JP2019537578A - アデノ随伴ウイルス製剤 - Google Patents
アデノ随伴ウイルス製剤 Download PDFInfo
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- JP2019537578A JP2019537578A JP2019522442A JP2019522442A JP2019537578A JP 2019537578 A JP2019537578 A JP 2019537578A JP 2019522442 A JP2019522442 A JP 2019522442A JP 2019522442 A JP2019522442 A JP 2019522442A JP 2019537578 A JP2019537578 A JP 2019537578A
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- pharmaceutical composition
- aav
- sodium chloride
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- certain embodiments
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- 238000002360 preparation method Methods 0.000 title description 3
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 247
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- 238000000034 method Methods 0.000 claims abstract description 76
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims abstract description 72
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- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims abstract description 72
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- DPVHGFAJLZWDOC-PVXXTIHASA-N (2r,3s,4s,5r,6r)-2-(hydroxymethyl)-6-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxane-3,4,5-triol;dihydrate Chemical group O.O.O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DPVHGFAJLZWDOC-PVXXTIHASA-N 0.000 claims description 4
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- 230000029812 viral genome replication Effects 0.000 description 1
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- 229940093612 zein Drugs 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- XDWXRAYGALQIFG-UHFFFAOYSA-L zinc;propanoate Chemical compound [Zn+2].CCC([O-])=O.CCC([O-])=O XDWXRAYGALQIFG-UHFFFAOYSA-L 0.000 description 1
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- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
- 239000011590 β-tocopherol Substances 0.000 description 1
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- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 description 1
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Abstract
Description
本明細書で用いられる場合、用語「AAV」は、自然発生および組換え形態(rAAV)の両方のアデノ随伴ウイルスを意味し、AAVの突然変異型も包含する。用語AAVはさらに、それらに限定はされないが、AAV1型、AAV2型、AAV3型、AAV4型、AAV5型、AAV6型、AAV7型、AAV8型、AAV9型、AAV10型、トリAAV、ウシAAV、イヌAAV、ウマAAV、ヒツジAAV、霊長類AAV、および非霊長類AAVを含む。ある実施形態では、AAVはAAV8である。
例示的態様では、本開示の医薬組成物は、アデノ随伴ウイルス(AAV)、ならびに約5mM〜約25mMの緩衝剤、約0mM〜約150mMの薬学的に許容される塩、約0.001%(w/v)〜約0.01%(w/v)の非イオン性界面活性剤、および約1%(w/v)〜約10%(w/v)の糖または糖アルコールを含む。
例示的実施形態では、本開示の製剤または医薬組成物は、追加の薬学的に許容される成分を含む。例示的態様では、製剤または医薬組成物は下記の内のいずれか1つまたはそれらの組合せを含む:酸性化剤、添加剤、吸着剤、エアロゾル噴射剤、空気置換剤、アルカリ化剤、固化防止剤、抗凝固剤、抗菌防腐剤、抗酸化剤、抗腐食剤、基剤、結合剤、緩衝剤、キレート剤、コーティング剤、着色剤、乾燥剤、洗浄剤、希釈剤、殺菌消毒剤、崩壊剤、分散剤、溶解促進剤、色素、軟化剤、乳化剤、乳化安定剤、充填剤、成膜剤、風味増強剤、香味剤、流動促進剤、ゲル化剤、造粒剤、保湿剤、潤滑剤、粘着付与剤、軟膏基剤、軟膏、油性ビヒクル、有機塩基、トローチ基剤、顔料、可塑剤、研磨剤、防腐剤、金属イオン封鎖剤、皮膚浸透剤、可溶化剤、溶媒、安定化剤、坐剤の基剤、表面活性剤、界面活性剤、懸濁剤、甘味剤、治療剤、粘度付与剤、等張化剤、毒性剤、増粘剤、吸水剤、水混和性共溶媒、軟水化剤または湿潤剤など。一部の実施形態では、本開示の製剤または医薬組成物は下記の成分の内のいずれか1つまたはそれらの組合せを含む:アカシア、アセスルファムカリウム、アセチルクエン酸トリブチル、アセチルクエン酸トリエチル、寒天、アルブミン、アルコール、脱水アルコール、変性アルコール、希アルコール、アロイリット酸、アルギン酸、脂肪族ポリエステル、アルミナ、水酸化アルミニウム、ステアリン酸アルミニウム、アミロペクチン、α−アミロース、アスコルビン酸、アスコルビルパルミタート、アスパルテーム、注射用静菌水、ベントナイト、マグマベントナイト、塩化ベンザルコニウム、塩化ベンゼトニウム、安息香酸、ベンジルアルコール、安息香酸ベンジル、ブロノポール、ブチル化ヒドロキシアニソール、ブチル化ヒドロキシトルエン、ブチルパラベン、ブチルパラベンナトリウム、アルギン酸カルシウム、アスコルビン酸カルシウム、炭酸カルシウム、シクラミン酸カルシウム、無水リン酸水素カルシウム、脱水リン酸水素カルシウム、リン酸三カルシウム、プロピオン酸カルシウム、ケイ酸カルシウム、ソルビン酸カルシウム、ステアリン酸カルシウム、硫酸カルシウム、硫酸カルシウム半水和物、キャノーラ油、カルボマー、二酸化炭素、カルボキシメチルセルロースカルシウム、カルボキシメチルセルロースナトリウム、β−カロテン、カラギーナン、ひまし油、硬化ひまし油、カチオン性乳化ワックス、酢酸セルロース、酢酸フタル酸セルロース、エチルセルロース、微結晶セルロース、粉末セルロース、ケイ化微結晶セルロース、カルボキシメチルセルロースナトリウム、セトステアリルアルコール、セトリミド、セチルアルコール、クロルヘキシジン、クロロブタノール、クロロクレゾール、コレステロール、酢酸クロルヘキシジン、グルコン酸クロルヘキシジン、塩酸クロルヘキシジン、クロロジフルオロエタン(HCFC)、クロロジフルオロメタン、クロロフロオロカーボン(CFC)クロロフェノキシエタノール、クロロキシレノール、コーンシロップ固体、無水クエン酸、クエン酸一水和物、カカオバター、着色剤、コーン油、綿実油、クレゾール、m−クレゾール、o−クレゾール、p−クレゾール、クロスカルメロースナトリウム、クロスポビドン、シクラミン酸、シクロデキストリン、デキストレート、デキストリン、ブドウ糖、ブドウ糖(無水)、ジアゾリジニル尿素、フタル酸ジブチル、セバシン酸ジブチル、ジエタノールアミン、フタル酸ジエチル、ジフルオロエタン(HFC)、ジメチル−β−シクロデキストリン、Captisol(登録商標)などのシクロデキストリンタイプの化合物、ジメチルエーテル、フタル酸ジメチル、エデト酸二カリウム、エデト酸二ナトリウム、リン酸水素二ナトリウム、ドクサートカルシウム、ドクサートカリウム、ドクサートナトリウム、没食子酸ドデシル、ドデシルトリメチルアンモニウムブロミド、エデト酸カルシウム二ナトリウム、エデト酸、エグルミン、エチルアルコール、エチルセルロース、没食子酸エチル、ラウリン酸エチル、エチルマルトール、オレイン酸エチル、エチルパラベン、エチルパラベンカリウム、エチルパラベンナトリウム、エチルバニリン、フルクトース、フルクトース液、粉砕フルクトース、フルクトース(パイロジェンフリー)、粉末フルクトース、フマル酸、ゼラチン、グルコース、液体グルコース、飽和植物脂肪酸のグリセリド混合物、グリセリン、ベヘン酸グリセリル、モノオレイン酸グリセリル、モノステアリン酸グリセリル、自己乳化型モノステアリン酸グリセリル、パルミトステアリン酸グリセリル、グリシン、グリコール、グリコフロール、グアーガム、ヘプタフルオロプロパン(HFC)、ヘキサデシルトリメチルアンモニウムブロミド、高フルクトースシロップ、ヒト血清アルブミン、炭化水素(HC)、希塩酸、硬化植物油タイプII、ヒドロキシエチルセルロース、2−ヒドロキシエチル−β−シクロデキストリン、ヒドロキシプロピルセルロース、低置換度ヒドロキシプロピルセルロース、2−ヒドロキシプロピル−β−シクロデキストリン、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルメチルセルロースフタレート、イミド尿素、インジゴカルミン、イオン交換体、酸化鉄、イソプロピルアルコール、ミリスチン酸イソプロピル、パルミチン酸イソプロピル、等張食塩水、カオリン、乳酸、ラクチトール、ラクトース、ラノリン、ラノリンアルコール、無水ラノリン、レシチン、ケイ酸アルミニウムマグネシウム、炭酸マグネシウム、正炭酸マグネシウム、炭酸マグネシウム(無水)、炭酸水酸化マグネシウム、水酸化マグネシウム、ラウリル硫酸マグネシウム、酸化マグネシウム、ケイ酸マグネシウム、ステアリン酸マグネシウム、三ケイ酸マグネシウム、三ケイ酸マグネシウム(無水)、リンゴ酸、麦芽、マルチトール、マルチトール溶液、マルトデキストリン、マルトール、マルトース、マンニトール、中鎖トリグリセリド、メグルミン、メントール、メチルセルロース、メチルメタクリラート、オレイン酸メチル、メチルパラベン、メチルパラベンカリウム、メチルパラベンナトリウム、微結晶セルロースおよびカルボキシメチルセルロースナトリウム、鉱物油、軽鉱物油、鉱物油およびラノリンアルコール、油、オリーブ油、モノエタノールアミン、モンモリロナイト、没食子酸オクチル、オレイン酸、パルミチン酸、パラフィン、ピーナッツ油、ワセリン、ワセリンおよびラノリンアルコール、医薬用グレーズ、フェノール、液状フェノール、フェノキシエタノール、フェノキシプロパノール、フェニルエチルアルコール、酢酸フェニル水銀、ホウ酸フェニル水銀、硝酸フェニル水銀、ポラクリリン、ポラクリリンカリウム、ポロキサマー、ポリデキストロース、ポリエチレングリコール、ポリエチレンオキシド、ポリアクリラート、ポリエチレン−ポリオキシプロピレン−ブロックポリマー、ポリメタクリラート、ポリオキシエチレンアルキルエーテル、ポリオキシエチレンひまし油誘導体、ポリオキシエチレンソルビトール脂肪酸エステル、ステアリン酸ポリオキシエチレン、ポリビニルアルコール、ポリビニルピロリドン、アルギン酸カリウム、安息香酸カリウム、炭酸水素カリウム、亜硫酸水素カリウム、塩化カリウム、クエン酸カリウム、クエン酸カリウム(無水)、リン酸水素カリウム、ピロ亜硫酸カリウム、リン酸二水素カリウム、プロピオン酸カリウム、ソルビン酸カリウム、ポビドン、プロパノール、プロピオン酸、炭酸プロピレン、プロピレングリコール、アルギン酸プロピレングリコール、没食子酸プロピル、プロピルパラベン、プロピルパラベンカリウム、プロピルパラベンナトリウム、硫酸プロタミン、ナタネ油、リンゲル液、サッカリン、サッカリンアンモニウム、サッカリンカルシウム、サッカリンナトリウム、ベニバナ油、サポナイト、血清タンパク質、ゴマ油、コロイドシリカ、コロイド状二酸化ケイ素、アルギン酸ナトリウム、アスコルビン酸ナトリウム、安息香酸ナトリウム、炭酸水素ナトリウム、亜硫酸水素ナトリウム、塩化ナトリウム、クエン酸ナトリウム(無水)、クエン酸ナトリウム(脱水)、塩化ナトリウム、シクラミン酸ナトリウム、エデト酸ナトリウム、ドデシル硫酸ナトリウム、ラウリル硫酸ナトリウム、ピロ亜硫酸ナトリウム、リン酸水素二ナトリウム、リン酸ナトリウム、リン酸二水素ナトリウム、プロピオン酸ナトリウム(無水)、プロピオン酸ナトリウム、ソルビン酸ナトリウム、デンプングリコール酸ナトリウム、フマル酸ステアリルナトリウム、亜硫酸ナトリウム、ソルビン酸、ソルビタンエステル(ソルビタン脂肪酸エステル)、ソルビトール、ソルビトール液70%、ダイズ油、鯨蝋、デンプン、トウモロコシデンプン、ジャガイモデンプン、アルファ化デンプン、滅菌可能なトウモロコシデンプン、ステアリン酸、精製ステアリン酸、ステアリルアルコール、ショ糖、糖、圧縮用砂糖、粉砂糖、製菓用砂糖、白糖球状顆粒、転化糖、Sugartab、サンセットイエローFCF、合成パラフィン、タルク、酒石酸、タートラジン、テトラフルオロエタン(HFC)、カカオ油、チメロサール、二酸化チタン、アルファトコフェロール、酢酸トコフェロール、α−トコフェロールコハク酸エステル、β−トコフェロール、δ−トコフェロール、γ−トコフェロール、トラガカント、トリアセチン、クエン酸トリブチル、トリエタノールアミン、クエン酸トリエチル、トリメチル−β−シクロデキストリン、臭化トリメチルテトラデシルアンモニウム、トリスバッファー、エデト酸三ナトリウム、バニリン、タイプIの硬化植物油、水、軟水、硬水、二酸化炭素を含まない水、発熱性物質除去水、注射用水、吸入用滅菌水、注射用滅菌水、灌水用滅菌水、ワックス、アニオン性乳剤ワックス、カルナバロウ、カチオン性乳化ワックス、セチルエステルワックス、マイクロクリスタリンワックス、非イオン性乳剤ワックス、坐剤用蝋、白蝋、黄蝋、白色ワセリン、羊毛蝋、キサンタンガム、キシリトール、ゼイン、プロピオン酸亜鉛、亜鉛塩、ステアリン酸亜鉛、あるいは、Remington’s Pharmaceutical Sciences, Sixteenth Edition, E. W. Martin (Mack Publishing Co., Easton, Pa., 1980)Handbook of Pharmaceutical Excipients, Third Edition, A. H. Kibbe (Pharmaceutical Press, London, UK, 2000)(参照によりその全体が組み込まれる)に記載の任意の賦形剤。Remington’s Pharmaceutical Sciences, Sixteenth Edition, E. W. Martin (Mack Publishing Co., Easton, Pa., 1980)(あらゆる意図される目的のために参照によりその全てが本明細書に組み込まれる)は、薬学的に許容される組成物を調製するのに用いられるさまざまな成分、ならびにそれを調製するための公知技術を開示する。あらゆる従来の薬剤について、それが本医薬組成物と不適合である場合を除いて、医薬組成物におけるその使用が企図されている。例示的実施形態では、本開示の製剤または医薬組成物は、上記の成分の1つまたは組合せを含まない。例示的実施形態では、本開示の製剤または医薬組成物は、これら成分のいずれも含まない。例示的態様では、本開示の医薬組成物はデキストランを含まない。例示的態様では、本開示の医薬組成物は塩化カルシウムを含まない。
例示的実施形態では、本開示の医薬組成物は生理学的に適合するpHを有する。従って、ある実施形態では、製剤を中性pHに維持するのに適した緩衝剤を含有するAAV製剤を提供する。
例示的実施形態では、本開示の医薬組成物は、約200〜約400mOsmol/kg、約250〜約400mOsmol/kg、または約290〜約390mOsmol/kgのオスモル濃度を有する。ある実施形態では、本明細書に提供されるAAV製剤は、例えば、約200mOsmol/L、約210mOsmol/L、約220mOsmol/L、約230mOsmol/L、約240mOsmol/L、約250mOsmol/L、約260mOsmol/L、約270mOsmol/L、約280mOsmol/L、約290mOsmol/L、約300mOsmol/L、約310mOsmol/L、約320mOsmol/L、約330mOsmol/L、約340mOsmol/L、約350mOsmol/L、約360mOsmol/L、約370mOsmol/L、約380mOsmol/L、約390mOsmol/L、または約400mOsmol/Lのオスモル濃度を有する。例示的態様では、本開示の医薬組成物は、約250mOsmol/kg〜約400mOsmol/kgのオスモル濃度を有する。例示的態様では、本開示の医薬組成物は約300±10mOsmol/kgまたは約380±10mOsmol/kgのオスモル濃度を有する。ある実施形態では、本開示の医薬組成物は約300±10mOsmol/kgのオスモル濃度を有する。ある実施形態では、本開示の医薬組成物は約380±10mOsmol/kgのオスモル濃度を有する。
例示的実施形態では、本開示の医薬組成物はAAVを含む。AAVは任意のAAV血清型であってよい。例示的態様では、AAVは、AAV1血清型、AAV2血清型、AAV3血清型、AAV4血清型、AAV5血清型、AAV6血清型、AAV7血清型、AAV8血清型、AAV9血清型、またはAAV10血清型であってよい。例示的態様では、AAVはAAV8血清型である。
AAVを含む医薬組成物を調製する方法をここにさらに提供する。例示的態様では、その方法は、約5mM〜約25mMの緩衝剤、約50mM〜約150mMまたは約100mM未満の薬学的に許容される塩、約0.001%(w/v)〜約0.01%(w/v)の非イオン性界面活性剤、約1%(w/v)〜約10%(w/v)の糖および/または糖アルコール、ならびにAAVを配合し、それによってAAVを含む医薬組成物を得ることを含む。例示的態様では、その方法は、約5mM〜約25mMの緩衝剤、約50mM〜約150mMまたは約100mM未満の薬学的に許容される塩、約0.001%(w/v)〜約0.01%(w/v)の非イオン性界面活性剤、約1%(w/v)〜約10%(w/v)の糖および/または糖アルコールを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約20mMの緩衝剤、約70mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、および約5%(w/v)の糖および/または糖アルコールを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約100mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約80mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約70mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約60mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約50mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約40mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約30mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約20mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約10mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約10mMの緩衝剤、約0mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約5%(w/v)の糖および/または糖アルコール、および約50mMのグリシンを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。例示的態様では、その方法は、約20mMの緩衝剤、約60mMの薬学的に許容される塩、約0.005%(w/v)の非イオン性界面活性剤、約35mMの糖および/または糖アルコール、および約110mMのマンニトールを含む組成物、例えば水溶液を調製し、さらにその組成物にAAVを添加することを含む。ある実施形態では、水溶液は凍結乾燥される。
この実施例は、更なる開発のための3つの製剤の選択につながる最初の試験を示す。
この実施例は、3つの製剤の追加試験および更なる開発を実証する。
この実施例は、異なるバイアルおよびチューブの内部表面への吸着に関する2つの製剤の追加検査を実証する。
この実施例は、製剤4における様々なAAVサブタイプの安定性を実証する。
この実施例は、AAV製剤を凍結乾燥すること、特に製剤4におけるAAVの凍結乾燥の、実施可能性を実証する。
この実施例は、凍結乾燥製剤の追加試験および更なる開発を実証する。
この実施例は更なる製剤を実証する。
この実施例は更なる製剤を実証する。
Claims (52)
- アデノ随伴ウイルス(AAV);ならびに
(i)約5mM〜約25mMの緩衝剤;
(ii)約50mM〜約150mMの薬学的に許容される塩;
(iii)約0.001%(w/v)〜約0.01%(w/v)の非イオン性界面活性剤;および
(iv)約1%〜約10%(w/v)の糖、糖アルコールまたはそれらの組合せ
を含む、医薬組成物。 - アデノ随伴ウイルス(AAV);ならびに
(i)約5mM〜約25mMの緩衝剤;
(ii)約100mM未満の薬学的に許容される塩;
(iii)約0.001%(w/v)〜約0.01%(w/v)の非イオン性界面活性剤;および
(iv)約1%〜約10%(w/v)の糖、糖アルコールまたはそれらの組合せ
を含む、医薬組成物。 - 約6.9〜約7.7のpH、任意選択で約7.0または約7.5のpHを有する、請求項1または2に記載の医薬組成物。
- 前記緩衝剤がL−ヒスチジンである、請求項1〜3のいずれか1項に記載の医薬組成物。
- 約5mM〜約25mMまたは約10mM〜約20mMのL−ヒスチジンを含む、請求項4に記載の医薬組成物。
- 前記薬学的に許容される塩が、ナトリウム塩、アンモニウム塩、またはカリウム塩である、請求項1〜5のいずれか1項に記載の医薬組成物。
- 約50mM〜約120mMの塩化ナトリウムを含む、請求項6に記載の医薬組成物。
- 約0mM〜約100mM、約0mM〜約60mM、30mM〜約100mM、30mM〜約80mM、または30mM〜約60mMの塩化ナトリウムを含む、請求項6または7に記載の医薬組成物。
- 約60mM〜約100mMまたは約60mM〜約80mMの塩化ナトリウムを含む、請求項6〜8のいずれか1項に記載の医薬組成物。
- 前記非イオン性界面活性剤がPS80である、請求項1〜9のいずれか1項に記載の医薬組成物。
- 約0.0025%〜約0.0075%(w/v)のPS80を含む、請求項10に記載の医薬組成物。
- 前記糖が、ショ糖、トレハロースまたはそれらの組合せである、請求項1〜11のいずれか1項に記載の医薬組成物。
- 約1%(w/v)〜約5%(w/v)のショ糖、トレハロースまたはそれらの組合せを含む、請求項12に記載の医薬組成物。
- トレハロースはトレハロース二水和物である、請求項12または13に記載の医薬組成物。
- グリシンをさらに含む、請求項1〜14のいずれか1項に記載の医薬組成物。
- 約35mM〜約65mMのグリシンを含む、請求項15に記載の医薬組成物。
- マンニトールをさらに含む、請求項1〜16のいずれか1項に記載の医薬組成物。
- 約80mM〜約120mMのマンニトールを含む、請求項17に記載の医薬組成物。
- デキストランを含まない、請求項1〜18のいずれか1項に記載の医薬組成物。
- グリシンまたはマンニトールを含む、請求項1〜19のいずれか1項に記載の医薬組成物。
- PS80がSuper Refined(商標)PS80である、請求項10〜20のいずれか1項に記載の医薬組成物。
- アデノ随伴ウイルス(AAV)、ならびに
(i)約20mMのL−ヒスチジン、
(ii)約70mMの塩化ナトリウム、
(iii)約0.005%(w/v)のポリソルベート80(PS80)、および
(iv)約5%(w/v)のショ糖
を含む、医薬組成物。 - アデノ随伴ウイルス(AAV)、ならびに
(i)約10mMのL−ヒスチジン、
(ii)約100mMの塩化ナトリウム、
(iii)約0.005%(w/v)のポリソルベート80(PS80)、
(iv)約5%(w/v)のトレハロース、および
(v)約50mMのグリシン
を含む、医薬組成物。 - アデノ随伴ウイルス(AAV)、ならびに
(i)約10mMのL−ヒスチジン、
(ii)約100mM未満の塩化ナトリウム、
(iii)約0.005%(w/v)のポリソルベート80(PS80)、
(iv)約5%(w/v)のトレハロース、および
(v)約50mMのグリシン
を含む、医薬組成物。 - 約80mMの塩化ナトリウムを含む、請求項1〜21および24のいずれか1項に記載の医薬組成物。
- 約70mMの塩化ナトリウムを含む、請求項1〜21および24のいずれか1項に記載の医薬組成物。
- 約60mMの塩化ナトリウムを含む、請求項1〜21および24のいずれか1項に記載の医薬組成物。
- 約50mMの塩化ナトリウムを含む、請求項1〜21および24のいずれか1項に記載の医薬組成物。
- 約40mMの塩化ナトリウムを含む、請求項1〜21および24のいずれか1項に記載の医薬組成物。
- 約30mMの塩化ナトリウムを含む、請求項1〜21および24のいずれか1項に記載の医薬組成物。
- 約0mMの塩化ナトリウムを含む、請求項1〜21および24のいずれか1項に記載の医薬組成物。
- アデノ随伴ウイルス(AAV)、ならびに
(i)約20mMのL−ヒスチジン、
(ii)約60mMの塩化ナトリウム、
(iii)約0.005%(w/v)のポリソルベート80(PS80)、
(iv)約35mMのトレハロース、および
(v)約110mMのマンニトール
を含む、医薬組成物。 - AAVを含む、請求項1〜32のいずれか1項に記載の医薬組成物。
- AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9、またはAAV10含む、請求項1〜33のいずれか1項に記載の医薬組成物。
- AAV8含む、請求項1〜34のいずれか1項に記載の医薬組成物。
- 液体である、請求項1〜35のいずれか1項に記載の医薬組成物。
- 凍結乾燥されている、請求項1〜36のいずれか1項に記載の医薬組成物。
- 単位用量容器中に存在する、請求項1〜37のいずれか1項に記載の医薬組成物。
- 前記単位用量容器がバイアルである、請求項38に記載の医薬組成物。
- 前記バイアルが密封ガラスバイアルである、請求項39に記載の医薬組成物。
- アデノ随伴ウイルス(AAV)を含む医薬組成物を調製する方法であって、請求項1〜40のいずれか1項に記載の医薬組成物の緩衝剤、薬学的に許容される塩、非イオン性界面活性剤、および糖、糖アルコールまたはそれらの組合せを配合して、AAVを含む医薬組成物を得ることを含む、方法。
- アデノ随伴ウイルス(AAV)を含む医薬組成物を調製する方法であって、約5mM〜約25mMのL−ヒスチジン、約0mM〜約150mMの塩化ナトリウム、約0.001%(w/v)〜約0.01%(w/v)のポリソルベート80(PS80)、約1%(w/v)〜約10%(w/v)のショ糖、トレハロースまたはそれらの組合せ、およびAAVを配合して、AAVを含む医薬組成物を得ることを含む、方法。
- 対象において出血性疾患を治療する方法であって、疾患または疾病を治療するのに有効な量で請求項1〜40のいずれか1項に記載の医薬組成物を対象に投与することを含む、方法。
- 疾患または疾病が出血性疾患である、請求項43に記載の方法。
- AAVを含む組成物を保管する方法であって、請求項1〜40のいずれか1項に記載の医薬組成物の緩衝剤、薬学的に許容される塩、非イオン性界面活性剤、および糖、糖アルコールまたはそれらの組合せを配合することを含む、方法。
- AAVを含む組成物を保管する方法であって、約5mM〜約25mMのL−ヒスチジン、約0mM〜約150mMの塩化ナトリウム、約0.001%(w/v)〜約0.01%(w/v)のポリソルベート80(PS80)、約1%〜約10%(w/v)のショ糖、トレハロースまたはそれらの組合せ、およびAAVを配合することを含む、方法。
- 約50mM〜約150mMの塩化ナトリウムを含む、請求項42または46に記載の方法。
- 約30mM〜約100mM未満の塩化ナトリウムを含む、請求項42または46に記載の方法。
- 約0mM〜約100mM未満の塩化ナトリウムを含む、請求項42および46〜48のいずれか1項に記載の方法。
- 約30mMの塩化ナトリウムを含む、請求項42および46〜49のいずれか1項に記載の方法。
- 約60mMの塩化ナトリウムを含む、請求項42および46〜49のいずれか1項に記載の方法。
- 約0mMの塩化ナトリウムを含む、請求項42および46〜49のいずれか1項に記載の方法。
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CA3226803A1 (en) | 2021-08-04 | 2023-02-09 | Christian Fiedler | Adeno-associated virus separation on a cation exchanger |
EP4392016A1 (en) * | 2021-08-24 | 2024-07-03 | Oxford Biomedica (US) LLC | Adeno-associated virus formulations |
CN117180455A (zh) * | 2022-06-07 | 2023-12-08 | 成都弘基生物科技有限公司 | 腺相关病毒药物组合物及其用途 |
CN115337408A (zh) * | 2022-09-16 | 2022-11-15 | 上海信致医药科技有限公司 | 腺相关病毒制剂 |
WO2024079657A1 (en) * | 2022-10-11 | 2024-04-18 | Meiragtx Uk Ii Limited | Formulations for aav gene therapy |
WO2024112230A1 (en) * | 2022-11-24 | 2024-05-30 | Joint Stock Company "Biocad" | Pharmaceutical composition of non-enveloped virus |
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CA3042689A1 (en) | 2018-07-12 |
EP3534922A1 (en) | 2019-09-11 |
US20190255126A1 (en) | 2019-08-22 |
CN110300591A (zh) | 2019-10-01 |
BR112019009113A2 (pt) | 2019-07-16 |
IL266264A (en) | 2019-06-30 |
RU2019116442A (ru) | 2020-12-04 |
KR20190080922A (ko) | 2019-07-08 |
AU2017391165A1 (en) | 2019-05-23 |
JP2022137241A (ja) | 2022-09-21 |
US11583563B2 (en) | 2023-02-21 |
PT3534922T (pt) | 2024-06-07 |
RU2769196C2 (ru) | 2022-03-29 |
EP4360652A3 (en) | 2024-06-26 |
IL266264B2 (en) | 2023-11-01 |
JP2024097059A (ja) | 2024-07-17 |
MX2019005088A (es) | 2019-08-12 |
EP3534922B1 (en) | 2024-04-17 |
WO2018128689A1 (en) | 2018-07-12 |
AU2017391165B2 (en) | 2023-02-02 |
EP4360652A2 (en) | 2024-05-01 |
RU2019116442A3 (ja) | 2021-06-21 |
KR102574849B1 (ko) | 2023-09-06 |
US20230241139A1 (en) | 2023-08-03 |
IL266264B1 (en) | 2023-07-01 |
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