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1.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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公开(公告)号：US08067416B2
公开(公告)日：2011-11-29
申请号：US12508209
申请日：2009-07-23
申请人： Daniel I. Oppenheimer , Emil D. Kakkis , Fredric D. Price , Alejandro Dorenbaum , Rudolf Moser , Viola Groehn , Thomas Egger , Fritz Blatter
发明人： Daniel I. Oppenheimer , Emil D. Kakkis , Fredric D. Price , Alejandro Dorenbaum , Rudolf Moser , Viola Groehn , Thomas Egger , Fritz Blatter
IPC分类号： A61K31/495 , A61K31/40 , A61K31/445 , A01N43/54
CPC分类号： A61K31/519 , A23L33/15 , A23L33/155 , A23L33/16 , A23L33/17 , A23L33/175 , A61K9/0053 , A61K31/00 , A61K31/198 , A61K31/5025
摘要： The present invention is directed to a novel methods and compositions for the therapeutic intervention in hyperphenylalaninemia. More specifically, the specification describes methods and compositions for treating various types of phenylketonurias using compositions comprising BH4. Combination therapies of BH4 and other therapeutic regimens are contemplated.
摘要翻译： 本发明涉及用于治疗性介入高苯丙氨酸血症的新方法和组合物。 更具体地，说明书描述了使用包含BH4的组合治疗各种类型的苯丙酮尿症的方法和组合物。 预期BH4和其他治疗方案的组合疗法。
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3.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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公开(公告)号：US20090238818A1
公开(公告)日：2009-09-24
申请号：US12412986
申请日：2009-03-27
IPC分类号： A61K39/395 , A61K38/13 , A61K38/43 , A61K39/00 , A61K39/385 , A61P37/06
CPC分类号： A61K39/00 , A61K31/522 , A61K31/7024 , A61K38/00 , A61K38/11 , A61K38/13 , A61K2300/00
摘要： Antigen specific immune tolerance is induced in a mammalian host by administration of a toleragen in combination with a regimen of immunosuppression. The methods optionally include a preceding conditioning period, where immunosuppressive agents are administered in the absence of the toleragen. After the tolerizing regimen, the host is withdrawn from the suppressive agents, but is able to maintain specific immune tolerance to the immunogenic epitopes present on the toleragen. Optimally, the toleragen will have high uptake properties that allow uptake in vivo at low concentrations in a wide variety of tolerizing cell types.
摘要翻译： 通过与免疫抑制方案组合施用耐受性，在哺乳动物宿主中诱导抗原特异性免疫耐受性。 所述方法任选地包括前述调节期，其中在不存在耐受性的情况下施用免疫抑制剂。 在耐受方案之后，宿主从抑制剂中排出，但能够对存在于耐受性上的免疫原性表位保持特异性的免疫耐受性。 最佳地，耐受性将具有高吸收性质，其允许在多种耐受细胞类型中以低浓度体内摄取。
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5.发明授权Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof 有权原核苯丙氨酸氨裂解酶的组合物及其组合物的使用方法公开(公告)号：US07534595B2
公开(公告)日：2009-05-19
申请号：US11807227
申请日：2007-05-25
摘要： The present invention is directed to phenylalanine ammonia-lyase (PAL) produced by prokaryotes, wherein such prokaryotic PAL wherein the PAL variant has a greater phenylalanine-converting activity and/or a reduced immunogenicity as compared to a wild-type PAL. The invention thus provides compositions of bacterial PAL and biologically active fragments, mutants, variants and analogs thereof, as well as methods for the production, purification, and use of such compositions for therapeutic and industrial purposes.
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），其中与野生型PAL相比，PAL变体具有更高的苯丙氨酸转化活性和/或免疫原性降低的原核PAL。 因此，本发明提供细菌PAL和生物活性片段，突变体，变体和类似物的组合物，以及用于制备，纯化和使用这些组合物用于治疗和工业目的的方法。
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6.发明授权Recombinant &agr;-L-iduronidase, methods for producing and purifying the same and methods for treating disease caused by deficiencies thereof 有权重组α-L-艾杜糖醛酸酶，其制备及纯化方法及其缺陷治疗疾病的方法公开(公告)号：US06585971B1
公开(公告)日：2003-07-01
申请号：US09711205
申请日：2000-11-09
申请人： Emil D. Kakkis
发明人： Emil D. Kakkis
IPC分类号： A61K3843
CPC分类号： C12Y302/01076 , A61K38/47 , A61K48/00 , C12N9/2402 , C12N9/88 , C12Y302/01014 , C12Y302/01075 , C12Y402/02004
摘要： The present invention provides a recombinant human &agr;-L-iduronidase and biologically active fragments and mutants thereof, large scale methods to produce and purify commercial grade recombinant human &agr;-L-iduronidase enzyme as well as methods to treat certain genetic disorders including &agr;-L-iduronidase deficiency and mucopolysaccharidosis I (MPS 1).
摘要翻译： 本发明提供了重组人α-L-真蛋白酶及其生物活性片段和突变体，大规模生产和纯化商业级重组人α-L-真蛋白酶的方法以及治疗某些遗传病症（包括α-L - 糖尿病病毒缺乏和粘多糖贮积症I（MPS 1）。
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7.发明授权Recombinant &agr;-L-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof 有权重组α-L-艾杜糖醛酸酶，其制备和纯化方法以及用于治疗由其缺陷引起的疾病的方法公开(公告)号：US06426208B1
公开(公告)日：2002-07-30
申请号：US09439923
申请日：1999-11-12
申请人： Emil D. Kakkis , Becky Tanamachi
发明人： Emil D. Kakkis , Becky Tanamachi
IPC分类号： C12N900
CPC分类号： C12N9/88 , A61K38/47 , A61K48/00 , C12N9/2402 , C12Y302/01014 , C12Y302/01075 , C12Y302/01076 , C12Y402/02004
摘要： The present invention provides a recombinant &agr;-L-iduronidase and biologically active fragments and mutants thereof, methods to produce and purify this enzyme as well as methods to treat certain genetic disorders including- &agr;-L-iduronidase deficiency and mucopolysaccharidosis I (MPS 1).
摘要翻译： 本发明提供了一种重组α-L-艾杜糖醛酸酶及其生物活性片段和突变体，产生和纯化该酶的方法以及治疗某些遗传病症包括-α-L-艾杜糖醛酸酶缺乏和粘多糖贮积症I（MPS 1）的方法， 。
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公开(公告)号：US09044473B2
公开(公告)日：2015-06-02
申请号：US11630446
申请日：2004-08-30
申请人： Emil D. Kakkis
发明人： Emil D. Kakkis
CPC分类号： A61K38/465 , A61K9/0085 , A61K38/47 , C12Y301/06008 , C12Y302/0105
摘要： The present invention relates to the intrathecal (IT) administration of recombinant enzyme to treat lysosomal storage disorders. In an exemplary embodiment, intrathecal administration of human α-L-iduronidase (rhIDU) injections in MPS I affected animals resulted in significant enzyme uptake, significant rh-iduronidase activity in brain and meninges and a decrease of glycosaminoglycan (GAG) storage in cells of MPS I subjects to that of normal subjects. Intrathecal administration proved more effective than intravenous treatment at alleviating MPS I symptoms, indicating it is a useful method of treating lysosomal storage disorders.
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9.发明申请METHODS AND COMPOSITIONS FOR THE TREATMENT OF PULMONARY HYPERTENSION OF THE NEWBORN 审中-公开治疗新生儿肺动脉高压的方法和组合公开(公告)号：US20100130500A1
公开(公告)日：2010-05-27
申请号：US11720815
申请日：2005-12-08
申请人： Emil D. Kakkis
发明人： Emil D. Kakkis
IPC分类号： A61K31/4985 , A61P9/12
CPC分类号： A61K31/505
摘要： The present invention is directed to a novel methods and compositions for the therapeutic intervention in persistent pulmonary hypertension of the newborn (PPHN). More specifically, the specification describes methods and compositions for treating various types of PPHN using compositions comprising BH4. Combination therapies of BH4 and other therapeutic regimens are contemplated.
摘要翻译： 本发明涉及用于新生儿持续性肺动脉高压（PPHN）的治疗性干预的新颖方法和组合物。 更具体地说，说明书描述了使用包含BH4的组合来处理各种类型的PPHN的方法和组合物。 预期BH4和其他治疗方案的组合疗法。
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10.发明授权Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof 有权原核苯丙氨酸氨裂解酶的组合物及其组合物的使用方法公开(公告)号：US07531341B1
公开(公告)日：2009-05-12
申请号：US11451999
申请日：2006-06-12
CPC分类号： C12N9/88 , A61K38/00 , C12Y403/01005
摘要： The present invention is directed to phenylalanine ammonia lyase (PAL) produced by prokaryotes, wherein such prokaryotic PAL wherein the PAL variant has a greater phenylalanine-converting activity as compared to a wild-type PAL. The invention thus provides compositions of bacterial PAL and biologically active fragments, mutants, variants and analogs thereof, as well as methods for the production, purification, and use of such compositions for therapeutic and industrial purposes.
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），其中与野生型PAL相比，PAL变体具有更大的苯丙氨酸转化活性的原核PAL。 因此，本发明提供细菌PAL和生物活性片段，突变体，变体和类似物的组合物，以及用于制备，纯化和使用这些组合物用于治疗和工业目的的方法。
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