JP6473535B2 - C1エステラーゼ抑制因子欠乏に関連する障害の予防及び治療のためのc1−inh組成物ならびに方法 - Google Patents
C1エステラーゼ抑制因子欠乏に関連する障害の予防及び治療のためのc1−inh組成物ならびに方法 Download PDFInfo
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- JP6473535B2 JP6473535B2 JP2018073690A JP2018073690A JP6473535B2 JP 6473535 B2 JP6473535 B2 JP 6473535B2 JP 2018073690 A JP2018073690 A JP 2018073690A JP 2018073690 A JP2018073690 A JP 2018073690A JP 6473535 B2 JP6473535 B2 JP 6473535B2
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Description
本発明の実施形態において、例えば以下の項目が提供される。
(項目1)
障害の治療、抑制、または予防を必要とする対象におけるC1エステラーゼ抑制因子の欠乏に関連する障害を治療、抑制、または予防するための方法であって、該方法が、少なくとも1つのC1エステラーゼ抑制因子を含む組成物を投与することを含み、該C1エステラーゼ抑制因子が、約400U/ml以上で存在する、前記方法。
(項目2)
該組成物が皮下投与される、項目1に記載の前記方法。
(項目3)
該組成物が静脈内投与される、項目1に記載の前記方法。
(項目4)
該障害が遺伝性血管性浮腫である、項目1に記載の前記方法。
(項目5)
該C1エステラーゼ抑制因子が、ヒトC1エステラーゼ抑制因子である、項目1に記載の前記方法。
(項目6)
該ヒトC1エステラーゼ抑制因子が、血漿から精製される、項目5に記載の前記方法。(項目7)
該組成物がクエン酸塩を含む、項目3に記載の前記方法。
(項目8)
該組成物がリン酸塩を含む、項目2に記載の前記方法。
(項目9)
該組成物が約6.5を超えるpHを有する、項目1に記載の前記方法。
(項目10)
少なくとも1つのC1エステラーゼを約400U/ml以上で含む、組成物。
(項目11)
少なくとも1つの薬学的に許容される担体をさらに含む、項目10に記載の前記組成物。
(項目13)
少なくとも1つの項目10に記載の組成物を含む、キット。
(項目14)
少なくとも1つのシリンジ及び/または再構成緩衝液をさらに含む、項目13に記載の前記キット。
(項目15)
該シリンジに該組成物が予め充填されている、項目14に記載の前記キット。
「1つの(a)」、「1つの(an)」、及び「その(the)」という単数形は、文脈が別途明確に指示しない限り、複数形の指示対象を含む。
タンパク質をスピン濃縮器に充填し、5〜10分間10,500rpmで回転させた。試料が回転を停止したとき、スピン濃縮器内の最終容積を記録し、それぞれのおおまかなタンパク質濃度を算定した。追加のタンパク質をスピン濃縮器に加え、所望のタンパク質濃度に達するまで回転させ、この時点でUV測定を行った。それぞれの標的タンパク質濃度において、UV及び粘度の測定を実施した。タンパク質の粘度が試料のさらなる濃縮を防止するまで、上記の手順を続けた。
ゲルを充填するピペット先端の所定の距離まで試料が引き込まれるのにかかった時間の量を測定することによって、粘度を判定した。試料粘度を算定するために、既知の粘度を有する一連の標準を使用して、標準曲線をまず調製した。スクロース(またはBrix)溶液が、かかる曲線を調製するために好適だが、規定の温度で既知の粘度を有するいかなる材料も適切であろう。
本実施例は、単一製剤(monoformulation)としての、より高濃度のC1 IΝΗの液体製剤を開発するための能力を判定した。初期研究は、スピン濃縮法を使用してC1 IΝΗの原液の濃度に着目した。溶液を、はじめにpHについて調節したが、他の賦形剤は添加しなかった。3つのpH値を調査した(pH5.9、6.9、及び7.9)。スピン濃縮すると、溶液のすべてが、試験したpH値すべてについて、最大約500U/ml(およそ100mg/ml)の濃度まで、澄んだままであった(表1)。これらの研究では可溶性限度に達しなかったが、濃度が300U/mlを超えると粘度に測定可能な上昇があった(図2)。すべてのpH値において、C1 INH濃度が400U/mlを超えると、粘度が顕著に上昇し始める。
Claims (30)
- C1エステラーゼ抑制因子と、クエン酸ナトリウムとを含む薬学的組成物であって、6.5〜8.0のpH範囲を有し、該C1エステラーゼ抑制因子は約400〜600U/mlの濃度を有し、該C1エステラーゼ抑制因子は、配列番号1の残基23〜500のアミノ酸配列を含む、薬学的組成物。
- 前記pHが約6.5〜約7.5である、請求項1に記載の薬学的組成物。
- 前記pHが約6.5〜約7.0である、請求項1に記載の薬学的組成物。
- 前記クエン酸ナトリウムが約10mM〜約30mMで存在する、請求項1に記載の薬学的組成物。
- 前記クエン酸ナトリウムが10mM〜30mMで存在する、請求項1に記載の薬学的組成物。
- 前記クエン酸ナトリウムが約10mMで存在する、請求項1に記載の薬学的組成物。
- 少なくとも1つのアミノ酸またはその塩をさらに含む、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、約1500U〜約2500Uの範囲で前記組成物中に存在する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、少なくとも約2000Uで前記組成物中に存在する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、約2000Uで前記組成物中に存在する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、約5000U未満で前記組成物中に存在する、請求項9に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、約5000Uで前記組成物中に存在する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、ヒト血漿から単離または精製されている、請求項1に記載の薬学的組成物。
- ヒト血漿から単離または精製されている前記C1エステラーゼ抑制因子が、ナノ濾過されている、請求項13に記載の薬学的組成物。
- ヒト血漿から単離または精製されている前記C1エステラーゼ抑制因子が、低温殺菌されている、請求項13に記載の薬学的組成物。
- 液体形態で調製されている、請求項1に記載の薬学的組成物。
- 少なくとも1つの凍結乾燥粉末から水で再構成されている、請求項1に記載の薬学的組成物。
- 約20mPa−s未満の粘度を有する、請求項1に記載の薬学的組成物。
- 約10mPa−s未満の粘度を有する、請求項1に記載の薬学的組成物。
- 前記組成物中に存在する前記C1エステラーゼ抑制因子が、前記組成物中の全タンパク質のうちの少なくとも50〜60%を構成する、請求項1に記載の薬学的組成物。
- 前記組成物中に存在する前記C1エステラーゼ抑制因子が、前記組成物中の全タンパク質のうちの少なくとも75%を構成する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、4℃で2年間保管した場合にモノマー含量において約10%未満損失する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、40℃で1週間保管した場合にモノマー含量損失において約20%未満損失する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、25℃で2週間保管した場合にモノマー含量損失において約10%未満損失する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、40℃で1週間保管した場合に純度において約2%未満損失する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、40℃で1週間保管した場合に純度において約1%未満損失する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、25℃で2週間保管した場合に純度において約2%未満損失する、請求項1に記載の薬学的組成物。
- 前記C1エステラーゼ抑制因子が、25℃で2週間保管した場合に純度において約1%未満損失する、請求項1に記載の薬学的組成物。
- 薬学的活性成分の単一製剤である、請求項1に記載の薬学的組成物であって、該薬学的活性成分がC1エステラーゼ抑制因子から本質的になる、薬学的組成物。
- 少なくとも約2000UのC1エステラーゼ抑制因子かつ約5000U未満のC1エステラーゼ抑制因子で、C1エステラーゼ抑制因子と、クエン酸ナトリウムとを含む凍結乾燥された薬学的組成物であって、該凍結乾燥された組成物が400〜600U/mlの濃度のC1エステラーゼ抑制因子を含む溶液を調製するように滅菌水中に再構成された場合に、該溶液はHAEを処置するために皮下投与するのに適しており、前記クエン酸ナトリウムは少なくとも10mMの濃度を有し、該溶液は6.5〜8.0のpH範囲を有し、該C1エステラーゼ抑制因子は、配列番号1の残基23〜500のアミノ酸配列を含む、薬学的組成物。
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Families Citing this family (17)
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NZ710730A (en) | 2013-03-15 | 2021-07-30 | Viropharma Biologics Llc | C1-inh compositions and methods for the prevention and treatment of disorders associated with c1 esterase inhibitor deficiency |
KR102312817B1 (ko) * | 2013-11-22 | 2021-10-13 | 다케다 야쿠힌 고교 가부시키가이샤 | C1-에스테라제 억제제를 사용한 장기 이식 환자에서의 항체-매개성 거부반응의 치료 방법 |
RU2017132449A (ru) * | 2015-02-20 | 2019-03-21 | Цсл Беринг Гмбх | Фармацевтические композиции ингибитора c1-эстеразы |
CN108025047B (zh) * | 2015-05-28 | 2021-11-19 | 康奈尔大学 | 腺相关病毒介导的c1ei递送作为用于血管性水肿的疗法 |
JP7189767B2 (ja) * | 2015-11-19 | 2022-12-14 | 武田薬品工業株式会社 | 組換えヒトc1エステラーゼインヒビター及びその使用 |
EP3493832A1 (en) | 2016-08-05 | 2019-06-12 | CSL Behring GmbH | Pharmaceutical formulations of c1 esterase inhibitor |
JP2019534240A (ja) * | 2016-08-23 | 2019-11-28 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | C1エステラーゼ阻害剤欠乏に関連する遺伝性血管浮腫の急性発作を予防する方法 |
MX2019013711A (es) * | 2017-05-16 | 2020-01-30 | Octapharma Ag | Preparacion de inhibidor de c1 esterasa. |
WO2019166572A1 (en) | 2018-02-28 | 2019-09-06 | Pharming Intellectual Property B.V. | Pharmaceutical system for transdermal administration of a c1 -esterase inhibitor |
BR112020017626A2 (pt) | 2018-02-28 | 2020-12-22 | Pharming Intellectual Property B.V. | Tratamento e prevenção de pré-eclâmpsia |
CN112584843A (zh) | 2018-06-22 | 2021-03-30 | 顺天生化股份有限公司 | 用于诱发感染性免疫耐受的组合物 |
CA3104797A1 (en) | 2018-06-22 | 2019-12-26 | Junten Bio Co., Ltd. | Antibody capable of inducing immune tolerance produced using cell mixture having complexed state, and induced lymphocyte or cell therapeutic agent and cell therapy method each using induced lymphocyte |
KR20210025062A (ko) | 2018-06-22 | 2021-03-08 | 가부시키가이샤 준텐 바이오 | 면역 관용을 유도하는 항체, 유도된 림프구, 또한 유도된 림프구를 이용하는 세포 치료제 치료법 |
JPWO2021124793A1 (ja) * | 2019-12-16 | 2021-06-24 | ||
EP3895726A1 (en) | 2020-04-17 | 2021-10-20 | Pharming Intellectual Property BV | Using c1 esterase inhibitor to treat viral infection-related acute respiratory distress |
JP2024525084A (ja) | 2021-07-09 | 2024-07-09 | ファーミング・インテレクチュアル・プロパティー・ビー.ブイ. | C1エステラーゼ阻害剤によるウイルス感染関連症状の治療 |
KR20230046146A (ko) | 2021-09-29 | 2023-04-05 | 주식회사 엘지에너지솔루션 | 배터리 제어 시스템 및 방법 |
Family Cites Families (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5304482A (en) | 1989-03-06 | 1994-04-19 | The Board Of Regents Of The University Of Texas System | Serine protease mutants of the chymotrypsin superfamily resistant to inhibition by their cognate inhibitors |
WO1992022320A1 (en) | 1991-06-14 | 1992-12-23 | Genentech, Inc. | C1 inhibitor variants and treating inflammatory response with c1 inhibitor |
ES2171465T3 (es) * | 1993-09-01 | 2002-09-16 | Sanquin Bloedvoorziening | Inhibidor de la esterasa de c1 para reducir lesiones de miocardio durante un infarto de miocardio agudo. |
JP2000507204A (ja) | 1995-12-18 | 2000-06-13 | ステイヒテイング・サンキン・ブロードボールジーニング | C1―インヒビターの補体及び血液凝固阻害特性の強化 |
AT409336B (de) * | 1999-12-22 | 2002-07-25 | Baxter Ag | Verfahren zur herstellung einer c1-esterase-inhibitor (c1-inh)-hältigen zusammensetzung |
DE60132169T2 (de) | 2000-01-31 | 2008-12-11 | Pharming Intellectual Property Bv | Humaner c1 inhibitor hergestellt in der milch transgener säugetiere |
US7067713B2 (en) * | 2000-01-31 | 2006-06-27 | Pharming Intellectual Property B.V. | C1 Inhibitor produced in the milk of transgenic non-human mammals |
SI1324776T2 (en) | 2000-10-12 | 2018-06-29 | Genentech, Inc. | Concentrated protein formulations with reduced viscosity |
DE10112617A1 (de) | 2001-03-14 | 2002-10-02 | Aventis Behring Gmbh | Verwendung eines C1-Esterase-Inhibitors zur Verhinderung oder Verzögerung der Abstoßung von Xenotransplantaten in Säugetieren |
WO2004034971A2 (en) | 2002-09-25 | 2004-04-29 | The Center For Blood Research, Inc. | Methods for treating and preventing sepsis using modified c1 inhibitor or fragments thereof |
WO2004110356A2 (en) | 2003-05-15 | 2004-12-23 | Cbr Institute For Biomedical Research, Inc. | Methods for modulating cell-to-cell adhesion using an agonist of c1inh-type protein activity |
PL1626736T3 (pl) | 2003-05-16 | 2021-05-04 | Pharming Intellectual Property B.V. | Inhibitor c1 o krótkim okresie półtrwania do leczenia przejściowego |
US20060233776A1 (en) | 2003-08-19 | 2006-10-19 | Norbert Heimburger | C1-inh as a drug for treating viruses pathogenic to humans |
US8501705B2 (en) | 2003-09-11 | 2013-08-06 | The Board Of Regents Of The University Of Texas System | Methods and materials for treating autoimmune and/or complement mediated diseases and conditions |
EP1598428A1 (en) | 2004-05-18 | 2005-11-23 | Georg Dewald | Methods and kits to detect Hereditary angioedema type III |
CA2654440C (en) | 2005-06-06 | 2013-09-03 | Girish J. Kotwal | Methods for treatment or prophylaxis of atherosclerosis and reperfusion injury |
WO2007047995A2 (en) | 2005-10-21 | 2007-04-26 | Catalyst Biosciences, Inc. | Modified proteases that inhibit complement activation |
ATE516043T1 (de) | 2005-12-21 | 2011-07-15 | Pharming Intellectual Pty Bv | Verwendung von c1-inhibitor zur prävention von ischämischen reperfusionsschäden |
ES2369522T3 (es) * | 2005-12-21 | 2011-12-01 | Pharming Intellectual Property B.V. | Uso de un inhibidor c1 para la prevención de lesiones por isquemia-reperfusión. |
US7837992B2 (en) | 2006-06-22 | 2010-11-23 | Beth Israel Deaconess Medical Center | C-1 inhibitor prevents non-specific plasminogen activation by a prourokinase mutant without impeding fibrin-specific fibrinolysis |
EP2109457B1 (en) | 2007-02-12 | 2016-01-06 | CSL Behring GmbH | Therapeutic application of kazal-type serine protease inhibitors |
CA2707483A1 (en) | 2007-11-30 | 2009-06-11 | Wolfgang Fraunhofer | Protein formulations and methods of making same |
US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
US20100143325A1 (en) | 2008-12-09 | 2010-06-10 | Vascular Laboratory, Inc. | Composition And Methods Involving Thrombolytic Agents |
JP5871798B2 (ja) | 2009-07-02 | 2016-03-01 | エムユーエスシー ファウンデーション フォー リサーチ ディベロップメント | 肝再生を刺激する方法 |
RU2600876C2 (ru) | 2009-10-16 | 2016-10-27 | Омерос Корпорейшен | Способ лечения диссеминированного внутрисосудистого свертывания крови путем ингибирования masp-2 зависимой активации комплемента |
WO2011107591A1 (en) | 2010-03-05 | 2011-09-09 | Rigshospitalet | Chimeric inhibitor molecules of complement activation |
US20130085111A1 (en) * | 2010-03-18 | 2013-04-04 | Thrombolytic Science, Llc | Production of human c1 inhibitor in human cells |
WO2013013017A2 (en) * | 2011-07-21 | 2013-01-24 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for modifying the glycosylation of lysosomal storage disorder therapeutics |
CN104010656B (zh) | 2011-09-24 | 2016-02-24 | 德国杰特贝林生物制品有限公司 | 使用免疫球蛋白和c1-抑制剂的联合疗法 |
CA2858984C (en) | 2011-12-22 | 2021-01-05 | Csl Behring Gmbh | Use of c1-inhibitor for the treatment of secondary edema of the central nervous system |
WO2013138730A1 (en) | 2012-03-16 | 2013-09-19 | Enzon Pharmaceuticals, Inc. | Polymeric conjugates of c1-inhibitors |
US20160033511A1 (en) | 2013-03-13 | 2016-02-04 | Creatics Llc | Methods and compositions for detecting pancreatic cancer |
NZ710730A (en) * | 2013-03-15 | 2021-07-30 | Viropharma Biologics Llc | C1-inh compositions and methods for the prevention and treatment of disorders associated with c1 esterase inhibitor deficiency |
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