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1. 发明授权

US08569032B2 Proteins having acquired A-galactosidase activity 有权
标题翻译：已获得α-半乳糖苷酶活性的蛋白质
公开(公告)号：US08569032B2
公开(公告)日：2013-10-29
申请号：US12600497
申请日：2008-05-19
申请人： Hitoshi Sakuraba , Youichi Tajima , Ikuo Kawashima , Seiichi Aikawa , Fumiko Aikawa
发明人： Hitoshi Sakuraba , Youichi Tajima , Ikuo Kawashima , Seiichi Aikawa , Fumiko Aikawa
IPC分类号： C12N9/40
CPC分类号： C12N9/2465 , A61K38/47 , A61K48/005
摘要： The present invention provides a pharmaceutical composition comprising a protein having α-galactosidase activity for treating Fabry disease, which causes no allergic side effect, which is highly stable in blood (plasma) and which can readily be taken up by a cell of an affected organ. The pharmaceutical composition for treating Fabry disease of the invention comprises, for example, a protein which acquires an α-galactosidase activity through alteration of the structure of the active site of wild-type human α-N-acetylgalactosaminidase.
摘要翻译：本发明提供一种药物组合物，其包含具有用于治疗法布里病的α-半乳糖苷酶活性的蛋白质，其不引起过敏性副作用，其在血液（血浆）中高度稳定并且可容易地被受影响器官的细胞摄取。用于治疗本发明的法布里病的药物组合物包括例如通过改变野生型人α-N-乙酰半乳糖胺酶的活性位点的结构获得α-半乳糖苷酶活性的蛋白质。

2. 发明授权

US08323640B2 Highly functional enzyme having α-galactosidase activity 有权
标题翻译：具有α-半乳糖苷酶活性的高功能酶
公开(公告)号：US08323640B2
公开(公告)日：2012-12-04
申请号：US13052632
申请日：2011-03-21
申请人： Hitoshi Sakuraba , Youichi Tajima , Mai Ito , Seiichi Aikawa , Fumiko Aikawa
发明人： Hitoshi Sakuraba , Youichi Tajima , Mai Ito , Seiichi Aikawa , Fumiko Aikawa
IPC分类号： A61K38/43 , C12N9/40 , C12N15/00 , C12P21/06 , C12P19/34 , C07H21/04 , C07K1/00
CPC分类号： C12N9/2465 , A61K38/00 , C12N9/2402 , C12Y302/01022 , C12Y302/01049
摘要： The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having α-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired α-galactosidase activity by changing the structure of the active site of wild-type human α-N-acetylgalactosaminidase.
摘要翻译：本发明提供作为法布里病的酶替代疗法的酶，不具有过敏性副作用的具有α-半乳糖苷酶活性的蛋白质在血液中显示高稳定性，并且可以容易地加入到受影响器官的细胞。本发明的蛋白质是通过改变野生型人α-N-乙酰半乳糖胺酶活性位点的结构而获得α-半乳糖苷酶活性的蛋白质。

3. 发明申请

US20110171198A1 HIGHLY FUNCTIONAL ENZYME HAVING ALPHA-GALACTOSIDASE ACTIVITY 有权
标题翻译：具有ALPHA-GALACTOSIDASE活性的高功能酶
公开(公告)号：US20110171198A1
公开(公告)日：2011-07-14
申请号：US13052632
申请日：2011-03-21
申请人： Hitoshi Sakuraba , Youichi Tajima , Mai Ito , Seiichi Aikawa , Fumiko Aikawa
发明人： Hitoshi Sakuraba , Youichi Tajima , Mai Ito , Seiichi Aikawa , Fumiko Aikawa
IPC分类号： C12N9/40 , C12N15/56 , C12N15/85 , C12N5/10 , C12P21/02 , A61K38/47 , A61P3/00
CPC分类号： C12N9/2465 , A61K38/00 , C12N9/2402 , C12Y302/01022 , C12Y302/01049
摘要： The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having α-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired α-galactosidase activity by changing the structure of the active site of wild-type human α-N-acetylgalactosaminidase.
摘要翻译：本发明提供作为法布里病的酶替代疗法的酶，不具有过敏性副作用的具有α-半乳糖苷酶活性的蛋白质在血液中显示高稳定性，并且可以容易地加入到受影响器官的细胞。本发明的蛋白质是通过改变野生型人α-N-乙酰半乳糖胺酶活性位点的结构而获得α-半乳糖苷酶活性的蛋白质。

4. 发明申请

US20100166728A1 Novel Highly Functional Enzyme Having Modified Substrate-Specificity 有权
标题翻译：具有修饰底物特异性的新型高功能酶
公开(公告)号：US20100166728A1
公开(公告)日：2010-07-01
申请号：US12084982
申请日：2006-11-17
申请人： Hitoshi Sakuraba , Youichi Tajima , Mai Ito , Seiichi Aikawa , Fumiko Aikawa
发明人： Hitoshi Sakuraba , Youichi Tajima , Mai Ito , Seiichi Aikawa , Fumiko Aikawa
IPC分类号： A61K38/47 , A61P3/00 , A61P13/12 , A61P27/02 , A61P25/00 , A61P9/04 , A61P17/00 , A61P29/00 , C12N9/40 , C12N15/56 , C12N15/63 , C12N5/00
CPC分类号： C12N9/2465 , A61K38/00 , C12N9/2402 , C12Y302/01022 , C12Y302/01049
摘要： The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having α-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired α-galactosidase activity by changing the structure of the active site of wild-type human α-N-acetylgalactosaminidase.
摘要翻译：本发明提供作为法布里病的酶替代疗法的酶，不具有过敏性副作用的具有α-半乳糖苷酶活性的蛋白质在血液中显示高稳定性，并且可以容易地加入到受影响器官的细胞。本发明的蛋白质是通过改变野生型人α-N-乙酰半乳糖胺酶活性位点的结构而获得α-半乳糖苷酶活性的蛋白质。

5. 发明授权

US07935336B2 Highly functional enzyme having α-galactosidase activity 有权
标题翻译：具有α-半乳糖苷酶活性的高功能酶
公开(公告)号：US07935336B2
公开(公告)日：2011-05-03
申请号：US12084982
申请日：2006-11-17
申请人： Hitoshi Sakuraba , Youichi Tajima , Mai Ito , Seiichi Aikawa , Fumiko Aikawa
发明人： Hitoshi Sakuraba , Youichi Tajima , Mai Ito , Seiichi Aikawa , Fumiko Aikawa
IPC分类号： A61K38/47 , A61K38/43 , C12N9/40 , C12N15/00 , C12P21/06 , C12P19/34 , C07H21/04
CPC分类号： C12N9/2465 , A61K38/00 , C12N9/2402 , C12Y302/01022 , C12Y302/01049
摘要： The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having α-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired α-galactosidase activity by changing the structure of the active site of wild-type human α-N-acetylgalactosaminidase.
摘要翻译：本发明提供作为法布里病的酶替代疗法的酶，不具有过敏性副作用的具有α-半乳糖苷酶活性的蛋白质在血液中显示高稳定性，并且可以容易地加入到受影响器官的细胞。本发明的蛋白质是通过改变野生型人α-N-乙酰半乳糖胺酶活性位点的结构而获得α-半乳糖苷酶活性的蛋白质。

6. 发明授权

US07579166B2 Glycoprotein and process for producing the same 失效
标题翻译：糖蛋白及其制备方法
公开(公告)号：US07579166B2
公开(公告)日：2009-08-25
申请号：US10480790
申请日：2002-06-14
申请人： Yasunori Chiba , Yoshifumi Jigami , Hitoshi Sakuraba , Kazuo Kobayashi , Makoto Takeuchi , Yoriko Takeuchi, legal representative
发明人： Yasunori Chiba , Yoshifumi Jigami , Hitoshi Sakuraba , Kazuo Kobayashi , Makoto Takeuchi
IPC分类号： C12N15/00 , C12P21/00 , C12Q1/68 , C07K14/00
CPC分类号： C12P21/005 , A61K36/064 , A61K38/17 , C12N9/1051 , A61K2300/00
摘要： A process for producing a lysosomal enzyme having a mannose-6-phosphate-containing acidic sugar chain, wherein the process comprising: culturing in a medium yeast cells obtained by introducing a lysosomal enzyme gene into a sugar chain biosynthetic enzyme gene mutant strain of yeast, collecting a lysosomal enzyme having a phosphate-containing sugar chain from the culture, and then treating the enzyme with α-mannosidase; and pharmaceutical compositions for treatment of human lysosomal enzyme deficiencies produced by the process. The genetic engineering technique using the yeast according to the present invention allows large-amount and high-purity production of a glycoprotein having a phosphate-containing acidic sugar chain which can serve as a labeling marker for transporting into lysosomes in cells of mammals such as human. The glycoprotein having a phosphate-containing acidic sugar chain according to the invention may be utilized as a drug effective in treatment of human lysosomal enzyme deficiencies, etc.
摘要翻译：一种生产含有甘露糖-6-磷酸的酸性糖链的溶酶体酶的方法，其中所述方法包括：在通过将溶酶体酶基因导入酵母的糖链生物合成酶基因突变菌株获得的培养基中培养酵母，从培养物中收集含有含磷酸盐糖链的溶酶体酶，然后用α-甘露糖苷酶处理酶; 以及用于治疗由该方法产生的人溶酶体酶缺陷的药物组合物。使用根据本发明的酵母的基因工程技术允许大量和高纯度产生具有含磷酸盐的酸性糖链的糖蛋白，其可以用作在诸如人类的哺乳动物的细胞中输送到溶酶体的标记标记。具有根据本发明的含磷酸盐酸性糖链的糖蛋白可以用作治疗人溶酶体酶缺陷等的药物。

7. 发明申请

US20050064539A1 Glycoprotein and process for producing the same 失效
标题翻译：糖蛋白及其制备方法
公开(公告)号：US20050064539A1
公开(公告)日：2005-03-24
申请号：US10480790
申请日：2002-06-14
申请人： Yasunori Chiba , Yoshifumi Jigami , Hitoshi Sakuraba , Kazuo Kobayashi , Makoto Takeuchi , Yoriko Takeuchi
发明人： Yasunori Chiba , Yoshifumi Jigami , Hitoshi Sakuraba , Kazuo Kobayashi , Makoto Takeuchi , Yoriko Takeuchi
IPC分类号： C12N15/09 , A61K36/064 , A61K38/00 , A61K38/17 , A61P9/00 , A61P9/14 , A61P13/12 , A61P17/00 , A61P19/00 , A61P27/02 , A61P43/00 , C08B37/00 , C12N9/10 , C12N9/40 , C12P21/00 , C12P21/06 , C12N1/18
CPC分类号： C12P21/005 , A61K36/064 , A61K38/17 , C12N9/1051 , A61K2300/00
摘要： A process for producing a lysosomal enzyme having a mannose-6-phosphate-containing acidic sugar chain, wherein the process comprising: culturing in a medium yeast cells obtained by introducing a lysosomal enzyme gene into a sugar chain biosynthetic enzyme gene mutant strain of yeast, collecting a lysosomal enzyme having a phosphate-containing sugar chain from the culture, and then treating the enzyme with α-mannosidase; and pharmaceutical compositions for treatment of human lysosomal enzyme deficiencies produced by the process. The genetic engineering technique using the yeast according to the present invention allows large-amount and high-purity production of a glycoprotein having a phosphate-containing acidic sugar chain which can serve as a labeling marker for transporting into lysosomes in cells of mammals such as human. The glycoprotein having a phosphate-containing acidic sugar chain according to the invention may be utilized as a drug effective in treatment of human lysosomal enzyme deficiencies, etc.
摘要翻译：一种生产含有甘露糖-6-磷酸的酸性糖链的溶酶体酶的方法，其中所述方法包括：在通过将溶酶体酶基因导入酵母的糖链生物合成酶基因突变菌株获得的培养基中培养酵母，从培养物中收集含有含磷酸盐糖链的溶酶体酶，然后用α-甘露糖苷酶处理酶; 以及用于治疗由该方法产生的人溶酶体酶缺陷的药物组合物。使用根据本发明的酵母的基因工程技术允许大量和高纯度产生具有含磷酸盐的酸性糖链的糖蛋白，其可以用作在诸如人类的哺乳动物的细胞中输送到溶酶体的标记标记。具有根据本发明的含磷酸盐酸性糖链的糖蛋白可以用作治疗人溶酶体酶缺陷等的药物。

8. 发明申请

US20100291059A1 PHARMACEUTICAL COMPOSITION FOR ENZYME REPLACEMENT THERAPY 有权
标题翻译：用于酶替代治疗的药物组合物
公开(公告)号：US20100291059A1
公开(公告)日：2010-11-18
申请号：US12600497
申请日：2008-05-19
申请人： Hitoshi Sakuraba , Youichi Tajima , Ikuo Kawashima , Seiichi Aikawa , Fumiko Aikawa
发明人： Hitoshi Sakuraba , Youichi Tajima , Ikuo Kawashima , Seiichi Aikawa , Fumiko Aikawa
IPC分类号： A61K38/47 , C12N9/40 , C07H21/04 , C12N15/63 , A61P43/00
CPC分类号： C12N9/2465 , A61K38/47 , A61K48/005
摘要： The present invention provides a pharmaceutical composition comprising a protein having α-galactosidase activity for treating Fabry disease, which causes no allergic side effect, which is highly stable in blood (plasma) and which can readily be taken up by a cell of an affected organ. The pharmaceutical composition for treating Fabry disease of the invention comprises, for example, a protein which acquires an α-galactosidase activity through alteration of the structure of the active site of wild-type human α-N-acetylgalactosaminidase.
摘要翻译：本发明提供一种药物组合物，其包含具有α-半乳糖苷酶活性的蛋白质，用于治疗法布里病，其不引起过敏性副作用，其在血液（血浆）中高度稳定，并且可容易地被受影响器官的细胞摄取。用于治疗本发明的法布里病的药物组合物包括例如通过改变野生型人α-N-乙酰半乳糖胺酶的活性位点的结构而获得α-半乳糖苷酶活性的蛋白质。

9. 发明申请

US20090297592A1 Lipid Vesicle Composition 审中-公开
标题翻译：脂质囊泡组成
公开(公告)号：US20090297592A1
公开(公告)日：2009-12-03
申请号：US11920094
申请日：2006-05-11
申请人： Hitoshi Sakuraba , Youichi Tajima , Ikuo Kawashima , Mai Ito , Shinji Takeoka , Katsuji Ohta , Manabu Ito , Atsushi Mizuno
发明人： Hitoshi Sakuraba , Youichi Tajima , Ikuo Kawashima , Mai Ito , Shinji Takeoka , Katsuji Ohta , Manabu Ito , Atsushi Mizuno
IPC分类号： A61K9/127 , A61K38/47 , A61P3/00
CPC分类号： A61K9/1272 , A61K9/0019 , A61K9/1271 , A61K38/47
摘要： It is an object of the present invention to provide an enzyme preparation which is excellent in stability in blood (blood residence) and in transfer to a target organ (targeting property), and can be used effectively in enzyme replacement therapy or the like.This problem is solved by a lipid vesicle composition wherein vesicles composed of a lipid bilayer membrane are encapsulating an enzyme, the composition being capable of retaining stably the activity of the enzyme even outside the stable pH range of the enzyme.
摘要翻译：本发明的目的是提供一种在血液中的稳定性（血液停留）和转移至靶器官（靶向特性）优异的酶制剂，可以有效地用于酶替代疗法等。这个问题是通过脂质囊泡组合物来解决的，其中由脂质双层膜组成的囊泡正在封装酶，该组合物能够稳定地保持酶的活性甚至在酶的稳定pH范围之外。

10. 发明授权

US07470471B2 Resin composition, prepreg and laminate using the composition 失效
标题翻译：树脂组合物，预浸料和使用该组合物的层压材料
公开(公告)号：US07470471B2
公开(公告)日：2008-12-30
申请号：US10978379
申请日：2004-11-02
申请人： Kousuke Hirota , Koutarou Asahina , Kenji Shima , Hitoshi Sakuraba , Takashi Iiyama
发明人： Kousuke Hirota , Koutarou Asahina , Kenji Shima , Hitoshi Sakuraba , Takashi Iiyama
IPC分类号： B32B27/04
CPC分类号： C08K3/34 , H05K1/0373 , H05K2201/0209 , Y10T428/31504 , Y10T428/31721
摘要： The present invention is to provide a resin composition having sufficient rigidity and superior in the workability as well even if the thickness is as thin as 0.2 mm or less, and a prepreg and a laminate obtained from the resin composition. The resin composition comprises resin component containing a (A) compound having a maleimide group and (B) calcinated talc, wherein the calcinated talc is contained not less than 30 weight parts and not more than 250 weight parts to 100 weight parts of the total amount of the resin component containing a (A) compound having a maleimide group.
摘要翻译：本发明提供一种树脂组合物，即使厚度薄至0.2mm以下也能够得到刚性好，加工性优异的树脂组合物，以及由树脂组合物得到的预浸料和层叠体。树脂组合物包含含有具有马来酰亚胺基团的（A）化合物和（B）煅烧滑石的树脂组分，其中煅烧滑石含有不少于30重量份且不超过250重量份至100重量份的总量的树脂组分含有具有马来酰亚胺基团的（A）化合物。

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