ZA200307992B - Modified interferon beta with reduced immunogenicity. - Google Patents
Modified interferon beta with reduced immunogenicity. Download PDFInfo
- Publication number
- ZA200307992B ZA200307992B ZA200307992A ZA200307992A ZA200307992B ZA 200307992 B ZA200307992 B ZA 200307992B ZA 200307992 A ZA200307992 A ZA 200307992A ZA 200307992 A ZA200307992 A ZA 200307992A ZA 200307992 B ZA200307992 B ZA 200307992B
- Authority
- ZA
- South Africa
- Prior art keywords
- molecule
- amino acid
- peptide
- sequence
- modified
- Prior art date
Links
- 102000003996 Interferon-beta Human genes 0.000 title claims description 73
- 108090000467 Interferon-beta Proteins 0.000 title claims description 72
- 229960001388 interferon-beta Drugs 0.000 title claims description 66
- 230000005847 immunogenicity Effects 0.000 title claims description 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 230
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 95
- 230000027455 binding Effects 0.000 claims description 93
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 91
- 108090000623 proteins and genes Proteins 0.000 claims description 83
- 102000004169 proteins and genes Human genes 0.000 claims description 81
- 238000000034 method Methods 0.000 claims description 67
- 102000043131 MHC class II family Human genes 0.000 claims description 61
- 108091054438 MHC class II family Proteins 0.000 claims description 61
- 150000001413 amino acids Chemical class 0.000 claims description 61
- 238000006467 substitution reaction Methods 0.000 claims description 61
- 125000000539 amino acid group Chemical group 0.000 claims description 58
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 35
- 210000004027 cell Anatomy 0.000 claims description 35
- 239000003446 ligand Substances 0.000 claims description 35
- 230000006870 function Effects 0.000 claims description 29
- 229920001184 polypeptide Polymers 0.000 claims description 26
- 230000004071 biological effect Effects 0.000 claims description 23
- 230000002163 immunogen Effects 0.000 claims description 23
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 claims description 18
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 claims description 18
- 230000004075 alteration Effects 0.000 claims description 18
- 230000000638 stimulation Effects 0.000 claims description 17
- 230000002209 hydrophobic effect Effects 0.000 claims description 13
- 238000001727 in vivo Methods 0.000 claims description 13
- 230000001225 therapeutic effect Effects 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 12
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 238000000126 in silico method Methods 0.000 claims description 10
- 238000000338 in vitro Methods 0.000 claims description 10
- 230000004048 modification Effects 0.000 claims description 9
- 238000012986 modification Methods 0.000 claims description 9
- 230000009467 reduction Effects 0.000 claims description 9
- 238000012360 testing method Methods 0.000 claims description 9
- 238000007792 addition Methods 0.000 claims description 8
- 238000004166 bioassay Methods 0.000 claims description 8
- 230000004663 cell proliferation Effects 0.000 claims description 8
- 238000012217 deletion Methods 0.000 claims description 8
- 230000037430 deletion Effects 0.000 claims description 8
- 230000008859 change Effects 0.000 claims description 7
- 101000999325 Homo sapiens Cobalamin binding intrinsic factor Proteins 0.000 claims description 6
- 108020004511 Recombinant DNA Proteins 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 230000009149 molecular binding Effects 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000005070 sampling Methods 0.000 claims description 2
- 102220562888 Bromodomain-containing protein 1_L57K_mutation Human genes 0.000 claims 5
- 102220625448 Arylamine N-acetyltransferase 1_F70A_mutation Human genes 0.000 claims 4
- 102220499318 Squalene monooxygenase_I69A_mutation Human genes 0.000 claims 4
- 102220609878 Vasoactive intestinal polypeptide receptor 1_L63A_mutation Human genes 0.000 claims 4
- 102200050480 rs1494558 Human genes 0.000 claims 4
- 229960005486 vaccine Drugs 0.000 claims 4
- 102220562889 Bromodomain-containing protein 1_I59K_mutation Human genes 0.000 claims 3
- 102220597349 DNA-directed RNA polymerases I, II, and III subunit RPABC2_Y60N_mutation Human genes 0.000 claims 3
- 102220469877 Protein argonaute-3_F50A_mutation Human genes 0.000 claims 3
- 238000002255 vaccination Methods 0.000 claims 3
- 235000018102 proteins Nutrition 0.000 description 79
- 235000001014 amino acid Nutrition 0.000 description 67
- 229940024606 amino acid Drugs 0.000 description 55
- 241000282414 Homo sapiens Species 0.000 description 45
- 125000004429 atom Chemical group 0.000 description 40
- 229910052739 hydrogen Inorganic materials 0.000 description 29
- 239000001257 hydrogen Substances 0.000 description 28
- 230000003993 interaction Effects 0.000 description 22
- 230000028993 immune response Effects 0.000 description 14
- 102000014150 Interferons Human genes 0.000 description 13
- 108010050904 Interferons Proteins 0.000 description 13
- 229940079322 interferon Drugs 0.000 description 13
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 11
- 230000004044 response Effects 0.000 description 10
- 108700028369 Alleles Proteins 0.000 description 9
- 108091008874 T cell receptors Proteins 0.000 description 9
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 238000004364 calculation method Methods 0.000 description 9
- 125000001931 aliphatic group Chemical group 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 102100040019 Interferon alpha-1/13 Human genes 0.000 description 7
- 230000001028 anti-proliverative effect Effects 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 238000000205 computational method Methods 0.000 description 7
- 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 7
- 230000014509 gene expression Effects 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 230000006052 T cell proliferation Effects 0.000 description 6
- 239000000370 acceptor Substances 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000004913 activation Effects 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 238000001516 cell proliferation assay Methods 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000000386 donor Substances 0.000 description 5
- 230000008030 elimination Effects 0.000 description 5
- 238000003379 elimination reaction Methods 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 108010005716 Interferon beta-1a Proteins 0.000 description 4
- 108010038807 Oligopeptides Proteins 0.000 description 4
- 102000015636 Oligopeptides Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000000612 antigen-presenting cell Anatomy 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 239000012737 fresh medium Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000035755 proliferation Effects 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
- 238000011282 treatment Methods 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 3
- 108010078049 Interferon alpha-2 Proteins 0.000 description 3
- 102100039350 Interferon alpha-7 Human genes 0.000 description 3
- 108010005714 Interferon beta-1b Proteins 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 229940021459 betaseron Drugs 0.000 description 3
- 238000002884 conformational search Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000012997 ficoll-paque Substances 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 210000003292 kidney cell Anatomy 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 108020001756 ligand binding domains Proteins 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 108010016626 Dipeptides Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101150007193 IFNB1 gene Proteins 0.000 description 2
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 2
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 241000255964 Pieridae Species 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 229940003504 avonex Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000009795 derivation Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 238000003032 molecular docking Methods 0.000 description 2
- 238000012900 molecular simulation Methods 0.000 description 2
- 231100000219 mutagenic Toxicity 0.000 description 2
- 230000003505 mutagenic effect Effects 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 229940038850 rebif Drugs 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000003211 trypan blue cell staining Methods 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 241001227713 Chiron Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 239000012571 GlutaMAX medium Substances 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102100029966 HLA class II histocompatibility antigen, DP alpha 1 chain Human genes 0.000 description 1
- 108010010378 HLA-DP Antigens Proteins 0.000 description 1
- 102000015789 HLA-DP Antigens Human genes 0.000 description 1
- 108010062347 HLA-DQ Antigens Proteins 0.000 description 1
- 101000864089 Homo sapiens HLA class II histocompatibility antigen, DP alpha 1 chain Proteins 0.000 description 1
- 101000930802 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 1 chain Proteins 0.000 description 1
- 101000968032 Homo sapiens HLA class II histocompatibility antigen, DR beta 3 chain Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 101150103227 IFN gene Proteins 0.000 description 1
- 101150030057 IFNB gene Proteins 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 239000012807 PCR reagent Substances 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound 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 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- -1 aromatic amino acids Chemical class 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000000852 hydrogen donor Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229960004461 interferon beta-1a Drugs 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 238000000324 molecular mechanic Methods 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 102000014187 peptide receptors Human genes 0.000 description 1
- 108010011903 peptide receptors Proteins 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 238000002922 simulated annealing Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000003614 tolerogenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- C07K14/555—Interferons [IFN]
- C07K14/565—IFN-beta
-
- 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
- A61P31/12—Antivirals
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01106539 | 2001-03-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200307992B true ZA200307992B (en) | 2005-01-14 |
Family
ID=8176796
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200307992A ZA200307992B (en) | 2001-03-15 | 2003-10-14 | Modified interferon beta with reduced immunogenicity. |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US7381795B2 (ja) |
| EP (1) | EP1368377A2 (ja) |
| JP (1) | JP2004529633A (ja) |
| KR (1) | KR20030084992A (ja) |
| CN (1) | CN1496369A (ja) |
| BR (1) | BR0208041A (ja) |
| CA (1) | CA2441095A1 (ja) |
| HU (1) | HUP0303534A3 (ja) |
| MX (1) | MXPA03008310A (ja) |
| PL (1) | PL362870A1 (ja) |
| RU (1) | RU2003129072A (ja) |
| WO (1) | WO2002074783A2 (ja) |
| ZA (1) | ZA200307992B (ja) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7381795B2 (en) * | 2001-03-15 | 2008-06-03 | Merck Patent Gmbh | Modified interferon beta with reduced immunogenicity |
| US20030198624A1 (en) * | 2002-03-02 | 2003-10-23 | Mohapatra Shyam S. | Method of treating allergic disease and asthma by recombinant adenovirus- and adeno-associated virus- mediated IFN-gamma gene transfer |
| CA2484251C (en) * | 2002-04-30 | 2015-06-23 | University Of South Florida | Materials and methods for inhibition of respiratory syncytial virus infection |
| DE60332556D1 (de) * | 2002-05-01 | 2010-06-24 | Danisco Us Inc | Cytokine und cytokinrezeptoren mit reduzierter immunogenität |
| US7595303B1 (en) | 2002-09-05 | 2009-09-29 | University Of South Florida | Genetic adjuvants for immunotherapy |
| DE60332358D1 (de) * | 2002-09-09 | 2010-06-10 | Hanall Pharmaceutical Co Ltd | Protease-resistente modifizierte interferon alpha polypeptide |
| CA2516188C (en) * | 2003-02-14 | 2012-04-17 | University Of South Florida | Chitosan-derivatives for gene delivery and expression |
| WO2005003157A2 (en) * | 2003-06-10 | 2005-01-13 | Xencor, Inc. | Interferon variants with improved properties |
| US20050266093A1 (en) * | 2004-04-27 | 2005-12-01 | Mohapatra Shyam S | Nanogene therapy for cell proliferation disorders |
| US7670595B2 (en) * | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| US20080038224A1 (en) * | 2006-03-28 | 2008-02-14 | Thierry Guyon | Modified interferon-beta (IFN-beta) polypeptides |
| EP2423221B1 (en) | 2007-01-30 | 2015-04-29 | Epivax, Inc. | Regulatory t cell epitopes, compositions and uses thereof |
| CN103965347B (zh) | 2007-05-02 | 2017-07-18 | Ambrx公司 | 经修饰干扰素β多肽和其用途 |
| US20090010966A1 (en) * | 2007-06-21 | 2009-01-08 | Angelica Therapeutics, Inc. | Modified diphtheria toxins |
| EP2268297A4 (en) * | 2008-02-29 | 2011-11-16 | Angelica Therapeutics Inc | MODIFIED TOXINS |
| MX2011011044A (es) | 2009-04-22 | 2011-11-04 | Merck Patent Gmbh | Proteinas de fusion de anticuerpos con sitios de enlace de receptor fc neonatal (fcrn) modificados. |
| IN2014CN02982A (ja) | 2011-10-01 | 2015-07-03 | Glytech Inc | |
| US10059750B2 (en) | 2013-03-15 | 2018-08-28 | Angelica Therapeutics, Inc. | Modified toxins |
| BR112015024423B1 (pt) | 2013-03-29 | 2023-04-25 | Glytech, Inc | Polipeptídeo glicosilado tendo atividade de interferon ?, composição farmacêutica e uso de um polipeptídeo glicosilado |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4737462A (en) * | 1982-10-19 | 1988-04-12 | Cetus Corporation | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of interferon-β |
| GB8317880D0 (en) * | 1983-07-01 | 1983-08-03 | Searle & Co | Structure and synthesis of interferons |
| ES2258817T3 (es) * | 1997-05-21 | 2006-09-01 | Biovation Limited | Metodo para la produccion de proteinas no inmunogenas. |
| BR9915548A (pt) * | 1998-10-16 | 2001-08-14 | Biogen Inc | Proteìnas de fusão de interferon-beta e usos |
| EP1051432B1 (en) * | 1998-12-08 | 2007-01-24 | Biovation Limited | Method for reducing immunogenicity of proteins |
| US6514729B1 (en) * | 1999-05-12 | 2003-02-04 | Xencor, Inc. | Recombinant interferon-beta muteins |
| US6531122B1 (en) * | 1999-08-27 | 2003-03-11 | Maxygen Aps | Interferon-β variants and conjugates |
| US7381795B2 (en) * | 2001-03-15 | 2008-06-03 | Merck Patent Gmbh | Modified interferon beta with reduced immunogenicity |
-
2002
- 2002-03-15 US US10/471,894 patent/US7381795B2/en not_active Expired - Fee Related
- 2002-03-15 CN CNA028065972A patent/CN1496369A/zh active Pending
- 2002-03-15 EP EP02726180A patent/EP1368377A2/en not_active Withdrawn
- 2002-03-15 BR BR0208041-9A patent/BR0208041A/pt not_active IP Right Cessation
- 2002-03-15 MX MXPA03008310A patent/MXPA03008310A/es unknown
- 2002-03-15 RU RU2003129072/13A patent/RU2003129072A/ru not_active Application Discontinuation
- 2002-03-15 KR KR10-2003-7011997A patent/KR20030084992A/ko not_active Application Discontinuation
- 2002-03-15 CA CA002441095A patent/CA2441095A1/en not_active Abandoned
- 2002-03-15 HU HU0303534A patent/HUP0303534A3/hu unknown
- 2002-03-15 WO PCT/EP2002/002925 patent/WO2002074783A2/en active Application Filing
- 2002-03-15 JP JP2002573792A patent/JP2004529633A/ja active Pending
- 2002-03-15 PL PL02362870A patent/PL362870A1/xx unknown
-
2003
- 2003-10-14 ZA ZA200307992A patent/ZA200307992B/en unknown
-
2008
- 2008-03-17 US US12/077,120 patent/US7615615B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002074783A2 (en) | 2002-09-26 |
| BR0208041A (pt) | 2004-02-25 |
| HUP0303534A2 (hu) | 2004-01-28 |
| EP1368377A2 (en) | 2003-12-10 |
| KR20030084992A (ko) | 2003-11-01 |
| CN1496369A (zh) | 2004-05-12 |
| MXPA03008310A (es) | 2003-12-11 |
| RU2003129072A (ru) | 2005-04-20 |
| US7615615B2 (en) | 2009-11-10 |
| US20050054052A1 (en) | 2005-03-10 |
| US20090043076A1 (en) | 2009-02-12 |
| JP2004529633A (ja) | 2004-09-30 |
| HUP0303534A3 (en) | 2005-12-28 |
| CA2441095A1 (en) | 2002-09-26 |
| WO2002074783A3 (en) | 2003-08-28 |
| US7381795B2 (en) | 2008-06-03 |
| PL362870A1 (en) | 2004-11-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7615615B2 (en) | Modified interferon beta with reduced immunogenicity | |
| US20040254106A1 (en) | Modified factor ix | |
| US20040072291A1 (en) | Modified human brain-derived neutrophic factor (bdnf) with reduced immunogenicity | |
| US20060062761A1 (en) | Modified interferon alpha with reduced immunogenicity | |
| EP1366074B1 (en) | Modified granulocyte macrophage colony stimulating factor (gm-csf) with reduced immunogenicity | |
| CA2437272A1 (en) | Modified erythropoietin (epo) with reduced immunogenicity | |
| US20040076991A1 (en) | Modified interleukin-1 receptor antagonist(il-1ra) with reduced immunogenicity | |
| US20040121443A1 (en) | Modified protamine with reduced immunogenicity | |
| US20050020494A1 (en) | Modified human growth hormone | |
| EP1392731B1 (en) | Modified granulocyte colony stimulating factor (g-csf) with reduced immunogenicity | |
| US20060019885A1 (en) | Modified bryodin 1 with reduced immunogenicity | |
| US20040063634A1 (en) | Modified kertinocyte growth factor (kgf) with reduced immunogenicity | |
| AU2002256681A1 (en) | Modified interferon beta with reduced immunogenicity | |
| AU2002257596A1 (en) | Modified interferon alpha with reduced immunogenicity | |
| AU2002304824A1 (en) | Modified human granulocyte macrophage colony stimulating factor (GM-CSF) with reduced immunogenicity | |
| AU2002257579A1 (en) | Modified granulocyte colony stimulating factor (G-CSF) with reduced immunogenicity | |
| AU2002249180A1 (en) | Modified keratinocyte growth factor (KGF) with reduced immunogenicity |