JP2015510871A - Aβ抗体製剤 - Google Patents
Aβ抗体製剤 Download PDFInfo
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- JP2015510871A JP2015510871A JP2014560323A JP2014560323A JP2015510871A JP 2015510871 A JP2015510871 A JP 2015510871A JP 2014560323 A JP2014560323 A JP 2014560323A JP 2014560323 A JP2014560323 A JP 2014560323A JP 2015510871 A JP2015510871 A JP 2015510871A
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Abstract
Description
− 約50mg/ml〜200mg/mlのAβ抗体、
− 約0.01%〜0.1%のポロキサマー、好ましくはポロキサマー188、
− 約5mM〜50mMのバッファー、
− 約100mM〜300mMの安定化剤
をpH約4.5〜7.0で含む、安定な液体薬学的抗体製剤を提供する。
− 配列番号4のアミノ酸配列を含むCDR1、
− 配列番号5のアミノ酸配列を含むCDR2、
− 配列番号6のアミノ酸配列を含むCDR3配列
を含むVHドメインを含む。
− 配列番号7のアミノ酸配列を含むCDR1、
− 配列番号8のアミノ酸配列を含むCDR2、
− 配列番号9のアミノ酸配列を含むCDR3配列
を含むVLドメインを含む。
DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA(配列番号1)を有する。Aβ41、Aβ40、Aβ39では、それぞれC末端アミノ酸A、IAおよびVIAが欠如している。Aβ43形態では、追加的なトレオニン残基が上記配列(配列番号1)のC末端に含まれる。
抗体は、リコンビナント法およびリコンビナント組成物を使用して、例えば米国特許第4,816,567号に記載されているように製造することができる。一態様では、本明細書記載の抗[[PRO]]抗体をコードする単離された核酸が提供される。そのような核酸は、抗体のVLを含むアミノ酸配列および/またはVHを含むアミノ酸配列をコードしうる(例えば抗体の軽鎖および/または重鎖)。さらなる一態様では、そのような核酸を含む一つまたは複数のベクター(例えば発現ベクター)が提供される。さらなる一態様では、そのような核酸を含むホスト細胞が提供される。そのような一態様では、ホスト細胞は、(1)抗体のVLを含むアミノ酸配列および抗体のVHを含むアミノ酸配列をコードする核酸を含むベクター、または(2)抗体のVLを含むアミノ酸配列をコードする核酸を含む第1のベクターおよび抗体のVHを含むアミノ酸配列をコードする核酸を含む第2のベクターを含む(例えばそれでトランスフォーメーションされている)。一態様では、ホスト細胞は、真核細胞、例えばチャイニーズハムスター卵巣(CHO)細胞またはリンパ系細胞(例えばY0、NS0、Sp20細胞)である。一態様では、抗[[PRO]]抗体の製造方法であって、上記に提供されるような抗体をコードする核酸を含むホスト細胞を、抗体の発現に適した条件で培養すること、および場合によりホスト細胞(またはホスト細胞の培養液)から抗体を回収することを含む方法が提供される。
本発明による皮下投与用液体医薬品製剤を以下のように開発した。
以下のAβ液体製剤を、タンパク質濃度150mg/mlで調製した。
− UV分光法
− サイズ排除クロマトグラフィー(SEC)
− イオン交換クロマトグラフィー(IEC)
− 溶液の透明性および乳光
− 目視検査
によって試料を分析した。
Claims (19)
- − 約50mg/ml〜200mg/mlのAβ抗体、
− 約0.01%〜0.1%のポロキサマー、好ましくはポロキサマー188、
− 約5mM〜50mMのバッファー、
− 約100mM〜300mMの安定化剤
をpH約4.5〜7.0で含む、安定な液体薬学的抗体製剤。 - Aβ抗体の濃度が、約100mg/ml〜200mg/ml、好ましくは約150mg/mlである、請求項1記載の薬学的製剤。
- ポロキサマーが、濃度約0.02%〜0.06%、好ましくは約0.04%で存在する、請求項1または2記載の薬学的製剤。
- バッファーが、酢酸ナトリウムバッファーまたはヒスチジンバッファー、好ましくはヒスチジン/ヒスチジン-HClバッファーである、請求項1〜3記載の薬学的製剤。
- バッファーが、濃度約10〜30mM、好ましくは約20mMを有する、請求項1〜4記載の薬学的製剤。
- 製剤のpHが、約5〜6、好ましくは約5.5である、請求項1〜5記載の薬学的製剤。
- 安定化剤が、糖およびアミノ酸より選択される、請求項1〜6記載の薬学的製剤。
- 安定化剤が、トレハロースおよびアルギニンより選択される、請求項7記載の薬学的製剤。
- 安定化剤が、濃度約100mM〜300mMを有する、請求項7または8記載の薬学的製剤。請求項10.安定化剤が、トレハロースであり、濃度約150mM〜250mM、好ましくは約200mMを有する、請求項8または9記載の薬学的製剤。
- 安定化剤が、アルギニンであり、濃度約100mM〜150mM、好ましくは約135mMを有する、請求項8または9記載の薬学的製剤。
- Aβ抗体が、重鎖および軽鎖を含むモノクローナル抗体である、請求項1〜10記載の薬学的製剤。
- Aβ抗体の重鎖が、
− 配列番号4のアミノ酸配列を含むCDR1、
− 配列番号5のアミノ酸配列を含むCDR2、
− 配列番号6のアミノ酸配列を含むCDR3配列
を含むVHドメインを含む、請求項11記載の薬学的製剤。 - Aβ抗体の軽鎖が、
− 配列番号7のアミノ酸配列を含むCDR1、
− 配列番号8のアミノ酸配列を含むCDR2、
− 配列番号9のアミノ酸配列を含むCDR3配列
を含むVLドメインを含む、請求項11または12記載の薬学的製剤。 - Aβ抗体のVHドメインが、配列番号2のアミノ酸配列を含み、Aβ抗体のVLドメインが、配列番号3のアミノ酸配列を含む、請求項12〜13記載の薬学的製剤。
- Aβ抗体の重鎖が、配列番号10のアミノ酸配列を含む、請求項11〜14記載の薬学的製剤。
- Aβ抗体の軽鎖が、配列番号11のアミノ酸配列を含む、請求項11〜15記載の薬学的製剤。
- モノクローナルAβ抗体が、モノグリコシル化Aβ抗体と二重グリコシル化Aβ抗体との混合物であり、ここで、モノグリコシル化抗体が、一方の抗体結合部位のVHドメイン中の配列番号2の位置52にグリコシル化アスパラギン(Asn)を含み、ここで、二重グリコシル化抗体が、両方の抗体結合部位のVHドメイン中の配列番号2の位置52にグリコシル化アスパラギン(Asn)を含み、その際、該混合物が、VHドメイン中の配列番号2の位置52でグリコシル化されていない抗体を5%未満含む、請求項11〜16記載の薬学的製剤。
- Aβ抗体の皮下投与のための、請求項1〜17記載の薬学的製剤の使用。
- 本明細書記載の発明。
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JP7265591B2 (ja) | 2017-05-30 | 2023-04-26 | 森永乳業株式会社 | 脳機能改善用組成物 |
JP2020531520A (ja) * | 2017-08-22 | 2020-11-05 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | 抗ベータアミロイド抗体を含有する医薬組成物 |
JP7263320B2 (ja) | 2017-08-22 | 2023-04-24 | バイオジェン・エムエイ・インコーポレイテッド | 抗ベータアミロイド抗体を含有する医薬組成物 |
US11655289B2 (en) | 2017-08-22 | 2023-05-23 | Biogen Ma Inc. | Pharmaceutical compositions containing anti-beta amyloid antibodies |
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