公开(公告)号：EP3025728B1

公开(公告)日：2018-08-08

申请号：EP15202466.7

申请日：2011-02-03

申请人： BioMarin Pharmaceutical Inc.

发明人： KAKKIS, Emil D. ,  VELLARD, Michel Claude ,  WENDT, Daniel J. ,  MUTHALIF, Mubarack ,  OKHAMAFE, Augustus O. ,  BELL, Sean M. ,  ZECHERLE, G. Nick ,  ANTONSEN, Kris ,  ZHANG, Yanhong ,  LY, Kieu Y. ,  FITZPATRICK, Paul A.

IPC分类号： A61K38/51 ,  A61K47/10 ,  A61K47/18 ,  C12N9/88 ,  A61P3/00

CPC分类号： C12N9/88 ,  A61K9/0019 ,  A61K38/51 ,  A61K47/60 ,  C07K1/14 ,  C12Y403/01024

摘要： The present invention provides a method for purifying an Anabaena variabilis phenylalanine ammonia-lyase (AvPAL) variant with minimal aggregation. The method comprises the steps of (a) lysing bacterial cells containing the AvPAL variant by homogenization to generate a cell lysate; (b) heating the cell lysate to 65°C for 30 to 120 minutes; (c) centrifuging the heated cell lysate, wherein a supernatant comprising the AvPAL variant is retained; (d) filtering the supernatant to remove precipitates; and (e) separating the AvPAL variant from contaminating proteins by sequential chromatography over an anion exchange (AIEX) column followed by a hydrophobic interaction (HIC) column, wherein the eluate from the HIC column comprises the AvPAL variant, wherein the cysteine residues at positions 503 and 565 of said AvPAL variant have been substituted by serine residues (SEQ ID NO:11).

公开(公告)号：EP4406599A2

公开(公告)日：2024-07-31

申请号：EP24162497.2

申请日：2016-08-01

申请人： BioMarin Pharmaceutical Inc.

发明人： BULLENS, Sherry ,  BUNTING, Stuart ,  CHOU, Tianwei ,  OKHAMAFE, Augustus O ,  PRICE, Christopher P. ,  WENDT, Daniel J. ,  YAP, Clarence

IPC分类号： A61P19/08

CPC分类号： A61K38/1709 ,  A61K38/2242 ,  A61K9/19 ,  A61K9/0019 ,  A61K47/12 ,  A61K47/26 ,  A61K47/20 ,  A61P19/08

摘要： The present disclosure provides for use of variants of C-type natriuretic peptide (CNP), and novel pharmaceutical compositions and formulations comprising CNP variant peptides for the treatment of skeletal dysplasias, one or more symptoms of skeletal dysplasias, such as long bone growth or growth velocity, and other disorders having a skeletal dysplasia and/or CNP-associated symptom or component.

公开(公告)号：EP4406599A3

公开(公告)日：2024-11-06

申请号：EP24162497.2

申请日：2016-08-01

申请人： BioMarin Pharmaceutical Inc.

发明人： BULLENS, Sherry ,  BUNTING, Stuart ,  CHOU, Tianwei ,  OKHAMAFE, Augustus O ,  PRICE, Christopher P. ,  WENDT, Daniel J. ,  YAP, Clarence

IPC分类号： A61K9/00 ,  A61K9/19 ,  A61K38/17 ,  A61K38/22 ,  A61K47/12 ,  A61K47/20 ,  A61K47/26 ,  A61P19/08

摘要： The present disclosure provides for use of variants of C-type natriuretic peptide (CNP), and novel pharmaceutical compositions and formulations comprising CNP variant peptides for the treatment of skeletal dysplasias, one or more symptoms of skeletal dysplasias, such as long bone growth or growth velocity, and other disorders having a skeletal dysplasia and/or CNP-associated symptom or component.

公开(公告)号：EP3025728A1

公开(公告)日：2016-06-01

申请号：EP15202466.7

申请日：2011-02-03

申请人： BioMarin Pharmaceutical Inc.

发明人： KAKKIS, Emil D. ,  VELLARD, Michel Claude ,  WENDT, Daniel J. ,  MUTHALIF, Mubarack ,  OKHAMAFE, Augustus O. ,  BELL, Sean M. ,  ZECHERLE, G. Nick ,  ANTONSEN, Kris ,  ZHANG, Yanhong ,  LY, Kieu Y. ,  FITZPATRICK, Paul A.

IPC分类号： A61K38/51 ,  A61K47/10 ,  A61K47/18 ,  A61K47/48 ,  C12N9/88 ,  A61P3/00

CPC分类号： C12N9/88 ,  A61K9/0019 ,  A61K38/51 ,  A61K47/60 ,  C12Y403/01024

摘要： The present invention provides a method for purifying an Anabaena variabilis phenylalanine ammonia-lyase (AvPAL) variant with minimal aggregation. The method comprises the steps of (a) lysing bacterial cells containing the AvPAL variant by homogenization to generate a cell lysate; (b) heating the cell lysate to 65°C for 30 to 120 minutes; (c) centrifuging the heated cell lysate, wherein a supernatant comprising the AvPAL variant is retained; (d) filtering the supernatant to remove precipitates; and (e) separating the AvPAL variant from contaminating proteins by sequential chromatography over an anion exchange (AIEX) column followed by a hydrophobic interaction (HIC) column, wherein the eluate from the HIC column comprises the AvPAL variant, wherein the cysteine residues at positions 503 and 565 of said AvPAL variant have been substituted by serine residues (SEQ ID NO:11).

摘要翻译： 本发明提供了一种以最小的聚集来纯化鱼腥藻变异型苯丙氨酸氨裂解酶（AvPAL）变体的方法。 该方法包括以下步骤：（a）通过均质裂解含有AvPAL变体的细菌细胞以产生细胞裂解物; （b）将细胞裂解物加热至65℃30至120分钟; （c）离心加热的细胞裂解物，其中保留包含AvPAL变体的上清液; （d）过滤上清液以除去沉淀物; 和（e）通过在阴离子交换（AIEX）柱上随后是疏水相互作用（HIC）柱的顺序层析分离所述AvPAL变体与污染性蛋白质，其中来自HIC柱的洗脱液包含AvPAL变体，其中位置处的半胱氨酸残基 所述AvPAL变体的503和565已被丝氨酸残基（SEQ ID NO：11）取代。