JPWO2021011903A5 - - Google Patents

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JPWO2021011903A5
JPWO2021011903A5 JP2022503450A JP2022503450A JPWO2021011903A5 JP WO2021011903 A5 JPWO2021011903 A5 JP WO2021011903A5 JP 2022503450 A JP2022503450 A JP 2022503450A JP 2022503450 A JP2022503450 A JP 2022503450A JP WO2021011903 A5 JPWO2021011903 A5 JP WO2021011903A5
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Priority claimed from PCT/US2020/042627 external-priority patent/WO2021011903A1/en
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関連出願の相互参照
本出願は、２０１９年７月１７日に出願された米国仮特許出願第６２／８７５，３０９号の利益及び優先権を主張するものであり、同仮特許出願の開示内容は、あらゆる目的のために全体として参照により本明細書に組み込まれる。
本出願には、ＡＳＣＩＩフォーマットで電子提出され、参照により全体として本明細書に組み込まれる配列表が含まれる。２０２０年８月４日に作成された前記ＡＳＣＩＩコピーは、ＧＥＭ－０１３ＷＯ＿ＳＬ．ｔｘｔという名称であり、１８，０３７バイトのサイズである。
CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62/875,309, filed July 17, 2019, the disclosure of which is , which is incorporated herein by reference in its entirety for all purposes.
The present application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy made on August 4, 2020 is GEM-013WO_SL. txt and is 18,037 bytes in size.

Claims (34)

Ｈ因子（ＦＨ）の補体制御タンパク質ドメイン１８（ＣＣＰ１８）に特異的に結合する、単離型、合成型、もしくは組換え型の抗体またはその抗原結合性フラグメントであって、
－ 配列ＳＳＶＴＹ（配列番号１）または配列ＴＳＶＴＹ（配列番号１３）を含む軽鎖ＣＤＲ１配列、
－ 配列ＡＴＳ（配列番号２）または配列ＡＳＳ（配列番号１４）を含む軽鎖ＣＤＲ２配列、
－ 配列ＱＨＲＳＳＳＮＰＬＴ（配列番号３）を含む軽鎖ＣＤＲ３配列、
－ 配列ＧＦＳＬＴＮＹＧ（配列番号５）を含む重鎖ＣＤＲ１配列、
－ 配列ＩＷＳＧＧＴＴ（配列番号１０）または配列ＶＷＳＧＧＴＴ（配列番号６）を含む重鎖ＣＤＲ２配列、及び
－ 配列ＡＲＮＦＧＮＹＡＭＤＦ（配列番号１１）または配列ＡＲＮＦＧＮＹＡＭＤＹ（配列番号７）を含む重鎖ＣＤＲ３配列
を含む、前記抗体またはその抗原結合性フラグメント。 An isolated, synthetic, or recombinant antibody or antigen-binding fragment thereof that specifically binds to complement regulatory protein domain 18 (CCP18) of factor H (FH), comprising:
- a light chain CDR1 sequence comprising the sequence SSVTY (SEQ ID NO: 1) or the sequence TSVTY (SEQ ID NO: 13),
- a light chain CDR2 sequence comprising the sequence ATS (SEQ ID NO: 2) or the sequence ASS (SEQ ID NO: 14),
- a light chain CDR3 sequence comprising the sequence QHRSSNPLT (SEQ ID NO: 3),
- a heavy chain CDR1 sequence comprising the sequence GFSLTNYG (SEQ ID NO: 5),
- a heavy chain CDR2 sequence comprising the sequence IWSGGTT (SEQ ID NO: 10) or the sequence VWSGGTT (SEQ ID NO: 6) and - a heavy chain CDR3 sequence comprising the sequence ARNFGNYAMDF (SEQ ID NO: 11) or the sequence ARNFGNYAMDY (SEQ ID NO: 7) said antibody or antigen-binding fragment thereof. － 配列ＳＳＶＴＹ（配列番号１）を含む軽鎖ＣＤＲ１配列、
－ 配列ＡＴＳ（配列番号２）を含む軽鎖ＣＤＲ２配列、
－ 配列ＱＨＲＳＳＳＮＰＬＴ（配列番号３）を含む軽鎖ＣＤＲ３配列、
－ 配列ＧＦＳＬＴＮＹＧ（配列番号５）を含む重鎖ＣＤＲ１配列、
－ 配列ＩＷＳＧＧＴＴ（配列番号１０）を含む重鎖ＣＤＲ２配列、及び
－ 配列ＡＲＮＦＧＮＹＡＭＤＦ（配列番号１１）を含む重鎖ＣＤＲ３配列
を含む、請求項１に記載の抗体またはフラグメント。 - a light chain CDR1 sequence comprising the sequence SSVTY (SEQ ID NO: 1),
- a light chain CDR2 sequence comprising the sequence ATS (SEQ ID NO: 2),
- a light chain CDR3 sequence comprising the sequence QHRSSNPLT (SEQ ID NO: 3),
- a heavy chain CDR1 sequence comprising the sequence GFSLTNYG (SEQ ID NO: 5),
- a heavy chain CDR2 sequence comprising the sequence IWSGGTT (SEQ ID NO: 10); and - a heavy chain CDR3 sequence comprising the sequence ARNFGNYAMDF (SEQ ID NO: 11). － 配列ＳＳＶＴＹ（配列番号１）を含む軽鎖ＣＤＲ１配列、
－ 配列ＡＴＳ（配列番号２）を含む軽鎖ＣＤＲ２配列、
－ 配列ＱＨＲＳＳＳＮＰＬＴ（配列番号３）を含む軽鎖ＣＤＲ３配列、
－ 配列ＧＦＳＬＴＮＹＧ（配列番号５）を含む重鎖ＣＤＲ１配列、
－ 配列ＶＷＳＧＧＴＴ（配列番号６）を含む重鎖ＣＤＲ２配列、及び
－ 配列ＡＲＮＦＧＮＹＡＭＤＹ（配列番号７）を含む重鎖ＣＤＲ３配列
を含む、請求項１に記載の抗体またはフラグメント。 - a light chain CDR1 sequence comprising the sequence SSVTY (SEQ ID NO: 1),
- a light chain CDR2 sequence comprising the sequence ATS (SEQ ID NO: 2),
- a light chain CDR3 sequence comprising the sequence QHRSSNPLT (SEQ ID NO: 3),
- a heavy chain CDR1 sequence comprising the sequence GFSLTNYG (SEQ ID NO: 5),
- a heavy chain CDR2 sequence comprising the sequence VWSGGTT (SEQ ID NO: 6); and - a heavy chain CDR3 sequence comprising the sequence ARNFGNYAMDY (SEQ ID NO: 7). － 配列ＴＳＶＴＹ（配列番号１３）を含む軽鎖ＣＤＲ１配列、
－ 配列ＡＳＳ（配列番号１４）を含む軽鎖ＣＤＲ２配列、
－ 配列ＱＨＲＳＳＳＮＰＬＴ（配列番号３）を含む軽鎖ＣＤＲ３配列、
－ 配列ＧＦＳＬＴＮＹＧ（配列番号５）を含む重鎖ＣＤＲ１配列、
－ 配列ＶＷＳＧＧＴＴ（配列番号６）を含む重鎖ＣＤＲ２配列、及び
－ 配列ＡＲＮＦＧＮＹＡＭＤＹ（配列番号７）を有する重鎖ＣＤＲ３配列
を含む、請求項１に記載の抗体またはフラグメント。 - a light chain CDR1 sequence comprising the sequence TSVTY (SEQ ID NO: 13),
- a light chain CDR2 sequence comprising the sequence ASS (SEQ ID NO: 14),
- a light chain CDR3 sequence comprising the sequence QHRSSNPLT (SEQ ID NO: 3),
- a heavy chain CDR1 sequence comprising the sequence GFSLTNYG (SEQ ID NO: 5),
- a heavy chain CDR2 sequence comprising the sequence VWSGGTT (SEQ ID NO: 6); and - a heavy chain CDR3 sequence having the sequence ARNFGNYAMDY (SEQ ID NO: 7). － 配列ＴＳＶＴＹ（配列番号１３）を含む軽鎖ＣＤＲ１配列、
－ 配列ＡＳＳ（配列番号１４）を含む軽鎖ＣＤＲ２配列、
－ 配列ＱＨＲＳＳＳＮＰＬＴ（配列番号３）を含む軽鎖ＣＤＲ３配列、
－ 配列ＧＦＳＬＴＮＹＧ（配列番号５）を含む重鎖ＣＤＲ１配列、
－ 配列ＩＷＳＧＧＴＴ（配列番号１０）を含む重鎖ＣＤＲ２配列、及び
－ 配列ＡＲＮＦＧＮＹＡＭＤＦ（配列番号１１）を含む重鎖ＣＤＲ３配列
を含む、請求項１に記載の抗体またはフラグメント。 - a light chain CDR1 sequence comprising the sequence TSVTY (SEQ ID NO: 13),
- a light chain CDR2 sequence comprising the sequence ASS (SEQ ID NO: 14),
- a light chain CDR3 sequence comprising the sequence QHRSSNPLT (SEQ ID NO: 3),
- a heavy chain CDR1 sequence comprising the sequence GFSLTNYG (SEQ ID NO: 5),
- a heavy chain CDR2 sequence comprising the sequence IWSGGTT (SEQ ID NO: 10); and - a heavy chain CDR3 sequence comprising the sequence ARNFGNYAMDF (SEQ ID NO: 11). 前記抗体またはフラグメントは、ＦＨに対して２．５×１０－８Ｍ以下のＫＤの結合親和性及び／またはＣＣＰ１８～２０から成るＦＨフラグメントに対して０．１×１０－９Ｍ以下のＫＤの結合親和性を有するか、あるいは、前記抗体またはフラグメントは、ＦＨに対して１．２５×１０－８Ｍ以下のＫＤの結合親和性及び／またはＣＣＰ１８～２０から成るＦＨフラグメントに対して０．０４×１０－９Ｍ以下のＫＤの結合親和性を有する、請求項１～５のいずれか１項に記載の抗体またはフラグメント。 Said antibody or fragment has a binding affinity for FH with a K D of 2.5×10 −8 M or less and/or a K of 0.1×10 −9 M or less for the FH fragment consisting of CCP18-20 Alternatively, said antibody or fragment has a binding affinity of K D for FH of 1.25×10 −8 M or less and/or for the FH fragment consisting of CCP18-20 An antibody or fragment according to any one of claims 1 to 5, which has a binding affinity of K D of 0.04 x 10 -9 M or less. 前記抗体またはフラグメントは、ＦＨに対して２．５×１０－８Ｍ以下のＫＤの結合親和性及び／またはＣＣＰ１８～２０から成るＦＨフラグメントに対して０．１×１０－９Ｍ以下のＫＤの結合親和性を有するか、あるいは、前記抗体またはフラグメントは、ＦＨに対して０．６×１０－８Ｍ以下のＫＤの結合親和性及び／またはＣＣＰ１８～２０から成るＦＨフラグメントに対して０．６×１０－１１Ｍ以下のＫＤの結合親和性を有する、請求項１～５のいずれか１項に記載の抗体またはフラグメント。 Said antibody or fragment has a binding affinity for FH with a K D of 2.5×10 −8 M or less and/or a K of 0.1×10 −9 M or less for the FH fragment consisting of CCP18-20 Alternatively, said antibody or fragment has a binding affinity of K D for FH of 0.6×10 −8 M or less and/or for the FH fragment consisting of CCP18-20 An antibody or fragment according to any one of claims 1 to 5, which has a binding affinity of K D of 0.6 x 10 -11 M or less. 前記抗体またはフラグメントは、
－ １０％（ｖ／ｖ）の血清の存在下で、ｉｎ ｖｉｔｒｏのリポ多糖におけるＣ３ｂ沈着を、３８ｎＭ以下のＩＣ５０値、例えば３０ｎＭ以下のＩＣ５０値で阻害する、及び／または
－ １０％（ｖ／ｖ）の血清の存在下で、ｉｎ ｖｉｔｒｏの溶血活性を、１５０ｎＭ以下のＩＣ５０値、例えば１３０ｎＭ以下のＩＣ５０値で阻害する、及び／または
－ ｉｎ ｖｉｔｒｏのＣ３ｂに対するＦＨのＫＤを最大で２μＭまで減少させる（結合親和性を増加させる）、及び／またはｉｎ ｖｉｔｒｏのＣ３ｂに対するＦＨの結合親和性を少なくとも３倍増加させる、請求項１～７のいずれか１項に記載の抗体またはフラグメント。 Said antibody or fragment is
- inhibits C3b deposition on lipopolysaccharide in vitro in the presence of 10% (v/v) serum with an IC50 value of 38 nM or less, such as an IC50 value of 30 nM or less, and/or - 10% (v/v) inhibits hemolytic activity in vitro with an IC 50 value of 150 nM or less, such as an IC 50 value of 130 nM or less, and/or - K D of FH for C3b in vitro up to 2 μM (increase binding affinity) and/or increase the binding affinity of FH to C3b in vitro by at least 3-fold or fragment. － 配列番号４または配列番号１６に対して少なくとも８０％、少なくとも８５％、少なくとも９０％、少なくとも９１％、少なくとも９２％、少なくとも９３％、少なくとも９４％、少なくとも９５％、少なくとも９６％、少なくとも９７％、少なくとも９８％、少なくとも９９％、または１００％の配列同一性を有する配列を含む可変軽鎖配列、および
－ 配列番号１２または配列番号８に対して少なくとも８０％、少なくとも８５％、少なくとも９０％、少なくとも９１％、少なくとも９２％、少なくとも９３％、少なくとも９４％、少なくとも９５％、少なくとも９６％、少なくとも９７％、少なくとも９８％、少なくとも９９％、または１００％の配列同一性を有する配列を含む可変重鎖配列
を含む、請求項１～８のいずれか１項に記載の抗体またはフラグメント。 - at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97% relative to SEQ ID NO: 4 or SEQ ID NO: 16 , variable light chain sequences comprising sequences having at least 98%, at least 99%, or 100% sequence identity, and
- at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97% relative to SEQ ID NO : 12 or SEQ ID NO: 8 , a variable heavy chain sequence comprising a sequence having at least 98%, at least 99%, or 100% sequence identity. 配列番号４に対して少なくとも８０％、少なくとも８５％、少なくとも９０％、少なくとも９１％、少なくとも９２％、少なくとも９３％、少なくとも９４％、少なくとも９５％、少なくとも９６％、少なくとも９７％、少なくとも９８％、少なくとも９９％、または１００％の配列同一性を有する配列を含む可変軽鎖配列と、配列番号１２に対して少なくとも８０％、少なくとも８５％、少なくとも９０％、少なくとも９１％、少なくとも９２％、少なくとも９３％、少なくとも９４％、少なくとも９５％、少なくとも９６％、少なくとも９７％、少なくとも９８％、少なくとも９９％、または１００％の配列同一性を有する配列を含む可変重鎖配列とを含む、請求項１～９のいずれか１項に記載の抗体またはフラグメント。at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, relative to SEQ ID NO:4; A variable light chain sequence comprising a sequence having at least 99% or 100% sequence identity to SEQ ID NO: 12 at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93 %, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. 10. The antibody or fragment of any one of 9. 配列番号４に対して少なくとも８０％、少なくとも８５％、少なくとも９０％、少なくとも９１％、少なくとも９２％、少なくとも９３％、少なくとも９４％、少なくとも９５％、少なくとも９６％、少なくとも９７％、少なくとも９８％、少なくとも９９％、または１００％の配列同一性を有する配列を含む可変軽鎖配列と、配列番号８に対して少なくとも８０％、８５％、９０％、９１％、９２％、９３％、９４％、９５％、９６％、９７％、９８％、９９％、または１００％の配列同一性を有する配列を含む可変重鎖配列とを含む、請求項１～９のいずれか１項に記載の抗体またはフラグメント。 at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, relative to SEQ ID NO:4; A variable light chain sequence comprising a sequence having at least 99% or 100% sequence identity to SEQ ID NO :8 at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, variable heavy chain sequences comprising sequences having 95%, 96%, 97%, 98%, 99%, or 100% sequence identity; or fragment. 配列番号１６に対して少なくとも８０％、少なくとも８５％、少なくとも９０％、少なくとも９１％、少なくとも９２％、少なくとも９３％、少なくとも９４％、少なくとも９５％、少なくとも９６％、少なくとも９７％、少なくとも９８％、少なくとも９９％、または１００％の配列同一性を有する配列を含む可変軽鎖配列と、配列番号８に対して少なくとも８０％、少なくとも８５％、少なくとも９０％、少なくとも９１％、少なくとも９２％、少なくとも９３％、少なくとも９４％、少なくとも９５％、少なくとも９６％、少なくとも９７％、少なくとも９８％、少なくとも９９％、または１００％の配列同一性を有する配列を含む可変重鎖配列とを含む、請求項１～９のいずれか１項に記載の抗体またはフラグメント。 at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% relative to SEQ ID NO: 16, A variable light chain sequence comprising a sequence having at least 99% or 100% sequence identity to SEQ ID NO:8 at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93% %, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. 10. The antibody or fragment of any one of 9. 配列番号１６に対して少なくとも８０％、少なくとも８５％、少なくとも９０％、少なくとも９１％、少なくとも９２％、少なくとも９３％、少なくとも９４％、少なくとも９５％、少なくとも９６％、少なくとも９７％、少なくとも９８％、少なくとも９９％、または１００％の配列同一性を有する配列を含む可変軽鎖配列と、配列番号１２に対して少なくとも８０％、少なくとも８５％、少なくとも９０％、少なくとも９１％、少なくとも９２％、少なくとも９３％、少なくとも９４％、少なくとも９５％、少なくとも９６％、少なくとも９７％、少なくとも９８％、少なくとも９９％、または１００％の配列同一性を有する配列を含む可変重鎖配列とを含む、請求項１～９のいずれか１項に記載の抗体またはフラグメント。 at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% relative to SEQ ID NO: 16, A variable light chain sequence comprising a sequence having at least 99% or 100% sequence identity to SEQ ID NO: 12 at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93 %, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. 10. The antibody or fragment of any one of 9. 前記抗体またはフラグメントは、ＦＨ活性を増強し、場合により、前記ＦＨ活性は、代替補体活性化の阻害であり、さらに場合により、代替補体活性化の阻害は、
－ 溶血活性の阻害、
－ Ｃ３ｂ沈着の阻害、及び／または
－ Ｃ３ｂ、ｉＣ３ｂ及び／またはＣ３ｄに対するＦＨの結合の増加
を含む、請求項１～１３のいずれか１項に記載の抗体またはフラグメント。 Said antibody or fragment enhances FH activity, optionally said FH activity is inhibition of alternative complement activation, further optionally inhibition of alternative complement activation is
- inhibition of hemolytic activity,
Antibody or fragment according to any one of claims 1 to 13, comprising - inhibition of C3b deposition and/or - increased binding of FH to C3b, iC3b and/or C3d. 前記抗体またはフラグメントは、免疫グロブリン重鎖可変領域及び免疫グロブリン軽鎖可変領域を含み、免疫グロブリン重鎖定常領域及び免疫グロブリン軽鎖定常領域をさらに含む、請求項１～１４のいずれか１項に記載の抗体またはフラグメント。 15. The antibody or fragment of any one of claims 1-14, comprising an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region, further comprising an immunoglobulin heavy chain constant region and an immunoglobulin light chain constant region. An antibody or fragment as described. 前記抗体またはフラグメントは、Ｆａｂフラグメントを含む、請求項１～１５のいずれか１項に記載の抗体またはフラグメント。 16. The antibody or fragment of any one of claims 1-15, wherein said antibody or fragment comprises a Fab fragment. 前記抗体またはフラグメントは、モノクローナルである、請求項１～１６のいずれか１項に記載の抗体またはフラグメント。 17. The antibody or fragment of any one of claims 1-16, wherein said antibody or fragment is monoclonal. 前記抗体またはフラグメントは、ヒト軽鎖及び重鎖定常領域を含む、請求項１～１７のいずれか１項に記載の抗体またはフラグメント。 18. The antibody or fragment of any one of claims 1-17, wherein said antibody or fragment comprises human light and heavy chain constant regions. 定常領域がヒトＩｇＧ４のＦｃドメインを含む、請求項１８に記載の抗体またはフラグメント。19. The antibody or fragment of claim 18, wherein the constant region comprises the Fc domain of human IgG4. ヒトＩｇＧ４のＦｃドメインが２９７位にアミノ酸残基ＡｌａまたはＧｌｎを含む、請求項１９に記載の抗体またはフラグメント。20. The antibody or fragment of claim 19, wherein the Fc domain of human IgG4 comprises amino acid residue Ala or Gln at position 297. 前記抗体またはフラグメントは、ＰＥＧ化されている、請求項１～２０のいずれか１項に記載の抗体またはフラグメント。 21. The antibody or fragment of any one of claims 1-20 , wherein said antibody or fragment is pegylated. 前記抗体またはフラグメントは、ＰＥＧ化されたＦａｂフラグメントである、請求項２１に記載の抗体またはフラグメント。 22. The antibody or fragment of claim 21 , wherein said antibody or fragment is a PEGylated Fab fragment. 請求項１～２２のいずれか１項に記載の抗体またはフラグメントをコードする核酸配列を含む、単離型、合成型、もしくは組換え型の核酸。 An isolated, synthetic, or recombinant nucleic acid comprising a nucleic acid sequence encoding the antibody or fragment of any one of claims 1-22 . 請求項２３に記載の核酸を含むベクター。 A vector comprising the nucleic acid of claim 23 . 前記ベクターは、ＡＡＶベクターである、請求項２４に記載のベクター。 25. The vector of claim 24 , wherein said vector is an AAV vector. 前記ＡＡＶベクターは、ＡＡＶ１、ＡＡＶ２、ＡＡＶ３、ＡＡＶ４、ＡＡＶ５、ＡＡＶ６、ＡＡＶ７、ＡＡＶ８、ＡＡＶ９、ＡＡＶ１０、ＡＡＶ１１、及びＡＡＶ１２からなる群から選択される、請求項２５に記載のベクター。 26. The vector of claim 25 , wherein said AAV vector is selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. 請求項２３に記載の核酸、または請求項２４～２６のいずれか１項に記載のベクターを含む、組換え型細胞。 A recombinant cell comprising a nucleic acid according to claim 23 or a vector according to any one of claims 24-26 . 請求項１～２２のいずれか１項に記載の抗体もしくはフラグメント、請求項２３に記載の核酸、請求項２４～２６のいずれか１項に記載のベクター、または請求項２７に記載の組換え型細胞、ならびに薬学的に許容されるキャリア、希釈剤、及び／または賦形剤を含む、医薬組成物。 An antibody or fragment according to any one of claims 1 to 22 , a nucleic acid according to claim 23 , a vector according to any one of claims 24 to 26 , or a recombinant according to claim 27 . A pharmaceutical composition comprising cells and a pharmaceutically acceptable carrier, diluent and/or excipient. 療法において使用するための、請求項１～２２のいずれか１項に記載の抗体もしくはフラグメント、請求項２３に記載の核酸、請求項２４～２６のいずれか１項に記載のベクター、請求項２７に記載の組換え型細胞、または請求項２８に記載の医薬組成物。 An antibody or fragment according to any one of claims 1 to 22 , a nucleic acid according to claim 23 , a vector according to any one of claims 24 to 26 , claim 27 , for use in therapy or the pharmaceutical composition of claim 28 . 代替補体活性化を阻害するのに使用するための、請求項１～２２のいずれか１項に記載の抗体もしくはフラグメント、請求項２３に記載の核酸、請求項２４～２６のいずれか１項に記載のベクター、請求項２７に記載の組換え型細胞、または請求項２８に記載の医薬組成物。 An antibody or fragment according to any one of claims 1 to 22 , a nucleic acid according to claim 23 , any one of claims 24 to 26, for use in inhibiting alternative complement activation. 28. The vector of claim 27, the recombinant cell of claim 27 , or the pharmaceutical composition of claim 28 . 代替経路補体活性化に関連する障害の治療、緩和、または防止において使用するための、請求項１～２２のいずれか１項に記載の抗体もしくはフラグメント、請求項２３に記載の核酸、請求項２４～２６のいずれか１項に記載のベクター、請求項２７に記載の組換え型細胞、または請求項２８に記載の医薬組成物。 an antibody or fragment of any one of claims 1 to 22 , a nucleic acid of claim 23, a nucleic acid of claim 23 , for use in treating, alleviating or preventing a disorder associated with alternative pathway complement activation The vector of any one of claims 24-26 , the recombinant cell of claim 27 , or the pharmaceutical composition of claim 28 . 前記障害は、非典型溶血性尿毒症症候群（ａＨＵＳ）、発作性夜間ヘモグロビン尿症（ＰＮＨ）、加齢性黄斑変性（ＡＭＤ）、膜性増殖性糸球体腎炎（ＭＰＧＮ）、及びＩｇＡ腎症からなる群から選択される、請求項３１に記載の使用のための抗体もしくはフラグメント、核酸、組換え型細胞、または医薬組成物。 The disorders include atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), age-related macular degeneration (AMD), membranous proliferative glomerulonephritis (MPGN), and IgA nephropathy. 32. An antibody or fragment, nucleic acid, recombinant cell, or pharmaceutical composition for use according to claim 31 selected from the group consisting of: 抗体またはフラグメントを生成する方法であって、請求項２３に記載の核酸または請求項２４～２６のいずれか１項に記載のベクターを細胞に供給することと、前記核酸またはベクターに含まれる前記核酸配列を前記細胞に翻訳させることにより、請求項１～２２のいずれか１項に記載の抗体またはフラグメントを生成することとを含む前記方法。 A method of producing an antibody or fragment comprising providing a cell with a nucleic acid according to claim 23 or a vector according to any one of claims 24-26 and said nucleic acid or said nucleic acid contained in a vector producing the antibody or fragment of any one of claims 1-22 by translating a sequence into said cell. 前記抗体またはフラグメントを採取、精製、及び／または単離することをさらに含む、請求項３３に記載の方法。 34. The method of claim 33 , further comprising harvesting, purifying, and/or isolating said antibody or fragment.
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