JP2021097677A - アレルゲンに対する反応を予防するための遺伝子治療 - Google Patents
アレルゲンに対する反応を予防するための遺伝子治療 Download PDFInfo
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Abstract
Description
本特許出願は、2016年3月29日出願の米国仮特許出願第62/314,740号及び2015年4月9日出願の米国仮特許出願第62/145,035号(参照により組み込まれる)の利益を主張する。
本明細書と同時提出され、且つ、以下の通り識別されるコンピューター可読のヌクレオチド/アミノ酸の配列表が、参照により、本明細書中にその全体が組み込まれる:2016年3月29日付ファイル名「722135_ST25.TXT」、5,718バイトのASCII(テキスト)ファイル1件。
アレルゲンは、感受性のある個体において、発疹から致死的なアナフィラキシー反応に及ぶ、様々な反応を引き起こす。これらの反応は、アレルゲン抗原特異的免疫グロブリンE(IgE)に関連するI型過敏反応によって媒介される。アレルゲン特異的IgEがアナフィラキシーを誘発するのを妨げる治療法で、アレルギー個体を治療することに、相当な関心が存在している。かかるアプローチの1つは、組換えDNA由来のヒト化IgG1κモノクローナル抗体、オマリズマブ(Xolair(登録商標))(ヒトIgEに結合する)による治療である。オマリズマブは、IgEの、肥満細胞及び好塩基球の表面上のIgE受容体への結合を阻害し、従って、アレルギー応答のメディエータ放出の程度を制限する。
本発明は、抗IgE抗体又はその抗原結合断片をコードするか、又は可溶性IgE受容体、好酸球(eosinophil)、好塩基球(basophil)、IL−13又はIL−4をコードする核酸配列に、作動可能に連結されたプロモーターを含むベクターを提供する。本発明はまた、ベクターを含む組成物、及び哺乳動物における、アレルゲンに対する免疫応答又はアレルギー反応を阻害又は軽減するためのベクターを使用する方法を提供する。更に、本発明は、アレルギーの組換えヒト化マウスモデルを提供する方法を提供する。
本発明は、遺伝子治療ベクター及びそれを使用する方法を提供し、哺乳動物における、アレルゲンに対する免疫応答又はアレルギー反応を阻害又は軽減するための、治療用導入遺伝子の持続的発現を提供する。ベクターは、抗IgE抗体又はその抗原結合断片をコードするか、又は可溶性IgE受容体、好酸球、好塩基球、IL−13、又はIL−4をコードする核酸配列に、作動可能に連結されたプロモーターを含むか、それから実質的に成るか、又はそれから成る。ベクターは、ベクターに実質的に影響を及ぼさない追加の構成要素(例、インビトロでのベクター操作を容易にするポリ(A)配列又は制限酵素部位等の遺伝学的エレメント)を含み得る。しかしながら、いくつかの実施形態においては、ベクターは、任意の追加の構成要素(即ち、ベクターに内因性ではなく、核酸配列の発現をもたらし、それによって抗体を提供するために必要とされない構成要素)を含まない。
それから実質的になり得るか、又はそれからなり得る。かかるベクターの例としては、アデノ随伴ウイルス(AAV)ベクター、アデノウイルスベクター、レンチウイルスベクター、レトロウイルスベクター、及びプラスミドが挙げられる。好ましい実施形態においては、ベクターはAAVベクターである。
al.,上記を参照)。種々のAAV血清型のゲノム配列及びその比較は、例えば、GenBank受入番号U89790、J01901、AF043303、及びAF085716、Chiorini et al.,J.Virol.,71:6823−33(1997);Srivastava et al.,J.Virol.,45:555−64(1983);Chiorini et al.,J.Virol.,73:1309−1319(1999);Rutledge et al.,J.Virol.,72:309−319(1998);及びWu et al.,J.Virol.,74:8635−47(2000))に開示されている。
Gene Ther.,17(8):1042−1051(2010);及びMao et al.,Hum.Gene Therapy,22:1525−1535(2011)を参照)。
その抗原結合断片、可溶性IgE受容体、好酸球、好塩基球、IL−13又はIL−4をコードする。核酸配列は、活性タンパク質(例、可溶性IgE受容体、好酸球、好塩基球、IL−13、IL−4又はアレルギー反応を阻止する任意の治療遺伝子)及び第2の部分、通常は活性タンパク質の特性(例えば、有効性、溶解性、又は半減期)を改善するタンパク質、で構成される融合タンパク質もコードし得る。第2の部分の例は、当該技術分野で公知であり、例えば、免疫グロブリンのFcドメイン及びポリエチレングリコール(PEG)が挙げられる。一実施形態においては、プロモーターに作動可能に連結された核酸配列は、抗IgE抗体又はその抗原結合断片のみをコードする。
in Enzymology,Vol.185,Academic Press,San Diego,CA.(1990)に記載されている。
又はDNA構造の変化を調節し得る。種々の異なるソース由来の多数のエンハンサーが当該技術分野で周知であり、クローニングされたポリヌクレオチドとして又はその内部で(例、ATCC等の寄託機関並びに他の商業的又は個別のソースから)入手可能である。(一般的に用いられるCMVプロモーター等の)プロモーターを含む多くのポリヌクレオチドは、エンハンサー配列も含む。エンハンサーは、コード配列の上流、内部、又は下流に位置し得る。抗IgE抗体又はその抗原結合断片、可溶性IgE受容体、好中球、好塩基球、IL−13、又はIL−4をコードする核酸配列は、CMVエンハンサー/ニワトリβアクチンプロモーター(CAGプロモーターとも呼ばれる)に作動可能に連結され得る(例、Niwa et al.,Gene,108:193−199(1991);Daly et al.,Proc.Natl.Acad.Sci.U.S.A.,96:2296−2300(1999);及びSondhi et al.,Mol.Ther.,15:481−491(2007)を参照)。
Williams & Wilkins,Philadelphia,PA(2001)(例)に記載されている従来技術に従って生成され得る。
する。例えば、イブプロフェン又はステロイド等の、炎症を制御する因子は、ベクターのインビボ投与に伴う腫脹及び炎症を軽減するための組成物の一部であり得る。抗生物質、即ち殺菌剤及び防カビ剤は、既存の感染症を治療し、及び/又は遺伝子移入手順に関連する感染等の将来の感染リスクを低下させるために、存在し得る。
bean)、ゼラチン(ブタ、ウシ、魚)、カボチャ種子、亜麻仁(flaxseed)/亜麻仁(linseed)、コリアンダー/シラントロ、ブラックベリー、アナトー種子、キビ、カリフラワー、菜種油、ヒヨコマメ(chick pea)(ヒヨコマメ(garbanzo bean))、ブドウ、トマト、キウイ、パパイヤ、セロリ、アボカド、ソバ、アルファgal、コメ、チョコレート、チキン、シチメンチョウ、子羊、白インゲンマメ、ライ麦、大麦、カゼイン、キャベツ、レタス、コショウ、牛肉/肉豚、マンゴー、ナシ、ホウレンソウ、卵白、卵黄、卵全体、パパイヤ、ココナッツ、アンズ、ブルーベリー、ハネデューメロン(honeydew)、メロン、カンタロープ、カラシ、茶、バニラ、レモン、ライム、ブロッコリー、シナモン、タマネギ、パイナップル、ニンニク、グレープフルーツ、レンズマメ、麦芽、コーヒー、マッシュルーム、メキシコ唐辛子、ココア、食品添加物(パン酵母、アスコルビン酸、アスパルテーム、硝酸塩、グアール、MSG、カラギーナン)等の食物アレルゲン;
on)投与することができる。インプラント(例、米国特許第5,443,505号参照)、移植可能なデバイス(例、機械的リザーバ若しくはインプラント又はポリマー組成物を含む装置)等のデバイス(例、米国特許第4,863,457号参照)は、AAVベクターの投与に特に有用である。組成物はまた、例えばゲルフォーム、ヒアルロン酸、ゼラチン、コンドロイチン硫酸、ビス−2−ヒドロキシエチル−テレフタレート(BHET)、及び/又はポリ乳酸−グリコール酸等のポリリン酸エステルを含む持続放出製剤(例、米国特許第5,378,475号参照)の形態で投与され得る。
に罹患するヒト被験体由来であり得る。好ましい実施形態においては、PBMCは、ピーナッツアレルギー及びアナフィラキシーの臨床歴を有するヒト被験体由来である。
本実施例は、ピーナッツアレルギーの組換えヒト化マウスモデルの作出を実例で示す。
の減少を示した(図1E)。これらの臨床的特徴は、非アレルギー性個体由来の血液単核細胞を受容した動物では観察されなかった。ピーナッツアレルギードナー由来の血液単核細胞で再構成し、次いでピーナッツ粗抽出物でチャレンジしたマウスにおけるヒスタミンレベルは、非ピーナッツアレルギー性非アトピー性ドナー由来の血液単核細胞で再構成したマウスと比較すると、ピーナッツチャレンジ後、ヒスタミンのレベル上昇を示した(図1G)。
本実施例は、抗hIgE抗体をコードする核酸配列に作動可能に連結されたプロモーターを含むAAVベクターの設計及び発現を実例で示す。
3;並びにE2、E4及びVA RNAのアデノウィルスヘルパー機能を有するプラスミドと共に、pAAVプラスミドのヒト胎児腎臓293T細胞(HEK 293T;アメリカンタイプカルチャーコレクション)への共トランスフェクションにより製造した。AAVanti−hIgEベクター(「AAVrh.10anti−hIgE」と呼ばれる)は、イオジキサノール勾配及びQHP陰イオン交換クロマトグラフィーによって精製した。ベクターゲノム力価は、定量的TaqManリアルタイムPCR解析によって決定した。インビボ研究のためのコントロールとして、関係性の無い、ニコチンに対する抗体、AAVantiNic(「AAVrh.10IgGcontrol」と呼ばれる)をコードするベクターを用いた。
Kit (Life Technologies,Grand Island,NY)により定量した。図3Cに示す通り、200μg/mlを超えるレベルでのヒト抗IgEの発現が、実験期間(44週)で実証されたが、コントロール処置動物からは、ヒト抗IgEは検出されなかった。図3D〜3Eに示す通り、ヒト抗IgEの発現は、AAV抗IgEベクターのそれぞれについて実証されたが、コントロール処置動物からは、ヒト抗I
gEは検出されなかった。
本実施例は、アレルゲンに対するアレルギー反応を軽減するための、AAV−抗−hIgEベクターによる予防療法を実例で示す。
この実施例は、抗原への曝露後のベクター投与の有効性を実証する。
レベルを固定間隔(2週間)で評価した(図6A)。ヒトIgGレベルを2、4及び8週目に評価した。ヒトIgEを4週目及び6週目に、遊離IgEレベルを4週目及び6週目に、そしてピーナッツ特異的IgEを4週目に評価した。7週目及び10週目の各ピーナッツチャレンジの30分後に、アナフィラキシースコア及び臨床スコアを評価した。自発運動は、7及び10週目に、ヒスタミンレベルは6及び9週目に、そして受動皮膚アナフィラキシーは7及び10週目に評価した。
eosinophilic inclusion)が肺組織に見られた。小腸組織は、GVHDと一致する組織学的特徴、即ち、好酸球、好中球及びリンパ球の浸潤を示した。
に特記しないか文脈と明らかに矛盾しない限り、単数形及び複数形の両方をカバーすると解釈すべきである。1以上の事項の列記の後での用語「少なくとも1の」の使用(例えば、「A及びBのうち少なくとも1の」)は、本明細書中に特記しない又は文脈と明らかに矛盾しない限り、列記した事項から選択された1の事項(A若しくはB)又は列記した事項のうち2以上の任意の組み合わせ(A及びB)を意味すると解釈されるべきである。用語「含む(comprising)」、「有する(having)」、「含む(including)」及び「含有する(containing)」は、特記しない限り、オープンエンドの用語(即ち、「〜を含むがそれらに限定されない」を意味する)と解釈すべきである。本明細書中の値の範囲の記述は、本明細書中に特記しない限り、その範囲内に入る各個別の値に個々に言及する省略方法として働くことのみを意図しており、各個別の値は、それが本明細書中に個々に記述されているかのように本明細書中に組み込まれる。本明細書中に記載される全ての方法は、本明細書中に特記しない又は文脈と明らかに矛盾しない限り、任意の好適な順序で実施できる。本明細書中に提供される任意の及び全ての例又は例示的語句(例、「等(such as)」)の使用は、本発明をよりよく説明することのみを意図しており、特段特許請求されない限り、本発明の範囲に限定を課すものではない。本明細書中の全ての語句は、特許請求されていない任意の要素を本発明の実施に必須のものとして示していると解釈すべきではない。
Claims (26)
- 抗IgE抗体若しくはその抗原結合断片をコードするか、又は可溶性IgE受容体、好酸球、好塩基球、IL−13若しくはIL−4をコードする核酸配列に、作動可能に連結されたプロモーターを含むベクター。
- ベクターが、アデノ随伴ウイルス(AAV)、アデノウイルス、レンチウイルス、レトロウイルス及びプラスミドからなる群から選択される、請求項1のベクター。
- ベクターがAAVベクターである、請求項2のベクター。
- AAVベクターが非ヒトアデノ随伴ウイルスである、請求項3のベクター。
- 非ヒトアデノ随伴ウイルスがアカゲザルアデノ随伴ウイルスである、請求項4のベクター。
- アカゲザルアデノ随伴ウイルスがアデノ随伴ウイルス血清型rh.10である、請求項5のベクター。
- プロモーターが構成的に活性なプロモーターである、請求項1のベクター。
- プロモーターが細胞種特異的プロモーターである、請求項1のベクター。
- プロモーターが誘導性プロモーターである、請求項1のベクター。
- 構成的に活性なプロモーターがニワトリベータアクチンプロモーターである、請求項7のベクター。
- 核酸配列が、抗IgE抗体又はその抗原結合断片をコードし、抗体又はその抗原結合断片が、3つの相補性決定領域(CDR)を含む重鎖ポリペプチドであって、ここでCDR−H1は配列番号1の核酸配列を含み、CDR−H2は配列番号2の核酸配列を含み、及びCDR−H3は配列番号3の核酸配列を含む、重鎖ポリペプチド;並びに
3つのCDRを含む軽鎖ポリペプチドであって、ここでCDR−L1は配列番号4の核酸配列を含み、CDR−L2は配列番号5の核酸配列を含み、CDR−L3は配列番号6の核酸配列を含む、軽鎖ポリペプチド、
を含む、請求項1のベクター。 - 抗IgE抗体が、配列番号7を含む重鎖可変領域及び配列番号8を含む軽鎖可変領域を含む、請求項11のベクター。
- ベクターが配列番号9の核酸配列を含む、請求項1のベクター。
- ベクターが、オマリズマブをコードする核酸配列を含む、請求項1のベクター。
- 核酸配列が、F(ab’)2、Fab’、Fab、Fv、scFv、dsFv、dAb及び一本鎖結合ポリペプチドからなる群から選択される抗IgE抗体断片をコードする、請求項1のベクター。
- 請求項1〜15のいずれか1項のベクター及び医薬的に許容可能な担体を含む、組成物。
- 哺乳動物における、アレルゲンに対する免疫応答又はアレルギー反応を阻害又は軽減する方法であって、哺乳動物に請求項1〜15のいずれかのベクターを投与することを含み、そうして核酸が発現し、アレルゲンに対する免疫応答又はアレルギー反応が抑制又は軽減される、方法。
- 組成物が、約30日以内に1回以下で哺乳動物に投与される、請求項17の方法。
- 組成物の投与後、哺乳動物で、治療レベル又は予防レベルの、抗IgE抗体若しくはその抗原結合断片、又は可溶性IgE受容体、好酸球、好塩基球、IL−13、若しくはIL−4が、約30日間以上発現する、請求項18の方法。
- 組成物が、予防的に哺乳動物に投与される、請求項17〜19のいずれか1項の方法。
- アレルゲンが、食物アレルゲン、花粉、イエダニ、昆虫毒、ハチ刺毒、ピーナッツ、及び堅果からなる群から選択される、請求項17〜20のいずれか1項の方法。
- アレルギー反応がアナフィラキシーである、請求項17〜20のいずれか1項の方法。
- 哺乳動物がヒトである、請求項17〜22のいずれか1項の方法。
- 組成物が、口腔内、筋肉内、経皮、静脈内、動脈内、皮下、皮内、及び腹腔内からなる群から選択される投与経路によって哺乳動物に投与される、請求項17〜23のいずれか1項の方法。
- アレルギーの組換えヒト化マウスモデルを提供する方法であって、免疫不全マウスに、アレルギーとアナフィラキシーの臨床歴とを有するヒト被験体由来の末梢血単核細胞を送達することを含む、方法。
- 末梢血単核細胞が、ピーナッツアレルギー及びアナフィラキシーの臨床病歴を有するヒト被験体由来である、請求項25のヒト化マウスモデル。
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008506389A (ja) * | 2004-07-13 | 2008-03-06 | セル ジェネシス インコーポレイテッド | Aavベクター組成物および免疫グロブリンの発現の増強のための方法ならびにその使用方法 |
JP2010532158A (ja) * | 2007-04-02 | 2010-10-07 | アムジェン フレモント インク. | 抗IgE抗体 |
WO2014197624A1 (en) * | 2013-06-07 | 2014-12-11 | The Regents Of The University Of California | Cycle adenosine monophosphate-incompetent adenylyl cyclase and compositions and methods for treating heart failure and increasing cardiac function |
Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4797368A (en) | 1985-03-15 | 1989-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Adeno-associated virus as eukaryotic expression vector |
US4863457A (en) | 1986-11-24 | 1989-09-05 | Lee David A | Drug delivery device |
US5378475A (en) | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
US5464758A (en) | 1993-06-14 | 1995-11-07 | Gossen; Manfred | Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters |
US5814618A (en) | 1993-06-14 | 1998-09-29 | Basf Aktiengesellschaft | Methods for regulating gene expression |
US5443505A (en) | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
US6342390B1 (en) | 1994-11-23 | 2002-01-29 | The United States Of America As Represented By The Secretary Of Health And Human Services | Lipid vesicles containing adeno-associated virus rep protein for transgene integration and gene therapy |
CN1131314C (zh) * | 1996-04-29 | 2003-12-17 | 仁文有限公司 | 含有过敏原基因的重组真核载体及其应用 |
US5994511A (en) | 1997-07-02 | 1999-11-30 | Genentech, Inc. | Anti-IgE antibodies and methods of improving polypeptides |
EP2361635A3 (en) * | 2000-08-30 | 2011-09-14 | Pfizer Products Inc. | Anti IgE vaccines |
FR2814642B1 (fr) | 2000-10-03 | 2005-07-01 | Ass Pour Le Dev De La Rech En | Souris transgenique pour la recombinaison ciblee mediee par la cre-er modifiee |
US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
EP1585768A2 (en) * | 2003-01-23 | 2005-10-19 | Genentech, Inc. | Methods for producing humanized antibodies and improving yield of antibodies or antigen binding fragments in cell culture |
CN1317304C (zh) * | 2004-03-10 | 2007-05-23 | 伍祥贵 | 一种融合蛋白及其编码基因与表达方法和应用 |
CN101062949B (zh) * | 2006-04-26 | 2011-07-27 | 上海抗体药物国家工程研究中心有限公司 | 重组抗人IgE单克隆抗体及其制备方法和用途 |
DE102007001370A1 (de) * | 2007-01-09 | 2008-07-10 | Curevac Gmbh | RNA-kodierte Antikörper |
US20100136030A1 (en) | 2007-02-27 | 2010-06-03 | Lamhamedi-Cherradi Salah-Eddine | Antagonist ox40 antibodies and their use in the treatment of inflammatory and autoimmune diseases |
US8242093B2 (en) * | 2008-02-07 | 2012-08-14 | Ceregene, Inc. | Rescue of photoreceptors by intravitreal administration of an expression vector encoding a therapeutic protein |
JP5634272B2 (ja) * | 2008-03-14 | 2014-12-03 | ヒューマンザイム リミテッド | ヒト細胞発現系を用いる真正ヒトタンパク質の組換え生産 |
US8859210B2 (en) * | 2008-10-17 | 2014-10-14 | Mead Johnson Nutrition Company | Method for identifying allergenic proteins and peptides |
GB0917044D0 (en) | 2009-09-29 | 2009-11-18 | Cytoguide As | Agents, uses and methods |
MX2013005847A (es) | 2010-11-24 | 2013-12-12 | Glaxo Group Ltd | Proteinas de union a antigeno multiespecificas que eligen como blanco a hgf. |
MX356947B (es) * | 2011-08-23 | 2018-06-20 | Roche Glycart Ag | Anticuerpos bioespecíficos específicos para antígenos que activan células t y un antígeno tumoral y métodos de uso. |
EP3539568A1 (en) * | 2011-11-22 | 2019-09-18 | The Children's Hospital of Philadelphia | Virus vectors for highly efficient transgene delivery |
US11408899B2 (en) * | 2013-07-12 | 2022-08-09 | The Children's Hospital Of Philadelphia | AAV vector and assay for anti-AAV (adeno-associated virus) neutralizing antibodies |
-
2016
- 2016-04-11 WO PCT/US2016/026977 patent/WO2016164920A1/en unknown
- 2016-04-11 EP EP16777501.4A patent/EP3280445B1/en active Active
- 2016-04-11 JP JP2017553166A patent/JP6878301B2/ja active Active
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- 2016-04-11 CN CN201680033587.3A patent/CN107635584B/zh active Active
-
2021
- 2021-02-15 JP JP2021022067A patent/JP2021097677A/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008506389A (ja) * | 2004-07-13 | 2008-03-06 | セル ジェネシス インコーポレイテッド | Aavベクター組成物および免疫グロブリンの発現の増強のための方法ならびにその使用方法 |
JP2010532158A (ja) * | 2007-04-02 | 2010-10-07 | アムジェン フレモント インク. | 抗IgE抗体 |
WO2014197624A1 (en) * | 2013-06-07 | 2014-12-11 | The Regents Of The University Of California | Cycle adenosine monophosphate-incompetent adenylyl cyclase and compositions and methods for treating heart failure and increasing cardiac function |
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CN107635584A (zh) | 2018-01-26 |
CA2982213C (en) | 2022-10-18 |
JP6878301B2 (ja) | 2021-05-26 |
US10293059B2 (en) | 2019-05-21 |
EP3280445A1 (en) | 2018-02-14 |
CN107635584B (zh) | 2022-06-17 |
EP3280445A4 (en) | 2019-05-15 |
WO2016164920A1 (en) | 2016-10-13 |
CA2982213A1 (en) | 2016-10-13 |
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