JP2022180615A - 病理学的タウタンパク質の免疫学的標的化方法 - Google Patents
病理学的タウタンパク質の免疫学的標的化方法 Download PDFInfo
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Abstract
Description
[本発明1001]
被験体におけるアルツハイマー病または他のタウオパシーを治療または予防する方法であって、
配列番号2-75からなる群より選択されるアミノ酸配列を含む1つ以上の免疫原性タウペプチド、または配列番号2-75および101-103からなる群より選択されるアミノ酸配列を含む免疫原性タウエピトープを認識する1つ以上の抗体を、被験体におけるアルツハイマー病または他のタウオパシーを治療または予防するために有効な条件下で、被験体に投与する段階
を包含する、方法。
[本発明1002]
アルツハイマー病もしくは他のタウオパシーを有するか、またはそのリスクがある被験体を選択する段階をさらに包含し、ここで、1つ以上の免疫原性タウペプチド、または免疫原性タウエピトープを認識する1つ以上の抗体が、選択された被験体に投与される、
本発明1001の方法。
[本発明1003]
前記1つ以上の免疫原性タウペプチドが、1つ以上のアミノ酸残基においてリン酸化されており、かつ前記1つ以上の抗体が、リン酸化された免疫原性タウペプチドを認識する、本発明1001の方法。
[本発明1004]
免疫原性キャリアが免疫原性タウペプチドに連結されている、本発明1001の方法。
[本発明1005]
アジュバントが、前記1つ以上の免疫原性タウペプチドまたは抗体を投与する段階の前、その後、またはそれと同時に投与される、本発明1001の方法。
[本発明1006]
1つ以上のさらなる免疫原性タウペプチドが、前記1つ以上の免疫原性タウペプチドを投与する段階の前、その後、またはそれと同時に投与される、本発明1001の方法。
[本発明1007]
前記1つ以上のさらなる免疫原性タウペプチドが、配列番号81-100からなる群より選択されるアミノ酸配列を含む、本発明1006の方法。
[本発明1008]
前頭側頭型認知症、第17染色体に連鎖するパーキンソニズム(FTDP-17)、進行性核上麻痺、大脳皮質基底核変性症、ピック病、進行性皮質下グリオーシス、タングル限定認知症(tangle only dementia)、石灰沈着を伴うびまん性神経原線維変化病、嗜銀性グレイン型認知症、筋萎縮性側索硬化症、パーキンソン認知症複合体、ボクサー認知症、ダウン症候群、ゲルストマン-シュトロイスラー-シャインカー病、ハレルフォルデン-スパッツ病、封入体筋炎、クロイツフェルト-ヤコブ病、多系統萎縮症、C型ニーマン-ピック病、プリオンタンパク質脳アミロイドアンギオパシー、亜急性硬化性全脳炎、筋強直性ジストロフィー、神経原線維タングルを伴う非グアム型運動ニューロン疾患、慢性外傷性脳障害、および脳炎後パーキンソニズムからなる群より選択されるタウオパシーが、治療または予防される、
本発明1001の方法。
[本発明1009]
被験体の脳からのタウ凝集物のクリアランスを促進する方法であって、
配列番号2-75からなる群より選択されるアミノ酸配列を含む1つ以上の免疫原性タウペプチド、または配列番号2-75および101-103からなる群より選択されるアミノ酸配列を含む免疫原性タウエピトープを認識する1つ以上の抗体を、被験体の脳からのタウ凝集物のクリアランスを促進するために有効な条件下で、被験体に投与する段階
を包含する、方法。
[本発明1010]
脳におけるタウ凝集物を有する被験体を選択する段階をさらに包含し、ここで、1つ以上の免疫原性タウペプチド、または免疫原性タウエピトープを認識する1つ以上の抗体が、選択された被験体に投与される、
本発明1009の方法。
[本発明1011]
前記1つ以上の免疫原性タウペプチドが、1つ以上のアミノ酸残基においてリン酸化されており、かつ前記1つ以上の抗体が、リン酸化された免疫原性タウペプチドを認識する、本発明1009の方法。
[本発明1012]
免疫原性キャリアが免疫原性タウペプチドに連結されている、本発明1009の方法。
[本発明1013]
アジュバントが、前記1つ以上の免疫原性タウペプチドまたは抗体を投与する段階の前、その後、またはそれと同時に投与される、本発明1009の方法。
[本発明1014]
1つ以上のさらなる免疫原性タウペプチドが、前記1つ以上の免疫原性タウペプチドを投与する段階の前、その後、またはそれと同時に投与される、本発明1009の方法。
[本発明1015]
前記1つ以上のさらなる免疫原性タウペプチドが、配列番号81-100からなる群より選択されるアミノ酸配列を含む、本発明1014の方法。
[本発明1016]
凝集物が神経原線維タングルまたはそれらの病理学的タウ前駆体である、本発明1009の方法。
[本発明1017]
被験体におけるタウ病理学関連行動表現型の進行を遅延させる方法であって、
配列番号2-75からなる群より選択されるアミノ酸配列を含む1つ以上の免疫原性タウペプチド、または配列番号2-75および101-103からなる群より選択されるアミノ酸配列を含む免疫原性タウエピトープを認識する1つ以上の抗体を、被験体におけるタウ病理学関連行動表現型の進行を遅延させるために有効な条件下で、被験体に投与する段階
を包含する、方法。
[本発明1018]
タウ病理学関連行動表現型を有する被験体を選択する段階をさらに包含し、ここで、1つ以上の免疫原性タウペプチド、または免疫原性タウエピトープを認識する1つ以上の抗体が、選択された被験体に投与される、
本発明1017の方法。
[本発明1019]
前記1つ以上の免疫原性タウペプチドが、1つ以上のアミノ酸残基においてリン酸化されており、かつ前記1つ以上の抗体が、リン酸化された免疫原性タウペプチドを認識する、本発明1017の方法。
[本発明1020]
免疫原性キャリアが免疫原性タウペプチドに連結されている、本発明1017の方法。
[本発明1021]
アジュバントが、前記1つ以上の免疫原性タウペプチドまたは抗体を投与する段階の前、その後、またはそれと同時に投与される、本発明1017の方法。
[本発明1022]
1つ以上のさらなる免疫原性タウペプチドが、前記1つ以上の免疫原性タウペプチドを投与する段階の前、その後、またはそれと同時に投与される、本発明1017の方法。
[本発明1023]
前記1つ以上のさらなる免疫原性タウペプチドが、配列番号81-100からなる群より選択されるアミノ酸配列を含む、本発明1022の方法。
[本発明1024]
配列番号2-75および101-103からなる群より選択されるアミノ酸配列を含む、単離されたタウペプチド。
[本発明1025]
1つ以上のアミノ酸残基においてリン酸化されている、本発明1024の単離されたタウペプチド。
[本発明1026]
前記単離されたペプチドに連結された免疫原性キャリアをさらに含む、本発明1024の単離されたタウペプチド。
[本発明1027]
1つ以上の本発明1024の単離されたペプチドおよび薬学的キャリアを含む薬学的組成物。
[本発明1028]
薬学的に許容可能なアジュバントをさらに含む、本発明1027の薬学的組成物。
[本発明1029]
配列番号81-100からなる群より選択されるアミノ酸配列を有する1つ以上のさらなる免疫原性タウペプチドをさらに含む、本発明1027の薬学的組成物。
[本発明1030]
本発明1024の単離されたタウペプチドについての抗原特異性を有する、抗体またはその結合部分。
[本発明1031]
単離されたペプチドがリン酸化されている、本発明1030の抗体またはその結合部分。
[本発明1032]
抗体がモノクローナル抗体、ポリクローナル抗体、またはその活性結合部分である、本発明1030の抗体またはその結合部分。
[本発明1033]
本発明1030の抗体、および
1つ以上の異なるアミロイド形成タンパク質またはペプチドを認識する1つ以上の抗体またはその結合部分
を含む、組み合わせ免疫治療剤。
[本発明1034]
1つ以上のアミロイド形成タンパク質またはペプチドが、ベータタンパク質前駆体、プリオンおよびプリオンタンパク質、αシヌクレイン、アミロイドβ、島アミロイドポリペプチド、アポリポプロテインAI、アポリポプロテインAII、リゾチーム、シスタチンC、ゲルソリン、心房性ナトリウム利尿因子、カルシトニン、ケラトエピセリン、ラクトフェリン、免疫グロブリン軽鎖、トランスサイレチン、Aアミロイドーシス、β2マイクログロブリン、免疫グロブリン重鎖、フィブリノーゲンアルファ鎖、プロラクチン、ケラチン、およびメディン(medin)からなる群より選択される、本発明1033の組み合わせ免疫治療剤。
[本発明1035]
被験体におけるアルツハイマー病または他のタウオパシーを診断する方法であって、
本発明1030の抗体またはその活性結合フラグメントを含む診断用試薬を使用して病理学的タウタンパク質コンフォーマーの存在を被験体において検出する段階、および
前記検出に基づいて被験体におけるアルツハイマー病または他のタウオパシーを診断する段階
を包含する、方法。
[本発明1036]
前記検出する段階が、
被験体から生物学的サンプルを入手すること;
診断用試薬が前記サンプル中の病理学的タウタンパク質コンフォーマーに結合するために有効な条件下で、前記被験体からの生物学的サンプルを、診断用試薬と接触させること;および
サンプル中の病理学的タウタンパク質コンフォーマーへの診断用試薬の結合を検出すること
を包含する、本発明1035の方法。
[本発明1037]
前記検出する段階が、
検出可能な標識を含有する診断用試薬を被験体に投与すること、および
インビボ画像化デバイスを使用して、被験体において標識された診断用試薬を検出すること
を包含する、本発明1035の方法。
[本発明1038]
本発明1030の単離された抗体および検出可能な標識を備える、診断キット。
ペプチド免疫原は、Keck施設(the Keck facility)(Yale University)において、p-メチル-ベンズヒドリルアミン樹脂上での固相技術によって、Biosearch SAM 2合成装置(Biosearch,Inc.,San Rafael,Ca.)を使用して合成された。これらのペプチドは、HFを用いて樹脂から切断され、次いで、エーテルおよび酢酸を用いて抽出され、その後凍結乾燥された。続いて、ペプチドは、0.78×30cmカラム上での逆相支持媒体(Delta-Bondapak)の使用を伴い、0.1% TFA中のアセトニトリルの0-66%直線状グラジエントを用いるHPLCによって精製された。
研究は、いくつかの脳領域および脊髄に神経原線維タングルを発生するトランスジェニック(Tg)JNPL3 P301Lマウスモデルにおいて実施された(Taconic,Germantown,NY)(Lewis et al.,「Neurofibrillary Tangles,Amyotrophy and Progressive Motor Disturbance in Mice Expressing Mutant(P301L)Tau Protein」,Nat Genet 25:402-405(2000)、これはその全体が参照により組み込まれる)。このモデルは、ADのために理想的ではないが、これは、タングルの発生の結果を研究するため、およびこれらの凝集物の生成を妨害し得る治療をスクリーニングするための優秀なモデルである。これらの動物の別の利点は、比較的初期の病理の発症である。ホモ接合性系統において、タウ病理に付随する行動の異常は、少なくとも3ヶ月まで初期に観察できるが、動物は、少なくとも8ヶ月齢まで比較的健常のままである。換言すれば、8ヶ月目において、動物は、治療の効果がモニターされることを可能にするために十分良好に移動し、それら自体で摂食し、そして行動学的な作業を実施できる。
Phos-タウペプチドは、Adju-Phosアジュバント(Brenntag Biosector,Denmark)と1mg/mLの濃度で混合され、この溶液は、投与の前に4℃で一晩回転され、リン酸アルミニウム粒子にペプチドが吸着することを可能にした。
マウスは研究の開始前(T0)、3回目の注射の1週間後、その後定期的に、そして屠殺の際(Tf)に採血された。ワクチンに対する抗体応答は、血漿の希釈により(他に示されない場合、1:200)、ELISAアッセイを使用して、以前に記載されたように決定され(Sigurdsson et al.,「Immunization with a Non-Toxic/Non-Fibrillar Amyloid-β Homologous Peptide Reduces Alzheimer's Disease Associated Pathology in Transgenic Mice」Am J Pathol.159:439-447(2001)and Sigurdsson et al.,「An Attenuated Immune Response is Sufficient to Enhance Cognition in an Alzheimer's Disease Mouse Model Immunized with Amyloid-beta Derivatives」J Neurosci.24:6277-6282(2004)、これらはそれらの全体が参照により組み込まれる)、ここで、免疫原はImmulon(登録商標)マイクロタイターウェル(Thermo Fischer Scientific,Waltham,MA,)にコートされた。検出のために、西洋ワサビペルオキシダーゼに連結されたヤギ抗マウスIgG(Pierce,Rockford,IL)または抗マウスIgM(Sigma,St.Louis,MO)が1:3000希釈で使用された。テトラメチルベンジジン(Pierce)が基質であった。
タウ病理の組織学的分析のために、マウスは、フェノバルビタールナトリウム(120 mg/kg,i.p.)で麻酔され、動脈を横切ってPBSで潅流され、そして以前に記載されたように脳が処理された(Sigurdsson et al.,「Immunization with a Non-Toxic/Non-Fibrillar Amyloid-β Homologous Peptide Reduces Alzheimer's Disease Associated Pathology in transgenic Mice」Am J Pathol 159:439-447(2001);Sigurdsson et al.,「An Attenuated Immune Response is Sufficient to Enhance Cognition in an Alzheimer's Disease Mouse Model Immunized with Amyloid-beta Derivatives」J Neurosci 24:6277-6282(2004);およびSigurdsson E.,「Histological Staining of Amyloid-beta in Mouse Brains」Methods Mol Biol 299:299-308(2005)これらはそれらの全体が参照により組み込まれる)。手短に述べると、右半球が、過ヨウ素酸-リジン-パラホルムアルデヒド(PLP)中で一晩浸漬固定され、一方、左半球は、タウタンパク質分析のために素早く凍結された。固定後、脳は、20% グリセロールおよび2% ジメチルスルホキシド(DMSO)を含有するリン酸緩衝液に移され、切片化するまで4℃で保存された。連続冠状脳切片(40μm)が切断され、10番目毎に、PHFタウタンパク質のC末端上の微小管結合反復の中に位置するリン酸化セリン396および404を認識するPHF1モノクローナル抗体で染色された(Otvos et al.,「Monoclonal Antibody PHF-1 Recognizes Tau Protein Phosphorylated at Serine Residues 396 and 404」J Neurosci Res 39:669-673(1994),これはその全体が参照により組み込まれる)。
タウ免疫治療がP301Lにおいて観察される加齢関連感覚運動異常を予防もしくは逆転するか否か、またはこれがhtau/PS1マウスにおいていかなる運動不全も引き起こすか否かを決定するために、免疫原性Tau 260-264[P-Ser262](配列番号3)またはTau 379-408[P-Ser396,404](配列番号82)を投与された動物が、以下に記載される種々の感覚運動試験および認知試験を使用して評価された。
脳組織は、0.1mM 2-(N-モルホリノ)エタン(ethano)スルホン酸、0.5mM MgSO4、1mM EGTA、2mM ジチオスレイトール、pH 6.8、0.75mM NaCl、2mM フェニルメチルスルホニルフルオリド、完全ミニプロテアーゼ阻害剤混合物(Complete mini protease inhibitor mixture)(10mLの水中に1タブレット;Roche)、およびホスファターゼ阻害剤(20mM NaFおよび0.5mM オルトバナジウム酸ナトリウム)を含む緩衝液中で均質化された。次いで、このホモジネートは、4℃で30分間遠心分離され(20,000×g)、可溶性細胞質画分(上清1)および不溶性画分(ペレット1)を分離する。このペレットは、プロテアーゼ阻害剤およびホスファターゼ阻害剤を有さないが、1%(v/v)Triton X-100および0.25%(w/v)デオキシ(desoxy)コール酸ナトリウムを含んだ同じ体積の緩衝液に再懸濁され、50,000で30分間超遠心分離を行って、不溶性画分として分析された、界面活性剤で抽出された上清2を得た。上清1および2は100℃で5分間加熱され、同じ量のタンパク質が12%(w/v)ポリアクリルアミドゲル上で電気泳動された。ブロットはTBS中0.1% Tween-20を有する5%ノンファットミルクでブロックされ、様々な抗体とともに一晩インキュベートされ、次いで、ペルオキシダーゼ結合体化抗マウスまたは抗ウサギIgGとともに室温で1時間インキュベートされた。続いて、結合した抗体は、ECL(Pierce)によって検出された。イムノブロットのデンシトメトリー分析は、NIH Image Jプログラムによって実施された。ある研究は、病理生理学的条件の変化および細胞外マトリックス成分との相互作用はアクチンタンパク質合成を変化し得、アクチンを内部標準として不適切にすると報告しているので、病理学的タウのレベルはアクチンレベルの代わりに全体のタウタンパク質の量と比較して正常化された。
受動免疫の実行可能性を決定するために、ホモ接合性P301Lマウスは、P301L(JNPL3)マウスモデルおよびADにおいてNFTおよび前タングルを認識するモノクローナルタウ抗体であるPHF1(Dr.Peter Daviesより恵与)を腹腔内(i.p.)注射された(Lewis et al,「Neurofibrillary Tangles,Amyotrophy and Progressive Motor Disturbance in Mice Expressing Mutant(P301L)Tau Protein」,Nat Genet 25:402-40522(2000),これはその全体が参照により組み込まれる)。このモノクローナル抗体は、タウのC末端におけるセリンアミノ酸404および396上でリン酸化されたタウを認識する(Greenberg et al.,「Hydrofluoric Acid-Treated Tau PHF Proteins Display the Same Biochemical Properties as Normal Tau」,J Biol Chem 267:564-569(1992)これはその全体が参照により組み込まれる)。従って、これは、1つの積極的な免疫アプローチの表現型のモノクローナル類似体である(Asuni et al.,「Immunotherapy Targeting Pathological Tau Conformers in a Tangle Mouse Model Reduces Brain Pathology with Associated Functional Improvements」,J Neurosci 27:9115-9129(2007),これはその全体が参照により組み込まれる)、PHF1抗体エピトープを含有するTau379-408[P-Ser396,404]である。
10匹のbalb/cマウスは、N末端に加えられたシステイン残基を介してKLHに連結されたTau386-408[P-Ser396,404](配列番号13)で免疫される。血漿の段階希釈によって検出されるように、免疫原のタウ部分に対して強力な抗体力価が生成された(図13A)。2匹のマウスが細胞融合のために選択され、最初のスクリーニングが、KLHなしの同免疫ペプチドを用いて実施された。二次スクリーニングが、同じペプチド、ならびにTau386-408[P-Ser396],Tau386-408[P-Ser404]、および非ホスホペプチドTau386-408(図13B)を用いて実施された。このスクリーニングに基づいて、クローンが最初および2回目のサブクローニングのために選択された。重要なことに、多数の強力にポジティブなクローンが同定され(>50)、そして、この領域の中でホスホ-エピトープを特異的に認識し、またはこの領域の中のリン酸化されていない部位に結合し、それによって、分子の同じ領域の中のホスホまたは非ホスホタウエピトープに結合する抗体の効力および安全性のプロフィールの比較を可能にする、安定なクローンが同定された。
SEQUENCE LISTING
<110> NEW YORK UNIVERSITY
<120> IMMUNOLOGICAL TARGETING OF PATHOLOGICAL TAU PROTEINS
<150> US 61/185,895
<151> 2009-06-10
<160> 103
<170> PatentIn version 3.5
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Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
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1 5 10
<210> 35
<211> 30
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (21)..(21)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (23)..(23)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 35
Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly
1 5 10 15
Ser Arg Ser Arg Xaa Pro Xaa Leu Pro Thr Pro Pro Thr Arg
20 25 30
<210> 36
<211> 30
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (14)..(14)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (21)..(21)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (23)..(23)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 36
Gly Asp Arg Ser Gly Tyr Ser Xaa Pro Gly Xaa Pro Gly Xaa Pro Gly
1 5 10 15
Ser Arg Ser Arg Xaa Pro Xaa Leu Pro Thr Pro Pro Thr Arg
20 25 30
<210> 37
<211> 30
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (21)..(21)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (23)..(23)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (26)..(26)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 37
Gly Asp Arg Ser Gly Tyr Ser Xaa Pro Gly Ser Pro Gly Thr Pro Gly
1 5 10 15
Ser Arg Ser Arg Xaa Pro Xaa Leu Pro Xaa Pro Pro Thr Arg
20 25 30
<210> 38
<211> 30
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (14)..(14)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 38
Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Xaa Pro Gly Xaa Pro Gly
1 5 10 15
Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg
20 25 30
<210> 39
<211> 30
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (15)..(15)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 39
Pro Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser Arg Xaa Pro Xaa Leu
1 5 10 15
Pro Thr Pro Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val
20 25 30
<210> 40
<211> 37
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (35)..(35)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 40
Cys Gly Xaa Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln Val
1 5 10 15
Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser Lys
20 25 30
Ile Gly Xaa Leu Asp
35
<210> 41
<211> 12
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 41
Ile Gly Xaa Thr Glu Asn Leu Lys His Gln Pro Gly
1 5 10
<210> 42
<211> 23
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (19)..(19)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 42
Thr Asp His Gly Ala Glu Ile Val Tyr Lys Xaa Pro Val Val Ser Gly
1 5 10 15
Asp Thr Xaa Pro Arg His Leu
20
<210> 43
<211> 24
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (22)..(22)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 43
Leu Gln Xaa Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr
1 5 10 15
Ser Asp Ala Lys Ser Xaa Pro Thr
20
<210> 44
<211> 5
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 44
Thr Pro Xaa Leu Glu
1 5
<210> 45
<211> 5
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 45
Ile Ala Xaa Pro Arg
1 5
<210> 46
<211> 5
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 46
Ala Lys Xaa Pro Pro
1 5
<210> 47
<211> 17
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (15)..(15)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 47
Pro Gly Xaa Pro Gly Xaa Arg Xaa Arg Xaa Pro Xaa Leu Pro Xaa Pro
1 5 10 15
Pro
<210> 48
<211> 5
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 48
Pro Lys Xaa Pro Ser
1 5
<210> 49
<211> 9
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 49
Val Lys Xaa Lys Ile Gly Xaa Thr Glu
1 5
<210> 50
<211> 5
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 50
Val Gln Xaa Lys Cys
1 5
<210> 51
<211> 5
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 51
Ile Gly Xaa Leu Asp
1 5
<210> 52
<211> 19
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (15)..(17)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 52
Val Val Xaa Gly Asp Xaa Ser Pro Arg His Leu Xaa Asn Val Xaa Xaa
1 5 10 15
Xaa Gly Ser
<210> 53
<211> 18
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (14)..(14)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (16)..(16)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 53
Val Asp Xaa Pro Gln Leu Ala Xaa Leu Ala Asp Glu Val Xaa Ala Xaa
1 5 10 15
Leu Ala
<210> 54
<211> 4
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 54
Pro Gly Xaa Pro
1
<210> 55
<211> 5
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 55
Pro Gly Xaa Pro Gly
1 5
<210> 56
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (17)..(17)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (21)..(21)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 56
Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys
1 5 10 15
Xaa Lys Ile Ala Xaa Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln
20 25 30
<210> 57
<211> 30
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (18)..(18)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (26)..(26)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 57
Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile Val Tyr
1 5 10 15
Lys Xaa Pro Val Val Ser Gly Asp Thr Xaa Pro Arg His Leu
20 25 30
<210> 58
<211> 30
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (14)..(14)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (21)..(21)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (23)..(23)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 58
Gly Asp Arg Ser Gly Tyr Ser Xaa Pro Gly Xaa Pro Gly Xaa Pro Gly
1 5 10 15
Ser Arg Ser Arg Xaa Pro Xaa Leu Pro Thr Pro Pro Thr Arg
20 25 30
<210> 59
<211> 30
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (15)..(15)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 59
Arg Glu Pro Lys Lys Val Ala Val Val Arg Xaa Pro Pro Lys Xaa Pro
1 5 10 15
Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met
20 25 30
<210> 60
<211> 29
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (14)..(16)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (19)..(19)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (22)..(22)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (25)..(25)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (27)..(27)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (29)..(29)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 60
Xaa Ser Gly Glu Pro Pro Lys Xaa Gly Asp Arg Ser Gln Xaa Xaa Xaa
1 5 10 15
Pro Gly Xaa Pro Gly Xaa Pro Gly Xaa Arg Xaa Arg Xaa
20 25
<210> 61
<211> 30
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (18)..(18)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (29)..(29)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 61
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Xaa Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Xaa Thr
20 25 30
<210> 62
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (17)..(17)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (21)..(21)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (23)..(23)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (27)..(27)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 62
Thr Met His Gln Asp Gln Glu Gly Asp Xaa Asp Ala Gly Leu Lys Glu
1 5 10 15
Xaa Pro Leu Gln Xaa Pro Xaa Glu Asp Gly Xaa Glu Glu Pro Gly
20 25 30
<210> 63
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (9)..(10)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 63
Gly Ser Glu Thr Ser Asp Ala Lys Xaa Xaa Pro Xaa Ala Glu Asp Val
1 5 10 15
Thr Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala
20 25 30
<210> 64
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (12)..(13)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (24)..(24)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 64
Ala Ala Gln Pro His Xaa Glu Ile Pro Glu Gly Xaa Xaa Ala Glu Glu
1 5 10 15
Ala Gly Ile Gly Asp Thr Pro Xaa Leu Glu Asp Glu Ala Ala Gly
20 25 30
<210> 65
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (30)..(30)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 65
Gly His Val Xaa Gln Ala Arg Met Val Ser Lys Xaa Lys Asp Gly Thr
1 5 10 15
Gly Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Xaa Lys
20 25 30
<210> 66
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (26)..(26)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 66
Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln
1 5 10 15
Ala Asn Ala Thr Arg Ile Pro Ala Lys Xaa Pro Pro Ala Pro Lys
20 25 30
<210> 67
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (5)..(6)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (18)..(20)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (23)..(23)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (26)..(26)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (29)..(29)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 67
Lys Xaa Pro Pro Xaa Xaa Gly Glu Pro Pro Lys Ser Gly Asp Arg Ser
1 5 10 15
Gly Xaa Xaa Xaa Pro Gly Xaa Pro Gly Xaa Pro Gly Xaa Arg Ser
20 25 30
<210> 68
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (22)..(22)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (26)..(26)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (28)..(29)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 68
Ser Arg Xaa Pro Xaa Leu Pro Xaa Pro Pro Thr Arg Glu Pro Lys Lys
1 5 10 15
Val Ala Val Val Arg Xaa Pro Pro Lys Xaa Pro Xaa Xaa Ala Lys
20 25 30
<210> 69
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (23)..(23)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 69
Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn
1 5 10 15
Val Lys Ser Lys Ile Gly Xaa Thr Glu Asn Leu Lys His Gln Pro
20 25 30
<210> 70
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (24)..(24)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 70
Pro Gly Gly Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser
1 5 10 15
Asn Val Gln Ser Lys Cys Gly Xaa Lys Asp Asn Ile Lys His Val
20 25 30
<210> 71
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (25)..(25)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 71
Val Pro Gly Gly Gly Ser Val Gln Ile Val Xaa Lys Pro Val Asp Leu
1 5 10 15
Ser Lys Val Thr Ser Lys Cys Gly Xaa Leu Gly Asn Ile His His
20 25 30
<210> 72
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (27)..(27)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 72
His Lys Pro Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu Asp
1 5 10 15
Phe Lys Asp Arg Val Gln Ser Lys Ile Gly Xaa Leu Asp Asn Ile
20 25 30
<210> 73
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (14)..(14)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (27)..(27)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 73
Ile Xaa His Val Pro Gly Gly Gly Asn Lys Lys Ile Glu Xaa His Lys
1 5 10 15
Leu Thr Phe Arg Glu Asn Ala Lys Ala Lys Xaa Asp His Gly Ala
20 25 30
<210> 74
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (14)..(15)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (20)..(20)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (23)..(24)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 74
Ala Glu Ile Val Xaa Lys Xaa Pro Val Val Xaa Gly Asp Xaa Xaa Pro
1 5 10 15
Arg His Leu Xaa Asn Val Xaa Xaa Thr Gly Ser Ile Asp Met Val
20 25 30
<210> 75
<211> 31
<212> PRT
<213> Artificial
<220>
<223> pseudophosphorylated tau peptide
<220>
<221> MISC_FEATURE
<222> (2)..(3)
<223> Xaa is glutamic acid or aspartic acid residue
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa is glutamic acid or aspartic acid residue
<400> 75
Val Xaa Xaa Thr Gly Ser Ile Asp Met Val Asp Xaa Pro Gln Leu Ala
1 5 10 15
Thr Leu Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu
20 25 30
<210> 76
<211> 21
<212> PRT
<213> Artificial
<220>
<223> T-helper cell epitope
<400> 76
Phe Asn Asn Phe Thr Val Ser Phe Trp Leu Arg Val Pro Lys Val Ser
1 5 10 15
Ala Ser His Leu Glu
20
<210> 77
<211> 13
<212> PRT
<213> Artificial
<220>
<223> T-helper cell epitope
<400> 77
Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr
1 5 10
<210> 78
<211> 4
<212> PRT
<213> Artificial
<220>
<223> linker
<400> 78
Gly Pro Ser Leu
1
<210> 79
<211> 4
<212> PRT
<213> Artificial
<220>
<223> linker
<400> 79
Gly Ser Gly Ser
1
<210> 80
<211> 5
<212> PRT
<213> Artificial
<220>
<223> linker
<400> 80
Gly Ser Gly Ser Gly
1 5
<210> 81
<211> 30
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 81
Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys
1 5 10 15
Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln
20 25 30
<210> 82
<211> 30
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (18)..(18)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (26)..(26)
<223> PHOSPHORYLATION
<400> 82
Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile Val Tyr
1 5 10 15
Lys Ser Pro Val Val Ser Gly Asp Thr Ser Pro Arg His Leu
20 25 30
<210> 83
<211> 30
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (8)..(8)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (11)..(11)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (14)..(14)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (21)..(21)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (23)..(23)
<223> PHOSPHORYLATION
<400> 83
Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly
1 5 10 15
Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg
20 25 30
<210> 84
<211> 30
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (11)..(11)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (15)..(15)
<223> PHOSPHORYLATION
<400> 84
Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro
1 5 10 15
Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met
20 25 30
<210> 85
<211> 29
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 85
Ser Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg Ser Gln Tyr Ser Ser
1 5 10 15
Pro Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr
20 25
<210> 86
<211> 30
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (18)..(18)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (29)..(29)
<223> PHOSPHORYLATION
<400> 86
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr
20 25 30
<210> 87
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 87
Thr Met His Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu
1 5 10 15
Ser Pro Leu Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly
20 25 30
<210> 88
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 88
Gly Ser Glu Thr Ser Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val
1 5 10 15
Thr Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala
20 25 30
<210> 89
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 89
Ala Ala Gln Pro His Thr Glu Ile Pro Glu Gly Thr Thr Ala Glu Glu
1 5 10 15
Ala Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly
20 25 30
<210> 90
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 90
Gly His Val Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr
1 5 10 15
Gly Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys
20 25 30
<210> 91
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (26)..(26)
<223> PHOSPHORYLATION
<400> 91
Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln
1 5 10 15
Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys
20 25 30
<210> 92
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (2)..(2)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (5)..(6)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (18)..(20)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (23)..(23)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (26)..(26)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (29)..(29)
<223> PHOSPHORYLATION
<400> 92
Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg Ser
1 5 10 15
Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser
20 25 30
<210> 93
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (3)..(3)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (5)..(5)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (8)..(8)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (22)..(22)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (26)..(26)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (28)..(29)
<223> PHOSPHORYLATION
<400> 93
Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys Lys
1 5 10 15
Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
20 25 30
<210> 94
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (23)..(23)
<223> PHOSPHORYLATION
<400> 94
Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn
1 5 10 15
Val Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro
20 25 30
<210> 95
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (24)..(24)
<223> PHOSPHORYLATION
<400> 95
Pro Gly Gly Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser
1 5 10 15
Asn Val Gln Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val
20 25 30
<210> 96
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (11)..(11)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (25)..(25)
<223> PHOSPHORYLATION
<400> 96
Val Pro Gly Gly Gly Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu
1 5 10 15
Ser Lys Val Thr Ser Lys Cys Gly Ser Leu Gly Asn Ile His His
20 25 30
<210> 97
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (27)..(27)
<223> PHOSPHORYLATION
<400> 97
His Lys Pro Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu Asp
1 5 10 15
Phe Lys Asp Arg Val Gln Ser Lys Ile Gly Ser Leu Asp Asn Ile
20 25 30
<210> 98
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 98
Ile Thr His Val Pro Gly Gly Gly Asn Lys Lys Ile Glu Thr His Lys
1 5 10 15
Leu Thr Phe Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala
20 25 30
<210> 99
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (5)..(5)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (7)..(7)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (11)..(11)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (14)..(15)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (20)..(20)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (23)..(24)
<223> PHOSPHORYLATION
<400> 99
Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser Gly Asp Thr Ser Pro
1 5 10 15
Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser Ile Asp Met Val
20 25 30
<210> 100
<211> 31
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<220>
<221> MOD_RES
<222> (2)..(3)
<223> PHOSPHORYLATION
<220>
<221> MOD_RES
<222> (12)..(12)
<223> PHOSPHORYLATION
<400> 100
Val Ser Ser Thr Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu Ala
1 5 10 15
Thr Leu Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu
20 25 30
<210> 101
<211> 15
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 101
His Leu Ser Asn Val Ser Ser Thr Gly Ser Ile Asp Met Val Asp
1 5 10 15
<210> 102
<211> 13
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 102
Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu
1 5 10
<210> 103
<211> 186
<212> PRT
<213> Artificial
<220>
<223> tau peptide
<400> 103
Glu Ser Pro Leu Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly
1 5 10 15
Ser Glu Thr Ser Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr
20 25 30
Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln
35 40 45
Pro His Thr Glu Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile
50 55 60
Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln
65 70 75 80
Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys
85 90 95
Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly
100 105 110
Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro
115 120 125
Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro
130 135 140
Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly
145 150 155 160
Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr
165 170 175
Arg Glu Pro Lys Lys Val Ala Val Val Arg
180 185
Claims (33)
- タウペプチド部分を含む免疫原性ペプチド:
ここで、該タウペプチド部分のアミノ酸配列は、以下のアミノ酸配列からなる;
IGS*TENLKHQPG (SEQ ID NO:12); または
IGXTENLKHQPG (SEG ID NO:41);
ここで、Xはグルタミン酸もしくはアスパラギン酸残基;
S*はリン酸化セリン残基。 - 前記タウペプチドがアミノ酸配列IGS*TENLKHQPG (SEQ ID NO:12)からなる、請求項1記載の免疫原性ペプチド。
- 前記タウペプチドがアミノ酸配列IGXTENLKHQPG (SEG ID NO:41)からなる、請求項1記載の免疫原性ペプチド。
- 組換えにより産生された抗体、またはその活性結合部分:
ここで、該組換えにより産生された抗体は、タウペプチド部分を含む免疫原性ペプチドで免疫されて誘導された抗体の活性結合部分のアミノ酸配列を含み、ここで、該タウペプチド部分のアミノ酸配列は、以下のアミノ酸配列からなる:
IGS*TENLKHQPG (SEQ ID NO:12);または
IGXTENLKHQPG (SEG ID NO:41);
ここで、Xはグルタミン酸もしくはアスパラギン酸残基;
S*はリン酸化セリン残基。 - 前記タウペプチドがアミノ酸配列IGS*TENLKHQPG (SEQ ID NO:12)からなる、請求項4記載の組換えにより産生された抗体、またはその活性結合部分。
- 前記タウペプチドがアミノ酸配列IGXTENLKHQPG (SEG ID NO:41)からなる、請求項4記載の組換えにより産生された抗体、またはその活性結合部分。
- 前記組換えにより産生された抗体または前記その活性結合部分が、ヒト化された、または、前記抗体がヒト抗体である、請求項4~6のいずれか一項記載の組換えにより産生された抗体、またはその活性結合部分。
- 前記免疫原性ペプチド、前記組換えにより産生された抗体、まはた前記その活性結合部分が、被験体におけるアルツハイマー病の治療用である、請求項1~3のいずれか一項記載の免疫原性ペプチド、または、請求項4~7のいずれか一項記載の組換えにより産生された抗体またはその活性結合部分。
- タウペプチド部分を含む免疫原性ペプチドを含む薬学的組成物であって、ここで、該タウペプチド部分のアミノ酸配列は以下のアミノ酸配列からなり;
IGS*TENLKHQPG (SEQ ID NO:12); または
IGXTENLKHQPG (SEG ID NO:41);
ここで、Xはグルタミン酸もしくはアスパラギン酸残基;
S*はリン酸化セリン残基;
以下の使用のための、薬学的組成物:
(1)被験体におけるアルツハイマー病または他のタウオパシーの治療もしくは予防における使用;
(2)被験体の脳からのタウ凝集物のクリアランスを促進させることにおける使用;
(3)被験体におけるタウ病理学関連行動表現型の進行を遅延させることにおける使用;または
(4)アルツハイマー病の疑いがあり、または既にアルツハイマー病に罹患している患者における軽度の認知障害の治療における使用。 - 前記薬学的組成物がアジュバントを追加的に含む、請求項9記載の薬学的組成物。
- 前記タウペプチドがアミノ酸配列IGS*TENLKHQPG (SEQ ID NO:12)からなる、請求項9または10記載の薬学的組成物。
- 前記タウペプチドがアミノ酸配列IGXTENLKHQPG (SEG ID NO:41)からなる、請求項9または10記載の薬学的組成物。
- 組換えにより産生された抗体、またはその活性結合部分を含む薬学的組成物であって、該組換えにより産生された抗体および該その活性結合部分が、請求項1の免疫原性ペプチドで免疫されて誘導された抗体の活性結合部分のアミノ酸配列を含み、以下の使用のための、薬学的組成物:
(1)被験体におけるアルツハイマー病または他のタウオパシーの治療もしくは予防における使用;
(2)被験体の脳からのタウ凝集物のクリアランスを促進させることにおける使用;
(3)被験体におけるタウ病理学関連行動表現型の進行を遅延させることにおける使用;または
(4)アルツハイマー病の疑いがあり、または既にアルツハイマー病に罹患している患者における軽度の認知障害の治療における使用。 - 前記免疫原性ペプチドのタウペプチド部分が、アミノ酸配列IGS*TENLKHQPG (SEQ ID NO:12)からなる、請求項13記載の薬学的組成物。
- 前記免疫原性ペプチドのタウペプチド部分が、アミノ酸配列IGXTENLKHQPG (SEG ID NO:41)からなる、請求項13記載の薬学的組成物。
- 前記組成物が組換えにより産生された抗体を含む、請求項13~15のいずれか一項記載の薬学的組成物。
- 前記組成物が組換えにより産生された抗体の活性結合部分を含む、請求項13~15のいずれか一項記載の薬学的組成物。
- 前記組換えにより産生された抗体もしくは前記その活性結合部分がヒト化された、または、前記抗体がヒト抗体である、請求項13~17のいずれか一項記載の薬学的組成物。
- 前記薬学的組成物が、被験体におけるアルツハイマー病または他のタウオパシーの治療もしくは予防用である、請求項9~18のいずれか一項記載の薬学的組成物。
- 前記使用が、前頭側頭型認知症、第17染色体に連鎖するパーキンソニズム(FTDP-17)、進行性核上麻痺、大脳皮質基底核変性症、ピック病、進行性皮質下グリオーシス、タングル限定認知症(tangle only dementia)、石灰沈着を伴うびまん性神経原線維変化病、嗜銀性グレイン型認知症、筋萎縮性側索硬化症、パーキンソン認知症複合体、ボクサー認知症、ダウン症候群、ゲルストマン-シュトロイスラー-シャインカー病、ハレルフォルデン-スパッツ病、封入体筋炎、クロイツフェルト-ヤコブ病、多系統萎縮症、C型ニーマン-ピック病、プリオンタンパク質脳アミロイドアンギオパシー、亜急性硬化性全脳炎、筋強直性ジストロフィー、神経原線維タングルを伴う非グアム型運動ニューロン疾患、慢性外傷性脳障害、および脳炎後パーキンソニズムからなる群より選択されるタウオパシーの治療用である、請求項19記載の薬学的組成物。
- 前記薬学的組成物が、被験体の脳からのタウ凝集物のクリアランス促進用である、請求項9~18のいずれか一項記載の薬学的組成物。
- 前記タウ凝集物が神経原線維タングルまたはそれらの病理学的タウ前駆体である、請求項21記載の薬学的組成物。
- 前記薬学的組成物が、被験体におけるタウ病理学関連行動表現型の進行遅延用である、請求項9~18のいずれか一項記載の薬学的組成物。
- 前記薬学的組成物が、アルツハイマー病の疑いがある患者、または、アルツハイマー病を既に罹患している患者における軽度の認知障害の治療用である、請求項9~18のいずれか一項記載の薬学的組成物。
- 前記薬学的組成物が、既に罹患している患者におけるアルツハイマー病の治療用である、請求項24記載の薬学的組成物。
- 請求項4~7のいずれか一項記載の組換えにより産生された抗体またはその活性結合部分、または、請求項13~18のいずれか一項記載の薬学的組成物、および
1つ以上の異なるアミロイド形成タンパク質またはペプチドを認識する1つ以上の抗体またはその結合部分
を含む、組み合わせ免疫治療剤:
ここで、該組み合わせ免疫治療剤は、被験体におけるアルツハイマー病または他のタウオパシーの治療用である。 - 1つ以上のアミロイド形成タンパク質またはペプチドが、ベータタンパク質前駆体、プリオンおよびプリオンタンパク質、αシヌクレイン、アミロイドβ、島アミロイドポリペプチド、アポリポプロテインAI、アポリポプロテインAII、リゾチーム、シスタチンC、ゲルソリン、心房性ナトリウム利尿因子、カルシトニン、ケラトエピセリン、ラクトフェリン、免疫グロブリン軽鎖、トランスサイレチン、Aアミロイドーシス、β2マイクログロブリン、免疫グロブリン重鎖、フィブリノーゲンアルファ鎖、プロラクチン、ケラチン、およびメディン(medin)からなる群より選択される、請求項26記載の組み合わせ免疫治療剤。
- 請求項4~7のいずれか一項記載の1つ以上の組換えにより産生された抗体またはその活性結合部分、または、請求項13~18のいずれか一項記載の薬学的組成物を含む、アルツハイマー病または他のタウオパシーの診断用薬学的組成物であって、ここで、該抗体もしくはその活性結合部分は検出可能なように標識されている、薬学的組成物。
- 前記薬学的組成物が、前記組換えにより産生された1つ以上の抗体、または、その活性結合部分を含む、請求項28記載の薬学的組成物。
- 請求項28~29のいずれか一項に記載の薬学的組成物を含む、アルツハイマー病または他のタウオパシーの診断用キット。
- 前記薬学的組成物が、前記組換えにより産生される抗体を含む、請求項30に記載のキット。
- 前記薬学的組成物が、前記組換えにより産生される抗体の活性結合部分を含む、請求項30に記載のキット。
- 前記組換えにより産生された抗体がヒト化された、またはヒト抗体である、請求項30~32のいずれか一項に記載のキット。
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Families Citing this family (89)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090142766A1 (en) * | 2007-11-09 | 2009-06-04 | Washington University In St. Louis | Methods for measuring the metabolism of cns derived biomolecules in vivo |
UA107571C2 (xx) | 2009-04-03 | 2015-01-26 | Фармацевтична композиція | |
CN106390107B (zh) * | 2009-06-10 | 2019-12-31 | 纽约大学 | 病理tau蛋白的免疫靶向 |
KR20130127547A (ko) * | 2009-07-30 | 2013-11-22 | 화이자 백신스 엘엘씨 | 항원성 타우 펩타이드 및 이의 용도 |
US9320793B2 (en) * | 2010-07-14 | 2016-04-26 | Acumen Pharmaceuticals, Inc. | Method for treating a disease associated with soluble, oligomeric species of amyloid beta 1-42 |
MY164376A (en) * | 2010-10-07 | 2017-12-15 | Univ Leuven Kath | Phosphospecific antibodies recognizing tau |
AU2013205313B2 (en) * | 2010-10-07 | 2016-05-19 | Ac Immune S.A. | Phosphospecific antibodies recognising tau |
EA031698B1 (ru) * | 2010-10-11 | 2019-02-28 | Байоджен Интернэшнл Нейросайенз Гмбх | Человеческие анти-тау антитела |
CA2826286C (en) | 2011-01-31 | 2021-09-21 | Intellect Neurosciences Inc. | Treatment of tauopathies |
WO2012149365A2 (en) | 2011-04-27 | 2012-11-01 | Northwestern University | Antibodies selective for pathological tau dimers and prefibrillar pathological tau oligomers and their uses in treatment, diagnosis and monitoring of tauopathies |
GB201111361D0 (en) * | 2011-07-04 | 2011-08-17 | Nordic Bioscience As | Biochemical markers for neurodegenerative conditions |
GB201112056D0 (en) * | 2011-07-14 | 2011-08-31 | Univ Leuven Kath | Antibodies |
MY183989A (en) | 2011-09-19 | 2021-03-17 | Axon Neuroscience Se | Protein-based therapy and diagnosis of tau-mediated pathology in alzheimer's disease |
AR092779A1 (es) | 2011-10-07 | 2015-05-06 | Ac Immune Sa | Composicon farmaceutica que comprende anticuerpos que se unen a conformeros de proteinas tau |
WO2013059786A1 (en) * | 2011-10-21 | 2013-04-25 | The Ohio State University | Methylated peptides derived from tau protein and their antibodies for diagnosis and therapy of alzheimer's disease |
AU2012359039B2 (en) | 2011-12-20 | 2017-08-24 | Janssen Biotech, Inc. | Anti-PHF-tau antibodies and their uses |
CA2869438C (en) | 2012-04-05 | 2021-08-17 | Ac Immune S.A. | Humanized tau antibody |
SG10201805410XA (en) | 2012-05-31 | 2018-08-30 | Univ Osaka City | Therapeutic agent or prophylactic agent for dementia |
RU2668159C2 (ru) | 2012-07-03 | 2018-09-26 | Вашингтон Юниверсити | Антитела против тау |
BR112015003326A2 (pt) | 2012-08-16 | 2017-07-04 | Ipierian Inc | métodos de tratamento de uma tauopatia |
EP2887955B1 (en) * | 2012-08-21 | 2020-08-19 | Institute for Molecular Medicine, Inc. | Compositions and methods related to diseases associated with deposits of amyloid, tau, and alpha-synuclein |
US20140056901A1 (en) * | 2012-08-21 | 2014-02-27 | The Institute For Molecular Medicine | Anti-tau antibodies and compositions for and methods of making and using in treatment, diagnosis and monitoring of tauopathies |
US9200068B2 (en) * | 2012-12-18 | 2015-12-01 | Regents Of The University Of Minnesota | Compositions and methods related to tauopathy |
US9598484B2 (en) * | 2012-12-21 | 2017-03-21 | Biogen Ma Inc. | Human anti-tau antibodies |
US8980270B2 (en) | 2013-01-18 | 2015-03-17 | Ipierian, Inc. | Methods of treating a tauopathy |
JP6674888B2 (ja) * | 2013-03-13 | 2020-04-01 | プロセナ バイオサイエンシーズ リミテッド | タウ免疫療法 |
JP6568514B2 (ja) | 2013-03-15 | 2019-08-28 | エーシー イミューン エス.エー. | 抗タウ抗体及び使用方法 |
US20160355573A1 (en) * | 2013-09-05 | 2016-12-08 | Cornell University | Gene therapy for alzheimer's and other neurodegenerative diseases and conditions |
BR112016010454A2 (pt) * | 2013-11-27 | 2017-12-05 | Ipierian Inc | métodos para tratar uma taupatia |
EP3080611B1 (en) * | 2013-12-13 | 2018-11-14 | The General Hospital Corporation | Soluble high molecular weight (hmw) tau species and applications thereof |
CA2938152A1 (en) * | 2014-02-10 | 2015-08-13 | Merck Sharp & Dohme Corp. | Antibodies that bind to human tau and assay for quantifying human tau using the antibodies |
US10400018B2 (en) | 2014-02-14 | 2019-09-03 | Ipierian, Inc. | Tau peptides, anti-tau antibodies, and methods of use thereof |
US10400034B2 (en) | 2014-06-26 | 2019-09-03 | Janssen Vaccines & Prevention, B.V. | Antibodies and antigen-binding fragments that specifically bind to microtubule-associated protein tau |
ZA201608812B (en) | 2014-06-26 | 2019-08-28 | Janssen Vaccines & Prevention Bv | Antibodies and antigen-binding fragments that specifically bind to microtubule-associated protein tau |
TWI664190B (zh) | 2014-06-27 | 2019-07-01 | 美商C2N醫療診斷有限責任公司 | 人類化抗-tau抗體 |
WO2016007414A1 (en) | 2014-07-08 | 2016-01-14 | New York University | Tau imaging ligands and their uses in the diagnosis and treatment of tauopathy |
EP3200832B1 (en) | 2014-09-30 | 2020-07-29 | Washington University | Tau kinetic measurements |
WO2016131987A1 (en) * | 2015-02-20 | 2016-08-25 | Affibody Ab | Alzheimer abeta peptide binding polypeptide |
JO3576B1 (ar) | 2015-02-26 | 2020-07-05 | Lilly Co Eli | أجسام مضادة لـ tau واستخداماتها |
US20180050097A1 (en) * | 2015-03-25 | 2018-02-22 | Stc. Unm | Immunotherapy compositions and methods for treatment of tauopathy and transgenic mouse |
JO3627B1 (ar) | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
MX2017015908A (es) | 2015-07-06 | 2018-03-15 | Ucb Biopharma Sprl | Anticuerpos de union a tau. |
JO3711B1 (ar) | 2015-07-13 | 2021-01-31 | H Lundbeck As | أجسام مضادة محددة لبروتين تاو وطرق استعمالها |
US10358503B2 (en) * | 2015-08-13 | 2019-07-23 | New York University | Antibody-based molecules selective for the {P}Ser404 epitope of Tau and their uses in the diagnosis and treatment of tauopathy |
JP6913078B2 (ja) * | 2015-08-13 | 2021-08-04 | ニューヨーク・ユニバーシティ | タウの短縮型Asp421エピトープに特異的な、抗体を基にした分子、ならびにタウ異常症の診断および治療におけるそれらの使用 |
EP3366770A4 (en) * | 2015-10-22 | 2019-04-24 | Immunotherapy Development Inc. | DNA VACCINE AGAINST AMYLOID BETA AND TAU |
SI3171174T1 (en) | 2015-11-20 | 2018-04-30 | Geroa Diagnostics, S.L. | Lactoferrin for use in the diagnosis or prognosis of Alzheimer's disease |
US10702571B2 (en) | 2015-12-03 | 2020-07-07 | The University Of North Carolina At Pembroke | Materials for cathepsin B enhancement and methods of use |
KR102533675B1 (ko) | 2016-05-02 | 2023-05-22 | 프로테나 바이오사이언시즈 리미티드 | 타우 인식 항체 |
EA201892417A1 (ru) | 2016-05-02 | 2019-05-31 | Протена Биосайенсис Лимитед | Антитела, распознающие тау |
FI3452507T3 (fi) | 2016-05-02 | 2022-12-15 | Tau-immuunihoito | |
US10034861B2 (en) | 2016-07-04 | 2018-07-31 | H. Lundbeck A/S | 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors |
GEP20217222B (en) | 2016-07-12 | 2021-02-10 | Lundbeck A/S H | Antibodies specific for hyperphosphorylated tau and methods of use thereof |
US10988529B2 (en) | 2016-08-09 | 2021-04-27 | Eli Lilly And Company | Combination therapy |
EP3532064B1 (en) | 2016-10-28 | 2020-07-29 | H. Lundbeck A/S | Combination treatments comprising imidazopyrazinones for the treatment of psychiatric and/or cognitive disorders |
CA3041595A1 (en) | 2016-10-28 | 2018-05-03 | H. Lundbeck A/S | Combination treatments comprising administration of imidazopyrazinones |
WO2018106889A1 (en) * | 2016-12-09 | 2018-06-14 | Cogwellin L.L.C. | Diagnosis of alzheimer's disease |
KR102032314B1 (ko) * | 2016-12-21 | 2019-10-16 | 주식회사 아델 | 변이된 타우 단백질 단편 및 이의 용도 |
MA47205A (fr) | 2017-01-04 | 2019-11-13 | H Lundbeck As | Anticorps spécifiques de la protéine tau hyperphosphorylée pour traiter des maladies oculaires |
WO2018152359A1 (en) | 2017-02-17 | 2018-08-23 | Denali Therapeutics Inc. | Anti-tau antibodies and methods of use thereof |
JOP20180021A1 (ar) | 2017-03-16 | 2019-01-30 | Janssen Biotech Inc | الأجسام المضادة لتكتلات خيوط بروتين تاو (tau) الحلزونية المزدوجة واستخداماتها |
WO2018178078A1 (en) * | 2017-03-28 | 2018-10-04 | INSERM (Institut National de la Santé et de la Recherche Médicale) | New tau species |
CN110881274A (zh) | 2017-05-02 | 2020-03-13 | 普罗塞纳生物科学有限公司 | 识别tau的抗体 |
JP6851549B2 (ja) | 2017-10-16 | 2021-03-31 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 抗タウ抗体及びその使用 |
US11124552B2 (en) | 2017-10-25 | 2021-09-21 | Ac Immune Sa | Compositions of phosphorylated tau peptides and uses thereof |
US11773148B2 (en) * | 2017-10-27 | 2023-10-03 | United Neuroscience | Tau peptide immunogen constructs |
AR113926A1 (es) | 2017-12-14 | 2020-07-01 | H Lundbeck As | Derivados de 1h-pirazolo[4,3-b]piridinas |
SG11202005361RA (en) | 2017-12-14 | 2020-07-29 | H Lundbeck As | Combination treatments comprising administration of 1h-pyrazolo[4,3-b]pyridines |
US11535611B2 (en) | 2017-12-20 | 2022-12-27 | H. Lundbeck A/S | Pyrazolo[3,4-B]pyridines and imidazo[1,5-B]pyridazines as PDE1 inhibitors |
AU2019232630A1 (en) * | 2018-03-05 | 2020-09-24 | Janssen Pharmaceutica Nv | Assays to detect neurodegeneration |
CN110548135B (zh) * | 2018-05-31 | 2023-06-06 | 长春百克生物科技股份公司 | 磷酸化多肽抗原疫苗及其制备方法和应用 |
WO2020028141A1 (en) | 2018-07-31 | 2020-02-06 | Eli Lilly And Company | Combination therapy |
EP3883602A4 (en) * | 2018-11-19 | 2023-04-12 | The Board Of Regents Of The University Of Texas System | TAU PEPTIDE ANTIGENS AND ANTIBODIES BINDING TO THEM FOR THE TREATMENT OF TAUOPATHIES |
US20220041697A1 (en) * | 2018-12-10 | 2022-02-10 | New York University | Monoclonal antibodies targeting c-terminal region of phosphorylated tau |
CN111323597A (zh) * | 2018-12-14 | 2020-06-23 | 陈志成 | 用于检测受试者中mci和/或ad的方法、试剂盒及筛选化合物的方法 |
EP3920966A2 (en) * | 2019-02-08 | 2021-12-15 | AC Immune S.A. | Method of safe administration of phosphorylated tau peptide vaccine |
BR112021016947A2 (pt) | 2019-03-03 | 2021-11-03 | Prothena Biosciences Ltd | Anticorpos que reconhecem tau |
CN113874078A (zh) | 2019-04-05 | 2021-12-31 | Tauc3生物制品有限公司 | 抗tauc3抗体及其应用 |
BR112021021213A2 (pt) | 2019-04-24 | 2021-12-21 | Ac Immune Sa | Administração heteróloga de vacinas de tau |
GB201909393D0 (en) | 2019-06-28 | 2019-08-14 | Gen2 Neuroscience Ltd | Tau epitope and binding molecules |
GB2585252A (en) | 2019-07-05 | 2021-01-06 | Gen2 Neuroscience Ltd | Tau epitope and binding molecules |
CN110317814A (zh) * | 2019-07-19 | 2019-10-11 | 莫丁丁 | β-淀粉样蛋白环状核糖核酸、多肽及其应用 |
EP4028040A2 (en) | 2019-09-09 | 2022-07-20 | Axon Neuroscience SE | Biomarkers and treatments of alzheimer's disease and mild cognitive impairment |
CN110684122B (zh) * | 2019-10-29 | 2021-03-02 | 中国人民解放军军事科学院军事医学研究院 | 重组Tau表位嵌合多聚体抗原、其制备方法和应用 |
US20230265175A1 (en) | 2020-06-25 | 2023-08-24 | Merck Sharp & Dohme Llc | High affinity antibodies targeting tau phosphorylated at serine 413 |
WO2022054795A1 (ja) * | 2020-09-08 | 2022-03-17 | 国立大学法人大阪大学 | リン酸化タウタンパク質を標的とする免疫原性組成物 |
CA3228878A1 (en) * | 2021-08-12 | 2023-02-16 | Andrea Pfeifer | Liposomes containing phosphorylated tau peptides for inducing sustained immune responses |
WO2024005008A1 (ja) * | 2022-06-28 | 2024-01-04 | 大塚製薬株式会社 | シヌクレイノパチーを判定するための方法 |
CN116948025B (zh) * | 2023-09-14 | 2024-04-02 | 北京凯祥弘康生物科技有限公司 | 一种抗Tau蛋白的抗体 |
Family Cites Families (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US5059421A (en) | 1985-07-26 | 1991-10-22 | The Liposome Company, Inc. | Preparation of targeted liposome systems of a defined size distribution |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
US5750373A (en) | 1990-12-03 | 1998-05-12 | Genentech, Inc. | Enrichment method for variant proteins having altered binding properties, M13 phagemids, and growth hormone variants |
US5328470A (en) | 1989-03-31 | 1994-07-12 | The Regents Of The University Of Michigan | Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor |
CA2017507C (en) | 1989-05-25 | 1996-11-12 | Gary Van Nest | Adjuvant formulation comprising a submicron oil droplet emulsion |
WO1991006658A2 (en) | 1989-10-24 | 1991-05-16 | Cetus Corporation | Infective protein delivery system |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
WO1992003918A1 (en) | 1990-08-29 | 1992-03-19 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
JP2916297B2 (ja) * | 1991-02-25 | 1999-07-05 | 三菱化学株式会社 | ホスホペプチド |
WO1993003369A1 (en) * | 1991-08-01 | 1993-02-18 | Voorheis Paul H | Diagnostic method for alzheimer's disease |
FR2681786A1 (fr) | 1991-09-27 | 1993-04-02 | Centre Nat Rech Scient | Vecteurs recombinants d'origine virale, leur procede d'obtention et leur utilisation pour l'expression de polypeptides dans des cellules musculaires. |
IL103059A0 (en) | 1991-09-30 | 1993-02-21 | Boehringer Ingelheim Int | Conjugates for introducing nucleic acid into higher eucaryotic cells |
NZ244306A (en) | 1991-09-30 | 1995-07-26 | Boehringer Ingelheim Int | Composition for introducing nucleic acid complexes into eucaryotic cells, complex containing nucleic acid and endosomolytic agent, peptide with endosomolytic domain and nucleic acid binding domain and preparation |
JP3909084B2 (ja) * | 1991-10-25 | 2007-04-25 | エヌ・ブイ・インノジェネティクス・ソシエテ・アノニム | 微小管結合タンパク質タウに対するモノクローナル抗体 |
EP0911390B1 (en) | 1991-12-06 | 2009-08-05 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Protein kinases as tools for the diagnosis and treatment of Alzheimer's disease |
US7408027B1 (en) | 1991-12-06 | 2008-08-05 | Max-Planck-Gesellschaft Zur Forderung Der Wissenchaften | Tools for the diagnosis and treatment of Alzheimer's disease |
GB9223084D0 (en) | 1992-11-04 | 1992-12-16 | Imp Cancer Res Tech | Compounds to target cells |
US6010913A (en) * | 1992-12-14 | 2000-01-04 | N.V. Innogenetics S.A. | Isolated human tau peptide |
US5631237A (en) | 1992-12-22 | 1997-05-20 | Dzau; Victor J. | Method for producing in vivo delivery of therapeutic agents via liposomes |
JPH08512056A (ja) | 1993-06-30 | 1996-12-17 | ジェネンテク・インコーポレイテッド | リポソームの製造法 |
US5516637A (en) | 1994-06-10 | 1996-05-14 | Dade International Inc. | Method involving display of protein binding pairs on the surface of bacterial pili and bacteriophage |
US5846782A (en) | 1995-11-28 | 1998-12-08 | Genvec, Inc. | Targeting adenovirus with use of constrained peptide motifs |
US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
DK0787200T3 (da) | 1994-10-28 | 2005-08-15 | Univ Pennsylvania | Forbedret adenovirus og fremgangsmåder til anvendelse heraf |
US5643599A (en) | 1995-06-07 | 1997-07-01 | President And Fellows Of Harvard College | Intracellular delivery of macromolecules |
ES2333425T5 (es) | 1995-06-15 | 2012-08-28 | Crucell Holland B.V. | Sistemas de empaquetado para adenovirus recombinante humano destinados a terapia génica |
US5871727A (en) | 1995-12-08 | 1999-02-16 | Uab Research Foundation | Targeted adenovirus vectors |
US5994132A (en) | 1996-10-23 | 1999-11-30 | University Of Michigan | Adenovirus vectors |
WO1998022120A1 (en) * | 1996-11-19 | 1998-05-28 | The Wistar Institute Of Anatomy & Biology | Diagnostic and therapeutic reagents for alzheimer's disease |
US5981225A (en) | 1998-04-16 | 1999-11-09 | Baylor College Of Medicine | Gene transfer vector, recombinant adenovirus particles containing the same, method for producing the same and method of use of the same |
JP2003534351A (ja) * | 2000-05-22 | 2003-11-18 | ニュー・ヨーク・ユニヴァーシティー | アミロイドβ及びアミロイド沈着物に対する免疫応答誘導のための、アミロイドβと相同的な、合成の、免疫原性だが非アミロイド原性ペプチド |
ATE360392T1 (de) | 2000-11-02 | 2007-05-15 | Cornell Res Foundation Inc | In vivo multiphoton diagnostische detektion und bilddarstellung einer neurodegenerativen erkrankung |
WO2002086096A2 (en) | 2001-01-23 | 2002-10-31 | University Of Rochester Medical Center | Methods of producing or identifying intrabodies in eukaryotic cells |
AT500379B8 (de) * | 2001-02-02 | 2009-08-15 | Axon Neuroscience | Tau-proteine |
AU2002314794A1 (en) * | 2001-05-23 | 2002-12-03 | New York University | Detection of alzheimer's amyloid by magnetic resonance imaging |
US6906169B2 (en) | 2001-05-25 | 2005-06-14 | United Biomedical, Inc. | Immunogenic peptide composition comprising measles virus Fprotein Thelper cell epitope (MUFThl-16) and N-terminus of β-amyloid peptide |
US20020197258A1 (en) * | 2001-06-22 | 2002-12-26 | Ghanbari Hossein A. | Compositions and methods for preventing protein aggregation in neurodegenerative diseases |
US7479482B2 (en) * | 2001-11-21 | 2009-01-20 | New York University | Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid β, prion protein, amylin, α-synuclein, or polyglutamine repeats for induction of an immune response thereto |
GB0226727D0 (en) | 2002-11-15 | 2002-12-24 | Medical Res Council | Intrabodies |
US20040247661A1 (en) | 2002-07-03 | 2004-12-09 | Dov Michaeli | Liposomal vaccine |
WO2004083431A1 (ja) * | 2003-03-19 | 2004-09-30 | Zoegene Corporation | 転写反応を調節するタンパク質のスクリーニング方法および活性測定方法 |
WO2004087733A2 (en) * | 2003-03-28 | 2004-10-14 | New York University | Prevention and treatment of alzheimer amyloid deposition |
US8685718B2 (en) * | 2003-05-20 | 2014-04-01 | New York University | Mucosal immunization to prevent prion infection |
MX2007013825A (es) * | 2005-05-05 | 2008-01-18 | Merck & Co Inc | Composiciones de un conjugado peptidico y metodos para la prevencion y tratamiento de la enfermedad de alzheimer. |
US8012936B2 (en) * | 2006-03-29 | 2011-09-06 | New York University | Tau fragments for immunotherapy |
US20100143371A1 (en) | 2006-10-31 | 2010-06-10 | Zhenping Zhu | Intrabodies |
WO2008140639A2 (en) * | 2007-02-08 | 2008-11-20 | Oligomerix, Inc. | Biomarkers and assays for alzheimer's disease |
SI2408807T1 (sl) * | 2009-03-18 | 2021-11-30 | Ac Immune Sa | Postopek za terapevtsko uporabo |
UA107571C2 (xx) * | 2009-04-03 | 2015-01-26 | Фармацевтична композиція | |
CN106390107B (zh) * | 2009-06-10 | 2019-12-31 | 纽约大学 | 病理tau蛋白的免疫靶向 |
KR20130127547A (ko) * | 2009-07-30 | 2013-11-22 | 화이자 백신스 엘엘씨 | 항원성 타우 펩타이드 및 이의 용도 |
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US20170183400A1 (en) | 2017-06-29 |
CN102596221A (zh) | 2012-07-18 |
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JP2019163268A (ja) | 2019-09-26 |
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CN106390107A (zh) | 2017-02-15 |
WO2010144711A3 (en) | 2011-05-26 |
JP6518727B2 (ja) | 2019-05-22 |
US20100316564A1 (en) | 2010-12-16 |
EP2440234A4 (en) | 2013-11-06 |
EP2440234A2 (en) | 2012-04-18 |
EA032675B1 (ru) | 2019-07-31 |
EP4218794A3 (en) | 2023-09-13 |
CN106390107B (zh) | 2019-12-31 |
JP2012530055A (ja) | 2012-11-29 |
EP3329932A1 (en) | 2018-06-06 |
JP5917394B2 (ja) | 2016-05-11 |
JP2016094426A (ja) | 2016-05-26 |
JP2017193571A (ja) | 2017-10-26 |
WO2010144711A2 (en) | 2010-12-16 |
US8748386B2 (en) | 2014-06-10 |
EP4218794A2 (en) | 2023-08-02 |
US20210061894A1 (en) | 2021-03-04 |
CA3120504A1 (en) | 2010-12-16 |
JP6795649B2 (ja) | 2020-12-02 |
CA2765099A1 (en) | 2010-12-16 |
JP7229980B2 (ja) | 2023-02-28 |
EA201171397A1 (ru) | 2012-05-30 |
CA3239368A1 (en) | 2010-12-16 |
CN102596221B (zh) | 2019-06-04 |
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