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    TYROSINE LIGATION PROCESS
    1.
    发明申请
    TYROSINE LIGATION PROCESS 有权
    酪氨酸生物过程

    公开(公告)号：US20140141034A1

    公开(公告)日：2014-05-22

    申请号：US14131150

    申请日：2012-07-05

    申请人： Roberto Adamo ,  Martin Allen ,  Francesco Berti ,  Elisa Danieli ,  Qi-Ying Hu

    发明人： Roberto Adamo ,  Martin Allen ,  Francesco Berti ,  Elisa Danieli ,  Qi-Ying Hu

    IPC分类号： A61K47/48

    CPC分类号： A61K47/4833 ,  A61K39/385 ,  A61K47/51 ,  A61K47/54 ,  A61K47/549 ,  A61K47/593 ,  A61K47/62 ,  A61K47/64 ,  A61K47/6415 ,  A61K47/646 ,  A61K2039/505

    摘要： A process is provided for preparing a conjugate of Formula (I-A) or (I) comprising a polypeptide containing n number of tyrosine units, where n is an integer greater than or equal to 1, dispersed within the amino acid chain having and amino terminus end (A1) and an acid terminus end (A2) of the protein or polypeptide and having a weight average molecular weight equal to or greater than 10,000 Daltons (10 kDa), wherein the conjugate comprises a number m of tyrosine conjugates (modified tyrosine residues) as depicted in Formula (I-A) or (I), where m is at least one and is less than or equal to n: where X, Lg, L and R are as defined herein.

    摘要翻译： 提供了一种制备式（IA）或（I）的缀合物的方法，其包含分散在具有氨基酸链的氨基酸链和氨基末端末端的含有n个数量的酪氨酸单元的多肽，其中n为大于或等于1的整数 （A1）和所述蛋白质或多肽的酸性末端（A2），并且具有等于或大于10,000道尔顿（10kDa）的重均分子量，其中所述缀合物包含数量m的酪氨酸缀合物（修饰的酪氨酸残基） 如式（IA）或（I）所示，其中m为至少一个且小于或等于n：其中X，Lg，L和R如本文所定义。

    Tyrosine ligation process
    2.
    发明授权
    Tyrosine ligation process 有权
    酪氨酸结扎过程

    公开(公告)号：US09149541B2

    公开(公告)日：2015-10-06

    申请号：US14131150

    申请日：2012-07-05

    申请人： Roberto Adamo ,  Martin Allen ,  Francesco Berti ,  Elisa Danieli ,  Qi-Ying Hu

    发明人： Roberto Adamo ,  Martin Allen ,  Francesco Berti ,  Elisa Danieli ,  Qi-Ying Hu

    IPC分类号： A61K38/04 ,  A61K39/385 ,  A61K47/48 ,  C07K5/00 ,  C07K17/00 ,  A61K39/00

    CPC分类号： A61K47/4833 ,  A61K39/385 ,  A61K47/51 ,  A61K47/54 ,  A61K47/549 ,  A61K47/593 ,  A61K47/62 ,  A61K47/64 ,  A61K47/6415 ,  A61K47/646 ,  A61K2039/505

    摘要： A process is provided for preparing a conjugate of Formula (I-A) or (I) comprising a polypeptide containing n number of tyrosine units, where n is an integer greater than or equal to 1, dispersed within the amino acid chain having and amino terminus end (A1) and an acid terminus end (A2) of the protein or polypeptide and having a weight average molecular weight equal to or greater than 10,000 Daltons (10 kDa), wherein the conjugate comprises a number m of tyrosine conjugates (modified tyrosine residues) as depicted in Formula (I-A) or (I), where m is at least one and is less than or equal to n: where X, Lg, L and R are as defined herein.

    摘要翻译： 提供了一种制备式（IA）或（I）的缀合物的方法，其包含分散在具有氨基酸链的氨基酸链和氨基末端末端的含有n个数量的酪氨酸单元的多肽，其中n为大于或等于1的整数 （A1）和蛋白质或多肽的酸性末端（A2），并且具有等于或大于10,000道尔顿（10kDa）的重均分子量，其中所述缀合物包含数量m的酪氨酸缀合物（修饰的酪氨酸残基） 如式（IA）或（I）所示，其中m为至少一个且小于或等于n：其中X，Lg，L和R如本文所定义。

    Organic compounds
    6.
    发明授权
    Organic compounds 有权
    有机化合物

    公开(公告)号：US08314097B2

    公开(公告)日：2012-11-20

    申请号：US11508445

    申请日：2006-08-23

    申请人： Gary Michael Ksander ,  Erik Meredith ,  Lauren G. Monovich ,  Julien Papillon ,  Fariborz Firooznia ,  Qi-Ying Hu

    发明人： Gary Michael Ksander ,  Erik Meredith ,  Lauren G. Monovich ,  Julien Papillon ,  Fariborz Firooznia ,  Qi-Ying Hu

    IPC分类号： A61K31/535 ,  A61K31/445 ,  A61K31/415 ,  A61P9/00 ,  C07D413/00 ,  C07D211/32 ,  C07D235/02 ,  C07D487/10 ,  C07D403/00

    CPC分类号： C07D471/04 ,  A61K31/4188 ,  A61K31/437 ,  A61K31/454 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/06 ,  C07D487/04

    摘要： The present invention provides a compound of formula I: Said compound is inhibitor of aldosterone synthase and aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase or aromatase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, atrial fibrillation, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, inflammation, increased formation of collagen, fibrosis such as cardiac or myocardiac fibrosis and remodeling following hypertension and endothelial dysfunction, gynecomastia, osteoporosis, prostate cancer, endometriosis, uterine fibroids, dysfunctional uterine bleeding, endometrial hyperplasia, polycystic ovarian disease, infertility, fibrocystic breast disease, breast cancer and fibrocystic mastopathy. Finally, the present invention also provides a pharmaceutical composition.

    摘要翻译： 本发明提供式I化合物：所述化合物是醛固酮合成酶和芳香酶的抑制剂，因此可用于治疗由醛固酮合成酶或芳香酶介导的病症或疾病。 因此，式I化合物可用于治疗低钾血症，高血压，充血性心力衰竭，心房颤动，肾衰竭，特别是慢性肾衰竭，再狭窄，动脉粥样硬化，综合征X，肥胖症，肾病，心肌梗塞后， 冠状动脉心脏病，炎症，胶原蛋白形成增加，纤维化如心脏或心肌纤维化，以及高血压和内皮功能障碍后重塑，男子乳腺发育不良，骨质疏松症，前列腺癌，子宫内膜异位症，子宫肌瘤，功能障碍性子宫出血，子宫内膜增生，多囊卵巢疾病，不育症 ，纤维囊性乳腺疾病，乳腺癌和纤维囊性乳腺病。 最后，本发明还提供药物组合物。

    ORGANIC COMPOUNDS
    7.
    发明申请
    ORGANIC COMPOUNDS 失效
    有机化合物

    公开(公告)号：US20100048562A1

    公开(公告)日：2010-02-25

    申请号：US12519697

    申请日：2007-12-14

    申请人： Christopher Adams ,  Qi-Ying Hu ,  Gary Michael Ksander ,  Julien Papillon

    发明人： Christopher Adams ,  Qi-Ying Hu ,  Gary Michael Ksander ,  Julien Papillon

    IPC分类号： A61K31/5377 ,  C07D233/22 ,  A61K31/415 ,  C07D413/02

    CPC分类号： C07D233/64 ,  C07D233/58 ,  C07D233/88 ,  C07D233/90 ,  C07D401/04 ,  C07D405/04 ,  C07D409/04 ,  C07D409/10 ,  C07D413/04

    摘要： The present invention provides a compound of formula I: said compound is inhibitor of aldosterone synthase (CYP11B2), and/or 11 beta-hydroxylase (CYP11B1), and/or aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase, aromatase, or CYP11B1. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, increased formation of collagen, fibrosis and remodeling following hypertension and endothelial dysfunction. Finally, the present invention also provides a pharmaceutical composition.

    摘要翻译： 本发明提供式I化合物：所述化合物是醛固酮合酶（CYP11B2）和/或11β-羟化酶（CYP11B1）和/或芳香酶的抑制剂，因此可用于治疗疾病或疾病 由醛固酮合酶，芳香酶或CYP11B1介导。 因此，式I化合物可用于治疗低钾血症，高血压，充血性心力衰竭，肾衰竭，特别是慢性肾功能衰竭，再狭窄，动脉粥样硬化，X综合症，肥胖症，肾病，心肌梗塞后，冠心病 增加胶原蛋白的形成，纤维化和高血压和内皮功能障碍后的重塑。 最后，本发明还提供药物组合物。

    ORGANIC COMPOUNDS
    8.
    发明申请
    ORGANIC COMPOUNDS 审中-公开
    有机化合物

    公开(公告)号：US20090264420A1

    公开(公告)日：2009-10-22

    申请号：US12438811

    申请日：2007-08-23

    申请人： Gary Michael Ksander ,  Qi-Ying Hu

    发明人： Gary Michael Ksander ,  Qi-Ying Hu

    IPC分类号： A61K31/519 ,  C07D487/04 ,  A61K31/551 ,  A61P9/00 ,  A61P3/00

    CPC分类号： C07D487/04

    摘要： The present invention provides a compound of formula I: said compound is inhibitor of aldosterone synthase, and/or 11 beta-hydroxylase (CYPL11B1), and/or aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase, aromatase, or CYPL11B1. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, increased formation of collagen, fibrosis and remodeling following hypertension and endothelial dysfunction. Finally, the present invention also provides a pharmaceutical composition.

    摘要翻译： 本发明提供式I化合物：所述化合物是醛固酮合酶抑制剂和/或11β-羟化酶（CYPL11B1）和/或芳香酶，因此可用于治疗由醛固酮介导的病症或疾病 合酶，芳香酶或CYPL11B1。 因此，式I化合物可用于治疗低钾血症，高血压，充血性心力衰竭，肾衰竭，特别是慢性肾功能衰竭，再狭窄，动脉粥样硬化，X综合症，肥胖症，肾病，心肌梗塞后，冠心病 增加胶原蛋白的形成，纤维化和高血压和内皮功能障碍后的重塑。 最后，本发明还提供药物组合物。

    Methods for making conjugates from disulfide-containing proteins
    9.
    发明授权
    Methods for making conjugates from disulfide-containing proteins 有权

    公开(公告)号：US10022256B2

    公开(公告)日：2018-07-17

    申请号：US14648325

    申请日：2013-11-26

    申请人： Qi-Ying Hu ,  Hidetomo Imase

    发明人： Qi-Ying Hu ,  Hidetomo Imase

    IPC分类号： A61K9/00 ,  A61F5/00 ,  A61F5/56 ,  A61C5/90

    摘要： The invention provides methods to prepare protein conjugates from proteins having at least two cysteines. In one embodiment, a protein with a disulfide linkage is reduced to provide two free cysteines for reaction with a 1,3-dihaloacetone or similar reactant, linking the sulfur atoms of the two cysteines together. The ketone inserted between the sulfur atoms is then used to form a Schiff base to an aminated payload molecule, thus conjugating the protein to a payload. In another embodiment, two cysteine residues are tied together by reaction with a 1,3-dihaloacetone or similar reactant. The linkage between the sulfur atoms in each case holds the protein or peptide in a constrained conformation, while also providing a convenient place for attaching a payload with good specificity and efficiency.

    Organic Compounds
    10.
    发明申请
    Organic Compounds 审中-公开
    有机化合物

    公开(公告)号：US20120277215A1

    公开(公告)日：2012-11-01

    申请号：US13540113

    申请日：2012-07-02

    申请人： Gary Michael Ksander ,  Erik Meredith ,  Lauren G. Monovich ,  Julien Papillon ,  Fariborz Firooznia ,  Qi-Ying Hu

    发明人： Gary Michael Ksander ,  Erik Meredith ,  Lauren G. Monovich ,  Julien Papillon ,  Fariborz Firooznia ,  Qi-Ying Hu

    IPC分类号： C07D487/04 ,  A61K31/5377 ,  A61K31/454 ,  C07D487/20 ,  C07D471/04 ,  A61K31/437 ,  A61K31/55 ,  A61P9/12 ,  A61P9/04 ,  A61P13/12 ,  A61P9/10 ,  A61P3/00 ,  A61P3/04 ,  A61P9/00 ,  A61P29/00 ,  A61P19/10 ,  A61P35/00 ,  A61P15/08 ,  A61K31/4188

    CPC分类号： C07D471/04 ,  A61K31/4188 ,  A61K31/437 ,  A61K31/454 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/06 ,  C07D487/04

    摘要： The present invention provides a compound of formula I: Said compound is inhibitor of aldosterone synthase and aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase or aromatase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, atrial fibrillation, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, inflammation, increased formation of collagen, fibrosis such as cardiac or myocardiac fibrosis and remodeling following hypertension and endothelial dysfunction, gynecomastia, osteoporosis, prostate cancer, endometriosis, uterine fibroids, dysfunctional uterine bleeding, endometrial hyperplasia, polycystic ovarian disease, infertility, fibrocystic breast disease, breast cancer and fibrocystic mastopathy. Finally, the present invention also provides a pharmaceutical composition.

    摘要翻译： 本发明提供式I化合物：所述化合物是醛固酮合成酶和芳香酶的抑制剂，因此可用于治疗由醛固酮合成酶或芳香酶介导的病症或疾病。 因此，式I化合物可用于治疗低钾血症，高血压，充血性心力衰竭，心房颤动，肾衰竭，特别是慢性肾衰竭，再狭窄，动脉粥样硬化，综合征X，肥胖症，肾病，心肌梗塞后， 冠状动脉心脏病，炎症，胶原蛋白形成增加，纤维化如心脏或心肌纤维化，以及高血压和内皮功能障碍后重塑，男子乳腺发育不良，骨质疏松症，前列腺癌，子宫内膜异位症，子宫肌瘤，功能障碍性子宫出血，子宫内膜增生，多囊卵巢疾病，不育症 ，纤维囊性乳腺疾病，乳腺癌和纤维囊性乳腺病。 最后，本发明还提供药物组合物。