JPWO2019236345A5

JPWO2019236345A5 -

Info

Publication number: JPWO2019236345A5
Application number: JP2020567198A
Authority: JP
Publication date: 2022-05-17

Description

別の実施形態では、患者の慢性腎臓病（ＣＫＤ：ｃｈｒｏｎｉｃｋｉｄｎｅｙｄｉｓｅａｓｅ）は、治療開始後、一つ以上のステージ（例えば、１、２、３、４、または５ステージ）まで改善する。別の実施形態では、患者のＣＫＤは、治療開始後１５０日以上（例えば、１５０日、１５１日、１５２日、１５３日、１５４日、１５５日、１５６日、１５７日、１５８日、１５９日、１６０日、１６１日、１６２日、１６３日、１６４日、１６５日、１６６日、１６７日、１６８日、１６９日、１７０日、１７１日、１７２日、１７３日、１７４日、１７５日、１７６日、１７７日、１７８日、１７９日、１８０日、１８１日、１８２日、１８３日、１８４日、１８５日、１８６日、１８７日、１８８日、１８９日、１９０日、１９１日、１９２日、１９３日、１９４日、１９５日、１９６日、１９７日、１９８日、１９９日、２００日、２０５日、２１０日、２１５日、２２０日または２２５日）、一つ以上のステージまで改善する。
本発明は、例えば、以下の項目を提供する。
(項目１)
非典型溶血性尿毒症症候群（ａＨＵＳ）を有するヒト小児患者の治療方法であって、前記患者に、それぞれ配列番号１９、１８および３に記載されるＣＤＲ１、ＣＤＲ２、およびＣＤＲ３の重鎖配列と、それぞれ配列番号４、５および６に記載されるＣＤＲ１、ＣＤＲ２、およびＣＤＲ３の軽鎖配列とを含む、抗Ｃ５抗体またはその抗原結合断片の有効量を投与することを含み、前記抗Ｃ５抗体またはその抗原結合断片は、
（ａ）１日目に、
ｉ．体重５ｋｇ以上１０ｋｇ未満の患者に６００ｍｇ、
ii．体重１０ｋｇ以上２０ｋｇ未満の患者に６００ｍｇ、
iii．体重２０ｋｇ以上３０ｋｇ未満の患者に９００ｍｇ、
iv．体重３０ｋｇ以上４０ｋｇ未満の患者に１２００ｍｇ、
ｖ．体重４０ｋｇ以上６０ｋｇ未満の患者に２４００ｍｇ、
vi．体重６０ｋｇ以上１００ｋｇ未満の患者に２７００ｍｇ、または
vii．体重１００ｋｇ以上の患者に３０００ｍｇ、の負荷用量で１回、および
（ｂ）１５日目に、
ｉ．体重５ｋｇ以上１０ｋｇ未満の患者に３００ｍｇ、
ii．体重１０ｋｇ以上２０ｋｇ未満の患者に６００ｍｇ、
iii．体重２０ｋｇ以上３０ｋｇ未満の患者に２１００ｍｇ、
iv．体重３０ｋｇ以上４０ｋｇ未満の患者に２７００ｍｇ、
ｖ．体重４０ｋｇ以上６０ｋｇ未満の患者に３０００ｍｇ、
vi．体重６０ｋｇ以上１００ｋｇ未満の患者に３３００ｍｇ、または
vii．体重１００ｋｇ以上の患者に３６００ｍｇ、の維持用量で、投与され
体重２０ｋｇ未満の患者はその後、４週間ごとに追加の維持用量を与えられ、体重が２０ｋｇ以上の患者はその後、８週間ごとに追加の維持用量を与えられる、方法。
(項目２)
非典型溶血性尿毒症症候群（ａＨＵＳ）を有するヒト小児患者の治療方法であって、それぞれ配列番号１９、１８および３に記載されるＣＤＲ１、ＣＤＲ２、およびＣＤＲ３の重鎖配列、それぞれ配列番号４、５および６に記載されるＣＤＲ１、ＣＤＲ２、およびＣＤＲ３の軽鎖配列、およびヒト新生児型Ｆｃ受容体（ＦｃＲｎ）に結合するバリアントヒトＦｃ定常領域を含む抗Ｃ５抗体またはその抗原結合断片の有効量を前記患者に投与することを含み、前記バリアントヒトＦｃＣＨ３定常領域は、各々ＥＵナンバリング規定に従って、メチオニン４２８およびアスパラギン４３４に対応する残基で、Ｍｅｔ４２９ＬｅｕおよびＡｓｎ４３５Ｓｅｒの置換を含み、前記抗Ｃ５抗体またはその抗原結合断片が、
（ａ）１日目に、
ｉ．体重５ｋｇ以上１０ｋｇ未満の患者に６００ｍｇ、
ii．体重１０ｋｇ以上２０ｋｇ未満の患者に６００ｍｇ、
iii．体重２０ｋｇ以上３０ｋｇ未満の患者に９００ｍｇ、
iv．体重３０ｋｇ以上４０ｋｇ未満の患者に１２００ｍｇ、
ｖ．体重４０ｋｇ以上６０ｋｇ未満の患者に２４００ｍｇ、
vi．体重６０ｋｇ以上１００ｋｇ未満の患者に２７００ｍｇ、または
vii．体重１００ｋｇ以上の患者に３０００ｍｇ、の負荷用量で１回、および
（ｂ）１５日目に、
ｉ．体重５ｋｇ以上１０ｋｇ未満の患者に３００ｍｇ、
ii．体重１０ｋｇ以上２０ｋｇ未満の患者に６００ｍｇ、
iii．体重２０ｋｇ以上３０ｋｇ未満の患者に２１００ｍｇ、
iv．体重３０ｋｇ以上４０ｋｇ未満の患者に２７００ｍｇ、
ｖ．体重４０ｋｇ以上６０ｋｇ未満の患者に３０００ｍｇ、
vi．体重６０ｋｇ以上１００ｋｇ未満の患者に３３００ｍｇ、または
vii．体重１００ｋｇ以上の患者に３６００ｍｇ、の維持用量で、投与され
体重２０ｋｇ未満の患者はその後、４週間ごとに追加の維持用量を与えられ、体重が２０ｋｇ以上の患者はその後、８週間ごとに追加の維持用量を与えられる、方法。
(項目３)
前記抗Ｃ５抗体が、配列番号１２に記載される重鎖可変領域と、配列番号８に記載される軽鎖可変領域とを含む、項目１または２に記載の方法。
(項目４)
前記抗Ｃ５抗体が、配列番号１３に記載される重鎖定常領域をさらに含む、項目１～３のいずれか一項に記載の方法。
(項目５)
前記抗体が、配列番号１４に記載されるアミノ酸配列を含む重鎖ポリペプチドと、配列番号１１に記載されるアミノ酸配列を含む軽鎖ポリペプチドとを含む、項目１～４のいずれか一項に記載の方法。
(項目６)
前記抗Ｃ５抗体は、ｐＨ７．４および２５Ｃで、０．１ｎＭ～１ｎＭの範囲にある親和性解離定数（Ｋ _Ｄ）でヒトＣ５に結合する、項目１～５のいずれか一項に記載の方法。
(項目７)
前記抗Ｃ５抗体が、Ｋ _Ｄ ≧１０ｎＭで、ｐＨ６．０および２５ＣでヒトＣ５に結合する、項目１～６のいずれか一項に記載の方法。
(項目８)
前記抗Ｃ５抗体が、体重５ｋｇ以上１０ｋｇ未満の患者に、
（ａ）１日目に１回、６００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、３００ｍｇの維持用量で、およびその後は４週間ごとに投与される、項目１～７のいずれか一項に記載の方法。
(項目９)
前記抗Ｃ５抗体が、体重１０ｋｇ以上２０ｋｇ未満の患者に、
（ａ）１日目に１回、６００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、６００ｍｇの維持用量で、およびその後は４週間ごとに投与される、項目１～７のいずれか一項に記載の方法。
(項目１０)
前記抗Ｃ５抗体が、体重２０ｋｇ以上３０ｋｇ未満の患者に、
（ａ）１日目に１回、９００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、２１００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目１～７のいずれか一項に記載の方法。
(項目１１)
前記抗Ｃ５抗体が、体重３０ｋｇ以上４０ｋｇ未満の患者に、
（ａ）１日目に１回、１２００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、２７００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目１～７のいずれか一項に記載の方法。
(項目１２)
前記抗Ｃ５抗体が、体重４０ｋｇ以上６０ｋｇ未満の患者に、
（ａ）１日目に１回、２４００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、３０００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目１～７のいずれか一項に記載の方法。
(項目１３)
前記抗Ｃ５抗体が、体重６０ｋｇ以上１００ｋｇ未満の患者に、
（ａ）１日目に１回、２７００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、３３００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目１～７のいずれか一項に記載の方法。
(項目１４)
前記抗Ｃ５抗体が、体重１００ｋｇ以上の患者に、
（ａ）１日目に１回、３０００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、３６００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目１～７のいずれか一項に記載の方法。
(項目１５)
前記治療が、前記抗Ｃ５抗体またはその抗原結合断片の血清トラフ濃度を１００μｇ／ｍＬ以上に維持する、項目１～１４のいずれか一項に記載の方法。
(項目１６)
前記治療が、前記抗Ｃ５抗体またはその抗原結合断片の血清トラフ濃度を２００μｇ／ｍＬ以上に維持する、項目１～１５のいずれか一項に記載の方法。
(項目１７)
前記治療が、０．３０９～０．５μｇ／ｍＬ以下の遊離Ｃ５濃度を維持する、項目１～１６のいずれか一項に記載の方法。
(項目１８)
前記抗Ｃ５抗体は、治療後、最大で２年間、４週間ごとに３００ｍｇまたは６００ｍｇの用量で投与される、項目１～１７のいずれか一項に記載の方法。
(項目１９)
前記抗Ｃ５抗体は、治療後、最大で２年間、８週間ごとに２１００ｍｇ、２７００ｍｇ、３０００ｍｇ、３３００ｍｇ、または３６００ｍｇの用量で投与される、項目１～１８のいずれか一項に記載の方法。
(項目２０)
前記抗Ｃ５抗体が、静脈内投与用に製剤化される、項目１～１９のいずれか一項に記載の方法。
(項目２１)
前記患者が、過去に補体阻害剤を用いて治療されていない、項目１～２０のいずれか一項に記載の方法。
(項目２２)
前記患者が、１８歳未満である、項目１～２１のいずれか一項に記載の方法。
(項目２３)
前記治療が、合計２６週間の治療を含む投与サイクルである、項目１～２２のいずれか一項に記載の方法。
(項目２４)
前記治療が、終末補体阻害をもたらす、項目１～２３のいずれか一項に記載の方法。
(項目２５)
前記治療が、完全な血栓性微小血管症（ＴＭＡ）応答をもたらす、項目１～２４のいずれか一項に記載の方法。
(項目２６)
前記治療が、血清クレアチニンレベルにおいて、基準と比較して２５％以上の減少をもたらす、項目１～２５のいずれか一項に記載の方法。
(項目２７)
前記治療が、基準と比較して血小板数の増加をもたらす、項目１～２６のいずれか一項に記載の方法。
(項目２８)
前記治療が、乳酸脱水素酵素（ＬＤＨ）レベルにより評価されたときに基準と比較して溶血の減少をもたらす、項目１～２７のいずれか一項に記載の方法。
(項目２９)
前記治療が、基準と比較して、重度の高血圧、尿タンパク、尿毒症、倦怠、疲労、過敏、血小板減少症、微小血管症性溶血性貧血および腎機能障害からなる群から選択される少なくとも一つの治療マーカーの低下または停止を生じさせる、項目１または２に記載の方法。
(項目３０)
前記治療が、基準と比較して、第Ｂａ因子、可溶性腫瘍壊死因子受容体１（ｓＴＮＦＲ１）、可溶性血管接着分子１（ｓＶＣＡＭ１）、トロンボモジュリン、Ｄ－ダイマー、およびシスタチンＣからなる群から選択されるマーカーの正常レベルへのシフトを生じさせる、項目１～２９のいずれか１項に記載の方法。
(項目３１)
前記治療が、基準と比較して、輸血の必要性の減少をもたらす、項目１～３０のいずれか一項に記載の方法。
(項目３２)
前記治療が、基準と比較して、主要有害血管事象（ＭＡＶＥ）の減少を生じさせる、項目１～３１のいずれか一項に記載の方法。
(項目３３)
前記治療が、基準と比較して、慢性疾患治療の機能評価（ＦＡＣＩＴ：ＦｕｎｃｔｉｏｎａｌＡｓｓｅｓｓｍｅｎｔｏｆＣｈｒｏｎｉｃＩｌｌｎｅｓｓＴｈｅｒａｐｙ）‐疲労尺度、第４版、または欧州癌研究治療機関（ＥｕｒｏｐｅａｎＯｒｇａｎｉｓａｔｉｏｎｆｏｒＲｅｓｅａｒｃｈａｎｄＴｒｅａｔｍｅｎｔｏｆＣａｎｃｅｒ）、クオリティ・オブ・ライフ質問票‐コア３０尺度（ＱｕａｌｉｔｙｏｆＬｉｆｅＱｕｅｓｔｉｏｎｎａｉｒｅ‐Ｃｏｒｅ３０Ｓｃａｌｅ）を介して評価される、クオリティ・オブ・ライフにおいて、基準からの変化を生じさせる、項目１～３２のいずれか一項に記載の方法。
(項目３４)
ヒト小児患者における非典型溶血性尿毒症症候群（ａＨＵＳ）を治療するためのキットであって、
（ａ）配列番号１２に記載される配列を有する重鎖可変領域のＣＤＲ１、ＣＤＲ２、およびＣＤＲ３ドメインと、配列番号８に記載される配列を有する軽鎖可変領域のＣＤＲ１、ＣＤＲ２、およびＣＤＲ３ドメインとを含む、抗Ｃ５抗体またはその抗原結合断片の用量、および
（ｂ）項目１または２に記載の方法において、前記抗Ｃ５抗体またはその抗原結合断片を使用するための指示書、を含む、キット。
(項目３５)
前記抗Ｃ５抗体またはその抗原結合断片は、体重５ｋｇ以上１０ｋｇ未満の患者に、
（ａ）１日目に１回、６００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、３００ｍｇの維持用量で、およびその後は４週間ごとに投与される、項目３４に記載のキット。
(項目３６)
前記抗Ｃ５抗体またはその抗原結合断片は、体重１０ｋｇ以上２０ｋｇ未満の患者に、
（ａ）１日目に１回、６００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、６００ｍｇの維持用量で、およびその後は４週間ごとに投与される、項目３４に記載のキット。
(項目３７)
前記抗Ｃ５抗体またはその抗原結合断片は、体重２０ｋｇ以上３０ｋｇ未満の患者に、
（ａ）１日目に１回、９００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、２１００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目３４に記載のキット。
(項目３８)
前記抗Ｃ５抗体またはその抗原結合断片は、体重３０ｋｇ以上４０ｋｇ未満の患者に、
（ａ）１日目に１回、１２００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、２７００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目３４に記載のキット。
(項目３９)
前記抗Ｃ５抗体またはその抗原結合断片は、体重４０ｋｇ以上６０ｋｇ未満の患者に、
（ａ）１日目に１回、２４００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、３０００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目３４に記載のキット。
(項目４０)
前記抗Ｃ５抗体またはその抗原結合断片は、体重６０ｋｇ以上１００ｋｇ未満の患者に、
（ａ）１日目に１回、２７００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、３３００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目３４に記載のキット。
(項目４１)
前記抗Ｃ５抗体またはその抗原結合断片は、体重１００ｋｇ以上の患者に、
（ａ）１日目に１回、３０００ｍｇの負荷用量で投与され、および
（ｂ）１５日目に１回、３６００ｍｇの維持用量で、およびその後は８週間ごとに投与される、項目３４に記載のキット。
(項目４２)
配列番号１２に記載される配列を有する重鎖可変領域のＣＤＲ１、ＣＤＲ２、およびＣＤＲ３ドメインと、配列番号８に記載される配列を有する軽鎖可変領域のＣＤＲ１、ＣＤＲ２、およびＣＤＲ３ドメインとを含む、抗Ｃ５抗体またはその抗原結合断片であって、前記抗Ｃ５抗体またはその抗原結合断片が、
（ａ）１日目に、
ｉ．体重５ｋｇ以上１０ｋｇ未満の患者に６００ｍｇ、
ii．体重１０ｋｇ以上２０ｋｇ未満の患者に６００ｍｇ、
iii．体重２０ｋｇ以上３０ｋｇ未満の患者に９００ｍｇ、
iv．体重３０ｋｇ以上４０ｋｇ未満の患者に１２００ｍｇ、
ｖ．体重４０ｋｇ以上６０ｋｇ未満の患者に２４００ｍｇ、
vi．体重６０ｋｇ以上１００ｋｇ未満の患者に２７００ｍｇ、または
vii．体重１００ｋｇ以上の患者に３０００ｍｇ、の負荷用量で１回、および
（ｂ）１５日目に、
ｉ．体重５ｋｇ以上１０ｋｇ未満の患者に３００ｍｇ、
ii．体重１０ｋｇ以上２０ｋｇ未満の患者に６００ｍｇ、
iii．体重２０ｋｇ以上３０ｋｇ未満の患者に２１００ｍｇ、
iv．体重３０ｋｇ以上４０ｋｇ未満の患者に２７００ｍｇ、
ｖ．体重４０ｋｇ以上６０ｋｇ未満の患者に３０００ｍｇ、
vi．体重６０ｋｇ以上１００ｋｇ未満の患者に３３００ｍｇ、または
vii．体重１００ｋｇ以上の患者に３６００ｍｇ、の維持用量で、投与され
体重２０ｋｇ未満の患者はその後、４週間ごとに追加の維持用量を与えられ、体重が２０ｋｇ以上の患者はその後、８週間ごとに追加の維持用量を与えられる、抗Ｃ５抗体またはその抗原結合断片。
(項目４３)
前記抗体が、ａＨＵＳ患者における複数回のＩＶ投与の後に、安全であり、忍容性であり、有効で、および充分に非免疫原性であると判定される、項目４２に記載の抗体。
In another embodiment, a patient's chronic kidney disease (CKD) is improved to one or more stages (eg, 1, 2, 3, 4, or 5 stages) after the start of treatment. In another embodiment, the patient's CKD is 150 days or more after the start of treatment (eg, 150 days, 151 days, 152 days, 153 days, 154 days, 155 days, 156 days, 157 days, 158 days, 159 days, 160 days, 161 days, 162 days, 163 days, 164 days, 165 days, 166 days, 167 days, 168 days, 169 days, 170 days, 171 days, 172 days, 173 days, 174 days, 175 days, 176 days. 177th, 178th, 179th, 180th, 181st, 182nd, 183rd, 184th, 185th, 186th, 187th, 188th, 189th, 190th, 191st, 192nd, 193rd. 194 days, 195 days, 196 days, 197 days, 198 days, 199 days, 200 days, 205 days, 210 days, 215 days, 220 days or 225 days), improving to one or more stages.
The present invention provides, for example, the following items.
(Item 1)
A method of treating a human pediatric patient with atypical hemolytic urinary toxicosis syndrome (aHUS), wherein the patient is given the heavy chain sequences of CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 19, 18 and 3, respectively. Containing administration of an effective amount of an anti-C5 antibody or antigen-binding fragment thereof, comprising the light chain sequences of CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 4, 5 and 6, respectively, said anti-C5 antibody or said thereof. The antigen-binding fragment is
(A) On the first day,
i. 600 mg for patients weighing 5 kg or more and less than 10 kg,
ii. 600 mg for patients weighing 10 kg or more and less than 20 kg,
iii. 900 mg for patients weighing 20 kg or more and less than 30 kg,
iv. 1200 mg for patients weighing 30 kg or more and less than 40 kg,
v. 2400 mg for patients weighing 40 kg or more and less than 60 kg,
vi. 2700 mg, or 2700 mg for patients weighing 60 kg or more and less than 100 kg
vii. For patients weighing 100 kg or more, once at a loading dose of 3000 mg, and
(B) On the 15th day,
i. 300 mg for patients weighing 5 kg or more and less than 10 kg,
ii. 600 mg for patients weighing 10 kg or more and less than 20 kg,
iii. 2100 mg for patients weighing 20 kg or more and less than 30 kg,
iv. 2700 mg for patients weighing 30 kg or more and less than 40 kg,
v. 3000 mg for patients weighing 40 kg or more and less than 60 kg,
vi. 3300 mg or 3300 mg for patients weighing 60 kg or more and less than 100 kg
vii. Administered at a maintenance dose of 3600 mg to patients weighing 100 kg or more
A method in which patients weighing less than 20 kg are then given an additional maintenance dose every 4 weeks and patients weighing more than 20 kg are subsequently given an additional maintenance dose every 8 weeks.
(Item 2)
A method of treating a human pediatric patient with atypical hemolytic urinary toxicosis syndrome (aHUS), the heavy chain sequences of CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 19, 18 and 3, respectively, SEQ ID NO: 4, Effective amounts of an anti-C5 antibody or antigen-binding fragment thereof comprising the light chain sequences of CDR1, CDR2, and CDR3 described in 5 and 6 and a variant human Fc constant region that binds to a human neonatal Fc receptor (FcRn). The variant human Fc CH3 constant region, which comprises administration to the patient, comprises the substitution of Met429Leu and Asn435Ser at the residues corresponding to methionine 428 and asparagine 434, respectively, according to EU numbering regulations, said anti-C5 antibody or the anti-C5 antibody thereof. The antigen-binding fragment
(A) On the first day,
i. 600 mg for patients weighing 5 kg or more and less than 10 kg,
ii. 600 mg for patients weighing 10 kg or more and less than 20 kg,
iii. 900 mg for patients weighing 20 kg or more and less than 30 kg,
iv. 1200 mg for patients weighing 30 kg or more and less than 40 kg,
v. 2400 mg for patients weighing 40 kg or more and less than 60 kg,
vi. 2700 mg, or 2700 mg for patients weighing 60 kg or more and less than 100 kg
vii. For patients weighing 100 kg or more, once at a loading dose of 3000 mg, and
(B) On the 15th day,
i. 300 mg for patients weighing 5 kg or more and less than 10 kg,
ii. 600 mg for patients weighing 10 kg or more and less than 20 kg,
iii. 2100 mg for patients weighing 20 kg or more and less than 30 kg,
iv. 2700 mg for patients weighing 30 kg or more and less than 40 kg,
v. 3000 mg for patients weighing 40 kg or more and less than 60 kg,
vi. 3300 mg or 3300 mg for patients weighing 60 kg or more and less than 100 kg
vii. Administered at a maintenance dose of 3600 mg to patients weighing 100 kg or more
A method in which patients weighing less than 20 kg are then given an additional maintenance dose every 4 weeks and patients weighing more than 20 kg are subsequently given an additional maintenance dose every 8 weeks.
(Item 3)
The method of item 1 or 2, wherein the anti-C5 antibody comprises a heavy chain variable region set forth in SEQ ID NO: 12 and a light chain variable region set forth in SEQ ID NO: 8.
(Item 4)
The method according to any one of items 1 to 3, wherein the anti-C5 antibody further comprises the heavy chain constant region set forth in SEQ ID NO: 13.
(Item 5)
Item 2. The method described.
(Item 6)
The method according to any one of items 1 to 5, wherein the anti-C5 antibody binds to human C5 at pH 7.4 and 25C with an affinity dissociation constant (KD) in the range of 0.1 nM to 1 nM _. ..
(Item 7)
The method according to any one of items 1 to 6, wherein the anti-C5 antibody binds to human C5 at pH 6.0 and 25C at _KD ≧ 10 nM.
(Item 8)
The anti-C5 antibody is applied to patients weighing 5 kg or more and less than 10 kg.
(A) Once daily, administered at a loading dose of 600 mg, and
(B) The method according to any one of items 1 to 7, which is administered once on the 15th day at a maintenance dose of 300 mg and every 4 weeks thereafter.
(Item 9)
The anti-C5 antibody is applied to patients weighing 10 kg or more and less than 20 kg.
(A) Once daily, administered at a loading dose of 600 mg, and
(B) The method according to any one of items 1 to 7, which is administered once on the 15th day at a maintenance dose of 600 mg and every 4 weeks thereafter.
(Item 10)
The anti-C5 antibody is applied to patients weighing 20 kg or more and less than 30 kg.
(A) Once daily, administered at a loading dose of 900 mg, and
(B) The method according to any one of items 1 to 7, which is administered once on the 15th day at a maintenance dose of 2100 mg and every 8 weeks thereafter.
(Item 11)
The anti-C5 antibody is applied to patients weighing 30 kg or more and less than 40 kg.
(A) Once daily, administered at a loading dose of 1200 mg, and
(B) The method according to any one of items 1 to 7, which is administered once on the 15th day at a maintenance dose of 2700 mg and every 8 weeks thereafter.
(Item 12)
The anti-C5 antibody is applied to patients weighing 40 kg or more and less than 60 kg.
(A) Once daily, administered at a loading dose of 2400 mg, and
(B) The method according to any one of items 1 to 7, which is administered once on the 15th day at a maintenance dose of 3000 mg and every 8 weeks thereafter.
(Item 13)
The anti-C5 antibody is applied to patients weighing 60 kg or more and less than 100 kg.
(A) Once daily, administered at a loading dose of 2700 mg, and
(B) The method according to any one of items 1 to 7, which is administered once on the 15th day at a maintenance dose of 3300 mg and every 8 weeks thereafter.
(Item 14)
The anti-C5 antibody is applied to patients weighing 100 kg or more.
(A) Once daily, administered at a loading dose of 3000 mg, and
(B) The method according to any one of items 1 to 7, which is administered once on the 15th day at a maintenance dose of 3600 mg and every 8 weeks thereafter.
(Item 15)
The method according to any one of items 1 to 14, wherein the treatment maintains a serum trough concentration of the anti-C5 antibody or an antigen-binding fragment thereof at 100 μg / mL or higher.
(Item 16)
The method according to any one of items 1 to 15, wherein the treatment maintains a serum trough concentration of the anti-C5 antibody or an antigen-binding fragment thereof at 200 μg / mL or higher.
(Item 17)
The method according to any one of items 1 to 16, wherein the treatment maintains a free C5 concentration of 0.309 to 0.5 μg / mL or less.
(Item 18)
The method according to any one of items 1 to 17, wherein the anti-C5 antibody is administered at a dose of 300 mg or 600 mg every 4 weeks for a maximum of 2 years after treatment.
(Item 19)
The method according to any one of items 1 to 18, wherein the anti-C5 antibody is administered at a dose of 2100 mg, 2700 mg, 3000 mg, 3300 mg, or 3600 mg every 8 weeks for a maximum of 2 years after treatment.
(Item 20)
The method according to any one of items 1 to 19, wherein the anti-C5 antibody is formulated for intravenous administration.
(Item 21)
The method according to any one of items 1 to 20, wherein the patient has not been treated with a complement inhibitor in the past.
(Item 22)
The method according to any one of items 1 to 21, wherein the patient is under the age of 18.
(Item 23)
The method according to any one of items 1 to 22, wherein the treatment is a dosing cycle comprising a total of 26 weeks of treatment.
(Item 24)
The method according to any one of items 1 to 23, wherein the treatment results in terminal complement inhibition.
(Item 25)
The method according to any one of items 1 to 24, wherein the treatment results in a complete thrombotic microangiopathy (TMA) response.
(Item 26)
The method according to any one of items 1 to 25, wherein the treatment results in a 25% or greater reduction in serum creatinine levels as compared to a reference.
(Item 27)
The method according to any one of items 1-26, wherein the treatment results in an increase in platelet count as compared to a reference.
(Item 28)
The method of any one of items 1-27, wherein the treatment results in a reduction in hemolysis as compared to a criterion when assessed by lactate dehydrogenase (LDH) levels.
(Item 29)
The treatment is selected from the group consisting of severe hypertension, urinary protein, uremia, malaise, fatigue, hypersensitivity, thrombocytopenia, microangiogenic hemolytic anemia and renal dysfunction compared to the criteria. The method of item 1 or 2, which causes a decrease or cessation of one therapeutic marker.
(Item 30)
The treatment is selected from the group consisting of Factor Ba, soluble tumor necrosis factor receptor 1 (sTNFR1), soluble vascular adhesion molecule 1 (sVCAM1), thrombomodulin, D-dimer, and cystatin C as compared to the criteria. The method of any one of items 1-29, which causes a shift of the marker to a normal level.
(Item 31)
The method according to any one of items 1 to 30, wherein the treatment results in a reduced need for blood transfusion as compared to the criteria.
(Item 32)
The method of any one of items 1-31, wherein the treatment results in a reduction in major adverse vascular events (MAVE) as compared to the criteria.
(Item 33)
The treatment is compared to the criteria for functional assessment of chronic disease treatment (FACIT) -fatigue scale, 4th edition, or European Canceration for Research and Treatment. , Quality of Life Questionnaire-Any of items 1-32 that cause a change from the standard in the Quality of Life, evaluated via the Quality of Life Questionnaire-Core 30 Scale. The method described in item 1.
(Item 34)
A kit for the treatment of atypical hemolytic urinary toxicosis syndrome (aHUS) in human pediatric patients.
(A) the CDR1, CDR2, and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 12, and the CDR1, CDR2, and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO: 8. The dose of anti-C5 antibody or antigen-binding fragment thereof, including, and
(B) A kit comprising the instructions for using the anti-C5 antibody or antigen-binding fragment thereof in the method according to item 1 or 2.
(Item 35)
The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 5 kg or more and less than 10 kg.
(A) Once daily, administered at a loading dose of 600 mg, and
(B) The kit of item 34, which is administered once on the 15th day at a maintenance dose of 300 mg and every 4 weeks thereafter.
(Item 36)
The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 10 kg or more and less than 20 kg.
(A) Once daily, administered at a loading dose of 600 mg, and
(B) The kit of item 34, which is administered once on the 15th day at a maintenance dose of 600 mg and every 4 weeks thereafter.
(Item 37)
The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 20 kg or more and less than 30 kg.
(A) Once daily, administered at a loading dose of 900 mg, and
(B) The kit of item 34, which is administered once on the 15th day at a maintenance dose of 2100 mg and every 8 weeks thereafter.
(Item 38)
The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 30 kg or more and less than 40 kg.
(A) Once daily, administered at a loading dose of 1200 mg, and
(B) The kit of item 34, which is administered once on the 15th day at a maintenance dose of 2700 mg and every 8 weeks thereafter.
(Item 39)
The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 40 kg or more and less than 60 kg.
(A) Once daily, administered at a loading dose of 2400 mg, and
(B) The kit of item 34, administered once on the 15th day at a maintenance dose of 3000 mg and every 8 weeks thereafter.
(Item 40)
The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 60 kg or more and less than 100 kg.
(A) Once daily, administered at a loading dose of 2700 mg, and
(B) The kit of item 34, which is administered once on the 15th day at a maintenance dose of 3300 mg and every 8 weeks thereafter.
(Item 41)
The anti-C5 antibody or an antigen-binding fragment thereof can be applied to a patient weighing 100 kg or more.
(A) Once daily, administered at a loading dose of 3000 mg, and
(B) The kit of item 34, which is administered once on the 15th day at a maintenance dose of 3600 mg and every 8 weeks thereafter.
(Item 42)
It comprises the CDR1, CDR2, and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 12 and the CDR1, CDR2, and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO: 8. An anti-C5 antibody or an antigen-binding fragment thereof, wherein the anti-C5 antibody or an antigen-binding fragment thereof is used.
(A) On the first day,
i. 600 mg for patients weighing 5 kg or more and less than 10 kg,
ii. 600 mg for patients weighing 10 kg or more and less than 20 kg,
iii. 900 mg for patients weighing 20 kg or more and less than 30 kg,
iv. 1200 mg for patients weighing 30 kg or more and less than 40 kg,
v. 2400 mg for patients weighing 40 kg or more and less than 60 kg,
vi. 2700 mg, or 2700 mg for patients weighing 60 kg or more and less than 100 kg
vii. For patients weighing 100 kg or more, once at a loading dose of 3000 mg, and
(B) On the 15th day,
i. 300 mg for patients weighing 5 kg or more and less than 10 kg,
ii. 600 mg for patients weighing 10 kg or more and less than 20 kg,
iii. 2100 mg for patients weighing 20 kg or more and less than 30 kg,
iv. 2700 mg for patients weighing 30 kg or more and less than 40 kg,
v. 3000 mg for patients weighing 40 kg or more and less than 60 kg,
vi. 3300 mg or 3300 mg for patients weighing 60 kg or more and less than 100 kg
vii. Administered at a maintenance dose of 3600 mg to patients weighing 100 kg or more
An anti-C5 antibody or antigen-binding fragment thereof, wherein patients weighing less than 20 kg are then given an additional maintenance dose every 4 weeks, and patients weighing 20 kg or more are then given an additional maintenance dose every 8 weeks.
(Item 43)
42. The antibody of item 42, wherein said antibody is determined to be safe, tolerable, effective, and sufficiently non-immunogenic after multiple IV doses in aHUS patients.

Claims

Compositions for treating human pediatric patients with atypical hemolytic urinary toxicosis syndrome (aHUS), the weights of CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 19, 18 and 3 , respectively . The composition comprises an anti-C5 antibody or antigen-binding fragment thereof comprising a chain sequence and the light chain sequences of CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 4, 5 and 6, respectively.
(A) On the first day,
i. 600 mg of the anti-C5 antibody or an antigen-binding fragment thereof for a patient weighing 5 kg or more and less than 10 kg.
ii. 600 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 10 kg or more and less than 20 kg.
iii. 900 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 20 kg or more and less than 30 kg.
iv. 1200 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 30 kg or more and less than 40 kg.
v. 2400 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 40 kg or more and less than 60 kg.
vi. 2700 mg of the anti-C5 antibody or the antigen-binding fragment thereof, or 2700 mg of the anti-C5 antibody or an antigen-binding fragment thereof for a patient weighing 60 kg or more and less than 100 kg.
vii. Once at a loading dose of 3000 mg of the anti-C5 antibody or antigen-binding fragment thereof to a patient weighing 100 kg or more, and (b) on day 15.
i. 300 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 5 kg or more and less than 10 kg.
ii. 600 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 10 kg or more and less than 20 kg.
iii. 2100 mg of the anti-C5 antibody or an antigen-binding fragment thereof for a patient weighing 20 kg or more and less than 30 kg.
iv. 2700 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 30 kg or more and less than 40 kg.
v. 3000 mg of the anti-C5 antibody or its antigen-binding fragment for a patient weighing 40 kg or more and less than 60 kg.
vi. 3300 mg of the anti-C5 antibody or the antigen-binding fragment thereof, or 3300 mg of the anti-C5 antibody or an antigen-binding fragment thereof for a patient weighing 60 kg or more and less than 100 kg.
vii. Patients weighing 100 kg or more were administered with a maintenance dose of 3600 mg of the anti-C5 antibody or the antigen-binding fragment thereof , and patients weighing less than 20 kg were subsequently given an additional maintenance dose every 4 weeks and weighed 20 kg or more. The composition is characterized in that the patient is subsequently given an additional maintenance dose every 8 weeks.

Compositions for treating human pediatric patients with atypical hemolytic urinary toxicosis syndrome (aHUS), heavy chain sequences of CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 19, 18 and 3, respectively. Anti-C5 antibody or antigen binding thereof comprising the light chain sequences of CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 4, 5 and 6, respectively, and a variant human Fc constant region that binds to a human neonatal Fc receptor (FcRn). The variant human Fc CH3 constant region comprising a fragment , each comprising a substitution of Met429Leu and Asn435Ser at residues corresponding to methionine 428 and asparagine 434, according to EU numbering regulations, said composition .
(A) On the first day,
i. 600 mg of the anti-C5 antibody or an antigen-binding fragment thereof for a patient weighing 5 kg or more and less than 10 kg.
ii. 600 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 10 kg or more and less than 20 kg.
iii. 900 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 20 kg or more and less than 30 kg.
iv. 1200 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 30 kg or more and less than 40 kg.
v. 2400 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 40 kg or more and less than 60 kg.
vi. 2700 mg of the anti-C5 antibody or the antigen-binding fragment thereof, or 2700 mg of the anti-C5 antibody or an antigen-binding fragment thereof for a patient weighing 60 kg or more and less than 100 kg.
vii. Once at a loading dose of 3000 mg of the anti-C5 antibody or antigen-binding fragment thereof to a patient weighing 100 kg or more, and (b) on day 15.
i. 300 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 5 kg or more and less than 10 kg.
ii. 600 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 10 kg or more and less than 20 kg.
iii. 2100 mg of the anti-C5 antibody or an antigen-binding fragment thereof for a patient weighing 20 kg or more and less than 30 kg.
iv. 2700 mg of the anti-C5 antibody or the antigen-binding fragment thereof for a patient weighing 30 kg or more and less than 40 kg.
v. 3000 mg of the anti-C5 antibody or its antigen-binding fragment for a patient weighing 40 kg or more and less than 60 kg.
vi. 3300 mg of the anti-C5 antibody or the antigen-binding fragment thereof, or 3300 mg of the anti-C5 antibody or an antigen-binding fragment thereof for a patient weighing 60 kg or more and less than 100 kg.
vii. Patients weighing 100 kg or more were administered with a maintenance dose of 3600 mg of the anti-C5 antibody or the antigen-binding fragment thereof , and patients weighing less than 20 kg were subsequently given an additional maintenance dose every 4 weeks and weighed 20 kg or more. The composition is characterized in that the patient is subsequently given an additional maintenance dose every 8 weeks.

The composition according to claim 1 or 2, wherein the anti-C5 antibody comprises a heavy chain variable region set forth in SEQ ID NO: 12 and a light chain variable region set forth in SEQ ID NO: 8.

The composition according to any one of claims 1 to 3, wherein the anti-C5 antibody further comprises the heavy chain constant region set forth in SEQ ID NO: 13.

One of claims 1 to 4, wherein the antibody comprises a heavy chain polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 14 and a light chain polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 11. The composition according to .

The anti-C5 antibody according to any one of claims 1 to 5, wherein the anti-C5 antibody binds to human C5 at pH 7.4 and 25C with an affinity dissociation constant ( _KD ) in the range of 0.1 nM to 1 nM. Composition .

The composition according to any one of claims 1 to 6, wherein the anti-C5 antibody binds to human C5 at pH 6.0 and 25C at _KD ≧ 10 nM.

For patients whose composition weighs 5 kg or more and less than 10 kg
(A) once on day 1 at a loading dose of 600 mg of the anti-C5 antibody or said antigen-binding fragment thereof , and (b) once on day 15 of 300 mg of said anti-C5 antibody or said antigen thereof. The composition according to any one of claims 1 to 7, characterized in that it is administered at a maintenance dose of the bound fragment and every 4 weeks thereafter.

For patients whose body weight is 10 kg or more and less than 20 kg
(A) once on day 1 at a loading dose of 600 mg of the anti-C5 antibody or said antigen-binding fragment thereof , and (b) once on day 15 of 600 mg of said anti-C5 antibody or said antigen thereof. The composition according to any one of claims 1 to 7, characterized in that it is administered at a maintenance dose of the bound fragment and every 4 weeks thereafter.

For patients whose composition weighs 20 kg or more and less than 30 kg
(A) once on day 1 at a loading dose of 900 mg of the anti-C5 antibody or said antigen-binding fragment thereof , and (b) once on day 15 of 2100 mg of said anti-C5 antibody or said antigen thereof. The composition according to any one of claims 1 to 7, characterized in that it is administered at a maintenance dose of the bound fragment and every 8 weeks thereafter.

For patients whose composition weighs 30 kg or more and less than 40 kg
(A) once on day 1 at a loading dose of 1200 mg of the anti-C5 antibody or said antigen-binding fragment thereof , and (b) once on day 15 of 2700 mg of said anti-C5 antibody or said antigen thereof. The composition according to any one of claims 1 to 7, characterized in that it is administered at a maintenance dose of the bound fragment and every 8 weeks thereafter.

For patients whose composition weighs 40 kg or more and less than 60 kg
(A) once on day 1 at a loading dose of 2400 mg of the anti-C5 antibody or said antigen-binding fragment thereof , and (b) once on day 15 of 3000 mg of said anti-C5 antibody or said antigen thereof. The composition according to any one of claims 1 to 7, characterized in that it is administered at a maintenance dose of the bound fragment and every 8 weeks thereafter.

For patients whose composition weighs 60 kg or more and less than 100 kg
(A) once on day 1 at a loading dose of 2700 mg of the anti-C5 antibody or said antigen-binding fragment thereof , and (b) once on day 15 of 3300 mg of said anti-C5 antibody or said antigen thereof. The composition according to any one of claims 1 to 7, characterized in that it is administered at a maintenance dose of the bound fragment and every 8 weeks thereafter.

The composition is used for patients weighing 100 kg or more.
(A) once on day 1 at a loading dose of 3000 mg of the anti-C5 antibody or said antigen-binding fragment thereof , and (b) once on day 15 of 3600 mg of said anti-C5 antibody or said antigen thereof. The composition according to any one of claims 1 to 7, characterized in that it is administered at a maintenance dose of the bound fragment and every 8 weeks thereafter.

The composition according to any one of claims 1 to 14, wherein the treatment maintains a serum trough concentration of the anti-C5 antibody or an antigen-binding fragment thereof at 100 μg / mL or more.

The composition according to any one of claims 1 to 15, wherein the treatment maintains a serum trough concentration of the anti-C5 antibody or an antigen-binding fragment thereof at 200 μg / mL or more.

The composition according to any one of claims 1 to 16, wherein the treatment maintains a free C5 concentration of 0.309 to 0.5 μg / mL or less.

Any of claims 1-17, wherein the composition is administered at a dose of 300 mg or 600 mg of the anti-C5 antibody or antigen-binding fragment thereof every 4 weeks for up to 2 years after treatment. The composition according to one item.

The composition is characterized by being administered at a dose of 2100 mg, 2700 mg, 3000 mg, 3300 mg, or 3600 mg of the anti-C5 antibody or antigen-binding fragment thereof every 8 weeks for up to 2 years after treatment. The composition according to any one of claims 1 to 18.

The composition according to any one of claims 1 to 19, wherein the composition is formulated for intravenous administration.

The composition according to any one of claims 1 to 20, wherein the patient has not been treated with a complement inhibitor in the past.

The composition according to any one of claims 1 to 21, wherein the patient is under the age of 18.

The composition according to any one of claims 1 to 22, wherein the treatment is a dosing cycle comprising a total of 26 weeks of treatment.

The composition according to any one of claims 1 to 23, wherein the treatment results in inhibition of terminal complement.

The composition according to any one of claims 1 to 24, wherein the treatment results in a complete thrombotic microangiopathy (TMA) response.

The composition according to any one of claims 1 to 25, wherein the treatment results in a 25% or greater reduction in serum creatinine levels as compared to a reference.

The composition according to any one of claims 1 to 26, wherein the treatment results in an increase in platelet count as compared to a reference.

The composition according to any one of claims 1-27, wherein the treatment results in a reduction in hemolysis as compared to a reference when assessed by lactate dehydrogenase (LDH) levels.

At least one of the treatments selected from the group consisting of severe hypertension, urinary protein, uremia, malaise, fatigue, hypersensitivity, thrombocytopenia, microangiogenic hemolytic anemia and renal dysfunction compared to the criteria. The composition according to claim 1 or 2, which causes a decrease or cessation of one therapeutic marker.

The treatment is selected from the group consisting of Factor Ba, soluble tumor necrosis factor receptor 1 (sTNFR1), soluble vascular adhesion molecule 1 (sVCAM1), thrombomodulin, D-dimer, and cystatin C as compared to the criteria. The composition according to any one of claims 1-29, which causes a shift of the marker to a normal level.

The composition according to any one of claims 1 to 30, wherein the treatment results in a reduced need for blood transfusion as compared to a reference.

The composition according to any one of claims 1-31, wherein the treatment results in a reduction in major adverse vascular event (MAVE) as compared to a reference.

The treatment is compared to the criteria for functional assessment of chronic disease treatment (FACIT) -fatigue scale, 4th edition, or European Canceration for Research and Treatment. , Claims 1-32, which cause a change from the standard in the quality of life, evaluated via the Quality of Life Questionnaire-Core 30 Scale. The composition according to any one.

A kit for the treatment of atypical hemolytic urinary toxicosis syndrome (aHUS) in human pediatric patients.
(A) the CDR1, CDR2, and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 12, and the CDR1, CDR2, and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO: 8. A kit comprising the dose of an anti-C5 antibody or an antigen-binding fragment thereof, and (b) instructions for using the anti-C5 antibody or an antigen-binding fragment thereof in the method according to claim 1 or 2. ..

The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 5 kg or more and less than 10 kg.
(A) Once on day 1 at a loading dose of 600 mg, and (b) once on day 15 at a maintenance dose of 300 mg, and thereafter every 4 weeks, claim 34. The kit described.

The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 10 kg or more and less than 20 kg.
(A) Once on day 1 at a loading dose of 600 mg, and (b) once on day 15 at a maintenance dose of 600 mg, and thereafter every 4 weeks, claim 34. The kit described.

The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 20 kg or more and less than 30 kg.
(A) Once on day 1 at a loading dose of 900 mg, and (b) once on day 15 at a maintenance dose of 2100 mg, and thereafter every 8 weeks, claim 34. The kit described.

The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 30 kg or more and less than 40 kg.
(A) Once on day 1 at a loading dose of 1200 mg, and (b) once on day 15 at a maintenance dose of 2700 mg, and every 8 weeks thereafter, claim 34. The kit described.

The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 40 kg or more and less than 60 kg.
(A) Once on day 1 at a loading dose of 2400 mg, and (b) once on day 15 at a maintenance dose of 3000 mg, and every 8 weeks thereafter, claim 34. The kit described.

The anti-C5 antibody or an antigen-binding fragment thereof is used for patients weighing 60 kg or more and less than 100 kg.
(A) Once on day 1 at a loading dose of 2700 mg, and (b) once on day 15 at a maintenance dose of 3300 mg, and thereafter every 8 weeks, claim 34. The kit described.

The anti-C5 antibody or an antigen-binding fragment thereof can be applied to a patient weighing 100 kg or more.
(A) Once on day 1 at a loading dose of 3000 mg, and (b) once on day 15 at a maintenance dose of 3600 mg, and every 8 weeks thereafter, claim 34. The kit described.

It comprises the CDR1, CDR2, and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 12 and the CDR1, CDR2, and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO: 8. An anti-C5 antibody or an antigen-binding fragment thereof, wherein the anti-C5 antibody or an antigen-binding fragment thereof is used.
(A) On the first day,
i. 600 mg for patients weighing 5 kg or more and less than 10 kg,
ii. 600 mg for patients weighing 10 kg or more and less than 20 kg,
iii. 900 mg for patients weighing 20 kg or more and less than 30 kg,
iv. 1200 mg for patients weighing 30 kg or more and less than 40 kg,
v. 2400 mg for patients weighing 40 kg or more and less than 60 kg,
vi. 2700 mg, or 2700 mg for patients weighing 60 kg or more and less than 100 kg
vii. Once at a loading dose of 3000 mg for patients weighing 100 kg or more, and (b) on day 15.
i. 300 mg for patients weighing 5 kg or more and less than 10 kg,
ii. 600 mg for patients weighing 10 kg or more and less than 20 kg,
iii. 2100 mg for patients weighing 20 kg or more and less than 30 kg,
iv. 2700 mg for patients weighing 30 kg or more and less than 40 kg,
v. 3000 mg for patients weighing 40 kg or more and less than 60 kg,
vi. 3300 mg or 3300 mg for patients weighing 60 kg or more and less than 100 kg
vii. Patients weighing 100 kg or more were given a maintenance dose of 3600 mg, patients weighing less than 20 kg were subsequently given an additional maintenance dose every 4 weeks, and patients weighing 20 kg or more were subsequently given an additional maintenance dose every 8 weeks. An anti-C5 antibody or antigen-binding fragment thereof given a maintenance dose.

42. The antibody of claim 42, wherein said antibody is determined to be safe, tolerable, effective, and sufficiently non-immunogenic after multiple IV doses in aHUS patients.