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filingDate 2015-07-22-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationDate 2017-10-12-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber JP-2017529870-A
titleOfInvention Method for suppressing intracellularly activated RAS using antibody having cytoplasmic penetrating ability in complete immunoglobulin form and use thereof
abstract The present invention relates to a method for suppressing intracellularly activated RAS using an antibody having cytoplasmic penetrating ability in the form of a complete immunoglobulin (immunoglobulin). In addition, the present invention is directed to the binding of an intact immunoglobulin form of an antibody to the cytoplasm of a living cell through endocytosis and endosome escape and activating cytoplasmic activation. The present invention relates to a heavy chain variable region (VH) that induces and antibodies containing the same. The present invention also relates to a method for suppressing the growth of cancer or tumor cells using the antibody and a method for treating cancer or tumor. The present invention also relates to a method for screening a heavy chain variable region that specifically binds to cytoplasmic RAS. The present invention also relates to a bioactive molecule selected from the group consisting of peptides, proteins, small molecule drugs, nanoparticles and liposomes fused to the antibody. The present invention also provides a composition for preventing, treating or diagnosing cancer comprising the antibody or a bioactive molecule selected from the group consisting of peptides, proteins, small molecule drugs, nanoparticles and liposomes fused thereto. About. The present invention also relates to the polynucleotide encoding the light chain variable region and the antibody. The method of suppressing intracellularly activated RAS using an antibody having cytoplasmic penetrating ability in the form of a complete immunoglobulin provided in the present invention, wherein the antibody penetrates inside living cells. Activated (GTP-conjugated) RAS located in the cytoplasm is achieved by an antibody capable of specific recognition, thereby activating (GTP) located in the inner cytoplasm of living cells. RAS can be targeted and its activity can be inhibited. Further, the light chain variable region of the antibody provided in the present invention or an antibody containing the same can penetrate into living cells and be distributed in the cytoplasm without a special external protein transmission system. In particular, the light chain variable region of the antibody provided by the present invention has characteristics that it can easily interact with various human heavy chain variable regions (VH) and can remain in the cytoplasm through cytoplasmic penetration. A complete IgG form of a single clone antibody containing the light chain variable region is distributed in the internal penetration and cytoplasm of the cell and exhibits no non-specific cytotoxicity to the cell. The heavy chain variable region of the antibody according to the present invention, and an antibody comprising the same can selectively inhibit RAS mutation, which is a major drug resistance-related factor of various existing tumor therapeutic agents, and Effective anticancer activity can be expected through parallel therapy. Using the antibody in the form of a cytoplasmic penetrating complete immunoglobulin according to the present invention, it can penetrate into the inside of a cell without affecting the high antigen specificity and high affinity of the heavy chain variable region (VH) of a human antibody. It is possible to add the characteristics that remain in the cytoplasm, and it exists in the cytoplasm that is classified as a target substance for disease treatment using current small molecule drugs, but through a wide and flat surface between proteins. Thus, it can be expected to be highly effective in the treatment and diagnosis of tumor-related and disease-related factors having a complex structure interaction.
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priorityDate 2014-07-22-04:00^^<http://www.w3.org/2001/XMLSchema#date>
type http://data.epo.org/linked-data/def/patent/Publication

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