MODIFIED MEMBRANE TYPE SERINE PROTEASE 1 (MTSP-1) POLYPEPTIDES AND METHODS OF USE

• Main Authors: MADISON EDWIN, SOROS VANESSA, POPKOV MIKHAIL
• Format: Patent
• Language: Chinese; English
• Published: 05.05.2020
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

Provided are MTSP-1 polypeptides modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to inhibit its activity and thereby inhibit complement activation. The modified MTSP-1 polypeptides that inhibit complement activation can be used for treatment of diseases and conditions in which complement activation plays a role. Such diseases and conditions include inflammatory diseases and diseases with an inflammatory component. Exemplary of these disorders are ischemic and reperfusion disorders, including myocardial infarction andstroke, sepsis, autoimmune diseases, ophthalmic disorders, such as diabetic retinopathies and macular degeneration, including age-related macular degeneration (AMD), and transplanted organ rejection,such as renal delayed graft function (DGF). 提供的是经修饰为具有改变的活性和/或特异性的MTSP-1多肽，使得它们切割补体蛋白，例如补体蛋白C3，以抑制其活性并从而抑制补体活化。抑制补体活化的经修饰的MTSP-1多肽可以用于治疗其中补体活化发挥作用的疾病和状况。此类疾病和状况包括炎性疾病和具有炎性组分的疾病。这些病症的示例是缺血和再灌注病症，包括心肌梗塞和中风，败血症，自身免疫疾病，眼科病症例如糖尿病性