JP2013536180A5 - - Google Patents
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- JP2013536180A5 JP2013536180A5 JP2013521998A JP2013521998A JP2013536180A5 JP 2013536180 A5 JP2013536180 A5 JP 2013536180A5 JP 2013521998 A JP2013521998 A JP 2013521998A JP 2013521998 A JP2013521998 A JP 2013521998A JP 2013536180 A5 JP2013536180 A5 JP 2013536180A5
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- JP
- Japan
- Prior art keywords
- growth factor
- protein
- factor
- soluble polymer
- group
- 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.)
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- 102000004169 proteins and genes Human genes 0.000 claims description 312
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- 230000001225 therapeutic effect Effects 0.000 claims description 123
- JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 claims description 114
- 150000001720 carbohydrates Chemical group 0.000 claims description 99
- -1 polyethylene Polymers 0.000 claims description 88
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 70
- 210000000988 bone and bone Anatomy 0.000 claims description 70
- 230000000921 morphogenic effect Effects 0.000 claims description 69
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 claims description 64
- 241000872931 Myoporum sandwicense Species 0.000 claims description 60
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 59
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 57
- 239000002202 Polyethylene glycol Substances 0.000 claims description 56
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 56
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- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 38
- 229920000765 poly(2-oxazolines) Polymers 0.000 claims description 37
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- 230000001590 oxidative effect Effects 0.000 claims description 22
- 229920000642 polymer Polymers 0.000 claims description 22
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 21
- 229920001661 Chitosan Polymers 0.000 claims description 21
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 21
- 229920000045 Dermatan sulfate Polymers 0.000 claims description 21
- 239000004698 Polyethylene Substances 0.000 claims description 21
- 239000004373 Pullulan Substances 0.000 claims description 21
- 229920001218 Pullulan Polymers 0.000 claims description 21
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 21
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 claims description 21
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- 229960002086 dextran Drugs 0.000 claims description 21
- 229920000573 polyethylene Polymers 0.000 claims description 21
- 235000019423 pullulan Nutrition 0.000 claims description 21
- 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 20
- 239000004793 Polystyrene Substances 0.000 claims description 20
- 229940045110 chitosan Drugs 0.000 claims description 20
- 230000021615 conjugation Effects 0.000 claims description 20
- 229920002674 hyaluronan Polymers 0.000 claims description 20
- 229960003160 hyaluronic acid Drugs 0.000 claims description 20
- 229920002627 poly(phosphazenes) Polymers 0.000 claims description 20
- 229920002223 polystyrene Polymers 0.000 claims description 20
- 238000004587 chromatography analysis Methods 0.000 claims description 19
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 18
- 108010076282 Factor IX Proteins 0.000 claims description 18
- 108010054218 Factor VIII Proteins 0.000 claims description 18
- 102000001690 Factor VIII Human genes 0.000 claims description 18
- 108010054265 Factor VIIa Proteins 0.000 claims description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 18
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- 238000005859 coupling reaction Methods 0.000 claims description 18
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- 229940012414 factor viia Drugs 0.000 claims description 18
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
- 229940053128 nerve growth factor Drugs 0.000 claims description 18
- 239000000872 buffer Substances 0.000 claims description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 17
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 17
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 17
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 17
- XLPJNCYCZORXHG-UHFFFAOYSA-N 1-morpholin-4-ylprop-2-en-1-one Chemical compound C=CC(=O)N1CCOCC1 XLPJNCYCZORXHG-UHFFFAOYSA-N 0.000 claims description 16
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- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 claims description 16
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- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 16
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 16
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- ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 claims description 16
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| DK2598172T3 (da) * | 2010-07-30 | 2019-07-01 | Baxalta GmbH | Nukleofile katalysatorer til oximforbindelse |
| EP2654794B8 (en) | 2010-12-22 | 2020-04-22 | Baxalta GmbH | Materials and methods for conjugating a water soluble fatty acid derivative to a protein |
| GB2516388A (en) * | 2012-04-16 | 2015-01-21 | Cantab Biopharmaceuticals Patents Ltd | Optimised subcutaneous therapeutic agents |
| AU2013204754C1 (en) * | 2012-05-16 | 2018-10-11 | Takeda Pharmaceutical Company Limited | Nucleophilic Catalysts for Oxime Linkage |
| MA39711A (fr) * | 2014-04-03 | 2015-10-08 | Nektar Therapeutics | Conjugués d'une fraction d'il-15 et d'un polymère |
| MX2018004296A (es) | 2015-10-08 | 2018-08-01 | Nektar Therapeutics | Combinacion de un agonista selectivo de il-2rbeta y un agonista il-15 de accion prolongada. |
| US20170349644A1 (en) * | 2015-12-03 | 2017-12-07 | Baxalta Incorporated | Factor viii with extended half-life and reduced ligand-binding properties |
| EP3487538A1 (en) | 2016-07-22 | 2019-05-29 | Nektar Therapeutics | Conjugates of a factor viii moiety having an oxime-containing linkage |
| WO2018213341A1 (en) | 2017-05-15 | 2018-11-22 | Nektar Therapeutics | Long-acting interleukin-15 receptor agonists and related immunotherapeutic compositions and methods |
| SG11202107497XA (en) | 2019-01-23 | 2021-08-30 | Regeneron Pharma | Treatment of ophthalmic conditions with angiopoietin-like 7 (angptl7) inhibitors |
| US11845989B2 (en) | 2019-01-23 | 2023-12-19 | Regeneron Pharmaceuticals, Inc. | Treatment of ophthalmic conditions with angiopoietin-like 7 (ANGPTL7) inhibitors |
| EP4298219A1 (en) | 2021-02-26 | 2024-01-03 | Regeneron Pharmaceuticals, Inc. | Treatment of inflammation with glucocorticoids and angiopoietin-like 7 (angptl7) inhibitors |
| WO2025133203A1 (en) * | 2023-12-22 | 2025-06-26 | Pam Theragnostics Gmbh | Compounds and methods for a long-lasting pam |
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