MODIFIED SERPINS FOR TREATMENT OF BLEEDING DISORDERS

• Main Authors: JAMES ANDREW HUNTINGTON, TREVOR BAGLIN, STEPHANIE POLDERDIJK
• Format: Patent
• Language: English; Japanese
• Published: 14.03.2019
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

To provide modified serpin molecules with altered specificity, in particular serpin molecules modified to have increased specificity for anticoagulant proteases, such as activated Protein C (APC).SOLUTION: The invention provides a modified serpin having mutations at one or both of residues P1' and P2 and optionally at residues P1 and/or P4 in the reactive center loop (RCL) thereof. A pharmaceutical composition for the treatment or prevention of bleeding or the promotion of hemostasis in an individual comprises a modified serpin and a pharmaceutically acceptable excipient.SELECTED DRAWING: Figure 1 【課題】変更された特異性を有する改変セルピン分子、特に活性化プロテインＣ（ＡＰＣ）等の抗凝固性プロテアーゼに対する特異性を増すように改変されたセルピン分子の提供。【解決手段】反応中心ループ（ＲＣＬ）の残基Ｐ１'及び残基Ｐ２うちの一方又は両方と、任意に残基Ｐ１及び／又は残基Ｐ４とに変異を有する改変セルピン、並びに、改変セルピンと薬学的に許容可能な賦形剤とを含む個体における出血の治療若しくは予防、又は止血の促進に対する医薬組成物。【選択図】図１