ES2362386T3 - Proteínas activas biológicas que tienen estabilidad aumentada in vivo y/o in vitro. - Google Patents
Proteínas activas biológicas que tienen estabilidad aumentada in vivo y/o in vitro. Download PDFInfo
- Publication number
- ES2362386T3 ES2362386T3 ES08773567T ES08773567T ES2362386T3 ES 2362386 T3 ES2362386 T3 ES 2362386T3 ES 08773567 T ES08773567 T ES 08773567T ES 08773567 T ES08773567 T ES 08773567T ES 2362386 T3 ES2362386 T3 ES 2362386T3
- Authority
- ES
- Spain
- Prior art keywords
- pas
- amino acid
- ifna2b
- biologically active
- protein
- 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
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 297
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 275
- 230000001965 increasing effect Effects 0.000 title claims abstract description 25
- 238000000338 in vitro Methods 0.000 title claims abstract description 24
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 124
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 83
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 57
- 230000004071 biological effect Effects 0.000 claims abstract description 56
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 51
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 51
- 238000001727 in vivo Methods 0.000 claims abstract description 41
- 239000013598 vector Substances 0.000 claims abstract description 39
- 239000000203 mixture Substances 0.000 claims abstract description 29
- 235000018102 proteins Nutrition 0.000 claims description 267
- 235000001014 amino acid Nutrition 0.000 claims description 140
- 150000001413 amino acids Chemical class 0.000 claims description 134
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 63
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 55
- 229920001184 polypeptide Polymers 0.000 claims description 53
- 210000004027 cell Anatomy 0.000 claims description 50
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 42
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 36
- 235000004279 alanine Nutrition 0.000 claims description 36
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 34
- 239000012634 fragment Substances 0.000 claims description 34
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 20
- 230000002035 prolonged effect Effects 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 10
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 102000019298 Lipocalin Human genes 0.000 claims description 8
- 108050006654 Lipocalin Proteins 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 210000000440 neutrophil Anatomy 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 6
- -1 reteplasa Proteins 0.000 claims description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 5
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 102000005962 receptors Human genes 0.000 claims description 5
- 108020003175 receptors Proteins 0.000 claims description 5
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- 102000013382 Gelatinases Human genes 0.000 claims description 4
- 108010026132 Gelatinases Proteins 0.000 claims description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 229940088597 hormone Drugs 0.000 claims description 4
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 4
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 102000004127 Cytokines Human genes 0.000 claims description 3
- 108090000695 Cytokines Proteins 0.000 claims description 3
- 102000003951 Erythropoietin Human genes 0.000 claims description 3
- 108090000394 Erythropoietin Proteins 0.000 claims description 3
- 102000001690 Factor VIII Human genes 0.000 claims description 3
- 108010054218 Factor VIII Proteins 0.000 claims description 3
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 3
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 3
- 102000002265 Human Growth Hormone Human genes 0.000 claims description 3
- 108010000521 Human Growth Hormone Proteins 0.000 claims description 3
- 239000000854 Human Growth Hormone Substances 0.000 claims description 3
- 108010047761 Interferon-alpha Proteins 0.000 claims description 3
- 102000006992 Interferon-alpha Human genes 0.000 claims description 3
- 102000008070 Interferon-gamma Human genes 0.000 claims description 3
- 108010074328 Interferon-gamma Proteins 0.000 claims description 3
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 claims description 3
- 108010002350 Interleukin-2 Proteins 0.000 claims description 3
- 102000000588 Interleukin-2 Human genes 0.000 claims description 3
- 206010063837 Reperfusion injury Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 101710090322 Truncated surface protein Proteins 0.000 claims description 3
- 229960004238 anakinra Drugs 0.000 claims description 3
- 229940105778 coagulation factor viii Drugs 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 229940105423 erythropoietin Drugs 0.000 claims description 3
- 229940044627 gamma-interferon Drugs 0.000 claims description 3
- 239000003102 growth factor Substances 0.000 claims description 3
- 239000000816 peptidomimetic Substances 0.000 claims description 3
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 3
- 208000035473 Communicable disease Diseases 0.000 claims description 2
- 108010011459 Exenatide Proteins 0.000 claims description 2
- 102000003996 Interferon-beta Human genes 0.000 claims description 2
- 108090000467 Interferon-beta Proteins 0.000 claims description 2
- 108090001090 Lectins Proteins 0.000 claims description 2
- 102000004856 Lectins Human genes 0.000 claims description 2
- 206010054094 Tumour necrosis Diseases 0.000 claims description 2
- 208000007502 anemia Diseases 0.000 claims description 2
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 229960001519 exenatide Drugs 0.000 claims description 2
- 239000000122 growth hormone Substances 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 239000002523 lectin Substances 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 230000007812 deficiency Effects 0.000 claims 1
- 230000003054 hormonal effect Effects 0.000 claims 1
- 230000002458 infectious effect Effects 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 229920000642 polymer Polymers 0.000 description 222
- 102000013519 Lipocalin-2 Human genes 0.000 description 93
- 108010051335 Lipocalin-2 Proteins 0.000 description 93
- 210000002381 plasma Anatomy 0.000 description 64
- 238000001228 spectrum Methods 0.000 description 57
- 230000004927 fusion Effects 0.000 description 48
- 102000037865 fusion proteins Human genes 0.000 description 48
- 108020001507 fusion proteins Proteins 0.000 description 48
- 239000000872 buffer Substances 0.000 description 41
- 108020004414 DNA Proteins 0.000 description 40
- 239000002953 phosphate buffered saline Substances 0.000 description 39
- 241001465754 Metazoa Species 0.000 description 36
- XQLBWXHVZVBNJM-FXQIFTODSA-N Pro-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 XQLBWXHVZVBNJM-FXQIFTODSA-N 0.000 description 34
- 230000004962 physiological condition Effects 0.000 description 32
- 102000009634 interleukin-1 receptor antagonist activity proteins Human genes 0.000 description 31
- 108040001669 interleukin-1 receptor antagonist activity proteins Proteins 0.000 description 31
- 108091028043 Nucleic acid sequence Proteins 0.000 description 29
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 29
- 239000013612 plasmid Substances 0.000 description 29
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 28
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 28
- 108010028230 Trp-Ser- His-Pro-Gln-Phe-Glu-Lys Proteins 0.000 description 28
- 210000004369 blood Anatomy 0.000 description 28
- 239000008280 blood Substances 0.000 description 28
- 238000012360 testing method Methods 0.000 description 26
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 24
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 230000014509 gene expression Effects 0.000 description 24
- 230000000694 effects Effects 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- 241000404883 Pisa Species 0.000 description 20
- 239000012505 Superdex™ Substances 0.000 description 20
- 239000012528 membrane Substances 0.000 description 20
- 239000002773 nucleotide Substances 0.000 description 20
- 125000003729 nucleotide group Chemical group 0.000 description 20
- 239000007983 Tris buffer Substances 0.000 description 19
- 230000037396 body weight Effects 0.000 description 18
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 18
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 18
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 238000001514 detection method Methods 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 16
- 239000013604 expression vector Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 14
- 238000002347 injection Methods 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 14
- 238000010790 dilution Methods 0.000 description 13
- 239000012895 dilution Substances 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 210000004899 c-terminal region Anatomy 0.000 description 12
- 238000003780 insertion Methods 0.000 description 12
- 230000037431 insertion Effects 0.000 description 12
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 12
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 11
- 238000002965 ELISA Methods 0.000 description 11
- 238000011534 incubation Methods 0.000 description 11
- 239000013615 primer Substances 0.000 description 11
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- 102000034238 globular proteins Human genes 0.000 description 10
- 108091005896 globular proteins Proteins 0.000 description 10
- 238000003119 immunoblot Methods 0.000 description 10
- 238000005406 washing Methods 0.000 description 10
- 241000588724 Escherichia coli Species 0.000 description 9
- 108010058846 Ovalbumin Proteins 0.000 description 9
- 102000004338 Transferrin Human genes 0.000 description 9
- 108090000901 Transferrin Proteins 0.000 description 9
- 229940098773 bovine serum albumin Drugs 0.000 description 9
- 238000002983 circular dichroism Methods 0.000 description 9
- 230000000295 complement effect Effects 0.000 description 9
- 238000005227 gel permeation chromatography Methods 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 229940092253 ovalbumin Drugs 0.000 description 9
- 239000012581 transferrin Substances 0.000 description 9
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 8
- 102000003846 Carbonic anhydrases Human genes 0.000 description 8
- 108090000209 Carbonic anhydrases Proteins 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 8
- 238000010367 cloning Methods 0.000 description 8
- 238000010828 elution Methods 0.000 description 8
- 238000002523 gelfiltration Methods 0.000 description 8
- 238000009396 hybridization Methods 0.000 description 8
- 230000000670 limiting effect Effects 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 7
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 7
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 7
- 102000014914 Carrier Proteins Human genes 0.000 description 7
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 238000001042 affinity chromatography Methods 0.000 description 7
- 238000010241 blood sampling Methods 0.000 description 7
- 239000013613 expression plasmid Substances 0.000 description 7
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 7
- QEIFSLUFHRCVQL-UHFFFAOYSA-N (5-bromo-4-chloro-1h-indol-3-yl) hydrogen phosphate;(4-methylphenyl)azanium Chemical compound CC1=CC=C(N)C=C1.C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QEIFSLUFHRCVQL-UHFFFAOYSA-N 0.000 description 6
- 241000672609 Escherichia coli BL21 Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 239000000020 Nitrocellulose Substances 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 6
- 108091008324 binding proteins Proteins 0.000 description 6
- 238000000978 circular dichroism spectroscopy Methods 0.000 description 6
- 239000000470 constituent Substances 0.000 description 6
- 238000010276 construction Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 238000010253 intravenous injection Methods 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 229920001220 nitrocellulos Polymers 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 239000012460 protein solution Substances 0.000 description 6
- 230000017854 proteolysis Effects 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 230000003252 repetitive effect Effects 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 238000004611 spectroscopical analysis Methods 0.000 description 6
- 229930101283 tetracycline Natural products 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 5
- 108091006905 Human Serum Albumin Proteins 0.000 description 5
- 102000008100 Human Serum Albumin Human genes 0.000 description 5
- 108010050904 Interferons Proteins 0.000 description 5
- 102000014150 Interferons Human genes 0.000 description 5
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 5
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 5
- 108010090804 Streptavidin Proteins 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 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 5
- 230000008030 elimination Effects 0.000 description 5
- 238000003379 elimination reaction Methods 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- 230000007717 exclusion Effects 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 229910052742 iron Inorganic materials 0.000 description 5
- 238000004445 quantitative analysis Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 4
- 238000001712 DNA sequencing Methods 0.000 description 4
- 241000238557 Decapoda Species 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 102000016943 Muramidase Human genes 0.000 description 4
- 108010014251 Muramidase Proteins 0.000 description 4
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 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 4
- 108700005078 Synthetic Genes Proteins 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 4
- 229960000723 ampicillin Drugs 0.000 description 4
- 229960000074 biopharmaceutical Drugs 0.000 description 4
- 238000011088 calibration curve Methods 0.000 description 4
- 239000004202 carbamide Substances 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 229940079322 interferon Drugs 0.000 description 4
- 239000012160 loading buffer Substances 0.000 description 4
- 229960000274 lysozyme Drugs 0.000 description 4
- 239000004325 lysozyme Substances 0.000 description 4
- 235000010335 lysozyme Nutrition 0.000 description 4
- 229910001629 magnesium chloride Inorganic materials 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- OFVLGDICTFRJMM-WESIUVDSSA-N tetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O OFVLGDICTFRJMM-WESIUVDSSA-N 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 3
- 239000007836 KH2PO4 Substances 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- SSJMZMUVNKEENT-IMJSIDKUSA-N Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CO SSJMZMUVNKEENT-IMJSIDKUSA-N 0.000 description 3
- 239000000589 Siderophore Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 238000007605 air drying Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 3
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 description 3
- 235000019800 disodium phosphate Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229920001519 homopolymer Polymers 0.000 description 3
- 229940127121 immunoconjugate Drugs 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000002751 lymph Anatomy 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 description 3
- FSVCQIDHPKZJSO-UHFFFAOYSA-L nitro blue tetrazolium dichloride Chemical compound [Cl-].[Cl-].COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 FSVCQIDHPKZJSO-UHFFFAOYSA-L 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 238000003118 sandwich ELISA Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 229920001059 synthetic polymer Polymers 0.000 description 3
- 210000005253 yeast cell Anatomy 0.000 description 3
- WIIZWVCIJKGZOK-IUCAKERBSA-N 2,2-dichloro-n-[(1s,2s)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide Chemical compound ClC(Cl)C(=O)N[C@@H](CO)[C@@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-IUCAKERBSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- IPWKGIFRRBGCJO-IMJSIDKUSA-N Ala-Ser Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](CO)C([O-])=O IPWKGIFRRBGCJO-IMJSIDKUSA-N 0.000 description 2
- 108010039627 Aprotinin Proteins 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 241001086826 Branta bernicla Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 102100030497 Cytochrome c Human genes 0.000 description 2
- 108010075031 Cytochromes c Proteins 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 2
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 2
- 125000000773 L-serino group Chemical group [H]OC(=O)[C@@]([H])(N([H])*)C([H])([H])O[H] 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 102100030856 Myoglobin Human genes 0.000 description 2
- 108010062374 Myoglobin Proteins 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 102100035405 Neutrophil gelatinase-associated lipocalin Human genes 0.000 description 2
- 108010079246 OMPA outer membrane proteins Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 241000223109 Trypanosoma cruzi Species 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000004847 absorption spectroscopy Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000013103 analytical ultracentrifugation Methods 0.000 description 2
- 239000012805 animal sample Substances 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- 210000003567 ascitic fluid Anatomy 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 150000001720 carbohydrates Chemical group 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 238000012412 chemical coupling Methods 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000000032 diagnostic agent Substances 0.000 description 2
- 229940039227 diagnostic agent Drugs 0.000 description 2
- 239000012470 diluted sample Substances 0.000 description 2
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- VJYFKVYYMZPMAB-UHFFFAOYSA-N ethoprophos Chemical compound CCCSP(=O)(OCC)SCCC VJYFKVYYMZPMAB-UHFFFAOYSA-N 0.000 description 2
- 238000002270 exclusion chromatography Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 102000046438 human CXCL10 Human genes 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000000984 immunochemical effect Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)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)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 2
- 229910052939 potassium sulfate Inorganic materials 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000010453 quartz Substances 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 239000013074 reference sample Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000001370 static light scattering Methods 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 230000005030 transcription termination Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 102100036826 Aldehyde oxidase Human genes 0.000 description 1
- 102100024092 Aldo-keto reductase family 1 member C4 Human genes 0.000 description 1
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010061075 Enterobactin Proteins 0.000 description 1
- SERBHKJMVBATSJ-UHFFFAOYSA-N Enterobactin Natural products OC1=CC=CC(C(=O)NC2C(OCC(C(=O)OCC(C(=O)OC2)NC(=O)C=2C(=C(O)C=CC=2)O)NC(=O)C=2C(=C(O)C=CC=2)O)=O)=C1O SERBHKJMVBATSJ-UHFFFAOYSA-N 0.000 description 1
- 101710198774 Envelope protein US9 Proteins 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- 229910002553 FeIII Inorganic materials 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 101150094690 GAL1 gene Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 102100028501 Galanin peptides Human genes 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010056438 Growth hormone deficiency Diseases 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 1
- 101100121078 Homo sapiens GAL gene Proteins 0.000 description 1
- 101000952234 Homo sapiens Sphingolipid delta(4)-desaturase DES1 Proteins 0.000 description 1
- 230000005353 IP-10 production Effects 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 108010015372 Low Density Lipoprotein Receptor-Related Protein-2 Proteins 0.000 description 1
- 102100021922 Low-density lipoprotein receptor-related protein 2 Human genes 0.000 description 1
- 101710147507 Neutrophil gelatinase-associated lipocalin Proteins 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 108700020962 Peroxidase Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- FELJDCNGZFDUNR-WDSKDSINSA-N Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 FELJDCNGZFDUNR-WDSKDSINSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 101100053822 Rattus norvegicus Zdhhc7 gene Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 102100037416 Sphingolipid delta(4)-desaturase DES1 Human genes 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 239000008049 TAE buffer Substances 0.000 description 1
- 101710153009 Uterocalin Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- HGEVZDLYZYVYHD-UHFFFAOYSA-N acetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound CC(O)=O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O HGEVZDLYZYVYHD-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 108010080374 albuferon Proteins 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 238000005460 biophysical method Methods 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-L catecholate(2-) Chemical compound [O-]C1=CC=CC=C1[O-] YCIMNLLNPGFGHC-UHFFFAOYSA-L 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 238000001142 circular dichroism spectrum Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000010405 clearance mechanism Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000012937 correction 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
- 238000004132 cross linking Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000001516 effect on protein Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 229940073621 enbrel Drugs 0.000 description 1
- 238000011013 endotoxin removal Methods 0.000 description 1
- SERBHKJMVBATSJ-BZSNNMDCSA-N enterobactin Chemical compound OC1=CC=CC(C(=O)N[C@@H]2C(OC[C@@H](C(=O)OC[C@@H](C(=O)OC2)NC(=O)C=2C(=C(O)C=CC=2)O)NC(=O)C=2C(=C(O)C=CC=2)O)=O)=C1O SERBHKJMVBATSJ-BZSNNMDCSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 231100000001 growth retardation Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229950000038 interferon alfa Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000000111 isothermal titration calorimetry Methods 0.000 description 1
- 210000001985 kidney epithelial cell Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 208000006178 malignant mesothelioma Diseases 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000007003 mineral medium Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 108010068617 neonatal Fc receptor Proteins 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940002988 pegasys Drugs 0.000 description 1
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 108010094020 polyglycine Proteins 0.000 description 1
- 229920000232 polyglycine polymer Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 108010026466 polyproline Proteins 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000013878 renal filtration Effects 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 108010051412 reteplase Proteins 0.000 description 1
- 229960002917 reteplase Drugs 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108010004486 trans-sialidase Proteins 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000005945 translocation 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
- 201000008827 tuberculosis Diseases 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- 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
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/545—IL-1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
- C07K14/56—IFN-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Emergency Medicine (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07012219 | 2007-06-21 | ||
| EP07012219 | 2007-06-21 | ||
| US71705 | 2008-05-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2362386T3 true ES2362386T3 (es) | 2011-07-04 |
Family
ID=39776993
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08773567T Active ES2362386T3 (es) | 2007-06-21 | 2008-06-20 | Proteínas activas biológicas que tienen estabilidad aumentada in vivo y/o in vitro. |
| ES11158295T Active ES2422007T3 (es) | 2007-06-21 | 2008-06-20 | Proteínas activas biológicas que tienen estabilidad aumentada in vivo y/o in vitro |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11158295T Active ES2422007T3 (es) | 2007-06-21 | 2008-06-20 | Proteínas activas biológicas que tienen estabilidad aumentada in vivo y/o in vitro |
Country Status (19)
Families Citing this family (219)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7855279B2 (en) * | 2005-09-27 | 2010-12-21 | Amunix Operating, Inc. | Unstructured recombinant polymers and uses thereof |
| US7846445B2 (en) * | 2005-09-27 | 2010-12-07 | Amunix Operating, Inc. | Methods for production of unstructured recombinant polymers and uses thereof |
| US8841255B2 (en) | 2005-12-20 | 2014-09-23 | Duke University | Therapeutic agents comprising fusions of vasoactive intestinal peptide and elastic peptides |
| US8178495B2 (en) | 2008-06-27 | 2012-05-15 | Duke University | Therapeutic agents comprising a GLP-1 receptor agonist and elastin-like peptide |
| US8334257B2 (en) | 2005-12-20 | 2012-12-18 | Duke University | Methods and compositions for delivering active agents with enhanced pharmacological properties |
| US20130172274A1 (en) | 2005-12-20 | 2013-07-04 | Duke University | Methods and compositions for delivering active agents with enhanced pharmacological properties |
| ES2385114T3 (es) | 2007-03-30 | 2012-07-18 | Ambrx, Inc. | Polipéptidos de FGF-21 modificados y sus usos |
| EA021222B8 (ru) | 2007-06-21 | 2015-11-30 | ИксЭль-ПРОТЕИН ГМБХ | Биологически активные белки, имеющие повышенную стабильность in vivo и/или in vitro |
| EP2185701A4 (en) | 2007-08-15 | 2011-03-02 | Amunix Operating Inc | COMPOSITIONS AND METHODS FOR ENHANCING THE PRODUCTION OF RECOMBINANT POLYPEPTIDES |
| LT2279007T (lt) | 2008-04-29 | 2016-10-10 | Ascendis Pharma Growth Disorders Division A/S | Pegiliuoto rekombinantinio žmogaus augimo hormono junginiai |
| WO2009140599A1 (en) | 2008-05-15 | 2009-11-19 | Transmolecular, Inc. | Treatment of metastatic tumors |
| US8680050B2 (en) | 2009-02-03 | 2014-03-25 | Amunix Operating Inc. | Growth hormone polypeptides fused to extended recombinant polypeptides and methods of making and using same |
| US8957021B2 (en) | 2009-02-03 | 2015-02-17 | Amunix Operating Inc. | Glucose-regulating polypeptides and methods of making and using same |
| DK3178835T3 (da) | 2009-02-03 | 2019-06-24 | Amunix Pharmaceuticals Inc | Forlængede rekombinante polypeptider og sammensætninger omfattende samme |
| US8703717B2 (en) | 2009-02-03 | 2014-04-22 | Amunix Operating Inc. | Growth hormone polypeptides and methods of making and using same |
| US9849188B2 (en) | 2009-06-08 | 2017-12-26 | Amunix Operating Inc. | Growth hormone polypeptides and methods of making and using same |
| PE20121539A1 (es) * | 2009-06-08 | 2012-12-06 | Amunix Operating Inc | Polipeptidos de la hormona de crecimiento y metodos de preparacion |
| CN102741422B (zh) * | 2009-08-24 | 2016-06-08 | 阿穆尼克斯运营公司 | 凝血因子ⅶ组合物及其制备和使用方法 |
| DK2512450T3 (en) | 2009-12-15 | 2018-04-23 | Ascendis Pharma Endocrinology Div A/S | Dry growth hormone composition transiently bound to a polymer carrier |
| WO2011075185A1 (en) | 2009-12-18 | 2011-06-23 | Oligasis | Targeted drug phosphorylcholine polymer conjugates |
| CN106995493B (zh) | 2010-02-04 | 2021-09-24 | 卫材公司 | 氯毒素多肽和结合物及其应用 |
| US8557961B2 (en) | 2010-04-02 | 2013-10-15 | Amunix Operating Inc. | Alpha 1-antitrypsin compositions and methods of making and using same |
| EP4450523A3 (en) * | 2010-04-02 | 2025-03-12 | Amunix Pharmaceuticals, Inc. | Binding fusion proteins, binding fusion protein-drug conjugates, xten-drug conjugates and methods of making and using same |
| TWI510246B (zh) | 2010-04-30 | 2015-12-01 | Molecular Partners Ag | 抑制ｖｅｇｆ－ａ受體交互作用的經修飾結合性蛋白質 |
| EP3165533B1 (en) | 2010-05-11 | 2020-04-08 | Fred Hutchinson Cancer Research Center | Chlorotoxin variants, conjugates and methods for their use |
| MX357674B (es) | 2010-05-21 | 2018-07-18 | Xl Protein Gmbh | Polipeptidos biosinteticos de espira aleatoria de prolina/alanina y sus usos. |
| WO2011146902A1 (en) | 2010-05-21 | 2011-11-24 | Merrimack Pharmaceuticals, Inc. | Bi-specific fusion proteins |
| WO2011157819A2 (en) | 2010-06-18 | 2011-12-22 | Xiberscience Gmbh | Peptides as active agents to stabilize biological barriers |
| LT2598526T (lt) | 2010-07-29 | 2018-10-10 | Eleven Biotherapeutics, Inc. | Chimeriniai il-1 receptoriaus i tipo agonistai ir antagonistai |
| EP2643348B1 (en) | 2010-11-26 | 2025-02-12 | Molecular Partners AG | Improved capping modules for designed ankyrin repeat proteins |
| IL210093A0 (en) * | 2010-12-19 | 2011-06-30 | David Helman | Membrane bound reporter molecules and their use in cell sorting |
| WO2012103240A2 (en) | 2011-01-25 | 2012-08-02 | Eleven Biotherapeutics, Inc. | Receptor binding agents |
| HUE043894T2 (hu) | 2011-06-10 | 2019-09-30 | Bioverativ Therapeutics Inc | Koagulációt elõsegítõ vegyületek és alkalmazásuk módszerei |
| JP2014522838A (ja) | 2011-07-08 | 2014-09-08 | バイオジェン アイデック ヘモフィリア インコーポレイテッド | 第ｖｉｉｉ因子キメラおよびハイブリッドポリペプチドならびにその使用法 |
| US10656167B2 (en) | 2011-07-25 | 2020-05-19 | Bioverativ Therapeutics Inc. | Assays to monitor bleeding disorders |
| SG10201606218WA (en) | 2011-07-29 | 2016-09-29 | Eleven Biotherapeutics Inc | Purified Proteins |
| WO2013024052A1 (en) | 2011-08-12 | 2013-02-21 | Ascendis Pharma A/S | Carrier-linked treprostinil prodrugs |
| CA2843504C (en) * | 2011-08-12 | 2020-08-25 | Ascendis Pharma A/S | Protein carrier-linked prodrugs |
| EP2804623B1 (en) | 2012-01-12 | 2019-08-07 | Bioverativ Therapeutics Inc. | Chimeric factor viii polypeptides and uses thereof |
| US20130210747A1 (en) | 2012-02-13 | 2013-08-15 | University Of Southern California | Methods and Therapeutics Comprising Ligand-Targeted ELPs |
| JP6383666B2 (ja) | 2012-02-15 | 2018-08-29 | バイオベラティブ セラピューティクス インコーポレイテッド | 組換え第ｖｉｉｉ因子タンパク質 |
| EP2814840B1 (en) | 2012-02-15 | 2019-11-13 | Bioverativ Therapeutics Inc. | Factor viii compositions and methods of making and using same |
| MX366864B (es) | 2012-02-27 | 2019-07-26 | Amunix Operating Inc | Composiciones de conjugados de xten y métodos para realizarlas. |
| PT2846836T (pt) | 2012-05-07 | 2019-10-29 | Allergan Inc | Método de tratamento de dmi em doentes refratários à terapia anti-vegf |
| EP2858659B1 (en) | 2012-06-08 | 2019-12-25 | Bioverativ Therapeutics Inc. | Procoagulant compounds |
| WO2013185114A2 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Chimeric clotting factors |
| AU2013283296A1 (en) | 2012-06-28 | 2015-02-05 | Molecular Partners Ag | Designed ankyrin repeat proteins binding to platelet-derived growth factor |
| EP2870250B2 (en) | 2012-07-06 | 2022-06-29 | Bioverativ Therapeutics Inc. | Cell line expressing single chain factor viii polypeptides and uses thereof |
| SG10201701037WA (en) | 2012-07-11 | 2017-03-30 | Amunix Operating Inc | Factor viii complex with xten and von willebrand factor protein, and uses thereof |
| US20150218280A1 (en) | 2012-08-10 | 2015-08-06 | University Of Southern California | CD20 scFv-ELPs METHODS AND THERAPEUTICS |
| US20140092376A1 (en) * | 2012-10-01 | 2014-04-03 | Momentive Performance Materials, Inc. | Container and method for in-line analysis of protein compositions |
| WO2014063108A1 (en) | 2012-10-18 | 2014-04-24 | Biogen Idec Ma Inc. | Methods of using a fixed dose of a clotting factor |
| WO2014070953A1 (en) | 2012-10-30 | 2014-05-08 | Biogen Idec Ma Inc. | Methods of Using FVIII Polypeptide |
| US20150290328A1 (en) | 2012-11-20 | 2015-10-15 | Phasebio Pharmaceuticals, Inc. | Formulations of active agents for sustained release |
| EP2738180A1 (en) | 2012-11-30 | 2014-06-04 | Molecular Partners AG | Binding proteins comprising at least two binding domains against HER2. |
| BR112015013525A2 (pt) | 2012-12-10 | 2017-11-14 | Hutchinson Fred Cancer Res | método para produção de uma proteína de fusão, bem como composição compreendendo uma proteína de fusão |
| TWI674270B (zh) | 2012-12-11 | 2019-10-11 | 英商梅迪繆思有限公司 | 用於治療肥胖之升糖素與glp-1共促效劑 |
| SI2956477T2 (sl) | 2013-02-15 | 2024-05-31 | Bioverativ Therapeutics Inc. | Optimiran gen dejavnika VIII |
| BR112015022587A2 (pt) | 2013-03-13 | 2017-10-24 | Eleven Biotherapeutics Inc | formulações de citocina quimérica para entrega ocular |
| EP3238734A1 (en) | 2013-03-14 | 2017-11-01 | Medimmune Limited | Pegylated glucagon and glp-1 co-agonists for the treatment of obesity |
| EA037906B1 (ru) | 2013-03-15 | 2021-06-04 | Биовератив Терапьютикс Инк. | Препараты полипептида фактора ix |
| LT2968477T (lt) | 2013-03-15 | 2020-03-10 | Bioverativ Therapeutics Inc. | Faktoriaus viii polipeptido kompozicijos |
| HK1223302A1 (zh) | 2013-06-28 | 2017-07-28 | Bioverativ Therapeutics Inc. | 具有xten的凝血酶可裂解连接子和其用途 |
| WO2015022326A1 (en) | 2013-08-12 | 2015-02-19 | Xiber Science Gmbh | Peptides as active agents for treating primary graft dysfunction |
| EP3033098B1 (en) | 2013-08-14 | 2022-06-22 | Bioverativ Therapeutics Inc. | Recombinant factor viii proteins |
| EP3033097B1 (en) | 2013-08-14 | 2021-03-10 | Bioverativ Therapeutics Inc. | Factor viii-xten fusions and uses thereof |
| LT3041513T (lt) | 2013-09-08 | 2020-11-25 | Kodiak Sciences Inc. | Viii faktoriaus cviterioninių polimerų konjugatai |
| US11559580B1 (en) | 2013-09-17 | 2023-01-24 | Blaze Bioscience, Inc. | Tissue-homing peptide conjugates and methods of use thereof |
| EP3903599A1 (en) | 2013-09-25 | 2021-11-03 | Bioverativ Therapeutics Inc. | On-column viral inactivation methods |
| PL3065761T3 (pl) | 2013-11-05 | 2020-05-18 | Allergan, Inc. | Sposób leczenia schorzeń oczu za pomocą darpinu przeciwko vegf |
| US10584147B2 (en) | 2013-11-08 | 2020-03-10 | Biovertiv Therapeutics Inc. | Procoagulant fusion compound |
| CA2929201A1 (en) | 2013-11-11 | 2015-05-14 | Ascendis Pharma Relaxin Division A/S | Relaxin prodrugs |
| DE102013113156A1 (de) | 2013-11-28 | 2015-05-28 | Freie Universität Berlin | Verbindung und Verfahren zur selektiven Radiomarkierung von Polypeptiden mittels Festphasensynthese |
| EP3082848B1 (en) | 2013-12-06 | 2023-10-18 | Bioverativ Therapeutics Inc. | Population pharmacokinetics tools and uses thereof |
| EP3102224B1 (en) * | 2013-12-20 | 2019-02-20 | NephroGenesis, LLC. | Apparatuses for kidney dialysis and lipocalin protein for use in the prevention or treatment of uremia by dialysis |
| HRP20220960T1 (hr) | 2014-01-10 | 2022-10-28 | Bioverativ Therapeutics Inc. | Kimerni proteini faktora viii i njihova upotreba |
| WO2015132004A1 (en) | 2014-03-05 | 2015-09-11 | Merz Pharma Gmbh & Co. Kgaa | Novel recombinant clostridial neurotoxins with increased duration of effect |
| KR102385372B1 (ko) | 2014-03-24 | 2022-04-11 | 바이오버라티브 테라퓨틱스 인크. | 동결건조된 ix 인자 제형 |
| EP2937096B1 (en) | 2014-04-23 | 2019-08-21 | Julius-Maximilians-Universität Würzburg | Peptides derived from RS1 which down-regulate glucose absorption after a glucose rich meal and increase insulin sensitivity |
| US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
| US11008561B2 (en) | 2014-06-30 | 2021-05-18 | Bioverativ Therapeutics Inc. | Optimized factor IX gene |
| US9616114B1 (en) | 2014-09-18 | 2017-04-11 | David Gordon Bermudes | Modified bacteria having improved pharmacokinetics and tumor colonization enhancing antitumor activity |
| AP2017009826A0 (en) | 2014-09-26 | 2017-03-31 | Bayer Pharma AG | Stabilized adrenomedullin derivatives and use thereof |
| CA2963053C (en) | 2014-09-30 | 2024-01-23 | Thena Biotech S.r.l. | A fusion protein, a nanoparticle composed by a plurality of monomers of said fusion protein, and uses thereof |
| CA2964317C (en) | 2014-10-14 | 2021-10-05 | Halozyme, Inc. | Compositions of adenosine deaminase-2 (ada2), variants thereof and methods of using same |
| JP6849590B2 (ja) | 2014-10-17 | 2021-03-24 | コディアック サイエンシーズ インコーポレイテッドＫｏｄｉａｋ Ｓｃｉｅｎｃｅｓ Ｉｎｃ． | ブチリルコリンエステラーゼ両性イオン性ポリマーコンジュゲート |
| MA40835A (fr) | 2014-10-23 | 2017-08-29 | Biogen Ma Inc | Anticorps anti-gpiib/iiia et leurs utilisations |
| CN114853868A (zh) | 2014-10-24 | 2022-08-05 | 百时美施贵宝公司 | 修饰的fgf-21多肽及其用途 |
| MA40861A (fr) | 2014-10-31 | 2017-09-05 | Biogen Ma Inc | Anticorps anti-glycoprotéines iib/iiia |
| SG11201703870UA (en) | 2014-11-18 | 2017-06-29 | Ascendis Pharma Endocrinology Div As | Novel polymeric hgh prodrugs |
| JP7075757B2 (ja) | 2014-11-21 | 2022-05-26 | フェーズバイオ ファーマシューティカルズ，インコーポレイテッド | 制御放出および持続的放出のためのｅｌｐ融合タンパク質 |
| HUE056849T2 (hu) | 2014-11-21 | 2022-03-28 | Ascendis Pharma Endocrinology Div A/S | Hosszú hatástartalmú növekedési hormon adagolási formák |
| CA2970478A1 (en) | 2014-12-10 | 2016-06-16 | S-Aima Holding Company, Llc | Generation of hemoglobin-based oxygen carriers using elastin-like polypeptides |
| CN107427556B (zh) | 2015-02-09 | 2022-02-25 | 费斯生物制药公司 | 用于治疗肌肉疾病和病症的方法和组合物 |
| US10478394B2 (en) | 2015-03-11 | 2019-11-19 | Wayne State University | Compositions and methods to promote wound healing |
| IL276944B (en) | 2015-04-02 | 2022-07-01 | Molecular Partners Ag | Designed ankyrin repeat domains with binding specificity for serum albumin |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| TWI726889B (zh) | 2015-06-10 | 2021-05-11 | 英商梅迪繆思有限公司 | 蛋白酶抗性之脂化肽 |
| TW201718627A (zh) | 2015-06-11 | 2017-06-01 | 梅茲製藥有限兩合公司 | 重組梭菌神經毒素及其使用與形成方法、包括其之醫藥組合物及對應其之前驅物、編碼前驅物之核酸序列及其獲得方法與前驅物之形成方法、載體與包括核酸序列之重組宿主細胞 |
| WO2017024060A1 (en) | 2015-08-03 | 2017-02-09 | Biogen Ma Inc. | Factor ix fusion proteins and methods of making and using same |
| IL319047A (en) | 2015-08-28 | 2025-04-01 | Amunix Operating Inc | Chimeric polypeptide composition and methods for its preparation and use |
| US10040840B2 (en) | 2015-10-02 | 2018-08-07 | Silver Creek Pharmaceuticals, Inc. | Bi-specific annexin A5/IGF-1 proteins and methods of use thereof to promote regeneration and survival of tissue |
| WO2017083491A2 (en) * | 2015-11-10 | 2017-05-18 | Proteothera, Inc. | Methods of producing and purifying matrix-binding fusion proteins by ion-exchange chromatography |
| HUE055267T2 (hu) * | 2015-12-22 | 2021-11-29 | Xl Protein Gmbh | Kevés repetitív nukleotid szekvenciával rendelkezõ, prolinban és alaninban gazdag repetitív aminosavszekvenciákat kódoló nukleinsavak |
| AU2016381964B2 (en) | 2015-12-30 | 2024-02-15 | Kodiak Sciences Inc. | Antibodies and conjugates thereof |
| US10835578B2 (en) | 2016-01-08 | 2020-11-17 | Ascendis Pharma Growth Disorders A/S | CNP prodrugs with large carrier moieties |
| MY195190A (en) | 2016-01-08 | 2023-01-11 | Ascendis Pharma Growth Disorders As | Controlled-Release Cnp Agonists With Increased Nep Stability |
| IL318754A (en) | 2016-01-08 | 2025-04-01 | Ascendis Pharma Growth Disorders As | Controlled-release CNP agonists with low initial NPR-B activity |
| EP3400021A1 (en) | 2016-01-08 | 2018-11-14 | Ascendis Pharma Growth Disorders A/S | Controlled-release cnp agonists with low npr-c binding |
| US11389511B2 (en) | 2016-01-08 | 2022-07-19 | Ascendis Pharma Growth Disorders A/S | Controlled-release CNP agonists with reduced side-effects |
| JP6968802B2 (ja) | 2016-01-08 | 2021-11-17 | アセンディス ファーマ グロース ディスオーダーズ エー／エス | 環部分にキャリア結合を有するｃｎｐプロドラッグ |
| US11078472B2 (en) | 2016-01-20 | 2021-08-03 | Merz Pharma Gmbh & Co., Kgaa | Recombinant clostridial neurotoxins with increased duration of effect |
| PT3411478T (pt) | 2016-02-01 | 2022-09-13 | Bioverativ Therapeutics Inc | Genes do fator viii otimizados |
| MA45277A (fr) | 2016-03-01 | 2019-01-09 | Ascendis Pharma Bone Diseases As | Promédicaments de pth |
| US11969461B2 (en) | 2016-03-02 | 2024-04-30 | Merz Pharma Gmbh & Co. Kgaa | Composition comprising botulinum toxin |
| US10676517B2 (en) | 2016-03-10 | 2020-06-09 | Medimmune Limited | Glucagon and GLP-1 co-agonists for the treatment of obesity |
| CA3021011A1 (en) | 2016-04-15 | 2017-10-19 | Blaze Bioscience, Inc. | Methods of treating breast cancer |
| CA3022751A1 (en) * | 2016-05-04 | 2017-11-09 | Navigo Proteins Gmbh | Targeted compounds for the site-specific coupling of chemical moieties comprising a peptide linker |
| EP4043010A1 (en) | 2016-05-06 | 2022-08-17 | Phasebio Pharmaceuticals, Inc. | Elp fusion proteins for controlled and sustained release |
| US11896671B2 (en) | 2016-07-13 | 2024-02-13 | Ascendis Pharma A/S | Conjugation method for carrier-linked prodrugs |
| LT3518930T (lt) | 2016-09-29 | 2023-05-10 | Ascendis Pharma Growth Disorders A/S | Kompleksinė terapija su kontroliuojamo išskyrimo cnp agonistais |
| CA3037447A1 (en) | 2016-09-29 | 2018-04-05 | Ascendis Pharma Bone Diseases A/S | Pth compounds with low peak-to-trough ratios |
| PL3518960T3 (pl) | 2016-09-29 | 2023-12-27 | Ascendis Pharma Bone Diseases A/S | Schemat dawkowania związku pth o kontrolowanym uwalnianiu |
| SMT202500059T1 (it) | 2016-09-29 | 2025-03-12 | Ascendis Pharma Bone Diseases As | Composti pth a rilascio controllato |
| KR20190091292A (ko) | 2016-12-02 | 2019-08-05 | 바이오버라티브 테라퓨틱스 인크. | 응고 인자에 대한 면역 내성 유도 방법 |
| IL266972B2 (en) | 2016-12-02 | 2024-04-01 | Bioverativ Therapeutics Inc | Methods of treating hemophilic arthropathy using chimeric clotting factors |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| EP3562840A1 (en) | 2016-12-16 | 2019-11-06 | Biogen MA Inc. | Stabilized proteolytically activated growth differentiation factor 11 |
| TW201831521A (zh) | 2017-01-31 | 2018-09-01 | 美商生物化學醫療公司 | 因子ｉｘ融合蛋白以及其製備方法及使用方法 |
| LT3596116T (lt) | 2017-03-16 | 2023-11-10 | Alpine Immune Sciences, Inc. | Imunomoduliacinių baltymų pd-l1 variantai ir jų naudojimo būdai |
| WO2018170026A2 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Cd80 variant immunomodulatory proteins and uses thereof |
| CA3053812A1 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Pd-l2 variant immunomodulatory proteins and uses thereof |
| WO2018191548A2 (en) | 2017-04-14 | 2018-10-18 | Kodiak Sciences Inc. | Complement factor d antagonist antibodies and conjugates thereof |
| IL269895B2 (en) * | 2017-04-21 | 2024-06-01 | Volution Immuno Pharmaceuticals Sa | Coversin for the treatment of autoimmune blistering diseases |
| EP3642222A1 (en) | 2017-06-20 | 2020-04-29 | Merz Pharma GmbH & Co. KGaA | Novel recombinant botulinum toxin with increased duration of effect |
| EP3642340B1 (en) | 2017-06-21 | 2024-03-20 | Jazz Pharmaceuticals Ireland Limited | Modified l-asparaginase |
| CN110891612A (zh) | 2017-06-21 | 2020-03-17 | Xl-蛋白有限责任公司 | 蛋白质药物与p/a肽的缀合物 |
| US10174302B1 (en) | 2017-06-21 | 2019-01-08 | Xl-Protein Gmbh | Modified L-asparaginase |
| EP3649143B1 (en) | 2017-07-06 | 2022-08-31 | Merz Pharma GmbH & Co. KGaA | Novel recombinant botulinum neurotoxins with increased duration of effect |
| KR102780287B1 (ko) | 2017-08-09 | 2025-03-14 | 바이오버라티브 테라퓨틱스 인크. | 핵산 분자 및 이의 용도 |
| MY203416A (en) | 2017-10-18 | 2024-06-27 | Alpine Immune Sciences Inc | Variant icos ligand immunomodulatory proteins and related compositions and methods |
| ES2923152T3 (es) * | 2017-11-06 | 2022-09-23 | Thena Biotech S R L | Proteínas de fusión basadas en ferritina humana y péptidos escindibles por proteasas y su uso como vehículos quimioterapéuticos |
| EP3483619A1 (en) * | 2017-11-13 | 2019-05-15 | Technische Universität München | Automated noninvasive determining the sex of an embryo of and the fertility of a bird's egg |
| JP2021507706A (ja) | 2017-12-21 | 2021-02-25 | アムニクス ファーマシューティカルズ， インコーポレイテッド | 放出セグメントおよびそれを含む結合組成物 |
| BR112020013236A2 (pt) | 2018-01-03 | 2020-12-01 | Alpine Immune Sciences, Inc. | proteínas imunomoduladoras de múltiplos domínios e métodos de seu uso |
| AU2019215063B2 (en) | 2018-02-01 | 2025-10-16 | Bioverativ Therapeutics, Inc. | Use of lentiviral vectors expressing Factor VIII |
| WO2019169341A1 (en) | 2018-03-02 | 2019-09-06 | Kodiak Sciences Inc. | Il-6 antibodies and fusion constructs and conjugates thereof |
| GB201804092D0 (en) * | 2018-03-14 | 2018-04-25 | Imperial Innovations Ltd | Methods and compositions |
| MX2020009857A (es) | 2018-03-28 | 2021-01-08 | Ascendis Pharma Oncology Div A/S | Conjugados de interleucina-2 (il-2). |
| KR102824112B1 (ko) | 2018-03-28 | 2025-06-24 | 브리스톨-마이어스 스큅 컴퍼니 | 인터루킨-2/인터루킨-2 수용체 알파 융합 단백질 및 사용 방법 |
| WO2019185706A1 (en) | 2018-03-28 | 2019-10-03 | Ascendis Pharma A/S | Conjugates |
| BR112020022306A2 (pt) | 2018-05-18 | 2021-02-23 | Ascendis Pharma Bone Diseases A/S | dose de partida de conjugados de pth |
| CA3099049A1 (en) | 2018-05-18 | 2019-11-21 | Bioverativ Therapeutics Inc. | Methods of treating hemophilia a |
| WO2019241758A1 (en) | 2018-06-15 | 2019-12-19 | Alpine Immune Sciences, Inc. | Pd-1 variant immunomodulatory proteins and uses thereof |
| CN112601517A (zh) | 2018-07-03 | 2021-04-02 | 百时美施贵宝公司 | Fgf-21配制品 |
| BR112021002017A2 (pt) | 2018-08-09 | 2021-05-11 | Bioverativ Therapeutics Inc. | moléculas de ácido nucleico e usos das mesmas para terapia genética não viral |
| JP2021535739A (ja) | 2018-08-27 | 2021-12-23 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | 下流精製でのラマン分光法の使用 |
| US20220047673A1 (en) | 2018-09-10 | 2022-02-17 | Volution Immuno Pharmaceuticals Sa | Coversin for Use in the Treatment of Rheumatic Diseases |
| KR20250154552A (ko) | 2018-09-27 | 2025-10-28 | 실리오 디벨럽먼트, 인크. | 마스킹된 사이토카인 폴리펩타이드 |
| CN111040021B (zh) * | 2018-10-12 | 2023-06-02 | 浙江道尔生物科技有限公司 | 一种改善生物活性蛋白性质的载体蛋白 |
| JP2022013959A (ja) * | 2018-11-02 | 2022-01-19 | 味の素株式会社 | 融合タンパク質 |
| CN116102621A (zh) | 2018-11-07 | 2023-05-12 | 浙江道尔生物科技有限公司 | 用于改善活性蛋白或多肽性能的人工重组蛋白及其应用 |
| US20220025344A1 (en) | 2018-11-26 | 2022-01-27 | Novartis Ag | Lpl-gpihbp1 fusion polypeptides |
| US20220372106A1 (en) | 2018-11-30 | 2022-11-24 | Alpine Immune Sciences, Inc. | Cd86 variant immunomodulatory proteins and uses thereof |
| CN113396223A (zh) | 2018-12-06 | 2021-09-14 | 比奥维拉迪维治疗股份有限公司 | 表达因子ix的慢病毒载体的用途 |
| CN113423383A (zh) | 2019-02-11 | 2021-09-21 | 阿森迪斯药物骨疾病股份有限公司 | Pth缀合物的液体药物制剂 |
| KR102893903B1 (ko) | 2019-02-11 | 2025-12-01 | 아센디스 파마 그로우쓰 디스오더스 에이/에스 | Cnp 접합체의 건조 약학 제제 |
| MX2021010286A (es) | 2019-03-04 | 2021-09-23 | Ascendis Pharma Endocrinology Div A/S | Formas de dosificacion de la hormona del crecimiento de accion prolongada con eficacia superior a la somatropina diaria. |
| CN114008069A (zh) | 2019-04-17 | 2022-02-01 | 科迪亚克生物科学公司 | 外来体和aav的组合物 |
| GB201905810D0 (en) * | 2019-04-25 | 2019-06-05 | Volution Immuno Pharmaceuticals Sa | Method of treatment |
| WO2020245171A1 (en) | 2019-06-04 | 2020-12-10 | Molecular Partners Ag | Designed ankyrin repeat domain with improved stability |
| EP3986918A1 (en) | 2019-06-18 | 2022-04-27 | Bayer Aktiengesellschaft | Adrenomedullin-analogues for long-term stabilization and their use |
| EP3986471A1 (en) | 2019-06-21 | 2022-04-27 | Ascendis Pharma A/S | Conjugates of an electron-donating nitrogen or tertiary amine comprising compounds |
| CA3143442A1 (en) | 2019-06-21 | 2020-12-24 | Ascendis Pharma A/S | Conjugates of heteroaromatic nitrogen-comprising compounds |
| KR20220024690A (ko) | 2019-06-21 | 2022-03-03 | 아센디스 파마 에이에스 | π 전자쌍 공여 헤테로방향족 질소 포함 화합물의 컨쥬게이트 |
| CA3152665A1 (en) | 2019-08-27 | 2021-03-04 | Tonix Pharma Limited | Modified tff2 polypeptides |
| US20220370556A1 (en) | 2019-09-27 | 2022-11-24 | Volution Immuno Pharmaceuticals Sa | Method of Treatment |
| US12290603B2 (en) | 2019-09-27 | 2025-05-06 | Duke University | Tabletization of peptide self-assemblies and methods of making and using the same |
| JP2022549932A (ja) | 2019-09-30 | 2022-11-29 | バイオベラティブ セラピューティクス インコーポレイテッド | レンチウイルスベクター製剤 |
| CN114786731A (zh) | 2019-10-10 | 2022-07-22 | 科达制药股份有限公司 | 治疗眼部病症的方法 |
| CN115260313B (zh) | 2019-12-31 | 2023-07-18 | 北京质肽生物医药科技有限公司 | Glp-1和gdf15的融合蛋白以及其缀合物 |
| WO2021136808A1 (en) | 2020-01-03 | 2021-07-08 | Ascendis Pharma A/S | Conjugates undergoing intramolecular rearrangements |
| CN113728013B (zh) | 2020-01-11 | 2022-06-14 | 北京质肽生物医药科技有限公司 | Glp-1和fgf21的融合蛋白的缀合物 |
| JP2023510790A (ja) | 2020-01-13 | 2023-03-15 | アセンディス ファーマ ボーン ディジージズ エー／エス | 副甲状腺機能低下症の治療 |
| PE20230494A1 (es) | 2020-05-08 | 2023-03-23 | Alpine Immune Sciences Inc | Proteinas inmunomoduladoras inhibidoras de april y baff y metodos de uso de las mismas |
| JP2023527919A (ja) | 2020-06-03 | 2023-06-30 | アセンディス ファーマ オンコロジー ディヴィジョン エー／エス | Ｉｌ－２配列及びその使用 |
| US12173307B2 (en) | 2020-06-24 | 2024-12-24 | Bioverativ Therapeutics Inc. | Methods for the purification of viral vectors |
| US20220031812A1 (en) | 2020-07-30 | 2022-02-03 | Silver Creek Pharmaceuticals, Inc. | Chimeric Proteins and Methods of Use for Treatment of Central Nervous System Disorders |
| CA3184998A1 (en) | 2020-08-05 | 2022-02-10 | Samuel WEISBROD | Conjugates comprising reversible linkers and uses thereof |
| JP2023538533A (ja) | 2020-08-07 | 2023-09-08 | ブリストル－マイヤーズ スクイブ カンパニー | 線維症の処置のための、ｃｃｒ２／５拮抗剤と組み合わせたｆｇｆ２１ |
| MX2023002047A (es) | 2020-08-28 | 2023-03-15 | Ascendis Pharma Oncology Div A/S | Proteinas de interleucina 2 (il-2) glucosiladas y usos de las mismas. |
| TW202228784A (zh) | 2020-09-23 | 2022-08-01 | 奧地利商艾柏力維亞生技有限公司 | 用以於一患者中螯合非預期的抗ｐｅｇ抗體的化合物 |
| US20230364199A1 (en) | 2020-09-28 | 2023-11-16 | Ascendis Pharma Bone Diseases A/S | Improvement of physical and mental well-being of patients with hypoparathyroidism |
| WO2022068920A1 (en) | 2020-09-30 | 2022-04-07 | Beijing Ql Biopharmaceutical Co., Ltd. | Polypeptide conjugates and methods of uses |
| US20240123031A1 (en) | 2020-11-25 | 2024-04-18 | Bristol-Myers Squibb Company | Methods of treating liver diseases |
| EP4259199A1 (en) | 2020-12-11 | 2023-10-18 | Friedrich Miescher Institute for Biomedical Research | Hdac6 binding proteins and their anti-viral use |
| WO2022136582A1 (en) | 2020-12-22 | 2022-06-30 | Xl-Protein Gmbh | Antibodies specific for structurally disordered sequences |
| CN117396497A (zh) | 2021-04-01 | 2024-01-12 | 阿森迪斯药物股份有限公司 | 长效生长激素用于治疗炎症诱导的疾病的用途 |
| WO2022221395A1 (en) | 2021-04-14 | 2022-10-20 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
| CA3218973A1 (en) * | 2021-05-14 | 2022-11-17 | Antlia Bioscience, Inc. | Modified b-type natriuretic peptide |
| TW202313974A (zh) | 2021-06-08 | 2023-04-01 | 瑞典商阿斯特捷利康公司 | 用於治療肝病之組合療法 |
| JP2024534123A (ja) | 2021-08-23 | 2024-09-18 | バイオベラティブ セラピューティクス インコーポレイテッド | バキュロウイルス発現システム |
| KR20240082355A (ko) | 2021-09-22 | 2024-06-10 | 아센디스 파마 본 디지즈 에이/에스 | 장시간 작용형 pth 화합물 치료 |
| WO2023110758A1 (en) | 2021-12-13 | 2023-06-22 | Ascendis Pharma Growth Disorders A/S | Effective doses of cnp conjugates |
| JP2025512832A (ja) | 2022-03-30 | 2025-04-22 | ベイジン キューエル バイオファーマシューティカル カンパニー，リミテッド | ポリペプチドコンジュゲートの液体医薬組成物およびその使用の方法 |
| US20250195617A1 (en) | 2022-05-23 | 2025-06-19 | Ascendis Pharma Growth Disorders A/S | Liquid Pharmaceutical Formulations of CNP Compounds |
| EP4342460A1 (en) | 2022-09-21 | 2024-03-27 | NovoArc GmbH | Lipid nanoparticle with nucleic acid cargo |
| EP4611891A1 (en) | 2022-11-02 | 2025-09-10 | Ascendis Pharma Bone Diseases A/S | Pth treatment regimen comprising two pth compounds |
| WO2024104922A1 (en) | 2022-11-14 | 2024-05-23 | Ascendis Pharma Growth Disorders A/S | Method of improving skeletal muscle function |
| GB202218084D0 (en) | 2022-12-01 | 2023-01-18 | Volution Immuno Pharmaceuticals Sa | Fusion proteins |
| WO2024194300A1 (en) | 2023-03-20 | 2024-09-26 | Ascendis Pharma Growth Disorders A/S | Method of treatment of a thoracolumbar deformity in a human subject with achondroplasia |
| WO2025030053A1 (en) | 2023-08-01 | 2025-02-06 | Insmed Incorporated | Novel igg proteases and methods of use thereof |
| WO2025046121A1 (en) | 2023-09-01 | 2025-03-06 | Novoarc Gmbh | Lipid nanoparticle with nucleic acid cargo and ionizable lipid |
| WO2025051711A1 (en) | 2023-09-04 | 2025-03-13 | Ascendis Pharma Bone Diseases A/S | Pth treatment of chronic kidney disease |
| WO2025088192A1 (en) | 2023-10-27 | 2025-05-01 | Xl-Protein Gmbh | Methods for the coupling of di(alkyl)amines to polypeptides |
| WO2025088193A1 (en) | 2023-10-27 | 2025-05-01 | Xl-Protein Gmbh | Methods for efficient recombinant production of polypeptides |
| WO2025233381A1 (en) | 2024-05-07 | 2025-11-13 | Technische Universität München, in Vertretung des Freistaates Bayern | Enzymes that eliminate pyrimidine and/or purine nucleosides for treating cancer |
| GB202408081D0 (en) | 2024-06-06 | 2024-07-24 | Volution Immuno Pharmaceuticals Sa | Methods of removing impurities |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI92601C (fi) * | 1992-03-11 | 1994-12-12 | Marja Makarow | Menetelmä hyötyproteiinien erittämiseksi hiivoista |
| US20030190740A1 (en) * | 1998-10-13 | 2003-10-09 | The University Of Georgia Research Foundation, Inc | Stabilized bioactive peptides and methods of identification, synthesis, and use |
| JP2004504016A (ja) | 2000-06-30 | 2004-02-12 | マキシゲン・エイピーエス | ペプチド拡張されたグリコシル化ポリペプチド |
| WO2006081249A2 (en) | 2005-01-25 | 2006-08-03 | Cell Therapeutics, Inc. | Conjugates of biologically active proteins having a modified in vivo half-life |
| EP1871785B1 (en) * | 2005-04-20 | 2010-05-05 | Viromed Co., Ltd | Compositions and methods for fusion protein separation |
| US7855279B2 (en) | 2005-09-27 | 2010-12-21 | Amunix Operating, Inc. | Unstructured recombinant polymers and uses thereof |
| AU2007223888A1 (en) | 2006-03-06 | 2007-09-13 | Amunix, Inc. | Genetic packages and uses thereof |
| EA021222B8 (ru) | 2007-06-21 | 2015-11-30 | ИксЭль-ПРОТЕИН ГМБХ | Биологически активные белки, имеющие повышенную стабильность in vivo и/или in vitro |
| DK3178835T3 (da) | 2009-02-03 | 2019-06-24 | Amunix Pharmaceuticals Inc | Forlængede rekombinante polypeptider og sammensætninger omfattende samme |
-
2008
- 2008-06-20 EA EA201000040A patent/EA021222B8/ru active IP Right Grant
- 2008-06-20 AU AU2008266448A patent/AU2008266448B2/en active Active
- 2008-06-20 DE DE602008005596T patent/DE602008005596D1/de active Active
- 2008-06-20 SI SI200830250T patent/SI2173890T1/sl unknown
- 2008-06-20 KR KR1020157020384A patent/KR101701080B1/ko active Active
- 2008-06-20 US US12/665,565 patent/US8563521B2/en active Active
- 2008-06-20 JP JP2010512606A patent/JP5351889B2/ja active Active
- 2008-06-20 DK DK08773567.6T patent/DK2173890T3/da active
- 2008-06-20 ES ES08773567T patent/ES2362386T3/es active Active
- 2008-06-20 SI SI200830978T patent/SI2369005T1/sl unknown
- 2008-06-20 DK DK11158295.3T patent/DK2369005T3/da active
- 2008-06-20 EP EP11158295A patent/EP2369005B1/en active Active
- 2008-06-20 PL PL08773567T patent/PL2173890T3/pl unknown
- 2008-06-20 KR KR1020097025293A patent/KR101631323B1/ko active Active
- 2008-06-20 CN CN200880019017.4A patent/CN101970678B/zh active Active
- 2008-06-20 WO PCT/EP2008/005020 patent/WO2008155134A1/en not_active Ceased
- 2008-06-20 CA CA2691386A patent/CA2691386C/en active Active
- 2008-06-20 PT PT08773567T patent/PT2173890E/pt unknown
- 2008-06-20 HR HR20110368T patent/HRP20110368T1/hr unknown
- 2008-06-20 EP EP08773567A patent/EP2173890B1/en active Active
- 2008-06-20 PL PL11158295T patent/PL2369005T3/pl unknown
- 2008-06-20 ES ES11158295T patent/ES2422007T3/es active Active
- 2008-06-20 AT AT08773567T patent/ATE502114T1/de active
- 2008-06-20 NZ NZ580670A patent/NZ580670A/en unknown
-
2011
- 2011-05-27 CY CY20111100514T patent/CY1111491T1/el unknown
-
2013
- 2013-08-09 US US13/963,953 patent/US9260494B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2362386T3 (es) | Proteínas activas biológicas que tienen estabilidad aumentada in vivo y/o in vitro. | |
| JP6038248B2 (ja) | プロリン／アラニンランダムコイルポリペプチドの生合成およびその使用 | |
| ES2670442T3 (es) | Dominios de unión a albúmina de consenso no naturales | |
| ES2538122T3 (es) | Moléculas de una sola cadena de TNFSF | |
| ES2675568T3 (es) | Ligandos modificados mediante permutación circular como agonistas y antagonistas | |
| ES2438444T3 (es) | Variantes de la familia de IL-1 | |
| ES2806205T3 (es) | Cadena alfa del receptor de IgE de alta afinidad de fusión Fc | |
| CN117279618A (zh) | 用于靶标分子的选择性耗竭的组合物和方法 | |
| AU2013203326B2 (en) | Biological active proteins having increased in vivo and/or in vitro stability | |
| HK1156980B (en) | Biological active proteins having increased in vivo and/or vitro stability | |
| WO2016167291A1 (ja) | 環状化サイトカイン及びその製法 | |
| HK1219902B (zh) | 生物合成的脯氨酸/丙氨酸无规卷曲多肽及其用途 |