JPWO2020239558A5 - - Google Patents

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JPWO2020239558A5
JPWO2020239558A5 JP2021569567A JP2021569567A JPWO2020239558A5 JP WO2020239558 A5 JPWO2020239558 A5 JP WO2020239558A5 JP 2021569567 A JP2021569567 A JP 2021569567A JP 2021569567 A JP2021569567 A JP 2021569567A JP WO2020239558 A5 JPWO2020239558 A5 JP WO2020239558A5
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Priority claimed from PCT/EP2020/064024 external-priority patent/WO2020239558A1/en
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前述の説明および実施例は、本発明の特定の具体的な実施形態を詳述しており、本発明者らによって企図される最良の形態を記載している。しかし、前述したものが文書上ではどれほど詳細に見える場合があっても、本発明を多くの方法で実施してよく、本発明は、添付の特許請求の範囲およびその任意の均等物に従って解釈されるべきであることを理解されたい。

以下に、本願の当初の特許請求の範囲に記載された発明を付記する。
［１］ がんを処置する方法であって、それを必要としている対象に、所定量のサイクリン依存性キナーゼ（ＣＤＫ）阻害剤を、所定量のＰＤ－１軸結合アンタゴニストと組み合わせて投与することを含み、所定量は合わせて、がんの処置に有効な量であり、前記ＣＤＫ阻害剤が、ＣＤＫ４およびＣＤＫ６の阻害剤（ＣＤＫ４／６阻害剤）、またはＣＤＫ２、ＣＤＫ４、およびＣＤＫ６の阻害剤（ＣＤＫ２／４／６阻害剤）である、方法。
［２］ 所定量の：
ａ．ＯＸ４０アゴニスト、
ｂ．４－１ＢＢアゴニスト、または
ｃ．ＯＸ４０アゴニストおよび４－１ＢＢアゴニスト
を、前記対象に組み合わせて投与することをさらに含み、所定量は合わせて、がんの処置に有効な量である、［１］に記載の方法。
［３］ 前記ＰＤ－１軸結合アンタゴニストが、ＰＤ－１結合アンタゴニスト、ＰＤ－Ｌ１結合アンタゴニスト、またはＰＤ－Ｌ２結合アンタゴニストを含む、［１］または［２］に記載の方法。
［４］ 前記ＰＤ－１軸結合アンタゴニストがＰＤ－１結合アンタゴニストを含む、［３］に記載の方法。
［５］ 前記ＰＤ－１結合アンタゴニストが抗ＰＤ－１抗体である、［４］に記載の方法。
［６］ 前記抗ＰＤ－１抗体が、ニボルマブ（ＭＤＸ１１０６）、ペンブロリズマブ（ＭＫ－３４７５）、ピジリズマブ（ＣＴ－０１１）、セミプリマブ（ＲＥＧＮ２８１０）、チスレリズマブ（ＢＧＢ－Ａ３１７）、スパルタリズマブ（ＰＤＲ００１）、ＲＮ８８８、ｍＡｂ１５、ＭＥＤＩ－０６８０（ＡＭＰ－５１４）、ＢＧＢ－１０８、もしくはＡＧＥＮ－２０３４、またはその組合せである、［５］に記載の方法。
［７］ 前記ＰＤ－１軸結合アンタゴニストがＰＤ－Ｌ１結合アンタゴニストを含む、［３］に記載の方法。
［８］ 前記ＰＤ－Ｌ１結合アンタゴニストが抗ＰＤ－Ｌ１抗体である、［７］に記載の方法。
［９］ 前記抗ＰＤ－Ｌ１抗体が、ＢＭＳ－９３６５５９（ＭＤＸ－１１０５）、ＡＭＰ－７１４、アテゾリズマブ（ＭＰＤＬ３２８０Ａ）、デュルバルマブ（ＭＥＤＩ４７３６）、アベルマブ、もしくは、ＡＴＣＣ受託番号ＰＴＡ－１２１１８３を有する発現ベクターによって作られたＶＨ領域を含み、ＡＴＣＣ受託番号ＰＴＡ－１２１１８２を有する発現ベクターによって作られたＶＬ領域を有する抗体、またはその組合せである、［８］に記載の方法。
［１０］ 前記ＯＸ４０アゴニストが、抗ＯＸ４０抗体、ＯＸ４０Ｌアゴニスト断片、ＯＸ４０オリゴマー受容体、三量体ＯＸ４０Ｌ－Ｆｃタンパク質、もしくはＯＸ４０イムノアドヘシン、またはその組合せである、［２］に記載の方法。
［１１］ 前記ＯＸ４０アゴニストが抗ＯＸ４０抗体である、［１０］に記載の方法。
［１２］ 前記抗ＯＸ４０抗体が、ＭＥＤＩ６４６９、ＭＥＤＩ０５６２、ＭＥＤＩ６３８３、ＭＯＸＲ０９１６、もしくはＧＳＫ３１７４９９８、またはその組合せである、［１１］に記載の方法。
［１３］ 前記４－１ＢＢアゴニストが抗４－１ＢＢ抗体である、［２］に記載の方法。
［１４］ 前記４－１ＢＢアゴニストが、ウトミルマブ（ＰＦ－０５０８２５６６）、１Ｄ８、３Ｅｌｏｒ、４Ｂ４、Ｈ４－１ＢＢ－Ｍ１２７、ＢＢＫ２、１４５５０１、ＡＴＣＣ番号ＨＢ－１１２４８として寄託された細胞系によって産生される抗体、５Ｆ４、Ｃ６５－４８５、ウレルマブ（ＢＭＳ－６６３５１３）、２０Ｈ４．９－ＩｇＧ－１（ＢＭＳ－６６３０３１）、４Ｅ９、ＢＭＳ－５５４２７１、ＢＭＳ－４６９４９２、３Ｈ３、ＢＭＳ－４６９４９７、３Ｅｌ、５３Ａ２、または３Ｂ８である、［２］に記載の方法。
［１５］ 前記ＣＤＫ阻害剤がＣＤＫ４／６阻害剤である、［１］から［１４］のいずれかに記載の方法。
［１６］ 前記ＣＤＫ４／６阻害剤が、パルボシクリブまたは薬学的に許容できるその塩である、［１５］に記載の方法。
［１７］ 前記ＣＤＫ阻害剤がＣＤＫ２／４／６阻害剤である、［１］から［１４］のいずれかに記載の方法。
［１８］ 前記ＣＤＫ２／４／６阻害剤が、６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンまたは薬学的に許容できるその塩である、［１７］に記載の方法。
［１９］ 前記対象がヒトである、［１］から［１８］のいずれかに記載の方法。
［２０］ 前記がんが、脳腫瘍、頭部／頸部がん（頭頸部の扁平細胞癌（ＳＣＣＨＮ）を含む）、前立腺がん、卵巣がん、膀胱がん（尿路上皮癌腫を含み、移行細胞癌（ＴＣＣ）としても知られる）、肺がん（扁平細胞癌、小細胞肺がん（ＳＣＬＣ）、および非小細胞肺がん（ＮＳＣＬＣ）を含む）、乳がん、骨がん、結腸直腸がん、腎臓がん、肝臓がん（肝細胞癌（ＨＣＣ）を含む）、胃がん、膵がん、食道がん、子宮頸がん、肉腫、皮膚がん（黒色腫およびメルケル細胞癌（ＭＣＣ）を含む）、多発性骨髄腫、中皮腫、悪性ラブドイド腫瘍、神経芽細胞腫、びまん性内在性橋膠腫（ＤＩＰＧ）、癌腫、リンパ腫、びまん性大細胞型Ｂ細胞リンパ腫（ＤＬＢＣＬ）、原発性縦隔Ｂ細胞リンパ腫（ＰＭＢＣＬ）、濾胞性リンパ腫、急性リンパ芽球性白血病（ＡＬＬ）、急性骨髄性白血病（ＡＭＬ）、慢性リンパ球性白血病（ＣＬＬ）、慢性骨髄性白血病（ＣＭＬ）、濾胞性リンパ腫、ホジキンリンパ腫（ＨＬ）、古典的ホジキンリンパ腫（ｃＨＬ）、マントル細胞リンパ腫（ＭＣＬ）、多発性骨髄腫（ＭＭ）、骨髄細胞白血病－１タンパク質（Ｍｃｌ－１）、脊髄形成異常症候群（ＭＤＳ）、非ホジキンリンパ腫（ＮＨＬ）、小リンパ球性リンパ腫（ＳＬＬ）、ならびにＳＷＩ／ＳＮＦ変異がんからなる群から選択される、［１］から［１９］のいずれかに記載の方法。
［２１］ 対象におけるがんの処置に使用するための、
ａ．（ｉ）パルボシクリブもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニスト、
ｂ．（ｉ）パルボシクリブもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニストと（ｉｉｉ）ＯＸ４０アゴニスト、
ｃ．（ｉ）パルボシクリブもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニストと（ｉｉｉ）４－１ＢＢアゴニスト、または
ｄ．（ｉ）パルボシクリブもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニストと（ｉｉｉ）ＯＸ４０アゴニストと（ｉｖ）４－１ＢＢアゴニスト
を含む、組合せ物。
［２２］ 対象におけるがんの処置に使用するための、
ａ．（ｉ）パルボシクリブもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－Ｌ１結合アンタゴニスト、
ｂ．（ｉ）パルボシクリブもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－Ｌ１結合アンタゴニストと（ｉｉｉ）ＯＸ４０アゴニスト、
ｃ．（ｉ）パルボシクリブもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－Ｌ１結合アンタゴニストと（ｉｉｉ）４－１ＢＢアゴニスト、
ｄ．（ｉ）パルボシクリブもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－Ｌ１結合アンタゴニストと（ｉｉｉ）ＯＸ４０アゴニストと（ｉｖ）４－１ＢＢアゴニスト、または
ｅ．（ｉ）パルボシクリブもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニストと（ｉｉｉ）ＰＤ－Ｌ１結合アンタゴニストと（ｉｖ）ＯＸ４０アゴニストと（ｖ）４－１ＢＢアゴニスト
を含む、組合せ物。
［２３］ 対象におけるがんの処置に使用するための、
ａ．（ｉ）６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニスト、
ｂ．（ｉ）６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニストと（ｉｉｉ）ＯＸ４０アゴニスト、
ｃ．（ｉ）６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニストと（ｉｉｉ）４－１ＢＢアゴニスト、または
ｄ．（ｉ）６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニストと（ｉｉｉ）ＯＸ４０アゴニストと（ｉｖ）４－１ＢＢアゴニスト
を含む、組合せ物。
［２４］ 対象におけるがんの処置に使用するための、
ａ．（ｉ）６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－Ｌ１結合アンタゴニスト、
ｂ．（ｉ）６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－Ｌ１結合アンタゴニストと（ｉｉｉ）ＯＸ４０アゴニスト、
ｃ．（ｉ）６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－Ｌ１結合アンタゴニストと（ｉｉｉ）４－１ＢＢアゴニスト、
ｄ．（ｉ）６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－Ｌ１結合アンタゴニストと（ｉｉｉ）ＯＸ４０アゴニストと（ｉｖ）４－１ＢＢアゴニスト、または
ｅ．（ｉ）６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と（ｉｉ）ＰＤ－１結合アンタゴニストと（ｉｉｉ）ＰＤ－Ｌ１結合アンタゴニストと（ｉｖ）ＯＸ４０アゴニストと（ｖ）抗４－１ＢＢ抗体
を含む、組合せ物。
［２５］ 前記ＰＤ－１結合アンタゴニストが抗ＰＤ－１抗体である、前記ＯＸ４０アゴニストが抗ＯＸ４０抗体である、および／または前記４－１ＢＢアゴニストが抗４－１ＢＢ抗体である、［２１］または［２３］に記載の組合せ物。
［２６］ 前記ＰＤ－１結合アンタゴニストが抗ＰＤ－１抗体である、前記ＰＤ－Ｌ１結合アンタゴニストが抗ＰＤ－Ｌ１抗体である、前記ＯＸ４０アゴニストが抗ＯＸ４０抗体である、および／または前記４－１ＢＢアゴニストが抗４－１ＢＢ抗体である、［２２］または［２４］に記載の組合せ物。
The foregoing description and examples detail certain specific embodiments of the invention and describes the best mode contemplated by the inventors. However detailed the foregoing may appear on paper, the invention may be embodied in many ways and the invention is construed in accordance with the appended claims and any equivalents thereof. It should be understood that

The following is a supplementary description of the inventions originally claimed in this application.
[1] A method of treating cancer comprising administering to a subject in need thereof an amount of a cyclin dependent kinase (CDK) inhibitor in combination with an amount of a PD-1 axis binding antagonist. wherein the predetermined amount together is an amount effective to treat cancer, wherein the CDK inhibitor is an inhibitor of CDK4 and CDK6 (CDK4/6 inhibitor), or an inhibitor of CDK2, CDK4, and CDK6 (CDK2/4/6 inhibitor).
[2] A predetermined amount of:
a. an OX40 agonist,
b. a 4-1BB agonist, or
c. OX40 agonist and 4-1BB agonist
to the subject in combination, wherein the predetermined amounts together are effective amounts for treating cancer.
[3] The method of [1] or [2], wherein the PD-1 axis binding antagonist comprises a PD-1 binding antagonist, a PD-L1 binding antagonist, or a PD-L2 binding antagonist.
[4] The method of [3], wherein the PD-1 axis binding antagonist comprises a PD-1 binding antagonist.
[5] The method of [4], wherein the PD-1 binding antagonist is an anti-PD-1 antibody.
[6] the anti-PD-1 antibody is nivolumab (MDX1106), pembrolizumab (MK-3475), pidilizumab (CT-011), semiplimab (REGN2810), tislelizumab (BGB-A317), spartalizumab (PDR001), RN888 , mAb15, MEDI-0680 (AMP-514), BGB-108, or AGEN-2034, or a combination thereof.
[7] The method of [3], wherein the PD-1 axis binding antagonist comprises a PD-L1 binding antagonist.
[8] The method of [7], wherein the PD-L1 binding antagonist is an anti-PD-L1 antibody.
[9] the anti-PD-L1 antibody is BMS-936559 (MDX-1105), AMP-714, atezolizumab (MPDL3280A), durvalumab (MEDI4736), avelumab, or produced by an expression vector having ATCC accession number PTA-121183; The method of [8], wherein the antibody comprises an engineered VH region and has a VL region made by an expression vector having ATCC Accession No. PTA-121182, or a combination thereof.
[10] The method of [2], wherein the OX40 agonist is an anti-OX40 antibody, an OX40L agonist fragment, an OX40 oligomeric receptor, a trimeric OX40L-Fc protein, or an OX40 immunoadhesin, or a combination thereof.
[11] The method of [10], wherein the OX40 agonist is an anti-OX40 antibody.
[12] The method of [11], wherein the anti-OX40 antibody is MEDI6469, MEDI0562, MEDI6383, MOXR0916, or GSK3174998, or a combination thereof.
[13] The method of [2], wherein the 4-1BB agonist is an anti-4-1BB antibody.
[14] an antibody wherein said 4-1BB agonist is produced by a cell line deposited as Utomilumab (PF-05082566), 1D8, 3Elor, 4B4, H4-1BB-M127, BBK2, 145501, ATCC No. HB-11248; 5F4, C65-485, Urelumab (BMS-663513), 20H4.9-IgG-1 (BMS-663031), 4E9, BMS-554271, BMS-469492, 3H3, BMS-469497, 3El, 53A2, or 3B8 , the method described in [2].
[15] The method of any one of [1] to [14], wherein the CDK inhibitor is a CDK4/6 inhibitor.
[16] The method of [15], wherein the CDK4/6 inhibitor is palbociclib or a pharmaceutically acceptable salt thereof.
[17] The method of any one of [1] to [14], wherein the CDK inhibitor is a CDK2/4/6 inhibitor.
[18] the CDK2/4/6 inhibitor is 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidine- 4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof.
[19] The method of any one of [1] to [18], wherein the subject is human.
[20] the cancer is brain tumor, head/neck cancer (including squamous cell carcinoma of the head and neck (SCCHN)), prostate cancer, ovarian cancer, bladder cancer (including urothelial carcinoma; transitional cell carcinoma (TCC)), lung cancer (including squamous cell carcinoma, small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC)), breast cancer, bone cancer, colorectal cancer, renal cancer, liver cancer (including hepatocellular carcinoma (HCC)), gastric cancer, pancreatic cancer, esophageal cancer, cervical cancer, sarcoma, skin cancer (including melanoma and Merkel cell carcinoma (MCC)), Multiple myeloma, mesothelioma, malignant rhabdoid tumor, neuroblastoma, diffuse intrinsic pontine glioma (DIPG), carcinoma, lymphoma, diffuse large B-cell lymphoma (DLBCL), primary mediastinum B cellular lymphoma (PMBCL), follicular lymphoma, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), follicular lymphoma, Hodgkin Lymphoma (HL), classical Hodgkin's lymphoma (cHL), mantle cell lymphoma (MCL), multiple myeloma (MM), myeloid leukemia-1 protein (Mcl-1), myelodysplastic syndrome (MDS), non-Hodgkin's The method of any of [1] to [19], wherein the method is selected from the group consisting of lymphoma (NHL), small lymphocytic lymphoma (SLL), and SWI/SNF mutated cancer.
[21] for use in treating cancer in a subject,
a. (i) palbociclib or a pharmaceutically acceptable salt thereof and (ii) a PD-1 binding antagonist;
b. (i) palbociclib or a pharmaceutically acceptable salt thereof and (ii) a PD-1 binding antagonist and (iii) an OX40 agonist,
c. (i) palbociclib or a pharmaceutically acceptable salt thereof and (ii) a PD-1 binding antagonist and (iii) a 4-1BB agonist, or
d. (i) palbociclib or a pharmaceutically acceptable salt thereof; (ii) a PD-1 binding antagonist; (iii) an OX40 agonist; and (iv) a 4-1BB agonist
combinations, including
[22] for use in treating cancer in a subject,
a. (i) palbociclib or a pharmaceutically acceptable salt thereof and (ii) a PD-L1 binding antagonist;
b. (i) palbociclib or a pharmaceutically acceptable salt thereof; (ii) a PD-L1 binding antagonist; and (iii) an OX40 agonist;
c. (i) palbociclib or a pharmaceutically acceptable salt thereof and (ii) a PD-L1 binding antagonist and (iii) a 4-1BB agonist,
d. (i) palbociclib or a pharmaceutically acceptable salt thereof and (ii) a PD-L1 binding antagonist and (iii) an OX40 agonist and (iv) a 4-1BB agonist, or
e. (i) palbociclib or a pharmaceutically acceptable salt thereof; (ii) a PD-1 binding antagonist; (iii) a PD-L1 binding antagonist; (iv) an OX40 agonist; and (v) a 4-1BB agonist
combinations, including
[23] for use in treating cancer in a subject,
a. (i) 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido[2,3- d] pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof and (ii) a PD-1 binding antagonist,
b. (i) 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido[2,3- d] pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof and (ii) a PD-1 binding antagonist and (iii) an OX40 agonist,
c. (i) 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido[2,3- d] pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof and (ii) a PD-1 binding antagonist and (iii) a 4-1BB agonist, or
d. (i) 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido[2,3- d] pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof and (ii) a PD-1 binding antagonist and (iii) an OX40 agonist and (iv) a 4-1BB agonist
combinations, including
[24] for use in treating cancer in a subject,
a. (i) 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido[2,3- d] pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof and (ii) a PD-L1 binding antagonist;
b. (i) 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido[2,3- d] pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof and (ii) a PD-L1 binding antagonist and (iii) an OX40 agonist,
c. (i) 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido[2,3- d] pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof and (ii) a PD-L1 binding antagonist and (iii) a 4-1BB agonist,
d. (i) 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido[2,3- d] pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof and (ii) a PD-L1 binding antagonist and (iii) an OX40 agonist and (iv) a 4-1BB agonist, or
e. (i) 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido[2,3- d] pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof, (ii) a PD-1 binding antagonist, (iii) a PD-L1 binding antagonist, (iv) an OX40 agonist, and (v) an anti-4-1BB antibody
combinations, including
[25] said PD-1 binding antagonist is an anti-PD-1 antibody, said OX40 agonist is an anti-OX40 antibody, and/or said 4-1BB agonist is an anti-4-1BB antibody, [21] or [ 23].
[26] the PD-1 binding antagonist is an anti-PD-1 antibody, the PD-L1 binding antagonist is an anti-PD-L1 antibody, the OX40 agonist is an anti-OX40 antibody, and/or the 4-1BB The combination of [22] or [24], wherein the agonist is an anti-4-1BB antibody.

Claims (14)

ＰＤ－Ｌ１結合アンタゴニストと組み合わせて、がんの処置において使用するための、サイクリン依存性キナーゼ（ＣＤＫ）阻害剤または薬学的に許容できるその塩であって、前記ＣＤＫ阻害剤および前記ＰＤ－Ｌ１結合アンタゴニストは、合わせてがんの処置に有効な量で対象に投与され、前記ＣＤＫ阻害剤は、ＣＤＫ４およびＣＤＫ６の阻害剤（ＣＤＫ４／６阻害剤）、またはＣＤＫ２、ＣＤＫ４、およびＣＤＫ６の阻害剤（ＣＤＫ２／４／６阻害剤）である、ＣＤＫ阻害剤または薬学的に許容できるその塩。 A cyclin dependent kinase (CDK) inhibitor or a pharmaceutically acceptable salt thereof for use in treating cancer in combination with a PD-L1 binding antagonist , said CDK inhibitor and said PD-L1 binding The antagonists are administered to the subject together in an amount effective to treat cancer, wherein said CDK inhibitor is an inhibitor of CDK4 and CDK6 (CDK4/6 inhibitor), or an inhibitor of CDK2, CDK4 and CDK6 ( A CDK inhibitor, or a pharmaceutically acceptable salt thereof , which is a CDK2/4/6 inhibitor). 前記がんの処置は、
ａ．ＯＸ４０アゴニスト、
ｂ．４－１ＢＢアゴニスト、または
ｃ．ＯＸ４０アゴニストおよび４－１ＢＢアゴニスト
を、これらを合わせてがんの処置に有効な量で、前記対象に組み合わせて投与することをさらに含む、請求項１に記載のＣＤＫ阻害剤または薬学的に許容できるその塩。 The treatment of said cancer comprises:
a. an OX40 agonist,
b. a 4-1BB agonist, or c. 2. The CDK inhibitor or pharmaceutically acceptable CDK inhibitor of claim 1 , further comprising administering in combination to said subject an OX40 agonist and a 4-1BB agonist in amounts which together are effective to treat cancer. That salt you can . 前記ＰＤ－Ｌ１結合アンタゴニストが抗ＰＤ－Ｌ１抗体であり、好ましくはＢＭＳ－９３６５５９（ＭＤＸ－１１０５）、ＡＭＰ－７１４、アテゾリズマブ（ＭＰＤＬ３２８０Ａ）、デュルバルマブ（ＭＥＤＩ４７３６）、アベルマブ、もしくは、ＡＴＣＣ受託番号ＰＴＡ－１２１１８３を有する発現ベクターによって作られたＶＨ領域を含み、ＡＴＣＣ受託番号ＰＴＡ－１２１１８２を有する発現ベクターによって作られたＶＬ領域を有する抗体、またはその組合せである、請求項１または２に記載のＣＤＫ阻害剤または薬学的に許容できるその塩。 The PD-L1 binding antagonist is an anti-PD-L1 antibody, preferably BMS-936559 (MDX-1105), AMP-714, atezolizumab (MPDL3280A), durvalumab (MEDI4736), avelumab, or ATCC Accession No. PTA- 3. The CDK inhibition of claim 1 or 2 , which is an antibody comprising a VH region made by an expression vector having ATCC Accession No. 121183 and having a VL region made by an expression vector having ATCC Accession No. PTA-121182, or a combination thereof. agent or a pharmaceutically acceptable salt thereof . 前記ＯＸ４０アゴニストが、抗ＯＸ４０抗体、ＯＸ４０Ｌアゴニスト断片、ＯＸ４０オリゴマー受容体、三量体ＯＸ４０Ｌ－Ｆｃタンパク質、もしくはＯＸ４０イムノアドヘシン、またはその組合せである、請求項２または３に記載のＣＤＫ阻害剤または薬学的に許容できるその塩。 4. The CDK inhibitor of claim 2 or 3 , wherein said OX40 agonist is an anti-OX40 antibody, an OX40L agonist fragment, an OX40 oligomeric receptor, a trimeric OX40L-Fc protein, or an OX40 immunoadhesin, or a combination thereof, or a pharmaceutically acceptable salt thereof ; 前記ＯＸ４０アゴニストが抗ＯＸ４０抗体であり、好ましくはＭＥＤＩ６４６９、ＭＥＤＩ０５６２、ＭＥＤＩ６３８３、ＭＯＸＲ０９１６、もしくはＧＳＫ３１７４９９８、またはその組合せである、請求項２～４のいずれか一項に記載のＣＤＫ阻害剤または薬学的に許容できるその塩。 CDK inhibitor according to any one of claims 2 to 4 , or a pharmaceutically Its salt acceptable . 前記４－１ＢＢアゴニストが抗４－１ＢＢ抗体である、請求項２～５のいずれか一項に記載のＣＤＫ阻害剤または薬学的に許容できるその塩。 The CDK inhibitor or a pharmaceutically acceptable salt thereof according to any one of claims 2 to 5 , wherein said 4-1BB agonist is an anti-4-1BB antibody. 前記４－１ＢＢアゴニストが、ウトミルマブ（ＰＦ－０５０８２５６６）、１Ｄ８、３Ｅｌｏｒ、４Ｂ４、Ｈ４－１ＢＢ－Ｍ１２７、ＢＢＫ２、１４５５０１、ＡＴＣＣ番号ＨＢ－１１２４８として寄託された細胞系によって産生される抗体、５Ｆ４、Ｃ６５－４８５、ウレルマブ（ＢＭＳ－６６３５１３）、２０Ｈ４．９－ＩｇＧ－１（ＢＭＳ－６６３０３１）、４Ｅ９、ＢＭＳ－５５４２７１、ＢＭＳ－４６９４９２、３Ｈ３、ＢＭＳ－４６９４９７、３Ｅｌ、５３Ａ２、または３Ｂ８である、請求項２～６のいずれか一項に記載のＣＤＫ阻害剤または薬学的に許容できるその塩。 The 4-1BB agonist is utomilumab (PF-05082566), 1D8, 3Elor, 4B4, H4-1BB-M127, BBK2, 145501, an antibody produced by the cell line deposited as ATCC No. HB-11248, 5F4, C65 -485, Urelumab (BMS-663513), 20H4.9-IgG-1 (BMS-663031), 4E9, BMS-554271, BMS-469492, 3H3, BMS-469497, 3El, 53A2, or 3B8 2. The CDK inhibitor according to any one of 2 to 6 or a pharmaceutically acceptable salt thereof. 前記ＣＤＫ阻害剤がＣＤＫ４／６阻害剤であり、好ましくはパルボシクリブまたは薬学的に許容できるその塩である、請求項１～７のいずれか一項に記載のＣＤＫ阻害剤または薬学的に許容できるその塩。 CDK inhibitor or pharmaceutically acceptable according to any one of claims 1 to 7 , wherein said CDK inhibitor is a CDK4/6 inhibitor, preferably palbociclib or a pharmaceutically acceptable salt thereof the salt . 前記ＣＤＫ阻害剤がＣＤＫ２／４／６阻害剤であり、好ましくは６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンまたは薬学的に許容できるその塩である、請求項１～７のいずれか一項に記載のＣＤＫ阻害剤または薬学的に許容できるその塩。 Said CDK inhibitor is a CDK2/4/6 inhibitor, preferably 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-( The CDK according to any one of claims 1 to 7 , which is methylsulfonyl)piperidin-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof. inhibitor or a pharmaceutically acceptable salt thereof . 前記がんが、脳腫瘍、頭部／頸部がん、前立腺がん、卵巣がん、膀胱がん、肺がん、乳がん、骨がん、結腸直腸がん、腎臓がん、肝臓がん、胃がん、膵がん、食道がん、子宮頸がん、肉腫、皮膚がん、多発性骨髄腫、中皮腫、悪性ラブドイド腫瘍、神経芽細胞腫、びまん性内在性橋膠腫（ＤＩＰＧ）、癌腫、リンパ腫、びまん性大細胞型Ｂ細胞リンパ腫（ＤＬＢＣＬ）、原発性縦隔Ｂ細胞リンパ腫（ＰＭＢＣＬ）、濾胞性リンパ腫、急性リンパ芽球性白血病（ＡＬＬ）、急性骨髄性白血病（ＡＭＬ）、慢性リンパ球性白血病（ＣＬＬ）、慢性骨髄性白血病（ＣＭＬ）、濾胞性リンパ腫、ホジキンリンパ腫（ＨＬ）、古典的ホジキンリンパ腫（ｃＨＬ）、マントル細胞リンパ腫（ＭＣＬ）、多発性骨髄腫（ＭＭ）、骨髄細胞白血病－１タンパク質（Ｍｃｌ－１）、脊髄形成異常症候群（ＭＤＳ）、非ホジキンリンパ腫（ＮＨＬ）、小リンパ球性リンパ腫（ＳＬＬ）、ならびにＳＷＩ／ＳＮＦ変異がん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ＣＤＫ阻害剤または薬学的に許容できるその塩。 said cancer is brain cancer, head/neck cancer, prostate cancer, ovarian cancer, bladder cancer, lung cancer, breast cancer, bone cancer, colorectal cancer, kidney cancer, liver cancer, gastric cancer, pancreatic cancer, esophageal cancer, cervical cancer, sarcoma, skin cancer , multiple myeloma, mesothelioma, malignant rhabdoid tumor, neuroblastoma, diffuse intrinsic pontine glioma (DIPG), Carcinoma, lymphoma, diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic Lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), follicular lymphoma, Hodgkin's lymphoma (HL), classical Hodgkin's lymphoma (cHL), mantle cell lymphoma (MCL), multiple myeloma (MM), bone marrow selected from the group consisting of cellular leukemia-1 protein (Mcl-1), myelodysplastic syndrome (MDS), non-Hodgkin's lymphoma (NHL), small lymphocytic lymphoma (SLL), and SWI/SNF mutated cancer; A CDK inhibitor or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 9 . 対象におけるがんの処置に使用するための、
（ｉ）パルボシクリブまたは６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩と、（ｉｉ）ＰＤ－Ｌ１結合アンタゴニストと
を含む、組合せ物。 for use in treating cancer in a subject,
(i) palbociclib or 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido [2, 3-d]pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof and (ii) a PD-L1 binding antagonist
combinations, including （ｉｉｉ）ＯＸ４０アゴニストおよび／または（ｉｖ）４－１ＢＢアゴニストをさらに含む、請求項１１に記載の組合せ物。12. A combination according to claim 11, further comprising (iii) an OX40 agonist and/or (iv) a 4-1BB agonist. （ｉ）パルボシクリブまたは６－（ジフルオロメチル）－８－（（１Ｒ，２Ｒ）－２－ヒドロキシ－２－メチルシクロペンチル）－２－（１－（メチルスルホニル）ピペリジン－４－イルアミノ）ピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オンもしくは薬学的に許容できるその塩、（ｉｉ）ＰＤ－Ｌ１結合アンタゴニスト、（ｉｉｉ）ＯＸ４０アゴニストおよび（ｉｖ）４－１ＢＢアゴニストを含む、請求項１２に記載の組合せ物。(i) palbociclib or 6-(difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrido [2, 3-d]pyrimidin-7(8H)-one or a pharmaceutically acceptable salt thereof, (ii) a PD-L1 binding antagonist, (iii) an OX40 agonist and (iv) a 4-1BB agonist. Combinations as described. 前記ＰＤ－Ｌ１結合アンタゴニストが抗ＰＤ－Ｌ１抗体である、前記ＯＸ４０アゴニストが抗ＯＸ４０抗体である、および／または前記４－１ＢＢアゴニストが抗４－１ＢＢ抗体である、請求項１１～１３のいずれか一項に記載の組合せ物。
 14. Any of claims 11 to 13, wherein said PD-L1 binding antagonist is an anti-PD-L1 antibody, said OX40 agonist is an anti-OX40 antibody, and/or said 4-1BB agonist is an anti-4-1BB antibody. A combination according to claim 1 .
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Family Cites Families (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1984003506A1 (en) 1983-03-08 1984-09-13 Commw Serum Lab Commission Antigenically active amino acid sequences
US4708871A (en) 1983-03-08 1987-11-24 Commonwealth Serum Laboratories Commission Antigenically active amino acid sequences
NZ207394A (en) 1983-03-08 1987-03-06 Commw Serum Lab Commission Detecting or determining sequence of amino acids
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
NZ215865A (en) 1985-04-22 1988-10-28 Commw Serum Lab Commission Method of determining the active site of a receptor-binding analogue
US5091513A (en) 1987-05-21 1992-02-25 Creative Biomolecules, Inc. Biosynthetic antibody binding sites
US5571689A (en) 1988-06-16 1996-11-05 Washington University Method of N-acylating peptide and proteins with diheteroatom substituted analogs of myristic acid
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5663143A (en) 1988-09-02 1997-09-02 Dyax Corp. Engineered human-derived kunitz domains that inhibit human neutrophil elastase
US5225538A (en) 1989-02-23 1993-07-06 Genentech, Inc. Lymphocyte homing receptor/immunoglobulin fusion proteins
DE3920358A1 (en) 1989-06-22 1991-01-17 Behringwerke Ag BISPECIFIC AND OLIGO-SPECIFIC, MONO- AND OLIGOVALENT ANTI-BODY CONSTRUCTS, THEIR PRODUCTION AND USE
DK0558671T3 (en) 1990-11-21 1999-09-13 Iterex Pharma Lp Synthesis of equimolar multiple oligomer mixtures, especially of oligopeptide mixtures
EP0564531B1 (en) 1990-12-03 1998-03-25 Genentech, Inc. Enrichment method for variant proteins with altered binding properties
AU3178993A (en) 1991-11-25 1993-06-28 Enzon, Inc. Multivalent antigen-binding proteins
EP1060247B2 (en) 1998-02-24 2011-10-26 Sisters of Providence in Oregon Ox-40 receptor binding agent for use in methods for enhancing tumour antigen-specific immune response
DE69942671D1 (en) 1998-12-01 2010-09-23 Facet Biotech Corp HUMANIZED ANTIKOERPER AGAINST GAMMA INTERFERON
US20020064528A1 (en) 2000-01-28 2002-05-30 Zhenping Zhu Antibodies specific to KDR and uses thereof
GEP20063909B (en) 2002-01-22 2006-08-25 Warner Lambert Co 2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3d] PYRIMIDIN-7-ONES
AU2003281200A1 (en) 2002-07-03 2004-01-23 Tasuku Honjo Immunopotentiating compositions
US7217797B2 (en) 2002-10-15 2007-05-15 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
AU2003301882A1 (en) 2002-11-01 2004-06-07 The Regents Of The University Of Colorado, A Body Corporate Quantitative analysis of protein isoforms using matrix-assisted laser desorption/ionization time of flight mass spectrometry
AU2003288675B2 (en) 2002-12-23 2010-07-22 Medimmune Limited Antibodies against PD-1 and uses therefor
EP1591527B1 (en) 2003-01-23 2015-08-26 Ono Pharmaceutical Co., Ltd. Substance specific to human pd-1
EP1648889B1 (en) 2003-07-11 2008-10-29 Warner-Lambert Company LLC Isethionate salt of a selective cdk4 inhibitor
CN109485727A (en) 2005-05-09 2019-03-19 小野药品工业株式会社 The human monoclonal antibodies of programmed death-1 (PD-1) and the method for carrying out treating cancer using anti-PD-1 antibody
MX2007015942A (en) 2005-07-01 2008-03-07 Medarex Inc Human monoclonal antibodies to programmed death ligand 1 (pd-l1).
BRPI0716880A2 (en) 2006-09-08 2013-10-15 Pfizer Prod Inc SYNTHESIS OF 2- (PYRIDIN-2-YLAMINO) -PYRID [2,3-D] PYRIMIDIN-7-ONAS
WO2008083174A2 (en) 2006-12-27 2008-07-10 Emory University Compositions and methods for the treatment of infections and tumors
DK2170959T3 (en) 2007-06-18 2014-01-13 Merck Sharp & Dohme ANTIBODIES AGAINST HUMAN PROGRAMMED DEATH RECEPTOR PD-1
ES2526887T3 (en) 2007-12-14 2015-01-16 Bristol-Myers Squibb Company Method for producing human OX40 receptor binding molecules
US8168757B2 (en) 2008-03-12 2012-05-01 Merck Sharp & Dohme Corp. PD-1 binding proteins
CA2734908A1 (en) 2008-08-25 2010-03-11 Amplimmune, Inc. Compositions of pd-1 antagonists and methods of use
CN102264762B (en) 2008-09-26 2018-03-27 达纳-法伯癌症研究公司 The anti-PD 1 of people, PD L1 and PD L2 antibody and its application
TWI686405B (en) 2008-12-09 2020-03-01 建南德克公司 Anti-pd-l1 antibodies and their use to enhance t-cell function
EP3192811A1 (en) 2009-02-09 2017-07-19 Université d'Aix-Marseille Pd-1 antibodies and pd-l1 antibodies and uses thereof
EP2504028A4 (en) 2009-11-24 2014-04-09 Amplimmune Inc Simultaneous inhibition of pd-l1/pd-l2
RS60033B1 (en) 2009-11-24 2020-04-30 Medimmune Ltd Targeted binding agents against b7-h1
EP2614082B1 (en) 2010-09-09 2018-10-03 Pfizer Inc 4-1bb binding molecules
KR102049817B1 (en) 2011-08-01 2019-12-02 제넨테크, 인크. Methods of treating cancer using pd-1 axis binding antagonists and mek inhibitors
JP6038920B2 (en) 2011-08-23 2016-12-07 ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム Anti-OX40 antibody and method of using the same
AU2013201121A1 (en) 2011-09-20 2013-04-04 Vical Incorporated Synergistic anti-tumor efficacy using alloantigen combination immunotherapy
BR112014012819B1 (en) 2011-11-28 2022-08-16 Merck Patent Gmbh ANTI-PD-L1 ANTIBODY OR ANTIGEN BINDING FRAGMENT AND COMPOSITION
US9828432B2 (en) 2012-02-06 2017-11-28 Providence Health & Services—Oregon Cancer treatment and monitoring methods using OX40 agonists
EP2822957A1 (en) 2012-03-07 2015-01-14 Aurigene Discovery Technologies Limited Peptidomimetic compounds as immunomodulators
US9212224B2 (en) 2012-05-15 2015-12-15 Bristol-Myers Squibb Company Antibodies that bind PD-L1 and uses thereof
AR093984A1 (en) 2012-12-21 2015-07-01 Merck Sharp & Dohme ANTIBODIES THAT JOIN LEGEND 1 OF SCHEDULED DEATH (PD-L1) HUMAN
EP2958916B1 (en) 2013-02-21 2018-09-12 Pfizer Inc Solid forms of a selective cdk4/6 inhibitor
EP3041828B1 (en) 2013-09-06 2018-05-23 Aurigene Discovery Technologies Limited 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as immunomodulators
CA2922607C (en) 2013-09-06 2022-08-30 Aurigene Discovery Technologies Limited 1,2,4-oxadiazole derivatives as immunomodulators
ES2792183T3 (en) 2013-09-13 2020-11-10 Beigene Switzerland Gmbh Anti-PD1 antibodies and their use as therapeutic and diagnostic products
CA2926856A1 (en) 2013-10-25 2015-04-30 Dana-Farber Cancer Institute, Inc. Anti-pd-l1 monoclonal antibodies and fragments thereof
EA035037B1 (en) 2013-12-12 2020-04-21 Шанхай Хэнжуй Фармасьютикал Ко., Лтд. Pd-1 antibody, antigen-binding fragment thereof, and medical application thereof
EP3527587A1 (en) 2013-12-17 2019-08-21 F. Hoffmann-La Roche AG Combination therapy comprising ox40 binding agonists and pd-l1 binding antagonists
TWI681969B (en) 2014-01-23 2020-01-11 美商再生元醫藥公司 Human antibodies to pd-1
JOP20200094A1 (en) 2014-01-24 2017-06-16 Dana Farber Cancer Inst Inc Antibody molecules to pd-1 and uses thereof
US20150282460A1 (en) 2014-04-04 2015-10-08 Crown Bioscience Inc. (Taicang) Animal model with human immune system
CN110156892B (en) 2014-07-03 2023-05-16 百济神州有限公司 anti-PD-L1 antibodies and their use as therapeutic and diagnostic agents
CN114920840A (en) 2014-10-14 2022-08-19 诺华股份有限公司 Antibody molecules against PD-L1 and uses thereof
US11220545B2 (en) 2014-12-08 2022-01-11 Dana-Farber Cancer Institute, Inc. Methods for upregulating immune responses using combinations of anti-RGMb and anti-PD-1 agents
TWI595006B (en) 2014-12-09 2017-08-11 禮納特神經系統科學公司 Anti-pd-1 antibodies and methods of use thereof
MX2017011644A (en) 2015-03-13 2017-12-04 Cytomx Therapeutics Inc Anti-pdl1 antibodies, activatable anti-pdl1 antibodies, and methods of use thereof.
EP3271483B1 (en) 2015-03-17 2021-07-21 Mayo Foundation for Medical Education and Research Methods and materials for assessing and treating cancer
US20180134771A1 (en) 2015-05-07 2018-05-17 Bioxcel Corporation Novel immunomodulatory therapeutic strategies targeting tumors in cancer
KR20180034426A (en) 2015-07-29 2018-04-04 노파르티스 아게 Combination of anti-PD-1 and anti-M-CSF antibodies in the treatment of cancer
PE20231958A1 (en) 2015-07-30 2023-12-06 Macrogenics Inc BINDING MOLECULES TO PD-1 AND METHODS OF USE THEREOF
CN106397592A (en) 2015-07-31 2017-02-15 苏州康宁杰瑞生物科技有限公司 Single-domain antibody directed at programmed death ligand (PD-L1) and derived protein thereof
WO2017024465A1 (en) 2015-08-10 2017-02-16 Innovent Biologics (Suzhou) Co., Ltd. Pd-1 antibodies
CN106999591B (en) 2015-09-28 2021-02-23 苏州盛迪亚生物医药有限公司 anti-PD-1 antibody preparation and application thereof in medicine
CN106632674B (en) 2015-10-30 2018-11-16 泽达生物医药有限公司 A kind of anti-PD-1 monoclonal antibody, its medical composition and its use
CN109608544B (en) 2015-11-17 2022-09-16 苏州盛迪亚生物医药有限公司 PD-L1 antibody, antigen binding fragment thereof and medical application thereof
US11137404B2 (en) 2015-12-18 2021-10-05 Institut Gustave Roussy Method for assessing the response to PD-1/PDL-1 targeting drugs
CN109069597A (en) 2015-12-22 2018-12-21 诺华股份有限公司 Mesothelin Chimeric antigen receptor (CAR) and the combination of anti-PD-L1 antibody inhibition are in anticancer therapy
WO2017132827A1 (en) 2016-02-02 2017-08-10 Innovent Biologics (Suzhou) Co., Ltd. Pd-1 antibodies
EP3433277A4 (en) 2016-03-23 2020-06-17 Mabspace Biosciences (Suzhou) Co., Ltd Novel anti-pd-l1 antibodies
WO2017205213A1 (en) 2016-05-23 2017-11-30 Eli Lilly And Company Combination therapy of abemaciclib and immune checkpoint modulators for use in the treatment of cancer
AU2017278325A1 (en) 2016-06-07 2019-01-24 Macrogenics, Inc. Combination therapy
US10590199B2 (en) 2016-06-29 2020-03-17 Checkpoint Therapeutics, Inc. PD-L1-specific antibodies and methods of using the same
RU2656181C1 (en) 2016-07-13 2018-05-31 Закрытое Акционерное Общество "Биокад" Anti-pd-1 antibodies, method for their production, and method of application
KR102236605B1 (en) 2016-08-15 2021-04-05 화이자 인코포레이티드 Pyridopyrimidineone CDK2/4/6 inhibitor
CA3035932A1 (en) 2016-09-14 2018-03-22 Abbvie Biotherapeutics Inc. Anti-pd-1 antibodies and their uses
WO2018055503A1 (en) 2016-09-20 2018-03-29 Novartis Ag Combination comprising a pd-1 antagonist and an fgfr4 inhibitor
CA3037407C (en) 2016-09-21 2022-10-18 Cstone Pharmaceuticals The novel monoclonal antibodies to programmed death 1 (pd-1)
JP6967515B2 (en) 2016-10-15 2021-11-17 イノベント バイオロジックス （スウツォウ） カンパニー，リミテッド PD-1 antibody
CN108778332B (en) 2016-10-21 2019-10-18 苏州盛迪亚生物医药有限公司 PD-1 antibody is combined with IDO inhibitor is preparing the purposes in anti-tumor drug
EP3689419A1 (en) 2016-11-01 2020-08-05 AnaptysBio, Inc. Antibodies directed against t cell immunoglobulin and mucin protein 3 (tim-3)
WO2018106529A1 (en) 2016-12-08 2018-06-14 Eli Lilly And Company Anti-tim-3 antibodies for combination with anti-pd-l1 antibodies
WO2018111890A1 (en) 2016-12-12 2018-06-21 Genentech, Inc. Methods of treating cancer using anti-pd-l1 antibodies and antiandrogens
AU2018368731A1 (en) * 2017-11-16 2020-05-14 Novartis Ag Combination therapies

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