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1. 发明授权

US08563269B2 Modified antibody compositions, methods of making and using thereof 有权
标题翻译：改良的抗体组合物，其制备和使用方法
公开(公告)号：US08563269B2
公开(公告)日：2013-10-22
申请号：US13315623
申请日：2011-12-09
申请人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Frederick W. Gluck , Jason Sagert , Patrick Daugherty
发明人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Frederick W. Gluck , Jason Sagert , Patrick Daugherty
IPC分类号： C12P21/08 , C12N15/74 , C12N9/00 , C12N15/62 , C07H21/04 , C07K16/28 , C07K16/46 , C07K14/00
CPC分类号： C07K16/22 , A61K39/3955 , A61K47/6845 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K7/06 , C07K7/08 , C07K14/001 , C07K16/00 , C07K16/18 , C07K16/241 , C07K16/28 , C07K16/2818 , C07K16/2845 , C07K16/2863 , C07K16/2866 , C07K16/2875 , C07K16/2896 , C07K16/30 , C07K2317/20 , C07K2317/21 , C07K2317/34 , C07K2317/40 , C07K2317/51 , C07K2317/515 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/92 , C07K2317/94 , C07K2319/30 , C07K2319/31 , C07K2319/50 , G01N33/6845 , G01N33/6854
摘要： The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.
摘要翻译：本公开提供了修饰的抗体，其含有用掩蔽部分（MM）修饰的抗体或抗体片段（AB）。这样的修饰抗体可以进一步与可切割部分（CM）偶联，产生可激活抗体（AAs），其中CM能够被切割，还原，光解或以其它方式修饰。 AAs可以表现出可激活的构象，使得AB在例如通过在能够切割，还原或光解所述蛋白质的试剂存在下，通过CM的切割，还原或光解来除去MM来更容易地进行靶标厘米。本公开进一步提供了制备和使用这些修饰抗体和可激活抗体的方法。

2. 发明授权

US07410788B2 Compositions and methods for production of disulfide bond containing proteins in host cells 有权
标题翻译：用于在宿主细胞中生产含二硫键的蛋白质的组合物和方法
公开(公告)号：US07410788B2
公开(公告)日：2008-08-12
申请号：US11058926
申请日：2005-02-16
申请人： Jonathan Beckwith , Fredrik Aslund , Paul H. Bessette , George Georgiou , Daniel Ritz , Jackie Eun-ah Lim
发明人： Jonathan Beckwith , Fredrik Aslund , Paul H. Bessette , George Georgiou , Daniel Ritz , Jackie Eun-ah Lim
IPC分类号： C12N1/21 , C12N7/00 , C12P21/00 , C12N15/63
CPC分类号： C12N9/0004 , C12P21/02
摘要： The invention provides composition and methods for producing proteins of interest which comprise at least one disulfide bond, include proteins which in their mature form do not contain disulfide bonds, but whose precursor molecule contained at least one disulfide bond. The methods employ a host cell modified to more efficiently produce properly folded disulfide bond containing proteins. The host cells generally contain a mutation in one or more reductase genes, and can be further genetically modified to increase their growth rate, and are further optionally modified to increase the expression of a catalyst of disulfide bond formation. Host cells, methods for using such to produce proteins of interest, proteins of interest produced by these methods are within the scope of the invention.
摘要翻译：本发明提供用于产生包含至少一个二硫键的感兴趣蛋白质的组合物和方法，包括其成熟形式不含二硫键但其前体分子含有至少一个二硫键的蛋白质。该方法使用修饰的宿主细胞以更有效地产生适当折叠的含二硫键的蛋白质。宿主细胞通常在一个或多个还原酶基因中含有突变，并且可进行进一步遗传修饰以增加其生长速率，并进一步任选地修饰以增加二硫键形成催化剂的表达。宿主细胞，使用其产生感兴趣的蛋白质的方法，通过这些方法生产的感兴趣的蛋白质在本发明的范围内。

3. 发明授权

US08399219B2 Protease activatable interferon alpha proprotein 有权
标题翻译：蛋白酶活化的干扰素α前蛋白
公开(公告)号：US08399219B2
公开(公告)日：2013-03-19
申请号：US12711199
申请日：2010-02-23
申请人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Jason Sagert
发明人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Jason Sagert
IPC分类号： C12P21/04 , C12N5/10 , C12N15/00 , A61K38/21 , C07H21/04
CPC分类号： C07K14/56 , A61K38/00 , A61K47/64 , A61K47/65 , C07K14/00 , C07K14/555 , C07K14/565 , C07K14/57 , C07K14/705 , C07K16/00 , C07K19/00 , C07K2319/10 , C07K2319/31 , C07K2319/33 , C07K2319/50 , C07K2319/70 , C07K2319/90 , C12N15/1037 , G01N33/6866
摘要： The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.
摘要翻译：本公开内容提供了蛋白质和可激活的前蛋白组合物。前蛋白含有功能蛋白（即其全长蛋白质或其功能片段），其与抑制功能蛋白与其靶标或结合配偶体的结合的肽掩模偶联。可激活的蛋白质包含与肽掩模偶联的功能性蛋白质，并进一步与可活化接头偶联，其中在非活化状态下，肽掩模抑制功能性蛋白质与其靶标或结合配偶体的结合，并且在活化状态下肽掩模不抑制功能蛋白与其靶或结合配偶体的结合。前体蛋白可以提供如果不抑制结合其结合配偶体的功能性蛋白质在非处理部位的结合，则可以提供降低的毒性和不良副作用。前体蛋白可进一步提供改善的生物分布特征。含有肽掩模的前体蛋白可以显示比不含肽掩模的相应功能蛋白质更长的体内或血清半衰期。本公开进一步提供筛选，制备和使用这些蛋白质的方法。

4. 发明申请

US20120149061A1 Modified Antibody Compositions, Methods of Making and Using Thereof 有权
公开(公告)号：US20120149061A1
公开(公告)日：2012-06-14
申请号：US13315623
申请日：2011-12-09
申请人： NANCY E. STAGLIANO , JAMES W. WEST , KATHRYN KAMATH , PAUL H. BESSETTE , FREDERICK W. GLUCK , JASON SAGERT , PATRICK DAUGHERTY
发明人： NANCY E. STAGLIANO , JAMES W. WEST , KATHRYN KAMATH , PAUL H. BESSETTE , FREDERICK W. GLUCK , JASON SAGERT , PATRICK DAUGHERTY
IPC分类号： C12P21/00 , C07K16/00
CPC分类号： C07K16/22 , A61K39/3955 , A61K47/6845 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K7/06 , C07K7/08 , C07K14/001 , C07K16/00 , C07K16/18 , C07K16/241 , C07K16/28 , C07K16/2818 , C07K16/2845 , C07K16/2863 , C07K16/2866 , C07K16/2875 , C07K16/2896 , C07K16/30 , C07K2317/20 , C07K2317/21 , C07K2317/34 , C07K2317/40 , C07K2317/51 , C07K2317/515 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/92 , C07K2317/94 , C07K2319/30 , C07K2319/31 , C07K2319/50 , G01N33/6845 , G01N33/6854
摘要： The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

5. 发明授权

US07256038B2 Polypeptide display libraries and methods of making and using thereof 有权
标题翻译：多肽显示库及其制备和使用方法
公开(公告)号：US07256038B2
公开(公告)日：2007-08-14
申请号：US10920244
申请日：2004-08-18
申请人： Patrick S. Daugherty , Paul H. Bessette , Jeffrey Rice
发明人： Patrick S. Daugherty , Paul H. Bessette , Jeffrey Rice
IPC分类号： C12N15/00 , C12N5/00 , C12N1/00 , G01N33/53
CPC分类号： C12N15/1037 , C07K14/245 , C12N15/1044 , C40B30/04 , C40B40/10 , G01N33/554
摘要： Disclosed herein are expression vectors which display a passenger polypeptide on the outer surface of a biological entity. As disclosed herein the displayed passenger polypeptide is capable of interacting or binding with a given ligand. Also disclosed are methods of making and using the expression vectors. N/C terminal fusion expression vectors and methods of making and using are also disclosed.
摘要翻译：本文公开了在生物实体的外表面上显示乘客多肽的表达载体。如本文所公开的，显示的乘客多肽能够与给定的配体相互作用或结合。还公开了制备和使用表达载体的方法。还公开了N / C末端融合表达载体及其制备和使用方法。

6. 发明申请

US20100221212A1 PROPROTEINS AND METHODS OF USE THEREOF 有权
标题翻译：优点及其使用方法
公开(公告)号：US20100221212A1
公开(公告)日：2010-09-02
申请号：US12711199
申请日：2010-02-23
申请人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Jason Sagert
发明人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Jason Sagert
IPC分类号： A61K38/21 , C07K14/00 , C07K14/555 , C07K16/00 , A61K38/16 , A61K39/395 , A61P35/04
CPC分类号： C07K14/56 , A61K38/00 , A61K47/64 , A61K47/65 , C07K14/00 , C07K14/555 , C07K14/565 , C07K14/57 , C07K14/705 , C07K16/00 , C07K19/00 , C07K2319/10 , C07K2319/31 , C07K2319/33 , C07K2319/50 , C07K2319/70 , C07K2319/90 , C12N15/1037 , G01N33/6866
摘要： The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.
摘要翻译：本公开内容提供了蛋白质和可激活的前蛋白组合物。前蛋白含有功能蛋白（即其全长蛋白质或其功能片段），其与抑制功能蛋白与其靶标或结合配偶体的结合的肽掩模偶联。可激活的蛋白质包含与肽掩模偶联的功能性蛋白质，并进一步与可活化接头偶联，其中在非活化状态下，肽掩模抑制功能性蛋白质与其靶标或结合配偶体的结合，并且在活化状态下肽掩模不抑制功能蛋白与其靶或结合配偶体的结合。前体蛋白可以提供如果不抑制结合其结合配偶体的功能性蛋白质在非处理部位的结合，则可以提供降低的毒性和不良副作用。前体蛋白可进一步提供改善的生物分布特征。含有肽掩模的前体蛋白可以显示比不含肽掩模的相应功能蛋白质更长的体内或血清半衰期。本公开进一步提供筛选，制备和使用这些蛋白质的方法。

7. 发明申请

US20100189651A1 MODIFIED ANTIBODY COMPOSITIONS, METHODS OF MAKING AND USING THEREOF 审中-公开
标题翻译：改性抗体组合物，制备方法及其用途
公开(公告)号：US20100189651A1
公开(公告)日：2010-07-29
申请号：US12686344
申请日：2010-01-12
申请人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Frederick Gluck , Jason Sagert , Patrick Daugherty
发明人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Frederick Gluck , Jason Sagert , Patrick Daugherty
IPC分类号： A61K49/00 , C07K1/107 , C07K16/00 , A61K39/395 , A61P35/00
CPC分类号： C07K16/22 , A61K39/3955 , A61K47/6845 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K7/06 , C07K7/08 , C07K14/001 , C07K16/00 , C07K16/18 , C07K16/241 , C07K16/28 , C07K16/2818 , C07K16/2845 , C07K16/2863 , C07K16/2866 , C07K16/2875 , C07K16/2896 , C07K16/30 , C07K2317/20 , C07K2317/21 , C07K2317/34 , C07K2317/40 , C07K2317/51 , C07K2317/515 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/92 , C07K2317/94 , C07K2319/30 , C07K2319/31 , C07K2319/50 , G01N33/6845 , G01N33/6854
摘要： The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.
摘要翻译：本公开提供了修饰的抗体，其含有用掩蔽部分（MM）修饰的抗体或抗体片段（AB）。这样的修饰抗体可以进一步与可切割部分（CM）偶联，产生可激活抗体（AAs），其中CM能够被切割，还原，光解或以其它方式修饰。 AAs可以表现出可激活的构象，使得AB在例如通过在能够切割，还原或光解所述蛋白质的试剂存在下，通过CM的切割，还原或光解去除MM来更容易地进行靶标厘米。本公开进一步提供了制备和使用这些修饰抗体和可激活抗体的方法。

8. 发明申请

US20100113303A1 Polypeptide Display Libraries and Methods of Making and Using Thereof 有权
标题翻译：多肽显示库及其制作和使用方法
公开(公告)号：US20100113303A1
公开(公告)日：2010-05-06
申请号：US12563897
申请日：2009-09-21
申请人： Patrick S. Daugherty , Paul H. Bessette , Jeffrey Rice
发明人： Patrick S. Daugherty , Paul H. Bessette , Jeffrey Rice
IPC分类号： C40B40/02
CPC分类号： C12N15/1037 , C07K14/245 , C12N15/1044 , C40B30/04 , C40B40/10 , G01N33/554
摘要： Disclosed herein are expression vectors which display a passenger polypeptide on the outer surface of a biological entity. As disclosed herein the displayed passenger polypeptide is capable of interacting or binding with a given ligand. Also disclosed are methods of making and using the expression vectors. N/C terminal fusion expression vectors and methods of making and using are also disclosed.
摘要翻译：本文公开了在生物实体的外表面上显示乘客多肽的表达载体。如本文所公开的，显示的乘客多肽能够与给定的配体相互作用或结合。还公开了制备和使用表达载体的方法。还公开了N / C末端融合表达载体及其制备和使用方法。

9. 发明授权

US07612019B2 Polypeptide display libraries and methods of making and using thereof 有权
标题翻译：多肽显示库及其制备和使用方法
公开(公告)号：US07612019B2
公开(公告)日：2009-11-03
申请号：US11612757
申请日：2006-12-19
申请人： Patrick S. Daugherty , Paul H. Bessette , Jeffrey Rice
发明人： Patrick S. Daugherty , Paul H. Bessette , Jeffrey Rice
IPC分类号： C40B30/04 , C40B30/08 , C40B20/00 , C40B40/02 , C12N1/00
CPC分类号： C12N15/1037 , C07K14/245 , C12N15/1044 , C40B30/04 , C40B40/10 , G01N33/554
摘要： Disclosed herein are expression vectors which display a passenger polypeptide on the outer surface of a biological entity. As disclosed herein the displayed passenger polypeptide is capable of interacting or binding with a given ligand. Also disclosed are methods of making and using the expression vectors. N/C terminal fusion expression vectors and methods of making and using are also disclosed.
摘要翻译：本文公开了在生物实体的外表面上显示乘客多肽的表达载体。如本文所公开的，显示的乘客多肽能够与给定的配体相互作用或结合。还公开了制备和使用表达载体的方法。还公开了N / C末端融合表达载体及其制备和使用方法。

10. 发明授权

US08513390B2 Modified antibody compositions, methods of making and using thereof 有权
公开(公告)号：US08513390B2
公开(公告)日：2013-08-20
申请号：US13455924
申请日：2012-04-25
申请人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Fred Gluck , Jason Sagert , Patrick Daugherty
发明人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Fred Gluck , Jason Sagert , Patrick Daugherty
IPC分类号： C07K16/28 , C07K14/00 , C07K16/46 , A61K39/00 , A61K38/10 , A61K38/08
CPC分类号： C07K16/22 , A61K39/3955 , A61K47/6845 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K7/06 , C07K7/08 , C07K14/001 , C07K16/00 , C07K16/18 , C07K16/241 , C07K16/28 , C07K16/2818 , C07K16/2845 , C07K16/2863 , C07K16/2866 , C07K16/2875 , C07K16/2896 , C07K16/30 , C07K2317/20 , C07K2317/21 , C07K2317/34 , C07K2317/40 , C07K2317/51 , C07K2317/515 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/92 , C07K2317/94 , C07K2319/30 , C07K2319/31 , C07K2319/50 , G01N33/6845 , G01N33/6854
摘要： The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

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