PT77512B - Process for preparing cystein-depleted muteins of biologically active proteins - Google Patents
Process for preparing cystein-depleted muteins of biologically active proteins Download PDFInfo
- Publication number
- PT77512B PT77512B PT77512A PT7751283A PT77512B PT 77512 B PT77512 B PT 77512B PT 77512 A PT77512 A PT 77512A PT 7751283 A PT7751283 A PT 7751283A PT 77512 B PT77512 B PT 77512B
- Authority
- PT
- Portugal
- Prior art keywords
- mutein
- serine
- ifn
- read
- cysteine residue
- Prior art date
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 90
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 53
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 title claims description 19
- 238000004519 manufacturing process Methods 0.000 title claims 5
- 235000018102 proteins Nutrition 0.000 claims abstract description 50
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims abstract description 48
- 150000001413 amino acids Chemical class 0.000 claims abstract description 41
- 235000001014 amino acid Nutrition 0.000 claims abstract description 32
- 230000004071 biological effect Effects 0.000 claims abstract description 19
- 238000002741 site-directed mutagenesis Methods 0.000 claims abstract description 10
- 230000001580 bacterial effect Effects 0.000 claims abstract description 6
- 108010002350 Interleukin-2 Proteins 0.000 claims description 51
- 108020004414 DNA Proteins 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 46
- 102000000588 Interleukin-2 Human genes 0.000 claims description 44
- 108020004705 Codon Proteins 0.000 claims description 42
- 210000004027 cell Anatomy 0.000 claims description 40
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 34
- 229940024606 amino acid Drugs 0.000 claims description 30
- 230000000694 effects Effects 0.000 claims description 27
- 108091034117 Oligonucleotide Proteins 0.000 claims description 25
- 230000008569 process Effects 0.000 claims description 22
- 235000018417 cysteine Nutrition 0.000 claims description 20
- 239000013612 plasmid Substances 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 15
- 241000588724 Escherichia coli Species 0.000 claims description 14
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 13
- 239000004473 Threonine Substances 0.000 claims description 13
- 239000002773 nucleotide Substances 0.000 claims description 13
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 12
- 125000003729 nucleotide group Chemical group 0.000 claims description 12
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
- 102000053602 DNA Human genes 0.000 claims description 9
- 108091027305 Heteroduplex Proteins 0.000 claims description 9
- 230000000295 complement effect Effects 0.000 claims description 9
- 241000894006 Bacteria Species 0.000 claims description 8
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 8
- 241000700605 Viruses Species 0.000 claims description 8
- 238000012360 testing method Methods 0.000 claims description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 7
- 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 7
- 235000004279 alanine Nutrition 0.000 claims description 7
- 229930182817 methionine Natural products 0.000 claims description 7
- 230000000869 mutational effect Effects 0.000 claims description 7
- 108010074328 Interferon-gamma Proteins 0.000 claims description 6
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 6
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 6
- 239000013604 expression vector Substances 0.000 claims description 6
- 238000007918 intramuscular administration Methods 0.000 claims description 6
- 230000007935 neutral effect Effects 0.000 claims description 6
- 239000004471 Glycine Substances 0.000 claims description 5
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 claims description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000012217 deletion Methods 0.000 claims description 5
- 230000037430 deletion Effects 0.000 claims description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 5
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 5
- 229960000310 isoleucine Drugs 0.000 claims description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 5
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims description 4
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 4
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 4
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 claims description 4
- 108020004682 Single-Stranded DNA Proteins 0.000 claims description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 4
- 230000010261 cell growth Effects 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 239000012153 distilled water Substances 0.000 claims description 4
- 230000036737 immune function Effects 0.000 claims description 4
- 238000001802 infusion Methods 0.000 claims description 4
- 230000010076 replication Effects 0.000 claims description 4
- 239000004474 valine Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000012981 Hank's balanced salt solution Substances 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 3
- 230000008030 elimination Effects 0.000 claims description 3
- 238000003379 elimination reaction Methods 0.000 claims description 3
- -1 factor Proteins 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 3
- 241000233866 Fungi Species 0.000 claims description 2
- 102000008070 Interferon-gamma Human genes 0.000 claims description 2
- 108010002352 Interleukin-1 Proteins 0.000 claims description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 2
- 230000003321 amplification Effects 0.000 claims description 2
- 238000011161 development Methods 0.000 claims description 2
- 238000003745 diagnosis Methods 0.000 claims description 2
- 238000002405 diagnostic procedure Methods 0.000 claims description 2
- 230000012010 growth Effects 0.000 claims description 2
- 239000003102 growth factor Substances 0.000 claims description 2
- 238000003384 imaging method Methods 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 2
- 229920001184 polypeptide Polymers 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 230000001737 promoting effect Effects 0.000 claims description 2
- 238000000163 radioactive labelling Methods 0.000 claims description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 2
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 7
- 238000009472 formulation Methods 0.000 claims 6
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 4
- JSLGXODUIAFWCF-WDSKDSINSA-N Arg-Asn Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(O)=O JSLGXODUIAFWCF-WDSKDSINSA-N 0.000 claims 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 claims 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 claims 2
- LUMXICQAOKVQOB-YWIQKCBGSA-N Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)[C@@H](C)O LUMXICQAOKVQOB-YWIQKCBGSA-N 0.000 claims 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims 2
- 238000012258 culturing Methods 0.000 claims 2
- 102000055277 human IL2 Human genes 0.000 claims 2
- 108010044348 lysyl-glutamyl-aspartic acid Proteins 0.000 claims 2
- 230000001105 regulatory effect Effects 0.000 claims 2
- XLZCLJRGGMBKLR-PCBIJLKTSA-N Asn-Ile-Phe Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XLZCLJRGGMBKLR-PCBIJLKTSA-N 0.000 claims 1
- OMSMPWHEGLNQOD-UWVGGRQHSA-N Asn-Phe Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OMSMPWHEGLNQOD-UWVGGRQHSA-N 0.000 claims 1
- USNJAPJZSGTTPX-XVSYOHENSA-N Asp-Phe-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O USNJAPJZSGTTPX-XVSYOHENSA-N 0.000 claims 1
- 231100000023 Cell-mediated cytotoxicity Toxicity 0.000 claims 1
- 206010057250 Cell-mediated cytotoxicity Diseases 0.000 claims 1
- 102000003712 Complement factor B Human genes 0.000 claims 1
- 108090000056 Complement factor B Proteins 0.000 claims 1
- TUTIHHSZKFBMHM-WHFBIAKZSA-N Glu-Asn Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(O)=O TUTIHHSZKFBMHM-WHFBIAKZSA-N 0.000 claims 1
- AUTNXSQEVVHSJK-YVNDNENWSA-N Glu-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O AUTNXSQEVVHSJK-YVNDNENWSA-N 0.000 claims 1
- LGYZYFFDELZWRS-DCAQKATOSA-N Glu-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O LGYZYFFDELZWRS-DCAQKATOSA-N 0.000 claims 1
- SNFUTDLOCQQRQD-ZKWXMUAHSA-N Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O SNFUTDLOCQQRQD-ZKWXMUAHSA-N 0.000 claims 1
- BCYGDJXHAGZNPQ-DCAQKATOSA-N Glu-Lys-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O BCYGDJXHAGZNPQ-DCAQKATOSA-N 0.000 claims 1
- QOOFKCCZZWTCEP-AVGNSLFASA-N Glu-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O QOOFKCCZZWTCEP-AVGNSLFASA-N 0.000 claims 1
- JPVGHHQGKPQYIL-KBPBESRZSA-N Gly-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 JPVGHHQGKPQYIL-KBPBESRZSA-N 0.000 claims 1
- XBGGUPMXALFZOT-VIFPVBQESA-N Gly-Tyr Chemical compound NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-VIFPVBQESA-N 0.000 claims 1
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 claims 1
- HZYHBDVRCBDJJV-HAFWLYHUSA-N Ile-Asn Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@H](C(O)=O)CC(N)=O HZYHBDVRCBDJJV-HAFWLYHUSA-N 0.000 claims 1
- YKRIXHPEIZUDDY-GMOBBJLQSA-N Ile-Asn-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YKRIXHPEIZUDDY-GMOBBJLQSA-N 0.000 claims 1
- UYNXBNHVWFNVIN-HJWJTTGWSA-N Ile-Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)CC)CC1=CC=CC=C1 UYNXBNHVWFNVIN-HJWJTTGWSA-N 0.000 claims 1
- 102100026720 Interferon beta Human genes 0.000 claims 1
- 108090000467 Interferon-beta Proteins 0.000 claims 1
- GGAPIOORBXHMNY-ULQDDVLXSA-N Lys-Arg-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)N)O GGAPIOORBXHMNY-ULQDDVLXSA-N 0.000 claims 1
- FLCMXEFCTLXBTL-DCAQKATOSA-N Lys-Asp-Arg Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N FLCMXEFCTLXBTL-DCAQKATOSA-N 0.000 claims 1
- LLSUNJYOSCOOEB-GUBZILKMSA-N Lys-Glu-Asp Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O LLSUNJYOSCOOEB-GUBZILKMSA-N 0.000 claims 1
- ODUQLUADRKMHOZ-JYJNAYRXSA-N Lys-Glu-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N)O ODUQLUADRKMHOZ-JYJNAYRXSA-N 0.000 claims 1
- UAPZLLPGGOOCRO-IHRRRGAJSA-N Met-Asn-Phe Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N UAPZLLPGGOOCRO-IHRRRGAJSA-N 0.000 claims 1
- FRMKIPSIZSFTTE-HJOGWXRNSA-N Phe-Tyr-Phe Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O FRMKIPSIZSFTTE-HJOGWXRNSA-N 0.000 claims 1
- WDVSHHCDHLJJJR-UHFFFAOYSA-N Proflavine Chemical compound C1=CC(N)=CC2=NC3=CC(N)=CC=C3C=C21 WDVSHHCDHLJJJR-UHFFFAOYSA-N 0.000 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 1
- 108091081021 Sense strand Proteins 0.000 claims 1
- YSXYEJWDHBCTDJ-DVJZZOLTSA-N Thr-Gly-Trp Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O YSXYEJWDHBCTDJ-DVJZZOLTSA-N 0.000 claims 1
- WBZOZLNLXVBCNW-LTHWPDAASA-N Trp-Thr-Ile Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(O)=O)[C@@H](C)O)=CNC2=C1 WBZOZLNLXVBCNW-LTHWPDAASA-N 0.000 claims 1
- ONWMQORSVZYVNH-UWVGGRQHSA-N Tyr-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 ONWMQORSVZYVNH-UWVGGRQHSA-N 0.000 claims 1
- PMDWYLVWHRTJIW-STQMWFEESA-N Tyr-Gly-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PMDWYLVWHRTJIW-STQMWFEESA-N 0.000 claims 1
- ZQOOYCZQENFIMC-STQMWFEESA-N Tyr-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)C1=CC=C(O)C=C1 ZQOOYCZQENFIMC-STQMWFEESA-N 0.000 claims 1
- 239000013566 allergen Substances 0.000 claims 1
- 230000009141 biological interaction Effects 0.000 claims 1
- 230000005890 cell-mediated cytotoxicity Effects 0.000 claims 1
- 230000002950 deficient Effects 0.000 claims 1
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 claims 1
- 108010087823 glycyltyrosine Proteins 0.000 claims 1
- 230000036039 immunity Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 229960003130 interferon gamma Drugs 0.000 claims 1
- 229960001388 interferon-beta Drugs 0.000 claims 1
- 210000004698 lymphocyte Anatomy 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 210000000822 natural killer cell Anatomy 0.000 claims 1
- 244000045947 parasite Species 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 108010003137 tyrosyltyrosine Proteins 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 238000004132 cross linking Methods 0.000 abstract description 2
- 239000013615 primer Substances 0.000 description 38
- 239000000872 buffer Substances 0.000 description 14
- 239000000284 extract Substances 0.000 description 13
- 238000009396 hybridization Methods 0.000 description 13
- 235000004400 serine Nutrition 0.000 description 13
- 239000000523 sample Substances 0.000 description 12
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 9
- 239000002299 complementary DNA Substances 0.000 description 9
- 239000012634 fragment Substances 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 7
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 7
- 108091033380 Coding strand Proteins 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 108091008146 restriction endonucleases Proteins 0.000 description 6
- 229920001817 Agar Polymers 0.000 description 5
- 102000012410 DNA Ligases Human genes 0.000 description 5
- 108010061982 DNA Ligases Proteins 0.000 description 5
- 102000004594 DNA Polymerase I Human genes 0.000 description 5
- 108010017826 DNA Polymerase I Proteins 0.000 description 5
- 108010050904 Interferons Proteins 0.000 description 5
- 102000014150 Interferons Human genes 0.000 description 5
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 5
- 239000008272 agar Substances 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 239000011543 agarose gel Substances 0.000 description 4
- 229940079322 interferon Drugs 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 229960004799 tryptophan Drugs 0.000 description 4
- 240000005369 Alstonia scholaris Species 0.000 description 3
- 241000972773 Aulopiformes Species 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 241001524679 Escherichia virus M13 Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 239000000020 Nitrocellulose Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 230000000120 cytopathologic effect Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 229920001220 nitrocellulos Polymers 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 235000019515 salmon Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 239000003155 DNA primer Substances 0.000 description 2
- 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 2
- 241001646716 Escherichia coli K-12 Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 102000003960 Ligases Human genes 0.000 description 2
- 108090000364 Ligases Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000002009 allergenic effect Effects 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 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 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 150000001945 cysteines Chemical class 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 2
- 210000000287 oocyte Anatomy 0.000 description 2
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- NTASFODDPBHBAM-UHFFFAOYSA-N 1-hydroxyethylazanium;chloride Chemical compound [Cl-].CC([NH3+])O NTASFODDPBHBAM-UHFFFAOYSA-N 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 101000991414 Aspergillus oryzae (strain ATCC 42149 / RIB 40) Nuclease S1 Proteins 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000193388 Bacillus thuringiensis Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 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 1
- 241000282412 Homo Species 0.000 description 1
- 101100232904 Homo sapiens IL2 gene Proteins 0.000 description 1
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100522111 Oryza sativa subsp. japonica PHT1-11 gene Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NSOXQYCFHDMMGV-UHFFFAOYSA-N Tetrakis(2-hydroxypropyl)ethylenediamine Chemical compound CC(O)CN(CC(C)O)CCN(CC(C)O)CC(C)O NSOXQYCFHDMMGV-UHFFFAOYSA-N 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000269368 Xenopus laevis Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229940097012 bacillus thuringiensis Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- RCTYPNKXASFOBE-UHFFFAOYSA-M chloromercury Chemical compound [Hg]Cl RCTYPNKXASFOBE-UHFFFAOYSA-M 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 208000027618 chronic mucocutaneous candidiasis due to lymphokine deficiency Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N cystine group Chemical group C([C@@H](C(=O)O)N)SSC[C@@H](C(=O)O)N LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 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 1
- 230000008034 disappearance Effects 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001962 electrophoresis Methods 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
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000013636 protein dimer Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000010405 reoxidation reaction Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 208000005925 vesicular stomatitis Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
-
- 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]
- C07K14/55—IL-2
-
- 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
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/808—Materials and products related to genetic engineering or hybrid or fused cell technology, e.g. hybridoma, monoclonal products
- Y10S530/809—Fused cells, e.g. hybridoma
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/14—Lymphokine; related peptides
- Y10S930/141—Interleukin
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/14—Lymphokine; related peptides
- Y10S930/142—Interferon
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Plant Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43515482A | 1982-10-19 | 1982-10-19 | |
| US48616283A | 1983-04-15 | 1983-04-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PT77512A PT77512A (en) | 1983-11-01 |
| PT77512B true PT77512B (en) | 1987-11-24 |
Family
ID=27030446
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT77512A PT77512B (en) | 1982-10-19 | 1983-10-17 | Process for preparing cystein-depleted muteins of biologically active proteins |
Country Status (23)
| Country | Link |
|---|---|
| EP (4) | EP0192811B1 (enExample) |
| JP (2) | JPS6128392A (enExample) |
| KR (1) | KR910009900B1 (enExample) |
| AT (4) | ATE61407T1 (enExample) |
| AU (1) | AU563962B2 (enExample) |
| BE (1) | BE898016A (enExample) |
| CA (1) | CA1340861C (enExample) |
| CH (1) | CH669395A5 (enExample) |
| DE (4) | DE3382528D1 (enExample) |
| DK (2) | DK168767B1 (enExample) |
| ES (4) | ES526541A0 (enExample) |
| FI (1) | FI82266C (enExample) |
| FR (1) | FR2534594B1 (enExample) |
| GB (1) | GB2130219B (enExample) |
| GR (1) | GR79408B (enExample) |
| IE (1) | IE56026B1 (enExample) |
| IL (1) | IL69970A (enExample) |
| LU (3) | LU88761I2 (enExample) |
| NL (2) | NL930119I2 (enExample) |
| NO (1) | NO173740C (enExample) |
| NZ (1) | NZ205922A (enExample) |
| PH (2) | PH20343A (enExample) |
| PT (1) | PT77512B (enExample) |
Families Citing this family (125)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE56026B1 (en) * | 1982-10-19 | 1991-03-27 | Cetus Corp | Cysteine-depleted muteins of biologically active proteins |
| DK265384A (da) * | 1983-06-01 | 1984-12-02 | Hoffmann La Roche | Polypeptider med interferonaktivitet |
| WO1985000817A1 (en) * | 1983-08-10 | 1985-02-28 | Amgen | Microbial expression of interleukin ii |
| GB8334102D0 (en) * | 1983-12-21 | 1984-02-01 | Searle & Co | Interferons with cysteine pattern |
| US4530787A (en) * | 1984-03-28 | 1985-07-23 | Cetus Corporation | Controlled oxidation of microbially produced cysteine-containing proteins |
| EP0211835B1 (en) | 1984-03-28 | 1990-01-03 | Cetus Corporation | Pharmaceutical compositions of microbially produced interleukin-2 |
| EP0163603B1 (en) * | 1984-05-08 | 1989-12-13 | Genetics Institute, Inc. | A human t-cell growth factor |
| GB8412564D0 (en) * | 1984-05-17 | 1984-06-20 | Searle & Co | Structure and properties |
| US5683688A (en) * | 1984-05-31 | 1997-11-04 | Genentech, Inc. | Unglycosylated recombinant human lymphotoxin polypeptides and compositions |
| NZ212207A (en) * | 1984-05-31 | 1991-07-26 | Genentech Inc | Recombinant lymphotoxin |
| US5672347A (en) * | 1984-07-05 | 1997-09-30 | Genentech, Inc. | Tumor necrosis factor antagonists and their use |
| CA1275954C (en) | 1984-08-31 | 1990-11-06 | Hing Cheug Wong | 3'-expression enhancing fragments and method |
| WO1986002068A1 (fr) * | 1984-09-26 | 1986-04-10 | Takeda Chemical Industries, Ltd. | Separation mutuelle de proteines |
| IL76360A0 (en) | 1984-09-26 | 1986-01-31 | Takeda Chemical Industries Ltd | Mutual separation of proteins |
| US4857316A (en) * | 1984-10-03 | 1989-08-15 | Syntex (U.S.A.) Inc. | Synergistic antiviral composition |
| US4606917A (en) * | 1984-10-03 | 1986-08-19 | Syntex (U.S.A) Inc. | Synergistic antiviral composition |
| US4959314A (en) | 1984-11-09 | 1990-09-25 | Cetus Corporation | Cysteine-depleted muteins of biologically active proteins |
| US4572798A (en) * | 1984-12-06 | 1986-02-25 | Cetus Corporation | Method for promoting disulfide bond formation in recombinant proteins |
| US6107465A (en) * | 1984-12-21 | 2000-08-22 | Otsuka Pharmaceutical Co., Ltd. | IL-1β and derivatives thereof and drugs |
| DK172052B1 (da) * | 1984-12-21 | 1997-09-29 | Otsuka Pharma Co Ltd | Antitumor-aktivt stof, fremgangsmåde til dets fremstilling, lægemiddel indeholdende stoffet, gen kodende for stoffet, vektor indeholdende genet samt rekombinant mikroorganisme transformet med en sådan vektor |
| US5342614A (en) * | 1984-12-21 | 1994-08-30 | Otsuka Pharmaceutical Co., Ltd. | Method of treating arthritus or inflammation with IL-1β or derivatives thereof |
| DE3500681A1 (de) * | 1985-01-11 | 1986-07-17 | Hoechst Ag, 6230 Frankfurt | Verfahren zur isolierung und reinigung von lymphokinen |
| US4863849A (en) * | 1985-07-18 | 1989-09-05 | New York Medical College | Automatable process for sequencing nucleotide |
| US6004548A (en) | 1985-08-23 | 1999-12-21 | Amgen, Inc. | Analogs of pluripotent granulocyte colony-stimulating factor |
| US4810643A (en) * | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
| CA1297003C (en) * | 1985-09-20 | 1992-03-10 | Jack H. Nunberg | Composition and method for treating animals |
| US5359035A (en) * | 1985-12-21 | 1994-10-25 | Hoechst Aktiengesellschaft | Bifunctional proteins including interleukin-2 (IL-2) and granuloctyte macrophage colony stimulating factor (GM-CSF) |
| US5008374A (en) * | 1986-03-14 | 1991-04-16 | Otsuka Pharmaceutical Co., Ltd. | IL-1α derivatives and drugs |
| AU595864B2 (en) * | 1986-03-14 | 1990-04-12 | Otsuka Pharmaceutical Co., Ltd. | Il-1 alpha derivatives and drugs |
| DE3683910D1 (de) * | 1986-09-05 | 1992-03-26 | Cetus Corp | Oxidationsresistente muteine von beta-interferon, deren herstellung und diese muteine enthaltende praeparate. |
| JP2526965B2 (ja) * | 1987-02-24 | 1996-08-21 | 武田薬品工業株式会社 | ムテイン，ｄｎａおよびその用途 |
| US4987070A (en) * | 1987-03-04 | 1991-01-22 | Suntory Limited | Use of a 97 amino acid leader sequence from the E. coli B-galactosidase gene for the production of hanp and hptc as fusion proteins |
| EP0298723A1 (en) * | 1987-07-07 | 1989-01-11 | California Biotechnology, Inc. | Recombinant fibroblast growth factors |
| EP0383837B1 (en) * | 1987-11-04 | 1998-02-04 | Byk Gulden Lomberg Chemische Fabrik GmbH | Alveolar surfactant proteins |
| EP0355460B1 (en) * | 1988-08-24 | 2000-12-27 | American Cyanamid Company | Stabilization of somatotropins by modification of cysteine residues utilizing site directed mutagenesis or chemical derivatization |
| US5079230A (en) * | 1988-09-12 | 1992-01-07 | Pitman-Moore, Inc. | Stable bioactive somatotropins |
| CA2003886A1 (en) * | 1988-12-16 | 1990-06-16 | Anthony F. Purchio | Cloning and expression of simian transforming growth factor-beta 1 |
| JP3207416B2 (ja) * | 1989-01-31 | 2001-09-10 | ファルマシア・アンド・アップジョン・カンパニー | ソマトトロピン・アナログ類 |
| ATE133993T1 (de) * | 1989-02-17 | 1996-02-15 | Merck & Co Inc | Protein-antikrebsmittel |
| US5621078A (en) * | 1989-03-22 | 1997-04-15 | Merck & Co., Inc. | Modified pseudomonas exotoxin PE40 |
| AU5355790A (en) * | 1989-04-19 | 1990-11-16 | Cetus Corporation | Multifunctional m-csf proteins and genes encoding therefor |
| US6207798B1 (en) | 1989-08-03 | 2001-03-27 | Merck & Co., Inc. | Modified PE40 toxin fusion proteins |
| US5173297A (en) * | 1991-07-01 | 1992-12-22 | Quest International Flavors & Food Ingredients Company Division Of Indopco, Inc. | Bacteriocin from lactococcus lactis subspecies lactis |
| IL98528A0 (en) * | 1990-06-21 | 1992-07-15 | Merck & Co Inc | Pharmaceutical compositions containing hybrid for killing bladder cancer cells |
| FR2671554A1 (fr) * | 1991-01-11 | 1992-07-17 | Clonatec Sa | Peptides synthetiques derivant de l'antigene hbc du virus de l'hepatite b, leurs applications a la detection d'une infection par ce virus et a la vaccination contre l'hepatite b. |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| US5545723A (en) * | 1994-03-15 | 1996-08-13 | Biogen Inc. | Muteins of IFN-β |
| US5814485A (en) * | 1995-06-06 | 1998-09-29 | Chiron Corporation | Production of interferon-β (IFN-β) in E. coli |
| DE19544167A1 (de) * | 1995-11-17 | 1997-05-22 | Schering Ag | Verwendung von Interferon-ß zur Behandlung von Bronchialkarzinom bei Bestrahlungstherapie |
| AU6399996A (en) * | 1996-06-19 | 1998-01-07 | Chiron Corporation | Bacterial production of interferon-beta using low levels of sodium and potassium ions |
| CN1100875C (zh) * | 1998-03-06 | 2003-02-05 | 上海华晨生物技术研究所 | 新型重组人白细胞介素2的制备方法及其表达载体和工程菌 |
| AU2001274809A1 (en) | 2000-04-12 | 2001-10-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| EP1935431A3 (en) | 2000-05-15 | 2008-08-13 | Health Research, Inc. | Cancer treatments by using a combination of an antibody against her2 and interleukin-2 |
| DE10112825A1 (de) | 2001-03-16 | 2002-10-02 | Fresenius Kabi De Gmbh | HESylierung von Wirkstoffen in wässriger Lösung |
| US6887462B2 (en) | 2001-04-09 | 2005-05-03 | Chiron Corporation | HSA-free formulations of interferon-beta |
| EP1435979A4 (en) * | 2001-09-18 | 2008-01-23 | Novartis Vaccines & Diagnostic | METHODS OF TREATING MULTIPLE SCLEROSIS |
| KR100511749B1 (ko) * | 2001-11-06 | 2005-09-02 | 선바이오(주) | 변형된 인터페론-베타, 및 이의 화학적으로 변형된 배합체 |
| ES2425738T3 (es) | 2001-12-21 | 2013-10-17 | Human Genome Sciences, Inc. | Proteínas de fusión de la albúmina |
| DE10209821A1 (de) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung von Proteinen an ein modifiziertes Polysaccharid |
| DE10209822A1 (de) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung niedermolekularer Substanzen an ein modifiziertes Polysaccharid |
| CN100348618C (zh) | 2002-09-11 | 2007-11-14 | 弗雷泽纽斯卡比德国有限公司 | 生产羟烷基淀粉衍生物的方法 |
| US7538092B2 (en) | 2002-10-08 | 2009-05-26 | Fresenius Kabi Deutschland Gmbh | Pharmaceutically active oligosaccharide conjugates |
| EP1594530A4 (en) | 2003-01-22 | 2006-10-11 | Human Genome Sciences Inc | HYBRID PROTEINS OF ALBUMIN |
| WO2005014655A2 (en) | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
| JP5019881B2 (ja) | 2003-11-04 | 2012-09-05 | ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド | アンタゴニスト抗ｃｄ４０モノクローナル抗体およびそれらを使用するための方法 |
| KR20070003934A (ko) * | 2004-03-05 | 2007-01-05 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 치료제의 환자 내약성을 예측하기 위한 시험관 내 테스트시스템 |
| SG151261A1 (en) | 2004-03-11 | 2009-04-30 | Fresenius Kabi De Gmbh | Conjugates of hydroxyalkyl starch and a protein, prepared by reductive amination |
| EP1786917A4 (en) * | 2004-07-26 | 2008-05-28 | Enzon Pharmaceuticals Inc | OPTIMIZED INTERFERON BETA-GEN |
| GB0523282D0 (en) | 2005-11-15 | 2005-12-21 | Isis Innovation | Methods using pores |
| GB2453377A (en) | 2007-10-05 | 2009-04-08 | Isis Innovation | Transmembrane protein pores and molecular adapters therefore. |
| EP2070950A1 (en) | 2007-12-14 | 2009-06-17 | Fresenius Kabi Deutschland GmbH | Hydroxyalkyl starch derivatives and process for their preparation |
| ES2382058T3 (es) | 2008-01-17 | 2012-06-04 | Philogen S.P.A. | Combinación de una proteína de fusión de un anticuerpo dirigido contra el EDB de la fibronectina-IL-2, y una molécula de unión a los linfocitos B, progenitores de los linfocitos B y/o sus homólogos cancerosos |
| US9447152B2 (en) | 2008-07-07 | 2016-09-20 | Oxford Nanopore Technologies Limited | Base-detecting pore |
| EP2682460B1 (en) | 2008-07-07 | 2017-04-26 | Oxford Nanopore Technologies Limited | Enzyme-pore constructs |
| US9077937B2 (en) * | 2008-11-06 | 2015-07-07 | Alcatel Lucent | Method and apparatus for fast channel change |
| GB0820927D0 (en) | 2008-11-14 | 2008-12-24 | Isis Innovation | Method |
| US20120100530A1 (en) | 2009-01-30 | 2012-04-26 | Oxford Nanopore Technologies Limited | Enzyme mutant |
| CA2750879C (en) | 2009-01-30 | 2018-05-22 | Oxford Nanopore Technologies Limited | Adaptors for nucleic acid constructs in transmembrane sequencing |
| GB0905140D0 (en) | 2009-03-25 | 2009-05-06 | Isis Innovation | Method |
| KR101939420B1 (ko) | 2011-02-11 | 2019-01-16 | 옥스포드 나노포어 테크놀로지즈 리미티드 | 돌연변이체 세공 |
| PL3443979T3 (pl) | 2011-03-11 | 2020-11-16 | Assistance Publique - Hôpitaux De Paris | Schemat dawkowania il-2 do leczenia tocznia rumieniowatego układowego |
| BR112014001699A2 (pt) | 2011-07-25 | 2017-06-13 | Oxford Nanopore Tech Ltd | método para sequenciar de um polinucleotídeo alvo de filamento duplo, kit, métodos para preparar um polinucleotídeo alvo de filamento duplo para sequenciamento e para sequenciar um polinucleotídeo alvo de filamento duplo, e, aparelho |
| GB201119244D0 (en) | 2011-11-08 | 2011-12-21 | British American Tobacco Co | Smoking article |
| KR102083695B1 (ko) | 2012-04-10 | 2020-03-02 | 옥스포드 나노포어 테크놀로지즈 리미티드 | 돌연변이체 리세닌 기공 |
| US11155860B2 (en) | 2012-07-19 | 2021-10-26 | Oxford Nanopore Technologies Ltd. | SSB method |
| GB201314695D0 (en) | 2013-08-16 | 2013-10-02 | Oxford Nanopore Tech Ltd | Method |
| CN105209634B (zh) | 2013-03-08 | 2020-05-12 | 牛津纳米孔技术公司 | 酶停滞方法 |
| GB201313477D0 (en) | 2013-07-29 | 2013-09-11 | Univ Leuven Kath | Nanopore biosensors for detection of proteins and nucleic acids |
| WO2014206899A1 (en) | 2013-06-25 | 2014-12-31 | Icm (Institut Du Cerveau Et De La Moelle Épinière) | Boosting treg cells for treating alzheimer disease and related disorders |
| GB201403096D0 (en) | 2014-02-21 | 2014-04-09 | Oxford Nanopore Tech Ltd | Sample preparation method |
| EP2918285A1 (en) | 2014-03-11 | 2015-09-16 | Université Pierre et Marie Curie (Paris 6) | Interleukin-2 for treating food allergy |
| CN106459159B (zh) | 2014-05-02 | 2021-11-30 | 牛津纳米孔技术公司 | 突变孔 |
| KR20250130441A (ko) | 2014-09-01 | 2025-09-01 | 브이아이비 브이지더블유 | 돌연변이체 csgg 포어 |
| WO2016055778A1 (en) | 2014-10-07 | 2016-04-14 | Oxford Nanopore Technologies Limited | Mutant pores |
| GB201418159D0 (en) | 2014-10-14 | 2014-11-26 | Oxford Nanopore Tech Ltd | Method |
| US10801023B2 (en) * | 2015-04-24 | 2020-10-13 | University Of Florida Research Foundation, Inc. | Methods of identifying biologically active random peptides in plants and libraries of plants expressing candidate biologically active random peptides |
| WO2016172445A2 (en) * | 2015-04-24 | 2016-10-27 | The University Of Florida Research Foundation, Inc. | Methods of identifying biologically active random peptides in plants and libraries of plants expressing candidate biologically active random peptides |
| US10876109B2 (en) | 2015-04-24 | 2020-12-29 | University Of Florida Research Foundation, Inc. | Methods of identifying biologically active random peptides in prokaryotic cells and libraries of prokaryotic cells expressing candidate biologically active random peptides |
| JP7038655B2 (ja) | 2015-10-22 | 2022-03-18 | イルトゥー・ファルマ | Ｉｌ－２医薬組成物 |
| GB201609220D0 (en) | 2016-05-25 | 2016-07-06 | Oxford Nanopore Tech Ltd | Method |
| WO2017220704A1 (en) | 2016-06-22 | 2017-12-28 | David Klatzmann | Genetically modified t lymphocytes |
| KR20190129077A (ko) | 2017-03-15 | 2019-11-19 | 팬디온 테라퓨틱스, 인코포레이티드 | 표적화된 면역관용 |
| MX2019013517A (es) | 2017-05-24 | 2020-08-17 | Pandion Operations Inc | Inmunotolerancia dirigida. |
| USRE50550E1 (en) | 2017-12-06 | 2025-08-26 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
| US10946068B2 (en) | 2017-12-06 | 2021-03-16 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
| US10174092B1 (en) | 2017-12-06 | 2019-01-08 | Pandion Therapeutics, Inc. | IL-2 muteins |
| EP3752178A1 (en) | 2018-02-16 | 2020-12-23 | Iltoo Pharma | Use of interleukin 2 for treating sjögren's syndrome |
| GB201807793D0 (en) | 2018-05-14 | 2018-06-27 | Oxford Nanopore Tech Ltd | Method |
| WO2019241315A1 (en) | 2018-06-12 | 2019-12-19 | Obsidian Therapeutics, Inc. | Pde5 derived regulatory constructs and methods of use in immunotherapy |
| WO2020007937A1 (en) | 2018-07-03 | 2020-01-09 | Iltoo Pharma | Use of interleukin-2 for treating systemic sclerosis |
| ES3030707T3 (en) | 2018-08-13 | 2025-07-01 | Iltoo Pharma | Combination of interleukin-2 with an interleukin 1 inhibitor, conjugates and therapeutic uses thereof |
| US12352765B2 (en) | 2018-11-15 | 2025-07-08 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods of prognosis and classification for preeclampsia |
| WO2020236875A1 (en) | 2019-05-20 | 2020-11-26 | Pandion Therapeutics, Inc. | Madcam targeted immunotolerance |
| CA3159468A1 (en) | 2019-12-12 | 2021-06-17 | David Klatzmann | Interleukin 2 chimeric constructs |
| US11981715B2 (en) | 2020-02-21 | 2024-05-14 | Pandion Operations, Inc. | Tissue targeted immunotolerance with a CD39 effector |
| WO2021176044A1 (en) | 2020-03-06 | 2021-09-10 | Centre Hospitalier Universitaire De Nimes | Low dose human interleukin-2 for the treatment of amyotrophic lateral sclerosis |
| BR112022022035A2 (pt) * | 2020-04-29 | 2023-01-03 | Abion Inc | Interferon-beta humano variante, polinucleotídeo, vetor de expressão, célula animal transformada, métodos para preparar um interferon-beta humano variante, melhorar a estabilidade de um interferon-beta r27t humano variante e tratar uma doença, composição farmacêutica e uso |
| JP7610816B2 (ja) * | 2020-04-29 | 2025-01-09 | ジェノファーム インク． | インターフェロンβ変異体と抗体が融合された組換えタンパク質およびそれを含む薬学的組成物 |
| BR112023003614A2 (pt) * | 2020-08-28 | 2023-03-28 | Biocad Joint Stock Co | Domínio de ligação, ácido nucleico isolado, cassete e vetor de expressão, vírus recombinante e seu uso, composição farmacêutica, vacina baseada em aav5 para indução de imunidade específica ao sars-cov-2 e/ou prevenção de infecção por coronavírus relacionada ao sars-cov-2 |
| US20240376172A1 (en) | 2021-10-06 | 2024-11-14 | Iltoo Pharma | Interleukin 2 chimeric constructs with targeting specificy to inflamed tissues |
| EP4436985A4 (en) * | 2022-05-24 | 2025-10-15 | Jhm Biopharmaceutical Hangzhou Co Ltd | RECOMBINANT BOTULINUM NEUROTOXIN TYPE A AND PROCESS FOR ITS PREPARATION |
| US20240076343A1 (en) | 2022-06-16 | 2024-03-07 | Cephalon Llc | Anti-pd-1 antibody-attenuated il-2 immunoconjugates and uses thereof |
| IL319435A (en) | 2022-09-12 | 2025-05-01 | Inserm Institut National De La Sant? Et De La Rech M?Dicale | Interleukin-2 for use in the treatment of autism spectrum disorder |
| EP4630035A1 (en) | 2022-12-05 | 2025-10-15 | Centre Hospitalier Universitaire de Nimes | Low dose human interleukin-2 for the treatment of amyotrophic lateral sclerosis in a subgroup of patients |
| WO2025032158A1 (en) | 2023-08-08 | 2025-02-13 | Institut National de la Santé et de la Recherche Médicale | Method to treat tauopathies |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5359688A (en) * | 1976-11-11 | 1978-05-29 | Tanpakushitsu Kenkiyuu Shiyour | Production of novel polypeptide |
| US4399216A (en) * | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| YU45104B (en) * | 1980-04-03 | 1992-03-10 | Biogen Nv | Process for producing recombinant dnk molecule, capable of inducting polypeptide expression in an one-cell host |
| JPS58110548A (ja) * | 1981-12-24 | 1983-07-01 | Asahi Chem Ind Co Ltd | 新規な生理活性ペプチド |
| US6936694B1 (en) * | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
| IE56026B1 (en) * | 1982-10-19 | 1991-03-27 | Cetus Corp | Cysteine-depleted muteins of biologically active proteins |
| DK265384A (da) * | 1983-06-01 | 1984-12-02 | Hoffmann La Roche | Polypeptider med interferonaktivitet |
| WO1985000817A1 (en) * | 1983-08-10 | 1985-02-28 | Amgen | Microbial expression of interleukin ii |
| US4959314A (en) * | 1984-11-09 | 1990-09-25 | Cetus Corporation | Cysteine-depleted muteins of biologically active proteins |
-
1983
- 1983-10-10 IE IE2380/83A patent/IE56026B1/en active Protection Beyond IP Right Term
- 1983-10-10 FI FI833681A patent/FI82266C/fi not_active IP Right Cessation
- 1983-10-11 NZ NZ205922A patent/NZ205922A/en unknown
- 1983-10-12 CA CA000438878A patent/CA1340861C/en not_active Expired - Lifetime
- 1983-10-12 AU AU20086/83A patent/AU563962B2/en not_active Expired
- 1983-10-12 PH PH29685A patent/PH20343A/en unknown
- 1983-10-13 AT AT85109295T patent/ATE61407T1/de not_active IP Right Cessation
- 1983-10-13 EP EP85109295A patent/EP0192811B1/en not_active Expired - Lifetime
- 1983-10-13 AT AT86110595T patent/ATE46539T1/de active
- 1983-10-13 DE DE8787103350T patent/DE3382528D1/de not_active Expired - Lifetime
- 1983-10-13 DE DE8383306221T patent/DE3376271D1/de not_active Expired
- 1983-10-13 EP EP86110595A patent/EP0218825B1/en not_active Expired
- 1983-10-13 EP EP83306221A patent/EP0109748B1/en not_active Expired
- 1983-10-13 EP EP87103350A patent/EP0234599B1/en not_active Expired - Lifetime
- 1983-10-13 AT AT87103350T patent/ATE73493T1/de not_active IP Right Cessation
- 1983-10-13 LU LU88761C patent/LU88761I2/fr unknown
- 1983-10-13 DE DE8585109295T patent/DE3382197D1/de not_active Expired - Lifetime
- 1983-10-13 DE DE8686110595T patent/DE3380598D1/de not_active Expired
- 1983-10-13 GB GB08327490A patent/GB2130219B/en not_active Expired
- 1983-10-13 AT AT83306221T patent/ATE33503T1/de not_active IP Right Cessation
- 1983-10-14 IL IL69970A patent/IL69970A/xx not_active IP Right Cessation
- 1983-10-17 GR GR72712A patent/GR79408B/el unknown
- 1983-10-17 PT PT77512A patent/PT77512B/pt unknown
- 1983-10-18 NO NO833793A patent/NO173740C/no not_active IP Right Cessation
- 1983-10-18 ES ES526541A patent/ES526541A0/es active Granted
- 1983-10-18 CH CH5667/83A patent/CH669395A5/fr not_active IP Right Cessation
- 1983-10-18 FR FR8316543A patent/FR2534594B1/fr not_active Expired
- 1983-10-18 KR KR1019830004927A patent/KR910009900B1/ko not_active Expired
- 1983-10-18 BE BE0/211722A patent/BE898016A/fr not_active IP Right Cessation
- 1983-10-19 DK DK481383A patent/DK168767B1/da not_active IP Right Cessation
-
1984
- 1984-06-01 ES ES533053A patent/ES8506089A1/es not_active Expired
- 1984-06-01 ES ES533054A patent/ES533054A0/es active Granted
- 1984-09-08 JP JP18730184A patent/JPS6128392A/ja active Granted
-
1985
- 1985-05-03 ES ES542829A patent/ES8608043A1/es not_active Expired
-
1986
- 1986-03-13 PH PH33519A patent/PH23702A/en unknown
-
1988
- 1988-03-14 JP JP63058544A patent/JPS6420096A/ja active Pending
-
1992
- 1992-08-26 DK DK105892A patent/DK171681B1/da not_active IP Right Cessation
-
1993
- 1993-06-30 NL NL930119C patent/NL930119I2/nl unknown
- 1993-07-01 LU LU88357C patent/LU88357I2/fr unknown
-
1996
- 1996-05-29 NL NL960013C patent/NL960013I2/nl unknown
-
1999
- 1999-07-07 LU LU90413C patent/LU90413I2/fr unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PT77512B (en) | Process for preparing cystein-depleted muteins of biologically active proteins | |
| US4853332A (en) | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of biologically active proteins | |
| USRE33653E (en) | Human recombinant interleukin-2 muteins | |
| US4588585A (en) | Human recombinant cysteine depleted interferon-β muteins | |
| US4959314A (en) | Cysteine-depleted muteins of biologically active proteins | |
| US4737462A (en) | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of interferon-β | |
| US5116943A (en) | Oxidation-resistant muteins of Il-2 and other protein | |
| US4752585A (en) | Oxidation-resistant muteins | |
| US4677063A (en) | Human tumor necrosis factor | |
| JP2561255B2 (ja) | 組換コロニ−刺激因子▲下−▼１ | |
| EP0237073B1 (en) | IL-1alpha derivatives and drugs | |
| KR950000712B1 (ko) | 인터로이킨1활성을가지는폴리펩티드의제조방법 | |
| JPH0240080B2 (enExample) | ||
| EP0200748B1 (en) | Human tumor necrosis factor | |
| JPH057996B2 (enExample) | ||
| EP0260350B1 (en) | Oxidation-resistant interferon-beta muteins and their production; formulations containing such muteins | |
| EP0098863A1 (en) | Interferon-alpha 61 | |
| BG60506B2 (bg) | Човешки рекомбинантни интерлевкин-2 мутеини | |
| BG60510B2 (bg) | Структурни гени,плазмиди и трансформирани клетки за получаване на бедни на цистеин мутеини на биологично активни протеини | |
| JPS58189197A (ja) | 新規ｄｎａおよびその用途 | |
| FI105203B (fi) | Menetelmä rekombinantti-ihmisinterferoni-beta-muteiinin valmistamiseksi | |
| NO306951B1 (no) | DNA-sekvens som koder for et modifisert human-IFM-(beta) samt fremgangsmåte for fremstilling derav | |
| HK1003115B (en) | Il-1alpha derivatives and drugs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PC3A | Transfer or assignment |
Free format text: 961114 CHIRON CORPORATION US |
|
| PD3A | Change of proprietorship |