JP2021514379A - B7−h4抗体製剤 - Google Patents
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Abstract
Description
4.
本明細書で使用されるとき、「B7−H4」という用語は、ネイティブのB7−H4ポリペプチド及びB7−H4ポリペプチドのアイソフォームを含むがこれらに限定されない哺乳動物B7−H4ポリペプチドを指す。「B7−H4」は完全長、未処理のB7−H4ポリペプチド、と同様に細胞内の処理から生じるB7−H4ポリペプチドの形態を包含する。「B7−H4ポリヌクレオチド」、「B7−H4ヌクレオチド」または「B7−H4核酸」は、B7−H4をコードするポリヌクレオチドを指す。
本明細書で提供されるのは、抗B7−H4抗体またはその抗原結合断片(例えば、以下のセクション5.3で論じられるような)を含む医薬組成物(例えば、水性医薬組成物)である。
一実施形態では、医薬組成物は、18mM〜22mMのクエン酸塩、250mM〜290mMのスクロース、及び0.035%〜0.065%のPS20にて10mg/mL〜25 mg/mLのB7−H4抗体またはその断片(例えば、非フコシル化抗体20502) を含む。一実施形態では、医薬組成物約4.5〜約6、例えば、約5.5のpHを有する。一実施形態では、医薬組成物は液体である。
本明細書で提供されるのは、B7−H4(例えば、ヒトB7−H4)に特異的に結合する抗体(例えば、キメラ抗体、ヒト化抗体、またはヒト抗体のようなモノクローナル抗体)及びその抗原結合断片を含む医薬組成物である。本明細書で提供されている医薬組成物で使用することができる例示的なB7−H4抗体及びその抗原結合断片は、当該技術分野で既知である。ヒト、カニクイザル、マウス、及びラットのB7−H4のアミノ酸配列は当該技術分野で既知であり、それぞれ配列番号1〜4によって表されるように本明細書でも提供されている。
ヒトB7−H4:
MASLGQILFWSIISIIIILAGAIALIIGFGISGRHSITVTTVASAGNIGEDGILSCTFEPDIKLSDIVIQWLKEGVLGLVHEFKEGKDELSEQDEMFRGRTAVFADQVIVGNASLRLKNVQLTDAGTYKCYIITSKGKGNANLEYKTGAFSMPEVNVDYNASSETLRCEAPRWFPQPTVVWASQVDQGANFSEVSNTSFELNSENVTMKVVSVLYNVTINNTYSCMIENDIAKATGDIKVTESEIKRRSHLQLLNSKASLCVSSFFAISWALLPLSPYLMLK(配列番号1)
カニクイザルB7−H4:
MASLGQILFWSIISIIFILAGAIALIIGFGISGRHSITVTTVASAGNIGEDGILSCTFEPDIKLSDIVIQWLKEGVIGLVHEFKEGKDELSEQDEMFRGRTAVFADQVIVGNASLRLKNVQLTDAGTYKCYIITSKGKGNANLEYKTGAFSMPEVNVDYNASSETLRCEAPRWFPQPTVVWASQVDQGANFSEVSNTSFELNSENVTMKVVSVLYNVTINNTYSCMIENDIAKATGDIKVTESEIKRRSHLQLLNSKASLCVSSFLAISWALLPLAPYLMLK(配列番号2)
マウスB7−H4
MASLGQIIFWSIINIIIILAGAIALIIGFGISGKHFITVTTFTSAGNIGEDGTLSCTFEPDIKLNGIVIQWLKEGIKGLVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNASLRLKNVQLTDAGTYTCYIRTSKGKGNANLEYKTGAFSMPEINVDYNASSESLRCEAPRWFPQPTVAWASQVDQGANFSEVSNTSFELNSENVTMKVVSVLYNVTINNTYSCMIENDIAKATGDIKVTDSEVKRRSQLQLLNSGPSPCVFSSAFVAGWALLSLSCCLMLR(配列番号3)
ラットB7−H4
MASLGQIIFWSIINVIIILAGAIVLIIGFGISGKHFITVTTFTSAGNIGEDGTLSCTFEPDIKLNGIVIQWLKEGIKGLVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNASLRLKNVQLTDAGTYTCYIHTSKGKGNANLEYKTGAFSMPEINVDYNASSESLRCEAPRWFPQPTVAWASQVDQGANFSEVSNTSFELNSENVTMKVVSVLYNVTINNTYSCMIENDIAKATGDIKVTDSEVKRRSQLELLNSGPSPCVSSVSAAGWALLSLSCCLMLR(配列番号4)
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(配列番号23)。
CGGACCGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT(配列番号24)。
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(配列番号25)。
GCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGGGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA(配列番号26)。
B7−H4(例えば、ヒトB7−H4)に免疫特異的に結合する抗体及びその抗原結合断片は、抗体及びその抗原結合断片の合成について当該技術分野で既知の任意の方法によって、例えば、化学合成によってまたは組換え発現技術によって作り出すことができる。本明細書に記載されている方法は、特に指示されない限り、分子生物学、微生物学、遺伝子分析、組換えDNA、有機化学、生化学、PCR、オリゴヌクレオチドの合成及び修飾、核酸のハイブリッド形成、及び当該技術の範囲内の関連分野における従来の技法を採用する。これらの技法は、例えば、本明細書に引用される参考文献に記載されており、文献で完全に説明されている。例えば、Sambrook,J.et al.,(2001),Molecular Cloning:A Laboratory Manual,Cold Spring Harbor Laboratory Press,Cold Spring Harbor,NY;Ausubel,FM.et al.,Current Protocols in Molecular Biology,John Wiley & Sons(1987 and annual updates);Current Protocols in Immunology,John Wiley & Sons(1987 and annual updates)Gait(ed.)(1984),Oligonucleotide Synthesis:A Practical Approach,IRL Press;Eckstein(ed.)(1991),Oligonucleotides and Analogues:A Practical Approach,IRL Press;Birren,B.et al.,(eds.)(1999),Genome Analysis:A Laboratory Manual,Cold Spring Harbor Laboratory Pressを参照のこと。
一態様では、本明細書で提供されるのは、B7−H4抗体またはその抗原結合断片を含む本明細書で提供されている医薬組成物をそれを必要とする対象に投与することを含む、対象にて1以上の免疫機能を調節する方法である。
I.抗体産生
20502抗体は、FUT8遺伝子(α1,6−フコシルトランスフェラーゼ)を欠くCHO細胞株で生成されたので、実施例2〜9のすべてで使用された20502抗体は非フコシル化されている。それらは抗体のFc部分のASN297にて末端フコースを欠く。
モノクローナル抗体(mAb)の試料は、20kD分子量カットオフ(MWCO)の透析膜デバイスを用いて、ポリソルベートを含まない原薬(非フコシル化20502)を透析することにより、さまざまな製剤で調製した。透析後、mAbの濃度は1.47cm−1[g/L]−1の吸光係数を用いてUV分光法によって測定した。緩衝液交換した試料のタンパク質濃度を透析緩衝液で所望の値に調整し、10%PS20ストック溶液を0.05%(w/v)PS20の最終濃度で各製剤に添加した。製剤は、0.22μmフィルターユニットを用いて滅菌ろ過し、層流フードにて適切な容器/閉鎖系に入れた。試料は試験設計ごとにさまざまな保管条件に置かれ、それらの安定性は指定された時点でさまざまな方法を用いて分析した。
目視検査(AD−Gen−002/00):蛍光照明下で、黒と白の双方の背景に対して視覚的評価を行った。色、透明度、及び目に見える粒子の存在について試料を調べた。
抗B7−H4抗体20502はモノクローナル抗体である。知識ベースの製剤開発アプローチを用いて、タンパク質に最大の安定性を提供する適切な組成物を特定した。これを行うには、分子の固有の特性と、タンパク質の安定性に影響を与える得る外因性の配合成分の双方が考慮される。
製剤のpHはタンパク質の安定性に影響を及ぼす。製剤のpHは、脱アミド化、異性化、酸化のような生化学的分解経路、と同様にタンパク質間の相互作用や環境との相互作用による凝集や断片化のような生物物理学的分解にも影響を与えることができる。
予備的なpHスクリーニング試験の結果は、抗体20502がpH5〜6付近で最も安定していることを示した。4.5〜6.5の範囲で最大の安定性を提供するpHを特定するために、詳細なpH試験を行った。配合組成の詳細を表14でリストにする。この試験は、mAbの安定性に対する緩衝液の種類の考えられる影響を最小限に抑えるために、クエン酸緩衝液を用いて実施した。10mg/mLでの抗体20502の安定性を、最大3週間のストレス(40℃)条件下での視覚的外観、凝集、断片化(SE−HPLCによる)、及び電荷変異体(iCE)に基づいて調べた。
pHと同様に、緩衝液の種類はタンパク質の安定性に対してさまざまな程度に影響を及ぼす。10mg/mLでの20502の加速安定性は、pH5.0からpH6.5で最大の安定性を提供する緩衝液を決定する目的で、pKaに基づいて0.5単位の増分でpH5.0からpH6.5までの酢酸塩、クエン酸塩、コハク酸塩、及びヒスチジンの緩衝液で評価した。詳細な配合組成を表15に提供する。これらの緩衝液は、外観、凝集、断片化、及び電荷変異体に基づいてタンパク質の安定性への影響について調べた。
増量剤のような製剤賦形剤は製品の安定性に影響を与えることができる。抗体20502の安定性に対する賦形剤の効果を評価するために、20mg/mLでの抗体を塩化ナトリウム(NaCl)、トレハロース、ソルビトール、またはスクロースを等張濃度で含有する酢酸塩製剤及びクエン酸塩製剤に製剤化した。クエン酸塩製剤はpH5.5で製剤化し、酢酸塩製剤はpH5.0で製剤化した。スクロースを含む2つの追加の酢酸塩製剤もpH4.5及び5.5で調製した。詳細な配合組成を表16にて提供する。賦形剤は、40℃、25℃、及び5℃の保管条件下で視覚的外観、凝集、断片化、及び電荷変異体に基づいてタンパク質の安定性に対するその影響について調べた。
凍結/融解試験は、500mLのスケールでpH5.0での20mMの酢酸塩、270mMのスクロース、0.05%のPS20の製剤における20mg/mLのタンパク質として製剤化された20502バルク原薬を−70℃で凍結し、5サイクルを経て常温で融解することによって実施した。外観、可溶性凝集体、または目に見えない粒子状物質の明らかな変化は検出されなかった(表17)。
20502原薬を3ccのガラス製バイアルに充填し、試料バイアルをオービタルシェーカーに水平に置き、試料を室温にて72時間300RPMで振盪することにより、20502に攪拌ストレスをかけた。20502はpH5.0での20mMの酢酸塩、270mMのスクロース、0.05%PS20の製剤にて20mg/mLのタンパク質として製剤化された。20502製剤試料では、外観、可溶性凝集体、電荷変異体プロファイル、または目に見えない粒子状物質の明らかな変化は検出されなかった(表18)。すべての試験は20±5℃の室温で行われた。すべての試料は、目に見える粒子がなく、無色透明の外観を有した。
2つの製剤(i)pH5.0での20mMの酢酸塩、270mMのスクロース、及び0.05%PS20にて20mg/mLのタンパク質を含む製剤と、(ii)pH5.5での20mMのクエン酸塩、270mMのスクロース、及び0.05%PS20にて20mg/mLのタンパク質を含有する製剤における20502の安定性を評価するために安定性試験を実施した。製剤化した溶液1.5mLを、13mmのネックが付いた13mmのWest4023/50グレイのブロモブチル血清ストッパーでキャップをし、且つアルミニウムシールで密封した3ccの1型ガラスバイアルに充填した。容器閉鎖系と抗体20502との適合性はバイアルを逆さにして評価した。この安定性試験では、5℃、25℃、及び40℃での保管条件を使用した。酢酸塩製剤については表19〜表21及びクエン酸塩製剤については表22〜表24に示されている6ヵ月の安定性データ。
Claims (68)
- 医薬組成物であって、(i)ヒトB7−H4に特異的に結合する抗体またはその抗原結合断片と、(ii)酢酸塩またはクエン酸塩から成る群から選択される緩衝液と、(iii)糖とを含み、前記組成物のpHが約4.5〜約6である、前記医薬組成物。
- 医薬組成物であって、(i)ヒトB7−H4に特異的に結合し、配列番号5〜10のVH CDR1、VH CDR2、VH CDR3及びVL CDR1、CDR2、及びCDR3の配列を含む抗体またはその抗原結合断片と、(ii)緩衝液と、及び(iii)約4.5〜約6のpHとを含む、前記医薬組成物。
- 医薬組成物であって、ヒトB7−H4に特異的に結合する抗体またはその抗原結合断片を含み、前記組成物が5℃で6ヵ月後、前記抗体またはその抗原結合断片の酸性変異体を45%以下で含む、前記医薬組成物。
- 医薬組成物であって、ヒトB7−H4に特異的に結合する抗体またはその抗原結合断片を含み、前記組成物が5℃で6ヵ月後、前記抗体またはその抗原結合断片の酸性変異体を約30%〜約45%含む、前記医薬組成物。
- 医薬組成物であって、ヒトB7−H4に特異的に結合する抗体またはその抗原結合断片を含み、前記組成物が5℃で6ヵ月後、前記抗体またはその抗原結合断片の塩基性変異体を約20%以下で含む、前記医薬組成物。
- 医薬組成物であって、ヒトB7−H4に特異的に結合する抗体またはその抗原結合断片を含み、前記組成物が5℃で6ヵ月後、前記抗体またはその抗原結合断片の塩基性変異体を約9%〜約18%含む、前記医薬組成物。
- 医薬組成物であって、ヒトB7−H4に特異的に結合する抗体またはその抗原結合断片を含み、前記組成物が5℃で6ヵ月後、前記抗体またはその抗原結合断片の酸性変異体及び塩基性変異体を60%以下で含む、前記医薬組成物。
- 組成物が、5℃で6ヵ月後、前記抗体またはその抗原結合断片の酸性変異体を約30%〜約40%含む、請求項1〜7のいずれか1項に記載の組成物。
- 前記組成物が、5℃で6ヵ月後、前記抗体またはその抗原結合断片の酸性変異体を約35%〜約40%含む、請求項8に記載の組成物。
- 前記組成物が、5℃で6ヵ月後、前記抗体またはその抗原結合断片の塩基性変異体を約10%〜約17%含む、請求項1〜9のいずれか1項に記載の組成物。
- 前記組成物が、5℃で6ヵ月後、前記抗体またはその抗原結合断片の塩基性変異体を約11%〜約16%含む、請求項10に記載の組成物。
- 前記組成物が、5℃で6ヵ月後、前記抗体またはその抗原結合断片の酸性変異体及び塩基性変異体を55%以下で含む、請求項1〜11のいずれか1項に記載の組成物。
- 前記抗体またはその抗原結合断片がそれぞれ、配列番号5〜10のVH CDR1、VH CDR2、VH CDR3及びVL CDR1、CDR2、及びCDR3の配列を含む、請求項1または3〜12のいずれか1項に記載の組成物。
- 前記組成物の前記pHが約4.5〜約6である、請求項3〜13のいずれか1項に記載の組成物。
- 前記組成物が緩衝液を含む、請求項3〜14のいずれか1項に記載の組成物。
- 前記緩衝液が酢酸塩またはクエン酸塩である、請求項2または15に記載の組成物。
- 前記組成物が糖をさらに含む、請求項2〜15のいずれか1項に記載の組成物。
- 前記糖が、スクロース、ソルビトール、及びトレハロースから成る群から選択される、請求項1または17に記載の組成物。
- 前記緩衝液の濃度が約15〜約25mMである、請求項1、2及び15〜18のいずれか1項に記載の組成物。
- 前記緩衝液の前記濃度が約18mM〜約22mMである、請求項19に記載の組成物。
- 前記緩衝液の前記濃度が約20mMである、請求項20に記載の組成物。
- 前記糖の濃度が、約225mM〜約300mMである、請求項1及び請求項17〜21のいずれか1項に記載の組成物。
- 前記糖の前記濃度が約250mM〜約290mMである、請求項22に記載の組成物。
- 前記糖の前記濃度が約270mMである、請求項23に記載の組成物。
- 前記糖の前記濃度が前記緩衝液の前記濃度の約10〜約15倍であり、任意で、前記糖の前記濃度が前記緩衝液の前記濃度の約13.5倍である、請求項1及び17〜24のいずれか1項に記載の組成物。
- 前記組成物が界面活性剤をさらに含む、請求項1〜25のいずれか1項に記載の組成物。
- 前記界面活性剤がポリソルベートであり、任意で前記ポリソルベートがポリソルベート20である、請求項26に記載の組成物。
- 前記界面活性剤の前記濃度が約0.025%〜約0.075重量/体積(w/v)%である、請求項26または27に記載の組成物。
- 前記界面活性剤の前記濃度が約0.035%〜約0.065重量/体積(w/v)%である、請求項28に記載の組成物。
- 前記界面活性剤の前記濃度が約0.005重量/体積(w/v)%である、請求項29に記載の組成物。
- 前記抗体またはその抗原結合断片の濃度が約5mg/mL〜約30mg/mLである、請求項1〜30のいずれか1項に記載の組成物。
- 前記抗体またはその抗原結合断片の前記濃度が約10〜約25mg/mLである、請求項31記載の組成物。
- 前記抗体またはその抗原結合断片の前記濃度が約20mg/mLである、請求項32記載の組成物。
- 前記pHが約5.0〜約6.0である、請求項1〜33のいずれか1項に記載の組成物。
- 前記pHが約5である、請求項1〜33のいずれか1項に記載の組成物。
- 前記pHが約5.5である、請求項1〜33のいずれか1項に記載の組成物。
- 前記組成物が液体である、請求項1〜36のいずれか1項に記載の組成物。
- 前記組成物が非経口投与用である、請求項1〜37のいずれか1項に記載の組成物。
- 前記組成物が静脈内投与用である、請求項1〜37のいずれか1項に記載の組成物。
- 前記緩衝液が酢酸塩であり、前記賦形剤がスクロースである、請求項1〜39のいずれか1項に記載の組成物。
- 約20mMの酢酸塩と、約270mMのスクロースと、約20mg/mLの前記抗体またはその抗原結合断片と、約0.05%のポリソルベート20とを含み、前記pHが約5.0である、請求項1〜40のいずれか1項に記載の組成物。
- 酢酸塩の濃度の約13.5倍である濃度のスクロースと、約20mg/mLの前記抗体またはその抗原結合断片と、約0.05%のポリソルベート20とを含み、前記pHが約5.0である、請求項1〜40のいずれか1項に記載の組成物。
- 前記緩衝液がクエン酸塩であり、前記賦形剤がスクロースである、請求項1〜39のいずれか1項に記載の組成物。
- 約20mMのクエン酸塩と、約270mMのスクロースと、約20mg/mLの前記抗体またはその抗原結合断片と、約0.05%のポリソルベート20とを含み、前記pHが約5.5である、請求項1〜39または43のいずれか1項に記載の組成物。
- クエン酸塩の濃度の約13.5倍である濃度のスクロースと、約20mg/mLの前記抗体またはその抗原結合断片と、約0.05%のポリソルベート20とを含み、前記pHが約5.5である、請求項1〜39または43のいずれか1項に記載の組成物。
- 前記抗体が、配列番号11で示されるアミノ酸配列を含むVH及び/または配列番号12で示されるアミノ酸配列を含むVLを含む請求項1〜45のいずれか1項に記載の組成物。
- 前記抗体が、配列番号21で示されるアミノ酸配列を含む重鎖及び/または配列番号22で示されるアミノ酸配列を含む軽鎖を含む、請求項46に記載の組成物。
- 前記組成物における前記抗体またはその抗原結合断片の少なくとも95%が非フコシル化されている、請求項1〜47のいずれか1項に記載の組成物。
- 前記組成物においてフコシル化が検出できない、請求項1〜47のいずれか1項に記載の組成物。
- 完全長の抗体を含む、請求項1〜49のいずれか1項に記載の組成物。
- 抗原結合断片を含む、請求項1〜49のいずれか1項に記載の組成物。
- 前記抗原結合断片が、Fab、Fab’、F(ab’)2、単鎖Fv(scFv)、ジスルフィド結合Fv、V−NARドメイン、IgNar、イントラボディ、IgGΔCH2、ミニボディ、F(ab’)3、テトラボディ、トリアボディ、ジアボディ、単一ドメイン抗体、DVD−Ig、Fcab、mAb2、(scFv)2、またはscFv−Fcを含む、請求項51に記載の組成物。
- 前記抗体またはその抗原結合断片がカニクイザルB7−H4に特異的に結合する、請求項1〜52のいずれか1項に記載の組成物。
- 前記抗体またはその抗原結合断片がラットB7−H4に特異的に結合する、請求項1〜53のいずれか1項に記載の組成物。
- 前記抗体またはその抗原結合断片がマウスB7−H4に特異的に結合する、請求項1〜54のいずれか1項に記載の組成物。
- 前記抗体またはその抗原結合断片が、ヒトB7−H4のIgVドメインに特異的に結合する、請求項1〜55のいずれか1項に記載の組成物。
- 前記抗体またはその抗原結合断片のpIが約8.2である、請求項1〜56のいずれか1項に記載の組成物。
- 医薬組成物であって、(i)配列番号21で示されるアミノ酸配列を含む重鎖及び/または配列番号22で示されるアミノ酸配列を含む軽鎖を含む抗体と、(ii)約20mMの酢酸塩と、(iii)約270mMのスクロースと、(iv)約0.05重量/体積%のポリソルベート20とから成り、前記組成物のpHが約5.0である、前記医薬組成物。
- 医薬組成物であって、(i)配列番号21で示されるアミノ酸配列を含む重鎖及び/または配列番号22で示されるアミノ酸配列を含む軽鎖を含む抗体と、(ii)約20mMのクエン酸塩と、(iii)約270mMのスクロースと、(iv)約0.05重量/体積%のポリソルベート20とから成り、前記組成物のpHが約5.5である、前記医薬組成物。
- 請求項1〜59のいずれか1項に記載の組成物を含む、シリンジまたはバイアル。
- 対象にてB7−H4を発現しているがんを治療する方法であって、前記方法が請求項1〜59のいずれか1項に記載の医薬組成物を前記対象に投与することを含む、前記方法。
- 前記がんが固形腫瘍である、請求項61に記載の方法。
- 前記がんが、乳癌、乳管癌、子宮内膜癌、卵巣癌、非小細胞肺癌、膵臓癌、甲状腺癌、腎臓癌及び膀胱癌から成る群から選択される、請求項61または62に記載の方法。
- 前記乳癌がトリプルネガティブ乳癌またはホルモン受容体陽性乳癌である、請求項63に記載の方法。
- 前記非小細胞肺癌が扁平上皮癌である、請求項63に記載の方法。
- 前記対象がヒトである、請求項61〜65のいずれか1項に記載の方法。
- 前記医薬組成物が非経口投与される、請求項61〜66いずれか1項に記載の方法。
- 前記医薬組成物が静脈内に投与される、請求項61〜66のいずれか1項に記載の方法。
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AU2019228600A1 (en) | 2018-03-02 | 2020-09-24 | Five Prime Therapeutics, Inc. | B7-H4 antibodies and methods of use thereof |
KR20230137339A (ko) | 2021-01-04 | 2023-10-04 | 메르사나 테라퓨틱스, 인코포레이티드 | B7h4-표적화된 항체-약물 접합체 및 이의 사용 방법 |
MX2023011310A (es) | 2021-03-26 | 2023-10-05 | Innate Pharma | Anclajes de citocina para proteinas de celulas nk de union a nkp46. |
CA3214582A1 (en) * | 2021-05-07 | 2022-11-10 | Martin SAHLIN | Pharmaceutical compositions comprising bispecific antibodies binding to b7h4 and cd3 |
WO2022258678A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkp30, a cytokine receptor, a tumour antigen and cd16a |
WO2022258691A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkg2d, a cytokine receptor, a tumour antigen and cd16a |
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BR112020016986A2 (pt) | 2021-03-02 |
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