Claims for Patent: 11,874,283

Summary for Patent: 11,874,283

Title:	Method and compositions for the treatment and detection of endothelin-1 related kidney diseases
Abstract:	The present application relates to methods of treating HIV-associated nephropathy (HIVAN) and/or focal segmental glomerulosclerosis (FSGS) using endothelin-1 (ET-1) antagonists. The application further relates to a composition for the treatment of HIVAN and/or FSGS. A kit for detecting the presence of ET-1 or ET-1-associated biomarker in a biological sample is also disclosed.
Inventor(s):	Gale W. Newman, James W. Lillard, Jr., Chamberlain Obialo
Assignee:	Morehouse School of Medicine Inc
Application Number:	US17/244,214
Patent Claims:	1. A method of treating IgA nephropathy directly linked to increased levels of ET-1 compared to ET-1 levels in those without IgA nephropathy, in a mammalian subject in need thereof and diagnosed at a qualified medical center as having said IgA nephropathy, by administering an effective amount of a pharmaceutical composition comprising: (1) an active ingredient consisting of an ET-1 antagonist; and (2) a pharmaceutically acceptable carrier, wherein the active ingredient is the only active ingredient in the pharmaceutical composition, wherein the subject has an increased level of ET-1 compared to a control subject, and wherein the ET-1 antagonist is selected from the group consisting of sitaxentan, ambrisentan, atrasentan, BQ-123, bosentan and tezosentan. 2. The method of claim 1, wherein the ET-1 antagonist is ambrisentan. 3. The method of claim 1, wherein the ET-1 antagonist is administered by a local infusion into a kidney of the subject. 4. A method of monitoring the effectiveness of a treatment for IgA nephropathy directly linked to increased levels of ET-1 compared to ET-1 levels in those without IgA nephropathy, in a mammalian subject in need thereof and diagnosed at a qualified medical center as having said IgA nephropathy, comprising the steps of: (a) administering to a subject with IgA nephropathy directly linked to increased levels of ET-1 compared to ET-1 levels in those without IgA nephropathy, in a mammalian subject in need thereof and diagnosed at a qualified medical center as having said IgA nephropathy, a pharmaceutical composition comprising: (1) an active ingredient consisting of an ET-1 antagonist; and (2) a pharmaceutically acceptable carrier, wherein the active ingredient is the only active ingredient in the pharmaceutical composition and wherein the ET-1 antagonist is selected from the group consisting of sitaxentan, ambrisentan, atrasentan, BQ-123, bosentan and tezosentan; (b) performing a first measurement of an ET-1-associated biomarker in a first biological sample from the subject, wherein the first biological sample is harvested prior to the initiation of the treatment in step (a); (c) comparing the first measurement of an ET-1-associated biomarker to a control subject; (d) performing a second measurement of the ET-1-associated biomarker in a second biological sample from the subject, wherein the second biological sample is harvested after the initiation of the treatment in step (a); and (e) determining the effectiveness of treatment for IgA nephropathy directly linked to increased levels of ET-1, based on the results from step (d) in comparison to step (b) as to the level of ET-1 as the ET-1-associated biomarker and adjusting the amount of ET-1 inhibitor administration based thereon; and separately determining the effect of treatment for IgA nephropathy directly linked to increased levels of ET-1, based on the results from step (d) in comparison to step (b) as to the level of any one or more ET-1-associated biomarkers selected from the group consisting of preproendothelin (ppET-1), proendothelin-1 (pET-1), BIG ET-1, endothelin converting enzyme (ECE), cystatin C, creatinine and albumin-creatinine ratio (ACR), and adjusting the amount of ET-1 inhibitor administration based thereon. 5. The method of claim 4, wherein ET-1 antagonist is administered by a local infusion into a kidney of the subject. 6. The method of claim 1, wherein the ET-1 antagonist is atrasentan.