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- JP2014113157A5 JP2014113157A5 JP2014002379A JP2014002379A JP2014113157A5 JP 2014113157 A5 JP2014113157 A5 JP 2014113157A5 JP 2014002379 A JP2014002379 A JP 2014002379A JP 2014002379 A JP2014002379 A JP 2014002379A JP 2014113157 A5 JP2014113157 A5 JP 2014113157A5
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- 改変第ＶＩＩ因子（ＦＶＩＩ）ポリペプチドであって、
ａ）該ＦＶＩＩポリペプチドは：
配列番号１〜３および１８〜７４のいずれかに示されるアミノ酸の配列を含む非改変ＦＶＩＩポリペプチドと比較して、１、２、３、４、５、６または７つのみのアミノ酸交換、または
配列番号１〜３および１８〜７４のいずれかに示されるアミノ酸の配列を含む非改変ＦＶＩＩポリペプチドと比較して、１、２、３、４、５、６または７つのみのアミノ酸交換、およびＧｌａドメインのすべてまたは一部分の交換を有し；
ｂ）１つのアミノ酸交換が、配列番号３に示されるアミノ酸の配列を有するＦＶＩＩポリペプチドにおける位置２８６に対応する位置にあり；かつ
ｃ）位置２８６での交換が、位置２８６に改変を有していないＦＶＩＩポリペプチドと比較して増加した血液凝固活性を示す改変ＦＶＩＩポリペプチドをもたらす、アルギニン（Ａｒｇ、Ｒ）との交換である、
改変第ＶＩＩ因子（ＦＶＩＩ）ポリペプチド。 - 活性化ＦＶＩＩａポリペプチドである、請求項１に記載の改変ＦＶＩＩポリペプチド。
- 位置２９８での交換を含む、請求項１または２に記載の改変ＦＶＩＩポリペプチド。
- 非改変ＦＶＩＩポリペプチドが、配列番号３に示されるアミノ酸の配列を含む、請求項１または２に記載の改変ＦＶＩＩポリペプチド。
- 非改変ＦＶＩＩポリペプチドが、配列番号３に示されるアミノ酸の配列からなる、請求項１または２に記載の改変ＦＶＩＩポリペプチド。
- アミノ酸交換Ｑ２８６Ｒを含む、請求項１に記載の改変ＦＶＩＩポリペプチド。
- ２８６Ｒに対応する交換に加えて、アミノ酸交換が、５１、５２、５４、６０、６６、６８、１０９、１１９、１２２、１２４、１３０、１３２、１５８、１６１、１７５、１９６、１９７、１９９、２０２、２１６、２２２、２３７、２３９、２５７、２８６、２８７、２９０、２９２、２９４、２９６、２９８、３０５、３１４、３１８、３２１、３３７、３４１、３６６、３７３、３７４、３９４、３９５および３９６から選択される位置に対応する位置にある、請求項１および４〜６のいずれかに記載の改変ＦＶＩＩポリペプチド。
- Ｄ１９６Ｋ、Ｄ１９６Ｒ、Ｄ１９６Ａ、Ｄ１９６Ｙ、Ｄ１９６Ｆ、Ｄ１９６Ｗ、Ｄ１９６Ｌ、Ｄ１９６Ｉ、Ｋ１９７Ｙ、Ｋ１９７Ａ、Ｋ１９７Ｅ、Ｋ１９７Ｄ、Ｋ１９７Ｌ、Ｋ１９７Ｍ、Ｋ１９７Ｉ、Ｋ１９７Ｖ、Ｋ１９７Ｆ、Ｋ１９７Ｗ、Ｋ１９９Ａ、Ｋ１９９Ｄ、Ｋ１９９Ｅ、Ｇ２３７Ｗ、Ｇ２３７Ｔ、Ｇ２３７Ｉ、Ｇ２３７Ｖ、Ｔ２３９Ａ、Ｒ２９０Ａ、Ｒ２９０Ｅ、Ｒ２９０Ｄ、Ｒ２９０Ｎ、Ｒ２９０Ｑ、Ｒ２９０Ｋ、Ｒ２９０Ｍ、Ｒ２９０Ｖ、Ｋ３４１Ｅ、Ｋ３４１Ｒ、Ｋ３４１Ｑ、Ｋ３４１Ｎ、Ｋ３４１Ｍ、Ｋ３４１Ｄ、Ｔ２３９Ｓ、Ｔ２３９Ｎ、Ｔ２３９Ｑ、Ｔ２３９Ｖ、Ｔ２３９Ｌ、Ｔ２３９Ｈ、Ｔ２３９Ｉ、Ｌ２８７Ｔ、Ｍ２９８Ｑ、Ｐ３２１Ｋ、Ｐ３２１Ｅ、Ｐ３２１Ｙ、Ｐ３２１Ｓ、Ｑ３６６Ｄ、Ｑ３６６Ｅ、Ｑ３６６Ｎ、Ｑ３６６Ｔ、Ｑ３６６Ｓ、Ｑ３６６Ｖ、Ｑ３６６Ｉ、Ｑ３６６Ｌ、Ｑ３６６Ｍ、Ｈ３７３Ｄ、Ｈ３７３Ｅ、Ｈ３７３Ｓ、Ｈ３７３Ｌ、Ｈ３７３Ｉ、Ｈ３７３Ｆ、Ｈ３７３Ａ、Ｋ１６１Ｓ、Ｋ１６１Ａ、Ｋ１６１Ｖ、Ｈ２１６Ｓ、Ｈ２１６Ａ、Ｈ２１６Ｋ、Ｈ２１６Ｒ、Ｓ２２２Ａ、Ｓ２２２Ｋ、Ｓ２２２Ｖ、Ｓ２２２Ｎ、Ｓ２２２Ｅ、Ｓ２２２Ｄ、Ｈ２５７Ａ、Ｈ２５７Ｓ、Ｇｌａ Ｓｗａｐ ＦＩＸ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｅ４０Ｌ｝、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｋ４３Ｉ｝、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｑ４４Ｓ｝、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｍ１９Ｋ｝、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｍ１９Ｋ／Ｅ４０Ｌ／Ｋ４３Ｉ／Ｑ４４Ｓ｝、Ｇｌａ Ｓｗａｐ ＦＸ、Ｇｌａ Ｓｗａｐ Ｐｒｏｔ Ｃ、Ｇｌａ Ｓｗａｐ Ｐｒｏｔ Ｓ、Ｇｌａ Ｓｗａｐ トロンビン、Ｓ５２Ａ、Ｓ６０Ａ、Ｅ３９４Ｎ、Ｐ３９５Ａ、Ｒ３９６Ｓ、Ｒ２０２Ｓ、Ａ２９２Ｎ、Ａ２９４Ｓ、Ｇ３１８Ｎ、Ａ１７５Ｓ、Ｋ１０９Ｎ、Ａ１２２Ｎ、Ｇ１２４Ｓ、Ａ５１Ｎ、Ｔ１３０Ｎ、Ｅ１３２Ｓ、Ｓ５２Ｎ、Ｐ５４Ｓ、Ｓ１１９Ｎ、Ｌ１２１Ｓ、Ｔ１２８Ｎ、Ｐ１２９Ａ、Ｑ６６Ｎ、Ｙ６８Ｓ、Ｖ１５８Ｔ、Ｖ１５８Ｄ、Ｌ２８７ＴおよびＥ２９６Ｖから選択されるアミノ酸交換を含む、請求項１〜７のいずれかに記載の改変ＦＶＩＩポリペプチド。
- Ｑ２８６Ｒ、Ｑ２８６Ｒ／Ｈ２５７Ａ、Ｑ２８６Ｒ／Ｓ２２２Ａ、Ｑ２８６Ｒ／Ｓ２２２Ａ／Ｈ２５７Ａ、Ｑ２８６Ｒ／Ｓ２２２Ａ／Ｇｌａ Ｓｗａｐ ＦＩＸ、Ｑ２８６Ｒ／Ｈ２５７Ａ／Ｇｌａ Ｓｗａｐ ＦＩＸ、Ｑ２８６Ｒ／Ｓ２２２Ａ／Ｈ２５７Ａ／Ｇｌａ Ｓｗａｐ ＦＩＸ、Ｑ２８６Ｒ／Ｑ３６６Ｖ、Ｑ２８６Ｒ／Ａ２９２Ｎ／Ａ２９４Ｓ／Ｑ３６６Ｖ、Ａ１７５Ｓ／Ｑ２８６Ｒ／Ｑ３６６Ｖ、Ｓ２２２Ａ／Ｑ２８６Ｒ／Ｑ３６６Ｖ、Ｈ２５７Ｓ／Ｑ２８６Ｒ、Ｈ２５７Ｓ／Ｑ２８６Ｒ／Ｑ３６６Ｖ、Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｑ３６６Ｖ、Ｑ２８６Ｒ／Ｈ３７３Ａ、Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｑ２８６Ｒ／Ｋ３４１Ｄ、Ｑ２８６Ｒ／Ｑ３６６Ｄ、Ｑ２８６Ｒ／Ｑ３６６Ｎ、Ｑ２８６Ｒ／Ｈ３７３Ｆ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｈ３７３Ｆ、Ｓ５２Ａ／Ｓ６０Ａ／Ｑ２８６Ｒ、Ｓ５２Ａ／Ｓ６０Ａ／Ｑ２８６Ｒ／Ｈ３７３Ｆ、Ｔ２３９Ｖ／Ｑ２８６Ｒ、Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｈ３７３Ｆ、Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｈ３７３Ｆ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ａ１７５Ｓ／Ｑ２８６Ｒ、Ａ１２２Ｎ／Ｇ１２４Ｓ／Ａ１７５Ｓ／Ｑ２８６Ｒ、Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｋ３４１Ｑ、Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｋ１９９Ｅ、Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｇｌａ Ｓｗａｐ ＦＩＸ、Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｄ、Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｅ４０Ｌ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｋ４３Ｉ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｑ４４Ｓ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｍ１９Ｋ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｍ１９Ｋ／Ｅ４０Ｌ／Ｋ４３Ｉ／Ｑ４４Ｓ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｖ１５８Ｄ／Ｑ２８６Ｒ／Ｅ２９６Ｖ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｓ５２Ａ／Ｓ６０Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｓ５２Ａ／Ｓ６０Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｓ５２Ａ／Ｓ６０Ａ／Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｓ５２Ａ／Ｓ６０Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｓ２２２Ａ／Ｔ２３９Ｖ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｓ２２２Ａ／Ｔ２３９Ｉ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｓ２２２Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｓ２２２Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｖ１５８Ｄ／Ｑ２８６Ｒ／Ｅ２９６Ｖ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｈ２５７Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｓ２２２Ａ／Ｈ２５７Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｈ２５７Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｓ２２２Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｓ２２２Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ａ１７５Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ａ１２２Ｎ／Ｇ１２４Ｓ／Ａ１７５Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ａ１７５Ｓ／Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ａ１２２Ｎ／Ｇ１２４Ｓ／Ａ１７５Ｓ／Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ａ１７５Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ａ１２２Ｎ／Ｇ１２４Ｓ／Ａ１７５Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｋ４３Ｉ｝／Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｋ４３Ｉ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｋ４３Ｉ｝／Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、Ｖ１５８Ｄ／Ｑ２８６Ｒ／Ｅ２９６Ｖ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ／Ｈ３７３Ｆ、Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｓ２２２Ａ／Ｔ２３９Ｖ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８ＱおよびＴ１２８Ｎ／Ｐ１２９Ａ／Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆから選択されるアミノ酸交換を含む、請求項１〜８のいずれかに記載の改変ＦＶＩＩポリペプチド。
- Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ／Ｈ３７３Ｆ、Ｖ１５８Ｄ／Ｑ２８６Ｒ／Ｅ２９６Ｖ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ａ１２２Ｎ／Ｇ１２４Ｓ／Ａ１７５Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ａ１７５Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ａ１２２Ｎ／Ｇ１２４Ｓ／Ａ１７５Ｓ／Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ａ１７５Ｓ／Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ａ１２２Ｎ／Ｇ１２４Ｓ／Ａ１７５Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ａ１７５Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｓ２２２Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｓ２２２Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｓ２２２Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｓ２２２Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｓ２２２Ａ／Ｈ２５７Ｓ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｓ２２２Ａ／Ｔ２３９Ｉ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ２３９Ｉ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｓ２２２Ａ／Ｔ２３９Ｖ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｓ２２２Ａ／Ｔ２３９Ｖ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｔ２３９Ｖ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｖ１５８Ｄ／Ｑ２８６Ｒ／Ｅ２９６Ｖ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｈ３７３Ｆ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ Ｋ［４３］Ｉ｝／Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ Ｋ［４３］Ｉ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、Ｑ２８６Ｒ／Ｍ２９８Ｑ／Ｑ３６６Ｎ、Ｓ５２Ａ／Ｓ６０Ａ／Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｓ２２２Ａ／Ｈ２５７Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｋ４３Ｉ｝／Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｓ５２Ａ／Ｓ６０Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、Ｓ５２Ａ／Ｓ６０Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｍ１９Ｋ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｑ４４Ｓ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｋ４３Ｉ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ、｛Ｇｌａ Ｓｗａｐ ＦＩＸ／Ｅ［４０］Ｌ｝／Ｑ２８６Ｒ／Ｍ２９８Ｑ、およびＧｌａ Ｓｗａｐ ＦＩＸ／Ｔ１２８Ｎ／Ｐ１２９Ａ／Ｑ２８６Ｒ／Ｍ２９８Ｑから選択される改変を含む、請求項１〜９のいずれかに記載の改変ＦＶＩＩポリペプチド。
- 配列番号１１８、１３１〜１５７、２７４〜２８２、２８５〜２８８、２９０、２９２、２９４〜２９７、２９９、３０１〜３０５、３０８、３１０〜３１８、３２０〜３２６、３２８、３３４〜３４２、３５５〜３５８、３６０および３６４〜３７１のいずれかに示すアミノ酸の配列を含む請求項１〜１０のいずれかに記載の改変ＦＶＩＩポリペプチド。
- 配列番号３に示すアミノ酸の配列を有するＦＶＩＩポリペプチドにおける位置２９８に対応する位置におけるアミノ酸交換を含み、位置２９８での交換がグルタミン（Ｇｌｎ、Ｑ）との交換である、請求項１〜１０のいずれかに記載の改変ＦＶＩＩポリペプチド。
- 突然変異Ｑ２８６Ｒ／Ｍ２９８Ｑを含む、請求項１〜１２のいずれかに記載の改変ＦＶＩＩポリペプチド。
- グリコシル化部位を導入する、１以上のアミノ酸交換を含む請求項１〜１３のいずれかに記載の改変ＦＶＩＩポリペプチドであって、１以上の追加のグリコシル化部位が、Ｓ５２Ａ、Ｓ６０Ａ、Ｅ３９４Ｎ／Ｐ３９５Ａ／Ｒ３９６Ｓ、Ｒ２０２Ｓ、Ａ２９２Ｎ／Ａ２９４Ｓ、Ｇ３１８Ｎ、Ａ１７５Ｓ、Ｋ１０９Ｎ、Ａ１２２Ｎ／Ｇ１２４Ｓ、Ａ５１Ｎ、Ｔ１３０Ｎ／Ｅ１３２Ｓ、Ａ１２２Ｎ／Ｇ１２４Ｓ／Ｅ３９４Ｎ／Ｐ３９５Ａ／Ｒ３９６Ｓ、Ａ１２２Ｎ／Ｇ１２４Ｓ／Ｅ３９４Ｎ／Ｐ３９５Ａ／Ｒ３９６Ｓ／Ｇ３１８Ｎ、Ｓ５２Ａ／Ｓ６０Ａ、Ｓ５２Ｎ／Ｐ５４Ｓ、Ｓ１１９Ｎ／Ｌ１２１Ｓ、Ｔ１２８Ｎ／Ｐ１２９Ａ、Ｑ６６Ｎ／Ｙ６８Ｓ、Ｓ５２Ｎ／Ｐ５４Ｓ／Ａ１２２Ｎ／Ｇ１２４Ｓ／Ｅ３９４Ｎ／Ｐ３９５Ａ／Ｒ３９６Ｓ、Ｋ１０９Ｎ／Ａ２９２Ｎ／Ａ２９４Ｓ、Ｋ１０９Ｎ／Ａ１７５Ｓ、Ｓ１１９Ｎ／Ｌ１２１Ｓ／Ａ１７５Ｓ、Ｔ１２８Ｎ／Ｐ１２９Ａ／Ａ１７５ＳおよびＡ１２２Ｎ／Ｇ１２４Ｓ／Ａ１７５Ｓから選択される改変によって導入される、
改変ＦＶＩＩポリペプチド。 - 異種Ｇｌａドメインまたはリン脂質結合を行うのに十分なその部分を含む、請求項１〜１４のいずれかに記載の改変ＦＶＩＩポリペプチド。
- 異種Ｇｌａドメインが、第ＩＸ因子（ＦＩＸ）、第Ｘ因子（ＦＸ）、プロトロンビン、プロテインＣ、プロテインＳ、オステオカルシン、マトリックスＧｌａタンパク質、増殖停止特異的タンパク質６（Ｇａｓ６）、およびプロテインＺにおけるＧｌａドメインの中から選択される、請求項１５に記載の改変ＦＶＩＩポリペプチド。
- 化学改変または翻訳後改変を含む、請求項１〜１６のいずれかに記載の改変ＦＶＩＩポリペプチド。
- ＦＶＩＩポリペプチドが、グリコシル化、カルボキシル化、ヒドロキシル化、硫酸化、リン酸化、アルブミン化、またはポリエチレングリコール（ＰＥＧ）部分にコンジュゲートされる、請求項１５に記載の改変ＦＶＩＩポリペプチド。
- 二本鎖ＦＶＩＩａポリペプチドである、請求項１〜１８のいずれかに記載の改変ＦＶＩＩポリペプチド。
- 活性化されている、請求項１〜１９のいずれかに記載の改変ＦＶＩＩポリペプチド。
- 配列番号３の残基Ｒ１５２および残基Ｉ１５３の間でのタンパク質分解による切断によって活性化されている、単一のジスルフィド結合によって連結された二本鎖プロテアーゼ（ＦＶＩＩａ）をもたらす、ＦＶＩＩａポリペプチドである、請求項１〜２０のいずれかに記載の改変ＦＶＩＩポリペプチド。
- 一本鎖ポリペプチドである、請求項１〜１８のいずれかに記載の改変ＦＶＩＩポリペプチド。
- 請求項１〜２２のいずれかに記載の改変ＦＶＩＩポリペプチドをコードするヌクレオチドの配列を含む核酸分子。
- 請求項２３に記載の核酸分子を含むベクター。
- 請求項２４に記載のベクターを含む細胞。
- 薬学的に許容可能な媒体中に、治療有効濃度または治療有効量の、請求項１〜２２のいずれかに記載の改変ＦＶＩＩポリペプチドを含む医薬組成物。
- 薬学的に許容可能な媒体中に、請求項２４に記載のベクターを含む医薬組成物。
- 薬学的に許容可能な媒体中に、請求項２５に記載の細胞を含む医薬組成物。
- 単回投与用に製剤されている、請求項２６〜２８のいずれかに記載の医薬組成物。
- 経口投与、経鼻投与、経肺投与、頬側投与、経皮投与、皮下投与、十二指腸内投与、経腸投与、非経口投与、静脈内投与、または筋肉内投与用に製剤されている、請求項２６〜２９のいずれかに記載の医薬組成物。
- 凍結乾燥されている、請求項２６〜３０のいずれかに記載の医薬組成物。
- 処置されることとなる疾患または状態が、血液凝固障害、血液障害、出血性障害、血友病、第ＶＩＩ因子欠乏症、出血障害、手術による出血、または外傷による出血の中から選択される、ＦＶＩＩまたは凝固促進剤の投与によって処置される疾患または状態を処置するための、請求項１〜２２のいずれかに記載の改変ＦＶＩＩポリペプチドの使用。
- 疾患または状態が血友病であり、血友病が、血友病Ａまたは血友病Ｂまたは血友病Ｃである、請求項３２に記載の使用。
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