JP2021524858A - 筋萎縮性側索硬化症(als)を治療するための組成物、及び治療のためにそれを使用する方法 - Google Patents
筋萎縮性側索硬化症(als)を治療するための組成物、及び治療のためにそれを使用する方法 Download PDFInfo
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Abstract
Description
本願は、2018年5月31日出願の米国仮特許出願第62/678,316号の優先権を主張するものであり、この特許出願の全内容を本明細書の一部を構成するものとしてここに援用する。
本願の出願と同時に提出された、2019年5月29日作成の485バイトのASCIIファイル「77740SequenceListing.txt」を本明細書の一部を構成するものとしてここに援用する。
1.臨床的、電気生理学的又は神経病理学的検査による下位運動ニューロン(LMN)変性の徴候、
2.臨床検査による上位運動ニューロン(UMN)変性の徴候、及び
3.ある領域内又は他の領域への徴候の進行的な広がりを示すと共に、
LMN変性及び/又はUMN変性の徴候を説明することが可能な他の疾患プロセスの電気生理学的証拠、及び
観察された臨床的及び電気生理学的徴候を説明することが可能な他の疾患プロセスの神経画像証拠がない。
材料と方法
IPL344の処方と投薬:IPL344、7個のアミノ酸から成る合成ペプチド[LPPLPYP(配列番号1)、本明細書に記載のものは塩基性ペプチドである]を水溶液に処方する[ペプチドをdPBS(Ca++とMg++含有)に溶解、濃度は50mg/mL(即ち、5%塩基ペプチド、酢酸塩と不純物を含まない)]。ペプチド濃度は280nmでの吸光度(A280、Thermo Fisher Scientific社)から求め、そこからHPLCによって原薬(DS)放出時に同定された不純物を差し引いた値とした。
・過敏症のグレード3の有害事象(洞性頻脈、激しい呼吸、又は静脈や他の場所に沿った発疹で定義される)。
・一過性(発症から6時間以内に回復)のグレード3の試験薬物関連有害事象。
・死亡(原因に関わらず)
・生命を脅かす有害事象又は疑わしい副作用
・参加者が入院している場合、又は臨床AEに関連する既存の入院の延長(医療施設での最低1泊の滞在を含む参加者の入院)
・持続的又は重大な障害/無能力又は通常の生活機能を実行する能力の実質的な崩壊
・先天性異常又は先天性欠損症
・介入が必要である。
・用量の変更が必要である(減少、中止、中断)。
・他の治療/療法が必要である。
・他の診断又は病状に関連する。
・所見の臨床的重要性を考慮した後の治験責任者の決定。
(a)ハンドヘルドダイナモメトリー(HHD)/握力測定は、高度な専用強度測定デバイス(例えば、ハンドグリップやハンドヘルドダイナモメーター)を使用した筋力試験の方法である。ハンドグリップダイナモメーターにおいて、ダイナモメーターの湾曲したハンドルは拳を作るときの手のパターンを模倣する。ハンドルはしなやかであり、それに対する圧力を受け入れる。ハンドグリップには、握りの強さを示すモニターが取り付けられている。
(b)手動筋肉試験(MMT):手動筋肉試験は、重力と手動に関連する効果的な動きに基づいて、個々の筋肉と筋肉群の機能と強度を評価するための手順である。MMTでは以下の基準:筋肉が重力に逆らってレバーアームを動かすことができる(3/5〜5/5)、重力なしで動かすことができる(2/5)、又は触知可能な収縮を示す(1/5)に従って、筋力をスコア化する。
AUC0−t:時間0から線形台形法で計算された最後の定量化可能濃度(Ct)の時間(t)までの血漿中濃度−時間曲線下の面積。
Cmax:観察された最大血漿中濃度。
Tmax:最大血漿中濃度に達するまでの観察時間。
λz:LN変換された血漿中濃度対時間曲線の末端線形部分の回帰直線の負勾配から計算された末端相指数速度定数。
T1/2:ln(2)/λzとして計算された見かけの末端指数半減期。
IPL344治療プロトコル
本発明の幾つかの実施形態のALS治療用IPL344の静脈内(IV)投与のためのプロトコルを以下の表4に要約する。
Claims (35)
- 筋萎縮性側索硬化症(ALS)の治療を必要とするヒト対象においてALSを治療する方法であって、配列番号1に記載のアミノ酸配列を含むペプチド2〜5mg/kgを前記対象に静脈内(IV)投与して、前記対象のALSを治療することを含む方法。
- 筋萎縮性側索硬化症(ALS)の治療を必要とするヒト対象においてALSを治療する方法であって、配列番号1に記載のアミノ酸配列を含むペプチド1.7〜5mg/kgを用量漸増的に前記対象に繰り返し静脈内(IV)投与して、前記対象のALSを治療することを含む方法。
- ALS機能評価尺度(ALSFRS)、呼吸機能、筋力及び/又は認知機能によって前記対象をモニターすることを含む、請求項1又は2に記載の方法。
- 配列番号1に記載のアミノ酸配列を含む、筋萎縮性側索硬化症(ALS)の治療を必要とするヒト対象においてALSを治療するために使用するペプチドであって、2〜5mg/kgの用量を前記対象に静脈内(IV)投与するペプチド。
- 配列番号1に記載のアミノ酸配列を含む、筋萎縮性側索硬化症(ALS)の治療を必要とするヒト対象においてALSを治療するために使用するペプチドであって、1.7〜5mg/kgを用量漸増的に前記対象に繰り返し静脈内(IV)投与するペプチド。
- 前記用量漸増は0.3〜0.5mg/kgずつである、請求項2に記載の方法又は請求項5に記載の使用用のペプチド。
- 前記用量漸増を2〜7日毎に行う、請求項2及び5〜6のいずれか一項に記載の方法又は使用用ペプチド。
- 前記ペプチドに関連する過敏症又は有害事象(AE)が生じた場合には前記用量漸増を停止する、請求項2及び5〜7のいずれか一項に記載の方法又は使用用ペプチド。
- 前記ALSはALS関連うつ病である、請求項1〜8のいずれか一項に記載の方法又は使用用ペプチド。
- 前記ALSは急速進行性ALSである、請求項1〜8のいずれか一項に記載の方法又は使用用ペプチド。
- 前記ALSは非緩徐進行性ALSである、請求項1〜8のいずれか一項に記載の方法又は使用用ペプチド。
- 配列番号1に記載のアミノ酸配列を含むペプチドを5%含む組成物であって、pHが4.5〜5.5の組成物。
- PBS及び/又はdPBSを含む、請求項12に記載の組成物。
- 生理食塩水を含む、請求項12に記載の組成物。
- 配列番号1に記載のアミノ酸配列を含むペプチドを5%含む組成物に、前記ペプチドを処方し、前記組成物はpHが4.5〜5.5である、請求項1〜11のいずれか一項に記載の方法又は使用用ペプチド。
- 前記投与を毎日行う、請求項1〜3、6〜11及び15のいずれか一項に記載の方法。
- 前記投与をボーラス注射で行う、請求項1〜3、6〜11及び15〜16のいずれか一項に記載の方法。
- 前記投与を静脈内注入で行う、請求項1〜3、6〜11及び15〜16のいずれか一項に記載の方法。
- 前記対象に毎日投与する、請求項4〜11及び15のいずれか一項に記載の使用用ペプチド。
- 前記対象にボーラス注射で投与する、請求項4〜11、15及び19のいずれか一項に記載の使用用ペプチド。
- 前記対象に静脈内注入で投与する、請求項4〜11、15及び19のいずれか一項に記載の使用用ペプチド。
- 前記1.7〜5mg/kgは2〜5mg/kgである、請求項2及び5〜8のいずれか一項に記載の方法又は使用用ペプチド。
- 前記2〜5mg/kgは2.5〜4.5mg/kgである、請求項1、3〜4、9〜11及び15〜22のいずれか一項に記載の方法又は使用用ペプチド。
- 前記2〜5mg/kgは3〜4mg/kgである、請求項1,3〜4、9〜11及び15〜22のいずれか一項に記載の方法又は使用用ペプチド。
- 前記対象は急速進行性ALS及び/又はALS関連うつ病を有する、請求項1〜11及び15〜24のいずれか一項に記載の方法又は使用用ペプチド。
- 静脈内(IV)投与用に処方された、配列番号1に記載のアミノ酸配列を含むペプチドを140〜350mg含む単位剤形。
- 前記140〜350mgは140〜315mgである、請求項26に記載の単位剤形。
- 前記140〜350mgは210〜280mgである、請求項26に記載の単位剤形。
- 静脈内(IV)投与用に処方された、配列番号1に記載のアミノ酸配列を含むペプチドを35〜90mg含む単位剤形。
- 前記35〜90mgは35〜80mgである、請求項29に記載の単位剤形。
- 前記35〜90mgは50〜70mgである、請求項29に記載の単位剤形。
- 配列番号1に記載のアミノ酸配列を含むペプチドを5%含む組成物に前記ペプチドを処方し、前記組成物はpHが4.5〜5.5である、請求項26〜31のいずれか一項に記載の単位剤形。
- 前記ペプチドをPBS及び/又はdPBSを含む組成物に処方する、請求項1〜11及び15〜32のいずれか一項に記載の方法、使用用ペプチド又は単位剤形。
- 前記PBS及び/又は前記dPBSはカルシウムとマグネシウムを含む、請求項13に記載の組成物、又は請求項33に記載の方法、使用用ペプチド及び単位剤形。
- 前記ペプチドを生理食塩水を含む組成物に処方する、請求項1〜11及び15〜32のいずれか一項に記載の方法、使用用ペプチド又は単位剤形。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862678316P | 2018-05-31 | 2018-05-31 | |
US62/678,316 | 2018-05-31 | ||
PCT/IL2019/050619 WO2019229757A1 (en) | 2018-05-31 | 2019-05-30 | Compositions and methods of using same for treating amyotrophic lateral sclerosis (als) |
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JP2003528151A (ja) * | 2000-03-31 | 2003-09-24 | スミスクライン ビーチャム パブリック リミテッド カンパニー | 神経変性疾患等の疾患の治療または予防のためのcrf受容体アゴニストの使用 |
JP2008510796A (ja) * | 2004-08-23 | 2008-04-10 | イエダ リサーチ アンド デベロップメント カンパニー リミテッド | ストレス応答を媒介するためのペプチド阻害剤 |
JP2010509345A (ja) * | 2006-11-10 | 2010-03-25 | ジェナボン バイオファーマシューティカルズ エルエルシー | Mntfペプチドおよびその類似体を用いて神経細胞障害を治療する方法 |
US20160033529A1 (en) * | 2011-05-23 | 2016-02-04 | Universitätsklinikum Hamburg-Eppendorf | Use of akt phosphorylation as a biomarker for prognosing neurodegenerative diseases and treating same |
WO2016040877A1 (en) * | 2014-09-12 | 2016-03-17 | Lixte Biotechnology, Inc. | Human dosing of phosphatase inhibitor |
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US20030140362A1 (en) * | 2001-06-08 | 2003-07-24 | Dennis Macejak | In vivo models for screening inhibitors of hepatitis B virus |
BRPI0519996A2 (pt) * | 2004-10-28 | 2009-04-07 | Warner Lambert Co | processo para formar atorvastatina amorfa |
CN104367988A (zh) * | 2007-06-07 | 2015-02-25 | 凯亚林生物科学有限公司 | 卡贝缩宫素鼻用制剂和治疗孤独症的方法 |
US10597660B2 (en) * | 2014-11-14 | 2020-03-24 | Voyager Therapeutics, Inc. | Compositions and methods of treating amyotrophic lateral sclerosis (ALS) |
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JP2003528151A (ja) * | 2000-03-31 | 2003-09-24 | スミスクライン ビーチャム パブリック リミテッド カンパニー | 神経変性疾患等の疾患の治療または予防のためのcrf受容体アゴニストの使用 |
JP2008510796A (ja) * | 2004-08-23 | 2008-04-10 | イエダ リサーチ アンド デベロップメント カンパニー リミテッド | ストレス応答を媒介するためのペプチド阻害剤 |
JP2010509345A (ja) * | 2006-11-10 | 2010-03-25 | ジェナボン バイオファーマシューティカルズ エルエルシー | Mntfペプチドおよびその類似体を用いて神経細胞障害を治療する方法 |
US20160033529A1 (en) * | 2011-05-23 | 2016-02-04 | Universitätsklinikum Hamburg-Eppendorf | Use of akt phosphorylation as a biomarker for prognosing neurodegenerative diseases and treating same |
WO2016040877A1 (en) * | 2014-09-12 | 2016-03-17 | Lixte Biotechnology, Inc. | Human dosing of phosphatase inhibitor |
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US20210100869A1 (en) | 2021-04-08 |
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AU2019277920A1 (en) | 2021-01-07 |
JP7350019B2 (ja) | 2023-09-25 |
CA3099846A1 (en) | 2019-12-05 |
EP3785279A1 (en) | 2021-03-03 |
IL279108A (en) | 2021-01-31 |
WO2019229757A1 (en) | 2019-12-05 |
IL279108B1 (en) | 2024-06-01 |
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