The invention relates to an isolated antibody that binds to a non-ligand binding membrane proximal region of an extracellular domain of human Notch1 receptor and comprises a heavy chain CDR1 comprising RGYWIE, a heavy chain CDR2 comprising QILPGTGRTNYNEKFKG, and a heavy chain CDR3 comprising FDGNYGYYAMDY, and a light chain CDR1 comprising RSSTGAVTTSNYAN, a light chain CDR2 comprising GTNNRAP, and a light chain CDR3 comprising ALWYSNHWVFGGGTKL. The invention also relates to a polynucleotide encoding said antibody； an expression vector comprising this polynucleotide； and a host cell comprising said vector and producing said antibody. Another aspect of the invention is a pharmaceutical composition for treating Notch1-associated cancer comprising an effective amount of the antibody by the present invention and a pharmaceutically acceptable carrier. The invention further includes the use of said antibody to obtain an agent for treating Notch1-associated cancer or an agent for reducing frequency of cancer stem cells in a tumor. Another aspects of the invention are a method of treating Notch1-associated cancer that comprises administering the antibody in combination with at least one additional therapeutic agent which is used for treating said cancer, or in combination with at least one chemotherapeutic agent； and a method of treating Notch1-associated cancer that comprises administering the antibody in combination with at least one additional antibody which is used for treating said cancer.Изобретение относится к выделенному антителу, которое связывается с нелигандсвязывающей проксимальной областью мембраны внеклеточного домена рецептора Notch1 человека и содержит CDR1 тяжелой цепи, содержащую RGYWIE, CDR2 тяжелой цепи, содержащую QILPGTGRTNYNEKFKG, и CDR3 тяжелой цепи, содержащую FDGNYGYYAMDY； и CDR1 легкой цепи, содержащую RSSTGAVTTSNYAN, CDR2 легкой цепи, содержащую GTNNRAP, и CDR3 легкой цепи, содержащую ALWYSNHWVFGGGTKL. Также изобретение относится к полинуклеотиду,
