
| CA2976671A Expired - Fee Related CA2976671C (en) | 2010-03-01 | 2011-03-01 | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
| CA2791685A Expired - Fee Related CA2791685C (en) | 2010-03-01 | 2011-03-01 | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2976671A Expired - Fee Related CA2976671C (en) | 2010-03-01 | 2011-03-01 | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
| CA2791685A Expired - Fee Related CA2791685C (en) | 2010-03-01 | 2011-03-01 | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
Country Status (37)
Families Citing this family (16)
| 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) |
| US8361469B2 (en) | 2008-12-22 | 2013-01-29 | Novo Nordisk A/S | Antibodies against tissue factor pathway inhibitor |
| SI3345615T1 (sl) * | 2010-03-01 | 2020-03-31 | Bayer Healthcare Llc | Optimizirana monoklonska protitelesa proti zaviralcu poti tkivnega faktorja (TFPI) |
| US9260518B2 (en) * | 2010-06-30 | 2016-02-16 | Novo Nordisk A/S | Antibodies that are capable of specifically binding tissue factor pathway inhibitor |
| SG193594A1 (en) * | 2011-04-01 | 2013-10-30 | Bayer Healthcare Llc | Monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
| CN104185474B (zh) * | 2012-03-30 | 2017-08-25 | 拜尔健康护理有限责任公司 | 蛋白酶调节的抗体 |
| US9592297B2 (en) * | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
| CN105452298B (zh) * | 2013-03-15 | 2021-08-31 | 拜尔健康护理有限责任公司 | 改善药代动力学的具有跨pH范围差异结合的抗TFPI抗体变体 |
| WO2014144689A1 (en) * | 2013-03-15 | 2014-09-18 | Bayer Healthcare Llc | Pro-drug antibodies against tissue factor pathway inhibitor |
| MY178445A (en) * | 2015-02-25 | 2020-10-13 | Mogam Inst Biomedical Res | Novel antibody binding to tfpi and composition comprising the same |
| CN114163531B (zh) | 2015-08-19 | 2025-06-13 | 辉瑞公司 | 组织因子途径抑制剂抗体及其用途 |
| KR102337683B1 (ko) * | 2018-09-21 | 2021-12-13 | 주식회사 녹십자 | 고효율 항-tfpi 항체 조성물 |
| AU2019359540B2 (en) * | 2018-10-11 | 2024-07-11 | Pfizer Inc. | Dosage regimen for TFPI antagonists |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| DE3782737T3 (de) | 1987-08-21 | 1999-05-20 | Imcera Group Inc., Northbrook, Ill. | 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 |
| JPH03504605A (ja) | 1988-05-27 | 1991-10-09 | セントカー・インコーポレーテツド | 抗体産生物の凍結乾燥した配合物 |
| JPH04504253A (ja) | 1989-03-27 | 1992-07-30 | セントカー・インコーポレーテツド | ＩｇＭ抗体の安定化のための配合物 |
| 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 |
| CN1108823C (zh) | 1993-02-23 | 2003-05-21 | 基因技术股份有限公司 | 运用赋形剂对有机溶剂处理的多肽的稳定化方法 |
| 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 |
| US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
| SI2275119T1 (sl) | 1995-07-27 | 2013-12-31 | Genentech, Inc. | Stabilna izotonična liofilizirana proteinska formulacija |
| 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 |
| US5770700A (en) | 1996-01-25 | 1998-06-23 | Genetics Institute, Inc. | Liquid factor IX formulations |
| KR100505772B1 (ko) | 1996-01-25 | 2005-10-25 | 쉐링 악티엔게젤샤프트 | 개선된정맥투여용농축주사액및주입액 |
| 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 |
| ATE318316T1 (de) | 1997-03-26 | 2006-03-15 | Imp 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 |
| WO1999003496A1 (en) | 1997-07-21 | 1999-01-28 | 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 |
| CA2302708A1 (en) | 1997-08-21 | 1999-03-04 | Siemens Aktiengesellschaft | Method for transmitting user data that can be allocated to different applications |
| 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 |
| CA2322728A1 (en) | 1998-03-12 | 1999-09-16 | 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 |
| WO2001064241A1 (en) | 2000-02-29 | 2001-09-07 | Chugai Seiyaku Kabushiki Kaisha | Preparations stabilized over long time |
| AU2001251336B2 (en) | 2000-04-07 | 2006-09-14 | Signal Coordinating Therapy, Inc. | Methods and compositions for treating neoplasms |
| 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 |
| MXPA02012434A (es) | 2000-06-16 | 2004-09-06 | Cambridge Antibody Tech | Anticuerpos que se unen inmunoespecificamente a estimulador de linfocitos ii. |
| 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 |
| ES2644275T3 (es) | 2000-08-11 | 2017-11-28 | Chugai Seiyaku Kabushiki Kaisha | Preparaciones estabilizadas que contienen anticuerpos |
| KR20030027077A (ko) | 2000-09-01 | 2003-04-03 | 쥬가이 세이야쿠 가부시키가이샤 | 장기 안정화 용액 제제 |
| US6875432B2 (en) | 2000-10-12 | 2005-04-05 | 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 |
| EP1379549A2 (fr) | 2001-02-07 | 2004-01-14 | Institut Pasteur | Sequence du genome de photorhabdus luminescens souche tto1 et utilisations |
| 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 |
| ATE454137T1 (de) | 2001-07-25 | 2010-01-15 | Facet Biotech Corp | Stabile lyophilisierte pharmazeutische formulierung des igg-antikörpers daclizumab |
| US20040142325A1 (en) | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
| JP3665324B2 (ja) * | 2001-10-15 | 2005-06-29 | 麒麟麦酒株式会社 | 抗ｈｌａ−ｄｒ抗体 |
| AU2002335815A1 (en) | 2001-10-16 | 2003-04-28 | Rxkinetix, Inc. | High-concentration protein formulations and method of manufacture |
| US20040029129A1 (en) | 2001-10-25 | 2004-02-12 | Liangsu Wang | Identification of essential genes in microorganisms |
| US20030166004A1 (en) | 2001-11-01 | 2003-09-04 | Jeno Gyuris | Endothelial-cell binding peptides for diagnosis and therapy |
| ATE556591T1 (de) | 2001-11-08 | 2012-05-15 | Abbott Biotherapeutics Corp | Stabile pharmazeutische flüssigformulierung von igg-antikörpern |
| AU2002363925A1 (en) | 2001-11-29 | 2003-06-17 | Wyeth Holdings Corporation | ALLOIOCOCCUS OTITIDIS OPEN READING FRAMES (ORFs) ENCODING POLYPEPTIDE ANTIGENS, IMMUNOGENIC 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 |
| JP3792698B2 (ja) | 2002-02-14 | 2006-07-05 | 中外製薬株式会社 | 抗体含有溶液製剤 |
| US7314974B2 (en) | 2002-02-21 | 2008-01-01 | Monsanto Technology, Llc | Expression of microbial proteins in plants for production of plants with improved properties |
| DE60322513D1 (de) | 2002-02-27 | 2008-09-11 | Immunex Corp | Stabilisierte TNFR-Fc Formulierung mit Arginin |
| WO2003076575A2 (en) | 2002-03-04 | 2003-09-18 | Fidelity Systems, Inc., Et Al. | The 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 |
| AU2005254062B2 (en) | 2002-04-11 | 2011-02-17 | Medimmune, Llc | High pressure spray-dry of bioactive materials |
| 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 |
| CA2490423A1 (en) | 2002-06-21 | 2003-12-31 | Biogen Idec Inc. | Buffered formulations for concentrating antibodies and methods of use thereof |
| EP1539235A2 (en) | 2002-07-01 | 2005-06-15 | Human Genome Sciences, Inc. | Antibodies that specifically bind to reg iv |
| CN1703233A (zh) | 2002-07-12 | 2005-11-30 | 米德列斯公司 | 防止蛋白氧化降解的方法和组合物 |
| 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 |
| AU2003285864C1 (en) | 2002-10-08 | 2010-07-01 | Rinat Neuroscience Corp. | Methods for treating post-surgical pain by administering a nerve growth factor antagonist and compositions containing the same |
| KR100542401B1 (ko) | 2002-10-23 | 2006-01-11 | 한국전자통신연구원 | 인터넷 차별 서비스 망에서의 연결 수락 제어방법 |
| CN1878795A (zh) | 2002-12-02 | 2006-12-13 | 阿布格尼克斯公司 | 针对磷脂酶a2的抗体及其应用 |
| AU2003293543A1 (en) | 2002-12-13 | 2004-07-09 | 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 |
| SI2270048T1 (sl) | 2002-12-24 | 2016-01-29 | Rinat Neuroscience Corp. | Protitelesa proti NGF-ju in postopki uporabe le-teh |
| BRPI0408157B8 (pt) | 2003-03-07 | 2021-05-25 | Dsm Food Specialties B V | ácido nucléico recombinante, polipeptídeo recombinante com atividade lipase, célula transformada, métodos empregando os mesmos e composição |
| 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 |
| ES2349779T5 (es) | 2003-04-04 | 2013-11-26 | Genentech, Inc. | Formulaciones de anticuerpos y de proteínas a concentración elevada |
| CN1816351A (zh) * | 2003-06-27 | 2006-08-09 | 艾伯吉尼斯公司 | 针对表皮生长因子受体的缺失突变体的抗体及其使用 |
| EP1648509B8 (en) | 2003-07-15 | 2012-10-24 | Amgen Inc. | Human anti-ngf neutralizing antibodies as selective ngf pathway inhibitors |
| EP1648998B1 (en) | 2003-07-18 | 2014-10-01 | Amgen Inc. | Specific binding agents to hepatocyte growth factor |
| 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 |
| HUE026793T2 (en) | 2003-10-01 | 2016-07-28 | Kyowa Hakko Kirin Co Ltd | A method for stabilizing an antibody and a stabilized solution-type antibody preparation |
| 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 |
| AU2004296768B2 (en) | 2003-12-03 | 2010-06-24 | University Of Rochester | Recombinant factor VIII having increased specific activity |
| EP1712240B1 (en) | 2003-12-25 | 2015-09-09 | Kyowa Hakko Kirin Co., Ltd. | Stable water-based medicinal preparation containing antibody |
| EP2298797A3 (en) | 2004-01-09 | 2011-05-18 | Novozymes Inc. | Increased bacillus YweA expression |
| US20060041961A1 (en) | 2004-03-25 | 2006-02-23 | Abad Mark S | Genes and uses for pant improvement |
| PL2314620T3 (pl) | 2004-05-27 | 2013-11-29 | Crucell Holland Bv | Sposób identyfikowania cząsteczek wiążących zdolnych do neutralizowania wirusa wścieklizny |
| US20080008719A1 (en) | 2004-07-10 | 2008-01-10 | Bowdish Katherine S | Methods and compositions for the treatment of prostate cancer |
| US20080287309A1 (en) | 2004-07-10 | 2008-11-20 | Alexion Pharmaceuticals, Inc. | Methods for Discovering Antibodies Specific to Cancer Cells and Antibodies Discovered Thereby |
| 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 . |
| SI1838733T1 (sl) | 2004-12-21 | 2011-12-30 | Medimmune Ltd | Protitelesa usmerjena na angiopoietin-2 in njih uporaba |
| US20080148432A1 (en) | 2005-12-21 | 2008-06-19 | Mark Scott Abad | Transgenic plants with enhanced agronomic traits |
| CA2590164A1 (en) | 2005-01-26 | 2006-08-03 | Amgen Fremont Inc. | Antibodies against interleukin-1 beta |
| WO2006109191A2 (en) | 2005-01-27 | 2006-10-19 | Novimmune S.A. | Human anti-interferon gamma antibodies and methods of use thereof |
| GT200600031A (es) | 2005-01-28 | 2006-08-29 | Formulacion anticuerpo anti a beta | |
| JP2008528638A (ja) | 2005-01-28 | 2008-07-31 | ワイス | ポリペプチドの安定化液体処方 |
| MX2007009545A (es) | 2005-02-08 | 2008-03-11 | Genzyme Corp | Anticuerpos para tgfbeta. |
| US8088976B2 (en) | 2005-02-24 | 2012-01-03 | Monsanto Technology Llc | Methods for genetic control of plant pest infestation and compositions thereof |
| WO2006092449A2 (en) | 2005-03-02 | 2006-09-08 | Metanomics Gmbh | Process for the production of fine chemicals |
| ATE505488T1 (de) | 2005-03-04 | 2011-04-15 | Univ Illinois | Modulator von coagulationskaskaden und fibrinolytischen kaskaden |
| LT2620450T (lt) | 2005-03-08 | 2019-02-11 | Pfizer Products Inc. | Anti-ctla-4 antikūnų kompozicijos |
| AR054428A1 (es) | 2005-03-08 | 2007-06-27 | Pharmacia & Upjohn Co Llc | Composiciones de anticuerpos anti factor estimulante de colonia de macrofagos (anti-m-csf) que tienen menores niveles de endotoxina |
| AU2005330672B2 (en) | 2005-04-18 | 2011-07-28 | 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 |
| EP1917030A4 (en) | 2005-08-03 | 2011-03-09 | Immunogen Inc | IMMUNKONJUGATFORMULIERUNGEN |
| CA2618068C (en) | 2005-08-05 | 2016-02-16 | 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 |
| CN104984352A (zh) | 2005-11-21 | 2015-10-21 | 圣诺菲·帕斯图尔有限公司 | 重组病毒的稳定制剂 |
| JP5808070B2 (ja) | 2005-12-02 | 2015-11-10 | ジェネンテック， インコーポレイテッド | 結合ポリペプチド及びその使用 |
| US7669228B2 (en) | 2005-12-27 | 2010-02-23 | Cisco Technology, Inc. | System and method for changing network behavior based on presence information |
| US9084777B2 (en) | 2005-12-28 | 2015-07-21 | Chugai Seiyaku Kabushiki Kaisha | Stabilized antibody-containing formulations |
| 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 |
| WO2007112054A2 (en) | 2006-03-23 | 2007-10-04 | Sea Lane Biotechnologies, Llc | Facilitation of translocation of molecules through the gastrointestinal tract |
| JP2009540015A (ja) | 2006-06-14 | 2009-11-19 | イムクローン・リミテッド・ライアビリティ・カンパニー | 抗ｅｇｆｒ抗体の凍結乾燥製剤 |
| 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 |
| EP2076287A2 (en) | 2006-10-12 | 2009-07-08 | Wyeth | Methods and compositions with reduced opalescence |
| CL2007003583A1 (es) | 2006-12-11 | 2008-07-18 | Hoffmann La Roche | Formulacion farmaceutica estable, parenteral, del anticuerpo contra el peptido beta amiloide (abeta); y uso de la formulacion para el tratamiento de la enfermedad de alzheimer. |
| EP2077859A4 (en) | 2007-03-30 | 2010-11-24 | Medimmune Llc | ANTIBODY FORMULATION |
| GB0707938D0 (en) | 2007-04-25 | 2007-05-30 | Univ Strathclyde | Precipitation stabilising compositions |
| PT2170390T (pt) | 2007-06-14 | 2019-02-12 | Biogen Ma Inc | Formulações com anticorpo natalizumab |
| UA107557C2 (xx) | 2007-07-06 | 2015-01-26 | Композиція антитіла офатумумабу | |
| DK2222707T3 (en) * | 2007-11-21 | 2016-04-11 | Univ Oregon Health & Science | Monoclonal anti-factor XI antibodies and method of use thereof |
| US9308257B2 (en) | 2007-11-28 | 2016-04-12 | Medimmune, Llc | Protein formulation |
| CA3102679A1 (en) | 2007-12-14 | 2009-06-25 | Birgitte Urso | Antibodies against human nkg2d and uses thereof |
| EP2234600B1 (en) | 2007-12-21 | 2014-08-20 | F. Hoffmann-La Roche AG | Antibody formulation |
| AU2008342942A1 (en) | 2007-12-28 | 2009-07-09 | Biolnvent International Ab | Formulation |
| CA2714296A1 (en) | 2008-02-20 | 2009-08-27 | G2 Inflammation Pty Ltd | Humanized anti-c5ar antibodies |
| WO2009120684A1 (en) | 2008-03-25 | 2009-10-01 | Medimmune, Llc | Antibody formulation |
| WO2010000721A1 (en) | 2008-06-30 | 2010-01-07 | Novo Nordisk A/S | Anti-human interleukin-20 antibodies |
| UA112050C2 (uk) | 2008-08-04 | 2016-07-25 | БАЄР ХЕЛСКЕР ЛЛСі | Терапевтична композиція, що містить моноклональне антитіло проти інгібітора шляху тканинного фактора (tfpi) |
| RU2518278C2 (ru) | 2008-09-19 | 2014-06-10 | Пфайзер Инк. | Стабильный жидкий препарат антитела |
| AU2009319856A1 (en) | 2008-11-28 | 2010-06-03 | Abbvie Inc. | Stable antibody compositions and methods for stabilizing same |
| EP2196476A1 (en) | 2008-12-10 | 2010-06-16 | Novartis Ag | Antibody formulation |
| KR101792032B1 (ko) | 2008-12-19 | 2017-11-02 | 백스터 인터내셔널 인코포레이티드 | Ｔｆｐｉ 억제제 및 사용 방법 |
| US8361469B2 (en) | 2008-12-22 | 2013-01-29 | Novo Nordisk A/S | Antibodies against tissue factor pathway inhibitor |
| EP2379599B1 (en) | 2008-12-22 | 2015-09-02 | Novo Nordisk A/S | Antibodies against tissue factor pathway inhibitor (tfpi) |
| KR20110128333A (ko) | 2009-03-06 | 2011-11-29 | 제넨테크, 인크. | 항체 제제 |
| US20120114646A1 (en) | 2009-06-18 | 2012-05-10 | Wyeth Llc | Lyophilized formulations for small modular immunopharmaceuticals |
| HRP20251316T1 (hr) | 2009-09-03 | 2025-12-05 | Ablynx Nv | Stabilne formulacije polipeptida i njihova upotreba |
| EP2332995A1 (en) | 2009-12-10 | 2011-06-15 | Bayer Schering Pharma Aktiengesellschaft | Neutralizing prolactin receptor antibodies and their therapeutic use |
| WO2011104381A2 (en) | 2010-02-26 | 2011-09-01 | Novo Nordisk A/S | Stable antibody containing compositions |
| SI3345615T1 (sl) * | 2010-03-01 | 2020-03-31 | Bayer Healthcare Llc | Optimizirana monoklonska protitelesa proti zaviralcu poti tkivnega faktorja (TFPI) |
| NZ603028A (en) | 2010-03-19 | 2014-11-28 | Baxter Healthcare Sa | 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 |
| CA2827160A1 (en) | 2011-02-11 | 2012-08-16 | Baxter Healthcare S.A. | Aptamers to tissue factor pathway inhibitor and their use as bleeding disorder therapeutics |
| SG193594A1 (en) | 2011-04-01 | 2013-10-30 | Bayer Healthcare Llc | Monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
| WO2013142153A2 (en) | 2012-03-22 | 2013-09-26 | Baxter International Inc. | 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 |
| CN105452298B (zh) | 2013-03-15 | 2021-08-31 | 拜尔健康护理有限责任公司 | 改善药代动力学的具有跨pH范围差异结合的抗TFPI抗体变体 |
| MY178445A (en) | 2015-02-25 | 2020-10-13 | Mogam Inst Biomedical Res | Novel antibody binding to tfpi and composition comprising the same |
| CN114163531B (zh) | 2015-08-19 | 2025-06-13 | 辉瑞公司 | 组织因子途径抑制剂抗体及其用途 |
-
2011
- 2011-03-01 SI SI201131830T patent/SI3345615T1/sl unknown
- 2011-03-01 NZ NZ702494A patent/NZ702494A/en not_active IP Right Cessation
- 2011-03-01 CA CA3101298A patent/CA3101298A1/en not_active Abandoned
- 2011-03-01 KR KR1020177034610A patent/KR101903931B1/ko not_active Expired - Fee Related
- 2011-03-01 PT PT171721996T patent/PT3345615T/pt unknown
- 2011-03-01 HR HRP20171472TT patent/HRP20171472T1/hr unknown
- 2011-03-01 MX MX2012010198A patent/MX2012010198A/es active IP Right Grant
- 2011-03-01 NZ NZ602115A patent/NZ602115A/en not_active IP Right Cessation
- 2011-03-01 HU HUE11751244A patent/HUE036655T2/hu unknown
- 2011-03-01 SG SG10201502587SA patent/SG10201502587SA/en unknown
- 2011-03-01 WO PCT/US2011/026766 patent/WO2011109452A1/en not_active Ceased
- 2011-03-01 CN CN201510319455.4A patent/CN105001335B/zh not_active Expired - Fee Related
- 2011-03-01 US US15/208,498 patent/USRE47150E1/en not_active Expired - Fee Related
- 2011-03-01 HU HUE17172199A patent/HUE047173T2/hu unknown
- 2011-03-01 KR KR1020187022511A patent/KR101974980B1/ko not_active Expired - Fee Related
- 2011-03-01 CA CA2976671A patent/CA2976671C/en not_active Expired - Fee Related
- 2011-03-01 DK DK11751244.2T patent/DK2542257T3/en active
- 2011-03-01 SG SG10201903166PA patent/SG10201903166PA/en unknown
- 2011-03-01 PL PL11751244T patent/PL2542257T3/pl unknown
- 2011-03-01 SI SI201131308T patent/SI2542257T1/en unknown
- 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 EP EP11751244.2A patent/EP2542257B1/en active Active
- 2011-03-01 KR KR1020127025683A patent/KR101807894B1/ko not_active Expired - Fee Related
- 2011-03-01 EP EP17172199.6A patent/EP3345615B1/en active Active
- 2011-03-01 ME MEP-2019-366A patent/ME03578B/me unknown
- 2011-03-01 CA CA2791685A patent/CA2791685C/en not_active Expired - Fee Related
- 2011-03-01 SM SM20170454T patent/SMT201700454T1/it unknown
- 2011-03-01 SG SG2012062121A patent/SG183443A1/en unknown
- 2011-03-01 RS RS20170978A patent/RS56409B1/sr unknown
- 2011-03-01 ES ES11751244.2T patent/ES2642512T3/es active Active
- 2011-03-01 CN CN201711202426.5A patent/CN107987166A/zh active Pending
- 2011-03-01 JP JP2012556192A patent/JP6025570B2/ja not_active Expired - Fee Related
- 2011-03-01 EA EA201290849A patent/EA032189B9/ru not_active IP Right Cessation
- 2011-03-01 CN CN201610539997.7A patent/CN106188301A/zh active Pending
- 2011-03-01 CN CN201911010357.7A patent/CN110835373A/zh active Pending
- 2011-03-01 BR BR112012022258A patent/BR112012022258A2/pt active Search and Examination
- 2011-03-01 CN CN201180022078.8A patent/CN102939098B/zh not_active Expired - Fee Related
- 2011-03-01 PH PH1/2012/501742A patent/PH12012501742A1/en unknown
- 2011-03-01 DK DK17172199.6T patent/DK3345615T3/da active
- 2011-03-01 AU AU2011223710A patent/AU2011223710B2/en not_active Ceased
- 2011-03-01 ES ES17172199T patent/ES2765418T3/es active Active
- 2011-03-01 LT LTEP11751244.2T patent/LT2542257T/lt unknown
- 2011-03-01 LT LTEP17172199.6T patent/LT3345615T/lt unknown
- 2011-03-01 PT PT117512442T patent/PT2542257T/pt unknown
- 2011-03-01 RS RS20191646A patent/RS59830B1/sr unknown
- 2011-03-01 EA EA201892184A patent/EA201892184A1/ru unknown
- 2011-03-01 MY MYPI2012003902A patent/MY174760A/en 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 GT GT201200252A patent/GT201200252A/es unknown
- 2012-08-30 CU CU20120126A patent/CU23982B1/es active IP Right Grant
- 2012-08-31 EC ECSP12012134 patent/ECSP12012134A/es unknown
- 2012-08-31 CO CO12149294A patent/CO6620068A2/es unknown
- 2012-08-31 DO DO2012000239A patent/DOP2012000239A/es unknown
- 2012-08-31 CL CL2012002415A patent/CL2012002415A1/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 PH12018500641A patent/PH12018500641A1/en unknown
- 2018-03-22 PH PH12018500639A patent/PH12018500639A1/en unknown
- 2018-03-22 PH PH12018500640A patent/PH12018500640A1/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 |
|---|---|---|
| CA2791685C (en) | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) | |
| CA3081514C (en) | Monoclonal antibodies against tissue factor pathway inhibitor (tfpi) | |
| AU2018271420B2 (en) | Optimized monoclonal antibodies against tissue factor pathway inhibitor (TFPI) | |
| AU2013202745B2 (en) | Optimized monoclonal antibodies against tissue factor pathway inhibitor (TFPI) | |
| HK40018254A (en) | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20201201 |
|
| EEER | Examination request |
Effective date: 20201201 |
|
| FZDE | Discontinued |
Effective date: 20230307 |
|
| FZDE | Discontinued |
Effective date: 20230307 |