JP2017528450A - 疾患の予防及び治療のための方法及び組成物 - Google Patents
疾患の予防及び治療のための方法及び組成物 Download PDFInfo
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Abstract
Description
本出願は、2014年8月21日出願の米国出願第62/040,236号の利益及び優先権を主張し、その内容は、参照によりその全体が本明細書に組み込まれる。
少なくとも1つの正味正電荷と、
最低4個のアミノ酸と、
最大約20個のアミノ酸と、
正味正電荷の最小数(pm)とアミノ酸残基の合計数(r)との間の関係性であって、3pmが、r+1以下である最大数である、関係性と、芳香族基の最小数(a)と正味正電荷の合計数(pt)との間の関係性であって、aが1である場合、ptもまた1であってもよいことを除いて、2aが、pt+1以下である最大数である、関係性と、を有するペプチドである。特定の実施形態では、哺乳類対象は、ヒトである。
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)
(iv)
(v)
R3、R4、R5、R6、R7、R8、R9、R10、R11、及びR12は、各々独立して、
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)C1〜C6アルコキシ、
(iv)アミノ、
(v)C1〜C4アルキルアミノ、
(vi)C1〜C4ジアルキルアミノ、
(vii)ニトロ、
(viii)ヒドロキシル、
(ix)ハロゲンから選択され、「ハロゲン」は、クロロ、フルオロ、ブロモ、及びヨードを包含し、
nは、1〜5の整数である。
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)
(iv)
(v)
R3及びR4は、各々独立して、
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)C1〜C6アルコキシ、
(iv)アミノ、
(v)C1〜C4アルキルアミノ、
(vi)C1〜C4ジアルキルアミノ、
(vii)ニトロ、
(viii)ヒドロキシル、
(ix)ハロゲンから選択され、「ハロゲン」は、クロロ、フルオロ、ブロモ、及びヨードを包含し、
R5、R6、R7、R8、及びR9は、各々独立して、
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)C1〜C6アルコキシ、
(iv)アミノ、
(v)C1〜C4アルキルアミノ、
(vi)C1〜C4ジアルキルアミノ、
(vii)ニトロ、
(viii)ヒドロキシル、
(ix)ハロゲンから選択され、「ハロゲン」は、クロロ、フルオロ、ブロモ、及びヨードを包含し、
nは、1〜5の整数である。
特定の実施形態では、R1及びR2は、水素であり、R3及びR4は、メチルであり、R5、R6、R7、R8、及びR9は、全て水素であり、nは、4である。
いくつかの実施形態では、本技術の芳香族カチオン性ペプチドは、芳香族アミノ酸及びカチオン性アミノ酸交互のコア構造モチーフを有する。例えば、ペプチドは、下に記載される式A〜Fのうちのいずれかによって定義されたテトラペプチドであってもよい。
芳香族−カチオン性−芳香族−カチオン性(式A)
カチオン性−芳香族−カチオン性−芳香族(式B)
芳香族−芳香族−カチオン性−カチオン性(式C)
カチオン性−カチオン性−芳香族−芳香族(式D)
芳香族−カチオン性−カチオン性−芳香族(式E)
カチオン性−芳香族−芳香族−カチオン性(式F)
芳香族カチオン性ペプチド
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)
(iv)
(v)
R3、R4、R5、R6、R7、R8、R9、R10、R11、及びR12は、各々独立して、
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)C1〜C6アルコキシ、
(iv)アミノ、
(v)C1〜C4アルキルアミノ、
(vi)C1〜C4ジアルキルアミノ、
(vii)ニトロ、
(viii)ヒドロキシル、
(ix)ハロゲンから選択され、「ハロゲン」は、クロロ、フルオロ、ブロモ、及びヨードを包含し、
nは、1〜5の整数である。
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)
(iv)
(v)
R3及びR4は、各々独立して、
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)C1〜C6アルコキシ、
(iv)アミノ、
(v)C1〜C4アルキルアミノ、
(vi)C1〜C4ジアルキルアミノ、
(vii)ニトロ、
(viii)ヒドロキシル、
(ix)ハロゲンから選択され、「ハロゲン」は、クロロ、フルオロ、ブロモ、及びヨードを包含し、
R5、R6、R7、R8、及びR9は、各々独立して、
(i)水素、
(ii)直鎖または分岐鎖C1〜C6アルキル、
(iii)C1〜C6アルコキシ、
(iv)アミノ、
(v)C1〜C4アルキルアミノ、
(vi)C1〜C4ジアルキルアミノ、
(vii)ニトロ、
(viii)ヒドロキシル、
(ix)ハロゲンから選択され、「ハロゲン」は、クロロ、フルオロ、ブロモ、及びヨードを包含し、
nは、1〜5の整数である。
特定の実施形態では、R1及びR2は、水素であり、R3及びR4は、メチルであり、R5、R6、R7、R8、及びR9は、全て水素であり、nは、4である。
いくつかの実施形態では、本技術の芳香族カチオン性ペプチドは、芳香族アミノ酸及びカチオン性アミノ酸交互のコア構造モチーフを有する。例えば、ペプチドは、下に記載される式A〜Fのうちのいずれかによって定義されたテトラペプチドであってもよい。
芳香族−カチオン性−芳香族−カチオン性(式A)
カチオン性−芳香族−カチオン性−芳香族(式B)
芳香族−芳香族−カチオン性−カチオン性(式C)
カチオン性−カチオン性−芳香族−芳香族(式D)
芳香族−カチオン性−カチオン性−芳香族(式E)
カチオン性−芳香族−芳香族−カチオン性(式F)
表2.アミノ酸数及び正味正電荷(3pm≦p+1)
表3.アミノ酸数及び正味正電荷(2pm≦p+1)
表4.芳香族基及び正味正電荷(3a≦pt+1またはa=pt=1)
表5.芳香族基及び正味正電荷(2a≦pt+1またはa=pt=1)
(a)非極性アミノ酸:Ala(A)Ser(S)Thr(T)Pro(P)Gly(G)Cys(C)、
(b)酸性アミノ酸:Asn(N)Asp(D)Glu(E)Gln(Q)、
(c)塩基性アミノ酸:His(H)Arg(R)Lys(K)、
(d)疎水性アミノ酸:Met(M)Leu(L)Ile(I)Val(V)、及び
(e)芳香族アミノ酸:Phe(F)Tyr(Y)Trp(W)His(H)。
表7.ミュー−オピオイド活性を有するペプチド類似体
Dab=ジアミノ酪
Dap=ジアミノプロピオン酸
Dmt=ジメチルチロシン
Mmt=2′−メチルチロシン
Tmt=N,2′,6′−トリメチルチロシン
Hmt=2′−ヒドロキシ,6′−メチルチロシン
dnsDap=β−ダンシル−L−α,β−ジアミノプロピオン酸
atnDap=β−アントラニロイル−L−α,β−ジアミノプロピオン酸
Bio=ビオチン
表8.ミュー−オピオイド活性を欠くペプチド類似体
Cha=シクロヘキシルアラニン
アルポート症候群
アルポート症候群の遺伝パターン
臨床症状
病理
診断
発端者に対して最も軽度の、または任意の数の女性を通じて関連付けられる男性親類における説明できない血尿症の腎炎の家族歴;
糸球体基底膜疾患、多発性嚢胞腎疾患、またはIgA腎症等の、別の可能性のある遺伝性腎症の証拠がない持続性血尿症;
2000〜8000Hz範囲の両側感覚神経性難聴;聴覚喪失は段階的に発達し、小児期には存在せず、一般に30歳前に現れる;
COL4A3、COL4A4、またはCOL4A5における突然変異;
糸球体、もしくは上皮基底膜、または両方におけるアルポートエピトープの完全または部分的欠失の免疫組織化学的証拠;
広範囲のGBM超微細構造の異常、特に肥厚化、菲薄化、及び分裂;
前部円錐水晶体、円錐角膜、後嚢下白内障、後部多形性角膜ジストロフィー、及び網膜斑点を含む眼の病変;
少なくとも2つの家族メンバーの発端者における末期腎疾患の段階的進行;
メイ・ヘグリン異常と同様の巨大血小板性血小板減少症または顆粒球包含;及び
食道もしくは女性器、または両方のびまん性平滑筋腫症。
現在の治療
治療方法
予防方法
芳香族カチオン性ペプチドベースの治療の生物学的効果の決定
投与の様式及び有効投与量
芳香族カチオン性ペプチドとの複合療法
実施例1−ヒトにおけるアルポート症候群の治療での芳香族カチオン性ペプチドの使用
方法
結果
実施例2−ヒトにおけるアルポート症候群の予防での芳香族カチオン性ペプチドの使用
方法
結果
実施例3−マウスモデルにおけるアルポート症候群の治療での芳香族カチオン性ペプチドの使用
方法
(1)健康な野生型対照
(2)水で処置されたCol4a3ヌルマウス
(3)1mg/kgのD−Arg−2′,6′−Dmt−Lys−Phe−NH2で処置されたCol4a3ヌルマウス
(4)5mg/kgのD−Arg−2′,6′−Dmt−Lys−Phe−NH2で処置されたCol4a3ヌルマウス
(5)5mg/kgのD−Arg−2′,6′−Dmt−Lys−Phe−NH2で処置されたCol4a3ヌルマウス(薬物動態群)
結果
実施例4−Col4a4及びCol4a5の減少した発現を特徴とする病態の治療における芳香族カチオン性ペプチドの使用
方法
(1)健康な野生型対照
(2)水で処置されたCol4a4及びCol4a5欠乏マウス
(3)1mg/kgのD−Arg−2′,6′−Dmt−Lys−Phe−NH2で処置されたCol4a4及びCol4a5欠乏マウス
(4)5mg/kgのD−Arg−2′,6′−Dmt−Lys−Phe−NH2で処置されたCol4a4及びCol4a5欠乏マウス
(5)5mg/kgのD−Arg−2′,6′−Dmt−Lys−Phe−NH2で処置されたCol4a4及びCol4a5欠乏マウス(薬物動態群)
結果
均等論
Claims (37)
- アルポート症候群の治療または予防を必要とする対象においてアルポート症候群を治療または予防するための方法であって、治療有効量のペプチドD−Arg−2′,6′−Dmt−Lys−Phe−NH2またはその薬学的に許容される塩を前記対象に投与することを含む、前記方法。
- 対象が、正常な対照対象と比較してADAM8、フィブロネクチン、ミオシン10、MMP−2、MMP−9、及びポドシンのうちの1つ以上の異常なタンパク質レベル及び/または機能を示し、ペプチド治療が、前記タンパク質のレベル及び/または機能を回復させる、請求項1に記載の方法。
- ペプチドが、6週間以上にわたって毎日投与される、請求項1〜2のいずれか一項に記載の方法。
- ペプチドが、12週間以上にわたって毎日投与される、請求項1〜3のいずれか一項に記載の方法。
- 対象が、アルポート症候群を有すると診断された、請求項1〜4のいずれか一項に記載の方法。
- アルポート症候群の前記徴候または症状が、血尿症、タンパク尿症、円柱尿症、白血球尿症、高血圧、浮腫、微量アルブミン尿症、糸球体濾過量減少、間質性線維症、間質炎、尿細管損傷、GBM超微細構造異常、ネフローゼ症候群、糸球体腎炎、末期腎疾患、慢性貧血、巨大血小板性血小板減少症、骨形成異常症、感覚神経性難聴、前部円錐水晶体、ドットアンドフレック網膜症、後部多形性角膜変性症、再発性角膜びらん、一時黄斑菲薄化、白内障、流涙、羞明、視力喪失、円錐角膜、及び平滑筋腫症のうちの1つ以上を含む、請求項5に記載の方法。
- 対象がヒトである、請求項1〜6のいずれか一項に記載の方法。
- ペプチドが、経口的に、局所的に、鼻腔内に、全身的に、静脈内に、皮下に、腹腔内に、皮内に、眼内に、イオン泳動的に、経粘膜的に、または筋肉内に投与される、請求項1〜7のいずれか一項に記載の方法。
- 1つ以上の追加の治療剤を前記対象に個別に、順次に、または同時に投与することを更に含む、請求項1〜8のいずれか一項に記載の方法。
- 追加の治療剤が、アンジオテンシンII変換酵素阻害剤(ACE阻害剤)、アンジオテンシンII受容体遮断剤(ARB)、HMG−CoA還元酵素阻害剤、アルドステロン阻害剤、アリスキレン、カルシネウリン阻害剤(例えば、シクロスポリンA、タクロリムス)、エンドセリン受容体拮抗薬(例えば、シタキセンタン、アンブリセンタン(LETAIRIS)、アントラセンタン、BQ−123、ジボテンタン、ボセンタン(TRACLEER)、マシテンタン、テゾセンタン、BQ−788、及びA192621)、スロデキシド、バソペプチダーゼ阻害剤(例えば、AVE7688)、抗トランスフォーミング成長因子−β1抗体、ケモカイン受容体1遮断剤、骨形成タンパク質−7、PPARγ作動薬(例えば、ロシグリタゾン、ピオグリタゾン、MRL24、Fmoc−L−Leu、SR1664、SR1824、GW0072、MCC555、CLX−0921、PAT5A、L−764406、nTZDpa、CDDO(2−シアノ−3,12−ジオキソオレアナ−1,9−ジエン−28−オイック酸)、ラガグリタザル、O−アリールマンデル酸、及びNSAID)、ならびにBAY−12−9566からなる群から選択される、請求項9に記載の方法。
- ペプチド及び追加の治療剤の組み合わせが、アルポート症候群の前記予防または治療において相乗効果を有する、請求項9または10に記載の方法。
- 薬学的に許容される塩が、酢酸塩、酒石酸塩、またはトリフルオロ酢酸塩を含む、請求項1〜11のいずれか一項に記載の方法。
- ペプチド治療が、未治療のアルポート症候群対象と比較して上昇したMfn1発現及び/または機能をもたらす、請求項1〜12のいずれか一項に記載の方法。
- アルポート症候群の危険性の低減を必要とする対象におけるアルポート症候群の危険性を低減するための方法であって、治療有効量のペプチドD−Arg−2′,6′−Dmt−Lys−Phe−NH2またはその薬学的に許容される塩を前記対象に投与することを含む、方法。
- 対象が、COL4A3、COL4A4、及びCOL4A5のうちの1つ以上に突然変異を内包する、請求項14に記載の方法。
- ペプチドが、6週間以上にわたって毎日投与される、請求項14〜15のいずれか一項に記載の方法。
- ペプチドが、12週間以上にわたって毎日投与される、請求項14〜16のいずれか一項に記載の方法。
- 対象がヒトである、請求項14〜17のいずれか一項に記載の方法。
- ペプチドが、経口的に、局所的に、鼻腔内に、全身的に、静脈内に、皮下に、腹腔内に、皮内に、眼内に、イオン泳動的に、経粘膜的に、または筋肉内に投与される、請求項14〜18のいずれか一項に記載の方法。
- 1つ以上の追加の治療剤を前記対象に個別に、順次に、または同時に投与することを更に含む、請求項14〜19のいずれか一項に記載の方法。
- 追加の治療剤が、アンジオテンシンII変換酵素阻害剤(ACE阻害剤)、アンジオテンシンII受容体遮断剤(ARB)、HMG−CoA還元酵素阻害剤、アルドステロン阻害剤、アリスキレン、カルシネウリン阻害剤(例えば、シクロスポリンA、タクロリムス)、エンドセリン受容体拮抗薬(例えば、シタキセンタン、アンブリセンタン(LETAIRIS)、アントラセンタン、BQ−123、ジボテンタン、ボセンタン(TRACLEER)、マシテンタン、テゾセンタン、BQ−788、及びA192621)、スロデキシド、バソペプチダーゼ阻害剤(例えば、AVE7688)、抗トランスフォーミング成長因子−β1抗体、ケモカイン受容体1遮断剤、骨形成タンパク質−7、PPARγ作動薬(例えば、ロシグリタゾン、ピオグリタゾン、MRL24、Fmoc−L−Leu、SR1664、SR1824、GW0072、MCC555、CLX−0921、PAT5A、L−764406、nTZDpa、CDDO(2−シアノ−3,12−ジオキソオレアナ−1,9−ジエン−28−オイック酸)、ラガグリタザル、O−アリールマンデル酸、及びNSAID)、ならびにBAY−12−9566からなる群から選択される、請求項20に記載の方法。
- ペプチド及び追加の治療剤の組み合わせが、アルポート症候群の危険性を低減することにおいて相乗効果を有する、請求項20または21に記載の方法。
- 薬学的に許容される塩が、酢酸塩、酒石酸塩、またはトリフルオロ酢酸塩を含む、請求項14〜22のいずれか一項に記載の方法。
- ペプチド治療が、未治療のアルポート症候群対象と比較して上昇したMfn1発現及び/または機能をもたらす、請求項14〜23のいずれか一項に記載の方法。
- COL4A3、COL4A4、及びCOL4A5遺伝子のうちの1つ以上の機能の低減、減少した発現レベル、または欠乏を特徴とする疾患または病態の治療を必要とする対象における、前記疾患または病態を治療するための方法であって、治療有効量の芳香族カチオン性ペプチドD−Arg−2′,6′−Dmt−Lys−Phe−NH2またはその薬学的に許容される塩を前記対象に投与することを含む、方法。
- 薬学的に許容される塩が、酢酸塩、酒石酸塩、またはトリフルオロ酢酸塩を含む、請求項25に記載の方法。
- 疾患または病態が、正常な対照対象と比較してCOL4A3、COL4A4、及びCOL4A5のうちの1つ以上の機能の低減を特徴とする、請求項25〜26のいずれか一項に記載の方法。
- 疾患または病態が、COL4A3、COL4A4、及びCOL4A5のうちの1つ以上の欠乏を特徴とする、請求項25〜27のいずれか一項に記載の方法。
- 疾患または病態が、正常な対照対象と比較してCOL4A3、COL4A4、及びCOL4A5のうちの1つ以上の減少した発現レベルを特徴とする、請求項25〜28のいずれか一項に記載の方法。
- 対象がヒトである、請求項25〜29のいずれか一項に記載の方法。
- ペプチド治療が、疾患または病態を有する未治療の対象と比較して上昇したMfn1発現及び/または機能をもたらす、請求項25〜30のいずれか一項に記載の方法。
- 芳香族カチオン性ペプチドが、経口的に、局所的に、鼻腔内に、全身的に、静脈内に、皮下に、腹腔内に、皮内に、眼内に、イオン泳動的に、経粘膜的に、または筋肉内に投与される、請求項25〜31のいずれか一項に記載の方法。
- ペプチドが、6週間以上にわたって毎日投与される、請求項25〜32のいずれか一項に記載の方法。
- ペプチドが、12週間以上にわたって毎日投与される、請求項25〜33のいずれか一項に記載の方法。
- 1つ以上の追加の治療剤を対象に個別に、順次に、または同時に投与することを更に含む、請求項25〜34のいずれか一項に記載の方法。
- 追加の治療剤が、アンジオテンシンII変換酵素阻害剤(ACE阻害剤)、アンジオテンシンII受容体遮断剤(ARB)、HMG−CoA還元酵素阻害剤、アルドステロン阻害剤、アリスキレン、カルシネウリン阻害剤(例えば、シクロスポリンA、タクロリムス)、エンドセリン受容体拮抗薬(例えば、シタキセンタン、アンブリセンタン(LETAIRIS)、アントラセンタン、BQ−123、ジボテンタン、ボセンタン(TRACLEER)、マシテンタン、テゾセンタン、BQ−788、及びA192621)、スロデキシド、バソペプチダーゼ阻害剤(例えば、AVE7688)、抗トランスフォーミング成長因子−β1抗体、ケモカイン受容体1遮断剤、骨形成タンパク質−7、PPARγ作動薬(例えば、ロシグリタゾン、ピオグリタゾン、MRL24、Fmoc−l−Leu、SR1664、SR1824、GW0072、MCC555、CLX−0921、PAT5A、l−764406、nTZDpa、CDDO(2−シアノ−3,12−ジオキソオレアナ−1,9−ジエン−28−オイック酸)、ラガグリタザル、O−アリールマンデル酸、及びNSAID)、ならびにBAY−12−9566からなる群から選択される、請求項35に記載の方法。
- ペプチド及び追加の治療剤の組み合わせが、COL4A3、COL4A4、及びCOL4A5遺伝子のうちの1つ以上の機能の低減、減少した発現レベル、または欠乏を特徴とする疾患または病態の予防または治療において相乗効果を有する、請求項35または36に記載の方法。
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CN (1) | CN107106637B (ja) |
CA (1) | CA2958585C (ja) |
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EP3903802A1 (en) * | 2014-08-21 | 2021-11-03 | Stealth Biotherapeutics Corp | Peptide d-arg-2',6'-dmt-lys-phe-nh2 for treating alport syndrome |
JP6633812B2 (ja) * | 2016-11-08 | 2020-01-22 | リアタ ファーマシューティカルズ インコーポレイテッド | バルドキソロンメチルまたはその類似体を使用してアルポート症候群を処置する方法 |
WO2018187400A1 (en) | 2017-04-05 | 2018-10-11 | Stealth Biotherapeutics Corp. | Crystalline salt forms of boc-d-arg-dmt-lys-(boc)-phe-nh2 |
US10676506B2 (en) | 2018-01-26 | 2020-06-09 | Stealth Biotherapeutics Corp. | Crystalline bis- and tris-hydrochloride salt of elamipretide |
WO2019199979A1 (en) | 2018-04-10 | 2019-10-17 | The General Hospital Corporation | Antibacterial compounds |
WO2019226417A1 (en) * | 2018-05-23 | 2019-11-28 | University Of Miami | Methods of treating renal disease associated with chronic kidney disease such as alport syndrome |
JP2021532191A (ja) * | 2018-07-25 | 2021-11-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | アルポート症候群の治療に使用するためのエンパグリフロジン |
EP3917509A4 (en) | 2019-01-28 | 2022-11-09 | Mitochondria Emotion, Inc. | ACTIVATORS OF TRANS-4-HYDROXYCYCLOHEXYLPHENYLAMIDE DERIVATIVES OF MITOFUSIN AND METHODS OF USE THEREOF |
AU2019427489A1 (en) | 2019-01-28 | 2021-07-22 | Mitochondria Emotion, Inc. | Mitofusin activators and methods of use thereof |
WO2022076452A1 (en) * | 2020-10-05 | 2022-04-14 | Father Flanagan's Boys' Home Doing Business As Boys Town National Research Hospital | Combination therapy for alport renal disease |
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US20090214488A1 (en) * | 2005-11-10 | 2009-08-27 | Raghu Kalluri | Methods and compositions for treating basement membrane disorders |
CN101472589A (zh) * | 2006-04-06 | 2009-07-01 | 先灵公司 | 用于治疗心血管疾病的含有凝血酶受体拮抗剂的组合物制剂之用途 |
CN104056248A (zh) * | 2008-02-26 | 2014-09-24 | 康奈尔大学 | 用于防止和治疗急性肾损伤的方法 |
US20120192298A1 (en) * | 2009-07-24 | 2012-07-26 | Sigma Aldrich Co. Llc | Method for genome editing |
WO2011082324A1 (en) * | 2009-12-31 | 2011-07-07 | Stealth Peptides International, Inc. | Methods for the prevention or treatment of vessel occlusion injury |
US8697657B2 (en) * | 2010-03-15 | 2014-04-15 | Stealth Peptides International, Inc. | Combination therapies using cyclosporine and aromatic cationic peptides |
UA116639C2 (uk) * | 2012-10-09 | 2018-04-25 | Рег'Юлес Терап'Ютікс Інк. | Способи лікування синдрому альпорта |
WO2014088631A1 (en) * | 2012-12-06 | 2014-06-12 | Stealth Peptides International, Inc. | Peptide therapeutics and methods for using same |
WO2014210056A1 (en) * | 2013-06-27 | 2014-12-31 | Stealth Peptides International, Inc. | Peptide therapeutics and methods for using same |
EP3903802A1 (en) * | 2014-08-21 | 2021-11-03 | Stealth Biotherapeutics Corp | Peptide d-arg-2',6'-dmt-lys-phe-nh2 for treating alport syndrome |
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EP3182989A2 (en) | 2017-06-28 |
US20230043587A1 (en) | 2023-02-09 |
CA2958585C (en) | 2024-01-09 |
WO2016029027A3 (en) | 2016-08-18 |
JP6641356B2 (ja) | 2020-02-05 |
EP3903802A1 (en) | 2021-11-03 |
EP3182989A4 (en) | 2018-04-11 |
WO2016029027A2 (en) | 2016-02-25 |
US10744178B2 (en) | 2020-08-18 |
CN107106637A (zh) | 2017-08-29 |
CA2958585A1 (en) | 2016-02-25 |
US20200376072A1 (en) | 2020-12-03 |
EP3182989B1 (en) | 2021-04-14 |
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