JP2021512906A - 妊娠患者におけるファブリー病の治療のためのミガラスタットの使用 - Google Patents
妊娠患者におけるファブリー病の治療のためのミガラスタットの使用 Download PDFInfo
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Abstract
【選択図】図4
Description
「00790785.TXT」(22Kb、2019年2月6日作成)として同定される本明細書に添えて提出された配列リストテキストファイルは、本明細書によって参照により援用される。
本明細書で使用される用語は、本発明の文脈の中で、及び各用語が使用される具体的な文脈において、概して当該技術分野におけるその通常の意味を有する。本発明の製剤及び方法並びにそれをどのように作成、使用及び実行すればよいかを説明するにおいて実施者に更なる手引きを与えるため、特定の用語を以下で、又は本明細書中の他の箇所で考察する。
LSDに関連する酵素の小分子阻害薬の結合は、突然変異酵素及び対応する野生型酵素の両方の安定性を増加させることができる(米国特許第6,274,597号明細書;同第6,583,158号明細書;同第6,589,964号明細書;同第6,599,919号明細書;同第6,916,829号明細書、及び同第7,141,582号明細書を参照のこと、全て参照により本明細書に援用される)。詳細には、幾つかの標的リソソーム酵素の特異的で選択的な競合阻害薬であるグルコース及びガラクトースの小分子誘導体を投与すると、インビトロで細胞内の酵素の安定性が有効に増加し、ひいてはリソソームへの酵素のトラフィッキングが増加した。従って、リソソーム内の酵素量が増加することにより、酵素基質の加水分解が増加するものと予想される。この戦略の背後にあった当初の理論は以下のとおりであった:突然変異酵素タンパク質はERにおいて不安定であるため(Ishii et al.,Biochem.Biophys.Res.Comm.1996;220:812−815)、酵素タンパク質は正常な輸送経路(ER→ゴルジ体→エンドソーム→リソソーム)において遅れ、早まって分解される。従って、突然変異酵素に結合してその安定性を増加させる化合物が酵素の「シャペロン」として働き、ERを出てリソソームに移ることのできる量を増加させ得る。加えて、一部の野生型タンパク質のフォールディング及びトラフィッキングは不完全で、場合によっては一部の野生型タンパク質の最大70%がその最終的な細胞部位に到達する前に分解されるため、シャペロンを野生型酵素の安定化に使用して、ERを出てリソソームに輸送されることのできる酵素の量を増加させることができる。このストラテジーは、β−グルコセレブロシダーゼ及びα−グルコシダーゼ(それぞれ、その欠損がゴーシェ病及びポンペ病に関連する)をはじめとする幾つかのリソソーム酵素をインビトロ及びインビボで増加させることが示されている。
従って、1つ以上の実施形態において、ファブリー患者にミガラスタット又はその塩が1日おきに1回(「QOD」とも称される)の頻度で投与される。様々な実施形態において、本明細書に記載される用量は、ミガラスタット塩酸塩又は等価な用量のミガラスタット若しくは塩酸塩以外のその塩に関する。一部の実施形態において、これらの用量はミガラスタットの遊離塩基に関する。代替的実施形態において、これらの用量はミガラスタットの塩に関する。更なる実施形態において、ミガラスタットの塩はミガラスタット塩酸塩である。
2005年10月、腎生検及び突然変異解析に基づいてコーカサス人の女性をファブリー病と診断した(GLA p.R112H)。2009年、アガルシダーゼα(ERT)を用いて患者のファブリー病の治療を始めた。治療の開始後、患者は、腎症状も心症状も神経症状も進行を見せなかった。
以上の実施例に示されるように、少なくとも妊娠の最初の16週間にわたりミガラスタットを摂取した患者は、順調な妊娠を有し、胎齢に基づいて正常体重の子を出産した。このことから、ミガラスタットにより治療された患者は、妊娠し得るとともに治療時に正常な子を出産できることが示される。
Claims (59)
- 必要とされる妊娠患者においてファブリー病を治療する方法であって、約100mg〜約150mg遊離塩基当量(FBE)の治療有効用量のミガラスタット又はその塩を含む製剤を1日おきに1回の頻度で前記患者に投与することを含む、方法。
- 前記患者が前記治療の開始後に妊娠する、請求項1に記載の方法。
- 前記患者が、前記治療時に有効な受胎調節を行うように前記治療の開始前に指示されなかった、請求項2に記載の方法。
- 前記患者が治療時に有効な受胎調節を利用していなかった、請求項2又は3に記載の方法。
- 前記患者が前記治療の開始前に妊娠している、請求項1に記載の方法。
- 前記患者が前記治療の開始前に妊娠していることが分かっていない、請求項5に記載の方法。
- 前記治療が前記患者の妊娠の同定時に中断される、請求項1〜6のいずれか一項に記載の方法。
- 前記患者が前記治療の開始前に妊娠していることが分かっている、請求項5に記載の方法。
- 前記患者の妊娠が少なくとも37週の胎齢を有する子の出生ををもたらす、請求項1〜8のいずれか一項に記載の方法。
- 前記患者の妊娠が前記子の胎齢に基づいて正常体重の子の出生をもたらす、請求項1〜9のいずれか一項に記載の方法。
- 前記患者の妊娠が出生時欠損を伴うことなく子をもたらす、請求項1〜10のいずれか一項に記載の方法。
- 前記治療有効用量が約123mg遊離塩基当量(FBE)のミガラスタット又はその塩である、請求項1〜11のいずれか一項に記載の方法。
- 前記治療有効用量が約123mgのミガラスタット遊離塩基である、請求項1〜12のいずれか一項に記載の方法。
- 前記ミガラスタットの塩がミガラスタット塩酸塩である、請求項1〜12のいずれか一項に記載の方法。
- 前記治療有効用量が約150mgのミガラスタット塩酸塩である、請求項14に記載の方法。
- 前記製剤が前記患者の妊娠中に少なくとも2週間にわたり投与される、請求項1〜15のいずれか一項に記載の方法。
- 前記製剤が前記妊娠中に少なくとも6週間にわたり投与される、請求項1〜16のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠中に少なくとも12週間にわたり投与される、請求項1〜17のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠の第1三半期に投与される、請求項1〜18のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠の第2三半期に投与される、請求項1〜19のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠の最初の16週間で投与される、請求項1〜20のいずれか一項に記載の方法。
- 前記製剤が固形製剤を含む、請求項1〜21のいずれか一項に記載の方法。
- 前記製剤が経口剤形を含む、請求項1〜22のいずれか一項に記載の方法。
- 前記経口剤形が錠剤、カプセル又は溶液を含む、請求項23に記載の方法。
- 前記患者がα−ガラクトシダーゼAのHEKアッセイ適用可能突然変異を有する、請求項1〜24のいずれか一項に記載の方法。
- 前記突然変異が薬理学的参照表に開示される、請求項25に記載の方法。
- 前記薬理学的参照表が、ファブリー病の治療が承認されたミガラスタット製品の製品ラベルに提供される、請求項26に記載の方法。
- 前記薬理学的参照表がGALAFOLD(登録商標)の製品ラベルに提供される、請求項27に記載の方法。
- 前記薬理学的参照表がウェブサイトに提供される、請求項27に記載の方法。
- 前記ウェブサイトがwww.galafoldamenabilitytable.com又はwww.fabrygenevariantsearch.comの1つ以上である、請求項29に記載の方法。
- 出産能のある女性患者におけるファブリー病の治療方法であって、約100mg〜約150mg遊離塩基当量(FBE)の治療有効用量のミガラスタット又はその塩を含む製剤を1日おきに1回の頻度で前記患者に投与することを含み、前記治療時に有効な受胎調節を行うように前記治療の開始前に前記患者に指示されない、方法。
- 前記患者が前記治療の開始後に妊娠する、請求項31に記載の方法。
- 前記患者が前記治療時に有効な受胎調節を利用しない、請求項31又は32に記載の方法。
- 前記治療が前記患者の妊娠の同定時に中断される、請求項32又は33に記載の方法。
- 前記患者の妊娠が少なくとも37週の胎齢を有する子の出生をもたらす、請求項32〜34のいずれか一項に記載の方法。
- 前記患者の妊娠が子の胎齢に基づいて正常体重の子の出生をもたらす、請求項32〜35のいずれか一項に記載の方法。
- 前記患者の妊娠が出生時欠損を伴うことなく子をもたらす、請求項32〜36のいずれか一項に記載の方法。
- 前記治療有効用量が約123mg遊離塩基当量(FBE)のミガラスタット又はその塩である、請求項31〜37のいずれか一項に記載の方法。
- 前記治療有効用量が約123mgのミガラスタット遊離塩基である、請求項31〜38のいずれか一項に記載の方法。
- 前記ミガラスタットの塩がミガラスタット塩酸塩である、請求項31〜38のいずれか一項に記載の方法。
- 前記治療有効用量が約150mgのミガラスタット塩酸塩である、請求項40に記載の方法。
- 前記製剤が少なくとも2週間にわたり投与される、請求項31〜41のいずれか一項に記載の方法。
- 前記製剤が少なくとも6週間にわたり投与される、請求項31〜42のいずれか一項に記載の方法。
- 前記製剤が少なくとも12週間にわたり投与される、請求項31〜43のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠中に少なくとも2週間にわたり投与される、請求項32〜44のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠中に少なくとも6週間にわたり投与される、請求項32〜45のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠中に少なくとも12週間にわたり投与される、請求項32〜46のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠の第1三半期に投与される、請求項32〜47のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠の第2三半期に投与される、請求項32〜48のいずれか一項に記載の方法。
- 前記製剤が前記患者の妊娠の最初の16週間で投与される、請求項32〜49のいずれか一項に記載の方法。
- 前記製剤が固形製剤を含む、請求項31〜50のいずれか一項に記載の方法。
- 前記製剤が経口剤形を含む、請求項31〜51のいずれか一項に記載の方法。
- 前記経口剤形が錠剤、カプセル又は溶液を含む、請求項52に記載の方法。
- 前記患者がα−ガラクトシダーゼAのHEKアッセイ適用可能突然変異を有する、請求項31〜53のいずれか一項に記載の方法。
- 前記突然変異が薬理学的参照表に開示される、請求項54に記載の方法。
- 前記薬理学的参照表が、ファブリー病の治療が承認されたミガラスタット製品の製品ラベルに提供される、請求項55に記載の方法。
- 前記薬理学的参照表がGALAFOLD(登録商標)の製品ラベルに提供される、請求項56に記載の方法。
- 前記薬理学的参照表がウェブサイトに提供される、請求項56に記載の方法。
- 前記ウェブサイトがwww.galafoldamenabilitytable.com又はwww.fabrygenevariantsearch.comの1つ以上である、請求項58に記載の方法。
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EP2533050B3 (en) | 2006-05-16 | 2015-06-24 | Amicus Therapeutics, Inc. | Treatment Options For Fabry Disease |
EP2946785B1 (en) | 2008-02-12 | 2018-10-24 | Amicus Therapeutics, Inc. | Method to predict response to pharmacological chaperone treatment of diseases |
CA3224529A1 (en) | 2017-05-30 | 2018-12-06 | Amicus Therapeutics, Inc. | Methods of treating fabry patients having renal impairment |
EP3749307A1 (en) | 2018-02-06 | 2020-12-16 | Amicus Therapeutics, Inc. | Use of migalastat for treating fabry disease in pregnant patients |
CA3147055A1 (en) | 2019-08-07 | 2021-02-11 | Elfrida Benjamin | Methods of treating fabry disease in patients having a mutation in the gla gene |
US11623916B2 (en) | 2020-12-16 | 2023-04-11 | Amicus Therapeutics, Inc. | Highly purified batches of pharmaceutical grade migalastat and methods of producing the same |
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AU2005286626B2 (en) * | 2004-09-24 | 2012-11-08 | Beth Israel Deaconess Medical Center | Methods of diagnosing and treating complications of pregnancy |
ES2537089T3 (es) | 2005-06-08 | 2015-06-02 | Amicus Therapeutics, Inc. | Purificación de imino- y amino-azúcares |
EP2533050B3 (en) | 2006-05-16 | 2015-06-24 | Amicus Therapeutics, Inc. | Treatment Options For Fabry Disease |
WO2008121826A2 (en) | 2007-03-30 | 2008-10-09 | Amicus Therapeutics, Inc. | Method for the treatment of fabry disease using pharmacological chaperones |
EP2150254A4 (en) | 2007-04-26 | 2010-11-10 | Amicus Therapeutics Inc | DOSAGES FOR THE TREATMENT OF LYSOSOMAL STORAGE DISEASES WITH PHARMACOLOGICAL CHAPTERONES |
US9999618B2 (en) | 2007-04-26 | 2018-06-19 | Amicus Therapeutics, Inc. | Dosing regimens for the treatment of lysosomal storage diseases using pharmacological chaperones |
EP2946785B1 (en) | 2008-02-12 | 2018-10-24 | Amicus Therapeutics, Inc. | Method to predict response to pharmacological chaperone treatment of diseases |
US8321148B2 (en) | 2008-10-24 | 2012-11-27 | Amicus Therapeutics, Inc. | Multiple compartment dosing model |
US9206457B2 (en) | 2009-05-26 | 2015-12-08 | Amicus Therapeutics, Inc. | Utilization of pharmacological chaperones to improve manufacturing and purification of biologics |
US9066939B2 (en) | 2009-11-17 | 2015-06-30 | Baylor Research Institute | Urinary triaosylceramide (GB3) as a marker of cardiac disease |
EP3698792A1 (en) * | 2011-03-11 | 2020-08-26 | Amicus Therapeutics, Inc. | Dosing regimens for the treatment of fabry disease |
US9694056B2 (en) | 2012-07-17 | 2017-07-04 | Amicus Therapeutics, Inc. | α-galactosidase A and 1-deoxygalactonojirimycin co-formulation |
US10155027B2 (en) | 2012-07-17 | 2018-12-18 | Amicus Therapeutics, Inc. | Alpha-galactosidase A and 1-deoxygalactonojirimycin co-formulation for the treatment of fabry disease |
JP7098529B2 (ja) | 2016-03-22 | 2022-07-11 | アミカス セラピューティックス インコーポレイテッド | Gla遺伝子にg9331a変異を有する患者においてファブリー病を処置する方法 |
EP3568152A1 (en) | 2017-01-10 | 2019-11-20 | Amicus Therapeutics, Inc. | Recombinant alpha-galactosidase a for treatment of fabry disease |
CA3224529A1 (en) | 2017-05-30 | 2018-12-06 | Amicus Therapeutics, Inc. | Methods of treating fabry patients having renal impairment |
CA3074450A1 (en) | 2017-08-28 | 2019-03-07 | Amicus Therapeutics, Inc. | Methods of enhancing and/or stabilizing cardiac function in patients with fabry disease |
KR20200128675A (ko) | 2018-02-06 | 2020-11-16 | 아미쿠스 세라퓨틱스, 인코포레이티드 | 전형적 파브리병 환자의 치료 |
EP3749307A1 (en) | 2018-02-06 | 2020-12-16 | Amicus Therapeutics, Inc. | Use of migalastat for treating fabry disease in pregnant patients |
KR20210046729A (ko) | 2018-08-20 | 2021-04-28 | 아미쿠스 세라퓨틱스, 인코포레이티드 | Gla 유전자에 돌연변이를 갖는 환자에서 파브리 질병을 치료하는 방법 |
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CA3147055A1 (en) | 2019-08-07 | 2021-02-11 | Elfrida Benjamin | Methods of treating fabry disease in patients having a mutation in the gla gene |
JP2023513700A (ja) | 2020-02-10 | 2023-04-03 | アミカス セラピューティックス インコーポレイテッド | ファブリー病の治療方法 |
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