JPWO2020204765A5 - - Google Patents

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JPWO2020204765A5
JPWO2020204765A5 JP2021559026A JP2021559026A JPWO2020204765A5 JP WO2020204765 A5 JPWO2020204765 A5 JP WO2020204765A5 JP 2021559026 A JP2021559026 A JP 2021559026A JP 2021559026 A JP2021559026 A JP 2021559026A JP WO2020204765 A5 JPWO2020204765 A5 JP WO2020204765A5
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disease
pharmaceutical composition
aqueous pharmaceutical
amount
netakimab
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JP2021559026A
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Japanese (ja)
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JP2022528119A (en
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Priority claimed from RU2019109641A external-priority patent/RU2754760C2/en
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Publication of JP2022528119A publication Critical patent/JP2022528119A/en
Publication of JPWO2020204765A5 publication Critical patent/JPWO2020204765A5/ja
Priority to JP2024080645A priority Critical patent/JP2024119827A/en
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[00994]１２０ｍｇの用量（例えば、本明細書で示唆された用量）までのネタキマブは、ＡＳ活性の減少、機能、軸方向の可動性、炎症のＭＲＩ徴候および生活の質の改善をもたらす有益な安全性プロファイルを有する良好な耐容性を示す薬物である。
本発明は、非限定的に以下の態様を含む。
［態様１］
ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物であって、
ＶＨＨ誘導体ドメインおよび可変ＶＬドメインを含む薬学的に有効な量の抗ＩＬ１７ａ抗体；
ヒスチジンベースの緩衝剤；ならびに
浸透圧剤としての有効量の糖ベースのアルコール
を含む水性医薬組成物。
［態様２］
前記抗ＩＬ１７ａ抗体の前記ＶＨＨ誘導体ドメインが、３つの超可変領域ＨＣＤＲ１、ＨＣＤＲ２およびＨＣＤＲ３を含み、
ＨＣＤＲ１が配列番号１のアミノ酸配列を含み；
ＨＣＤＲ２が配列番号２のアミノ酸配列を含み；
ＨＣＤＲ３が配列番号３のアミノ酸配列を含み；そして、
前記抗ＩＬ１７ａ抗体の前記可変ＶＬドメインが配列番号４のアミノ酸配列を含む、態様１に記載の水性医薬組成物。
［態様３］
前記抗ＩＬ１７ａ抗体がネタキマブである、態様１に記載の水性医薬組成物。
［態様４］
前記ネタキマブが、５ｍｇ／ｍＬ～１５０ｍｇ／ｍＬの量である、態様１から３のいずれか一項に記載の水性医薬組成物。
［態様５］
前記ネタキマブが、１０ｍｇ／ｍＬ～１００ｍｇ／ｍＬの量である、態様１から３のいずれか一項に記載の水性医薬組成物。
［態様６］
前記ネタキマブが、４０ｍｇ／ｍＬの量である、態様１から３のいずれか一項に記載の水性医薬組成物。
［態様７］
前記ネタキマブが、６０ｍｇ／ｍＬの量である、態様１から３のいずれか一項に記載の水性医薬組成物。
［態様８］
前記ネタキマブが、７０ｍｇ／ｍＬの量である、態様１から３のいずれか一項に記載の水性医薬組成物。
［態様９］
前記糖ベースのアルコールがマンニトールである、態様１から８のいずれか一項に記載の水性医薬組成物。
［態様１０］
前記マンニトールが、２５～６０ｍｇ／ｍＬの量である、態様９に記載の水性医薬組成物。
［態様１１］
前記ヒスチジンベースの緩衝剤の適切な量が、約５．５～約６．５のｐＨに達するように加えられる、態様１から１０のいずれか一項に記載の水性医薬組成物。
［態様１２］
前記緩衝剤が、
０．４ｍｇ／ｍＬ～１．６ｍｇ／ｍＬの量のＬ－ヒスチジン；および
０．４ｍｇ／ｍＬ～１．６ｍｇ／ｍＬの量のヒスチジン塩酸塩一水和物
から構成される、態様１１に記載の水性医薬組成物。
［態様１３］
適切な可溶化剤をさらに含む、態様１から１２のいずれか一項に記載の水性医薬組成物。
［態様１４］
前記可溶化剤がポロキサマー１８８である、態様１３に記載の水性医薬組成物。
［態様１５］
前記ポロキサマー１８８が、０ｍｇ／ｍＬより多いが、１ｍｇ／ｍＬ以下の量である、態様１４に記載の水性医薬組成物。
［態様１６］
ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物であって、
ネタキマブ ４０ｍｇ／ｍＬ
Ｌ－ヒスチジン ０．４ｍｇ／ｍＬ
Ｌ－ヒスチジン塩酸塩一水和物 ０．４ｍｇ／ｍＬ
マンニトール ５４．５ｍｇ／ｍＬ
ポロキサマー１８８ ０～１ｍｇ／ｍＬ
ｐＨ ６．０±０．５
を含む水性医薬組成物。
［態様１７］
ａ）前記ポロキサマー１８８が０．５ｍｇ／ｍＬの量であるか；または
ｂ）前記ポロキサマー１８８が１ｍｇ／ｍＬの量である、
態様１６に記載の水性医薬組成物。
［態様１８］
ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物であって、
ＶＨＨ誘導体ドメインおよび可変ＶＬドメインを含む薬学的に有効な量の抗ＩＬ１７ａ抗体；
酢酸塩ベースの緩衝剤；ならびに
浸透圧剤としての二糖
を含む水性医薬組成物。
［態様１９］
前記抗ＩＬ１７ａ抗体の前記ＶＨＨ誘導体ドメインが、３つの超可変領域ＨＣＤＲ１、ＨＣＤＲ２およびＨＣＤＲ３を含み、
ＨＣＤＲ１が配列番号１のアミノ酸配列を含み；
ＨＣＤＲ２が配列番号２のアミノ酸配列を含み；
ＨＣＤＲ３が配列番号３のアミノ酸配列を含み；そして、
前記抗ＩＬ１７ａ抗体の前記可変ＶＬドメインが配列番号４のアミノ酸配列を含む、態様１８に記載の水性医薬組成物。
［態様２０］
前記抗ＩＬ１７ａ抗体がネタキマブである、態様１９に記載の水性医薬組成物。
［態様２１］
前記ネタキマブが、５ｍｇ／ｍＬ～１５０ｍｇ／ｍＬの量である、態様１８から２０のいずれか一項に記載の水性医薬組成物。
［態様２２］
前記ネタキマブが、１０ｍｇ／ｍＬ～１２０ｍｇ／ｍＬの量である、態様１８から２０のいずれか一項に記載の水性医薬組成物。
［態様２３］
前記ネタキマブが、６０ｍｇ／ｍＬの量である、態様１８から２０のいずれか一項に記載の水性医薬組成物。
［態様２４］
前記ネタキマブが、１００ｍｇ／ｍＬの量である、態様１８から２０のいずれか一項に記載の水性医薬組成物。
［態様２５］
前記ネタキマブが、１２０ｍｇ／ｍＬの量である、態様１８から２０のいずれか一項に記載の水性医薬組成物。
［態様２６］
前記二糖がトレハロースである、態様１８から２５のいずれか一項に記載の水性医薬組成物。
［態様２７］
前記トレハロースが、５０ｍｇ／ｍＬ～１２０ｍｇ／ｍＬの量でトレハロース二水和物として前記組成物に加えられる、態様２６に記載の水性医薬組成物。
［態様２８］
前記酢酸塩ベースの緩衝剤の量が、
０．４ｍｇ／ｍＬ～１．８ｍｇ／ｍＬの酢酸ナトリウム三水和物；および、
両端の値を含めて４．０～６．０の前記組成物のｐＨに達するのに適切な量の酢酸
から構成される、態様１８から２７のいずれか一項に記載の水性医薬組成物。
［態様２９］
適切な可溶化剤をさらに含む、態様１８から２８のいずれか一項に記載の水性医薬組成物。
［態様３０］
前記可溶化剤がポロキサマー１８８である、態様２９に記載の水性医薬組成物。
［態様３１］
前記ポロキサマー１８８が、０ｍｇ／ｍＬ超～１．０ｍｇ／ｍＬ以下の量である、態様３０に記載の水性医薬組成物。
［態様３２］
ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物であって、
ネタキマブ ６０ｍｇ／ｍＬ
酢酸ナトリウム三水和物 １．７４ｍｇ／ｍＬ
トレハロース二水和物 ８０ｍｇ／ｍＬ
氷酢酸 ｐＨ５．０まで
ｐＨ ５．０±０．５
を含む水性医薬組成物。
［態様３３］
ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物であって、
ネタキマブ ６０ｍｇ／ｍＬ
酢酸ナトリウム三水和物 １．７４ｍｇ／ｍＬ
トレハロース二水和物 ８０ｍｇ／ｍＬ
ポロキサマー１８８ ０～１ｍｇ／ｍＬ
氷酢酸 ｐＨ５．０まで
ｐＨ ５．０±０．５
を含む水性医薬組成物。
［態様３４］
ａ）前記ポロキサマー１８８が０．５ｍｇ／ｍＬの量であるか；または
ｂ）前記ポロキサマー１８８が１ｍｇ／ｍＬの量である、
態様３３に記載の水性医薬組成物。
［態様３５］
ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物であって、
ネタキマブ １２０ｍｇ／ｍＬ
酢酸ナトリウム三水和物 １．７４ｍｇ／ｍＬ
トレハロース二水和物 ８０ｍｇ／ｍＬ
氷酢酸 ｐＨ５．０まで
ｐＨ ５．０±０．５
を含む水性医薬組成物。
［態様３６］
ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物であって、
ネタキマブ １２０ｍｇ／ｍＬ
酢酸ナトリウム三水和物 １．７４ｍｇ／ｍＬ
トレハロース二水和物 ８０ｍｇ／ｍＬ
ポロキサマー１８８ ０～１ｍｇ／ｍＬ
氷酢酸 ｐＨ５．０まで
ｐＨ ５．０±０．５
を含む水性医薬組成物。
［態様３７］
ａ）前記ポロキサマー１８８が０．５ｍｇ／ｍＬの量であるか；または
ｂ）前記ポロキサマー１８８が１ｍｇ／ｍＬの量である、
態様３６に記載の水性医薬組成物。
［態様３８］
ＩＬ１７ａ媒介性疾患を治療するための態様１から３７のいずれか一項に記載の水性医薬組成物の使用。
［態様３９］
前記ＩＬ１７ａ媒介性疾患または障害が、関節リウマチ、若年性関節リウマチ、全身型若年性関節リウマチ、骨関節炎、若年性慢性関節炎、乾癬性関節炎、反応性関節炎、血清反応陰性関節炎、多関節若年性特発性関節炎、腱付着部炎関連関節炎；腱付着部炎；脊椎関節症、軸性脊椎関節炎；ベーチェット病；炎症性腸疾患、クローン病、潰瘍性結腸炎；ぜんそく、アレルギー性障害、アトピー性アレルギー；魚鱗癬；毛孔性紅色粃糠疹；丘疹膿疱性酒さ；壊疽性膿皮症；化膿性汗腺炎；乾癬、乾癬性関節症、Ｉ型乾癬、ＩＩ型乾癬、プラーク乾癬；皮膚炎、アトピー性皮膚炎、自己免疫性皮膚炎、皮膚病変；全身性硬化症；移植、移植片対宿主病、移植片拒絶、臓器移植と関連する急性または慢性免疫疾患、急性移植関連免疫疾患、慢性移植関連免疫疾患、小腸移植片拒絶、膵臓移植片拒絶、任意の臓器または組織移植片拒絶、心移植拒絶反応、軟骨移植片拒絶、腎移植拒絶反応、肝移植拒絶反応、同種移植片拒絶、皮膚同種移植片拒絶、任意の臓器または組織についての異種移植片拒絶、骨移植片拒絶、骨髄移植（ＢＭＴ）拒絶反応、副甲状腺移植片拒絶；骨侵食；サルコイドーシス、アテローム性動脈硬化症、ウェゲナー疾患、腎障害を伴う顕微鏡的多発性血管炎、ブドウ膜炎、水晶体起因性ブドウ膜炎、非感染性ブドウ膜炎、悪液質、急性横断性脊髄炎、原発性胆汁性肝硬変、多腺性自己免疫症候群Ｉ型およびＩＩ型、シュミット症候群、急性呼吸促迫症候群；関節症、血清反応陰性関節症、潰瘍性結腸炎と関連する関節症、ライター症候群、腸疾患性滑膜炎、アテローム疾患／冠状動脈硬化症、自己免疫性水疱性疾患、天疱瘡、落葉状天疱瘡、線状ＩｇＡ疾患、自己免疫性溶血性貧血、頭蓋巨大動脈炎、原発性硬化性肝炎、特発性自己免疫性肝炎、特発性線維化性肺胞炎、間質性肺疾患と関連する全身性皮膚硬化症、間質性肺疾患と関連する関節リウマチ、肺疾患と関連する全身性エリテマトーデス、肺疾患と関連する皮膚筋炎／多発性筋炎、肺疾患と関連するシェーグレン病、肺疾患と関連する強直性脊椎炎、血管炎、びまん性肺血管炎、原発性血管炎、線維症、リンパ球浸潤を伴う肺疾患、自己免疫性肝炎、自己免疫性肝炎Ｉ型（古典的自己免疫性またはルポイド肝炎）、自己免疫性肝炎ＩＩ型（抗ＬＫＭ抗体関連）、自己免疫性低血糖症、変形性関節症、原発性硬化性胆管炎、エリテマトーデス；全身性エリテマトーデス、円板状エリテマトーデス、ループス腎炎；多発性硬化症（全ての型）、交感性眼炎、結合組織疾患続発性肺高血圧、グッドパスチャー症候群、結節性多発動脈炎の肺症状、急性リウマチ熱、リウマチ性脊椎炎、スティル病、全身性強皮症、強皮症疾患、強皮症、シェーグレン症候群、高安病／関節炎；自己免疫性血小板減少症、特発性血小板減少症；自己免疫性甲状腺障害、甲状腺機能亢進症、自己免疫性甲状腺機能低下症（橋本病）、萎縮性自己免疫性甲状腺機能低下症；白斑、急性肝疾患、慢性肝疾患、胆汁鬱滞、Ｔｈ１およびＴｈ２媒介性疾患；悪性腫瘍、例えば、肺がん、乳がん、胃がん、膀胱がん、結腸直腸がん、膵臓がん、膵臓癌、卵巣がん、前立腺がんおよび造血器悪性腫瘍（白血病およびリンパ腫）、急性白血病、急性リンパ性白血病、急性骨髄性白血病、腺癌、Ｂ細胞リンパ腫、バーキットリンパ腫、バイパスに対する炎症反応、慢性骨髄性白血病（ＣＭＬ）、慢性炎症性病変、慢性リンパ性白血病（ＣＬＬ）、直腸結腸癌、嚢胞性線維症、悪性リンパ腫、悪性組織球増殖症、悪性黒色腫、多発性骨髄腫、非ホジキンリンパ腫、鼻咽頭がん、固形腫瘍、ヘアリー細胞白血病、ホジキン病、肉腫、骨髄異形成症候群、サイトカイン療法誘導性障害、脱髄疾患、炎症性脱髄疾患、肺線維症、特発性肺線維症、通常型間質性肺炎、虹彩毛様体炎／ブドウ膜炎／視神経炎、リンパ浮腫、混合性結合組織疾患、単クローン性免疫グロブリン血症（ｍｏｎｏｃｌｏｎａｌ ｇａｍｍａｐａｔｈｙ）、新生児慢性肺疾患、腎炎、ネフローゼ、神経変性障害、骨粗鬆症、腫瘍随伴疾患／腫瘍関連高カルシウム血症、レイノー現象および疾患、皮膚変化、包括的全身性炎症反応症候群、血小板減少症、毒性、蕁麻疹、急性冠動脈症候群、成人型スティル病、再生不良性貧血、冠動脈硬化症、アトピー性湿疹；連鎖球菌感染に関連する自己免疫障害、自己免疫性腸疾患、自己免疫性難聴、自己免疫性リンパ増殖症候群（ＡＬＰＳ）、自己免疫性心筋炎、自己免疫性未成熟卵巣不全；セリアック病、頸部脊椎症、多発性硬化症のリスクを伴う臨床単離症候群（ｃｉｓ）、多形性紅斑、重症多形性紅斑、類天疱瘡、水疱性類天疱瘡、瘢痕性類天疱瘡、粘膜性類天疱瘡、妊娠性類天疱瘡、虹彩炎、角膜炎、運動ニューロン疾患、非Ａ、非Ｂ型肝炎、視神経炎、少数関節ＪＩＡ、結節性多発動脈炎、多発性軟骨炎、白毛症、多発性筋炎、再発性視神経脊髄炎、リウマチ性心疾患、ＳＡＰＨＯ（滑膜炎、ざ瘡、膿疱症、骨増殖症および骨炎）、続発性アミロイドーシス、強直性脊椎炎、全身性炎症反応症候群、頭蓋動脈炎、およびエルシニア属またはサルモネラ属関連関節症から選択される、態様３８に記載の使用。
［態様４０］
ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物を製造する方法であって、
ＶＨＨ誘導体ドメインおよび可変ＶＬドメインを含む薬学的に有効な量の抗ＩＬ１７ａ抗体を、
ヒスチジンベースの緩衝剤；および
浸透圧剤としての有効量のマンニトール、
と合わせるステップを含む方法。
［態様４１］
前記抗ＩＬ１７ａ抗体がネタキマブである、態様４０に記載の方法。
［態様４２］
ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物を製造する方法であって、
ＶＨＨ誘導体ドメインおよび可変ＶＬドメインを含む薬学的に有効な量の抗ＩＬ１７ａ抗体を、
酢酸塩ベースの緩衝剤；および
浸透圧剤としての有効量のトレハロース
と合わせるステップを含む方法。
［態様４３］
前記抗ＩＬ１７ａ抗体がネタキマブである、態様４２に記載の方法。 [00994] Netakimab up to a dose of 120 mg (e.g., the doses suggested herein) is beneficial in reducing AS activity, improving function, axial mobility, MRI signs of inflammation and quality of life. It is a well-tolerated drug with a safety profile.
The present invention includes, but is not limited to, the following aspects.
[Aspect 1]
1. An aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity, comprising:
a pharmaceutically effective amount of an anti-IL17a antibody comprising a VHH derivative domain and a variable VL domain;
An aqueous pharmaceutical composition comprising a histidine-based buffer; and an effective amount of a sugar-based alcohol as an osmotic agent.
[Aspect 2]
said VHH derivative domain of said anti-IL17a antibody comprises three hypervariable regions HCDR1, HCDR2 and HCDR3;
HCDR1 comprises the amino acid sequence of SEQ ID NO: 1;
HCDR2 comprises the amino acid sequence of SEQ ID NO:2;
HCDR3 comprises the amino acid sequence of SEQ ID NO:3; and
2. The aqueous pharmaceutical composition of aspect 1, wherein said variable VL domain of said anti-IL17a antibody comprises the amino acid sequence of SEQ ID NO:4.
[Aspect 3]
Aqueous pharmaceutical composition according to aspect 1, wherein said anti-IL17a antibody is netakimab.
[Aspect 4]
4. The aqueous pharmaceutical composition according to any one of aspects 1-3, wherein said netakimab is in an amount of 5 mg/mL to 150 mg/mL.
[Aspect 5]
4. The aqueous pharmaceutical composition according to any one of aspects 1-3, wherein said netakimab is in an amount of 10 mg/mL to 100 mg/mL.
[Aspect 6]
4. The aqueous pharmaceutical composition according to any one of aspects 1-3, wherein said netakimab is in an amount of 40 mg/mL.
[Aspect 7]
4. The aqueous pharmaceutical composition according to any one of aspects 1-3, wherein said netakimab is in an amount of 60 mg/mL.
[Aspect 8]
4. The aqueous pharmaceutical composition according to any one of aspects 1-3, wherein said netakimab is in an amount of 70 mg/mL.
[Aspect 9]
9. The aqueous pharmaceutical composition according to any one of aspects 1-8, wherein said sugar-based alcohol is mannitol.
[Aspect 10]
10. The aqueous pharmaceutical composition according to aspect 9, wherein said mannitol is in an amount of 25-60 mg/mL.
[Aspect 11]
11. The aqueous pharmaceutical composition according to any one of aspects 1-10, wherein a suitable amount of said histidine-based buffering agent is added to reach a pH of about 5.5 to about 6.5.
[Aspect 12]
The buffer is
12. Aspect 11, comprising: L-histidine in an amount from 0.4 mg/mL to 1.6 mg/mL; and histidine hydrochloride monohydrate in an amount from 0.4 mg/mL to 1.6 mg/mL. Aqueous pharmaceutical composition.
[Aspect 13]
13. The aqueous pharmaceutical composition according to any one of aspects 1-12, further comprising a suitable solubilizer.
[Aspect 14]
14. The aqueous pharmaceutical composition according to aspect 13, wherein said solubilizer is poloxamer 188.
[Aspect 15]
15. The aqueous pharmaceutical composition according to aspect 14, wherein said poloxamer 188 is in an amount greater than 0 mg/mL but less than or equal to 1 mg/mL.
[Aspect 16]
1. An aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity, comprising:
Netakimab 40 mg/mL
L-histidine 0.4 mg/mL
L-histidine hydrochloride monohydrate 0.4mg/mL
Mannitol 54.5 mg/mL
Poloxamer 188 0-1 mg/mL
pH 6.0±0.5
An aqueous pharmaceutical composition comprising
[Aspect 17]
a) said Poloxamer 188 is in an amount of 0.5 mg/mL; or b) said Poloxamer 188 is in an amount of 1 mg/mL.
17. An aqueous pharmaceutical composition according to aspect 16.
[Aspect 18]
1. An aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity, comprising:
a pharmaceutically effective amount of an anti-IL17a antibody comprising a VHH derivative domain and a variable VL domain;
An aqueous pharmaceutical composition comprising an acetate-based buffer; and a disaccharide as an osmotic agent.
[Aspect 19]
said VHH derivative domain of said anti-IL17a antibody comprises three hypervariable regions HCDR1, HCDR2 and HCDR3;
HCDR1 comprises the amino acid sequence of SEQ ID NO: 1;
HCDR2 comprises the amino acid sequence of SEQ ID NO:2;
HCDR3 comprises the amino acid sequence of SEQ ID NO:3; and
19. The aqueous pharmaceutical composition of aspect 18, wherein said variable VL domain of said anti-IL17a antibody comprises the amino acid sequence of SEQ ID NO:4.
[Aspect 20]
20. The aqueous pharmaceutical composition according to aspect 19, wherein said anti-IL17a antibody is netakimab.
[Aspect 21]
21. The aqueous pharmaceutical composition according to any one of aspects 18-20, wherein said netakimab is in an amount from 5 mg/mL to 150 mg/mL.
[Aspect 22]
21. The aqueous pharmaceutical composition according to any one of aspects 18-20, wherein said netakimab is in an amount of 10 mg/mL to 120 mg/mL.
[Aspect 23]
21. The aqueous pharmaceutical composition according to any one of aspects 18-20, wherein said netakimab is in an amount of 60 mg/mL.
[Aspect 24]
21. The aqueous pharmaceutical composition according to any one of aspects 18-20, wherein said netakimab is in an amount of 100 mg/mL.
[Aspect 25]
21. The aqueous pharmaceutical composition according to any one of aspects 18-20, wherein said netakimab is in an amount of 120 mg/mL.
[Aspect 26]
26. The aqueous pharmaceutical composition according to any one of aspects 18-25, wherein said disaccharide is trehalose.
[Aspect 27]
27. The aqueous pharmaceutical composition according to aspect 26, wherein said trehalose is added to said composition as trehalose dihydrate in an amount of 50 mg/mL to 120 mg/mL.
[Aspect 28]
The amount of said acetate-based buffer is
0.4 mg/mL to 1.8 mg/mL sodium acetate trihydrate; and
28. The aqueous pharmaceutical composition according to any one of aspects 18-27, comprising an amount of acetic acid suitable to reach a pH of said composition of 4.0 to 6.0 inclusive.
[Aspect 29]
29. The aqueous pharmaceutical composition according to any one of aspects 18-28, further comprising a suitable solubilizer.
[Aspect 30]
30. The aqueous pharmaceutical composition according to aspect 29, wherein said solubilizer is poloxamer 188.
[Aspect 31]
31. The aqueous pharmaceutical composition of aspect 30, wherein said poloxamer 188 is in an amount from greater than 0 mg/mL to 1.0 mg/mL or less.
[Aspect 32]
1. An aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity, comprising:
Netakimab 60 mg/mL
Sodium acetate trihydrate 1.74 mg/mL
Trehalose dihydrate 80 mg/mL
Glacial acetic acid up to pH 5.0 pH 5.0±0.5
An aqueous pharmaceutical composition comprising
[Aspect 33]
1. An aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity, comprising:
Netakimab 60 mg/mL
Sodium acetate trihydrate 1.74 mg/mL
Trehalose dihydrate 80 mg/mL
Poloxamer 188 0-1 mg/mL
Glacial acetic acid up to pH 5.0 pH 5.0±0.5
An aqueous pharmaceutical composition comprising
[Aspect 34]
a) said Poloxamer 188 is in an amount of 0.5 mg/mL; or b) said Poloxamer 188 is in an amount of 1 mg/mL.
34. An aqueous pharmaceutical composition according to aspect 33.
[Aspect 35]
1. An aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity, comprising:
Netakimab 120 mg/mL
Sodium acetate trihydrate 1.74 mg/mL
Trehalose dihydrate 80 mg/mL
Glacial acetic acid up to pH 5.0 pH 5.0±0.5
An aqueous pharmaceutical composition comprising
[Aspect 36]
1. An aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity, comprising:
Netakimab 120 mg/mL
Sodium acetate trihydrate 1.74 mg/mL
Trehalose dihydrate 80 mg/mL
Poloxamer 188 0-1 mg/mL
Glacial acetic acid up to pH 5.0 pH 5.0±0.5
An aqueous pharmaceutical composition comprising
[Aspect 37]
a) said Poloxamer 188 is in an amount of 0.5 mg/mL; or b) said Poloxamer 188 is in an amount of 1 mg/mL.
37. An aqueous pharmaceutical composition according to aspect 36.
[Aspect 38]
38. Use of an aqueous pharmaceutical composition according to any one of aspects 1-37 for treating an IL17a-mediated disease.
[Aspect 39]
said IL17a-mediated disease or disorder is rheumatoid arthritis, juvenile rheumatoid arthritis, systemic juvenile rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, psoriatic arthritis, reactive arthritis, seronegative arthritis, polyarticular juvenile idiopathic spondyloarthropathy, axial spondyloarthritis; Behcet's disease; inflammatory bowel disease, Crohn's disease, ulcerative colitis; asthma, allergic disorders, atopic allergy; pyoderma gangrenosum; hidradenitis suppurativa; psoriasis, psoriatic arthritis, type I psoriasis, type II psoriasis, plaque psoriasis; dermatitis, atopic Dermatitis, autoimmune dermatitis, skin lesions; systemic sclerosis; transplantation, graft-versus-host disease, graft rejection, acute or chronic immune disease associated with organ transplantation, acute transplant-related immune disease, chronic transplant-related immunity disease, small bowel graft rejection, pancreatic graft rejection, any organ or tissue graft rejection, heart transplant rejection, cartilage graft rejection, kidney transplant rejection, liver transplant rejection, allograft rejection, skin allograft rejection, xenograft rejection of any organ or tissue, bone graft rejection, bone marrow transplantation (BMT) rejection, parathyroid graft rejection; bone erosion; sarcoidosis, atherosclerosis, Wegener's disease, renal damage. Accompanied microscopic polyangiitis, uveitis, lenticular uveitis, non-infectious uveitis, cachexia, acute transverse myelitis, primary biliary cirrhosis, polyglandular autoimmune syndrome type I and type II, Schmidt's syndrome, acute respiratory distress syndrome; arthritis, seronegative arthritis, arthropathy associated with ulcerative colitis, Reiter's syndrome, enteropathic synovitis, atherosclerosis/coronary arteriosclerosis, auto Immune bullous disease, pemphigus, pemphigus foliaceus, linear IgA disease, autoimmune hemolytic anemia, cranial giant arteritis, primary sclerosing hepatitis, idiopathic autoimmune hepatitis, idiopathic fibrosing lung alveolitis, systemic dermatosclerosis associated with interstitial lung disease, rheumatoid arthritis associated with interstitial lung disease, systemic lupus erythematosus associated with lung disease, dermatomyositis/polymyositis associated with lung disease, pulmonary Sjogren's disease associated with disease, ankylosing spondylitis associated with pulmonary disease, vasculitis, diffuse pulmonary vasculitis, primary vasculitis, fibrosis, lung disease with lymphocytic infiltration, autoimmune hepatitis, autoimmune Hepatitis I (classical autoimmune or lupoid hepatitis), autoimmune hepatitis II (anti-LKM antibody associated), autoimmune hypoglycemia, osteoarthritis, primary sclerosing cholangitis, lupus erythematosus; systemic lupus erythematosus, discoid lupus erythematosus, lupus nephritis; multiple sclerosis (all types), sympathetic ophthalmia, connective tissue disease secondary pulmonary hypertension, Goodpasture's syndrome, pulmonary manifestations of polyarteritis nodosa, acute rheumatic fever, Rheumatoid spondylitis, Still's disease, systemic sclerosis, scleroderma disease, scleroderma, Sjögren's syndrome, Takayasu's disease/arthritis; autoimmune thrombocytopenia, idiopathic thrombocytopenia; autoimmune thyroid disorders, Hyperthyroidism, autoimmune hypothyroidism (Hashimoto's disease), atrophic autoimmune hypothyroidism; vitiligo, acute liver disease, chronic liver disease, cholestasis, Th1 and Th2 mediated diseases; malignancies, For example, lung cancer, breast cancer, gastric cancer, bladder cancer, colorectal cancer, pancreatic cancer, pancreatic cancer, ovarian cancer, prostate cancer and hematopoietic malignancies (leukemia and lymphoma), acute leukemia, acute lymphocytic leukemia, Acute myelogenous leukemia, adenocarcinoma, B-cell lymphoma, Burkitt's lymphoma, inflammatory response to bypass, chronic myelogenous leukemia (CML), chronic inflammatory lesions, chronic lymphocytic leukemia (CLL), colorectal cancer, cystic fibrosis , malignant lymphoma, malignant histiocytosis, malignant melanoma, multiple myeloma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, solid tumor, hairy cell leukemia, Hodgkin's disease, sarcoma, myelodysplastic syndrome, cytokine therapy-induced disorders , demyelinating disease, inflammatory demyelinating disease, pulmonary fibrosis, idiopathic pulmonary fibrosis, common interstitial pneumonia, iridocyclitis/uveitis/optic neuritis, lymphedema, mixed connective tissue disease, Monoclonal gammapathy, neonatal chronic lung disease, nephritis, nephrosis, neurodegenerative disorders, osteoporosis, paraneoplastic/tumor-associated hypercalcemia, Raynaud's phenomenon and disease, skin changes, global systemic Inflammatory response syndrome, thrombocytopenia, toxicity, urticaria, acute coronary syndrome, adult-onset Still's disease, aplastic anemia, coronary arteriosclerosis, atopic eczema; autoimmune disorders associated with streptococcal infection, autoimmune bowel disease , autoimmune deafness, autoimmune lymphoproliferative syndrome (ALPS), autoimmune myocarditis, autoimmune premature ovarian failure; celiac disease, cervical spondylosis, clinical isolation syndrome with risk of multiple sclerosis (cis), erythema multiforme, erythema multiforme severe, pemphigoid, bullous pemphigoid, cicatricial pemphigoid, mucosal pemphigoid, gestational pemphigoid, iritis, keratitis, exercise Neuronal disease, non-A, non-B hepatitis, optic neuritis, oligarticular JIA, polyarteritis nodosa, polychondritis, albinism, polymyositis, recurrent neuromyelitis optica, rheumatic heart disease, SAPHO ( synovitis, acne, pustulosis, osteophytosis and osteitis), secondary amyloidosis, ankylosing spondylitis, systemic inflammatory response syndrome, cranial arteritis, and Yersinia or Salmonella-associated arthropathy 39. Use according to aspect 38.
[Aspect 40]
1. A method of making an aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity comprising:
a pharmaceutically effective amount of an anti-IL17a antibody comprising a VHH derivative domain and a variable VL domain;
a histidine-based buffer; and an effective amount of mannitol as an osmotic agent,
A method comprising the step of matching with
[Aspect 41]
41. The method of aspect 40, wherein said anti-IL17a antibody is netakimab.
[Aspect 42]
1. A method of making an aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity comprising:
a pharmaceutically effective amount of an anti-IL17a antibody comprising a VHH derivative domain and a variable VL domain;
an acetate-based buffer; and an effective amount of trehalose as an osmotic agent.
[Aspect 43]
43. The method of aspect 42, wherein said anti-IL17a antibody is netakimab.

Claims (33)

ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物であって、
ＶＨＨ誘導体ドメインおよび可変ＶＬドメインを含む薬学的に有効な量の抗ＩＬ１７ａ抗体；
ヒスチジンベースの緩衝剤；ならびに
浸透圧剤としての有効量の糖ベースのアルコール
を含む水性医薬組成物。 1. An aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity, comprising:
a pharmaceutically effective amount of an anti-IL17a antibody comprising a VHH derivative domain and a variable VL domain;
An aqueous pharmaceutical composition comprising a histidine-based buffer; and an effective amount of a sugar-based alcohol as an osmotic agent. 前記抗ＩＬ１７ａ抗体の前記ＶＨＨ誘導体ドメインが、３つの超可変領域ＨＣＤＲ１、ＨＣＤＲ２およびＨＣＤＲ３を含み、
ＨＣＤＲ１が配列番号１のアミノ酸配列を含み；
ＨＣＤＲ２が配列番号２のアミノ酸配列を含み；
ＨＣＤＲ３が配列番号３のアミノ酸配列を含み；そして、
前記抗ＩＬ１７ａ抗体の前記可変ＶＬドメインが配列番号４のアミノ酸配列を含む、請求項１に記載の水性医薬組成物。 said VHH derivative domain of said anti-IL17a antibody comprises three hypervariable regions HCDR1, HCDR2 and HCDR3;
HCDR1 comprises the amino acid sequence of SEQ ID NO: 1;
HCDR2 comprises the amino acid sequence of SEQ ID NO:2;
HCDR3 comprises the amino acid sequence of SEQ ID NO:3; and
2. The aqueous pharmaceutical composition of claim 1, wherein said variable VL domain of said anti-IL17a antibody comprises the amino acid sequence of SEQ ID NO:4. 前記抗ＩＬ１７ａ抗体がネタキマブである、請求項１に記載の水性医薬組成物。 2. The aqueous pharmaceutical composition of claim 1, wherein said anti-IL17a antibody is netakimab. 前記ネタキマブが、５ｍｇ／ｍＬ～１５０ｍｇ／ｍＬの量である、請求項１に記載の水性医薬組成物。 2. The aqueous pharmaceutical composition of claim 1 , wherein said netakimab is in an amount of 5 mg/mL to 150 mg/mL. 前記ネタキマブが、１０ｍｇ／ｍＬ～１００ｍｇ／ｍＬの量である、請求項１に記載の水性医薬組成物。 2. The aqueous pharmaceutical composition of claim 1 , wherein said netakimab is in an amount of 10 mg/mL to 100 mg/mL. 前記ネタキマブが、４０ｍｇ／ｍＬの量である、または、
前記ネタキマブが、６０ｍｇ／ｍＬの量である、または、
前記ネタキマブが、７０ｍｇ／ｍＬの量である、
請求項１に記載の水性医薬組成物。 the netakimab is in an amount of 40 mg/mL, or
the netakimab is in an amount of 60 mg/mL, or
wherein said netakimab is in an amount of 70 mg/mL;
The aqueous pharmaceutical composition according to claim 1 . 前記糖ベースのアルコールがマンニトールである、請求項１に記載の水性医薬組成物。 2. The aqueous pharmaceutical composition of claim 1, wherein said sugar-based alcohol is mannitol. 前記マンニトールが、２５～６０ｍｇ／ｍＬの量である、請求項７に記載の水性医薬組成物。 The aqueous pharmaceutical composition according to claim 7 , wherein said mannitol is in an amount of 25-60 mg/mL. 前記ヒスチジンベースの緩衝剤の適切な量が、約５．５～約６．５のｐＨに達するように加えられる、請求項１に記載の水性医薬組成物。 2. The aqueous pharmaceutical composition of claim 1 , wherein a suitable amount of said histidine-based buffering agent is added to reach a pH of about 5.5 to about 6.5. 前記緩衝剤が、
０．４ｍｇ／ｍＬ～１．６ｍｇ／ｍＬの量のＬ－ヒスチジン；および
０．４ｍｇ／ｍＬ～１．６ｍｇ／ｍＬの量のヒスチジン塩酸塩一水和物
から構成される、請求項９に記載の水性医薬組成物。 The buffer is
L-histidine in an amount from 0.4 mg/mL to 1.6 mg/mL; and histidine hydrochloride monohydrate in an amount from 0.4 mg/mL to 1.6 mg/mL. Aqueous pharmaceutical composition of 適切な可溶化剤をさらに含む、請求項１に記載の水性医薬組成物。 2. The aqueous pharmaceutical composition of Claim 1 , further comprising a suitable solubilizer. 前記可溶化剤がポロキサマー１８８である、請求項１１に記載の水性医薬組成物。 12. The aqueous pharmaceutical composition of claim 11 , wherein said solubilizer is poloxamer 188. 前記ポロキサマー１８８が、０ｍｇ／ｍＬより多いが、１ｍｇ／ｍＬ以下の量である、請求項１２に記載の水性医薬組成物。 13. The aqueous pharmaceutical composition of Claim 12, wherein said poloxamer 188 is in an amount greater than 0 mg/mL but not greater than 1 mg/mL. ネタキマブ ４０ｍｇ／ｍＬ
Ｌ－ヒスチジン ０．４ｍｇ／ｍＬ
Ｌ－ヒスチジン塩酸塩一水和物 ０．４ｍｇ／ｍＬ
マンニトール ５４．５ｍｇ／ｍＬ
ポロキサマー１８８ ０～１ｍｇ／ｍＬ
ｐＨ ６．０±０．５
を含む、請求項１に記載の水性医薬組成物。 Netakimab 40 mg/mL
L-histidine 0.4 mg/mL
L-histidine hydrochloride monohydrate 0.4mg/mL
Mannitol 54.5 mg/mL
Poloxamer 188 0-1 mg/mL
pH 6.0±0.5
2. The aqueous pharmaceutical composition of claim 1, comprising ａ）前記ポロキサマー１８８が０．５ｍｇ／ｍＬの量であるか；または
ｂ）前記ポロキサマー１８８が１ｍｇ／ｍＬの量である、
請求項１４に記載の水性医薬組成物。 a) said Poloxamer 188 is in an amount of 0.5 mg/mL; or b) said Poloxamer 188 is in an amount of 1 mg/mL.
15. Aqueous pharmaceutical composition according to claim 14 . ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物であって、
ＶＨＨ誘導体ドメインおよび可変ＶＬドメインを含む薬学的に有効な量の抗ＩＬ１７ａ抗体；
酢酸塩ベースの緩衝剤；ならびに
浸透圧剤としての二糖
を含む水性医薬組成物。 1. An aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity, comprising:
a pharmaceutically effective amount of an anti-IL17a antibody comprising a VHH derivative domain and a variable VL domain;
An aqueous pharmaceutical composition comprising an acetate-based buffer; and a disaccharide as an osmotic agent. 前記抗ＩＬ１７ａ抗体の前記ＶＨＨ誘導体ドメインが、３つの超可変領域ＨＣＤＲ１、ＨＣＤＲ２およびＨＣＤＲ３を含み、
ＨＣＤＲ１が配列番号１のアミノ酸配列を含み；
ＨＣＤＲ２が配列番号２のアミノ酸配列を含み；
ＨＣＤＲ３が配列番号３のアミノ酸配列を含み；そして、
前記抗ＩＬ１７ａ抗体の前記可変ＶＬドメインが配列番号４のアミノ酸配列を含む、請求項１６に記載の水性医薬組成物。 said VHH derivative domain of said anti-IL17a antibody comprises three hypervariable regions HCDR1, HCDR2 and HCDR3;
HCDR1 comprises the amino acid sequence of SEQ ID NO: 1;
HCDR2 comprises the amino acid sequence of SEQ ID NO:2;
HCDR3 comprises the amino acid sequence of SEQ ID NO:3; and
17. The aqueous pharmaceutical composition of claim 16 , wherein said variable VL domain of said anti-IL17a antibody comprises the amino acid sequence of SEQ ID NO:4. 前記抗ＩＬ１７ａ抗体がネタキマブである、請求項１７に記載の水性医薬組成物。 18. The aqueous pharmaceutical composition of claim 17 , wherein said anti-IL17a antibody is netakimab. 前記ネタキマブが、５ｍｇ／ｍＬ～１５０ｍｇ／ｍＬの量である、請求項１６に記載の水性医薬組成物。 17. The aqueous pharmaceutical composition of claim 16 , wherein said netakimab is in an amount of 5 mg/mL to 150 mg/mL. 前記ネタキマブが、１０ｍｇ／ｍＬ～１２０ｍｇ／ｍＬの量である、請求項１６に記載の水性医薬組成物。 17. The aqueous pharmaceutical composition of claim 16, wherein said netakimab is in an amount of 10 mg/mL to 120 mg/mL. 前記ネタキマブが、６０ｍｇ／ｍＬの量である、または、
前記ネタキマブが、１００ｍｇ／ｍＬの量である、または、
前記ネタキマブが、１２０ｍｇ／ｍＬの量である、
請求項１６に記載の水性医薬組成物。 the netakimab is in an amount of 60 mg/mL, or
the netakimab is in an amount of 100 mg/mL, or
wherein said netakimab is in an amount of 120 mg/mL;
17. Aqueous pharmaceutical composition according to claim 16 . 前記二糖がトレハロースである、請求項１６に記載の水性医薬組成物。 17. The aqueous pharmaceutical composition according to claim 16 , wherein said disaccharide is trehalose. 前記トレハロースが、５０ｍｇ／ｍＬ～１２０ｍｇ／ｍＬの量でトレハロース二水和物として前記組成物に加えられる、請求項２２に記載の水性医薬組成物。 23. The aqueous pharmaceutical composition of claim 22, wherein said trehalose is added to said composition as trehalose dihydrate in an amount of 50 mg/mL to 120 mg/mL. 前記酢酸塩ベースの緩衝剤の量が、
０．４ｍｇ／ｍＬ～１．８ｍｇ／ｍＬの酢酸ナトリウム三水和物；および、
両端の値を含めて４．０～６．０の前記組成物のｐＨに達するのに適切な量の酢酸
から構成される、請求項１６に記載の水性医薬組成物。 The amount of said acetate-based buffer is
0.4 mg/mL to 1.8 mg/mL sodium acetate trihydrate; and
17. The aqueous pharmaceutical composition of claim 16 , comprising an amount of acetic acid suitable to reach a pH of said composition of 4.0 to 6.0 inclusive. 適切な可溶化剤をさらに含む、請求項１６に記載の水性医薬組成物。 17. Aqueous pharmaceutical composition according to claim 16 , further comprising a suitable solubilizer. 前記可溶化剤がポロキサマー１８８である、請求項２５に記載の水性医薬組成物。 26. The aqueous pharmaceutical composition of claim 25 , wherein said solubilizer is poloxamer 188. 前記ポロキサマー１８８が、０ｍｇ／ｍＬ超～１．０ｍｇ／ｍＬ以下の量である、請求項２６に記載の水性医薬組成物。 27. The aqueous pharmaceutical composition of claim 26, wherein said poloxamer 188 is in an amount from greater than 0 mg/mL to 1.0 mg/mL or less. （ｉ）
ネタキマブ ６０ｍｇ／ｍＬ
酢酸ナトリウム三水和物 １．７４ｍｇ／ｍＬ
トレハロース二水和物 ８０ｍｇ／ｍＬ
氷酢酸 ｐＨ５．０まで
ｐＨ ５．０±０．５、
または、
（ｉｉ）
ネタキマブ ６０ｍｇ／ｍＬ
酢酸ナトリウム三水和物 １．７４ｍｇ／ｍＬ
トレハロース二水和物 ８０ｍｇ／ｍＬ
ポロキサマー１８８ ０～１ｍｇ／ｍＬ
氷酢酸 ｐＨ５．０まで
ｐＨ ５．０±０．５、
または、
（ｉｉｉ）
ネタキマブ １２０ｍｇ／ｍＬ
酢酸ナトリウム三水和物 １．７４ｍｇ／ｍＬ
トレハロース二水和物 ８０ｍｇ／ｍＬ
氷酢酸 ｐＨ５．０まで
ｐＨ ５．０±０．５、
または、
（ｉｖ）
ネタキマブ １２０ｍｇ／ｍＬ
酢酸ナトリウム三水和物 １．７４ｍｇ／ｍＬ
トレハロース二水和物 ８０ｍｇ／ｍＬ
ポロキサマー１８８ ０～１ｍｇ／ｍＬ
氷酢酸 ｐＨ５．０まで
ｐＨ ５．０±０．５
を含む、請求項１６に記載の水性医薬組成物。 (i)
Netakimab 60 mg/mL
Sodium acetate trihydrate 1.74 mg/mL
Trehalose dihydrate 80 mg/mL
Glacial acetic acid up to pH 5.0 pH 5.0 ± 0.5,
or,
(ii)
Netakimab 60 mg/mL
Sodium acetate trihydrate 1.74 mg/mL
Trehalose dihydrate 80 mg/mL
Poloxamer 188 0-1 mg/mL
Glacial acetic acid up to pH 5.0 pH 5.0 ± 0.5,
or,
(iii)
Netakimab 120 mg/mL
Sodium acetate trihydrate 1.74 mg/mL
Trehalose dihydrate 80 mg/mL
Glacial acetic acid up to pH 5.0 pH 5.0 ± 0.5,
or,
(iv)
Netakimab 120 mg/mL
Sodium acetate trihydrate 1.74 mg/mL
Trehalose dihydrate 80 mg/mL
Poloxamer 188 0-1 mg/mL
Glacial acetic acid up to pH 5.0 pH 5.0±0.5
17. The aqueous pharmaceutical composition of claim 16 , comprising ａ）前記ポロキサマー１８８が０．５ｍｇ／ｍＬの量であるか；または
ｂ）前記ポロキサマー１８８が１ｍｇ／ｍＬの量である、
請求項２８に記載の水性医薬組成物。 a) said Poloxamer 188 is in an amount of 0.5 mg/mL; or b) said Poloxamer 188 is in an amount of 1 mg/mL.
29. An aqueous pharmaceutical composition according to claim 28 . ＩＬ１７ａ媒介性疾患を治療するための請求項１から２９のいずれか一項に記載の水性医薬組成物の使用。 30. Use of an aqueous pharmaceutical composition according to any one of claims 1 to 29 for treating IL17a-mediated diseases. 前記ＩＬ１７ａ媒介性疾患または障害が、関節リウマチ、若年性関節リウマチ、全身型若年性関節リウマチ、骨関節炎、若年性慢性関節炎、乾癬性関節炎、反応性関節炎、血清反応陰性関節炎、多関節若年性特発性関節炎、腱付着部炎関連関節炎；腱付着部炎；脊椎関節症、軸性脊椎関節炎；ベーチェット病；炎症性腸疾患、クローン病、潰瘍性結腸炎；ぜんそく、アレルギー性障害、アトピー性アレルギー；魚鱗癬；毛孔性紅色粃糠疹；丘疹膿疱性酒さ；壊疽性膿皮症；化膿性汗腺炎；乾癬、乾癬性関節症、Ｉ型乾癬、ＩＩ型乾癬、プラーク乾癬；皮膚炎、アトピー性皮膚炎、自己免疫性皮膚炎、皮膚病変；全身性硬化症；移植、移植片対宿主病、移植片拒絶、臓器移植と関連する急性または慢性免疫疾患、急性移植関連免疫疾患、慢性移植関連免疫疾患、小腸移植片拒絶、膵臓移植片拒絶、任意の臓器または組織移植片拒絶、心移植拒絶反応、軟骨移植片拒絶、腎移植拒絶反応、肝移植拒絶反応、同種移植片拒絶、皮膚同種移植片拒絶、任意の臓器または組織についての異種移植片拒絶、骨移植片拒絶、骨髄移植（ＢＭＴ）拒絶反応、副甲状腺移植片拒絶；骨侵食；サルコイドーシス、アテローム性動脈硬化症、ウェゲナー疾患、腎障害を伴う顕微鏡的多発性血管炎、ブドウ膜炎、水晶体起因性ブドウ膜炎、非感染性ブドウ膜炎、悪液質、急性横断性脊髄炎、原発性胆汁性肝硬変、多腺性自己免疫症候群Ｉ型およびＩＩ型、シュミット症候群、急性呼吸促迫症候群；関節症、血清反応陰性関節症、潰瘍性結腸炎と関連する関節症、ライター症候群、腸疾患性滑膜炎、アテローム疾患／冠状動脈硬化症、自己免疫性水疱性疾患、天疱瘡、落葉状天疱瘡、線状ＩｇＡ疾患、自己免疫性溶血性貧血、頭蓋巨大動脈炎、原発性硬化性肝炎、特発性自己免疫性肝炎、特発性線維化性肺胞炎、間質性肺疾患と関連する全身性皮膚硬化症、間質性肺疾患と関連する関節リウマチ、肺疾患と関連する全身性エリテマトーデス、肺疾患と関連する皮膚筋炎／多発性筋炎、肺疾患と関連するシェーグレン病、肺疾患と関連する強直性脊椎炎、血管炎、びまん性肺血管炎、原発性血管炎、線維症、リンパ球浸潤を伴う肺疾患、自己免疫性肝炎、自己免疫性肝炎Ｉ型（古典的自己免疫性またはルポイド肝炎）、自己免疫性肝炎ＩＩ型（抗ＬＫＭ抗体関連）、自己免疫性低血糖症、変形性関節症、原発性硬化性胆管炎、エリテマトーデス；全身性エリテマトーデス、円板状エリテマトーデス、ループス腎炎；多発性硬化症（全ての型）、交感性眼炎、結合組織疾患続発性肺高血圧、グッドパスチャー症候群、結節性多発動脈炎の肺症状、急性リウマチ熱、リウマチ性脊椎炎、スティル病、全身性強皮症、強皮症疾患、強皮症、シェーグレン症候群、高安病／関節炎；自己免疫性血小板減少症、特発性血小板減少症；自己免疫性甲状腺障害、甲状腺機能亢進症、自己免疫性甲状腺機能低下症（橋本病）、萎縮性自己免疫性甲状腺機能低下症；白斑、急性肝疾患、慢性肝疾患、胆汁鬱滞、Ｔｈ１およびＴｈ２媒介性疾患；悪性腫瘍、例えば、肺がん、乳がん、胃がん、膀胱がん、結腸直腸がん、膵臓がん、膵臓癌、卵巣がん、前立腺がんおよび造血器悪性腫瘍（白血病およびリンパ腫）、急性白血病、急性リンパ性白血病、急性骨髄性白血病、腺癌、Ｂ細胞リンパ腫、バーキットリンパ腫、バイパスに対する炎症反応、慢性骨髄性白血病（ＣＭＬ）、慢性炎症性病変、慢性リンパ性白血病（ＣＬＬ）、直腸結腸癌、嚢胞性線維症、悪性リンパ腫、悪性組織球増殖症、悪性黒色腫、多発性骨髄腫、非ホジキンリンパ腫、鼻咽頭がん、固形腫瘍、ヘアリー細胞白血病、ホジキン病、肉腫、骨髄異形成症候群、サイトカイン療法誘導性障害、脱髄疾患、炎症性脱髄疾患、肺線維症、特発性肺線維症、通常型間質性肺炎、虹彩毛様体炎／ブドウ膜炎／視神経炎、リンパ浮腫、混合性結合組織疾患、単クローン性免疫グロブリン血症（ｍｏｎｏｃｌｏｎａｌ ｇａｍｍａｐａｔｈｙ）、新生児慢性肺疾患、腎炎、ネフローゼ、神経変性障害、骨粗鬆症、腫瘍随伴疾患／腫瘍関連高カルシウム血症、レイノー現象および疾患、皮膚変化、包括的全身性炎症反応症候群、血小板減少症、毒性、蕁麻疹、急性冠動脈症候群、成人型スティル病、再生不良性貧血、冠動脈硬化症、アトピー性湿疹；連鎖球菌感染に関連する自己免疫障害、自己免疫性腸疾患、自己免疫性難聴、自己免疫性リンパ増殖症候群（ＡＬＰＳ）、自己免疫性心筋炎、自己免疫性未成熟卵巣不全；セリアック病、頸部脊椎症、多発性硬化症のリスクを伴う臨床単離症候群（ｃｉｓ）、多形性紅斑、重症多形性紅斑、類天疱瘡、水疱性類天疱瘡、瘢痕性類天疱瘡、粘膜性類天疱瘡、妊娠性類天疱瘡、虹彩炎、角膜炎、運動ニューロン疾患、非Ａ、非Ｂ型肝炎、視神経炎、少数関節ＪＩＡ、結節性多発動脈炎、多発性軟骨炎、白毛症、多発性筋炎、再発性視神経脊髄炎、リウマチ性心疾患、ＳＡＰＨＯ（滑膜炎、ざ瘡、膿疱症、骨増殖症および骨炎）、続発性アミロイドーシス、強直性脊椎炎、全身性炎症反応症候群、頭蓋動脈炎、およびエルシニア属またはサルモネラ属関連関節症から選択される、請求項３０に記載の使用。 said IL17a-mediated disease or disorder is rheumatoid arthritis, juvenile rheumatoid arthritis, systemic juvenile rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, psoriatic arthritis, reactive arthritis, seronegative arthritis, polyarticular juvenile idiopathic spondyloarthropathy, axial spondyloarthritis; Behcet's disease; inflammatory bowel disease, Crohn's disease, ulcerative colitis; asthma, allergic disorders, atopic allergy; pyoderma gangrenosum; hidradenitis suppurativa; psoriasis, psoriatic arthritis, type I psoriasis, type II psoriasis, plaque psoriasis; dermatitis, atopic Dermatitis, autoimmune dermatitis, skin lesions; systemic sclerosis; transplantation, graft-versus-host disease, graft rejection, acute or chronic immune disease associated with organ transplantation, acute transplant-related immune disease, chronic transplant-related immunity disease, small bowel graft rejection, pancreatic graft rejection, any organ or tissue graft rejection, heart transplant rejection, cartilage graft rejection, kidney transplant rejection, liver transplant rejection, allograft rejection, skin allograft rejection, xenograft rejection of any organ or tissue, bone graft rejection, bone marrow transplantation (BMT) rejection, parathyroid graft rejection; bone erosion; sarcoidosis, atherosclerosis, Wegener's disease, renal damage. Accompanied microscopic polyangiitis, uveitis, lenticular uveitis, non-infectious uveitis, cachexia, acute transverse myelitis, primary biliary cirrhosis, polyglandular autoimmune syndrome type I and type II, Schmidt's syndrome, acute respiratory distress syndrome; arthritis, seronegative arthritis, arthropathy associated with ulcerative colitis, Reiter's syndrome, enteropathic synovitis, atherosclerosis/coronary arteriosclerosis, auto Immune bullous disease, pemphigus, pemphigus foliaceus, linear IgA disease, autoimmune hemolytic anemia, cranial giant arteritis, primary sclerosing hepatitis, idiopathic autoimmune hepatitis, idiopathic fibrosing lung alveolitis, systemic dermatosclerosis associated with interstitial lung disease, rheumatoid arthritis associated with interstitial lung disease, systemic lupus erythematosus associated with lung disease, dermatomyositis/polymyositis associated with lung disease, pulmonary Sjogren's disease associated with disease, ankylosing spondylitis associated with pulmonary disease, vasculitis, diffuse pulmonary vasculitis, primary vasculitis, fibrosis, lung disease with lymphocytic infiltration, autoimmune hepatitis, autoimmune Hepatitis I (classical autoimmune or lupoid hepatitis), autoimmune hepatitis II (anti-LKM antibody associated), autoimmune hypoglycemia, osteoarthritis, primary sclerosing cholangitis, lupus erythematosus; systemic lupus erythematosus, discoid lupus erythematosus, lupus nephritis; multiple sclerosis (all types), sympathetic ophthalmia, connective tissue disease secondary pulmonary hypertension, Goodpasture's syndrome, pulmonary manifestations of polyarteritis nodosa, acute rheumatic fever, Rheumatoid spondylitis, Still's disease, systemic sclerosis, scleroderma disease, scleroderma, Sjögren's syndrome, Takayasu's disease/arthritis; autoimmune thrombocytopenia, idiopathic thrombocytopenia; autoimmune thyroid disorders, Hyperthyroidism, autoimmune hypothyroidism (Hashimoto's disease), atrophic autoimmune hypothyroidism; vitiligo, acute liver disease, chronic liver disease, cholestasis, Th1 and Th2 mediated diseases; malignancies, For example, lung cancer, breast cancer, gastric cancer, bladder cancer, colorectal cancer, pancreatic cancer, pancreatic cancer, ovarian cancer, prostate cancer and hematopoietic malignancies (leukemia and lymphoma), acute leukemia, acute lymphocytic leukemia, Acute myelogenous leukemia, adenocarcinoma, B-cell lymphoma, Burkitt's lymphoma, inflammatory response to bypass, chronic myelogenous leukemia (CML), chronic inflammatory lesions, chronic lymphocytic leukemia (CLL), colorectal cancer, cystic fibrosis , malignant lymphoma, malignant histiocytosis, malignant melanoma, multiple myeloma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, solid tumor, hairy cell leukemia, Hodgkin's disease, sarcoma, myelodysplastic syndrome, cytokine therapy-induced disorders , demyelinating disease, inflammatory demyelinating disease, pulmonary fibrosis, idiopathic pulmonary fibrosis, common interstitial pneumonia, iridocyclitis/uveitis/optic neuritis, lymphedema, mixed connective tissue disease, Monoclonal gammapathy, neonatal chronic lung disease, nephritis, nephrosis, neurodegenerative disorders, osteoporosis, paraneoplastic/tumor-associated hypercalcemia, Raynaud's phenomenon and disease, skin changes, global systemic Inflammatory response syndrome, thrombocytopenia, toxicity, urticaria, acute coronary syndrome, adult-onset Still's disease, aplastic anemia, coronary arteriosclerosis, atopic eczema; autoimmune disorders associated with streptococcal infection, autoimmune bowel disease , autoimmune deafness, autoimmune lymphoproliferative syndrome (ALPS), autoimmune myocarditis, autoimmune premature ovarian failure; celiac disease, cervical spondylosis, clinical isolation syndrome with risk of multiple sclerosis (cis), erythema multiforme, erythema multiforme severe, pemphigoid, bullous pemphigoid, cicatricial pemphigoid, mucosal pemphigoid, gestational pemphigoid, iritis, keratitis, exercise Neuronal disease, non-A, non-B hepatitis, optic neuritis, oligarticular JIA, polyarteritis nodosa, polychondritis, albinism, polymyositis, recurrent neuromyelitis optica, rheumatic heart disease, SAPHO ( synovitis, acne, pustulosis, osteophytosis and osteitis), secondary amyloidosis, ankylosing spondylitis, systemic inflammatory response syndrome, cranial arteritis, and Yersinia or Salmonella-associated arthropathy 31. Use according to claim 30 . ＩＬ１７ａタンパク質活性を阻害するための対象への非経口投与に適した水性医薬組成物を製造する方法であって、
（ｉ）ＶＨＨ誘導体ドメインおよび可変ＶＬドメインを含む薬学的に有効な量の抗ＩＬ１７ａ抗体を、
ヒスチジンベースの緩衝剤；および
浸透圧剤としての有効量のマンニトール、
と合わせるステップを含む、
あるいは、
（ｉｉ）ＶＨＨ誘導体ドメインおよび可変ＶＬドメインを含む薬学的に有効な量の抗ＩＬ１７ａ抗体を、
酢酸塩ベースの緩衝剤；および
浸透圧剤としての有効量のトレハロース
と合わせるステップを含む、
前記方法。 1. A method of making an aqueous pharmaceutical composition suitable for parenteral administration to a subject for inhibiting IL17a protein activity comprising:
(i) a pharmaceutically effective amount of an anti-IL17a antibody comprising a VHH derivative domain and a variable VL domain,
a histidine-based buffer; and an effective amount of mannitol as an osmotic agent,
including the step of matching with
or,
(ii) a pharmaceutically effective amount of an anti-IL17a antibody comprising a VHH derivative domain and a variable VL domain,
an acetate-based buffer; and an effective amount of trehalose as an osmotic agent .
the aforementioned method . 前記抗ＩＬ１７ａ抗体がネタキマブである、請求項３２に記載の方法。 33. The method of claim 32 , wherein said anti-IL17a antibody is netakimab.
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