JP6318221B2 - 結腸切除の予防のための方法 - Google Patents
結腸切除の予防のための方法 Download PDFInfo
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- JP6318221B2 JP6318221B2 JP2016218270A JP2016218270A JP6318221B2 JP 6318221 B2 JP6318221 B2 JP 6318221B2 JP 2016218270 A JP2016218270 A JP 2016218270A JP 2016218270 A JP2016218270 A JP 2016218270A JP 6318221 B2 JP6318221 B2 JP 6318221B2
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Description
5’−G*G*A*ACAGTTCGTCCAT*G*G*C−3’(配列番号:1)におけるアスタリスク(*)により示すことができ、CGジヌクレオチドが、メチル化されていない。
クレオチドが、ホスホロチオエート修飾またはホスホロジチオエート修飾を有する少なくとも1つのヌクレオチドを有する、医薬組成物が提供される。
2年半にわたって、14人の慢性活動性UC外来患者を、彼らの現在の療法に対するアドオンとして、DIMS0150(配列番号:1)により治療し、3人の対象は、曝露の機会の間、4週間で、3用量のDIMS0150(配列番号:1)を受けた。UCの診断は、臨床上の特徴、内視鏡検査の特徴、および組織学的な特徴に基づいて、すべての患者において確定された。すべての患者は、高用量i.vグルココルチコイドを含む利用可能な療法の有効な投薬レジメンに対して十分に応答しないという文書化された病歴により、療法が失敗しているとして判断され、治療している内科医および外科医の評価に基づいて、選択的結腸切除と見なされた。ベースラインの特徴を、表1に示す。即座の臨床的介入をおそらく必要とするであろうと考えられる対象または結腸切除が予測される症例は、考慮に入れなかった。
DIMS0150(配列番号:1)の適合性は、結腸切除が好ましい療法の選択肢として選ばれた場合に、6か月の中期方式で、結腸切除を予防するための可能性のあるレスキュー療法として評価した。他の目的により、6か月以上の長期方式で、応答(ベースラインからの、≧5単位のCAIスコアにおける減少)または寛解(CAIスコア≦4ポイント)および結腸切除の予防について検討した。
11人の患者は、彼らの現在の療法に加えて、50mLの滅菌水中で希釈した30mgのDIMS0150(配列番号:1)の単一の結腸内投与を受けた。薬剤の適用は、結腸鏡検査生検経路を通して挿入された噴霧カテーテルの助けにより、結腸鏡検査の間に実行し、およそ、下行結腸の上方部または横行領域に送達した。再発の場合(≧4 CAI単位の疾患の増悪によって決定される)、DIMS0150(配列番号:1)のさらなる曝露を提供し、患者を続いて経過観察した。
DIMS0150(配列番号:1)による療法の後、患者の73%(8/11)は、臨床応答を有し、27%(3/11)は、4週目までに寛解した。12週目に、臨床応答および寛解率は、それぞれ、91%(10/11)および73%(8/11)であり、2つの症例が、完全な臨床的寛解であった。図1は、12週間の期間にわたって、単一のまたは複数の曝露を受けた対象において観察された中央CAIスコアを示す。
3人の患者(p12〜14)に、それぞれの曝露の間に、4週間の間隔で、現在の療法に対するアドオンとして、30mg DIMS0150(配列番号:1)の3回の曝露量を投与した。臨床応答パラメーターを、表3に提供する、また、興味深いことに、単一の曝露だけで実現された値と比較した場合に、12週目に効能パラメーターにおいて明らかな改善がある。この改善はまた、図2、3、および4からも明白である。まとめて考えると、2つのグループの対象の間で見られたデータは、曝露の間の4週間の時間枠での複数の曝露が、臨床転帰の改善をもたらしたことを示唆する。
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Claims (15)
- 抗炎症療法に対して不応性であるまたは応答が不十分であるまたは不耐性である対象における慢性活動性潰瘍性大腸炎の治療に用いるための医薬組成物の製造におけるオリゴヌクレオチドの使用において、前記オリゴヌクレオチドが、配列5’−GGAACAGTTCGTCCATGGC−3’(配列番号:2)を含み、少なくとも1つのCGジヌクレオチドが、メチル化されておらず、前記オリゴヌクレオチドが、コルチコステロイドまたはグルココルチコステロイドと組み合わせた投与に用いられないことを特徴とする使用。
- 請求項1に記載の使用において、前記オリゴヌクレオチドにおける少なくとも1つのヌクレオチドが、主鎖修飾を有することを特徴とする使用。
- 請求項2に記載の使用において、前記主鎖修飾が、ホスホロチオエート修飾またはホスホロジチオエート修飾によるホスフェート主鎖修飾であることを特徴とする使用。
- 請求項2または3に記載の使用において、前記主鎖修飾が、前記オリゴヌクレオチドの5’−および/または3’−末端部に位置することを特徴とする使用。
- 請求項1及至4の何れか1項に記載の使用において、前記オリゴヌクレオチドが、配列5’−G*G*A*ACAGTTCGTCCAT*G*G*C−3’(配列番号:1)を有し、前記CGジヌクレオチドが、メチル化されていないことを特徴とする使用。
- 請求項1及至5の何れか1項に記載の使用において、前記オリゴヌクレオチドの個別の用量が、単一の曝露量として反復投与に用いられることを特徴とする使用。
- 請求項1及至6の何れか1項に記載の使用において、前記オリゴヌクレオチドの2又はそれ以上の用量が、4〜70週間の間隔で、2またはそれ以上の別々の機会の投与に用いられることを特徴とする使用。
- 請求項1及至7の何れか1項に記載の使用において、投与に用いる前記オリゴヌクレオチドの量が、約0.3mg〜約100mgの範囲であり、好ましくは約25mg〜約60mgであることを特徴とする使用。
- 請求項1及至8の何れか1項に記載の使用において、投与に用いる前記オリゴヌクレオチドの量が、約30mgであることを特徴とする使用。
- 請求項1及至9の何れか1項に記載の使用において、前記オリゴヌクレオチドが、シクロスポリン、インフリキシマブ、アダリムマブ、天然IFN−β、S−オメプラゾール、5−Asa、またはアザチオプリンと組み合わせた投与に用いられることを特徴とする使用。
- 請求項1及至10の何れか1項に記載の使用において、前記オリゴヌクレオチドが、粘膜に対する局所的投与に用いられることを特徴とする使用。
- 請求項1及至11の何れか1項に記載の使用において、前記オリゴヌクレオチドが、結腸内への投与に用いられることを特徴とする使用。
- 請求項1及至12の何れか1項に記載の使用において、前記対象が、結腸切除に対して選択的であることを特徴とする使用。
- 請求項1及至13の何れか1項に記載の使用において、前記オリゴヌクレオチドが、1またはそれ以上の薬学的に許容できる賦形剤および/またはキャリヤと一緒に前記オリゴヌクレオチドを含む医薬組成物の形での投与に用いられることを特徴とする使用。
- 請求項14に記載の使用において、前記組成物が、前記オリゴヌクレオチドと水を含むことを特徴とする使用。
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- 2012-11-23 US US14/359,945 patent/US9492516B2/en active Active
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- 2012-11-23 DK DK12790904.2T patent/DK2782602T3/da active
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2016
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- 2016-11-08 JP JP2016218270A patent/JP6318221B2/ja active Active
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2017
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Also Published As
Publication number | Publication date |
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CY1122089T1 (el) | 2020-11-25 |
EP2782602A1 (en) | 2014-10-01 |
HUE046154T2 (hu) | 2020-02-28 |
WO2013076262A1 (en) | 2013-05-30 |
PL2782602T3 (pl) | 2019-12-31 |
DK2782602T3 (da) | 2019-09-30 |
SI2782602T1 (sl) | 2019-11-29 |
JP2017061508A (ja) | 2017-03-30 |
EP3556403A1 (en) | 2019-10-23 |
ES2745677T3 (es) | 2020-03-03 |
HRP20191723T1 (hr) | 2019-12-13 |
JP2015504438A (ja) | 2015-02-12 |
LT2782602T (lt) | 2019-10-10 |
EP2782602B1 (en) | 2019-06-26 |
PT2782602T (pt) | 2019-10-14 |
EP2596806A1 (en) | 2013-05-29 |
JP6193248B2 (ja) | 2017-09-06 |
CA2892203A1 (en) | 2013-05-30 |
US20150004187A1 (en) | 2015-01-01 |
US20170014442A1 (en) | 2017-01-19 |
US9492516B2 (en) | 2016-11-15 |
US20180015117A1 (en) | 2018-01-18 |
US9795627B2 (en) | 2017-10-24 |
RS59358B1 (sr) | 2019-11-29 |
CA2892203C (en) | 2021-11-16 |
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