JPWO2021113702A5 - - Google Patents
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- JPWO2021113702A5 JPWO2021113702A5 JP2022533368A JP2022533368A JPWO2021113702A5 JP WO2021113702 A5 JPWO2021113702 A5 JP WO2021113702A5 JP 2022533368 A JP2022533368 A JP 2022533368A JP 2022533368 A JP2022533368 A JP 2022533368A JP WO2021113702 A5 JPWO2021113702 A5 JP WO2021113702A5
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Description
特定の実施形態において、本開示の方法は、それを必要としている対象の自己免疫障害を治療することに関し、本方法は、対象に薬学的に有効な量の免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を投与することを含み、ここで対象は、ＩＬＴ７結合タンパク質の投与前に高値の血中Ｉ型ＩＦＮＧＳレベルを有すると決定される。一部の態様において、ＩＬＴ７結合タンパク質は、配列番号３、４、５、６、７、及び８のアミノ酸配列をそれぞれ含む、重鎖相補性決定領域（ＨＣＤＲ）ＨＣＤＲ１、ＨＤＲ２、ＨＣＤＲ３及び軽鎖相補性決定領域（ＬＣＤＲ）ＬＣＤＲ１、ＬＣＤＲ２、及びＬＣＤＲ３を含む抗体である。一部の態様において、ＩＬＴ７結合タンパク質は、配列番号１と少なくとも８５％、９０％、９５％、９６％、９７％、９８％又は９９％同一の可変重鎖（ＶＨ）及び／又は配列番号２と少なくとも８５％、９０％、９５％、９６％、９７％、９８％又は９９％同一の可変軽鎖（ＶＬ）を含む抗体である。特定の態様において、ＩＬＴ７結合タンパク質は、配列番号１の重鎖可変領域（ＶＨ）及び配列番号２の軽鎖可変領域（ＶＬ）を含む抗体である。一部の態様において、抗体はアフコシル化されている。
[本発明１００１]
それを必要としている対象のＩ型インターフェロン遺伝子シグネチャ（ＩＦＮＧＳ）を減少させるための方法であって、前記方法が、前記対象に薬学的に有効な量の免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を投与することを含み、ここで、正常対象の前記Ｉ型ＩＦＮＧＳと比べて前記対象の前記Ｉ型ＩＦＮＧＳが上昇しているときに、前記ＩＬＴ７結合タンパク質が前記対象に投与される、方法。
[本発明１００２]
前記Ｉ型ＩＦＮＧＳが、前記対象から採取された検査生体試料で測定され、前記検査試料が、血液、喀痰、唾液、皮膚細胞、皮膚生検試料、腎細胞、肺細胞、肝細胞、心臓細胞、脳細胞、神経組織、甲状腺細胞、眼細胞、骨格筋細胞、軟骨、骨組織、及び培養細胞からなる群から選択される、本発明１００１の方法。
[本発明１００３]
前記検査生体試料が、血液、皮膚細胞又は皮膚生検試料である、本発明１００２の方法。
[本発明１００４]
前記Ｉ型ＩＦＮＧＳが、前記検査生体試料中では、正常生体試料と比べて少なくとも約４倍に上昇している、先行本発明のいずれかの方法。
[本発明１００５]
前記Ｉ型ＩＦＮＧＳが、２種以上のＩ型インターフェロン（ＩＦＮ）誘導性遺伝子の集合的発現レベルを含む、先行本発明のいずれかの方法。
[本発明１００６]
前記２種以上のＩ型インターフェロン（ＩＦＮ）誘導性遺伝子が、ＳＰＡＴＳ２Ｌ、ＥＰＳＴＩ１、ＨＥＲＣ５、ＩＦＩ２７、ＩＦＩ４４、ＩＦＩ４４Ｌ、ＩＦＩ６、ＩＦＩＴ１、ＩＦＩＴ３、ＩＳＧ１５、ＬＡＭＰ３、ＬＹ６Ｅ、ＭＸ１、ＯＡＳ１、ＯＡＳ２、ＯＡＳ３、ＰＬＳＣＲ１、ＲＳＡＤ２、ＲＴＰ４、ＳＩＧＬＥＣ１、及びＵＳＰ１８からなる群から選択される、本発明１００５の方法。
[本発明１００７]
前記Ｉ型ＩＦＮＧＳが、ＳＰＡＴＳ２Ｌ、ＥＰＳＴＩ１、ＨＥＲＣ５、ＩＦＩ２７、ＩＦＩ４４、ＩＦＩ４４Ｌ、ＩＦＩ６、ＩＦＩＴ１、ＩＦＩＴ３、ＩＳＧ１５、ＬＡＭＰ３、ＬＹ６Ｅ、ＭＸ１、ＯＡＳ１、ＯＡＳ２、ＯＡＳ３、ＰＬＳＣＲ１、ＲＳＡＤ２、ＲＴＰ４、ＳＩＧＬＥＣ１、及びＵＳＰ１８の全ての集合的発現レベルを含む、本発明１００５の方法。
[本発明１００８]
前記Ｉ型ＩＦＮＧＳが、前記検査生体試料中の前記２種以上のＩ型インターフェロン（ＩＦＮ）誘導性遺伝子のｍＲＮＡレベルをアッセイすることにより決定される、本発明１００５の方法。
[本発明１００９]
前記Ｉ型ＩＦＮＧＳが、前記検査生体試料中の２１種のＩ型インターフェロン（ＩＦＮ）誘導性遺伝子のｍＲＮＡレベルをアッセイすることにより決定される、本発明１００７の方法。
[本発明１０１０]
前記ＩＬＴ７結合タンパク質を投与すると、前記対象において形質細胞様樹状細胞（ｐＤＣ）の減少が生じる、先行本発明のいずれかの方法。
[本発明１０１１]
前記ｐＤＣが、循環ｐＤＣである、本発明１０１０の方法。
[本発明１０１２]
前記ｐＤＣの前記減少が可逆的である、本発明１０１０又は１０１１の方法。
[本発明１０１３]
前記Ｉ型ＩＦＮＧＳを減少させることにより、前記対象の自己免疫疾患が治療される、先行本発明のいずれかの方法。
[本発明１０１４]
前記自己免疫疾患が、全身性エリテマトーデス（ＳＬＥ）、ループス腎炎、皮膚エリテマトーデス（ＣＬＥ）、シェーグレン症候群、炎症性筋炎、例えば、皮膚筋炎、封入体筋炎、若年性筋炎及び多発性筋炎など、全身性硬化症、糖尿病、橋本病、自己免疫性副腎不全、赤芽球ろう、多発性硬化症、リウマチ性心炎、乾癬、乾癬性関節炎、関節リウマチ、慢性炎症、慢性リウマチ、白斑、円形脱毛症、化膿性汗腺炎、セリアック病、急性及び慢性移植片対宿主病（ＧＶＨＤ）、血管炎症、心筋梗塞、並びに１型インターフェロン症からなる群から選択される、本発明１０１３の方法。
[本発明１０１５]
前記自己免疫疾患が、ＳＬＥ又はＣＬＥである、本発明１０１４の方法。
[本発明１０１６]
前記自己免疫疾患が、シェーグレン症候群である、本発明１０１４の方法。
[本発明１０１７]
前記自己免疫疾患が、皮膚筋炎である、本発明１０１４の方法。
[本発明１０１８]
前記自己免疫疾患が、多発性筋炎である、本発明１０１４の方法。
[本発明１０１９]
前記自己免疫疾患が、全身性硬化症である、本発明１０１４の方法。
[本発明１０２０]
前記自己免疫疾患が、化膿性汗腺炎である、本発明１０１４の方法。
[本発明１０２１]
前記自己免疫疾患が、白斑である、本発明１０１４の方法。
[本発明１０２２]
前記ＩＬＴ７結合タンパク質が、配列番号３、４、５、６、７、及び８のアミノ酸配列をそれぞれ含む、重鎖相補性決定領域（ＨＣＤＲ）ＨＣＤＲ１、ＨＤＲ２、ＨＣＤＲ３並びに軽鎖相補性決定領域（ＬＣＤＲ）ＬＣＤＲ１、ＬＣＤＲ２、及びＬＣＤＲ３を含む抗体である、先行本発明のいずれかの方法。
[本発明１０２３]
前記ＩＬＴ７結合タンパク質が、配列番号１と少なくとも８５％、９０％、９５％、９６％、９７％、９８％又は９９％同一の可変重鎖（ＶＨ）及び／又は配列番号２と少なくとも８５％、９０％、９５％、９６％、９７％、９８％又は９９％同一の可変軽鎖（ＶＬ）を含む抗体である、先行本発明のいずれかの方法。
[本発明１０２４]
前記ＩＬＴ７結合タンパク質が、配列番号１の重鎖可変領域（ＶＨ）及び配列番号２の軽鎖可変領域（ＶＬ）を含む抗体である、先行本発明のいずれかの方法。
[本発明１０２５]
前記抗体がアフコシル化されている、本発明１０２２～１０２４のいずれかの方法。
[本発明１０２６]
前記ＩＬＴ７結合タンパク質の前記薬学的に有効な量が、約０．１ｍｇ～約１０００ｍｇの範囲である、先行本発明のいずれかの方法。
[本発明１０２７]
前記ＩＬＴ７結合タンパク質の前記薬学的に有効な量が、約１ｍｇ、約５ｍｇ、約１５ｍｇ、約５０ｍｇ、約１００ｍｇ、又は約１５０ｍｇである、本発明１０２６の方法。
[本発明１０２８]
前記ＩＬＴ７結合タンパク質が皮下注射によって投与される、先行本発明のいずれかの方法。
[本発明１０２９]
前記ＩＬＴ７結合タンパク質を投与すると、前記ＩＬＴ７結合タンパク質の投与前の前記Ｉ型ＩＦＮＧＳと比較して、前記対象の前記Ｉ型ＩＦＮＧＳの少なくとも約５０％の減少につながる、先行本発明のいずれかの方法。
[本発明１０３０]
前記ＩＬＴ７結合タンパク質が、ｐＤＣに対する抗体依存性細胞媒介性細胞傷害（ＡＤＣＣ）活性を誘導する、先行本発明のいずれかの方法。
[本発明１０３１]
前記ＩＬＴ７結合タンパク質が、ｐＤＣからのＩ型インターフェロン（ＩＦＮ）の放出を抑制する、本発明１００１～１０２９のいずれかの方法。
[本発明１０３２]
前記Ｉ型ＩＦＮが、ＩＦＮαである、本発明１０３１の方法。
[本発明１０３３]
前記ＩＬＴ７結合タンパク質がＩＬＴ７に特異的に結合する、本発明１００１～１０３２のいずれかの方法。
[本発明１０３４]
前記ＩＬＴ７がｐＤＣ上にある、本発明１０３３の方法。
[本発明１０３５]
対象における活性化した形質細胞様樹状細胞（ｐＤＣ）を特徴とする病態の治療の有効性をモニタする方法であって、
（ａ）Ｉ型インターフェロン遺伝子シグネチャ（ＩＦＮＧＳ）のベースライン値を入手するために、前記対象から採取された生体試料中のＩ型ＩＦＮＧＳを測定するステップ；及び
（ｂ）治療を施した後に前記対象から採取された生体試料中の前記Ｉ型ＩＦＮＧＳを測定するステップであって、前記治療が、免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を前記対象に投与することを含む、ステップ
を含む、方法。
[本発明１０３６]
それを必要としている対象の組織中の形質細胞様樹状細胞（ｐＤＣ）を減少させる方法であって、前記対象に薬学的に有効な量の免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を投与することを含む、方法。
[本発明１０３７]
前記組織が、皮膚細胞、皮膚生検試料、腎細胞、肺細胞、肝細胞、心臓細胞、脳細胞、神経組織、甲状腺細胞、眼細胞、骨格筋細胞、軟骨、骨組織、及び気道細胞からなる群から選択される、本発明１０３６の方法。
[本発明１０３８]
前記組織が皮膚細胞である、本発明１０３７の方法。
[本発明１０３９]
前記組織が皮膚生検試料である、本発明１０３７の方法。
[本発明１０４０]
ベースライン値と比較した前記組織中のｐＤＣの低下を生じさせる、本発明１０３６～１０３９のいずれかの方法。
[本発明１０４１]
前記ベースライン値と比較した前記組織中のｐＤＣの前記低下が、約１％～約９９％の範囲である、本発明１０４０の方法。
[本発明１０４２]
前記ベースライン値と比較した前記組織中のｐＤＣの前記低下が、少なくとも約５０％である、本発明１０４０又は１０４１の方法。
[本発明１０４３]
前記ＩＬＴ７結合タンパク質が、配列番号３、４、５、６、７、及び８のアミノ酸配列をそれぞれ含む、重鎖相補性決定領域（ＨＣＤＲ）ＨＣＤＲ１、ＨＤＲ２、ＨＣＤＲ３並びに軽鎖相補性決定領域（ＬＣＤＲ）ＬＣＤＲ１、ＬＣＤＲ２、及びＬＣＤＲ３を含む抗体である、本発明１０３６～１０４２のいずれかの方法。
[本発明１０４４]
それを必要としている対象の自己免疫障害を治療する方法であって、前記方法が、前記対象に薬学的に有効な量の免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を投与することを含み、前記ＩＬＴ７結合タンパク質の前記薬学的に有効な量が、約１ｍｇ、約５ｍｇ、約１５ｍｇ、約５０ｍｇ、約１００ｍｇ、又は約１５０ｍｇである、方法。
[本発明１０４５]
前記ＩＬＴ７結合タンパク質の前記薬学的に有効な量が、約５０ｍｇである、本発明１００１～１０３４、又は１０４４のいずれかの方法。
[本発明１０４６]
前記ＩＬＴ７結合タンパク質の前記薬学的に有効な量が、約１５０ｍｇである、本発明１００１～１０３４、又は１０４４のいずれかの方法。
[本発明１０４７]
それを必要としている対象の自己免疫障害を治療する方法であって、前記方法が、前記対象に薬学的に有効な量の免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を投与することを含み、前記ＩＬＴ７結合タンパク質の前記薬学的に有効な量が、約５０ｍｇである、方法。
[本発明１０４８]
それを必要としている対象の自己免疫障害を治療する方法であって、前記方法が、前記対象に薬学的に有効な量の免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を投与することを含み、前記ＩＬＴ７結合タンパク質の前記薬学的に有効な量が、約１５０ｍｇである、方法。
[本発明１０４９]
それを必要としている対象の組織中の形質細胞様樹状細胞（ｐＤＣ）を減少させる方法であって、前記方法が、前記対象に薬学的に有効な量の免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を投与することを含み、前記ＩＬＴ７結合タンパク質の前記薬学的に有効な量が、約５０ｍｇである、方法。
[本発明１０５０]
それを必要としている対象の組織中の形質細胞様樹状細胞（ｐＤＣ）を減少させる方法であって、前記方法が、前記対象に薬学的に有効な量の免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を投与することを含み、前記ＩＬＴ７結合タンパク質の前記薬学的に有効な量が、約１５０ｍｇである、方法。
[本発明１０５１]
前記ベースライン値と比較した前記組織中のｐＤＣの前記低下が、約１％～約９９％の範囲である、本発明１０４９又は１０５０の方法。
[本発明１０５２]
前記ベースライン値と比較した前記組織中のｐＤＣの前記低下が、少なくとも約５０％である、本発明１０４９又は１０５０の方法。
[本発明１０５３]
前記対象が、前記ＩＬＴ７結合タンパク質の投与前に高値の血中Ｉ型ＩＦＮＧＳレベルを有する、本発明１００１～１０５２のいずれかの方法。
[本発明１０５４]
前記対象が、前記ＩＬＴ７結合タンパク質の投与前に高値の組織生検材料中ｐＤＣレベルを有する、本発明１００１～１０５３のいずれかの方法。
[本発明１０５５]
前記自己免疫疾患が、全身性エリテマトーデス（ＳＬＥ）、ループス腎炎、皮膚エリテマトーデス（ＣＬＥ）、シェーグレン症候群、炎症性筋炎、例えば、皮膚筋炎、封入体筋炎、若年性筋炎及び多発性筋炎など、全身性硬化症、糖尿病、橋本病、自己免疫性副腎不全、赤芽球ろう、多発性硬化症、リウマチ性心炎、乾癬、乾癬性関節炎、関節リウマチ、慢性炎症、慢性リウマチ、白斑、円形脱毛症、化膿性汗腺炎、セリアック病、急性及び慢性移植片対宿主病（ＧＶＨＤ）、血管炎症、心筋梗塞、並びに１型インターフェロン症である、本発明１０４４～１０５４のいずれかの方法。
[本発明１０５６]
前記自己免疫疾患が、ＳＬＥである、本発明１０５５の方法。
[本発明１０５７]
前記自己免疫疾患が、ＣＬＥである、本発明１０５５の方法。
[本発明１０５８]
前記自己免疫疾患が、ループスである、本発明１０４４～１０５４のいずれかの方法。
[本発明１０５９]
前記対象が、円板状エリテマトーデス（ＤＬＥ）を有しない、本発明１０５６～１０５８のいずれかの方法。
[本発明１０６０]
患者をＩＬＴ７結合タンパク質による治療用に選択するための方法であって、
（ｉ）前記患者のベースライン血中Ｉ型ＩＦＮＧＳレベルを決定すること、及び
（ｉｉ）ベースライン血中Ｉ型ＩＦＮＧＳレベルが高値の患者を、前記ＩＬＴ７結合タンパク質による治療用に選択すること
を含む、方法。
[本発明１０６１]
それを必要としている対象の自己免疫障害を治療する方法であって、前記方法が、前記対象に薬学的に有効な量の免疫グロブリン様転写物７（ＩＬＴ７）結合タンパク質を投与することを含み、前記対象が、前記ＩＬＴ７結合タンパク質の投与前に高値の血中Ｉ型ＩＦＮＧＳレベルを有すると決定される、方法。
[本発明１０６２]
前記ＩＬＴ７結合タンパク質が、配列番号３、４、５、６、７、及び８のアミノ酸配列をそれぞれ含む、重鎖相補性決定領域（ＨＣＤＲ）ＨＣＤＲ１、ＨＤＲ２、ＨＣＤＲ３並びに軽鎖相補性決定領域（ＬＣＤＲ）ＬＣＤＲ１、ＬＣＤＲ２、及びＬＣＤＲ３を含む抗体である、本発明１０４４～１０６１のいずれかの方法。
[本発明１０６３]
前記ＩＬＴ７結合タンパク質が、配列番号１と少なくとも８５％、９０％、９５％、９６％、９７％、９８％又は９９％同一の可変重鎖（ＶＨ）及び／又は配列番号２と少なくとも８５％、９０％、９５％、９６％、９７％、９８％又は９９％同一の可変軽鎖（ＶＬ）を含む抗体である、本発明１０４４～１０６２のいずれかの方法。
[本発明１０６４]
前記ＩＬＴ７結合タンパク質が、配列番号１の重鎖可変領域（ＶＨ）及び配列番号２の軽鎖可変領域（ＶＬ）を含む抗体である、本発明１０４４～１０６３のいずれかの方法。
[本発明１０６５]
前記抗体がアフコシル化されている、本発明１０６０～１０６４のいずれかの方法。
In certain embodiments, the methods of the present disclosure relate to treating an autoimmune disorder in a subject in need thereof, the methods comprising administering to the subject a pharmaceutically effective amount of immunoglobulin-like transcript 7 (ILT7). administering a binding protein, wherein the subject is determined to have elevated blood type I IFNGS levels prior to administration of the ILT7 binding protein. In some embodiments, the ILT7 binding protein comprises heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3 and light chain complementarity determining regions (HCDRs) comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. An antibody containing sex determining regions (LCDRs) LCDR1, LCDR2, and LCDR3. In some embodiments, the ILT7 binding protein has a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 1 and/or SEQ ID NO: 2. An antibody comprising a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to. In certain embodiments, the ILT7 binding protein is an antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2. In some embodiments, the antibody is afucosylated.
[Present invention 1001]
A method for reducing a type I interferon gene signature (IFNGS) in a subject in need thereof, said method comprising administering to said subject a pharmaceutically effective amount of immunoglobulin-like transcript 7 (ILT7) binding protein. wherein the ILT7 binding protein is administered to the subject when the type I IFNGS of the subject is elevated compared to the type I IFNGS of a normal subject.
[Present invention 1002]
The type I IFNGS is measured in a test biological sample collected from the subject, and the test sample is blood, sputum, saliva, skin cells, skin biopsy sample, kidney cells, lung cells, hepatocytes, heart cells, The method of the invention 1001, wherein the cell is selected from the group consisting of brain cells, neural tissue, thyroid cells, eye cells, skeletal muscle cells, cartilage, bone tissue, and cultured cells.
[Present invention 1003]
1002. The method of the invention 1002, wherein the test biological sample is blood, skin cells, or a skin biopsy sample.
[Present invention 1004]
The method of any preceding invention, wherein the type I IFNGS is elevated in the test biological sample by at least about 4 times as compared to a normal biological sample.
[Present invention 1005]
Any method of the preceding invention, wherein the type I IFNGS comprises collective expression levels of two or more type I interferon (IFN)-inducible genes.
[Present invention 1006]
The two or more type I interferon (IFN)-induced genes are SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, The method of the invention 1005, selected from the group consisting of RSAD2, RTP4, SIGLEC1, and USP18.
[Present invention 1007]
The type I IFNGS is SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, All of SIGLEC1 and USP18 1005. The method of the invention 1005, comprising the collective expression level of.
[Present invention 1008]
1005. The method of the invention 1005, wherein said type I IFNGS is determined by assaying mRNA levels of said two or more type I interferon (IFN)-inducible genes in said test biological sample.
[Present invention 1009]
1007. The method of the invention 1007, wherein said type I IFNGS is determined by assaying mRNA levels of 21 type I interferon (IFN)-inducible genes in said test biological sample.
[Present invention 1010]
The method of any preceding invention, wherein administering said ILT7 binding protein results in a decrease in plasmacytoid dendritic cells (pDC) in said subject.
[Present invention 1011]
The method of the invention 1010, wherein the pDCs are circulating pDCs.
[Present invention 1012]
The method of invention 1010 or 1011, wherein said reduction of said pDCs is reversible.
[Present invention 1013]
The method of any preceding invention, wherein an autoimmune disease in said subject is treated by reducing said type I IFNGS.
[Present invention 1014]
The autoimmune disease may include systemic lupus erythematosus (SLE), lupus nephritis, cutaneous lupus erythematosus (CLE), Sjögren's syndrome, inflammatory myositis, such as dermatomyositis, inclusion body myositis, juvenile myositis, and polymyositis, systemic sclerosis. disease, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, erythroblastic fistula, multiple sclerosis, rheumatic carditis, psoriasis, psoriatic arthritis, rheumatoid arthritis, chronic inflammation, chronic rheumatoid arthritis, vitiligo, alopecia areata, suppuration The method of the invention 1013 is selected from the group consisting of hidradenitis, celiac disease, acute and chronic graft-versus-host disease (GVHD), vascular inflammation, myocardial infarction, and type 1 interferonosis.
[Present invention 1015]
1014. The method of the invention 1014, wherein the autoimmune disease is SLE or CLE.
[Present invention 1016]
1014. The method of the invention 1014, wherein the autoimmune disease is Sjögren's syndrome.
[Present invention 1017]
1014. The method of invention 1014, wherein said autoimmune disease is dermatomyositis.
[This invention 1018]
1014. The method of the invention 1014, wherein the autoimmune disease is polymyositis.
[This invention 1019]
1014. The method of the invention 1014, wherein the autoimmune disease is systemic sclerosis.
[This invention 1020]
1014. The method of the invention 1014, wherein the autoimmune disease is hidradenitis suppurativa.
[Present invention 1021]
1014. The method of the invention 1014, wherein the autoimmune disease is vitiligo.
[Present invention 1022]
The ILT7 binding protein comprises heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3 and light chain complementarity determining regions (LCDRs) comprising amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. ) The method of any of the preceding inventions is an antibody comprising LCDR1, LCDR2, and LCDR3.
[Present invention 1023]
the ILT7 binding protein has a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 1 and/or at least 85% identical to SEQ ID NO: 2; The method of any of the preceding inventions, wherein the antibody comprises variable light chains (VL) that are 90%, 95%, 96%, 97%, 98% or 99% identical.
[Present invention 1024]
Any method of the preceding invention, wherein the ILT7 binding protein is an antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2.
[Present invention 1025]
The method of any of inventions 1022-1024, wherein said antibody is afucosylated.
[Present invention 1026]
The method of any preceding invention, wherein said pharmaceutically effective amount of said ILT7 binding protein ranges from about 0.1 mg to about 1000 mg.
[Invention 1027]
1026. The method of the invention 1026, wherein the pharmaceutically effective amount of the ILT7 binding protein is about 1 mg, about 5 mg, about 15 mg, about 50 mg, about 100 mg, or about 150 mg.
[Invention 1028]
The method of any preceding invention, wherein said ILT7 binding protein is administered by subcutaneous injection.
[Invention 1029]
The method of any preceding invention, wherein administering the ILT7 binding protein leads to a decrease in the Type I IFNGS of the subject by at least about 50% compared to the Type I IFNGS before administration of the ILT7 binding protein. .
[This invention 1030]
The method of any preceding invention, wherein said ILT7 binding protein induces antibody-dependent cell-mediated cytotoxicity (ADCC) activity against pDCs.
[Present invention 1031]
The method of any of the inventions 1001 to 1029, wherein the ILT7 binding protein suppresses the release of type I interferon (IFN) from pDCs.
[Present invention 1032]
1032. The method of the invention 1031, wherein the type I IFN is IFNα.
[Present invention 1033]
The method according to any one of the present inventions 1001 to 1032, wherein the ILT7 binding protein specifically binds to ILT7.
[Present invention 1034]
1033. The method of the invention 1033, wherein said ILT7 is on a pDC.
[Present invention 1035]
1. A method of monitoring the effectiveness of treatment of a condition characterized by activated plasmacytoid dendritic cells (pDCs) in a subject, the method comprising:
(a) measuring type I IFNGS in a biological sample collected from the subject to obtain a baseline value of type I interferon gene signature (IFNGS); and
(b) measuring the type I IFNGS in a biological sample collected from the subject after administering a treatment, the treatment comprising administering to the subject an immunoglobulin-like transcript 7 (ILT7) binding protein; steps, including doing
including methods.
[Present invention 1036]
A method for reducing plasmacytoid dendritic cells (pDC) in a tissue of a subject in need thereof, the method comprising administering to said subject a pharmaceutically effective amount of immunoglobulin-like transcript 7 (ILT7) binding protein. A method including:
[Present invention 1037]
The tissue consists of skin cells, skin biopsy samples, kidney cells, lung cells, liver cells, heart cells, brain cells, nerve tissue, thyroid cells, eye cells, skeletal muscle cells, cartilage, bone tissue, and airway cells. 1036. A method of the invention 1036 selected from the group.
[Present invention 1038]
1037. The method of invention 1037, wherein the tissue is a skin cell.
[Present invention 1039]
1037. The method of the invention 1037, wherein the tissue is a skin biopsy sample.
[Present invention 1040]
1039. The method of any of the inventions 1036-1039, which results in a decrease in pDCs in said tissue compared to baseline values.
[Present invention 1041]
1040. The method of the invention 1040, wherein the reduction in pDCs in the tissue compared to the baseline value ranges from about 1% to about 99%.
[Present invention 1042]
The method of the invention 1040 or 1041, wherein the reduction in pDCs in the tissue compared to the baseline value is at least about 50%.
[Present invention 1043]
The ILT7 binding protein comprises heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3 and light chain complementarity determining regions (LCDRs) comprising amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. ) The method according to any one of the present invention 1036 to 1042, which is an antibody comprising LCDR1, LCDR2, and LCDR3.
[Present invention 1044]
A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutically effective amount of immunoglobulin-like transcript 7 (ILT7) binding protein; The method, wherein the pharmaceutically effective amount of the ILT7 binding protein is about 1 mg, about 5 mg, about 15 mg, about 50 mg, about 100 mg, or about 150 mg.
[Present invention 1045]
The method of any of the inventions 1001-1034 or 1044, wherein the pharmaceutically effective amount of the ILT7 binding protein is about 50 mg.
[Present invention 1046]
The method of any of the inventions 1001-1034 or 1044, wherein the pharmaceutically effective amount of the ILT7 binding protein is about 150 mg.
[Present invention 1047]
A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutically effective amount of immunoglobulin-like transcript 7 (ILT7) binding protein; The method, wherein the pharmaceutically effective amount of the ILT7 binding protein is about 50 mg.
[Present invention 1048]
A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutically effective amount of immunoglobulin-like transcript 7 (ILT7) binding protein; The method, wherein the pharmaceutically effective amount of the ILT7 binding protein is about 150 mg.
[Present invention 1049]
A method of reducing plasmacytoid dendritic cells (pDC) in a tissue of a subject in need thereof, the method comprising: providing a pharmaceutically effective amount of immunoglobulin-like transcript 7 (ILT7) to said subject. administering a binding protein, wherein the pharmaceutically effective amount of the ILT7 binding protein is about 50 mg.
[This invention 1050]
A method of reducing plasmacytoid dendritic cells (pDC) in a tissue of a subject in need thereof, the method comprising: providing a pharmaceutically effective amount of immunoglobulin-like transcript 7 (ILT7) to said subject. administering a binding protein, wherein the pharmaceutically effective amount of the ILT7 binding protein is about 150 mg.
[Present invention 1051]
The method of invention 1049 or 1050, wherein said reduction in pDCs in said tissue compared to said baseline value ranges from about 1% to about 99%.
[Present invention 1052]
The method of the invention 1049 or 1050, wherein the reduction in pDCs in the tissue compared to the baseline value is at least about 50%.
[Present invention 1053]
The method of any of the inventions 1001-1052, wherein the subject has elevated blood type I IFNGS levels prior to administration of the ILT7 binding protein.
[Present invention 1054]
The method of any of the inventions 1001-1053, wherein said subject has elevated pDC levels in a tissue biopsy prior to administration of said ILT7 binding protein.
[Present invention 1055]
The autoimmune disease may include systemic lupus erythematosus (SLE), lupus nephritis, cutaneous lupus erythematosus (CLE), Sjögren's syndrome, inflammatory myositis, such as dermatomyositis, inclusion body myositis, juvenile myositis, and polymyositis, systemic sclerosis. disease, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, erythroblastic fistula, multiple sclerosis, rheumatic carditis, psoriasis, psoriatic arthritis, rheumatoid arthritis, chronic inflammation, chronic rheumatoid arthritis, vitiligo, alopecia areata, suppuration The method of any of the invention 1044-1054, which is hidradenitis, celiac disease, acute and chronic graft-versus-host disease (GVHD), vascular inflammation, myocardial infarction, and type 1 interferonosis.
[Present invention 1056]
1055. The method of the invention 1055, wherein the autoimmune disease is SLE.
[Present invention 1057]
1055. The method of the invention 1055, wherein the autoimmune disease is CLE.
[Present invention 1058]
The method according to any one of Inventions 1044 to 1054, wherein the autoimmune disease is lupus.
[Present invention 1059]
The method of any of inventions 1056-1058, wherein said subject does not have discoid lupus erythematosus (DLE).
[Present invention 1060]
1. A method for selecting a patient for treatment with an ILT7 binding protein, the method comprising:
(i) determining the patient's baseline blood type I IFNGS level; and
(ii) selecting patients with high baseline blood type I IFNGS levels for treatment with said ILT7 binding protein;
including methods.
[Present invention 1061]
A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutically effective amount of immunoglobulin-like transcript 7 (ILT7) binding protein; The method, wherein the subject is determined to have elevated blood type I IFNGS levels prior to administration of the ILT7 binding protein.
[Present invention 1062]
The ILT7 binding protein comprises heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3 and light chain complementarity determining regions (LCDRs) comprising amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. ) The method according to any one of the present invention 1044 to 1061, which is an antibody comprising LCDR1, LCDR2, and LCDR3.
[Present invention 1063]
the ILT7 binding protein has a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 1 and/or at least 85% identical to SEQ ID NO: 2; The method of any of the inventions 1044-1062, wherein the antibody comprises variable light chains (VL) that are 90%, 95%, 96%, 97%, 98% or 99% identical.
[Present invention 1064]
The method according to any of the inventions 1044 to 1063, wherein the ILT7 binding protein is an antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2.
[Present invention 1065]
The method of any of inventions 1060-1064, wherein said antibody is afucosylated.
Claims (20)
ｉ．形質細胞様樹状細胞（ｐＤＣ）；
ｉｉ．Ｉ型ＩＦＮＧＳ；および／または
ｉｉｉ．前記ｐＤＣおよび前記Ｉ型ＩＦＮＧＳ。 The pharmaceutical composition of claim 1 , wherein said administration is effective to reduce the level of :
i. Plasmacytoid dendritic cells (pDC);
ii. type I IFNGS; and/or
iii. The pDC and the type I IFNGS .
Applications Claiming Priority (11)
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| US201962944845P | 2019-12-06 | 2019-12-06 | |
| US62/944,845 | 2019-12-06 | ||
| US202063023820P | 2020-05-12 | 2020-05-12 | |
| US63/023,820 | 2020-05-12 | ||
| US202063024182P | 2020-05-13 | 2020-05-13 | |
| US63/024,182 | 2020-05-13 | ||
| US202063083649P | 2020-09-25 | 2020-09-25 | |
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| US202063109923P | 2020-11-05 | 2020-11-05 | |
| US63/109,923 | 2020-11-05 | ||
| PCT/US2020/063396 WO2021113702A1 (en) | 2019-12-06 | 2020-12-04 | Methods of treatment using ilt7 binding proteins |
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| JP2023505203A JP2023505203A (en) | 2023-02-08 |
| JPWO2021113702A5 true JPWO2021113702A5 (en) | 2023-12-11 |
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| US (1) | US20220403020A1 (en) |
| EP (1) | EP4069288A4 (en) |
| JP (1) | JP2023505203A (en) |
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| CN (1) | CN115135337A (en) |
| AU (1) | AU2020395232A1 (en) |
| BR (1) | BR112022010786A2 (en) |
| CA (1) | CA3159511A1 (en) |
| IL (1) | IL293572A (en) |
| MX (1) | MX2022006689A (en) |
| WO (1) | WO2021113702A1 (en) |
Families Citing this family (3)
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| CA3017197A1 (en) | 2016-03-10 | 2017-09-14 | Viela Bio, Inc. | Ilt7 binding molecules and methods of using the same |
| EP4333877A1 (en) | 2021-05-04 | 2024-03-13 | Viela Bio, Inc. | Methods of treatment of autoimmune disorders using ilt7 binding proteins |
| WO2024026388A1 (en) | 2022-07-27 | 2024-02-01 | Viela Bio, Inc. | Formulations comprising an immunoglobulin-like transcript 7 (ilt7)-binding protein |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030148316A1 (en) * | 2001-08-01 | 2003-08-07 | Lipford Grayson B. | Methods and compositions relating to plasmacytoid dendritic cells |
| SG170749A1 (en) * | 2005-12-20 | 2011-05-30 | Sbi Biotech Co Ltd | Anti-ilt7 antibody |
| US20110311558A1 (en) * | 2008-12-01 | 2011-12-22 | The Board Of Regents Of The University Of Texas System | Recombinant Bone Marrow Stromal Antigen-2 in the Treatment of Autoimmune Diseases |
| AR086074A1 (en) * | 2011-04-26 | 2013-11-13 | Genentech Inc | COMPOSITIONS AND METHOD TO TREAT AUTOIMMUNE DISEASES |
| CA3017197A1 (en) * | 2016-03-10 | 2017-09-14 | Viela Bio, Inc. | Ilt7 binding molecules and methods of using the same |
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2020
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- 2020-12-04 AU AU2020395232A patent/AU2020395232A1/en active Pending
- 2020-12-04 MX MX2022006689A patent/MX2022006689A/en unknown
- 2020-12-04 CA CA3159511A patent/CA3159511A1/en active Pending
- 2020-12-04 EP EP20895720.9A patent/EP4069288A4/en active Pending
- 2020-12-04 CN CN202080095832.XA patent/CN115135337A/en active Pending
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- 2020-12-04 JP JP2022533368A patent/JP2023505203A/en active Pending
- 2020-12-04 WO PCT/US2020/063396 patent/WO2021113702A1/en unknown
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2022
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