公开(公告)号：WO2012027247A2

公开(公告)日：2012-03-01

申请号：PCT/US2011/048565

申请日：2011-08-22

Applicant: VERTEX PHARMACEUTICALS INCORPORATED ,  ALARGOVA, Rossitza, Gueorguieva ,  DUNBAR, Craig, Antony ,  KADIYALA, Irina, Nikolaevna

Inventor： ALARGOVA, Rossitza, Gueorguieva ,  DUNBAR, Craig, Antony ,  KADIYALA, Irina, Nikolaevna

IPC: A61K9/20

CPC classification number: A61K31/404 ,  A61K9/1623 ,  A61K9/1652 ,  A61K9/2018 ,  A61K9/2054 ,  A61K9/2077

Abstract: A pharmaceutical composition comprising Compound 1, (R)-l-(2,2-difluorobenzo[d][l,3]dioxol-5-yl)-N-(l-(2,3-dihydroxypropyl)-6-fluoro-2-(l-hydroxy-2- methylpropan-2-yl)-lH-indol-5-yl)cyclopropanecarboxamide, and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering the pharmaceutical composition of Compound 1 are also disclosed.

Abstract translation: （R）-1-（2,2-二氟苯并[d] [1,3]间二氧杂环戊烯-5-基）-N-（1-（2,2,2-三氟 - （1-羟基-2-甲基丙烷-2-基）-1H-吲哚-5-基）环丙烷甲酰胺和至少一种选自以下的赋形剂：填充剂，稀释剂， 崩解剂，表面活性剂，助流剂和润滑剂，所述组合物适合于口服给予有需要的患者以治疗CFTR介导的疾病，例如囊性纤维化。 还公开了治疗有需要的患者的方法，包括施用化合物1的药物组合物。

公开(公告)号：WO2011127241A3

公开(公告)日：2012-02-02

申请号：PCT/US2011031519

申请日：2011-04-07

Applicant: VERTEX PHARMA ,  VERWIJS MARINUS JACOBUS ,  ALARGOVA ROSSITZA GUEORGUIEVA ,  KAUSHIK RITU ROHIT ,  KADIYALA IRINA NIKOLAEVNA ,  YOUNG CHRISTOPHER RYAN

Inventor： VERWIJS MARINUS JACOBUS ,  ALARGOVA ROSSITZA GUEORGUIEVA ,  KAUSHIK RITU ROHIT ,  KADIYALA IRINA NIKOLAEVNA ,  YOUNG CHRISTOPHER RYAN

IPC: A61K9/16 ,  A61K9/20 ,  A61K9/28 ,  C07D213/75 ,  C07D405/12 ,  C07D405/14

CPC classification number: A61K31/443 ,  A61K9/0053 ,  A61K9/1682 ,  A61K9/2009 ,  A61K9/2013 ,  A61K9/2027 ,  A61K9/2054 ,  A61K9/2077 ,  A61K9/2095 ,  A61K31/47

Abstract: A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2- difluorobenzo [d] [ 1,3 ] dioxol-5 -y1) cyclopropanecarboxamido)-3 -methylpyridin-2-y1)benzoic acid), and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a binder, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering an oral pharmaceutical formulation of Compound 1 to the patient.

Abstract translation: 包含化合物1（3-（6-（1-（2,2-二氟苯并[d] [1,3]二氧杂环戊烯-5-基）环丙烷甲酰氨基）-3-甲基吡啶-2-基）苯甲酸的药物组合物 和至少一种选自：填料，稀释剂，崩解剂，表面活性剂，粘合剂，助流剂和润滑剂的赋形剂，所述组合物适合于有需要的患者口服给药以治疗CFTR介导的疾病，例如 作为囊性纤维化。 用于治疗有需要的患者的方法包括向患者施用化合物1的口服药物制剂。

公开(公告)号：WO2008106151A2

公开(公告)日：2008-09-04

申请号：PCT/US2008/002568

申请日：2008-02-27

Applicant: VERTEX PHARMACEUTICALS INCORPORATED ,  CONNELLY, Patrick, R. ,  KADIYALA, Irina ,  STAVROPOLUS, Kathy ,  ZHANG, Yuegang ,  JOHNSTON, Steve ,  BHISETTI, Govinda, Rao ,  JURKAUSKAS, Valdas ,  ROSE, Peter

Inventor： CONNELLY, Patrick, R. ,  KADIYALA, Irina ,  STAVROPOLUS, Kathy ,  ZHANG, Yuegang ,  JOHNSTON, Steve ,  BHISETTI, Govinda, Rao ,  JURKAUSKAS, Valdas ,  ROSE, Peter

CPC classification number: C07K5/0812 ,  C07D403/12

Abstract: The invention relates to compositions and co-crystals each comprising VX-950 and a co-crystal former selected from the group consisting of 4-hydroxybenzoic acid, 4-amino salicylic acid, phenylalanine, threonline, tartaric acid, adipic acid, succinic acetate, proline, methyl 4-hydroxybenzoate, anthranilic acid, and d-Biotin. Also within the scope of this invention are methods of making and using the same.

Abstract translation: 本发明涉及各自包含VX-950和选自4-羟基苯甲酸，4-氨基水杨酸，苯丙氨酸，苏氨酸，酒石酸的共晶体形成物的组合物和共晶体 酸，己二酸，琥珀酸乙酸酯，脯氨酸，4-羟基苯甲酸甲酯，邻氨基苯甲酸和d-生物素。 也在本发明的范围内的是制造和使用它们的方法。

公开(公告)号：WO2007142951A3

公开(公告)日：2007-12-13

申请号：PCT/US2007/012715

申请日：2007-05-30

Applicant: VERTEX PHARMACEUTICALS INCORPORATED ,  KADIYALA, Irina, Nikolaevna ,  LIN, Wu ,  HURTER, Patricia

Inventor： KADIYALA, Irina, Nikolaevna ,  LIN, Wu ,  HURTER, Patricia

IPC: A61K9/16 ,  A61K9/20 ,  A61K31/401

Abstract: The invention relates to a controlled release formulation for an oral cytokine inhibitor of interleukin-1 beta converting enzyme.

公开(公告)号：WO03060473A3

公开(公告)日：2005-09-15

申请号：PCT/US0301405

申请日：2003-01-14

Applicant: VERTEX PHARMA ,  KADIYALA IRINA ,  PANICUCCI RICCARDO

Inventor： KADIYALA IRINA ,  PANICUCCI RICCARDO

IPC: C07K14/47 ,  C07K17/00 ,  G01N33/538 ,  C07K1/14 ,  C07K1/16 ,  C07K1/20 ,  C07K4/12 ,  C07K14/435 ,  C07K17/02 ,  C07K17/14 ,  C12P7/06

CPC classification number: G01N33/538 ,  C07K14/4727 ,  C07K17/00 ,  G01N2333/4725

Abstract: An in vitro high-throughput screening method that models the absorption of drugs across the epithelial mucosa is provided. The invention discloses an in vitro mucin immobilized chromatography model to estimate drug permeability coefficients. The invention describes compositions for mucin immobilized chromatography media and methods to prepare this media. The invention also discloses a method to estimate in vitro drug permeability coefficients using mucin immobilized chromatography media. The invention also discloses methods to determine absorption processes in the digestive system and discloses methods of use for mucin chromatography media in column, batch, assay, diagnostic, or high-throughput screening analyses.

Abstract translation: 提供了一种模拟通过上皮粘膜吸收药物的体外高通量筛选方法。 本发明公开了一种用于估计药物渗透系数的体外粘蛋白固定化色谱模型。 本发明描述了用于粘蛋白固定的色谱介质的组合物和制备该介质的方法。 本发明还公开了使用粘蛋白固定化色谱介质估计体外药物渗透系数的方法。 本发明还公开了确定消化系统中吸收过程的方法，并公开了在柱，批，测定，诊断或高通量筛选分析中使用粘蛋白色谱介质的方法。

公开(公告)号：WO2011133951A1

公开(公告)日：2011-10-27

申请号：PCT/US2011/033687

申请日：2011-04-22

Applicant: VERTEX PHARMACEUTICALS INCORPORATED ,  VAN GOOR, Fredrick, F. ,  ALARGOVA, Rossitza, Gueorguieva ,  ALCACIO, Tim, Edward ,  AREKAR, Sneha, G. ,  JOHNSTON, Steven, C. ,  KADIYALA, Irina, Nikolaevna ,  KESHAVARZ-SHOKRI, Ali ,  KRAWIEC, Mariusz ,  LEE, Elaine, Chungmin ,  MEDEK, Ales ,  MUDUNURI, Praveen ,  SULLIVAN, Mark, Jeffrey ,  ZAMAN, Noreen, Tasneem ,  ZHANG, Beili ,  ZHANG, Yuegang ,  ZLOKARNIK, Gregor

Inventor： VAN GOOR, Fredrick, F. ,  ALARGOVA, Rossitza, Gueorguieva ,  ALCACIO, Tim, Edward ,  AREKAR, Sneha, G. ,  JOHNSTON, Steven, C. ,  KADIYALA, Irina, Nikolaevna ,  KESHAVARZ-SHOKRI, Ali ,  KRAWIEC, Mariusz ,  LEE, Elaine, Chungmin ,  MEDEK, Ales ,  MUDUNURI, Praveen ,  SULLIVAN, Mark, Jeffrey ,  ZAMAN, Noreen, Tasneem ,  ZHANG, Beili ,  ZHANG, Yuegang ,  ZLOKARNIK, Gregor

IPC: A61K31/4704 ,  A61K31/404 ,  A61K31/443

CPC classification number: A61K31/47 ,  A61K31/404 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4704 ,  G01N33/5032 ,  G01N2500/04 ,  A61K2300/00

Abstract: The present invention relates to pharmaceutical compositions comprising a compound of Formula I in combination with one or both of a Compound of Formula II and/or a Compound of Formula III. The invention also relates to solid forms and to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis.

Abstract translation: 本发明涉及药物组合物，其包含与式II化合物和/或式III化合物中的一种或两种结合的式I化合物。 本发明还涉及固体形式及其药物制剂，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。

公开(公告)号：WO2011127241A2

公开(公告)日：2011-10-13

申请号：PCT/US2011/031519

申请日：2011-04-07

Applicant: VERTEX PHARMACEUTICALS INCORPORATED ,  VERWIJS, Marinus, Jacobus ,  ALARGOVA, Rossitza, Gueorguieva ,  KAUSHIK, Ritu, Rohit ,  KADIYALA, Irina, Nikolaevna ,  YOUNG, Christopher, Ryan

Inventor： VERWIJS, Marinus, Jacobus ,  ALARGOVA, Rossitza, Gueorguieva ,  KAUSHIK, Ritu, Rohit ,  KADIYALA, Irina, Nikolaevna ,  YOUNG, Christopher, Ryan

IPC: A61K9/20

CPC classification number: A61K31/443 ,  A61K9/0053 ,  A61K9/1682 ,  A61K9/2009 ,  A61K9/2013 ,  A61K9/2027 ,  A61K9/2054 ,  A61K9/2077 ,  A61K9/2095 ,  A61K31/47

Abstract: A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2- difluorobenzo [d] [ 1,3 ] dioxol-5 -y1) cyclopropanecarboxamido)-3 -methylpyridin-2-y1)benzoic acid), and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a binder, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering an oral pharmaceutical formulation of Compound 1 to the patient.

Abstract translation: 包含化合物1（3-（6-（1-（2,2-二氟苯并[d] [1,3]二氧杂环戊烯-5-基）环丙烷甲酰氨基）-3-甲基吡啶-2-基）苯甲酸的药物组合物 和至少一种选自：填料，稀释剂，崩解剂，表面活性剂，粘合剂，助流剂和润滑剂的赋形剂，所述组合物适合于有需要的患者口服给药以治疗CFTR介导的疾病，例如 作为囊性纤维化。 用于治疗有需要的患者的方法包括向患者施用化合物1的口服药物制剂。

公开(公告)号：WO2007103468A3

公开(公告)日：2008-05-29

申请号：PCT/US2007005882

申请日：2007-03-07

Applicant: VERTEX PHARMA ,  MOHANLAL RAMON ,  KAUFFMAN ROBERT ,  ALAM JOHN ,  GODFREY CHRISTOPHER ,  KADIYALA IRINA

Inventor： MOHANLAL RAMON ,  KAUFFMAN ROBERT ,  ALAM JOHN ,  GODFREY CHRISTOPHER ,  KADIYALA IRINA

IPC: A61K31/455 ,  A61K31/519 ,  A61K39/395 ,  A61P19/02 ,  A61P29/00

CPC classification number: A61K31/519 ,  A61K31/44 ,  A61K31/455 ,  A61K39/395 ,  A61K2300/00

Abstract: The present invention relates to methods and compositions for treating RA in subjects in need thereof. The invention also relates to kits and pharmaceutical packs comprising compositions and dosage forms.

Abstract translation: 本发明涉及在有需要的受试者中治疗RA的方法和组合物。 本发明还涉及包含组合物和剂型的试剂盒和药物包装。

公开(公告)号：WO2012170061A1

公开(公告)日：2012-12-13

申请号：PCT/US2011/051725

申请日：2011-09-15

Applicant: VERTEX PHARMACEUTICALS INCORPORATED ,  ALARGOVA, Rossitza, Gueorguieva ,  KADIYALA, Irina, Nikolaevna ,  ZAMAN, Noreen, Tasneem

Inventor： ALARGOVA, Rossitza, Gueorguieva ,  KADIYALA, Irina, Nikolaevna ,  ZAMAN, Noreen, Tasneem

IPC: A61K47/10 ,  A61K47/22 ,  A61K9/00 ,  A61P11/00

CPC classification number: A61K31/404 ,  A61K9/0095 ,  A61K45/06 ,  A61K47/10

Abstract: The present invention relates to formulations of ( R )-l-(2,2- difluorobenzo[d][l,3]dioxol-5-yl)-N-(l-(2,3-dihydroxypropyl)-6-fluoro-2-(l-hydroxy-2- methylpropan-2-yl)-lH-indol-5-yl)cyclopropanecarboxamide (Compound 1), pharmaceutical packs or kits thereof, and methods of treatment therewith.

Abstract translation: 本发明涉及（R）-1-（2,2-二氟苯并[d] [1,3]间二氧杂环戊烯-5-基）-N-（1-（2,3-二羟丙基）-6-氟 -2-（1-羟基-2-甲基丙-2-基）-1H-吲哚-5-基）环丙烷甲酰胺（化合物1），药物包装或其试剂盒及其处理方法。

公开(公告)号：WO2011133956A1

公开(公告)日：2011-10-27

申请号：PCT/US2011/033693

申请日：2011-04-22

Applicant: VERTEX PHARMACEUTICALS INCORPORATED ,  VAN GOOR, Fredrick, F. ,  ALARGOVA, Rossitza, Gueorguieva ,  ALCACIO, Tim, Edward ,  BINCH, Hayley, Marie ,  BOTFIELD, Martyn, Curtis ,  FANNING, Lev Tyler, Dewey ,  GROOTENHUIS, Peter Diederik, Jan ,  HURLEY, Dennis, James ,  KADIYALA, Irina, Nikolaevna ,  KAUSHIK, Ritu, Rohit ,  KESHAVARZ-SHOKRI, Ali ,  KRAWIEC, Mariusz ,  LEE, Elaine, Chungmin ,  LUISI, Brian ,  MEDEK, Ales ,  NUMA, Mehdi ,  SHETH, Urvi, Jagdishbhai ,  SILINA, Alina ,  VERWIJS, Marinus, Jacobus ,  YANG, Xiaoqing ,  YOUNG, Christopher Ryan ,  ZAMAN, Noreen, Tasneem ,  ZHANG, Beili ,  ZHANG, Yuegang ,  ZLOKARNIK, Gregor

Inventor： VAN GOOR, Fredrick, F. ,  ALARGOVA, Rossitza, Gueorguieva ,  ALCACIO, Tim, Edward ,  BINCH, Hayley, Marie ,  BOTFIELD, Martyn, Curtis ,  FANNING, Lev Tyler, Dewey ,  GROOTENHUIS, Peter Diederik, Jan ,  HURLEY, Dennis, James ,  KADIYALA, Irina, Nikolaevna ,  KAUSHIK, Ritu, Rohit ,  KESHAVARZ-SHOKRI, Ali ,  KRAWIEC, Mariusz ,  LEE, Elaine, Chungmin ,  LUISI, Brian ,  MEDEK, Ales ,  NUMA, Mehdi ,  SHETH, Urvi, Jagdishbhai ,  SILINA, Alina ,  VERWIJS, Marinus, Jacobus ,  YANG, Xiaoqing ,  YOUNG, Christopher Ryan ,  ZAMAN, Noreen, Tasneem ,  ZHANG, Beili ,  ZHANG, Yuegang ,  ZLOKARNIK, Gregor

IPC: A61K31/4704 ,  A61K31/404 ,  A61K31/443

CPC classification number: A61K31/4709 ,  A61K31/404 ,  A61K31/443 ,  A61K31/4704 ,  A61K45/06 ,  C07D405/12 ,  C12Q1/34 ,  G01N2500/04 ,  G01N2500/20 ,  A61K2300/00

Abstract: The present invention relates to pharmaceutical compositions comprising a compound of Formula I in combination with one or both of a Compound of Formula II and/or a Compound of Formula III. The invention also relates to solid forms and to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis.(Formula I), (Formula II), (Formula III).

Abstract translation: 本发明涉及药物组合物，其包含与式II化合物和/或式III化合物中的一种或两种结合的式I化合物。 本发明还涉及固体形式及其药物制剂，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法（式I），（式II），（式III）。