Cancer-cell-specific anti-TMEM-180 monoclonal antibody, anticancer drug, and cancer testing method
Inventors
Matsumura, Yasuhiro • Yasunaga, Masahiro • Saijou, Shinji • Hanaoka, Shingo
Assignees
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Publication Number
US-11524074-B2
Publication Date
2022-12-13
Expiration Date
Abstract
An object of the present invention is to provide an anticancer drug capable of treating cancer by finding a target molecule specifically expressed in cancer cells and by specifically acting on the target molecule, and to provide a cancer testing method including a step of measuring the target molecule in a sample. The present invention provides an anticancer drug containing, as an active ingredient thereof, an anti-transmembrane protein 180 (TMEM-180) antibody or an antigen-binding fragment thereof. In addition, the present invention provides a cancer testing method including a step of measuring the amount of TMEM-180 in a sample collected from a subject.
Core Innovation
Anti-transmembrane protein 180 (TMEM-180) monoclonal antibodies and antigen-binding fragments are defined by specific heavy-chain and light-chain CDR sequences. The antibodies comprise heavy chain CDR1, CDR2, and CDR3 sequences together with light chain CDR1, CDR2, and CDR3 sequences, with the CDR sequences provided by SEQ ID NOs. Clone 1052 and clone 1105 are associated with amino-acid sequence information, including coding table segments labeled as CDR1, CDR2, and CDR3 for heavy- and light-chain variable regions.
A cancer testing method section is described for quantifying TMEM-180 protein. The method includes an ELISA workflow to quantify TMEM-180 protein in cancer cell culture supernatants and patient plasma, with TMEM-180 levels reported as elevated in tested samples and changing with surgery and recurrence. The description additionally discusses sandwich ELISA using other clones, including clone 669 and clone 1361, for comparison with CEA.
The antibody features and sequence information are positioned to enable immunoassay detection and measurement of TMEM-180 protein in samples. The claim set includes diagnostic immunoassay measurement of the amount of TMEM-180 protein in a sample collected from a subject using an anti-TMEM-180 monoclonal antibody or antigen-binding fragment. The claim set also defines TMEM-180 monoclonal antibody embodiments as IgM and provides molecular definition via specific CDR sequences.
Claims Coverage
Two independent claims are identified, both centered on anti-TMEM-180 monoclonal antibodies or antigen-binding fragments defined by heavy-chain and light-chain CDR sequences; the claim set further includes IgM specification in one independent claim and assay, production, and Fc-glycosylation narrowing in dependent claims.
CDR-defined anti-TMEM-180 monoclonal antibody
An anti-transmembrane protein 180 (TMEM-180) monoclonal antibody or an antigen-binding fragment thereof, wherein the antibody and the antigen-binding fragment thereof comprise heavy chain CDR1 SNGVG, heavy chain CDR2 TIWSGGGTNYNSAVQS, heavy chain CDR3 EEKGFAY, light chain CDR1 KASQNVGINVG, light chain CDR2 WASNRDT, and light chain CDR3 LQHNSYPRA.
IgM CDR-defined anti-TMEM-180 monoclonal antibody
An anti-transmembrane protein 180 (TMEM-180) monoclonal antibody or an antigen-binding fragment thereof comprising the same CDR sequences, wherein said anti-transmembrane protein 180 (TMEM-180) monoclonal antibody is an IgM antibody.
Immunoassay detection of TMEM-180 amount
An assay method for detecting or measuring the amount of a TMEM-180 protein in a sample by performing an immunoassay using the anti-TMEM-180 monoclonal antibody or its antigen-binding fragment.
Cancer treatment when cancer expresses TMEM-180
A method of treating a subject's cancer by administering the anti-TMEM-180 monoclonal antibody or its antigen-binding fragment when the cancer expresses TMEM-180.
Fc N-linked oligosaccharide lacking fucose binding
An anti-TMEM-180 monoclonal antibody wherein the antibody comprises an N-linked oligosaccharide attached to the Fc region, where fucose is not bound to N-acetylglucosamine at the reducing end of the N-linked oligosaccharide.
Isolated nucleic acid encoding the antibody
An isolated nucleic acid that encodes an anti-TMEM-180 monoclonal antibody or its antigen-binding fragment as defined in claim 1.
Producing by expression in an isolated transformant
A method for producing the anti-TMEM-180 monoclonal antibody or its antigen-binding fragment by expressing it in an isolated transformant with an expression vector encoding the antibody or fragment, and then recovering the produced antibody or fragment.
Overall, the claim coverage defines anti-TMEM-180 monoclonal antibodies and antigen-binding fragments by specific heavy- and light-chain CDR sequence sets, with one independent claim additionally specifying that the antibody is an IgM. The dependent claim set further narrows into TMEM-180 immunoassay detection and measurement, therapeutic administration for cancers expressing TMEM-180, a defined Fc fucosylation feature, and genetic and production embodiments.
Stated Advantages
Clone-dependent binding to multiple cancer types.
Cytocidal activity against TMEM-180-positive colon and other cancer cells.
Lack of effect on hematologic K562 cells is described.
TMEM-180 detection performance is described in comparison with conventional marker CEA, including plasma changes before and after surgery and at recurrence.
Elevated TMEM-180 levels are reported in tested samples.
TMEM-180 levels change with surgery and recurrence.
TMEM-180 measurement is described for cancer testing using ELISA and sandwich ELISA, including comparison with CEA.
Documented Applications
Cancer testing by measuring TMEM-180 levels in patient samples, including detection of plasma changes before and after surgery and at recurrence, and comparison with conventional marker CEA.
Immunoassay, ELISA, and sandwich immunoassay-based testing embodiments and kits for detecting TMEM-180.
Latex agglutination-based testing kit embodiment for detecting TMEM-180.
Treating a subject's cancer by administering the anti-TMEM-180 monoclonal antibody or antigen-binding fragment when the cancer expresses TMEM-180.
Use of antibody compositions in combination embodiments that include cancer vaccine peptide sequences is described.
Cancer testing by quantifying TMEM-180 protein in cancer cell culture supernatants and patient plasma using an ELISA workflow.
Use of sandwich ELISA for TMEM-180 detection with comparison to CEA, using other clones including clone 669 and clone 1361.
Therapeutic use at the claim level for treating a subject's cancer by administering an anti-TMEM-180 monoclonal antibody or antigen-binding fragment when the cancer expresses TMEM-180.
Diagnostic immunoassay use at the claim level for detecting or measuring the amount of TMEM-180 protein in a sample collected from a subject using an anti-TMEM-180 monoclonal antibody or antigen-binding fragment.
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