JP2014521687A - 体液性および細胞傷害性tリンパ球(ctl)免疫応答を生成する合成ナノキャリア - Google Patents
体液性および細胞傷害性tリンパ球(ctl)免疫応答を生成する合成ナノキャリア Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Abstract
Description
本出願は、米国特許法第119条の下で、それぞれ2011年7月29日に出願された米国仮特許出願第61/513,496号、同第61/513,526号および同第61/513,527号の利益を主張するものであり、これらの仮特許出願のそれぞれの内容全体が、参照により本明細書に援用される。
治療または予防ワクチンによる、HIV、マラリヤ、B型肝炎、および癌などの難病の治療は、組み合わされた体液性およびCTL免疫応答によって強化され、またはある状況下では組み合わされた体液性およびCTL免疫応答を必要とし得る。ワクチンの手法が、組み合わされたCTLおよび体液性免疫応答を生成するために提案されている一方、代替的な手法が、臨床的有効性、安全性、および/または製造可能性の有益な改善を提供し得る。強力でかつ有効な体液性およびCTL免疫応答を生成することが既に示されていないと考えられる、合成ナノキャリア組成物を使用するための方法、および関連する組成物が、本明細書に提供される。このような組成物は、より有効な免疫応答を生成するために、対象とする免疫細胞を有効に標的にすることができる。
「アジュバント」は、特定の抗原ではないが、同時に投与された抗原に対する免疫応答の強度および持続性(longevity)を高める物質を意味する。このようなアジュバントとしては、以下に限定はされないが、RIG−1およびNOD様受容体(NLR)などのToll様受容体などのパターン認識受容体の刺激薬、ミョウバンなどの無機塩、大腸菌(Escherichia coli)、サルモネラ・ミネソタ(Salmonella minnesota)、ネズミチフス菌(Salmonella typhimurium)、またはフレクスナー赤痢菌(Shigella flexneri)などの腸内細菌のモノホスホリル脂質(MPL)Aと組み合わされたミョウバンまたは特にMPL(登録商標)(AS04)、上記の細菌のMPL Aと別々に組み合わされたミョウバン、QS−21、Quil−A、ISCOM、ISCOMATRIX(商標)などのサポニン、MF59(商標)、Montanide(登録商標)ISA 51およびISA 720、AS02(QS21+スクアレン+MPL(登録商標))などのエマルジョン、AS01などのリポソームおよびリポソーム製剤、淋菌(N.gonorrheae)、クラミジア・トラコマチス(Chlamydia trachomatis)などの細菌由来の外膜小胞(OMV)などの合成されたまたは特異的に調製された微粒子およびマイクロキャリア、またはキトサン粒子、Pluronic(登録商標)ブロックコポリマーなどのデポー形成剤、ムラミルジペプチドなどの特異的に修飾または調製されたペプチド、RC529などのアミノアルキルグルコサミニド4−ホスフェート、あるいは細菌トキソイドまたは毒素フラグメントなどのタンパク質が挙げられる。「サポニン−コレステロールアジュバント」は、コレステロールとの混合によって安定化されるサポニンアジュバントである。このようなアジュバントとしては、例えば、ISCOMおよびISCOMATRIXアジュバントが挙げられる。好ましくは、ある実施形態において、本明細書に提供される合成ナノキャリアは、このようなアジュバントではなく、またはこのようなアジュバントを含まない。他の実施形態において、本明細書に提供される組成物は、このようなアジュバントを含まない。
有効な体液性およびCTL免疫応答の生成のための方法および関連する組成物が本明細書に提供される。同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含むタンパク質が結合される合成ナノキャリアであって、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法である合成ナノキャリアが、有効でかつ強力な体液性およびCTL免疫応答を生成するのに使用され得ることが分かった。提供される組成物は、ワクチン接種などの、様々な所望の臨床的エンドポイントに使用され得る。
合成ナノキャリアは、当該技術分野において公知の様々な方法を用いて調製され得る。例えば、合成ナノキャリアは、ナノ析出(nanoprecipitation)、流体チャネルを用いたフローフォーカシング(flow focusing)、噴霧乾燥、単一および二重乳化溶媒蒸発、溶媒抽出、相分離、ミリング、マイクロエマルジョン法、マイクロ加工、ナノ加工(nanofabrication)、犠牲層、単純コアセルベーションおよび複合コアセルベーション、並びに当業者に周知の他の方法のような方法によって形成され得る。その代わりにまたはそれに加えて、単分散半導体ナノ材料、伝導性ナノ材料、磁性ナノ材料、有機ナノ材料、および他のナノ材料のための水性および有機溶媒合成が、記載されている(Pellegrino et al.,2005,Small,1:48;Murray et al.,2000,Ann.Rev.Mat.Sci.,30:545;およびTrindade et al.,2001,Chem.Mat.,13:3843)。更なる方法が、文献に記載されている(例えば、Doubrow,Ed.,“Microcapsules and Nanoparticles in Medicine and Pharmacy,” CRC Press,Boca Raton,1992;Mathiowitz et al.,1987,J.Control.Release,5:13;Mathiowitz et al.,1987,Reactive Polymers,6:275;およびMathiowitz et al.,1988,J.Appl.Polymer Sci.,35:755;米国特許第5578325号明細書および同第6007845号明細書;P.Paolicelli et al.,“Surface−modified PLGA−based Nanoparticles that can Efficiently Associate and Deliver Virus−like Particles” Nanomedicine.5(6):843−853(2010)を参照されたい)。
材料
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701.製品コード3048)から購入した。3:1のラクチド対グリコリド比および12.7% w/wの共役R848含量を有するPLGAから作製された約5,200DaのPLGA−R848を合成した。約5,000Daのニコチン末端PEGブロックおよび約19,000DaのDL−PLAブロックを有するPLA−PEG−ニコチンを合成した。0.21dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。ポリビニルアルコール(分子量=11,000〜31,000、87〜89%加水分解されたもの)を、J.T.Baker(パーツ番号U232−08)から購入した。
溶液を以下のとおりに調製した:
溶液1:10mMのリン酸緩衝液中20mg/mLのオボアルブミンタンパク質。
溶液2:ジクロロメタン中50mg/mLのPLGA−R848、25mg/mLのPLA−PEG−ニコチン、25mg/mlのPLA。100mg/mLの各ポリマーをジクロロメタンに別々に溶解させ、次に、2部のPLGA−R848溶液を1部の各PLA−PEG−ニコチン溶液およびPLA溶液に加えることによって溶液を混合することによって、溶液を調製した。
溶液3:100mMのリン酸緩衝液(pH8)中、100mM中50mg/mLのポリビニルアルコール。
溶液4:70mMのリン酸緩衝液(pH8)。
材料
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701.製品コード3048)から購入した。オボアルブミンペプチド323−339アミド酢酸塩を、Bachem Americas Inc.(3132 Kashiwa Street,Torrance CA 90505.製品コード4065609)から購入した。3:1のラクチド対グリコリド比および12.7% w/wの共役R848含量を有するPLGAから作製された約5,200DaのPLGA−R848を合成した。約5,000Daのニコチン末端PEGブロックおよび約19,000DaのDL−PLAブロックを有するPLA−PEG−ニコチンを合成した。0.21dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。ポリビニルアルコール(分子量=11,000〜31,000、87〜89%加水分解されたもの)を、J.T.Baker(パーツ番号U232−08)から購入した。
溶液を以下のとおりに調製した:
溶液1A:10mMのリン酸緩衝液中40mg/mLのオボアルブミンタンパク質。
溶液1B:希塩酸水溶液中40mg/mLのオボアルブミンペプチドアミド323−339。
溶液2:ジクロロメタン中50mg/mLのPLGA−R848、25mg/mLのPLA−PEG−ニコチン、25mg/mlのPLA。100mg/mLの各ポリマーをジクロロメタンに別々に溶解させ、次に、2部のPLGA−R848溶液を1部の各PLA−PEG−ニコチン溶液およびPLA溶液に加えることによって溶液を混合することによって、溶液を調製した。
溶液3:100mMのリン酸緩衝液(pH8)中、100mM中50mg/mLのポリビニルアルコール。
溶液4:70mMのリン酸緩衝液(pH8)。
材料
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701.製品コード3048)から購入した。3:1のラクチド対グリコリド比および12.7% w/wの共役R848含量を有するPLGAから作製された約5,200DaのPLGA−R848を合成した。2,000Daのメチルエーテル末端PEGブロックおよび約19,000DaのDL−PLAブロックを有するPLA−PEG−OMeブロックコポリマーを合成した。0.21dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。ポリビニルアルコール(分子量=11,000〜31,000、87〜89%加水分解されたもの)を、J.T.Baker(パーツ番号U232−08)から購入した。
溶液を以下のとおりに調製した:
溶液1:10mMのリン酸緩衝液中20mg/mLのオボアルブミンタンパク質。
溶液2:ジクロロメタン中50mg/mLのPLGA−R848、25mg/mLのPLA−PEG−OMe、25mg/mlのPLA。100mg/mLの各ポリマーをジクロロメタンに別々に溶解させ、次に、2部のPLGA−R848溶液を1部の各PLA−PEG−OMe溶液およびPLA溶液に加えることによって溶液を混合することによって、溶液を調製した。
溶液3:100mMのリン酸緩衝液(pH8)中、100mM中50mg/mLのポリビニルアルコール。
溶液4:70mMのリン酸緩衝液(pH8)。
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701.製品コード3048)から購入した。オボアルブミンペプチド323−339アミド酢酸塩を、Bachem Americas Inc.(3132 Kashiwa Street,Torrance CA 90505.製品コード4065609)から購入した。3:1のラクチド対グリコリド比および12.7% w/wの共役R848含量を有するPLGAから作製された約5,200DaのPLGA−R848を合成した。2,000Daのメチルエーテル末端PEGブロックおよび約19,000DaのDL−PLAブロックを有するPLA−PEG−OMeブロックコポリマーを合成した。0.21dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。ポリビニルアルコール(分子量=11,000〜31,000、87〜89%加水分解されたもの)を、J.T.Baker(パーツ番号U232−08)から購入した。
溶液を以下のとおりに調製した:
溶液1A:10mMのリン酸緩衝液中40mg/mLのオボアルブミンタンパク質。
溶液1B:希塩酸水溶液中40mg/mLのオボアルブミンペプチドアミド323−339。
溶液2:ジクロロメタン中50mg/mLのPLGA−R848、25mg/mLのPLA−PEG−OMe、25mg/mlのPLA。100mg/mLの各ポリマーをジクロロメタンに別々に溶解させ、次に、2部のPLGA−R848溶液を1部の各PLA−PEG−OMe溶液およびPLA溶液に加えることによって溶液を混合することによって、溶液を調製した。
溶液3:100mMのリン酸緩衝液(pH8)中、100mM中50mg/mLのポリビニルアルコール。
溶液4:70mMのリン酸緩衝液(pH8)。
材料
SIINFEKL(配列番号1)(オボアルブミンペプチド[257−264])を、Bachem Americas Inc.(3132 Kashiwa Street,Torrance CA 90505.製品コードH−4866)から購入した。オボアルブミンペプチド323−339アミド酢酸塩を、Bachem Americas Inc.(3132 Kashiwa Street,Torrance CA 90505.製品コード4065609)から購入した。3:1のラクチド対グリコリド比および15% w/wの共役R848含量を有するPLGAから作製された約4,500DaのPLGA−R848を合成した。約5,000Daのニコチン末端PEGブロックおよび約17,000DaのDL−PLAブロックを有するPLA−PEG−ニコチンを合成した。0.21dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。ポリビニルアルコール(分子量=11,000〜31,000、87〜89%加水分解されたもの)を、J.T.Baker(パーツ番号U232−08)から購入した。
溶液を以下のとおりに調製した:
溶液1A:DMSO中200mg/mLのSIINFEKL(配列番号1)。
溶液1B:希塩酸水溶液中20mg/mLのオボアルブミンペプチドアミド323−339。
溶液2:ジクロロメタン中50mg/mLのPLGA−R848、25mg/mLのPLA−PEG−ニコチン、25mg/mlのPLA。100mg/mLの各ポリマーをジクロロメタンに別々に溶解させ、次に、2部のPLGA−R848溶液を1部の各PLA−PEG−ニコチン溶液およびPLA溶液に加えることによって溶液を混合することによって、溶液を調製した。
溶液3:100mMのリン酸緩衝液(pH8)中、100mM中50mg/mLのポリビニルアルコール。
溶液4:70mMのリン酸緩衝液(pH8)。
第3および第4の生体内(C57BL/6マウス)免疫化試験を行った。TLRアゴニスト(R848)および封入されたオボアルブミンタンパク質(OVA)を送達する上記のポリマーナノキャリア製剤(#3)を導入し、局所リンパおよび脾臓細胞からの高い抗体力価(例えば、約1e6の抗OVA IgG力価)および強力な抗原特異的CTL活性を生成した。
材料
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701)から購入した。製品コードLS003054。3:1のラクチド対グリコリド比および8.5% w/wの共役レシキモド含量を有するPLGAから作製された約7,800DaのPLGA−R848、ポリ−D/L−ラクチド−コ−グリコリド、4−アミノ−2−(エトキシメチル)−α,α−ジメチル−1H−イミダゾ[4,5−c]キノリン−1−エタノールアミドを、Princeton Global Synthesis(300 George Patterson Drive #206,Bristol,PA 19007)においてカスタム製造した。ロット番号PGS 16−52。0.21dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。1H−NMRによる約5,000Daのメチルエーテル末端PEGブロックおよび約21,000DaのPLAブロック(21kDaのMn)を有するPLA−PEG−OMeブロックコポリマーを合成した。EMPROVE(登録商標)ポリビニルアルコール5−88、USP(85〜89%加水分解されたもの、4.3〜5.7mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027.パーツ番号1.41354)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)。Mediatech Inc.製(9345 Discovery Blvd.Manassas,VA 20109)。製品コード21−040−CV。
溶液を以下のとおりに調製した:
溶液1:20mg/mLのオボアルブミンタンパク質を、室温で1倍のPBS中で調製した。
溶液2:化学ヒュームフード(chemical fume hood)中で、1mLのジクロロメタン当たり100mgのPLAを溶解させることによって、PLAを調製した。
溶液3:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLA−PEG−OMeを溶解させることによって、PLA−PEG−OMeを調製した。
溶液4:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGA−R848を溶解させることによって、PLGA−R848を調製した。
溶液5:100mMのリン酸緩衝液(pH8)中、100mM中50mg/mLのポリビニルアルコール。
溶液6:70mMのリン酸緩衝液(pH8)。
材料
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701)から購入した。製品コードLS003054。3:1のラクチド対グリコリド比および8.5% w/wの共役レシキモド含量を有するPLGAから作製された約7,800DaのPLGA−R848、ポリ−D/L−ラクチド−コ−グリコリド、4−アミノ−2−(エトキシメチル)−α,α−ジメチル−1H−イミダゾ[4,5−c]キノリン−1−エタノールアミドを、Princeton Global Synthesis(300 George Patterson Drive #206,Bristol,PA 19007)においてカスタム製造した。ロット番号PGS 16−52。0.21dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。1H−NMRによる約5,000Daのメチルエーテル末端PEGブロックおよび約21,000DaのPLAブロック(21kDaのMn)を有するPLA−PEG−OMeブロックコポリマーを合成した。EMPROVE(登録商標)ポリビニルアルコール5−88、USP(85〜89%加水分解されたもの、4.3〜5.7mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027.パーツ番号1.41354)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)。Mediatech Inc.製(9345 Discovery Blvd.Manassas,VA 20109)。製品コード21−040−CV。
溶液を以下のとおりに調製した:
溶液1:5mg/mLのオボアルブミンタンパク質を、室温で1倍のPBS中で調製した。
溶液2:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLAを溶解させることによって、PLAを調製した。
溶液3:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLA−PEG−OMeを溶解させることによって、PLA−PEG−OMeを調製した。
溶液4:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGA−R848を溶解させることによって、PLGA−R848を調製した。
溶液5:100mMのリン酸緩衝液(pH8)中、100mM中50mg/mLのポリビニルアルコール。
溶液6:70mMのリン酸緩衝液(pH8)。
材料
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701)から購入した。製品コードLS003054。3:1のラクチド対グリコリド比および8.5% w/wの共役レシキモド含量を有するPLGAから作製された約7,800DaのPLGA−R848、ポリ−D/L−ラクチド−コ−グリコリド、4−アミノ−2−(エトキシメチル)−α,α−ジメチル−1H−イミダゾ[4,5−c]キノリン−1−エタノールアミドを、Princeton Global Synthesis(300 George Patterson Drive #206,Bristol,PA 19007)においてカスタム製造した。0.21dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。1H−NMRによる約5,000Daのメチルエーテル末端PEGブロックおよび約21,000DaのPLAブロック(21kDaのMn)を有するPLA−PEG−OMeブロックコポリマーを合成した。EMPROVE(登録商標)ポリビニルアルコール5−88、USP(85〜89%加水分解されたもの、4.3〜5.7mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027.パーツ番号1.41354)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)。Mediatech Inc.製(9345 Discovery Blvd.Manassas,VA 20109)。製品コード21−040−CV。
溶液を以下のとおりに調製した:
溶液1:20mg/mLのオボアルブミンタンパク質を、室温で1倍のPBS中で調製した。
溶液2:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLAを溶解させることによって、PLAを調製した。
溶液3:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLA−PEG−OMeを溶解させることによって、PLA−PEG−OMeを調製した。
溶液4:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGA−R848を溶解させることによって、PLGA−R848を調製した。
溶液5:100mMのリン酸緩衝液(pH8)中、100mM中50mg/mLのポリビニルアルコール。
溶液6:70mMのリン酸緩衝液(pH8)。
R848およびOVAを送達する合成ナノキャリアは、中央(脾臓)OVA特異的CTL応答の生成、また、同程度に強力な(またはより強力な)OVA特異的体液性応答の生成において、高用量のPS−CpGおよび6倍高い投与量の遊離OVAからなる陽性比較対照と同程度に良好であった。
材料−ロット番号9
3:1のラクチド対グリコリド比および8.5% w/wの共役レシキモド含量を有するPLGAから作製された約7,800DaのPLGA−R848(S−205)、ポリ−D/L−ラクチド−コ−グリコリド、4−アミノ−2−(エトキシメチル)−α,α−ジメチル−1H−イミダゾ[4,5−c]キノリン−1−エタノールアミドを、Princeton Global Synthesis(300 George Patterson Drive #206,Bristol,PA 19007)においてカスタム製造した。0.19dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。約5,000Daのメチルエーテル末端PEGブロックおよび約28,000DaのPLAブロックを有するPLA−PEG−OMeブロックコポリマーを、SurModics Pharmaceuticals(製品コード100 DL mPEG 5000 5CE)から購入した。EMPROVE(登録商標)ポリビニルアルコール4−88、USP(85〜89%加水分解されたもの、3.4〜4.6mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)。Mediatech Inc.製(9345 Discovery Blvd.Manassas,VA 20109)。製品コード21−040−CV。
溶液を以下のとおりに調製した:
溶液1:PLGA−R848、PLA、およびPLA−PEG−OMe粉末を、2:1:1の重量比で量り分けて、次に、混合されたポリマーをジクロロメタンに溶解させて、1mL当たり100mgの総ポリマー濃度を得ることによって、PLGA−R848を調製した。
溶液2:100mMのリン酸緩衝液(pH8)中35mg/mLのポリビニルアルコール。
3:1のラクチド対グリコリド比および8.5% w/wの共役レシキモド含量を有するPLGAから作製された約7,800DaのPLGA−R848(S−205)、ポリ−D/L−ラクチド−コ−グリコリド、4−アミノ−2−(エトキシメチル)−α,α−ジメチル−1H−イミダゾ[4,5−c]キノリン−1−エタノールアミドを、Princeton Global Synthesis(300 George Patterson Drive #206,Bristol,PA 19007)においてカスタム製造した。0.19dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード100 DL 2A)から購入した。約5,000Daのメチルエーテル末端PEGブロックおよび約28,000DaのPLAブロックを有するPLA−PEG−OMeブロックコポリマーを、SurModics Pharmaceuticals(製品コード100 DL mPEG 5000 5CE)から購入した。EMPROVE(登録商標)ポリビニルアルコール4−88、USP(85〜89%加水分解されたもの、3.4〜4.6mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)。Mediatech Inc.製(9345 Discovery Blvd.Manassas,VA 20109)。製品コード21−040−CV。
溶液を以下のとおりに調製した:
溶液1:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGA−R848を溶解させることによって、PLGA−R848を調製した。
溶液2:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLAを溶解させることによって、PLAを調製した。
溶液3:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLA−PEG−OMeを溶解させることによって、PLA−PEG−OMeを調製した。
溶液4:100mMのリン酸緩衝液(pH8)中50mg/mLのポリビニルアルコール。
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701)から購入した。製品コードLS003054。75%のラクチドおよび25%のグリコリド含量ならびに0.24dL/gの固有粘度を有するPLGAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード7525 DLG 2.5A)から購入した。0.2dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(製品コード100 DL 2A)から購入した。約5,000Daのメチルエーテル末端PEGブロックおよび約21,000DaのPLAブロックを有するPLA−PEG−OMeブロックコポリマーを合成した。EMPROVE(登録商標)ポリビニルアルコール4−88、USP(85〜89%加水分解されたもの、3.4〜4.6mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)。Mediatech Inc.製(9345 Discovery Blvd.Manassas,VA 20109)。製品コード21−040−CV。
溶液を以下のとおりに調製した:
溶液1:50mg/mLのオボアルブミンタンパク質を、室温で1倍のPBS中で調製した。
溶液2:PLGA、PLA、およびPLA−PEG−OMeを、2:1:1の重量比で量り分け、化学ヒュームフード中でジクロロメタンに溶解させて、1mL当たり100mgの最終的な総ポリマー濃度を得た。
溶液3:100mMのリン酸緩衝液(pH8)中50mg/mLのポリビニルアルコール。
溶液4:70mMのリン酸緩衝液(pH8)。
材料−ロット番号12
ナトリウム対イオンを有する、ヌクレオチド配列5’−TCC ATG ACG TTC CTG ACG TT−3’(配列番号2)を有するホスホジエステル骨格を有するPO−1826 DNAオリゴヌクレオチドを、Oligo Factory(120 Jeffrey Avenue,Holliston,MA 01746)から購入した。54%のラクチドおよび46%のグリコリド含量ならびに0.24dL/gの固有粘度を有するPLGAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード5050 DLG 2.5A)から購入した。約2,000Daのメチルエーテル末端PEGブロックおよび約88,000Daの75%のラクチド/25%のグリコリドPLGAブロックを有するPLGA−PEG−OMeブロックコポリマーを、SurModics Pharmaceuticals(製品コード7525 DLG PEG 2000 7E−P)から購入した。EMPROVE(登録商標)ポリビニルアルコール4−88、USP(85〜89%加水分解されたもの、3.4〜4.6mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)。Mediatech Inc.製(9345 Discovery Blvd.Manassas,VA 20109)。製品コード21−040−CV。
溶液を以下のとおりに調製した:
溶液1:エンドトキシンを含まない水1mL当たり250mgのコール酸Naを含有する水溶液1mL当たり40mgを溶解させることによって、PO−1826を調製した。
溶液2:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLAを溶解させることによって、PLGAを調製した。
溶液3:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGA−PEG−OMeを溶解させることによって、PLGA−PEG−OMeを調製した。
溶液4:100mMのリン酸緩衝液(pH8)中50mg/mLのポリビニルアルコール。
溶液5:70mMのリン酸緩衝液(pH8)。
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701)から購入した。製品コードLS003054。75%のラクチドおよび25%のグリコリド含量ならびに0.2dL/gの固有粘度を有するPLGAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード7525 DLG 2A)から購入した。1H−NMRによる約5,000Daのメチルエーテル末端PEGブロックおよび約21,000DaのPLAブロック(21kDaのMn)を有するPLA−PEG−OMeブロックコポリマーを合成した。EMPROVE(登録商標)ポリビニルアルコール4−88、USP(85〜89%加水分解されたもの、3.4〜4.6mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)。Mediatech Inc.製(9345 Discovery Blvd.Manassas,VA 20109)。製品コード21−040−CV。
溶液を以下のとおりに調製した:
溶液1:50mg/mLのオボアルブミンタンパク質を、室温で1倍のPBS中で調製した。
溶液2:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGAを溶解させることによって、PLGAを調製した。
溶液3:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLA−PEG−OMeを溶解させることによって、PLA−PEG−OMeを調製した。
溶液4:100mMのリン酸緩衝液(pH8)中50mg/mLのポリビニルアルコール。
溶液5:70mMのリン酸緩衝液(pH8)。
オボアルブミンタンパク質を、Worthington Biochemical Corporation(730 Vassar Avenue,Lakewood,NJ 08701.製品コードLS003054)から購入した。76%のラクチドおよび24%のグリコリド含量ならびに0.69dL/gの固有粘度を有するPLGAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード7525 DLG 7A)から購入した。0.22dL/gの固有粘度を有するPLAを、SurModics Pharmaceuticals(製品コード100 DL 2A)から購入した。約5,000Daのメチルエーテル末端PEGブロックおよび約21,000DaのPLAブロックを有するPLA−PEG−OMeブロックコポリマーを合成した。EMPROVE(登録商標)ポリビニルアルコール4−88、USP(85〜89%加水分解されたもの、3.4〜4.6mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)を、Mediatech Inc.(9345 Discovery Blvd.Manassas,VA 20109)から購入した。製品コード21−040−CV。
溶液を以下のとおりに調製した:
溶液1:50mg/mLのオボアルブミンタンパク質を、室温で1倍のPBS中で調製した。
溶液2:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGAを溶解させることによって、PLGAを調製した。
溶液3:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGAを溶解させることによって、PLAを調製した。
溶液4:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLA−PEG−OMeを溶解させることによって、PLA−PEG−OMeを調製した。
溶液5:100mMのリン酸緩衝液(pH8)中50mg/mLのポリビニルアルコール。
溶液6:70mMのリン酸緩衝液(pH8)。
ナトリウム対イオンを有する、ヌクレオチド配列5’−TCC ATG ACG TTC CTG ACG TT−3’(配列番号2)を有するホスホジエステル骨格を有するPO−1826 DNAオリゴヌクレオチドを、Oligo Factory(120 Jeffrey Avenue,Holliston,MA 01746)から購入した。54%のラクチドおよび46%のグリコリド含量ならびに0.24dL/gの固有粘度を有するPLGAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード5050 DLG 2.5A)から購入した。約5,000Daのメチルエーテル末端PEGブロックおよび約21,000DaのPLAブロックを有するPLA−PEG−OMeブロックコポリマーを合成した。EMPROVE(登録商標)ポリビニルアルコール4−88、USP(85〜89%加水分解されたもの、3.4〜4.6mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027)から購入した。コール酸Naを、Sigma Aldrich LLC.(3050 Spruce St.St.Louis,MO 6310.製品コードC6445−100G)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)を、Mediatech Inc.(9345 Discovery Blvd.Manassas,VA 20109.製品コード21−040−CV)から購入した。
溶液を以下のとおりに調製した:
溶液1:エンドトキシンを含まない水1mL当たり150mgのKClを含有する水溶液1mL当たり40mgを溶解させることによって、PO−1826を調製した。
溶液2:室温で1mLの1倍のPBS当たり200mgの乾燥粉末を溶解させることによって、コール酸Naを調製した。
溶液3:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGAを溶解させることによって、PLGAを調製した。
溶液4:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGA−PEG−OMeを溶解させることによって、PLGA−PEG−OMeを調製した。
溶液5:100mMのリン酸緩衝液(pH8)中50mg/mLのポリビニルアルコール。
溶液6:70mMのリン酸緩衝液(pH8)。
ナトリウム対イオンを有する、ヌクレオチド配列5’−TCC ATG ACG TTC CTG ACG TT−3’(配列番号2)を有するホスホジエステル骨格を有するPO−1826 DNAオリゴヌクレオチドを、Oligo Factory(120 Jeffrey Avenue,Holliston,MA 01746)から購入した。54%のラクチドおよび46%のグリコリド含量ならびに0.24dL/gの固有粘度を有するPLGAを、SurModics Pharmaceuticals(756 Tom Martin Drive,Birmingham,AL 35211.製品コード5050 DLG 2.5A)から購入した。約5,000Daのメチルエーテル末端PEGブロックおよび約21,000DaのPLAブロックを有するPLA−PEG−OMeブロックコポリマーを合成した。EMPROVE(登録商標)ポリビニルアルコール4−88、USP(85〜89%加水分解されたもの、3.4〜4.6mPa.sの粘度)を、EMD Chemicals Inc.(480 South Democrat Road Gibbstown,NJ 08027)から購入した。1倍のリン酸緩衝生理食塩水(1倍のPBS)を、Mediatech Inc.(9345 Discovery Blvd.Manassas,VA 20109.製品コード21−040−CV)から購入した。
溶液を以下のとおりに調製した:
溶液1:エンドトキシンを含まない水1mL当たり150mgのKClを含有する水溶液1mL当たり40mgを溶解させることによって、PO−1826を調製した。
溶液2:100mMのリン酸緩衝液(pH8)中100mg/mLのポリビニルアルコール。
溶液3:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGAを溶解させることによって、PLGAを調製した。
溶液4:化学ヒュームフード中で、1mLのジクロロメタン当たり100mgのPLGA−PEG−OMeを溶解させることによって、PLGA−PEG−OMeを調製した。
溶液5:100mMのリン酸緩衝液(pH8)中100mg/mLのポリビニルアルコール。
溶液6:70mMのリン酸緩衝液(pH8)。
Claims (52)
- 第1のタンパク質に対する体液性および細胞傷害性Tリンパ球(CTL)免疫応答を必要とする被験体を同定する工程と、
前記第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物を、前記被験体に投与する工程と
を含む方法であって;
前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法である方法。 - 第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物を、被験体に投与する工程を含む方法であって;
前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法であり、前記組成物が、ワクチン接種計画にしたがって投与される方法。 - 第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物を、被験体に投与する工程を含む方法であって;
前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法であり、前記組成物が、一人以上の被験体における前記第1のタンパク質に特異的な体液性およびCTL免疫応答をもたらすことが既に示されたプロトコルにしたがって投与される方法。 - 前記第1のタンパク質に対する体液性および細胞傷害性Tリンパ球(CTL)免疫応答を必要とする被験体を同定する工程をさらに含む、請求項2または3に記載の方法。
- 前記組成物が、ワクチン接種計画にしたがって投与される、請求項1または3に記載の方法。
- 前記組成物が、一人以上の被験体における前記第1のタンパク質に特異的な体液性およびCTL免疫応答をもたらすことが既に示されたプロトコルにしたがって投与される、請求項1または2に記載の方法。
- 前記組成物が、前記第1のタンパク質に対する体液性およびCTL免疫応答を生成するのに有効な量で投与される、請求項1〜6のいずれか一項に記載の方法。
- 前記組成物が、1つ以上のアジュバントをさらに含む、請求項1〜7のいずれか一項に記載の方法。
- 1つ以上のアジュバントを投与する工程をさらに含む、請求項1〜7のいずれか一項に記載の方法。
- 前記1つ以上のアジュバントが、パターン認識受容体の刺激薬またはアゴニスト、無機塩、ミョウバン、腸内細菌のモノホスホリル脂質A(MPL)、MPL(登録商標)(AS04)と組み合わされたミョウバン、AS15、サポニン、QS−21、Quil−A、ISCOM、ISCOMATRIX(商標)、MF59(商標)、Montanide(登録商標)ISA 51、Montanide(登録商標)ISA 720、AS02、リポソームおよびリポソーム製剤、AS01、合成されたまたは特異的に調製された微粒子およびマイクロキャリア、淋菌(N.gonorrheae)またはクラミジア・トラコマチス(Chlamydia trachomatis)の細菌由来の外膜小胞、キトサン粒子、デポー形成剤、Pluronic(登録商標)ブロックコポリマー、特異的に修飾または調製されたペプチド、ムラミルジペプチド、アミノアルキルグルコサミニド4−ホスフェート、RC529、細菌トキソイド、毒素フラグメント、Toll様受容体2、3、4、5、7、8、9および/またはそれらの組合せのアゴニスト;アデニン誘導体;免疫刺激性DNA;免疫刺激性RNA;イミダゾキノリンアミン、イミダゾピリジンアミン、6,7−縮合シクロアルキルイミダゾピリジンアミン、1,2−架橋イミダゾキノリンアミン;イミキモド;レシキモド;DC表面分子CD40のためのアゴニスト;I型インターフェロン;ポリI:C;細菌性リポ多糖(LPS);VSV−G;HMGB−1;フラジェリンまたはその一部もしくは誘導体;CpGを含む免疫刺激性DNA分子;壊死細胞から放出される炎症誘発性刺激;尿酸結晶;補体カスケードの活性化成分;免疫複合体の活性化成分;補体受容体アゴニスト;サイトカイン;またはサイトカイン受容体アゴニストを含む、請求項8または9に記載の方法。
- 前記1つ以上のアジュバントが、Toll様受容体2、3、4、7、8または9のアゴニストを含む、請求項10に記載の方法。
- 前記1つ以上のアジュバントが、イミダゾキノリンまたはオキソアデニンを含む、請求項10に記載の方法。
- 前記イミダゾキノリンが、レシキモドまたはイミキモドを含む、請求項12に記載の方法。
- 前記1つ以上のアジュバントが、合成ナノキャリアの前記集団の前記合成ナノキャリアに結合される、請求項8〜13のいずれか一項に記載の方法。
- 前記組成物が、合成ナノキャリアの別の集団をさらに含み、または前記方法が、合成ナノキャリアの別の集団を投与する工程をさらに含み、前記1つ以上のアジュバントが、合成ナノキャリアの前記別の集団の前記合成ナノキャリアに結合される、請求項8〜13のいずれか一項に記載の方法。
- 前記1つ以上のアジュバントが、合成ナノキャリアに結合されない、請求項8〜13のいずれか一項に記載の方法。
- 前記組成物が、1つ以上のさらなる抗原をさらに含む、請求項1〜16のいずれか一項に記載の方法。
- 1つ以上のさらなる抗原を投与する工程をさらに含む、請求項1〜16のいずれか一項に記載の方法。
- 前記1つ以上のさらなる抗原が、第2のタンパク質を含む、請求項17または18に記載の方法。
- 前記1つ以上のさらなる抗原が、体液性エピトープおよび/またはMHCクラスI拘束性エピトープを含む、請求項17〜19のいずれか一項に記載の方法。
- 前記1つ以上のさらなる抗原が、体液性エピトープおよびMHCクラスI拘束性エピトープを含む、請求項20に記載の方法。
- 前記1つ以上のさらなる抗原が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含む、請求項20または21に記載の方法。
- 前記1つ以上のさらなる抗原が、前記合成ナノキャリアに結合される、請求項17〜22のいずれか一項に記載の方法。
- 前記組成物が、合成ナノキャリアの別の集団をさらに含み、または前記方法が、合成ナノキャリアの別の集団を投与する工程をさらに含み、前記1つ以上のさらなる抗原が、合成ナノキャリアの前記別の集団の前記合成ナノキャリアに結合される、請求項17〜22のいずれか一項に記載の方法。
- 前記1つ以上のさらなる抗原が、合成ナノキャリアに結合されない、請求項17〜22のいずれか一項に記載の方法。
- 前記合成ナノキャリアおよび/または他の合成ナノキャリアが、ポリマーナノ粒子、金属ナノ粒子、デンドリマー、バッキーボール、ナノワイヤ、ウイルス様粒子またはペプチドもしくはタンパク質粒子を含む、請求項1〜25のいずれか一項に記載の方法。
- 前記合成ナノキャリアおよび/または他の合成ナノキャリアが、1つ以上のポリマーを含む、請求項1〜26のいずれか一項に記載の方法。
- 前記1つ以上のポリマーが、ポリエステル、ポリアミノ酸、ポリカーボネート、ポリアセタール、ポリケタール、多糖、ポリエチルオキサゾリンまたはポリエチレンイミンを含む、請求項27に記載の方法。
- 前記1つ以上のポリマーが、ポリエステルを含む、請求項27または28に記載の方法。
- 前記ポリエステルが、ポリ(乳酸)、ポリ(グリコール酸)、ポリ(乳酸−コ−グリコール酸)またはポリカプロラクトンを含む、請求項29に記載の方法。
- 前記ポリエステルが、ポリエーテルに結合される、請求項29または30に記載の方法。
- 前記ポリエーテルが、ポリエチレングリコールを含む、請求項31に記載の方法。
- 前記第1のタンパク質および/または1つ以上のさらなる抗原が、癌、感染または感染症、非自己免疫性または変性疾患、HIV、マラリヤ、リーシュマニア、ヒトフィロウイルス、トガウイルス、アルファウイルス、アレナウイルス、ブニヤウイルス、フラビウイルス、ヒトパピローマウイルス、ヒトインフルエンザA型ウイルス、B型肝炎またはC型肝炎に関連する抗原である、請求項1〜32のいずれか一項に記載の方法。
- 前記被験体が、癌、感染または感染症あるいは非自己免疫性または変性疾患に罹患しているかまたは罹患するリスクがある、請求項1〜33のいずれか一項に記載の方法。
- 前記被験体が、HIV、マラリヤ、リーシュマニア症、ヒトフィロウイルス感染、トガウイルス感染、アルファウイルス感染、アレナウイルス感染、ブニヤウイルス感染、フラビウイルス感染、ヒトパピローマウイルス感染、ヒトインフルエンザA型ウイルス感染、B型肝炎感染またはC型肝炎感染に罹患しているかまたは罹患するリスクがある、請求項34に記載の方法。
- 生成される前記体液性およびCTL免疫応答が、臨床的に有効である、請求項1〜35のいずれか一項に記載の方法。
- 前記体液性およびCTL免疫応答が、前記被験体における癌、感染または感染症あるいは非自己免疫性または変性疾患を治療または予防するのに有効である、請求項36に記載の方法。
- 前記体液性およびCTL免疫応答が、HIV、マラリヤ、リーシュマニア症、ヒトフィロウイルス感染、トガウイルス感染、アルファウイルス感染、アレナウイルス感染、ブニヤウイルス感染、フラビウイルス感染、ヒトパピローマウイルス感染、ヒトインフルエンザA型ウイルス感染、B型肝炎感染またはC型肝炎感染を治療または予防するのに有効である、請求項37に記載の方法。
- 前記組成物が、薬学的に許容できる賦形剤をさらに含む、請求項1〜38のいずれか一項に記載の方法。
- 前記組成物が滅菌されている、請求項1〜39のいずれか一項に記載の方法。
- 前記組成物が、凍結乾燥形態から再構成される、請求項1〜40のいずれか一項に記載の方法。
- 前記組成物が剤形である、請求項1〜41のいずれか一項に記載の方法。
- 前記組成物がワクチンである、請求項1〜42のいずれか一項に記載の方法。
- 前記組成物が、静脈内、経口、皮下、経肺、鼻腔内、皮内、経粘膜、粘膜内または筋肉内投与によって投与される、請求項1〜43のいずれか一項に記載の方法。
- 治療または予防に使用するための、第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物であって、前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法である組成物。
- 請求項1〜44のいずれか一項に記載の方法に使用するための、第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物であって、前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法である組成物。
- ワクチン接種に使用するための、第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物であって、前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法である組成物。
- 被験体における第1のタンパク質に対する体液性およびCTL免疫応答を生成するのに使用するための、前記第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物であって、前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法である組成物。
- 癌、感染または感染症、非自己免疫性または変性疾患、HIV、マラリヤ、リーシュマニア症、ヒトフィロウイルス感染、トガウイルス感染、アルファウイルス感染、アレナウイルス感染、ブニヤウイルス感染、フラビウイルス感染、ヒトパピローマウイルス感染、ヒトインフルエンザA型ウイルス感染、B型肝炎感染またはC型肝炎感染の治療または予防の方法に使用するための、第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物であって、前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法である組成物。
- 静脈内、経口、皮下、経肺、鼻腔内、皮内、粘膜内、経粘膜または筋肉内投与による投与を含む治療または予防の方法に使用するための、第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物であって、前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法である組成物。
- 請求項1〜44のいずれか一項に記載の方法に使用するための薬剤、例えばワクチンの製造のための、第1のタンパク質に結合された合成ナノキャリアの集団を含む組成物の使用であって、前記第1のタンパク質が、同じエピトープではない、少なくとも1つの体液性エピトープおよび少なくとも1つのMHCクラスI拘束性エピトープを含み、合成ナノキャリアの前記集団が、サポニン−コレステロールアジュバントを含まず、合成ナノキャリアの前記集団の動的光散乱を用いて得られる粒度分布の平均が、20nm〜250nmの最大寸法である使用。
- 請求項45〜50のいずれか一項に記載の使用のための組成物または請求項51に記載の使用であって、前記組成物が、請求項1〜44のいずれか一項に記載されるとおりである組成物または使用。
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BR112014002139A2 (pt) | 2017-02-21 |
US10933129B2 (en) | 2021-03-02 |
AU2017261562A1 (en) | 2017-12-07 |
AU2012290306A1 (en) | 2014-01-23 |
AU2019236653A1 (en) | 2019-10-17 |
IL273674A (en) | 2020-05-31 |
EP2736537A4 (en) | 2015-04-15 |
CN103702687A (zh) | 2014-04-02 |
WO2013019669A3 (en) | 2013-07-04 |
WO2013019648A1 (en) | 2013-02-07 |
WO2013019669A2 (en) | 2013-02-07 |
CN109172819A (zh) | 2019-01-11 |
US20130039954A1 (en) | 2013-02-14 |
US20130028941A1 (en) | 2013-01-31 |
EA201490381A1 (ru) | 2014-06-30 |
EP2736537A2 (en) | 2014-06-04 |
IL230269B (en) | 2020-04-30 |
CA2843274A1 (en) | 2013-02-07 |
WO2013019658A2 (en) | 2013-02-07 |
US20130028857A1 (en) | 2013-01-31 |
WO2013019658A3 (en) | 2013-04-25 |
MX2014001142A (es) | 2014-02-27 |
AU2012290306B2 (en) | 2017-08-17 |
KR20140050698A (ko) | 2014-04-29 |
CN109125722A (zh) | 2019-01-04 |
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