Cancer-cell-specific anti-transmembrane protein 180 antibody, anticancer drug, and cancer testing method
Inventors
Matsumura, Yasuhiro • Yasunaga, Masahiro • Saijou, Shinji • Hanaoka, Shingo
Assignees
National Cancer Center Japan • RIN Institute Inc • National Cancer Center Korea
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Publication Number
US-10471146-B2
Publication Date
2019-11-12
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
The invention relates to an anti-transmembrane protein 180 (TMEM-180) antibody or an antigen-binding fragment thereof comprising defined heavy-chain and light-chain CDR sequences. The heavy-chain CDR1, CDR2, and CDR3 sequences and the corresponding light-chain CDR1, CDR2, and CDR3 sequences are specified as the defining features for the antibody or antigen-binding fragment.
TMEM-180 is identified as a cancer-associated membrane protein expressed in colon cancer cell lines and not expressed in healthy tissues. The document supports this identification by mRNA expression profiling and assays including DNA microarray, quantitative PCR, in situ hybridization, and database-based normal tissue profiling.
The anti-TMEM-180 antibody is described as exhibiting cytocidal effects on TMEM-180+ cancer cells, with specificity supported by TMEM-180 knockout controls. The document further discloses use of the antibody as an anticancer drug, including formulation in a pharmaceutical context and delivery of toxic anticancer substances to TMEM-180+ cells.
In addition, a cancer testing method/kit is disclosed in which TMEM-180 is measured in a subject sample. The document states that TMEM-180 measurement supports improved sensitivity for recurrence compared with conventional colon marker CEA, and describes immunoassay/kit formats for measuring TMEM-180.
Claims Coverage
The consolidated claim coverage includes one core independent feature set for an anti-TMEM-180 antibody defined by specific heavy-chain and light-chain CDR sequences, and one composition claim comprising that antibody with a pharmaceutically acceptable carrier or additive. Dependent coverage extends to TMEM-180 immunoassay detection in subject samples, treatment of TMEM-180-expressing cancer including colon cancer, an isolated nucleic acid encoding the antibody or antigen-binding fragment, and an Fc glycosylation feature involving fucose absence.
Defined anti-TMEM-180 antibody CDR sequence set
An anti-transmembrane protein 180 (TMEM-180) antibody or an antigen-binding fragment thereof comprising specific heavy-chain CDR1, heavy-chain CDR2, heavy-chain CDR3, and light-chain CDR1, light-chain CDR2, light-chain CDR3 sequences as provided in the claim.
Composition comprising TMEM-180 antibody defined by CDR sequences with carrier or additive
A composition comprising an anti-TMEM-180 antibody or an antigen-binding fragment thereof comprising the specified heavy-chain and light-chain CDR sequences, and a pharmaceutically acceptable carrier or pharmaceutically acceptable additive.
TMEM-180 immunoassay for detecting or measuring TMEM-180 protein
A method for detecting or measuring the amount of a TMEM-180 protein in a sample collected from a subject using an immunoassay with an anti-TMEM-180 antibody or its antigen-binding fragment.
Administration of anti-TMEM-180 antibody for treating TMEM-180-expressing cancer
A method for treating a cancer in a subject by administering an anti-TMEM-180 antibody or an antigen binding fragment, wherein the cancer expresses TMEM-180.
Treating colon cancer using the anti-TMEM-180 antibody
The method for treating cancer specifies that the cancer is colon cancer.
Isolated nucleic acid encoding the anti-TMEM-180 antibody
An isolated nucleic acid encoding the anti-TMEM-180 antibody or its antigen-binding fragment defined by the CDR sequences.
Fc-associated N-linked oligosaccharide with fucose absence
An anti-TMEM-180 antibody that includes an Fc-bound N-linked oligosaccharide wherein fucose is not attached to N-acetylglucosamine at the reducing end of the oligosaccharide.
The claims center on an anti-TMEM-180 antibody or antigen-binding fragment defined by specific heavy- and light-chain CDR sequences, with a composition claim built on the same antibody definition. The remaining claim coverage extends to TMEM-180 detection by immunoassay, treatment of TMEM-180-expressing cancer including colon cancer, nucleic acids encoding the antibody, and an Fc glycosylation feature specified as fucose absence at the reducing-end attachment site.
Stated Advantages
Improved sensitivity for recurrence compared with conventional colon marker CEA (TMEM-180 measurement).
Cytocidal effects on TMEM-180+ cancer cells (with specificity supported by TMEM-180 knockout controls).
Documented Applications
Cancer testing method/kit: measuring TMEM-180 in a subject sample to support recurrence assessment, with improved sensitivity compared with conventional colon marker CEA.
Therapeutic application: treating a cancer in a subject by administering an anti-TMEM-180 antibody or antigen-binding fragment when the cancer expresses TMEM-180, including colon cancer.
Anticancer drug formulation/application: using the anti-TMEM-180 antibody in a pharmaceutical context and delivery of toxic anticancer substances to TMEM-180+ cells.
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