CA2307142C - N-terminally chemically modified protein compositions and methods - Google Patents
N-terminally chemically modified protein compositions and methods Download PDFInfo
- Publication number
- CA2307142C CA2307142C CA2307142A CA2307142A CA2307142C CA 2307142 C CA2307142 C CA 2307142C CA 2307142 A CA2307142 A CA 2307142A CA 2307142 A CA2307142 A CA 2307142A CA 2307142 C CA2307142 C CA 2307142C
- Authority
- CA
- Canada
- Prior art keywords
- consensus interferon
- csf
- protein
- moiety
- pegylated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 87
- 239000000203 mixture Substances 0.000 title abstract description 33
- 102000035118 modified proteins Human genes 0.000 title description 11
- 108091005573 modified proteins Proteins 0.000 title description 11
- 102000014150 Interferons Human genes 0.000 claims abstract description 61
- 108010050904 Interferons Proteins 0.000 claims abstract description 61
- 229940079322 interferon Drugs 0.000 claims abstract description 58
- 238000002360 preparation method Methods 0.000 claims abstract description 36
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 25
- 229920001223 polyethylene glycol Polymers 0.000 claims description 83
- 239000002202 Polyethylene glycol Substances 0.000 claims description 58
- 229920000642 polymer Polymers 0.000 claims description 46
- 125000003827 glycol group Chemical group 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 229920001577 copolymer Polymers 0.000 claims description 5
- 229920002307 Dextran Polymers 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 229920001519 homopolymer Polymers 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 229920001583 poly(oxyethylated polyols) Polymers 0.000 claims description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 3
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- TWNDEXHSZJGRBX-UHFFFAOYSA-N boric acid;n-methylmethanamine Chemical compound CNC.OB(O)O TWNDEXHSZJGRBX-UHFFFAOYSA-N 0.000 claims description 2
- PWYPGEFOZYBWDP-UHFFFAOYSA-N boric acid;pyridine Chemical compound OB(O)O.C1=CC=NC=C1 PWYPGEFOZYBWDP-UHFFFAOYSA-N 0.000 claims description 2
- 239000012279 sodium borohydride Substances 0.000 claims description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims 2
- 229920002554 vinyl polymer Polymers 0.000 claims 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 abstract description 131
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 abstract description 131
- 102000004169 proteins and genes Human genes 0.000 abstract description 121
- 108090000623 proteins and genes Proteins 0.000 abstract description 121
- 235000018102 proteins Nutrition 0.000 description 119
- 239000000463 material Substances 0.000 description 48
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 37
- 235000018977 lysine Nutrition 0.000 description 37
- 239000004472 Lysine Substances 0.000 description 36
- 238000005932 reductive alkylation reaction Methods 0.000 description 30
- 108090000765 processed proteins & peptides Proteins 0.000 description 24
- 241000894007 species Species 0.000 description 21
- 239000000047 product Substances 0.000 description 19
- 230000001225 therapeutic effect Effects 0.000 description 19
- 230000004071 biological effect Effects 0.000 description 17
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 14
- 238000007385 chemical modification Methods 0.000 description 13
- 230000006320 pegylation Effects 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- 239000000872 buffer Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 150000001299 aldehydes Chemical class 0.000 description 10
- 230000008901 benefit Effects 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 238000003556 assay Methods 0.000 description 9
- 238000004255 ion exchange chromatography Methods 0.000 description 9
- 210000000265 leukocyte Anatomy 0.000 description 9
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 9
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000001542 size-exclusion chromatography Methods 0.000 description 8
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- 125000005647 linker group Chemical group 0.000 description 7
- 238000012510 peptide mapping method Methods 0.000 description 7
- CXCHEKCRJQRVNG-UHFFFAOYSA-N 2,2,2-trifluoroethanesulfonyl chloride Chemical compound FC(F)(F)CS(Cl)(=O)=O CXCHEKCRJQRVNG-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 238000004820 blood count Methods 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000010254 subcutaneous injection Methods 0.000 description 6
- 239000007929 subcutaneous injection Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- 230000002776 aggregation Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
- 230000009145 protein modification Effects 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000001632 sodium acetate Substances 0.000 description 5
- 235000017281 sodium acetate Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 108091006006 PEGylated Proteins Proteins 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000002523 gelfiltration Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- 210000000440 neutrophil Anatomy 0.000 description 4
- -1 poly(n-vinyl pyrrolidone) Polymers 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 3
- 108091029865 Exogenous DNA Proteins 0.000 description 3
- 102000006992 Interferon-alpha Human genes 0.000 description 3
- 108010047761 Interferon-alpha Proteins 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 239000008118 PEG 6000 Substances 0.000 description 3
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000001212 derivatisation Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 108010050848 glycylleucine Proteins 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000005342 ion exchange Methods 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 108010029961 Filgrastim Proteins 0.000 description 2
- 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 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- PINHPJWGVBKQII-SRVKXCTJSA-N Lys-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N PINHPJWGVBKQII-SRVKXCTJSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 2
- 101800000135 N-terminal protein Proteins 0.000 description 2
- 101800001452 P1 proteinase Proteins 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- UPLYXVPQLJVWMM-KKUMJFAQSA-N Ser-Phe-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O UPLYXVPQLJVWMM-KKUMJFAQSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 102000019197 Superoxide Dismutase Human genes 0.000 description 2
- 108010012715 Superoxide dismutase Proteins 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000006948 antiviral bioactivity Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 230000006323 depegylation Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229940047124 interferons Drugs 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000000734 protein sequencing Methods 0.000 description 2
- 230000029983 protein stabilization Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007974 sodium acetate buffer Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- IPDRTIBDOPMMIQ-VAOFZXAKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)-2-methyloxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@]1(C)O[C@H](CO)[C@@H](O)C1 IPDRTIBDOPMMIQ-VAOFZXAKSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- 241000776564 Acetobacter cerevisiae Species 0.000 description 1
- 102000055025 Adenosine deaminases Human genes 0.000 description 1
- CCDFBRZVTDDJNM-GUBZILKMSA-N Ala-Leu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O CCDFBRZVTDDJNM-GUBZILKMSA-N 0.000 description 1
- 108010011667 Ala-Phe-Ala Proteins 0.000 description 1
- KYDYGANDJHFBCW-DRZSPHRISA-N Ala-Phe-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N KYDYGANDJHFBCW-DRZSPHRISA-N 0.000 description 1
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 1
- CREYEAPXISDKSB-FQPOAREZSA-N Ala-Thr-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CREYEAPXISDKSB-FQPOAREZSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- KWKQGHSSNHPGOW-BQBZGAKWSA-N Arg-Ala-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)NCC(O)=O KWKQGHSSNHPGOW-BQBZGAKWSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100338243 Caenorhabditis elegans hil-6 gene Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- SWJYSDXMTPMBHO-FXQIFTODSA-N Cys-Pro-Ser Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O SWJYSDXMTPMBHO-FXQIFTODSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 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 1
- KVYVOGYEMPEXBT-GUBZILKMSA-N Gln-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O KVYVOGYEMPEXBT-GUBZILKMSA-N 0.000 description 1
- GHYJGDCPHMSFEJ-GUBZILKMSA-N Gln-Gln-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N GHYJGDCPHMSFEJ-GUBZILKMSA-N 0.000 description 1
- VSXBYIJUAXPAAL-WDSKDSINSA-N Gln-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O VSXBYIJUAXPAAL-WDSKDSINSA-N 0.000 description 1
- HYPVLWGNBIYTNA-GUBZILKMSA-N Gln-Leu-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O HYPVLWGNBIYTNA-GUBZILKMSA-N 0.000 description 1
- UWMDGPFFTKDUIY-HJGDQZAQSA-N Gln-Pro-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O UWMDGPFFTKDUIY-HJGDQZAQSA-N 0.000 description 1
- MUSGDMDGNGXULI-DCAQKATOSA-N Glu-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O MUSGDMDGNGXULI-DCAQKATOSA-N 0.000 description 1
- GJBUAAAIZSRCDC-GVXVVHGQSA-N Glu-Leu-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O GJBUAAAIZSRCDC-GVXVVHGQSA-N 0.000 description 1
- QXUPRMQJDWJDFR-NRPADANISA-N Glu-Val-Ser Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O QXUPRMQJDWJDFR-NRPADANISA-N 0.000 description 1
- 102000004547 Glucosylceramidase Human genes 0.000 description 1
- 108010017544 Glucosylceramidase Proteins 0.000 description 1
- PYTZFYUXZZHOAD-WHFBIAKZSA-N Gly-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CN PYTZFYUXZZHOAD-WHFBIAKZSA-N 0.000 description 1
- IXKRSKPKSLXIHN-YUMQZZPRSA-N Gly-Cys-Leu Chemical compound [H]NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O IXKRSKPKSLXIHN-YUMQZZPRSA-N 0.000 description 1
- BHPQOIPBLYJNAW-NGZCFLSTSA-N Gly-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN BHPQOIPBLYJNAW-NGZCFLSTSA-N 0.000 description 1
- HAXARWKYFIIHKD-ZKWXMUAHSA-N Gly-Ile-Ser Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O HAXARWKYFIIHKD-ZKWXMUAHSA-N 0.000 description 1
- DBJYVKDPGIFXFO-BQBZGAKWSA-N Gly-Met-Ala Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O DBJYVKDPGIFXFO-BQBZGAKWSA-N 0.000 description 1
- GLACUWHUYFBSPJ-FJXKBIBVSA-N Gly-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN GLACUWHUYFBSPJ-FJXKBIBVSA-N 0.000 description 1
- BAYQNCWLXIDLHX-ONGXEEELSA-N Gly-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN BAYQNCWLXIDLHX-ONGXEEELSA-N 0.000 description 1
- 108010054017 Granulocyte Colony-Stimulating Factor Receptors Proteins 0.000 description 1
- 102100039622 Granulocyte colony-stimulating factor receptor Human genes 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- UROVZOUMHNXPLZ-AVGNSLFASA-N His-Leu-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CN=CN1 UROVZOUMHNXPLZ-AVGNSLFASA-N 0.000 description 1
- PYNPBMCLAKTHJL-SRVKXCTJSA-N His-Pro-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O PYNPBMCLAKTHJL-SRVKXCTJSA-N 0.000 description 1
- ZHHLTWUOWXHVQJ-YUMQZZPRSA-N His-Ser-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)O)N ZHHLTWUOWXHVQJ-YUMQZZPRSA-N 0.000 description 1
- PZAJPILZRFPYJJ-SRVKXCTJSA-N His-Ser-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O PZAJPILZRFPYJJ-SRVKXCTJSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- MJOZZTKJZQFKDK-GUBZILKMSA-N Leu-Ala-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(N)=O MJOZZTKJZQFKDK-GUBZILKMSA-N 0.000 description 1
- FJUKMPUELVROGK-IHRRRGAJSA-N Leu-Arg-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N FJUKMPUELVROGK-IHRRRGAJSA-N 0.000 description 1
- CLVUXCBGKUECIT-HJGDQZAQSA-N Leu-Asp-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CLVUXCBGKUECIT-HJGDQZAQSA-N 0.000 description 1
- ZTLGVASZOIKNIX-DCAQKATOSA-N Leu-Gln-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ZTLGVASZOIKNIX-DCAQKATOSA-N 0.000 description 1
- LOLUPZNNADDTAA-AVGNSLFASA-N Leu-Gln-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LOLUPZNNADDTAA-AVGNSLFASA-N 0.000 description 1
- CQGSYZCULZMEDE-UHFFFAOYSA-N Leu-Gln-Pro Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)N1CCCC1C(O)=O CQGSYZCULZMEDE-UHFFFAOYSA-N 0.000 description 1
- KVMULWOHPPMHHE-DCAQKATOSA-N Leu-Glu-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O KVMULWOHPPMHHE-DCAQKATOSA-N 0.000 description 1
- YFBBUHJJUXXZOF-UWVGGRQHSA-N Leu-Gly-Pro Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O YFBBUHJJUXXZOF-UWVGGRQHSA-N 0.000 description 1
- JNDYEOUZBLOVOF-AVGNSLFASA-N Leu-Leu-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JNDYEOUZBLOVOF-AVGNSLFASA-N 0.000 description 1
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 1
- DCGXHWINSHEPIR-SRVKXCTJSA-N Leu-Lys-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)O)N DCGXHWINSHEPIR-SRVKXCTJSA-N 0.000 description 1
- DRWMRVFCKKXHCH-BZSNNMDCSA-N Leu-Phe-Leu Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)CC1=CC=CC=C1 DRWMRVFCKKXHCH-BZSNNMDCSA-N 0.000 description 1
- XWEVVRRSIOBJOO-SRVKXCTJSA-N Leu-Pro-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O XWEVVRRSIOBJOO-SRVKXCTJSA-N 0.000 description 1
- BRTVHXHCUSXYRI-CIUDSAMLSA-N Leu-Ser-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O BRTVHXHCUSXYRI-CIUDSAMLSA-N 0.000 description 1
- 241000084928 Lysinibacillus parviboronicapiens Species 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- VQILILSLEFDECU-GUBZILKMSA-N Met-Pro-Ala Chemical compound [H]N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O VQILILSLEFDECU-GUBZILKMSA-N 0.000 description 1
- NDJSSFWDYDUQID-YTWAJWBKSA-N Met-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCSC)N)O NDJSSFWDYDUQID-YTWAJWBKSA-N 0.000 description 1
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- UHRNIXJAGGLKHP-DLOVCJGASA-N Phe-Ala-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O UHRNIXJAGGLKHP-DLOVCJGASA-N 0.000 description 1
- BKWJQWJPZMUWEG-LFSVMHDDSA-N Phe-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 BKWJQWJPZMUWEG-LFSVMHDDSA-N 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 229920002538 Polyethylene Glycol 20000 Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- IFMDQWDAJUMMJC-DCAQKATOSA-N Pro-Ala-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O IFMDQWDAJUMMJC-DCAQKATOSA-N 0.000 description 1
- NXEYSLRNNPWCRN-SRVKXCTJSA-N Pro-Glu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NXEYSLRNNPWCRN-SRVKXCTJSA-N 0.000 description 1
- 241000219492 Quercus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- OJPHFSOMBZKQKQ-GUBZILKMSA-N Ser-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CO OJPHFSOMBZKQKQ-GUBZILKMSA-N 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- XUGYQLFEJYZOKQ-NGTWOADLSA-N Thr-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N XUGYQLFEJYZOKQ-NGTWOADLSA-N 0.000 description 1
- VZBWRZGNEPBRDE-HZUKXOBISA-N Trp-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N VZBWRZGNEPBRDE-HZUKXOBISA-N 0.000 description 1
- QYSBJAUCUKHSLU-JYJNAYRXSA-N Tyr-Arg-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O QYSBJAUCUKHSLU-JYJNAYRXSA-N 0.000 description 1
- RYSNTWVRSLCAJZ-RYUDHWBXSA-N Tyr-Gln-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 RYSNTWVRSLCAJZ-RYUDHWBXSA-N 0.000 description 1
- FZSPNKUFROZBSG-ZKWXMUAHSA-N Val-Ala-Asp Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O FZSPNKUFROZBSG-ZKWXMUAHSA-N 0.000 description 1
- AZSHAZJLOZQYAY-FXQIFTODSA-N Val-Ala-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O AZSHAZJLOZQYAY-FXQIFTODSA-N 0.000 description 1
- PAPWZOJOLKZEFR-AVGNSLFASA-N Val-Arg-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N PAPWZOJOLKZEFR-AVGNSLFASA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229940060205 adagen Drugs 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 1
- 108010047495 alanylglycine Proteins 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000007998 bicine buffer Substances 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical compound NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229960004177 filgrastim Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 108010072405 glycyl-aspartyl-glycine Proteins 0.000 description 1
- 108010066198 glycyl-leucyl-phenylalanine Proteins 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 108010025306 histidylleucine Proteins 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 238000001738 isopycnic centrifugation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004989 laser desorption mass spectroscopy Methods 0.000 description 1
- 108010083708 leucyl-aspartyl-valine Proteins 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 150000002669 lysines Chemical group 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 229940029345 neupogen Drugs 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 230000003448 neutrophilic effect Effects 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
- 238000005457 optimization Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108700042769 prolyl-leucyl-glycine Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 108010048818 seryl-histidine Proteins 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 108010051110 tyrosyl-lysine Proteins 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
- C07K14/56—IFN-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Communicable Diseases (AREA)
- Neurology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002472085A CA2472085A1 (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/321,510 US5824784A (en) | 1994-10-12 | 1994-10-12 | N-terminally chemically modified protein compositions and methods |
| US08/321,510 | 1994-10-12 | ||
| CA002178752A CA2178752C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002178752A Division CA2178752C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002472085A Division CA2472085A1 (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2307142A1 CA2307142A1 (en) | 1996-04-25 |
| CA2307142C true CA2307142C (en) | 2010-09-21 |
Family
ID=23250903
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2307142A Expired - Lifetime CA2307142C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
| CA002178752A Expired - Lifetime CA2178752C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
| CA002472085A Abandoned CA2472085A1 (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002178752A Expired - Lifetime CA2178752C (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
| CA002472085A Abandoned CA2472085A1 (en) | 1994-10-12 | 1995-02-08 | N-terminally chemically modified protein compositions and methods |
Country Status (19)
| Country | Link |
|---|---|
| US (7) | US5824784A (enExample) |
| EP (5) | EP2392594A1 (enExample) |
| JP (8) | JP3177251B2 (enExample) |
| KR (2) | KR100248111B1 (enExample) |
| CN (4) | CN1229388C (enExample) |
| AT (2) | ATE179991T1 (enExample) |
| CA (3) | CA2307142C (enExample) |
| DE (3) | DE10299044I1 (enExample) |
| DK (1) | DK0733067T3 (enExample) |
| ES (2) | ES2131811T3 (enExample) |
| GR (1) | GR3030526T3 (enExample) |
| IL (3) | IL134754A (enExample) |
| LU (1) | LU91006I2 (enExample) |
| MX (1) | MX9602259A (enExample) |
| NL (1) | NL300106I2 (enExample) |
| NZ (1) | NZ281469A (enExample) |
| PT (1) | PT822199E (enExample) |
| WO (1) | WO1996011953A1 (enExample) |
| ZA (1) | ZA951008B (enExample) |
Families Citing this family (567)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020177688A1 (en) * | 1988-12-22 | 2002-11-28 | Kirin-Amgen, Inc., | Chemically-modified G-CSF |
| EP0401384B1 (en) * | 1988-12-22 | 1996-03-13 | Kirin-Amgen, Inc. | Chemically modified granulocyte colony stimulating factor |
| US5581476A (en) * | 1993-01-28 | 1996-12-03 | Amgen Inc. | Computer-based methods and articles of manufacture for preparing G-CSF analogs |
| US5951974A (en) * | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
| DE69521880T2 (de) * | 1994-02-08 | 2002-01-03 | Amgen Inc., Thousand Oaks | Orales verabreichungssystem von chemischmodifizierten proteinen g-csf |
| US6001968A (en) | 1994-08-17 | 1999-12-14 | The Rockefeller University | OB polypeptides, modified forms and compositions |
| US6429290B1 (en) | 1994-08-17 | 2002-08-06 | The Rockefeller University | OB polypeptides, modified forms and derivatives |
| US20030053982A1 (en) * | 1994-09-26 | 2003-03-20 | Kinstler Olaf B. | N-terminally chemically modified protein compositions and methods |
| US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| CA2204726A1 (en) * | 1994-11-09 | 1996-12-27 | Robin E. Offord | Functionalized polymers for site-specific attachment |
| US5795587A (en) | 1995-01-23 | 1998-08-18 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
| US6008202A (en) * | 1995-01-23 | 1999-12-28 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
| US5908621A (en) | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| ES2214551T3 (es) | 1995-11-02 | 2004-09-16 | Schering Corporation | Terapia de infusion continua de citocinas a baja dosis. |
| TW517067B (en) * | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
| CA2273852C (en) | 1996-12-06 | 2009-09-29 | Amgen Inc. | Combination therapy using an il-1 inhibitor for treating il-1 mediated diseases |
| AU5773798A (en) * | 1997-01-29 | 1998-08-18 | Polymasc Pharmaceuticals Plc | Pegylation process |
| ATE469166T1 (de) | 1997-06-06 | 2010-06-15 | Kyowa Hakko Kirin Co Ltd | Chemisch modifizierte polypeptide |
| ATE375363T1 (de) * | 1997-07-14 | 2007-10-15 | Bolder Biotechnology Inc | Derivate des wachstumshormons und verwandte proteine |
| US20080076706A1 (en) | 1997-07-14 | 2008-03-27 | Bolder Biotechnology, Inc. | Derivatives of Growth Hormone and Related Proteins, and Methods of Use Thereof |
| US6753165B1 (en) * | 1999-01-14 | 2004-06-22 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
| US6017876A (en) * | 1997-08-15 | 2000-01-25 | Amgen Inc. | Chemical modification of granulocyte-colony stimulating factor (G-CSF) bioactivity |
| US5981709A (en) * | 1997-12-19 | 1999-11-09 | Enzon, Inc. | α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same |
| US5985263A (en) * | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| DE69936409T2 (de) * | 1998-04-28 | 2008-04-17 | Laboratoires Serono S.A., Coinsins | Verfahren zur schrittweise Bindung von Polyethylenglykol (PEG) an Polypeptide |
| DE69901321T2 (de) * | 1998-05-15 | 2002-12-12 | Schering Corp., Kenilworth | Kombinationstherapie enthaltend Ribavirin und Interferon alpha bei Patienten mit chronischer Hepatitis C Infektion, die nicht antiviral vorbehandelt sind |
| NL1009601C2 (nl) * | 1998-07-09 | 2000-01-11 | Univ Utrecht | Verbinding welke de binding van een eiwit aan mestcellen kan remmen, toepassing van de verbinding voor de bereiding van een geneesmiddel, een farmaceutisch preparaat, een werkwijze voor het diagnostiseren van een ziekte en een selectiewerkwijze. |
| CA2335096A1 (en) * | 1998-07-16 | 2000-01-27 | Hyseq, Inc. | Methods and materials relating to novel cd39-like polypeptides |
| ATE298251T1 (de) | 1998-08-06 | 2005-07-15 | Mountain View Pharmaceuticals | Peg-uricase konjugate und verwendung davon |
| US6783965B1 (en) | 2000-02-10 | 2004-08-31 | Mountain View Pharmaceuticals, Inc. | Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates |
| US6420339B1 (en) * | 1998-10-14 | 2002-07-16 | Amgen Inc. | Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility |
| AU766190B2 (en) * | 1998-10-16 | 2003-10-09 | Biogen Idec Ma Inc. | Interferon-beta fusion proteins and uses |
| DK1656952T3 (da) | 1998-10-16 | 2014-01-20 | Biogen Idec Inc | Polyalkylenglycolkonjugater af interferon beta-1A og anvendelser deraf |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| US7488590B2 (en) | 1998-10-23 | 2009-02-10 | Amgen Inc. | Modified peptides as therapeutic agents |
| ATE348163T1 (de) * | 1998-10-23 | 2007-01-15 | Amgen Inc | Thrombopoietin substitute |
| JP2002531089A (ja) * | 1998-11-30 | 2002-09-24 | イーライ・リリー・アンド・カンパニー | 赤血球産生性化合物 |
| US8288126B2 (en) | 1999-01-14 | 2012-10-16 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
| AU775937B2 (en) | 1999-01-14 | 2004-08-19 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
| SI1157037T1 (en) * | 1999-01-29 | 2003-12-31 | F. Hoffmann-La Roche Ag | Gcsf conjugates |
| WO2000044785A1 (en) * | 1999-01-29 | 2000-08-03 | F. Hoffmann-La Roche Ag | Gcsf conjugates |
| AU2824700A (en) * | 1999-03-01 | 2000-09-21 | Kyowa Hakko Kogyo Co. Ltd. | Chemically modified g-csf preparations |
| US6485718B1 (en) | 1999-04-13 | 2002-11-26 | Pharmacia Corporation | Site specific ligation of proteins to synthetic particles |
| US6924264B1 (en) * | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| US8106098B2 (en) * | 1999-08-09 | 2012-01-31 | The General Hospital Corporation | Protein conjugates with a water-soluble biocompatible, biodegradable polymer |
| US7459540B1 (en) | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
| US7074878B1 (en) * | 1999-12-10 | 2006-07-11 | Harris J Milton | Hydrolytically degradable polymers and hydrogels made therefrom |
| US6348558B1 (en) | 1999-12-10 | 2002-02-19 | Shearwater Corporation | Hydrolytically degradable polymers and hydrogels made therefrom |
| US6646110B2 (en) * | 2000-01-10 | 2003-11-11 | Maxygen Holdings Ltd. | G-CSF polypeptides and conjugates |
| US6831158B2 (en) * | 2000-01-10 | 2004-12-14 | Maxygen Holdings Ltd. | G-CSF conjugates |
| HUP0203751A3 (en) | 2000-01-10 | 2005-01-28 | Maxygen Holdings Ltd Redwood C | G-csf conjugates |
| US6555660B2 (en) * | 2000-01-10 | 2003-04-29 | Maxygen Holdings Ltd. | G-CSF conjugates |
| US7049761B2 (en) * | 2000-02-11 | 2006-05-23 | Altair Engineering, Inc. | Light tube and power supply circuit |
| WO2001058935A2 (en) | 2000-02-11 | 2001-08-16 | Maxygen Aps | FACTOR VII OR VIIa-LIKE MOLECULES |
| ATE269716T1 (de) | 2000-02-29 | 2004-07-15 | Pfizer Prod Inc | Stabilisierter granulozyten-kolonie- stimulierender faktor |
| US20020064820A1 (en) * | 2000-03-13 | 2002-05-30 | Jean-Michel Dayer | Apo-A-I regulation of T-cell signaling |
| WO2001076639A2 (en) * | 2000-04-06 | 2001-10-18 | Pharmacia Corporation | Chemically-modified myelopoietin conjugates |
| US6586398B1 (en) * | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
| EP1280924A2 (en) * | 2000-04-14 | 2003-02-05 | University of South Carolina Research Foundation | Cloning of corynebacteriaceae histidine ammonia lyase and therapeutic uses |
| DK1290013T3 (da) | 2000-04-21 | 2006-06-26 | Amgen Inc | Apo-A1/All-peptidderivater |
| US6677136B2 (en) | 2000-05-03 | 2004-01-13 | Amgen Inc. | Glucagon antagonists |
| US20030211094A1 (en) * | 2001-06-26 | 2003-11-13 | Nelsestuen Gary L. | High molecular weight derivatives of vitamin k-dependent polypeptides |
| MXPA03000310A (es) * | 2000-07-12 | 2004-12-13 | Gryphon Therapeutics Inc | Quimiocinas sinteticas bioactivas, modificadas con polimeros y metodos para su elaboracion y uso. |
| US7118737B2 (en) * | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
| US20030191291A1 (en) * | 2000-09-08 | 2003-10-09 | Kochendoerfer Gerd G. | Synthetic erythropoiesis stimulating proteins |
| US7052686B2 (en) * | 2000-09-29 | 2006-05-30 | Schering Corporation | Pegylated interleukin-10 |
| AU2001290312A1 (en) * | 2000-10-16 | 2002-04-29 | Chugai Seiyaku Kabushiki Kaisha | Peg-modified erythropoietin |
| EP2316490A3 (en) * | 2000-10-31 | 2012-02-01 | PR Pharmaceuticals, Inc. | Methods and compositions for enhanced delivery of bioactive molecules |
| WO2002036626A1 (en) * | 2000-11-02 | 2002-05-10 | Maxygen Aps | Single-chain multimeric polypeptides |
| CN1321134C (zh) * | 2000-11-23 | 2007-06-13 | 赵剑 | 一种生物活性蛋白质的非均一制品及其制备方法 |
| EP2123293A3 (en) * | 2000-12-14 | 2010-09-08 | Amylin Pharmaceuticals, Inc. | Peptide YY and petide YY agonists for treatment of metabolic disorders |
| TW593427B (en) * | 2000-12-18 | 2004-06-21 | Nektar Therapeutics Al Corp | Synthesis of high molecular weight non-peptidic polymer derivatives |
| US7053150B2 (en) | 2000-12-18 | 2006-05-30 | Nektar Therapeutics Al, Corporation | Segmented polymers and their conjugates |
| AU3323002A (en) * | 2000-12-20 | 2002-07-01 | Hoffmann La Roche | Erythropoietin conjugates |
| US7442370B2 (en) | 2001-02-01 | 2008-10-28 | Biogen Idec Ma Inc. | Polymer conjugates of mutated neublastin |
| KR20030074785A (ko) * | 2001-02-06 | 2003-09-19 | 메르크 파텐트 게엠베하 | 감소된 면역원성을 갖는 개질 과립구 집락 자극인자(g-csf) |
| EP1234583A1 (en) | 2001-02-23 | 2002-08-28 | F. Hoffmann-La Roche Ag | PEG-conjugates of HGF-NK4 |
| EP1366075B1 (en) | 2001-02-27 | 2009-05-27 | Maxygen Aps | New interferon beta-like molecules |
| US7276580B2 (en) | 2001-03-12 | 2007-10-02 | Biogen Idec Ma Inc. | Neurotrophic factors |
| JP2004535388A (ja) * | 2001-04-30 | 2004-11-25 | ターゲティッド ジェネティクス コーポレイション | 脂質含有薬物送達複合体およびそれらの生成方法 |
| US7247618B2 (en) * | 2001-04-30 | 2007-07-24 | Tripathi Rajavashisth | Methods for inhibiting macrophage colony stimulating factor and c-FMS-dependent cell signaling |
| HU229910B1 (hu) | 2001-05-11 | 2014-12-29 | Amgen Inc Thousand Oaks | A TALL-1-hez kötõdõ peptidek és rokon molekulák |
| ATE414711T1 (de) * | 2001-06-28 | 2008-12-15 | Mountain View Pharmaceuticals | Polymerstabilisierte proteinasen |
| KR100961859B1 (ko) * | 2001-07-11 | 2010-06-09 | 맥시겐 홀딩스 엘티디 | 지-씨에스에프 접합체 |
| US20040077835A1 (en) * | 2001-07-12 | 2004-04-22 | Robin Offord | Chemokine receptor modulators, production and use |
| US7084257B2 (en) | 2001-10-05 | 2006-08-01 | Amgen Inc. | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity |
| BR0213103A (pt) * | 2001-10-05 | 2004-09-21 | Intermune Inc | Método para tratamento de infecção pelo vìrus da hepatite com um perfil de liberação de interferon multifásico |
| US6908963B2 (en) * | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
| US7214660B2 (en) * | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| US7157277B2 (en) | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
| US7173003B2 (en) | 2001-10-10 | 2007-02-06 | Neose Technologies, Inc. | Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF |
| US7138370B2 (en) | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
| US7056500B2 (en) | 2001-10-18 | 2006-06-06 | Nektar Therapeutics Al, Corporation | Polymer conjugates of opioid antagonists |
| KR100704158B1 (ko) * | 2001-11-19 | 2007-04-05 | 교와 핫꼬 고교 가부시끼가이샤 | 다분화능 줄기세포를 조직으로부터 말초혈로 동원하는약제 |
| OA13063A (en) * | 2001-11-20 | 2006-11-10 | Pharmacia Corp | Chemically-modified human growth hormone conjugates. |
| US20030171285A1 (en) * | 2001-11-20 | 2003-09-11 | Finn Rory F. | Chemically-modified human growth hormone conjugates |
| KR100480432B1 (ko) * | 2001-12-04 | 2005-04-06 | 선바이오(주) | G-csf와 폴리에틸렌글리콜 유도체의 배합체 |
| AU2002346686A1 (en) * | 2001-12-07 | 2003-06-23 | Intermune, Inc. | Compositions and method for treating hepatitis virus infection |
| WO2003059988A2 (en) | 2002-01-14 | 2003-07-24 | The General Hospital Corporation | Biodegradable polyketal polymers and methods for their formation and use |
| PT3025726T (pt) * | 2002-01-18 | 2020-01-09 | Biogen Ma Inc | Compostos do polímero polialquileno e utilizações dos mesmos |
| DE10209821A1 (de) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung von Proteinen an ein modifiziertes Polysaccharid |
| US20030191056A1 (en) * | 2002-04-04 | 2003-10-09 | Kenneth Walker | Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins |
| US20030199464A1 (en) * | 2002-04-23 | 2003-10-23 | Silviu Itescu | Regeneration of endogenous myocardial tissue by induction of neovascularization |
| US20060122106A1 (en) * | 2002-06-14 | 2006-06-08 | Amylin Pharmaceuticals, Inc | Prevention and/or treatment of inflammatory bowel disease using pyy or agonists thereof |
| US20040002451A1 (en) * | 2002-06-20 | 2004-01-01 | Bruce Kerwin | Compositions of pegylated soluble tumor necrosis factor receptors and methods of preparing |
| AU2003256613A1 (en) * | 2002-07-19 | 2004-02-09 | Amgen Inc. | Protein conjugates with a water-soluble biocompatible, biogradable polymer |
| CA2492803C (en) | 2002-07-19 | 2013-11-05 | The General Hospital Corporation | Oxime conjugates and methods for their formation and use |
| WO2004019866A2 (en) | 2002-08-28 | 2004-03-11 | Immunex Corporation | Compositions and methods for treating cardiovascular disease |
| JP4764630B2 (ja) | 2002-09-09 | 2011-09-07 | ネクター セラピューティックス | 水溶性ポリマーアルカナール |
| US8129330B2 (en) | 2002-09-30 | 2012-03-06 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| WO2004032971A1 (en) | 2002-10-08 | 2004-04-22 | Fresenius Kabi Deutschland Gmbh | Pharmaceutically active oligosaccharide conjugates |
| JP2004196770A (ja) * | 2002-10-24 | 2004-07-15 | Effector Cell Institute Inc | 樹状細胞前駆体の血中レベル上昇剤 |
| US20050075279A1 (en) * | 2002-10-25 | 2005-04-07 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
| US7314613B2 (en) | 2002-11-18 | 2008-01-01 | Maxygen, Inc. | Interferon-alpha polypeptides and conjugates |
| PA8588901A1 (es) * | 2002-11-20 | 2005-02-04 | Pharmacia Corp | Conjugados de hormona de crecimiento humana pegilados n-terminales y proceso para su preparacion |
| WO2004063221A1 (ja) | 2002-12-26 | 2004-07-29 | Takeda Pharmaceutical Company Limited | メタスチン誘導体およびその用途 |
| GEP20084486B (en) * | 2002-12-26 | 2008-09-25 | Mountain View Pharmaceuticals | Polymer conjugates of interferon-beta with enhanced biological potency |
| RS20050501A (sr) | 2002-12-26 | 2007-08-03 | Mountain View Pharmaceuticals Inc., | Polimerni konjugati citokina,hemokina,faktora rasta, polipeptidnih hormona i njihovih antagonista sa očuvanom aktivnošću vezivanja receptora |
| US8034900B2 (en) * | 2002-12-30 | 2011-10-11 | Amylin Pharmaceuticals, Inc. | Water-soluble thioester and selenoester compounds and methods for making and using the same |
| US7803362B2 (en) * | 2003-01-24 | 2010-09-28 | Synageva Biopharma Corp. | Glycosylated interferon alpha |
| CN1997666A (zh) * | 2003-02-26 | 2007-07-11 | 印特缪恩股份有限公司 | 聚乙二醇修饰的干扰素组合物及其使用方法 |
| US20070077225A1 (en) * | 2003-02-28 | 2007-04-05 | Blatt Lawrence M | Continuous delivery methods for treating hepatitis virus infection |
| US7871607B2 (en) | 2003-03-05 | 2011-01-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases |
| EP2330213A1 (en) | 2003-03-05 | 2011-06-08 | Halozyme, Inc. | Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof |
| US20060104968A1 (en) | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
| AU2004221824B2 (en) | 2003-03-14 | 2009-08-27 | Ratiopharm Gmbh | Branched water-soluble polymers and their conjugates |
| AU2004224466B2 (en) * | 2003-03-28 | 2008-01-03 | Biopolymed Inc. | Biologically active material conjugated with biocompatible polymer with 1:1 complex, preparation method thereof and pharmaceutical composition comprising the same |
| US20060134736A1 (en) * | 2003-03-28 | 2006-06-22 | Jacobs John W | Human growth hormone conjugated with biocompatible polymer |
| US7610156B2 (en) | 2003-03-31 | 2009-10-27 | Xencor, Inc. | Methods for rational pegylation of proteins |
| US7642340B2 (en) | 2003-03-31 | 2010-01-05 | Xencor, Inc. | PEGylated TNF-α variant proteins |
| US7587286B2 (en) | 2003-03-31 | 2009-09-08 | Xencor, Inc. | Methods for rational pegylation of proteins |
| CA2522345A1 (en) | 2003-04-09 | 2004-11-18 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
| US8791070B2 (en) | 2003-04-09 | 2014-07-29 | Novo Nordisk A/S | Glycopegylated factor IX |
| US9040664B2 (en) | 2003-04-11 | 2015-05-26 | Antriabio, Inc. | Materials and methods for preparing protein-polymer conjugates |
| EP1613274B1 (en) | 2003-04-15 | 2010-03-03 | GlaxoSmithKline LLC | Human il-18 substitution mutants and their conjugates |
| EP1897552B1 (en) | 2003-04-18 | 2009-06-17 | Biogen Idec MA Inc. | Polymer-conjugated glycosylated neublastin |
| CA2525647A1 (en) | 2003-05-16 | 2005-02-24 | Intermune, Inc. | Synthetic chemokine receptor ligands and methods of use thereof |
| PL1656410T3 (pl) * | 2003-07-22 | 2010-08-31 | Nektar Therapeutics | Sposób wytwarzania sfunkcjonalizowanych polimerów z polimerycznych alkoholi |
| JP2007500132A (ja) | 2003-07-25 | 2007-01-11 | アムジェン インコーポレイテッド | Ldcamのアンタゴニストおよびアゴニスト、並びにその使用法 |
| WO2005012484A2 (en) | 2003-07-25 | 2005-02-10 | Neose Technologies, Inc. | Antibody-toxin conjugates |
| WO2005014655A2 (en) | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
| WO2005019260A1 (ja) * | 2003-08-25 | 2005-03-03 | Toray Industries, Inc. | インターフェロンβ複合体 |
| GB0320638D0 (en) | 2003-09-03 | 2003-10-01 | Novartis Ag | Organic compounds |
| CN1852740B (zh) | 2003-09-17 | 2011-05-11 | 耐科塔医药公司 | 多支链聚合物的药物前体 |
| EP1673385B1 (en) * | 2003-09-22 | 2011-03-02 | Boehringer Ingelheim International GmbH | Macrocyclic peptides active against the hepatitis c virus |
| EP1675620B1 (en) * | 2003-10-09 | 2019-05-08 | Ambrx, Inc. | Polymer derivatives |
| DE602004029173D1 (de) | 2003-10-10 | 2010-10-28 | Novo Nordisk As | Il-21-derivate |
| EP1675871A2 (en) | 2003-10-10 | 2006-07-05 | Xencor Inc. | Protein based tnf-alpha variants for the treatment of tnf-alpha related disorders |
| WO2005037214A2 (en) | 2003-10-14 | 2005-04-28 | Intermune, Inc. | Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of hcv replication |
| ES2428358T3 (es) | 2003-10-17 | 2013-11-07 | Novo Nordisk A/S | Terapia de combinación |
| WO2005040758A2 (en) * | 2003-10-24 | 2005-05-06 | Intermune, Inc. | Use of pirfenidone in therapeutic regimens |
| US7220407B2 (en) * | 2003-10-27 | 2007-05-22 | Amgen Inc. | G-CSF therapy as an adjunct to reperfusion therapy in the treatment of acute myocardial infarction |
| US8637650B2 (en) | 2003-11-05 | 2014-01-28 | Genovoxx Gmbh | Macromolecular nucleotide compounds and methods for using the same |
| US20080305992A1 (en) | 2003-11-24 | 2008-12-11 | Neose Technologies, Inc. | Glycopegylated erythropoietin |
| US8633157B2 (en) | 2003-11-24 | 2014-01-21 | Novo Nordisk A/S | Glycopegylated erythropoietin |
| US20060040856A1 (en) | 2003-12-03 | 2006-02-23 | Neose Technologies, Inc. | Glycopegylated factor IX |
| WO2005053730A1 (ja) * | 2003-12-05 | 2005-06-16 | Kirin Beer Kabushiki Kaisha | 末期心不全治療剤 |
| WO2005067963A1 (en) * | 2003-12-23 | 2005-07-28 | Intermune, Inc. | Use of polyethylene glycol-modified interferon-alpha in therapeutic dosing regimens |
| GB0500020D0 (en) | 2005-01-04 | 2005-02-09 | Novartis Ag | Organic compounds |
| NZ548123A (en) | 2004-01-08 | 2010-05-28 | Novo Nordisk As | O-linked glycosylation of peptides |
| WO2005070955A1 (en) * | 2004-01-21 | 2005-08-04 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis c virus |
| BRPI0507169A (pt) | 2004-02-02 | 2007-06-26 | Ambrx Inc | polipeptìdeos do hormÈnio de crescimento humano modificados e seu usos |
| KR20140011431A (ko) * | 2004-02-11 | 2014-01-28 | 아밀린 파마슈티칼스, 엘엘씨. | 선택가능한 특성을 갖는 하이브리드 폴리펩티드 |
| EP1789440A4 (en) | 2004-02-11 | 2008-03-12 | Amylin Pharmaceuticals Inc | REASONS FOR THE FAMILY OF PANCREATIC POLYPEPTIDES AND POLYPEPTIDES CONTAINING THEM |
| US8076288B2 (en) * | 2004-02-11 | 2011-12-13 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides having glucose lowering activity |
| US20090214472A1 (en) * | 2004-03-01 | 2009-08-27 | Enzon Pharmaceuticals Inc. | Interferon-beta polymer conjugates |
| MXPA06010764A (es) * | 2004-03-23 | 2006-12-15 | Amgen Inc | Metodos y composiciones de proteinas quimicamente modificadas. |
| JP2008505853A (ja) | 2004-04-13 | 2008-02-28 | クインテセンス バイオサイエンシーズ インコーポレーティッド | 細胞傷害性薬剤としての非天然のリボヌクレアーゼ複合体 |
| EP1586334A1 (en) * | 2004-04-15 | 2005-10-19 | TRASTEC scpa | G-CSF conjugates with peg |
| WO2005113592A2 (en) | 2004-05-19 | 2005-12-01 | Maxygen, Inc. | Interferon-alpha polypeptides and conjugates |
| US20060018875A1 (en) * | 2004-06-14 | 2006-01-26 | Blatt Lawrence M | Interferon compositions and methods of use thereof |
| EP1771205B1 (en) | 2004-06-18 | 2016-10-26 | Ambrx, Inc. | Novel antigen-binding polypeptides and their uses |
| WO2006001499A2 (en) | 2004-06-25 | 2006-01-05 | Takeda Pharmaceutical Company Limited | Metastin derivatives and use thereof |
| WO2006004959A2 (en) * | 2004-06-30 | 2006-01-12 | Egen Corporation | Pegylated interferon alpha-1b |
| EP1773400A2 (en) * | 2004-07-08 | 2007-04-18 | Amgen Inc. | Therapeutic peptides |
| WO2006010143A2 (en) | 2004-07-13 | 2006-01-26 | Neose Technologies, Inc. | Branched peg remodeling and glycosylation of glucagon-like peptide-1 [glp-1] |
| JP2008507280A (ja) | 2004-07-21 | 2008-03-13 | アンブレツクス・インコーポレイテツド | 非天然コードアミノ酸を用いた生合成ポリペプチド |
| US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
| DK1786454T3 (da) | 2004-08-19 | 2010-09-06 | Biogen Idec Inc | Neublastinvarianter |
| CN101043899B (zh) | 2004-08-19 | 2011-03-30 | 比奥根艾迪克Ma公司 | 重折叠转化型生长因子beta家族蛋白 |
| WO2006031811A2 (en) | 2004-09-10 | 2006-03-23 | Neose Technologies, Inc. | Glycopegylated interferon alpha |
| WO2006034455A2 (en) | 2004-09-23 | 2006-03-30 | Vasgene Therapeutics, Inc. | Polipeptide compounds for inhibiting angiogenesis and tumor growth |
| CA2580796C (en) | 2004-09-24 | 2013-03-26 | Amgen Inc. | Modified fc molecules having peptides inserted in internal loop regions |
| EP1814573B1 (en) | 2004-10-29 | 2016-03-09 | ratiopharm GmbH | Remodeling and glycopegylation of fibroblast growth factor (fgf) |
| AU2005306894B2 (en) | 2004-11-05 | 2011-11-24 | Northwestern University | Use of SCF and G-CSF in the treatment of cerebral ischemia and neurological disorders |
| EP2360180A3 (en) | 2004-12-13 | 2012-02-08 | Amylin Pharmaceuticals Inc. | Pancreatic polypeptide family motifs, polypeptides and methods comprising the same |
| CA2594557C (en) | 2004-12-22 | 2016-04-26 | Ambrx, Inc. | Modified human growth hormone |
| NZ555308A (en) | 2004-12-22 | 2010-10-29 | Ambrx Inc | Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides |
| JP2008525032A (ja) | 2004-12-22 | 2008-07-17 | アンブレツクス・インコーポレイテツド | 組換えヒト成長ホルモンを発現及び精製するための方法 |
| EP1674113A1 (en) | 2004-12-22 | 2006-06-28 | F. Hoffmann-La Roche Ag | Conjugates of insulin-like growth factor-1 (IGF-1) and poly(ethylene glycol) |
| BRPI0519170A8 (pt) * | 2004-12-22 | 2018-05-08 | Ambrx Inc | formulações de hormônio de crescimento humano que compreendem um aminoácido não naturalmente codificado |
| JP4990792B2 (ja) * | 2004-12-22 | 2012-08-01 | アンブレツクス・インコーポレイテツド | アミノアシル−tRNAシンテターゼの組成物およびこの使用 |
| CA2593682C (en) | 2005-01-10 | 2016-03-22 | Neose Technologies, Inc. | Glycopegylated granulocyte colony stimulating factor |
| CA2595695A1 (en) | 2005-01-25 | 2006-08-03 | Cell Therapeutics, Inc. | Biologically active protein conjugates comprising (nn[s/t]) peptide repeats and having increased plasma half-life |
| US7662781B2 (en) * | 2005-01-31 | 2010-02-16 | Eci, Inc. | Immunopotentiating agent |
| US7402730B1 (en) | 2005-02-03 | 2008-07-22 | Lexicon Pharmaceuticals, Inc. | Knockout animals manifesting hyperlipidemia |
| CA2597649A1 (en) | 2005-02-11 | 2006-08-17 | Amylin Pharmaceuticals, Inc. | Gip analog and hybrid polypeptides with selectable properties |
| US8263545B2 (en) * | 2005-02-11 | 2012-09-11 | Amylin Pharmaceuticals, Inc. | GIP analog and hybrid polypeptides with selectable properties |
| WO2006094530A1 (en) * | 2005-03-11 | 2006-09-14 | Siegfried Ltd. | Di-polymer protein conjugates and processes for their preparation |
| WO2007010552A2 (en) * | 2005-03-17 | 2007-01-25 | Serum Institute Of India Limited | N- terminal peg conjugate of erythropoietin |
| KR20080003849A (ko) | 2005-03-31 | 2008-01-08 | 아밀린 파마슈티칼스, 인크. | 비만 및 섭식 장애의 조절, 예방 및 치료를 위한 조성물 및방법 |
| EP1868652A2 (en) | 2005-04-05 | 2007-12-26 | Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A. | Method for shielding functional sites or epitopes on proteins |
| US9187546B2 (en) | 2005-04-08 | 2015-11-17 | Novo Nordisk A/S | Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants |
| KR20080009111A (ko) | 2005-04-11 | 2008-01-24 | 새비언트 파마수티컬즈 인크. | 유레이트 옥시다아제의 변이형 및 이의 용도 |
| US7833979B2 (en) | 2005-04-22 | 2010-11-16 | Amgen Inc. | Toxin peptide therapeutic agents |
| CA2607651A1 (en) | 2005-05-18 | 2007-04-19 | Maxygen, Inc. | Evolved interferon-alpha polypeptides |
| US20080255026A1 (en) | 2005-05-25 | 2008-10-16 | Glycopegylated Factor 1X | Glycopegylated Factor Ix |
| EP1885404A2 (en) * | 2005-06-01 | 2008-02-13 | Alza Corporation | Bioconjugation reactions for acylating polyethlene glycol reagents |
| KR20080027291A (ko) * | 2005-06-01 | 2008-03-26 | 맥시겐 홀딩스 엘티디 | 피이지화된 지-씨에스에프 폴리펩타이드 및 그 제조방법 |
| WO2007009208A1 (en) * | 2005-06-02 | 2007-01-25 | Cangene Corporation | Poly(ethylene glocol) modified human gm-csf with increased biological activity |
| KR20080026135A (ko) * | 2005-06-03 | 2008-03-24 | 암브룩스, 인코포레이티드 | 개선된 인간 인터페론 분자 및 이의 용도 |
| MX2007015819A (es) * | 2005-06-13 | 2008-02-22 | Nastech Pharm Co | Suministro de derivados peptidicos a traves de la mucosa. |
| KR100694994B1 (ko) * | 2005-06-13 | 2007-03-14 | 씨제이 주식회사 | 사람 과립구 콜로니 형성인자 동종체 |
| RU2427372C2 (ru) | 2005-06-17 | 2011-08-27 | Новартис Аг | Применение санглиферина для лечения вируса гепатита с |
| US8633300B2 (en) | 2005-06-17 | 2014-01-21 | Novo Nordisk Healthcare Ag | Selective reduction and derivatization of engineered proteins comprising at least one non-native cysteine |
| US7695710B2 (en) * | 2005-06-20 | 2010-04-13 | Pepgen Corporation | Antitumor and antiviral combination therapies using low-toxicity, long-circulating human interferon-alpha analogs |
| AU2006262151A1 (en) * | 2005-06-20 | 2007-01-04 | Pepgen Corporation | Low-toxicity, long-circulating chimeras of human interferon- alpha analogs and interferon tau |
| EP1926768B1 (en) | 2005-07-18 | 2011-09-14 | Nektar Therapeutics | Branched functionalized polymers using branched polyol cores |
| KR100735784B1 (ko) * | 2005-07-20 | 2007-07-06 | 재단법인 목암생명공학연구소 | 인간 과립구콜로니자극인자 변이체 및 이의 화학적 접합물 |
| EP2305696A3 (en) | 2005-07-25 | 2011-10-12 | Intermune, Inc. | Macrocyclic inhibitors of Hepatitis C virus replication |
| WO2007015591A1 (en) * | 2005-08-02 | 2007-02-08 | Cheil Industries Inc. | Epoxy resin composition for packaging semiconductor device |
| BRPI0614257A2 (pt) * | 2005-08-04 | 2011-03-15 | Nektar Therapeutics Al Corp | conjugados de uma porção de g-csf e um polìmero |
| EP2330125A3 (en) | 2005-08-11 | 2012-12-12 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides with selectable properties |
| EP1922336B1 (en) * | 2005-08-11 | 2012-11-21 | Amylin Pharmaceuticals, LLC | Hybrid polypeptides with selectable properties |
| US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
| WO2007021297A1 (en) | 2005-08-18 | 2007-02-22 | Ambrx, Inc. | COMPOSITIONS OF tRNA AND USES THEREOF |
| US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
| PL2347762T3 (pl) | 2005-08-19 | 2019-09-30 | Amylin Pharmaceuticals, Llc | Eksendyna do leczenia cukrzycy i zmniejszania masy ciała |
| EA200801050A1 (ru) | 2005-10-11 | 2008-12-30 | Интермьюн, Инк. | Соединения и способы ингибирования репликации вирусного гепатита с |
| US20090304754A1 (en) * | 2005-10-12 | 2009-12-10 | Srebrenka Robic | Pegylated glutenase polypeptides |
| KR20080074120A (ko) | 2005-10-13 | 2008-08-12 | 휴먼 게놈 사이언시즈, 인코포레이티드 | 자가항체 양성 질환 환자의 치료에 유용한 방법 및 조성물 |
| CN101291684A (zh) * | 2005-10-21 | 2008-10-22 | 阿维季尼克斯股份有限公司 | 甘醇化和糖基化的禽类来源的治疗性蛋白 |
| US20080171696A1 (en) * | 2005-10-21 | 2008-07-17 | Avigenics, Inc. | Pharmacodynamically enhanced therapeutic proteins |
| US8168592B2 (en) * | 2005-10-21 | 2012-05-01 | Amgen Inc. | CGRP peptide antagonists and conjugates |
| US20090048440A1 (en) | 2005-11-03 | 2009-02-19 | Neose Technologies, Inc. | Nucleotide Sugar Purification Using Membranes |
| HRP20110404T1 (hr) * | 2005-11-08 | 2011-08-31 | Ambrx | Ubrzivači za modifikaciju ne-prirodnih aminokiselina i polipeptida ne-prirodnih aminokiselina |
| AR056806A1 (es) | 2005-11-14 | 2007-10-24 | Amgen Inc | Moleculas quimericas de anticuerpo rankl- pth/ pthrp |
| EP1951890A4 (en) * | 2005-11-16 | 2009-06-24 | Ambrx Inc | PROCESSES AND COMPOSITIONS WITH NON-NATURAL AMINO ACIDS |
| KR101423898B1 (ko) * | 2005-12-14 | 2014-07-28 | 암브룩스, 인코포레이티드 | 비-천연 아미노산 및 폴리펩티드를 함유하는 조성물, 비-천연 아미노산 및 폴리펩티드를 포함하는 방법, 및 비-천연 아미노산 및 폴리펩티드의 용도 |
| US8404643B2 (en) | 2005-12-22 | 2013-03-26 | Takeda Pharmaceutical Company Limited | Metastin derivatives and use thereof |
| CA2841386A1 (en) | 2005-12-30 | 2007-07-12 | Zensun (Shanghai) Science & Technology Limited | Extended release of neuregulin for improved cardiac function |
| WO2007080942A1 (ja) | 2006-01-12 | 2007-07-19 | The Kitasato Institute | インターフェロンαを含む口腔組成物 |
| CN100475270C (zh) * | 2006-01-20 | 2009-04-08 | 清华大学 | 一种治疗肿瘤的药物及其应用 |
| US20070179094A1 (en) | 2006-01-31 | 2007-08-02 | Bayer Schering Pharma Ag | Modulation of MDL-1 activity for treatment of inflammatory disease |
| EP2319542B1 (en) | 2006-02-21 | 2018-03-21 | Nektar Therapeutics | Segmented degradable polymers and conjugates made therefrom |
| TWI501774B (zh) | 2006-02-27 | 2015-10-01 | Biogen Idec Inc | 神經性病症之治療 |
| JP2009529915A (ja) | 2006-03-20 | 2009-08-27 | ゾーマ テクノロジー リミテッド | ガストリン物質に対して特異的なヒト抗体および方法 |
| CA2648053A1 (en) * | 2006-03-31 | 2007-10-11 | Centocor, Inc. | Binding partners with immunoglobulin domains modified to have extended half-life |
| EP2518079A3 (en) | 2006-04-11 | 2012-12-12 | Novartis AG | HCV/HIV inhibitors and their uses |
| US9283260B2 (en) | 2006-04-21 | 2016-03-15 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
| EP2029160A2 (en) * | 2006-05-12 | 2009-03-04 | Amylin Pharmaceuticals, Inc. | Methods to restore glycemic control |
| CN103255162A (zh) | 2006-05-19 | 2013-08-21 | 格利科菲公司 | 促红细胞生成素组合物 |
| AU2007253264A1 (en) | 2006-05-24 | 2007-11-29 | Novo Nordisk Health Care Ag | Factor IX analogues having prolonged in vivo half life |
| US7981425B2 (en) | 2006-06-19 | 2011-07-19 | Amgen Inc. | Thrombopoietic compounds |
| US8840882B2 (en) * | 2006-06-23 | 2014-09-23 | Quintessence Biosciences, Inc. | Modified ribonucleases |
| CA2787343C (en) | 2006-06-26 | 2016-08-02 | Amgen Inc. | Compositions comprising modified lcat and uses thereof |
| WO2008010991A2 (en) | 2006-07-17 | 2008-01-24 | Quintessence Biosciences, Inc. | Methods and compositions for the treatment of cancer |
| CN101516388B (zh) | 2006-07-21 | 2012-10-31 | 诺和诺德公司 | 通过o-联糖基化序列的肽的糖基化 |
| CN103169984B (zh) * | 2006-07-25 | 2016-08-03 | 利普生技术有限公司 | N末端聚唾液酸化 |
| GB0615067D0 (en) * | 2006-07-28 | 2006-09-06 | Ttp Communications Ltd | Reconfigurable signal processing scheme |
| CN101534847A (zh) | 2006-08-04 | 2009-09-16 | 普罗龙药品公司 | 修饰型促红细胞生成素 |
| ITMI20061624A1 (it) * | 2006-08-11 | 2008-02-12 | Bioker Srl | Mono-coniugati sito-specifici di g-csf |
| US8497240B2 (en) | 2006-08-17 | 2013-07-30 | Amylin Pharmaceuticals, Llc | DPP-IV resistant GIP hybrid polypeptides with selectable properties |
| BRPI0715754A2 (pt) * | 2006-08-31 | 2013-07-09 | Hoffmann La Roche | mÉtodo para a produÇço de fator do crescimento similar Á insulina i |
| CL2007002502A1 (es) | 2006-08-31 | 2008-05-30 | Hoffmann La Roche | Variantes del factor de crecimiento similar a insulina-1 humano (igf-1) pegilados en lisina; metodo de produccion; proteina de fusion que la comprende; y su uso para tratar la enfermedad de alzheimer. |
| CN101511856B (zh) * | 2006-09-08 | 2016-01-20 | Ambrx公司 | 脊椎动物细胞中抑制因子trna的转录 |
| KR20090060294A (ko) | 2006-09-08 | 2009-06-11 | 암브룩스, 인코포레이티드 | 변형된 인간 혈장 폴리펩티드 또는 Fc 스캐폴드 및 그의 용도 |
| AU2007292892B9 (en) * | 2006-09-08 | 2013-02-28 | Ambrx, Inc. | Hybrid suppressor tRNA for vertebrate cells |
| US7985783B2 (en) | 2006-09-21 | 2011-07-26 | The Regents Of The University Of California | Aldehyde tags, uses thereof in site-specific protein modification |
| NZ597098A (en) | 2006-09-28 | 2013-05-31 | Merck Sharp & Dohme | Use of pegylated il-10 to treat cancer |
| US8969532B2 (en) | 2006-10-03 | 2015-03-03 | Novo Nordisk A/S | Methods for the purification of polypeptide conjugates comprising polyalkylene oxide using hydrophobic interaction chromatography |
| WO2008060780A2 (en) * | 2006-10-04 | 2008-05-22 | Novo Nordisk A/S | Glycerol linked pegylated sugars and glycopeptides |
| WO2008051383A2 (en) * | 2006-10-19 | 2008-05-02 | Amgen Inc. | Use of alcohol co-solvents to improve pegylation reaction yields |
| JO3048B1 (ar) | 2006-10-25 | 2016-09-05 | Takeda Pharmaceuticals Co | مشتقات متاستين واستخدامها |
| PE20081140A1 (es) | 2006-10-25 | 2008-09-22 | Amgen Inc | Agentes terapeuticos a base de peptidos derivados de toxinas |
| KR101079993B1 (ko) * | 2006-11-17 | 2011-11-04 | 동아제약주식회사 | 폴리에틸렌글리콜 과립구 콜로니 자극인자 접합체 |
| AU2007325838B2 (en) | 2006-11-22 | 2013-09-19 | Bristol-Myers Squibb Company | Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including IGF-IR |
| ZA200904022B (en) | 2006-12-08 | 2010-08-25 | Lexicon Pharmaceuticals Inc | Monoclonal antibodies against ANGPTL3 |
| EP2111228B1 (en) | 2007-02-02 | 2011-07-20 | Bristol-Myers Squibb Company | 10Fn3 domain for use in treating diseases associated with inappropriate angiogenesis |
| CN101245109B (zh) * | 2007-02-12 | 2011-12-14 | 杭州九源基因工程有限公司 | 一种聚乙二醇单修饰的重组人粒细胞集落刺激因子突变体及其制备方法 |
| CA2682147C (en) | 2007-03-30 | 2017-08-08 | Ambrx, Inc. | Modified fgf-21 polypeptides and their uses |
| EP2144923B1 (en) | 2007-04-03 | 2013-02-13 | BioGeneriX AG | Methods of treatment using glycopegylated g-csf |
| JP2008266219A (ja) * | 2007-04-20 | 2008-11-06 | National Institute Of Advanced Industrial & Technology | リジン及びシステイン残基を含まないタンパク質 |
| TWI445544B (zh) | 2007-05-01 | 2014-07-21 | Biogen Idec Inc | 增進血管形成之組合物及方法 |
| CN101675071B (zh) | 2007-05-02 | 2014-06-18 | Ambrx公司 | 经修饰干扰素β多肽和其用途 |
| MX2009012609A (es) | 2007-05-22 | 2009-12-07 | Amgen Inc | Composiciones y metodos para producir proteinas de fusion bioactivas. |
| EP2162535A4 (en) * | 2007-06-04 | 2011-02-23 | Novo Nordisk As | O-linked glycosylation using N-acetylglucosamine transferases |
| WO2008154639A2 (en) | 2007-06-12 | 2008-12-18 | Neose Technologies, Inc. | Improved process for the production of nucleotide sugars |
| WO2009003188A2 (en) * | 2007-06-27 | 2008-12-31 | Cedars-Sinai Medical Center | N-terminal specific chemical labeling for proteomics applications |
| SI2489731T1 (sl) | 2007-07-26 | 2014-12-31 | Amgen Inc. Patent Operations, M/S 28-2-C | Modificirani encimi lecitin-holesterol aciltransferaze |
| CN101352573B (zh) * | 2007-07-27 | 2011-02-09 | 杭州九源基因工程有限公司 | 聚乙二醇单修饰的重组人集落细胞刺激因子赖氨酸缺陷体 |
| EP2578677A1 (en) | 2007-08-09 | 2013-04-10 | Genzyme Corporation | Method of treating autoimmune disease with mesenchymal stem cells |
| CL2008002399A1 (es) * | 2007-08-16 | 2009-01-02 | Pharmaessentia Corp | Conjugado sustancialmente puro que posee una porcion polimerica, una porcion proteica (interferon alfa 2b) y un ligante alifatico de 1 a 10 atomos de carbono, util en el tratamiento de las hepatitis b o c. |
| US8546328B2 (en) | 2007-08-27 | 2013-10-01 | Biogenerix Ag | Liquid formulation of G-CSF conjugate |
| US8207112B2 (en) | 2007-08-29 | 2012-06-26 | Biogenerix Ag | Liquid formulation of G-CSF conjugate |
| US8758761B2 (en) * | 2007-09-30 | 2014-06-24 | University Of Florida Research Foundation, Inc. | Combination therapies for treating type 1 diabetes |
| CA2702043A1 (en) * | 2007-10-08 | 2009-04-16 | Quintessence Biosciences, Inc. | Compositions and methods for ribonuclease-based therapies |
| MX2010004400A (es) * | 2007-10-23 | 2010-05-20 | Nektar Therapeutics | Polimeros de multiples brazos dirigidos a la hidroxiapatita y conjugados de estos. |
| CA2703830A1 (en) | 2007-11-20 | 2009-05-28 | Ambrx, Inc. | Modified insulin polypeptides and their uses |
| WO2009073977A1 (en) * | 2007-12-13 | 2009-06-18 | Biovectra Inc. | Polypeptides modified by protein trans-splicing technology |
| US8557534B2 (en) | 2007-12-27 | 2013-10-15 | Baxter International Inc. | Method and compositions for specifically detecting physiologically acceptable polymer molecules |
| US20100316702A1 (en) * | 2008-01-08 | 2010-12-16 | The Regents Of The University Of California | Compositions and methods for regulating erythropoeitin expression and ameliorating anemia and stimulating erythropoiesis |
| CN102037004A (zh) * | 2008-01-08 | 2011-04-27 | 生物种属学股份公司 | 使用寡糖基转移酶的多肽的糖缀合 |
| US20090183503A1 (en) * | 2008-01-18 | 2009-07-23 | Alberto Verdesi | Exhaust apparatus |
| PL3219795T3 (pl) | 2008-01-18 | 2024-09-16 | Biomarin Pharmaceutical Inc. | Wytwarzanie aktywnych wysoce fosforylowanych ludzkich enzymów sulfatazy lizosomalnej i ich zastosowania |
| SG188143A1 (en) | 2008-02-08 | 2013-03-28 | Ambrx Inc | Modified leptin polypeptides and their uses |
| WO2009103199A1 (zh) | 2008-02-18 | 2009-08-27 | 江苏恒瑞医药股份有限公司 | 水溶性聚合物修饰的g-csf偶联物 |
| US20130189239A1 (en) | 2008-02-27 | 2013-07-25 | Novo Nordisk A/S | Conjugated Factor VIII Molecules |
| TWI395593B (zh) | 2008-03-06 | 2013-05-11 | Halozyme Inc | 可活化的基質降解酵素之活體內暫時性控制 |
| US20110045510A1 (en) * | 2008-04-03 | 2011-02-24 | Kurt Lang | Pegylated insulin-like-growth-factor assay |
| JP5458416B2 (ja) | 2008-04-03 | 2014-04-02 | バイオスティード ジーン エクスプレッション テック. カンパニー リミテッド | 二本鎖ポリエチレングリコール化成長ホルモン、その製造方法およびその使用 |
| WO2009128917A2 (en) | 2008-04-14 | 2009-10-22 | Halozyme, Inc. | Modified hyaluronidases and uses in treating hyaluronan-associated diseases and conditions |
| TWI394580B (zh) | 2008-04-28 | 2013-05-01 | Halozyme Inc | 超快起作用胰島素組成物 |
| ES2552646T3 (es) | 2008-05-21 | 2015-12-01 | Amylin Pharmaceuticals, Inc. | Exendinas para disminuir el colesterol y los triglicéridos |
| AR071874A1 (es) | 2008-05-22 | 2010-07-21 | Bristol Myers Squibb Co | Proteinas de dominio de armazon basadas en fibronectina multivalentes |
| SG193860A1 (en) | 2008-06-04 | 2013-10-30 | Amgen Inc | Fgf21 mutants and uses thereof |
| GB0811743D0 (en) | 2008-06-26 | 2008-07-30 | Hemosol Biopharma Inc | Composition |
| WO2009158432A2 (en) | 2008-06-27 | 2009-12-30 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| EP2318029B1 (en) | 2008-07-23 | 2017-11-01 | Ambrx, Inc. | Modified bovine g-csf polypeptides and their uses |
| WO2010013762A1 (ja) * | 2008-07-30 | 2010-02-04 | 武田薬品工業株式会社 | メタスチン誘導体およびその用途 |
| JP5639585B2 (ja) * | 2008-07-31 | 2014-12-10 | ファーマエッセンティア コーポレイション | ペプチド−ポリマー共役体 |
| KR101671537B1 (ko) | 2008-08-11 | 2016-11-01 | 넥타르 테라퓨틱스 | 다분지형 중합체 알카노에이트 컨쥬게이트 |
| EP2331139B1 (en) | 2008-09-11 | 2019-04-17 | Nektar Therapeutics | Polymeric alpha-hydroxy aldehyde and ketone reagents and conjugation method |
| PE20110480A1 (es) | 2008-09-26 | 2011-07-01 | Ambrx Inc | Microorganismos y vacunas dependientes de replicacion de aminoacidos no naturales |
| US8278418B2 (en) | 2008-09-26 | 2012-10-02 | Ambrx, Inc. | Modified animal erythropoietin polypeptides and their uses |
| BRPI0920743A2 (pt) | 2008-10-01 | 2016-09-20 | Quintessence Biosciences Inc | ribonucleases terapeuticas |
| NZ592009A (en) | 2008-10-10 | 2012-11-30 | Amgen Inc | Fgf21 mutants and uses thereof |
| AU2009303368B2 (en) | 2008-10-15 | 2012-04-05 | Takeda Pharmaceutical Company Limited | Pegylation of recombinant blood coagulation factors in the presence of bound antibodies |
| PT2349342T (pt) | 2008-10-17 | 2018-10-26 | Baxalta Inc | Factores sanguíneos modificados que compreendem um baixo grau de polímero solúvel na água |
| MX2011004195A (es) | 2008-10-20 | 2011-09-27 | Usv Ltd | Un proceso mejorado para la pegilacion de proteinas. |
| JP5775820B2 (ja) * | 2008-10-21 | 2015-09-09 | バクスター・インターナショナル・インコーポレイテッドBaxter International Incorp0Rated | 遊離可能peg試薬を有するプロドラッグpegタンパク質結合体において活性成分(インビトロ脱ペグ化)を決定する方法 |
| CA2742064A1 (en) * | 2008-10-31 | 2010-05-06 | Amgen Inc. | Materials and methods relating to stem cell mobilization by multi-pegylated granulocyte colony stimulating factor |
| IT1392655B1 (it) | 2008-11-20 | 2012-03-16 | Bio Ker S R L | Site-specific monoconjugated insulinotropic glp-1 peptides. |
| TWI496582B (zh) | 2008-11-24 | 2015-08-21 | 必治妥美雅史谷比公司 | 雙重專一性之egfr/igfir結合分子 |
| CN102307993B (zh) | 2008-12-09 | 2014-06-25 | 哈洛齐梅公司 | 延长的可溶性ph20多肽及其用途 |
| JP5568091B2 (ja) | 2008-12-11 | 2014-08-06 | バクスター・インターナショナル・インコーポレイテッド | 近赤外分光法を用いた生理学的に許容されるポリマー分子の検出 |
| ES2957546T3 (es) | 2008-12-17 | 2024-01-22 | Merck Sharp & Dohme | Producción de mono- y di-PEG-IL10; y usos |
| CA2757645C (en) * | 2009-04-06 | 2018-05-15 | Mayo Foundation For Medical Education And Research | Methods and materials for delivering molecules |
| US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| BRPI1011404B1 (pt) | 2009-05-05 | 2022-05-03 | Amgen Inc | Polipeptídeos mutantes fgf21, polipeptídeo de fusão, multímero, composição farmacêutica, ácido nucleico isolado, vetor e célula hospedeira |
| AU2010246038A1 (en) | 2009-05-05 | 2011-12-01 | Amgen Inc. | FGF21 mutants and uses thereof |
| EP2432489B1 (en) | 2009-05-20 | 2016-10-05 | BioMarin Pharmaceutical Inc. | Variants of c-type natriuretic peptide |
| JP2012530493A (ja) | 2009-06-17 | 2012-12-06 | アムジエン・インコーポレーテツド | キメラポリペプチドおよびその使用 |
| CN102647998A (zh) | 2009-06-19 | 2012-08-22 | 医学免疫有限责任公司 | 蛋白酶变体 |
| JP2012531596A (ja) | 2009-06-25 | 2012-12-10 | サヴィエント・ファーマシューティカルズ・インコーポレイテッド | Peg化ウリカーゼ療法における血清尿酸をモニタリングすることにより注入反応の危険性および抗体媒介性効果消失を予測するための方法およびキット |
| US20110027229A1 (en) | 2009-07-31 | 2011-02-03 | Medtronic, Inc. | Continuous subcutaneous administration of interferon-alpha to hepatitis c infected patients |
| PT2477603E (pt) | 2009-09-17 | 2016-06-16 | Baxalta Inc | Co-formulação estável de hialuronidase e imunoglobulina e métodos para a sua utilização |
| AU2010298036B2 (en) | 2009-09-25 | 2015-05-21 | Xoma Technology Ltd. | Screening methods |
| US8926976B2 (en) | 2009-09-25 | 2015-01-06 | Xoma Technology Ltd. | Modulators |
| EP2480578A4 (en) * | 2009-09-25 | 2013-04-17 | Vybion Inc | MODIFICATION OF POLYPEPTIDE |
| WO2011050938A1 (de) | 2009-10-26 | 2011-05-05 | Genovoxx Gmbh | Konjugate von nukleotiden und methoden zu deren anwendung |
| BR112012009801A8 (pt) | 2009-10-30 | 2016-08-30 | Cns Therapeutics Inc | Polipeptídeo neurturina e variante de neurturina |
| KR20120106942A (ko) | 2009-10-30 | 2012-09-27 | 베링거 인겔하임 인터내셔날 게엠베하 | Bi201335, 인터페론 알파 및 리바비린을 포함하는 hcv 병용 치료요법을 위한 투여 용법 |
| JP2013511287A (ja) | 2009-11-23 | 2013-04-04 | アミリン・ファーマシューティカルズ,リミテッド・ライアビリティ・カンパニー | ポリペプチド・コンジュゲート |
| CA2781682A1 (en) | 2009-12-04 | 2011-06-09 | Genentech, Inc. | Multispecific antibodies, antibody analogs, compositions, and methods |
| UA109888C2 (uk) | 2009-12-07 | 2015-10-26 | ІЗОЛЬОВАНЕ АНТИТІЛО АБО ЙОГО ФРАГМЕНТ, ЩО ЗВ'ЯЗУЄТЬСЯ З β-КЛОТО, РЕЦЕПТОРАМИ FGF І ЇХНІМИ КОМПЛЕКСАМИ | |
| EA201290541A1 (ru) | 2009-12-21 | 2013-05-30 | Амбркс, Инк. | Модифицированные бычьи соматотропиновые полипептиды и их применение |
| JP2013515081A (ja) | 2009-12-21 | 2013-05-02 | アンブルックス,インコーポレイテッド | 修飾されているブタのソマトトロピンポリペプチドおよびそれらの使用 |
| US20110152188A1 (en) * | 2009-12-23 | 2011-06-23 | Hanns-Christian Mahler | Pharmaceutical compositions of igf/i proteins |
| EP2536753B1 (en) | 2010-02-16 | 2017-12-20 | Novo Nordisk A/S | Factor viii molecules with reduced vwf binding |
| MX2012010148A (es) | 2010-03-04 | 2013-01-22 | Pfenex Inc | Metodo para producir proteinas de interferon recombinantes solubles sin desnaturalizacion. |
| PL2552949T3 (pl) | 2010-04-01 | 2017-01-31 | Pfenex Inc. | Sposoby wytwarzania G-CSF w komórce gospodarza Pseudomonas |
| WO2011130417A2 (en) | 2010-04-15 | 2011-10-20 | Amgen Inc. | HUMAN FGF RECEPTOR AND β-KLOTHO BINDING PROTEINS |
| CA2797093C (en) | 2010-04-26 | 2019-10-29 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-trna synthetase |
| CA2797362C (en) | 2010-04-27 | 2020-12-08 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of isoleucyl trna synthetases |
| WO2011139853A2 (en) | 2010-04-28 | 2011-11-10 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of alanyl trna synthetases |
| EP2563383B1 (en) | 2010-04-29 | 2017-03-01 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of valyl trna synthetases |
| US8986680B2 (en) | 2010-04-29 | 2015-03-24 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Asparaginyl tRNA synthetases |
| CN102234310B (zh) * | 2010-04-30 | 2017-02-08 | 杭州九源基因工程有限公司 | 一种聚乙二醇修饰蛋白的分离纯化方法 |
| CA2797977C (en) | 2010-05-03 | 2019-08-20 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-alpha-trna synthetases |
| WO2011139986A2 (en) | 2010-05-03 | 2011-11-10 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of arginyl-trna synthetases |
| CN103140233B (zh) | 2010-05-03 | 2017-04-05 | Atyr 医药公司 | 与甲硫氨酰‑tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的发现 |
| EP2566499B1 (en) | 2010-05-04 | 2017-01-25 | aTyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of p38 multi-trna synthetase complex |
| EP2569331A1 (en) | 2010-05-10 | 2013-03-20 | Perseid Therapeutics LLC | Polypeptide inhibitors of vla4 |
| CA2799197C (en) | 2010-05-14 | 2019-10-29 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-beta-trna synthetases |
| JP2013533217A (ja) | 2010-05-17 | 2013-08-22 | セビックス・インコーポレイテッド | Peg化c−ペプチド |
| US9034598B2 (en) | 2010-05-17 | 2015-05-19 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of leucyl-tRNA synthetases |
| EP3091028A1 (en) | 2010-05-26 | 2016-11-09 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins having improved stability |
| AU2011258106B2 (en) | 2010-05-27 | 2017-02-23 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-tRNA synthetases |
| CN103118694B (zh) | 2010-06-01 | 2016-08-03 | Atyr医药公司 | 与赖氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的发现 |
| US20120123338A1 (en) | 2010-06-16 | 2012-05-17 | Medtronic, Inc. | Damping systems for stabilizing medications in drug delivery devices |
| AU2011268498A1 (en) | 2010-06-24 | 2013-01-31 | Genoscience Pharma Sas | Treatment of hepatitis C virus related diseases using hydroxychloroquine or a combination of hydroxychloroquine and an anti-viral agent |
| JP6116479B2 (ja) | 2010-07-12 | 2017-04-19 | エータイアー ファーマ, インコーポレイテッド | グリシルtRNA合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見 |
| JP2013532176A (ja) | 2010-07-15 | 2013-08-15 | ノヴォ ノルディスク アー/エス | 安定化させた第viii因子バリアント |
| DK2595624T3 (en) | 2010-07-20 | 2018-03-26 | Halozyme Inc | Methods of treating or preventing adverse side effects associated with administration of an anti-hyaluronan agent |
| AR082319A1 (es) | 2010-07-22 | 2012-11-28 | Biomarin Pharm Inc | Produccion de una n-acetilgalactosamina-6-sulfatasa humana activa altamente fosforilada y sus usos |
| CA2807552A1 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| RU2446173C1 (ru) * | 2010-08-13 | 2012-03-27 | Зао "Биокад" | Новый функционально активный, высокоочищенный стабильный конъюгат гранулоцитарного колониестимулирующего фактора (г-ксф) с полиэтиленгликолем с пролонгированным биологическим действием, пригодный для медицинского применения, и иммунобиологическое средство на его основе |
| US9567386B2 (en) | 2010-08-17 | 2017-02-14 | Ambrx, Inc. | Therapeutic uses of modified relaxin polypeptides |
| PE20140160A1 (es) | 2010-08-17 | 2014-02-08 | Ambrx Inc | Polipeptidos de relaxina modificados y sus usos |
| JP5964304B2 (ja) | 2010-08-25 | 2016-08-03 | エータイアー ファーマ, インコーポレイテッド | チロシルtRNA合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見 |
| CN104788557A (zh) | 2010-09-15 | 2015-07-22 | 诺沃—诺迪斯克有限公司 | 具有减少的细胞摄取的因子viii变体 |
| TWI480288B (zh) | 2010-09-23 | 2015-04-11 | Lilly Co Eli | 牛顆粒細胞群落刺激因子及其變體之調配物 |
| MX349054B (es) | 2010-09-28 | 2017-07-07 | Aegerion Pharmaceuticals Inc | Leptinas altamente solubles. |
| WO2012045704A1 (en) | 2010-10-05 | 2012-04-12 | Novartis Ag | New treatments of hepatitis c virus infection |
| CN103179966B (zh) | 2010-10-08 | 2017-03-15 | 诺瓦提斯公司 | 磺酰胺ns3抑制剂的维生素e制剂 |
| CN103933577B (zh) * | 2010-10-25 | 2014-12-10 | 北京凯因科技股份有限公司 | 重组集成干扰素变异体聚乙二醇偶联物的制备和应用 |
| CN102453089B (zh) * | 2010-10-25 | 2014-06-04 | 北京凯因科技股份有限公司 | 重组集成干扰素变异体聚乙二醇偶联物的制备和应用 |
| US9023791B2 (en) | 2010-11-19 | 2015-05-05 | Novartis Ag | Fibroblast growth factor 21 mutations |
| MX385858B (es) | 2010-11-24 | 2025-03-18 | Lexicon Pharmaceuticals Inc | Anticuerpos que se unen a notum pectinacetilesterasa. |
| RU2013129824A (ru) | 2010-11-30 | 2015-01-10 | Новартис Аг | Новое лечение инфекции вируса гепатита с |
| CN102485742A (zh) * | 2010-12-02 | 2012-06-06 | 山东新时代药业有限公司 | 一种聚乙二醇单修饰的重组人粒细胞集落刺激因子的制备及分离纯化方法 |
| US20140371258A1 (en) | 2010-12-17 | 2014-12-18 | Nektar Therapeutics | Water-Soluble Polymer Conjugates of Topotecan |
| WO2012088282A1 (en) | 2010-12-21 | 2012-06-28 | Nektar Therapeutics | Multi-arm polymeric prodrug conjugates of pemetrexed-based compounds |
| US20130331443A1 (en) | 2010-12-22 | 2013-12-12 | Nektar Therapeutics | Multi-arm polymeric prodrug conjugates of taxane-based compounds |
| US10894087B2 (en) | 2010-12-22 | 2021-01-19 | Nektar Therapeutics | Multi-arm polymeric prodrug conjugates of cabazitaxel-based compounds |
| EP2907504B1 (en) | 2011-02-08 | 2017-06-28 | Halozyme, Inc. | Composition and lipid formulation of a hyaluronan-degrading enzyme and the use thereof for treatment of benign prostatic hyperplasia |
| PH12013501865A1 (en) | 2011-03-16 | 2014-01-06 | Amgen Inc | Potent and selective inhibitors of nav1.3 and nav1.7 |
| US20140171365A1 (en) * | 2011-03-25 | 2014-06-19 | The Trustees Of Columbia University In The City Of New York | Pegylated human hdl particle and process for production thereof |
| KR20140007927A (ko) | 2011-03-31 | 2014-01-20 | 노파르티스 아게 | C형 간염 바이러스 감염을 치료하기 위한 알리스포리비르 |
| WO2012131061A1 (en) | 2011-04-01 | 2012-10-04 | Novartis Ag | Treatment for infection with hepatitis b virus alone or in combination with hepatitis delta virus and associated liver diseases |
| RU2013150344A (ru) | 2011-04-13 | 2015-05-20 | Новартис Аг | Лечение инфекции вируса гепатита алисповиром |
| US20140187488A1 (en) | 2011-05-17 | 2014-07-03 | Bristol-Myers Squibb Company | Methods for maintaining pegylation of polypeptides |
| EP2714735B1 (en) | 2011-06-03 | 2021-07-21 | XOMA Technology Ltd. | Antibodies specific for tgf-beta |
| US9993529B2 (en) | 2011-06-17 | 2018-06-12 | Halozyme, Inc. | Stable formulations of a hyaluronan-degrading enzyme |
| US20130022592A1 (en) | 2011-06-17 | 2013-01-24 | Daniel Edward Vaughn | Continuous subcutaneous insulin infusion methods with a hyaluronan-degrading enzyme |
| RU2654231C2 (ru) | 2011-06-28 | 2018-05-17 | Алтернатив Инновейтив Текнолоджиз, Ллц | Способ применения белков теплового шока-70 (бтш70) для повышения выносливости и лечения бтш70-зависимых заболеваний (варианты) |
| AU2012280474A1 (en) | 2011-07-01 | 2014-01-16 | Bayer Intellectual Property Gmbh | Relaxin fusion polypeptides and uses thereof |
| AU2012278944B2 (en) | 2011-07-05 | 2015-09-17 | Bioasis Technologies Inc. | p97-antibody conjugates and methods of use |
| DK2729160T3 (da) | 2011-07-08 | 2019-07-01 | Aegerion Pharmaceuticals Inc | Manipulerede polypeptider, der har forbedret virkningstid og reduceret immunogenicitet |
| CN102952067A (zh) * | 2011-08-30 | 2013-03-06 | 苏州欣诺科生物科技有限公司 | 用于蛋白质n端聚乙二醇修饰的吡哆醛衍生物、制备方法及其应用 |
| WO2013033452A2 (en) | 2011-08-31 | 2013-03-07 | Amgen Inc. | Method of treating or ameliorating type 1 diabetes using fgf21 |
| US20130071394A1 (en) | 2011-09-16 | 2013-03-21 | John K. Troyer | Compositions and combinations of organophosphorus bioscavengers and hyaluronan-degrading enzymes, and methods of use |
| US9458214B2 (en) | 2011-09-26 | 2016-10-04 | Novartis Ag | Dual function fibroblast growth factor 21 proteins |
| JO3476B1 (ar) | 2011-09-26 | 2020-07-05 | Novartis Ag | بروتينات مندمجة لعلاج الاضطرابات الايضية |
| US20140228281A1 (en) | 2011-09-27 | 2014-08-14 | Novartis Ag | Alisporivr for treatment of hepatitis c virus infection |
| WO2013056197A1 (en) | 2011-10-14 | 2013-04-18 | Alternative Innovative Technologies Llc | Degradation resistant hsp70 formulations and uses thereof |
| CA2853358A1 (en) | 2011-10-24 | 2013-05-02 | Halozyme, Inc. | Companion diagnostic for anti-hyaluronan agent therapy and methods of use thereof |
| US9186295B2 (en) | 2011-10-25 | 2015-11-17 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US10350139B2 (en) | 2011-10-25 | 2019-07-16 | Corning Incorporated | Pharmaceutical glass packaging assuring pharmaceutical sterility |
| US9522951B2 (en) | 2011-10-31 | 2016-12-20 | Bristol-Myers Squibb Company | Fibronectin binding domains with reduced immunogenicity |
| US8962553B2 (en) | 2011-11-17 | 2015-02-24 | Cebix Ab | Method of treating a diabetic subject having a microvascular impairment disorder by a pegylated C-peptide |
| RU2685867C2 (ru) | 2011-12-15 | 2019-04-23 | Алтернатив Инновейтив Текнолоджиз Ллц | Гибридные белки и белковые конъюгаты на основе белка теплового шока-70 (БТШ70) и способы их применения (варианты) |
| SG11201403714TA (en) | 2011-12-30 | 2014-07-30 | Halozyme Inc | Ph20 polypeptide variants, formulations and uses thereof |
| JP2015506369A (ja) | 2012-01-30 | 2015-03-02 | アレコー リミテッド | 安定化された水性抗体組成物 |
| EP2814514B1 (en) | 2012-02-16 | 2017-09-13 | Atyr Pharma, Inc. | Histidyl-trna synthetases for treating autoimmune and inflammatory diseases |
| CN104302408B (zh) | 2012-02-27 | 2016-12-14 | 阿穆尼克斯运营公司 | Xten缀合组合物和制造其的方法 |
| US20150030564A1 (en) | 2012-02-29 | 2015-01-29 | Toray Industries, Inc. | Inhibitory agent for body cavity fluid accumulation |
| PL2822575T3 (pl) | 2012-03-03 | 2020-08-10 | Immungene, Inc. | Zmodyfikowane sposobami inżynierii cząsteczki fuzyjne przeciwciało-mutant interferonu |
| JP2015509980A (ja) | 2012-03-14 | 2015-04-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Hcv−hiv同時感染患者集団のhcv感染症を治療するための併用療法 |
| WO2013143581A1 (en) | 2012-03-28 | 2013-10-03 | Boehringer Ingelheim International Gmbh | Combination therapy for treating hcv infection in specific patient subgenotype sub-population |
| HK1206610A1 (en) | 2012-03-30 | 2016-01-15 | Sorrento Therapeutics, Inc. | Fully human antibodies that bind to vegfr2 |
| EP2833905B1 (en) | 2012-04-04 | 2018-05-02 | Halozyme, Inc. | Combination therapy with hyaluronidase and a tumor-targeted taxane |
| US9175082B2 (en) | 2012-05-31 | 2015-11-03 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind PD-L1 |
| US9738724B2 (en) | 2012-06-08 | 2017-08-22 | Sutro Biopharma, Inc. | Antibodies comprising site-specific non-natural amino acid residues, methods of their preparation and methods of their use |
| CN105051065A (zh) | 2012-06-22 | 2015-11-11 | 索伦托治疗有限公司 | 与ccr2结合的抗原结合蛋白 |
| EP3135690A1 (en) | 2012-06-26 | 2017-03-01 | Sutro Biopharma, Inc. | Modified fc proteins comprising site-specific non-natural amino acid residues, conjugates of the same, methods of their preparation and methods of their use |
| WO2014022515A1 (en) | 2012-07-31 | 2014-02-06 | Bioasis Technologies, Inc. | Dephosphorylated lysosomal storage disease proteins and methods of use thereof |
| SI2890402T1 (sl) | 2012-08-31 | 2019-07-31 | Sutro Biopharma, Inc. | Modificirane aminokisline vsebujoče acido skupino |
| WO2014062856A1 (en) | 2012-10-16 | 2014-04-24 | Halozyme, Inc. | Hypoxia and hyaluronan and markers thereof for diagnosis and monitoring of diseases and conditions and related methods |
| CN104884056A (zh) | 2012-11-12 | 2015-09-02 | 雷德伍德生物科技股份有限公司 | 用于制备缀合物的化合物和方法 |
| WO2014078733A1 (en) | 2012-11-16 | 2014-05-22 | The Regents Of The University Of California | Pictet-spengler ligation for protein chemical modification |
| US9310374B2 (en) | 2012-11-16 | 2016-04-12 | Redwood Bioscience, Inc. | Hydrazinyl-indole compounds and methods for producing a conjugate |
| US20140205566A1 (en) | 2012-11-30 | 2014-07-24 | Novartis Ag | Cyclic nucleuoside derivatives and uses thereof |
| US9383357B2 (en) | 2012-12-07 | 2016-07-05 | Northwestern University | Biomarker for replicative senescence |
| EP3907237A1 (en) | 2012-12-20 | 2021-11-10 | Amgen Inc. | Apj receptor agonists and uses thereof |
| CN103908660B (zh) * | 2013-01-05 | 2015-02-04 | 石药集团百克(山东)生物制药有限公司 | 一种聚乙二醇修饰的rhG-CSF药物组合物及其制备方法 |
| US20150361159A1 (en) | 2013-02-01 | 2015-12-17 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins |
| CN103113466B (zh) * | 2013-03-01 | 2015-06-03 | 中国科学院过程工程研究所 | 聚乙二醇修饰的重组人干扰素β-1b及制备方法 |
| WO2014165277A2 (en) | 2013-03-12 | 2014-10-09 | Amgen Inc. | POTENT AND SELECTIVE INHIBITORS OF Nav1.7 |
| NZ711373A (en) | 2013-03-13 | 2020-07-31 | Bioasis Technologies Inc | Fragments of p97 and uses thereof |
| RU2535002C2 (ru) * | 2013-04-04 | 2014-12-10 | Федеральное государственное бюджетное учреждение "Научно-исследовательский институт фармакологии" Сибирского отделения Российской академии медицинских наук | Средство коррекции отдаленных последствий нарушений сперматогенеза, вызванных цитостатическим воздействием |
| EP2986306A4 (en) | 2013-04-18 | 2016-12-07 | Armo Biosciences Inc | METHOD FOR USE OF INTERLEUKIN-10 FOR THE TREATMENT OF ILLNESSES AND SUFFERING |
| US9603775B2 (en) | 2013-04-24 | 2017-03-28 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9707154B2 (en) | 2013-04-24 | 2017-07-18 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9713572B2 (en) | 2013-04-24 | 2017-07-25 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9849066B2 (en) | 2013-04-24 | 2017-12-26 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9839579B2 (en) | 2013-04-24 | 2017-12-12 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9700486B2 (en) | 2013-04-24 | 2017-07-11 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9707155B2 (en) | 2013-04-24 | 2017-07-18 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9717649B2 (en) | 2013-04-24 | 2017-08-01 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9700485B2 (en) | 2013-04-24 | 2017-07-11 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9717648B2 (en) | 2013-04-24 | 2017-08-01 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| US9707153B2 (en) | 2013-04-24 | 2017-07-18 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| CA2914837A1 (en) | 2013-06-17 | 2014-12-24 | Armo Biosciences, Inc. | Method for assessing protein identity and stability |
| TW201534726A (zh) | 2013-07-03 | 2015-09-16 | Halozyme Inc | 熱穩定ph20玻尿酸酶變異體及其用途 |
| WO2015006555A2 (en) | 2013-07-10 | 2015-01-15 | Sutro Biopharma, Inc. | Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use |
| US20150093399A1 (en) | 2013-08-28 | 2015-04-02 | Bioasis Technologies, Inc. | Cns-targeted conjugates having modified fc regions and methods of use thereof |
| US10010588B2 (en) | 2013-08-30 | 2018-07-03 | Armo Biosciences, Inc. | Methods of using pegylated interleukin-10 for treating hyperlipidemia |
| JP2016535080A (ja) | 2013-10-02 | 2016-11-10 | ノバルティス アーゲー | 療法における使用のためのインスリン様成長因子模倣物 |
| WO2015054658A1 (en) | 2013-10-11 | 2015-04-16 | Sutro Biopharma, Inc. | Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use |
| EP3057605A1 (en) | 2013-10-18 | 2016-08-24 | Novartis AG | Methods of treating diabetes and related disorders |
| KR20160079114A (ko) | 2013-11-11 | 2016-07-05 | 아르모 바이오사이언시스 인코포레이티드 | 질환 및 장애를 치료하기 위한 인터류킨-10을 사용하는 방법 |
| WO2015073727A1 (en) | 2013-11-13 | 2015-05-21 | Aequus Biopharma, Inc. | Engineered glycoproteins and uses thereof |
| CN115504924A (zh) | 2013-11-27 | 2022-12-23 | 雷德伍德生物科技股份有限公司 | 肼基-吡咯并化合物及用于生成缀合物的方法 |
| UY35874A (es) | 2013-12-12 | 2015-07-31 | Novartis Ag | Un proceso para la preparación de una composición de proteínas pegiladas |
| WO2015130963A2 (en) | 2014-02-27 | 2015-09-03 | Xenetic Biosciences, Inc. | Compositions and methods for administering insulin or insulin-like protein to the brain |
| WO2015187295A2 (en) | 2014-06-02 | 2015-12-10 | Armo Biosciences, Inc. | Methods of lowering serum cholesterol |
| US10941182B2 (en) | 2014-06-10 | 2021-03-09 | Amgen Inc. | Apelin polypeptides |
| BR122021025449B1 (pt) | 2014-06-12 | 2024-02-15 | Ra Pharmaceuticals, Inc | Composto, polipeptídeo e composição compreendendo o mesmo |
| SG11201701382PA (en) | 2014-08-22 | 2017-03-30 | Sorrento Therapeutics Inc | Antigen binding proteins that bind cxcr3 |
| EP3186281B1 (en) | 2014-08-28 | 2019-04-10 | Halozyme, Inc. | Combination therapy with a hyaluronan-degrading enzyme and an immune checkpoint inhibitor |
| EP3206713A4 (en) | 2014-10-14 | 2018-06-27 | Armo Biosciences, Inc. | Interleukin-15 compositions and uses thereof |
| AU2015332533B2 (en) | 2014-10-14 | 2018-08-30 | Halozyme, Inc. | Compositions of adenosine deaminase-2 (ADA2), variants thereof and methods of using same |
| AU2015336101A1 (en) | 2014-10-22 | 2017-04-20 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| MX2017004947A (es) | 2014-10-24 | 2017-06-29 | Bristol Myers Squibb Co | Polipeptidos del factor de crecimiento de fibroblastos 2 (fgf-21) modificados y usos de los mismos. |
| AU2015342908B2 (en) | 2014-11-06 | 2021-06-24 | Pharmaessentia Corporation | Dosage regimen for pegylated interferon |
| US20160151511A1 (en) | 2014-12-02 | 2016-06-02 | Antriabio, Inc. | Proteins and protein conjugates with increased hydrophobicity |
| CN104491843B (zh) * | 2015-01-23 | 2017-09-12 | 石药集团百克(山东)生物制药有限公司 | 一种聚乙二醇修饰的rhG‑CSF活性药物组合物 |
| SMT202100688T1 (it) | 2015-01-28 | 2022-01-10 | Ra Pharmaceuticals Inc | Modulatori di attività del complemento |
| US10618970B2 (en) | 2015-02-03 | 2020-04-14 | Armo Biosciences, Inc. | Method of treating cancer with IL-10 and antibodies that induce ADCC |
| WO2016141111A1 (en) | 2015-03-03 | 2016-09-09 | Xoma (Us) Llc | Treatment of post-prandial hyperinsulinemia and hypoglycemia after bariatric surgery |
| TWI708611B (zh) * | 2015-03-03 | 2020-11-01 | 香港商南沙生物科技(香港)有限公司 | 聚乙二醇化介白素-11之組合物及方法 |
| ES2820768T3 (es) | 2015-04-03 | 2021-04-22 | Xoma Technology Ltd | Tratamiento del cáncer usando inhibidores de TGF-beta y PD-1 |
| US20180118799A1 (en) | 2015-04-13 | 2018-05-03 | National Institute Of Advanced Industrial Science And Technology | Cyclized cytokine and method for producing same |
| ES2903448T3 (es) | 2015-05-01 | 2022-04-01 | Allysta Pharmaceuticals Inc | Peptidomiméticos de adiponectina para el tratamiento de trastornos oculares |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| WO2016191587A1 (en) | 2015-05-28 | 2016-12-01 | Armo Biosciences, Inc. | Pegylated interleukin-10 for use in treating cancer |
| JP2018532693A (ja) | 2015-08-06 | 2018-11-08 | ゾーマ (ユーエス) リミテッド ライアビリティ カンパニー | インスリン受容体に対する抗体断片及び低血糖を治療するためのその使用 |
| CA2995120A1 (en) | 2015-08-25 | 2017-03-02 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| KR102152437B1 (ko) | 2015-09-18 | 2020-09-07 | 고쿠리츠 다이가쿠 호징 미야자키 다이가쿠 | 장시간 작용형 아드레노메둘린 유도체 |
| CA3000697A1 (en) | 2015-10-01 | 2017-04-06 | Amgen Inc. | Treatment of bile acid disorders |
| US10935276B2 (en) | 2015-10-20 | 2021-03-02 | Steven Michalski | Air mixing device |
| WO2017083306A1 (en) | 2015-11-09 | 2017-05-18 | R.P. Scherer Technologies, Llc | Anti-cd22 antibody-maytansine conjugates and methods of use thereof |
| DK3386531T3 (da) | 2015-12-08 | 2022-01-03 | Biomarin Pharm Inc | Anvendelse af c-type natriuretiske peptidvarianter til behandling af osteoarthritis |
| KR20260070290A (ko) | 2015-12-16 | 2026-05-18 | 유씨비 홀딩스 인코포레이티드 | 보체 활성의 조절인자 |
| EP4710947A3 (en) | 2016-01-08 | 2026-06-17 | Ascendis Pharma Growth Disorders A/S | Controlled-release cnp agonists with reduced side-effects |
| ES2986360T3 (es) | 2016-01-29 | 2024-11-11 | Yuhan Corp | Proteínas de unión a antígeno que se unen a PD-L1 |
| WO2017180998A2 (en) | 2016-04-15 | 2017-10-19 | Beckman Coulter, Inc. | Photoactive macromolecules and uses thereof |
| CN118530358A (zh) | 2016-08-01 | 2024-08-23 | 佐马美国有限公司 | 甲状旁腺激素受体1(pth1r)抗体和其用途 |
| US10858428B2 (en) | 2016-09-28 | 2020-12-08 | Xoma (Us) Llc | Antibodies that bind interleukin-2 and uses thereof |
| RU2768747C2 (ru) | 2016-09-29 | 2022-03-24 | Асцендис Фарма Гроус Дизордерс А/С | Комбинаторная терапия с агонистами cnp контролируемого высвобождения |
| CN116637177A (zh) | 2016-11-11 | 2023-08-25 | 好利恩治疗美国公司 | 泼尼松和尿酸酶分子的组合疗法及其用途 |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| JP7301741B2 (ja) | 2016-12-07 | 2023-07-03 | ラ ファーマシューティカルズ インコーポレイテッド | 補体活性のモジュレータ |
| CN109923179A (zh) | 2016-12-12 | 2019-06-21 | 贝克顿·迪金森公司 | 水溶性聚合物染料 |
| SG10201912034UA (en) | 2017-02-08 | 2020-02-27 | Bristol Myers Squibb Co | Modified relaxin polypeptides comprising a pharmacokinetic enhancer and uses thereof |
| PE20200697A1 (es) | 2017-06-22 | 2020-06-16 | Catalyst Biosciences Inc | Polipeptidos de serina proteasa 1 de tipo membrana modificada (mtsp-1) y metodos de uso |
| KR102020995B1 (ko) | 2017-10-30 | 2019-09-16 | 한국코러스 주식회사 | 콜로니자극인자와 폴리올이 접합된 접합물을 고수율로 제조하는 방법 |
| WO2019133399A1 (en) | 2017-12-26 | 2019-07-04 | Becton, Dickinson And Company | Deep ultraviolet-excitable water-solvated polymeric dyes |
| JP2021509805A (ja) | 2017-12-27 | 2021-04-08 | カウンシル オブ サイエンティフィック アンド インダストリアル リサーチ | 顆粒球コロニー刺激因子活性を示すポリペプチド |
| JP2021517143A (ja) * | 2018-03-14 | 2021-07-15 | バ、ヨン | Peg化不凍タンパク質およびそれを作製する方法およびそれを使用する方法 |
| CN112384573A (zh) | 2018-03-30 | 2021-02-19 | 贝克顿·迪金森公司 | 含侧基发色团的水溶性聚合染料 |
| CN112105344B (zh) | 2018-04-24 | 2024-10-15 | 安进公司 | 用于制备可注射药物组合物的方法 |
| WO2019222435A1 (en) | 2018-05-16 | 2019-11-21 | Halozyme, Inc. | Methods of selecting subjects for combination cancer therapy with a polymer-conjugated soluble ph20 |
| KR102167755B1 (ko) | 2018-05-23 | 2020-10-19 | 주식회사 큐어바이오 | 단편화된 grs 폴리펩타이드, 이의 변이체 및 이들의 용도 |
| EP3813867A1 (en) | 2018-07-22 | 2021-05-05 | Bioasis Technologies Inc. | Treatment of lymmphatic metastases |
| KR20210057124A (ko) | 2018-09-11 | 2021-05-20 | 암브룩스, 인코포레이티드 | 인터류킨-2 폴리펩타이드 접합체 및 그의 용도 |
| JP2022512746A (ja) | 2018-10-19 | 2022-02-07 | アンブルックス,インコーポレイテッド | インターロイキン-10ポリペプチド複合体、その二量体、およびそれらの使用 |
| JP7604376B2 (ja) | 2018-12-28 | 2024-12-23 | バーテックス ファーマシューティカルズ インコーポレイテッド | 改変ウロキナーゼ型プラスミノゲンアクティベータポリペプチドおよび使用方法 |
| WO2020160325A1 (en) | 2019-01-30 | 2020-08-06 | Horizon Pharma Rheumatology Llc | Reducing immunogenicity to pegloticase |
| US12121566B2 (en) | 2019-01-30 | 2024-10-22 | Horizon Therapeutics Usa, Inc. | Methods for treating gout |
| CN119455003A (zh) | 2019-02-12 | 2025-02-18 | Ambrx公司 | 包含抗体-tlr激动剂缀合物的组合物、方法和用途 |
| US10882954B2 (en) | 2019-04-11 | 2021-01-05 | Sunbio Inc. | Tertiary alkoxy polyethylene glycol and derivatives thereof |
| US12448488B2 (en) | 2019-04-15 | 2025-10-21 | Nof Corporation | Conjugate of bio-related substance and block polymer, and block polymer derivative for obtaining said conjugate |
| CA3136602A1 (en) | 2019-04-15 | 2020-10-22 | Qwixel Therapeutics Llc | Fusion protein composition(s) comprising targeted masked type i interferons (ifna and ifnb) and an antibody against tumor antigen, for use in the treatment of cancer |
| ES2973767T3 (es) | 2019-06-04 | 2024-06-24 | Ra Pharmaceuticals Inc | Tratamiento de enfermedades inflamatorias con inhibidores del complemento |
| EP4117732A1 (en) | 2020-03-11 | 2023-01-18 | Ambrx, Inc. | Interleukin-2 polypeptide conjugates and methods of use thereof |
| EP4121448A2 (en) | 2020-03-20 | 2023-01-25 | Amgen Inc. | Determination of free n-terminus of pegfilgrastim using an acid protease |
| US20210355468A1 (en) | 2020-05-18 | 2021-11-18 | Bioasis Technologies, Inc. | Compositions and methods for treating lewy body dementia |
| US20210393787A1 (en) | 2020-06-17 | 2021-12-23 | Bioasis Technologies, Inc. | Compositions and methods for treating frontotemporal dementia |
| WO2022040596A1 (en) | 2020-08-20 | 2022-02-24 | Ambrx, Inc. | Antibody-tlr agonist conjugates, methods and uses thereof |
| US11602598B1 (en) * | 2020-08-27 | 2023-03-14 | Fresenius Kabi Deutschland Gmbh | Prefilled syringe with pegfilgrastim having optimized dose and methods related thereto |
| CN112710826A (zh) * | 2020-11-17 | 2021-04-27 | 北京九强生物技术股份有限公司 | 一种提高试剂稳定性的包被和封闭方法 |
| US11952461B2 (en) | 2021-03-22 | 2024-04-09 | Sunbio, Inc. | Siloxy polyethylene glycol and derivatives thereof |
| WO2022212899A1 (en) | 2021-04-03 | 2022-10-06 | Ambrx, Inc. | Anti-her2 antibody-drug conjugates and uses thereof |
| CN113214328B (zh) * | 2021-05-08 | 2022-06-28 | 宁波经济技术开发区弘翔生化科技有限公司 | 一种双水相体系以及基于双水相体系的单糖分离方法 |
| EP4155349A1 (en) | 2021-09-24 | 2023-03-29 | Becton, Dickinson and Company | Water-soluble yellow green absorbing dyes |
| US20250383357A1 (en) | 2022-07-01 | 2025-12-18 | Beckman Coulter, Inc. | Novel fluorescent dyes and polymers from dihydrophenanthrene derivatives |
| WO2024044327A1 (en) | 2022-08-26 | 2024-02-29 | Beckman Coulter, Inc. | Dhnt monomers and polymer dyes with modified photophysical properties |
| WO2024196805A1 (en) | 2023-03-17 | 2024-09-26 | Beckman Coulter, Inc. | Benzothienopyrrole cyanine dyes |
| US12269875B2 (en) | 2023-08-03 | 2025-04-08 | Jeff R. Peterson | Gout flare prevention methods using IL-1BETA blockers |
| CN121866309A (zh) | 2023-09-21 | 2026-04-14 | 贝克曼库尔特有限公司 | 用于流式细胞术的二氢菲(dhp)桥接染料 |
| WO2025227129A2 (en) | 2024-04-25 | 2025-10-30 | Starrock Pharma Llc | Delivery vehicles comprising proglucagon derived polypeptides and anabolic polypeptides and uses thereof |
| US20250341516A1 (en) | 2024-05-01 | 2025-11-06 | BioLegend, Inc. | Compositions for use with multiple fluorophores and methods of using |
| WO2026043823A2 (en) | 2024-08-19 | 2026-02-26 | Sutro Biopharma, Inc. | Antibodies comprising site-specific non-natural amino acid residues, methods of preparation and uses thereof |
Family Cites Families (96)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1609546A (en) * | 1925-11-19 | 1926-12-07 | Petroleum Rectifying Co | Process of separating water from emulsions |
| DE2047413C3 (de) * | 1970-09-26 | 1980-05-29 | F. Hoffmann-La Roche & Co Ag, Basel (Schweiz) | Verfahren zur Herstellung von Peptiden in homogener Phase |
| US4002714A (en) * | 1972-08-14 | 1977-01-11 | Fumio Usui | Method for producing a tapered pipe of reinforced synthetic resin |
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4002531A (en) * | 1976-01-22 | 1977-01-11 | Pierce Chemical Company | Modifying enzymes with polyethylene glycol and product produced thereby |
| DE2930542A1 (de) | 1979-07-27 | 1981-02-12 | Hoechst Ag | Neue insulinderivate und verfahren zu ihrer herstellung |
| JPS57192435A (en) | 1981-05-20 | 1982-11-26 | Toyobo Co Ltd | Modified polypeptide |
| DE3139483C2 (de) | 1981-10-03 | 1985-06-13 | Dr.-Ing. Rudolf Hell Gmbh, 2300 Kiel | Verfahren und Schaltungsanordnung zur Kontraststeigerung |
| US6936694B1 (en) * | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
| JPS58225025A (ja) * | 1982-06-24 | 1983-12-27 | Nippon Chem Res Kk | 効力持続性組成物 |
| US4609546A (en) * | 1982-06-24 | 1986-09-02 | Japan Chemical Research Co., Ltd. | Long-acting composition |
| WO1985003934A1 (fr) | 1984-03-06 | 1985-09-12 | Takeda Chemical Industries, Ltd. | Proteine modifiee chimiquement et son procede de preparation |
| DE3572982D1 (en) * | 1984-03-06 | 1989-10-19 | Takeda Chemical Industries Ltd | Chemically modified lymphokine and production thereof |
| JPS61227526A (ja) * | 1984-07-25 | 1986-10-09 | Chugai Pharmaceut Co Ltd | 新規なコロニー刺激因子 |
| JPS6142558A (ja) | 1984-08-06 | 1986-03-01 | Matsushita Electric Works Ltd | アミノ樹脂成形材料 |
| EP0215126B1 (en) | 1985-02-08 | 1991-07-31 | Chugai Seiyaku Kabushiki Kaisha | Human granulocyte colony stimulating factor |
| JPS62129298A (ja) | 1985-12-02 | 1987-06-11 | Chugai Pharmaceut Co Ltd | 新規ポリペプチド |
| US5532341A (en) * | 1985-03-28 | 1996-07-02 | Sloan-Kettering Institute For Cancer Research | Human pluripotent hematopoietic colony stimulating factor |
| US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| EP0229108B1 (en) | 1985-06-26 | 1990-12-27 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| ES8800982A1 (es) | 1985-07-05 | 1987-12-01 | Takeda Chemical Industries Ltd | Un metodo para producir la enzima superoxido-dismutasa modificada con derivados de polietilenglicol y triazina. |
| US4810643A (en) | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
| JPS63500636A (ja) | 1985-08-23 | 1988-03-10 | 麒麟麦酒株式会社 | 多分化能性顆粒球コロニー刺激因子をコードするdna |
| JPS62236497A (ja) | 1985-09-17 | 1987-10-16 | Chugai Pharmaceut Co Ltd | 顆粒球コロニー刺激因子活性を有する糖蛋白質の製造方法 |
| JP2514950B2 (ja) * | 1986-03-10 | 1996-07-10 | エフ・ホフマン―ラ ロシユ アーゲー | 化学修飾蛋白質,その製造法および中間体 |
| DK203187A (da) * | 1986-04-22 | 1987-10-23 | Immunex Corp | Human g-csf proteinekspression |
| US6673347B1 (en) * | 1986-04-30 | 2004-01-06 | Gryphon Therapeutics | Polypeptide and protein derivatives and process for their preparation |
| CA1283046C (en) | 1986-05-29 | 1991-04-16 | Nandini Katre | Tumor necrosis factor formulation |
| JPS63126900A (ja) | 1986-06-26 | 1988-05-30 | Takeda Chem Ind Ltd | 化学修飾蛋白質 |
| US4791192A (en) * | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| JPS63152393A (ja) * | 1986-07-03 | 1988-06-24 | Takeda Chem Ind Ltd | グリコシル誘導体 |
| GR871067B (en) | 1986-07-18 | 1987-11-19 | Chugai Pharmaceutical Co Ltd | Process for producing stable pharmaceutical preparation containing granulocyte colony stimulating factor |
| AU7675487A (en) | 1986-08-11 | 1988-05-19 | Cetus Corporation | Expression of granulocyte colony-stimulating factor |
| JPS6360938A (ja) | 1986-09-02 | 1988-03-17 | Meiji Milk Prod Co Ltd | 修飾組織型プラスミノ−ゲン活性化因子およびその製造方法 |
| US4894226A (en) * | 1986-11-14 | 1990-01-16 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polyproline conjugation |
| US5214132A (en) * | 1986-12-23 | 1993-05-25 | Kyowa Hakko Kogyo Co., Ltd. | Polypeptide derivatives of human granulocyte colony stimulating factor |
| NO176799C (no) * | 1986-12-23 | 1995-05-31 | Kyowa Hakko Kogyo Kk | DNA som koder for et polypeptid, rekombinant plasmid som koder for og kan uttrykke et polypeptid og fremgangsmåte for fremstilling av dette polypeptid |
| US5194592A (en) * | 1986-12-23 | 1993-03-16 | Kyowa Hakko Kogyo Co. Ltd. | Monoclonal antibodies to novel polypeptide derivatives of human granulocyte colony stimulating factor |
| US5362853A (en) * | 1986-12-23 | 1994-11-08 | Kyowa Hakko Kogyo Co., Ltd. | Polypeptide derivatives of human granulocyte colony stimulating factor |
| JPH086063B2 (ja) | 1987-07-22 | 1996-01-24 | 日本ペイント株式会社 | 親水性表面処理剤及び処理方法 |
| US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
| US4847325A (en) * | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| CA1340810C (en) * | 1988-03-31 | 1999-11-02 | Motoo Yamasaki | Polypeptide derivatives of human granulocyte colony stimulating factor |
| JP2958019B2 (ja) | 1988-05-06 | 1999-10-06 | 住友製薬株式会社 | ポリエチレングリコール誘導体、修飾ペプチドおよびその製造方法 |
| EP0719860B1 (en) * | 1988-05-13 | 2009-12-16 | Amgen Inc. | Process for isolating and purifying G-CSF |
| US5218092A (en) | 1988-09-29 | 1993-06-08 | Kyowa Hakko Kogyo Co., Ltd. | Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains |
| GB8824591D0 (en) * | 1988-10-20 | 1988-11-23 | Royal Free Hosp School Med | Fractionation process |
| US5349052A (en) * | 1988-10-20 | 1994-09-20 | Royal Free Hospital School Of Medicine | Process for fractionating polyethylene glycol (PEG)-protein adducts and an adduct for PEG and granulocyte-macrophage colony stimulating factor |
| AU4660789A (en) | 1988-11-23 | 1990-06-12 | Genentech Inc. | Polypeptide derivatives |
| US6166183A (en) * | 1992-11-30 | 2000-12-26 | Kirin-Amgen, Inc. | Chemically-modified G-CSF |
| EP0401384B1 (en) * | 1988-12-22 | 1996-03-13 | Kirin-Amgen, Inc. | Chemically modified granulocyte colony stimulating factor |
| JPH04503607A (ja) | 1989-02-24 | 1992-07-02 | イムノセラピューティックス・インコーポレイテッド | 固定化サイトカイン類 |
| US5324844A (en) * | 1989-04-19 | 1994-06-28 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| US5166322A (en) * | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| JPH04502164A (ja) * | 1989-10-10 | 1992-04-16 | アムジエン・インコーポレーテツド | 犬科・猫科動物における感染の治療または予防のための化学組成物及び方法 |
| JP2978187B2 (ja) | 1989-11-02 | 1999-11-15 | 日本ケミカルリサーチ株式会社 | 修飾スーパーオキサイドディスムターゼの製造法 |
| JPH04218000A (ja) * | 1990-02-13 | 1992-08-07 | Kirin Amgen Inc | 修飾ポリペプチド |
| DE4009661C1 (enExample) | 1990-03-26 | 1991-03-07 | Aisa Automation Industrielle S.A., Vouvry, Ch | |
| GB9107846D0 (en) | 1990-04-30 | 1991-05-29 | Ici Plc | Polypeptides |
| DE4014750A1 (de) * | 1990-05-08 | 1991-11-14 | Boehringer Mannheim Gmbh | Muteine des granulozyten-stimulierenden faktors (g-csf) |
| US5126324A (en) * | 1990-06-07 | 1992-06-30 | Genentech, Inc. | Method of enhancing growth in patients using combination therapy |
| IE912365A1 (en) * | 1990-07-23 | 1992-01-29 | Zeneca Ltd | Continuous release pharmaceutical compositions |
| US5372808A (en) * | 1990-10-17 | 1994-12-13 | Amgen Inc. | Methods and compositions for the treatment of diseases with consensus interferon while reducing side effect |
| ES2128348T3 (es) * | 1990-10-17 | 1999-05-16 | Amgen Inc | Obtencion de composiciones para el tratamiento de alteraciones de la proliferacion celular. |
| US5252714A (en) * | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
| US5124297A (en) | 1990-12-07 | 1992-06-23 | Amoco Corporation | Olefin polymerization and copolymerization catalyst |
| CH682636A5 (de) * | 1990-12-21 | 1993-10-29 | Bucher Guyer Ag Masch | Verfahren zum selektiven Entfernen von Zucker aus Getränken. |
| GEP20002142B (en) | 1991-01-18 | 2000-06-25 | Amgen Inc | Method for Treatment and Prevention of TNF Mediated Diseases |
| DE4105480A1 (de) | 1991-02-21 | 1992-08-27 | Boehringer Mannheim Gmbh | Verbesserte aktivierung von rekombinanten proteinen |
| AU1674292A (en) | 1991-03-15 | 1992-10-21 | Synergen, Inc. | Pegylation of polypeptides |
| US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
| WO1993000109A1 (en) | 1991-06-28 | 1993-01-07 | Genentech, Inc. | Method of stimulating immune response using growth hormone |
| US5281698A (en) * | 1991-07-23 | 1994-01-25 | Cetus Oncology Corporation | Preparation of an activated polymer ester for protein conjugation |
| US5197592A (en) * | 1991-08-05 | 1993-03-30 | Fmc Corporation | Wire frame idler roll support |
| NZ244778A (en) * | 1991-10-21 | 1994-03-25 | Ortho Pharma Corp | Peg imidates and protein derivatives thereof |
| US5589365A (en) * | 1991-11-29 | 1996-12-31 | Banyu Pharmaceutical Co., Ltd. | Process for producing glycosylated indolopyrrolocarbazole derivatives by culturing certain microorganisms |
| JP3235855B2 (ja) | 1991-12-19 | 2001-12-04 | 住友製薬株式会社 | 細胞接着活性ペプチド及びその高分子修飾体 |
| JP3387519B2 (ja) * | 1992-03-04 | 2003-03-17 | 株式会社日立製作所 | 情報記録再生方式及びデイスク状記録媒体 |
| FR2692736B1 (fr) | 1992-06-23 | 1996-12-20 | Thomson Csf | Filtre radioelectrique de forte et moyenne puissance. |
| US5382657A (en) * | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
| CA2149048A1 (en) | 1992-11-25 | 1994-06-09 | George N. Cox | Modified insulin-like growth factors |
| US5581476A (en) * | 1993-01-28 | 1996-12-03 | Amgen Inc. | Computer-based methods and articles of manufacture for preparing G-CSF analogs |
| AU7113594A (en) * | 1993-06-21 | 1995-01-17 | Enzon, Inc. | Site specific synthesis of conjugated peptides |
| US5589356A (en) * | 1993-06-21 | 1996-12-31 | Vanderbilt University | Litigation of sidechain unprotected peptides via a masked glycoaldehyde ester and O,N-acyl rearrangement |
| US5481571A (en) | 1993-11-12 | 1996-01-02 | Pacific Communication Sciences, Inc. | Method and apparatus for switching between radio frequency circuits |
| US5795569A (en) * | 1994-03-31 | 1998-08-18 | Amgen Inc. | Mono-pegylated proteins that stimulate megakaryocyte growth and differentiation |
| EE9600121A (et) * | 1994-03-31 | 1997-04-15 | Amgen Inc. | Megakarüotsüütide kasvu ja diferentseerumist stimuleerivad kompositsioonid ja meetodid |
| US5646113A (en) * | 1994-04-07 | 1997-07-08 | Genentech, Inc. | Treatment of partial growth hormone insensitivity syndrome |
| US5935924A (en) * | 1994-04-15 | 1999-08-10 | Genentech, Inc. | Treatment of congestive heart failure |
| US5661122A (en) * | 1994-04-15 | 1997-08-26 | Genentech, Inc. | Treatment of congestive heart failure |
| EP0756494A1 (en) | 1994-05-24 | 1997-02-05 | Amgen Boulder Inc. | Modified insulin-like growth factors |
| US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| US5770577A (en) * | 1994-11-14 | 1998-06-23 | Amgen Inc. | BDNF and NT-3 polypeptides selectively linked to polyethylene glycol |
| JP3708151B2 (ja) | 1994-12-15 | 2005-10-19 | 協和醗酵工業株式会社 | Peg化したヒト顆粒球コロニー刺激因子の定量法 |
| US5672662A (en) * | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
| KR101441331B1 (ko) | 2013-07-19 | 2014-09-17 | 주식회사 슈프리마 | 광학식 지문 인식 장치 |
-
1994
- 1994-10-12 US US08/321,510 patent/US5824784A/en not_active Expired - Lifetime
-
1995
- 1995-02-08 CA CA2307142A patent/CA2307142C/en not_active Expired - Lifetime
- 1995-02-08 PT PT97117514T patent/PT822199E/pt unknown
- 1995-02-08 DE DE2002199044 patent/DE10299044I1/de active Pending
- 1995-02-08 WO PCT/US1995/001729 patent/WO1996011953A1/en not_active Ceased
- 1995-02-08 ES ES95910233T patent/ES2131811T3/es not_active Expired - Lifetime
- 1995-02-08 AT AT95910233T patent/ATE179991T1/de active
- 1995-02-08 EP EP10183858A patent/EP2392594A1/en not_active Withdrawn
- 1995-02-08 ES ES97117514T patent/ES2224197T3/es not_active Expired - Lifetime
- 1995-02-08 DE DE69509628T patent/DE69509628T2/de not_active Expired - Lifetime
- 1995-02-08 MX MX9602259A patent/MX9602259A/es active IP Right Grant
- 1995-02-08 IL IL134754A patent/IL134754A/en not_active IP Right Cessation
- 1995-02-08 EP EP97117514A patent/EP0822199B1/en not_active Revoked
- 1995-02-08 DE DE69533556T patent/DE69533556T2/de not_active Revoked
- 1995-02-08 JP JP51319196A patent/JP3177251B2/ja not_active Expired - Lifetime
- 1995-02-08 CN CNB001309749A patent/CN1229388C/zh not_active Expired - Lifetime
- 1995-02-08 NZ NZ281469A patent/NZ281469A/en not_active IP Right Cessation
- 1995-02-08 CN CN2008101276757A patent/CN101381409B/zh not_active Expired - Lifetime
- 1995-02-08 DK DK95910233T patent/DK0733067T3/da active
- 1995-02-08 KR KR1019960703099A patent/KR100248111B1/ko not_active Expired - Lifetime
- 1995-02-08 ZA ZA951008A patent/ZA951008B/xx unknown
- 1995-02-08 IL IL11258595A patent/IL112585A/xx not_active IP Right Cessation
- 1995-02-08 EP EP10180124A patent/EP2399930A1/en not_active Withdrawn
- 1995-02-08 CN CNA2005101137680A patent/CN1896103A/zh active Pending
- 1995-02-08 EP EP95910233A patent/EP0733067B1/en not_active Expired - Lifetime
- 1995-02-08 CN CN95191454A patent/CN1071760C/zh not_active Expired - Lifetime
- 1995-02-08 CA CA002178752A patent/CA2178752C/en not_active Expired - Lifetime
- 1995-02-08 AT AT97117514T patent/ATE277078T1/de active
- 1995-02-08 EP EP04015640A patent/EP1564219A1/en not_active Withdrawn
- 1995-02-08 CA CA002472085A patent/CA2472085A1/en not_active Abandoned
-
1996
- 1996-07-22 JP JP19257696A patent/JP3177449B2/ja not_active Expired - Lifetime
-
1997
- 1997-06-20 US US08/879,760 patent/US5985265A/en not_active Expired - Lifetime
-
1999
- 1999-03-19 JP JP11076959A patent/JPH11310600A/ja active Pending
- 1999-06-16 GR GR990401601T patent/GR3030526T3/el unknown
- 1999-10-23 KR KR1019997009836A patent/KR100261030B1/ko not_active Expired - Lifetime
-
2000
- 2000-02-27 IL IL13475400A patent/IL134754A0/xx unknown
-
2001
- 2001-03-26 US US09/817,725 patent/US7090835B2/en not_active Expired - Fee Related
-
2002
- 2002-10-01 JP JP2002288746A patent/JP2003155299A/ja not_active Withdrawn
- 2002-11-04 NL NL300106C patent/NL300106I2/nl unknown
-
2003
- 2003-01-29 LU LU91006C patent/LU91006I2/fr unknown
- 2003-04-10 JP JP2003106520A patent/JP2003327600A/ja active Pending
-
2005
- 2005-09-30 JP JP2005286189A patent/JP2006045243A/ja not_active Withdrawn
- 2005-09-30 JP JP2005286188A patent/JP2006077021A/ja not_active Withdrawn
-
2006
- 2006-04-26 US US11/411,321 patent/US7662933B2/en not_active Expired - Fee Related
-
2009
- 2009-12-16 US US12/639,398 patent/US8258262B2/en not_active Expired - Fee Related
-
2010
- 2010-06-14 JP JP2010134726A patent/JP5350330B2/ja not_active Expired - Lifetime
-
2012
- 2012-08-02 US US13/565,447 patent/US20120296072A1/en not_active Abandoned
-
2013
- 2013-03-19 US US13/847,290 patent/US20130189219A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0822199B1 (en) | N-terminally monopegylated polypeptides and process for their preparation. | |
| US6956027B2 (en) | N-terminally chemically modified protein compositions and methods | |
| AU741659B2 (en) | N-terminally chemically modified protein compositions and methods | |
| Gabriel et al. | United States Patent (19) | |
| AU2004235682B2 (en) | N-Terminally chemically modified protein compositions and methods | |
| HK1008787B (en) | N-terminally monopegylated polypeptides and process for their preparation | |
| HK1078879A (en) | N-terminally monopegylated polypeptides and process for their preparation | |
| HK1008826B (en) | N-terminally chemically modified protein compositions and methods |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20150209 |