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-9993567-B2
Publication Date
2018-06-12
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 ENDO180 (CD280/MRC2/uPARAP), a recycling endocytic receptor associated with extracellular matrix remodeling, collagen turnover, plasmin/TGF-b2 activation, and cell motility. ENDO180 is linked to fibrosis and tumor progression. The invention provides anti-ENDO180 antibodies and antigen-binding fragments that bind ENDO180 on the surface of cells and are internalized.
The invention identifies anti-ENDO180 antibodies including an isolated monoclonal antibody produced by the hybridoma cell line E3-8D8 deposited with the BCCM under Accession Number LMBP 7203CB. The invention further provides humanized and chimeric versions of the antibody, and antigen-binding fragments comprising both the light chain variable regions and the heavy chain variable regions of the respective antibody versions. The invention also provides defined scFv/miniantibody formats and antigen-binding fragments intended to bind ENDO180 and undergo internalization upon contact with ENDO180-expressing cells.
The invention also provides conjugates and compositions in which the anti-ENDO180 antibodies or antigen-binding fragments are linked to moieties including radioisotopes, detectable labels, cytotoxic agents, and therapeutic agents, with therapeutic agents preferably including oligonucleotide therapeutics such as chemically modified siRNA that inhibit target gene expression. The invention describes delivery and diagnostic concepts for ENDO180-expressing cells, including nanoparticle and lipid particle carrier concepts, and relates the compositions to treating proliferative diseases including multiple solid tumors and hematologic malignancies, as well as fibrotic diseases.
Claims Coverage
The document provides one independent claim covering anti-ENDO180 antibodies and antigen-binding fragments that bind ENDO180 on the cell surface and are internalized, with coverage that includes specific antibody sources and versions. Additional inventive features extend to formulations, moiety linkage, particle carrier concepts, and therapeutic use.
ENDO180-binding antibody and internalizing antigen-binding fragment
An anti-ENDO180 antibody or an antigen-binding fragment thereof selected to include an isolated monoclonal antibody produced by hybridoma E3-8D8 deposited with BCCM under Accession Number LMBP 7203CB or antigen-binding fragments comprising both light chain variable regions and heavy chain variable regions of that monoclonal antibody, and includes humanized and chimeric versions and corresponding antigen-binding fragments, wherein upon contact with a cell expressing ENDO180 the antibody or antigen-binding fragment binds to ENDO180 on the cell surface and is internalized into the cell.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition comprising an anti-ENDO180 antibody or its antigen-binding fragment together with a pharmaceutically acceptable carrier.
Composition comprising antibody linked to functional moiety
A composition further comprising a moiety selected from a detectable label, a cytotoxic agent, a therapeutic agent, or combinations thereof.
Particle carrier with encapsulated moiety and immobilized antibody
A carrier composition wherein particles are selected from lipid particles, polysaccharide particles, lipidated polysaccharide particles, or combinations thereof, the moiety is encapsulated in the particle, and an anti-ENDO180 antibody or antigen-binding fragment is immobilized on the particle.
Conjugation of antibody or fragment to a moiety directly or via linker
The anti-ENDO180 antibody or antigen-binding fragment is conjugated to a moiety either directly or through a linker connecting the antibody or fragment to the moiety.
Treatment of cancer or fibrosis using the antibody-based composition
Treating a subject afflicted with cancer or fibrosis by administering a composition in an amount effective to treat the subject.
Overall, the claims cover internalizing anti-ENDO180 antibodies and antigen-binding fragments, with dependent coverage extending to pharmaceutical formulations, detectable labels, cytotoxic and therapeutic moieties, particle carrier architectures with encapsulated moieties and immobilized antibody, conjugation directly or via a linker, and treatment of cancer and fibrosis.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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