JPWO2019165140A5 - - Google Patents

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JPWO2019165140A5
JPWO2019165140A5 JP2020543145A JP2020543145A JPWO2019165140A5 JP WO2019165140 A5 JPWO2019165140 A5 JP WO2019165140A5 JP 2020543145 A JP2020543145 A JP 2020543145A JP 2020543145 A JP2020543145 A JP 2020543145A JP WO2019165140 A5 JPWO2019165140 A5 JP WO2019165140A5
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Priority claimed from PCT/US2019/019042 external-priority patent/WO2019165140A1/en
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ＩＬ－２２Ｆｃ融合タンパク質を含む、炎症性腸疾患（ｉｎｆｌａｍｍａｔｏｒｙ ｂｏｗｅｌ ｄｉｓｅａｓｅ：ＩＢＤ）を有する対象を治療するための医薬であって、少なくとも第１の投与サイクルを含む投与計画において、ＩＬ－２２Ｆｃ融合タンパク質が投与され、第１の投与サイクルが、２～１０回の投与を含み、合計約６０μｇ／ｋｇ～約９００μｇ／ｋｇのＩＬ－２２Ｆｃ融合タンパク質が、第１の投与サイクルで対象に投与される、医薬。 A drug for treating a subject with inflammatory bowel disease (IBD), which comprises an IL - 22Fc fusion protein, wherein the IL-22Fc fusion protein is used in a dosing regimen comprising at least the first dosing cycle. Administered, the first dosing cycle comprises 2-10 doses, with a total of about 60 μg / kg to about 900 μg / kg of IL- 22Fc fusion protein administered to the subject in the first dosing cycle. , Medicine . 投与が、毎週（ｑ１ｗ）、２週間毎（ｑ２ｗ）、４週間毎（ｑ４ｗ）、又は６週間毎（ｑ６ｗ）に対象へ投与される、請求項１に記載の医薬。 The medicine according to claim 1, wherein the administration is administered to the subject every week (q1w), every two weeks (q2w), every four weeks (q4w), or every six weeks (q6w). 合計約９０μｇ／ｋｇ、約１８０μｇ／ｋｇ、約２７０μｇ／ｋｇ、約３６０μｇ／ｋｇ、又は約５４０μｇ／ｋｇのＩＬ－２２Ｆｃ融合タンパク質が、第１の投与サイクルで対象へ投与される、請求項１又は２に記載の医薬。 Claim that a total of about 90 μg / kg, about 180 μg / kg, about 270 μg / kg, about 360 μg / kg, or about 540 μg / kg of IL- 22Fc fusion protein is administered to the subject in the first dosing cycle. The medicine according to 1 or 2. 第１の投与サイクルの長さが、約５週間～約１５週間である、請求項１～３のいずれか一項に記載の医薬。 The medicine according to any one of claims 1 to 3, wherein the length of the first administration cycle is about 5 weeks to about 15 weeks. 第１の投与サイクルの長さが、約８週間である、請求項４に記載の医薬。 The medicine according to claim 4, wherein the length of the first administration cycle is about 8 weeks. 第１の投与サイクルが、ＩＬ－２２Ｆｃ融合タンパク質の第１の投与（Ｃ１Ｄ１）、第２の投与（Ｃ１Ｄ２）、及び第３の投与（Ｃ１Ｄ３）を含む、請求項１～５のいずれか一項に記載の医薬。 One of claims 1-5, wherein the first dosing cycle comprises a first dosing (C1D1), a second dosing (C1D2), and a third dosing ( C1D3 ) of the IL-22Fc fusion protein. The drug described in the section. 第１の投与サイクルが、Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ３からなる、請求項６に記載の医薬。 The medicine according to claim 6, wherein the first dosing cycle comprises C 1D1, C 1D2, and C 1D3. Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ３が、それぞれ約１５μｇ／ｋｇ～約９０μｇ／ｋｇである、請求項６又は７に記載の医薬。 The medicine according to claim 6 or 7, wherein C 1D1, C 1D2, and C 1D3 are about 15 μg / kg to about 90 μg / kg, respectively. Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ３が、それぞれ約３０μｇ／ｋｇである、請求項８に記載の医薬。 The medicine according to claim 8, wherein C 1D1, C 1D2, and C 1D3 are each about 30 μg / kg. Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ３が、それぞれ約６０μｇ／ｋｇである、請求項８に記載の医薬。 The medicine according to claim 8, wherein C 1D1, C 1D2, and C 1D3 are each about 60 μg / kg. Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ３が、それぞれ約９０μｇ／ｋｇである、請求項８に記載の医薬。 The medicine according to claim 8, wherein C 1D1, C 1D2, and C 1D3 are each about 90 μg / kg. Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ３が、第１の投与サイクルの、それぞれ１週目、４週目、及び８週目に、又は約１週目、約４週目、及び約８週目に投与される、請求項６～１１のいずれか一項に記載の医薬。 C 1D1, C 1D2, and C 1D3 are at week 1, 4, and 8, respectively, or about week 1, about 4, and about 8 of the first dosing cycle. The medicine according to any one of claims 6 to 11, which is administered. 投与計画が、第２の投与サイクルを更に含む、請求項１～１２のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 1 to 12, wherein the dosing regimen further comprises a second dosing cycle. 第２の投与サイクルの長さが、約１０週間～約４０週間である、請求項１３に記載の医薬。 13. The apparatus of claim 13, wherein the length of the second dosing cycle is from about 10 weeks to about 40 weeks. 第２の投与サイクルが、無期限に続く、又は臨床的寛解まで続く、請求項１３に記載の医薬。 13. The apparatus of claim 13, wherein the second dosing cycle lasts indefinitely or continues to clinical remission . 第２の投与サイクルが、臨床的寛解後に停止され、次いでＩＢＤの再発後に再開される、請求項１５に記載の医薬。 15. The apparatus of claim 15, wherein the second dosing cycle is stopped after clinical remission and then resumed after a recurrence of IBD . 第２の投与サイクルの投与が、毎週（ｑ１ｗ）、２週間毎（ｑ２ｗ）、４週間毎（ｑ４ｗ）、６週間毎（ｑ６ｗ）、８週間毎（ｑ８ｗ）、１０週間毎（ｑ１０ｗ）、又は１２週間毎（ｑ１２ｗ）に対象へ投与される、請求項１３～１６のいずれか一項に記載の医薬。 The administration of the second administration cycle is weekly (q1w), every 2 weeks (q2w), every 4 weeks (q4w), every 6 weeks (q6w), every 8 weeks (q8w), every 10 weeks (q10w), The medicine according to any one of claims 13 to 16, which is administered to the subject every 12 weeks (q12w). 第２の投与サイクルの投与が、８週間毎（ｑ８ｗ）に対象へ投与される、請求項１７に記載の医薬。 17. The apparatus of claim 17, wherein the administration of the second dosing cycle is administered to the subject every 8 weeks ( q8w ). 第２の投与サイクルの各投与が、約３０μｇ／ｋｇ～約９０μｇ／ｋｇである、請求項１３～１８のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 13 to 18, wherein each dose in the second dosing cycle is from about 30 μg / kg to about 90 μg / kg. 第２の投与サイクルの各投与が、約６０μｇ／ｋｇである、請求項１９に記載の医薬。 29. The pharmaceutical according to claim 19, wherein each dose in the second dosing cycle is about 60 μg / kg. 第２の投与サイクルの第１の投与が、第１の投与サイクルの最後の投与から約６週間後～約１０週間後に対象へ投与される、請求項１３～２０のいずれか一項に記載の医薬。 13 . _ _ Medicine . 第２の投与サイクルの第１の投与が、第１の投与サイクルの最後の投与から約７週間後～約９週間後に対象へ投与される、請求項２１に記載の医薬。 21. The apparatus of claim 21, wherein the first dose of the second dosing cycle is administered to the subject about 7 to about 9 weeks after the last dose of the first dosing cycle. 第２の投与サイクルの第１の投与が、第１の投与サイクルの最後の投与から約８週間後に対象へ投与される、請求項２２に記載の医薬。 22. The apparatus of claim 22, wherein the first dose of the second dosing cycle is administered to the subject approximately 8 weeks after the last dose of the first dosing cycle. ＩＢＤを有する対象を治療するための医薬であって、投与計画において、対象がＩＢＤの臨床的寛解となるまで、ＩＬ－２２Ｆｃ融合タンパク質が４週間毎（ｑ４ｗ）で対象へ投与される、医薬。 A drug for treating a subject with IBD, wherein the IL-22Fc fusion protein is administered to the subject every 4 weeks ( q4w ) until the subject is in clinical remission of IBD in a dosing regimen. 投与計画の各投与が、約１５μｇ／ｋｇ～約９０μｇ／ｋｇである、請求項２４に記載の医薬。 24. The apparatus of claim 24, wherein each dose in the dosing regimen is from about 15 μg / kg to about 90 μg / kg. 投与計画の各投与が、約６０μｇ／ｋｇである、請求項２５に記載の医薬。 25. The apparatus of claim 25, wherein each dose in the dosing regimen is about 60 μg / kg. ＩＬ－２２Ｆｃ融合タンパク質を含む、ＩＢＤを有する対象を治療するための医薬であって、
約８週の長さである投与サイクルを含む投与計画において、ＩＬ－２２Ｆｃ融合タンパク質が対象へ投与され、投与サイクルは、ＩＬ－２２Ｆｃ融合タンパク質の第１の投与（Ｃ１Ｄ１）、第２の投与（Ｃ１Ｄ２）、及び第３の投与（Ｃ１Ｄ３）を含み、Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ３は、それぞれ、約３０μｇ／ｋｇ、約６０μｇ／ｋｇ、又は約９０μｇ／ｋｇであり、Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ３は、投与サイクルの、それぞれ１週目、４週目、及び８週目に、又は約１週目、約４週目、及び約８週目に対象へ投与される、医薬。 A drug for treating a subject with IBD, which comprises an IL-22Fc fusion protein .
In a dosing regimen that includes a dosing cycle that is approximately 8 weeks long, the IL-22Fc fusion protein is administered to the subject and the dosing cycle is the first dose ( C1D1 ), second dose of the IL-22Fc fusion protein. C 1D1, C 1D2, and C 1D3 are about 30 μg / kg, about 60 μg / kg, or about 90 μg / kg, respectively, including the administration of (C1D2) and the third administration ( C1D3 ). , C 1D2, and C 1D3 are administered to the subject at week 1, 4, and 8, respectively, or about week 1, about 4, and about 8 of the dosing cycle. , Medicine . ＩＬ－２２Ｆｃ融合タンパク質を含む、ＩＢＤを有する対象を治療するための医薬であって、
少なくとも第１の投与サイクル及び第２の投与サイクルを含む投薬計画において、ＩＬ－２２Ｆｃ融合タンパク質が対象へ投与され、
（ａ）第１の投与サイクルは、約８週の長さであり、ＩＬ－２２Ｆｃ融合タンパク質の第１の投与（Ｃ１Ｄ１）、第２の投与（Ｃ１Ｄ２）、及び第３の投与（Ｃ１Ｄ３）を含み、ここで、Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ３は、それぞれ、約３０μｇ／ｋｇ、約６０μｇ／ｋｇ、又は約９０μｇ／ｋｇであり、Ｃ１Ｄ１、Ｃ１Ｄ２、及びＣ１Ｄ２は、第１の投与サイクルの、それぞれ１週目、４週目、及び８週目に、又は約１週目、約４週目、及び約８週目に対象へ投与され、
（ｂ）第２の投与サイクルは、無期限に続くか、又は臨床的寛解まで続き、約６０μｇ／ｋｇのＩＬ－２２Ｆｃ融合タンパク質を対象へ８週間毎（ｑ８ｗ）に投与することを含み、ここで、第２の投与サイクルの第１の投与が、第１の投与サイクルの最後の投与から約８週間後に対象へ投与される、医薬。 A drug for treating a subject with IBD, which comprises an IL-22Fc fusion protein .
The IL-22Fc fusion protein is administered to the subject in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle.
(A) The first dosing cycle is approximately 8 weeks long, with a first dosing (C1D1), a second dosing (C1D2), and a third dosing ( C1D3 ) of the IL-22Fc fusion protein. Here, C 1D1, C 1D2, and C 1D3 are about 30 μg / kg, about 60 μg / kg, or about 90 μg / kg, respectively, and C 1D1, C 1D2, and C 1D2 are the first. Is administered to the subject at the 1st, 4th, and 8th weeks, or about the 1st, 4th, and 8th weeks of the dosing cycle, respectively.
(B) The second dosing cycle comprises indefinitely or until clinical remission and administration of approximately 60 μg / kg IL- 22Fc fusion protein to the subject every 8 weeks (q8w). Where the first dose of the second dosing cycle is administered to the subject approximately 8 weeks after the last dosing of the first dosing cycle. （ｉ）治療がＩＢＤの１つ以上の症状を回復させる、及び／又は治療が臨床的寛解をもたらす、請求項１～２８のいずれか一項に記載の医薬。 ( I ) The pharmaceutical according to any one of claims 1-28, wherein the treatment relieves one or more symptoms of IBD and / or the treatment results in clinical remission. ＩＢＤの１つ以上の症状が、排便回数、直腸出血、又は粘膜外観を含む、請求項２９に記載の医薬。 I. The pharmaceutical according to claim 29, wherein one or more symptoms of BD include defecation frequency, rectal bleeding, or mucosal appearance. 臨床的寛解が、修正Ｍａｙｏ臨床的スコア（Ｍａｙｏ Ｃｌｉｎｉｃ Ｓｃｏｒｅ：ＭＣＳ）約２点以下、及びＭａｙｏ直腸出血サブスコア０点、並びに他のＭａｙｏサブスコア約１点以下である、請求項２９に記載の医薬。 The pharmaceutical according to claim 29, wherein the clinical remission is a modified Mayo clinical score (MCS) of about 2 points or less, a Mayo rectal bleeding subscore of 0 points, and another Mayo subscore of about 1 point or less. .. 臨床的寛解が、持続的寛解である、請求項２９又は３１に記載の医薬。 The pharmaceutical according to claim 29 or 31, wherein the clinical remission is a sustained remission. 治療が、（ｉ）臨床反応、（ｉｉ）内視鏡的治癒、（ｉｉｉ）内視鏡的寛解、（ｉｖ）潰瘍性大腸炎患者報告アウトカム徴候及び症状（Ｕｌｃｅｒａｔｉｖｅ Ｃｏｌｉｔｉｓ Ｐａｔｉｅｎｔ－Ｒｅｐｏｒｔｅｄ Ｏｕｔｃｏｍｅ Ｓｉｇｎｓ ａｎｄ Ｓｙｍｐｔｏｍｓ：ＵＣ－ＰＲＯ／ＳＳ）スコアによって評価された、対象の腸管運動の徴候及び症状におけるベースラインからの変化、（ｖ）ＵＣ－ＰＲＯ／ＳＳスコアによって評価された、対象の腹部徴候及び症状におけるベースラインからの変化、（ｖｉ）炎症性腸疾患質問票（Ｉｎｆｌａｍｍａｔｏｒｙ Ｂｏｗｅｌ Ｄｉｓｅａｓｅ Ｑｕｅｓｔｉｏｎｎａｉｒｅ：ＩＢＤＱ）スコアによって評価された、対象の患者報告による健康関連の生活の質（ｑｕａｌｉｔｙ ｏｆ ｌｉｆｅ：ＱＯＬ）、（ｖｉｉ）粘膜治癒、（ｖｉｉｉ）対象のＵＣ内視鏡重症度指数（ＵＣ Ｅｎｄｏｓｃｏｐｉｃ Ｉｎｄｅｘ ｏｆ Ｓｅｖｅｒｉｔｙ）におけるベースラインからの変化、及び／又は（ｉｘ）組織学的治癒をもたらす、請求項１～３２のいずれか一項に記載の医薬。 Treatment includes (i) clinical response, (ii) endoscopic cure, (iii) endoscopic remission, (iv) inflammatory bowel inflammation patient-reported outcome signs and symptoms (Ulcerative Colonitis Patient-Reported Outcome Signs and) Changes from baseline in the signs and symptoms of intestinal motility of the subject as assessed by the Symptoms (UC-PRO / SS) score, (v) Abdominal signs of the subject as assessed by the UC-PRO / SS score. And changes from baseline in symptoms, (vi) Health of life (QOL) as assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) score, according to the subject 's patient report. ), (Vii) mucosal healing, (viii) changes from baseline in the UC Endoscopic Index of Severity of the subject , and / or (ix) histological healing. The pharmaceutical agent according to any one of 1 to 32. 臨床反応が、（ｉ）ベースラインｍＭＣＳスコアに対する対象のｍＭＣＳスコアでの低減、又は（ｉｉ）ベースラインＭａｙｏ直腸出血サブスコア又はＭａｙｏ直腸出血サブスコア０若しくは１点に対する、対象のＭａｙｏ直腸出血サブスコアでの低減を含む、請求項３３に記載の医薬。 The clinical response is (i) a reduction in the subject 's mMCS score relative to the baseline mMCS score, or (ii) the subject 's Mayo rectal bleeding subscore for 0 or 1 baseline Mayo rectal bleeding subscore or Mayo rectal bleeding subscore. 33. The pharmaceutical agent according to claim 33. ＩＢＤの１つ以上の症状の回復、臨床的寛解、及び／又は臨床反応が、治療終了から少なくとも１ヶ月間維持される、請求項２９～３４のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 29 to 34, wherein recovery, clinical remission, and / or clinical response of one or more symptoms of IBD is maintained for at least one month from the end of treatment . 症状の回復、臨床的寛解、及び／又は臨床反応が、治療終了から少なくとも３ヶ月間維持される、請求項３５に記載の医薬。 35. The apparatus of claim 35, wherein symptom recovery, clinical remission , and / or clinical response is maintained for at least 3 months from the end of treatment . ＩＢＤが、潰瘍性大腸炎（ｕｌｃｅｒａｔｉｖｅ ｃｏｌｉｔｉｓ：ＵＣ）又はクローン病である、請求項１～３６のいずれか一項に記載の医薬。 The medicine according to any one of claims 1 to 36, wherein the I BD is ulcerative colitis (UC) or Crohn's disease. ＩＢＤが、ＵＣである、請求項３７に記載の医薬。 The medicine according to claim 37, wherein the I BD is UC. ＵＣが、中等度～重度のＵＣである、請求項３８に記載の医薬。 The medicine according to claim 38, wherein the UC is a moderate to severe UC. ＩＢＤが、クローン病である、請求項３７に記載の医薬。 The medicine according to claim 37, wherein I BD is Crohn's disease. 対象が、先行する免疫抑制治療に対する不充分な反応、反応の損失、又は不耐性を有した、請求項１～４０のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 1 to 40, wherein the subject has an inadequate response, loss of response, or intolerance to a preceding immunosuppressive treatment. ＩＬ－２２Ｆｃ融合タンパク質を含む、対象における移植片対宿主病（ｇｒａｆｔ ｖｅｒｓｕｓ ｈｏｓｔ ｄｉｓｅａｓｅ：ＧＶＨＤ）を治療又は予防するための医薬であって、投与サイクルを含む投与計画においてＩＬ－２２Ｆｃ融合タンパク質が対象に投与され、投与サイクルが、２～１０回の投与を含み、合計約６０μｇ／ｋｇ～約９００μｇ／ｋｇのＩＬ－２２Ｆｃ融合タンパク質が、投与サイクルで対象に投与される、医薬。 A drug for treating or preventing graft-versus-host disease (GVHD) in a subject, including the IL-22Fc fusion protein , which is targeted at the IL-22Fc fusion protein in a dosing regimen that includes a dosing cycle. A pharmaceutical , wherein the administration cycle comprises 2 to 10 doses, and a total of about 60 μg / kg to about 900 μg / kg of IL- 22Fc fusion protein is administered to the subject in the administration cycle. 投与が、毎週（ｑ１ｗ）、２週間毎（ｑ２ｗ）、４週間毎（ｑ４ｗ）、又は６週間毎（ｑ６ｗ）に対象へ投与される、請求項４２に記載の医薬。 42. The apparatus of claim 42, wherein the administration is administered to the subject weekly (q1w), every two weeks (q2w), every four weeks (q4w), or every six weeks ( q6w ). 投与が、２週間毎（ｑ２ｗ）に対象へ投与される、請求項４２又は４３に記載の医薬。 42 or 43, wherein the administration is administered to the subject every two weeks ( q2w ). 投与サイクルの第１の投与が、同種造血幹細胞移植（ａｌｌｏｇｅｎｅｉｃ ｈｅｍａｔｏｐｏｉｅｔｉｃ ｓｔｅｍ ｃｅｌｌ ｔｒａｎｓｐｌａｎｔａｔｉｏｎ：ａｌｌｏ－ＨＳＣＴ）の約３（±２）日前に、対象へ投与される、請求項４２～４４のいずれか一項に記載の医薬。 Any of claims 42-44, wherein the first dose of the dosing cycle is administered to the subject approximately 3 (± 2) days prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The medicine described in paragraph 1. 第２の投与が、ａｌｌｏ－ＨＳＣＴから、１１日目に、又は約１１日目に投与される、請求項４５に記載の医薬。 The pharmaceutical according to claim 45, wherein the second administration is administered from allo -HSCT on the 11th day or about the 11th day. 合計約４８０μｇ／ｋｇのＩＬ－２２Ｆｃ融合タンパク質が、投与サイクルで対象へ投与される、請求項４２～４６のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 42 to 46, wherein a total of about 480 μg / kg of IL- 22Fc fusion protein is administered to the subject in a dosing cycle. 投与サイクルが、ＩＬ－２２Ｆｃ融合タンパク質の第１の投与（Ｃ１Ｄ１）、第２の投与（Ｃ１Ｄ２）、第３の投与（Ｃ１Ｄ３）、第４の投与（Ｃ１Ｄ４）、第５の投与（Ｃ１Ｄ５）、第６の投与（Ｃ１Ｄ６）、第７の投与（Ｃ１Ｄ７）、及び第８の投与（Ｃ１Ｄ８）を含む、請求項４２～４７のいずれか一項に記載の医薬。 The dosing cycle consists of a first dose (C1D1), a second dose (C1D2), a third dose (C1D3), a fourth dose (C1D4), and a fifth dose ( C1D5 ) of the IL-22Fc fusion protein. ), The sixth administration (C1D6), the seventh administration (C1D7), and the eighth administration ( C1D8 ). 投与サイクルが、ＩＬ－２２Ｆｃ融合タンパク質の第１の投与（Ｃ１Ｄ１）、第２の投与（Ｃ１Ｄ２）、第３の投与（Ｃ１Ｄ３）、第４の投与（Ｃ１Ｄ４）、第５の投与（Ｃ１Ｄ５）、第６の投与（Ｃ１Ｄ６）、第７の投与（Ｃ１Ｄ７）、及び第８の投与（Ｃ１Ｄ８）からなる、請求項４８に記載の医薬。 The dosing cycle consists of a first dose (C1D1), a second dose (C1D2), a third dose (C1D3), a fourth dose (C1D4), and a fifth dose ( C1D5 ) of the IL-22Fc fusion protein. ), The sixth administration (C1D6), the seventh administration (C1D7), and the eighth administration ( C1D8 ). Ｃ１Ｄ１、Ｃ１Ｄ２、Ｃ１Ｄ３、Ｃ１Ｄ４、Ｃ１Ｄ５、Ｃ１Ｄ６、Ｃ１Ｄ７、及びＣ１Ｄ８が、それぞれ約１５μｇ／ｋｇ～約９０μｇ／ｋｇである、請求項４８又は４９に記載の医薬。 28. The pharmaceutical according to claim 48 or 49, wherein C 1D1, C 1D2, C 1D3, C 1D4, C 1D5, C 1D6, C 1D7, and C 1D8 are about 15 μg / kg to about 90 μg / kg, respectively. Ｃ１Ｄ１、Ｃ１Ｄ２、Ｃ１Ｄ３、Ｃ１Ｄ４、Ｃ１Ｄ５、Ｃ１Ｄ６、Ｃ１Ｄ７、及びＣ１Ｄ８が、それぞれ約６０μｇ／ｋｇである、請求項４８～５０のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 48 to 50, wherein C 1D1, C 1D2, C 1D3, C 1D4, C 1D5, C 1D6, C 1D7, and C 1D8 are each about 60 μg / kg. 投与サイクルの長さが、約２週間～約２０週間である、請求項４２～５１のいずれか一項に記載の医薬。 The medicine according to any one of claims 42 to 51, wherein the administration cycle has a length of about 2 weeks to about 20 weeks. 投与サイクルの長さが、約９６日間である、請求項５２に記載の医薬。 52. The apparatus of claim 52, wherein the dosing cycle has a length of about 96 days. 投与計画を含む対象におけるＧＶＨＤを治療するための医薬であって、投与計画は、対象がＧＶＨＤの臨床的寛解となるまで、ＩＬ－２２Ｆｃ融合タンパク質を２週間毎（ｑ２ｗ）に対象へ投与することを含む、医薬。 A drug for treating GVHD in a subject, including a dosing regimen, the dosing regimen is to administer the IL-22Fc fusion protein to the subject every two weeks (q2w) until the subject is in clinical remission of GVHD. Medicine , including doing. ＧＶＨＤが、慢性ＧＶＨＤ又は急性ＧＶＨＤである、請求項４２～５４のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 42 to 54, wherein the GVHD is a chronic GVHD or an acute GVHD. ＧＶＨＤが、急性ＧＶＨＤである、請求項５５に記載の医薬。 The medicine according to claim 55, wherein the GVHD is an acute GVHD. ＧＶＨＤを予防するための、請求項４２～５３、５５、又は５６のいずれか一項に記載の医薬。 The medicine according to any one of claims 42 to 53, 55, or 56 for preventing GVHD . ＩＬ－２２Ｆｃ融合タンパク質を含む、対象における急性ＧＶＨＤを予防するための医薬であって、
約９６日の長さである投与サイクルを含む投与計画においてＩＬ－２２Ｆｃ融合タンパク質が対象へ投与され、投与サイクルが、ＩＬ－２２Ｆｃ融合タンパク質の第１の投与（Ｃ１Ｄ１）、第２の投与（Ｃ１Ｄ２）、第３の投与（Ｃ１Ｄ３）、第４の投与（Ｃ１Ｄ４）、第５の投与（Ｃ１Ｄ５）、第６の投与（Ｃ１Ｄ６）、第７の投与（Ｃ１Ｄ７）、及び第８の投与（Ｃ１Ｄ８）を含み、Ｃ１Ｄ１、Ｃ１Ｄ２、Ｃ１Ｄ３、Ｃ１Ｄ４、Ｃ１Ｄ５、Ｃ１Ｄ６、Ｃ１Ｄ７、及びＣ１Ｄ８が、それぞれ約６０μｇ／ｋｇであり、Ｃ１Ｄ１が、ａｌｌｏ－ＨＳＣＴの約３（±２）日前に対象へ投与され、Ｃ１Ｄ２が、ａｌｌｏ－ＨＳＣＴから約１１日後に投与され、Ｃ１Ｄ３、Ｃ１Ｄ４、Ｃ１Ｄ５、Ｃ１Ｄ６、Ｃ１Ｄ７、及びＣ１Ｄ８が、Ｃ１Ｄ２の投与後に対象へ２週間毎（ｑ２ｗ）に投与される、医薬。 A drug for preventing acute GVHD in a subject , including the IL-22Fc fusion protein .
The IL-22Fc fusion protein is administered to the subject in a dosing regimen that includes a dosing cycle that is approximately 96 days long, with the dosing cycle being the first dose ( C1D1 ), the second dose (C1D1) of the IL-22Fc fusion protein. C1D2), 3rd administration (C1D3), 4th administration (C1D4), 5th administration (C1D5), 6th administration (C1D6), 7th administration (C1D7), and 8th administration (C1D8) ), C 1D1, C 1D2, C 1D3, C 1D4, C 1D5, C 1D6, C 1D7, and C 1D8 are each about 60 μg / kg, and C 1D1 is about 3 (±) of allo-HSCT. 2) Administered to the subject 1 day before, C1D2 administered approximately 11 days after alllo-HSCT, and C1D3, C1D4 , C1D5 , C1D6 , C1D7 , and C1D8 to the subject for 2 weeks after administration of C1D2. A drug administered every (q2w). ＧＶＨＤが、腸管ＧＶＨＤである、請求項４２～５８のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 42 to 58, wherein the GVHD is an intestinal GVHD. グレードＩＩ～ＩＶの急性ＧＶＨＤである、請求項４２～５９のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 42 to 59, which is an acute GVHD of grades II to IV. ａｌｌｏ－ＨＳＣＴから１００日後におけるグレードＩＩ～ＩＶの急性ＧＶＨＤを予防する、請求項６０に記載の医薬。 The pharmaceutical according to claim 60, which prevents grade II-IV acute GVHD 100 days after a llo-HSCT. グレードＩＩ～ＩＶの急性ＧＶＨＤが、ＭＡＧＩＣ ＧＶＨＤ標的臓器病期分類によって評価される、請求項６０又は６１に記載の医薬。 The pharmaceutical according to claim 60 or 61, wherein the grade II-IV acute GVHD is assessed by MAGIC GVHD target organ staging. 皮膚、腸管、及び肝臓のステージ１、ステージ２、ステージ３、又はステージ４である急性ＧＶＨＤの発生を低減する、請求項４２～６２のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 42 to 62, which reduces the occurrence of acute GVHD which is stage 1, stage 2, stage 3, or stage 4 of the skin , intestine, and liver. 皮膚、腸管、及び肝臓のステージ１、ステージ２、ステージ３、又はステージ４である急性ＧＶＨＤの発生が、ＭＡＧＩＣ ＧＶＨＤ標的臓器病期分類によって評価される、請求項６３に記載の医薬。 33. The apparatus of claim 63, wherein the development of acute GVHD, stage 1, stage 2, stage 3, or stage 4 of the skin , intestine, and liver is assessed by MAGIC GVHD target organ staging . グレードＩ、グレードＩＩ、グレードＩＩＩ、又はグレードＩＶである急性ＧＶＨＤの発生を低減する、請求項４２～６４のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 42 to 64, which reduces the occurrence of acute GVHD which is Grade I, Grade II, Grade III, or Grade IV. グレードＩ、グレードＩＩ、グレードＩＩＩ、又はグレードＩＶである急性ＧＶＨＤの発生が、ＭＡＧＩＣ ＧＶＨＤ標的臓器病期分類によって評価される、請求項６５に記載の医薬。 25. The apparatus of claim 65, wherein the development of acute GVHD of grade I, grade II, grade III, or grade IV is assessed by the MAGIC GVHD target organ staging . （ｉ）対象の消化管（ＧＩ）急性ＧＶＨＤ無病生存率を改善する、（ｉｉ）対象の全生存率を改善する、（ｉｉｉ）対象の無再発生存率を改善する、及び／又は（ｉｖ）対象における慢性ＧＶＨＤの発生を低減する、請求項４２～６６のいずれか一項に記載の医薬。 ( I) Improve subject gastrointestinal (GI) acute GVHD disease-free survival, (ii) improve overall subject survival, (iii) improve subject recurrence-free survival, and / or (Iv) The pharmaceutical according to any one of claims 42 to 66, which reduces the occurrence of chronic GVHD in a subject . ＩＬ－２２Ｆｃ融合タンパク質が、リンカーによってＦｃ領域と連結したＩＬ－２２ポリペプチドを含む、請求項１～６７のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 1 to 67, wherein the IL-22 Fc fusion protein comprises an IL-22 polypeptide linked to the Fc region by a linker. ＩＬ－２２ポリペプチドがグリコシル化されている、及び／又はＦｃ領域がグリコシル化されていない、請求項６８に記載の医薬。 The pharmaceutical according to claim 68, wherein the IL -22 polypeptide is glycosylated and / or the Fc region is not glycosylated. （ｉ）Ｆｃ領域のＥＵインデックスでの２９７位のアミノ酸残基が、Ｇｌｙ又はＡｌａである、及び／又は（ｉｉ）Ｆｃ領域のＥＵインデックスでの２９９位のアミノ酸残基が、Ａｌａ、Ｇｌｙ、又はＶａｌである、請求項６９に記載の医薬。 (I) The amino acid residue at position 297 in the EU index of the F c region is Gly or Ala, and / or (ii) the amino acid residue at position 299 in the EU index of the F c region is. The pharmaceutical according to claim 69, which is Ala, Gly, or Val. Ｆｃ領域が、ＩｇＧ１又はＩｇＧ４のＣＨ２及びＣＨ３ドメインを含む、請求項６８～７０のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 68 to 70, wherein the Fc region comprises the CH2 and CH3 domains of IgG1 or IgG4. Ｆｃ領域が、ＩｇＧ４のＣＨ２及びＣＨ３ドメインを含む、請求項７１に記載の医薬。 The pharmaceutical according to claim 71, wherein the Fc region comprises the CH2 and CH3 domains of IgG4 . ＩＬ－２２Ｆｃ融合タンパク質が、配列番号８のアミノ酸配列に少なくとも９５％の配列同一性を有するアミノ酸配列を含む、請求項１～７２のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 1 to 72, wherein the IL- 22Fc fusion protein comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 8. ＩＬ－２２Ｆｃ融合タンパク質が、配列番号８、配列番号１０、又は配列番号１６のアミノ酸配列を含む、請求項１～７３のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 1 to 73, wherein the IL- 22Fc fusion protein comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 16. ＩＬ－２２Ｆｃ融合タンパク質が、配列番号８のアミノ酸配列を含む、又は配列番号８のアミノ酸配列からなる、請求項７４に記載の医薬。 The pharmaceutical according to claim 74, wherein the IL- 22Fc fusion protein comprises the amino acid sequence of SEQ ID NO: 8 or comprises the amino acid sequence of SEQ ID NO: 8. ＩＬ－２２Ｆｃ融合タンパク質が、二量体ＩＬ－２２Ｆｃ融合タンパク質である、請求項１～７５のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 1 to 75, wherein the IL- 22Fc fusion protein is a dimer IL-22Fc fusion protein. ＩＬ－２２Ｆｃ融合タンパク質が、単量体ＩＬ－２２Ｆｃ融合タンパク質である、請求項１～７５のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 1 to 75, wherein the IL- 22Fc fusion protein is a monomeric IL-22Fc fusion protein. ＩＬ－２２ポリペプチドが、ヒトＩＬ－２２ポリペプチドである、請求項６８～７７のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 68 to 77, wherein the IL -22 polypeptide is a human IL-22 polypeptide. ＩＬ－２２ポリペプチドが、配列番号４のアミノ酸配列を含む、請求項７８に記載の医薬。 28. The pharmaceutical according to claim 78, wherein the IL-22 polypeptide comprises the amino acid sequence of SEQ ID NO: 4. リンカーが、アミノ酸配列ＲＶＥＳＫＹＧＰＰ（配列番号４４）を含む、又はアミノ酸配列ＲＶＥＳＫＹＧＰＰ（配列番号４４）からなる、請求項６８～７９のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 68 to 79, wherein the linker comprises the amino acid sequence RVESKYGPP (SEQ ID NO: 44) or comprises the amino acid sequence RVESKYGPP (SEQ ID NO: 44). ＩＬ－２２Ｆｃ融合タンパク質が、ＩＬ－２２受容体へ結合する、請求項１～８０のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 1 to 80, wherein the IL- 22Fc fusion protein binds to the IL-22 receptor. ＩＬ－２２受容体が、ヒトＩＬ－２２受容体である、請求項８１に記載の医薬。 The pharmaceutical according to claim 81, wherein the IL -22 receptor is a human IL-22 receptor. ＩＬ－２２Ｆｃ融合タンパク質が、医薬組成物で対象へ投与される、請求項６８～８２のいずれか一項に記載の医薬。 The pharmaceutical according to any one of claims 68 to 82, wherein the IL- 22Fc fusion protein is administered to the subject in a pharmaceutical composition. 医薬組成物が、ＩＬ－２２Ｆｃ融合タンパク質１モル当たり８～１２モルのシアル酸の範囲で平均シアル酸含量を有する、請求項８３に記載の医薬。 38. The pharmaceutical composition of claim 83, wherein the pharmaceutical composition has an average sialic acid content in the range of 8-12 mol sialic acid per mole of IL- 22Fc fusion protein. 医薬組成物が、ＩＬ－２２Ｆｃ融合タンパク質１モル当たり８～９モルのシアル酸の範囲で平均シアル酸含量を有する、請求項８４に記載の医薬。 58. The pharmaceutical composition of claim 84, wherein the pharmaceutical composition has an average sialic acid content in the range of 8-9 moles of sialic acid per mole of IL- 22Fc fusion protein. ＩＬ－２２Ｆｃ融合タンパク質が、対象へ単剤療法として投与される、請求項１～８５のいずれか一項に記載の医薬。 The drug according to any one of claims 1 to 85, wherein the IL- 22Fc fusion protein is administered to the subject as monotherapy. ＩＬ－２２Ｆｃ融合タンパク質が、対象へ併用療法として投与される、請求項１～８５のいずれか一項に記載の医薬。 The drug according to any one of claims 1 to 85, wherein the IL- 22Fc fusion protein is administered to the subject as a combination therapy. ＩＬ－２２Ｆｃ融合タンパク質が、追加の治療剤と同時に対象へ投与される、請求項８７に記載の医薬。 28. The apparatus of claim 87, wherein the IL- 22Fc fusion protein is administered to the subject at the same time as an additional therapeutic agent. ＩＬ－２２Ｆｃ融合タンパク質が、追加の治療剤の投与前に、対象へ投与される、請求項８７に記載の医薬。 28. The apparatus of claim 87, wherein the IL- 22Fc fusion protein is administered to a subject prior to administration of an additional therapeutic agent. ＩＬ－２２Ｆｃ融合タンパク質が、アミノサリチレート、免疫調節剤、腫瘍壊死因子（ｔｕｍｏｒ ｎｅｃｒｏｓｉｓ ｆａｃｔｏｒ：ＴＮＦ）アンタゴニスト、抗インテグリン剤、粘膜アドレシン細胞接着分子（ｍｕｃｏｓａｌ ａｄｄｒｅｓｓｉｎ ｃｅｌｌ ａｄｈｅｓｉｏｎ ｍｏｌｅｃｕｌｅ：ＭＡｄＣＡＭ）アンタゴニスト、ＩＬ－２３アンタゴニスト、ＩＬ－１２アンタゴニスト、ＩＬ－１２／ＩＬ－２３アンタゴニスト、抗生物質、又はコルチコステロイドから選択される、追加のＩＢＤ療法と組み合わせて投与される、請求項８７～８９のいずれか一項に記載の医薬。 The IL- 22Fc fusion protein is an aminosalicylate, immunomodulator, tumor necrosis factor (TNF) antagonist, anti-integrin agent, mucosal addressin cell adhesion molecule (MAdCAM) antagonist, IL. One of claims 87-89, administered in combination with additional IBD therapy, selected from -23 antagonists, IL-12 antagonists, IL-12 / IL-23 antagonists, antibiotics, or corticosteroids. The medicines listed in the section. ＩＬ－２２Ｆｃ融合タンパク質が、免疫抑制剤、化学療法剤、ＴＮＦアンタゴニスト、ステロイド、光線療法、ヒドロキシクロロキン、抗線維化剤、モノクローナル抗体、又はそれらの組合せから選択される、追加のＧＶＨＤ療法と組み合わせて投与される、請求項８７～８９のいずれか一項に記載の医薬。 The IL- 22Fc fusion protein is combined with additional GVHD therapy selected from immunosuppressants, chemotherapeutic agents, TNF antagonists, steroids, phototherapy, hydroxychlorokin, antifibrotic agents, monoclonal antibodies, or combinations thereof. The pharmaceutical agent according to any one of claims 87 to 89, which is administered. 追加のＧＶＨＤ療法が、免疫抑制剤である、請求項９１に記載の医薬。 The medicine according to claim 91, wherein the additional GVHD therapy is an immunosuppressive agent. 免疫抑制剤が、シクロスポリン又はタクロリムスである、請求項９２に記載の医薬。 The pharmaceutical according to claim 92, wherein the immunosuppressive agent is cyclosporine or tacrolimus. 追加のＧＶＨＤ療法が、急性ＧＶＨＤ予防の標準治療である、請求項９１～９３のいずれか一項に記載の医薬。 The medicine according to any one of claims 91 to 93, wherein the additional GVHD therapy is a standard treatment for the prevention of acute GVHD. 投与が、静脈内注入によるものである、請求項１～９４のいずれか一項に記載の医薬。 The apparatus according to any one of claims 1 to 94, wherein the administration is by intravenous infusion . 投与が、皮下投与によるものである、請求項１～９４のいずれか一項に記載の医薬。 The apparatus according to any one of claims 1 to 94, wherein the administration is by subcutaneous administration. ＩＬ－２２Ｆｃ融合タンパク質と、請求項１～４１、６８～９０、９５、及び９６のいずれか一項に記載の投与計画に従って、ＩＢＤに罹患している対象へＩＬ－２２Ｆｃ融合タンパク質を投与するための指示書とを含む、キット。 The IL-22Fc fusion protein and the IL- 22Fc fusion protein are administered to subjects suffering from IBD according to the dosing regimen according to any one of claims 1-41, 68-90, 95, and 96. Kit, including instructions for. ＩＬ－２２Ｆｃ融合タンパク質と、請求項４２～８９及び９１～９６のいずれか一項に記載の投与計画に従って、ＧＶＨＤに罹患している対象又はＧＶＨＤのリスクがある対象へ、ＩＬ－２２Ｆｃ融合タンパク質を投与するための指示書とを含む、キット。 The IL-22Fc fusion protein and the IL- 22Fc fusion protein to subjects suffering from or at risk of GVHD according to the dosing regimen according to any one of claims 42-89 and 91-96. A kit that includes instructions and instructions for administering.
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