JP2022119854A - 抗cd19抗体製剤 - Google Patents
抗cd19抗体製剤 Download PDFInfo
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- 238000002424 x-ray crystallography Methods 0.000 description 1
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Abstract
Description
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度のショ糖
を更に含む。
別の実施形態において、安定な凍結乾燥医薬製剤が本明細書で提供され、製剤は、約20mg/ml~約125mg/mlの濃度の抗CD19抗体、緩衝液、約0.005%(w/v)~約0.06%(w/v)の濃度のポリソルベート、及び約6.0のpHを含み、製剤は、a)約180mM~約240mMの濃度のトレハロース、又は
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度のショ糖
を更に含む。
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度のショ糖
を更に含む。
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度のショ糖
を更に含む。
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度のショ糖
を更に含む。
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度のショ糖
を更に含む。
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度のショ糖
を更に含む。
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度のショ糖
を更に含み、前記抗CD19抗体は、配列SYVMH(配列番号1)のHCDR1領域、配列NPYNDG(配列番号2)のHCDR2領域、配列GTYYYGTRVFDY(配列番号3)のHCDR3領域、配列RSSKSLQNVNGNTYLY(配列番号4)のLCDR1領域、配列RMSNLNS(配列番号5)のLCDR2領域、及び配列MQHLEYPIT(配列番号6)のLCDR3領域を含む。
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度のショ糖
を更に含み、前記抗CD19抗体は、配列
の可変重鎖と、配列
の可変軽鎖とを含む。
b)約180mM~約240mMの濃度のマンニトール及び約10mM~約50mMの濃度
のショ糖を更に含み、前記抗CD19抗体は、配列
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
a)約200mMの濃度のトレハロース、又は
b)約219mMの濃度のマンニトール及び約29mMの濃度のショ糖
を更に含み、前記抗CD19抗体は、配列SYVMH(配列番号1)のHCDR1領域、配列NPYNDG(配列番号2)のHCDR2領域、配列GTYYYGTRVFDY(配列番号3)のHCDR3領域、配列RSSKSLQNVNGNTYLY(配列番号4)のLCDR1領域、配列RMSNLNS(配列番号5)のLCDR2領域、及び配列MQHLEYPIT(配列番号6)のLCDR3領域を含む。
a)約200mMの濃度のトレハロース、又は
b)約219mMの濃度のマンニトール及び約29mMの濃度のショ糖
を更に含み、前記抗CD19抗体は、配列
の可変重鎖と、配列
の可変軽鎖とを含む。
a)約200mMの濃度のトレハロース、又は
b)約219mMの濃度のマンニトール及び約29mMの濃度のショ糖
を更に含み、前記抗CD19抗体は、配列
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
a)約200mMの濃度のトレハロース、又は
b)約219mMの濃度のマンニトール及び約29mMの濃度のショ糖
を更に含み、前記抗CD19抗体は、配列
に対して少なくとも85%、86%、87%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、又は99%同一性を有する可変重鎖と、配列
に対して少なくとも85%、86%、87%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、又は99%同一性を有する可変軽鎖とを含む。
a)約200mMの濃度のトレハロース、又は
b)約219mMの濃度のマンニトール及び約29mMの濃度のショ糖
を更に含み、前記抗CD19抗体は、配列
に対して少なくとも85%、86%、87%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、又は99%同一性を有する重鎖定常ドメインと、配列
に対して少なくとも85%、86%、87%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、又は99%同一性を有する軽鎖定常ドメインとを含む。
の可変重鎖と、配列
の可変軽鎖とを含む。
の可変重鎖と、配列
の可変軽鎖とを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
の可変重鎖及び配列
の可変軽鎖を含む。
の可変重鎖と、配列
の可変軽鎖とを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
の重鎖定常ドメインと、配列
の軽鎖定常ドメインとを含む。
特徴付け、予備処方スクリーニング及び高濃度実現可能性を目的として、MOR208の生物物理学的特性を分析した。
- クエン酸(pH5.5;6.0)
- ヒスチジン(pH6.0;6.5;7.0)
MOR208の生物物理学的特徴付けに基づき、安定性研究において以下の6つの異なる液体製剤を試験した。
・製剤F1:10mMクエン酸、pH6.0+0.01% PS 20+150mM NaCl
・製剤F2:25mMクエン酸、pH6.0+0.02% PS 20+125mM NaCl
・製剤F3:25mMクエン酸、pH6.0+0.02% PS 20+200mMトレハロース
・製剤F4:25mMクエン酸、pH6.0+0.02% PS 20+210mMショ糖
・製剤F5:25mMヒスチジン、pH6.0+0.02% PS 20+140mM NaCl
・製剤F6:25mMヒスチジン、pH6.0+0.02% PS 20+230mMトレハロース
・製剤F7:25mMスクシナト(Succinat)、pH6.0+0.02% PS 20+215mMトレハロース
・製剤F8:25mMヒスチジン、pH6.5+0.02% PS 20+240mMトレハロース
・製剤F1:10mMクエン酸、pH6.0+0.01% PS 20+150mM NaCl
・製剤F3:25mMクエン酸、pH6.0+0.02% PS 20+200mMトレハロース
・製剤F5:25mMヒスチジン、pH6.0+0.02% PS 20+140mM NaCl
40mg/mlの濃度のMOR208を用いた凍結乾燥実現可能性研究には、製剤3及び新たな製剤9が含まれていた。
200mMトレハロース二水和物
0.02%ポリソルベート20
pH6.0
219mMマンニトール
29mMショ糖
0.02%ポリソルベート20
pH6.0
両方の製剤の凍結乾燥ケーキ(lyo cake)の外観は、許容できるものであった。トレハロース含有製剤は、完全に非晶質であり、より高い収縮度を示したが、これは、単に見かけ上の観察事項であり、一般に製品の品質又は安定性と関連性がない。マンニトール含有製剤は、部分的に結晶質であり、収縮のない、より高い医薬的上質性のケーキを提供する。
凍結乾燥実現可能性研究が問題なく終了した後、40℃(75% rH)で3カ月間の第1の安定性研究を行って両方の製剤を比較した。安定性試験は、色及び可視粒子に関する試験を含んでいた。更に、製品をHP-SEC(凝集)、HIC、IEC、結合アッセイ(CD16 Biacore)、MFI(サブビジブル粒子)及びSDS-Pageで試験した。
凍結乾燥実現可能性研究により、両方の製剤及び40mg/mLのタンパク質濃度を用いて、製品品質に影響を与えずにMOR208を凍結乾燥できることが示された。安定性条件は、40℃(75% rH)で3か月の期間であった。この安定性研究中、トレハロース含有製剤は、マンニトール/ショ糖製剤と比較して高い安定性を有するとして特定された。
長期安定性研究のために、製剤3中のMOR208を5℃±3℃でのリアルタイム保管及び25℃±2℃での促進された保管試験に供した。
HP-SECの安定性指示特性は、関連したストレスサンプルの分析により示された。また、凝集体検出の能力は、分析用超遠心分離法により検証された。
断片の検出のために、非還元CGEを適用する。脱アミドのような荷電変異体をもたらす化学修飾をIECにより検出した。
製品特異的な活性アッセイ、CD19結合アッセイ(FACS)、CD16結合アッセイ(SPR)及びADCC効力アッセイは、関連したストレスサンプルに対する感受性を示した。
含有量及び活性
3つの異なる活性アッセイ:CD19結合アッセイ(FACS)、CD16結合アッセイ(SPR)及びADCCベースの効力アッセイを用いて、MOR208の機能的活性を監視した。これらの3つのアッセイの組み合わせにより、抗原結合、関連エフェクター結合、及び主要な作用モード(ADCC)が包含される。
5±3℃の意図される保管温度での36カ月の保管中、純度アッセイ(即ちHP-SEC、IEC、還元及び非還元CGE)の何れも製品純度における重大な変化を示さない。25℃±2℃での促進された条件下において、HP-SECは、最近の試験時点において唯一の値の変化を示す(一増分に関するモノマーの低下/断片値の増大)が、これは、長期データに反映されず、従って無視できると見なされる。IECは、長期条件下の傾向を示さないが、促進された条件下での主要ピーク群の低下/塩基性ピーク群の増大の明らかな傾向を示す。
5±3℃の意図される保管温度での36カ月間の保管中、医薬試験の何れも経時的に重大な変化を示さなかった。要約すると、全医薬試験が十分に規格の範囲内であり、36カ月間にわたって製品品質の重大な変化を示さない。
Claims (15)
- 請求項1に記載の製剤において、前記製剤中の前記抗CD19抗体は、40mg/mlであることを特徴とする製剤。
- 請求項1又は2に記載の製剤において、前記緩衝液は、クエン酸緩衝液又はリン酸緩衝液であることを特徴とする製剤。
- 請求項3に記載の製剤において、前記クエン酸緩衝液又はリン酸緩衝液は、20~50mMの濃度であることを特徴とする製剤。
- 請求項4に記載の製剤において、前記クエン酸緩衝液又はリン酸緩衝液は、25mMの濃度であることを特徴とする製剤。
- 請求項1乃至5の何れか1項に記載の製剤において、前記製剤中の前記トレハロースは、200mMであることを特徴とする製剤。
- 請求項1乃至5の何れか1項に記載の製剤において、前記製剤中の前記マンニトールは、219mMであり、及び前記製剤中の前記ショ糖は、29mMであることを特徴とする製剤。
- 請求項1乃至7の何れか1項に記載の製剤において、前記製剤中の前記ポリソルベートは、ポリソルベート20であることを特徴とする製剤。
- 請求項1乃至8の何れか1項に記載の製剤において、前記製剤中の前記ポリソルベートは、0.02%であることを特徴とする製剤。
- 請求項1乃至9の何れか1項に記載の製剤において、前記抗CD19抗体は、IgG1、IgG2、IgG3又はIgG4抗体であることを特徴とする製剤。
- 請求項1乃至10の何れか1項に記載の製剤において、2~8℃で少なくとも6カ月間、少なくとも12カ月間、少なくとも18カ月間、少なくとも24カ月間又は少なくとも36カ月間にわたって安定であることを特徴とする製剤。
- 請求項1乃至5の何れか1項に記載の製剤において、前記抗CD19抗体は、40mg/mLの量であり、前記クエン酸緩衝液は、25mMの濃度であり、前記トレハロースは、200mMの濃度であり、ポリソルベートは、0.02%(w/v)の濃度であり、及び前記製剤は、6.0のpHを有することを特徴とする製剤。
- 請求項1乃至5の何れか1項に記載の製剤において、前記抗CD19抗体は、40mg/mLの量であり、前記クエン酸緩衝液は、25mMの濃度であり、前記マンニトールは、219mMの濃度であり、前記ショ糖は、29mMの濃度であり、ポリソルベートは、0.02%(w/v)の濃度であり、及び前記製剤は、6.0のpHを有することを特徴とする製剤。
- 製品において、請求項1乃至13の何れか1項に記載の安定な凍結乾燥医薬製剤を保持する容器を含むことを特徴とする製品。
- 対象における疾病又は疾患を処置する方法において、有効量の請求項1乃至13の何れか1項に記載の製剤を前記対象に投与するステップを含み、前記疾病又は疾患は、癌であることを特徴とする方法。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PE20212185A1 (es) | 2019-02-18 | 2021-11-11 | Lilly Co Eli | Formulacion de anticuerpos terapeuticos |
EP4038194A1 (en) | 2019-10-04 | 2022-08-10 | Ultragenyx Pharmaceutical Inc. | Methods for improved therapeutic use of recombinant aav |
TW202131949A (zh) | 2019-10-31 | 2021-09-01 | 德商莫菲西斯公司 | 包含抗CD19抗體及γδ T細胞之抗腫瘤組合療法 |
KR20230030636A (ko) | 2020-06-22 | 2023-03-06 | 모르포시스 아게 | 항-CD19 항체, 및 SIRPα-CD47 선천성 면역 체크포인트를 차단하는 폴리펩티드를 포함하는 항-종양 조합 요법 |
WO2022074206A1 (en) | 2020-10-08 | 2022-04-14 | Affimed Gmbh | Trispecific binders |
WO2023007023A1 (en) | 2021-07-30 | 2023-02-02 | Affimed Gmbh | Duplexbodies |
WO2023073645A1 (en) | 2021-10-29 | 2023-05-04 | Takeda Pharmaceutical Company Limited | Therapy comprising anti-cd19 antibody and sumo-activating enzyme inhibitor |
AR127568A1 (es) | 2021-11-03 | 2024-02-07 | Affimed Gmbh | Ligandos biespecíficos de cd16a |
WO2023215674A1 (en) * | 2022-05-03 | 2023-11-09 | Xencor, Inc. | Methods for treating lymphoma |
WO2024038115A1 (en) | 2022-08-17 | 2024-02-22 | Morphosys Ag | Therapy comprising anti-cd19 antibody and ezh2 modulators |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010500882A (ja) * | 2006-08-14 | 2010-01-14 | ゼンコー・インコーポレイテッド | Cd19を標的とする最適化抗体 |
JP2015130883A (ja) * | 2007-09-26 | 2015-07-23 | 中外製薬株式会社 | Cdrのアミノ酸置換により抗体の等電点を改変する方法 |
WO2015157286A1 (en) * | 2014-04-07 | 2015-10-15 | Seattle Genetics, Inc. | Stable formulations for anti-cd19 antibodies and antibody-drug conjugates |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4708871A (en) | 1983-03-08 | 1987-11-24 | Commonwealth Serum Laboratories Commission | Antigenically active amino acid sequences |
ATE395413T1 (de) | 2001-12-03 | 2008-05-15 | Amgen Fremont Inc | Antikörperkategorisierung auf der grundlage von bindungseigenschaften |
US20080260731A1 (en) * | 2002-03-01 | 2008-10-23 | Bernett Matthew J | Optimized antibodies that target cd19 |
US7902338B2 (en) | 2003-07-31 | 2011-03-08 | Immunomedics, Inc. | Anti-CD19 antibodies |
CA2534639C (en) | 2003-07-31 | 2013-07-30 | Immunomedics, Inc. | Anti-cd19 antibodies |
CA2611814A1 (en) | 2005-06-20 | 2007-01-04 | Medarex, Inc. | Cd19 antibodies and their uses |
KR101397290B1 (ko) | 2005-12-30 | 2014-05-21 | 메르크 파텐트 게엠베하 | 감소한 면역원성을 가지는 항-cd19 항체 |
MX2009002414A (es) | 2006-09-08 | 2009-05-20 | Medimmune Llc | Anticuerpos anti-cd19 humanizados y su uso en el tratamiento de oncologia, transplante y enfermedad autoinmunitaria. |
ES2659517T3 (es) | 2007-05-30 | 2018-03-16 | Xencor, Inc. | Métodos y composiciones para inhibir células que expresan CD32B |
EP2211904B1 (en) | 2007-10-19 | 2016-08-17 | Seattle Genetics, Inc. | Cd19 binding agents and uses thereof |
JP2012518404A (ja) | 2009-02-23 | 2012-08-16 | グレンマーク・ファーマシューティカルズ・エスエー | Cd19に結合するヒト化抗体及びその使用 |
EP2403532A4 (en) * | 2009-03-06 | 2012-12-05 | Medimmune Llc | HUMANIZED ANTI-CD19 ANTIBODY FORMULATIONS |
WO2011147834A1 (en) | 2010-05-26 | 2011-12-01 | Roche Glycart Ag | Antibodies against cd19 and uses thereof |
EP2409712A1 (en) | 2010-07-19 | 2012-01-25 | International-Drug-Development-Biotech | Anti-CD19 antibody having ADCC and CDC functions and improved glycosylation profile |
EP2409993A1 (en) | 2010-07-19 | 2012-01-25 | International-Drug-Development-Biotech | Anti-CD19 antibody having ADCC function with improved glycosylation profile |
EP2524929A1 (en) | 2011-05-17 | 2012-11-21 | Sanofi | Use of anti-CD19 maytansinoid immunoconjugate antibody for the treatment of CD19+ B-cell malignancies syptoms |
WO2014160490A1 (en) | 2013-03-13 | 2014-10-02 | Genetech, Inc. | Antibody formulations |
EP2968466B1 (en) | 2013-03-13 | 2018-07-25 | F.Hoffmann-La Roche Ag | Formulations with reduced oxidation |
US10513555B2 (en) * | 2013-07-04 | 2019-12-24 | Prothena Biosciences Limited | Antibody formulations and methods |
BR112016006397B1 (pt) | 2013-09-27 | 2024-01-16 | Genentech, Inc | Formulações de anticorpo de anti-pdl1, seu uso, artigo de fabricação e composição |
CN106163567B (zh) * | 2013-11-21 | 2021-06-11 | 根马布股份公司 | 抗体-药物缀合物冻干制剂 |
-
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-
2019
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-
2021
- 2021-06-14 CY CY20211100532T patent/CY1124521T1/el unknown
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-
2022
- 2022-03-22 US US17/700,809 patent/US20220213190A1/en active Pending
- 2022-05-18 JP JP2022081779A patent/JP2022119854A/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010500882A (ja) * | 2006-08-14 | 2010-01-14 | ゼンコー・インコーポレイテッド | Cd19を標的とする最適化抗体 |
JP2015130883A (ja) * | 2007-09-26 | 2015-07-23 | 中外製薬株式会社 | Cdrのアミノ酸置換により抗体の等電点を改変する方法 |
WO2015157286A1 (en) * | 2014-04-07 | 2015-10-15 | Seattle Genetics, Inc. | Stable formulations for anti-cd19 antibodies and antibody-drug conjugates |
Non-Patent Citations (5)
Title |
---|
INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 185, no. 2, JPN6021020280, 1999, pages 129 - 188, ISSN: 0005077887 * |
JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 104, no. 12, JPN5019006017, December 2015 (2015-12-01), pages 4170 - 4184, ISSN: 0005077884 * |
JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 105, no. 8, JPN5019006015, 9 June 2016 (2016-06-09), pages 2302 - 2309, ISSN: 0005077886 * |
JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 90, no. 3, JPN5019006016, March 2001 (2001-03-01), pages 310 - 321, ISSN: 0005077885 * |
JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 91, no. 4, JPN6021020276, 2002, pages 914 - 922, ISSN: 0005077883 * |
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