JPWO2020047374A5 - - Google Patents

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JPWO2020047374A5
JPWO2020047374A5 JP2021511561A JP2021511561A JPWO2020047374A5 JP WO2020047374 A5 JPWO2020047374 A5 JP WO2020047374A5 JP 2021511561 A JP2021511561 A JP 2021511561A JP 2021511561 A JP2021511561 A JP 2021511561A JP WO2020047374 A5 JPWO2020047374 A5 JP WO2020047374A5
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Priority claimed from PCT/US2019/048994 external-priority patent/WO2020047374A1/en
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ＣＤ３３に結合する単離された抗体であって、前記抗体は、ＨＶＲ－Ｈ１、ＨＶＲ－Ｈ２、及びＨＶＲ－Ｈ３を含む重鎖可変領域並びにＨＶＲ－Ｌ１、ＨＶＲ－Ｌ２、及びＨＶＲ－Ｌ３を含む軽鎖可変領域を含み、
ＨＶＲ－Ｈ１が配列番号８のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号９のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５４のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号９のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号９のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５５のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１１のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１２のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１３のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１４のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１５のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１６のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１７のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１８のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号１９のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２１のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２２のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２３のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２４のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２５のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２６のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２７のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２８のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５８のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２９のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５９のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２９のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６０のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２９のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６１のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２９のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６２のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号３０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号４０のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５９のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号３０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号４０のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６０のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号３０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号４０のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６１のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号３０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号４０のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６２のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号３０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６０のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号３０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６２のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２３のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６０のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２３のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６２のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号３０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５９のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号３０のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６１のアミノ酸配列を含む；
ＨＶＲ－Ｈ１が配列番号２３のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号５９のアミノ酸配列を含む；または
ＨＶＲ－Ｈ１が配列番号２３のアミノ酸配列を含み、ＨＶＲ－Ｈ２が配列番号３３のアミノ酸配列を含み、ＨＶＲ－Ｈ３が配列番号３９のアミノ酸配列を含み、ＨＶＲ－Ｌ１が配列番号４７のアミノ酸配列を含み、ＨＶＲ－Ｌ２が配列番号５３のアミノ酸配列を含み、及びＨＶＲ－Ｌ３が配列番号６１のアミノ酸配列を含む、抗体。 An isolated antibody that binds to CD33, said antibody comprising a heavy chain variable region comprising HVR-H1, HVR-H2 and HVR-H3 and HVR-L1, HVR-L2 and HVR-L3 comprising a light chain variable region;
HVR-H1 contains the amino acid sequence of SEQ ID NO:8, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO:9, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:54 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO:9, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO:9, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:55 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 10, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 11, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 12, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 13, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 14, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 15, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 16, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 17, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 18, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 19, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 20, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO:21, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO:22, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 23, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO:24, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 25, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO:26, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 27, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO:28, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:58;
HVR-H1 contains the amino acid sequence of SEQ ID NO:29, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:59;
HVR-H1 contains the amino acid sequence of SEQ ID NO:29, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:60;
HVR-H1 contains the amino acid sequence of SEQ ID NO:29, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:61;
HVR-H1 contains the amino acid sequence of SEQ ID NO:29, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:62;
HVR-H1 contains the amino acid sequence of SEQ ID NO:30, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:40, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:59;
HVR-H1 contains the amino acid sequence of SEQ ID NO:30, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:40, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:60;
HVR-H1 contains the amino acid sequence of SEQ ID NO:30, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:40, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:61;
HVR-H1 contains the amino acid sequence of SEQ ID NO:30, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:40, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:62;
HVR-H1 contains the amino acid sequence of SEQ ID NO:30, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:60;
HVR-H1 contains the amino acid sequence of SEQ ID NO:30, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:62;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 23, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:60;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 23, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:62;
HVR-H1 contains the amino acid sequence of SEQ ID NO:30, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:59;
HVR-H1 contains the amino acid sequence of SEQ ID NO:30, HVR-H2 contains the amino acid sequence of SEQ ID NO:33, HVR-H3 contains the amino acid sequence of SEQ ID NO:39, and HVR-L1 contains the amino acid sequence of SEQ ID NO:47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:61;
HVR-H1 contains the amino acid sequence of SEQ ID NO: 23, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:59; or
HVR-H1 contains the amino acid sequence of SEQ ID NO: 23, HVR-H2 contains the amino acid sequence of SEQ ID NO: 33, HVR-H3 contains the amino acid sequence of SEQ ID NO: 39, and HVR-L1 contains the amino acid sequence of SEQ ID NO: 47. wherein HVR-L2 comprises the amino acid sequence of SEQ ID NO:53 and HVR-L3 comprises the amino acid sequence of SEQ ID NO:61 . 前記抗体が、
配列番号６８のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号６９のアミノ酸配列を含む重鎖可変領域、及び配列番号９８のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号６９のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号６９のアミノ酸配列を含む重鎖可変領域、及び配列番号９９のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７０のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７１のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７２のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７３のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７４のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７５のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７６のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７７のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７８のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号７９のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８０のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８１のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８２のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８３のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８４のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８５のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８６のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８７のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８８のアミノ酸配列を含む重鎖可変領域、及び配列番号９７のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８９のアミノ酸配列を含む重鎖可変領域、及び配列番号１００のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８９のアミノ酸配列を含む重鎖可変領域、及び配列番号１０１のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８９のアミノ酸配列を含む重鎖可変領域、及び配列番号１０２のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８９のアミノ酸配列を含む重鎖可変領域、及び配列番号１０３のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９０のアミノ酸配列を含む重鎖可変領域、及び配列番号１００のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９０のアミノ酸配列を含む重鎖可変領域、及び配列番号１０１のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９０のアミノ酸配列を含む重鎖可変領域、及び配列番号１０２のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９０のアミノ酸配列を含む重鎖可変領域、及び配列番号１０３のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９１のアミノ酸配列を含む重鎖可変領域、及び配列番号１００のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９１のアミノ酸配列を含む重鎖可変領域、及び配列番号１０１のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９１のアミノ酸配列を含む重鎖可変領域、及び配列番号１０２のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９１のアミノ酸配列を含む重鎖可変領域、及び配列番号１０３のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９２のアミノ酸配列を含む重鎖可変領域、及び配列番号１０１のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９２のアミノ酸配列を含む重鎖可変領域、及び配列番号１０３のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９３のアミノ酸配列を含む重鎖可変領域、及び配列番号１０１のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９３のアミノ酸配列を含む重鎖可変領域、及び配列番号１０３のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８３のアミノ酸配列を含む重鎖可変領域、及び配列番号１０１のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８３のアミノ酸配列を含む重鎖可変領域、及び配列番号１０３のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９２のアミノ酸配列を含む重鎖可変領域、及び配列番号１００のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９２のアミノ酸配列を含む重鎖可変領域、及び配列番号１０２のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９３のアミノ酸配列を含む重鎖可変領域、及び配列番号１００のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号９３のアミノ酸配列を含む重鎖可変領域、及び配列番号１０２のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８３のアミノ酸配列を含む重鎖可変領域、及び配列番号１００のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号８３のアミノ酸配列を含む重鎖可変領域、及び配列番号１０２のアミノ酸配列を含む軽鎖可変領域を含む；
配列番号１２０のアミノ酸配列を含む重鎖、及び配列番号１２２のアミノ酸配列を含む軽鎖を含む；または
配列番号１２１のアミノ酸配列を含む重鎖、及び配列番号１２２のアミノ酸配列を含む軽鎖を含む
請求項１に記載の抗体。 the antibody
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:68 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:69 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:98;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:69 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:69 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:99;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:70 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:71 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:72 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:73 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:74 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:75 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:76 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:77 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:78 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:79 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:80 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:81 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:82 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:83 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:84 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:85 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:86 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:87 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:88 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:97;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:89 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:100;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:89 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:101;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:89 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:102;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:89 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:103;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:90 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:100;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:90 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:101;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:90 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:102;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:90 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:103;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:91 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:100;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:91 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:101;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:91 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:102;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:91 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:103;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:92 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:101;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:92 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:103;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:93 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:101;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:93 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:103;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:83 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:101;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:83 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:103;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:92 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:100;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:92 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:102;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:93 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:100;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:93 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:102;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:83 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:100;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:83 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:102;
a heavy chain comprising the amino acid sequence of SEQ ID NO: 120 and a light chain comprising the amino acid sequence of SEQ ID NO: 122; or
A heavy chain comprising the amino acid sequence of SEQ ID NO: 121 and a light chain comprising the amino acid sequence of SEQ ID NO: 122
The antibody of claim 1 . 重鎖可変領域が、配列番号２３のアミノ酸配列を含むＨＶＲ－Ｈ１、配列番号３３のアミノ酸配列を含むＨＶＲ－Ｈ２、及び配列番号３９のアミノ酸配列を含むＨＶＲ－Ｈ３を含み、且つ軽鎖可変領域が、配列番号４７のアミノ酸配列を含むＨＶＲ－Ｌ１、配列番号５３のアミノ酸配列を含むＨＶＲ－Ｌ２、及び配列番号６１のアミノ酸配列を含むＨＶＲ－Ｌ３を含む、請求項１に記載の抗体。 The heavy chain variable region comprises HVR-H1 comprising the amino acid sequence of SEQ ID NO:23, HVR-H2 comprising the amino acid sequence of SEQ ID NO:33, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:39, and the light chain variable region comprises HVR-L1 comprising the amino acid sequence of SEQ ID NO:47, HVR-L2 comprising the amino acid sequence of SEQ ID NO:53, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:61 . 前記抗体が、
（ａ）配列番号８３のアミノ酸配列を含む重鎖可変領域、及び配列番号１０２のアミノ酸配列を含む軽鎖可変領域を含む；
（ｂ）配列番号１２０のアミノ酸配列を含む重鎖、及び配列番号１２２のアミノ酸配列を含む軽鎖を含む；または
（ｃ）配列番号１２１のアミノ酸配列を含む重鎖、及び配列番号１２２のアミノ酸配列を含む軽鎖を含む
請求項２に記載の抗体。 the antibody
(a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:83 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:102;
(b) a heavy chain comprising the amino acid sequence of SEQ ID NO:120 and a light chain comprising the amino acid sequence of SEQ ID NO:122; or
(c) a heavy chain comprising the amino acid sequence of SEQ ID NO: 121 and a light chain comprising the amino acid sequence of SEQ ID NO: 122
3. The antibody of claim 2 . （ｉ）前記抗体は、モノクローナル抗体である；及び／または
（ｉｉ）前記抗体は、ＩｇＧクラス、ＩｇＭクラス、またはＩｇＡクラスのものであり、任意選択的に、前記抗体は、ＩｇＧクラスのものであり、ＩｇＧ１、ＩｇＧ２、ＩｇＧ３、またはＩｇＧ４アイソタイプを有する、請求項１～４のいずれか１項に記載の抗体。 (i) said antibody is a monoclonal antibody; and/or
(ii) said antibody is of the IgG, IgM or IgA class, optionally said antibody is of the IgG class and has an IgG1, IgG2, IgG3 or IgG4 isotype. Item 5. The antibody according to any one of items 1 to 4 . （ｉ）前記抗体は、Ｆｃ領域においてＣ１２７Ｓ、Ｌ２３４Ａ、Ｌ２３４Ｆ、Ｌ２３５Ａ、Ｌ２３５Ｅ、Ｓ２６７Ｅ、Ｋ３２２Ａ、Ｌ３２８Ｆ、Ａ３３０Ｓ、Ｐ３３１Ｓ、Ｅ３４５Ｒ、Ｅ４３０Ｇ、Ｓ４４０Ｙ、及びこれらの任意の組み合わせからなる群から選択される残基位置に１つ以上のアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従う；
（ｉｉ）前記抗体は、ＩｇＧ４アイソタイプを有し、残基位置２２８にＳ２２８Ｐアミノ酸置換、残基位置２３４にＬ２３４Ａアミノ酸置換、及び残基位置２３５にＬ２３５Ａアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従う；または
（ｉｉｉ）：
（ａ）Ｆｃ領域は、位置Ｅ４３０Ｇにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｂ）Ｆｃ領域は、位置Ｌ２３４Ａ、Ｌ２３５Ａ、及びＰ３３１Ｓにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｃ）Ｆｃ領域は、位置Ｌ２３４Ａ、Ｌ２３５Ａ、Ｐ３３１Ｓ、及びＥ４３０Ｇにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｄ）Ｆｃ領域は、位置Ｋ３２２Ａ及びＥ４３０Ｇにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｅ）Ｆｃ領域は、位置Ｐ３３１Ｓ及びＥ４３０Ｇにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｆ）Ｆｃ領域は、位置Ａ３３０Ｓ、Ｐ３３１Ｓ、及びＥ４３０Ｇにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｇ）Ｆｃ領域は、位置Ｋ３２２Ａ、Ａ３３０Ｓ、及びＰ３３１Ｓにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｈ）Ｆｃ領域は、位置Ｋ３２２Ａ、Ｐ３３１Ｓ、及びＥ４３０Ｇにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｉ）Ｆｃ領域は、位置Ｅ４３０Ｇにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｊ）Ｆｃ領域は、位置Ａ３３０Ｓ、Ｐ３３１Ｓ、及びＥ４３０Ｇにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｋ）Ｆｃ領域は、位置Ｓ２６７Ｅ及びＬ３２８Ｆにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｌ）Ｆｃ領域は、位置Ｃ１２７Ｓにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｍ）Ｆｃ領域は、位置Ｅ３４５Ｒ、Ｅ４３０Ｇ、及びＳ４４０Ｙにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、
（ｎ）Ｆｃ領域は、位置Ｐ３３１Ｓにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従うか、または
（ｏ）Ｆｃ領域は、位置Ｌ２３４Ａ、Ｌ２３５Ａ、及びＰ３３１Ｓにアミノ酸置換を含み、前記残基位置のナンバリングは、ＥＵナンバリングに従う、
請求項１～５のいずれか１項に記載の抗体。 (i) the antibody has a residue selected from the group consisting of C127S, L234A, L234F, L235A, L235E, S267E, K322A, L328F, A330S, P331S, E345R, E430G, S440Y, and any combination thereof in the Fc region; containing one or more amino acid substitutions at a radical position, the numbering of said residue positions according to EU numbering;
(ii) said antibody has an IgG4 isotype and comprises a S228P amino acid substitution at residue position 228, a L234A amino acid substitution at residue position 234, and a L235A amino acid substitution at residue position 235, wherein said residue position numbering is , according to EU numbering; or
(iii):
(a) the Fc region comprises an amino acid substitution at position E430G, the numbering of said residue positions according to EU numbering;
(b) the Fc region comprises amino acid substitutions at positions L234A, L235A, and P331S, wherein the numbering of said residue positions is according to EU numbering;
(c) the Fc region comprises amino acid substitutions at positions L234A, L235A, P331S, and E430G, wherein the numbering of said residue positions follows EU numbering;
(d) the Fc region comprises amino acid substitutions at positions K322A and E430G, wherein the numbering of said residue positions is according to EU numbering, or
(e) the Fc region comprises amino acid substitutions at positions P331S and E430G, the numbering of said residue positions according to EU numbering;
(f) the Fc region comprises amino acid substitutions at positions A330S, P331S, and E430G, the numbering of said residue positions according to EU numbering, or
( g) the Fc region comprises amino acid substitutions at positions K322A, A330S, and P331S, the numbering of said residue positions according to EU numbering, or
(h) the Fc region comprises amino acid substitutions at positions K322A, P331S, and E430G, the numbering of said residue positions according to EU numbering;
(i) the Fc region comprises an amino acid substitution at position E430G, the numbering of said residue positions according to EU numbering;
(j) the Fc region comprises amino acid substitutions at positions A330S, P331S, and E430G, the numbering of said residue positions according to EU numbering;
(k) the Fc region comprises amino acid substitutions at positions S267E and L328F, wherein the numbering of said residue positions is according to EU numbering;
(l) the Fc region comprises an amino acid substitution at position C127S, the numbering of said residue positions according to EU numbering, or
( m) the Fc region comprises amino acid substitutions at positions E345R, E430G, and S440Y, the numbering of said residue positions according to EU numbering;
(n) the Fc region comprises an amino acid substitution at position P331S, the numbering of said residue positions according to EU numbering, or
(o) the Fc region comprises amino acid substitutions at positions L234A, L235A, and P331S, the numbering of said residue positions according to EU numbering;
The antibody according to any one of claims 1-5 . （ｉ）前記抗体は、ヒトＣＤ３３または哺乳動物ＣＤ３３タンパク質上のアミノ酸残基を含むエピトープに結合する抗体断片である；
（ｉｉ）前記抗体は、ヒトＣＤ３３、ヒトＣＤ３３の天然に存在するバリアント、及びヒトＣＤ３３の疾患バリアントからなる群から選択される１つ以上のヒトタンパク質に結合する抗体断片であり、
任意選択的に、前記抗体断片は、ヒトＣＤ３３、ヒトＣＤ３３の天然に存在するバリアント、及びヒトＣＤ３３の疾患バリアントからなる群から選択される１つ以上のヒトタンパク質に結合する第２の抗体断片に架橋されている、及び／または前記断片は、Ｆａｂ、Ｆａｂ′、Ｆａｂ′－ＳＨ、Ｆ（ａｂ′）２、Ｆｖ、またはｓｃＦｖ断片である、
請求項１～６のいずれか１項に記載の抗体。 (i) the antibody is an antibody fragment that binds to an epitope comprising amino acid residues on human CD33 or mammalian CD33 protein;
(ii) said antibody is an antibody fragment that binds to one or more human proteins selected from the group consisting of human CD33, naturally occurring variants of human CD33, and disease variants of human CD33;
Optionally, said antibody fragment binds to one or more human proteins selected from the group consisting of human CD33, naturally occurring variants of human CD33, and disease variants of human CD33. is cross-linked and/or said fragment is a Fab, Fab', Fab'-SH, F(ab')2, Fv or scFv fragment;
The antibody according to any one of claims 1-6 . （ｉ）前記抗体は、配列番号３のアミノ酸配列を含む重鎖可変領域及び配列番号４のアミノ酸配列を含む軽鎖可変領域を含む抗ＣＤ３３抗体よりも少なくとも１．８倍低いヒトＣＤ３３についての解離定数（Ｋ Ｄ ）を有し、前記Ｋ Ｄ は、ＢｉｏＬａｙｅｒ干渉法によって決定される；
（ｉｉ）前記抗体は、約２ｎＭ～約２００ｐＭの範囲、または約２００ｐＭ未満のヒトＣＤ３３についての解離定数（Ｋ Ｄ ）を有し、前記Ｋ Ｄ は、ＢｉｏＬａｙｅｒ干渉法によって決定される；
（ｉｉｉ）前記抗体は、フローサイトメトリーによって測定して４０ｐＭ未満の半数有効濃度（ＥＣ ５０ ）で、ｉｎ ｖｉｔｒｏでＣＤ３３の細胞表面レベルを低下させる；及び／または
（ｉｖ）前記抗体は、配列番号１１８のアミノ酸配列を含むＦｃ領域を含む、
請求項１～７のいずれか１項に記載の抗体。 (i) the antibody dissociates human CD33 at least 1.8-fold lower than an anti-CD33 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:3 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4 has a constant (K D ), said K D being determined by BioLayer interferometry;
(ii) said antibody has a dissociation constant (K D ) for human CD33 in the range of about 2 nM to about 200 pM, or less than about 200 pM, said K D determined by BioLayer interferometry;
(iii) said antibody reduces cell surface levels of CD33 in vitro with a half effective concentration (EC50) of less than 40 pM as measured by flow cytometry; and / or
(iv) said antibody comprises an Fc region comprising the amino acid sequence of SEQ ID NO: 118;
The antibody according to any one of claims 1-7 . 請求項１～８のいずれか１項に記載の抗体の軽鎖及び重鎖をコードする核酸配列を含む、１つ以上の単離された核酸。 One or more isolated nucleic acids comprising nucleic acid sequences encoding the light and heavy chains of the antibody of any one of claims 1-8 . 請求項９に記載の１つ以上の核酸を含む、１つ以上のベクター。 One or more vectors comprising one or more nucleic acids according to claim 9 . 請求項１０に記載の１つ以上のベクターを含む、単離された宿主細胞。 An isolated host cell comprising one or more vectors of claim 10 . ＣＤ３３に結合する抗体を生成する方法であって、前記抗体が生成されるように請求項１１に記載の細胞を培養することを含む、方法。 12. A method of producing an antibody that binds to CD33, comprising culturing the cells of claim 11 such that said antibody is produced . 前記細胞によって生成された前記抗体を回収することを更に含む、請求項１２に記載の方法。 13. The method of claim 12, further comprising collecting said antibodies produced by said cells . 請求項１～８のいずれか１項に記載の抗体並びに薬学的に許容される担体を含む、医薬組成物。 A pharmaceutical composition comprising the antibody of any one of claims 1-8 and a pharmaceutically acceptable carrier . 認知症、前頭側頭型認知症、アルツハイマー病、血管性認知症、混合型認知症、タウパチー病、感染症、及びがんからなる群から選択される疾患、障害、または傷害を予防し、そのリスクを低下させ、または治療する方法であって、それを必要とする個体に、治療有効量の抗体を投与することを含む方法において使用するための、請求項１～８のいずれか１項に記載の抗体。 preventing a disease, disorder, or injury selected from the group consisting of dementia, frontotemporal dementia, Alzheimer's disease, vascular dementia, mixed dementia, taupathy disease, infectious disease, and cancer; 9. The method of any one of claims 1-8 for use in a method of risk reduction or treatment comprising administering a therapeutically effective amount of the antibody to an individual in need thereof. Antibodies as indicated .
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