JP2018162299A - オキシントモジュリンと免疫グロブリンのフラグメントとを含むタンパク質結合体の液状製剤 - Google Patents
オキシントモジュリンと免疫グロブリンのフラグメントとを含むタンパク質結合体の液状製剤 Download PDFInfo
- Publication number
- JP2018162299A JP2018162299A JP2018123264A JP2018123264A JP2018162299A JP 2018162299 A JP2018162299 A JP 2018162299A JP 2018123264 A JP2018123264 A JP 2018123264A JP 2018123264 A JP2018123264 A JP 2018123264A JP 2018162299 A JP2018162299 A JP 2018162299A
- Authority
- JP
- Japan
- Prior art keywords
- oxyntomodulin
- sustained
- oxyntomodulin conjugate
- conjugate
- continuous
- 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.)
- Granted
Links
- PXZWGQLGAKCNKD-DPNMSELWSA-N molport-023-276-326 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 PXZWGQLGAKCNKD-DPNMSELWSA-N 0.000 title claims abstract description 266
- 101800001388 Oxyntomodulin Proteins 0.000 title claims abstract description 234
- 102400000319 Oxyntomodulin Human genes 0.000 title claims abstract description 227
- 239000012669 liquid formulation Substances 0.000 title claims abstract description 23
- 108090000623 proteins and genes Proteins 0.000 title description 35
- 102000004169 proteins and genes Human genes 0.000 title description 34
- 102000008394 Immunoglobulin Fragments Human genes 0.000 title description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 title description 2
- 108060003951 Immunoglobulin Proteins 0.000 claims abstract description 54
- 102000018358 immunoglobulin Human genes 0.000 claims abstract description 54
- 150000005846 sugar alcohols Chemical class 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 42
- 239000000872 buffer Substances 0.000 claims abstract description 27
- 239000002736 nonionic surfactant Substances 0.000 claims abstract description 23
- 239000012634 fragment Substances 0.000 claims abstract description 6
- 239000002243 precursor Substances 0.000 claims abstract description 6
- 230000002459 sustained effect Effects 0.000 claims description 85
- 150000001413 amino acids Chemical class 0.000 claims description 78
- 238000002360 preparation method Methods 0.000 claims description 56
- 239000007788 liquid Substances 0.000 claims description 52
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 43
- 239000003381 stabilizer Substances 0.000 claims description 41
- 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 claims description 39
- 229930195725 Mannitol Natural products 0.000 claims description 39
- 239000000594 mannitol Substances 0.000 claims description 39
- 235000010355 mannitol Nutrition 0.000 claims description 39
- 229920000642 polymer Polymers 0.000 claims description 33
- 239000003755 preservative agent Substances 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 20
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 19
- 229930182817 methionine Natural products 0.000 claims description 19
- 230000002335 preservative effect Effects 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 18
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 16
- 239000007951 isotonicity adjuster Substances 0.000 claims description 16
- 102000051325 Glucagon Human genes 0.000 claims description 15
- 108060003199 Glucagon Proteins 0.000 claims description 15
- 229960004666 glucagon Drugs 0.000 claims description 14
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 14
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 13
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 claims description 13
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 13
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 13
- 229940068977 polysorbate 20 Drugs 0.000 claims description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- 239000002202 Polyethylene glycol Substances 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- 229920001223 polyethylene glycol Polymers 0.000 claims description 12
- 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 claims description 11
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 11
- 239000007853 buffer solution Substances 0.000 claims description 11
- 239000000600 sorbitol Substances 0.000 claims description 11
- 235000010356 sorbitol Nutrition 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 235000000346 sugar Nutrition 0.000 claims description 9
- 230000000975 bioactive effect Effects 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 235000011187 glycerol Nutrition 0.000 claims description 6
- 230000002085 persistent effect Effects 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 6
- 102000009027 Albumins Human genes 0.000 claims description 5
- 108010088751 Albumins Proteins 0.000 claims description 5
- 150000008163 sugars Chemical class 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000004626 polylactic acid Substances 0.000 claims description 4
- 229920002101 Chitin Polymers 0.000 claims description 3
- 229920002307 Dextran Polymers 0.000 claims description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 3
- 229920002988 biodegradable polymer Polymers 0.000 claims description 3
- 239000004621 biodegradable polymer Substances 0.000 claims description 3
- 150000004676 glycans Chemical class 0.000 claims description 3
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 3
- 229960000502 poloxamer Drugs 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 229920001451 polypropylene glycol Polymers 0.000 claims description 3
- 229920001282 polysaccharide Polymers 0.000 claims description 3
- 239000005017 polysaccharide Substances 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 3
- 229950008882 polysorbate Drugs 0.000 claims description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 239000000539 dimer Substances 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229960003160 hyaluronic acid Drugs 0.000 claims description 2
- 150000002632 lipids Chemical class 0.000 claims description 2
- 239000008363 phosphate buffer Substances 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 2
- 229920001583 poly(oxyethylated polyols) Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 238000010188 recombinant method Methods 0.000 claims description 2
- 239000012929 tonicity agent Substances 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 2
- 238000013268 sustained release Methods 0.000 claims 2
- 239000012730 sustained-release form Substances 0.000 claims 2
- 108010058003 Proglucagon Proteins 0.000 claims 1
- 102000035554 Proglucagon Human genes 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000003717 m-cresyl group Chemical group [H]C1=C([H])C(O*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims 1
- 238000003860 storage Methods 0.000 abstract description 41
- 108091006905 Human Serum Albumin Proteins 0.000 abstract description 5
- 102000008100 Human Serum Albumin Human genes 0.000 abstract description 5
- 230000001766 physiological effect Effects 0.000 abstract description 4
- 208000036142 Viral infection Diseases 0.000 abstract description 3
- 230000009385 viral infection Effects 0.000 abstract description 3
- 230000005923 long-lasting effect Effects 0.000 abstract 4
- 230000002035 prolonged effect Effects 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 53
- 229940024606 amino acid Drugs 0.000 description 52
- 238000004255 ion exchange chromatography Methods 0.000 description 42
- 238000004007 reversed phase HPLC Methods 0.000 description 42
- 230000000694 effects Effects 0.000 description 39
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 39
- 235000018102 proteins Nutrition 0.000 description 32
- 210000004369 blood Anatomy 0.000 description 28
- 239000008280 blood Substances 0.000 description 28
- 208000008589 Obesity Diseases 0.000 description 27
- 235000020824 obesity Nutrition 0.000 description 27
- 239000003814 drug Substances 0.000 description 23
- 239000004475 Arginine Substances 0.000 description 20
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 20
- 235000004279 alanine Nutrition 0.000 description 20
- 229960003767 alanine Drugs 0.000 description 20
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 20
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 19
- 229960001153 serine Drugs 0.000 description 19
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- 235000013922 glutamic acid Nutrition 0.000 description 18
- 239000004220 glutamic acid Substances 0.000 description 18
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical group NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 17
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 17
- 239000004472 Lysine Substances 0.000 description 17
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 17
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 17
- 235000004554 glutamine Nutrition 0.000 description 17
- 235000018977 lysine Nutrition 0.000 description 17
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 16
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 16
- 102100040918 Pro-glucagon Human genes 0.000 description 16
- 102000004196 processed proteins & peptides Human genes 0.000 description 16
- 230000001965 increasing effect Effects 0.000 description 15
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 13
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 13
- 206010012601 diabetes mellitus Diseases 0.000 description 13
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical group OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 12
- 125000000524 functional group Chemical group 0.000 description 11
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 10
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 10
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 10
- 239000008103 glucose Substances 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 description 9
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 9
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 9
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 9
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 9
- 229960003136 leucine Drugs 0.000 description 9
- 235000005772 leucine Nutrition 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 239000004474 valine Substances 0.000 description 9
- 229960004295 valine Drugs 0.000 description 9
- 239000004471 Glycine Substances 0.000 description 8
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 8
- 235000018417 cysteine Nutrition 0.000 description 8
- QHSCIWIRXWFIGH-LURJTMIESA-N (2s)-2-amino-2-methylpentanedioic acid Chemical compound OC(=O)[C@](N)(C)CCC(O)=O QHSCIWIRXWFIGH-LURJTMIESA-N 0.000 description 7
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical group CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 7
- 108010063919 Glucagon Receptors Proteins 0.000 description 7
- 102100040890 Glucagon receptor Human genes 0.000 description 7
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 7
- 235000003704 aspartic acid Nutrition 0.000 description 7
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 7
- -1 dihydrogen salts Chemical class 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 7
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 6
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical group CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 6
- 125000003172 aldehyde group Chemical group 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 239000007979 citrate buffer Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229960000310 isoleucine Drugs 0.000 description 6
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 6
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical group CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 5
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 5
- 108010011459 Exenatide Proteins 0.000 description 5
- 102000035195 Peptidases Human genes 0.000 description 5
- 108091005804 Peptidases Proteins 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 5
- 238000011109 contamination Methods 0.000 description 5
- 229960001519 exenatide Drugs 0.000 description 5
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
- 206010033307 Overweight Diseases 0.000 description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 230000003579 anti-obesity Effects 0.000 description 4
- 235000009582 asparagine Nutrition 0.000 description 4
- 229960001230 asparagine Drugs 0.000 description 4
- 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 4
- 230000036541 health Effects 0.000 description 4
- 230000003914 insulin secretion Effects 0.000 description 4
- 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 4
- 230000000813 microbial effect Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 210000000577 adipose tissue Anatomy 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 238000004925 denaturation Methods 0.000 description 3
- 230000036425 denaturation Effects 0.000 description 3
- 230000037149 energy metabolism Effects 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 235000012631 food intake Nutrition 0.000 description 3
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- ZJIFDEVVTPEXDL-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) hydrogen carbonate Chemical compound OC(=O)ON1C(=O)CCC1=O ZJIFDEVVTPEXDL-UHFFFAOYSA-N 0.000 description 2
- AASBXERNXVFUEJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) propanoate Chemical compound CCC(=O)ON1C(=O)CCC1=O AASBXERNXVFUEJ-UHFFFAOYSA-N 0.000 description 2
- 229930195711 D-Serine Natural products 0.000 description 2
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 102000000019 Sterol Esterase Human genes 0.000 description 2
- 108010055297 Sterol Esterase Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 150000001299 aldehydes Chemical group 0.000 description 2
- 150000003862 amino acid derivatives Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 235000021229 appetite regulation Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 208000016097 disease of metabolism Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229940125542 dual agonist Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000004130 lipolysis Effects 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 2
- 229960001243 orlistat Drugs 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 2
- 229960003015 rimonabant Drugs 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 2
- 229960004425 sibutramine Drugs 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 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
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 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
- 241000270322 Lepidosauria Species 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010029719 Nonspecific reaction Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 208000021017 Weight Gain Diseases 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229940012193 contrave Drugs 0.000 description 1
- 230000006240 deamidation Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 230000010030 glucose lowering effect Effects 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000005661 hydrophobic surface Effects 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000002366 lipolytic effect Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000006318 protein oxidation Effects 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 229940124272 protein stabilizer Drugs 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
-
- 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
- A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
-
- 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
- A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Child & Adolescent Psychology (AREA)
- Mycology (AREA)
- Emergency Medicine (AREA)
- Microbiology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
アラニン A
アルギニン R
アスパラギン N
アスパラギン酸 D
システイン C
グルタミン酸 E
グルタミン Q
グリシン G
ヒスチジン H
イソロイシン I
ロイシン L
リシン K
メチオニン M
フェニルアラニン F
プロリン P
セリン S
トレオニン T
トリプトファン W
チロシン Y
バリン V
R1−X1−X2−GTFTSD−X3−X4−X5−X6−X7−X8−X9−X10−X11−X12−X13−X14−X15−X16−X17−X18−X19−X20−X21−X22−X23−X24−R2(一般式1)
R1−A−R3(一般式2)
R1−B−C−R4(一般式3)
R1−SQGTFTSDYSKYLD−D1−D2−D3−D4−D5−LFVQW−D6−D7−N−D8−R3(一般式4)
R1−E1−QGTFTSDYSKYLD−E2−E3−RA−E4−E5−FV−E6−WLMNT−E7−R5(一般式5)
R1−X1−X2−GTFTSD−X3−X4−X5−X6−X7−X8−X9−X10−X11−X12−X13−X14−X15−X16−X17−X18−X19−X20−X21−X22−X23−X24−R2(一般式6)
本発明の液状製剤におけるオキシントモジュリン及びオキシントモジュリン誘導体の安定性を測定するために、下記アミノ酸配列を有するオキシントモジュリン誘導体を合成した(表1)。
まず、MAL−10K−ALD PEGをオキシントモジュリン誘導体(配列番号25)のアミノ酸配列の30位のシステイン残基にペグ化するために、オキシントモジュリン誘導体(配列番号25)とMAL−10K−ALD PEGのモル比を1:3、タンパク質の濃度を3mg/mlとし、常温で3時間反応させた。ここで、反応は、50mMのTris緩衝液(pH8.0)に1Mのグアニジンが添加された環境下で行った。反応終了後に、前記反応液をSOURCE Sにかけ、システインにモノペグ化オキシントモジュリン誘導体を精製した(Column:SOURCE S,流速:2.0ml/分,勾配:A0→100%50分B(A:20mMのNa−citrate,pH3.0+45%エタノール,B:A+1MのKCl))(図1a)。図1aはSOURCE S精製カラムによりモノペグ化オキシントモジュリン誘導体(配列番号25)を精製した結果を示すグラフである。
実施例2で作製された持続型オキシントモジュリン結合体の液状製剤における安定性を確認するために、下記表2に示す組成にて25℃で0〜2週間保管した後にイオン交換クロマトグラフィー法(Ion Exchange-High Performance Liquid Chromatography, IE-HPLC)、サイズ排除クロマトグラフィー法(Size Exclusion-High Performance Liquid Chromatography, SE-HPLC)、逆相クロマトグラフィー法(Reverse Phase-High Performance Liquid Chromatography, RP-HPLC)を用いて分析した。緩衝液としてはクエン酸緩衝液を用い、糖アルコールとしてはマンニトールを用い、非イオン性界面活性剤としてはポリソルベート20を用いた。表3、4、5において、IE−HPLC(%)、SE−HPLC(%)及びRP−HPLC(%)は(Area%/Start Area%)であり、初期値に対する持続型オキシントモジュリン結合体の残存率を示す。表3は保管後の持続型オキシントモジュリンのIE−HPLC残存率を示し、表4は保管後の持続型オキシントモジュリンのSE−HPLC残存率を示し、表5は保管後の持続型オキシントモジュリンのRP−HPLC残存率を示す。
本発明において、安定化剤としての糖アルコールの種類及び等張化剤としての塩化ナトリウムの有無が持続型オキシントモジュリン結合体の安定性に及ぼす影響について実験した。上記実施例により選択したpH5.6のクエン酸緩衝液を基準とし、下記表6に示す組成にて25℃で0〜4週間保管した後にIE−HPLC、SE−HPLC、RP−HPLCを用いて分析した。表7、8、9において、IE−HPLC(%)、SE−HPLC(%)及びRP−HPLC(%)は(Area%/Start Area%)であり、初期値に対する持続型オキシントモジュリン結合体の残存率を示す。表7は保管後の持続型オキシントモジュリンのIE−HPLC残存率を示し、表8は保管後の持続型オキシントモジュリンのSE−HPLC残存率を示し、表9は保管後の持続型オキシントモジュリンのRP−HPLC残存率を示す。
本発明において、安定化剤としての糖アルコールの濃度が持続型オキシントモジュリン結合体の安定性に及ぼす影響について実験した。上記実施例により選択したpH5.6のクエン酸緩衝液及びマンニトールを基準とし、下記表10に示す組成にて25℃で0〜4週間保管した後にIE−HPLC、SE−HPLC、RP−HPLCを用いて分析した。表11、12、13において、IE−HPLC(%)、SE−HPLC(%)及びRP−HPLC(%)は(Area%/Start Area%)であり、初期値に対する持続型オキシントモジュリン結合体の残存率を示す。表11は保管後の持続型オキシントモジュリンのIE−HPLC残存率を示し、表12は保管後の持続型オキシントモジュリンのSE−HPLC残存率を示し、表13は保管後の持続型オキシントモジュリンのRP−HPLC残存率を示す。
本発明において、安定化剤としての界面活性剤の濃度及びアミノ酸の有無が持続型オキシントモジュリン結合体の安定性に及ぼす影響について実験した。上記実施例により選択したpH5.6のクエン酸緩衝液及び10%マンニトールを基準とし、下記表14に示す組成にて25℃で0〜4週間保管した後にIE−HPLC、SE−HPLC、RP−HPLCを用いて分析した。表15、16、17において、IE−HPLC(%)、SE−HPLC(%)及びRP−HPLC(%)は(Area%/Start Area%)であり、初期値に対する持続型オキシントモジュリン結合体の残存率を示す。表15は保管後の持続型オキシントモジュリンのIE−HPLC残存率を示し、表16は保管後の持続型オキシントモジュリンのSE−HPLC残存率を示し、表17は保管後の持続型オキシントモジュリンのRP−HPLC残存率を示す。
本発明において、安定化剤としての糖アルコールの濃度及びpHが持続型オキシントモジュリン結合体の安定性に及ぼす影響について実験した。上記実施例により選択した0.02%ポリソルベート20及び0.1mg/mLメチオニンを基準とし、下記表18に示す組成にて25℃で0〜4週間保管した後にIE−HPLC、SE−HPLC、RP−HPLCを用いて分析した。表19、20、21において、IE−HPLC(%)、SE−HPLC(%)及びRP−HPLC(%)は(Area%/Start Area%)であり、初期値に対する持続型オキシントモジュリン結合体の残存率を示す。表19は保管後の持続型オキシントモジュリンのIE−HPLC残存率を示し、表20は保管後の持続型オキシントモジュリンのSE−HPLC残存率を示し、表21は保管後の持続型オキシントモジュリンのRP−HPLC残存率を示す。
本発明において、安定化剤としての緩衝液の種類及びpHが持続型オキシントモジュリン結合体の安定性に及ぼす影響について実験した。上記実施例により選択した0.02%ポリソルベート20、0.1mg/mLメチオニン及び5%マンニトールを基準とし、下記表22に示す組成にて25℃で0〜4週間保管した後にIE−HPLC、SE−HPLC、RP−HPLCを用いて分析した。表23、24、25において、IE−HPLC(%)、SE−HPLC(%)及びRP−HPLC(%)は(Area%/Start Area%)であり、初期値に対する持続型オキシントモジュリン結合体の残存率を示す。
表23は保管後の持続型オキシントモジュリンのIE−HPLC残存率を示し、表24は保管後の持続型オキシントモジュリンのSE−HPLC残存率を示し、表25は保管後の持続型オキシントモジュリンのRP−HPLC残存率を示す。
本発明において、安定化剤としての保存剤の有無及び持続型オキシントモジュリン結合体の濃度が安定性に及ぼす影響について実験した。上記実施例により選択したpH5.6のヒスチジン緩衝液、0.02%ポリソルベート20、0.1mg/mLメチオニン及び5%マンニトールを基準とし、下記表26に示す組成にて25℃で0〜4週間保管した後にIE−HPLC、SE−HPLC、RP−HPLCを用いて分析した。表27、28、29において、IE−HPLC(%)、SE−HPLC(%)及びRP−HPLC(%)は(Area%/Start Area%)であり、初期値に対する持続型オキシントモジュリン結合体の残存率を示す。表27は保管後の持続型オキシントモジュリンのIE−HPLC残存率を示し、表28は保管後の持続型オキシントモジュリンのSE−HPLC残存率を示し、表29は保管後の持続型オキシントモジュリンのRP−HPLC残存率を示す。
Claims (31)
- 生理活性ペプチドであるオキシントモジュリンと免疫グロブリンFc領域が結合した薬理学的有効量の持続型オキシントモジュリン結合体及びアルブミン非含有安定化剤を含み、前記安定化剤は、緩衝液、糖アルコール及び非イオン性界面活性剤を含有する、持続型オキシントモジュリン結合体液状製剤。
- 前記安定化剤は、等張化剤、糖類、多価アルコール及びアミノ酸からなる群から選択される1個又はそれ以上の成分をさらに含む、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記オキシントモジュリンは、グルカゴンの前駆体であるプレグルカゴン(pre-glucagon)から作られるペプチドであり、配列番号1のアミノ酸配列からなる、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記オキシントモジュリンは、天然型オキシントモジュリン、前駆体(precursor)、誘導体(derivatives)、フラグメント(fragment)、変異体(variants)である、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記誘導体は、配列番号2〜34からなる群から選択されるいずれかのアミノ酸配列を有する、請求項4に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記免疫グロブリンFc領域は、IgG、IgA、IgD、IgE又はIgMに由来するFc領域である、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記免疫グロブリンFc領域は、それぞれのドメインがIgG、IgA、IgD、IgE、IgMからなる群から選択される免疫グロブリンに由来する異なる起源を有するドメインのハイブリッドである、請求項6に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記免疫グロブリンFc領域は、同一起源のドメインからなる単鎖免疫グロブリンで構成された二量体又は多量体である、請求項6に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記免疫グロブリンFc領域が、IgG4 Fc領域である、請求項6に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記免疫グロブリンFc領域が、ヒト非グリコシル化IgG4 Fc領域である、請求項9に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記結合体の結合方法は、非ペプチド性重合体を用いるか、組換え技術を用いて結合したものである、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記非ペプチド性重合体は、ポリプロピレングリコール、エチレングリコールとプロピレングリコールの共重合体、ポリオキシエチル化ポリオール、ポリビニルアルコール、ポリサッカライド、デキストラン、ポリビニルエチルエーテル、ポリ乳酸(polylactic acid、PLA)及びポリ乳酸−グリコール酸(polylactic-glycolic acid、PLGA)などの生分解性高分子、脂質重合体、キチン類、ヒアルロン酸及びそれらの組み合わせからなる、請求項11に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記非ペプチド性重合体が、ポリエチレングリコールである、請求項11に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記糖アルコールは、マンニトール、ソルビトール及びグリセリンからなる群から選択される少なくとも1つである、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記糖アルコールの濃度が、溶液全体の2〜15%(w/v)である、請求項14に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記緩衝液は、クエン酸、酢酸、ヒスチジン及びリン酸緩衝液からなる群から選択される少なくとも1つである、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記緩衝液のpH範囲が、4.5〜7.0である、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記等張化剤が、塩化ナトリウムである、請求項2に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記非イオン性界面活性剤が、ポリソルベート又はポロキサマーである、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記非イオン性界面活性剤の濃度が、0.001〜0.1%(w/v)である、請求項19に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記アミノ酸が、メチオニンである、請求項2に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記安定化剤は、pH4.8〜pH6.0の範囲の緩衝液、マンニトール及びソルビトールからなる群から選択される1個以上の糖アルコール、並びにポリソルベート20を含む、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- m−クレゾール、フェノール、ベンジルアルコールからなる群から選択される1個又はそれ以上の保存剤をさらに含むことを特徴とする、請求項1に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記保存剤の濃度が、溶液全体の0.001〜1%(w/v)である、請求項23に記載の持続型オキシントモジュリン結合体液状製剤。
- 前記保存剤が、m−クレゾールである、請求項23に記載の持続型オキシントモジュリン結合体液状製剤。
- 複数回投与用であることを特徴とする、請求項23に記載の持続型オキシントモジュリン結合体液状製剤。
- 生理活性ペプチドであるオキシントモジュリンと免疫グロブリンFc領域が結合した薬理学的有効量の持続型オキシントモジュリン結合体と、5mM〜50mMヒスチジン、2〜15%(w/v)マンニトール、0.01〜1mg/mLメチオニン及び0.001〜0.1%(w/v)ポリソルベート20を含有する、持続型オキシントモジュリン結合体液状製剤。
- 0.001〜1%(w/v)のm−クレゾールをさらに含む、請求項27に記載の液状製剤。
- a)持続型オキシントモジュリン結合体を作製するステップ;及び、
b)a)ステップで作製された持続型オキシントモジュリン結合体を緩衝液、糖アルコール及び非イオン性界面活性剤を含有する安定化剤と混合するステップを含む、請求項1〜22及び27のいずれかの持続型オキシントモジュリン結合体液状製剤の製造方法。 - a)持続型オキシントモジュリン結合体を作製するステップ;及び、
b)a)ステップで作製された持続型オキシントモジュリン結合体を緩衝液、糖アルコール及び非イオン性界面活性剤を含有する安定化剤及び保存剤を混合するステップを含む、請求項23〜26及び28のいずれかの持続型オキシントモジュリン結合体液状製剤の製造方法。 - 前記安定化剤は、等張化剤、糖類、多価アルコール及びアミノ酸からなる群から選択される1個又はそれ以上の成分をさらに含む、請求項29又は30に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20120124725 | 2012-11-06 | ||
KR10-2012-0124725 | 2012-11-06 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015540613A Division JP6363612B2 (ja) | 2012-11-06 | 2013-11-06 | オキシントモジュリンと免疫グロブリンのフラグメントとを含むタンパク質結合体の液状製剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018162299A true JP2018162299A (ja) | 2018-10-18 |
JP6694013B2 JP6694013B2 (ja) | 2020-05-13 |
Family
ID=50684883
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015540613A Active JP6363612B2 (ja) | 2012-11-06 | 2013-11-06 | オキシントモジュリンと免疫グロブリンのフラグメントとを含むタンパク質結合体の液状製剤 |
JP2018123264A Active JP6694013B2 (ja) | 2012-11-06 | 2018-06-28 | オキシントモジュリンと免疫グロブリンのフラグメントとを含むタンパク質結合体の液状製剤 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015540613A Active JP6363612B2 (ja) | 2012-11-06 | 2013-11-06 | オキシントモジュリンと免疫グロブリンのフラグメントとを含むタンパク質結合体の液状製剤 |
Country Status (27)
Country | Link |
---|---|
US (3) | US9724420B2 (ja) |
EP (2) | EP2916819B1 (ja) |
JP (2) | JP6363612B2 (ja) |
KR (2) | KR102311517B1 (ja) |
CN (1) | CN104884045B (ja) |
AR (2) | AR093387A1 (ja) |
AU (3) | AU2013342321B2 (ja) |
BR (1) | BR112015010235B1 (ja) |
CA (1) | CA2890324C (ja) |
CL (1) | CL2015001206A1 (ja) |
DK (1) | DK2916819T3 (ja) |
EA (3) | EA031852B1 (ja) |
ES (1) | ES2748158T3 (ja) |
HK (1) | HK1210044A1 (ja) |
IL (2) | IL238626B (ja) |
MX (2) | MX2015005698A (ja) |
MY (2) | MY197849A (ja) |
NZ (3) | NZ708103A (ja) |
PE (1) | PE20151421A1 (ja) |
PH (2) | PH12018501454A1 (ja) |
PL (1) | PL2916819T3 (ja) |
PT (1) | PT2916819T (ja) |
SG (2) | SG10201602801YA (ja) |
TW (3) | TWI602583B (ja) |
UA (2) | UA116364C2 (ja) |
WO (1) | WO2014073842A1 (ja) |
ZA (1) | ZA201503998B (ja) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2838503C (en) | 2011-06-10 | 2020-02-18 | Hanmi Science Co., Ltd. | Novel oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same |
PH12018501119A1 (en) | 2011-06-17 | 2019-02-04 | Hanmi Science Co Ltd | A conjugate comprising oxyntomodulin and an immunoglobulin fragment, and use thereof |
KR20130049671A (ko) | 2011-11-04 | 2013-05-14 | 한미사이언스 주식회사 | 생리활성 폴리펩타이드 결합체 제조 방법 |
AR090281A1 (es) | 2012-03-08 | 2014-10-29 | Hanmi Science Co Ltd | Proceso mejorado para la preparacion de un complejo polipeptidico fisiologicamente activo |
KR101968344B1 (ko) | 2012-07-25 | 2019-04-12 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 고지혈증 치료용 조성물 |
UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
EA031852B1 (ru) | 2012-11-06 | 2019-03-29 | Ханми Фарм. Ко., Лтд. | Жидкая композиция белкового конъюгата, содержащего оксинтомодулин и фрагмент иммуноглобулина |
KR101993393B1 (ko) | 2012-11-06 | 2019-10-01 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 당뇨병 또는 비만성 당뇨병 치료용 조성물 |
BR112015014510A2 (pt) | 2012-12-21 | 2017-11-21 | Sanofi Sa | agonistas de glp1/gip duais ou de glp1/gip/glucagon trigonais |
TW201609795A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 作為雙重glp-1/gip受體促效劑的艾塞那肽-4(exendin-4)胜肽類似物 |
WO2015086729A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/gip receptor agonists |
EP3080149A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Dual glp-1/glucagon receptor agonists |
WO2015086730A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Non-acylated exendin-4 peptide analogues |
PE20161153A1 (es) | 2014-01-20 | 2016-10-27 | Hanmi Pharm Ind Co Ltd | Insulina de accion prolongada y uso de la misma |
WO2015152618A1 (ko) * | 2014-03-31 | 2015-10-08 | 한미약품 주식회사 | 면역글로불린 fc 단편 결합을 이용한 단백질 및 펩타이드의 용해도를 개선시키는 방법 |
TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重glp-1/昇糖素受體激動劑之艾塞那肽-4衍生物 |
TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽-4(Exendin-4)之肽類雙重GLP-1/升糖素受體促效劑 |
TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自exendin-4之雙重glp-1/升糖素受體促效劑 |
AR100639A1 (es) | 2014-05-29 | 2016-10-19 | Hanmi Pharm Ind Co Ltd | Composición para tratar diabetes que comprende conjugados de análogos de insulina de acción prolongada y conjugados de péptidos insulinotrópicos de acción prolongada |
TWI684458B (zh) * | 2014-05-30 | 2020-02-11 | 南韓商韓美藥品股份有限公司 | 包含胰島素及glp-1/昇糖素雙重促效劑之治療糖尿病之組成物 |
US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
TWI802396B (zh) | 2014-09-16 | 2023-05-11 | 南韓商韓美藥品股份有限公司 | 長效glp-1/高血糖素受體雙促效劑治療非酒精性脂肝疾病之用途 |
CN105435221B (zh) * | 2014-09-22 | 2021-09-28 | 正大天晴药业集团股份有限公司 | 一种针对血管内皮生长因子的人源化抗体的药物组合物 |
KR102418477B1 (ko) | 2014-12-30 | 2022-07-08 | 한미약품 주식회사 | 글루카곤 유도체 |
PE20171154A1 (es) | 2014-12-30 | 2017-08-16 | Hanmi Pharm Ind Co Ltd | Derivados de glucagon con estabilidad mejorada |
AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
MX2017016845A (es) | 2015-06-30 | 2018-08-01 | Hanmi Pharm Ind Co Ltd | Derivado de glucagón y una composición que comprende un conjugado de acción prolongada del mismo. |
AR105284A1 (es) | 2015-07-10 | 2017-09-20 | Sanofi Sa | Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón |
UY36870A (es) | 2015-08-28 | 2017-03-31 | Hanmi Pharm Ind Co Ltd | Análogos de insulina novedosos |
US10702606B2 (en) * | 2015-12-10 | 2020-07-07 | Menicon Co., Ltd. | Peptide composition |
CN108699125B (zh) | 2015-12-31 | 2022-10-28 | 韩美药品株式会社 | 胰高血糖素/glp-1/gip受体三重激动剂 |
UA126662C2 (uk) * | 2016-06-29 | 2023-01-11 | Ханмі Фарм. Ко., Лтд. | Похідна глюкагону, її кон'югат, композиція, яка її містить, та її терапевтичне застосування |
KR20180033105A (ko) | 2016-09-23 | 2018-04-02 | 한미약품 주식회사 | 인슐린 수용체와의 결합력이 감소된, 인슐린 아날로그 및 이의 용도 |
JOP20190095A1 (ar) * | 2016-10-27 | 2019-04-28 | Janssen Pharmaceutica Nv | مركبات ببتيد تيروسين-تيروسين الحلقية كمعدلات لمستقبلات الببتيد العصبي y |
CN108299553B (zh) * | 2017-01-13 | 2021-07-16 | 博瑞生物医药(苏州)股份有限公司 | 胃泌酸调节素修饰物 |
AU2018239037B2 (en) | 2017-03-23 | 2022-05-26 | Hanmi Pharm. Co., Ltd. | Insulin analog complex with reduced affinity for insulin receptor and use thereof |
BR112021000933A2 (pt) * | 2018-07-19 | 2021-04-27 | D&D Pharmatech Inc. | polipeptídeo, composição farmacêutica, método de preparação dela e método de prevenção ou tratamento de doenças |
US20200262887A1 (en) | 2018-11-30 | 2020-08-20 | Opko Ireland Global Holdings, Ltd. | Oxyntomodulin peptide analog formulations |
WO2020167010A1 (ko) * | 2019-02-15 | 2020-08-20 | 한미정밀화학주식회사 | 생리활성 폴리펩타이드에 사용되는 신규한 중간체 및 이의 제조방법 |
BR112022023738A2 (pt) | 2020-05-22 | 2023-01-31 | Hanmi Pharm Ind Co Ltd | Formulação líquida |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008169195A (ja) * | 2007-01-05 | 2008-07-24 | Hanmi Pharmaceutical Co Ltd | キャリア物質を用いたインスリン分泌ペプチド薬物結合体 |
JP2011505355A (ja) * | 2007-11-29 | 2011-02-24 | ハンミ ファーマシューティカル カンパニー リミテッド | インスリン分泌ペプチド結合体を含む肥満関連疾患治療用医薬組成物 |
WO2011075393A2 (en) * | 2009-12-18 | 2011-06-23 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
WO2012008779A2 (en) * | 2010-07-14 | 2012-01-19 | Hanmi Holdings Co., Ltd. | A liquid formulation of long-acting human growth hormone conjugate |
WO2012057525A2 (en) * | 2010-10-26 | 2012-05-03 | Hanmi Holdings Co., Ltd. | Liquid formulations of long acting interferon alpha conjugate |
KR20120043208A (ko) * | 2010-10-26 | 2012-05-04 | 한미사이언스 주식회사 | 항 비만 펩타이드의 지속형 결합체 |
JP6038905B2 (ja) * | 2011-06-17 | 2016-12-07 | ハンミ サイエンス カンパニー リミテッド | オキシントモジュリンと免疫グロブリン断片とを含む結合体及びその用途 |
JP6363612B2 (ja) * | 2012-11-06 | 2018-07-25 | ハンミ ファーマシューティカル カンパニー リミテッド | オキシントモジュリンと免疫グロブリンのフラグメントとを含むタンパク質結合体の液状製剤 |
Family Cites Families (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
CA2249195A1 (en) | 1996-03-18 | 1997-09-25 | Board Of Regents, The University Of Texas System | Immunoglobin-like domains with increased half lives |
AU749815B2 (en) | 1998-03-06 | 2002-07-04 | Chugai Seiyaku Kabushiki Kaisha | Protein-free preparations |
US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
US6677136B2 (en) | 2000-05-03 | 2004-01-13 | Amgen Inc. | Glucagon antagonists |
GB0121709D0 (en) | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
US7217845B2 (en) | 2002-11-25 | 2007-05-15 | Sun Bio, Inc. | Bifunctional polyethylene glycol derivatives |
GB0300571D0 (en) | 2003-01-10 | 2003-02-12 | Imp College Innovations Ltd | Modification of feeding behaviour |
EP1594530A4 (en) | 2003-01-22 | 2006-10-11 | Human Genome Sciences Inc | HYBRID PROTEINS OF ALBUMIN |
US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
US20050176108A1 (en) | 2003-03-13 | 2005-08-11 | Young-Min Kim | Physiologically active polypeptide conjugate having prolonged in vivo half-life |
WO2005035761A1 (en) | 2003-10-16 | 2005-04-21 | Compugen Ltd. | Splice variants of preproglucagon, glucagon-like peptide-1 and oxyntomodulin |
US8263084B2 (en) | 2003-11-13 | 2012-09-11 | Hanmi Science Co., Ltd | Pharmaceutical composition for treating obesity-related disease comprising insulinotropic peptide conjugate |
CN103212084B (zh) | 2003-11-13 | 2018-07-13 | 韩美科学株式会社 | 含有免疫球蛋白fc区作为载体的药物组合物 |
US20090238838A1 (en) | 2003-11-13 | 2009-09-24 | Hanmi Pharm. Ind. Co. Ltd. | Insulinotropic peptide conjugate using an immunoglobulin fc |
CA2589800A1 (en) | 2004-12-02 | 2006-06-08 | Domantis Limited | Bispecific domain antibodies targeting serum albumin and glp-1 or pyy |
US8404637B2 (en) | 2005-02-11 | 2013-03-26 | Amylin Pharmaceuticals, Llc | GIP analog and hybrid polypeptides with selectable properties |
KR100754667B1 (ko) | 2005-04-08 | 2007-09-03 | 한미약품 주식회사 | 비펩타이드성 중합체로 개질된 면역글로불린 Fc 단편 및이를 포함하는 약제학적 조성물 |
WO2006134340A2 (en) | 2005-06-13 | 2006-12-21 | Imperial Innovations Limited | Oxyntomodulin analogues and their effects on feeding behaviour |
GB0511986D0 (en) | 2005-06-13 | 2005-07-20 | Imp College Innovations Ltd | Novel compounds and their effects on feeding behaviour |
EP2330124B1 (en) | 2005-08-11 | 2015-02-25 | Amylin Pharmaceuticals, LLC | Hybrid polypeptides with selectable properties |
US20090297496A1 (en) | 2005-09-08 | 2009-12-03 | Childrens Hospital Medical Center | Lysosomal Acid Lipase Therapy for NAFLD and Related Diseases |
CA2638800A1 (en) | 2006-02-22 | 2007-09-07 | Merck & Co., Inc. | Oxyntomodulin derivatives |
EP2046367A4 (en) | 2006-06-07 | 2009-11-11 | Human Genome Sciences Inc | ALBUM INFUSION PROTEINS |
GB0624868D0 (en) | 2006-12-13 | 2007-01-24 | Imp Innovations Ltd | Novel compounds and their effects on feeding behaviour |
TWI428346B (zh) | 2006-12-13 | 2014-03-01 | Imp Innovations Ltd | 新穎化合物及其等對進食行為影響 |
US20090098130A1 (en) | 2007-01-05 | 2009-04-16 | Bradshaw Curt W | Glucagon-like protein-1 receptor (glp-1r) agonist compounds |
KR20150116465A (ko) | 2007-02-15 | 2015-10-15 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 글루카곤/glp-1 수용체 공동-항진물질 |
EA201070121A1 (ru) | 2007-07-10 | 2010-06-30 | Эли Лилли Энд Компани | Лекарственная форма, содержащая слитый белок glp-1-fc |
CN101765372B (zh) | 2007-07-27 | 2013-09-04 | 拜尔农作物科学股份公司 | 三元活性化合物结合物 |
KR20100061679A (ko) | 2007-09-11 | 2010-06-08 | 몬도바이오테크 래보래토리즈 아게 | 치료적 적용을 위한 티로트로핀 방출 호르몬 |
CA2702289A1 (en) | 2007-10-30 | 2009-05-07 | Indiana University Research And Technology Corporation | Compounds exhibiting glucagon antagonist and glp-1 agonist activity |
US20090181037A1 (en) | 2007-11-02 | 2009-07-16 | George Heavner | Semi-Synthetic GLP-1 Peptide-FC Fusion Constructs, Methods and Uses |
WO2009099763A1 (en) | 2008-01-30 | 2009-08-13 | Indiana University Research And Technology Corporation | Ester-based peptide prodrugs |
JP5753779B2 (ja) | 2008-06-17 | 2015-07-22 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation | 生理学的pHの緩衝液中で向上した溶解性及び安定性を示すグルカゴン類縁体 |
NZ589847A (en) | 2008-06-17 | 2013-01-25 | Univ Indiana Res & Tech Corp | Glucagon/glp-1 receptor co-agonists |
WO2010013012A2 (en) | 2008-08-01 | 2010-02-04 | Lund University Bioscience Ab | Novel polypeptides and uses thereof |
US20110171312A1 (en) | 2008-09-19 | 2011-07-14 | Nektar Therapeutics | Modified therapeutic peptides, methods of their preparation and use |
WO2010033207A1 (en) | 2008-09-19 | 2010-03-25 | Nektar Therapeutics | Polymer conjugates of therapeutic peptides |
JP5635531B2 (ja) | 2008-12-15 | 2014-12-03 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン類似体 |
AR074811A1 (es) | 2008-12-19 | 2011-02-16 | Univ Indiana Res & Tech Corp | Profarmaco de peptido de la superfamilia de glucagon basados en amida |
WO2010096052A1 (en) | 2009-02-19 | 2010-08-26 | Merck Sharp & Dohme Corp. | Oxyntomodulin analogs |
EP2408800B1 (en) | 2009-03-20 | 2016-05-25 | Hanmi Science Co., Ltd. | Method for preparing a site-specific conjugate of a physiologically active polypeptide |
EP3385279B1 (en) * | 2009-03-20 | 2020-02-26 | Amgen Inc. | Carrier immunoglobulins and uses thereof |
KR20120087875A (ko) | 2009-06-16 | 2012-08-07 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | Gip 수용체-활성 글루카곤 화합물 |
ME02220B (me) | 2009-07-13 | 2016-02-20 | Zealand Pharma As | Analozi acilovanog glukagona |
US20120294855A1 (en) | 2009-11-03 | 2012-11-22 | Eli Lilly & Company | Glp-1 receptor agonist compounds for obstructive sleep apnea |
EP2509997B1 (en) | 2009-12-07 | 2017-08-30 | i2 Pharmaceuticals, Inc. | Conjugates comprising an antibody surrogate scaffold with improved pharmacokinetic properties |
AR079344A1 (es) | 2009-12-22 | 2012-01-18 | Lilly Co Eli | Analogo peptidico de oxintomodulina, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para tratar diabetes no insulinodependiente y/u obesidad |
JO2976B1 (en) | 2009-12-22 | 2016-03-15 | ايلي ليلي اند كومباني | Axentomodulin polypeptide |
MX2012008603A (es) | 2010-01-27 | 2013-01-25 | Univ Indiana Res & Tech Corp | Conjugados de antagonista de glucagon-agonista de gip y composiciones para el tratamiento de desordenes metabolicos y obesidad. |
US20130143798A1 (en) | 2010-03-26 | 2013-06-06 | Novo Nordisk A/S | Novel glucagon analogues |
AR081066A1 (es) | 2010-04-02 | 2012-06-06 | Hanmi Holdings Co Ltd | Conjugado de insulina donde se usa un fragmento de inmunoglobulina |
CA2797089A1 (en) | 2010-05-13 | 2011-11-17 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting g protein-coupled receptor activity |
WO2011163012A2 (en) | 2010-06-24 | 2011-12-29 | Indiana University Research And Technology Corporation | Amide based glucagon superfamily peptide prodrugs |
KR101314865B1 (ko) * | 2010-07-06 | 2013-10-04 | 김덕중 | 모바일 환경에서 tv 화면과 연동하는 증강 현실을 제공하는 방법, 이를 위한 부가 서비스 서버 및 방송 시스템 |
KR101382593B1 (ko) | 2010-07-21 | 2014-04-10 | 한미사이언스 주식회사 | 신규한 지속형 글루카곤 결합체 및 이를 포함하는 비만 예방 및 치료용 약학적 조성물 |
WO2012032567A1 (ja) | 2010-09-06 | 2012-03-15 | パナソニック株式会社 | 表示装置及びその制御方法 |
CN101974077A (zh) | 2010-09-15 | 2011-02-16 | 南京瑞年天平医药科技有限公司 | 一种新颖的多肽化合物 |
CN102010473A (zh) * | 2010-11-10 | 2011-04-13 | 曹鹏 | 重组胃泌酸调节素融合蛋白及其制备和应用 |
US8975223B2 (en) | 2010-12-22 | 2015-03-10 | Marcadia Biotech, Inc. | Methods for treating metabolic disorders and obesity with a peptide comprising the amino acid sequence of SEQ ID No. 146 |
JP6118500B2 (ja) | 2011-02-28 | 2017-04-19 | ローム アンド ハース エレクトロニック マテリアルズ エルエルシーRohm and Haas Electronic Materials LLC | フォトレジスト組成物、およびフォトリソグラフィパターンを形成する方法 |
KR101161526B1 (ko) | 2011-05-16 | 2012-07-02 | 숭실대학교산학협력단 | 연료전지용 촉매전극을 위한 코어/쉘 구조의 나노 지지체 및 그 제조방법 |
CA2838503C (en) | 2011-06-10 | 2020-02-18 | Hanmi Science Co., Ltd. | Novel oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same |
RU2014101697A (ru) * | 2011-06-22 | 2015-07-27 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Коагонисты рецепторов глюкагона/glp-1 |
KR101665009B1 (ko) | 2012-03-09 | 2016-10-11 | 한미사이언스 주식회사 | 비알콜성 지방간 질환의 예방 또는 치료용 약학적 조성물 |
SG11201406671RA (en) | 2012-04-19 | 2014-11-27 | Opko Biolog Ltd | Long-acting oxyntomodulin variants and methods of producing same |
EP2864351B1 (en) | 2012-06-21 | 2016-08-10 | Indiana University Research and Technology Corporation | Glucagon analogs exhibiting gip receptor activity |
KR101968344B1 (ko) | 2012-07-25 | 2019-04-12 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 고지혈증 치료용 조성물 |
KR101373563B1 (ko) | 2012-07-25 | 2014-03-12 | 전북대학교산학협력단 | Tof-mra를 이용한 혈류특성 및 mr-신호강도구배(전단율) 유도방법 |
AR092873A1 (es) | 2012-09-26 | 2015-05-06 | Cadila Healthcare Ltd | Peptidos como agonistas triples de los receptores de gip, glp-1 y glugagon |
KR101993393B1 (ko) | 2012-11-06 | 2019-10-01 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 당뇨병 또는 비만성 당뇨병 치료용 조성물 |
JP6137046B2 (ja) | 2014-05-09 | 2017-05-31 | 信越化学工業株式会社 | 単量体、高分子化合物、レジスト材料及びパターン形成方法 |
TWI802396B (zh) | 2014-09-16 | 2023-05-11 | 南韓商韓美藥品股份有限公司 | 長效glp-1/高血糖素受體雙促效劑治療非酒精性脂肝疾病之用途 |
WO2019171352A2 (en) | 2018-03-08 | 2019-09-12 | Janssen Pharmaceutica Nv | Methods of treating severe non-diabetic obesity |
-
2013
- 2013-11-06 EA EA201590758A patent/EA031852B1/ru not_active IP Right Cessation
- 2013-11-06 BR BR112015010235-2A patent/BR112015010235B1/pt active IP Right Grant
- 2013-11-06 EP EP13853118.1A patent/EP2916819B1/en active Active
- 2013-11-06 WO PCT/KR2013/009986 patent/WO2014073842A1/en active Application Filing
- 2013-11-06 AU AU2013342321A patent/AU2013342321B2/en active Active
- 2013-11-06 MY MYPI2018703890A patent/MY197849A/en unknown
- 2013-11-06 PE PE2015000593A patent/PE20151421A1/es unknown
- 2013-11-06 UA UAA201504473A patent/UA116364C2/uk unknown
- 2013-11-06 PL PL13853118T patent/PL2916819T3/pl unknown
- 2013-11-06 NZ NZ708103A patent/NZ708103A/en unknown
- 2013-11-06 SG SG10201602801YA patent/SG10201602801YA/en unknown
- 2013-11-06 ES ES13853118T patent/ES2748158T3/es active Active
- 2013-11-06 MX MX2015005698A patent/MX2015005698A/es active IP Right Grant
- 2013-11-06 EA EA201791143A patent/EA034499B1/ru not_active IP Right Cessation
- 2013-11-06 MY MYPI2015001169A patent/MY168536A/en unknown
- 2013-11-06 TW TW102140249A patent/TWI602583B/zh active
- 2013-11-06 UA UAA201711010A patent/UA126651C2/uk unknown
- 2013-11-06 KR KR1020130134412A patent/KR102311517B1/ko active IP Right Grant
- 2013-11-06 AR ARP130104071A patent/AR093387A1/es not_active Application Discontinuation
- 2013-11-06 EP EP19180160.4A patent/EP3610856B1/en active Active
- 2013-11-06 PH PH12018501454A patent/PH12018501454A1/en unknown
- 2013-11-06 TW TW108101828A patent/TWI816739B/zh active
- 2013-11-06 CA CA2890324A patent/CA2890324C/en active Active
- 2013-11-06 NZ NZ731658A patent/NZ731658A/en unknown
- 2013-11-06 SG SG11201503370WA patent/SG11201503370WA/en unknown
- 2013-11-06 TW TW106126398A patent/TWI652071B/zh active
- 2013-11-06 JP JP2015540613A patent/JP6363612B2/ja active Active
- 2013-11-06 DK DK13853118.1T patent/DK2916819T3/da active
- 2013-11-06 PT PT138531181T patent/PT2916819T/pt unknown
- 2013-11-06 CN CN201380069534.3A patent/CN104884045B/zh active Active
- 2013-11-06 US US14/440,422 patent/US9724420B2/en active Active
- 2013-11-06 EA EA201992760A patent/EA039082B1/ru unknown
- 2013-11-06 NZ NZ73906313A patent/NZ739063A/en unknown
-
2015
- 2015-05-04 IL IL238626A patent/IL238626B/en active IP Right Grant
- 2015-05-06 PH PH12015501008A patent/PH12015501008B1/en unknown
- 2015-05-06 CL CL2015001206A patent/CL2015001206A1/es unknown
- 2015-05-06 MX MX2020004114A patent/MX2020004114A/es unknown
- 2015-06-04 ZA ZA2015/03998A patent/ZA201503998B/en unknown
- 2015-11-05 HK HK15110919.0A patent/HK1210044A1/xx unknown
-
2017
- 2017-06-29 US US15/637,583 patent/US10279041B2/en active Active
- 2017-12-18 AU AU2017279583A patent/AU2017279583B2/en active Active
-
2018
- 2018-06-28 JP JP2018123264A patent/JP6694013B2/ja active Active
-
2019
- 2019-01-21 IL IL26436019A patent/IL264360B/en active IP Right Grant
- 2019-03-18 US US16/356,319 patent/US11071785B2/en active Active
-
2020
- 2020-01-29 AU AU2020200626A patent/AU2020200626B2/en active Active
-
2021
- 2021-04-26 AR ARP210101118A patent/AR121939A2/es unknown
- 2021-09-30 KR KR1020210129977A patent/KR102434280B1/ko active IP Right Grant
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008169195A (ja) * | 2007-01-05 | 2008-07-24 | Hanmi Pharmaceutical Co Ltd | キャリア物質を用いたインスリン分泌ペプチド薬物結合体 |
JP2011505355A (ja) * | 2007-11-29 | 2011-02-24 | ハンミ ファーマシューティカル カンパニー リミテッド | インスリン分泌ペプチド結合体を含む肥満関連疾患治療用医薬組成物 |
WO2011075393A2 (en) * | 2009-12-18 | 2011-06-23 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
WO2012008779A2 (en) * | 2010-07-14 | 2012-01-19 | Hanmi Holdings Co., Ltd. | A liquid formulation of long-acting human growth hormone conjugate |
WO2012057525A2 (en) * | 2010-10-26 | 2012-05-03 | Hanmi Holdings Co., Ltd. | Liquid formulations of long acting interferon alpha conjugate |
KR20120043208A (ko) * | 2010-10-26 | 2012-05-04 | 한미사이언스 주식회사 | 항 비만 펩타이드의 지속형 결합체 |
JP6038905B2 (ja) * | 2011-06-17 | 2016-12-07 | ハンミ サイエンス カンパニー リミテッド | オキシントモジュリンと免疫グロブリン断片とを含む結合体及びその用途 |
JP6363612B2 (ja) * | 2012-11-06 | 2018-07-25 | ハンミ ファーマシューティカル カンパニー リミテッド | オキシントモジュリンと免疫グロブリンのフラグメントとを含むタンパク質結合体の液状製剤 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6694013B2 (ja) | オキシントモジュリンと免疫グロブリンのフラグメントとを含むタンパク質結合体の液状製剤 | |
JP6903086B2 (ja) | オキシントモジュリン誘導体を含む高脂血症の治療のための組成物 | |
JP6345216B2 (ja) | オキシントモジュリンと免疫グロブリン断片とを含む結合体及びその用途 | |
JP2022048398A (ja) | オキシントモジュリン誘導体を含む糖尿病又は肥満性糖尿病の治療用組成物 | |
JP2021167352A (ja) | 免疫グロブリンFcフラグメント結合を用いたタンパク質及びペプチドの溶解度を改善する方法 | |
JP2023526551A (ja) | グルカゴン誘導体の持続型結合体の液状製剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180727 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180727 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190529 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190829 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191029 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200318 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200416 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6694013 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |