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Publication Number

US-10053510-B2

Patent

Publication Date

2018-08-21

Expiration Date


Abstract

Provided herein are an exogenous antibody that binds selectively to a misfolded form of human FasR, and methods and uses for said antibody. Specifically disclosed is the antibody designated AMF 3a-118 which selectively binds the peptide represented by LHHDGQFCH (SEQ ID NO:2) and the antibody designated AMF 3d-19 which selectively binds the peptide represented by NSTVCEH (SEQ ID NO:5).

Core Innovation

The disclosed invention provides anti-misfolded human Fas receptor (FasR) antibodies, including AMF 3a-118 and AMF 3d-19. Each antibody selectively binds a misfolded form of human FasR and recognizes disease-specific epitopes comprised of at least 5 contiguous residues of LHHDGQFCH (SEQ ID NO:2) and NSTVCEH (SEQ ID NO:5), respectively.

The antibodies are defined by heavy chain and light chain variable regions containing framework regions and complementarity determining regions (CDRs). For AMF 3a-118 and AMF 3d-19, CDR amino acid sequence sets are specified, including CDR1, CDR2, and CDR3 for both heavy and light chains, together with corresponding heavy/light chain and variable-region SEQ ID identifiers.

The disclosure further encompasses recombinant/polynucleotide/vector formats and Fc/effector engineering options, together with antibody forms including fragments. The document describes diagnostic and therapeutic uses including immunoconjugates with toxins or detectable labels, as well as pharmaceutical/vaccine formulations conceptually based on detecting antibody-bound complexes formed on FasR-misfolded cells.

Claims Coverage

The relevant independent claim is clm-00001. It includes a single antibody or fragment invention centered on selective binding to misfolded human FasR via a disease-specific epitope defined by at least 5 contiguous residues of LHHDGQFCH (SEQ ID No. 2) and specified heavy/light chain CDR sequences. Dependent claims further refine variable-region sequence identifiers and add formats and end uses such as immunoconjugates, diagnostic kits, and methods of detecting misfolded FasR-presenting cells.

Antibody selectively binding misfolded human FasR via LHHDGQFCH epitope and defined CDR sequences

An antibody or fragment thereof that binds selectively to a misfolded form of human Fas receptor (FasR), wherein the antibody binds to an epitope comprising at least 5 contiguous residues of LHHDGQFCH (SEQ ID No. 2) of the misfolded human FasR, the antibody comprising a heavy chain and a light chain with constant and variable regions, and wherein the CDRs comprise specified amino acid sequences (heavy-chain CDR1 (SEQ ID No. 33), CDR2 (SEQ ID No. 34), CDR3 (SEQ ID No. 35), and light-chain CDR1 (SEQ ID No. 36), CDR2 (SEQ ID No. 37), CDR3 (SEQ ID No. 38)).

Overall claim coverage centers on a selective anti-misfolded FasR antibody defined by epitope binding to LHHDGQFCH (SEQ ID No. 2) and specified heavy- and light-chain CDR sequences, with dependent refinements that specify particular heavy/light variable-region SEQ ID identifiers and extend the antibody into immunoconjugates, diagnostic kits, and antibody-bound-complex detection of misfolded FasR-presenting cells.

Stated Advantages

Selectively binds a misfolded form of human Fas receptor (FasR) to recognize disease-specific epitopes.

Enables detection of cells presenting misfolded human FasR via formation of an antibody-bound complex.

Provides formats including immunoconjugates with a toxin or a detectable label and associated diagnostic kit and pharmaceutical/vaccine formulations.

Documented Applications

Diagnostic kit for detecting cells presenting misfolded human FasR.

Method for detecting, in a biological sample, cells that present misfolded FasR by incubating with the antibody or immunoconjugate and detecting formation of an antibody-bound complex.

Immunoconjugates comprising the antibody or binding fragment conjugated with a toxin or a detectable label.

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