CA3060219A1 - Secretion-competent muteins of the human il-27 alpha-subunit - Google Patents
Secretion-competent muteins of the human il-27 alpha-subunit Download PDFInfo
- Publication number
- CA3060219A1 CA3060219A1 CA3060219A CA3060219A CA3060219A1 CA 3060219 A1 CA3060219 A1 CA 3060219A1 CA 3060219 A CA3060219 A CA 3060219A CA 3060219 A CA3060219 A CA 3060219A CA 3060219 A1 CA3060219 A1 CA 3060219A1
- Authority
- CA
- Canada
- Prior art keywords
- subunit
- human interleukin
- mutein
- seq
- amino acid
- 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.)
- Pending
Links
- 241000282414 Homo sapiens Species 0.000 title claims abstract description 65
- 101001128431 Homo sapiens Myeloid-derived growth factor Proteins 0.000 claims abstract description 492
- 102000056374 human MYDGF Human genes 0.000 claims abstract description 492
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 107
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 107
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 107
- 239000002773 nucleotide Substances 0.000 claims abstract description 77
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 77
- 108010066979 Interleukin-27 Proteins 0.000 claims abstract description 67
- 101100018698 Mus musculus Il27 gene Proteins 0.000 claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 35
- 125000000539 amino acid group Chemical group 0.000 claims description 241
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 169
- 229920001184 polypeptide Polymers 0.000 claims description 168
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 168
- 235000018417 cysteine Nutrition 0.000 claims description 166
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 143
- 102100036678 Interleukin-27 subunit alpha Human genes 0.000 claims description 78
- 235000001014 amino acid Nutrition 0.000 claims description 61
- 101000852964 Homo sapiens Interleukin-27 subunit beta Proteins 0.000 claims description 54
- 102100036712 Interleukin-27 subunit beta Human genes 0.000 claims description 51
- 150000001413 amino acids Chemical class 0.000 claims description 47
- 238000004519 manufacturing process Methods 0.000 claims description 44
- 229940024606 amino acid Drugs 0.000 claims description 42
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 27
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 26
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 24
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 24
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 24
- 150000001945 cysteines Chemical class 0.000 claims description 24
- 230000014509 gene expression Effects 0.000 claims description 24
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 239000004472 Lysine Substances 0.000 claims description 16
- 235000003704 aspartic acid Nutrition 0.000 claims description 16
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 16
- 235000013922 glutamic acid Nutrition 0.000 claims description 16
- 239000004220 glutamic acid Substances 0.000 claims description 16
- 235000018977 lysine Nutrition 0.000 claims description 16
- 239000013598 vector Substances 0.000 claims description 16
- 241000124008 Mammalia Species 0.000 claims description 15
- 206010040047 Sepsis Diseases 0.000 claims description 15
- 239000004475 Arginine Substances 0.000 claims description 14
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 14
- 235000009697 arginine Nutrition 0.000 claims description 14
- 208000037976 chronic inflammation Diseases 0.000 claims description 14
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 14
- 208000023275 Autoimmune disease Diseases 0.000 claims description 13
- 208000035473 Communicable disease Diseases 0.000 claims description 13
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 206010040070 Septic Shock Diseases 0.000 claims description 13
- 230000001154 acute effect Effects 0.000 claims description 13
- 208000006673 asthma Diseases 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 13
- 230000001684 chronic effect Effects 0.000 claims description 13
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 13
- 206010012601 diabetes mellitus Diseases 0.000 claims description 13
- 208000027866 inflammatory disease Diseases 0.000 claims description 13
- 230000001404 mediated effect Effects 0.000 claims description 13
- 230000036303 septic shock Effects 0.000 claims description 13
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 208000024908 graft versus host disease Diseases 0.000 claims description 11
- 238000002054 transplantation Methods 0.000 claims description 10
- 230000001105 regulatory effect Effects 0.000 claims description 9
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 claims description 8
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 claims description 8
- ZFOMKMMPBOQKMC-KXUCPTDWSA-N L-pyrrolysine Chemical compound C[C@@H]1CC=N[C@H]1C(=O)NCCCC[C@H]([NH3+])C([O-])=O ZFOMKMMPBOQKMC-KXUCPTDWSA-N 0.000 claims description 8
- 239000013592 cell lysate Substances 0.000 claims description 8
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 claims description 8
- 235000016491 selenocysteine Nutrition 0.000 claims description 8
- 229940055619 selenocysteine Drugs 0.000 claims description 8
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 7
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 4
- 230000002209 hydrophobic effect Effects 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 2
- 229960000310 isoleucine Drugs 0.000 claims description 2
- 102000015696 Interleukins Human genes 0.000 abstract description 16
- 108010063738 Interleukins Proteins 0.000 abstract description 16
- 102100033096 Interleukin-17D Human genes 0.000 abstract 4
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 110
- 210000004027 cell Anatomy 0.000 description 76
- 230000028327 secretion Effects 0.000 description 65
- 125000003275 alpha amino acid group Chemical group 0.000 description 39
- 108090000623 proteins and genes Proteins 0.000 description 36
- 102000004169 proteins and genes Human genes 0.000 description 33
- 235000018102 proteins Nutrition 0.000 description 32
- 101000852996 Mus musculus Interleukin-27 subunit alpha Proteins 0.000 description 30
- 108010065805 Interleukin-12 Proteins 0.000 description 25
- 102000013462 Interleukin-12 Human genes 0.000 description 25
- 238000002955 isolation Methods 0.000 description 25
- 239000002609 medium Substances 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 229940117681 interleukin-12 Drugs 0.000 description 22
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 20
- 102000004127 Cytokines Human genes 0.000 description 19
- 108090000695 Cytokines Proteins 0.000 description 19
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- -1 but not limited to Chemical class 0.000 description 15
- 241000894007 species Species 0.000 description 15
- 101710113110 B-cell receptor-associated protein 31 Proteins 0.000 description 14
- 101710139711 IkB-like protein Proteins 0.000 description 14
- 101710081123 Interleukin-27 subunit alpha Proteins 0.000 description 14
- 230000014759 maintenance of location Effects 0.000 description 14
- 230000035772 mutation Effects 0.000 description 14
- 101000852998 Homo sapiens Interleukin-27 subunit alpha Proteins 0.000 description 12
- 230000000717 retained effect Effects 0.000 description 12
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 12
- 239000006166 lysate Substances 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- 230000001419 dependent effect Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 108010036652 HSC70 Heat-Shock Proteins Proteins 0.000 description 9
- 102000012215 HSC70 Heat-Shock Proteins Human genes 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 210000002540 macrophage Anatomy 0.000 description 9
- 210000001744 T-lymphocyte Anatomy 0.000 description 8
- 239000007983 Tris buffer Substances 0.000 description 8
- 230000004186 co-expression Effects 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 238000000329 molecular dynamics simulation Methods 0.000 description 8
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 8
- 108010006519 Molecular Chaperones Proteins 0.000 description 7
- 241001529936 Murinae Species 0.000 description 7
- 108010020346 Polyglutamic Acid Proteins 0.000 description 7
- 230000000770 proinflammatory effect Effects 0.000 description 7
- 230000003248 secreting effect Effects 0.000 description 7
- 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 6
- 108010065637 Interleukin-23 Proteins 0.000 description 6
- 102000013264 Interleukin-23 Human genes 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 230000004962 physiological condition Effects 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 238000005734 heterodimerization reaction Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 229940047122 interleukins Drugs 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 4
- 102000003814 Interleukin-10 Human genes 0.000 description 4
- 108090000174 Interleukin-10 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102100040247 Tumor necrosis factor Human genes 0.000 description 4
- 241001147416 Ursus maritimus Species 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 239000000833 heterodimer Substances 0.000 description 4
- 230000002519 immonomodulatory effect Effects 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 230000003832 immune regulation Effects 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 238000003119 immunoblot Methods 0.000 description 4
- 210000003000 inclusion body Anatomy 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
- 230000012846 protein folding Effects 0.000 description 4
- 238000003908 quality control method Methods 0.000 description 4
- 238000002864 sequence alignment Methods 0.000 description 4
- 238000004088 simulation Methods 0.000 description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 230000004988 N-glycosylation Effects 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 241000289607 Sarcophilus harrisii Species 0.000 description 3
- 241000282898 Sus scrofa Species 0.000 description 3
- 230000008827 biological function Effects 0.000 description 3
- 238000006664 bond formation reaction Methods 0.000 description 3
- 238000000749 co-immunoprecipitation Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 102000043258 human EBI3 Human genes 0.000 description 3
- 125000001165 hydrophobic group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000001114 immunoprecipitation Methods 0.000 description 3
- 230000015788 innate immune response Effects 0.000 description 3
- 229940076144 interleukin-10 Drugs 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 230000031990 negative regulation of inflammatory response Effects 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 108091006112 ATPases Proteins 0.000 description 2
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 2
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 2
- 102100038493 Cytokine receptor-like factor 1 Human genes 0.000 description 2
- 241000238557 Decapoda Species 0.000 description 2
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 2
- 102100031853 Endoplasmic reticulum resident protein 44 Human genes 0.000 description 2
- 101710113885 Endoplasmic reticulum resident protein 44 Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102000003812 Interleukin-15 Human genes 0.000 description 2
- 108090000172 Interleukin-15 Proteins 0.000 description 2
- 102000013691 Interleukin-17 Human genes 0.000 description 2
- 108050003558 Interleukin-17 Proteins 0.000 description 2
- 102100040066 Interleukin-27 receptor subunit alpha Human genes 0.000 description 2
- 101710089672 Interleukin-27 receptor subunit alpha Proteins 0.000 description 2
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 2
- 102000005431 Molecular Chaperones Human genes 0.000 description 2
- 102000008300 Mutant Proteins Human genes 0.000 description 2
- 108010021466 Mutant Proteins Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical group N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 230000004721 adaptive immunity Effects 0.000 description 2
- 229960002648 alanylglutamine Drugs 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000002543 antimycotic Substances 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000022811 deglycosylation Effects 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 210000002288 golgi apparatus Anatomy 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000004957 immunoregulator effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 2
- 230000007112 pro inflammatory response Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000003146 transient transfection Methods 0.000 description 2
- 210000002993 trophoblast Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 1
- 241000270730 Alligator mississippiensis Species 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 102000007347 Apyrase Human genes 0.000 description 1
- 108010007730 Apyrase Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 241000251191 Callorhinchus milii Species 0.000 description 1
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000016989 Ciliary Neurotrophic Factor Receptor Human genes 0.000 description 1
- 108010000063 Ciliary Neurotrophic Factor Receptor Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000857788 Galkinius equus Species 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 241000282578 Gorilla gorilla gorilla Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 1
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 1
- 102000004556 Interleukin-15 Receptors Human genes 0.000 description 1
- 108010017535 Interleukin-15 Receptors Proteins 0.000 description 1
- 108010076561 Interleukin-23 Subunit p19 Proteins 0.000 description 1
- 102100036705 Interleukin-23 subunit alpha Human genes 0.000 description 1
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000283283 Orcinus orca Species 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 1
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
- 108010076818 TEV protease Proteins 0.000 description 1
- 210000000068 Th17 cell Anatomy 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 108010068908 cytokine-like factor-1 Proteins 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 102000052611 human IL6 Human genes 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000006028 immune-suppresssive effect Effects 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 230000008975 immunomodulatory function Effects 0.000 description 1
- 230000002434 immunopotentiative effect Effects 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229940124829 interleukin-23 Drugs 0.000 description 1
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 150000002614 leucines Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 230000031852 maintenance of location in cell Effects 0.000 description 1
- 230000010874 maintenance of protein location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 102200030294 rs267600971 Human genes 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 208000021043 septic peritonitis Diseases 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000012762 unpaired Student’s t-test Methods 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
-
- 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
- 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
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17169358 | 2017-05-04 | ||
| EP17169358.3 | 2017-05-04 | ||
| PCT/EP2018/061561 WO2018202876A1 (en) | 2017-05-04 | 2018-05-04 | Secretion-competent muteins of the human il-27 alpha-subunit |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3060219A1 true CA3060219A1 (en) | 2018-11-08 |
Family
ID=58669684
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3060219A Pending CA3060219A1 (en) | 2017-05-04 | 2018-05-04 | Secretion-competent muteins of the human il-27 alpha-subunit |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US11358998B2 (enExample) |
| EP (1) | EP3619228A1 (enExample) |
| JP (1) | JP7249955B2 (enExample) |
| CN (1) | CN110709413B (enExample) |
| AU (1) | AU2018262811B2 (enExample) |
| CA (1) | CA3060219A1 (enExample) |
| WO (1) | WO2018202876A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3955955B1 (en) | 2019-04-19 | 2025-02-26 | Synerkine Pharma B.V. | A fusion protein comprising il13 |
| JP2023501515A (ja) * | 2019-11-12 | 2023-01-18 | テクニッシェ ウニヴェルズィテート ミュンヘン | ヒトＩＬ－２７αサブユニットの均質ムテイン |
| WO2024213695A1 (en) * | 2023-04-14 | 2024-10-17 | Technische Universitaet Muenchen | Method for producing the subunits of human interleukin 35 from interleukin 12 and interleukin 27 |
| CN116832146B (zh) * | 2023-06-30 | 2024-02-13 | 广东暨安特博生物科技有限公司 | Il-27蛋白在制备治疗阿尔茨海默症的产品的应用 |
| WO2025140436A1 (zh) * | 2023-12-27 | 2025-07-03 | 上海药明生物技术有限公司 | 重组il-27蛋白及其制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4839434B2 (ja) * | 2005-03-14 | 2011-12-21 | 千葉県 | ｐ２８分子またはその遺伝子を含む医薬製剤 |
| HK1206764A1 (en) * | 2012-03-26 | 2016-01-15 | Axcella Health Inc. | Nutritive proteins and methods |
-
2018
- 2018-05-04 EP EP18726740.6A patent/EP3619228A1/en active Pending
- 2018-05-04 US US16/609,726 patent/US11358998B2/en active Active
- 2018-05-04 WO PCT/EP2018/061561 patent/WO2018202876A1/en not_active Ceased
- 2018-05-04 AU AU2018262811A patent/AU2018262811B2/en active Active
- 2018-05-04 JP JP2019560107A patent/JP7249955B2/ja active Active
- 2018-05-04 CN CN201880029727.9A patent/CN110709413B/zh active Active
- 2018-05-04 CA CA3060219A patent/CA3060219A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN110709413A (zh) | 2020-01-17 |
| US20200062817A1 (en) | 2020-02-27 |
| WO2018202876A1 (en) | 2018-11-08 |
| AU2018262811B2 (en) | 2021-10-21 |
| US11358998B2 (en) | 2022-06-14 |
| CN110709413B (zh) | 2023-11-28 |
| EP3619228A1 (en) | 2020-03-11 |
| JP2020518249A (ja) | 2020-06-25 |
| AU2018262811A1 (en) | 2019-12-19 |
| JP7249955B2 (ja) | 2023-03-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11358998B2 (en) | Cretion-competent muteins of the human IL-27 alpha-subunit | |
| Metcalfe et al. | Structural understanding of interleukin 6 family cytokine signaling and targeted therapies: focus on interleukin 11 | |
| JP7372036B2 (ja) | Ｔ細胞調節多量体ポリペプチド及びその使用方法 | |
| Müller et al. | A folding switch regulates interleukin 27 biogenesis and secretion of its α-subunit as a cytokine | |
| Zheng et al. | C-terminus of progranulin interacts with the beta-propeller region of sortilin to regulate progranulin trafficking | |
| JP2025108545A (ja) | Ｉｌ－２オルソログおよび使用法 | |
| JP2021097697A (ja) | フォリスタチン関連融合タンパク質およびその使用 | |
| EP2161287A1 (en) | OPTIMIZED TACI-Fc FUSION PROTEINS | |
| Guo et al. | Protection against Th17 cells differentiation by an interleukin-23 receptor cytokine-binding homology region | |
| Do et al. | Soluble prokaryotic overexpression and purification of bioactive human granulocyte colony-stimulating factor by maltose binding protein and protein disulfide isomerase | |
| JP2016525516A (ja) | 高度に低下された受容体結合親和性を有するサイトカインを含むフソカイン | |
| Liu et al. | Release of the neuregulin functional polypeptide requires its cytoplasmic tail | |
| JPH09508009A (ja) | Ｆａｓ抗原を結合するリガンド | |
| Müller et al. | An interspecies analysis reveals molecular construction principles of interleukin 27 | |
| JP2013521794A (ja) | 新規なシグナルペプチドおよび組換えタンパク質の生成のためのその使用 | |
| JP2023506956A (ja) | Ｉｌ－３７融合タンパク質及びその使用 | |
| JP6320973B2 (ja) | Ｂ細胞活性化因子の拮抗物質、その調製方法及び利用法 | |
| Darabi et al. | Codon optimization, cloning and expression of the human Leukemia Inhibitory Factor (hLIF) in E. coli | |
| US20220380426A1 (en) | Homogeneous muteins of the human il-27 alpha-subunit | |
| Wang et al. | Rational and efficient preparation of a chimeric protein containing a tandem dimer of thrombopoietin mimetic peptide fused to human growth hormone in Escherichia coli | |
| CN113195522A (zh) | 包含人类Lefty A蛋白变体的融合蛋白及其用途 | |
| Müller | Folding and quality control of the interleukin 12 family cytokines interleukin 27 and interleukin 35 | |
| Pamela | Investigation into the Molecular Biology of Human Genetic Sensory Disorders of Painlessness and Itch | |
| Lee et al. | High-yield production of recombinant CLCF1 protein fused with human serum albumin in animal cells and toxicity evaluation in rodents | |
| WO2024213695A1 (en) | Method for producing the subunits of human interleukin 35 from interleukin 12 and interleukin 27 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220819 |
|
| EEER | Examination request |
Effective date: 20220819 |
|
| EEER | Examination request |
Effective date: 20220819 |
|
| EEER | Examination request |
Effective date: 20220819 |
|
| EEER | Examination request |
Effective date: 20220819 |