JP6573991B2 - 血管性浮腫の治療としてのc1eiのアデノ随伴ウイルス介在性送達 - Google Patents
血管性浮腫の治療としてのc1eiのアデノ随伴ウイルス介在性送達 Download PDFInfo
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- JP6573991B2 JP6573991B2 JP2017560985A JP2017560985A JP6573991B2 JP 6573991 B2 JP6573991 B2 JP 6573991B2 JP 2017560985 A JP2017560985 A JP 2017560985A JP 2017560985 A JP2017560985 A JP 2017560985A JP 6573991 B2 JP6573991 B2 JP 6573991B2
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Description
本特許出願は、2015年5月28日に出願された合衆国仮特許出願第62/167,603号、2016年4月18日に出願された合衆国仮特許出願第62/324,183号及び2016年5月27日に出願された合衆国特許出願第15/167,729号の利益を主張し、ここで参照することにより、それらは本明細書に組み込まれる。
本明細書と同時に提出され、以下のとおり:2016年5月27日に作成された「724068_ST25.TXT」と名付けられた1つの41,866バイトの ASCII (Text) ファイル、と特定されたコンピュータ読み取り可能なヌクレオチド/アミノ酸配列表は、参照することによりその全体が本明細書中に組み込まれる。
遺伝性血管浮腫(HAE)は、皮膚や上気道もしくは消化管の粘膜組織で最も頻繁に起こる腫れを繰り返すことにより特徴づけられる、稀少かつ生命を脅かす可能性のある遺伝的状態である(例えば、Banerji, Ann Allergy Asthma Immunol, 111: 329-336 (2013) 及びAygoren-Pursun et al., Orphanet J Rare Dis.,9: 99 (2014)を参照)。この疾患は常染色体優性形式で遺伝し、10,000人に1人から15,000人に1人が罹患する。HAE(I型及びII型)の根本原因は、第11番染色体に位置するC1エステラーゼインヒビター遺伝子(C1EI遺伝子又はSERPING1遺伝子)における変異の常染色体優性遺伝に帰する。HAE症例の85%は、C1エステラーゼインヒビターの産生量が不足するI型である(例えば、Gower et al., World Allergy Organ J., 4: S9-S21 (2011); Cungo et al., Trends Mol Med, 15: 69-78 (2009); Gooptu et al., Annu Rev Biochem, 78: 147-176 (2009); 及びZuraw et al., J Allergy Clin Immunol Pract, 1: 458-467 (2013)を参照)。残りの症例は機能不全のC1エステラーゼインヒビターの発現により特徴づけられる。
本発明は、ヒトC1エラスターゼインヒビター(C1EI)をコードする核酸配列又は第XII因子をコードする核酸配列に作動可能に連結し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、該ベクターを含有する組成物及び該ベクターを用いて哺乳動物における血漿C1エステラーゼインヒビターの欠損を治療する方法、あるいはその任意の症状を治療もしくは予防する方法を提供する。さらに、本発明は、ヒト遺伝性血管浮腫のモデルとなる組換えマウスを提供する。該組換えマウスは、SERPING1変異を有しない同型のマウスと比較して、該マウスにおけるC1EI活性が低下するSERPING1変異を含む。
本特許又は出願ファイルは少なくとも1つのカラーで作製した図面を含む。カラー図面付きの本特許又は特許出願の公開の写しは、請求及び必要な手数料の支払いにより、庁より提供されるであろう。
本発明は、少なくとも幾分は、安全にヒトに投与され、治療導入遺伝子の持続的発現を提供するというベクターの能力に基づいている。本発明は、ヒトC1エステラーゼインヒビター(C1EI)をコードする核酸配列又は第XII因子をコードする核酸配列に作動可能に連結したプロモーターを含む、から実質的になる、あるいは、からなるベクターを提供する。本発明のベクターが、C1EIをコードする核酸配列又は第XII因子をコードする核酸配列に作動可能に連結したプロモーターから実質的になる場合、該ベクターに実質的に影響を与えない付加的構成要素(例えば、ポリ(A)配列又はインビトロでのベクターの操作を容易にする制限酵素部位等の遺伝的構成要素)を含み得る。該ベクターが、C1EIをコードする核酸配列又は第XII因子をコードする核酸配列に作動可能に連結したプロモーターから実質的になる場合、該ベクターはいかなる付加的構成要素(即ち、該ベクターに内在せず、それによって該タンパク質を提供する該核酸配列の発現をもたらすのに必要でない構成要素)も含まない。
Claims (15)
- 哺乳動物における機能的な血漿C1エステラーゼインヒビターの欠損の治療、又はその任意の症状の治療もしくは予防のための組成物であって、ヒトC1エステラーゼインヒビター(C1EI)をコードする核酸配列に作動可能に連結したプロモーターを含むアデノ随伴ウイルス(AAV)ベクターを含む、組成物。
- 哺乳動物が遺伝性血管浮腫を有する、請求項1に記載の組成物。
- 哺乳動物における粘膜下又は皮下浮腫を阻害又は軽減するための組成物であって、ヒトC1エステラーゼインヒビター(C1EI)をコードする核酸配列に作動可能に連結したプロモーターを含むアデノ随伴ウイルス(AAV)ベクターを含む、組成物。
- 組成物が、浮腫の発症前及び/又は発症後に1回哺乳動物に投与するためのものである、請求項3に記載の組成物。
- 組成物が、浮腫の発症前及び/又は発症後に2回以上哺乳動物に投与するためのものである、請求項3に記載の組成物。
- 組成物が予防的に哺乳動物に投与するためのものである、請求項1〜5のいずれかに記載の組成物。
- 哺乳動物がヒトである、請求項1〜6のいずれかに記載の組成物。
- 組成物が、口内、筋肉内、経皮、静脈内、動脈内、皮下、皮内又は腹腔内投与により哺乳動物に投与されるためのものである、請求項1〜7のいずれかに記載の組成物。
- AAVベクターが非ヒトアデノ随伴ウイルスベクターである、請求項1〜8のいずれかに記載の組成物。
- 非ヒトアデノ随伴ウイルスベクターが、アカゲザルアデノ随伴ウイルスベクターである、請求項9に記載の組成物。
- アカゲザルアデノ随伴ウイルスベクターがアデノ随伴ウイルス血清型rh.10ベクターである、請求項10に記載の組成物。
- プロモーターが構成的に活性なプロモーター、細胞種特異的プロモーター、又は誘導プロモーターである、請求項1〜11のいずれかに記載の組成物。
- プロモーターがニワトリβ-アクチンプロモーターである、請求項1〜12のいずれかに記載の組成物。
- AAVベクターがサイトメガロウイルス(CMV)エンハンサー配列をさらに含む、請求項1〜13のいずれかに記載の組成物。
- AAVベクターが配列番号1を含むC1EIをコードする核酸配列を含む、請求項1〜14のいずれかに記載の組成物。
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JP2022032186A JP7417303B2 (ja) | 2015-05-28 | 2022-03-02 | 血管性浮腫の治療としてのc1eiのアデノ随伴ウイルス介在性送達 |
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US15/167,729 US10214731B2 (en) | 2015-05-28 | 2016-05-27 | Adeno-associated virus mediated delivery of C1E1 as a therapy for angioedema |
PCT/US2016/034852 WO2016191746A1 (en) | 2015-05-28 | 2016-05-27 | Adeno-associated virus mediated delivery of c1ei as a therapy for angioedema |
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CN112553229A (zh) | 2014-11-05 | 2021-03-26 | 沃雅戈治疗公司 | 用于治疗帕金森病的aadc多核苷酸 |
JOP20190269A1 (ar) | 2017-06-15 | 2019-11-20 | Voyager Therapeutics Inc | بولي نوكليوتيدات aadc لعلاج مرض باركنسون |
CA3109924A1 (en) | 2018-08-24 | 2020-02-27 | Csl Behring Gene Therapy, Inc. | Vector production in serum free media |
CA3111047A1 (en) * | 2018-08-24 | 2020-02-27 | Spark Therapeutics, Inc. | Optimized promoter sequences, intron-free expression constructs and methods of use |
US20230043051A1 (en) * | 2019-10-23 | 2023-02-09 | Shire Human Genetic Therapies, Inc. | Adeno-associated virus vectors based gene therapy for hereditary angioedema |
EP4058475A1 (en) * | 2019-11-14 | 2022-09-21 | BioMarin Pharmaceutical Inc. | Treatment of hereditary angioedema with liver-specific gene therapy vectors |
US20220098615A1 (en) * | 2020-09-30 | 2022-03-31 | NGGT, Inc. | Dual functional expression vectors and methods of use thereof |
AU2022214192A1 (en) * | 2021-01-27 | 2023-07-27 | Spark Therapeutics, Inc. | Compositions and methods for treating hereditary angioedema |
EP4408481A2 (en) * | 2021-10-01 | 2024-08-07 | BioMarin Pharmaceutical Inc. | Treatment of hereditary angioedema with aav gene therapy vectors and therapeutic formulations |
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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 |
US7067713B2 (en) | 2000-01-31 | 2006-06-27 | Pharming Intellectual Property B.V. | C1 Inhibitor produced in the milk of transgenic non-human mammals |
US20030073652A1 (en) * | 2000-05-17 | 2003-04-17 | Harvey Pollard | Ex-vivo and in vivo factor XII gene therapy for hemophilia A and B |
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 |
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US20160355573A1 (en) * | 2013-09-05 | 2016-12-08 | Cornell University | Gene therapy for alzheimer's and other neurodegenerative diseases and conditions |
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JP2018516571A (ja) | 2018-06-28 |
AU2016267687B2 (en) | 2022-04-07 |
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US10214731B2 (en) | 2019-02-26 |
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