Compositions and methods for treating renal disease

Abstract

Compositions and methods are disclosed herein for treating or reducing the symptoms of a renal disease, such as focal segmental glomerulosclerosis (FSGS), hypertensive end-stage kidney disease (ESKD), and HIV-associated nephropathy (a distinct form of FSGS, also termed collapsing glomerulopathy). The compositions include the common variant of APOL1 and fragments thereof, as well as antibodies and fragments thereof that bind and neutralize pathogenic APOL1, nucleic acid molecules that encode the common variant of APOL1 and fragments thereof, and other compounds that bind and neutralize pathogenic APOL1. The methods of the invention include administering one or more of the compositions of the invention to a subject having or at risk of developing renal disease.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]More than one reissue application has been filed for the reissue of U.S. Pat. No. 9,023,355. This application is a divisional reissue application of U.S. patent application Ser. No. 15 / 896,744, filed on Feb. 14, 2018, which is a divisional reissue application of U.S. patent application Ser. No. 15 / 588,382, filed on May 5, 2017, which is a reissue application of U.S. Pat. No. 9,023,355, granted May 5, 2015, which claims priority to U.S. Provisional Patent Application No. 61 / 489,140, filed on May 23, 2011, and is a continuation-in-part application of International Application No. PCT / US2011 / 032924, filed on Apr. 18, 2011, which claims priority to U.S. Provisional Patent Application No. 61 / 325,343, filed on Apr. 18, 2010. This application is also a continuation-in-part application of International Application No. PCT / EP2010 / 062065, filed on Aug. 18, 2010, which claims priority to U.S. Provisional Patent Application No. 61 / 323,727, filed on A...

AI Technical Summary

Benefits of technology

The patent text describes a method for reducing the risk of developing a renal disease, such as focal segmental glomerulosclerosis (FSGS) or end-stage kidney disease (ESKD), in a subject. This is achieved by delivering a nucleic acid molecule that encodes a polypeptide that reduces the expression of a pathogenic APOL1 protein in cells of the subject. The nucleic acid molecule can also be used to manufacture a medicament for treating or reducing the likelihood of developing a renal disease. The patent also describes the use of agents, such as anti-APOL1 antibodies or a human APOL1 protein antagonist, to treat or reduce the symptoms of renal disease.

Problems solved by technology

End-stage kidney failure (ESKD) is a growing problem that now affects over half a million individuals in the United States.

The cost of caring for patients with ESKD is currently over 40 billion dollars per year.

There are no specific therapies for the vast majority of progressive kidney diseases.

Some types of chronic renal disease progression can be slowed by blood pressure control with specific agents, but nephrologists cannot accurately predict which patients will respond.

Moreover, while successful treatment typically slows progression, it neither prevents disease nor halts disease progression.

Images