[특허]Immune reactivity to HER-2/neu protein for diagnosis and treatment of malignancies in which the HER-2/neu oncogene is associated

University of Washington

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특허 상세정보

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Immune reactivity to HER-2/neu protein for diagnosis and treatment of malignancies in which the HER-2/neu oncogene is associated

특허상세정보
국가/구분	United States(US) Patent 등록
국제특허분류(IPC7판)	C07K-007/08 C07K-007/06 A61K-038/08 A61K-038/10
미국특허분류(USC)	530/328; 530/326; 530/300; 530/350; 530/403; 530/402; 424/184.1; 424/185.1; 424/277.1; 514/002; 514/014; 514/015; 930/010
출원번호	US-0354533 (1999-07-15)
발명자 / 주소	Cheever, Martin A. Disis, Mary L.
출원인 / 주소	University of Washington
대리인 / 주소	Seed Intellectual Property Law Group PLLC
인용정보	피인용 횟수 : 18 인용 특허 : 11

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Methods for the detection, monitoring and treatment of malignancies in which the HER-2/neu oncogene is associated are disclosed. Detection of specific T cell activation (e.g., by measuring the proliferation of T cells) in response to in vitro exposure to the HER-2/neu protein, or detection of immunocomplexes formed between the HER-2/neu protein and antibodies in body fluid, allows the diagnosis of the presence of a malignancy in which the HER-2/neu oncogene is associated. The present invention also discloses methods and compositions, including peptides, for treating such malignancies. a (6) each stands for a positive integer of 2 or smaller or 0 with the proviso that they are not all 0 at the same time. 5. The process according to claim 1, wherein Rs in said phosphazenium cation in the chemical formula (5), chemical formula (6) or chemical formula (7) are the same or different aliphatic hydrocarbon groups having 1 to 10 carbon atoms. 6. The process according to claim 1, wherein Rs on each common nitrogen atom in said phosphazenium cation in the chemical formula (5), chemical formula (6) or chemical formula (7) are coupled together to form a ring structure; and the resultant divalent substituent on said nitrogen atom is a tetramethylene or pentamethylene group. 7. The process according to claim 1, wherein Q-in said phosphazenium compound represented by the chemical formula (7) is an anion selected from the group consisting of a hydroxyl anion, alkoxyl anions derived from alcohols having 1 to 8 carbon atoms, aryloxyl anions derived from aromatic hydroxyl compounds having 6 to 18 carbon atoms, and carboxyl anions derived from carboxylic acids having 1 to 6 carbon atoms. 8. The process according to claim 1, wherein said active hydrogen compound is an active hydrogen compound selected from the group consisting of alcohols having 1 to 20 carbon atoms, polyhydric alcohols having 2 to 20 carbon atoms and 2 to 8 hydroxyl groups, saccharides and derivatives thereof the derivatives having an active hydrogen on an oxygen poly(alkylene oxides) having 2 to 8 terminals, 1 to 8 hydroxyl groups at said terminals and a molecular weight of from 100 to 50,000, polyamines having 2 to 20 carbon atoms and 2 to 3 primary or secondary amino groups, saturated cyclic secondary amines having 4 to 10 carbon atoms, and cyclic polyamines having 4 to 10 carbon atoms and 2 to 3 secondary amino groups. 9. The process according to claim 1, wherein upon polymerization of said alkylene oxide compound in the presence of said salt of said phosphazenium cation and said inorganic anion, said salt being represented by the chemical formula (5) or chemical formula (6), and said alkali metal or alkaline earth metal salt of said active hydrogen compound, or in the presence of said phosphazenium salt of said active hydrogen compound having been derived from said salt of said phosphazenium cation and said inorganic anion, said salt being represented by the chemical formula (5), and said alkali metal or alkaline earth metal salt of said active hydrogen compound, said polymerization is conducted in the additional presence of an active hydrogen compound which is the same as or different from said active hydrogen compound having formed said alkali metal or alkaline earth metal salt of said active hydrogen compound or said derived phosphazenium salt of said active hydrogen compound. 10. The process according to claim 1, wherein in said polymerization reaction of said alkylene oxide compound, said phosphazenium cation is used in an amount of from 1×10-7to 1×10-2mole per mole of said alkylene oxide compound. 11. The process according to claim 1, wherein at least two kinds of alkylene oxide compounds are successively polymerized to produce a block copolymer containing at least two kinds of poly(alkylene oxide) blocks. 12. A process for producing a poly (alkylene oxide) by polymerization of an alkylene oxide compound, which comprises polymerizing said alkylene oxide compound in the presence of a phosphazenium cation represented by the following chemical formula (1a): wherein a, b, c and d in the chemical formula (1a) each stands for the number of repeating units and is a positive integer of 3 or smaller or 0 with the proviso that a, b, c and d are not all 0 at the same time, Rs represent the same or different hydrocarbon groups having 1 to 10 carbon atoms, two Rs on each common nitrogen atom may be coupled together to form a ring structure, and an anion of an active hydrogen compound. 13. A process for producing a pol y(alkylene oxide) by polymerization of an alkylene oxide compound, which comprises polymerizing said alkylene oxide compound in the presence of: a phosphazenium compound represented by the following formula (7a): wherein a, b, c and d in the chemical formula (1a) each stands for the number of repeating units and is a positive integer of 3 or smaller or 0 with the proviso that a, b, c and d are not all 0 at the same time, Q-represents an alkoxyl anion, aryloxyl anion or carboxyl anion, Rs represent the same or different hydrocarbon groups having 1 to 10 carbon atoms, two Rs on each common nitrogen atom may be coupled together to form a ring structure, and an alkali metal or alkaline earth metal salt of an active hydrogen compound, or a phosphazenium salt of an active hydrogen compound, said phosphazenium salt having been derived from: a phosphazenium compound represented by the chemical formula (7a) defined above, and an alkali metal or alkaline earth metal salt of an active hydrogen compound. 14. The process according to claim 12 which further comprises polymerizing said alkylene oxide compound in the presence of the same kind or different kind of an active hydrogen compound. 15. A process for producing a poly(alkylene oxide) by polymerization of an alkylene oxide compound, which comprises polymerizing said alkylene oxide compound in the presence of: (I-i) (a) a salt of a phosphazenium cation and an inorganic anion, said salt being represented by the following chemical formula (5) or chemical formula (6): wherein a, b, c and d in the chemical formula (5) or e, f and g in the chemical formula (6) each stands for the number of repeating units and is a positive integer of 3 or smaller or 0 with the proviso that a, b, c and d or e, f and g are not all 0 at the same time, Rs represent the same or different hydrocarbon groups having 1 to 10 carbon atoms, two Rs on each common nitrogen atom may be coupled together to form a ring structure, r stands for an integer of from 1 to 3 and represents the number of phosphazenium cations and Tr-represents an r-valent inorganic anion of an inorganic acid selected from the group consisting of boric acid, tetrafluoroboric acid, hydrohalogenic acids, phosphoric acids, hexafluorophosphoric acid and perchloric acid, and (b) an alkali metal or alkaline earth metal salt of an active hydrogen compound, or (I-ii) a phosphazenium salt of an active hydrogen compound, said phosphazenium salt having been derived from: (a) a salt of a phosphazenium cation and an inorganic anion, said salt being represented by the chemical formula (5), and (b) an alkali metal or alkaline earth metal salt of an active hydrogen compound; or (II-i) (a) a phosphazenium compound represented by the following formula (7): wherein a, b, c, d and Rs have the same meanings as defined above, and Q-represents a hydroxyl anion, alkoxyl anion, aryloxyl anion or carboxyl anion, and (b) an active hydrogen compound, or (II-ii) a phosphazenium salt of an active hydrogen compound, said phosphazenium salt having been derived from: (a) a phosphazenium compound represented by the chemical formula (7), and (b) an active hydrogen compound. 16. A process for producing a poly(alkylene oxide) by polymerization of an alkylene oxide compound, which comprises polymerizing said alkylene oxide compound in the presence of: (I-i) (a) a salt of a phosphazenium cation and an inorganic anion said salt being represented by the following chemical formula (5) or chemical formula (6): wherein a, b, c and d in the chemical formula (5) or e, f and g in the chemical formula (6) each stands for the number of repeating units and is a positive integer of 3 or smaller or 0 with the proviso that a, b, c and d or e, f and g are not all 0 at the same time, Rs represent the same or different hydrocarbon groups having 1 to 10 carbon atoms, two Rs on each common nitrogen atom may be coupled togethe

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Immune reactivity to HER-2/neu protein for diagnosis and treatment of malignancies in which the HER-2/neu oncogene is associated

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Immune reactivity to HER-2/neu protein for diagnosis and treatment of malignancies in which the HER-2/neu oncogene is associated

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