公开(公告)号：US20170355731A1

公开(公告)日：2017-12-14

申请号：US15524197

申请日：2015-11-05

申请人： Jan Grunewald ,  Yunho Jin ,  Weijia Ou ,  Tetsuo Uno

发明人： Jan Grunewald ,  Yunho Jin ,  Weijia Ou ,  Tetsuo Uno

IPC分类号： C07K7/64 ,  C07K16/30 ,  C07K16/22

CPC分类号： C07K7/64 ,  C07K16/22 ,  C07K16/30 ,  C07K2319/30

摘要： The invention disclosed herein relates to cytotoxic cyclic peptides of Formula (I), methods of inhibiting RNA polymerase with such cyclic peptides, immunoconjugates comprising such cyclic peptides (i.e Antibody Drug Conjugates), pharmaceutical compositions comprising such cyclic peptides immunoconjugates, compositions comprising such cyclic peptides immunoconjugates with a therapeutic co-agent and methods of treatment using such cyclic peptides immunoconjugates:

公开(公告)号：US09988420B2

公开(公告)日：2018-06-05

申请号：US15104727

申请日：2014-12-17

申请人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Weijia Ou ,  Tetsuo Uno ,  Yongqin Wan ,  Xing Wang ,  Yunho Jin

发明人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Weijia Ou ,  Tetsuo Uno ,  Yongqin Wan ,  Xing Wang ,  Yunho Jin

IPC分类号： A61K38/00 ,  C07K5/02 ,  C07K7/02 ,  C07K16/32 ,  A61K47/68

CPC分类号： C07K5/0205 ,  A61K47/6817 ,  A61K47/6851 ,  C07K7/02 ,  C07K16/32

摘要： Disclosed herein are novel cytotoxic peptides of formula (I) as described herein: and the use of such peptides in making immunoconjugates (i.e Antibody Drug Conjugates) Also described herein are immunoconjugates (i.e Antibody Drug Conjugates) comprising such novel cytotoxic peptide linked to an antigen binding moiety, such as an antibody; where such immunoconjugates are useful for treating cell proliferative disorders. The invention further provides pharmaceutical compositions comprising these immunoconjugates, compositions comprising the immunoconjugates with a therapeutic co-agent, and methods to use these immunoconjugates and compositions for treating cell proliferation disorders.

公开(公告)号：US20110262963A1

公开(公告)日：2011-10-27

申请号：US13125547

申请日：2009-10-23

申请人： Bernhard Geierstanger ,  Weijia Ou ,  Susan E. Cellitti ,  Tetsuo Uno ,  Tiffany Crossgrove ,  Hsien-Po Chiu ,  Jan Grunewald ,  Xueshi Hao

发明人： Bernhard Geierstanger ,  Weijia Ou ,  Susan E. Cellitti ,  Tetsuo Uno ,  Tiffany Crossgrove ,  Hsien-Po Chiu ,  Jan Grunewald ,  Xueshi Hao

IPC分类号： C12P21/02 ,  C07D207/22 ,  C07K16/00 ,  C12P21/08 ,  C07K14/485 ,  C12N11/18 ,  C12N9/90 ,  C07K14/50 ,  C07K14/525 ,  C07K14/435 ,  C07K14/505

CPC分类号： C12P21/00 ,  C07D207/20 ,  C07D207/48 ,  C07K5/0215

摘要： Disclosed herein is pyrroline-carboxy-lysine (PCL), a pyrrolysine analogue, which is a natural, biosynthetically generated amino acid, and methods for biosynthetically generating PCL. Also disclosed herein are proteins, polypeptides and peptides that have PCL incorporated therein and methods for incorporating PCL into such proteins, polypeptides and peptides. Also disclosed herein is the site-specific derivatization of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein. Also disclosed herein is the crosslinking of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein.

摘要翻译： 本文公开的是吡咯啉 - 羧基赖氨酸（PCL），吡咯赖氨酸类似物，其是天然的，生物合成产生的氨基酸，以及用于生物合成生成PCL的方法。 本文还公开了具有并入其中的PCL的蛋白质，多肽和肽以及将PCL并入此类蛋白质，多肽和肽的方法。 本文还公开了具有并入其中的PCL或吡咯赖胺的蛋白质，多肽和肽的位点特异性衍生化。 本文还公开了具有并入其中的PCL或吡咯赖氨酸的蛋白质，多肽和肽的交联。

公开(公告)号：US09884817B2

公开(公告)日：2018-02-06

申请号：US15317532

申请日：2015-06-11

申请人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Weijia Ou ,  Shifeng Pan ,  Tetsuo Uno ,  Yongqin Wan ,  Xing Wang

发明人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Weijia Ou ,  Shifeng Pan ,  Tetsuo Uno ,  Yongqin Wan ,  Xing Wang

IPC分类号： C07D207/09 ,  A61K47/48 ,  C07D403/12 ,  C07D401/12 ,  C07D413/12 ,  C07D403/14 ,  C07K16/32

CPC分类号： C07D207/09 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6855 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D413/12 ,  C07K5/0205 ,  C07K16/32

摘要： Disclosed herein are novel compounds of formula (I) as described herein: and the use of such peptides in making immunoconjugates (i.e Antibody Drug Conjugates) Also described herein are immunoconjugates (i.e Antibody Drug Conjugates) comprising such novel compound linked to an antigen binding moiety, such as an antibody; where such immunoconjugates are useful for treating cell proliferative disorders. The invention further provides pharmaceutical compositions comprising these immunoconjugates, compositions comprising the immunoconjugates with a therapeutic co-agent, and methods to use these immunoconjugates and compositions for treating cell proliferation disorders.

公开(公告)号：US20170121282A1

公开(公告)日：2017-05-04

申请号：US15317532

申请日：2015-06-11

申请人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Weijia OU ,  Shifeng Pan ,  Tetsuo Uno ,  Yongqin Wan ,  Xing Wang

发明人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Weijia OU ,  Shifeng Pan ,  Tetsuo Uno ,  Yongqin Wan ,  Xing Wang

IPC分类号： C07D207/09 ,  C07K16/32 ,  C07D413/12 ,  C07D403/14 ,  C07D403/12 ,  C07D401/12

CPC分类号： C07D207/09 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6855 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D413/12 ,  C07K5/0205 ,  C07K16/32

摘要： Disclosed herein are novel compounds of formula (I) as described herein: and the use of such peptides in making immunoconjugates (i.e Antibody Drug Conjugates) Also described herein are immunoconjugates (i.e Antibody Drug Conjugates) comprising such novel compound linked to an antigen binding moiety, such as an antibody; where such immunoconjugates are useful for treating cell proliferative disorders. The invention further provides pharmaceutical compositions comprising these immunoconjugates, compositions comprising the immunoconjugates with a therapeutic co-agent, and methods to use these immunoconjugates and compositions for treating cell proliferation disorders.

公开(公告)号：US08785151B2

公开(公告)日：2014-07-22

申请号：US13125547

申请日：2009-10-23

申请人： Bernhard Geierstanger ,  Weijia Ou ,  Susan E. Cellitti ,  Tetsuo Uno ,  Tiffany Crossgrove ,  Hsien-Po Chiu ,  Jan Grunewald ,  Xueshi Hao

发明人： Bernhard Geierstanger ,  Weijia Ou ,  Susan E. Cellitti ,  Tetsuo Uno ,  Tiffany Crossgrove ,  Hsien-Po Chiu ,  Jan Grunewald ,  Xueshi Hao

IPC分类号： C12P21/02 ,  C07D207/22 ,  C07K16/00 ,  C07K14/50

CPC分类号： C12P21/00 ,  C07D207/20 ,  C07D207/48 ,  C07K5/0215

摘要： Disclosed herein is pyrroline-carboxy-lysine (PCL), a pyrrolysine analogue, which is a natural, biosynthetically generated amino acid, and methods for biosynthetically generating PCL. Also disclosed herein are proteins, polypeptides and peptides that have PCL incorporated therein and methods for incorporating PCL into such proteins, polypeptides and peptides. Also disclosed herein is the site-specific derivatization of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein. Also disclosed herein is the crosslinking of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein.

摘要翻译： 本文公开的是吡咯啉 - 羧基赖氨酸（PCL），吡咯赖氨酸类似物，其是天然的，生物合成产生的氨基酸，以及用于生物合成生成PCL的方法。 本文还公开了具有并入其中的PCL的蛋白质，多肽和肽以及将PCL并入此类蛋白质，多肽和肽的方法。 本文还公开了具有并入其中的PCL或吡咯赖胺的蛋白质，多肽和肽的位点特异性衍生化。 本文还公开了具有并入其中的PCL或吡咯赖氨酸的蛋白质，多肽和肽的交联。

公开(公告)号：US09624520B2

公开(公告)日：2017-04-18

申请号：US14279085

申请日：2014-05-15

申请人： Bernhard Geierstanger ,  Weijia Ou ,  Susan E. Cellitti ,  Tetsuo Uno ,  Tiffany Crossgrove ,  Hsien-Po Chiu ,  Jan Grunewald ,  Xueshi Hao

发明人： Bernhard Geierstanger ,  Weijia Ou ,  Susan E. Cellitti ,  Tetsuo Uno ,  Tiffany Crossgrove ,  Hsien-Po Chiu ,  Jan Grunewald ,  Xueshi Hao

IPC分类号： C07C229/28 ,  C07C247/12 ,  C07C323/25 ,  C12P21/00 ,  C07D207/20 ,  C07D207/48 ,  C07K5/02

CPC分类号： C12P21/00 ,  C07D207/20 ,  C07D207/48 ,  C07K5/0215

摘要： Disclosed herein is pyrroline-carboxy-lysine (PCL), a pyrrolysine analog, which is a natural, biosynthetically generated amino acid, and methods for biosynthetically generating PCL. Also disclosed herein are proteins, polypeptides and peptides that have PCL incorporated therein and methods for incorporating PCL into such proteins, polypeptides and peptides. Also disclosed herein is the site-specific derivatization of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein. Also disclosed herein is the crosslinking of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein.

公开(公告)号：US09585970B2

公开(公告)日：2017-03-07

申请号：US13906584

申请日：2013-05-31

申请人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Badry Bursulaya

发明人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Badry Bursulaya

IPC分类号： A61K39/395 ,  C07K16/30 ,  A61K47/48 ,  C07K16/00 ,  C07K16/32

CPC分类号： C07K16/32 ,  A61K47/6815 ,  A61K47/6817 ,  A61K47/6851 ,  A61K47/6889 ,  C07K16/00 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/94 ,  C07K2318/10 ,  C07K2319/90

摘要： The present invention provides methods of site-specific labeling of antibodies, using proteins having 4′-phosphopantetheinyl transferase activity that catalyze post-translational modification of peptide sequences (“peptide tags”) incorporated into one or more specific sites of an antibody of interest. Enzymatic labeling enables quantitative and irreversible covalent modification of a specific serine residue within the peptide tags incorporated into the antibody, and thus creates desirable antibody conjugates.

摘要翻译： 本发明提供使用具有4'-磷酸泛酰乙酰转移酶活性的蛋白质的抗体的位点特异性标记方法，所述蛋白质催化并入感兴趣抗体的一个或多个特定位点的肽序列（“肽标签”）的翻译后修饰。 酶标记可以使掺入抗体的肽标记内的特定丝氨酸残基进行定量和不可逆共价修饰，从而产生所需的抗体缀合物。

公开(公告)号：US20090263376A1

公开(公告)日：2009-10-22

申请号：US12322938

申请日：2009-02-07

申请人： Jan Grunewald ,  Meng-Lin Tsao ,  Roshan Perera ,  Richard A. Lerner ,  Vaughn V. Smider ,  Peter G. Schultz

发明人： Jan Grunewald ,  Meng-Lin Tsao ,  Roshan Perera ,  Richard A. Lerner ,  Vaughn V. Smider ,  Peter G. Schultz

IPC分类号： A61K39/395 ,  A61K39/00 ,  A61K39/02 ,  A61K39/12 ,  C12P21/00 ,  C07K14/00

CPC分类号： C07K16/241 ,  A61K31/19 ,  A61K39/0008 ,  C07K16/44 ,  Y02A50/491 ,  Y02A50/492

摘要： The present invention comprises methods and compositions for producing and/or enhancing an immunological response in a subject against a target moiety such as a disease-related moiety by administration of an antigenic version of the target moiety having one or more unnatural amino acid and/or by administration of an antibody against a version of a target moiety having one or more unnatural amino acid which antibody is cross reactive with the natural target moiety.

摘要翻译： 本发明包括用于通过施用具有一个或多个非天然氨基酸的靶部分的抗原性版本来产生和/或增强受试者中针对靶部分例如疾病相关部分的免疫应答的方法和组合物，和/或 通过施用针对具有一个或多个非天然氨基酸的靶部分版本的抗体，该抗体与天然靶标部分交叉反应。

公开(公告)号：US20150104468A1

公开(公告)日：2015-04-16

申请号：US14402808

申请日：2013-05-31

申请人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Badry Bursulaya

发明人： Bernhard Hubert Geierstanger ,  Jan Grunewald ,  Badry Bursulaya

IPC分类号： A61K47/48 ,  C07K16/32

CPC分类号： C07K16/32 ,  A61K47/6815 ,  A61K47/6817 ,  A61K47/6851 ,  A61K47/6889 ,  C07K16/00 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/94 ,  C07K2318/10 ,  C07K2319/90

摘要： The present disclosure provides methods of site-specific labeling of antibodies, using proteins having 4′-phosphopantetheinyl transferase activity that catalyze post-translational modification of peptide sequences (“peptide tags”) incorporated into one or more specific sites of an antibody of interest. Enzymatic labeling enables quantitative and irreversible covalent modification of a specific serine residue within the peptide tags incorporated into the antibody, and thus creates desirable antibody conjugates.

摘要翻译： 本公开提供使用具有4'-磷酸泛酰乙酰转移酶活性的蛋白质的抗体的位点特异性标记方法，所述蛋白质催化并入感兴趣抗体的一个或多个特定位点的肽序列（“肽标签”）的翻译后修饰。 酶标记可以使掺入抗体的肽标记内的特定丝氨酸残基进行定量和不可逆共价修饰，从而产生所需的抗体缀合物。