JP2021521205A - 抗pd−l1抗体の投与レジメンおよびその使用 - Google Patents
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Abstract
Description
本出願は、2018年4月13日に出願された米国仮特許出願第62/657,141号の利益を主張する。前記出願の内容は、全体が参照により本明細書に組み込まれる。
本出願は、ASCII形式で電子的に提出され、全体が参照により本明細書に組み込まれる配列表を含む。2019年4月9日に作成された前記ASCIIコピーは、C2160-7023WO_SL.txtという名称で、サイズが245,480バイトである。
一実施形態では、抗PD-L1抗体分子が、表3に示される、または表3に示されるヌクレオチド配列によってコードされるアミノ酸配列を含む重鎖および軽鎖可変領域から(例えば、表3に開示されるBAP058-Clone OまたはBAP058-Clone Nの重鎖および軽鎖可変領域配列から)の少なくとも1つ、2つ、3つ、4つ、5つまたは6つの相補性決定領域(CDR)(または集合的にCDRの全て)を含む。いくつかの実施形態では、CDRが、Kabatの定義に準ずる(例えば、表3に示される)。いくつかの実施形態では、CDRが、Chothiaの定義に準ずる(例えば、表3に示される)。いくつかの実施形態では、CDRが、KabatとChothiaの両方の組み合わせCDR定義に準ずる(例えば、表3に示される)。一実施形態では、VH CDR1のKabatとChothiaの組み合わせのCDRが、アミノ酸配列GYTFTSYWMY(配列番号647)を含む。一実施形態では、CDRの1つ以上(または集合的にCDRの全て)が、表3に示される、または表3に示されるヌクレオチド配列によってコードされるアミノ酸配列と比較して、1つ、2つ、3つ、4つ、5つ、6つ、またはそれ以上の変化、例えば、アミノ酸置換(例えば、保存的アミノ酸置換)または欠失を有する。
一実施形態では、抗PD-L1抗体分子が、MPDL3280A、RG7446、RO5541267、YW243.55.S70またはTECENTRIQTMとしても知られているアテゾリズマブ(Genentech/Roche)である。アテゾリズマブおよび他の抗PD-L1抗体は、全体が参照により組み込まれる米国特許第8,217,149号明細書に開示されている。一実施形態では、抗PD-L1抗体分子が、例えば、表4に開示される、アテゾリズマ(Atezolizuma)のCDR配列の1つ以上(または集合的にCDR配列の全て)、重鎖もしくは軽鎖可変領域配列、または重鎖もしくは軽鎖配列を含む。
本明細書に記載される抗PD-L1抗体分子は、本明細書に記載される対象への投与(例えば、静脈内投与)に適した製剤(例えば、用量製剤または剤形)に製剤化することができる。本明細書に記載される製剤は、液体製剤、凍結乾燥製剤または再構成製剤であることができる。
本明細書に記載される抗PD-L1抗体分子は、PD-L1の1つ以上の活性を阻害、低減または中和し、免疫チェックポイントの遮断または低減をもたらすことができる。したがって、本明細書に記載される抗PD-L1抗体分子は、対象の免疫応答の増強が望まれる障害(例えば、がん)を治療または予防するために使用することができる。
本明細書に記載の抗PD-L1抗体分子は、他の治療剤、手順または様式と組み合わせて使用することができる。
本明細書に記載される抗PD−L1抗体分子は、1つ以上の免疫調節剤と組み合わせて使用することができる。
一定の実施形態では、本明細書に開示される方法のいずれかが、対象(例えば、がん、例えば、本明細書に記載されるがんを有する対象)で、本明細書に記載される療法(例えば、単剤療法または併用療法)の有効性を評価または監視することをさらに含む。本方法は、療法に対する有効性の値を取得することを含み、前記値は、療法の有効性を示す。
(i)腫瘍浸潤リンパ球(TIL)表現型のパラメータ;
(ii)骨髄細胞集団のパラメータ;
(iii)表面発現マーカーのパラメータ;
(iv)免疫応答のバイオマーカーのパラメータ;
(v)全身性サイトカイン調節のパラメータ;
(vi)循環遊離DNA(cfDNA)のパラメータ;
(vii)全身性免疫調節のパラメータ;
(viii)マイクロバイオームのパラメータ;
(ix)循環免疫細胞における活性化のマーカーのパラメータ;または
(x)循環サイトカインのパラメータ。
(i)療法を対象に投与する;
(ii)療法の変更した投与を投与する;
(iii)療法のスケジュールまたは時間経過を変更する;
(iv)療法と組み合わせて追加の薬剤(例えば、本明細書に記載される治療剤)を対象に投与する;または
(v)代替療法を対象に投与する。
追加の用語は、以下でおよび出願全体を通して定義される。
PD−L1阻害剤、例えば、本明細書に記載される抗PD−L1抗体分子は、対象の障害、例えば、過剰増殖性状態または障害(例えば、がん)を治療(例えば、阻害、低減、改善または予防)するために、本明細書に記載される投与レジメンに従って投与することができる。一定の実施形態では、抗PD−L1抗体分子が、例えば、2、3、4、6または8週間に1回、約20mg〜約2000mgの用量で対象に投与される。
PD−L1の阻害剤、例えば、哺乳動物、例えば、ヒトPD−L1に結合する抗体分子を含む方法、組成物および製剤が本明細書に開示される。例えば、抗体分子は、PD−L1上のエピトープ、例えば、直鎖またはコンフォメーションエピトープ(例えば、本明細書に記載されるエピトープ)に特異的に結合する。
一実施形態では、PD−L1阻害剤が抗PD−L1抗体分子である。一実施形態では、PD−L1阻害剤が、全体が参照により組み込まれる、2016年4月21日に公開された「PD−L1に対する抗体分子およびその使用」と題された米国特許出願第2016/0108123号明細書に開示される抗PD−L1抗体分子である。
一実施形態では、抗PD−L1抗体分子が、MPDL3280A、RG7446、RO5541267、YW243.55.S70またはTECENTRIQTMとしても知られているアテゾリズマブ(Genentech/Roche)である。アテゾリズマブおよび他の抗PD−L1抗体は、全体が参照により組み込まれる米国特許第8,217,149号明細書に開示されている。一実施形態では、抗PD−L1抗体分子が、例えば、表4に開示される、アテゾリズマブのCDR配列の1つ以上(または集合的にCDR配列の全て)、重鎖もしくは軽鎖可変領域配列、または重鎖もしくは軽鎖配列を含む。
一定の実施形態では、本明細書に記載される抗PD−L1抗体分子が、PD−1阻害剤と組み合わせて投与される。いくつかの実施形態では、PD−1阻害剤が、PDR001(Novartis)、ニボルマブ(Bristol-Myers Squibb)、ペンブロリズマブ(Merck & Co)、ピジリズマブ(CureTech)、MEDI0680(Medimmune)、REGN2810(Regeneron)、TSR−042(Tesaro)、PF-06801591(Pfizer)、BGB-A317(Beigene)、BGB-108(Beigene)、INCSHR1210(Incyte)またはAMP-224(Amplimmune)から選択される。
一実施形態では、PD−1阻害剤が抗PD−1抗体分子である。一実施形態では、PD−1阻害剤が、全体が参照により組み込まれる、2015年7月30日に公開された「PD−1に対する抗体分子およびその使用」と題された米国特許出願公開第2015/0210769号明細書に記載される抗PD−1抗体分子である。
一実施形態では、抗PD−1抗体分子が、MDX−1106、MDX−1106−04、ONO−4538、BMS−936558またはOPDIVO(登録商標)としても知られているニボルマブ(Bristol-Myers Squibb)である。ニボルマブ(クローン5C4)および他の抗PD-1抗体は、全体が参照により組み込まれる米国特許第8,008,449号明細書および国際公開第2006/121168号パンフレットに開示されている。一実施形態では、抗PD−1抗体分子が、例えば、表2に開示される、ニボルマブのCDR配列の1つ以上(または集合的にCDR配列の全て)、重鎖もしくは軽鎖可変領域配列、または重鎖もしくは軽鎖配列を含む。
一定の実施形態では、本明細書に記載される抗PD−L1抗体分子が、LAG-3阻害剤と組み合わせて投与される。いくつかの実施形態では、LAG−3阻害剤が、LAG525(Novartis)、BMS−986016(Bristol-Myers Squibb)またはTSR−033(Tesaro)から選択される。
一実施形態では、LAG−3阻害剤が抗LAG−3抗体分子である。一実施形態では、LAG−3阻害剤が、全体が参照により組み込まれる、2015年9月17日に公開された「LAG−3に対する抗体分子およびその使用」と題された米国特許出願公開第2015/0259420号明細書に開示される抗LAG−3抗体分子である。
一実施形態では、抗LAG−3抗体分子が、BMS986016としても知られているBMS−986016(Bristol-Myers Squibb)である。BMS-986016および他の抗LAG-3抗体は、全体が参照により組み込まれる国際公開第2015/116539号パンフレットおよび米国特許第9,505,839号明細書に開示されている。一実施形態では、抗LAG-3抗体分子が、例えば、表6に開示される、BMS-986016のCDR配列の1つ以上(または集合的にCDR配列の全て)、重鎖もしくは軽鎖可変領域配列、または重鎖もしくは軽鎖配列を含む。
一定の実施形態では、本明細書に記載される抗PD−L1抗体分子が、TIM-3阻害剤と組み合わせて投与される。いくつかの実施形態では、TIM-3阻害剤が、MGB453(Novartis)またはTSR-022(Tesaro)である。
一実施形態では、TIM-3阻害剤が抗TIM-3抗体分子である。一実施形態では、TIM-3阻害剤が、全体が参照により組み込まれる、2015年8月6日に公開された「TIM-3に対する抗体分子およびその使用」と題された米国特許出願公開第2015/0218274号明細書に開示される抗TIM-3抗体分子である。
一実施形態では、抗TIM−3抗体分子がTSR−022(AnaptysBio/Tesaro)である。一実施形態では、抗TIM−3抗体分子が、TSR-022のCDR配列の1つ以上(または集合的にCDR配列の全て)、重鎖もしくは軽鎖可変領域配列、または重鎖もしくは軽鎖配列を含む。一実施形態では、抗TIM-3抗体分子が、例えば、表8に開示される、APE5137もしくはAPE5121のCDR配列の1つ以上(または集合的にCDR配列の全て)、重鎖もしくは軽鎖可変領域配列、または重鎖もしくは軽鎖配列を含む。APE5137、APE5121および他の抗TIM−3抗体は、全体が参照により組み込まれる国際公開第2016/161270号パンフレットに開示されている。
一定の実施形態では、本明細書に記載される抗PD−L1抗体分子が、GITRアゴニストと組み合わせて投与される。いくつかの実施形態では、GITRアゴニストが、GWN323(NVS)、BMS−986156、MK−4166もしくはMK−1248(Merck)、TRX518(Leap Therapeutics)、INCAGN1876(Incyte/Agenus)、AMG228(Amgen)またはINBRX−110(Inhibrx)である。
一実施形態では、GITRアゴニストが抗GITR抗体分子である。一実施形態では、GITRアゴニストが、全体が参照により組み込まれる、2016年4月14日に公開された「増強免疫応答およびがん療法のための組成物および使用方法」と題された国際公開第2016/057846号パンフレットに記載される抗GITR抗体分子である。
一実施形態では、抗GITR抗体分子が、BMS 986156またはBMS986156としても知られているBMS-986156(Bristol-Myers Squibb)である。BMS-986156および他の抗GITR抗体は、例えば、全体が参照により組み込まれる米国特許第9,228,016号明細書および国際公開第2016/196792号パンフレットに開示されている。一実施形態では、抗GITR抗体分子が、例えば、表10に開示される、BMS-986156のCDR配列の1つ以上(または集合的にCDR配列の全て)、重鎖もしくは軽鎖可変領域配列、または重鎖もしくは軽鎖配列を含む。
一定の実施形態では、本明細書に記載される抗PD−L1抗体分子が、IL-15/IL-15Ra複合体と組み合わせて投与される。いくつかの実施形態では、IL−15/IL−15Ra複合体が、NIZ985(Novartis)、ATL−803(Altor)またはCYP0150(Cytune)から選択される。
一実施形態では、IL−15/IL−15Ra複合体は、ヒトIL−15Raの可溶型と複合体形成したヒトIL−15を含む。複合体は、IL−15Raの可溶型に共有結合または非共有結合したIL−15を含んでもよい。特定の実施形態では、ヒトIL−15が、IL−15Raの可溶型に非共有結合している。特定の実施形態では、全体が参照により組み込まれる国際公開第2014/066527号パンフレットに記載されるように、組成物のヒトIL−15が、表11の配列番号1001のアミノ酸配列を含み、ヒトIL−15Raの可溶型が、表11の配列番号1002のアミノ酸配列を含む。本明細書に記載される分子は、全体が参照により組み込まれる国際公開第2007/084342号パンフレットに記載されるベクター、宿主細胞および方法によって作製することができる。
一実施形態では、IL−15/IL−15Ra複合体が、IL−15/IL−15Ra Fc融合タンパク質(IL−15N72D:IL−15RaSu/Fc可溶性複合体)であるALT−803である。ALT-803は、全体が参照により組み込まれる国際公開第2008/143794号パンフレットに開示されている。一実施形態では、IL−15/IL−15Ra Fc融合タンパク質が、表12に開示される配列を含む。
一定の実施形態では、本明細書に記載される抗PD−L1抗体分子が、トランスフォーミング増殖因子ベータ(TGFβ)阻害剤と組み合わせて投与される。いくつかの実施形態では、TGFβ阻害剤が、XOMA 089(Novartis)またはフレソリムマブ(Sanofi-Aventis)から選択される。
いくつかの実施形態では、TGFβ阻害剤が、XOMA 089、または全体が参照により組み込まれる国際特許出願公開第2012/167143号パンフレットに開示される化合物を含む。TGFβは、TGF−β、TGFbまたはTGF−ベータとしても知られており、本明細書では互換的に使用される。
いくつかの実施形態では、TGFβ阻害剤が、フレソリムマブ(CAS登録番号:948564−73−6)を含む。フレソリムマブはGC1008としても知られている。フレソリムマブは、TGF-ベータアイソフォーム1、2および3に結合し、これらを阻害するヒトモノクローナル抗体である。
別の態様では、本開示は、薬学的に許容される担体と合わせて製剤化された、本明細書に記載される抗PD−L1抗体分子を含む組成物、例えば、薬学的に許容される組成物を提供する。本明細書で使用される場合、「pharmaceutically acceptable carrier」(薬学的に許容される担体)には、生理学的に適合性である任意のおよび全ての溶媒、分散媒体、等張剤および吸収遅延剤などが含まれる。担体は、静脈内、筋肉内、皮下、非経口、直腸、脊髄または表皮投与(例えば、注射または注入による)に適していることができる。
本明細書に記載される抗PD−L1抗体分子を使用して、対象の免疫応答を改変することができる。いくつかの実施形態では、免疫応答が、増強、刺激または上方制御される。一定の実施形態では、免疫応答が、阻害、低減または下方制御される。例えば、これらの抗体分子を、培養中の細胞に、例えばインビトロもしくはエキソビボで、または対象に、例えばインビボで投与して、がん、免疫障害および感染性疾患などの様々な障害を治療、予防および/または診断することができる。
一態様では、本開示は、がん性腫瘍の成長が阻害または低減されるように、抗PD−L1抗体分子(例えば、本明細書に記載される抗PD−L1抗体分子)、または抗PD−L1を含む組成物もしくは製剤(例えば、本明細書に記載される組成物または製剤)を使用するインビボでの対象の治療に関する。
抗PD−L1抗体分子(例えば、本明細書に記載される抗PD−L1抗体分子)、または抗PD−L1を含む組成物もしくは製剤(例えば、本明細書に記載される組成物または製剤)を使用して感染性疾患を治療する方法が本明細書に開示される。一定の実施形態では、抗体分子、組成物または製剤が、本明細書に記載される投与レジメンに従って対象に投与される。
一定の実施形態では、本明細書に記載される抗PD−L1抗体分子、組成物または製剤が、ウイルス感染症またはウイルスに関連する疾患を治療するために使用される。
一定の実施形態では、本明細書に記載される抗PD-L1抗体分子、組成物または製剤が、細菌感染症または細菌に関連する疾患を治療するために使用される。
一定の実施形態では、本明細書に記載される抗PD-L1抗体分子、組成物または製剤が、真菌もしくは寄生生物感染症または真菌もしくは寄生生物に関連する疾患を治療するために使用される。
本明細書に記載される抗PD-L1抗体分子は、本明細書に記載される核酸によってコードすることができる。核酸を使用して、本明細書に記載される抗PD-L1抗体分子を作製することができる。
本明細書に記載される抗PD-L1抗体分子は、本明細書に記載される核酸を含む宿主細胞およびベクターを使用して作製することができる。核酸は、単一のベクターに存在してもよい、または同じ宿主細胞もしくは別個の宿主細胞に存在する別個のベクターに存在してもよい。
薬物動態(Pk)パラメータを、用量拡大試験で、FAZ053を投与されたヒト対象から収集した試料の血清濃度-時間プロファイルから計算した。試料を、3週間に1回(Q3W)、80mg、240mg、800mg、1200mgまたは1600mgの用量および6週間に1回(Q6W)、800mg、1200mgまたは1600mgの用量で静脈内注入によってFAZ053を投与された対象から分析した。Phoenix 6.4(Pharsight、Mountain View、CA)を使用して、ノンコンパートメント解析(NCA)を実施した。LC-MS/MSを使用して血清PK試料を分析した。アッセイの定量限界(LOQ)は0.25μg/mLであった。pKパラメータの要約を表13に示す。
PD-L1は、広範囲の腫瘍で発現される膜結合タンパク質である。PD-L1は、可溶型(sPD-L1)で体循環にも存在する。抗PD-L1抗体FAZ053のsPD-L1への結合を調査するために、実施例1に記載されるFAZ053を投与された対象から収集された総sPD-L1(遊離sPD-L1+sPD-L1−FAZ053複合体)試料を、ELISAベースの方法を使用して分析した。80mg、240mg、800mg、1200mgおよび1600mg Q3Wならびに800mg、1200mgおよび1600mg Q6Wの用量で静脈内注入によってFAZ053を投与された対象からの試料を分析した。
進行中の臨床試験では、様々な腫瘍タイプの対象に、80mg、240mg、800mg、1200mgおよび1600mg Q3Wならびに800mg、1200mgおよび1600mg Q6Wの用量で、静脈内注入を介して、単剤療法としてFAZ053を投与した。対象は、乳がん、子宮頸がん、結腸直腸がん、脊索腫、子宮内膜がん、非小細胞肺がん(NSCLC)、トリプルネガティブ乳がん(TNBC)、卵巣がん、肝細胞癌およびその他の形態のがんを有していた。800mg Q3Wおよび800mg Q6Wの用量レベルでの単剤療法としてのFAZ053治療で、RECIST v1.1で2つの確認された部分的応答が観察された(図4および図5)。
本明細書に言及される全ての刊行物、特許および受託番号は、各個々の刊行物または特許が参照により組み込まれることが具体的かつ個別に示されているかのように、全体が参照により本明細書に組み込まれる。
本発明の具体的な実施形態を論じてきたが、上記の明細書は例示的なものであり、限定的なものではない。本明細書および以下の特許請求の範囲を検討すると、本発明の多くの変形が当業者に明らかになるだろう。本発明の全範囲は、特許請求の範囲を、それらの等価物の全範囲、および明細書と共に、このような変形と共に参照することによって決定されるべきである。
Claims (47)
- 対象のがんの治療において、3週間に1回、約1000mg〜約1400mgの用量、または4週間に1回、約1400mg〜約1900mgの用量で使用するための抗PD−L1抗体分子であって、
前記抗PD−L1抗体分子が、配列番号601のVHCDR1アミノ酸配列、配列番号602のVHCDR2アミノ酸配列、および配列番号603のVHCDR3アミノ酸配列を含む重鎖可変領域(VH)と;配列番号609のVLCDR1アミノ酸配列、配列番号610のVLCDR2アミノ酸配列、および配列番号611のVLCDR3アミノ酸配列を含む軽鎖可変領域(VL)とを含む、
抗PD−L1抗体分子。 - 対象のがんを治療する方法であって、3週間に1回、約1000mg〜約1400mgの用量、または4週間に1回、約1400mg〜約1900mgの用量で抗PD−L1抗体分子を前記対象に投与することを含み、
前記抗PD−L1抗体分子が、配列番号601のVHCDR1アミノ酸配列、配列番号602のVHCDR2アミノ酸配列、および配列番号603のVHCDR3アミノ酸配列を含む重鎖可変領域(VH)と;配列番号609のVLCDR1アミノ酸配列、配列番号610のVLCDR2アミノ酸配列、および配列番号611のVLCDR3アミノ酸配列を含む軽鎖可変領域(VL)とを含む、
方法。 - 前記抗PD−L1抗体分子が、3週間に1回、約1100mg〜約1300mgの用量で使用される、請求項1に記載の使用のための抗体分子、または請求項2に記載の方法。
- 前記抗PD−L1抗体分子が、3週間に1回、約1200mgの用量で使用される、請求項3に記載の使用のための抗体分子、または請求項3に記載の方法。
- 前記抗PD−L1抗体分子が、4週間に1回、約1500mg〜約1700mgの用量で使用される、請求項1に記載の使用のための抗体分子、または請求項2に記載の方法。
- 前記抗PD−L1抗体分子が、4週間に1回、約1600mgの用量で使用される、請求項5に記載の使用のための抗体分子、または請求項5に記載の方法。
- 前記抗体分子が、配列番号606のアミノ酸配列を含むVHと、配列番号616のアミノ酸配列を含むVLとを含む、請求項1または3〜6のいずれかに記載の使用のための抗体分子、または請求項2〜6のいずれかに記載の方法。
- 前記抗体分子が、配列番号608のアミノ酸配列を含む重鎖と、配列番号618のアミノ酸配列を含む軽鎖とを含む、請求項1または3〜7のいずれかに記載の使用のための抗体分子、または請求項2〜7のいずれかに記載の方法。
- 前記抗体分子が、配列番号620のアミノ酸配列を含むVHと、配列番号624のアミノ酸配列を含むVLとを含む、請求項1または3〜6のいずれかに記載の使用のための抗体分子、または請求項2〜6のいずれかに記載の方法。
- 前記抗体分子が、配列番号622のアミノ酸配列を含む重鎖と、配列番号626のアミノ酸配列を含む軽鎖とを含む、請求項1、3〜6または9のいずれかに記載の使用のための抗体分子、または請求項2〜6または9のいずれかに記載の方法。
- 前記がんが、固形腫瘍、血液がん、またはその転移性病変である、請求項1または3〜10のいずれかに記載の使用のための抗体分子、または請求項2〜10のいずれかに記載の方法。
- 前記がんが、骨がん、皮膚がん、乳がん、子宮頸がん、結腸直腸がん、子宮内膜がん、肺がん、卵巣がん、肝臓がん、甲状腺がん、またはこれらの組み合わせから選択される、請求項1または3〜11のいずれかに記載の使用のための抗体分子、または請求項2〜11のいずれかに記載の方法。
- 前記骨がんが脊索腫である、請求項12に記載の使用のための抗体分子、または請求項12に記載の方法。
- 前記皮膚がんが、黒色腫またはメルケル細胞癌である、請求項12に記載の使用のための抗体分子、または請求項12に記載の方法。
- 前記黒色腫が皮膚黒色腫である、請求項14に記載の使用のための抗体分子、または請求項14に記載の方法。
- 前記乳がんが、乳癌またはトリプルネガティブ乳がん(TNBC)である、請求項12に記載の使用のための抗体分子、または請求項12に記載の方法。
- 前記肺がんが非小細胞肺がん(NSCLC)である、請求項12に記載の使用のための抗体分子、または請求項12に記載の方法。
- 前記結腸直腸がんが、再発性結腸直腸がんまたは転移性結腸直腸がんから選択される、請求項12に記載の使用のための抗体分子、または請求項12に記載の方法。
- 前記結腸直腸がんが、マイクロサテライト不安定性結腸直腸がん、マイクロサテライト安定性結腸直腸がん、ミスマッチ修復正常型結腸直腸がん、またはミスマッチ修復欠損型結腸直腸がんから選択される、請求項12に記載の使用のための抗体分子、または請求項12に記載の方法。
- 前記肝臓がんが肝細胞癌である、請求項12に記載の使用のための抗体分子、または請求項12に記載の方法。
- 前記子宮頸がんが子宮頸部の扁平上皮癌である、請求項12に記載の使用のための抗体分子、または請求項12に記載の方法。
- 前記甲状腺がんが甲状腺未分化がん(ATC)である、請求項12に記載の使用のための抗体分子、または請求項12に記載の方法。
- 前記抗PD−L1抗体分子が、第2の治療剤または様式と組み合わせて使用される、請求項1または3〜22のいずれかに記載の使用のための抗体分子、または請求項2〜22のいずれかに記載の方法。
- 前記抗PD−L1抗体分子がPD−1阻害剤と組み合わせて使用される、請求項1または3〜23のいずれかに記載の使用のための抗体分子、または請求項2〜23のいずれかに記載の方法。
- 前記PD−1阻害剤が、PDR001、ニボルマブ、ペンブロリズマブ、ピジリズマブ、MEDI0680、REGN2810、PF-06801591、BGB-A317、INCHR1210、TSR-042またはAMP-224から選択される、請求項24に記載の使用のための抗体分子、または請求項24に記載の方法。
- 前記PD−1阻害剤が、3週間に1回、約300mgの用量、または4週間に1回、約400mgの用量で使用される、請求項24または25に記載の使用のための抗体分子、または請求項24または25に記載の方法。
- 前記対象が、腫瘍浸潤リンパ球(TIL)においてPD−L1発現を有する、または有すると特定されている、請求項1または3〜26のいずれかに記載の使用のための抗体分子、または請求項2〜26のいずれかに記載の方法。
- 前記対象が、PD−L1を発現するがんを有する、または有すると特定されている、請求項1または3〜27のいずれかに記載の使用のための抗体分子、または請求項2〜27のいずれかに記載の方法。
- 対象のがんの治療において、3週間に1回、約1000mg〜約1400mgの用量、または4週間に1回、約1400mg〜約1900mgの用量で使用するための抗PD−L1抗体分子を含む医薬組成物または用量製剤であって、
前記抗PD−L1抗体分子は、配列番号601のVHCDR1アミノ酸配列、配列番号602のVHCDR2アミノ酸配列、および配列番号603のVHCDR3アミノ酸配列を含む重鎖可変領域(VH)と;配列番号609のVLCDR1アミノ酸配列、配列番号610のVLCDR2アミノ酸配列、および配列番号611のVLCDR3アミノ酸配列を含む軽鎖可変領域(VL)とを含む、
医薬組成物または用量製剤。 - 前記用量が、3週間に1回、約1100mg〜約1300mgである、請求項29に記載の医薬組成物または用量製剤。
- 前記用量が、4週間に1回、約1500mg〜約1700mgである、請求項29に記載の医薬組成物または用量製剤。
- 前記抗体分子が、配列番号606のアミノ酸配列を含むVHと、配列番号616のアミノ酸配列を含むVLとを含む、請求項29〜31のいずれかに記載の医薬組成物または用量製剤。
- 前記抗体分子が、配列番号608のアミノ酸配列を含む重鎖と、配列番号618のアミノ酸配列を含む軽鎖とを含む、請求項29〜32のいずれかに記載の医薬組成物または用量製剤。
- 前記抗体分子が、配列番号620のアミノ酸配列を含むVHと、配列番号624のアミノ酸配列を含むVLとを含む、請求項29〜31のいずれかに記載の医薬組成物または用量製剤。
- 前記抗体分子が、配列番号622のアミノ酸配列を含む重鎖と、配列番号626のアミノ酸配列を含む軽鎖とを含む、請求項29〜31または34のいずれかに記載の医薬組成物または用量製剤。
- がんを治療するために使用するための、請求項29〜35のいずれかに記載の医薬組成物または用量製剤。
- 前記がんが、固形腫瘍、血液がん、またはその転移性病変である、請求項36に記載の医薬組成物または用量製剤。
- 前記がんが、骨がん、皮膚がん、乳がん、子宮頸がん、結腸直腸がん、子宮内膜がん、肺がん、卵巣がん、肝臓がん、甲状腺がん、またはこれらの組み合わせから選択される、請求項36または37に記載の医薬組成物または用量製剤。
- 対象のがんを治療する方法であって、前記対象に抗PD−L1抗体分子を、前記対象からの血清または血清試料中の可溶性PD−L1の50%以上が前記抗PD−L1抗体分子によって結合される用量または投与スケジュールで投与することを含む、方法。
- 前記投与スケジュールが、前記対象からの血清または血清試料中の可溶性PD−L1の60%以上を、前記抗PD−L1抗体分子によって結合させる、請求項39に記載の方法。
- 前記投与スケジュールが、前記対象からの血清、または血清試料中の可溶性PD−L1の70%以上を、前記抗PD−L1抗体分子によって結合させる、請求項39または40に記載の方法。
- 前記抗PD−L1抗体分子が、配列番号601のVHCDR1アミノ酸配列、配列番号602のVHCDR2アミノ酸配列、および配列番号603のVHCDR3アミノ酸配列を含む重鎖可変領域(VH)と;配列番号609のVLCDR1アミノ酸配列、配列番号610のVLCDR2アミノ酸配列、および配列番号611のVLCDR3アミノ酸配列を含む軽鎖可変領域(VL)とを含む、請求項39〜41のいずれかに記載の方法。
- 前記抗体分子が、配列番号606のアミノ酸配列を含むVHと、配列番号616のアミノ酸配列を含むVLとを含む、請求項39〜42のいずれかに記載の方法。
- 前記抗体分子が、配列番号608のアミノ酸配列を含む重鎖と、配列番号618のアミノ酸配列を含む軽鎖とを含む、請求項39〜43のいずれかに記載の方法。
- 前記抗体分子が、配列番号620のアミノ酸配列を含むVHと、配列番号624のアミノ酸配列を含むVLとを含む、請求項39〜42のいずれかに記載の方法。
- 前記抗体分子が、配列番号622のアミノ酸配列を含む重鎖と、配列番号626のアミノ酸配列を含む軽鎖とを含む、請求項39〜42または45のいずれかに記載の方法。
- 前記抗PD−L1抗体分子が、3週間に1回、約1000mg〜約1400mgの用量、または4週間に1回、約1400mg〜約1900mgの用量で投与される、請求項39〜46のいずれかに記載の方法。
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WO2023232100A1 (zh) * | 2022-06-02 | 2023-12-07 | 正大天晴药业集团股份有限公司 | 用于治疗子宫恶性肿瘤的药物组合 |
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