JP2011524741A - インターロイキン10受容体(il−10r)抗体及び使用方法 - Google Patents
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Abstract
【解決手段】本発明は、例えば、病原体感染、病原体再活性化を処置するために、又はワクチン接種又は免疫付与のために、IL−10受容体アルファ(IL−10Rα)抗体又は部分配列を投与することを例えば含む、病原体感染、病原体再活性化を処置する方法、及び病原体感染に対してワクチン接種又は免疫付与する方法をとりわけ含む。
Description
本実施例には、種々の材料及び方法の記載を含む。
本実施例には、IL−10Rαに結合する典型的な抗体の記載を含む。
本実施例には、IL−10Rαに結合するヒトモノクローナル抗体の特徴付けの記載を含む。
本実施例には、クロスブロック試験の記載を含む。
本実施例には、ヒト抗ヒトIL−10Rα抗体のin vitro機能解析の記載を含む。
本実施例には、非ヒトIL−10Rαとの交差反応性の記載を含む。
Claims (128)
- IL−10受容体アルファタンパク質に特異的に結合し、かつIL−10受容体アルファタンパク質への136C5、136C8又は136D29抗体、又は配列番号29、31および33のいずれか1の重鎖可変領域配列並びに配列番号30、32および34のいずれか1の軽鎖可変領域配列を含む抗体の結合を減少、阻害又は競合するヒト若しくはヒト化抗体又はその部分配列。
- IL−10受容体アルファタンパク質に特異的に結合し、かつIL−10受容体アルファタンパク質への136C5、136C8又は136D29抗体、又は配列番号29、31および33のいずれか1の重鎖可変領域配列並びに配列番号30、32および34のいずれか1の軽鎖可変領域配列を含む抗体の結合を減少、阻害又は競合する単離若しくは精製抗体又はその部分配列。
- IL−10受容体アルファタンパク質に特異的に結合し、かつIL−10受容体アルファタンパク質への3F9、SPM466、又は37607抗体の結合を検出可能に減少、阻害又は競合しない単離若しくは精製抗体又はその部分配列。
- IL−10受容体アルファタンパク質に特異的に結合し、かつ3F9、SPM466、又は37607抗体が結合するエピトープと異なるエピトープに結合する抗体又はその部分配列。
- ヒトIL−10受容体アルファタンパク質に特異的に結合し、かつチンパンジーIL−10受容体アルファタンパク質に特異的に結合し、かつIL−10R/IL−10シグナル伝達活性を修飾する単離若しくは精製抗体又はその部分配列。
- ヒトIL−10受容体アルファタンパク質に特異的に結合し、かつチンパンジーIL−10受容体アルファタンパク質に特異的に結合し、かつマカクIL−10受容体アルファタンパク質に特異的に結合し、かつIL−10R/IL−10シグナル伝達活性を修飾する単離若しくは精製抗体又はその部分配列。
- 前記抗体又はその部分配列が、IL−10の存在下で、in vitroでLPSによって処理された、ヒト、チンパンジー又はマカクPBMCによるTNF−アルファ、IL−6、IL−1β又はIFN−ガンマ発現又は分泌を上昇させる請求項5又は6に記載の抗体。
- 前記抗体又はその部分配列が、IL−10受容体アルファタンパク質への136C5、136C8又は136D29抗体、又は配列番号29、31および33のいずれか1の重鎖可変領域配列並びに配列番号30、32および34のいずれか1の軽鎖可変領域配列を含む抗体の結合の約50%未満を減少、又は阻害する請求項1〜6のいずれか1項に記載の抗体。
- 前記抗体又はその部分配列が、IL−10受容体アルファタンパク質への136C5、136C8又は136D29抗体、又は配列番号29、31および33のいずれか1の重鎖可変領域配列、及び配列番号30、32および34のいずれかの軽鎖可変領域配列を含む抗体の結合の約50%以上を減少、又は阻害する請求項1〜6のいずれか1項に記載の抗体。
- 前記抗体又はその部分配列が、立体構造エピトープに結合又はそれを認識し、直線状エピトープに結合又はそれを認識しない請求項1〜6のいずれか1項に記載の抗体。
- 前記抗体又はその部分配列が、IL−10Rα変異体R212E(配列番号69)に対する136D29、3F9、SPM466又は37607の結合よりも高い親和性でIL−10Rα変異体R212E(配列番号69)に結合する請求項1〜6のいずれか1項に記載の抗体。
- IL−10受容体アルファタンパク質への前記抗体又はその部分配列の結合親和性、KDが、IL−10受容体アルファタンパク質への136C5、136C8又は136D29抗体、又は配列番号29、31および33のいずれか1の重鎖可変領域配列並びに配列番号30、32および34のいずれか1の軽鎖可変領域配列を含む抗体の結合親和性、KDの約1〜1000倍以内である請求項1〜6のいずれか1項に記載の抗体。
- IL−10受容体アルファタンパク質への前記抗体又はその部分配列の結合親和性、KDが、IL−10受容体アルファタンパク質への136C5、136C8又は136D29抗体、又は配列番号29、31および33のいずれか1の重鎖可変領域配列並びに配列番号30、32および34のいずれか1の軽鎖可変領域配列を含む抗体の結合親和性、KDよりも高いか、低い請求項1〜6のいずれか1項に記載の抗体。
- 前記抗体又は部分配列が、配列番号29、31又は33として示したいずれか1の重鎖可変領域配列と少なくとも80%一致する配列と、配列番号30、32又は34として示したいずれか1の軽鎖可変領域配列と少なくとも80%一致する配列とを含むIL−10受容体アルファタンパク質に特異的に結合する単離若しくは精製抗体又はその部分配列。
- 前記抗体又は部分配列が、配列番号29、31および33として示したいずれか1の重鎖可変領域配列と少なくとも85%一致する配列と、配列番号30、32および34として示したいずれか1の軽鎖可変領域配列と少なくとも85%一致する配列とを含む請求項14に記載の単離若しくは精製抗体又はその部分配列。
- 前記抗体又は部分配列が、配列番号29、31および33として示したいずれ1の重鎖可変領域配列と少なくとも90%一致する配列と、配列番号30、32および34として示したいずれか1の軽鎖可変領域配列と少なくとも90%一致する配列とを含む請求項14に記載の単離若しくは精製抗体又はその部分配列。
- 配列番号29、31および33のいずれか1に少なくとも80%一致する重鎖可変領域配列と、配列番号30、32および34のいずれか1に少なくとも80%一致する軽鎖可変領域配列とを含むIL−10受容体アルファタンパク質に特異的に結合する一本鎖抗体。
- 前記抗体又は部分配列が、配列番号29、31および33として示したいずれか1の重鎖可変領域配列と、配列番号30、32および34として示したいずれか1の軽鎖可変領域配列とを含み、前記抗体又はその部分配列が、配列番号29、31および33、並びに配列番号30、32および34の1つ以上のアミノ酸付加、欠失又は置換を有するIL−10受容体アルファタンパク質に特異的に結合する単離若しくは精製抗体又はその部分配列。
- 前記抗体又は部分配列が、配列番号29、31又は33として示したいずれか1の重鎖可変領域配列と少なくとも80%一致する配列と、配列番号30、32および34として示したいずれか1の軽鎖可変領域配列と少なくとも80%一致する配列とを含む請求項18に記載の単離若しくは精製抗体又はその部分配列。
- 前記置換が、同類又は非同類アミノ酸置換である請求項18に記載の抗体又はその部分配列。
- 前記置換が、相補性決定領域(CDR)又はフレームワーク領域(FR)内に位置する請求項18に記載の抗体又はその部分配列。
- 前記置換が、CDR又はFRの外側に位置する請求項18に記載の抗体又はその部分配列。
- IL−10受容体アルファタンパク質への前記抗体又はその部分配列の結合が、in vivo、又はin vitro、又は溶液中で細胞上に発現したIL−10受容体アルファタンパク質へのIL−10結合によって減少又は阻害される請求項1〜6、13、17及び18のいずれか1に記載の抗体又はその部分配列。
- 前記抗体又はその部分配列が、IL−10シグナル伝達活性を減少又は阻害する請求項1〜6、13、17及び18のいずれか1に記載の抗体又はその部分配列。
- IL−10シグナル伝達活性の減少又は阻害が、136D29、3F9、SPM466又は37607抗体のいずれか1によるIL−10シグナル伝達活性の減少又は阻害よりも高い請求項24に記載の抗体又はその部分配列。
- 前記抗体又はその部分配列が、IL−10の存在下で、PBMC又はNKT細胞によるTNF−アルファ又はIFN−ガンマ発現を上昇又は誘発し、IL−10の存在下でHLA−DR MHCクラスII分子の発現を少なくとも部分的に修復し、又はSTAT3のIL−10誘発リン酸化を阻害若しくは減少する請求項1〜6、13、17及び18のいずれか1に記載の抗体又はその部分配列。
- 前記抗体又はその部分配列が、リポ多糖類(LPS)によって処理したヒトPBMCによりTNFアルファ発現又は分泌のIL−10阻害を逆転又は阻害する請求項1〜6、13、17及び18のいずれか1に記載の抗体又はその部分配列。
- 前記抗体又はその部分配列が、炎症性又は適応的免疫応答、又はサイトカイン若しくはケモカインの産生を誘発、促進、刺激又は上昇させる請求項1〜6、13、17及び18のいずれか1に記載の抗体又はその部分配列。
- 前記炎症性免疫応答が、CD4+若しくはCD8+T細胞又はNKT細胞増殖、IL−2、IFN−ガンマ、IL−4、IL−5、又はTNF−アルファ、マクロファージ又は樹状細胞活性のCD4+若しくはCD8+T細胞又はNKT細胞産生、又はCD4+若しくはCD8+T細胞細胞毒性の1つ以上を含む請求項28に記載の抗体又はその部分配列。
- 前記サイトカインが、IL−1アルファ、IL−1ベータ、TNF−アルファ、IL−6、IL−9、IL−12、IL−18およびGM−CSFの1つ以上を含む請求項28に記載の抗体又はその部分配列。
- 前記ケモカインが、MCPl、MCP5、RANTES、IL−8、IP−10およびMIP−2の1つ以上を含む請求項28に記載の抗体又はその部分配列。
- 前記IL−10受容体アルファタンパク質が、哺乳類IL−10受容体アルファタンパク質である請求項1〜6、13、17及び18のいずれか1項に記載の抗体又はその部分配列。
- 前記IL−10受容体アルファタンパク質が、霊長類IL−10受容体アルファタンパク質である請求項32に記載の抗体又はその部分配列。
- 前記IL−10受容体アルファタンパク質が、ヒト、チンパンジー又はマカクIL−10受容体アルファタンパク質である請求項32に記載の抗体又はその部分配列。
- 前記抗体又はその部分配列が、チンパンジー及びマカクIL−10受容体アルファタンパク質に結合する請求項1〜6、13、17及び18のいずれか1項に記載の抗体又はその部分配列。
- 前記抗体又はその部分配列が、配列番号2若しくは配列番号8として示したIL−10受容体アルファタンパク質、又は配列番号4、配列番号6若しくは配列番号10のIL−10受容体アルファタンパク質細胞外ドメインに結合する請求項1〜6、13、17及び18のいずれか1項に記載の抗体又はその部分配列。
- 抗体アイソタイプが、IgM、IgG、IgA、IgD又はIgEアイソタイプを含む請求項1から6、13、17及び18のいずれか1項に記載の抗体又はその部分配列。
- IgG、又はIgAアイソタイプが、IgG1、IgG2、IgG3及びIgG4並びにIgA1及びIgA2から選択される請求項37に記載の抗体又はその部分配列。
- 前記抗体部分配列が、Fab、Fab’、F(ab’)2、Fv、Fd、一本鎖Fv(scFv)、ジスルフィド結合Fv(sdFv)、軽鎖可変領域VL、重鎖可変領域VH、三重特異性(Fab3)、二重特異性(Fab2)、ダイアボディ((VL−VH)2又は(VH−VL)2)、トリアボディ(三価)、テトラボディ(四価)、ミニボディ((scFv−CH3)2)、二重特異性一本鎖Fv(Bis−scFv)、IgGデルタCH2、scFv−Fc、(scFv)2−Fc及びIgG4PEから選択される請求項1から6、13、17及び18のいずれか1項に記載の抗体部分配列。
- 前記抗体が、配列番号29、31および33のいずれか1と一致する少なくとも80のアミノ酸を有する重鎖可変領域配列と、配列番号30、32および34のいずれか1と一致する少なくとも80のアミノ酸を有する軽鎖可変領域配列とを含む請求項1〜6、13、17及び18のいずれか1項に記載の抗体又はその部分配列。
- 前記抗体が、配列番号29、31および33のいずれか1と一致する少なくとも90のアミノ酸を有する重鎖可変領域配列と、配列番号30、32および34のいずれか1と一致する少なくとも90のアミノ酸を有する軽鎖可変領域配列とを含む請求項1〜6、13、17及び18のいずれか1項に記載の抗体又はその部分配列。
- 前記抗体は、霊長類化、ヒト化、又はヒトである請求項1〜6、13、17及び18のいずれか1項に記載の抗体又はその部分配列。
- 配列番号29、31および33のいずれか1の内部に重鎖CDR、又は配列番号30、32および34のいずれか1の内部に軽鎖CDRを含むIL−10受容体アルファタンパク質に特異的に結合する抗体又はその部分配列。
- 配列番号29、31および33のいずれか1の内部に重鎖CDRと、配列番号30、32および34のいずれか1の内部に軽鎖CDRとを含むIL−10受容体アルファタンパク質に特異的に結合する抗体又はその部分配列。
- 配列番号29、31および33のいずれか1つの内部に全ての重鎖CDRと、配列番号30、32および34のいずれか1つの内部に全ての軽鎖CDRとを含むIL−10受容体アルファタンパク質に特異的に結合する抗体又はその部分配列。
- 前記重鎖CDRが、SYSMN、YISTGSSTIYYADSVKG;ENYYGSGSYEDYFDY;YISTRSSTIYYADSVKG;ELSMH;GFDPDDGETIYAQKFQG;及びGGYYGPVGMDVから選択される1である請求項44〜46のいずれか1項に記載の抗体又はその部分配列。
- 前記軽鎖CDRが、RASQSVSSYLA;DASNRAT;QQRSNWPIFT;RASQGISIWLA;AASSLQS;及びQQYNSYPLTから選択される1である請求項44から46のいずれか1項に記載の抗体又はその部分配列。
- 抗体又はその部分配列が、CDRl(SYSMN)、CDR2(YISTGSSTIYYADSVKG)、CDR3(ENYYGSGSYEDYFDY)を有する重鎖可変領域配列と、CDRl(RASQSVSSYLA)、CDR2(DASNRAT)、CDR3(QQRSNWPIFT)を有する軽鎖可変領域配列と、CDRl(SYSMN)、CDR2(YISTRSSTIYYADSVKG)、CDR3(ENYYGSGSYEDYFDY)を有する重鎖可変領域配列と、CDRl(RASQSVSSYLA)、CDR2(DASNRAT)、CDR3(QQRSNWPIFT)を有する軽鎖可変領域配列と、CDRl(ELSMH)、CDR2(GFDPDDGETIYAQKFQG)、CDR3(GGYYGPVGMDV)を有する重鎖可変領域配列と、CDRl(RASQGISPWLA)、CDR2(AASSLQS)、CDR3(QQYNSYPLT)を有する軽鎖可変領域配列とのいずれか1を含むIL−10受容体アルファタンパク質に特異的に結合する抗体又はその部分配列。
- 前記抗体が、ハイブリドーマ細胞、CHO細胞株又はHEK293F細胞から産生される請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又はその部分配列。
- 前記抗体が、抗体マルチマーを含む請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又はその部分配列。
- 1つ以上の異種ドメインを更に含む請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又はその部分配列。
- 前記異種ドメインが、ラベル又はタグを含む請求項51に記載の抗体又は部分配列。
- 前記異種ドメインが、アミノ酸配列含む請求項51に記載の抗体又は部分配列。
- 配列番号29、31又は33で示される重鎖可変領域配列。
- 配列番号30、32又は34で示される軽鎖可変領域配列。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又はその部分配列の重鎖又は軽鎖可変領域配列をコードする核酸。
- 抗体の定常領域配列をコードする核酸を更に含む請求項56に記載の核酸。
- 発現制御要素を更に含む請求項56に記載の核酸。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又は部分配列をコードする核酸を含むベクター。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又は部分配列を発現する宿主細胞。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又は部分配列をコードする核酸で形質転換した宿主細胞。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又は部分配列の重鎖又は軽鎖可変領域配列を発現又は産生する非ヒト動物。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又は部分配列を発現又は産生する非ヒト動物。
- 前記抗体が、ヒト免疫グロブリンラムダ又はカッパ軽鎖をコードする遺伝子座から発現される請求項63に記載の非ヒト動物。
- 前記非ヒト動物が、ヒト免疫グロブリン核酸配列を含有する動物を含む請求項63に記載の非ヒト動物。
- 前記非ヒト動物が、トランスクロモソミック動物を含む請求項63に記載の非ヒト動物。
- 前記非ヒト動物が、哺乳類を含む請求項63に記載の非ヒト動物。
- 前記非ヒト動物が、マウス、ラット、モルモット、ウサギ、ヒツジ、ヤギ、ウシ、ブタ又はウマを含む請求項63に記載の非ヒト動物。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又はその部分配列を発現する植物。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又はその部分配列と、医薬的に許容し得る賦形剤又は担体とを含む医薬組成物。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の少なくとも2つの抗体又はその部分配列を含む組成物。
- 請求項1〜6、13、17、18、44〜46および48のいずれか1項に記載の抗体又はその部分配列、病原体抗原又はそのエピトープ、生若しくは弱毒化病原体、又は病原体抗原若しくはそのエピトープをコードする核酸、又は免疫刺激剤若しくは化合物を含む組成物。
- (2008年4月8日に寄託番号PTA−9131で寄託されたハイブリドーマにより産生された)136C5、(2008年4月8日に寄託番号PTA−9132で寄託されたハイブリドーマにより産生された)136C8、又は(2008年4月8日に寄託番号PTA−9133で寄託されたハイブリドーマにより産生された)136D29抗体又はその機能的配列。
- 請求項1〜6、13、17、18、44〜46、48および73のいずれか1項に記載の抗体又はその部分配列を含むキット。
- 患者を処置するために十分な、請求項1〜6、13、17、18、44〜46、48および73のいずれか1項に記載の抗体又はその部分配列の量を、必要とする患者に投与することを含む病原体感染の患者を処置する方法。
- 病原体抗原又はそのエピトープ、生若しくは弱毒化病原体、又は病原体抗原若しくはそのエピトープをコードする核酸と、病原体感染、潜伏からの再活性化に対する保護を患者に提供するために十分な、請求項1〜6、13、17、18、44〜46、48および73のいずれか1項に記載の抗体又はその部分配列の量とを、必要とする患者に投与することを含む病原体感染、潜伏からの再活性化に対する保護を患者に提供する方法。
- 前記病原体感染が、慢性又は急性である請求項75に記載の方法。
- 前記病原体感染が、潜伏感染である請求項75に記載の方法。
- 前記患者が、哺乳類である請求項75又は76に記載の方法。
- 前記患者が、ヒトである請求項75又は76に記載の方法。
- 前記病原体が、ウイルス、細菌、寄生生物又は真菌を含む請求項75又は76に記載の方法。
- 前記ウイルスが、ポックスウイルス、ヘルペスウイルス、肝炎ウイルス、免疫不全ウイルス、フラビウイルス、乳頭腫ウイルス(PV)、ポリオーマウイルス、ラブドウイルス、ミクソウイルス、アレナウイルス、コロナウイルス、アデノウイルス、レオウイルス、ピコルナウイルス、トガウイルス、ブニヤウイルス、パルボウイルス又はレトロウイルスを含む請求項81に記載の方法。
- 前記ポックスウイルスが、ワクシニアウイルス、伝染性軟属腫、大痘瘡又は小痘瘡天然痘ウイルス、牛痘、ラクダ痘、羊痘又はサル痘を含む請求項82に記載の方法。
- 前記ヘルペスウイルスが、アルファ−ヘルペスウイルス、ベータ−ヘルペスウイルス、ガンマ−ヘルペスウイルス、エプスタインバーウイルス(EBV)、サイトメガロウイルス(CMV)、水痘帯状疱疹ウイルス(VZV/HHV−3)、ヒトヘルペスウイルス1、2、4、5、6、7又は8型(HHV−8、カポジ肉腫会合ウイルス)を含む請求項82に記載の方法。
- 前記肝炎ウイルスが、A、B、C、D、E又はG型肝炎を含む請求項82に記載の方法。
- 前記免疫不全ウイルスが、ヒト免疫不全ウイルス(HIV)を含む請求項82に記載の方法。
- 前記HIVが、HIV−1、HIV−2又はHIV−3を含む請求項86に記載の方法。
- 前記フラビウイルスが、C型肝炎ウイルス、黄熱病ウイルス、デング熱ウイルス、並びに日本脳炎又は西ナイルウイルスを含む請求項82に記載の方法。
- 前記乳頭腫ウイルスが、ヒト乳頭腫ウイルス(HPV)を含む請求項82に記載の方法。
- 前記ヒト乳頭腫ウイルスが、HPV株1、6、11、16、18、30、31、42、43、44、45、51、52又は54を含む請求項89に記載の方法。
- 前記ポリオーマウイルスが、BKウイルス(BKV)又はJCウイルス(JCV)を含む請求項82に記載の方法。
- 前記ラブドウイルスが、狂犬病ウイルス又はベシクロウイルスを含む請求項82に記載の方法。
- 前記ミクソウイルスが、パラミクソウイルス又はオルトミクソウイルスを含む請求項82に記載の方法。
- 前記パラミクソウイルスが、麻疹、おたふく風邪、肺炎ウイルス又は呼吸器合胞体ウイルス(RSV)を含む請求項93に記載の方法。
- 前記オルトミクソウイルスが、インフルエンザウイルスを含む請求項93に記載の方法。
- 前記インフルエンザウイルスが、A型インフルエンザ、B型インフルエンザ、又はC型インフルエンザを含む請求項95に記載の方法。
- 前記アレナウイルスが、リンパ球性脈絡髄膜炎ウイルス(LCMV)、フニンウイルス、ラッサ熱ウイルス、グアナリトウイルス、サビアウイルス又はマチュポウイルスを含む請求項82に記載の方法。
- 前記コロナウイルスが、風邪又は重症急性呼吸器症候群(SARS)を引き起こすウイルスを含む請求項82に記載の方法。
- 前記アデノウイルスが、気管支、肺、胃、腸(胃腸炎)、眼(結膜炎)、膀胱(膀胱炎)又は皮膚のウイルス感染を含む請求項82に記載の方法。
- 前記レオウイルスが、ロタウイルス、サイポウイルス又はオルビウイルスを含む請求項82に記載の方法。
- 前記ピコルナウイルスが、ライノウイルス、アフトウイルス、ヘパトウイルス、エンテロウイルス、コクサッキーBウイルス又はカルジオウイルスを含む請求項82に記載の方法。
- 前記ライノウイルスが、風邪を引き起こす請求項101に記載の方法。
- 前記トガウイルスが、アルファウイルス、シンドビス(sindbus)ウイルス又は風疹ウイルスを含む請求項82に記載の方法。
- 前記ブニヤウイルスが、ハンタウイルス、フレボウイルス又はナイロウイルスを含む請求項82に記載の方法。
- 前記レトロウイルスには、アルファ、ベータ、デルタ、ガンマ、イプシロン、レンチウイルス、スプマウイルス又はヒトT細胞白血病ウイルスを含む請求項82に記載の方法。
- 前記レンチウイルスが、免疫不全ウイルスを含む請求項105に記載の方法。
- 前記免疫不全ウイルスが、ウシ、ブタ、ウマ、イヌ、ネコ又は霊長類ウイルスを含む請求項106に記載の方法。
- 前記ヒトT細胞白血病ウイルスが、ヒトT細胞白血病ウイルス1及び2型(HTLV−1及びHTLV−2)を含む請求項105に記載の方法。
- 前記細菌が、マイコバクテリア、リステリア菌、ヘリコバクター、ボルデテラ、連鎖球菌、サルモネラ又はクラミジアを含む請求項75又は76に記載の方法。
- 前記寄生生物が、原生動物又は線虫を含む請求項75又は76に記載の方法。
- 前記原生動物が、トキソプラズマ原虫、リーシュマニア、変形体又はクルーズトリパノソーマを含む請求項110に記載の方法。
- 前記線虫が、マンソン住血吸虫又は蠕虫を含む請求項110に記載の方法。
- 前記真菌が、カンジダアルビカンスを含む請求項75又は76に記載の方法。
- 前記処置が、病原体感染又は病変から保護し、病原体感染又は病変に対する感受性を低下、減少、若しくは制限し、病原体数又は力価を低下、減少、阻害、抑制、制限若しくは制御し、病原体増殖又は複製を低下、減少、阻害、抑制、制限若しくは制御し、病原体タンパク質の量を低下、減少、阻害、抑制、制限若しくは制御し、又は病原体核酸の量を低下、減少、阻害、抑制、制限若しくは制御するために十分である請求項75又は76に記載の方法。
- 前記処置が、病原体に対する免疫反応を上昇、促進、強化、誘発、増加又は刺激するために十分である請求項75又は76に記載の方法。
- 前記処置が、病原体排除又は除去を上昇、促進、強化、誘発、増加若しくは刺激し、潜伏からの再活性化を低下、減少、阻害、抑制、制限若しくは制御し、又は他の患者への病原体伝達を低下、減少、阻害、抑制、制限若しくは制御するために十分である請求項75又は76に記載の方法。
- 前記処置が、病原体感染又は潜伏からの病原体再活性化によって引き起こされる、又はそれと関連する1つ以上の有害な症状、障害、疾患、病変又は疾病、又は合併症を低下、減少、阻害、抑制、制限、制御、又は改善するために十分である請求項75又は76に記載の方法。
- 前記抗体又はその部分配列が、病原体に対する患者の曝露又は感染の前、実質的に同時、又は後に投与される請求項75又は76に記載の方法。
- 前記抗体又はその部分配列が、病原体感染又は潜伏からの病原体再活性化によって引き起こされる、又はそれと関連する病原体感染、病変又は有害な症状、障害、疾患、疾病、又は合併症の前、実質的に同時、又は後に投与される請求項75又は76に記載の方法。
- 患者における免疫細胞の数又は活性化を上昇させるために十分な、請求項1から6、13、17、18、44から46、48および73のいずれか1項に記載の抗体又はその部分配列の量を、患者に投与することを含む病原体感染を伴うか、又は病原体感染の危険を冒して、患者における免疫細胞の数又は活性化を上昇させる方法。
- 前記免疫細胞が、T細胞、ナチュラルキラーT(NKT)細胞、樹状細胞(DC)、マクロファージ、好中球、好酸球、又はマスト細胞を含む請求項120に記載の方法。
- IL−12が、樹状細胞(DC)又はマクロファージによって産生される請求項121に記載の方法。
- 前記免疫細胞が、CD4+又はCD8+、CD14+、CD11b+又はCD11c+細胞の1つ以上を含む請求項120に記載の方法。
- 患者における抗病原体CD8+又はCD4+T細胞応答を上昇又は誘発するために十分な、請求項1から6、13、17、18、44から46、48および73のいずれか1項に記載の抗体又はその部分配列の量を、患者に投与することを含む病原体感染を伴うか、又は病原体感染の危険を冒して、患者における抗病原体CD8+又はCD4+T細胞応答を上昇又は誘発する方法。
- 患者においてTh1サイトカイン産生を上昇させるために十分な、請求項1から6、13、17、18、44から46、48および73のいずれか1項に記載の抗体又はその部分配列の量を、患者に投与することを含むTh1又はTh2サイトカイン産生を上昇させる必要がある患者においてTh1又はTh2サイトカイン産生を上昇させる方法。
- 前記患者が、病原体感染を有するか、又は有する危険がある請求項125に記載の方法。
- 前記サイトカインが、インターフェロン(IFN)ガンマ、TNF−アルファ、IL−1アルファ、IL−1ベータ、IL−4、IL−5、IL−2、IL−6、IL−8、IL−12、IL−18又はGM−CSFを含む請求項125に記載の方法。
- IFNガンマが、病原体感染を含む病原体に特異的なCD8+T細胞によって産生される請求項127に記載の方法。
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JP6037043B2 (ja) * | 2014-08-22 | 2016-11-30 | 日東紡績株式会社 | TRACP−5b(酒石酸抵抗性酸性フォスファターゼ5b)に特異的なタンパク定量法 |
US10214592B2 (en) | 2014-08-22 | 2019-02-26 | Nitto Boseki Co., Ltd. | Protein assay method specific to TRACP-5b (tartrate resistant acid phosphatase 5b) |
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