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公开(公告)号：US20090047265A1
公开(公告)日：2009-02-19
申请号：US12107736
申请日：2008-04-22
CPC分类号： A61K38/164 , A61K38/51
摘要： The present invention is directed to phenylalanine ammonia-lyase (PAL) variants produced by prokaryotes, wherein such prokaryotic PAL variant has a greater phenylalanine-converting activity and/or a reduced immunogenicity as compared to a wild-type PAL. The invention provides compositions of prokaryotic PAL and biologically active fragments, mutants, variants or analogs thereof, as well as methods for the production, purification, and use of such compositions for therapeutic purposes, including the treatment of cancer.
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公开(公告)号：US07537923B2
公开(公告)日：2009-05-26
申请号：US12107736
申请日：2008-04-22
CPC分类号： A61K38/164 , A61K38/51
摘要： The present invention is directed to phenylalanine ammonia-lyase (PAL) variants produced by prokaryotes, wherein such prokaryotic PAL variant has a greater phenylalanine-converting activity and/or a reduced immunogenicity as compared to a wild-type PAL. The invention provides compositions of prokaryotic PAL and biologically active fragments, mutants, variants or analogs thereof, as well as methods for the production, purification, and use of such compositions for therapeutic purposes, including the treatment of cancer.
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3.发明申请COMPOSITIONS OF PROKARYOTIC PHENYLALANINE AMMONIA-LYASE VARIANTS AND METHODS OF USING COMPOSITIONS THEREOF 审中-公开原始苯丙氨酸氨基酸变体的组成及其组合物的使用方法公开(公告)号：US20130039898A1
公开(公告)日：2013-02-14
申请号：US13576625
申请日：2011-02-03
申请人： Augustus O. Okhamafe , Sean M. Bell , G. Nick Zecherle , Kris Antonsen , Yanhong Zhang , Kieu Ly Tran , Paul A. Fitzpatrick , Emil D. Kakkis , Michel Claude Vellard , Daniel J. Wendt , Mubarack Muthalif
发明人： Augustus O. Okhamafe , Sean M. Bell , G. Nick Zecherle , Kris Antonsen , Yanhong Zhang , Kieu Ly Tran , Paul A. Fitzpatrick , Emil D. Kakkis , Michel Claude Vellard , Daniel J. Wendt , Mubarack Muthalif
CPC分类号： C12N9/88 , A61K9/0019 , A61K38/51 , A61K47/60 , C07K1/14 , C12Y403/01024
摘要： Provided herein are phenylalanine ammonia-lyase (PAL) variants produced by prokaryotes, wherein such prokaryotic PAL variant has a greater phenylalanine-converting activity and/or a reduced immunogenicity as compared to a wild-type PAL. Further provided are compositions of prokaryotic PAL and biologically active fragments, mutants, variants or analogs thereof, as well as methods for the production, purification, formulation, and use of such compositions for industrial and therapeutic purposes, e.g., treating hyperphenylalaninemia, including phenylketonuria, and other disorders, including cancer.
摘要翻译： 本文提供了由原核生物产生的苯丙氨酸氨裂解酶（PAL）变体，其中与野生型PAL相比，这种原核PAL变体具有更大的苯丙氨酸转化活性和/或降低的免疫原性。 还提供了原核PAL和其生物活性片段，突变体，变体或类似物的组合物，以及用于生产，纯化，制备和使用这些组合物用于工业和治疗目的的方法，例如治疗高苯丙氨酸血症，包括苯丙酮尿症， 和其他疾病，包括癌症。
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4.发明申请COMPOSITIONS OF PROKARYOTIC PHENYLALANINE AMMONIA-LYASE AND METHODS OF TREATING CANCER USING COMPOSITIONS THEREOF 审中-公开原始苯丙氨酸氨基酸的组合物及其组合物治疗癌症的方法公开(公告)号：US20100278802A1
公开(公告)日：2010-11-04
申请号：US12833911
申请日：2010-07-09
CPC分类号： A61K38/164 , A61K38/51
摘要： The present invention is directed to phenylalanine ammonia-lyase (PAL) variants produced by prokaryotes, wherein such prokaryotic PAL variant has a greater phenylalanine-converting activity and/or a reduced immunogenicity as compared to a wild-type PAL. The invention provides compositions of prokaryotic PAL and biologically active fragments, mutants, variants or analogs thereof, as well as methods for the production, purification, and use of such compositions for therapeutic purposes, including the treatment of cancer.
摘要翻译： 本发明涉及由原核生物产生的苯丙氨酸氨裂解酶（PAL）变体，其中与野生型PAL相比，这种原核PAL变体具有较大的苯丙氨酸转化活性和/或降低的免疫原性。 本发明提供了原核PAL和其生物活性片段，突变体，变体或类似物的组合物，以及用于制备，纯化和使用这些组合物用于治疗目的，包括治疗癌症的方法。
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5.发明授权Compositions of prokaryotic phenylalanine ammonia-lyase and methods of treating cancer using compositions thereof 有权原核苯丙氨酸氨裂解酶的组合物及其组合物治疗癌症的方法公开(公告)号：US07790433B2
公开(公告)日：2010-09-07
申请号：US12421557
申请日：2009-04-09
CPC分类号： A61K38/164 , A61K38/51
摘要： The present invention is directed to phenylalanine ammonia-lyase (PAL) variants produced by prokaryotes, wherein such prokaryotic PAL variant has a greater phenylalanine-converting activity and/or a reduced immunogenicity as compared to a wild-type PAL. The invention provides compositions of prokaryotic PAL and biologically active fragments, mutants, variants or analogs thereof, as well as methods for the production, purification, and use of such compositions for therapeutic purposes, including the treatment of cancer.
摘要翻译： 本发明涉及由原核生物产生的苯丙氨酸氨裂解酶（PAL）变体，其中与野生型PAL相比，这种原核PAL变体具有较大的苯丙氨酸转化活性和/或降低的免疫原性。 本发明提供了原核PAL和其生物活性片段，突变体，变体或类似物的组合物，以及用于制备，纯化和使用这些组合物用于治疗目的，包括治疗癌症的方法。
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公开(公告)号：US20100297021A1
公开(公告)日：2010-11-25
申请号：US12784117
申请日：2010-05-20
申请人： Daniel J. Wendt , Shinong Long , Sianna Castillo , Christopher P. Price , Mika Aoyagi-Scharber , Michel C. Vellard , Augustus O. Okhamafe
发明人： Daniel J. Wendt , Shinong Long , Sianna Castillo , Christopher P. Price , Mika Aoyagi-Scharber , Michel C. Vellard , Augustus O. Okhamafe
IPC分类号： A61K38/16 , A61K49/00 , G01N33/53 , C12Q1/42 , C12P21/06 , C12N1/21 , G01N33/68 , A61K38/00 , A61K38/10 , C07K14/00 , C07K7/00 , A61P9/00 , A61P9/12 , A61P13/12 , A61P19/00
CPC分类号： C07K14/58 , A61K9/08 , A61K38/00 , A61K38/22 , A61K38/2242 , A61K47/10 , A61K47/20 , A61K47/22 , A61K47/26 , A61K47/60 , G01N2333/58 , G01N2800/10 , G01N2800/105 , G01N2800/385 , G01N2800/52
摘要： The present disclosure provides variants of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising CNP variants, and methods of making CNP variants. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders, such as skeletal dysplasias (e.g., achondroplasia), and vascular smooth muscle disorders (e.g., restenosis and arteriosclerosis).
摘要翻译： 本公开提供了C型利钠肽（CNP），包含CNP变体的药物组合物和制备CNP变体的方法的变体。 CNP变体可用作治疗针对CNP的疾病的治疗剂，包括但不限于骨相关疾病，例如骨骼发育不良（例如软骨发育不良）和血管平滑肌病（例如再狭窄和动脉硬化）。
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公开(公告)号：US08198242B2
公开(公告)日：2012-06-12
申请号：US12784117
申请日：2010-05-20
申请人： Daniel J. Wendt , Shinong Long , Sianna Castillo , Christopher P. Price , Mika Aoyagi-Scharber , Michel C. Vellard , Augustus O. Okhamafe
发明人： Daniel J. Wendt , Shinong Long , Sianna Castillo , Christopher P. Price , Mika Aoyagi-Scharber , Michel C. Vellard , Augustus O. Okhamafe
CPC分类号： C07K14/58 , A61K9/08 , A61K38/00 , A61K38/22 , A61K38/2242 , A61K47/10 , A61K47/20 , A61K47/22 , A61K47/26 , A61K47/60 , G01N2333/58 , G01N2800/10 , G01N2800/105 , G01N2800/385 , G01N2800/52
摘要： The present disclosure provides variants of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising CNP variants, and methods of making CNP variants. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders, such as skeletal dysplasias (e.g., achondroplasia), and vascular smooth muscle disorders (e.g., restenosis and arteriosclerosis).
摘要翻译： 本公开提供了C型利钠肽（CNP），包含CNP变体的药物组合物和制备CNP变体的方法的变体。 CNP变体可用作治疗针对CNP的疾病的治疗剂，包括但不限于骨相关疾病，例如骨骼发育不良（例如软骨发育不良）和血管平滑肌病（例如再狭窄和动脉硬化）。
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公开(公告)号：US08598121B2
公开(公告)日：2013-12-03
申请号：US13466672
申请日：2012-05-08
申请人： Daniel J. Wendt , Shinong Long , Sianna Castillo , Christopher P. Price , Mika Aoyagi-Scharber , Michel Claude Vellard , Augustus O. Okhamafe
发明人： Daniel J. Wendt , Shinong Long , Sianna Castillo , Christopher P. Price , Mika Aoyagi-Scharber , Michel Claude Vellard , Augustus O. Okhamafe
CPC分类号： C07K14/58 , A61K9/08 , A61K38/00 , A61K38/22 , A61K38/2242 , A61K47/10 , A61K47/20 , A61K47/22 , A61K47/26 , A61K47/60 , G01N2333/58 , G01N2800/10 , G01N2800/105 , G01N2800/385 , G01N2800/52
摘要： The present disclosure provides variants of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising CNP variants, and methods of making CNP variants. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders, such as skeletal dysplasias (e.g., achondroplasia), and vascular smooth muscle disorders (e.g., restenosis and arteriosclerosis).
摘要翻译： 本公开提供了C型利钠肽（CNP），包含CNP变体的药物组合物和制备CNP变体的方法的变体。 CNP变体可用作治疗针对CNP的疾病的治疗剂，包括但不限于骨相关疾病，例如骨骼发育不良（例如软骨发育不良）和血管平滑肌病（例如再狭窄和动脉硬化）。
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公开(公告)号：US20120316114A1
公开(公告)日：2012-12-13
申请号：US13466672
申请日：2012-05-08
申请人： Daniel J. Wendt , Shinong Long , Sianna Castillo , Christopher P. Price , Mika Aoyagi-Scharber , Michel C. Vellard , Augustus O. Okhamafe
发明人： Daniel J. Wendt , Shinong Long , Sianna Castillo , Christopher P. Price , Mika Aoyagi-Scharber , Michel C. Vellard , Augustus O. Okhamafe
IPC分类号： C07K14/575 , A61K38/22 , A61P19/00 , C12N5/10 , C12P21/02 , C12N1/21 , C12N1/19 , C07K7/08 , A61P21/00
CPC分类号： C07K14/58 , A61K9/08 , A61K38/00 , A61K38/22 , A61K38/2242 , A61K47/10 , A61K47/20 , A61K47/22 , A61K47/26 , A61K47/60 , G01N2333/58 , G01N2800/10 , G01N2800/105 , G01N2800/385 , G01N2800/52
摘要： The present disclosure provides variants of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising CNP variants, and methods of making CNP variants. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders, such as skeletal dysplasias (e.g., achondroplasia), and vascular smooth muscle disorders (e.g., restenosis and arteriosclerosis).
摘要翻译： 本公开提供了C型利钠肽（CNP），包含CNP变体的药物组合物和制备CNP变体的方法的变体。 CNP变体可用作治疗针对CNP的疾病的治疗剂，包括但不限于骨相关疾病，例如骨骼发育不良（例如软骨发育不良）和血管平滑肌病（例如再狭窄和动脉硬化）。
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公开(公告)号：US20120277434A1
公开(公告)日：2012-11-01
申请号：US13539872
申请日：2012-07-02
申请人： Shaopei Cai , Joyce Chou , Eric Harwood , Timothy MacHajewski , David Ryckman , Xiao Shang , Shuguang Zhu , Augustus O. Okhamafe , Marc S. Tesconi
发明人： Shaopei Cai , Joyce Chou , Eric Harwood , Timothy MacHajewski , David Ryckman , Xiao Shang , Shuguang Zhu , Augustus O. Okhamafe , Marc S. Tesconi
IPC分类号： C07D295/12
CPC分类号： C07D401/04 , A61K31/4375 , A61K31/4709 , A61K31/496 , A61K31/5377 , A61K31/541 , C07C51/412 , C07C59/08
摘要： A method of synthesizing a substituted or unsubstituted 4-amino-3-benzimidazolyl quinolinone compound includes reacting a first compound having the formula I with a second compound having the formula II in a suitable solvent in the presence of a sodium or potassium salt of a base. The first compound and the second compound have the following structures where the variables have the values described herein:
摘要翻译： 合成取代或未取代的4-氨基-3-苯并咪唑基喹啉酮化合物的方法包括在合适的溶剂中，在碱的钠盐或钾盐存在下使具有式I的第一化合物与式II的第二化合物反应 。 第一化合物和第二化合物具有以下结构，其中变量具有本文所述的值：
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