FIBRONECTIN BASED SCAFFOLD DOMAIN PROTEINS THAT BIND PCSK9

FIBRONECTIN BASED SCAFFOLD DOMAIN PROTEINS THAT BIND PCSK9

To provide improved fibronectin domain scaffold proteins that bind PCSK9 for therapeutic treatment of atherosclerosis, hypercholesterolemia and other cholesterol related diseases.SOLUTION: A polypeptide comprises a fibronectin type III tenth domain (10Fn3), where the 10Fn3 has at least one loop sele...

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Hauptverfasser: DASA LIPOVSEK, PARKER REX A, BOWMAN MIAO, RAY CAMPHAUSEN, SHARON T CLOAD, DOREE F SITKOFF, AMNA SAEED-KOTHE, LOW CHEE MENG, TRACY S MITCHELL, CHING-HSIUNG FREDERICK LO, KATIE A RUSSO, DAVIS JONATHAN H, FABIENNE M DENHEZ, GINGER C RAKESTRAW
Format: Patent
Sprache:eng ; jpn
Schlagworte:
CHEMISTRY
HUMAN NECESSITIES
HYGIENE
MEDICAL OR VETERINARY SCIENCE
METALLURGY
ORGANIC CHEMISTRY
PEPTIDES
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS
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Zusammenfassung:To provide improved fibronectin domain scaffold proteins that bind PCSK9 for therapeutic treatment of atherosclerosis, hypercholesterolemia and other cholesterol related diseases.SOLUTION: A polypeptide comprises a fibronectin type III tenth domain (10Fn3), where the 10Fn3 has at least one loop selected from loops BC, DE and FG having altered amino acid sequences relative to the sequences of the corresponding loops of the human 10Fn3 domain, where the polypeptide binds proprotein convertase subtilisin kexin type 9 (PCSK9).SELECTED DRAWING: Figure 6 【課題】アテローム性動脈硬化症、高コレステロール血症および他のコレステロール関連疾患の治療処置のための、ＰＣＳＫ９に結合する改善されたフィブロネクチンドメインスカフォールドタンパク質を提供する。【解決手段】フィブロネクチンＩＩＩ型第１０ドメイン（１０Ｆｎ３）を含むポリペプチドであって、該１０Ｆｎ３は、ヒト１０Ｆｎ３ドメインの対応するループの配列と比較して、改変されたアミノ酸配列を有するループＢＣ、ＤＥおよびＦＧから選択される少なくとも１つのループを有し、該ポリペプチドは（前駆タンパク質転換酵素サブチリシンケキシン９型）ＰＣＳＫ９に結合するポリペプチドである。【選択図】図６