Composition of anti-ENDO180 antibodies and methods of use for the treatment of cancer and fibrotic diseases
Inventors
Assignees
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Publication Number
US-8444983-B2
Publication Date
2013-05-21
Expiration Date
Abstract
The present invention provides antibodies or antigen-binding fragments thereof that specifically bind the ENDO180 polypeptide and are internalized thereby, to conjugates comprising the molecules, to compositions comprising the antibodies and conjugates and to methods of using the same for delivery of therapeutic agents to cells that express the ENDO180 polypeptide on the surface of the cell for treating cell proliferative diseases or disorders and fibrosis, and for controlling (modulating) tumor progression.
Core Innovation
The invention relates to anti-ENDO180 antibodies or antigen-binding fragments that bind ENDO180 on the surface of a cell expressing ENDO180 and are internalized into the cell. The subject matter includes isolated monoclonal antibodies and antigen-binding fragments selected from defined antibody sources, including a monoclonal antibody produced by the hybridoma cell line E3-8D8 deposited with the BCCM under Accession Number LMBP 7203CB, together with humanized and chimeric versions.
The invention further includes antibody-based conjugates in which the anti-ENDO180 antibody or an antigen-binding fragment is conjugated to a therapeutic agent or a diagnostic cargo. The disclosed cargo can include a radioisotope, a cytotoxic agent, or a detectable label, and the document also includes compositions comprising the anti-ENDO180 antibody or antigen-binding fragment together with a pharmaceutically acceptable carrier.
In addition, the document addresses ENDO180 biology and provides support for internalization and cellular binding. Internalization is illustrated using antibodies with fluorophore or biotin labels, and ENDO180 mRNA expression patterns are assessed in patient tumor samples using in situ hybridization. Disease models and therapeutic contexts are described for proliferative cancers and fibrotic diseases, including kidney fibrosis and diabetic nephropathy.
Claims Coverage
The provided material contains two independent claims. The first independent claim covers anti-ENDO180 antibodies/antigen-binding fragments with binding and internalization behavior, including specified hybridoma-derived humanized and chimeric versions. The second independent claim covers a specific deposited hybridoma cell line used to produce the antibodies.
Endo180-binding and internalization upon contact
The anti-ENDO180 antibody or antigen-binding fragment binds to ENDO180 on the surface of a cell expressing ENDO180 and is internalized into the cell upon contact.
Hybridoma-derived anti-Endo180 antibody and defined variant formats
The anti-ENDO180 antibody or antigen-binding fragment is selected from an isolated monoclonal antibody produced by the hybridoma cell line E3-8D8, deposited with the BCCM under Accession Number LMBP 7203CB, or an antigen-binding fragment of such isolated monoclonal antibody, including a humanized version or a chimeric version and corresponding antigen-binding fragments.
Deposited hybridoma cell line E3-8D8
A hybridoma cell line designated E3-8D8, deposited with the BCCM under Accession Number LMBP 7203CB.
Overall, the claims coverage centers on ENDO180-targeting antibody/antigen-binding fragments that bind ENDO180 on ENDO180-expressing cells and are internalized, with the antibodies linked to a deposited E3-8D8 hybridoma and its humanized and chimeric variant formats. A separate independent claim defines the deposited hybridoma cell line E3-8D8 itself.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Therapeutic methods for proliferative cancers.
Therapeutic methods for fibrotic diseases, including kidney fibrosis and diabetic nephropathy.
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