JP6170507B2 - B型インフルエンザウイルスに対する広範な保護を与えるヒトモノクローナル抗体及びその使用方法 - Google Patents
B型インフルエンザウイルスに対する広範な保護を与えるヒトモノクローナル抗体及びその使用方法 Download PDFInfo
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Classifications
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- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1018—Orthomyxoviridae, e.g. influenza virus
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
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- G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
- G01N2333/08—RNA viruses
- G01N2333/11—Orthomyxoviridae, e.g. influenza virus
Landscapes
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- Public Health (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
本願は、2012年1月31日付けで出願された米国仮特許出願第61/592,657号(その内容全体が引用することにより本明細書の一部をなす)の利益を主張するものである。
本明細書に記載される主題は、独立行政法人科学技術振興機構/独立行政法人国際協力機構による地球規模課題対応国際科学技術協力プログラム(Science and Technology Research Partnership for Sustainable Development)(JST/JICA、SATREPS);及び日本学術振興会による若手研究(Grant-in-Aidfor Young Scientists)(B)による安木真世に対する支援を少なくとも一部受けたものである。
本発明は、ヒトB型インフルエンザウイルスに対して中和活性を有する抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントであって、モノクローナル抗体がヒトモノクローナル抗体及び/又はヒト化モノクローナル抗体を含む、抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントを提供する。モノクローナル抗体又はその抗原結合フラグメントは、少なくともB/Florida/4/2006株、B/Shanghai/361/2002株、B/Johannesburg/5/1999株、B/Yamanashi/166/1998株、及びB/Mie/1/1993株に対する中和活性を有し得る。モノクローナル抗体又はその抗原結合フラグメントは、少なくともB/Florida/4/2006株、B/Shanghai/361/2002株、B/Johannesburg/5/1999株、B/Yamanashi/166/1998株、B/Mie/1/1993株、B/Malaysia/2506/04株、B/Shandong/7/1997株、及びB/Victoria/2/1987株に対する中和活性を有し得る。抗ヒトB型インフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントは、IgG、Fab、Fab’、F(ab’)2、scFv、dsFv、又は任意のそれらの組合せを含み得る。
1. 本発明は、ヒトB型インフルエンザウイルスに対する中和活性を備える抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントであって、該モノクローナル抗体がヒトモノクローナル抗体又はヒト化モノクローナル抗体を含む、抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントに関する。
2. 上記モノクローナル抗体又はその抗原結合フラグメントが、少なくともB/Florida/4/2006株、B/Shanghai/361/2002株、B/Johannesburg/5/1999株、B/Yamanashi/166/1998株、及びB/Mie/1/1993株に対する中和活性を有する、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
3. 上記モノクローナル抗体又はその抗原結合フラグメントが、少なくともB/Florida/4/2006株、B/Shanghai/361/2002株、B/Johannesburg/5/1999株、B/Yamanashi/166/1998株、B/Mie/1/1993株、B/Malaysia/2506/04株、B/Shandong/7/1997株、及びB/Victoria/2/1987株に対する中和活性を有する、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
4. 上記ヒトモノクローナル抗体が、B型インフルエンザウイルス感染症を患うヒト由来の末梢血単核球(PBMC)を、効率的な細胞融合を可能とする融合パートナー細胞と融合させることによって作製されるハイブリドーマにより産生される、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスヒトモノクローナル抗体。
5. 上記B型インフルエンザウイルスが、B/Florida/4/2006株、B/Shanghai/361/2002株、B/Johannesburg/5/1999株、B/Yamanashi/166/1998株、B/Mie/1/1993株、B/Malaysia/2506/04株、B/Shandong/7/1997株、及びB/Victoria/2/1987株の内の少なくとも1つを含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスヒトモノクローナル抗体。
6. 上記融合パートナー細胞がSPYMEG細胞である、任意の上記又は下記の実施形態/特徴/態様の抗ヒトB型インフルエンザウイルスヒトモノクローナル抗体。
7. IgG、Fab、Fab’、F(ab’)2、scFv、又はdsFvを含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトB型インフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
8. 配列番号1、配列番号7又は配列番号13を含む第1のアミノ酸配列を有する第1の相補性決定領域(CDR1)と、
配列番号2、配列番号8又は配列番号14を含む第2のアミノ酸配列を有する第2の相補性決定領域(CDR2)と、
配列番号3、配列番号9又は配列番号15を含む第3のアミノ酸配列を有する第3の相補性決定領域(CDR3)と、
を含む、重鎖可変領域と、
配列番号4、配列番号10又は配列番号16を含む第4のアミノ酸配列を有する第1の相補性決定領域(CDR1)と、
配列番号5、配列番号11又は配列番号17を含む第5のアミノ酸配列を有する第2の相補性決定領域(CDR2)と、
配列番号6、配列番号12又は配列番号18を含む第6のアミノ酸配列を有する第3の相補性決定領域(CDR3)と、
を含む、軽鎖可変領域と、
を含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
9. 上記第1のアミノ酸配列が配列番号1を含み、上記第2のアミノ酸配列が配列番号2を含み、上記第3のアミノ酸配列が配列番号3を含み、上記第4のアミノ酸配列が配列番号4を含み、上記第5のアミノ酸配列が配列番号5を含み、上記第6のアミノ酸配列が配列番号6を含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
10. 上記抗ヒトインフルエンザウイルスモノクローナル抗体が抗体5A7を含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
11. 上記第1のアミノ酸配列が配列番号7を含み、上記第2のアミノ酸配列が配列番号8を含み、上記第3のアミノ酸配列が配列番号9を含み、上記第4のアミノ酸配列が配列番号10を含み、上記第5のアミノ酸配列が配列番号11を含み、上記第6のアミノ酸配列が配列番号12を含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
12. 上記抗ヒトインフルエンザウイルスモノクローナル抗体が抗体3A2を含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
13. 上記第1のアミノ酸配列が配列番号13を含み、上記第2のアミノ酸配列が配列番号14を含み、上記第3のアミノ酸配列が配列番号15を含み、上記第4のアミノ酸配列が配列番号16を含み、上記第5のアミノ酸配列が配列番号17を含み、上記第6のアミノ酸配列が配列番号18を含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
14. 上記抗ヒトインフルエンザウイルスモノクローナル抗体が抗体10C4を含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。
15. 任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスヒトモノクローナル抗体又はその抗原結合フラグメントと、薬理学的に許容可能な担体とを含む、医薬組成物。
16. 任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスヒトモノクローナル抗体又はその抗原結合フラグメントを含む、ヒト被験体におけるヒトB型インフルエンザの予防、治療及び検出の少なくとも1つのためのキット。
17. ヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する方法であって、治療的に有効な量の任意の上記又は下記の実施形態/特徴/態様の抗ヒトB型インフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントをヒト被験体に投与することを含む、方法。
18. 患者をB型インフルエンザ感染症と診断することを更に含む、任意の上記又は下記の実施形態/特徴/態様のヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する方法。
19. B型インフルエンザ感染症の少なくとも1つの症状の軽減をモニタリングすることを更に含む、任意の上記又は下記の実施形態/特徴/態様のヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する方法。
20. 上記少なくとも1つの症状が、発熱、頭痛、疲労、悪寒、不快感、筋肉痛、関節痛、鼻閉、咽頭痛、咳、呼吸窮迫若しくは胃痛、又はそれらの任意の組合せを含む、任意の上記又は下記の実施形態/特徴/態様のヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する方法。
21. 請求項1に記載の抗ヒトインフルエンザウイルスヒトモノクローナル抗体又はその抗原結合フラグメントを、B型インフルエンザに関する1つ又は複数の更なる治療薬とともに投与する、任意の上記又は下記の実施形態/特徴/態様のヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する方法。
22. 上記組合せがB型インフルエンザ感染症の阻害又は治療に相乗的に作用する、任意の上記又は下記の実施形態/特徴/態様のヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する方法。
23. 上記1つ又は複数の更なる治療薬が、ノイラミニダーゼ阻害剤、血球凝集素阻害剤、抗炎症剤、又はそれらの任意の組合せを含む、任意の上記又は下記の実施形態/特徴/態様のヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する方法。
24. 上記ノイラミニダーゼ阻害剤が、ザナミビル、オセルタミビル、ペラミビル、ラニナミビル、それらの任意の薬学的に許容可能な塩、又はそれらの任意の組合せを含む、任意の上記又は下記の実施形態/特徴/態様のヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する方法。
25. ヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する薬剤の製造への任意の上記又は下記の実施形態/特徴/態様の抗ヒトB型インフルエンザウイルスヒトモノクローナル抗体又はその抗原結合フラグメントの使用。
26. ヒト被験体においてヒトB型インフルエンザを検出する方法であって、
上記ヒト被験体由来のサンプルを、任意の上記又は下記の実施形態/特徴/態様の抗ヒトB型インフルエンザウイルス抗体又はその抗原結合フラグメントに接触させることと、
上記抗体がヒトB型インフルエンザウイルスの血球凝集素(HA)タンパク質に結合するか否かに基づき、上記ヒト被験体におけるヒトB型インフルエンザウイルスの有無を検出することと、
を含む、方法。
27. 抗ヒトB型インフルエンザウイルスヒトモノクローナル抗体を作製する方法であって、
B型インフルエンザウイルス感染症を患うヒト由来の末梢血単核球(PBMC)を、効率的な細胞融合を可能とする融合パートナー細胞と融合させることによってハイブリドーマを作製することと、
上記ハイブリドーマから抗ヒトインフルエンザウイルスモノクローナル抗体を得ることと、
を含む、方法。
28. 上記B型インフルエンザウイルスが、B/Florida/4/2006株、B/Shanghai/361/2002株、B/Johannesburg/5/1999株、B/Yamanashi/166/1998株、B/Mie/1/1993株、B/Malaysia/2506/04株、B/Shandong/7/1997株、及びB/Victoria/2/1987株の内の少なくとも1つを含む、任意の上記又は下記の実施形態/特徴/態様の抗ヒトB型インフルエンザウイルスヒトモノクローナル抗体を作製する方法。
29. 上記融合パートナー細胞がSPYMEG細胞である、任意の上記又は下記の実施形態/特徴/態様の抗ヒトインフルエンザウイルスヒトモノクローナル抗体を作製する方法。
30. 任意の上記又は下記の実施形態/特徴/態様の方法によって作製される抗ヒトインフルエンザウイルスヒトモノクローナル抗体。
ヒトモノクローナル抗体(HuMAb)を、Kubota-Koketsu et al., Biochemical and Biophysical Research Communications 387:180-185 (2009)に記載の手法に従って準備した。健常なボランティアに、A/Brisbane/59/2007(H1N1)株、A/Uruguay/716/2007(H3N2)株及びB/Florida/4/2006株を含むHAスプリットワクチンの接種を行った。1週間〜2週間後、ワクチン接種を受けた人由来のPBMCとSPYMEG細胞とを融合させ、スクリーニング及びクローニング後、5A7、3A2及び10C4と指定されたHuMAbを産生する3つのハイブリドーマクローンを樹立した。HuMAbの反応性をIFA及びウェスタンブロッティングによって試験した。
3つのHuMAbにより認識されるB/Florida/4/2006のエピトープ領域を決定するために、エスケープ突然変異体を選択した。エスケープ突然変異体はB/Florida/4/2006とHuMAbとをインキュベートすることによって選択された。エスケープ突然変異体は、以前に記載のように(Gulati et al., Journal of Virology 76:12274-12280)、僅かに修正を加えてMAbの存在下でB/Florida/4/2006を培養することによって選択された。ウイルスを、(0.0025mcg/ml〜2.5mcg/mlという最終濃度が与えられるように)10倍で段階希釈したMAbとともに37℃で1時間インキュベートした。次いでMDCK細胞にこの混合物を接種させ、0.4% BSA、抗生物質及び2mcg/mlのアセチル化トリプシンが添加されたDMEM/F−12+GlutaMAX(商標)−I中で培養した。72時間培養した後、上清を回収して、VNアッセイ及びHIアッセイを行った。VN50及びHI力価の低下を示したウイルスサンプルに対して、HA遺伝子全体の直接シークエンシング分析を行った。
HuMAb 3A2はB/Shanghai/361/2002に対して低い反応性を示し、そのため更なる異なるエピトープ領域について調べた。これを行うために、HAの各種キメラ配列を、7つの残基(37位、40位、88位、131位、227位、249位、456位)が異なるB/Florida/4/2006及びB/Shanghai/361/2002から構築し、プラスミドで発現させ、293T細胞へとトランスフェクトした。293T細胞で発現したキメラHAタンパク質のIFAによって、131P及び227Sが3A2との反応に必須であることが示された(図3)。これらの結果から、3A2のエピトープが、131位、194位、196位及び227位の残基に依存し、10C4のエピトープが194位及び196位の残基に依存するものであることが示唆される。3つのHuMAbがマッピングされているエピトープ領域を、図4のHA三量体三次元モデルに示す。HuMAb 3A2及び10C4は、190ヘリックス抗原性部位を含む球状頭頂部を認識したが、5A7はウイルス膜と離れた軸部(stalk)領域と反応した。
B型インフルエンザウイルス感染症の受動伝達治療法としての5A7の活性をマウスで調べた。受動伝達実験において、感染前、マウスに、ペントバルビタールナトリウムの腹腔内投与によって麻酔をかけた(Somnopentyl;共立製薬株式会社、日本、東京)。日本SLC株式会社の6週齢のBALB/c雌マウスを使用した。マウスに25mcl(マイクロリットル)のマウス適合B/Ibaraki/2/1985ウイルスを致死用量(2.5×104FFU/マウス)でチャレンジした4時間、24時間、48時間又は72時間後、5mg/kg、10mg/kg又は15mg/kgのHuMAbを腹腔内に与えた。マウスを毎日秤量して、出発体重の60%まで落ちたら屠殺した。感染肺におけるウイルスを滴定するのに、B/Ibaraki/2/1985又はB/Florida/4/2006をそれぞれ、2.5×104FFU/マウス又は5.0×103FFU/マウスで感染させた。肺を感染後3日目及び6日目に回収して、肺ホモジネート中のウイルス力価をフォーカス形成アッセイによって決定した。
CHO−K1由来の5A7の中和有効性をin vitroで調べた。5A7をCHO−K1細胞において合成し、B型インフルエンザウイルスに対する中和有効性を調べた。CHO−K1細胞を、pQCベクター中の5A7の完全長可変領域遺伝子でトランスフェクトして、5A7を分泌する安定した細胞株(5A7/CHO−K1)を樹立した。哺乳動物細胞を用いた安定発現のために、CHO−K1細胞を、5% CO2下、10%ウシ胎児血清を含むDMEM中において37℃で培養した。6ウェルプレート(Corning、ニューヨーク州コーニング)で成長させた細胞を、Lipofectamine2000トランスフェクション試薬(Invitrogen)を用いたpQCXIP−hCH発現ベクター及びpQCXIH−hC λ発現ベクターでのトランスフェクションに使用した。トランスフェクトした細胞を、5% CO2下、1mcg/mlのピューロマイシン及び100mcg/mlのハイグロマイシンを含むDMEM中において37℃で3週間インキュベートした。次いで細胞を15cmの試験皿(Corning)に再プレーティングし、インキュベートして、コロニーを摘出し、IgGを安定して発現する推定細胞株として培養した。15cmの試験皿上での集密度(confluence)90%の形質転換体の培地を無血清栄養素混合F−12ハム培地(Sigma)へと交換した後、細胞を5% CO2下、37℃で1週間培養した。組換えIgGを、HiTrap Protein G HPカラムを用いて培養培地から精製した。精製したIgGをPBSに対して透析した後、Amicon超遠心フィルター(Millipore、マサチューセッツ州ビルリカ)を用いて濃縮した。in vitroウイルス中和試験を、精製した5A7/CHO−K1を用いて行い、調べたウイルス株の両方(B/Florida/4/2006及びB/Malaysia/2506/2004)に対して中和活性を見出した。注目すべきことに、5A7/CHO−K1の中和活性はハイブリドーマによって産生された5A7のものと同程度であった(図10)。
HuMab 5A7、3A2及び10C4に対して表面プラズモン共鳴分析を行い、それらの結合親和性を調べた。各HuMabをセンサチップの表面に固定化した。12.5nM、25nM、50nM、100nM及び200nM濃度のワクチン抗原であるB/Florida/4/2006のHaタンパク質をチップ表面に連続して注入して、会合段階及び解離段階をモニタリングした。5A7に関するKD値は、HAからの解離が困難であったことから正確に算出することができなかった(表5)。
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出願人らはこの開示における全ての引用文献の内容全体を具体的に援用している。さらに、量、濃度又は他の値若しくはパラメータが範囲、好ましい範囲、又は好ましい上限値と好ましい下限値とのリストのいずれかとして与えられる場合、これは範囲が別々に開示されているかに関わらず、任意の範囲上限又は好ましい値と、任意の範囲下限又は好ましい値との任意の組合せからなるあらゆる範囲を具体的に開示するものと理解されるものとする。数値の範囲が本明細書で言及されている場合、特に指定のない限り、範囲はその端点、並びに範囲内の全ての整数及び少数を含むことが意図される。本発明の範囲は、範囲を規定する場合に言及された特定の値に限定することは意図されない。
Claims (8)
- 配列番号1を含む第1のアミノ酸配列を有する第1の相補性決定領域(CDR1)と、配列番号2を含む第2のアミノ酸配列を有する第2の相補性決定領域(CDR2)と、配列番号3を含む第3のアミノ酸配列を有する第3の相補性決定領域(CDR3)とを含む重鎖可変領域と、
配列番号4を含む第4のアミノ酸配列を有する第1の相補性決定領域(CDR1)と、配列番号5を含む第5のアミノ酸配列を有する第2の相補性決定領域(CDR2)と、配列番号6を含む第6のアミノ酸配列を有する第3の相補性決定領域(CDR3)とを含む軽鎖可変領域を含む、
中和活性および血液凝集阻害活性(HI活性)を有する抗ヒトB型インフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメント。 - 請求項1に記載の抗ヒトB型インフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントと、薬理学的に許容可能な担体とを含む、医薬組成物。
- 請求項1に記載の抗ヒトB型インフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントを含む、ヒト被験体におけるヒトB型インフルエンザの予防、治療及び検出の少なくとも1つのためのキット。
- ヒト被験体においてヒトB型インフルエンザ感染症を阻害又は治療する薬剤の製造への請求項1に記載の抗ヒトB型インフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントの使用。
- ヒト被験体由来のサンプルにおいてヒトB型インフルエンザを検出する方法であって、
前記ヒト被験体由来のサンプルを、請求項1に記載の抗ヒトB型インフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントに接触させることと、
前記抗体がヒトB型インフルエンザウイルスの血球凝集素(HA)タンパク質に結合するか否かに基づき、前記ヒト被験体由来のサンプルにおけるヒトB型インフルエンザウイルスの有無を検出することと、
を含む、方法。 - 請求項1に記載の抗ヒトB型インフルエンザウイルスモノクローナル抗体又はその抗原結合フラグメントをコードするDNA。
- 請求項6に記載のDNAを含む発現ベクター。
- 請求項7に記載の発現ベクターを含む宿主細胞。
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