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1. 发明公开

EP3033097A4 FACTOR VIII-XTEN FUSIONS AND USES THEREOF 有权转让
标题翻译：因子VIII-X-TEN兼并及其用途
公开(公告)号：EP3033097A4
公开(公告)日：2017-01-25
申请号：EP14835828
申请日：2014-08-14
申请人： BIOGEN MA INC , AMUNIX OPERATING INC
发明人： LIU TONGYAO , CHANG PEI-YUN , KULMAN JOHN , SCHELLENBERGER VOLKER , JIANG HAIYAN , PETERS ROBERT T , CHHABRA EKTA SETH
IPC分类号： A61K38/36 , A61K35/14 , A61K38/37 , C07K1/00 , C07K14/745 , C07K14/755
CPC分类号： A61K38/37 , A61K9/0019 , A61K38/00 , C07K14/00 , C07K14/755 , C07K2319/31
摘要： The present invention provides chimeric proteins comprising a Factor VIII (FVIII) polypeptide and XTEN polypeptides. The FVIII polypeptide can have a reduced affinity for von Willebrand Factor (VWF). XTEN polypeptides of appropriate sizes are inserted into the FVIII polypeptide at particular locations in order to extend the half-life of the FVIII polypeptide. The invention also includes nucleotides, vectors, host cells, and methods of using the chimeric proteins, e.g., to treat bleeding diseases and disorders.

2. 发明专利

EA029685B1 КОМПЛЕКС ФАКТОРА VIII С XTEN И БЕЛКОМ ФАКТОРА ФОН ВИЛЛЕБРАНДА И ЕГО ПРИМЕНЕНИЕ (ВАРИАНТЫ) 未知
公开(公告)号：EA029685B1
公开(公告)日：2018-04-30
申请号：EA201590198
申请日：2013-07-10
申请人： AMUNIX OPERATING INC , BIOGEN MA INC
发明人： CHHABRA EKTA SETH , LIU TONGYAO , CHANG PEI-YUN , PETERS ROBERT T , KULMAN JOHN
IPC分类号： A61K38/37 , C12N15/00 , C12P21/08
摘要： Согласноизобретениюпредложенхимерныйбелок, содержащийбелокфакторафонВиллебранда (VWF), содержащийдомен D' идомен D3 факторафонВиллебранда, однуилиболеепоследовательностей XTEN ибелок FVIII, приэтомуказанный VWF фрагмент, последовательность XTEN илибелок FVIII связаныилиассоциированыдругс другом. Химерныйбелокможетдополнительносодержатьоднуилиболееконстантныхобластей Ig илиихчастей (например, область Fc). Полипептиднаяцепь, содержащая VWF фрагментсогласноизобретению, связываетсяилиассоциируетс полипептиднойцепью, содержащейбелок FVIII, связанныйс последовательностью XTEN, иуказаннаяполипептиднаяцепь, содержащая VWF фрагмент, можетпредотвращатьилиингибироватьсвязываниеэндогенногофакторафонВиллебрандас белком FVIII, связаннымс последовательностью XTEN. ПутемпредотвращенияилиингибированиясвязыванияэндогенногофакторафонВиллебрандас белком FVIII, которыйявляетсяфактором, ограничивающимпериодполувыведения FVIII, VWF фрагментможетиндуцироватьувеличениепериодаполувыведенияхимерногобелка, содержащегобелок FVIII. Изобретениетакжевключаетнуклеотиды, векторы, клетки-хозяева, способыприменения VWF фрагментаилихимерныхбелков.

3. 发明专利

NZ703366A Factor viii complex with xten and von willebrand factor protein, and uses thereof 未知
公开(公告)号：NZ703366A
公开(公告)日：2018-03-23
申请号：NZ70336613
申请日：2013-07-10
申请人： AMUNIX OPERATING INC , BIOGEN MA INC
发明人： CHHABRA EKTA SETH , PETERS ROBERT T , CHANG PEI-YUN , KULMAN JOHN , LIU TONGYAO
IPC分类号： A61K38/37 , C12N15/00 , C12P21/08
摘要： The present invention includes a chimeric protein comprising a VWF protein with D’ domain and D3 domain of VWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain of a VWF fragment is associated with a FVIII polypeptide chain linked to an XTEN sequence. The VWF fragment polypeptide chain can prevent or inhibit binding of endogenous VWF to FVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to FVIII protein, VWF fragment can extend half-life of chimeric protein comprising FVIII protein. The invention includes nucleotides, vectors, host cells, use of VWF fragment, or chimeric proteins.

4. 发明专利

SG11201500045RA FACTOR VIII COMPLEX WITH XTEN AND VON WILLEBRAND FACTOR PROTEIN, AND USES THEREOF 未知
公开(公告)号：SG11201500045RA
公开(公告)日：2015-02-27
申请号：SG11201500045R
申请日：2013-07-10
申请人： AMUNIX OPERATING INC , BIOGEN MA INC
发明人： CHHABRA EKTA SETH , LIU TONGYAO , CHANG PEI-YUN , PETERS ROBERT T , KULMAN JOHN
IPC分类号： A61K38/37 , C12N15/00 , C12P21/08
摘要： The present invention provides a chimeric protein comprising a VWF protein comprising the D' domain and D3 domain of VWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain comprising a VWF fragment of the invention binds to or is associated with a polypeptide chain comprising a FVIII protein linked to an XTEN sequence and the polypeptide chain comprising the VWF fragment can prevent or inhibit binding of endogenous VWF to the FVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to the FVIII protein, which is a half-life limiting factor for FVIII, the VWF fragment can induce extension of half-life of the chimeric protein comprising a FVIII protein. The invention also includes nucleotides, vectors, host cells, methods of using the VWF fragment, or the chimeric proteins.

5. 发明专利

AU2013290173B2 Factor VIII complex with XTEN and von Willebrand Factor protein, and uses thereof 未知
公开(公告)号：AU2013290173B2
公开(公告)日：2018-02-15
申请号：AU2013290173
申请日：2013-07-10
申请人： AMUNIX OPERATING INC , BIOGEN MA INC
发明人： CHHABRA EKTA SETH , LIU TONGYAO , CHANG PEI YUN , PETERS ROBERT T , KULMAN JOHN
IPC分类号： C07K14/755 , A61K38/37 , C12N15/00 , C12P21/08
摘要： The present invention includes a chimeric protein comprising a VWF protein with D' domain and D3 domain ofVWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain of a VWF fragment is associated with a FVIII polypeptide chain linked to an XTEN sequence. The VWF fragment polypeptide chain can prevent or inhibit binding of endogenous VWF toFVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to FVIII protein, VWF fragment can extend half-life of chimeric protein comprising FVIII protein. The invention includes nucleotides, vectors, host cells, use of VWF fragment, or chimeric proteins.

6. 发明专利

SG10201701037WA FACTOR VIII COMPLEX WITH XTEN AND VON WILLEBRAND FACTOR PROTEIN, AND USES THEREOF 未知
公开(公告)号：SG10201701037WA
公开(公告)日：2017-03-30
申请号：SG10201701037W
申请日：2013-07-10
申请人： AMUNIX OPERATING INC , BIOGEN MA INC
发明人： CHHABRA EKTA SETH , LIU TONGYAO , CHANG PEI-YUN , PETERS ROBERT T , KULMAN JOHN
摘要： The present invention provides a chimeric protein comprising a VWF protein comprising the D' domain and D3 domain of VWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain comprising a VWF fragment of the invention binds to or is associated with a polypeptide chain comprising a FVIII protein linked to an XTEN sequence and the polypeptide chain comprising the VWF fragment can prevent or inhibit binding of endogenous VWF to the FVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to the FVIII protein, which is a half-life limiting factor for FVIII, the VWF fragment can induce extension of half-life of the chimeric protein comprising a FVIII protein. The invention also includes nucleotides, vectors, host cells, methods of using the VWF fragment, or the chimeric proteins.

7. 发明公开

EP2882450A4 FACTOR VIII COMPLEX WITH XTEN AND VON WILLEBRAND FACTOR PROTEIN, AND USES THEREOF 有权转让
标题翻译：与XTEN和血管性血友病因子蛋白因子VIII复合及其用途
公开(公告)号：EP2882450A4
公开(公告)日：2016-06-22
申请号：EP13816031
申请日：2013-07-10
申请人： AMUNIX OPERATING INC , BIOGEN MA INC
发明人： CHHABRA EKTA SETH , LIU TONGYAO , CHANG PEI-YUN , PETERS ROBERT T , KULMAN JOHN
IPC分类号： A61K38/37 , A61K38/36 , C07K14/755 , C12N15/00 , C12N15/62 , C12P21/08
CPC分类号： C07K14/755 , A61K38/36 , A61K38/37 , A61K47/481 , A61K47/55 , C07K16/00 , C07K2319/00 , C07K2319/30 , C07K2319/31 , C07K2319/35 , C07K2319/50 , C12N15/11
摘要： The present invention includes a chimeric protein comprising a VWF protein with D′ domain and D3 domain of VWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain of a VWF fragment is associated with a FVIII polypeptide chain linked to an XTEN sequence. The VWF fragment polypeptide chain can prevent or inhibit binding of endogenous VWF to FVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to FVIII protein, VWF fragment can extend half-life of chimeric protein comprising FVIII protein. The invention includes nucleotides, vectors, host cells, use of VWF fragment, or chimeric proteins.

8. 发明申请

WO2015023891A2 FACTOR VIII-XTEN FUSIONS AND USES THEREOF 审中-公开
标题翻译：因子VIII-XTEN融合及其用途
公开(公告)号：WO2015023891A2
公开(公告)日：2015-02-19
申请号：PCT/US2014051144
申请日：2014-08-14
申请人： BIOGEN IDEC INC , AMUNIX OPERATING INC
发明人： LIU TONGYAO , CHANG PEI-YUN , KULMAN JOHN , SCHELLENBERGER VOLKER , JIANG HAIYAN , PETERS ROBERT T , CHHABRA EKTA SETH
IPC分类号： A61K38/17
CPC分类号： A61K38/37 , A61K9/0019 , A61K38/00 , C07K14/00 , C07K14/755 , C07K2319/31
摘要： The present invention provides chimeric proteins comprising a Factor VIII (FVIII) polypeptide and XTEN polypeptides. The FVIII polypeptide can have a reduced affinity for von Willebrand Factor (VWF). XTEN polypeptides of appropriate sizes are inserted into the FVIII polypeptide at particular locations in order to extend the half-life of the FVIII polypeptide. The invention also includes nucleotides, vectors, host cells, and methods of using the chimeric proteins, e.g., to treat bleeding diseases and disorders.
摘要翻译：本发明提供了包含因子VIII（FVIII）多肽和XTEN多肽的嵌合蛋白。 FVIII多肽可以对血管性血友病因子（VWF）具有降低的亲和力。适当大小的XTEN多肽在特定位置插入FVIII多肽中，以延长FVIII多肽的半衰期。本发明还包括核苷酸，载体，宿主细胞和使用嵌合蛋白的方法，例如治疗出血疾病和病症。

9. 发明申请

WO2014011819A3 FACTOR VIII COMPLEX WITH XTEN AND VON WILLEBRAND FACTOR PROTEIN, AND USES THEREOF 审中-公开
标题翻译：因子VIII与XTEN和VON WILLEBRAND因子蛋白质的复合物及其用途
公开(公告)号：WO2014011819A3
公开(公告)日：2014-03-06
申请号：PCT/US2013049989
申请日：2013-07-10
申请人： AMUNIX OPERATING INC , BIOGEN IDEC INC , CHHABRA EKTA SETH , LIU TONGYAO , CHANG PEI-YUN , PETERS ROBERT T , KULMAN JOHN
发明人： CHHABRA EKTA SETH , LIU TONGYAO , CHANG PEI-YUN , PETERS ROBERT T , KULMAN JOHN
IPC分类号： A61K38/37 , C12N15/00 , C12P21/08
CPC分类号： C07K14/755 , A61K38/36 , A61K38/37 , A61K47/481 , A61K47/55 , C07K16/00 , C07K2319/00 , C07K2319/30 , C07K2319/31 , C07K2319/35 , C07K2319/50 , C12N15/11
摘要： The present invention includes a chimeric protein comprising a VWF protein with D' domain and D3 domain ofVWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain of a VWF fragment is associated with a FVIII polypeptide chain linked to an XTEN sequence. The VWF fragment polypeptide chain can prevent or inhibit binding of endogenous VWF toFVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to FVIII protein, VWF fragment can extend half-life of chimeric protein comprising FVIII protein. The invention includes nucleotides, vectors, host cells, use of VWF fragment, or chimeric proteins.
摘要翻译：本发明包括嵌合蛋白，其包含具有D'结构域的VWF蛋白和VWF的D3结构域，一个或多个XTEN序列和FVIII蛋白，其中VWF片段，XTEN序列或FVIII蛋白与彼此。嵌合蛋白可进一步包含一个或多个Ig恒定区或其部分（例如Fc区）。 VWF片段的多肽链与与XTEN序列连接的FVIII多肽链相关。 VWF片段多肽链可以预防或抑制与XTEN序列连接的内源性VWF与FVIII蛋白的结合。通过预防或抑制内源VWF与FVIII蛋白的结合，VWF片段可以延长包含FVIII蛋白的嵌合蛋白的半衰期。本发明包括核苷酸，载体，宿主细胞，VWF片段或嵌合蛋白的用途。

10. 发明专利

UA116632C2 ХИМЕРНИЙ БІЛОК, ЯКИЙ МІСТИТЬ ФАКТОР VIII ТА ФАКТОР ВІЛЛЕБРАНДА, І ЙОГО ЗАСТОСУВАННЯ 未知
公开(公告)号：UA116632C2
公开(公告)日：2018-04-25
申请号：UAA201500228
申请日：2013-07-10
申请人： AMUNIX OPERATING INC , BIOVERATIV THERAPEUTICS INC
发明人： CHHABRA EKTA SETH , LIU TONGYAO , CHANG PEI-YUN , PETERS ROBERT T , KULMAN JOHN
IPC分类号： C07K14/755 , A61K38/37 , C07K16/00 , C12N15/11
摘要： Винахідстосуєтьсяхимерногобілка, якийміститьфрагментфактораВіллебранда, щоміститьдомен D' тадомен D3 фактораВіллебранда, послідовність XTEN табілок FVIIІ, причомуфрагментфактораВіллебранда, послідовність XTEN абобілок FVIII зв'язаніабоасоційованіодинз однимковалентнимзв’язком, атакожполінуклеотиду, вектора, клітини-хазяїна, фармацевтичноїкомпозиції, способуотриманнятакогобілка, способузапобіганняабоінгібуваннязв’язуваннябілка FVIII зендогеннимфакторомВіллебрандатаспособулікуваннязахворюванняабопорушення, пов’язаногоз кровотечею.

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