公开(公告)号：WO2012012718A2

公开(公告)日：2012-01-26

申请号：PCT/US2011045011

申请日：2011-07-22

Applicant: BIOMARIN PHARM INC ,  KOPPAKA VISH ,  VELLARD MICHEL CLAUDE ,  OKHAMAFE AUGUSTUS O ,  ARAYA KIDISTI

Inventor： KOPPAKA VISH ,  VELLARD MICHEL CLAUDE ,  OKHAMAFE AUGUSTUS O ,  ARAYA KIDISTI

IPC: A61K38/46 ,  C12N9/16

CPC classification number: C12N9/16 ,  A61K9/08 ,  A61K38/00 ,  A61K38/465 ,  C12Y301/06004

Abstract: This invention provides compositions of active highly phosphorylated human N- acetylgalactosamine-6-sulfatase (GALNS), and pharmaceutical compositions and formulations thereof, methods of producing and purifying GALNS, and its use in the diagnosis, prophylaxis, or treatment of diseases and conditions, including particularly lysosomal storage diseases that are caused by, or associated with, a deficiency in the GALNS enzyme, e.g., Mucopolysaccharidosis IVa (MPS IVa or Morquio A syndrome).

Abstract translation: 本发明提供了活性高度磷酸化人N-乙酰半乳糖胺-6-硫酸酯酶（GALNS）的组合物及其药物组合物和制剂，生产和纯化GALNS的方法及其在诊断，预防或治疗疾病和病症中的用途， 包括特别是由GALNS酶缺乏引起或与其相关的溶酶体贮积病，例如粘多糖贮积病IVa（MPS IVa或Morquio A综合征）。

公开(公告)号：WO2008011154A3

公开(公告)日：2008-06-26

申请号：PCT/US2007016469

申请日：2007-07-20

Applicant: NOVARTIS AG ,  HASHASH AHMAD ,  RITCHIE SEAN ,  LIN KANGWEN ,  SHEN PENG ,  OKHAMAFE AUGUSTUS ,  GULLAPALLI RAMPURNA

Inventor： HASHASH AHMAD ,  RITCHIE SEAN ,  LIN KANGWEN ,  SHEN PENG ,  OKHAMAFE AUGUSTUS ,  GULLAPALLI RAMPURNA

IPC: A61K9/107 ,  A61K31/00 ,  C07D401/14

CPC classification number: A61K9/1075 ,  A61K9/107 ,  A61K9/143 ,  A61K9/4858

Abstract: Formulations are provided, comprising: a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a mixture of any two or more thereof; and an ingredient selected from a hydrophilic solvent, a lipophilic solvent, an emulsifier, or a mixture of any two or more thereof; wherein the compound of Formula (I) is: In some embodiments, the formulations are liquids. In other embodiments, the formulations are solids. Also provided are methods of preparing such formulations.

Abstract translation: 提供制剂，其包含：式（I）的化合物，其药学上可接受的盐或其任何两种或多种的混合物; 和选自亲水性溶剂，亲脂性溶剂，乳化剂或其任何两种或更多种的混合物的成分; 其中式（I）的化合物是：在一些实施方案中，制剂是液体。 在其它实施方案中，制剂是固体。 还提供了制备这种制剂的方法。

公开(公告)号：WO2007103425A3

公开(公告)日：2008-01-31

申请号：PCT/US2007005814

申请日：2007-03-06

Applicant: NOVARTIS AG ,  OKHAMAFE AUGUSTUS ,  HUANG CHIN-YI

Inventor： OKHAMAFE AUGUSTUS ,  HUANG CHIN-YI

IPC: A61K9/00 ,  A61K38/57 ,  A61K47/12 ,  A61K47/18 ,  A61P11/00

CPC classification number: A61K9/08 ,  A61K9/0019 ,  A61K38/57 ,  A61K47/12 ,  A61K47/183

Abstract: The polypeptide Tissue Factor Pathway Inhibitor (TFPI) and variants thereof can be advantageously stored in a form (e.g., a concentrated aqueous solution) that exhibits high stability and thereafter converted (e.g., by mixing with a diluent) into a form that is therapeutically effective (e.g., in the treatment of severe Community Acquired Pneumonia) when administered parenterally (e.g., intravenously) to patients. The separate storage of components of pharmaceutical compositions comprising TFPI and TFPI variants provides several important advantages. The components are generally a concentrated polypeptide solution and a diluent.

Abstract translation: 多肽组织因子通路抑制剂（TFPI）及其变体可有利地以表现出高稳定性并随后转化（例如通过与稀释剂混合）形成治疗有效的形式（例如，浓缩水溶液） （例如，在严重的社区获得性肺炎的治疗中）当向患者肠胃外（例如，静脉内）施用时。 包含TFPI和TFPI变体的药物组合物的组分的单独储存提供了几个重要的优点。 组分通常是浓缩的多肽溶液和稀释剂。

公开(公告)号：WO2007124299A3

公开(公告)日：2008-01-03

申请号：PCT/US2007066757

申请日：2007-04-17

Applicant: NOVARTIS AG ,  XOMA TECHNOLOGY LTD ,  LU XIAOFENG ,  CHEN BAO-LU ,  ARAYA KIDISTI ,  OKHAMAFE AUGUSTUS

Inventor： LU XIAOFENG ,  CHEN BAO-LU ,  ARAYA KIDISTI ,  OKHAMAFE AUGUSTUS

IPC: C07K16/28

CPC classification number: C07K16/2878 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/94

Abstract: Stable liquid pharmaceutical compositions comprising an antagonist anti- CD40 antibody as a therapeutically or prophylactically active component and methods useful in their preparation are provided. These compositions comprise the antagonist anti-CD40 antibody, a buffering agent to maintain the pH of the composition between about pH 5.0 and about pH 7.0, and an amount of arginine-HCl sufficient to render the liquid composition near isotonic. The stable liquid antagonist anti-CD40 antibody -containing pharmaceutical compositions of the invention find use in methods for treating proliferative diseases and diseases having an autoimmune and/or inflammatory component.

Abstract translation: 提供了包含拮抗性抗CD40抗体作为治疗或预防活性成分的稳定的液体药物组合物和可用于其制备的方法。 这些组合物包含拮抗性抗-CD40抗体，保持组合物的pH在约pH5.0和约pH7.0之间的缓冲剂和足以使液体组合物接近等渗的精氨酸-HCl的量。 本发明的稳定的液体拮抗剂抗CD40抗体的药物组合物可用于治疗具有自身免疫和/或炎性成分的增殖性疾病和疾病的方法。

公开(公告)号：WO2011097335A2

公开(公告)日：2011-08-11

申请号：PCT/US2011/023534

申请日：2011-02-03

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

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

IPC: A61K38/51

CPC classification number: C12N9/88 ,  A61K9/0019 ,  A61K38/51 ,  A61K47/60 ,  C12Y403/01024

Abstract: 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.

Abstract translation: 本文提供了由原核生物产生的苯丙氨酸解氨酶（PAL）变体，其中与野生型PAL相比，此类原核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。 进一步提供了原核PAL和其生物活性片段，突变体，变体或类似物的组合物，以及用于工业和治疗目的的这种组合物的生产，纯化，配制和使用的方法，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。

公开(公告)号：WO2008128049A3

公开(公告)日：2009-11-19

申请号：PCT/US2008060041

申请日：2008-04-11

Applicant: BIOMARIN PHARM INC ,  OPPENHEIMER DANIEL I ,  DORENBAUM ALEJANDRO ,  OKHAMAFE AUGUSTUS ,  FOEHR ERIK ,  CASTILLO SIANNA ,  KOSTEL PAUL JOHN

Inventor： OPPENHEIMER DANIEL I ,  DORENBAUM ALEJANDRO ,  OKHAMAFE AUGUSTUS ,  FOEHR ERIK ,  CASTILLO SIANNA ,  KOSTEL PAUL JOHN

IPC: A61K31/519 ,  A61K45/06 ,  A61K47/12 ,  A61K47/14 ,  A61P3/00 ,  A61P3/02 ,  A61P25/06 ,  A61P25/16 ,  A61P25/24 ,  A61P25/28 ,  C07B63/00

CPC classification number: A61K31/519 ,  A61K9/0019 ,  A61K9/0053 ,  A61K9/0065 ,  A61K9/0095 ,  A61K9/08 ,  A61K9/1652 ,  A61K9/2027 ,  A61K9/2054 ,  A61K9/2086 ,  A61K9/4808 ,  A61K9/4858 ,  A61K9/4891 ,  A61K45/06 ,  C07B63/00 ,  C07D487/04 ,  G01N27/62 ,  G01N30/7233 ,  G01N33/6848 ,  H01J49/004 ,  Y10T436/147777 ,  A61K2300/00

Abstract: The present invention is directed to treatment methods of administering tetrahydrobiopterin, including in oral dosage forms, in intravenous formulations, and with food. Also disclosed herein are biopterin assays for measuring the amount of biopterin and metabolites of biopterin in a sample.

Abstract translation: 本发明涉及给予四氢生物喋呤的治疗方法，包括口服剂型，静脉内制剂和食物。 本文还公开了用于测量样品中生物蝶呤和生物蝶呤代谢物的量的生物蝶呤测定法。

公开(公告)号：WO2007064719A2

公开(公告)日：2007-06-07

申请号：PCT/US2006/045711

申请日：2006-11-29

Applicant: NOVARTIS AG ,  CHOU, Joyce ,  OKHAMAFE, Augustus ,  FRECH, Patricia ,  GULLAPALLI, Rampurma

Inventor： CHOU, Joyce ,  OKHAMAFE, Augustus ,  FRECH, Patricia ,  GULLAPALLI, Rampurma

CPC classification number: A61K47/12 ,  A61K9/4858 ,  A61K9/4866 ,  A61K31/496

Abstract: A pharmaceutical formulation, comprising: a compound of formula (I), a tautomer of the compound, a salt of the compound, a salt of the tautomer, or a mixture thereof and at least one ingredient selected from the group consisting of (i) cellulose; (ii) silicon dioxide; (iii) magnesium stearate; and (iv) an ingredient selected from crospovidone, starch, or lactose.

Abstract translation: 药物制剂，其包含：式（I）的化合物，该化合物的互变异构体，该化合物的盐，该互变异构体的盐或其混合物和至少一种选择的成分 来自由以下组成的组：（i）纤维素; （ii）二氧化硅; （iii）硬脂酸镁; 和（iv）选自交聚维酮，淀粉或乳糖的成分。

公开(公告)号：WO2007062076A2

公开(公告)日：2007-05-31

申请号：PCT/US2006045125

申请日：2006-11-20

Applicant: NOVARTIS AG ,  OKHAMAFE AUGUSTUS ,  HORA MININDER ,  FAKES DAVID ,  WEI REBECCA ,  DANI BHAS ,  HASHASH AHMAD

Inventor： OKHAMAFE AUGUSTUS ,  HORA MININDER ,  FAKES DAVID ,  WEI REBECCA ,  DANI BHAS ,  HASHASH AHMAD

IPC: A61K31/495 ,  A61K9/19 ,  A61P31/00

CPC classification number: A61K9/0019 ,  A61K9/19 ,  A61K31/495

Abstract: Improved formulations of dexrazoxane for making injectable solutions in a clinical setting are provided. In some embodiments, high pH formulations are provided to reduce or eliminate pain upon injection. According to various embodiments, dexrazoxane may be formulated as a lyophilized or non-lyophilized acid salt or as a lyophilized or non-lyophilized free base. In some embodiments, dexrazoxane is provided as a sterile dry milled powder of a free base or an isolated acid salt crystal. Formulations that require significantly reduced clinical preparation time are provided. Single-container presentations of unit doses of dexrazoxane are also provided. The formulations of the present invention may be provided in a vial, infusion bottle or infusion bag. In some embodiments, the container may be directly attachable to a diluent-containing container for easy preparation. In other embodiments, diluent may be added directly to the container. Improved methods of manufacturing dexrazoxane that allow greater processing latitude are also provided.

Abstract translation: 提供了用于在临床环境中制备可注射溶液的右旋唑烷的改进制剂。 在一些实施方案中，提供高pH制剂以减少或消除注射时的疼痛。 根据各种实施方案，地塞米松可以配制成冻干或非冻干的酸盐或冻干或非冻干的游离碱。 在一些实施方案中，将脱甲硅烷作为游离碱或分离的酸盐晶体的无菌干研磨粉末提供。 提供需要显着减少临床准备时间的制剂。 还提供了单位剂量的地塞米松的单容器介绍。 本发明的制剂可以提供在小瓶，输液瓶或输液袋中。 在一些实施方案中，容器可以直接附接到含稀释剂的容器以便于制备。 在其它实施方案中，可以将稀释剂直接加入到容器中。 还提供了改进的允许更大加工纬度的地塞米松的制造方法。

公开(公告)号：WO2005046589A3

公开(公告)日：2005-05-26

申请号：PCT/US2004/036941

申请日：2004-11-05

Applicant: CHIRON CORPORATION ,  CAI, Shaopei ,  CHOU, Joyce ,  HARWOOD, Eric ,  MACHAJEWSKI, Timothy D. ,  RYCKMAN, David ,  SHANG, Xiao ,  ZHU, Shuguang ,  OKHAMAFE, Augustus, O. ,  TESCONI, Marc, S.

Inventor： CAI, Shaopei ,  CHOU, Joyce ,  HARWOOD, Eric ,  MACHAJEWSKI, Timothy D. ,  RYCKMAN, David ,  SHANG, Xiao ,  ZHU, Shuguang ,  OKHAMAFE, Augustus, O. ,  TESCONI, Marc, S.

IPC: C07D471/04

Abstract: A lacate salt of a compound of Formula: (I) or a tautomer of the compound, wherein Formula (I) has the following structure and R 1 -R 9 and R 12 -R 14 are as defined herein.

公开(公告)号：WO2012012718A3

公开(公告)日：2012-01-26

申请号：PCT/US2011/045011

申请日：2011-07-22

Applicant: BIOMARIN PHARMACEUTICAL INC. ,  KOPPAKA, Vish ,  VELLARD, Michel, Claude ,  OKHAMAFE, Augustus, O. ,  ARAYA, Kidisti

Inventor： KOPPAKA, Vish ,  VELLARD, Michel, Claude ,  OKHAMAFE, Augustus, O. ,  ARAYA, Kidisti

IPC: A61K38/46 ,  C12N9/16

Abstract: This invention provides compositions of active highly phosphorylated human N- acetylgalactosamine-6-sulfatase (GALNS), and pharmaceutical compositions and formulations thereof, methods of producing and purifying GALNS, and its use in the diagnosis, prophylaxis, or treatment of diseases and conditions, including particularly lysosomal storage diseases that are caused by, or associated with, a deficiency in the GALNS enzyme, e.g. , Mucopolysaccharidosis IVa (MPS IVa or Morquio A syndrome).