JP2022500386A - Csf−1r抗体製剤 - Google Patents
Csf−1r抗体製剤 Download PDFInfo
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- JP2022500386A JP2022500386A JP2021513330A JP2021513330A JP2022500386A JP 2022500386 A JP2022500386 A JP 2022500386A JP 2021513330 A JP2021513330 A JP 2021513330A JP 2021513330 A JP2021513330 A JP 2021513330A JP 2022500386 A JP2022500386 A JP 2022500386A
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- 238000006317 isomerization reaction Methods 0.000 description 1
- BQINXKOTJQCISL-GRCPKETISA-N keto-neuraminic acid Chemical compound OC(=O)C(=O)C[C@H](O)[C@@H](N)[C@@H](O)[C@H](O)[C@H](O)CO BQINXKOTJQCISL-GRCPKETISA-N 0.000 description 1
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- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
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- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
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- CERZMXAJYMMUDR-UHFFFAOYSA-N neuraminic acid Natural products NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO CERZMXAJYMMUDR-UHFFFAOYSA-N 0.000 description 1
- 229960003301 nivolumab Drugs 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
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- 150000007523 nucleic acids Chemical class 0.000 description 1
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- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
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- 241000894007 species Species 0.000 description 1
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Classifications
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- A61K39/00—Medicinal preparations containing antigens or antibodies
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- A61K39/39591—Stabilisation, fragmentation
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- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
Description
−40mg/ml〜200mg/mlのCSF−1Rに対する抗体と、
−0.01%〜0.1%(w/v)の界面活性剤と、
−5mM〜100mMの緩衝剤と、
−10mM〜500mMの少なくとも1つの安定剤とを、
4.5〜7.0の範囲のpHで含む、医薬製剤を指す。
40〜100mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.03〜0.05%(w/v)のポリソルベート20と、
210〜230mMのスクロースと、
任意選択で、5〜25mMのメチオニンとを、
6.0±0.5のpHで含む、医薬製剤に関する。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
220mMのスクロースと、
10mMのメチオニンとを、
6.0±0.5のpHで含む。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
220mMのスクロースとを、
6.0±0.5のpHで含む、医薬製剤が本明細書で提供される。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポロキサマー188と、
220mMのスクロースとを、
6.0±0.5のpHで含む、医薬製剤が本明細書で提供される。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
130mMの塩化ナトリウムとを、
6.0±0.5のpHで含む、医薬製剤が本明細書で提供される。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
130mMの塩化ナトリウムと、
10mMのメチオニンとを、
6.0±0.5のpHで含む、医薬製剤が本明細書で提供される。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポロキサマー188と、
130mMの塩化ナトリウムとを、
6.0±0.5のpHで含む、医薬製剤が本明細書で提供される。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
220mMのスクロースとを、
5.5±0.5のpHで含む。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
220mMのスクロースと、
10mMのメチオニンとを、
5.5±0.5のpHで含む。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポロキサマー188と、
220mMのスクロースとを、
5.5±0.5のpHで含む。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
130mMの塩化ナトリウムとを、
5.5±0.5のpHで含む、医薬製剤が本明細書で提供される。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
130mMの塩化ナトリウムと、
10mMのメチオニンとを、
5.5±0.5のpHで含む、医薬製剤が本明細書で提供される。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポロキサマー188と、
130mMの塩化ナトリウムとを、
5.5±0.5のpHで含む、医薬製剤が本明細書で提供される。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
240mMのトレハロースとを、
6.0±0.5のpHで含む。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
240mMのトレハロースと、
10mMのメチオニンとを、
6.0±0.5のpHで含む。
50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポロキサマー188と、
240mMのトレハロースとを、
6.0±0.5のpHで含む。
(a)アミノ酸残基26−32(L1)、50−52(L2)、91−96(L3)、26−32(H1)、53−55(H2)、および96−101(H3)で生じる超可変ループ(Chothia and Lesk,J.Mol.Biol.196:901−917(1987))、
(b)アミノ酸残基24−34(L1)、50−56(L2)、89−97(L3)、31−35b(H1)、50−65(H2)、および95−102(H3)で生じるCDR(Kabat et al.,Sequences of Proteins of Immunological Interest,5th Ed.Public Health Service,National Institutes of Health,Bethesda,MD(1991))、ならびに
(c)アミノ酸残基27c−36(L1)、46−55(L2)、89−96(L3)、30−35b(H1)、47−58(H2)、および93−101(H3)で生じる抗原接触(MacCallum et al.J.Mol.Biol.262:732−745(1996))を含む。
表1に列挙されるhuMAb CSF−1R液体製剤F1〜F16を、50mg/mlのタンパク質濃度で調製した。
●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)
●溶液の透明度および乳白度
●分析タンパク質Aクロマトグラフィー
●目視検査
F1は、pH6.0で、50mg/mLの抗CSF−1R抗体、20mMのヒスチジンHCl、220mMのスクロース、0.04%のポリソルベート20の組成を有する液体製剤である。
Claims (22)
- 医薬製剤であって、
−40mg/ml〜200mg/mlのCSF−1Rに対する抗体と、
−0.01%〜0.1%(w/v)の界面活性剤と、
−5mM〜100mMの緩衝剤と、
−10mM〜500mMの少なくとも1つの安定剤とを、
4.5〜7.0の範囲のpHで含む、医薬製剤。 - 前記CSF−1Rに対する抗体が、配列番号1の重鎖CDR1(CDR−H1)、配列番号2のCDR−H2、および配列番号3のCDR−H3を含む重鎖可変領域と、配列番号4の軽鎖CDR1(CDR−L1)、配列番号5のCDR−L2、および配列番号6のCDR−L3を含む軽鎖可変領域と、を含む、請求項1に記載の医薬製剤。
- 前記CSF−1Rに対する抗体が、配列番号7のアミノ酸配列を含む重鎖可変領域と、配列番号8のアミノ酸配列を含む軽鎖可変領域と、を含む、請求項1または2に記載の医薬製剤。
- 前記CSF−1Rに対する抗体の濃度が、40mg/ml〜100mg/mlの範囲であり、特に、50mg/mlである、請求項1〜3のいずれか一項に記載の医薬製剤。
- 前記界面活性剤がポリソルベートである、請求項1〜4のいずれか一項に記載の医薬製剤。
- 前記ポリソルベートが、0.01%〜0.1%(w/v)の範囲の濃度、特に0.04%(w/v)の濃度で存在する、請求項1〜5のいずれか一項に記載の医薬製剤。
- 前記緩衝剤が、ヒスチジン緩衝液、特に、塩化ヒスチジン緩衝液である、請求項1〜6のいずれか一項に記載の医薬製剤。
- 前記緩衝剤が、10〜30mMの範囲の濃度、特に、20mMの濃度を有する、請求項1〜7のいずれか一項に記載の医薬製剤。
- 前記製剤のpHが、5.0〜6.5の範囲、特に、6.0である、請求項1〜8のいずれか一項に記載の医薬製剤。
- 少なくとも1つの安定剤が、塩類、糖類およびアミノ酸類からなる群から選択される、請求項1〜9のいずれか一項に記載の医薬製剤。
- 前記少なくとも1つの安定剤が、糖、特に、スクロースである、請求項1〜10のいずれか一項に記載の医薬製剤。
- 前記少なくとも1つの安定剤が、140〜250mMの範囲の濃度、特に、210〜230mMの範囲の濃度で存在する、請求項1〜11のいずれか一項に記載の医薬製剤。
- 塩類、糖類およびアミノ酸類の群から選択される第1の安定剤と、第2の安定剤としてのメチオニンと、を含む、請求項10に記載の医薬製剤。
- 前記第1の安定剤が、120〜300mMの濃度で存在し、前記第2の安定剤メチオニンが、5〜25mMの濃度で存在する、請求項13に記載の医薬製剤。
- 前記CSF−1Rに対する抗体が、ヒトCSF−1RフラグメントdelD4(配列番号11)およびヒトCSF−1R細胞外ドメイン(配列番号12)に1:50以下の比率で結合する、請求項1〜14のいずれか一項に記載の医薬製剤。
- 40〜100mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.03〜0.05%(w/v)のポリソルベート20と、
210〜230mMのスクロースと、
任意選択で、5〜25mMのメチオニンとを、
6.0±0.5のpHで含む、請求項1〜12のいずれか一項に記載の医薬製剤。 - 50mg/mlのCSF−1Rに対する抗体と、
20mMのL−ヒスチジンと、
0.04%(w/v)のポリソルベート20と、
220mMのスクロースと、
10mMのメチオニンとを、
6.0±0.5のpHで含む、請求項1〜16のいずれか一項に記載の医薬製剤。 - 液体形態、凍結乾燥した形態、または凍結乾燥した形態から再構築された液体形態である、請求項1〜17のいずれか一項に記載の医薬製剤。
- がんを治療する際に使用するための請求項1〜18のいずれか一項に記載の医薬製剤。
- 別の治療薬剤、特に、PD−L1/PD−1相互作用を遮断する薬剤と組み合わせて使用するための請求項1〜19のいずれか一項に記載の医薬製剤。
- 色素性絨毛結節性滑膜炎(PVNS)または腱滑膜巨細胞腫(TGCT)を治療する際に使用するための請求項1〜18のいずれか一項に記載の医薬製剤。
- がんを治療するため、または色素性絨毛結節性滑膜炎(PVNS)もしくは腱滑膜巨細胞腫(TGCT)を治療するために有用な医薬の調製のための請求項1〜18のいずれか一項に記載の製剤の使用。
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JP7304287B2 (ja) | 2016-12-22 | 2023-07-06 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | 抗pd-l1/pd1治療の不成功後の、抗pd-l1抗体との組み合わせでの抗csf-1r抗体を用いた腫瘍の治療 |
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