Antibodies targeting bone morphogenetic protein 9 (BMP9) and methods therefor

Abstract

The present invention relates to isolated antibodies and antigen-binding fragments thereof which bind human BMP9 and compositions and methods of use thereof.

Description

RELATED APPLICATIONS[0001]This application is a divisional application of U.S. patent application Ser. No. 15 / 165,150, filed on May 26, 2016, now U.S. Pat. No. 10,047,155, which claims priority to PCT Application No. PCT / CN2015 / 080887, filed Jun. 5, 2015, the entire contents of each of these applications are incorporated herein by reference in their entireties.SEQUENCE LISTING[0002]The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 4, 2016, is named PAT056928-US—NP_SL.txt and is 163,925 bytes in size.INTRODUCTION[0003]The present invention relates to antibodies and antigen-binding fragments thereof which bind human BMP9, and compositions and methods of use thereof.BACKGROUND OF THE INVENTION[0004]Fibrosis is a pathological process that refers to the aberrant formation or development of excess fibrous connective tissue by cells in an organ ...

AI Technical Summary

Benefits of technology

[0144]In one aspect of the present invention, the isolated antibody or antigen-binding fragment thereof reduces the activity of human BMP9 in vitro. In one aspect of the present invention, the isolated antibody or antigen-binding fragment thereof reduces the activity of human BMP9 in vitro, as measured in a HEK293T-BRE-Luc reporter gene assay, for example as described herein.

[0146]In one aspect of the present invention, the additional therapeutic agent reduces the activity of BMP9.

[0245]The term “chimeric antibody” (or antigen-binding fragment thereof) is an antibody molecule (or antigen-binding fragment thereof) in which (a) the constant region, or a portion thereof, is altered, replaced or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and / or species, or an entirely different molecule which confers new properties to the chimeric antibody, e.g., an enzyme, toxin, hormone, growth factor, drug, etc.; or (b) the variable region, or a portion thereof, is altered, replaced or exchanged with a variable region having a different or altered antigen specificity. For example, a mouse antibody can be modified by replacing its constant region with the constant region from a human immunoglobulin. Due to the replacement with a human constant region, the chimeric antibody can retain its specificity in recognizing the antigen while having reduced antigenicity in human as compared to the original mouse antibody.

[0252]The term “neutralizes” means that an antibody, upon binding to its target, reduces the activity, level or stability of the target; e.g., a BMP9 antibody, upon binding to BMP9 neutralizes BMP9 by at least partially reducing an activity, level or stability of BMP9, such as signaling or its role in phosphorylation of Smad1 / 5 / 8 and / or fibrosis, e.g., liver fibrosis.

Problems solved by technology

Although processes related to fibrosis can occur as part of normal tissue formation or repair, dysregulation of these processes can lead to altered cellular composition and excess connective tissue deposition that progressively impairs tissue or organ function.

Existing therapies for liver diseases, including fibrotic liver disease, including cirrhosis, can have low efficacy and undesirable side effects.

Moreover, there are currently no wholly effective treatments or cures for liver disease, including fibrotic liver diseases, including cirrhosis.

Images