JP6178349B2 - 抗pd−l1抗体およびt細胞機能を増強するためのそれらの使用 - Google Patents
抗pd−l1抗体およびt細胞機能を増強するためのそれらの使用 Download PDFInfo
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- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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Description
本願は、2008年12月9日に出願された米国仮出願第61/121092号の35 USC 119(e)の下で優先権の利益を主張し、その開示が参照によりその全体が本明細書に組み入れられる。
本発明は、一般的に、免疫機能およびT細胞機能を増強すること(細胞媒介性免疫応答のアップレギュレーションを含む)およびT細胞機能障害性障害の処置に関する。
T細胞に対する同時刺激または2つの別々のシグナルの提供は、抗原提示細胞(APC)による休止Tリンパ球のリンパ球活性化の広く受け入れられたモデルである。Lafferty et al., Aust. J. Exp. Biol. Med. Sci. 53: 27-42 (1975)。このモデルは、さらに、非自己から自己の識別および免疫寛容を提供する。Bretscher et al., Science 169: 1042-1049 (1970); Bretscher, P. A., P. N. A. S. USA 96: 185-190 (1999); Jenkins et al., J. Exp. Med. 165: 302-319 (1987)。一次シグナル、または抗原特異的シグナルが、主要組織適合複合体(MHC)に関連して提示される外来抗原ペプチドの認識に続いてT細胞受容体(TCR)を通じて伝達される。二次または同時刺激シグナルが、抗原提示細胞(APC)上で発現される同時刺激分子によりT細胞に送達され、T細胞のクローン増殖、サイトカイン分泌物、およびエフェクター機能の促進を誘導する。Lenschow et al., Ann. Rev. Immunol. 14: 233 (1996)。同時刺激の非存在において、T細胞は抗原刺激に抵抗性になりうる、効果的な免疫応答を開始しない、さらに外来抗原に対する消耗または寛容を招きうる。
ネガティブの二次シグナルがT細胞寛容の誘導のために必要と思われ、一方ではポジティブのシグナルがT細胞活性化を促進する。簡単な2シグナルモデルが依然としてナイーブリンパ球についての妥当な説明を提供する一方で、宿主の免疫応答は動的なプロセスであり、同時刺激シグナルは抗原に暴露されたT細胞に対しても提供されうる。
本発明は、抗PD−L1抗体(そのような抗体をコードする核酸およびそのような抗体を含む組成物を含む)、および細胞媒介性免疫応答をアップレギュレーションするためにT細胞機能を増強させるためのそれらの使用およびT細胞機能障害性障害(感染(例、急性および慢性)および腫瘍免疫を含む)の処置を提供する。
(a)HVR−H1配列がGFTFSX1SWIH(配列番号1)であり;
(b)HVR−H2配列がAWIX2PYGGSX3YYADSVKG(配列番号2)であり;
(c)HVR−H3配列がRHWPGGFDY(配列番号3)であり;
さらに、それにおいて:X1がDまたはGであり;X2がSまたはLであり;X3がTまたはSである。1つの特定の局面において、X1がDであり;X2がSであり、およびX3がTである。別の局面において、ポリペプチドは、さらに、以下の式のHVRの間に並置された重鎖可変領域フレームワーク配列:(HC−FR1)−(HVR−H1)−(HC−FR2)−(HVR−H2)−(HC−FR3)−(HVR−H3)−(HC−FR4)を含む。さらに別の局面において、フレームワーク配列は、ヒトコンセンサスフレームワーク配列に由来する。さらなる局面において、フレームワーク配列は、VHサブグループIIIコンセンサスフレームワークである。さらなる局面において、フレームワーク配列の少なくとも1つは以下:
HC−FR1はEVQLVESGGGLVQPGGSLRLSCAAS(配列番号4)であり;
HC−FR2はWVRQAPGKGLEWV(配列番号5)であり;
HC−FR3はRFTISADTSKNTAYLQMNSLRAEDTAVYYCAR(配列番号6)であり;
HC−FR4はWGQGTLVTVSA(配列番号7)
である。
さらなる局面において、重鎖ポリペプチドは、さらに、HVR−L1、HVR−L2、およびHVR−L3を含む軽鎖可変領域と組み合わされ、それにおいて:
(a)HVR−L1配列はRASQX4X5X6TX7X8A(配列番号8)であり;
(b)HVR−L2配列はSASX9LX10S(配列番号9)であり;
(c)HVR−L3配列はQQX11X12X13X14PX15T(配列番号10)であり;
さらに、それにおいて:X4はDまたはVであり;X5はVまたはIであり;X6はSまたはNであり;X7はAまたはFであり;X8はVまたはLであり;X9はFまたはTであり;X10はYまたはAであり;X11はY、G、F,またはSであり;X12はL、Y、FまたはWであり;X13はY、N、A、T、G、FまたはIであり;X14はH、V、P、TまたはIであり;X15はA、W、R、PまたはTである。
さらなる局面において、X4はDであり;X5はVであり;X6はSであり;X7はAであり;X8はVであり;X9はFであり;X10はYであり;X11はYであり;X12はLであり;X13はYであり;X14はHであり;X15はAである。さらなる局面において、軽鎖は、さらに、以下の式のHVRの間に並置された軽鎖可変領域フレームワーク配列:(LC−FR1)−(HVR−L1)−(LC−FR2)−(HVR−L2)−(LC−FR3)−(HVR−L3)−(LC−FR4)を含む。さらなる局面において、フレームワーク配列は、ヒトコンセンサスフレームワーク配列に由来する。さらなる局面において、フレームワーク配列は、VLカッパIコンセンサスフレームワークである。さらなる局面において、フレームワーク配列の少なくとも1つは以下:
LC−FR1はDIQMTQSPSSLSASVGDRVTITC(配列番号11)であり;
LC−FR2はWYQQKPGKAPKLLIY(配列番号12)であり;
LC−FR3はGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC(配列番号13)であり;
LC−FR4はFGQGTKVEIKR(配列番号14)
である。
(a)重鎖は、HVR−H1、HVR−H2、およびHVR−H3を含み、それにおいて、さらに:
(i)HVR−H1配列はGFTFSX1SWIH(配列番号1)であり;
(ii)HVR−H2配列はAWIX2PYGGSX3YYADSVKG(配列番号2)であり;
(iii)HVR−H3配列はRHWPGGFDY(配列番号3)であり;そして
(b)軽鎖はHVR−L1、HVR−L2、およびHVR−L3を含み、それにおいて、さらに:
(i)HVR−L1配列はRASQX4X5X6TX7X8A(配列番号8)であり;
(ii)HVR−L2配列はSASX9LX10S(配列番号9)であり;および
(iii)HVR−L3配列はQQX11X12X13X14PX15T(配列番号10)である。
HC−FR1 EVQLVESGGGLVQPGGSLRLSCAAS(配列番号4)
HC−FR2 WVRQAPGKGLEWV(配列番号5)
HC−FR3 RFTISADTSKNTAYLQMNSLRAEDTAVYYCAR(配列番号6)
HC−FR4 WGQGTLVTVSA(配列番号7)
である。
LC−FR1 DIQMTQSPSSLSASVGDRVTITC(配列番号11)
LC−FR2 WYQQKPGKAPKLLIY(配列番号12)
LC−FR3 GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC(配列番号13)
LC−FR4 FGQGTKVEIKR(配列番号14)
である。
(a)重鎖は、さらに、GFTFSDSWIH(配列番号15)、AWISPYGGSTYYADSVKG(配列番号16)、およびRHWPGGFDY(配列番号3)と少なくとも85%の配列同一性をそれぞれ有するHVR−H1、HVR−H2、およびHVR−H3配列を含み、または
(b)軽鎖は、さらに、RASQDVSTAVA(配列番号17)、SASFLYS(配列番号18)、およびQQYLYHPAT(配列番号19)と少なくとも85%の配列同一性をそれぞれ有するHVR−L1、HVR−L2、およびHVR−L3配列を含む。
HC−FR1 EVQLVESGGGLVQPGGSLRLSCAAS(配列番号4)
HC−FR2 WVRQAPGKGLEWV(配列番号5)
HC−FR3 RFTISADTSKNTAYLQMNSLRAEDTAVYYCAR(配列番号6)
HC−FR4 WGQGTLVTVSA(配列番号7)
である。
LC−FR1 DIQMTQSPSSLSASVGDRVTITC(配列番号11)
LC−FR2 WYQQKPGKAPKLLIY(配列番号12)
LC−FR3 GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC(配列番号13)
LC−FR4 FGQGTKVEIKR(配列番号14)
である。
(a)重鎖は、以下:
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSA(配列番号20)の重鎖配列と少なくとも85%の配列同一性を有し、または
(b)軽鎖は、以下:
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKR(配列番号21)
の軽鎖配列と少なくとも85%の配列同一性を有する。
HC−FR1 EVQLVESGGGLVQPGGSLRLSCAAS(配列番号4)
HC−FR2 WVRQAPGKGLEWV(配列番号5)
HC−FR3 RFTISADTSKNTAYLQMNSLRAEDTAVYYCAR(配列番号6)
HC−FR4 WGQGTLVTVSA(配列番号7)
である。
LC−FR1 DIQMTQSPSSLSASVGDRVTITC(配列番号11)
LC−FR2 WYQQKPGKAPKLLIY(配列番号12)
LC−FR3 GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC(配列番号13)
LC−FR4 FGQGTKVEIKR(配列番号14)
である。
(a)重鎖は、さらに、GFTFSDSWIH(配列番号15)、AWISPYGGSTYYADSVKG(配列番号16)、およびRHWPGGFDY(配列番号3)と少なくとも85%の配列同一性をそれぞれ有するHVR−H1、HVR−H2、およびHVR−H3配列を含み、そして
(b)軽鎖は、さらに、RASQDVSTAVA(配列番号17)、SASFLYS(配列番号18)、およびQQYLYHPAT(配列番号19)と少なくとも85%の配列同一性をそれぞれ有するHVR−L1、HVR−L2、およびHVR−L3配列を含む。
HC−FR1 EVQLVESGGGLVQPGGSLRLSCAAS(配列番号4)
HC−FR2 WVRQAPGKGLEWV(配列番号5)
HC−FR3 RFTISADTSKNTAYLQMNSLRAEDTAVYYCAR(配列番号6)
HC−FR4 WGQGTLVTVSA(配列番号7)
である。
LC−FR1 DIQMTQSPSSLSASVGDRVTITC(配列番号11)
LC−FR2 WYQQKPGKAPKLLIY(配列番号12)
LC−FR3 GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC(配列番号13)
LC−FR4 FGQGTKVEIKR(配列番号14)
である。
本明細書で言及した全ての参考文献が、参照により具体的に組み入れられる。
本発明の実行は、特記なき場合、当技術分野の技能の範囲内にある分子生物学(組換え技術を含む)、微生物学、細胞生物学、生化学、および免疫学の従来の技術を用いる。そのような技術は文献において十分に説明される。例えば、Molecular Cloning: A Laboratory Manual, second edition (Sambrook et al., 1989); Oligonucleotide Synthesis (M.J. Gait, ed., 1984); Animal Cell Culture (R.I. Freshney, ed., 1987); Methods in Enzymology (Academic Press, Inc.); Current Protocols in Molecular Biology (F.M. Ausubel et al., eds 1987, and periodic updates); PCR: The Polymerase Chain Reaction, (Mullis et al., ed., 1994); A Practical Guide to Molecular Cloning (Perbal Bernard V., 1988); Phage Display: A Laboratory Manual (Barbas et al., 2001)。
A.リンパ球の発生および活性化
ヒトにおける2つの主な型のリンパ球はT(胸腺由来)およびB(骨髄由来)である。これらの細胞は、リンパ系発生経路にコミットした骨髄および胎児肝臓中の造血幹細胞に由来する。これらの幹細胞の子孫は、BまたはTリンパ球中に成熟する多岐にわたる経路に従う。ヒトBリンパ球の発生は、完全に骨髄内で起こる。T細胞は、他方で、骨髄を離れ、血流を通じて胸腺まで移動する未成熟な前駆体から発生し、そこで、それらは、増殖し、成熟Tリンパ球に分化する。
Tリンパ球は免疫グロブリンを発現せず、しかし、代わりに、T細胞受容体(TCR)と呼ばれる表面タンパク質により外来物質の存在を検出する。これらの受容体は、直接的な接触によりまたは他の免疫細胞の活性に影響を与えることを通じて抗原を認識する。マクロファージと一緒に、T細胞は細胞媒介性免疫に関与する一次細胞型である。
他の身体の防御から区別される哺乳動物の免疫系の3つの一次機能特性は、以下:(1)特異性 − 大多数の標的分子の間で個別に認識するおよび応答するまたは応答しない能力、(2)識別 − 非自己から自己を決定するための能力(全ての無数のタンパク質および他の有機物質と穏やかに共存し、依然として身体に導入される外来物質に対してウイルス学的に応答するようにする)、および(3)記憶 − 経験により形成される能力(特定の外来病原体との後の遭遇が、最初の遭遇で生じたよりも迅速で活発な応答を惹起する)を含む。これらの機能の1つまたは複数が失敗している場合、病理学的状態がもたらされる。
1.B7.1/B7.2 − CD28/CTLA−4
恐らく、最も良く特徴付けられているT細胞同時刺激経路は、B7.1(CD80)/B7.2(CD86) − CD28/CTLA−4(CD152)を通じてシグナル伝達する経路である。このシグナル伝達経路はT細胞の活性化および寛容に決定的である。Karandikar et al., J. Neuroimmunol. 89: 10-18 (1998); Oosterwegal et al., Curr. Opin. Immunol. 11: 294-300 (1999); Salomon et al., Annu. Rev. Immunol. 19: 225-252 (2001); Sansom, D. M., Immunol. 101: 169-177 (2000); Chambers et al., Annu. Rev. Immunol. 19: 565-592 (2001)。
APCとT細胞の間での相互作用の別の経路は、ICOS(CD278)およびICOSL(B7−H2、CD275)を通じて生じる。ICOS/ICOSLシグナル伝達は、Tヘルパー細胞分化およびエフェクター機能を促進し、特にインターロイキン10(IL−10)産生のために重要であるが、しかし、T細胞増殖およびIL−2産生(調節性T細胞を含む)、T細胞寛容、および自己免疫を調節する際により適度な役割を果たす。
T細胞活性化を調節する重要なネガティブ同時刺激シグナルが、プログラム死1受容体(PD−1)(CD279)、ならびにそのリガンド結合パートナーPD−L1(B7−H1、CD274)およびPD−L2(B7−DC、CD273)により提供さる。PD−1のネガティブな調節的役割が、PD−1ノックアウト(Pdcd1−/−)により明らかにされ、それは自己免疫の傾向がある。Nishimura et al., Immunity 11: 141-51 (1999); Nishimura et al., Science 291: 319-22 (2001)。PD−1はCD28およびCTLA−4に関連するが、しかし、ホモ二量体化を可能にする膜近位システインを欠く。PD−1の細胞質ドメインは、免疫受容体チロシンベースの阻害モチーフ(ITIM、V/IxYxxL/V)を含む。PD−1はPD−L1およびPD−L2だけに結合する。Freeman et al., J. Exp. Med. 192: 1-9 (2000); Dong et al., Nature Med. 5: 1365-1369 (1999); Latchman et al., Nature Immunol. 2: 261-268 (2001); Tseng et al., J. Exp. Med. 193: 839-846 (2001)。
同時刺激シグナルは、また、B7−H3(B7RP−2、CD276、PRO352)を通じて提供され、それは広くリンパ系および非リンパ系組織において発現される。Chapoval et al., Nat. Immunol. 2: 269-74 (2001)。ヒトにおいて、B7−H3は4Igおよび2Igバリアントの両方を有し、4Ig形態が優勢であり、2Igバリアントがマウスにおいて優勢である。Sun et al., J. Immunol. 168: 6294-97 (2002); Steinberger et al., J. Immunol. 172: 2352-59 (2004); Ling et al., Genomics 82: 365-77 (2003)。
B7ファミリーへの最も最近の追加はB7−H4(B7x、B7−S1、B7−H.5、VTCN1、PRO1291)であり、それはT細胞応答のネガティブレギュレーターである。Zang et al., Proc. Natl. Acad. Sci. U.S.A. 100 (18), 10388-10392 (2003); Watanabe et al., Nat. Immunol. 4 (7), 670-679 (2003); Prasad, et al., Immunity 18(6), 863-873 (2003); Sica et al., Immunity 18 (6), 849-861 (2003)。ヒトおよびマウスの両方のB7−H4が、リンパ系器官(脾臓および胸腺)および非リンパ系器官(肺、肝臓、精巣、卵巣、胎盤、骨格筋、膵臓、および小腸を含む)において広く発現される。B7−H4は、正常ヒト組織において、IHCまたはB7−H4の翻訳レベルでの調節により検出されない。IHCでは、B7−H4が肺および卵巣の腫瘍において高度に発現されることが示され、リアルタイムポリメラーゼ連鎖反応(PCR)分析では、マウスB7−H4が前立腺、肺、および結腸の癌細胞株においても高度に発現されることが示される。B7−H4は、活性化T細胞(しかし、ナイーブT細胞ではない)上の未知の受容体に結合し、それはCTLA−4、ICOS、PD−1、およびB7−H3についての受容体とは別々である。BTLAがB7−H4についてのリガンドであると最初に報告されたが、野生型細胞(しかし、BTLA−/−細胞ではない)へのB7−H4/Ig融合物の報告された結合によって、HVEM(BTLAではない)がB7−H4についての固有のリガンドであるという結論に説得力がある。Sedy et al., Nat. Immunol. 6: 90-98 (2004)。
B7ファミリーメンバーBTLA(CD272、BTLA−1)は、PD−1およびCTLAと機能的に類似している。Th1細胞用の選択マーカーとして最初に同定され、BTLAはリンパ球だけで発現される。CTLA−4、ICOS、およびPD−1と同様に、BTLAは活性化の間にT細胞上で誘導される。しかし、ICOS(Th2細胞では上昇したままであるが、しかし、Th1細胞ではダウンレギュレーションされる)とは対照的に、BTLAはTh1細胞(しかし、Th2細胞ではない)では発現されたままである。PD−1と同様に、BTLAは、B細胞上でも発現される。Gavrieli et al., Biochem. Biophys. Res. Commun. 312: 1236-43 (2003)。しかし、BTLAは休止中のB細胞および活性化B細胞の両方で発現されるのに対し、PD−1は活性化B細胞でアップレギュレーションされる。BTLAは2つのITIMモチーフを有する。
1.OX40/OX40L(CD134)
OX40(CD134、TXPG1L、TNFRSF4)およびOX40L(CD134L、CD252、GP34、TNFSF4、TXGP1)欠損マウスは、ウイルス抗原および一般的なタンパク質抗原の両方に対しておよび接触過敏反応において低下した一次CD4+T細胞応答を有する。Chen et al., Immunity 11: 689-698 (1999); Kopf et al., Immunity 11: 699-708 (1999); Murata et al., J. Exp. Med. 191: 365-374 (2000); Gramaglia et al., J. Immunol. 165: 3043-3050 (2000)。より低い頻度の抗原特異的エフェクターT細胞が、一次応答における後期に生成され、より少ない記憶T細胞が発生する。Gramaglia et al., supra。CD27を欠損したT細胞とは対照的に、初期増殖は、OX40を欠損したナイーブCD4+T細胞集団において損なわれていない。しかし、低下した増殖および顕著なアポトーシス細胞死が活性化後4−5日目に生じ、結果としてわずかなT細胞しか長期間生存しない。Rogers et al., Immunity 15: 445-455 (2001)。OX40欠損CD8+T細胞を用いて、最初の細胞分裂は影響されず、しかし、一次エフェクター細胞の蓄積が抗原との遭遇後3−6日目に顕著に低下する。Croft et al., Nat. Immunol. 3: 609-620 (2003)。
OX40/OX40Lと同様に、4−1BB(CD137、TNFRSF9)および4−1BBL(TNFSF9)を欠くT細胞では、より少ない抗原反応性CD8+T細胞が、4−1BBLが存在しない場合に一次応答において蓄積し、より少ない記憶T細胞が発生することが示される。DeBenedette et al., J. Immunol. 163: 4833-4841 (1999); Tan et al., J. Immunol. 163: 4859-4868 (1999); Tan et al., J. Immunol. 164: 2320-2325 (2000)。また、4−1BBLを遮断することによって、CD8+T細胞の最初の増殖性応答は変化しないが、しかし、数回に分割された細胞のアポトーシスのため、3−6日後の一次応答のピークでエフェクターCTLの蓄積が抑制される。Cooper et al., Eur. J. Immunol. 32: 521-529 (2002)。アゴニスト抗4−1BB抗体および抗4−1BBL−トランスフェクトAPCも同様の結果を産生している:CTLおよびCD4+T細胞応答がin vivoで顕著に増加される。Melero et al., Nature Med. 3: 682-685 (1997); Melero et al., Eur. J. Immunol. 28: 1116-1121 (1998); Takahashi et al., J. Immunol. 162: 5037-5040 (1999); Guinn et al., J. Immunol. 162: 5003-5010 (1999); Halstead et al., Nature Immunol. 3: 536-541 (2002); Takahashi et al., Immunol. Lett. 76: 183-191 (2001); Bansal-Pakala et al., J. Immunol. 169: 5005-5009 (2002)。4−1BB−特異的抗体は最初の増殖性応答を変化させず、4−1BBL遮断実験からの結論を支持し、細胞−生存シグナルを供給する際での4−1BBの後期活性を指し示す。
T細胞応答の最初の段階におけるCD27(TNFRSF7、S152)およびCD27L(CD70、TNFSF7)シグナル伝達の重要性がin vitroでの遮断試験において実証されており、それにおいてCD27/CD70相互作用が破壊された。Oshima et al., Int. Immunol. 10: 517-526 (1998); Agematsu et al., J. Immunol. 153: 1421-1429 (1994); Hintzen et al., J. Immunol. 154: 2612-2623 (1995)。CD27を欠くT細胞は最初は正常に分裂するが、しかし、次に、活性化後3日目またはそれ以降に不良に増殖する。Hendriks et al., Nature Immunol. 1: 433-440 (2000)。これは、CD27が、T細胞死の早期抑制によりまたは細胞周期に作用することにより、ナイーブT細胞集団の最初の増殖の促進に関与し、活性化後2〜3日間持続的な分裂を可能にすることを示す。これはCD27欠損マウスでのin vivo試験により裏付けられ、それにおいて、より低い数の抗原特異的応答(4〜8日目)およびより少ない記憶T細胞が3週間またはそれ以上にわたり発生する。Hendriks et al., supra。CD27の発現は、T細胞活性化後、早期にアップレギュレーションされ、それが、エフェクター応答のピーク前に、早期増殖を保持するシグナルを主に送達することを示唆する。
CD30(TNFRSF8、Ki−1)およびCD30L(CD153、TNFSF8)シグナル伝達は、in vitroでのいくつかのT細胞機能について同時刺激的である。Del Prete et al., J. Exp. Med. 182: 1655-1661 (1995), Bowen et al., J. Immunol. 156: 442-449 (1995)。CD30Lに対する遮断試薬は、Th2細胞の発生を抑制し、in vitroでTh1細胞の発生を増強した。この活性は、CD30がTh2細胞および2型細胞傷害性Tc2細胞により優先的に発現されることを示すデータと一致する。Del Prete et al., supra, Nakamura et al., J. Immunol. 158: 2090-2098 (1996)。CD30は、非極性化された一次応答においてナイーブT細胞の活性化後3〜4日目に発現される。Nakamura et al., supra(その役割が2型サイトカイン支配的応答に制限されないことを示す)。
T細胞同時刺激に対するHVEM(HVEA、ATAR、LIGHTR、TNFRSF14、PRO509)およびLIGHT(CD258、HVEML、TR2、TNFSF14、PRO726)の効果は、1)LIGHTがリンホトキシンβ受容体(LTβR)にも結合する能力および2)HVEMが可溶性LTα3に結合する能力により複雑化される。このように、HVEM/LIGHTの効果の任意の試験では、また、このシグナル伝達系についての他の結合パートナーの効果を考慮に入れるべきである。LIGHTの遮断によって、同種混合リンパ球反応(MLR)において早期T細胞増殖およびサイトカイン分泌を阻害することができる。Tamada et al., J. Immunol. 164: 4105-4110 (2000), Kwon et al., J. Biol. Chem. 272: 14272-14276 (1997); Harrop et al., J. Immunol. 161: 1786-1794 (1998); Tamada et al., Nature Med. 6: 283-289 (2000)。炎症性サイトカインの産生は、LIGHTがMHC不適合心臓同種移植片において遮断される場合に抑制される。Ye et al., J. Exp. Med. 195: 795-800 (2002)。さらに、同種皮膚移植片が、LIGHTおよびCD28の両方を欠損するレシピエントにおいて遅延した動態で拒絶される。Scheu et al., J. Exp. Med. 195: 1613-1624 (2002)。遅延された移植片拒絶がT細胞クローン増殖またはサイトカイン産生の早期抑制を示しうるとの示唆。この結論は、(i)同種抗原に応答するLIGHT欠損脾細胞が、TH1およびTH2の両方のサイトカインの低下した産生ならびに細胞傷害性Tリンパ球活性(CTL)活性の弱い生成を有することを示すin vitro試験[Sheu et al., supra.]ならびに(ii)LIGHTの遮断がアロ反応性CTLの生成を低下させることを示すin vivo試験により裏付けられる。Tamada et al., Nature Med. 6: 283-289 (2000)。
「アレルゲン」または「免疫原」は、免疫応答を誘発することができる任意の分子である。本明細書で使用する通り、この用語は、抗原分子自体、またはその供給源(例えば花粉粒、動物のフケ、昆虫毒、または食物産物など)のいずれかを対象とする。これは抗原という、免疫グロブリンまたはT細胞受容体により特異的に認識されることができる分子を指す用語と対比される。免疫応答を誘導することが可能である任意の外来物質が、潜在的なアレルゲンである。天然および合成由来の多くの異なる化学物質が、アレルゲン性であることが公知である。複雑な天然有機化学物質、特にタンパク質が、抗体媒介性アレルギーを起こす可能性が高いのに対し、単純な有機化合物、無機化学物質、および金属はT細胞媒介性アレルギーをより優先的に起こす。一部の場合において、同じアレルゲンは1を上回る型のアレルギーに関与しうる。アレルゲンへの暴露は、吸入、注射、注射、または皮膚接触を通じうる。
siRNAは、上昇したインターフェロン合成、非特異的タンパク質合成阻害、およびRNA分解(哺乳動物細胞においてRNAiの使用に関連する細胞の自殺または死をしばしばもたらす)により特徴付けられる抗ウイルス応答を特異的に回避するよう設計される。Paddison et al., Proc Natl Acad Sci USA 99(3):1443-8.(2002)。
ループ Kabat AbM Chothia 接触
---- ----- --- ------- -------
L1 L24-L34 L24-L34 L26-L32 L30-L36
L2 L50-L56 L50-L56 L50-L52 L46-L55
L3 L89-L97 L89-L97 L91-L96 L89-L96
H1 H31-H35B H26-H35B H26-H32 H30-H35B
(Kabatナンバリング)
H1 H31-H35 H26-H35 H26-H32 H30-H35
(Chothiaナンバリング)
H2 H50-H65 H50-H58 H53-H55 H47-H58
H3 H95-H102 H95-H102 H96-H101 H93-H101
100×分数X/Y
(式中、Xは、AおよびBのそのプログラムのアラインメントにおける配列アラインメントプログラムALIGN−2による同一のマッチとしてスコア化されるアミノ酸残基の数であり、式中、YはBにおけるアミノ酸残基の総数である)の通りに算出する。アミノ酸配列Aの長さがアミノ酸配列Bの長さとは等しくない場合、AのBに対する%アミノ酸配列同一性は、BのAに対する%アミノ酸配列同一性とは等しくないと理解されるであろう。
特に腫瘍免疫の処置において、本発明の抗PD−L1抗体との組み合わせで有用な特に好ましい化学療法剤は、ゲムシタビンである。
A.ファージディスプレイを使用したヒト化
本明細書に記載する超可変領域を移植したバリアントは、各超可変領域について別々のオリゴヌクレオチドを使用して、ヒト受容体配列をコードする核酸のKunkel突然変異誘発により生成した。Kunkel et al., Methods Enzymol. 154: 367-382 (1987).適切な変化を、通常の技術を使用してフレームワークおよび/または超可変領域中に導入し、適した超可変領域−抗原相互作用を補正および再確立することができる。
本発明は、また、抗PD−L1抗体をコードする単離核酸、そのような核酸を含むベクターおよび宿主細胞、ならびに抗体の産生のための組換え技術を提供する。
a)ベクター構築
本発明の抗体のポリペプチド成分をコードするポリヌクレオチド配列を、標準的な組換え技術を使用して得ることができる。所望のポリヌクレオチド配列を、抗体産生細胞(例えばハイブリドーマ細胞など)から単離し、配列決定してもよい。あるいは、ポリヌクレオチドをヌクレオチドシンセサイザーまたはPCR技術を使用して合成することができる。一旦得られると、ポリペプチドをコードする配列を、原核生物宿主において異種ポリヌクレオチドを複製および発現することが可能な組換えベクター中に挿入する。当技術分野において利用可能で公知の多くのベクターを、本発明の目的のために使用することができる。適切なベクターの選択は、ベクター中に挿入される核酸のサイズおよびそのベクターを用いて形質転換される特定の宿主細胞に主に依存するであろう。各ベクターは、その機能(異種ポリヌクレオチドの増幅または発現、あるいは両方)およびそれが存在する特定の宿主細胞とのその適合性に依存して、種々の成分を含む。ベクター成分は、一般的に、限定はされないが、以下:複製起点、選択マーカー遺伝子、プロモーター、リボゾーム結合部位(RBS)、シグナル配列、異種核酸インサート、および転写終結配列を含む。
本発明の抗体を発現させるために適した原核生物宿主細胞は、古細菌と真正細菌、例えばグラム陰性またはグラム陽性生物などを含む。有用な細菌の例は、エシェリキア属(例、E.coli)、バシラス属(例、B. subtilis)、腸内細菌、シュードモナス属(例、P. aeruginosa)、サルモネラ・チフィリウム(Salmonella typhimurium)、セラチア・マルセッセンス(Serratia marcescans)、クレブシエラ属、プロテウス属、シゲラ属、根粒菌、ビトレオシラ属、またはパラコッカス属を含む。一実施態様において、グラム陰性細胞を使用する。一実施態様において、E.coli細胞を本発明のための宿主として使用する。E.coli株の例は、W3110株(Bachmann, Cellular and Molecular Biology, vol. 2 (Washington, D.C.: American Society for Microbiology, 1987), pp.1190-1219; ATCC Deposit No. 27,325)およびその派生体を含み、遺伝子型W3110 yfhuA (ytonA) ptr3 lac Iq lacL8 yompTy(nmpc−fepE) degP41 kanR(米国特許第5,639,635号)を有する33D3株を含む。他の株およびその派生体、例えばE.coli 294(ATCC 31,446)、E.coli B、E.coli 1776(ATCC 31,537)およびE.coli RV308(ATCC 31,608)なども適する。これらの例は、限定的よりも、むしろ説明的である。定義された遺伝子型を有する上記の最近のいずれかの派生体を構築するための方法が、当技術分野において公知であり、例えば、Bass et al., Proteins, 8:309-314 (1990)に記載される。一般的に、細菌の細胞におけるレプリコンの複製能を考慮に入れて適切な細菌を選択することが必要である。例えば、E.coli、セラチア属、またはサルモネラ属が、周知のプラスミド(例えばpBR322、pBR325、pACYC177、またはpKN410など)を、レプリコンを供給するために使用する場合、宿主として使用するのに適しうる。
宿主細胞を上記の発現ベクターを用いて形質転換し、プロモーターを誘導し、形質転換体を選択し、または所望の配列をコードする遺伝子を増幅するために適宜改変された従来の栄養培地中で培養する。形質転換はDNAを原核生物宿主中に導入し、DNAが、染色体外エレメントとしてまたは染色体組み込み体のいずれかとして複製可能であることを意味する。使用する宿主細胞に依存して、形質転換は、そのような細胞に適切である標準的な技術を使用して行う。塩化カルシウムを用いたカルシウム処理は、実質的な細胞壁バリアを含む細菌細胞のために一般的に使用される。形質転換のための別の方法ではポリエチレングリコール/DMSOを用いる。使用されるさらに別の技術は、エレクトロポレーションである。
本明細書において産生される抗体タンパク質をさらに精製し、さらなるアッセイおよび使用のための実質的に均質である調製物を得る。当技術分野において公知の標準的なタンパク質精製方法を用いることができる。以下の手順:免疫親和性カラムまたはイオン交換カラム上での分画、エタノール沈殿、逆相HPLC、シリカ上または陽イオン交換樹脂(例えばDEAEなど)上でのクロマトグラフィー、クロマトフォーカシング、SDS−PAGE、硫安塩析、およびゲルろ過(例えば、Sephadex G-75を使用)は、適した精製手順の例示である。
真核生物での発現のために、ベクター成分は、一般的に、限定はされないが、以下:シグナル配列、複製起点、1つまたは複数のマーカー遺伝子、ならびにエンハンサーエレメント、プロモーター、および転写終結配列の1つまたは複数を含む。
真核生物宿主における使用のためのベクターは、また、成熟タンパク質またはポリペプチドのN末端に特定の切断部位を有するシグナル配列または他のポリペプチドをコードするインサートを含んでもよい。選択される異種シグナル配列は、宿主細胞により認識され、プロセシングされる(即ち、シグナルペプチダーゼにより切断される)ものである。哺乳動物細胞での発現において、哺乳動物シグナル配列ならびにウイルス分泌リーダー、例えば、単純ヘルペスgDシグナルを利用可能である。
一般的に、複製起点成分は、哺乳動物発現ベクターのために必要とされない(SV40起点を典型的に使用してもよい。なぜなら、ただ、それは初期プロモーターを含むからである)。
発現ベクターおよびクローニングベクターは、選択遺伝子(選択可能マーカーとも呼ばれる)を含んでもよい。典型的な選択遺伝子は、(a)抗生物質または他の毒素(アンピシリン、ネオマイシン、メトトレキサート、またはテトラサイクリン)に対して耐性を付与する、(b)栄養要求性欠損を補完する、または(c)複雑な培地から利用可能ではない決定的な栄養分を供給するタンパク質をコードする(例、バシラス属についてのDアラニンラセマーゼをコードする遺伝子)。
発現ベクターおよびクローニングベクターは、通常、宿主生物により認識され、所望の抗体配列をコードする核酸に機能的に連結されたプロモーターを含む。事実上、全ての真核生物遺伝子が、転写が開始される部位から約25〜30塩基上流に位置付けられるATリッチ領域を有する。多くの遺伝子の転写の開始から70〜80塩基上流に見出される別の配列は、CNCAAT領域であり、そこでNは任意のヌクレオチドでありうる。大半の真核生物の3’末端は、AATAAA配列であり、それはコード配列の3’末端へのポリAテールの付加のためのシグナルでありうる。これらの配列の全てを、真核生物発現ベクター中に挿入してもよい。
より高い真核生物による本発明の抗体をコードするDNAの転写は、しばしば、ベクター中にエンハンサー配列を挿入することにより増加される。多くのエンハンサー配列が、現在、哺乳動物遺伝子から公知である(グロビン、エラスターゼ、アルブミン、α−フェトプロテイン、およびインスリン)。典型的に、しかし、真核細胞ウイルスからのエンハンサーが使用されうる。例は、複製開始点の後期側のSV40エンハンサー(bp 100−270)、サイトメガロウイルス初期プロモーターエンハンサー、複製開始点の後期側のポリオーマエンハンサー、およびアデノウイルスエンハンサーを含む。また、真核生物プロモーターの活性化のための増強エレメントに関するYaniv, Nature 297: 17-18 (1982)を参照のこと。エンハンサーは、抗体コード配列に対する位置5’または3’でベクター中にスプライシングされうるが、しかし、好ましくはプロモーターから部位5’に位置付けられる。
真核生物宿主細胞(酵母、真菌、昆虫、植物、動物、ヒト、または他の多細胞生物からの有核細胞)において使用される発現ベクターは、また、転写の終結のためにおよびmRNAを安定化させるために必要な配列を含みうる。そのような配列は、一般に、真核生物またはウイルスのDNAまたはcDNAの5’および、時には3’の非翻訳領域から利用可能である。これらの領域は、、抗体をコードするmRNAの非翻訳部分におけるポリアデニル化フラグメントとして転写されるヌクレオチドセグメントを含む。1つの有用な転写終結成分は、ウシ成長ホルモンポリアデニル化領域である。WO94/11026およびその中で開示される発現ベクターを参照のこと。
本明細書におけるベクター中でDNAをクローン化または発現するための適した宿主細胞は、本明細書に記載するより高い真核細胞(脊椎動物宿主細胞を含む)を含む。培養(組織培養)における脊椎動物細胞の増殖は、通常の手順になっている。有用な哺乳動物宿主細胞株の例は、以下:SV40により形質転換されたサル腎臓CV1株(COS−7, ATCC CRL 1651);ヒト胚腎臓株(293細胞または浮遊培養中での増殖のためにサブクローン化された293細胞、Graham et al., J. Gen Virol. 36: 59 (1977));仔ハムスター腎細胞(BHK, ATCC CCL 10);チャイニーズハムスター卵巣細胞/−DHFR(CHO, Urlaub et al., Proc. Natl. Acad. Sci. USA 77: 4216 (1980));マウスセルトリ細胞(TM4, Mather, Biol. Reprod. 23: 243-251 (1980) );サル腎臓細胞(CV1 ATCC CCL 70);アフリカミドリザル腎臓細胞(VERO−76, ATCC CRL−1587);ヒト子宮頚癌細胞(HELA, ATCC CCL 2);イヌ腎臓細胞(MDCK, ATCC CCL 34);バッファローラット肝細胞(BRL 3A, ATCC CRL 1442);ヒト肺細胞(W138, ATCC CCL 75);ヒト肝細胞(Hep G2, HB 8065);マウス乳癌(MMT 060562, ATCC CCL51);TRI細胞(Mather et al., Annals N.Y. Acad. Sci. 383: 44-68 (1982));MRC5細胞;FS4細胞;およびヒト肝細胞癌株(Hep G2)である。
本発明の抗体を産生するために使用される宿主細胞を、種々の培地中で培養してもよい。商業的に利用可能な培地、例えばHam’s F10(Sigma)、最小必須培地((MEM)、(Sigma)、RPMI−1640(Sigma)、およびダルベッコ改変イーグル培地((DMEM)、Sigma)などが、宿主細胞を培養するために適する。また、Ham et al., Meth. Enz. 58: 44 (1979)、Barnes et al., Anal. Biochem. 102: 255 (1980)、米国特許第4,767,704号;第4,657,866号;第4,927,762号;第4,560,655号;または第5,122,469号;WO90/03430;WO87/00195;またはU.S. Patent Re.30,985に記載される培地のいずれかを宿主細胞用の培養液として使用してもよい。これらの培地のいずれかに、必要に応じて、以下を補給してもよい:ホルモンおよび/または他の増殖因子(例えばインスリン、トランスフェリン、または上皮増殖因子など)、塩(例えば塩化ナトリウム、カルシウム、マグネシウム、およびリン酸など)、緩衝剤(例えばHEPESなど)、ヌクレオチド(例えばアデノシンおよびチミジンなど)、抗生物質(例えばGENTAMYCIN(商標)薬物など)、微量元素(通常マイクロモル範囲の最終濃度で存在する無機化合物と定義される)、およびグルコースまたは等価のエネルギー供給源。任意の他の必要な補給剤を、また、当業者に公知でありうる適切な濃度で含めてもよい。培養条件、例えば温度、pHなどは、発現のために選択された宿主細胞と共に以前に使用されたものであり、当業者に明らかであろう。
組換え技術を使用する場合、抗体は、細胞内に、ペリプラズム間隙中に産生されうる、または培地中に直接的に分泌されうる。抗体が細胞内に産生される場合、最初の工程として、微粒子細片、宿主細胞または溶解フラグメントを、例えば、遠心分離または限外ろ過により除去する。Carter et al., Bio/Technology 10: 163-167 (1992)には、E.coliのペリプラズム間隙に分泌される単離抗体のための手順が記載される。簡単に説明すると、細胞ペーストを、酢酸ナトリウム(pH3.5)、EDTA、およびフェニルメチルスルホニルフルオリド(PMSF)の存在において約30分にわたり溶解させる。細胞片を遠心分離により除去することができる。抗体が培地中に分泌される場合、そのような発現系からの上清を、一般的に、商業的に利用可能なタンパク質濃縮フィルター、例えば、AmiconまたはMillipore Pellicon限外ろ過ユニットを使用して最初に濃縮する。プロテアーゼ阻害剤、例えばPMSFなどを、先の工程のいずれかに含め、タンパク質分解を阻害してもよく、抗生物質を含め、外来性混入菌の増殖を予防してもよい。
1)ポリクローナル抗体
ポリクローナル抗体は、一般的に、関連抗原およびアジュバントの複数回の皮下(sc)または腹腔内(ip)注射により動物において産生される。関連抗原を、免疫化される種において免疫原性であるタンパク質、例えば、キーホールリンペットヘモシアニン(KLH)、血清アルブミン、ウシサイログロブリン、または大豆トリプシン阻害剤に、二官能性薬剤または誘導体化薬剤、例えば、マレイミドベンゾイルスルホスクシンイミドエステル(システイン残基を通じた抱合)、Nヒドロキシスクシンイミド(リジン(lysien)残基を通じて)、グルタルアルデヒド、無水コハク酸、SOCl2、またはR1N=C=NR(式中、RおよびR1は非依存的により低いアルキル基である)を使用して抱合することが有用でありうる。用いてもよいアジュバントの例は、フロイント完全アジュバントおよびMPL−TDMアジュバント(モノホスホリル脂質A、合成トレハロースジコリノミコラート)を含む。免疫化プロトコールは、過度の実験なしに当業者により選択されうる。
モノクローナル抗体を実質的に均質な抗体の集団から得る。即ち、その集団を含む個々の抗体は、少量で存在しうる、起こりうる天然突然変異および/または翻訳後修飾(例、異性化、アミド化)を除いて同一である。このように、修飾語「モノクローナル」は、別々の抗体の混合物ではないとして抗体の特徴を示す。
本発明の抗体は、さらに、ヒト化抗体またはヒト抗体を含みうる。非ヒト(例、マウス)抗体のヒト化形態は、非ヒト免疫グロブリンに由来する配列を最小に含む、キメラ免疫グロブリン、免疫グロブリン鎖、またはそのフラグメント(例えばFv、Fab、Fab’、F(ab’)2、または抗体の他の抗原結合サブ配列など)である。ヒト化抗体はヒト免疫グロブリン(レシピエント抗体)を含み、それにおいてレシピエントの相補性決定領域(CDR)(本明細書で使用されるHVR)からの残基が、非ヒト種(例えば所望の特異性、親和性、および能力を有するマウス、ラット、またはウサギなど)(ドナー抗体)のCDRからの残基により置換される。一部の例において、ヒト免疫グロブリンのFvフレームワーク残基は、対応する非ヒト残基により置換される。ヒト化抗体は、また、レシピエント抗体においてまたは移入されたCDRまたはフレームワーク配列において見出されない残基を含みうる。一般的に、ヒト化抗体は、少なくとも1つ、典型的には2つの可変ドメインの実質的に全てを含みうるが、それにおいてCDR領域の全てまたは実質的に全てが非ヒト免疫グロブリンのものに対応し、FR領域の全てまたは実質的に全てがヒト免疫グロブリンコンセンサス配列のものである。ヒト化抗体は、最適にはまた、免疫グロブリン定常領域(Fc)の少なくとも部分、典型的にはヒト免疫グロブリンのそれを含む。Jones et al., Nature 321: 522-525 (1986); Riechmann et al., Nature 332: 323-329 (1988)およびPresta, Curr. Opin. Struct. Biol. 2: 593-596 (1992)。
ヒト化に対する代替物として、ヒト抗体を生成することができる。例えば、免疫化時に、内因性の免疫グロブリン産生の非存在においてヒト抗体の完全レパートリーを産生することが可能であるトランスジェニック動物(例、マウス)を産生することが現在可能である。例えば、キメラマウスおよび生殖系列突然変異マウスにおける抗体重鎖連結領域(JH)遺伝子のホモ接合性欠失が、内因性の抗体産生の完全な阻害をもたらすことが記載されている。そのような生殖系列突然変異マウスにおけるヒト生殖系列免疫グロブリン遺伝子アレイの移入は、抗原攻撃時でのヒト抗体の産生をもたらす。例えば、Jakobovits et al., Proc. Natl. Acad. Sci. USA, 90: 2551 (1993); Jakobovits et al., Nature, 362: 255-258 (1993); Bruggermann et al., Year in Immuno., 7: 33 (1993);米国特許第5,591,669号およびWO97/17852を参照のこと。
特定の状況において、抗体全体よりむしろ抗体フラグメントを使用することに利点がある。より小さなフラグメントサイズは迅速なクリアランスを可能にし、固形腫瘍に対する改善されたアクセスに導きうる。
本発明の抗体を、また、ADEPTにおいて、プロドラッグ(例、ペプチジル化学療法剤、WO81/01145を参照のこと)を活性な抗癌薬物に変換するプロドラッグ活性化酵素に抗体を抱合させることにより使用してもよい。例えば、WO88/07378および米国特許第4,975,278号を参照のこと。
二特異性抗体(BsAb)は、少なくとも2つの異なるエピトープ(同じまたは別のタンパク質上のものを含む)について結合特異性を有する抗体である。あるいは、1つのアームは標的抗原に結合することができ、別のアームは、白血球上の誘発分子、例えばT細胞受容体分子(例、CD3)、またはIgGについてのFc受容体(FcγR)、例えばFcγR1(CD64)、FcγRII(CD32)、およびFcγRIII(CD16)などに結合するアームと組み合わせることができ、細胞防御機構を標的の抗原発現細胞に集中させ、局在化する。そのような抗体は、全長抗体または抗体フラグメント(例、F(ab’)2二特異性抗体)に由来しうる。
多価抗体は、抗体が結合する抗原を発現する細胞により、二価抗体よりも速くインターナリゼーションされうる(および/または異化されうる)。本発明の抗体は、3つまたはそれ以上の抗原結合部位(例、四価抗体)を伴う多価抗体(それはIgMクラス以外のものである)でありうるが、それは、抗体のポリペプチド鎖をコードする核酸の組換え発現により容易に産生することができる。多価抗体は、二量体化ドメインおよび3つまたはそれ以上の抗原結合部位を含むことができる。好ましい二量体化ドメインは、Fc領域またはヒンジ領域を含む(またはそれからなる)。このシナリオにおいて、抗体は、Fc領域およびFc領域のアミノ末端に3つまたはそれ以上の抗原結合部位を含みうる。本明細書における好ましい多価抗体は、3〜約8、しかし好ましくは4つの抗原結合部位を含む(またはそれからなる)。多価抗体は、少なくとも1つのポリペプチド鎖(および好ましくは2つのポリペプチド鎖)を含み、それにおいてポリペプチド鎖は2つまたはそれ以上の可変ドメインを含む。例えば、ポリペプチド鎖はVD1−(X1)n−VD2−(X2)n−Fcを含みうるが、それにおいてVD1は第1の可変ドメインであり、VD2は第2の可変ドメインであり、FcはFc領域の1つのポリペプチド鎖であり、X1およびX2はアミノ酸またはポリペプチドを表し、nは0または1である。例えば、ポリペプチド鎖は以下を含みうる:VH−CH1フレキシブルリンカーVH−CH1−Fc領域鎖;またはVH−CH1−VH−CH1−Fc領域鎖。本明細書における多価抗体は、好ましくは、少なくとも2つの(好ましくは4つの)軽鎖可変ドメインポリペプチドをさらに含む。本明細書における多価抗体は、例えば、約2〜約8つの軽鎖可変ドメインポリペプチドを含みうる。本明細書で検討する軽鎖可変ドメインポリペプチドは、軽鎖可変ドメインを含み、場合により、CLドメインをさらに含む。
ヘテロコンジュゲート抗体も本発明の範囲内にある。ヘテロコンジュゲート抗体は、2つの共有結合的に連結された抗体で構成される。例えば、ヘテロコンジュゲート中の抗体の1つをアビジンに、他をビオチンに共役することができる。そのような抗体は、例えば、免疫系細胞を不要な細胞に対して標的化すること(U.S.P.4,676,980)およびHIV感染の処置のために提案されている。WO91/00360、WO92/200373、およびEP0308936.抗体を、合成タンパク質化学において公知の方法(架橋薬剤を含むものを含む)を使用してin vitroで調製されうることが検討される。例えば、免疫毒素を、ジスルフィド交換反応を使用してまたはチオエーテル結合を形成することにより構築してもよい。この目的のための適した試薬の例は、イミノチオラート(iminothiolate)およびメチル−4−メルカプトブチルイミデートならびに、例えば、米国特許第4,676,980号に開示されるものを含む。ヘテロコンジュゲート抗体は、任意の便利な架橋方法を使用して作製してもよい。適した架橋薬剤は当技術分野において周知であり、米国特許第4,676,980号において、多くの架橋技術と共に開示される。
本発明の抗体を、Fcエフェクター機能に関して改変し、例えば、抗体の抗原依存性細胞媒介性細胞傷害(ADCC)および/または補体依存性細胞傷害(CDC)を改変する(例、増強または除去する)ことが望まれうる。好ましい実施態様において、抗PD−L1抗体のFcエフェクター機能を低下または除去する。これは、抗体のFc領域において1つまたは複数のアミノ酸置換を導入することにより達成されうる。あるいはまたは加えて、システイン残基をFc領域中に導入してもよく、それによりこの領域における鎖間ジスルフィド結合形成を可能にする。このようにして生成されたホモ二量体抗体は、改善されたインターナリゼーション能力および/または増加した補体媒介性細胞殺傷および抗体依存性細胞傷害(ADCC)を有しうる。Caron et al., J. Exp Med. 176: 1191-1195 (1992)およびShopes, B. J. Immunol. 148: 2918-2922 (1992)を参照のこと。増強した抗腫瘍活性を伴うホモ二量体抗体は、また、Wolff et al., Cancer Research 53: 2560-2565 (1993)に記載されるヘテロ二官能性架橋剤を使用して調製されうる。あるいは、二重Fc領域を有し、それにより増強した補体溶解およびADCC能力を有しうる抗体を操作することができる。Stevenson et al., Anti-Cancer Drug Design 3: 219-230 (1989)を参照のこと。
本明細書に記載する抗体のアミノ酸配列の改変を検討する。例えば、抗体の結合親和性および/または他の生物学的特性を改善することが望まれうる。抗体のアミノ酸配列バリアントを、抗体核酸中へ適切なヌクレオチド変化を導入することによりまたはペプチド合成により調製する。そのような改変は、例えば、抗体のアミノ酸配列内の残基からの欠失、および/またはその中への挿入、および/またはその置換を含む。欠失、挿入、および置換の任意の組み合わせを作製し、最終産物に達する(最終的な構築物が所望の特徴を保有するという条件で)。アミノ酸変化は、また、抗体の翻訳後プロセスを変化させうる(例えばグリコシル化部位の数または位置を変化させるなど)。
(1)疎水性:ノルロイシン、met、ala、val、leu、ile;
(2)中性疎水性:cys、ser、thr;
(3)酸性:asp、glu;
(4)塩基性:asn、gln、his、lys、arg;
(5)鎖の方向に影響を与える残基:gly、pro;および
(6)芳香族:trp、tyr、phe
本発明の抗体をさらに改変し、当技術分野において公知であり、容易に利用可能な追加の非タンパク質成分を含むことができる。好ましくは、抗体の誘導体化のために適した成分は、水溶性ポリマーである。水溶性ポリマーの非限定的な例は、限定はされないが、以下を含む:ポリエチレングリコール(PEG)、エチレングリコール/プロピレングリコールのコポリマー、カルボキシメチルセルロース、デキストラン、ポリビニルアルコール、ポリビニルピロリドン、ポリ−1,3−ジオキソラン、ポリ−1,3,6−トリオキサン、エチレン/無水マレイン酸コポリマー、ポリアミノ酸(ホモポリマーまたはランダムコポリマーのいずれか)、およびデキストランまたはポリ(n−ビニルピロリドン)ポリエチレングリコール、ポリプロピレングリコールホモポリマー、ポリプロピレンオキシド/酸化エチレンコポリマー、ポリオキシエチル化ポリオール(例、グリセロール)、ポリビニルアルコール、およびその混合物。ポリエチレングリコールプロピオンアルデヒドは、水中でのその安定性のため、製造において利点を有しうる。ポリマーは、任意の分子量でありうる、分岐または非分岐でありうる。抗体に付着するポリマーの数は変動しうるが、1つを上回るポリマーが付着する場合、それらは同じまたは異なる分子でありうる。一般的に、誘導体化のために使用されるポリマーの数および/または型は、抗体誘導体が限定条件下での治療において使用されるか否かなどにかかわらず、考察(限定はされないが、改善される抗体の特定の特性または機能を含む)に基づいて決定することができる。そのような技術および他の適した製剤が、Remington: The Science and Practice of Pharmacy, 20th Ed., Alfonso Gennaro, Ed., Philadelphia College of Pharmacy and Science (2000)に開示される。
治療用製剤は、保存のために、所望の程度の純度を有する活性成分を、任意の医薬的に許容可能な担体、賦形剤、または安定剤と混合することにより調製する(Remington: The Science and Practice of Pharmacy, 20th Ed., Lippincott Williams & Wiklins, Pub., Gennaro Ed., Philadelphia, PA 2000)。許容可能な担体、賦形剤、または安定剤は、用いられる投与量および濃度でレシピエントに対して無毒性であり、バッファー、抗酸化剤(アスコルビン酸を含む)、メチオニン、ビタミンE、メタ重亜硫酸ナトリウム;保存剤、等張剤、安定剤、金属複合体(例、Zn−タンパク質複合体);キレート剤(例えばEDTAおよび/または非イオン界面活性剤など)を含む。
疾患の予防または処置のために、活性薬剤の適切な投与量は、処置される疾患の型(上で定義する)、疾患の重症度および経過(薬剤が予防的または治療的な目的のために投与されるか否かにかかわらず)、過去の治療、患者の臨床歴および薬剤に対する応答、ならびに主治医の判断に依存しうる。薬剤は、患者に対して、1回でまたは一連の処置にわたり適切に投与される。
PD−1およびそのリガンド(「PD−1:PD−L」)は、急性および慢性感染を起こす病原体に対する免疫防御を調節する際に重要な役割を果たす。PD−1:PD−Lシグナル伝達は、効果的な抗菌免疫防御と免疫媒介性組織損傷の間でのバランスを調節する際に重要な役割を果たす。例えば、PD−1ノックアウトマウスは、それらの野生型の対応物よりも迅速にアデノウイルス感染を除去し、それらはより重度の肝細胞傷害を発生する。Iwai et al., J. Exp. Med. 198: 39-50 (2003)。ヘルペス間質性角膜炎のマウスモデルにおいて、抗PD−L1抗体の遮断は角膜炎を悪化させ、HSV−1特異的エフェクターCD4 T細胞増殖およびIFN−γ産生および生存を増加させた。Jun et al., FEBS Lett. 579: 6259-64 (2005)。
腫瘍免疫についての経験的な証拠は以下を含む:(i)自然寛解の観察、(ii)腫瘍に対する検出可能であるが、しかし、無効である宿主免疫応答の存在、(iii)免疫不全患者における原発および二次悪性腫瘍の増加した羅患率、(iv)腫瘍患者における増加レベルの抗体およびTリンパ球の検出、ならびに(v)試験動物を種々の腫瘍型に対して免疫化することができるとの観察。
試験では、大半のヒト腫瘍が、T細胞により認識されることができ、このように免疫応答を誘導することが潜在的に可能である腫瘍関連抗原(TAA)を発現することが示されている。Boon et al., Immunol. Today 16: 334-336 (1995)。初期段階の臨床試験が、TAAまたはTAAを用いてパルスされた専門の抗原提示細胞を用いて癌患者にワクチン接種することにより開始されている。Dudley et al., Science 298: 850-854 (2002); Gajewski et al., Clin. Cancer Res. 7: 895s-901s (2001); Marincola et al., Adv. Immunol. 74: 181-273 (2000); Peterson et al., J. Clin. Oncol. 21: 2342-2348 (2003)。腫瘍抗原特異的CD8+T細胞の誘導が、これらの試験の多くにおいて達成されている。Mackensen et al., Eur. Cytokine Netw 10: 329-336 (1999); Peterson et al., supra。腫瘍抗原特異的T細胞の患者中への養子移入も追求されており、増殖した細胞傷害性T細胞(CTL)の腫瘍部位への帰巣が明らかになっている。Meidenbauer et al., J. Immunol. 170: 2161-2169 (2003)。しかし、免疫エフェクター細胞の腫瘍浸潤にもかかわらず、腫瘍増殖はほとんど制御されなかった。
本発明の方法を、慢性感染または癌の処置の公知の方法と組み合わせることができる(組み合わせもしくは追加の処置工程としてまたは治療用製剤の追加成分として)。
腫瘍と戦うために宿主の免疫機能を増強することが、増加する興味の対象である。従来の方法は以下を含む:(i)APC増強、例えば(a)外来MHC同種抗原をコードするDNAの腫瘍中への注射、または(b)腫瘍の免疫抗原認識(例、免疫刺激性サイトカイン、GM−CSF、同時刺激分子B7.1、B7.2)の確率を増加させる遺伝子を用いた生検腫瘍細胞のトランスフェクション、(iii)活性化した腫瘍特異的T細胞を用いた養子細胞免疫療法、または処置。養子細胞免疫療法は、腫瘍浸潤宿主Tリンパ球を単離すること、in vitroで集団を増殖すること(例えばIL−2もしくは腫瘍または両方による刺激を通じて)を含む。加えて、機能障害性である単離T細胞を、また、本発明の抗PD−L1抗体のin vitro適用により活性化してもよい。そのようにして活性化されたT細胞を次に宿主に再投与してもよい。
感染(例、急性および/または慢性)の処置において、本発明の抗PD−L1抗体の投与を、感染に対する自然宿主免疫防御の刺激に加えてまたはその代わりに、従来の処置と組み合わせることができる。感染に対する自然宿主免疫防御は、限定はされないが、炎症、発熱、抗体媒介性宿主防御、Tリンパ球媒介性宿主防御(リンホカイン分泌および細胞傷害性T細胞(特にウイルス感染の間)を含む)、補体媒介性溶解およびオプソニン作用(食作用を促進)、ならびに食作用を含む。反応性機能障害性T細胞に対する本発明の抗PD−L1抗体の能力が、慢性感染、特に細胞媒介性免疫が完全回復のために決定的であるものを処置するために有用でありうる。
細菌感染に起因する感染のために、本発明の抗PD−L1抗体を、細菌感染を処置するための標準治療と同時の、その前の、またはそれに続く投与と組み合わせてもよい。細菌感染が、今日、抗菌抗生物質を用いて最も一般的に処置されるが、しかし、免疫化宿主からの病原体特異的抗体を含む血清も効果的でありうる。
ウイルスの原因に起因する感染について、本発明の抗PD−L1抗体を、ウイルス感染を処置するための標準的な治療の適用と同時の、その前の、またはそれに続く適用と組み合わせてもよい。そのような標準的治療は、ウイルスの型に依存して変動するが、ほぼ全例において、ウイルスに特異的なヒト血清含有抗体(例、IgA、IgG)の投与が効果的でありうる。
インフルエンザ感染は、発熱、咳、筋肉痛、頭痛、および倦怠感をもたらし、それらはしばしば季節的流行において生じる。インフルエンザは、また、多くの感染後障害、例えば脳炎、心筋心膜炎、グッドパスチャー症候群、およびライ症侯群などに関連する。インフルエンザ感染は、また、正常な肺の抗細菌防御(例えば患者のインフルエンザからの回復など)を抑制し、細菌性肺炎が発生する増加リスクを有する。
9〜11日間のインキュベーション後、麻疹ウイルスに感染した宿主は、発熱、咳、鼻感冒、および結膜炎を発生する。1〜2日間以内に、紅斑性、斑点状丘疹が発生し、急速に全身にわたり広がる。感染は、また、細胞性免疫を抑制するため、宿主には、細菌重複感染(中耳炎、肺炎、および感染後脳脊髄炎を含む)を発生するより大きなリスクがある。急性感染は、特に栄養不良の思春期の若者において、重大な罹患および死亡に関連する。
B型肝炎ウイルス(HB−V)は、最も感染性の高い公知の血液由来病原体である。それは、急性および慢性肝炎および肝臓癌、ならびに一生の慢性感染の主要な原因である。感染に続き、ウイルスが肝細胞において複製し、また、次に表面抗原HBsAgを放出する。血清中の過剰レベルのHBsAgの検出は、B型肝炎感染を診断するための標準的方法として使用される。急性感染は消散しうる、または、それは慢性の持続的感染に発生しうる。
C型肝炎ウイルス(HC−V)感染が、肝炎の慢性形態に導き、肝硬変(cirrosis)をもたらしうる。症状はB型肝炎に起因する感染と類似し(HB−Vとは明確に異なる)、感染宿主は10〜20年間にわたり無症候性でありうる。HC−V感染のための処置が、α−インターフェロンおよびリバビリンの組み合わせの投与を含む。HC−V感染についての有望な潜在的治療は、プロテアーゼ阻害剤テラプレビル(VX−960)である。追加の処置は以下を含む:抗PD−1抗体(MDX−1106、Medarex)、バビツキシマブ(bavituximab)(B2−糖タンパク質I依存的な様式で陰イオンリン脂質ホスファチジルセリンに結合する抗体、Peregrine Pharmaceuticals)、抗HPVウイルスコートタンパク質E2抗体(例、ATL 6865 − Ab68 + Ab65,XTL Pharmaceuticals)、およびCivacir(登録商標)(ポリクローナル抗HCVヒト免疫グロブリン)。本発明の抗PD−L1抗体は、治療的利点のためにC型肝炎感染のためのこれらの処置の1つまたは複数と組み合わせてもよい。
HIVはCD4+細胞(Tリンパ球、単球−マクロファージ、濾胞樹状細胞、およびランゲルハンス細胞を含む)を攻撃し、CD4+ヘルパー/誘導細胞が枯渇される。結果として、宿主は細胞媒介性免疫における重度の欠損を獲得する。HIV感染は、個人の少なくとも50%においてAIDSをもたらし、性的接触、感染した血液または血液産物の投与、感染した精液を用いた人工受精、血液を含む針またはシリンジへの暴露、および感染した母親から新生児への出産の間での伝達を介して伝達される。
サイトメガロウイルス(CMV)感染は、しばしば、持続的で、潜在的で、および再発性の感染に関連する。CMVが、単球および顆粒球−単球前駆細胞において感染し、潜在性のままである。CMVの臨床症状は、単核球症様症状(即ち、発熱、肥大した腺、倦怠感)および抗生物質に対するアレルギー性皮膚発疹を発生する傾向を含む。ウイルスは直接接触により広がる。ウイルスが、尿、唾液、精液、およびより少ない程度で他の体液に放出される。伝達は、また、感染した母親から彼女の胎児または新生児に、輸血および臓器移植により生じうる。CMV感染は細胞性免疫の全身損傷をもたらし、非特異的マイトジェンおよび特異的CMV抗原に対する損なわれた幼若化応答、細胞傷害能力の減弱、およびCD4+リンパ球のCD8リンパ球数の上昇により特徴付けられる。
エプスタイン・バーウイルス(EBV)は、持続的で潜在的な感染を確立することができ、主にB細胞を攻撃する。EBV感染は、感染性単核球症の臨床状態(発熱、咽頭炎(しばしば浸出物を伴う)、全身性リンパ節腫脹、および脾腫大を含む)をもたらす。肝炎も存在し、それは黄疸を発生しうる。
単純ヘルペスウイルス(HSV)は感染宿主との直接接触により伝達される。直接感染は無症候性でありうるが、しかし、典型的に、感染粒子を含む水疱をもたらす。疾患は疾患の活動期間のサイクルとして発現し、それにおいて病変は、ウイルスが続く大流行のために神経節に潜在的に感染するにつれて出現し消滅する。病変は、顔、生殖器、眼および/または手にありうる。一部の場合において、感染は脳炎も起こすことができる。
ヒトTリンパ向性ウイルス(HTLV−1、HTLV−2)は性的接触、授乳、または汚染血液への暴露を介して伝達される。ウイルスはTH細胞(Th1細胞と呼ばれる)のサブセットを活性化し、それらの過剰増殖およびTh1関連サイトカイン(例、IFN−γおよびTNF−α)の過剰産生をもたらす。これは、次に、Th2リンパ球の抑制およびTh2サイトカイン産生(例、IL−4、IL−5、IL−10、およびIL−13)の低下をもたらし、クリアランスのためにTh2依存性応答を必要とする侵入生物に対する適切な免疫応答を高める感染宿主の能力における低下を起こす(例、寄生虫感染、粘膜抗体および液性抗体の産生)。
ヒトパピローマウイルス(HPV)は主にケラチノサイトに影響を与え、2つの形態で生じる:皮膚および生殖器。伝達は、直接接触および/または性的活動を通じて生じると考えられる。皮膚および生殖器の両方のHPV感染は、疣贅および潜在的感染および時には再発性感染をもたらしうるが、それらは症状を制御し、疣贅の出現を遮断するが、しかし、感染を他に伝達することが可能である宿主を残す宿主免疫により制御される。
真菌感染、または真菌症は、一次感染または内因性微生物叢による免疫系低下を伴う宿主での日和見コロニー形成をもたらす。真菌症に対する免疫は主に細胞性であり、好中球、マクロファージ、リンパ球、および恐らくはナチュラルキラー(NK)細胞を含む。真菌症は、典型的に、抗体および補体による直接的な殺傷に感受性ではない。一次感染に起因する全身の非侵襲性真菌症は、ブラストミセス症、コクシジオイデス症(coccidioiodomycosis)、ヒストプラスマ症、およびパラコクシジオイデス症を含む。真菌感染に起因する慢性感染のために、本発明の抗PD−L1抗体を、これらの真菌症のための従来から公知の処置のいずれかの前に、それと同時に、またはそれに続いて投与してもよい。
寄生虫障害(例えばマラリア、住血吸虫症、およびレーシュマニア症など)に起因する疾患が、開発途上国において最も流行しており、重要な健康問題になっている。これらの疾患は特定の攻撃を引き起こす。なぜなら、それらは以下を含む種々の手段を通じて宿主免疫を回避しうるからである:1)宿主細胞内での生存(例、リーシュマニア属)、2)迅速に変化する表面抗原(例、トリパノソーマ)、および3)宿主抗原を提示することによりそれら自身を宿主細胞として「偽る」(例、住血吸虫症)。癌の処置における臓器移植と併用した免疫抑制薬物の使用、ならびにAIDの世界的な罹患率は、プラスモジウム属、トキソプラズマ属、リーシュマニア属、クリプトスポリジウム属、トリパノソーマ属、および蠕虫からの潜在的または無症状性感染を復活させることができる。
ワクチン接種または疾患に対して免疫を誘導するための抗原材料の投与を定期的に使用し、病原体による感染の効果を妨げる、または改善する。宿主免疫の増強は、感染性の病原体だけでなく、罹患した(例、癌性)宿主組織でも見出される非所望の抗原に使用することができる。従来、ワクチンは、弱められたまたは死んだ病原体の全体に由来するが、しかし、それらは、また、ヒトのクラスIまたはクラスII主要組織適合複合体(MHC)分子により特異的に認識されるインタクトな病原体上のペプチド提示エピトープでありうる。特定の目的のペプチド抗原は、T細胞により特異的に認識されるものである。
本発明の医薬的組成物の投与量および所望の濃度は、想定される特定の使用に依存して変動しうる。適切な投与量または投与経路の決定は、当業者の能力の十分に範囲内である。動物実験は、ヒトの治療のための有効量の決定のための信頼できるガイダンスを提供する。有効量の種間スケーリングは、Mordenti, J. and Chappell, W. "The Use of Interspecies Scaling in Toxicokinetics," In Toxicokinetics and New Drug Development, Yacobi et al., Eds, Pergamon Press, New York 1989, pp.42-46に定められる原理に従って実施することができる。
本発明の製剤は、限定はされないが、再構成された液体製剤を含み、抗PD−L1抗体を用いた処置を必要とする哺乳動物、好ましくはヒトへ、公知の方法に従って(例えばボーラスとしての静脈内投与、あるいはある期間にわたる持続的注入により、筋肉内、腹腔内、脳脊髄内、皮下、関節内、滑液内、髄腔内、経口、局所、または吸入経路により)投与される。
本発明の別の実施態様において、製造品が提供され、それは製剤を含む、好ましくはその使用のための説明書を提供する。製造品は容器を含む。適した容器は、例えば、ボトル、バイアル(例、二重チェンバーバイアル)、シリンジ(例えば一重または二重チェンバーシリンジなど)、および試験管を含む。容器は、種々の材料(例えばガラスまたはプラスチックなど)から形成されうる。容器は製剤を保持する。容器上にある、またはそれに関連するラベルは、再構成および/または使用のための指示を示しうる。ラベルは、さらに、製剤が皮下投与のために、および/またはT細胞機能障害性障害の処置のために有用である、または意図されることを示しうる。製剤を保持する容器は、再構成製剤の反復投与(例、2〜6回投与)を可能にする複数回使用バイアルでありうる。製造品は、さらに、適した希釈剤(例、BWFI)を含む第2の容器を含みうる。希釈剤および凍結乾燥製剤の混合時、再構成製剤中の最終的なタンパク質濃度は、一般的に、少なくとも50mg/mlでありうる。製造品は、さらに、市販のユーザーの見地から望ましい他の材料を含みうる(他の緩衝剤、希釈剤、フィルター、針、シリンジ、および添付文書(使用説明書を伴う)を含む)。
ファージライブラリーにおける抗PD−L1抗体の同定
抗PD−L1抗体を同定するためのライブラリー選別およびスクリーニング
ヒト(R&D Systems,cat# 156-B7)およびマウス(R&D Systems,cat# 1019-B7)PD−L1−Fc融合体を、代替ライブラリー選別のための抗原として使した。具体的には、ファージライブラリーを、最初にヒト抗原、続く3ラウンドにおいてマウス、ヒト、およびマウス抗原に対して選別した。Nunc 96 well Maxisorp(登録商標)を標的タンパク質(10μg/ml)と4℃で一晩コートし、室温で1時間にわたりファージブロッキングバッファーPBST(リン酸緩衝食塩水(PBS)および1%(w/v)ウシ血清アルブミン(BSA)および0.05%(v/v)tween-20)を用いてブロックした。抗体ファージライブラリーVH(例、Lee et al., J. Immunol. Meth. 284: 119-132, 2004を参照のこと)およびVH/VL(Liang et al., J. Mol. Biol .366: 815-829, 2007を参照のこと)を別々に抗原プレートに加え、室温で一晩インキュベートした。次の日、抗原コートされたプレートをPBT(0.05% Tween-20を伴うPBS)を用いて10回洗浄し、結合したファージを50mM HClおよび500mM NaClを用いて30分間にわたり溶出し、等容積の1M Trisベース(pH7.5)を用いて中和した。回収したファージをE.coli XL−1 Blue細胞において増幅させた。続く選択ラウンドの間、抗原コートプレートを用いた抗体ファージのインキュベーションを2〜3時間に低下させ、プレート洗浄のストリンジェンシーを徐々に増加させた。
ファージミドpW0703(ファージミドpV0350−2b(Lee et al., J. Mol.Biol 340: 1073-1093 (2004))に由来し、全てのCDR−L3位置に終始コドン(TAA)を含み、M13バクテリオファージの表面上に一価Fabを提示する)は、親和性成熟のためにVHライブラリーからの目的のクローンの重鎖可変ドメイン(VH)を移植するためのライブラリーテンプレートとしての役割を果たした。ハードおよびソフトの両方のランダム化戦略を親和性成熟のために使用した。ハードなランダム化のために、3つの軽鎖CDRの選択された位置を伴う1つの軽鎖ライブラリーを、天然ヒト抗体を模倣するように設計されたアミノ酸を使用してランダム化し、設計されたDNA縮重はLee et al.(J. Mol. Biol 340, 1073-1093 (2004)に記載された。ソフトなランダム化のために、CDR−L3の位置91〜94、および96、CDR−H1の28〜31および34〜35、CDR−H2の50、52、および53〜58、CDR−H3の95〜99および100Aを標的化した;ならびに、CDRループ(L3/H1/H2およびL3/H3)の2つの異なる組み合わせをランダム化のために選択した。ソフトなランダム化条件(それにより選択された位置での約50%の突然変異率が産生された)を達成するために、突然変異DNAを、野生型ヌクレオチドを支持する塩基の70−10−10−10混合物を用いて合成した(Gallop et al., Journal of Medicinal Chemistry 37:1233-1251 (1994))。
以前に同定されたファージクローンを、第1ラウンドのためのプレート選別に供し、5または6ラウンドの溶液選別が続いた。ライブラリーを、ヒトおよびマウスPD−L1−Fcに対してそれぞれ選別した(R&D Systems、それぞれcat.#156−B7、cat #1019−B7)。ヒトPD−L1−Fcのために、第1ラウンドのプレート選別で、3つのライブラリーを、標的コートプレート(NUNC Maxisorp(登録商標)プレート)に対して、1% BSAおよび0.05% Tween-20中のファージインプット(約3 O.D./ml)を別々に用いて、2時間にわたり室温で選別した。第1ラウンドのプレート選別後、溶液選別を実施し、選択のストリンジェンシーを増加した。溶液選別のために、第1ラウンドのプレート選別から増殖させた1 O.D./mlファージを、1% Superblock(Pierce Biotechnology)および0.05% Tween-20を含む100μL緩衝液中で20nmビオチン化標的タンパク質(濃度は、親クローンファージのIC50値に基づく)を用いて、30分間にわたり室温でインキュベートした。混合物を、さらに、1% Superblockを用いて10×希釈し、100μL/ウェルをニュートラアビジンコートされたウェル(5μg/ml)に、15分間にわたり室温で、穏やかに撹拌しながら(ビオチン化標的がファージに結合するように)適用した。ウェルをPBS−0.05% Tween-20を用いて10×洗浄した。バックグラウンド結合を決定するために、ビオチン化されなかった標的を伴うファージを含むコントロールウェルを、ニュートラアビジンコートされたプレート上で捕捉した。結合したファージを0.1N HClを用いて20分間にわたり溶出させ、1/10容積の1M Tris pH−11により中和し、滴定し、次のラウンドために増殖させた。次に、5を上回るラウンドの溶液選別を、増加する選択ストリンジェンシーの2つの方法を一緒に用いて行った。その第1は、ビオチン化標的タンパク質濃度を減少させる(4nMから0.5nMまで)ことによるオンレート選択のためであり、その第2は、過剰量の非ビオチン化標的タンパク質(100〜2000倍以上)を加え、弱い結合剤を室温または37℃のいずれかで競合除去することによるオフレート選択のためである。また、ファージインプットをより低いバックグラウンドファージ結合まで減少させた(0.1〜0.5O.D/ml)。マウスPD−L1−Fc標的について、ファージ選別方法は、ヒトPD−L1 Fc抗原について上で記載されるものと類似であり、少数の改変を伴う。具体的には、100nmビオチン化マウスPD−L1−Fcを、第1ラウンドのプレートパニングの直後に溶液パニングのために使用した。4回の続くラウンドの溶液パニングにおいて、ビオチン化標的を10nMから1nMまで低下させ、200〜500倍過剰の非ビオチン化標的を室温で加えた。
コロニーを、それぞれヒトおよびマウスのPD−L1標的についての7回目および6回目のラウンドのスクリーニングから選んだ。コロニーを、一晩37℃で、96ウェルプレート(Falcon)において150μL/ウェルの2YT培地(50μg/mlカルベニシリンおよび1E10/ml KO7)中で増殖させた。同じプレートから、親ファージの感染したXL−1コロニーをコントロールとして選んだ。96-well Nunc Maxisorp(登録商標)プレートを、PBS中の100μL/ウェルのヒトおよびマウスPD−L1−Fcタンパク質(2μg/ml)を別々に用いて、4℃で一晩または室温で2時間にわたりコートした。プレートを、65μLの1% BSAを用いて30分間にわたり、そして40μLの1% Tween-20を用いて別の30分間にわたりブロックした。
OD450nm低下(%)=[(競争相手を伴うウェルのOD450nm)/(競争相手を伴わないウェルのOD450nm)]×100
hPD−1−Fc、hPD−L1−Fc、hB7.1−Fc、mPD−1−Fc、mPD−L1−Fc、およびmB7.1をR & D Systemsから購入した。hPD−L1発現293細胞を、Genentechで、従来の技術を使用して生成した。F(ab’)2ヤギ抗ヒトIgG FcをJackson ImmunoResearch Laboratoriesから購入した。
PD−1−FcおよびB7.1−Fcタンパク質を、 EZ−Link sulfo−NHS−LC−LC−ビオチン(Pierce)を用いて30分間にわたり室温で、製造業者により記載される通りにビオチン化した。過剰の未反応ビオチンを、Quick Spin High Capacity Columns, G50-Sephadex(Roche)を用いて、製造業者により記載される通りに除去した。
hPD−L1発現293細胞へのhPD−1−Fcの結合の50%阻害(IC50)をもたらす抗体濃度を、電気化学発光(ECL)細胞結合アッセイにより測定した。hPD−L1発現293細胞を、リン酸緩衝食塩水(PBS)を用いて洗浄し、96ウェルHigh Bindプレート(Meso Scale Discovery)で25μLのPBS中に1ウェル当たり25,000個の細胞を播種した。プレートを室温でインキュベートし、細胞が、プレートのカーボン表面に付着することを可能にする。25μLの30% FBSを各ウェルに加え、プレートを30分間にわたり軽く撹拌しながらインキュベートし、非特異的結合部位をブロックする。プレートを3回、PBSを用いて、ELISAマイクロプレートウォッシャー(ELx405 Select, Bio-Tek Instruments)で、穏やかな分注および吸引条件下で洗浄する。ウェル中の過剰なPBSを、プレートをペーパータオル上で吸い取ることにより除去する。12.5μLの2×濃度の抗体を、PBS中の3%FBS(アッセイ緩衝液)中の各ウェルに、続いてアッセイ緩衝液中の12.5μLの4μg/ml(2×濃度)のhPD−1ビオチンを加え、プレートを1時間にわたり軽く撹拌しながらインキュベートする。プレートを、PBSを用いてマイクロプレートウォッシャーで3回洗浄し、プレートをペーパータオル上で吸い取る。25μLの2μg/mlのストレプトアビジン−ルテニウム(Meso Scale Discovery)を加え、アッセイ緩衝液中で、室温で30分間にわたり穏やかに撹拌しながらインキュベートする。PBSを用いてマイクロプレートウォッシャーで3回洗浄し、プレートをペーパータオル上で吸い取る。サーファクタントを伴わない150μLの1×MSD Read Buffer(Meso Scale Discovery)を加える。放出されたルミネセンス光をSector Imager 6000リーダー(Meso Scale Discovery)で、620nmで読み取る。ECL値を、アッセイにおいて使用されるテスト抗体の濃度を用いて、4パラメーターの非線形最小二乗法を使用して分析し、アッセイにおける各競合相手のIC50値を得た。
ヒトおよびマウスの両方のPD−L1に結合した、YW243.55に由来する15の固有ファージ抗体を選び、さらなる評価のために全長IgG1抗体に再フォーマットした。これらの抗体の軽鎖および重鎖可変領域配列を、図11AおよびBに報告する。
抗PD−L1抗体の特徴付け(BIAcore)
組換えヒトおよびマウスPD−L1に対する抗PD−L1ファージ抗体YW243.55およびYW243.55S70の結合親和性を、表面プラズモン共鳴(SRP)によりBIAcore(商標)−3000機器を使用して測定した。組換えヒトPD−L1−Fc(R&D Systems、cat#156−B7)および組換えマウスPD−L1−Fc(R&D Systems、cat#1019−B7)を、CM5バイオセンサーチップ上に直接コートし、約500応答単位(RU)を達成した。動態測定のために、2倍連続希釈物(3.9nm〜500nm)を、PBT緩衝液(0.05% Tween-20を伴うPBS)中で、25℃で、流速30μL/分で注射した。会合速度(kon)および解離速度(koff)を、簡単な1対1のLangmuir結合モデル(BIAcore Evaluation Softwareバージョン3.2)を使用して算出する。平衡解離定数(kD)を比率koff/konとして算出する。
ヒト、アカゲザル、およびマウスのPD−L1についての抗PD−L1 Abの特異性−FACSおよび放射性リガンド細胞結合アッセイ
この実施例は、ヒト、アカゲザル、およびマウスのPD−L1についての本発明の抗PD−L1抗体についての特異性を示す。また、それは、トランスフェクションされた293細胞上の細胞膜で発現されたマウスおよびヒトのPD−L1についてのAbの親和性を示す。
ヒトおよびマウスのPD−L1に対する抗PD−L1 Abの親和性測定−平衡結合放射性リガンド細胞結合アッセイ
ヒトまたはマウスのPD−L1を用いてトランスフェクションされた293細胞を増殖培地(10%ウシ胎仔血清(FBS)、2mM L−グルタミン、1×ペニシリン−ストレプトマイシンを添加したRPMI 1640培地からなる)中で、37℃で5% CO2において培養した。細胞を結合緩衝液(2% FBSおよび50mM Hepes,pH7.2を伴う50:50 DMEM/F12)を用いて洗浄し、96ウェルプレート中に、0.2mLの結合緩衝液中に約230,000個の細胞でプレーティングした。抗PD−L1抗体YW243.55.S70.hIgGを、Iodogen方法を使用してヨード化した。放射標識された抗PD−L1抗体を、遊離125I−NAから、ゲルろ過により、NAP−5カラムを使用して精製した;精製されたAbは17.41μCi/μgの比放射能を有した。一定濃度のヨード化抗体および減少濃度の連続希釈された非標識抗体を含む50μL容積の競合反応混合物を、96ウェルプレート中に置いた。ヒトPD−L1およびマウスPD−L1を発現する293安定的トランスフェクタント細胞株を、増殖培地(10%ウシ胎仔血清(FBS)、2mM L−グルタミン、1×ペニシリン−ストレプトマイシンを添加した50:50 DMEM/F12培地からなる)中で、37℃で5% CO2において培養した。細胞を結合緩衝液(2% FBS、50mM Hepes,pH7.2、および2mMアジ化ナトリウムを伴う50:50 DMEM/F12)を用いて洗浄し、50μLの競合反応混合物に、0.2mLの結合緩衝液中の約200,000個の細胞密度で加えた。細胞を伴う各競合反応におけるヨード化抗体の最終濃度は〜150pM(〜120,000cpm/0.25mL)であり、細胞を伴う競合反応における非標識抗体の最終濃度は変動し、500nMで開始し、次に10濃度について2倍ずつ減少した。細胞を伴う競合反応物を2時間にわたり室温でインキュベートした。非標識抗体の各濃度についての細胞を伴う競合反応物を3通りにアッセイした。2時間のインキュベーション後、競合反応物をMillipore Multiscreenフィルタープレートに移し、結合緩衝液を用いて4回洗浄し、結合ヨード化抗体から遊離物を分離した。フィルターをWallac Wizard 1470ガンマカウンター(PerkinElmer Life and Analytical Sciences Inc.Wellesley, MA)でカウントした。結合データを、NewLigandソフトウェア(Genentech)を使用して評価し、それはMunsonおよびRobardの適合アルゴリズムを使用し、抗体の結合親和性を決定する。Musson et al., Anal. Biochem. 107: 220-39 (1980)。
抗PD−L1 Abの選択性および親和性(IC 50 )
この実施例は、PD−1およびB7.1の両方に対するPD−L1の結合を遮断するためのその能力について本発明の全長抗PD−L1抗体を評価するために使用される結合選択性および親和性(IC50として)を示す。
hPD−L1−Fc ELISAに対するhB7.1−Fc−ビオチンおよびhPD−1−Fc−ビオチン結合(フォーマット4):
Nunc Maxisorp 384ウェルプレートを、PBS中の25μLの250ng/ml hPD−L1−Fcを用いてコートした。ウェルをPBS中の0.05% Tween(洗浄緩衝液)を用いてマイクロプレートウォッシャーで3回洗浄し、ウェルをPBS中の0.5% BSAを用いてブロックする。12.5μLの2×濃度の抗体を、各ウェルへ、PBS中の0.05% Tween、0.5% BSA(アッセイ希釈剤)中に、続いてアッセイ希釈剤中の12.5μLの250ng/ml(2×濃度)のhB7.1−Fc−ビオチンを加え、プレートを1時間半にわたり撹拌しながらインキュベートする。ウェルを、洗浄緩衝液を用いて6回洗浄し、25μLのストレプトアビジン−HRP(アッセイ希釈剤中の1:40,000、GE Healthcare)を加える。プレートを30分間にわたり撹拌しながらインキュベートし、洗浄緩衝液を用いて6回洗浄する。25μLのTMB基質(Kirkegaard and Perry Laboratories)を1時間にわたり加え、反応を25μLの1Mリン酸を用いて停止する。吸光度を450nmで読み、IC50値を、実施例1におけるECL細胞結合アッセイの下に記載される通りに分析する。
hPD−L1−FcへのhPD−1−Fc−ビオチン結合(フォーマット5)のために、フォーマットは、hPD−1−Fc−ビオチンがhB7.1−Fc−ビオチンの代わりに結合のために使用されたことを除き、上のアッセイと類似している。TMB基質の反応時間は17分であった。
指定された結合対の間での相互作用を遮断するための親和性成熟ファージ抗PD−L1抗体YW243.55.S70のIC50の評価を、表4に報告する。YW243.55S70は、hB7.1 FcへのヒトPD−L1の結合を遮断することができた(半最高阻害濃度は38pMであり、PD−L1/PD−1相互作用を遮断するためのそのIC50値(42pM)と比較的同程度の濃度である)。PD−L1とPD−1およびB7.1の両方との相互作用を遮断するためのYW243.55S70の能力を測定するBiacore試験は、これらのELISAでの結果と一致した(データ示さず)。
抗PD−L1抗体YW243.55.S70 PMEL/B16in vitroアッセイによるin vitroでのCD4+およびCD8+T細胞活性の増強
この実施例は、PMEL T細胞受容体トランスジェニックCD8+T細胞の活性化時での本発明の抗PD−L1抗体の効果を示す(メラノサイトペプチドgp100に応答したγ−IFN産生の増強により測定)。この手順において、CD8+T細胞が、CD8+T細胞がgp100ペプチドに特異的なTCRを発現するPMEL TCRトランスジェニックマウスから得られる。CD8+T細胞の精製に続き、複数回ラウンドの刺激を実施し、活性化CD8+T細胞を生成および増殖し、それは次にPD−1発現をアップレギュレーションする。並行して、B16メラノーマ細胞をIFN−γを用いて処置し、それらのPD−L1発現をアップレギュレーションする。次に、細胞を、抗PD−L1抗体の存在において同時培養し、IFN−γ産生に対する効果を評価する。B16細胞を三次刺激のために選んだ。なぜなら、それらは、低レベルのgp100ペプチドを内因性に発現するからである(ペプチドの外因性適用と反対)。さらに、これらの細胞が、また、PD−L2、B7.1、またはB7.2を発現しないため、PD−L1と無関係である追加シグナル伝達(例、PD−1を通じたCD28またはCTLA−4またはPD−L2誘導性シグナル伝達を通じたシグナル伝達)の効果が最小限になる。
図3に示す通り、抗PD−L1抗体は、IFN−γ産生PMEL CD8+T細胞のパーセンテージおよび指定量のgp100ペプチドに応答して産生されるIFN−γの平均レベルの両方を増強する。
Ova特異的TCR Tg CD4+T細胞を利用した同様のアッセイでは、PD−1の発現を誘導するためのOvaペプチドを用いた事前の刺激に続き、抗PD−L1 Abの存在における増強されたT細胞増殖が示される(図4)。最終刺激において、PD−L1を発現する照射A20 B細胞を使用し、DO.11.10 T細胞に対して指定濃度のOvaペプチドを提示した。とりわけ、PD−1/PD−L1軸の寄与が、より低い程度(生理学的に関連する大きさの刺激をより厳密に反映するレベル)の抗原受容体刺激でより顕著である。
PMELアッセイ
一次刺激(0〜4日目)
脾臓および腸間膜リンパ節をPMELトランスジェニックT細胞受容体マウスから収集した。臓器を単一の細胞懸濁液中に粉砕し、赤血球を溶解させた。CD8+T細胞を、CD8+T細胞単離キットおよびAutoMACSセルセパレーター(Miltenyi Biotec)を使用して、製造業者の指示の通りに単離した。
PMEL培養物をスピンダウンし、培地を、マルチチャネルピペットを使用して吸引した。新鮮培地を加え、混合して細胞を洗浄し、別のスピンが続いた。大部分の培地を除去し、抗体(Herceptin(登録商標)、YW243.55.S70、またはなし)を、最終濃度10μg/mlで加えた。条件を2通りのウェルにおいて設定し、平均IFN−γ産生をエンドポイントで評価できるようにした。
6日目の三次刺激の1日前に、B16メラノーマ細胞を、20ng/mlのマウスIFN−γ(R&D Systems)を用いて一晩インキュベートし、それらのPD−L1発現をアップレギュレーションした。
Golgi-Plug(BD Biosciences)を、培養の最後の5時間にわたり、製造業者の指示の通りに加えた。IFN−γ細胞内染色を、BD Biosciences Cytofix/Cytoperm Fixation/Permeabilization Solutionキットを使用して、製造業者の指示の通りに行い、全ての染色抗体もBD Biosciencesからであった。細胞を、CD8a PEおよびThy1.1 FITCを用いて表面染色し、飽和濃度のIFN−γ APCを用いて細胞内染色した。
DO11.10トランスジェニックマウスからの脾臓および腸間膜リンパ節を収集し、単一の細胞懸濁液中に粉砕し、赤血球を溶解させた。細胞を、72時間にわたり、6ウェルプレートにおいて密度1×106個細胞/mlで、Ovaペプチド(0.3μM)を用いて培養した。培養液は、RPMI 1640+10%ウシ胎仔血清+20μM HEPES、およびGibcoからの以下の添加剤の1:100希釈物:Gluta-MAX、ピルビン酸ナトリウム、ペニシリン/ストレプトマイシン、および非必須アミノ酸であった。
抗PD−L1による混合リンパ球反応におけるヒトCD8+T細胞の増強された増殖
図5は、MHC不適合ドナーからの細胞に応答した、ヒトCD8 T細胞の増殖を増強する抗PD−L1(例、YW243.55.S1)の能力を実証する。応答性CD8+T細胞を、ドナーAの全血から、最初にCD8+T細胞RosetteSep(登録商標)(StemCell Technologies)を製造業者の指示の通りに使用して濃縮した。細胞を次に等容積のリン酸緩衝食塩水(PBS)により希釈し、Ficoll-Paque Plus(GE Healthcare)に重層することにより勾配遠心分離により分離した。分離後、細胞を、CD8 APC(BD Biosciences)を用いて染色し、78%のCD8+T細胞であることが見出された。細胞を、2.5μMのCFSEトレーサー染料(Molecular Probes)を用いて蛍光標識した。
LCMVin vivoモデルに対するPD−L1遮断の効果
慢性刺激の条件下のT細胞は、阻害的受容体PD−1の発現をアップレギュレーションし、維持することが示されている。その2つのリガンドPD−L1およびPD−L2のいずれかによるPD−1の連結は、慢性的に活性化されたT細胞の抵抗状態に寄与し、その同種抗原に対するその応答を減弱する。リンパ球性脈絡髄膜炎ウイルス(LCMV)に持続感染したマウスにおいて、PD−1またはそのリガンドPD−L1の遮断は、慢性的に抵抗性であるT細胞を再活性化するために十分であり、抗ウイルスT細胞応答の大きさおよび機能的な質を増強する。同様に、HIVまたはHCVに慢性的に感染されたヒトは、その活性がPD−1またはPD−L1の遮断によりin vitroで増強されうる刺激に対して抵抗性であるT細胞を示す。従って、LCMVモデルにおけるPD−L1遮断の活性は、抗ウイルスおよび抗腫瘍免疫を増強するための治療的な潜在能力を示唆する。
LCMV gp33ペプチドに応答したCD8 T細胞による%IFNガンマ産生の決定
脾臓を感染マウスから単離し、単一の細胞懸濁液を、完全培地:IMDM(Invitrogen Inc., Carlsbad, CA)(10%熱不活化ウシ胎児血清、2mM L−グルタミン、100U/mlペニシリン/ストレプトマイシン、および10mM 2−メルカプトエタノールを含む)中で臓器を破砕することにより生成した。赤血球を、ACK溶解緩衝液(0.15M NH4Cl、10mM KHCO3、0.1mM EDTA)を使用して溶解した。抗原特異的CD8 T細胞応答を測定するために、脾細胞を完全培地中で洗浄し、LCMVペプチドGP33(KAVYNFATC, ProImmune Inc., Bradenton, FL)を用いて4時間にわたりin vitroで再刺激した。1×106個の脾細胞を96ウェル平底プレート中で100ng/mlのGP33ペプチドを用いて100単位/mlのヒトインターロイキン2(Sigma-Aldrich, St. Louis, MO)、1μL/mlのブレフェルジンA、および1μL/ml(1:1000希釈)のモネンシン(BD pharmingen)および抗CD107a FITC(クローンID4B, BD Biosciences, San Jose, CA)の存在において培養した。インキュベーション後、細胞を、2%ウシ胎児血清を含むPBS中で1回洗浄し、細胞表面マーカーを、蛍光色素抱合抗体を使用して染色した:抗CD8 APC(クローン53.67、BD Biosciences, San Jose, CA)、抗CD4 PerCp−Cy5.5(クローンRM4−5,BD Biosciences, San Jose, CA)、および抗PD−1 PE(クローンJ43、BD Biosciences, San Jose, CA)。細胞内IFN−γについての染色を、Cytofix Cytoperm Plusキット(BD Biosciences, San Jose, CA)を使用し、製造業者の指示に従い、抗IFN−γ PE−Cy7(クローンXMG1.2,eBioscience Inc. San Diego, CA)を使用して行った。GP33特異的CD8 T細胞の数を検出し、新鮮脾細胞をGP33五量体(APCに連結されたH2−Db,ProImmune Inc., Bradenton, FL)を用いて、製造業者の指示に従って染色した。データを、BD FACSAria(BD Biosciences, San Jose, CA)を使用して収集し、FlowJo Software(Tree Star Inc. Ashland OR)を用いて分析した。
MC57線維肉腫細胞を、完全IMDM中のLCMV含有血液または組織ホモジネートの10倍連続希釈物を用いて感染させる。反応物を、次に、組織培養インキュベーターにおいて37℃で2〜6時間にわたりインキュベートし、次に1%メチルセルロースを含むDMEMを用いて重層する。これには3〜5日間にわたるインキュベーションが続き、次に、メチルセルロース層を吸引により除去する。細胞をPBS/4%パラホルムアルデヒドを用いて固定し、次に0.5% Triton-xを用いて20分間にわたり透過性化し、PBS中で洗浄し、次に10% FCS中で1時間にわたり軽く揺らしながらブロックする。LCMVについての染色を、VL4抗体を用いて行い(1時間)、2回洗浄し、次にブロッキング緩衝液中の抗ラットHRP(1:400)を用いて現像する。これには3回の洗浄が続き、次にo−フェニレンジアミン基質(SIGMA P8806-50TAB 3mg/錠)をウェルに加えて現像する。
癌におけるPD−L1遮断
現在、多くの腫瘍が、PD−1リガンドの発現を、抗腫瘍T細胞応答を減弱させるための手段として利用することが明らかである。いくつかのヒトの癌が、腫瘍および腫瘍浸潤白血球の両方で上昇レベルのPD−L1を発現すると特徴付けられており、この上昇したPD−L1発現は、しばしば、より悪い予後と関連する。マウス腫瘍モデルでは、腫瘍内のPD−L1発現における類似の増加が実証され、腫瘍免疫を阻害する際でのPD−1/PD−L1経路についての役割が実証される。
グループ2:抗PD−L1抗体、10mg/kg IP、100μL、1日目、3×/週
グループ3:抗gp120抗体、10mg/kg IP、100μL、14日目、3×/週
グループ4:抗PD−L1抗体、10mg/kg IP、100μL、14日目、3×/週
グループ5:抗CTLA−4抗体、10mg/kg IP、100μL、14日目、3×/週
***グループ1および2は1日目に;グループ3、4、および5は14日目に投与を開始した。
抗腫瘍効果を提供するための他の薬剤との抗PD−L1の組み合わせまたは免疫増強治療−MC38.Ovaモデル
0日目に、150匹の動物に、100マイクロリットルのHBSS+matrigel中の0.5百万個のMC38.Ova細胞を用いて皮下接種した。マウスで腫瘍を増殖させる。マウスを体重測定し、11日目まで2×/週で測定した(腫瘍容積が100〜200mm3である場合)。11日目に、腫瘍測定に続き、マウスを以下の12処置群の1つに補充する。異なる腫瘍容積のために以下の処置群に補充されなかったマウスは、安楽死させる。ゲムシタビン(グループ4)処置は12日目に開始され、残りの抗体群のための処置は14日目に開始される。全容積は不活性賦形剤中で100μLであり、追加の詳細が以下に報告される:
グループ2:抗PD−L1抗体、10mg/kg IP、100μL、3×/週×5、n=10
グループ3:抗VEGF抗体、5mg/kg IP、100μL、2×/週×5、n=10
グループ4:ゲムシタビン、40mg/kg IP、100μL、12、16、20日目、n=10
グループ5:抗PD−L1抗体 + 抗gp120抗体、n=10
グループ6:抗PD−L1抗体 + 抗VEGF抗体、n=10
グループ7:抗PD−L1抗体 + ゲムシタビン、n=10
グループ8:抗gp120抗体 + ゲムシタビン、n=10
グループ9:抗gp120抗体 + 抗VEGF、n=10
14日目および22日目:グループ4からのマウスを、CBC分析のために、麻酔下で眼窩後から出血させた(100マイクロリットル)。
19日目:全てのマウス(グループ4を除く)を、CBC分析のために、麻酔下で眼窩後から出血させた(100マイクロリットル)。
26日目:全てのマウス(グループ4を除く)を、PK分析のために、麻酔下で眼窩後から出血させた(100マイクロリットル)。
哺乳動物細胞における抗PD−L1抗体の発現
この実施例は、哺乳動物細胞における組換え発現による、潜在的なグリコシル化形態の抗PD−L1抗体の調製を例示する。
E.coliにおける抗PD−L1抗体の発現
この実施例は、E.coliにおける組換え発現による非グリコシル化形態の抗PD−L1抗体の調製を例示する。
Claims (18)
- 抗PD−L1抗体またはその抗原結合性フラグメントの軽鎖および重鎖可変領域をコードする単離された核酸であって、それにおいて:
(a)重鎖可変領域が、配列GFTFSDSWIH(配列番号15)、AWISPYGGSTYYADSVKG(配列番号16)、およびRHWPGGFDY(配列番号3)をそれぞれ有するHVR−H1、HVR−H2、およびHVR−H3配列を含み、かつ
(b)軽鎖可変領域が、配列RASQDVSTAVA(配列番号17)、SASFLYS(配列番号18)、およびQQYLYHPAT(配列番号19)をそれぞれ有するHVR−L1、HVR−L2、およびHVR−L3配列を含み、
重鎖可変領域アミノ酸配列が、配列番号20の重鎖可変領域アミノ酸配列と少なくとも95%の配列同一性を有し、軽鎖可変領域アミノ酸配列が、配列番号21の軽鎖可変領域アミノ酸配列と少なくとも95%の配列同一性を有する、単離された核酸。 - 軽鎖可変領域アミノ酸配列が、配列番号21の軽鎖可変領域アミノ酸配列と少なくとも99%の配列同一性を有する、請求項1記載の核酸。
- 重鎖可変領域アミノ酸配列が、配列番号20の重鎖可変領域アミノ酸配列と少なくとも99%の配列同一性を有する、請求項1記載の核酸。
- 軽鎖可変領域アミノ酸配列が、配列番号21の軽鎖可変領域アミノ酸配列と少なくとも99%の配列同一性を有し、重鎖可変領域アミノ酸配列が、配列番号20の重鎖可変領域アミノ酸配列と少なくとも99%の配列同一性を有する、請求項1記載の核酸。
- 抗PD−L1抗体が、マウス抗体に由来する定常領域を含む、請求項1記載の核酸。
- 抗PD−L1抗体がヒト抗体に由来する定常領域を含む、請求項1記載の核酸。
- 定常領域が、IgG1である、請求項6記載の核酸。
- 抗PD−L1抗体が、低下したまたは最小のエフェクター機能を有する、請求項7記載の核酸。
- 最小のエフェクター機能が、エフェクターなしFc突然変異に起因する、請求項8記載の核酸。
- エフェクターなしFc突然変異が、N297Aである、請求項9記載の核酸。
- 請求項1〜10のいずれか1項記載の核酸を含むベクター。
- 請求項11記載のベクターを含む宿主細胞。
- 真核生物である請求項12記載の宿主細胞。
- 哺乳動物である請求項13記載の宿主細胞。
- チャイニーズハムスター卵巣(CHO)細胞である請求項14記載の宿主細胞。
- 原核生物である請求項12記載の宿主細胞。
- E.coliである請求項16記載の宿主細胞。
- 請求項12〜17のいずれか1項記載の宿主細胞を、抗PD−L1抗体またはその抗原結合性フラグメントをコードするベクターの発現のために適した条件下で培養すること、およびその抗体または抗原結合性フラグメントを回収することを含む、抗PD−L1抗体、又はその抗原結合性フラグメントを作製するためのプロセス。
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Families Citing this family (1491)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7030219B2 (en) | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
EP2277532A1 (en) | 2002-09-11 | 2011-01-26 | Genentech, Inc. | Novel composition and methods for the treatment of immune related diseases |
ES2500921T3 (es) | 2003-04-29 | 2014-10-01 | Sarepta Therapeutics, Inc. | Composiciones para potenciar el transporte y la eficacia antisentido de análogos de ácidos nucleicos en células |
US8067571B2 (en) | 2005-07-13 | 2011-11-29 | Avi Biopharma, Inc. | Antibacterial antisense oligonucleotide and method |
US20100016215A1 (en) | 2007-06-29 | 2010-01-21 | Avi Biopharma, Inc. | Compound and method for treating myotonic dystrophy |
WO2009079592A2 (en) * | 2007-12-17 | 2009-06-25 | California Institute Of Technology | Modulating immune system development and function through microrna mir-146 |
ES2848323T3 (es) | 2008-01-31 | 2021-08-06 | Inst Nat Sante Rech Med | Anticuerpos contra CD39 humano y uso de los mismos para inhibir la actividad de las células T reguladoras |
WO2009114085A2 (en) | 2008-03-03 | 2009-09-17 | The University Of Miami | Allogeneic cancer cell-based immunotherapy |
CA3179151A1 (en) | 2008-04-09 | 2009-10-15 | Genentech, Inc. | Novel compositions and methods for the treatment of immune related diseases |
US9017660B2 (en) | 2009-11-11 | 2015-04-28 | Advaxis, Inc. | Compositions and methods for prevention of escape mutation in the treatment of Her2/neu over-expressing tumors |
JP5757863B2 (ja) | 2008-05-19 | 2015-08-05 | アドバクシス インコーポレイテッド | 異種抗原のための二重送達システム |
US9650639B2 (en) | 2008-05-19 | 2017-05-16 | Advaxis, Inc. | Dual delivery system for heterologous antigens |
PL2350129T3 (pl) | 2008-08-25 | 2015-12-31 | Amplimmune Inc | Kompozycje antagonistów PD-1 i sposoby stosowania |
US8268314B2 (en) | 2008-10-08 | 2012-09-18 | Hoffmann-La Roche Inc. | Bispecific anti-VEGF/anti-ANG-2 antibodies |
SG196798A1 (en) | 2008-12-09 | 2014-02-13 | Genentech Inc | Anti-pd-l1 antibodies and their use to enhance t-cell function |
WO2011041613A2 (en) | 2009-09-30 | 2011-04-07 | Memorial Sloan-Kettering Cancer Center | Combination immunotherapy for the treatment of cancer |
US8741591B2 (en) | 2009-10-09 | 2014-06-03 | The Research Foundation For The State University Of New York | pH-insensitive glucose indicator protein |
US10016617B2 (en) | 2009-11-11 | 2018-07-10 | The Trustees Of The University Of Pennsylvania | Combination immuno therapy and radiotherapy for the treatment of Her-2-positive cancers |
CA2778714C (en) * | 2009-11-24 | 2018-02-27 | Medimmune Limited | Targeted binding agents against b7-h1 |
EP2504028A4 (en) * | 2009-11-24 | 2014-04-09 | Amplimmune Inc | SIMULTANEOUS INHIBITION OF PD-L1 / PD-L2 |
CN102791738B (zh) | 2009-12-10 | 2015-10-07 | 霍夫曼-拉罗奇有限公司 | 优先结合人csf1r胞外域4的抗体及其用途 |
JP5894538B2 (ja) * | 2010-02-04 | 2016-03-30 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 炎症性ヒトTh17細胞の増殖および機能を決定的に調節するICOS |
CA3090304A1 (en) * | 2010-05-13 | 2011-11-17 | Sarepta Therapeutics, Inc. | Antisense modulation of interleukins 17 and 23 signaling |
EP2575818A4 (en) | 2010-06-03 | 2013-11-06 | Pharmacyclics Inc | USE OF INHIBITORS OF BRUTON TYROSINE KINASE (BTK) |
US9226958B2 (en) | 2010-10-01 | 2016-01-05 | University Of Georgia Research Foundation, Inc. | Use of Listeria vaccine vectors to reverse vaccine unresponsiveness in parasitically infected individuals |
AR083847A1 (es) | 2010-11-15 | 2013-03-27 | Novartis Ag | Variantes de fc (fragmento constante) silenciosas de los anticuerpos anti-cd40 |
EP3332804A1 (en) | 2011-03-11 | 2018-06-13 | Advaxis, Inc. | Listeria-based adjuvants |
WO2012149540A1 (en) | 2011-04-28 | 2012-11-01 | The Broad Institute Inc | Inhibitors of histone deacetylase |
US9161948B2 (en) | 2011-05-05 | 2015-10-20 | Sarepta Therapeutics, Inc. | Peptide oligonucleotide conjugates |
EP2709453B1 (en) * | 2011-05-16 | 2019-10-23 | Romark Laboratories, L.C. | Use of thiazolide compounds for the prevention and treatment of viral diseases, cancer and diseases caused by intracellular infections |
AU2016201747B2 (en) * | 2011-05-16 | 2017-06-01 | Romark Laboratories, L.C. | Use of thiazolide compounds for the prevention and treatment of viral diseases, cancer and diseases caused by intracellular infections |
EP2723380B1 (en) | 2011-06-24 | 2019-08-21 | Stephen D. Gillies | Light chain immunoglobulin fusion proteins and methods of use thereof |
CN107519486B (zh) * | 2011-06-24 | 2021-06-11 | 台北荣民总医院 | 于感染性与恶性疾病的治疗中提升免疫反应的方法 |
PL3409278T3 (pl) | 2011-07-21 | 2021-02-22 | Sumitomo Pharma Oncology, Inc. | Heterocykliczne inhibitory kinazy białkowej |
JP6238459B2 (ja) | 2011-08-01 | 2017-11-29 | ジェネンテック, インコーポレイテッド | Pd−1軸結合アンタゴニストとmek阻害剤を使用する癌の治療方法 |
PT2785375T (pt) * | 2011-11-28 | 2020-10-29 | Merck Patent Gmbh | Anticorpos anti-pd-l1 e usos destes |
WO2013102123A2 (en) * | 2011-12-28 | 2013-07-04 | Novelmed Therapeutics, Inc. | Aglycosylated human antibody and fusion protein and uses thereof |
EP2804619B1 (en) * | 2012-01-16 | 2021-10-13 | Atox Bio Ltd. | Reltecimod for treatment of bacterial infections |
CN104411327A (zh) | 2012-03-12 | 2015-03-11 | 阿德瓦希斯公司 | 李斯特菌疫苗治疗以后的抑制细胞功能抑制 |
US20140004131A1 (en) | 2012-05-04 | 2014-01-02 | Novartis Ag | Antibody formulation |
SG10201700698WA (en) | 2012-05-15 | 2017-02-27 | Bristol Myers Squibb Co | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
ES2742379T3 (es) | 2012-05-31 | 2020-02-14 | Hoffmann La Roche | Procedimientos de tratamiento del cáncer usando antagonistas de unión al eje de PD-1 y antagonistas de VEGF |
EP2854843A4 (en) | 2012-05-31 | 2016-06-01 | Sorrento Therapeutics Inc | ANTIGEN BINDING PROTEINS THAT BIND PD-L1 |
BR112014030812B1 (pt) | 2012-06-13 | 2022-11-08 | Incyte Holdings Corporation | Compostos tricíclicos substituídos como inibidores de fgfr, seus usos, composição farmacêutica e método para inibir uma enzima fgfr |
AR091649A1 (es) | 2012-07-02 | 2015-02-18 | Bristol Myers Squibb Co | Optimizacion de anticuerpos que se fijan al gen de activacion de linfocitos 3 (lag-3) y sus usos |
CN104428315B (zh) | 2012-07-13 | 2017-09-29 | 罗氏格黎卡特股份公司 | 双特异性抗‑vegf/抗‑ang‑2抗体及其在治疗眼血管疾病中的应用 |
JP6575950B2 (ja) | 2012-07-24 | 2019-09-18 | ファーマサイクリックス エルエルシー | Bruton型チロシンキナーゼ(Btk)阻害剤に対する耐性を伴う変異 |
EP2877444B1 (en) | 2012-07-27 | 2020-09-02 | The Broad Institute, Inc. | Inhibitors of histone deacetylase |
WO2014028502A1 (en) * | 2012-08-13 | 2014-02-20 | ImmunGene Inc. | Engineered antibody-interferon fusion molecules for treatment of autoimmune diseases |
CN114984062A (zh) | 2012-08-30 | 2022-09-02 | 安姆根有限公司 | 使用单纯疱疹病毒和免疫检查点抑制剂治疗黑色素瘤的方法 |
RS56624B1 (sr) | 2012-10-02 | 2018-03-30 | Bristol Myers Squibb Co | Kombinacija anti-kir antitela i anti-pd-1 antitela u lečenju kancera |
AU2013337277B2 (en) | 2012-11-05 | 2018-03-08 | Foundation Medicine, Inc. | Novel NTRK1 fusion molecules and uses thereof |
WO2014083178A1 (en) * | 2012-11-30 | 2014-06-05 | F. Hoffmann-La Roche Ag | Identification of patients in need of pd-l1 inhibitor cotherapy |
CA2896797A1 (en) | 2013-01-11 | 2014-07-17 | Dingfu Biotarget Co., Ltd | Agents for treating tumours, use and method thereof |
EP2945652B1 (en) | 2013-01-18 | 2021-07-07 | Foundation Medicine, Inc. | Methods of treating cholangiocarcinoma |
EP2950814A4 (en) | 2013-01-31 | 2016-06-08 | Univ Jefferson | PD-L1 AND PD-L2 BASED FUSION PROTEINS AND USES THEREOF |
EP3626741A1 (en) | 2013-02-20 | 2020-03-25 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using humanized anti-egfrviii chimeric antigen receptor |
US9573988B2 (en) | 2013-02-20 | 2017-02-21 | Novartis Ag | Effective targeting of primary human leukemia using anti-CD123 chimeric antigen receptor engineered T cells |
LT2964638T (lt) | 2013-03-06 | 2017-12-27 | Astrazeneca Ab | Epidermio augimo faktoriaus receptoriaus aktyvinančių mutacijų formų chinazolino inhibitoriai |
AR095363A1 (es) * | 2013-03-15 | 2015-10-14 | Genentech Inc | Biomarcadores y métodos para el tratamiento de condiciones relacionadas con pd-1 y pd-l1 |
KR20230070054A (ko) | 2013-03-15 | 2023-05-19 | 제넨테크, 인크. | Pd-1 및 pd-l1 관련 상태를 치료하기 위한 바이오마커 및 방법 |
UY35468A (es) | 2013-03-16 | 2014-10-31 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19 |
AU2014251087B2 (en) | 2013-04-09 | 2019-05-02 | Lixte Biotechnology, Inc. | Formulations of oxabicycloheptanes and oxabicycloheptenes |
MX2015014181A (es) | 2013-04-09 | 2016-05-24 | Boston Biomedical Inc | 2-acetilnafto [2,3-b]furano -4,9-diona para uso en el tratamiento del cáncer. |
SG10201708520YA (en) | 2013-04-19 | 2017-12-28 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
AR095882A1 (es) | 2013-04-22 | 2015-11-18 | Hoffmann La Roche | Terapia de combinación de anticuerpos contra csf-1r humano con un agonista de tlr9 |
WO2014195852A1 (en) | 2013-06-03 | 2014-12-11 | Glaxosmithkline Intellectual Property (No.2) Limited | Combinations of an anti-pd-l1 antibody and a mek inhibitor and/or a braf inhibitor |
EP3004877A4 (en) | 2013-06-06 | 2017-04-19 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification, assessment prevention, and treatment of cancer using pd-l1 isoforms |
CN103304638B (zh) * | 2013-07-08 | 2014-12-03 | 郑州大学 | 具有抗肿瘤活性的pd-l1亲和肽及其应用 |
US9873740B2 (en) * | 2013-07-16 | 2018-01-23 | Genentech, Inc. | Methods of treating cancer using PD-1 axis binding antagonists and TIGIT inhibitors |
CA2917858A1 (en) * | 2013-08-02 | 2015-02-05 | Aduro Biotech Holdings, Europe B.V. | Combining cd27 agonists and immune checkpoint inhibition for immune stimulation |
ES2760249T3 (es) * | 2013-08-08 | 2020-05-13 | Cytune Pharma | Composición farmacéutica combinada |
DK3030575T3 (en) | 2013-08-08 | 2018-10-22 | Cytune Pharma | IL-15 AND IL-15R-ALFA-SUSHI DOMAIN-BASED MODULOKINES |
RU2705795C2 (ru) | 2013-08-20 | 2019-11-12 | Мерк Шарп И Доум Корп. | Лечение рака комбинацией антагониста pd-1 и динациклиба |
AR097306A1 (es) | 2013-08-20 | 2016-03-02 | Merck Sharp & Dohme | Modulación de la inmunidad tumoral |
CA2922607C (en) | 2013-09-06 | 2022-08-30 | Aurigene Discovery Technologies Limited | 1,2,4-oxadiazole derivatives as immunomodulators |
PL3041468T3 (pl) | 2013-09-06 | 2018-12-31 | Aurigene Discovery Technologies Limited | Pierścieniowe związki peptydomimetyczne jako immunomodulatory |
EP3041828B1 (en) | 2013-09-06 | 2018-05-23 | Aurigene Discovery Technologies Limited | 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as immunomodulators |
WO2015038538A1 (en) * | 2013-09-10 | 2015-03-19 | Medimmune, Llc | Compositions and methods for treating sepsis |
AR097584A1 (es) * | 2013-09-12 | 2016-03-23 | Hoffmann La Roche | Terapia de combinación de anticuerpos contra el csf-1r humano y anticuerpos contra el pd-l1 humano |
EP4130044A1 (en) | 2013-09-13 | 2023-02-08 | BeiGene Switzerland GmbH | Anti-pd1 antibodies and their use as therapeutics and diagnostics |
KR20240033088A (ko) | 2013-09-20 | 2024-03-12 | 브리스톨-마이어스 스큅 컴퍼니 | 종양을 치료하기 위한 항-lag-3 항체 및 항-pd-1 항체의 조합물 |
CA2925421C (en) | 2013-09-24 | 2023-08-29 | Medicenna Therapeutics, Inc. | Interleukin-2 fusion proteins and uses thereof |
EP3049442A4 (en) | 2013-09-26 | 2017-06-28 | Costim Pharmaceuticals Inc. | Methods for treating hematologic cancers |
EP3626742A1 (en) | 2013-09-27 | 2020-03-25 | F. Hoffmann-La Roche AG | Anti-pdl1 antibody formulations |
CN104558177B (zh) * | 2013-10-25 | 2020-02-18 | 苏州思坦维生物技术股份有限公司 | 拮抗抑制程序性死亡受体pd-1与其配体结合的单克隆抗体及其编码序列与用途 |
CA2926856A1 (en) | 2013-10-25 | 2015-04-30 | Dana-Farber Cancer Institute, Inc. | Anti-pd-l1 monoclonal antibodies and fragments thereof |
WO2015066413A1 (en) | 2013-11-01 | 2015-05-07 | Novartis Ag | Oxazolidinone hydroxamic acid compounds for the treatment of bacterial infections |
BR112016010716A8 (pt) | 2013-11-13 | 2020-04-22 | Novartis Ag | dose de reforço imunológico, baixa, de um inibidor de mtor, seu uso, e adjuvante de vacina |
EP3071697B1 (en) | 2013-11-22 | 2019-10-16 | DNAtrix, Inc. | Adenovirus expressing immune cell stimulatory receptor agonist(s) |
WO2015088930A1 (en) | 2013-12-10 | 2015-06-18 | Merck Sharp & Dohme Corp. | Immunohistochemical proximity assay for pd-1 positive cells and pd-ligand positive cells in tumor tissue |
WO2015094992A1 (en) | 2013-12-17 | 2015-06-25 | Merck Sharp & Dohme Corp. | Ifn-gamma gene signature biomarkers of tumor response to pd-1 antagonists |
DE202014010499U1 (de) | 2013-12-17 | 2015-10-20 | Kymab Limited | Targeting von humaner PCSK9 zur Cholesterinbehandlung |
US20150210772A1 (en) | 2013-12-17 | 2015-07-30 | Genentech, Inc. | Methods of treating cancer using pd-1 axis binding antagonists and an anti-cd20 antibody |
CN105934253A (zh) * | 2013-12-17 | 2016-09-07 | 豪夫迈·罗氏有限公司 | 使用pd-1轴结合拮抗剂和抗her2抗体治疗her2阳性癌症的方法 |
AU2014364606A1 (en) * | 2013-12-17 | 2016-07-07 | Genentech, Inc. | Combination therapy comprising OX40 binding agonists and PD-1 axis binding antagonists |
US10689432B2 (en) | 2013-12-18 | 2020-06-23 | Albert Einstein College Of Medicine | B7X and its derivatives for treating and preventing cardiovascular disease |
WO2015090230A1 (en) | 2013-12-19 | 2015-06-25 | Novartis Ag | Human mesothelin chimeric antigen receptors and uses thereof |
US10023636B2 (en) | 2013-12-20 | 2018-07-17 | Intervet Inc. | Caninized murine antibodies to human PD-1 |
EP3087071B1 (en) | 2013-12-24 | 2018-09-05 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
CA3193936A1 (en) * | 2014-01-15 | 2015-07-23 | Kadmon Corporation, Llc | Immunomodulatory agents |
JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
TWI680138B (zh) | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗pd-l1之人類抗體 |
JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
RU2744880C1 (ru) | 2014-02-04 | 2021-03-16 | Инсайт Корпорейшн | Комбинация антагониста pd-1 и ингибитора ido1 для лечения рака |
AU2015214390B2 (en) | 2014-02-04 | 2020-05-07 | Merck Sharp & Dohme LLC. | Combination of a PD-1 antagonist and a VEGFR inhibitor for treating cancer |
EP3686219A1 (en) | 2014-02-04 | 2020-07-29 | Pfizer Inc | Combination of a pd-1 antagonist and a 4-1bb agonist for treating cancer |
CA2934979A1 (en) | 2014-02-10 | 2015-08-13 | Merck Patent Gmbh | Targeted tgf.beta. inhibition |
WO2015131176A1 (en) * | 2014-02-28 | 2015-09-03 | Podack Eckhard R | Compositions, methods, and kits for treatment of cancer |
EP2915569A1 (en) | 2014-03-03 | 2015-09-09 | Cytune Pharma | IL-15/IL-15Ralpha based conjugates purification method |
GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
EP3114144A1 (en) | 2014-03-05 | 2017-01-11 | Bristol-Myers Squibb Company | Treatment of renal cancer using a combination of an anti-pd-1 antibody and another anti-cancer agent |
US10519237B2 (en) | 2014-03-12 | 2019-12-31 | Yeda Research And Development Co. Ltd | Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS |
CN108025068A (zh) * | 2014-03-12 | 2018-05-11 | 耶达研究与开发有限公司 | 降低系统性调节性t细胞水平或活性来治疗cns的疾病和损伤 |
US10618963B2 (en) | 2014-03-12 | 2020-04-14 | Yeda Research And Development Co. Ltd | Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS |
LT3116909T (lt) | 2014-03-14 | 2020-02-10 | Novartis Ag | Antikūno molekulės prieš lag-3 ir jų panaudojimas |
EP3119423B1 (en) | 2014-03-15 | 2022-12-14 | Novartis AG | Treatment of cancer using chimeric antigen receptor |
AP2016009374A0 (en) | 2014-03-24 | 2016-08-31 | Novartis Ag | Monobactam organic compounds for the treatment of bacterial infections |
SG11201607969XA (en) | 2014-03-31 | 2016-10-28 | Genentech Inc | Anti-ox40 antibodies and methods of use |
BR112016022345A2 (pt) | 2014-03-31 | 2017-10-10 | Genentech Inc | terapia de combinação compreendendo agentes antiangiogênese e agonistas de ligação de ox40 |
IL280215B (en) | 2014-04-07 | 2022-07-01 | Novartis Ag | Cancer treatment using a chimeric receptor antigen (car) against cd19 |
US20150307620A1 (en) * | 2014-04-16 | 2015-10-29 | University Of Connecticut | Linked immunotherapeutic agonists that costimulate multiple pathways |
CA2946398A1 (en) | 2014-04-24 | 2015-10-29 | The Board Of Trustees Of The Leland Stanford Junior University | Superagonists, partial agonists and antagonists of interleukin-2 |
CN103936835B (zh) * | 2014-04-29 | 2016-03-30 | 郑州大学 | 具有抗肿瘤活性的靶向PD-L1IgV亲和肽D1 |
CN103936836B (zh) * | 2014-04-29 | 2016-03-30 | 郑州大学 | 具有抗肿瘤活性的靶向PD-L1IgV亲和肽D2 |
CA2949121A1 (en) | 2014-05-15 | 2015-11-19 | Bristol-Myers Squibb Company | Treatment of lung cancer using a combination of an anti-pd-1 antibody and another anti-cancer agent |
US20170182003A1 (en) | 2014-05-23 | 2017-06-29 | Eisai R&D Management Co., Ltd. | Combination therapies for the treatment of cancer |
JP2017516779A (ja) | 2014-05-28 | 2017-06-22 | アイデニクス・ファーマシューティカルズ・エルエルシー | 癌治療のためのヌクレオシド誘導体 |
MA40041B1 (fr) | 2014-05-28 | 2021-03-31 | Memorial Sloan Kettering Cancer Center | Anticorps anti-gitr et leurs procédés d'utilisation |
JP6666905B2 (ja) | 2014-05-29 | 2020-03-18 | スプリング バイオサイエンス コーポレーション | Pd−l1抗体及びその使用 |
JP2017525753A (ja) | 2014-06-06 | 2017-09-07 | フレクサス・バイオサイエンシーズ・インコーポレイテッドFlexus Biosciences, Inc. | 免疫調節剤 |
MX2016015456A (es) | 2014-06-06 | 2017-02-23 | Bristol Myers Squibb Co | Anticuerpos contra el receptor del factor de necrosis tumoral inducido por glucocorticoides (gitr) y sus usos. |
CA2951278A1 (en) | 2014-06-19 | 2015-12-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized programmed cell death 1 gene |
CN104098651B (zh) * | 2014-06-30 | 2016-06-29 | 郑州大学 | 具有抗肿瘤活性的PD-L1 IgV亲和肽及其应用 |
KR102130600B1 (ko) * | 2014-07-03 | 2020-07-08 | 베이진 엘티디 | Pd-l1 항체와 이를 이용한 치료 및 진단 |
CA2954868C (en) * | 2014-07-11 | 2023-08-29 | Genentech, Inc. | Anti-pd-l1 antibodies and diagnostic uses thereof |
RU2733735C2 (ru) | 2014-07-15 | 2020-10-06 | Дженентек, Инк. | Композиции для лечения рака с применением антагонистов, связывающихся с компонентом сигнального пути pd-1, и ингибиторов mek |
CN106999561A (zh) | 2014-07-18 | 2017-08-01 | 阿德瓦希斯股份有限公司 | 用于治疗前列腺癌的pd‑1拮抗剂和基于李斯特菌的疫苗的组合 |
EP3172237A2 (en) | 2014-07-21 | 2017-05-31 | Novartis AG | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
EP3193915A1 (en) | 2014-07-21 | 2017-07-26 | Novartis AG | Combinations of low, immune enhancing. doses of mtor inhibitors and cars |
ES2805475T3 (es) | 2014-07-21 | 2021-02-12 | Novartis Ag | Tratamiento del cáncer utilizando un receptor antigénico quimérico de CD33 |
WO2016014553A1 (en) | 2014-07-21 | 2016-01-28 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
WO2016014688A2 (en) | 2014-07-22 | 2016-01-28 | Junzhuan Qiu | Anti-pd-1 antibodies |
EP3660042B1 (en) | 2014-07-31 | 2023-01-11 | Novartis AG | Subset-optimized chimeric antigen receptor-containing t-cells |
JP6909153B2 (ja) | 2014-08-05 | 2021-07-28 | アポロミクス インコーポレイテッド | 抗pd−l1抗体 |
EP3177593A1 (en) | 2014-08-06 | 2017-06-14 | Novartis AG | Quinolone derivatives as antibacterials |
DK3179992T3 (da) | 2014-08-11 | 2022-07-11 | Acerta Pharma Bv | Terapeutisk kombination af en btk-inhibitor, en pd-1-inhibitor og/eller en pd-l1-inhibitor |
AU2015301460B2 (en) | 2014-08-14 | 2021-04-08 | Novartis Ag | Treatment of cancer using GFR alpha-4 chimeric antigen receptor |
EP3070102A1 (en) | 2015-03-18 | 2016-09-21 | F. Hoffmann-La Roche AG | Combination therapy of antibodies human cd40 activating antibodies and anti human pld-1 antibodies |
AU2015303239A1 (en) * | 2014-08-14 | 2016-12-15 | F. Hoffmann-La Roche Ag | Combination therapy of antibodies activating human CD40 and antibodies against human PD-L1 |
EP3712171A1 (en) | 2014-08-19 | 2020-09-23 | Novartis AG | Treatment of cancer using a cd123 chimeric antigen receptor |
US10695426B2 (en) | 2014-08-25 | 2020-06-30 | Pfizer Inc. | Combination of a PD-1 antagonist and an ALK inhibitor for treating cancer |
WO2016033555A1 (en) | 2014-08-28 | 2016-03-03 | Halozyme, Inc. | Combination therapy with a hyaluronan-degrading enzyme and an immune checkpoint inhibitor |
EP3186284B1 (en) | 2014-08-28 | 2022-04-06 | BioAtla, Inc. | Conditionally active chimeric antigen receptors for modified t-cells |
DK3186283T3 (da) * | 2014-08-29 | 2020-03-02 | Hoffmann La Roche | Kombinationsbehandling med tumormålrettede IL-2- immuncytokinervarianter og antistoffer mod humant PD-L1 |
US9535074B2 (en) | 2014-09-08 | 2017-01-03 | Merck Sharp & Dohme Corp. | Immunoassay for soluble PD-L1 |
EP3659621A1 (en) | 2014-09-13 | 2020-06-03 | Novartis AG | Combination therapies for cancer |
DK3193931T3 (da) | 2014-09-16 | 2020-10-19 | Innate Pharma | Neutralisering af hæmmende veje i lymfocytter |
MX2017003645A (es) | 2014-09-17 | 2017-05-30 | Novartis Ag | Direccion de celulas citotoxicas con receptores quimericos para inmunoterapia adoptiva. |
AU2015320678B2 (en) | 2014-09-23 | 2021-07-22 | Genentech, Inc. | Method of using anti-CD79b immunoconjugates |
US20170209574A1 (en) | 2014-10-03 | 2017-07-27 | Novartis Ag | Combination therapies |
MA41044A (fr) | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
WO2016057705A1 (en) | 2014-10-08 | 2016-04-14 | Novartis Ag | Biomarkers predictive of therapeutic responsiveness to chimeric antigen receptor therapy and uses thereof |
EP3736294A3 (en) | 2014-10-10 | 2021-02-17 | Innate Pharma | Cd73 blockade |
ES2908056T3 (es) | 2014-10-10 | 2022-04-27 | Idera Pharmaceuticals Inc | Tratamiento del cáncer por agonistas del TLR9 con inhibidores del punto de control |
KR102122463B1 (ko) | 2014-10-14 | 2020-06-15 | 할로자임, 아이엔씨 | 아데노신 디아미네이즈-2(ada2)의 조성물, 이의 변이체 및 이를 사용하는 방법 |
PE20171067A1 (es) | 2014-10-14 | 2017-07-24 | Novartis Ag | Moleculas de anticuerpo que se unen a pd-l1 y usos de las mismas |
JP6687612B2 (ja) | 2014-10-24 | 2020-04-22 | アストラゼネカ アクチボラグ | 組合せ |
GB201419084D0 (en) | 2014-10-27 | 2014-12-10 | Agency Science Tech & Res | Anti-PD-1 antibodies |
TWI711463B (zh) | 2014-10-29 | 2020-12-01 | 美商戊瑞治療有限公司 | 用於癌症之組合療法 |
WO2016070001A1 (en) * | 2014-10-31 | 2016-05-06 | Jounce Therapeutics, Inc. | Methods of treating conditions with antibodies that bind b7-h4 |
KR20170086540A (ko) | 2014-11-03 | 2017-07-26 | 제넨테크, 인크. | T 세포 면역 하위세트를 검출하기 위한 검정 및 그의 사용 방법 |
US20160160290A1 (en) | 2014-11-03 | 2016-06-09 | Genentech, Inc. | Methods and biomarkers for predicting efficacy and evaluation of an ox40 agonist treatment |
JP7305300B2 (ja) | 2014-11-05 | 2023-07-10 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 併用免疫療法 |
UY36390A (es) | 2014-11-05 | 2016-06-01 | Flexus Biosciences Inc | Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen |
JP2017538678A (ja) | 2014-11-05 | 2017-12-28 | フレクサス・バイオサイエンシーズ・インコーポレイテッドFlexus Biosciences, Inc. | 免疫調節剤 |
AR102537A1 (es) | 2014-11-05 | 2017-03-08 | Flexus Biosciences Inc | Agentes inmunomoduladores |
US20190076452A1 (en) * | 2014-11-11 | 2019-03-14 | Medimmune Limited | Therapeutic combinations for treating neoplasia |
WO2016075670A1 (en) | 2014-11-14 | 2016-05-19 | Novartis Ag | Antibody drug conjugates |
CN106999583A (zh) * | 2014-11-17 | 2017-08-01 | 豪夫迈·罗氏有限公司 | 包含ox40结合激动剂和pd‑1轴结合拮抗剂的组合疗法 |
PT3220927T (pt) | 2014-11-20 | 2022-02-07 | Promega Corp | Sistemas e métodos para avaliar moduladores de pontos de verificação imunitária |
MX2017006610A (es) | 2014-11-20 | 2017-09-29 | Hoffmann La Roche | Terapia combinada de moleculas de union a antigeno biespecificas activadoras de celulas t y antagonistas de union de eje de pd-1. |
HUE050596T2 (hu) | 2014-11-21 | 2020-12-28 | Bristol Myers Squibb Co | Antitestek CD73 ellen és azok felhasználásai |
MX2017006323A (es) | 2014-11-21 | 2017-08-21 | Bristol Myers Squibb Co | Anticuerpos que comprenden regiones constantes pesadas modificadas. |
JP6771464B2 (ja) | 2014-11-27 | 2020-10-21 | ジェネンテック, インコーポレイテッド | Cbpおよび/またはep300インヒビターとしての、4,5,6,7−テトラヒドロ−1h−ピラゾロ[4,3−c]ピリジン−3−アミン化合物 |
WO2016090034A2 (en) | 2014-12-03 | 2016-06-09 | Novartis Ag | Methods for b cell preconditioning in car therapy |
US10442819B2 (en) | 2014-12-05 | 2019-10-15 | Merck Sharp & Dohme Corp. | Tricyclic compounds as inhibitors of mutant IDH enzymes |
US20160158360A1 (en) | 2014-12-05 | 2016-06-09 | Genentech, Inc. | Methods and compositions for treating cancer using pd-1 axis antagonists and hpk1 antagonists |
US10508108B2 (en) | 2014-12-05 | 2019-12-17 | Merck Sharp & Dohme Corp. | Tricyclic compounds as inhibitors of mutant IDH enzymes |
US10086000B2 (en) | 2014-12-05 | 2018-10-02 | Merck Sharp & Dohme Corp. | Tricyclic compounds as inhibitors of mutant IDH enzymes |
AU2015360736A1 (en) | 2014-12-09 | 2017-06-01 | Merck Sharp & Dohme Corp. | System and methods for deriving gene signature biomarkers of response to PD-1 antagonists |
CA2969803A1 (en) | 2014-12-16 | 2016-06-23 | Novartis Ag | Isoxazole hydroxamic acid compounds as lpxc inhibitors |
IL300202B2 (en) | 2014-12-18 | 2024-04-01 | Amgen Inc | Stable frozen formulation for herpes simplex virus |
US20170340733A1 (en) | 2014-12-19 | 2017-11-30 | Novartis Ag | Combination therapies |
WO2016100975A1 (en) | 2014-12-19 | 2016-06-23 | Massachsetts Institute Ot Technology | Molecular biomarkers for cancer immunotherapy |
AR103232A1 (es) | 2014-12-22 | 2017-04-26 | Bristol Myers Squibb Co | ANTAGONISTAS DE TGFbR |
BR112017013385A2 (pt) | 2014-12-23 | 2018-02-06 | Bristol-Myers Squibb Company | anticorpos para tigit |
GB201500319D0 (en) | 2015-01-09 | 2015-02-25 | Agency Science Tech & Res | Anti-PD-L1 antibodies |
US11161907B2 (en) | 2015-02-02 | 2021-11-02 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
WO2016124558A1 (en) | 2015-02-03 | 2016-08-11 | Ventana Medical Systems, Inc. | Histochemical assay for evaluating expression of programmed death ligand 1 (pd-l1) |
US10983128B2 (en) | 2015-02-05 | 2021-04-20 | Bristol-Myers Squibb Company | CXCL11 and SMICA as predictive biomarkers for efficacy of anti-CTLA4 immunotherapy |
AU2016215175B2 (en) | 2015-02-06 | 2021-09-16 | Heat Biologics, Inc. | Vector co-expressing vaccine and costimulatory molecules |
WO2016128912A1 (en) | 2015-02-12 | 2016-08-18 | Acerta Pharma B.V. | Therapeutic combinations of a btk inhibitor, a pi3k inhibitor, a jak-2 inhibitor, a pd-1 inhibitor, and/or a pd-l1 inhibitor |
MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
AU2016219822B2 (en) | 2015-02-20 | 2020-07-09 | Incyte Holdings Corporation | Bicyclic heterocycles as FGFR inhibitors |
EP4279087A3 (en) | 2015-02-26 | 2024-01-31 | Merck Patent GmbH | Pd-1 / pd-l1 inhibitors for the treatment of cancer |
MX371167B (es) | 2015-03-02 | 2020-01-21 | Rigel Pharmaceuticals Inc | Inhibidores de inhibidores del factor beta de crecimiento de transformacion (tgf-beta). |
WO2016141209A1 (en) | 2015-03-04 | 2016-09-09 | Merck Sharp & Dohme Corp. | Combination of a pd-1 antagonist and eribulin for treating cancer |
KR20170122809A (ko) | 2015-03-04 | 2017-11-06 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
MX2017011374A (es) | 2015-03-06 | 2018-01-23 | Beyondspring Pharmaceuticals Inc | Método de tratamiento de cáncer asociado con una mutación de ras. |
MX2017011375A (es) | 2015-03-06 | 2018-01-23 | Beyondspring Pharmaceuticals Inc | Método para tratar un tumor cerebral. |
US20180044429A1 (en) | 2015-03-09 | 2018-02-15 | Celldex Therapeutics, Inc. | Cd27 agonists |
US10449211B2 (en) | 2015-03-10 | 2019-10-22 | Aduro Biotech, Inc. | Compositions and methods for activating “stimulator of interferon gene”—dependent signalling |
WO2016142833A1 (en) | 2015-03-10 | 2016-09-15 | Aurigene Discovery Technologies Limited | 1,2,4-oxadiazole and thiadiazole compounds as immunomodulators |
IL292449B2 (en) | 2015-03-13 | 2024-02-01 | Cytomx Therapeutics Inc | Nucleic acids encoding antibodies against PDL1 and methods for their preparation |
EP3067062A1 (en) | 2015-03-13 | 2016-09-14 | Ipsen Pharma S.A.S. | Combination of tasquinimod or a pharmaceutically acceptable salt thereof and a pd1 and/or pdl1 inhibitor, for use as a medicament |
US20180133327A1 (en) | 2015-03-16 | 2018-05-17 | Amal Therapeutics Sa | Cell Penetrating Peptides and Complexes Comprising the Same |
KR20170128567A (ko) | 2015-03-23 | 2017-11-22 | 바이엘 파마 악티엔게젤샤프트 | 항-ceacam6 항체 및 그의 용도 |
KR102610592B1 (ko) * | 2015-03-30 | 2023-12-07 | 주식회사 에스티큐브 | 당화 pd-l1에 특이적인 항체 및 그의 사용 방법 |
WO2016161286A1 (en) | 2015-04-03 | 2016-10-06 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase for the treatment of cancer |
ES2820768T3 (es) | 2015-04-03 | 2021-04-22 | Xoma Technology Ltd | Tratamiento del cáncer usando inhibidores de TGF-beta y PD-1 |
JP6955445B2 (ja) | 2015-04-07 | 2021-10-27 | ジェネンテック, インコーポレイテッド | アゴニスト性の活性を有する抗原結合複合体及びその使用方法 |
EP3280439A1 (en) * | 2015-04-07 | 2018-02-14 | INSERM - Institut National de la Santé et de la Recherche Médicale | Anti-pd-l1 immunotoxin for use in therapy |
TWI738646B (zh) | 2015-04-07 | 2021-09-11 | 日商賽多利克公司 | 醫藥組成物 |
EP3280795B1 (en) | 2015-04-07 | 2021-03-24 | Novartis AG | Combination of chimeric antigen receptor therapy and amino pyrimidine derivatives |
WO2016162505A1 (en) | 2015-04-08 | 2016-10-13 | F-Star Biotechnology Limited | Her2 binding agent therapies |
BR112017021688A2 (pt) | 2015-04-17 | 2018-08-14 | Bristol-Myers Squibb Company | composições compreendendo uma combinação de um anticorpo anti-pd-1 e outro anticorpo |
US20180094058A1 (en) * | 2015-04-17 | 2018-04-05 | Bioxcel Corporation | Compositions and methods for preventing tumor growth and treating cancer by targeting lectin galactoside-binding soluble 3 binding protein |
CN108473957A (zh) | 2015-04-17 | 2018-08-31 | 诺华股份有限公司 | 改善嵌合抗原受体表达细胞的功效和扩增的方法 |
ES2844799T3 (es) | 2015-04-17 | 2021-07-22 | Merck Sharp & Dohme | Biomarcadores sanguíneos de sensibilidad tumoral a antagonistas de PD-1 |
EP3286211A1 (en) | 2015-04-23 | 2018-02-28 | Novartis AG | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
CN107406502A (zh) * | 2015-04-23 | 2017-11-28 | 豪夫迈·罗氏有限公司 | 结合血管生成素2的抗体与结合编程性死亡配体1的抗体的组合疗法 |
US20160362489A1 (en) | 2015-04-28 | 2016-12-15 | Bristol-Myers Squibb Company | Treatment of PD-L1-Positive Melanoma Using an Anti-PD-1 Antibody |
US10174113B2 (en) | 2015-04-28 | 2019-01-08 | Bristol-Myers Squibb Company | Treatment of PD-L1-negative melanoma using an anti-PD-1 antibody and an anti-CTLA-4 antibody |
US10683290B2 (en) | 2015-05-11 | 2020-06-16 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
ES2770349T3 (es) | 2015-05-12 | 2020-07-01 | Bristol Myers Squibb Co | Compuestos de 5H-pirido[3,2-b]indol como agentes antineoplásicos |
US9725449B2 (en) | 2015-05-12 | 2017-08-08 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
WO2016183326A1 (en) | 2015-05-12 | 2016-11-17 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
WO2016189055A1 (en) | 2015-05-27 | 2016-12-01 | Idenix Pharmaceuticals Llc | Nucleotides for the treatment of cancer |
US20180155429A1 (en) | 2015-05-28 | 2018-06-07 | Bristol-Myers Squibb Company | Treatment of pd-l1 positive lung cancer using an anti-pd-1 antibody |
KR20180013881A (ko) | 2015-05-29 | 2018-02-07 | 제넨테크, 인크. | 암에서의 pd-l1 프로모터 메틸화 |
MX2017015046A (es) | 2015-05-29 | 2018-05-17 | Agenus Inc | Anticuerpos anti-antigeno 4 del linfocito t citotoxico (ctla-4) y metodos para uso de los mismos. |
WO2016196298A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Therapeutic and diagnolstic methods for cancer |
US10751412B2 (en) | 2015-05-29 | 2020-08-25 | Merck Sharp & Dohme Corp. | Combination of a PD-1 antagonist and CPG-C type oligonucleotide for treating cancer |
LT3303396T (lt) | 2015-05-29 | 2023-01-10 | Bristol-Myers Squibb Company | Antikūnai prieš ox40 ir jų panaudojimo būdai |
WO2016196389A1 (en) | 2015-05-29 | 2016-12-08 | Bristol-Myers Squibb Company | Treatment of renal cell carcinoma |
JP2018521979A (ja) | 2015-06-03 | 2018-08-09 | ボストン バイオメディカル, インコーポレイテッド | 癌の治療に使用するための癌幹細胞性阻害剤および免疫療法剤を含む組成物 |
WO2016196897A1 (en) | 2015-06-04 | 2016-12-08 | Sarepta Therapeutics, Inc. | Methods and compounds for treatment of lymphocyte-related diseases and conditions |
WO2016200836A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies |
AU2016274584A1 (en) | 2015-06-08 | 2018-01-04 | Genentech, Inc. | Methods of treating cancer using anti-OX40 antibodies and PD-1 axis binding antagonists |
JP6865177B2 (ja) | 2015-06-11 | 2021-04-28 | バイオノミクス リミテッド | 医薬組み合わせおよびその使用 |
WO2016201354A1 (en) * | 2015-06-11 | 2016-12-15 | Globavir Biosciences, Inc. | Methods and compositions for treating cancer |
US10696745B2 (en) | 2015-06-11 | 2020-06-30 | Wuxi Biologics (Shanghai) Co. Ltd. | Anti-PD-L1 antibodies |
EP3307778A1 (en) | 2015-06-12 | 2018-04-18 | Bristol-Myers Squibb Company | Treatment of cancer by combined blockade of the pd-1 and cxcr4 signaling pathways |
MX2017016324A (es) * | 2015-06-16 | 2018-03-02 | Merck Patent Gmbh | Tratamientos de combinacion de antagonista de ligando 1 de muerte programada (pd-l1). |
JP6996983B2 (ja) * | 2015-06-16 | 2022-02-21 | ジェネンテック, インコーポレイテッド | 抗cll-1抗体及び使用方法 |
WO2016203432A1 (en) | 2015-06-17 | 2016-12-22 | Novartis Ag | Antibody drug conjugates |
JP6896650B2 (ja) | 2015-06-17 | 2021-06-30 | ジェネンテック, インコーポレイテッド | Pd−1軸結合アンタゴニスト及びタキサンを使用した局所進行性または転移性乳癌の治療方法 |
WO2016209936A1 (en) | 2015-06-22 | 2016-12-29 | Duke University | Synergistic nanotherapy systems and methods of use thereof |
MX2018000261A (es) | 2015-06-24 | 2018-03-08 | Janssen Biotech Inc | Modulacion y tratamiento inmunes de tumores solidos con anticuerpos que se unen especificamente a cd38. |
EP3108897A1 (en) | 2015-06-24 | 2016-12-28 | F. Hoffmann-La Roche AG | Antibodies against human csf-1r for use in inducing lymphocytosis in lymphomas or leukemias |
JP6892443B2 (ja) | 2015-06-24 | 2021-06-23 | イモデュロン セラピューティクス リミテッド | がん治療で使用するためのチェックポイント阻害剤及び全細胞マイコバクテリウム |
AU2016285920A1 (en) | 2015-06-29 | 2018-02-01 | Bristol-Myers Squibb Company | Antibodies to CD40 with enhanced agonist activity |
EA201890199A1 (ru) | 2015-07-02 | 2018-06-29 | Селджин Корпорейшн | Комбинированная терапия для лечения гемобластозов и солидных опухолей |
GB201511790D0 (en) | 2015-07-06 | 2015-08-19 | Iomet Pharma Ltd | Pharmaceutical compound |
CA2991059C (en) | 2015-07-13 | 2024-01-16 | Beyondspring Pharmaceuticals, Inc. | Plinabulin monohydrate polymorphs |
EP3322731B1 (en) | 2015-07-14 | 2021-01-13 | Bristol-Myers Squibb Company | Method of treating cancer using immune checkpoint inhibitor; antibody that binds to programmed death-1 receptor (pd-1) or programmed death ligand 1 (pd-l1) |
CA2991628C (en) | 2015-07-16 | 2020-04-07 | Bioxcel Therapeutics, Inc. | A novel approach for treatment of cancer using immunomodulation |
KR20210089270A (ko) | 2015-07-16 | 2021-07-15 | 바이오카인 테라퓨틱스 리미티드 | 암 치료용 조성물 및 방법 |
AR105433A1 (es) | 2015-07-21 | 2017-10-04 | Novartis Ag | Métodos para mejorar la eficacia y expansión de las células inmunes |
RU2018106515A (ru) | 2015-07-21 | 2019-08-21 | Зе Чилдрен'С Медикал Сентер Корпорейшн | Pd-l1-экспрессирующие гемопоэтические стволовые клетки и применения |
KR20180034548A (ko) | 2015-07-28 | 2018-04-04 | 브리스톨-마이어스 스큅 컴퍼니 | Tgf 베타 수용체 길항제 |
EP3328407A1 (en) | 2015-07-29 | 2018-06-06 | Novartis AG | Combination of pd-1 antagonist with an egfr inhibitor |
WO2017019897A1 (en) | 2015-07-29 | 2017-02-02 | Novartis Ag | Combination therapies comprising antibody molecules to tim-3 |
ES2878188T3 (es) | 2015-07-29 | 2021-11-18 | Novartis Ag | Terapias de combinación que comprenden moléculas de anticuerpos contra LAG-3 |
CN106397592A (zh) * | 2015-07-31 | 2017-02-15 | 苏州康宁杰瑞生物科技有限公司 | 针对程序性死亡配体(pd-l1)的单域抗体及其衍生蛋白 |
WO2017020291A1 (en) * | 2015-08-06 | 2017-02-09 | Wuxi Biologics (Shanghai) Co. Ltd. | Novel anti-pd-l1 antibodies |
CN106432494B9 (zh) * | 2015-08-11 | 2022-02-15 | 广州誉衡生物科技有限公司 | 新型抗-pd-1抗体 |
MX2018001644A (es) | 2015-08-11 | 2018-11-09 | Wuxi Biologics Cayman Inc | Anticuerpos anti-pd-1 novedosos. |
UA123701C2 (uk) | 2015-08-13 | 2021-05-19 | Мерк Шарп І Доум Корп. | Циклічні динуклеотидні сполуки як агоністи sting |
US11453697B1 (en) | 2015-08-13 | 2022-09-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
AR105654A1 (es) | 2015-08-24 | 2017-10-25 | Lilly Co Eli | Anticuerpos pd-l1 (ligando 1 de muerte celular programada) |
US20180250303A1 (en) | 2015-08-25 | 2018-09-06 | Bristol-Myers Squibb Company | Tgf beta receptor antagonists |
ES2955775T3 (es) | 2015-08-27 | 2023-12-07 | Inst Nat Sante Rech Med | Métodos para predecir el tiempo de supervivencia de pacientes que padecen cáncer de pulmón |
EP3344996A2 (en) | 2015-09-03 | 2018-07-11 | The Trustees Of The University Of Pennsylvania | Biomarkers predictive of cytokine release syndrome |
CN108348571B (zh) | 2015-09-03 | 2022-03-22 | 艾瑞朗医疗公司 | 拟肽大环化合物及其用途 |
MA44909A (fr) | 2015-09-15 | 2018-07-25 | Acerta Pharma Bv | Association thérapeutique d'un inhibiteur du cd19 et d'un inhibiteur de la btk |
BR112018005862A2 (pt) | 2015-09-25 | 2018-10-16 | Genentech, Inc. | anticorpos, anticorpos isolados, polinucleotídeo, vetor, célula hospedeira, método de produção do anticorpo, imunoconjugado, composição, usos dos anticorpos, métodos para tratar ou retardar a progressão de um câncer e de uma doença e para aumentar, potencializar ou estimular uma resposta ou função imune e kit |
WO2017055326A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of myeloid dendritic cells in a tissue sample |
WO2017055484A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for determining the metabolic status of lymphomas |
WO2017055320A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of cytotoxic lymphocytes in a tissue sample |
WO2017055325A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of nk cells in a tissue sample |
WO2017055327A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of endothelial cells in a tissue sample |
WO2017055324A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of cells of monocytic origin in a tissue sample |
WO2017055321A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of fibroblasts in a tissue sample |
WO2017055322A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of neutrophils in a tissue sample |
WO2017055319A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of b cells in a tissue sample |
JP2018529719A (ja) | 2015-09-30 | 2018-10-11 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | Alk陰性がんを処置するためのpd−1系結合アンタゴニストおよびalk阻害剤の組合せ |
ES2900482T3 (es) | 2015-10-01 | 2022-03-17 | Gilead Sciences Inc | Combinación de un inhibidor de Btk y un inhibidor de punto de control para el tratamiento del cáncer |
CR20180163A (es) | 2015-10-02 | 2018-05-25 | Hoffmann La Roche | Anticuerpos biespecíficos específicos para un receptor de tnf coestimulador |
WO2017060397A1 (en) | 2015-10-09 | 2017-04-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of subjects suffering from melanoma metastases |
CN106565836B (zh) * | 2015-10-10 | 2020-08-18 | 中国科学院广州生物医药与健康研究院 | 高亲和力的可溶性pdl-1分子 |
EP3362475B1 (en) | 2015-10-12 | 2023-08-30 | Innate Pharma | Cd73 blocking agents |
CN108135934A (zh) | 2015-10-19 | 2018-06-08 | 永恒生物科技股份有限公司 | 通过组合疗法治疗实体或淋巴肿瘤的方法 |
US10149887B2 (en) | 2015-10-23 | 2018-12-11 | Canbas Co., Ltd. | Peptides and peptidomimetics in combination with t cell activating and/or checkpoint inhibiting agents for cancer treatment |
MA44334A (fr) | 2015-10-29 | 2018-09-05 | Novartis Ag | Conjugués d'anticorps comprenant un agoniste du récepteur de type toll |
MA43186B1 (fr) | 2015-11-03 | 2022-03-31 | Janssen Biotech Inc | Anticorps se liant spécifiquement à pd-1 et leurs utilisations |
WO2017077382A1 (en) | 2015-11-06 | 2017-05-11 | Orionis Biosciences Nv | Bi-functional chimeric proteins and uses thereof |
WO2017087280A1 (en) | 2015-11-16 | 2017-05-26 | Genentech, Inc. | Methods of treating her2-positive cancer |
CN107614529B (zh) * | 2015-11-17 | 2019-11-12 | 苏州盛迪亚生物医药有限公司 | Pd-l1抗体、其抗原结合片段及其医药用途 |
JP2018538263A (ja) | 2015-11-18 | 2018-12-27 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 抗pd−1抗体および抗ctla−4抗体の組合せを用いる肺癌の処置法 |
KR20180081591A (ko) | 2015-11-19 | 2018-07-16 | 제넨테크, 인크. | B-raf 억제제 및 면역 체크포인트 억제제를 사용하여 암을 치료하는 방법 |
JP6983776B2 (ja) | 2015-11-19 | 2021-12-17 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | グルココルチコイド誘発腫瘍壊死因子受容体(gitr)に対する抗体およびその使用 |
MX2018006477A (es) | 2015-12-02 | 2018-09-03 | Agenus Inc | Anticuerpos y metodos de uso de estos. |
EP3366691A1 (en) | 2015-12-03 | 2018-08-29 | GlaxoSmithKline Intellectual Property Development Limited | Cyclic purine dinucleotides as modulators of sting |
RS61029B1 (sr) * | 2015-12-07 | 2020-12-31 | Merck Patent Gmbh | Vodena formulacija koja sadrži avelumab antitelo na pd-1 |
WO2017098421A1 (en) | 2015-12-08 | 2017-06-15 | Glaxosmithkline Intellectual Property Development Limited | Benzothiadiazine compounds |
EP3178848A1 (en) | 2015-12-09 | 2017-06-14 | F. Hoffmann-La Roche AG | Type ii anti-cd20 antibody for reducing formation of anti-drug antibodies |
KR20180085740A (ko) | 2015-12-09 | 2018-07-27 | 에프. 호프만-라 로슈 아게 | 항-약물 항체의 형성을 감소시키기 위한 ii형 항-cd20 항체 |
CN108602829A (zh) | 2015-12-15 | 2018-09-28 | 百时美施贵宝公司 | Cxcr4受体拮抗剂 |
WO2017106062A1 (en) | 2015-12-15 | 2017-06-22 | Merck Sharp & Dohme Corp. | Novel compounds as indoleamine 2,3-dioxygenase inhibitors |
MX2018007423A (es) | 2015-12-17 | 2018-11-09 | Novartis Ag | Moleculas de anticuerpo que se unen a pd-1 y usos de las mismas. |
GB201522311D0 (en) | 2015-12-17 | 2016-02-03 | Photocure Asa | Use |
GB201522309D0 (en) | 2015-12-17 | 2016-02-03 | Photocure Asa | Use |
CN109069623A (zh) | 2015-12-18 | 2018-12-21 | 诺华股份有限公司 | 靶向CD32b的抗体及其使用方法 |
WO2017106630A1 (en) | 2015-12-18 | 2017-06-22 | The General Hospital Corporation | Polyacetal polymers, conjugates, particles and uses thereof |
UA126113C2 (uk) | 2015-12-22 | 2022-08-17 | Інсайт Корпорейшн | Гетероциклічні сполуки як імуномодулятори |
US11413340B2 (en) | 2015-12-22 | 2022-08-16 | Novartis Ag | Mesothelin chimeric antigen receptor (CAR) and antibody against PD-L1 inhibitor for combined use in anticancer therapy |
EP4039699A1 (en) | 2015-12-23 | 2022-08-10 | ModernaTX, Inc. | Methods of using ox40 ligand encoding polynucleotides |
CN106939047B (zh) * | 2016-01-04 | 2021-08-31 | 江苏怀瑜药业有限公司 | 一种pd-l1抗体及其制备方法 |
US20200264165A1 (en) | 2016-01-04 | 2020-08-20 | Inserm (Institut National De La Sante Et De Larecherche Medicale) | Use of pd-1 and tim-3 as a measure for cd8+ cells in predicting and treating renal cell carcinoma |
US9938254B2 (en) | 2016-01-08 | 2018-04-10 | Celgene Corporation | Antiproliferative compounds, and their pharmaceutical compositions and uses |
EP3693019A1 (en) | 2016-01-08 | 2020-08-12 | Taiho Pharmaceutical Co., Ltd. | Anti-tumor agent containing immunomodulator |
KR20180097615A (ko) | 2016-01-08 | 2018-08-31 | 에프. 호프만-라 로슈 아게 | Pd-1 축 결합 길항물질 및 항-cea/항-cd3 이중특이성 항체를 사용하는 cea-양성 암의 치료 방법 |
AU2017205167B2 (en) | 2016-01-08 | 2021-07-01 | Celgene Corporation | Formulations of 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide |
US10189808B2 (en) | 2016-01-08 | 2019-01-29 | Celgene Corporation | Solid forms of 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide, and their pharmaceutical compositions and uses |
US20170198051A1 (en) | 2016-01-11 | 2017-07-13 | Inhibrx Lp | Multivalent and multispecific ox40-binding fusion proteins |
SG11201805532XA (en) | 2016-01-11 | 2018-07-30 | Inhibrx Inc | Multivalent and multispecific 41bb-binding fusion proteins |
HUE052893T2 (hu) | 2016-01-13 | 2021-05-28 | Acerta Pharma Bv | Antifolát és BTK-gátló terápiás kombinációi |
KR20180101549A (ko) | 2016-01-21 | 2018-09-12 | 이나뜨 파르마 | 림프구에서의 저해 경로의 중화 |
US10822415B2 (en) | 2016-01-28 | 2020-11-03 | Inserm (Institut National De La Santéet De La Recherche Médicale) | Methods for enhancing the potency of the immune checkpoint inhibitors |
US10918737B2 (en) | 2016-01-28 | 2021-02-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical composition for the treatment of cancer |
WO2017129763A1 (en) | 2016-01-28 | 2017-08-03 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of signet ring cell gastric cancer |
EP3411407B1 (en) | 2016-02-05 | 2024-04-03 | Orionis Biosciences BV | Bispecific signaling agents and uses thereof |
WO2017139231A1 (en) | 2016-02-08 | 2017-08-17 | Beyondspring Pharmaceuticals, Inc. | Compositions containing tucaresol or its analogs |
US11219635B2 (en) | 2016-02-19 | 2022-01-11 | City Of Hope | Bi-specific aptamer |
AU2017219216B2 (en) | 2016-02-19 | 2019-12-19 | Novartis Ag | Tetracyclic pyridone compounds as antivirals |
EP4086285A1 (en) | 2016-02-25 | 2022-11-09 | Cell Medica Switzerland AG | Binding members to pd-l1 |
MX2018010295A (es) | 2016-02-26 | 2019-06-06 | Inst Nat Sante Rech Med | Anticuerpos que tienen especificidad para atenuador de linfocitos b y t (btla) y usos de los mismos. |
CA3015913A1 (en) | 2016-02-29 | 2017-09-08 | Foundation Medicine, Inc. | Methods of treating cancer |
CN109196121B (zh) | 2016-02-29 | 2022-01-04 | 基因泰克公司 | 用于癌症的治疗和诊断方法 |
JP6918816B2 (ja) | 2016-03-01 | 2021-08-18 | ノース カロライナ ステート ユニバーシティ | マイクロニードルパッチ支援送達による強化されたがん免疫療法 |
SG10201601719RA (en) | 2016-03-04 | 2017-10-30 | Agency Science Tech & Res | Anti-LAG-3 Antibodies |
BR112018067368A2 (pt) | 2016-03-04 | 2019-01-15 | Bristol-Myers Squibb Company | terapia de combinação com anticorpos anti-cd73 |
EP3309177B1 (en) * | 2016-03-04 | 2020-05-13 | Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Pdl-1 antibody, pharmaceutical composition thereof, and uses thereof |
RU2018134771A (ru) | 2016-03-04 | 2020-04-06 | Новартис Аг | Клетки, экспрессирующие множество молекул химерных антигенных рецепторов (car), и их применение |
WO2017153433A1 (en) | 2016-03-08 | 2017-09-14 | Innate Pharma | Siglec neutralizing antibodies |
WO2017153952A1 (en) | 2016-03-10 | 2017-09-14 | Glaxosmithkline Intellectual Property Development Limited | 5-sulfamoyl-2-hydroxybenzamide derivatives |
WO2017156349A1 (en) | 2016-03-10 | 2017-09-14 | Cold Genesys, Inc. | Methods of treating solid or lymphatic tumors by combination therapy |
WO2017160599A1 (en) | 2016-03-14 | 2017-09-21 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Use of cd300b antagonists to treat sepsis and septic shock |
CN114085836B (zh) * | 2016-03-14 | 2024-01-26 | 豪夫迈·罗氏有限公司 | 用于减少pd-l1表达的寡核苷酸 |
US11767362B1 (en) | 2016-03-15 | 2023-09-26 | Chugai Seiyaku Kabushiki Kaisha | Methods of treating cancers using PD-1 axis binding antagonists and anti-GPC3 antibodies |
CA3016474A1 (en) | 2016-03-15 | 2017-09-21 | Mersana Therapeutics, Inc. | Napi2b-targeted antibody-drug conjugates and methods of use thereof |
WO2017161032A1 (en) | 2016-03-15 | 2017-09-21 | North Carolina State University | Nanoparticles, controlled-release dosage forms, and methods for delivering an immunotherapeutic agent |
FI3429618T3 (fi) | 2016-03-16 | 2024-03-15 | Amal Therapeutics Sa | Immuunijäjestelmän tarkistuspisteen modulaattorin ja soluun tunkeutuvan peptidin, cargon ja tlr-peptidiagonistin kompleksin yhdistelmä lääketieteelliseen käyttöön |
US11287428B2 (en) | 2016-03-16 | 2022-03-29 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | PD1 and PDL-1 expression during progression from myelodysplastic syndrome to acute myelogenous leukemia |
US10822416B2 (en) | 2016-03-23 | 2020-11-03 | Mabspace Biosciences (Suzhou) Co., Ltd | Anti-PD-L1 antibodies |
WO2017165742A1 (en) | 2016-03-24 | 2017-09-28 | Millennium Pharmaceuticals, Inc. | Methods of treating gastrointestinal immune-related adverse events in anti-ctla4 anti-pd-1 combination treatments |
US11760803B2 (en) | 2016-03-24 | 2023-09-19 | Takeda Pharmaceutical Company Limited | Methods of treating gastrointestinal immune-related adverse events in immune oncology treatments |
FI3433257T3 (fi) | 2016-03-24 | 2024-01-08 | Novartis Ag | Alkynyylinukleosidianalogeja ihmisen rinoviruksen estäjinä |
WO2017167921A1 (en) | 2016-03-30 | 2017-10-05 | Centre Léon-Bérard | Lymphocytes expressing cd73 in cancerous patient dictates therapy |
EP3225253A1 (en) | 2016-04-01 | 2017-10-04 | Deutsches Krebsforschungszentrum Stiftung des Öffentlichen Rechts | Cancer therapy with an oncolytic virus combined with a checkpoint inhibitor |
US11209441B2 (en) | 2016-04-05 | 2021-12-28 | Bristol-Myers Squibb Company | Cytokine profiling analysis |
CA3019630A1 (en) | 2016-04-07 | 2017-10-12 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides useful as protein modulators |
AU2017247806B2 (en) | 2016-04-07 | 2019-11-14 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides useful as protein modulators |
AU2017248354A1 (en) | 2016-04-08 | 2018-10-04 | Gilead Sciences, Inc. | Compositions and methods for treating cancer, inflammatory diseases and autoimmune diseases |
CA3020830A1 (en) | 2016-04-13 | 2017-10-19 | Vivia Biotech, S.L | Ex vivo bite.rtm. activated t cells |
IL262251B2 (en) | 2016-04-14 | 2023-09-01 | Ose Immunotherapeutics | New anti-syrap antibodies and their medical applications |
CA3019921A1 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Methods for monitoring and treating cancer |
MX2018012493A (es) | 2016-04-15 | 2019-06-06 | Genentech Inc | Métodos para controlar y tratar el cáncer. |
SG10201913248VA (en) | 2016-04-18 | 2020-02-27 | Celldex Therapeutics Inc | Agonistic antibodies that bind human cd40 and uses thereof |
RU2018140960A (ru) * | 2016-04-25 | 2020-05-26 | МЕДИММЬЮН, ЭлЭлСи | Композиции, содержащие комбинированный состав на основе антител к pd-l1 и ctla-4 |
CN105695406A (zh) * | 2016-04-27 | 2016-06-22 | 天津普瑞赛尔生物科技有限公司 | 制备具有高效肿瘤杀伤性dc-cik免疫细胞的方法及制得的dc-cik免疫细胞 |
EP3452030A4 (en) | 2016-05-04 | 2019-11-13 | Bristol-Myers Squibb Company | INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE AND METHOD FOR THEIR USE |
EP3452450A1 (en) | 2016-05-04 | 2019-03-13 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
WO2017192874A1 (en) | 2016-05-04 | 2017-11-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Albumin-binding immunomodulatory compositions and methods of use thereof |
JP2019516681A (ja) | 2016-05-04 | 2019-06-20 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | インドールアミン2,3−ジオキシゲナーゼ阻害剤およびその使用方法 |
JP2019516687A (ja) | 2016-05-04 | 2019-06-20 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | インドールアミン2,3−ジオキシゲナーゼ阻害剤およびその使用方法 |
WO2017192840A1 (en) | 2016-05-04 | 2017-11-09 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
US10604531B2 (en) | 2016-05-05 | 2020-03-31 | Glaxosmithkline Intellectual Property (No.2) Limited | Enhancer of zeste homolog 2 inhibitors |
JP6979971B2 (ja) * | 2016-05-09 | 2021-12-15 | アイジーエム バイオサイエンシズ インコーポレイテッド | 抗pd−l1抗体 |
SG10201603721TA (en) | 2016-05-10 | 2017-12-28 | Agency Science Tech & Res | Anti-CTLA-4 Antibodies |
CN109563141A (zh) | 2016-05-13 | 2019-04-02 | 奥里尼斯生物科学公司 | 对非细胞结构的治疗性靶向 |
TWI755395B (zh) | 2016-05-13 | 2022-02-21 | 美商再生元醫藥公司 | 抗-pd-1抗體與輻射治療癌症之組合 |
ES2930255T3 (es) | 2016-05-13 | 2022-12-09 | Bioatla Inc | Anticuerpos anti-Ror2, fragmentos de anticuerpos, sus inmunoconjugados y usos de los mismos |
WO2017197243A1 (en) * | 2016-05-13 | 2017-11-16 | Ohio State Innovation Foundation | Cblb inhibition for treating fungal infections |
CA3023883A1 (en) | 2016-05-13 | 2017-11-16 | Orionis Biosciences Nv | Targeted mutant interferon-beta and uses thereof |
CA3024465A1 (en) | 2016-05-17 | 2017-11-23 | Genentech, Inc. | Stromal gene signatures for diagnosis and use in immunotherapy |
EP3458083B1 (en) | 2016-05-18 | 2022-11-02 | ModernaTX, Inc. | Polynucleotides encoding interleukin-12 (il12) and uses thereof |
EP3458474B1 (en) | 2016-05-18 | 2022-07-06 | ModernaTX, Inc. | Combinations of mrnas encoding immune modulating polypeptides and uses thereof |
US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
MA45025A (fr) | 2016-05-20 | 2019-03-27 | Lilly Co Eli | Traitement d'association utilisant des inhibiteurs de notch et de pd-1 ou pd-l1 |
DK3458053T3 (da) | 2016-05-20 | 2022-02-21 | Biohaven Therapeutics Ltd | Anvendelse af riluzol, riluzolprodrugs eller riluzolanaloger med immunterapier til cancerbehandling |
JP7014736B2 (ja) | 2016-05-24 | 2022-02-01 | ジェネンテック, インコーポレイテッド | がんの処置のためのピラゾロピリジン誘導体 |
MA45122A (fr) | 2016-05-24 | 2019-04-10 | Constellation Pharmaceuticals Inc | Inhibiteurs hétérocycliques de cbp/ep300 et leur utilisation dans le traitement du cancer |
WO2017202962A1 (en) | 2016-05-24 | 2017-11-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of non small cell lung cancer (nsclc) that coexists with chronic obstructive pulmonary disease (copd) |
KR20230003387A (ko) | 2016-05-25 | 2023-01-05 | 엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔 | 암 치료 방법 및 조성물 |
BR112018074463A2 (pt) | 2016-05-27 | 2019-03-06 | Agenus Inc. | anticorpos anti-tim-3 e métodos de uso dos mesmos. |
EP3463405A4 (en) | 2016-05-27 | 2020-02-26 | DNAtrix, Inc. | ADENOVIRUS AND IMMUNOMODULATORY POLYTHERAPY |
US10994033B2 (en) | 2016-06-01 | 2021-05-04 | Bristol-Myers Squibb Company | Imaging methods using 18F-radiolabeled biologics |
WO2018220099A1 (en) | 2017-06-02 | 2018-12-06 | F. Hoffmann-La Roche Ag | Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer |
EP3252078A1 (en) | 2016-06-02 | 2017-12-06 | F. Hoffmann-La Roche AG | Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer |
PT3464368T (pt) | 2016-06-02 | 2023-08-17 | Bristol Myers Squibb Co | Utilização de um anticorpo anti-pd-1 em combinação com um anticorpo anti-cd30 no tratamento de linfoma |
KR20190015377A (ko) | 2016-06-02 | 2019-02-13 | 브리스톨-마이어스 스큅 컴퍼니 | 불응성 호지킨 림프종에서의 니볼루맙을 사용한 pd-1 차단 |
AU2017275782A1 (en) | 2016-06-02 | 2019-01-24 | Ultimovacs As | A vaccine in combination with an immune checkpoint inhibitor for use in treating cancer |
JP2019517512A (ja) | 2016-06-03 | 2019-06-24 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 結腸直腸癌を有する患者の処置における抗pd−1抗体の使用 |
WO2017210624A1 (en) | 2016-06-03 | 2017-12-07 | Bristol-Myers Squibb Company | Anti-pd-1 antibody for use in a method of treating a tumor |
EP3463454A1 (en) | 2016-06-03 | 2019-04-10 | Bristol-Myers Squibb Company | Anti-pd-1 antibody for use in a method of treatment of recurrent small cell lung cancer |
RU2760348C2 (ru) | 2016-06-06 | 2021-11-24 | Бейондспринг Фармасьютикалс, Инк. | Способ уменьшения нейтропении |
CN109563071B (zh) | 2016-06-08 | 2021-08-03 | 葛兰素史密斯克莱知识产权发展有限公司 | 作为atf4途径抑制剂的化学化合物 |
US10851053B2 (en) | 2016-06-08 | 2020-12-01 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds |
SG11201811003PA (en) | 2016-06-13 | 2019-01-30 | I Mab | Anti-pd-l1 antibodies and uses thereof |
AU2017283480A1 (en) | 2016-06-13 | 2019-01-24 | Torque Therapeutics, Inc. | Methods and compositions for promoting immune cell function |
HUE050796T2 (hu) | 2016-06-14 | 2021-01-28 | Novartis Ag | (R)-4-(5-(ciklopropiletinil)izoxazol-3-il)-N-hidroxi-2-metil-2-(metilszulfonil)butánamid kristályos formája baktériumellenes szerként |
WO2017216685A1 (en) | 2016-06-16 | 2017-12-21 | Novartis Ag | Pentacyclic pyridone compounds as antivirals |
WO2017216686A1 (en) | 2016-06-16 | 2017-12-21 | Novartis Ag | 8,9-fused 2-oxo-6,7-dihydropyrido-isoquinoline compounds as antivirals |
US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
WO2018029474A2 (en) | 2016-08-09 | 2018-02-15 | Kymab Limited | Anti-icos antibodies |
KR102531889B1 (ko) | 2016-06-20 | 2023-05-17 | 키맵 리미티드 | 항-pd-l1 및 il-2 사이토카인 |
MD3472167T2 (ro) | 2016-06-20 | 2023-02-28 | Incyte Corp | Compuși heterociclici ca imunomodulatori |
EP3474856B1 (en) | 2016-06-24 | 2022-09-14 | Infinity Pharmaceuticals, Inc. | Combination therapies |
WO2018006005A1 (en) | 2016-06-30 | 2018-01-04 | Oncorus, Inc. | Pseudotyped oncolytic viral delivery of therapeutic polypeptides |
AU2017293423B2 (en) | 2016-07-05 | 2023-05-25 | Beigene, Ltd. | Combination of a PD-1 antagonist and a RAF inhibitor for treating cancer |
WO2018009466A1 (en) | 2016-07-05 | 2018-01-11 | Aduro Biotech, Inc. | Locked nucleic acid cyclic dinucleotide compounds and uses thereof |
WO2018011166A2 (en) | 2016-07-12 | 2018-01-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of myeloid dendritic cells in a tissue sample |
WO2018014001A1 (en) | 2016-07-14 | 2018-01-18 | Fred Hutchinson Cancer Research Center | Multiple bi-specific binding domain constructs with different epitope binding to treat cancer |
US10077306B2 (en) | 2016-07-14 | 2018-09-18 | Bristol-Myers Squibb Company | Antibodies against TIM3 and uses thereof |
GB201612520D0 (en) | 2016-07-19 | 2016-08-31 | F-Star Beta Ltd | Binding molecules |
CA3031047A1 (en) | 2016-07-20 | 2018-01-25 | Glaxosmithkline Intellectual Property Development Limited | Isoquinoline derivatives as perk inhibitors |
WO2018017708A1 (en) | 2016-07-20 | 2018-01-25 | University Of Utah Research Foundation | Cd229 car t cells and methods of use thereof |
WO2018017633A1 (en) | 2016-07-21 | 2018-01-25 | Bristol-Myers Squibb Company | TGF Beta RECEPTOR ANTAGONISTS |
CN106243223B (zh) * | 2016-07-28 | 2019-03-05 | 北京百特美博生物科技有限公司 | 抗人pdl1抗体及其用途 |
JP2019525934A (ja) | 2016-07-29 | 2019-09-12 | イーライ リリー アンド カンパニー | 癌の治療に使用するためのメレスチニブおよび抗pd−l1または抗pd−1阻害剤を用いた組み合わせ治療 |
US20210369746A1 (en) | 2016-08-01 | 2021-12-02 | Molecular Templates, Inc. | Administration of hypoxia activated prodrugs in combination with immune modulatory agents for treating cancer |
ES2899036T3 (es) | 2016-08-04 | 2022-03-09 | Innovent Biologics Suzhou Co Ltd | Nanocuerpo anti-PD-L1 y su uso |
EP3495391A4 (en) * | 2016-08-05 | 2020-08-19 | Y-Biologics Inc. | ANTIBODIES AGAINST PROGRAMMED DEATH LIGAND 1 (PD-L1) AND USE OF IT |
WO2018026249A1 (ko) * | 2016-08-05 | 2018-02-08 | 주식회사 와이바이오로직스 | 프로그램화된 세포 사멸 단백질 리간드-1 (pd-l1)에 대한 항체 및 이의 용도 |
JP2019530434A (ja) | 2016-08-05 | 2019-10-24 | ジェネンテック, インコーポレイテッド | アゴニスト活性を有する多価及び多重エピトープ抗体ならびに使用方法 |
WO2018029124A1 (en) | 2016-08-08 | 2018-02-15 | F. Hoffmann-La Roche Ag | Therapeutic and diagnostic methods for cancer |
CN116640214A (zh) | 2016-08-09 | 2023-08-25 | 科马布有限公司 | 分离抗体及其应用 |
KR20190038829A (ko) | 2016-08-12 | 2019-04-09 | 제넨테크, 인크. | Mek 억제제, pd-1 축 억제제, 및 vegf 억제제를 사용한 조합 요법 |
WO2018029336A1 (en) | 2016-08-12 | 2018-02-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for determining whether a subject was administered with an activator of the ppar beta/delta pathway. |
EP3497130B1 (en) | 2016-08-12 | 2021-10-27 | Merck Patent GmbH | Combination therapy for cancer |
CA3032331A1 (en) | 2016-08-17 | 2018-02-22 | Compugen Ltd. | Anti-tigit antibodies, anti-pvrig antibodies and combinations thereof |
WO2018033135A1 (en) | 2016-08-19 | 2018-02-22 | Beigene, Ltd. | Use of a combination comprising a btk inhibitor for treating cancers |
US20210284733A1 (en) * | 2016-08-22 | 2021-09-16 | Arbutus Biopharma Corporation | Anti-pd-1 antibodies, or fragments thereof, for treating hepatitis b |
JP7138094B2 (ja) | 2016-08-25 | 2022-09-15 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | マクロファージ活性化剤と組み合わせた抗csf-1r抗体の間欠投与 |
KR20190040990A (ko) | 2016-08-26 | 2019-04-19 | 브리스톨-마이어스 스큅 컴퍼니 | 인돌아민 2,3-디옥시게나제의 억제제 및 그의 사용 방법 |
WO2018041118A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric pd-l1 |
CN107815466B (zh) | 2016-08-31 | 2020-03-13 | 百奥赛图江苏基因生物技术有限公司 | 人源化基因改造动物模型的制备方法及应用 |
CN110121352B (zh) | 2016-09-01 | 2020-12-11 | 嵌合体生物工程公司 | Gold优化的car t-细胞 |
CN110191720A (zh) | 2016-09-09 | 2019-08-30 | Tg治疗有限公司 | 用于治疗血液学癌症的抗-CD20抗体、PI 3激酶-δ抑制剂以及抗-PD-1或抗-PD-L1抗体的组合 |
WO2018048975A1 (en) | 2016-09-09 | 2018-03-15 | Bristol-Myers Squibb Company | Use of an anti-pd-1 antibody in combination with an anti-mesothelin antibody in cancer treatment |
WO2018047109A1 (en) | 2016-09-09 | 2018-03-15 | Novartis Ag | Polycyclic pyridone compounds as antivirals |
WO2018046736A1 (en) | 2016-09-12 | 2018-03-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of patients suffering from cancer |
WO2018046738A1 (en) | 2016-09-12 | 2018-03-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of patients suffering from cancer |
KR20230109771A (ko) * | 2016-09-13 | 2023-07-20 | 노쓰 캐롤라이나 스테이트 유니버시티 | 혈소판 조성물 및 치료제의 전달 방법 |
KR20190053909A (ko) | 2016-09-16 | 2019-05-20 | 바이오노믹스 리미티드 | 항체와 체크포인트 면역 억제제의 병용 요법 |
KR20230131498A (ko) | 2016-09-21 | 2023-09-13 | 아말 테라퓨틱스 에스에이 | 암 치료를 위한, 세포 투과 펩타이드, 멀티 에피토프 및 tlr 펩타이드 작용제를 포함하는 융합체 |
AU2017332161A1 (en) | 2016-09-21 | 2019-04-04 | The United States Government As Represented By The Department Of Veterans Affairs | Chimeric antigen receptor (car) that targets chemokine receptor CCR4 and its use |
WO2018055080A1 (en) | 2016-09-22 | 2018-03-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for reprograming immune environment in a subject in need thereof |
WO2018057955A1 (en) | 2016-09-23 | 2018-03-29 | Elstar Therapeutics, Inc. | Multispecific antibody molecules comprising lambda and kappa light chains |
CN117510643A (zh) | 2016-09-23 | 2024-02-06 | 美勒斯公司 | 调节细胞表达的生物活性的结合分子 |
CN109844536B (zh) | 2016-09-26 | 2023-04-14 | 豪夫迈·罗氏有限公司 | 预测对pd-1轴抑制剂的响应 |
MX2019003569A (es) | 2016-09-27 | 2020-07-22 | Oncologie Inc | Metodos para tratar el cancer con bavituximab en funcion de niveles de b2 glucoproteina 1 y ensayos de estos. |
JOP20190061A1 (ar) | 2016-09-28 | 2019-03-26 | Novartis Ag | مثبطات بيتا-لاكتاماز |
JP2019534251A (ja) | 2016-09-29 | 2019-11-28 | ジェネンテック, インコーポレイテッド | Mek阻害剤、pd−1軸阻害剤、及びタキサンを用いた併用療法 |
ES2893532T3 (es) | 2016-10-04 | 2022-02-09 | Merck Sharp & Dohme | Compuestos de benzo[b]tiofeno como agonistas de STING |
MX2019003934A (es) | 2016-10-06 | 2019-07-10 | Genentech Inc | Métodos terapéuticos y de diagnóstico para el cáncer. |
CA3039451A1 (en) | 2016-10-06 | 2018-04-12 | Pfizer Inc. | Dosing regimen of avelumab for the treatment of cancer |
EP3523331A1 (en) | 2016-10-07 | 2019-08-14 | Novartis AG | Chimeric antigen receptors for the treatment of cancer |
US11712465B2 (en) | 2016-10-07 | 2023-08-01 | Enterome S.A. | Microbiota sequence variants of tumor-related antigenic epitopes |
EP3522916A2 (en) | 2016-10-07 | 2019-08-14 | Enterome S.A. | Immunogenic compounds for cancer therapy |
KR20240007316A (ko) | 2016-10-07 | 2024-01-16 | 엔터롬 에스.에이. | 암 치료를 위한 면역원성 화합물 |
US11666649B2 (en) | 2016-10-11 | 2023-06-06 | University Of Miami | Vectors and vaccine cells for immunity against Zika virus |
EP3527216B1 (en) | 2016-10-11 | 2024-02-14 | NEC Corporation | A medicine comprising a toll-like receptor agonist, lag-3 protein, a hsp70-derived peptide and a gpc3-derived peptide |
IL265800B2 (en) | 2016-10-11 | 2023-10-01 | Agenus Inc | Anti-LAG-3 antibodies and methods of using them |
CA3040465A1 (en) | 2016-10-14 | 2018-04-19 | Merck Sharp & Dohme Corp. | Combination of a pd-1 antagonist and eribulin for treating urothelial cancer |
WO2018071576A1 (en) | 2016-10-14 | 2018-04-19 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Treatment of tumors by inhibition of cd300f |
WO2018073753A1 (en) | 2016-10-18 | 2018-04-26 | Novartis Ag | Fused tetracyclic pyridone compounds as antivirals |
WO2018075447A1 (en) | 2016-10-19 | 2018-04-26 | The Trustees Of Columbia University In The City Of New York | Combination of braf inhibitor, talimogene laherparepvec, and immune checkpoint inhibitor for use in the treatment cancer (melanoma) |
CN110114368A (zh) | 2016-10-24 | 2019-08-09 | 奥睿尼斯生物科学公司 | 靶向突变干扰素-γ及其用途 |
CN110099925A (zh) | 2016-10-28 | 2019-08-06 | 百时美施贵宝公司 | 使用抗pd-1抗体治疗尿道上皮癌的方法 |
WO2018081531A2 (en) | 2016-10-28 | 2018-05-03 | Ariad Pharmaceuticals, Inc. | Methods for human t-cell activation |
EP3532091A2 (en) | 2016-10-29 | 2019-09-04 | H. Hoffnabb-La Roche Ag | Anti-mic antibidies and methods of use |
JP7011657B2 (ja) * | 2016-10-30 | 2022-02-10 | シャンハイ・ヘンリウス・バイオテック・インコーポレイテッド | 抗pd-l1抗体および変異型 |
TWI788307B (zh) | 2016-10-31 | 2023-01-01 | 美商艾歐凡斯生物治療公司 | 用於擴增腫瘤浸潤性淋巴細胞之工程化人造抗原呈現細胞 |
MX2019004621A (es) | 2016-11-02 | 2019-11-28 | Engmab Sarl | Anticuerpo biespecifico contra bcma y cd3 y un farmaco inmunologico para uso combinado en el tratamiento del mieloma multiple. |
EP3534947A1 (en) | 2016-11-03 | 2019-09-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
CN110072890B (zh) | 2016-11-03 | 2022-11-29 | 百时美施贵宝公司 | 可活化的抗ctla-4抗体及其用途 |
AU2017355512A1 (en) | 2016-11-04 | 2019-05-23 | Aximmune, Inc. | Beta-alethine, immune modulators, and uses thereof |
US10342785B2 (en) | 2016-11-04 | 2019-07-09 | Askat Inc. | Use of EP4 receptor antagonists for the treatment of NASH-associated liver cancer |
EP3538140A1 (en) | 2016-11-14 | 2019-09-18 | Institut National de la Sante et de la Recherche Medicale (INSERM) | Methods and pharmaceutical compositions for modulating stem cells proliferation or differentiation |
TWI791471B (zh) | 2016-11-15 | 2023-02-11 | 美商建南德克公司 | 用於用抗cd20/抗cd3雙特異性抗體進行治療之給藥 |
US10660909B2 (en) | 2016-11-17 | 2020-05-26 | Syntrix Biosystems Inc. | Method for treating cancer using chemokine antagonists |
US11279694B2 (en) | 2016-11-18 | 2022-03-22 | Sumitomo Dainippon Pharma Oncology, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
WO2018091542A1 (en) | 2016-11-21 | 2018-05-24 | Idenix Pharmaceuticals Llc | Cyclic phosphate substituted nucleoside derivatives for the treatment of liver diseases |
WO2018098352A2 (en) | 2016-11-22 | 2018-05-31 | Jun Oishi | Targeting kras induced immune checkpoint expression |
US11135307B2 (en) | 2016-11-23 | 2021-10-05 | Mersana Therapeutics, Inc. | Peptide-containing linkers for antibody-drug conjugates |
WO2018102427A1 (en) | 2016-11-29 | 2018-06-07 | Boston Biomedical, Inc. | Naphthofuran derivatives, preparation, and methods of use thereof |
WO2018099539A1 (en) | 2016-11-29 | 2018-06-07 | Horst Lindhofer | Combination of t-cell redirecting multifunctional antibodies with immune checkpoint modulators and uses thereof |
AU2017368155B2 (en) | 2016-11-30 | 2022-02-24 | Oncomed Pharmaceuticals, Inc. | Methods for treatment of cancer comprising TIGIT-binding agents |
KR20190090822A (ko) | 2016-12-01 | 2019-08-02 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | 조합 요법 |
JP2020511407A (ja) | 2016-12-01 | 2020-04-16 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | 併用療法 |
CN110248678A (zh) | 2016-12-03 | 2019-09-17 | 朱诺治疗学股份有限公司 | 调节car-t细胞的方法 |
WO2018106738A1 (en) | 2016-12-05 | 2018-06-14 | Massachusetts Institute Of Technology | Brush-arm star polymers, conjugates and particles, and uses thereof |
LT3551660T (lt) | 2016-12-07 | 2023-12-27 | Agenus Inc. | Antikūnai prieš ctla-4 ir jų naudojimo būdai |
KR102603681B1 (ko) | 2016-12-07 | 2023-11-17 | 아게누스 인코포레이티드 | 항체 및 이의 사용방법 |
EP3552626A4 (en) | 2016-12-12 | 2020-06-10 | Daiichi Sankyo Company, Limited | ASSOCIATION OF AN ANTIBODY DRUG CONJUGATE AND AN IMMUNE CONTROL POINT INHIBITOR |
CN110366562A (zh) | 2016-12-12 | 2019-10-22 | 豪夫迈·罗氏有限公司 | 使用抗pd-l1抗体和抗雄激素治疗癌症的方法 |
AU2017378226A1 (en) | 2016-12-14 | 2019-06-20 | Janssen Biotech, Inc. | CD8A-binding fibronectin type III domains |
US10597438B2 (en) | 2016-12-14 | 2020-03-24 | Janssen Biotech, Inc. | PD-L1 binding fibronectin type III domains |
US10611823B2 (en) | 2016-12-14 | 2020-04-07 | Hanssen Biotech, Inc | CD137 binding fibronectin type III domains |
WO2018112360A1 (en) | 2016-12-16 | 2018-06-21 | Evelo Biosciences, Inc. | Combination therapies for treating cancer |
WO2018112364A1 (en) | 2016-12-16 | 2018-06-21 | Evelo Biosciences, Inc. | Combination therapies for treating melanoma |
CN117752798A (zh) | 2016-12-19 | 2024-03-26 | 豪夫迈·罗氏有限公司 | 用靶向性4-1bb(cd137)激动剂的组合疗法 |
MY197635A (en) | 2016-12-22 | 2023-06-29 | Incyte Corp | Benzooxazole derivatives as immunomodulators |
CN110072553B (zh) | 2016-12-22 | 2023-09-15 | 豪夫迈·罗氏有限公司 | 在抗pd-l1/pd1治疗失败之后抗csf-1r抗体与抗pd-l1抗体组合对肿瘤的治疗 |
MX2019007615A (es) | 2016-12-23 | 2019-11-05 | Univ Johns Hopkins | Imagenología de celulas tumorales e inmunitarias basadas en expresion de pd-l1. |
EP3558377A1 (en) | 2016-12-23 | 2019-10-30 | Virttu Biologics Limited | Treatment of cancer |
EP3559032A1 (en) | 2016-12-23 | 2019-10-30 | Innate Pharma | Heterodimeric antigen binding proteins |
EP3559045A4 (en) * | 2016-12-23 | 2020-08-19 | REMD Biotherapeutics, Inc. | IMMUNOTHERAPY USING ANTIBODIES THAT BIND TO A TIMED DEATH LIGAND 1 (PD-L1) |
WO2018122245A1 (en) | 2016-12-28 | 2018-07-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of predicting the survival time of patients suffering from cms3 colorectal cancer |
WO2018122249A1 (en) | 2016-12-28 | 2018-07-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of patients suffering from a microsatellite stable colorectal cancer |
US20190315852A1 (en) | 2017-01-05 | 2019-10-17 | Netris Pharma | Combined treatment with netrin-1 interfering drug and immune checkpoint inhibitors drugs |
US10961239B2 (en) | 2017-01-05 | 2021-03-30 | Bristol-Myers Squibb Company | TGF beta receptor antagonists |
CN110431135A (zh) | 2017-01-06 | 2019-11-08 | 大连万春布林医药有限公司 | 微管蛋白结合化合物及其治疗用途 |
US11584733B2 (en) | 2017-01-09 | 2023-02-21 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
EP3565560A4 (en) | 2017-01-09 | 2021-01-13 | Bioxcel Therapeutics, Inc. | PREDICTIVE AND DIAGNOSTIC PROCEDURES FOR PROSTATE CANCER |
US11034667B2 (en) | 2017-01-09 | 2021-06-15 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
MX2019008346A (es) | 2017-01-13 | 2019-09-09 | Agenus Inc | Receptores de celulas t que se unen a ny-eso-1 y metodos de uso de estos. |
AU2018211064A1 (en) | 2017-01-18 | 2019-09-05 | Genentech, Inc. | Idiotypic antibodies against anti-PD-L1 antibodies and uses thereof |
EP3570840A1 (en) | 2017-01-20 | 2019-11-27 | Exelixis, Inc. | Combinations of cabozantinib and atezolizumab to treat cancer |
TWI812494B (zh) | 2017-01-20 | 2023-08-11 | 美商阿克思生物科學有限公司 | 用於治療癌症相關病症之唑嘧啶 |
WO2018137681A1 (en) | 2017-01-25 | 2018-08-02 | Beigene, Ltd. | Crystalline forms of (s) -7- (1- (but-2-ynoyl) piperidin-4-yl) -2- (4-phenoxyphenyl) -4, 5, 6, 7-tetrahy dropyrazolo [1, 5-a] pyrimidine-3-carboxamide, preparation, and uses thereof |
AU2018212788A1 (en) | 2017-01-27 | 2019-07-25 | Janssen Biotech, Inc. | Cyclic dinucleotides as STING agonists |
AU2018212787B2 (en) | 2017-01-27 | 2023-10-26 | Janssen Biotech, Inc. | Cyclic dinucleotides as sting agonists |
WO2018140671A1 (en) | 2017-01-27 | 2018-08-02 | Celgene Corporation | 3-(1-oxo-4-((4-((3-oxomorpholino) methyl)benzyl)oxy)isoindolin-2-yl)piperidine-2,6-dione and isotopologues thereof |
CA3052190A1 (en) | 2017-02-01 | 2018-08-09 | Beyondspring Pharmaceuticals, Inc. | Method of reducing neutropenia |
JOP20190187A1 (ar) | 2017-02-03 | 2019-08-01 | Novartis Ag | مترافقات عقار جسم مضاد لـ ccr7 |
EP3577138A1 (en) | 2017-02-06 | 2019-12-11 | Innate Pharma | Immunomodulatory antibody drug conjugates binding to a human mica polypeptide |
JP2020505955A (ja) | 2017-02-06 | 2020-02-27 | オリオンズ バイオサイエンス インコーポレイテッド | 標的化改変型インターフェロン及びその使用 |
KR102642385B1 (ko) | 2017-02-06 | 2024-03-04 | 오리오니스 바이오사이언시스 엔브이 | 표적화된 키메라 단백질 및 이의 용도 |
WO2018146148A1 (en) | 2017-02-07 | 2018-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A method for predicting the response to checkpoint blockade cancer immunotherapy |
WO2018146128A1 (en) | 2017-02-07 | 2018-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Detection of kit polymorphism for predicting the response to checkpoint blockade cancer immunotherapy |
EP3579874B1 (en) | 2017-02-10 | 2021-07-21 | Novartis AG | 1-(4-amino-5-bromo-6-(1 h-pyrazol-1-yl)pyrimidin-2-yl)-1 h-pyrazol-4-ol and use thereof in the treatment of cancer |
ES2895641T3 (es) * | 2017-02-10 | 2022-02-22 | Chiome Bioscience Inc | Método para fomentar la diversificación de una región variable de anticuerpos |
WO2018151820A1 (en) | 2017-02-16 | 2018-08-23 | Elstar Therapeutics, Inc. | Multifunctional molecules comprising a trimeric ligand and uses thereof |
CN110662764B (zh) * | 2017-02-16 | 2023-08-22 | 湘潭腾华生物科技有限公司 | 抗程序性死亡配体1(pd-l1)抗体及其治疗用途 |
TWI674261B (zh) | 2017-02-17 | 2019-10-11 | 美商英能腫瘤免疫股份有限公司 | Nlrp3 調節劑 |
EP3585812A1 (en) | 2017-02-21 | 2020-01-01 | Regeneron Pharmaceuticals, Inc. | Anti-pd-1 antibodies for treatment of lung cancer |
CN108456251A (zh) * | 2017-02-21 | 2018-08-28 | 上海君实生物医药科技股份有限公司 | 抗pd-l1抗体及其应用 |
CA3052767A1 (en) | 2017-02-27 | 2018-08-30 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides as kinase inhibitors |
EP3585486A1 (en) | 2017-02-27 | 2020-01-01 | Novartis AG | Dosing schedule for a combination of ceritinib and an anti-pd-1 antibody molecule |
WO2018160538A1 (en) | 2017-02-28 | 2018-09-07 | Mersana Therapeutics, Inc. | Combination therapies of her2-targeted antibody-drug conjugates |
MX2019010295A (es) | 2017-03-01 | 2019-11-21 | Genentech Inc | Métodos de diagnóstico y terapéuticos para el cáncer. |
EP3592769A1 (en) | 2017-03-09 | 2020-01-15 | Genmab A/S | Antibodies against pd-l1 |
SG11201908391XA (en) | 2017-03-15 | 2019-10-30 | Cue Biopharma Inc | Methods for modulating an immune response |
AU2018235944B2 (en) | 2017-03-15 | 2024-01-04 | Amgen Inc. | Use of oncolytic viruses, alone or in combination with a checkpoint inhibitor, for the treatment of cancer |
EP3596075B1 (en) | 2017-03-15 | 2023-10-11 | F. Hoffmann-La Roche AG | Azaindoles as inhibitors of hpk1 |
JP7308150B2 (ja) | 2017-03-16 | 2023-07-13 | イナート・ファルマ・ソシエテ・アノニム | 癌を処置するための組成物及び方法 |
US20210186982A1 (en) | 2017-03-24 | 2021-06-24 | Universite Nice Sophia Antipolis | Methods and compositions for treating melanoma |
US20200048321A1 (en) * | 2017-03-24 | 2020-02-13 | Orpheus Bioscience Inc. | Pantids for treatment of autoimmune disorders |
CN108623686A (zh) | 2017-03-25 | 2018-10-09 | 信达生物制药(苏州)有限公司 | 抗ox40抗体及其用途 |
JP7029822B2 (ja) * | 2017-03-29 | 2022-03-04 | タイペイ・メディカル・ユニバーシティ | 抗原特異的t細胞及びその使用 |
KR102644408B1 (ko) | 2017-03-30 | 2024-03-07 | 메르크 파텐트 게엠베하 | 암의 치료를 위한 항-pd-l1 항체 및 dna-pk 억제제의 병용 |
MX2019011511A (es) | 2017-03-30 | 2019-11-18 | Hoffmann La Roche | Naftiridinas como inhibidores de cinasa 1 progenitora hematopoyetica (hpk1). |
US20200033324A1 (en) * | 2017-03-31 | 2020-01-30 | Sony Corporation | Information processing device, information processing method, and cell analyzing system |
EP3601355A1 (en) | 2017-03-31 | 2020-02-05 | Bristol-Myers Squibb Company | Methods of treating tumor |
KR20200020662A (ko) | 2017-04-03 | 2020-02-26 | 온콜로지, 인크. | 면역-종양학 제제와 함께 ps-표적화 항체를 사용하여 암을 치료하는 방법 |
WO2018187260A1 (en) | 2017-04-04 | 2018-10-11 | Heat Biologics, Inc. | Intratumoral vaccination |
US11603407B2 (en) | 2017-04-06 | 2023-03-14 | Regeneron Pharmaceuticals, Inc. | Stable antibody formulation |
TWI788340B (zh) | 2017-04-07 | 2023-01-01 | 美商必治妥美雅史谷比公司 | 抗icos促效劑抗體及其用途 |
KR102629972B1 (ko) | 2017-04-13 | 2024-01-29 | 아게누스 인코포레이티드 | 항-cd137 항체 및 이의 사용 방법 |
MX2019012187A (es) | 2017-04-13 | 2019-11-25 | Hoffmann La Roche | Un inmunoconjugado de interleuquina-2, un agonista de cd40 y opcionalmente un antagonista de union al eje pd-1 para uso en metodos para tratar cancer. |
CA3058478A1 (en) | 2017-04-14 | 2018-10-18 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
RU2665790C1 (ru) * | 2017-04-17 | 2018-09-04 | Закрытое Акционерное Общество "Биокад" | Моноклональное антитело к pd-l1 |
SG11201909041SA (en) * | 2017-04-18 | 2019-11-28 | R Pharm Overseas Inc | Anti-pd-l1 antibody and use thereof |
US11738009B2 (en) | 2017-04-18 | 2023-08-29 | Tempest Therapeutics, Inc. | Bicyclic compounds and their use in the treatment of cancer |
EP3612563A1 (en) | 2017-04-19 | 2020-02-26 | Elstar Therapeutics, Inc. | Multispecific molecules and uses thereof |
CN106939049B (zh) | 2017-04-20 | 2019-10-01 | 苏州思坦维生物技术股份有限公司 | 拮抗抑制人pd-1抗原与其配体结合的单克隆抗体及其制备方法与应用 |
BR112019022009A2 (pt) | 2017-04-21 | 2020-05-12 | Sillajen, Inc. | Terapia de combinação de vírus vaccinia oncolítico e inibidor de ponto de verificação |
TWI778050B (zh) | 2017-04-21 | 2022-09-21 | 美商醫肯納腫瘤學公司 | 吲哚ahr抑制劑及其用途 |
JP2020517699A (ja) | 2017-04-26 | 2020-06-18 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | ジスルフィド結合の還元を最小限にする抗体製造法 |
AR111419A1 (es) | 2017-04-27 | 2019-07-10 | Novartis Ag | Compuestos fusionados de indazol piridona como antivirales |
EP3615068A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
US20200385472A1 (en) | 2017-04-28 | 2020-12-10 | Elstar Therapeutics, Inc. | Multispecific molecules comprising a non-immunoglobulin heterodimerization domain and uses thereof |
US20200055948A1 (en) | 2017-04-28 | 2020-02-20 | Novartis Ag | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
AR111651A1 (es) | 2017-04-28 | 2019-08-07 | Novartis Ag | Conjugados de anticuerpos que comprenden agonistas del receptor de tipo toll y terapias de combinación |
UY37695A (es) | 2017-04-28 | 2018-11-30 | Novartis Ag | Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo |
CA3062061A1 (en) | 2017-05-01 | 2018-11-08 | Agenus Inc. | Anti-tigit antibodies and methods of use thereof |
AR111658A1 (es) | 2017-05-05 | 2019-08-07 | Novartis Ag | 2-quinolinonas tricíclicas como agentes antibacteriales |
WO2018209049A1 (en) | 2017-05-12 | 2018-11-15 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
EP3623389A4 (en) * | 2017-05-12 | 2021-01-20 | Jiangsu Hengrui Medicine Co., Ltd. | FUSION PROTEIN WITH TGF RECEPTOR AND ITS MEDICAL USES |
EP3621624B1 (en) | 2017-05-12 | 2023-08-30 | Merck Sharp & Dohme LLC | Cyclic di-nucleotide compounds as sting agonists |
JP7090347B2 (ja) | 2017-05-12 | 2022-06-24 | ハープーン セラピューティクス,インク. | メソテリン結合タンパク質 |
CA3062487A1 (en) * | 2017-05-16 | 2018-11-22 | Jiangsu Hengrui Medicine Co., Ltd. | Pd-l1 antibody pharmaceutical composition and use thereof |
KR20200006115A (ko) | 2017-05-16 | 2020-01-17 | 브리스톨-마이어스 스큅 컴퍼니 | 항-gitr 효능제 항체에 의한 암의 치료 |
EP3634417B1 (en) | 2017-05-17 | 2023-07-12 | Arcus Biosciences, Inc. | Quinazoline-pyrazole derivatives for the treatment of cancer-related disorders |
JP2020520923A (ja) | 2017-05-17 | 2020-07-16 | ボストン バイオメディカル, インコーポレイテッド | がんを処置するための方法 |
MA49144A (fr) | 2017-05-18 | 2020-03-25 | Tesaro Inc | Polythérapies pour le traitement du cancer |
WO2018213731A1 (en) | 2017-05-18 | 2018-11-22 | Modernatx, Inc. | Polynucleotides encoding tethered interleukin-12 (il12) polypeptides and uses thereof |
JP2020521751A (ja) | 2017-05-25 | 2020-07-27 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 修飾重鎖定常領域を含む抗体 |
AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
MX2019014192A (es) | 2017-05-29 | 2021-04-12 | Gamamabs Pharma | Inhibidor de inmunosupresion asociado al cancer. |
CA3065304A1 (en) | 2017-05-30 | 2018-12-06 | Bristol-Myers Squibb Company | Compositions comprising an anti-lag-3 antibody or an anti-lag-3 antibody and an anti-pd-1 or anti-pd-l1 antibody |
MX2019012038A (es) | 2017-05-30 | 2019-11-18 | Bristol Myers Squibb Co | Composiciones que comprenden una combinacion de un anticuerpo anti gen 3 de activacion del linfocito (lag-3), un inhibidor de la trayectoria del receptor de muerte programada 1 (pd-1), y un agente inmunoterapeutico. |
BR112019020610A2 (pt) | 2017-05-30 | 2020-04-22 | Bristol-Myers Squibb Company | tratamento de tumores positivos para o lag-3 |
WO2018222901A1 (en) | 2017-05-31 | 2018-12-06 | Elstar Therapeutics, Inc. | Multispecific molecules that bind to myeloproliferative leukemia (mpl) protein and uses thereof |
JOP20190279A1 (ar) | 2017-05-31 | 2019-11-28 | Novartis Ag | الصور البلورية من 5-برومو -2، 6-داي (1h-بيرازول -1-يل) بيريميدين -4- أمين وأملاح جديدة |
JP2020522512A (ja) | 2017-05-31 | 2020-07-30 | ストキューブ アンド シーオー., インコーポレイテッド | Btn1a1に免疫特異的に結合する抗体及び分子を用いて癌を治療する方法 |
WO2018223004A1 (en) | 2017-06-01 | 2018-12-06 | Xencor, Inc. | Bispecific antibodies that bind cd20 and cd3 |
BR112019025035A2 (pt) | 2017-06-01 | 2020-06-30 | Compugen Ltd. | método para tratar câncer |
EP3630839A1 (en) | 2017-06-01 | 2020-04-08 | Xencor, Inc. | Bispecific antibodies that bind cd 123 cd3 |
KR20200016899A (ko) | 2017-06-01 | 2020-02-17 | 싸이톰스 테라퓨틱스, 인크. | 활성화가능 항-pdl1 항체, 및 이의 이용 방법 |
CN110678483B (zh) | 2017-06-01 | 2023-09-22 | 百时美施贵宝公司 | 用抗pd-1抗体治疗肿瘤的方法 |
BR112019025403A2 (pt) | 2017-06-02 | 2020-08-18 | Juno Therapeutics Inc | artigos de fabricação e métodos para tratamento usando terapia celular adotiva |
US11542331B2 (en) | 2017-06-06 | 2023-01-03 | Stcube & Co., Inc. | Methods of treating cancer using antibodies and molecules that bind to BTN1A1 or BTN1A1-ligands |
EP3634496A4 (en) * | 2017-06-06 | 2021-09-08 | Dana-Farber Cancer Institute, Inc. | METHOD FOR RISING AWARENESS IN CANCER CELLS AGAINST T-CELL-MEDIATED KILLING BY MODULATING MOLECULAR SIGNAL PATHS |
WO2018225093A1 (en) | 2017-06-07 | 2018-12-13 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds as atf4 pathway inhibitors |
WO2018225033A1 (en) | 2017-06-09 | 2018-12-13 | Glaxosmithkline Intellectual Property Development Limited | Combination therapy |
CA3061959A1 (en) | 2017-06-09 | 2018-12-13 | Providence Health & Services - Oregon | Utilization of cd39 and cd103 for identification of human tumor reactive t cells for treatment of cancer |
WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
EP3641814A4 (en) | 2017-06-19 | 2021-06-23 | Medicenna Therapeutics Inc. | USES AND METHODS FOR IL-2 SUPERAGONISTS, AGONISTS, AND FUSIONS THEREOF |
GB201709808D0 (en) | 2017-06-20 | 2017-08-02 | Kymab Ltd | Antibodies |
JP2020524157A (ja) | 2017-06-20 | 2020-08-13 | アンスティテュート キュリー | がん併用療法における使用のためのsuv39h1ヒストンメチルトランスフェラーゼの阻害剤 |
BR112019027402A2 (pt) | 2017-06-22 | 2020-07-07 | Celgene Corporation | tratamento de carcinoma hepatocelular caracterizado por infecção pelo vírus da hepatite b |
EP3642240A1 (en) | 2017-06-22 | 2020-04-29 | Novartis AG | Antibody molecules to cd73 and uses thereof |
PE20200717A1 (es) | 2017-06-22 | 2020-07-21 | Novartis Ag | Moleculas de anticuerpo que se unen a cd73 y usos de las mismas |
WO2018235056A1 (en) | 2017-06-22 | 2018-12-27 | Novartis Ag | IL-1BETA BINDING ANTIBODIES FOR USE IN THE TREATMENT OF CANCER |
TW201904993A (zh) | 2017-06-22 | 2019-02-01 | 瑞士商諾華公司 | IL-1β 結合抗體之用途 |
CN110831972B (zh) * | 2017-06-25 | 2023-05-12 | 西雅图免疫公司 | 抗pd-l1抗体及其制备和使用方法 |
CA3066518A1 (en) | 2017-06-26 | 2019-01-03 | Beigene, Ltd. | Immunotherapy for hepatocellular carcinoma |
CA3066747A1 (en) | 2017-06-27 | 2019-01-03 | Novartis Ag | Dosage regimens for anti-tim-3 antibodies and uses thereof |
EP3645040A4 (en) | 2017-06-27 | 2021-05-05 | Neuracle Science Co., Ltd | USE OF ANTI-FAM19A5 ANTIBODIES FOR THE TREATMENT OF CANCERS |
JP2020526194A (ja) | 2017-06-29 | 2020-08-31 | ジュノー セラピューティクス インコーポレイテッド | 免疫療法薬と関連する毒性を評価するためのマウスモデル |
EP3644993B1 (en) | 2017-06-30 | 2023-08-02 | Bristol-Myers Squibb Company | Amorphous and crystalline forms of ido inhibitors |
MX2019015886A (es) | 2017-06-30 | 2020-09-10 | Celgene Corp | Composiciones y metodos de uso de 2-(4-clorofenil)-n-((2-(2,6-diox opiperidin-3-il)-1-0xoisoindolin-5-il)metil)-2,2-difluoroacetamid a. |
CA3068395A1 (en) | 2017-07-03 | 2019-01-10 | Glaxosmithkline Intellectual Property Development Limited | 2-(4-chlorophenoxy)-n-((1-(2-(4-chlorophenoxy)ethynazetidin-3-yl)methyl)acetamide derivatives and related compounds as atf4 inhibitors for treating cancer and other diseases |
JP2020525513A (ja) | 2017-07-03 | 2020-08-27 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | 癌および他の疾患を治療するためのatf4阻害剤としてのn−(3−(2−(4−クロロフェノキシ)アセトアミドビシクロ[1.1.1]ペンタン−1−イル)−2−シクロブタン−1−カルボキサミド誘導体および関連化合物 |
JP7438098B2 (ja) * | 2017-07-06 | 2024-02-26 | メルス ナムローゼ フェンノートシャップ | 細胞により発現される生物学的活性を調節する結合分子 |
AU2018298676A1 (en) | 2017-07-10 | 2019-12-19 | Innate Pharma | Siglec-9-neutralizing antibodies |
WO2019014100A1 (en) | 2017-07-10 | 2019-01-17 | Celgene Corporation | ANTIPROLIFERATIVE COMPOUNDS AND METHODS OF USE THEREOF |
SG11202000248UA (en) | 2017-07-14 | 2020-02-27 | Innate Tumor Immunity Inc | Nlrp3 modulators |
WO2019016174A1 (en) | 2017-07-18 | 2019-01-24 | Institut Gustave Roussy | METHOD FOR ASSESSING RESPONSE TO TARGETING DRUG PD-1 / PDL-1 MEDICINES |
JP2020527572A (ja) | 2017-07-20 | 2020-09-10 | ノバルティス アーゲー | 抗lag−3抗体の投薬量レジメンおよびその使用 |
AU2018304458B2 (en) | 2017-07-21 | 2021-12-09 | Foundation Medicine, Inc. | Therapeutic and diagnostic methods for cancer |
US11926664B2 (en) | 2017-07-25 | 2024-03-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for modulating monocytopoiesis |
WO2019021208A1 (en) | 2017-07-27 | 2019-01-31 | Glaxosmithkline Intellectual Property Development Limited | USEFUL INDAZOLE DERIVATIVES AS PERK INHIBITORS |
EP3658914A1 (en) | 2017-07-28 | 2020-06-03 | Bristol-Myers Squibb Company | Predictive peripheral blood biomarker for checkpoint inhibitors |
WO2019023525A1 (en) * | 2017-07-28 | 2019-01-31 | Dana-Farber Cancer Institute, Inc. | ENHANCED IMMUNOTHERAPY OF CANCER USING TARGETED TRANSCRIPTION MODULATORS |
AU2018311966A1 (en) | 2017-08-04 | 2020-02-13 | Merck Sharp & Dohme Llc | Benzo[b]thiophene sting agonists for cancer treatment |
CN116333131A (zh) | 2017-08-04 | 2023-06-27 | 健玛保 | 与pd-l1和cd137结合的结合剂及其用途 |
WO2019027857A1 (en) | 2017-08-04 | 2019-02-07 | Merck Sharp & Dohme Corp. | COMBINATIONS OF PD-1 ANTAGONISTS AND STING BENZO [B] THIOPHENIC AGONISTS FOR THE TREATMENT OF CANCER |
JP2020530003A (ja) | 2017-08-07 | 2020-10-15 | アムジェン インコーポレイテッド | 抗pd−l1抗体及び腫瘍溶解性ウイルスでの、肝転移を伴う三種陰性乳がん又は結腸直腸がんの処置 |
WO2019035938A1 (en) | 2017-08-16 | 2019-02-21 | Elstar Therapeutics, Inc. | MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF |
MX2020001793A (es) | 2017-08-17 | 2020-07-22 | Ikena Oncology Inc | Inhibidores del receptor de hidrocarburos de arilo (ahr) y usos de los mismos. |
TWI785098B (zh) | 2017-08-18 | 2022-12-01 | 開曼群島商科賽睿生命科學公司 | Tg02之多晶型 |
CN111094982A (zh) | 2017-08-28 | 2020-05-01 | 百时美施贵宝公司 | 用于治疗和诊断癌症的tim-3拮抗剂 |
CN111278854A (zh) | 2017-09-04 | 2020-06-12 | 艾吉纳斯公司 | 与混合谱系白血病(mll)特异性磷酸肽结合的t细胞受体和其使用方法 |
UY37866A (es) | 2017-09-07 | 2019-03-29 | Glaxosmithkline Ip Dev Ltd | Nuevos compuestos derivados de benzoimidazol sustituidos que reducen la proteína myc (c-myc) en las células e inhiben la histona acetiltransferasa de p300/cbp. |
WO2019053617A1 (en) | 2017-09-12 | 2019-03-21 | Glaxosmithkline Intellectual Property Development Limited | CHEMICAL COMPOUNDS |
US11497756B2 (en) | 2017-09-12 | 2022-11-15 | Sumitomo Pharma Oncology, Inc. | Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib |
EP3684410A1 (en) | 2017-09-19 | 2020-07-29 | Institut Curie | Agonist of aryl hydrocarbon receptor for use in cancer combination therapy |
EP3684413A1 (en) | 2017-09-20 | 2020-07-29 | Chugai Seiyaku Kabushiki Kaisha | Dosage regimen for combination therapy using pd-1 axis binding antagonists and gpc3 targeting agent |
JP7366031B2 (ja) | 2017-09-22 | 2023-10-20 | カイメラ セラピューティクス, インコーポレイテッド | タンパク質分解剤およびそれらの使用 |
WO2019060693A1 (en) | 2017-09-22 | 2019-03-28 | Kymera Therapeutics, Inc. | CRBN LIGANDS AND USES THEREOF |
WO2019060708A1 (en) * | 2017-09-22 | 2019-03-28 | The Children's Medical Center Corporation | TREATMENT OF TYPE 1 DIABETES AND AUTOIMMUNE DISEASES OR DISORDERS |
WO2019061324A1 (en) | 2017-09-29 | 2019-04-04 | Curis Inc. | CRYSTALLINE FORMS OF IMMUNOMODULATORS |
MX2020003770A (es) | 2017-09-30 | 2020-07-29 | Tesaro Inc | Terapias de combinacion para tratar cancer. |
EA039662B1 (ru) | 2017-10-03 | 2022-02-24 | Закрытое Акционерное Общество "Биокад" | Антитела, специфичные к cd47 и pd-l1 |
JP7291130B2 (ja) | 2017-10-05 | 2023-06-14 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | インターフェロン遺伝子の刺激物質(sting)の調節物質 |
EP3692033A1 (en) | 2017-10-05 | 2020-08-12 | GlaxoSmithKline Intellectual Property Development Limited | Modulators of stimulator of interferon genes (sting) useful in treating hiv |
US11801240B2 (en) | 2017-10-06 | 2023-10-31 | Tesaro, Inc. | Combination therapies and uses thereof |
BR112020006809A2 (pt) | 2017-10-06 | 2020-10-06 | Innate Pharma | anticorpos, agente, uso, composto, composição farmacêutica, kits e composição ou uso |
EP3694541A2 (en) | 2017-10-09 | 2020-08-19 | Enterome S.A. | Microbiota sequence variants of tumor-related antigenic epitopes |
US11649212B2 (en) | 2017-10-09 | 2023-05-16 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
WO2019074824A1 (en) | 2017-10-09 | 2019-04-18 | Bristol-Myers Squibb Company | INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS AND METHODS OF USE |
KR20200063153A (ko) | 2017-10-10 | 2020-06-04 | 누맙 세러퓨틱스 아게 | Cd137을 표적화하는 항체 및 이의 사용 방법 |
EP3470426A1 (en) | 2017-10-10 | 2019-04-17 | Numab Therapeutics AG | Multispecific antibody |
WO2019072868A1 (en) | 2017-10-10 | 2019-04-18 | Numab Therapeutics AG | MULTISPECIFIC ANTIBODIES |
US11230601B2 (en) | 2017-10-10 | 2022-01-25 | Tilos Therapeutics, Inc. | Methods of using anti-lap antibodies |
BR112020006669A2 (pt) | 2017-10-11 | 2020-09-24 | Aurigene Discovery Technologies Limited | formas cristalinas de 1,2,4-oxadiazol 3-substituído |
CN111511766A (zh) | 2017-10-13 | 2020-08-07 | Ose免疫疗法 | 修饰的抗SIRPa抗体及其应用 |
US20200239577A1 (en) | 2017-10-15 | 2020-07-30 | Bristol-Myers Squibb Company | Methods of treating tumor |
CA3079310A1 (en) | 2017-10-18 | 2019-04-25 | Vivia Biotech, S.L. | Bite-activated car-t cells |
TW201925223A (zh) | 2017-10-18 | 2019-07-01 | 美商艾爾潘免疫科學有限公司 | 變異型icos 配位體免疫調節蛋白及相關組合物及方法 |
MX2020004074A (es) | 2017-10-19 | 2020-10-16 | Debiopharm Int Sa | Producto de combinacion para el tratamiento de cancer. |
EP3700933A1 (en) | 2017-10-25 | 2020-09-02 | Novartis AG | Antibodies targeting cd32b and methods of use thereof |
US11718679B2 (en) | 2017-10-31 | 2023-08-08 | Compass Therapeutics Llc | CD137 antibodies and PD-1 antagonists and uses thereof |
US20210132042A1 (en) | 2017-11-01 | 2021-05-06 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
WO2019089921A1 (en) | 2017-11-01 | 2019-05-09 | Bristol-Myers Squibb Company | Immunostimulatory agonistic antibodies for use in treating cancer |
BR112020008323A2 (pt) | 2017-11-01 | 2020-11-03 | Juno Therapeutics Inc | anticorpos e receptores de antígenos quiméricos específicos para antígeno de maturação de células b |
EP3703692A4 (en) | 2017-11-01 | 2021-04-28 | Merck Sharp & Dohme Corp. | NEW SUBSTITUTED TETRAHYDROQUINOLINE COMPOUNDS USED AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) INHIBITORS |
KR20200116077A (ko) | 2017-11-01 | 2020-10-08 | 주노 쎄러퓨티크스 인코퍼레이티드 | B 세포 성숙 항원에 특이적인 키메라 항원 수용체 및 암호화 폴리뉴클레오타이드 |
US20200237906A1 (en) * | 2017-11-02 | 2020-07-30 | Nanjing Shunxin Pharmaceutical Co., Ltd. | Pharmaceutical Composition of Humanized Monoclonal Anti-PD-L1 Antibody |
EA202090746A1 (ru) | 2017-11-03 | 2020-08-17 | Ориджен Дискавери Текнолоджис Лимитед | Двойные ингибиторы путей tim-3 и pd-1 |
CN111213059B (zh) | 2017-11-06 | 2024-01-09 | 豪夫迈·罗氏有限公司 | 用于癌症的诊断和治疗方法 |
ES2925450T3 (es) | 2017-11-06 | 2022-10-18 | Bristol Myers Squibb Co | Compuestos de isofuranona útiles como inhibidores de HPK1 |
KR20200084333A (ko) | 2017-11-06 | 2020-07-10 | 오리진 디스커버리 테크놀로지스 리미티드 | 면역조절을 위한 병행 요법 |
US20210292415A1 (en) | 2017-11-06 | 2021-09-23 | Bristol-Myers Squibb Company | Methods of treating a tumor |
AU2018363880B2 (en) * | 2017-11-08 | 2022-04-07 | Epiaxis Therapeutics Pty Ltd | Immunogenic compositions and uses therefor |
US20200353050A1 (en) | 2017-11-10 | 2020-11-12 | Armo Biosciences, Inc. | Compositions and methods of use of interleukin-10 in combination with immune check-point pathway inhibitors |
MX2020004930A (es) | 2017-11-14 | 2020-08-27 | Merck Sharp & Dohme | Compuestos de biarilo sustituido novedosos como inhibidores de indolamina 2,3-dioxigenasa (ido). |
WO2019099294A1 (en) | 2017-11-14 | 2019-05-23 | Merck Sharp & Dohme Corp. | Novel substituted biaryl compounds as indoleamine 2,3-dioxygenase (ido) inhibitors |
TWI698238B (zh) | 2017-11-14 | 2020-07-11 | 美商輝瑞股份有限公司 | Ezh2抑制劑組合治療 |
US20210079015A1 (en) | 2017-11-17 | 2021-03-18 | Novartis Ag | Novel dihydroisoxazole compounds and their use for the treatment of hepatitis b |
AU2018367524B2 (en) | 2017-11-17 | 2022-09-15 | Merck Sharp & Dohme Llc | Antibodies specific for immunoglobulin-like transcript 3 (ILT3) and uses thereof |
BR112020010020A2 (pt) * | 2017-11-20 | 2020-11-10 | Taizhou Mabtech Pharmaceutical Co., Ltd | uma proteína de fusão bifuncional direcionada a cd47 e pd-l1 |
US11679148B2 (en) | 2017-11-24 | 2023-06-20 | Institut National De La Santé Et De La Recherche Médicale (Inserm) | Methods and compositions for treating cancers |
US11638760B2 (en) | 2017-11-27 | 2023-05-02 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepine antibody conjugates |
US11786529B2 (en) | 2017-11-29 | 2023-10-17 | Beigene Switzerland Gmbh | Treatment of indolent or aggressive B-cell lymphomas using a combination comprising BTK inhibitors |
TW201925782A (zh) | 2017-11-30 | 2019-07-01 | 瑞士商諾華公司 | 靶向bcma之嵌合抗原受體及其用途 |
MX2020005562A (es) | 2017-11-30 | 2020-08-20 | Genentech Inc | Anticuerpos anti-pd-l1 y métodos para utilizarlos para la detección de pd-l1. |
MY181242A (en) * | 2017-12-01 | 2020-12-21 | Sbi Pharmaceuticals Co Ltd | Pharmaceutical composition for enhancing antitumor effect by immune checkpoint inhibitor |
CN111615521A (zh) * | 2017-12-04 | 2020-09-01 | 北京韩美药品有限公司 | 抗pd-l1/抗cd47天然抗体结构样异源二聚体形式双特异抗体及其制备 |
EP3720881A1 (en) | 2017-12-08 | 2020-10-14 | Elstar Therapeutics, Inc. | Multispecific molecules and uses thereof |
KR20200099178A (ko) | 2017-12-15 | 2020-08-21 | 얀센 바이오테크 인코포레이티드 | Sting 작용제로서의 환상 다이뉴클레오티드 |
WO2019118937A1 (en) | 2017-12-15 | 2019-06-20 | Juno Therapeutics, Inc. | Anti-cct5 binding molecules and methods of use thereof |
US11629189B2 (en) | 2017-12-19 | 2023-04-18 | Kymab Limited | Bispecific antibody for ICOS and PD-L1 |
GB201721338D0 (en) | 2017-12-19 | 2018-01-31 | Kymab Ltd | Anti-icos Antibodies |
CN111741976A (zh) | 2017-12-19 | 2020-10-02 | F星贝塔有限公司 | 包括pd-l1抗原结合位点的fc结合片段 |
JP2021507906A (ja) | 2017-12-20 | 2021-02-25 | ノバルティス アーゲー | 抗ウイルス剤としての融合三環式ピラゾロ−ジヒドロピラジニル−ピリドン化合物 |
US11685761B2 (en) | 2017-12-20 | 2023-06-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
TW201929908A (zh) | 2017-12-21 | 2019-08-01 | 美商梅爾莎納醫療公司 | 吡咯并苯并二氮呯抗體共軛物 |
BR112020012997A2 (pt) | 2017-12-26 | 2020-12-01 | Kymera Therapeutics, Inc. | degradadores de irak e usos dos mesmos |
CN109970857B (zh) | 2017-12-27 | 2022-09-30 | 信达生物制药(苏州)有限公司 | 抗pd-l1抗体及其用途 |
WO2019129054A1 (zh) | 2017-12-27 | 2019-07-04 | 信达生物制药(苏州)有限公司 | 三链抗体、其制备方法及其用途 |
WO2019129137A1 (zh) | 2017-12-27 | 2019-07-04 | 信达生物制药(苏州)有限公司 | 抗lag-3抗体及其用途 |
CN111788227A (zh) | 2017-12-27 | 2020-10-16 | 百时美施贵宝公司 | 抗cd40抗体及其用途 |
CN109970856B (zh) | 2017-12-27 | 2022-08-23 | 信达生物制药(苏州)有限公司 | 抗lag-3抗体及其用途 |
WO2019129136A1 (zh) | 2017-12-27 | 2019-07-04 | 信达生物制药(苏州)有限公司 | 抗pd-l1抗体及其用途 |
TW201930350A (zh) * | 2017-12-28 | 2019-08-01 | 大陸商南京傳奇生物科技有限公司 | 針對pd-l1之抗體及其變異體 |
US11865081B2 (en) | 2017-12-29 | 2024-01-09 | Virogin Biotech Canada Ltd. | Oncolytic viral delivery of therapeutic polypeptides |
CN111867619A (zh) * | 2018-01-03 | 2020-10-30 | 曲生物制品公司 | 过继性细胞治疗的先天寻靶 |
EP3735590A1 (en) | 2018-01-04 | 2020-11-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma resistant |
WO2019136112A1 (en) | 2018-01-05 | 2019-07-11 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
EP3737408A1 (en) | 2018-01-08 | 2020-11-18 | Novartis AG | Immune-enhancing rnas for combination with chimeric antigen receptor therapy |
WO2019139921A1 (en) | 2018-01-09 | 2019-07-18 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
WO2019137397A1 (zh) * | 2018-01-10 | 2019-07-18 | 江苏恒瑞医药股份有限公司 | Pd-l1抗体、其抗原结合片段及医药用途 |
CA3084370A1 (en) | 2018-01-12 | 2019-07-18 | Bristol-Myers Squibb Company | Combination therapy with anti-il-8 antibodies and anti-pd-1 antibodies for treating cancer |
US20210177781A9 (en) | 2018-01-12 | 2021-06-17 | KDAc Therapeutics, Inc. | Combination of a selective histone deacetylase 3 (hdac3) inhibitor and an immunotherapy agent for the treatment of cancer |
CN111886255A (zh) | 2018-01-12 | 2020-11-03 | 百时美施贵宝公司 | 抗tim3抗体及其用途 |
US11485743B2 (en) | 2018-01-12 | 2022-11-01 | Kymera Therapeutics, Inc. | Protein degraders and uses thereof |
WO2019140387A1 (en) | 2018-01-12 | 2019-07-18 | Kymera Therapeutics, Inc. | Crbn ligands and uses thereof |
KR20200109339A (ko) | 2018-01-16 | 2020-09-22 | 브리스톨-마이어스 스큅 컴퍼니 | Tim3에 대한 항체를 사용하여 암을 치료하는 방법 |
EP3740509A4 (en) | 2018-01-17 | 2022-06-22 | Apexigen, Inc. | ANTI-PD-L1 ANTIBODIES AND METHODS OF USE |
WO2019144126A1 (en) | 2018-01-22 | 2019-07-25 | Pascal Biosciences Inc. | Cannabinoids and derivatives for promoting immunogenicity of tumor and infected cells |
BR112020014574A2 (pt) | 2018-01-22 | 2020-12-08 | Bristol-Myers Squibb Company | Composições e métodos para o tratamento do câncer |
US11786523B2 (en) | 2018-01-24 | 2023-10-17 | Beyondspring Pharmaceuticals, Inc. | Composition and method for reducing thrombocytopenia |
CA3089769A1 (en) | 2018-01-29 | 2019-08-01 | Merck Patent Gmbh | Gcn2 inhibitors and uses thereof |
SG11202006701TA (en) | 2018-01-29 | 2020-08-28 | Merck Patent Gmbh | Gcn2 inhibitors and uses thereof |
JP7383620B2 (ja) | 2018-01-31 | 2023-11-20 | セルジーン コーポレイション | 養子細胞療法およびチェックポイント阻害剤を使用する併用療法 |
EP3746116A1 (en) | 2018-01-31 | 2020-12-09 | Novartis AG | Combination therapy using a chimeric antigen receptor |
WO2019152979A1 (en) | 2018-02-05 | 2019-08-08 | Orionis Biosciences, Inc. | Fibroblast binding agents and use thereof |
WO2019157124A1 (en) | 2018-02-08 | 2019-08-15 | Bristol-Myers Squibb Company | Combination of a tetanus toxoid, anti-ox40 antibody and/or anti-pd-1 antibody to treat tumors |
EP3752203A1 (en) | 2018-02-13 | 2020-12-23 | Novartis AG | Chimeric antigen receptor therapy in combination with il-15r and il15 |
EP3756012A1 (en) | 2018-02-21 | 2020-12-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of sk1 as biomarker for predicting response to immunecheckpoint inhibitors |
WO2019165315A1 (en) | 2018-02-23 | 2019-08-29 | Syntrix Biosystems Inc. | Method for treating cancer using chemokine antagonists alone or in combination |
AU2019225249A1 (en) | 2018-02-26 | 2020-09-17 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-PD-L1 antagonist antibodies |
TW202000666A (zh) | 2018-02-27 | 2020-01-01 | 美商英塞特公司 | 作為a2a/a2b抑制劑之咪唑并嘧啶及三唑并嘧啶 |
US20200405763A1 (en) * | 2018-02-27 | 2020-12-31 | The Methodist Hospital System | Irf-4 engineered t cells and uses thereof in treating cancer |
CN111801331A (zh) | 2018-02-28 | 2020-10-20 | 诺华股份有限公司 | 吲哚-2-羰基化合物及其用于治疗乙型肝炎的用途 |
CA3090620A1 (en) | 2018-03-06 | 2019-09-12 | Institut Curie | Inhibitor of setdb1 histone methyltransferase for use in cancer combination therapy |
RU2020133451A (ru) | 2018-03-12 | 2022-04-12 | Инститьют Насьонал Де Ла Санте Et De La Решерш Медикаль (Инсерм) | Применение терапевтически эффективной комбинации химиотерапиии и ингибитора контрольной точки иммунного ответа с миметиком ограничения калорийности для лечения рака |
JP2021517130A (ja) | 2018-03-13 | 2021-07-15 | オーセ イミュノセラピューティクスOse Immunotherapeutics | 抗ヒトSIRPav1抗体の使用および抗v1抗体を製造する方法 |
EP3766499A4 (en) * | 2018-03-13 | 2021-04-21 | Osaka University | TUMOR IMMUNE STIMULATOR |
WO2019178362A1 (en) | 2018-03-14 | 2019-09-19 | Elstar Therapeutics, Inc. | Multifunctional molecules that bind to calreticulin and uses thereof |
US20210009711A1 (en) | 2018-03-14 | 2021-01-14 | Elstar Therapeutics, Inc. | Multifunctional molecules and uses thereof |
WO2019175243A1 (en) | 2018-03-14 | 2019-09-19 | Merck Patent Gmbh | Compounds and uses thereof to treat tumors in a subject |
MX2021015518A (es) | 2018-03-14 | 2022-07-21 | Surface Oncology Inc | Anticuerpos que se unen a cd39 y sus usos. |
US20210017283A1 (en) | 2018-03-21 | 2021-01-21 | Five Prime Therapeutics, Inc. | Antibodies Binding to Vista at Acidic pH |
US11332524B2 (en) | 2018-03-22 | 2022-05-17 | Surface Oncology, Inc. | Anti-IL-27 antibodies and uses thereof |
AU2019236865A1 (en) | 2018-03-23 | 2020-10-01 | Bristol-Myers Squibb Company | Antibodies against MICA and/or MICB and uses thereof |
WO2019184909A1 (zh) | 2018-03-27 | 2019-10-03 | 信达生物制药(苏州)有限公司 | 新型抗体分子、其制备方法及其用途 |
CN110305210B (zh) | 2018-03-27 | 2023-02-28 | 信达生物制药(苏州)有限公司 | 新型抗体分子、其制备方法及其用途 |
CN108546298B (zh) * | 2018-03-29 | 2021-05-14 | 中国人民解放军军事科学院军事医学研究院 | 一种特异性结合pd-1的单克隆抗体 |
WO2019185792A1 (en) | 2018-03-29 | 2019-10-03 | Philogen S.P.A | Cancer treatment using immunoconjugates and immune check-point inhibitors |
CN108546299B (zh) * | 2018-03-29 | 2019-09-24 | 中国人民解放军军事科学院军事医学研究院 | 解除pd-1对机体免疫抑制的靶向分子 |
JP2021519771A (ja) | 2018-03-30 | 2021-08-12 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 腫瘍を処置する方法 |
US11952424B2 (en) | 2018-03-30 | 2024-04-09 | Merus N.V. | Multivalent antibody |
EP3774765A4 (en) | 2018-04-03 | 2021-12-29 | Merck Sharp & Dohme Corp. | Aza-benzothiophene compounds as sting agonists |
KR20200139203A (ko) | 2018-04-03 | 2020-12-11 | 머크 샤프 앤드 돔 코포레이션 | Sting 효능제로서의 벤조티오펜 및 관련 화합물 |
JP2021520201A (ja) | 2018-04-04 | 2021-08-19 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 抗cd27抗体およびその使用 |
US11874276B2 (en) | 2018-04-05 | 2024-01-16 | Dana-Farber Cancer Institute, Inc. | STING levels as a biomarker for cancer immunotherapy |
WO2019193540A1 (en) | 2018-04-06 | 2019-10-10 | Glaxosmithkline Intellectual Property Development Limited | Heteroaryl derivatives of formula (i) as atf4 inhibitors |
WO2019193541A1 (en) | 2018-04-06 | 2019-10-10 | Glaxosmithkline Intellectual Property Development Limited | Bicyclic aromatic ring derivatives of formula (i) as atf4 inhibitors |
CN112218657A (zh) | 2018-04-12 | 2021-01-12 | 百时美施贵宝公司 | Cd73拮抗剂抗体和pd-1/pd-l1轴拮抗剂抗体的抗癌组合疗法 |
US20210147547A1 (en) | 2018-04-13 | 2021-05-20 | Novartis Ag | Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof |
AU2019254237A1 (en) | 2018-04-16 | 2020-12-03 | Onquality Pharmaceuticals China Ltd. | Method for preventing or treating side effects of cancer therapy |
CN108727504B (zh) * | 2018-04-16 | 2021-08-27 | 泉州向日葵生物科技有限公司 | 一种ifn与抗pd-l1抗体的融合蛋白及其应用 |
WO2019204257A1 (en) | 2018-04-16 | 2019-10-24 | Arrys Therapeutics, Inc. | Ep4 inhibitors and use thereof |
US10968201B2 (en) | 2018-04-17 | 2021-04-06 | Tempest Therapeutics, Inc. | Bicyclic carboxamides and methods of use thereof |
MX2020010910A (es) | 2018-04-18 | 2021-02-09 | Xencor Inc | Proteinas de fusion heterodimericas dirigidas a pd-1 que contienen proteinas de fusion il-15 / il-15ra fc y dominios de union al antigeno pd-1 y usos de los mismos. |
CA3097625A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Il-15/il-15ra heterodimeric fc fusion proteins and uses thereof |
EP3781689A1 (en) | 2018-04-19 | 2021-02-24 | Checkmate Pharmaceuticals, Inc. | Synthetic rig-i-like receptor agonists |
EP3781687A4 (en) | 2018-04-20 | 2022-02-09 | Merck Sharp & Dohme Corp. | NEW RIG-I SUBSTITUTED AGONISTS: COMPOSITIONS AND METHODS THEREOF |
BR112020021539A2 (pt) | 2018-04-25 | 2021-01-19 | Innate Tumor Immunity, Inc. | Moduladores de nlrp3 |
EP3784688A2 (en) | 2018-04-26 | 2021-03-03 | Agenus Inc. | Heat shock protein-binding peptide compositions and methods of use thereof |
WO2019207030A1 (en) | 2018-04-26 | 2019-10-31 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting a response with an immune checkpoint inhibitor in a patient suffering from a lung cancer |
EP3784351A1 (en) | 2018-04-27 | 2021-03-03 | Novartis AG | Car t cell therapies with enhanced efficacy |
EP3788369A1 (en) | 2018-05-01 | 2021-03-10 | Novartis Ag | Biomarkers for evaluating car-t cells to predict clinical outcome |
WO2019213340A1 (en) | 2018-05-03 | 2019-11-07 | Bristol-Myers Squibb Company | Uracil derivatives as mer-axl inhibitors |
WO2019211492A1 (en) | 2018-05-04 | 2019-11-07 | Tollys | Tlr3 ligands that activate both epithelial and myeloid cells |
TW202014201A (zh) | 2018-05-04 | 2020-04-16 | 德商馬克專利公司 | 用於治療癌症之PD-1/PD-L1,TGFβ及DNA-PK之組合抑制 |
KR20210018265A (ko) | 2018-05-04 | 2021-02-17 | 인사이트 코포레이션 | Fgfr 억제제의 고체 형태 및 이의 제조 방법 |
SG11202010882XA (en) | 2018-05-04 | 2020-11-27 | Incyte Corp | Salts of an fgfr inhibitor |
SG11202011117VA (en) | 2018-05-15 | 2020-12-30 | Medimmune Ltd | Treatment of cancer |
GB201807924D0 (en) | 2018-05-16 | 2018-06-27 | Ctxt Pty Ltd | Compounds |
CA3100731A1 (en) | 2018-05-18 | 2019-11-21 | Incyte Corporation | Fused pyrimidine derivatives as a2a / a2b inhibitors |
BR112020023756A2 (pt) | 2018-05-23 | 2021-02-09 | Celgene Corporation | tratamento de mieloma múltiplo e uso de biomarcadores para 4-(4-(4-(((2-(2,6-dioxopiperidin-3-il)-1-oxoisoindolin-4-il)oxi)metil)benzil)piperazin-1-il)-3-fluorobenzonitrila |
JP7293256B2 (ja) | 2018-05-23 | 2023-06-19 | セルジーン コーポレイション | 併用のためのbcma及びcd3に対する抗増殖性化合物及び二重特異性抗体 |
AR126019A1 (es) | 2018-05-30 | 2023-09-06 | Novartis Ag | Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación |
WO2019232244A2 (en) | 2018-05-31 | 2019-12-05 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
TW202017569A (zh) | 2018-05-31 | 2020-05-16 | 美商佩樂敦治療公司 | 用於抑制cd73之組合物及方法 |
US11352320B2 (en) | 2018-05-31 | 2022-06-07 | Merck Sharp & Dohme Corp. | Substituted [1.1.1] bicyclo compounds as indoleamine 2,3-dioxygenase inhibitors |
CN112165974A (zh) | 2018-05-31 | 2021-01-01 | 诺华股份有限公司 | 乙型肝炎抗体 |
TW202016136A (zh) | 2018-06-01 | 2020-05-01 | 瑞士商諾華公司 | 針對bcma之結合分子及其用途 |
CN112512578A (zh) | 2018-06-01 | 2021-03-16 | 诺华股份有限公司 | 结合cd123和cd3的双特异性抗体的给药 |
CN112566938A (zh) | 2018-06-03 | 2021-03-26 | 拉姆卡普生物测试有限公司 | 针对ceacam5和cd47的双特异性抗体 |
CN110563842B (zh) * | 2018-06-06 | 2022-07-29 | 浙江博锐生物制药有限公司 | 针对程序性死亡配体(pd-l1)的抗体及其应用 |
US11266615B2 (en) | 2018-06-08 | 2022-03-08 | Harrow Ip, Llc | Pyrimethamine-based pharmaceutical compositions and methods for fabricating thereof |
EP3813803A1 (en) | 2018-06-08 | 2021-05-05 | Harrow IP, LLC | Pyrimethamine-based pharmaceutical compositions and methods for fabricating thereof |
MX2020013443A (es) | 2018-06-13 | 2021-02-26 | Novartis Ag | Receptores de antigeno quimerico de bcma y usos de los mismos. |
KR20210035805A (ko) | 2018-06-15 | 2021-04-01 | 플래그쉽 파이어니어링 이노베이션스 브이, 인크. | 세포후 신호전달 인자의 조절을 통한 면역 활성의 증가 |
CN112334486A (zh) | 2018-06-18 | 2021-02-05 | 先天制药公司 | 用于治疗癌症的组合物和方法 |
JP7097465B2 (ja) | 2018-06-19 | 2022-07-07 | アルモ・バイオサイエンシーズ・インコーポレイテッド | キメラ抗原受容体細胞療法と併用するil-10剤の組成およびその使用方法 |
US11180531B2 (en) | 2018-06-22 | 2021-11-23 | Bicycletx Limited | Bicyclic peptide ligands specific for Nectin-4 |
MA52968A (fr) | 2018-06-23 | 2021-04-28 | Hoffmann La Roche | Méthodes de traitement du cancer du poumon à l'aide d'un antagoniste de liaison à l'axe pd-1, d'un agent de platine et d'un inhibiteur de la topoisomérase ii |
WO2020006016A1 (en) | 2018-06-27 | 2020-01-02 | Bristol-Myers Squibb Company | Naphthyridinone compounds useful as t cell activators |
PE20210469A1 (es) | 2018-06-27 | 2021-03-08 | Bristol Myers Squibb Co | Compuestos de naftiridinona sustituidos utiles como activadores de celulas t |
CA3105448A1 (en) | 2018-07-03 | 2020-01-09 | Elstar Therapeutics, Inc. | Anti-tcr antibody molecules and uses thereof |
EP3818082A1 (en) | 2018-07-04 | 2021-05-12 | F. Hoffmann-La Roche AG | Novel bispecific agonistic 4-1bb antigen binding molecules |
WO2020010177A1 (en) | 2018-07-06 | 2020-01-09 | Kymera Therapeutics, Inc. | Tricyclic crbn ligands and uses thereof |
TWI819024B (zh) | 2018-07-09 | 2023-10-21 | 美商戊瑞治療有限公司 | 結合至ilt4的抗體 |
US20210253528A1 (en) | 2018-07-09 | 2021-08-19 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds |
AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
AU2019301944B2 (en) | 2018-07-10 | 2022-02-24 | Novartis Ag | 3-(5-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and their use in the treatment of IKAROS Family Zinc Finger 2 (IKZF2)-dependent diseases |
CN112673092B (zh) | 2018-07-11 | 2024-03-29 | 阿克蒂姆治疗有限公司 | 工程化的免疫刺激性细菌菌株及其用途 |
PE20210687A1 (es) | 2018-07-11 | 2021-04-08 | Bristol Myers Squibb Co | Anticuerpos de union a vista a ph acido |
GB201811408D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | CD137 Binding Molecules |
WO2020011966A1 (en) | 2018-07-12 | 2020-01-16 | F-Star Beta Limited | Antibody molecules that bind cd137 and ox40 |
BR112021000394A2 (pt) | 2018-07-12 | 2021-04-06 | F-Star Beta Limited | Moléculas de anticorpo que se ligam a pd-l1 e cd137 |
WO2020014583A1 (en) | 2018-07-13 | 2020-01-16 | Bristol-Myers Squibb Company | Ox-40 agonist, pd-1 pathway inhibitor and ctla-4 inhibitor combination for use in a mehtod of treating a cancer or a solid tumor |
KR20210034622A (ko) | 2018-07-18 | 2021-03-30 | 제넨테크, 인크. | Pd-1 축 결합 길항제, 항 대사제, 및 백금 제제를 이용한 폐암 치료 방법 |
KR20210032488A (ko) | 2018-07-20 | 2021-03-24 | 서피스 온콜로지, 인크. | 항-cd112r 조성물 및 방법 |
US20210355113A1 (en) | 2018-07-23 | 2021-11-18 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
WO2020023355A1 (en) | 2018-07-23 | 2020-01-30 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
TW202012405A (zh) | 2018-07-24 | 2020-04-01 | 瑞士商赫孚孟拉羅股份公司 | 萘啶化合物及其用途 |
US20210301020A1 (en) | 2018-07-24 | 2021-09-30 | Amgen Inc. | Combination of lilrb1/2 pathway inhibitors and pd-1 pathway inhibitors |
EP3826722A1 (en) | 2018-07-24 | 2021-06-02 | F. Hoffmann-La Roche AG | Isoquinoline compounds and uses thereof |
CN112041348B (zh) | 2018-07-25 | 2023-09-22 | 天境生物科技(上海)有限公司 | 抗cd73抗pd-l1双特异性抗体 |
EP3826660A1 (en) | 2018-07-26 | 2021-06-02 | Bristol-Myers Squibb Company | Lag-3 combination therapy for the treatment of cancer |
US20210236633A1 (en) | 2018-08-06 | 2021-08-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers |
WO2020031107A1 (en) | 2018-08-08 | 2020-02-13 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds |
JP2021534101A (ja) | 2018-08-09 | 2021-12-09 | ヴェルソー セラピューティクス, インコーポレイテッド | Ccr2及びcsf1rを標的とするためのオリゴヌクレオチド組成物ならびにその使用 |
CN112601761A (zh) | 2018-08-13 | 2021-04-02 | 印希比股份有限公司 | 结合ox40的多肽及其用途 |
CN113038989A (zh) | 2018-08-16 | 2021-06-25 | 先天肿瘤免疫公司 | 咪唑并[4,5-c]喹啉衍生的nlrp3调节剂 |
CN112888677A (zh) | 2018-08-16 | 2021-06-01 | 先天肿瘤免疫公司 | 被取代的4-氨基-1H-咪唑并[4,5-c]喹啉化合物及其改进的制备方法 |
CN112996567A (zh) | 2018-08-16 | 2021-06-18 | 先天肿瘤免疫公司 | 咪唑并[4,5-c]喹啉衍生的nlrp3-调节剂 |
AU2019324388A1 (en) * | 2018-08-20 | 2021-03-18 | 1Globe Biomedical Co., Ltd. | Novel cancer immunotherapy antibody compositions |
EP3843849A1 (en) | 2018-08-27 | 2021-07-07 | Pieris Pharmaceuticals GmbH | Combination therapies comprising cd137/her2 bispecific agents and pd-1 axis inhibitors and uses thereof |
US10959986B2 (en) | 2018-08-29 | 2021-03-30 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
WO2020044206A1 (en) | 2018-08-29 | 2020-03-05 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides as kinase inhibitors for use in the treatment cancer |
US11253525B2 (en) | 2018-08-29 | 2022-02-22 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
JP7397874B2 (ja) | 2018-08-30 | 2023-12-13 | エイチシーダブリュー バイオロジックス インコーポレイテッド | 多鎖キメラポリペプチドおよびその使用 |
SG11202101780WA (en) | 2018-08-30 | 2021-03-30 | Hcw Biologics Inc | Single-chain chimeric polypeptides and uses thereof |
CA3109361A1 (en) | 2018-08-30 | 2020-03-05 | HCW Biologics, Inc. | Single-chain and multi-chain chimeric polypeptides and uses thereof |
TW202031273A (zh) | 2018-08-31 | 2020-09-01 | 美商艾歐凡斯生物治療公司 | 抗pd-1抗體難治療性之非小細胞肺癌(nsclc)病患的治療 |
TW202024023A (zh) | 2018-09-03 | 2020-07-01 | 瑞士商赫孚孟拉羅股份公司 | 治療性化合物及其使用方法 |
WO2020048942A1 (en) | 2018-09-04 | 2020-03-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for enhancing cytotoxic t lymphocyte-dependent immune responses |
WO2020051333A1 (en) | 2018-09-07 | 2020-03-12 | Pfizer Inc. | Anti-avb8 antibodies and compositions and uses thereof |
JP2021536476A (ja) * | 2018-09-07 | 2021-12-27 | ザ ジェネラル ホスピタル コーポレイション | 免疫チェックポイント阻害のための組成物および方法 |
EP3846793B1 (en) | 2018-09-07 | 2024-01-24 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
WO2020053742A2 (en) | 2018-09-10 | 2020-03-19 | Novartis Ag | Anti-hla-hbv peptide antibodies |
CA3112326A1 (en) | 2018-09-12 | 2020-03-19 | Novartis Ag | Antiviral pyridopyrazinedione compounds |
CA3111401A1 (en) | 2018-09-19 | 2020-03-26 | Genentech, Inc. | Therapeutic and diagnostic methods for bladder cancer |
EP3852752A1 (en) | 2018-09-19 | 2021-07-28 | F. Hoffmann-La Roche AG | Spirocyclic 2,3-dihydro-7-azaindole compounds and uses thereof |
JP2022511337A (ja) | 2018-09-19 | 2022-01-31 | インサーム (インスティテュート ナショナル デ ラ サンテ エ デ ラ ルシェルシェ メディカル) | 免疫チェックポイント治療に抵抗性のある癌の治療のための方法および医薬組成物 |
BR112021003678A2 (pt) | 2018-09-20 | 2021-05-18 | Iovance Biotherapeutics, Inc. | métodos para criopreservar tecido de tumor, para fabricar, para preparar e para expandir linfócitos infiltrantes de tumor, para tratar um indivíduo com câncer e para tratar câncer para um indivíduo humano, e, fragmento de tumor criopreservado . |
EP3857230B1 (en) | 2018-09-21 | 2023-06-07 | F. Hoffmann-La Roche AG | Diagnostic methods for triple-negative breast cancer |
JP7425049B2 (ja) | 2018-09-25 | 2024-01-30 | ハープーン セラピューティクス,インク. | Dll3結合タンパク質および使用方法 |
KR20210066837A (ko) | 2018-09-26 | 2021-06-07 | 메르크 파텐트 게엠베하 | 암 치료를 위한 pd-1 안타고니스트, atr 억제제 및 백금화제의 조합 |
JP7465272B2 (ja) | 2018-09-27 | 2024-04-10 | マレンゴ・セラピューティクス,インコーポレーテッド | Csf1r/ccr2多特異性抗体 |
US20210347851A1 (en) | 2018-09-28 | 2021-11-11 | Novartis Ag | Cd19 chimeric antigen receptor (car) and cd22 car combination therapies |
CN110960679A (zh) * | 2018-09-28 | 2020-04-07 | 江苏康缘药业股份有限公司 | 一种抗肿瘤的药物组合物及其应用 |
US20220047633A1 (en) | 2018-09-28 | 2022-02-17 | Novartis Ag | Cd22 chimeric antigen receptor (car) therapies |
IL305106A (en) | 2018-09-29 | 2023-10-01 | Novartis Ag | A process for producing a compound to inhibit the activity of SHP2 |
JP7433304B2 (ja) | 2018-09-30 | 2024-02-19 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | シンノリン化合物および癌などのhpk1依存性障害の治療 |
WO2020070053A1 (en) | 2018-10-01 | 2020-04-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of inhibitors of stress granule formation for targeting the regulation of immune responses |
TW202024053A (zh) | 2018-10-02 | 2020-07-01 | 美商建南德克公司 | 異喹啉化合物及其用途 |
WO2020072695A1 (en) | 2018-10-03 | 2020-04-09 | Genentech, Inc. | 8-aminoisoquinoline compounds and uses thereof |
EP3861016A2 (en) | 2018-10-03 | 2021-08-11 | Xencor, Inc. | Il-12 heterodimeric fc-fusion proteins |
CN112839962A (zh) | 2018-10-09 | 2021-05-25 | 百时美施贵宝公司 | 用于治疗癌症的抗mertk抗体 |
TW202035445A (zh) | 2018-10-10 | 2020-10-01 | 美商帝洛斯療法股份有限公司 | 抗lap抗體變異體及其用途 |
US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
US11377477B2 (en) | 2018-10-12 | 2022-07-05 | Xencor, Inc. | PD-1 targeted IL-15/IL-15RALPHA fc fusion proteins and uses in combination therapies thereof |
CN112867803A (zh) | 2018-10-16 | 2021-05-28 | 诺华股份有限公司 | 单独的或与免疫标志物组合的肿瘤突变负荷作为生物标志物用于预测对靶向疗法的应答 |
WO2020081493A1 (en) | 2018-10-16 | 2020-04-23 | Molecular Templates, Inc. | Pd-l1 binding proteins |
CA3116324A1 (en) | 2018-10-18 | 2020-04-23 | Genentech, Inc. | Diagnostic and therapeutic methods for sarcomatoid kidney cancer |
JP2022505113A (ja) | 2018-10-18 | 2022-01-14 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 固形腫瘍の処置のためのβig-h3アンタゴニストと免疫チェックポイント阻害剤との組み合わせ |
CN113286611A (zh) | 2018-10-19 | 2021-08-20 | 百时美施贵宝公司 | 用于黑色素瘤的组合疗法 |
MX2021004603A (es) | 2018-10-22 | 2021-09-08 | Glaxosmithkline Ip Dev Ltd | Dosificacion. |
JP2022505647A (ja) | 2018-10-23 | 2022-01-14 | ブリストル-マイヤーズ スクイブ カンパニー | 腫瘍の処置方法 |
US11564995B2 (en) | 2018-10-29 | 2023-01-31 | Wisconsin Alumni Research Foundation | Peptide-nanoparticle conjugates |
CA3117050A1 (en) | 2018-10-29 | 2020-05-07 | Mersana Therapeutics, Inc. | Cysteine engineered antibody-drug conjugates with peptide-containing linkers |
KR20210084552A (ko) | 2018-10-29 | 2021-07-07 | 위스콘신 얼럼나이 리서어치 화운데이션 | 향상된 암 면역요법을 위한 면역관문 억제제와 복합체화된 덴드리틱 폴리머 |
WO2020089811A1 (en) | 2018-10-31 | 2020-05-07 | Novartis Ag | Dc-sign antibody drug conjugates |
JP2022512917A (ja) | 2018-11-01 | 2022-02-07 | ジュノー セラピューティクス インコーポレイテッド | B細胞成熟抗原に特異的なキメラ抗原受容体を使用する処置方法 |
EP3873464A4 (en) | 2018-11-01 | 2022-06-08 | Merck Sharp & Dohme Corp. | NOVEL SUBSTITUTED PYRAZOLE COMPOUNDS AS INDOLAMINE-2,3-DIOXYGENASE INHIBITORS |
JP2022506598A (ja) | 2018-11-01 | 2022-01-17 | ジュノー セラピューティクス インコーポレイテッド | Gタンパク質共役受容体クラスcグループ5メンバーd(gprc5d)に特異的なキメラ抗原受容体 |
US20210403469A1 (en) | 2018-11-06 | 2021-12-30 | Merck Sharp & Dohme Corp. | Novel substituted tricyclic compounds as indoleamine 2,3-dioxygenase inhibitors |
CN113454111A (zh) | 2018-11-06 | 2021-09-28 | 健玛保 | 抗体配制剂 |
US20220001026A1 (en) | 2018-11-08 | 2022-01-06 | Modernatx, Inc. | Use of mrna encoding ox40l to treat cancer in human patients |
KR20210091152A (ko) | 2018-11-14 | 2021-07-21 | 바이엘 악티엔게젤샤프트 | 암의 치료를 위한 항-ceacam6 및 항-pd-1 또는 항-pd-l1 항체의 제약 조합물 |
WO2020102375A1 (en) | 2018-11-14 | 2020-05-22 | Regeneron Pharmaceuticals, Inc. | Intralesional administration of pd-1 inhibitors for treating skin cancer |
TW202028222A (zh) | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
AU2019380307A1 (en) | 2018-11-16 | 2021-07-01 | Bristol-Myers Squibb Company | Anti-NKG2A antibodies and uses thereof |
EP3880231A1 (en) | 2018-11-16 | 2021-09-22 | NeoImmuneTech, Inc. | Method of treating a tumor with a combination of il-7 protein and an immune checkpoint inhibitor |
KR20210104713A (ko) | 2018-11-16 | 2021-08-25 | 주노 쎄러퓨티크스 인코퍼레이티드 | B 세포 악성 종양 치료를 위한 조작된 t 세포 투약 방법 |
WO2020102804A2 (en) | 2018-11-16 | 2020-05-22 | Arqule, Inc. | Pharmaceutical combination for treatment of cancer |
WO2020106560A1 (en) | 2018-11-20 | 2020-05-28 | Merck Sharp & Dohme Corp. | Substituted amino triazolopyrimidine and amino triazolopyrazine adenosine receptor antagonists, pharmaceutical compositions and their use |
WO2020104496A1 (en) | 2018-11-20 | 2020-05-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Bispecific antibody targeting transferrin receptor 1 and soluble antigen |
JP2022507734A (ja) | 2018-11-20 | 2022-01-18 | メルク・シャープ・アンド・ドーム・コーポレーション | 置換アミノトリアゾロピリミジン及びアミノトリアゾロピラジンアデノシン受容体アンタゴニスト、医薬組成物及びそれらの使用 |
AU2019385497A1 (en) | 2018-11-20 | 2021-06-17 | Cornell University | Macrocyclic complexes of radionuclides and their use in radiotherapy of cancer |
WO2020104479A1 (en) | 2018-11-20 | 2020-05-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers and resistant cancers with anti transferrin receptor 1 antibodies |
EP3886842A1 (en) | 2018-11-26 | 2021-10-06 | Debiopharm International SA | Combination treatment of hiv infections |
EP3887397A1 (en) | 2018-11-28 | 2021-10-06 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
US20230008022A1 (en) | 2018-11-28 | 2023-01-12 | Merck Sharp & Dohme Corp. | Novel substituted piperazine amide compounds as indoleamine 2,3-dioxygenase (ido) inhibitors |
US20220018828A1 (en) | 2018-11-28 | 2022-01-20 | Inserm (Institut National De La Santé Et La Recherche Médicale | Methods and kit for assaying lytic potential of immune effector cells |
WO2020109570A1 (en) | 2018-11-30 | 2020-06-04 | Gbg Forschungs Gmbh | Method for predicting the response to cancer immunotherapy in cancer patients |
JOP20210117A1 (ar) | 2018-11-30 | 2023-01-30 | Merck Sharp & Dohme | مشتقات أمينو ترايازولو كوينازولين بها استبدال في الموضع-9 كمضادات مستقبل أدينوزين، تركيبات صيدلانية واستخدامها |
KR20210117260A (ko) | 2018-11-30 | 2021-09-28 | 주노 쎄러퓨티크스 인코퍼레이티드 | 입양 세포 요법을 사용한 치료방법 |
IL310831A (en) | 2018-11-30 | 2024-04-01 | Glaxosmithkline Ip Dev Ltd | Compounds useful in curing HIV |
WO2020113233A1 (en) | 2018-11-30 | 2020-06-04 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
EP3891508A1 (en) | 2018-12-04 | 2021-10-13 | Bristol-Myers Squibb Company | Methods of analysis using in-sample calibration curve by multiple isotopologue reaction monitoring |
EP3890749A4 (en) | 2018-12-04 | 2022-08-03 | Sumitomo Dainippon Pharma Oncology, Inc. | CDK9 INHIBITORS AND POLYMORPHS THEREOF FOR USE AS CANCER TREATMENT AGENT |
JP2022511502A (ja) | 2018-12-05 | 2022-01-31 | ジェネンテック, インコーポレイテッド | がんの免疫療法のための診断方法及び診断用組成物 |
WO2020115261A1 (en) | 2018-12-07 | 2020-06-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
WO2020115262A1 (en) | 2018-12-07 | 2020-06-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of cd26 and cd39 as new phenotypic markers for assessing maturation of foxp3+ t cells and uses thereof for diagnostic purposes |
EP3894401A2 (en) | 2018-12-11 | 2021-10-20 | Theravance Biopharma R&D IP, LLC | Naphthyridine and quinoline derivatives useful as alk5 inhibitors |
WO2020120592A1 (en) | 2018-12-12 | 2020-06-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for predicting and treating melanoma |
EP3897624A1 (en) | 2018-12-17 | 2021-10-27 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Use of sulconazole as a furin inhibitor |
WO2020127411A1 (en) | 2018-12-19 | 2020-06-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers by immuno-modulation using antibodies against cathespin-d |
TW202039542A (zh) | 2018-12-19 | 2020-11-01 | 美商庫爾生物製藥有限公司 | 多聚體t細胞調節多肽及其使用方法 |
EP3670659A1 (en) | 2018-12-20 | 2020-06-24 | Abivax | Biomarkers, and uses in treatment of viral infections, inflammations, or cancer |
CN113438961A (zh) | 2018-12-20 | 2021-09-24 | Xencor股份有限公司 | 含有IL-15/IL-15Rα和NKG2D抗原结合结构域的靶向异二聚体Fc融合蛋白 |
CN109627336A (zh) * | 2018-12-20 | 2019-04-16 | 南京昂科利医药科技创新研究院有限公司 | 一种表达pd-l1单链抗体的新城疫溶瘤病毒的制备方法及应用 |
EP3897637A1 (en) | 2018-12-20 | 2021-10-27 | Novartis AG | Dosing regimen and pharmaceutical combination comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
WO2020128637A1 (en) | 2018-12-21 | 2020-06-25 | Novartis Ag | Use of il-1 binding antibodies in the treatment of a msi-h cancer |
US20220025036A1 (en) | 2018-12-21 | 2022-01-27 | Novartis Ag | Use of il-1beta binding antibodies |
WO2020127885A1 (en) | 2018-12-21 | 2020-06-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Compositions for treating cancers and resistant cancers |
CN113474048A (zh) | 2018-12-21 | 2021-10-01 | Aim免疫科技有限公司 | 用于癌症治疗的组合物和方法 |
US20200369762A1 (en) | 2018-12-21 | 2020-11-26 | Novartis Ag | Use of il-1beta binding antibodies |
BR112021011900A2 (pt) | 2018-12-21 | 2021-09-08 | Novartis Ag | Anticorpos para pmel17 e conjugados dos mesmos |
WO2020128893A1 (en) | 2018-12-21 | 2020-06-25 | Pfizer Inc. | Combination treatments of cancer comprising a tlr agonist |
KR20210108422A (ko) | 2018-12-21 | 2021-09-02 | 노파르티스 아게 | IL-1β 결합 항체의 용도 |
CA3124690A1 (en) | 2018-12-27 | 2020-07-02 | Amgen Inc. | Lyophilized virus formulations |
KR20210110838A (ko) | 2018-12-28 | 2021-09-09 | 트랜스진 에스.에이. | M2 결함성 폭스바이러스 |
WO2020141199A1 (en) | 2019-01-03 | 2020-07-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for enhancing cd8+ t cell-dependent immune responses in subjects suffering from cancer |
US11660297B2 (en) | 2019-01-09 | 2023-05-30 | Celgene Corporation | Antiproliferative compounds and second active agents for combined use |
CA3125756A1 (en) | 2019-01-09 | 2020-07-16 | Celgene Corporation | Solid forms comprising (s)-4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl) benzyl)piperazin-1-yl)-3-fluorobenzonitrile and salts thereof, and compositions comprising and methods of using the same |
CN113597301A (zh) | 2019-01-09 | 2021-11-02 | 细胞基因公司 | 包含(s)-4-(4-(4-(((2-(2,6-二氧代哌啶-3-基)-1-氧代异吲哚啉-4-基)氧基)甲基)苄基)哌嗪-1-基)-3-氟苄腈的药物组合物以及使用它的方法 |
CN113301963A (zh) | 2019-01-14 | 2021-08-24 | 先天肿瘤免疫公司 | 用于治疗癌症的作为nlrp3调节剂的取代的喹唑啉类 |
EP3911417B1 (en) | 2019-01-14 | 2022-10-26 | Innate Tumor Immunity, Inc. | Heterocyclic nlrp3 modulators , for use in the treatment of cancer |
CN113286786A (zh) | 2019-01-14 | 2021-08-20 | 先天肿瘤免疫公司 | Nlrp3调节剂 |
JP2022517112A (ja) | 2019-01-14 | 2022-03-04 | イネイト・テューマー・イミュニティ・インコーポレイテッド | Nlrp3モジュレーター |
CN113710702A (zh) | 2019-01-14 | 2021-11-26 | 健泰科生物技术公司 | 用pd-1轴结合拮抗剂和rna疫苗治疗癌症的方法 |
CA3126741A1 (en) | 2019-01-15 | 2020-07-23 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Mutated interleukin-34 (il-34) polypeptides and uses thereof in therapy |
MA54863A (fr) | 2019-01-29 | 2021-12-08 | Juno Therapeutics Inc | Anticorps et récepteurs antigéniques chimériques spécifiques du récepteur orphelin-1 de type récepteur à tyrosine kinase (ror1) |
TWI829857B (zh) | 2019-01-29 | 2024-01-21 | 美商英塞特公司 | 作為a2a / a2b抑制劑之吡唑并吡啶及三唑并吡啶 |
JP7442536B2 (ja) | 2019-01-30 | 2024-03-04 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | ガンを患っている被験体が免疫チェックポイント阻害剤で反応を達成するかを特定するための方法及び組成物 |
WO2020161083A1 (en) | 2019-02-04 | 2020-08-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for modulating blood-brain barrier |
JP2022519649A (ja) | 2019-02-08 | 2022-03-24 | ジェネンテック, インコーポレイテッド | がんの診断および治療方法 |
WO2020167990A1 (en) | 2019-02-12 | 2020-08-20 | Tolero Pharmaceuticals, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
US20220098674A1 (en) | 2019-02-13 | 2022-03-31 | Inserm (Institut National De La Santé Et Dr La Recherch Médicale) | Methods and compositions for selecting a cancer treatment in a subject suffering from cancer |
EP3924521A4 (en) | 2019-02-15 | 2023-03-29 | IncellDx, Inc. | BLADDER-ASSOCIATED SPECIMEN ASSAY, IDENTIFICATION AND TREATMENT OF BLADDER-ASSOCIATED NEOPLASIA, AND KITS FOR USE THEREOF |
EA202192019A1 (ru) | 2019-02-15 | 2021-11-02 | Новартис Аг | Производные 3-(1-оксо-5-(пиперидин-4-ил)изоиндолин-2-ил)пиперидин-2,6-диона и пути их применения |
CN113329792A (zh) | 2019-02-15 | 2021-08-31 | 诺华股份有限公司 | 取代的3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途 |
US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
TW202045181A (zh) | 2019-02-15 | 2020-12-16 | 美商英塞特公司 | 細胞週期蛋白依賴性激酶2生物標記物及其用途 |
WO2020169472A2 (en) | 2019-02-18 | 2020-08-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of inducing phenotypic changes in macrophages |
CN113710270A (zh) | 2019-02-19 | 2021-11-26 | 迈斯特治疗公司 | 产生可用于治疗癌症的自体t细胞的方法及其组合物 |
EP3929213A4 (en) * | 2019-02-21 | 2023-03-08 | Eucure (Beijing) Biopharma Co., Ltd | ANTI-PD-L1 ANTIBODIES AND ITS USE |
MX2021010228A (es) | 2019-02-28 | 2021-10-26 | Regeneron Pharma | Administracion de inhibidores de pd-1 para el tratamiento de cancer de piel. |
WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
MX2021010458A (es) | 2019-03-05 | 2021-09-21 | Amgen Inc | Uso de virus oncoliticos para el tratamiento del cancer. |
CN113677707A (zh) | 2019-03-06 | 2021-11-19 | 瑞泽恩制药公司 | 用于在治疗癌症中增强效力的il-4/il-13途径抑制剂 |
US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
EP3938403A1 (en) | 2019-03-14 | 2022-01-19 | F. Hoffmann-La Roche AG | Treatment of cancer with her2xcd3 bispecific antibodies in combination with anti-her2 mab |
WO2020187998A1 (en) | 2019-03-19 | 2020-09-24 | Fundació Privada Institut D'investigació Oncològica De Vall Hebron | Combination therapy with omomyc and an antibody binding pd-1 or ctla-4 for the treatment of cancer |
JP2022525149A (ja) | 2019-03-20 | 2022-05-11 | スミトモ ダイニッポン ファーマ オンコロジー, インコーポレイテッド | ベネトクラクスが失敗した急性骨髄性白血病(aml)の処置 |
EP3941463A1 (en) | 2019-03-22 | 2022-01-26 | Sumitomo Dainippon Pharma Oncology, Inc. | Compositions comprising pkm2 modulators and methods of treatment using the same |
JP2022527298A (ja) | 2019-03-26 | 2022-06-01 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Stat3の低分子分解誘導剤 |
KR20210146349A (ko) | 2019-03-28 | 2021-12-03 | 브리스톨-마이어스 스큅 컴퍼니 | 종양을 치료하는 방법 |
EP3946625A1 (en) | 2019-03-28 | 2022-02-09 | Bristol-Myers Squibb Company | Methods of treating tumor |
JP2022526565A (ja) | 2019-03-29 | 2022-05-25 | ウニヴェルズィテート チューリッヒ | コンパートメント、特にCNSへの局所送達のためのFc修飾生物学的製剤 |
US20220185831A1 (en) | 2019-03-29 | 2022-06-16 | The Regents Of The University Of Michigan | Stat3 protein degraders |
WO2020205662A1 (en) | 2019-03-29 | 2020-10-08 | Myst Therapeutics, Inc. | Ex vivo methods for producing a t cell therapeutic and related compositions and methods |
EP3948289A1 (en) | 2019-03-29 | 2022-02-09 | F. Hoffmann-La Roche AG | Modulators of cell surface protein interactions and methods and compositions related to same |
US11919904B2 (en) | 2019-03-29 | 2024-03-05 | Incyte Corporation | Sulfonylamide compounds as CDK2 inhibitors |
TW202102543A (zh) | 2019-03-29 | 2021-01-16 | 美商安進公司 | 溶瘤病毒在癌症新輔助療法中之用途 |
WO2020201362A2 (en) | 2019-04-02 | 2020-10-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of predicting and preventing cancer in patients having premalignant lesions |
EP3946462A1 (en) | 2019-04-02 | 2022-02-09 | BicycleTX Limited | Bicycle toxin conjugates and uses thereof |
AU2020253955A1 (en) | 2019-04-03 | 2021-09-09 | Targimmune Therapeutics Ag | Immunotherapy for the treatment of cancer |
WO2020205688A1 (en) | 2019-04-04 | 2020-10-08 | Merck Sharp & Dohme Corp. | Inhibitors of histone deacetylase-3 useful for the treatment of cancer, inflammation, neurodegeneration diseases and diabetes |
SG11202110829YA (en) | 2019-04-05 | 2021-10-28 | Kymera Therapeutics Inc | Stat degraders and uses thereof |
WO2020208060A1 (en) | 2019-04-09 | 2020-10-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of sk2 inhibitors in combination with immune checkpoint blockade therapy for the treatment of cancer |
EA202192800A1 (ru) | 2019-04-12 | 2022-03-30 | Васкулар Биодженикс Лтд | Способы противоопухолевой терапии |
WO2020212484A1 (en) | 2019-04-17 | 2020-10-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treatment of nlrp3 inflammasome mediated il-1beta dependent disorders |
JP2022529269A (ja) * | 2019-04-18 | 2022-06-20 | キューエルエスエフ バイオセラピューティック インコーポレイテッド | ヒト化抗pd-l1抗体 |
CA3134522A1 (en) | 2019-04-19 | 2020-10-22 | Genentech, Inc. | Anti-mertk antibodies and their methods of use |
EP3725370A1 (en) * | 2019-04-19 | 2020-10-21 | ImmunoBrain Checkpoint, Inc. | Modified anti-pd-l1 antibodies and methods and uses for treating a neurodegenerative disease |
CA3136698A1 (en) | 2019-04-23 | 2020-10-29 | Innate Pharma | Cd73 blocking antibodies |
JP7212990B2 (ja) | 2019-04-26 | 2023-01-26 | アイ-エムエービー バイオファーマ ユーエス リミテッド | ヒトpd‐l1抗体 |
US20220220565A1 (en) | 2019-04-30 | 2022-07-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
WO2020223233A1 (en) | 2019-04-30 | 2020-11-05 | Genentech, Inc. | Prognostic and therapeutic methods for colorectal cancer |
WO2020223469A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-di hydro-1h-imidazo[4,5-h]quinazolin-8-amine derivatives and related compounds as cyclin-dependent kinase 2 (cdk2) inhibitors for treating cancer |
WO2020223558A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | Tricyclic amine compounds as cdk2 inhibitors |
AU2020270376A1 (en) | 2019-05-03 | 2021-10-07 | Genentech, Inc. | Methods of treating cancer with an anti-PD-L1 antibody |
WO2020227159A2 (en) | 2019-05-03 | 2020-11-12 | Flagship Pioneering Innovations V, Inc. | Methods of modulating immune activity |
WO2020225552A1 (en) | 2019-05-06 | 2020-11-12 | Medimmune Limited | Combination of monalizumab, durvalumab, chemotherapy and bevacizumab or cetuximab for the treatment of colorectal cancer |
IL287801A (en) | 2019-05-07 | 2022-07-01 | Immunicom Inc | Augmentation of responses to checkpoint inhibitors using in vitro apheresis |
JP2022533194A (ja) | 2019-05-16 | 2022-07-21 | スティングセラ インコーポレイテッド | ベンゾ[b][1,8]ナフチリジン酢酸誘導体および使用方法 |
EP3969438A1 (en) | 2019-05-16 | 2022-03-23 | Stingthera, Inc. | Oxoacridinyl acetic acid derivatives and methods of use |
IL266728B (en) | 2019-05-19 | 2020-11-30 | Yeda Res & Dev | Identification of recurrent mutant neopeptides |
CN114555610A (zh) | 2019-05-20 | 2022-05-27 | 麻省理工学院 | 硼酸酯前药及其用途 |
JP2022534889A (ja) | 2019-05-24 | 2022-08-04 | ファイザー・インコーポレイテッド | Cdk阻害剤を使用した組合せ療法 |
EP3976832A1 (en) | 2019-05-30 | 2022-04-06 | Bristol-Myers Squibb Company | Methods of identifying a subject suitable for an immuno-oncology (i-o) therapy |
JP2022534967A (ja) | 2019-05-30 | 2022-08-04 | ブリストル-マイヤーズ スクイブ カンパニー | 多腫瘍遺伝子シグネチャーおよびその使用 |
JP2022534981A (ja) | 2019-05-30 | 2022-08-04 | ブリストル-マイヤーズ スクイブ カンパニー | 細胞局在化シグネチャーおよび組み合わせ治療 |
CA3141826A1 (en) | 2019-05-31 | 2020-12-03 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
US11246906B2 (en) | 2019-06-11 | 2022-02-15 | Alkermes Pharma Ireland Limited | Compositions and methods for subcutaneous administration of cancer immunotherapy |
EP3983084A1 (en) | 2019-06-12 | 2022-04-20 | Vanderbilt University | Amino acid transport inhibitors and the uses thereof |
CN114269715A (zh) | 2019-06-12 | 2022-04-01 | 范德比尔特大学 | 作为氨基酸转运抑制剂的二苄基胺 |
WO2020248156A1 (zh) * | 2019-06-12 | 2020-12-17 | 苏州工业园区唯可达生物科技有限公司 | Pd-l1靶向结合剂及其用途 |
AU2020294797A1 (en) | 2019-06-21 | 2021-12-23 | HCW Biologics, Inc. | Multi-chain chimeric polypeptides and uses thereof |
KR20220036998A (ko) | 2019-06-25 | 2022-03-23 | 이노벤트 바이오로직스 (쑤저우) 컴퍼니, 리미티드 | 항 cd47/pd-l1 이중특이성 항체를 포함하는 제제, 이의 제조 방법 및 용도 |
WO2020260547A1 (en) | 2019-06-27 | 2020-12-30 | Rigontec Gmbh | Design method for optimized rig-i ligands |
AU2020298572A1 (en) | 2019-07-02 | 2021-11-18 | Fred Hutchinson Cancer Center | Recombinant Ad35 vectors and related gene therapy improvements |
WO2021003417A1 (en) | 2019-07-03 | 2021-01-07 | Sumitomo Dainippon Pharma Oncology, Inc. | Tyrosine kinase non-receptor 1 (tnk1) inhibitors and uses thereof |
US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
KR20220029651A (ko) | 2019-07-09 | 2022-03-08 | 다케다 야쿠힌 고교 가부시키가이샤 | Sting 작용제 및 관문 저해제의 투여 |
CA3138560A1 (en) | 2019-07-16 | 2021-01-21 | Shaomeng Wang | Imidazopyrimidines as eed inhibitors and the use thereof |
GB201910304D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
GB201910305D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
US11083705B2 (en) | 2019-07-26 | 2021-08-10 | Eisai R&D Management Co., Ltd. | Pharmaceutical composition for treating tumor |
WO2021019526A1 (en) | 2019-07-29 | 2021-02-04 | Yeda Research And Development Co. Ltd. | Methods of treating and diagnosing lung cancer |
WO2021026009A1 (en) | 2019-08-02 | 2021-02-11 | Mersana Therapeutics, Inc. | Bis-[n-((5-carbamoyl)-1h-benzo[d]imidazol-2-yl)-pyrazol-5-carboxamide] derivatives and related compounds as sting (stimulator of interferon genes) agonists for the treatment of cancer |
EP4007592A1 (en) | 2019-08-02 | 2022-06-08 | LanthioPep B.V. | Angiotensin type 2 (at2) receptor agonists for use in the treatment of cancer |
WO2021024020A1 (en) | 2019-08-06 | 2021-02-11 | Astellas Pharma Inc. | Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer |
AU2020328507A1 (en) | 2019-08-12 | 2022-03-17 | Purinomia Biotech, Inc. | Methods and compositions for promoting and potentiating T-cell mediated immune responses through ADCC targeting of CD39 expressing cells |
EP4013750A1 (en) | 2019-08-14 | 2022-06-22 | Incyte Corporation | Imidazolyl pyrimidinylamine compounds as cdk2 inhibitors |
GB201912107D0 (en) | 2019-08-22 | 2019-10-09 | Amazentis Sa | Combination |
US20220305048A1 (en) | 2019-08-26 | 2022-09-29 | Dana-Farber Cancer Institute, Inc. | Use of heparin to promote type 1 interferon signaling |
CA3151824A1 (en) | 2019-08-27 | 2021-03-04 | The Regents Of The University Of Michigan | Cereblon e3 ligase inhibitors |
AR119821A1 (es) | 2019-08-28 | 2022-01-12 | Bristol Myers Squibb Co | Compuestos de piridopirimidinonilo sustituidos útiles como activadores de células t |
CA3114467A1 (en) | 2019-08-29 | 2021-03-04 | Remegen Co., Ltd. | Anti pd-l1 antibody and use thereof |
CR20220076A (es) | 2019-08-30 | 2022-06-24 | Agenus Inc | Anticuerpos anti-cd96 y sus métodos de uso |
WO2021048292A1 (en) | 2019-09-11 | 2021-03-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
WO2021050964A1 (en) | 2019-09-13 | 2021-03-18 | Nimbus Saturn, Inc. | Hpk1 antagonists and uses thereof |
WO2021055329A1 (en) | 2019-09-16 | 2021-03-25 | Surface Oncology, Inc. | Anti-cd39 antibody compositions and methods |
CA3151022A1 (en) | 2019-09-17 | 2021-03-25 | Bial - R&D Investments, S.A. | Substituted n-heterocyclic carboxamides as acid ceramidase inhibitors and their use as medicaments |
CA3150700A1 (en) | 2019-09-17 | 2021-03-25 | Renato T. Skerlj | IMIDAZOLE SUBSTITUTE CARBOXAMIDES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS |
CA3150906A1 (en) | 2019-09-17 | 2021-03-25 | Renato T. Skerlj | Substituted, saturated and unsaturated n-heterocyclic carboxamides and related compounds for their use in the treatment of medical disorders |
KR20220064983A (ko) | 2019-09-18 | 2022-05-19 | 노파르티스 아게 | Nkg2d 융합 단백질 및 이의 용도 |
TW202124446A (zh) | 2019-09-18 | 2021-07-01 | 瑞士商諾華公司 | 與entpd2抗體之組合療法 |
WO2021055816A1 (en) | 2019-09-18 | 2021-03-25 | Molecular Templates, Inc. | Pd-l1 binding molecules comprising shiga toxin a subunit scaffolds |
KR20220113353A (ko) | 2019-09-18 | 2022-08-12 | 람캅 바이오 알파 에이지 | Ceacam5 및 cd3에 대한 이중특이적 항체 |
EP4031578A1 (en) | 2019-09-18 | 2022-07-27 | Novartis AG | Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies |
EP4031576A1 (en) | 2019-09-18 | 2022-07-27 | Molecular Templates, Inc. | Pd-l1 binding molecules comprising shiga toxin a subunit scaffolds |
US20220380368A1 (en) | 2019-09-19 | 2022-12-01 | The Regents Of The University Of Michigan | Spirocyclic androgen receptor protein degraders |
KR20220065816A (ko) | 2019-09-19 | 2022-05-20 | 브리스톨-마이어스 스큅 컴퍼니 | 산성 pH에서 VISTA에 결합하는 항체 |
CA3155090A1 (en) | 2019-09-20 | 2021-03-25 | Transgene | Combination of a poxvirus encoding hpv polypeptides and il-2 with an anti-pd-l1 antibody |
AU2020350795A1 (en) | 2019-09-22 | 2022-03-31 | Bristol-Myers Squibb Company | Quantitative spatial profiling for LAG-3 antagonist therapy |
AU2020353079A1 (en) | 2019-09-25 | 2022-04-14 | Bristol-Myers Squibb Company | Composite biomarker for cancer therapy |
TW202128752A (zh) | 2019-09-25 | 2021-08-01 | 美商表面腫瘤學公司 | 抗il﹘27抗體及其用途 |
TW202126649A (zh) | 2019-09-26 | 2021-07-16 | 瑞士商諾華公司 | 抗病毒吡唑并吡啶酮化合物 |
EP4034562A2 (en) | 2019-09-27 | 2022-08-03 | GlaxoSmithKline Intellectual Property Development Limited | Antigen binding proteins |
CR20220127A (es) | 2019-09-27 | 2022-05-27 | Genentech Inc | Administración de dosis para tratamiento con anticuerpos antagonistas anti-tigit y anti-pd-l1 |
EP4037693A1 (en) | 2019-09-30 | 2022-08-10 | Astrazeneca AB | Combination treatment for cancer |
EP3800201A1 (en) | 2019-10-01 | 2021-04-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Cd28h stimulation enhances nk cell killing activities |
EP4037700A2 (en) | 2019-10-03 | 2022-08-10 | Xencor, Inc. | Targeted il-12 heterodimeric fc-fusion proteins |
US20220354811A1 (en) | 2019-10-03 | 2022-11-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for modulating macrophages polarization |
US20220363776A1 (en) | 2019-10-04 | 2022-11-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical composition for the treatment of ovarian cancer, breast cancer or pancreatic cancer |
TW202128757A (zh) | 2019-10-11 | 2021-08-01 | 美商建南德克公司 | 具有改善之特性的 PD-1 標靶 IL-15/IL-15Rα FC 融合蛋白 |
EP4041731A1 (en) | 2019-10-11 | 2022-08-17 | Incyte Corporation | Bicyclic amines as cdk2 inhibitors |
US20210106649A1 (en) * | 2019-10-11 | 2021-04-15 | TOBEBIO Novel Drug Laboratory Co., Ltd. | Synergistic combination of chemotherapy and peptide for treating cancer |
CN114786682A (zh) | 2019-10-14 | 2022-07-22 | Aro生物疗法公司 | 结合cd71的纤维粘连蛋白iii型结构域 |
WO2021076574A2 (en) | 2019-10-14 | 2021-04-22 | Aro Biotherapeutics Company | Fn3 domain-sirna conjugates and uses thereof |
JP2022552324A (ja) | 2019-10-14 | 2022-12-15 | インサイト・コーポレイション | Fgfr阻害剤としての二環式複素環 |
WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
WO2021074391A1 (en) | 2019-10-17 | 2021-04-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for diagnosing nasal intestinal type adenocarcinomas |
BR112022007376A2 (pt) | 2019-10-21 | 2022-07-05 | Novartis Ag | Terapias de combinação com venetoclax e inibidores de tim-3 |
JP2022553306A (ja) | 2019-10-21 | 2022-12-22 | ノバルティス アーゲー | Tim-3阻害剤およびその使用 |
EP4048795A1 (en) | 2019-10-23 | 2022-08-31 | Checkmate Pharmaceuticals, Inc. | Synthetic rig-i-like receptor agonists |
TW202128761A (zh) | 2019-10-25 | 2021-08-01 | 日商第一三共股份有限公司 | 抗garp抗體與免疫調節劑之組合 |
CN112724127B (zh) | 2019-10-28 | 2023-02-17 | 中国科学院上海药物研究所 | 五元杂环氧代羧酸类化合物及其医药用途 |
WO2021083959A1 (en) | 2019-10-29 | 2021-05-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating uveal melanoma |
MX2022005056A (es) | 2019-10-29 | 2022-05-18 | Eisai R&D Man Co Ltd | Combinacion de un antagonista de pd-1, un inhibidor tirosina cinasa de vegfr/fgfr/ret y un inhibidor de cbp/beta-catenina para el tratamiento del cancer. |
US20220409642A1 (en) | 2019-11-04 | 2022-12-29 | Astrazeneca Ab | Combination therapy for treating cancer |
WO2021092220A1 (en) | 2019-11-06 | 2021-05-14 | Bristol-Myers Squibb Company | Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy |
WO2021092221A1 (en) | 2019-11-06 | 2021-05-14 | Bristol-Myers Squibb Company | Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy |
MX2022005400A (es) | 2019-11-06 | 2022-05-24 | Genentech Inc | Metodos de diagnostico y terapeuticos para el tratamiento de canceres hematologicos. |
EP4055609A1 (en) | 2019-11-07 | 2022-09-14 | Oncxerna Therapeutics, Inc. | Classification of tumor microenvironments |
BR112022008191A2 (pt) | 2019-11-08 | 2022-07-12 | Bristol Myers Squibb Co | Terapia com antagonista de lag-3 para melanoma |
BR112022009031A2 (pt) | 2019-11-11 | 2022-10-11 | Incyte Corp | Sais e formas cristalinas de um inibidor de pd-1/pd-l1 |
TW202130618A (zh) | 2019-11-13 | 2021-08-16 | 美商建南德克公司 | 治療性化合物及使用方法 |
EP4058465A1 (en) | 2019-11-14 | 2022-09-21 | Cohbar Inc. | Cxcr4 antagonist peptides |
MX2022005839A (es) | 2019-11-19 | 2022-06-09 | Bristol Myers Squibb Co | Compuestos utiles como inhibidores de la proteina helios. |
US20230000864A1 (en) | 2019-11-22 | 2023-01-05 | Sumitomo Pharma Oncology, Inc. | Solid dose pharmaceutical composition |
MX2022006213A (es) | 2019-11-22 | 2022-06-22 | Theravance Biopharma R&D Ip Llc | Piridinas sustituidas y metodos de uso. |
CN115279764A (zh) | 2019-11-26 | 2022-11-01 | 医肯纳肿瘤学公司 | 多晶型咔唑衍生物及其用途 |
WO2021108109A1 (en) * | 2019-11-26 | 2021-06-03 | Beijing Xuanyi Pharmasciences Co., Ltd. | Modulators of t-cell activity |
JP2023504400A (ja) | 2019-11-26 | 2023-02-03 | ブリストル-マイヤーズ スクイブ カンパニー | (r)-n-(4-クロロフェニル)-2-((1s,4s)-4-(6-フルオロキノリン-4-イル)シクロヘキシル)プロパンアミドの塩/共結晶 |
KR20220104217A (ko) | 2019-11-26 | 2022-07-26 | 노파르티스 아게 | Cd19 및 cd22 키메라 항원 수용체 및 이의 용도 |
US20220401540A1 (en) | 2019-11-27 | 2022-12-22 | Cytlimic Inc. | Pharmaceutical composition |
IL293350A (en) | 2019-11-27 | 2022-07-01 | Myst Therapeutics Llc | A method for producing tumor-reactive t cells using modulatory substances |
EP3831849A1 (en) | 2019-12-02 | 2021-06-09 | LamKap Bio beta AG | Bispecific antibodies against ceacam5 and cd47 |
EP4069695A1 (en) | 2019-12-04 | 2022-10-12 | Incyte Corporation | Derivatives of an fgfr inhibitor |
CA3163875A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
EP4069683A1 (en) | 2019-12-06 | 2022-10-12 | Mersana Therapeutics, Inc. | Dimeric compounds as sting agonists |
CR20220322A (es) | 2019-12-09 | 2022-07-28 | Genentech Inc | Formulaciones de anticuerpos anti-pd-l1 |
US20230114107A1 (en) | 2019-12-17 | 2023-04-13 | Flagship Pioneering Innovations V, Inc. | Combination anti-cancer therapies with inducers of iron-dependent cellular disassembly |
WO2021127283A2 (en) | 2019-12-17 | 2021-06-24 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
JP2023509366A (ja) | 2019-12-17 | 2023-03-08 | カイメラ セラピューティクス, インコーポレイテッド | Irak分解剤およびそれらの使用 |
MX2022006932A (es) | 2019-12-19 | 2022-07-11 | Bristol Myers Squibb Co | Combinaciones de inhibidores de diacilglicerol cinasas (dgk) y antagonistas de puntos de control. |
EP4076508A1 (en) | 2019-12-19 | 2022-10-26 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and vaccine compositions to treat cancers |
BR112022011902A2 (pt) | 2019-12-20 | 2022-09-06 | Novartis Ag | Terapias de combinação |
AR120823A1 (es) | 2019-12-23 | 2022-03-23 | Bristol Myers Squibb Co | Compuestos bicíclicos sustituidos útiles como activadores de células t |
EP4081524A1 (en) | 2019-12-23 | 2022-11-02 | Bristol-Myers Squibb Company | Substituted heteroaryl compounds useful as t cell activators |
KR20220120624A (ko) | 2019-12-23 | 2022-08-30 | 브리스톨-마이어스 스큅 컴퍼니 | T 세포 활성화제로서 유용한 치환된 피페라진 유도체 |
JP2023507847A (ja) | 2019-12-23 | 2023-02-27 | ブリストル-マイヤーズ スクイブ カンパニー | T細胞アクティベーターとして有用な置換キナゾリニル化合物 |
JP2023509394A (ja) | 2019-12-23 | 2023-03-08 | カイメラ セラピューティクス, インコーポレイテッド | Smarca分解剤およびそれらの使用 |
US20230061608A1 (en) | 2019-12-23 | 2023-03-02 | Bristol-Myers Squibb Company | Substituted quinolinonyl piperazine compounds useful as t cell activators |
CN110974958B (zh) * | 2019-12-25 | 2020-08-21 | 北京东方百泰生物科技有限公司 | 一种抗pd-l1单克隆抗体的注射制剂 |
CN113045655A (zh) | 2019-12-27 | 2021-06-29 | 高诚生物医药(香港)有限公司 | 抗ox40抗体及其用途 |
CA3166549A1 (en) | 2020-01-03 | 2021-07-08 | Incyte Corporation | Combination therapy comprising a2a/a2b and pd-1/pd-l1 inhibitors |
EP4084821A4 (en) | 2020-01-03 | 2024-04-24 | Marengo Therapeutics Inc | CD33-BINDING MULTIFUNCTIONAL MOLECULES AND THEIR USES |
JP2023517794A (ja) | 2020-01-06 | 2023-04-27 | ハイファイバイオ(ホンコン)リミテッド | 抗tnfr2抗体及びその使用 |
JP2023510429A (ja) | 2020-01-07 | 2023-03-13 | ハイファイバイオ (エイチケー) リミテッド | 抗ガレクチン-9抗体およびその使用 |
MX2022008214A (es) | 2020-01-09 | 2022-08-08 | Hoffmann La Roche | Nuevas moleculas de union al antigeno que contienen el trimero de 4-1bbl. |
US20230348458A1 (en) | 2020-01-10 | 2023-11-02 | Innate Tumor Immunity, Inc. | Nlrp3 modulators |
WO2021146370A1 (en) | 2020-01-15 | 2021-07-22 | Blueprint Medicines Corporation | Map4k1 inhibitors |
EP4090770A1 (en) | 2020-01-17 | 2022-11-23 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
CA3167413A1 (en) | 2020-01-17 | 2021-07-22 | Novartis Ag | Combination comprising a tim-3 inhibitor and a hypomethylating agent for use in treating myelodysplastic syndrome or chronic myelomonocytic leukemia |
WO2022050954A1 (en) | 2020-09-04 | 2022-03-10 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
CA3166407A1 (en) | 2020-01-29 | 2021-08-05 | Merus N.V. | Means and method for modulating fimmune cell engaging effects |
AU2021213969A1 (en) | 2020-01-30 | 2022-09-01 | ONA Therapeutics S.L. | Combination therapy for treatment of cancer and cancer metastasis |
WO2021152400A1 (en) | 2020-01-30 | 2021-08-05 | Gnubiotics Sciences Sa | Compositions comprising pig stomach mucins and uses thereof |
AU2021212197A1 (en) | 2020-01-31 | 2022-08-04 | BioNTech SE | Methods of inducing neoepitope-specific T cells with a PD-1 axis binding antagonist and an RNA vaccine |
WO2021156360A1 (en) | 2020-02-05 | 2021-08-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for discontinuing a treatment with a tyrosine kinase inhibitor (tki) |
CN115362167A (zh) | 2020-02-06 | 2022-11-18 | 百时美施贵宝公司 | Il-10及其用途 |
EP4100016A1 (en) | 2020-02-07 | 2022-12-14 | AI Therapeutics, Inc. | Anti-viral compositions and methods of use |
WO2021167885A1 (en) * | 2020-02-21 | 2021-08-26 | Macrogenics, Inc. | Cd137 binding molecules and uses thereof |
IL295896A (en) | 2020-02-26 | 2022-10-01 | Biograph 55 Inc | c19 c38 bispecific antibodies |
JP2023516636A (ja) | 2020-02-27 | 2023-04-20 | ミスト セラピューティクス リミテッド ライアビリティ カンパニー | 腫瘍反応性t細胞のエクスビボ富化および増大のための方法ならびに関連するその組成物 |
CN116568341A (zh) | 2020-02-28 | 2023-08-08 | 百时美施贵宝公司 | 基于纤连蛋白的放射性标记的支架和抗体及其治疗诊断用途 |
US20230113705A1 (en) | 2020-02-28 | 2023-04-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for diagnosing, prognosing and managing treatment of breast cancer |
TW202146452A (zh) | 2020-02-28 | 2021-12-16 | 瑞士商諾華公司 | 結合cd123和cd3之雙特異性抗體的給藥 |
AR121506A1 (es) | 2020-03-03 | 2022-06-08 | Pic Therapeutics Inc | Inhibidores del eif4e y sus usos |
KR20220150353A (ko) | 2020-03-05 | 2022-11-10 | 네오티엑스 테라퓨틱스 엘티디. | 면역 세포를 사용하여 암을 치료하기 위한 방법 및 조성물 |
AU2021230385A1 (en) | 2020-03-06 | 2022-09-22 | Incyte Corporation | Combination therapy comprising AXL/MER and PD-1/PD-L1 inhibitors |
MX2022010912A (es) | 2020-03-06 | 2022-11-09 | Celgene Quanticel Res Inc | Combinacion de un inhibidor de desmetilasa-1 especifica de lisina (lsd-1) y nivolumab para usarse en el tratamiento de cancer de pulmon de celulas peque?as (sclc) o cancer de pulmon de celulas no peque?as escamosas (sqnsclc). |
US20230235073A1 (en) | 2020-03-06 | 2023-07-27 | Ona Therapeutics, S.L. | Anti-cd36 antibodies and their use to treat cancer |
WO2021177980A1 (en) | 2020-03-06 | 2021-09-10 | Genentech, Inc. | Combination therapy for cancer comprising pd-1 axis binding antagonist and il6 antagonist |
US20230093147A1 (en) | 2020-03-09 | 2023-03-23 | President And Fellows Of Harvard College | Methods and compositions relating to improved combination therapies |
EP3878446A1 (en) | 2020-03-09 | 2021-09-15 | Universite De Geneve | Hsd11b1 inhibitors for use in immunotherapy and uses thereof |
US20230140384A1 (en) | 2020-03-09 | 2023-05-04 | Bristol-Myers Squibb Company | Antibodies to cd40 with enhanced agonist activity |
IL295569A (en) | 2020-03-19 | 2022-10-01 | Arcus Biosciences Inc | Tetralin and tetrahydroquinoline compounds as inhibitors of hif-2alpha |
IL296451A (en) | 2020-03-19 | 2022-11-01 | Kymera Therapeutics Inc | mdm2 joints and their uses |
JP2023519254A (ja) | 2020-03-23 | 2023-05-10 | ブリストル-マイヤーズ スクイブ カンパニー | がんを処置するための抗ccr8抗体 |
TW202140441A (zh) | 2020-03-23 | 2021-11-01 | 美商必治妥美雅史谷比公司 | 經取代之側氧基異吲哚啉化合物 |
US20230159573A1 (en) | 2020-03-26 | 2023-05-25 | The Regents Of The University Of Michigan | Small molecule stat protein degraders |
WO2021203131A1 (en) | 2020-03-31 | 2021-10-07 | Theravance Biopharma R&D Ip, Llc | Substituted pyrimidines and methods of use |
CN115698717A (zh) | 2020-04-03 | 2023-02-03 | 基因泰克公司 | 癌症的治疗和诊断方法 |
WO2021205444A1 (en) | 2020-04-06 | 2021-10-14 | Yeda Research And Development Co. Ltd. | Methods of diagnosing cancer and predicting responsiveness to therapy |
US20230272056A1 (en) | 2020-04-09 | 2023-08-31 | Merck Sharp & Dohme Llc | Affinity matured anti-lap antibodies and uses thereof |
WO2021207689A2 (en) | 2020-04-10 | 2021-10-14 | Juno Therapeutics, Inc. | Methods and uses related to cell therapy engineered with a chimeric antigen receptor targeting b-cell maturation antigen |
US20230149543A1 (en) | 2020-04-14 | 2023-05-18 | Glaxosmithkline Intellectual Property Development Limited | Combination treatment for cancer based upon an icos antbody and a pd-l1 antibody tgf-bets-receptor fusion protein |
AU2021254794A1 (en) | 2020-04-16 | 2022-12-15 | Incyte Corporation | Fused tricyclic KRAS inhibitors |
WO2021216920A1 (en) | 2020-04-22 | 2021-10-28 | Iovance Biotherapeutics, Inc. | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
TW202206100A (zh) | 2020-04-27 | 2022-02-16 | 美商西健公司 | 癌症之治療 |
JP2023523450A (ja) | 2020-04-28 | 2023-06-05 | ジェネンテック, インコーポレイテッド | 非小細胞肺がん免疫療法のための方法及び組成物 |
US20230181756A1 (en) | 2020-04-30 | 2023-06-15 | Novartis Ag | Ccr7 antibody drug conjugates for treating cancer |
EP4147052A1 (en) | 2020-05-05 | 2023-03-15 | F. Hoffmann-La Roche AG | Predicting response to pd-1 axis inhibitors |
BR112022022335A2 (pt) | 2020-05-05 | 2023-01-10 | Teon Therapeutics Inc | Moduladores de receptor canabinoide tipo 2 (cb2) e usos dos mesmos |
US20230183214A1 (en) | 2020-05-06 | 2023-06-15 | Merck Sharp & Dohme Llc | Il4i1 inhibitors and methods of use |
US11739102B2 (en) | 2020-05-13 | 2023-08-29 | Incyte Corporation | Fused pyrimidine compounds as KRAS inhibitors |
US20230192867A1 (en) | 2020-05-15 | 2023-06-22 | Bristol-Myers Squibb Company | Antibodies to garp |
WO2021239838A2 (en) | 2020-05-26 | 2021-12-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Severe acute respiratory syndrome coronavirus 2 (sars-cov-2) polypeptides and uses thereof for vaccine purposes |
IL298273A (en) | 2020-05-26 | 2023-01-01 | Regeneron Pharma | Methods for the treatment of cervical cancer using the administration of the pd-1 inhibitory antibody Semilimb |
WO2021243207A1 (en) | 2020-05-28 | 2021-12-02 | Modernatx, Inc. | Use of mrnas encoding ox40l, il-23 and il-36gamma for treating cancer |
US20230173095A1 (en) | 2020-05-29 | 2023-06-08 | President And Fellows Of Harvard College | Living cells engineered with polyphenol-functionalized biologically active nanocomplexes |
IL298608A (en) | 2020-06-01 | 2023-01-01 | Hcw Biologics Inc | Methods for treating disorders related to aging |
WO2021247003A1 (en) | 2020-06-01 | 2021-12-09 | HCW Biologics, Inc. | Methods of treating aging-related disorders |
PE20231078A1 (es) | 2020-06-02 | 2023-07-17 | Arcus Biosciences Inc | Anticuerpos anti-tigit |
TW202210483A (zh) | 2020-06-03 | 2022-03-16 | 美商凱麥拉醫療公司 | Irak降解劑之結晶型 |
WO2021245071A1 (en) | 2020-06-03 | 2021-12-09 | Mv Biotherapeutics Sa | Combination of an atp-hydrolyzing enzyme and an immune checkpoint modulator and uses thereof |
WO2021249969A1 (en) | 2020-06-10 | 2021-12-16 | Merck Patent Gmbh | Combination product for the treatment of cancer diseases |
TW202214623A (zh) | 2020-06-10 | 2022-04-16 | 美商施萬生物製藥研發 Ip有限責任公司 | 結晶型alk5抑制劑及其用途 |
JP2023529206A (ja) | 2020-06-12 | 2023-07-07 | ジェネンテック, インコーポレイテッド | がん免疫療法のための方法及び組成物 |
CA3181820A1 (en) | 2020-06-16 | 2021-12-23 | Genentech, Inc. | Methods and compositions for treating triple-negative breast cancer |
TW202200616A (zh) | 2020-06-18 | 2022-01-01 | 美商建南德克公司 | 使用抗tigit抗體及pd-1軸結合拮抗劑之治療 |
WO2021258010A1 (en) | 2020-06-19 | 2021-12-23 | Gossamer Bio Services, Inc. | Oxime compounds useful as t cell activators |
MX2022015852A (es) | 2020-06-23 | 2023-01-24 | Novartis Ag | Regimen de dosificacion que comprende derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona. |
WO2021262969A1 (en) | 2020-06-24 | 2021-12-30 | The General Hospital Corporation | Materials and methods of treating cancer |
KR20230027082A (ko) | 2020-06-25 | 2023-02-27 | 셀진 코포레이션 | 조합 요법을 사용한 암의 치료 방법 |
MX2022016548A (es) | 2020-06-26 | 2023-03-14 | Amgen Inc | Muteínas de il-10 y proteínas de fusión de las mismas. |
WO2022006179A1 (en) | 2020-06-29 | 2022-01-06 | Flagship Pioneering Innovations V, Inc. | Viruses engineered to promote thanotransmission and their use in treating cancer |
WO2022004760A1 (ja) * | 2020-06-30 | 2022-01-06 | 塩野義製薬株式会社 | 抗ccr8抗体と化学療法剤の併用 |
JP2023531305A (ja) | 2020-06-30 | 2023-07-21 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 術前補助療法後の固形癌患者の再発及び/又は死亡のリスクを予測するための方法。 |
US20230266322A1 (en) | 2020-06-30 | 2023-08-24 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the risk of recurrence and/or death of patients suffering from a solid cancer after preoperative adjuvant therapy and radical surgery |
WO2022003554A1 (en) | 2020-07-01 | 2022-01-06 | Pfizer Inc. | Biomarkers for pd-1 axis binding antagonist therapy |
WO2022010854A1 (en) | 2020-07-07 | 2022-01-13 | Celgene Corporation | Pharmaceutical compositions comprising (s)-4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)m ethyl) benzyl)piperazin-1-yl)-3-fluorobenzonitrile and methods of using the same |
JP2023532768A (ja) | 2020-07-07 | 2023-07-31 | バイオエヌテック エスエー | Hpv陽性癌の治療用rna |
US20230257365A1 (en) | 2020-07-10 | 2023-08-17 | The Regents Of The University Of Michigan | Small molecule androgen receptor protein degraders |
WO2022011205A1 (en) | 2020-07-10 | 2022-01-13 | The Regents Of The University Of Michigan | Androgen receptor protein degraders |
US11787775B2 (en) | 2020-07-24 | 2023-10-17 | Genentech, Inc. | Therapeutic compounds and methods of use |
US20230266332A1 (en) | 2020-07-28 | 2023-08-24 | Inserm (Institut National De La Santè Et De La Recherch Médicale) | Methods and compositions for preventing and treating a cancer |
KR20230044480A (ko) | 2020-07-30 | 2023-04-04 | 카이메라 쎄라퓨틱스 인코포레이티드 | 돌연변이 림프종의 치료 방법 |
EP4188549A1 (en) | 2020-08-03 | 2023-06-07 | Novartis AG | Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
WO2022031710A2 (en) * | 2020-08-04 | 2022-02-10 | Exelixis, Inc. | Multispecific binding agents and uses thereof |
AU2021320226A1 (en) | 2020-08-05 | 2023-03-23 | Synthekine, Inc. | gp130 binding molecules and methods of use |
CA3190415A1 (en) | 2020-08-05 | 2022-02-10 | Synthekine, Inc. | Il2rb/il2rg synthetic cytokines |
EP4192880A2 (en) | 2020-08-05 | 2023-06-14 | Synthekine, Inc. | Il10 receptor binding molecules and methods of use |
EP4192866A2 (en) | 2020-08-10 | 2023-06-14 | GV20 Therapeutics LLC | Compositions and methods for treating autoimmune diseases and cancers by targeting igsf8 |
WO2022036146A1 (en) | 2020-08-12 | 2022-02-17 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
JP2023537412A (ja) | 2020-08-13 | 2023-08-31 | ブリストル-マイヤーズ スクイブ カンパニー | 目的の細胞を標的とするためのil-2の向け直し方法 |
AU2021327130A1 (en) | 2020-08-17 | 2023-03-02 | Bicycletx Limited | Bicycle conjugates specific for Nectin-4 and uses thereof |
KR20230074487A (ko) | 2020-08-26 | 2023-05-30 | 마렝고 테라퓨틱스, 인크. | Trbc1 또는 trbc2를 검출하는 방법 |
CA3168743A1 (en) | 2020-08-26 | 2022-03-03 | Matthew G. Fury | Methods of treating cancer by administering a pd-1 inhibitor |
WO2022047189A1 (en) | 2020-08-28 | 2022-03-03 | Bristol-Myers Squibb Company | Lag-3 antagonist therapy for hepatocellular carcinoma |
WO2022047093A1 (en) | 2020-08-28 | 2022-03-03 | Incyte Corporation | Vinyl imidazole compounds as inhibitors of kras |
EP4204453A1 (en) | 2020-08-31 | 2023-07-05 | Bristol-Myers Squibb Company | Cell localization signature and immunotherapy |
CN111808196B (zh) * | 2020-08-31 | 2020-12-29 | 北京百奥赛图基因生物技术有限公司 | 抗pd-1抗体及其用途 |
EP4208482A1 (en) | 2020-09-02 | 2023-07-12 | Pharmabcine Inc. | Combination therapy of a pd-1 antagonist and an antagonist for vegfr-2 for treating patients with cancer |
US11932692B2 (en) | 2020-09-03 | 2024-03-19 | Regeneron Pharmaceuticals, Inc. | Methods of treating cancer pain by administering a PD-1 inhibitor |
CR20230155A (es) | 2020-09-14 | 2023-06-27 | Boehringer Ingelheim Int | Vacuna heteróloga de estímulo primario |
KR20230070256A (ko) | 2020-09-17 | 2023-05-22 | 상하이 린-크레스트 엔터프라이즈 매니지먼트 컴퍼니 리미티드 | 이중특이성 재조합 단백질 및 이의 용도 |
CN111920948B (zh) * | 2020-09-25 | 2021-02-02 | 安可瑞(山西)生物细胞有限公司 | 包含免疫细胞的药物组合物用于治疗癌症 |
WO2022072783A1 (en) | 2020-10-02 | 2022-04-07 | Incyte Corporation | Bicyclic dione compounds as inhibitors of kras |
CN116406369A (zh) | 2020-10-05 | 2023-07-07 | 百时美施贵宝公司 | 用于浓缩蛋白质的方法 |
WO2022076596A1 (en) | 2020-10-06 | 2022-04-14 | Codiak Biosciences, Inc. | Extracellular vesicle-aso constructs targeting stat6 |
WO2022074152A1 (en) | 2020-10-08 | 2022-04-14 | Targimmune Therapeutics Ag | Immunotherapy for the treatment of cancer |
CN116685325A (zh) | 2020-10-20 | 2023-09-01 | 豪夫迈·罗氏有限公司 | Pd-1轴结合拮抗剂和lrrk2抑制剂的组合疗法 |
AR123855A1 (es) | 2020-10-20 | 2023-01-18 | Genentech Inc | Anticuerpos anti-mertk conjugados con peg y métodos de uso |
US20240101666A1 (en) | 2020-10-23 | 2024-03-28 | Bristol-Myers Squibb Company | Lag-3 antagonist therapy for lung cancer |
WO2022084531A1 (en) | 2020-10-23 | 2022-04-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating glioma |
WO2022093981A1 (en) | 2020-10-28 | 2022-05-05 | Genentech, Inc. | Combination therapy comprising ptpn22 inhibitors and pd-l1 binding antagonists |
WO2022094567A1 (en) | 2020-10-28 | 2022-05-05 | Ikena Oncology, Inc. | Combination of an ahr inhibitor with a pdx inhibitor or doxorubicine |
AU2021374590A1 (en) | 2020-11-04 | 2023-06-01 | Genentech, Inc. | Subcutaneous dosing of anti-cd20/anti-cd3 bispecific antibodies |
IL302396A (en) | 2020-11-04 | 2023-06-01 | Genentech Inc | Dosage for treatment with bispecific anti-CD20/anti-CD3 antibodies |
EP4240493A2 (en) | 2020-11-04 | 2023-09-13 | Genentech, Inc. | Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies and anti-cd79b antibody drug conjugates |
MX2023005362A (es) | 2020-11-06 | 2023-06-22 | Incyte Corp | Proceso para hacer un inhibidor de proteina de muerte programada 1 (pd-1)/ligando de muerte programada 1 (pd-l1) y sales y formas cristalinas del mismo. |
WO2022099018A1 (en) | 2020-11-06 | 2022-05-12 | Incyte Corporation | Process of preparing a pd-1/pd-l1 inhibitor |
WO2022099075A1 (en) | 2020-11-06 | 2022-05-12 | Incyte Corporation | Crystalline form of a pd-1/pd-l1 inhibitor |
WO2022097060A1 (en) | 2020-11-06 | 2022-05-12 | Novartis Ag | Cd19 binding molecules and uses thereof |
TW202233248A (zh) | 2020-11-08 | 2022-09-01 | 美商西健公司 | 組合療法 |
KR20230106645A (ko) | 2020-11-11 | 2023-07-13 | 다이이찌 산쿄 가부시키가이샤 | 항체-약물 콘주게이트와 항 SIRPα 항체의 조합 |
JP2023554587A (ja) | 2020-11-12 | 2023-12-28 | アンセルム(アンスティチュート・ナシオナル・ドゥ・ラ・サンテ・エ・ドゥ・ラ・ルシェルシュ・メディカル) | Sars-cov-2 スパイクタンパク質の受容体結合ドメインにコンジュゲートまたは融合している抗体およびワクチン目的でのそれらの使用 |
WO2022103904A1 (en) | 2020-11-13 | 2022-05-19 | Genentech, Inc. | Methods and compositions comprising a krasg12c inhibitor and a pd-l1 binding antagonist for treating lung cancer |
EP4244391A1 (en) | 2020-11-16 | 2023-09-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for predicting and treating uveal melanoma |
EP4244392A1 (en) | 2020-11-16 | 2023-09-20 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and compositions for predicting and treating uveal melanoma |
WO2022101463A1 (en) | 2020-11-16 | 2022-05-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of the last c-terminal residues m31/41 of zikv m ectodomain for triggering apoptotic cell death |
CA3200671A1 (en) | 2020-11-17 | 2022-05-27 | Seagen Inc. | Methods of treating cancer with a combination of tucatinib and an anti-pd-1/anti-pd-l1 antibody |
KR20230110254A (ko) | 2020-11-18 | 2023-07-21 | 다케다 야쿠힌 고교 가부시키가이샤 | Sting 작용제, 관문 저해제, 및 방사선의 투여 |
AU2021392040A1 (en) | 2020-12-02 | 2023-06-29 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
WO2022119830A1 (en) | 2020-12-02 | 2022-06-09 | Genentech, Inc. | Methods and compositions for neoadjuvant and adjuvant urothelial carcinoma therapy |
WO2022120353A1 (en) | 2020-12-02 | 2022-06-09 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
WO2022120179A1 (en) | 2020-12-03 | 2022-06-09 | Bristol-Myers Squibb Company | Multi-tumor gene signatures and uses thereof |
CA3201219A1 (en) | 2020-12-04 | 2022-06-09 | Mir Ali | Ionizable cationic lipids and lipid nanoparticles, and methods of synthesis and use thereof |
WO2022125497A1 (en) | 2020-12-08 | 2022-06-16 | Infinity Pharmaceuticals, Inc. | Eganelisib for use in the treatment of pd-l1 negative cancer |
TW202237119A (zh) | 2020-12-10 | 2022-10-01 | 美商住友製藥腫瘤公司 | Alk﹘5抑制劑和彼之用途 |
CA3202416A1 (en) | 2020-12-16 | 2022-06-23 | Pieter Fokko VAN LOO | Multispecific antibodies for the treatment of cancer |
EP4262986A1 (en) | 2020-12-16 | 2023-10-25 | Gossamer Bio Services, Inc. | Compounds useful as t cell activators |
IL301701A (en) | 2020-12-18 | 2023-05-01 | Lamkap Bio Beta Ag | Bispecific antibodies against CEACAM5 and CD47 |
TW202245808A (zh) | 2020-12-21 | 2022-12-01 | 德商拜恩迪克公司 | 用於治療癌症之治療性rna |
WO2022135667A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Therapeutic rna for treating cancer |
WO2022135666A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Treatment schedule for cytokine proteins |
AU2021416156A1 (en) | 2020-12-28 | 2023-06-22 | Bristol-Myers Squibb Company | Methods of treating tumors |
JP2024503265A (ja) | 2020-12-28 | 2024-01-25 | ブリストル-マイヤーズ スクイブ カンパニー | 抗体組成物およびその使用の方法 |
KR20230157940A (ko) | 2020-12-29 | 2023-11-17 | 인사이트 코포레이션 | A2a/a2b 저해제, pd-1/pd-l1 저해제 및 항-cd73 항체를포함하는 병용 요법 |
WO2022148736A1 (en) | 2021-01-05 | 2022-07-14 | Transgene | Vectorization of muc1 t cell engager |
EP4274850A1 (en) | 2021-01-08 | 2023-11-15 | Bristol-Myers Squibb Company | Combination therapy using an anti-fucosyl-gm1 antibody |
KR20230146528A (ko) | 2021-01-11 | 2023-10-19 | 바이사이클티엑스 리미티드 | 암을 치료하기 위한 방법 |
WO2022150788A2 (en) | 2021-01-11 | 2022-07-14 | Synthekine, Inc. | Compositions and methods related to receptor pairing |
JP2024503654A (ja) | 2021-01-13 | 2024-01-26 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | 併用療法 |
CN116963773A (zh) | 2021-01-21 | 2023-10-27 | 浙江养生堂天然药物研究所有限公司 | 治疗肿瘤的组合物及方法 |
TW202241508A (zh) | 2021-01-29 | 2022-11-01 | 美商艾歐凡斯生物治療公司 | 細胞介素相關之腫瘤浸潤性淋巴球組合物及方法 |
WO2022162569A1 (en) | 2021-01-29 | 2022-08-04 | Novartis Ag | Dosage regimes for anti-cd73 and anti-entpd2 antibodies and uses thereof |
WO2022167445A1 (en) | 2021-02-02 | 2022-08-11 | Liminal Biosciences Limited | Gpr84 antagonists and uses thereof |
EP4288427A1 (en) | 2021-02-02 | 2023-12-13 | Liminal Biosciences Limited | Gpr84 antagonists and uses thereof |
WO2022171121A1 (zh) | 2021-02-10 | 2022-08-18 | 同润生物医药(上海)有限公司 | 治疗肿瘤的方法和组合 |
CR20230382A (es) | 2021-02-12 | 2023-09-06 | Hoffmann La Roche | Derivados de tetrahidroazepina bicíclicos para el tratamiento del cáncer |
TW202245789A (zh) | 2021-02-15 | 2022-12-01 | 美商凱麥拉醫療公司 | Irak4降解劑及其用途 |
CN116917273A (zh) | 2021-03-02 | 2023-10-20 | 葛兰素史克知识产权发展有限公司 | 作为dnmt1抑制剂的经取代的吡啶 |
WO2022187419A1 (en) | 2021-03-03 | 2022-09-09 | The Regents Of The University Of Michigan | Small molecule degraders of androgen receptor |
WO2022187423A1 (en) | 2021-03-03 | 2022-09-09 | The Regents Of The University Of Michigan | Cereblon ligands |
JP2024510947A (ja) | 2021-03-05 | 2024-03-12 | レアダルティス、ソシエダッド リミターダ | 三量体ポリペプチドおよびがん治療におけるその使用 |
JP2024509192A (ja) | 2021-03-05 | 2024-02-29 | ニンバス サターン, インコーポレイテッド | Hpk1アンタゴニスト及びその使用 |
EP4305041A1 (en) | 2021-03-08 | 2024-01-17 | Blueprint Medicines Corporation | Map4k1 inhibitors |
WO2022197641A1 (en) | 2021-03-15 | 2022-09-22 | Rapt Therapeutics, Inc. | 1h-pyrazolo[3,4-d]pyrimidin-6-yl-amine derivatives as hematopoietic progenitor kinase 1 (hpk1) modulators and/or inhibitors for the treatment of cancer and other diseases |
WO2022194908A1 (en) | 2021-03-17 | 2022-09-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
CN117321418A (zh) | 2021-03-18 | 2023-12-29 | 诺华股份有限公司 | 癌症生物标志物及其使用方法 |
CA3212571A1 (en) | 2021-03-19 | 2022-09-22 | Trained Therapeutix Discovery, Inc. | Compounds for regulating trained immunity, and their methods of use |
KR20230159590A (ko) | 2021-03-23 | 2023-11-21 | 리제너론 파아마슈티컬스, 인크. | Pd-1 억제제를 투여함에 의한 면역억제 또는 면역손상된 환자에서 암을 치료하는 방법 |
TW202304506A (zh) | 2021-03-25 | 2023-02-01 | 日商安斯泰來製藥公司 | 涉及抗claudin 18.2抗體的組合治療以治療癌症 |
EP4314348A1 (en) | 2021-03-25 | 2024-02-07 | Oncxerna Therapeutics, Inc. | Targeted therapies in cancer |
CA3207652A1 (en) | 2021-03-26 | 2022-09-29 | Stephanie Cornen | Cytokine anchors for nkp46-binding nk cell engager proteins |
EP4316518A1 (en) * | 2021-03-29 | 2024-02-07 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Drug combination of toll-like receptor 7 agonist and anti-pd-l1 antibody |
IL307262A (en) | 2021-03-29 | 2023-11-01 | Juno Therapeutics Inc | METHODS FOR DOSAGE AND THERAPY IN COMBINATION OF CHECKPOINT INHIBITOR AND CAR T CELL THERAPY |
EP4314060A1 (en) | 2021-03-31 | 2024-02-07 | GlaxoSmithKline Intellectual Property Development Limited | Antigen binding proteins and combinations thereof |
KR20230165276A (ko) | 2021-03-31 | 2023-12-05 | 플래그쉽 파이어니어링 이노베이션스 브이, 인크. | 타노트랜스미션 폴리펩티드 및 암의 치료에서의 이의 용도 |
EP4314068A1 (en) | 2021-04-02 | 2024-02-07 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
KR20230167067A (ko) | 2021-04-05 | 2023-12-07 | 브리스톨-마이어스 스큅 컴퍼니 | 암의 치료를 위한 피리디닐 치환된 옥소이소인돌린 화합물 |
JP2024515243A (ja) | 2021-04-06 | 2024-04-08 | ブリストル-マイヤーズ スクイブ カンパニー | ピリジニル置換されたオキソイソインドリン化合物 |
TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途 |
JP2024514836A (ja) | 2021-04-08 | 2024-04-03 | ニューリックス セラピューティクス,インコーポレイテッド | Cbl-b阻害化合物との組み合わせ療法 |
WO2022216993A2 (en) | 2021-04-08 | 2022-10-13 | Marengo Therapeutics, Inc. | Multifuntional molecules binding to tcr and uses thereof |
IL307419A (en) | 2021-04-09 | 2023-12-01 | Ose Immunotherapeutics | A new scaffold for bifunctional molecules with improved properties |
JP2024513246A (ja) | 2021-04-09 | 2024-03-22 | ジェネンテック, インコーポレイテッド | Raf阻害剤及びpd-1軸阻害剤を用いた併用治療 |
TW202304999A (zh) | 2021-04-09 | 2023-02-01 | 美商思進公司 | 以抗tigit抗體治療癌症之方法 |
WO2022214652A1 (en) | 2021-04-09 | 2022-10-13 | Ose Immunotherapeutics | Scaffold for bifunctioanl molecules comprising pd-1 or cd28 and sirp binding domains |
EP4323405A1 (en) | 2021-04-12 | 2024-02-21 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
KR20230170039A (ko) | 2021-04-13 | 2023-12-18 | 뉴베일런트, 아이엔씨. | Egfr 돌연변이를 지니는 암을 치료하기 위한 아미노-치환된 헤테로사이클 |
EP4322938A1 (en) | 2021-04-14 | 2024-02-21 | Institut National de la Santé et de la Recherche Médicale (INSERM) | New method to improve nk cells cytotoxicity |
EP4074835A1 (en) | 2021-04-15 | 2022-10-19 | Deutsches Krebsforschungszentrum - Stiftung des öffentlichen Rechts / Universität Heidelberg | H-1 pv expressing rnai effectors |
AU2022258829A1 (en) | 2021-04-16 | 2023-10-26 | Novartis Ag | Antibody drug conjugates and methods for making thereof |
KR20230172548A (ko) | 2021-04-16 | 2023-12-22 | 이케나 온콜로지, 인코포레이티드 | Mek 억제제 및 이의 용도 |
WO2022226100A1 (en) | 2021-04-20 | 2022-10-27 | Seagen Inc. | Modulation of antibody-dependent cellular cytotoxicity |
EP4326903A1 (en) | 2021-04-23 | 2024-02-28 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and compositions for treating cell senescence accumulation related disease |
WO2022229966A1 (en) | 2021-04-29 | 2022-11-03 | Yeda Research And Development Co. Ltd. | T cell receptors directed against ras-derived recurrent neoantigens and methods of identifying same |
JP2024516230A (ja) | 2021-04-30 | 2024-04-12 | ジェネンテック, インコーポレイテッド | がんのための治療及び診断方法並びに組成物 |
EP4330282A1 (en) | 2021-04-30 | 2024-03-06 | F. Hoffmann-La Roche AG | Dosing for combination treatment with anti-cd20/anti-cd3 bispecific antibody and anti-cd79b antibody drug conjugate |
WO2022227015A1 (en) | 2021-04-30 | 2022-11-03 | Merck Sharp & Dohme Corp. | Il4i1 inhibitors and methods of use |
KR20240005809A (ko) | 2021-05-07 | 2024-01-12 | 서피스 온콜로지, 엘엘씨 | 항-il-27 항체 및 이의 용도 |
AR125874A1 (es) | 2021-05-18 | 2023-08-23 | Novartis Ag | Terapias de combinación |
WO2022243378A1 (en) | 2021-05-18 | 2022-11-24 | Kymab Limited | Uses of anti-icos antibodies |
EP4341261A1 (en) | 2021-05-21 | 2024-03-27 | Arcus Biosciences, Inc. | Axl compounds |
WO2022242737A1 (zh) | 2021-05-21 | 2022-11-24 | 天津立博美华基因科技有限责任公司 | 药物组合及其用途 |
TW202313603A (zh) | 2021-05-21 | 2023-04-01 | 美商阿克思生物科學有限公司 | Axl抑制劑化合物 |
CN117412767A (zh) | 2021-05-25 | 2024-01-16 | 雪绒花免疫公司 | C-x-c基序趋化因子受体6(cxcr6)结合分子及其使用方法 |
WO2022247972A2 (es) | 2021-05-26 | 2022-12-01 | Centro De Inmunologia Molecular | Uso de composiciones terapéuticas para el tratamiento de pacientes con tumores de origen epitelial |
WO2022251359A1 (en) | 2021-05-26 | 2022-12-01 | Theravance Biopharma R&D Ip, Llc | Bicyclic inhibitors of alk5 and methods of use |
TW202307210A (zh) | 2021-06-01 | 2023-02-16 | 瑞士商諾華公司 | Cd19和cd22嵌合抗原受體及其用途 |
CA3218692A1 (en) | 2021-06-04 | 2022-12-08 | Boehringer Ingelheim International Gmbh | Anti-sirp-alpha antibodies |
GB202107994D0 (en) | 2021-06-04 | 2021-07-21 | Kymab Ltd | Treatment of cancer |
CA3218590A1 (en) | 2021-06-07 | 2022-12-15 | Providence Health & Services - Oregon | Cxcr5, pd-1, and icos expressing tumor reactive cd4 t cells and their use |
AR126102A1 (es) | 2021-06-09 | 2023-09-13 | Incyte Corp | Heterociclos tricíclicos como inhibidores de fgfr |
WO2022258691A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkg2d, a cytokine receptor, a tumour antigen and cd16a |
WO2022258678A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkp30, a cytokine receptor, a tumour antigen and cd16a |
TW202313610A (zh) | 2021-06-09 | 2023-04-01 | 美商英塞特公司 | 作為fgfr抑制劑之三環雜環 |
EP4352098A1 (en) | 2021-06-09 | 2024-04-17 | Innate Pharma | Multispecific proteins binding to nkp46, a cytokine receptor, a tumour antigen and cd16a |
KR20240026507A (ko) | 2021-06-29 | 2024-02-28 | 플래그쉽 파이어니어링 이노베이션스 브이, 인크. | 타노트랜스미션을 촉진시키도록 엔지니어링된 면역 세포 및 이의 용도 |
BR112023026966A2 (pt) | 2021-07-02 | 2024-03-12 | Hoffmann La Roche | Métodos para tratar um indivíduo com melanoma, para alcançar uma resposta clínica, para tratar um indivíduo com linfoma não hodgkin, para tratar uma população de indivíduos com linfoma não hodgkin e para tratar um indivíduo com câncer colorretal metastático |
WO2023280790A1 (en) | 2021-07-05 | 2023-01-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Gene signatures for predicting survival time in patients suffering from renal cell carcinoma |
TW202317565A (zh) | 2021-07-07 | 2023-05-01 | 美商英塞特公司 | 作為kras抑制劑的三環化合物 |
WO2023285552A1 (en) | 2021-07-13 | 2023-01-19 | BioNTech SE | Multispecific binding agents against cd40 and cd137 in combination therapy for cancer |
TW202321237A (zh) | 2021-07-14 | 2023-06-01 | 美商纜圖藥品公司 | Map4k1抑制劑 |
WO2023287896A1 (en) | 2021-07-14 | 2023-01-19 | Incyte Corporation | Tricyclic compounds as inhibitors of kras |
WO2023288264A1 (en) | 2021-07-15 | 2023-01-19 | Blueprint Medicines Corporation | Map4k1 inhibitors |
KR20240038991A (ko) | 2021-07-19 | 2024-03-26 | 리제너론 파마슈티칼스 인코포레이티드 | 암을 치료하기 위한 체크포인트 저해제 및 종양용해 바이러스의 조합 |
CA3224180A1 (en) | 2021-07-28 | 2023-02-02 | F. Hoffmann-La Roche Ag | Methods and compositions for treating cancer |
WO2023010094A2 (en) | 2021-07-28 | 2023-02-02 | Genentech, Inc. | Methods and compositions for treating cancer |
AU2022320051A1 (en) | 2021-07-30 | 2024-01-25 | ONA Therapeutics S.L. | Anti-cd36 antibodies and their use to treat cancer |
WO2023010080A1 (en) | 2021-07-30 | 2023-02-02 | Seagen Inc. | Treatment for cancer |
CN113413464A (zh) * | 2021-08-09 | 2021-09-21 | 中国人民解放军海军军医大学第一附属医院 | 抗pd-l1抗体在急性呼吸窘迫综合征治疗药物中的应用 |
WO2023016564A1 (zh) | 2021-08-12 | 2023-02-16 | 上海才致药成生物科技有限公司 | 靶向GPC3的抗体干扰素α融合蛋白及其用途 |
IL310662A (en) | 2021-08-23 | 2024-04-01 | Immunitas Therapeutics Inc | Anti-CD161 antibodies and their uses |
IL310924A (en) | 2021-08-25 | 2024-04-01 | Pic Therapeutics Inc | EIF4E inhibitors and their uses |
WO2023028238A1 (en) | 2021-08-25 | 2023-03-02 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
CA3229855A1 (en) | 2021-08-31 | 2023-03-09 | Incyte Corporation | Naphthyridine compounds as inhibitors of kras |
TW202325306A (zh) | 2021-09-02 | 2023-07-01 | 美商天恩治療有限公司 | 改良免疫細胞之生長及功能的方法 |
WO2023031366A1 (en) | 2021-09-02 | 2023-03-09 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Anti-cecam6 antibodies with reduced side-effects |
WO2023039089A1 (en) | 2021-09-08 | 2023-03-16 | Twentyeight-Seven, Inc. | Papd5 and/or papd7 inhibiting 4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives |
US20230151005A1 (en) | 2021-09-21 | 2023-05-18 | Incyte Corporation | Hetero-tricyclic compounds as inhibitors of kras |
WO2023056403A1 (en) | 2021-09-30 | 2023-04-06 | Genentech, Inc. | Methods for treatment of hematologic cancers using anti-tigit antibodies, anti-cd38 antibodies, and pd-1 axis binding antagonists |
WO2023051926A1 (en) | 2021-09-30 | 2023-04-06 | BioNTech SE | Treatment involving non-immunogenic rna for antigen vaccination and pd-1 axis binding antagonists |
CA3234375A1 (en) | 2021-10-01 | 2023-04-06 | Incyte Corporation | Pyrazoloquinoline kras inhibitors |
TW202327595A (zh) | 2021-10-05 | 2023-07-16 | 美商輝瑞大藥廠 | 用於治療癌症之氮雜內醯胺化合物的組合 |
TW202333802A (zh) | 2021-10-11 | 2023-09-01 | 德商拜恩迪克公司 | 用於肺癌之治療性rna(二) |
US11939328B2 (en) | 2021-10-14 | 2024-03-26 | Incyte Corporation | Quinoline compounds as inhibitors of KRAS |
CA3234821A1 (en) | 2021-10-28 | 2023-05-04 | Suman Kumar VODNALA | Methods for culturing immune cells |
AU2022375806A1 (en) | 2021-10-29 | 2023-12-14 | Bristol-Myers Squibb Company | Lag-3 antagonist therapy for hematological cancer |
WO2023078900A1 (en) | 2021-11-03 | 2023-05-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating triple negative breast cancer (tnbc) |
WO2023079428A1 (en) | 2021-11-03 | 2023-05-11 | Pfizer Inc. | Combination therapies using tlr7/8 agonist |
WO2023081730A1 (en) | 2021-11-03 | 2023-05-11 | Teon Therapeutics, Inc. | 4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide derivatives as cannabinoid cb2 receptor modulators for the treatment of cancer |
WO2023080900A1 (en) | 2021-11-05 | 2023-05-11 | Genentech, Inc. | Methods and compositions for classifying and treating kidney cancer |
WO2023083439A1 (en) | 2021-11-09 | 2023-05-19 | BioNTech SE | Tlr7 agonist and combinations for cancer treatment |
WO2023088968A1 (en) | 2021-11-17 | 2023-05-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Universal sarbecovirus vaccines |
TW202320792A (zh) | 2021-11-22 | 2023-06-01 | 美商英塞特公司 | 包含fgfr抑制劑及kras抑制劑之組合療法 |
US20230203062A1 (en) | 2021-11-24 | 2023-06-29 | Genentech, Inc. | Therapeutic compounds and methods of use |
WO2023097195A1 (en) | 2021-11-24 | 2023-06-01 | Genentech, Inc. | Therapeutic indazole compounds and methods of use in the treatment of cancer |
WO2023097211A1 (en) | 2021-11-24 | 2023-06-01 | The University Of Southern California | Methods for enhancing immune checkpoint inhibitor therapy |
US20230203010A1 (en) | 2021-12-03 | 2023-06-29 | Incyte Corporation | Bicyclic amine cdk12 inhibitors |
WO2023104910A1 (en) | 2021-12-08 | 2023-06-15 | Tessa Therapeutics Ltd. | Treatment of lymphoma |
US20230183251A1 (en) | 2021-12-10 | 2023-06-15 | Incyte Corporation | Bicyclic amines as cdk12 inhibitors |
WO2023114984A1 (en) | 2021-12-17 | 2023-06-22 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
WO2023118165A1 (en) | 2021-12-21 | 2023-06-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
WO2023122772A1 (en) | 2021-12-22 | 2023-06-29 | Gossamer Bio Services, Inc. | Oxime derivatives useful as t cell activators |
WO2023122777A1 (en) | 2021-12-22 | 2023-06-29 | Gossamer Bio Services, Inc. | Oxime derivatives useful as t cell activators |
WO2023122778A1 (en) | 2021-12-22 | 2023-06-29 | Gossamer Bio Services, Inc. | Pyridazinone derivatives useful as t cell activators |
US20230192722A1 (en) | 2021-12-22 | 2023-06-22 | Incyte Corporation | Salts and solid forms of an fgfr inhibitor and processes of preparing thereof |
WO2023129438A1 (en) | 2021-12-28 | 2023-07-06 | Wisconsin Alumni Research Foundation | Hydrogel compositions for use for depletion of tumor associated macrophages |
WO2023130081A1 (en) | 2021-12-30 | 2023-07-06 | Neoimmunetech, Inc. | Method of treating a tumor with a combination of il-7 protein and vegf antagonist |
WO2023137161A1 (en) | 2022-01-14 | 2023-07-20 | Amgen Inc. | Triple blockade of tigit, cd112r, and pd-l1 |
WO2023147371A1 (en) | 2022-01-26 | 2023-08-03 | Bristol-Myers Squibb Company | Combination therapy for hepatocellular carcinoma |
WO2023143478A1 (en) * | 2022-01-27 | 2023-08-03 | Crown Bioscience Inc. | Novel anti-cd4 and anti-pd-l1 bispecific antibodies |
JP7444182B2 (ja) | 2022-01-28 | 2024-03-06 | トヨタ自動車株式会社 | 車両用スロープ展開装置 |
WO2023147488A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Cytokine associated tumor infiltrating lymphocytes compositions and methods |
WO2023150186A1 (en) | 2022-02-01 | 2023-08-10 | Arvinas Operations, Inc. | Dgk targeting compounds and uses thereof |
WO2023154799A1 (en) | 2022-02-14 | 2023-08-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Combination immunotherapy for treating cancer |
TW202342474A (zh) | 2022-02-14 | 2023-11-01 | 美商基利科學股份有限公司 | 抗病毒吡唑并吡啶酮化合物 |
CN114181310B (zh) * | 2022-02-14 | 2022-07-05 | 中山康方生物医药有限公司 | 抗tigit抗体、其药物组合物及用途 |
WO2023159102A1 (en) | 2022-02-17 | 2023-08-24 | Regeneron Pharmaceuticals, Inc. | Combinations of checkpoint inhibitors and oncolytic virus for treating cancer |
WO2023161453A1 (en) | 2022-02-24 | 2023-08-31 | Amazentis Sa | Uses of urolithins |
WO2023164638A1 (en) | 2022-02-25 | 2023-08-31 | Bristol-Myers Squibb Company | Combination therapy for colorectal carcinoma |
WO2023166418A2 (en) | 2022-03-03 | 2023-09-07 | Pfizer Inc. | Multispecific antibodies and uses thereof |
WO2023168404A1 (en) | 2022-03-04 | 2023-09-07 | Bristol-Myers Squibb Company | Methods of treating a tumor |
US20230279004A1 (en) | 2022-03-07 | 2023-09-07 | Incyte Corporation | Solid forms, salts, and processes of preparation of a cdk2 inhibitor |
WO2023170606A1 (en) | 2022-03-08 | 2023-09-14 | Alentis Therapeutics Ag | Use of anti-claudin-1 antibodies to increase t cell availability |
WO2023173057A1 (en) | 2022-03-10 | 2023-09-14 | Ikena Oncology, Inc. | Mek inhibitors and uses thereof |
WO2023173053A1 (en) | 2022-03-10 | 2023-09-14 | Ikena Oncology, Inc. | Mek inhibitors and uses thereof |
WO2023174210A1 (en) | 2022-03-14 | 2023-09-21 | Laekna Limited | Combination treatment for cancer |
WO2023178192A1 (en) | 2022-03-15 | 2023-09-21 | Compugen Ltd. | Il-18bp antagonist antibodies and their use in monotherapy and combination therapy in the treatment of cancer |
WO2023178329A1 (en) | 2022-03-18 | 2023-09-21 | Bristol-Myers Squibb Company | Methods of isolating polypeptides |
WO2023191816A1 (en) | 2022-04-01 | 2023-10-05 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023192478A1 (en) | 2022-04-01 | 2023-10-05 | Bristol-Myers Squibb Company | Combination therapy with anti-il-8 antibodies and anti-pd-1 antibodies for treating cancer |
WO2023196988A1 (en) | 2022-04-07 | 2023-10-12 | Modernatx, Inc. | Methods of use of mrnas encoding il-12 |
WO2023196987A1 (en) | 2022-04-07 | 2023-10-12 | Bristol-Myers Squibb Company | Methods of treating tumor |
WO2023196964A1 (en) | 2022-04-08 | 2023-10-12 | Bristol-Myers Squibb Company | Machine learning identification, classification, and quantification of tertiary lymphoid structures |
WO2023194656A1 (en) | 2022-04-08 | 2023-10-12 | Tilt Biotherapeutics Oy | Monoclonal pd-l1 antibodies |
US20230406930A1 (en) | 2022-04-13 | 2023-12-21 | Genentech, Inc. | Pharmaceutical compositions of therapeutic proteins and methods of use |
WO2023201291A1 (en) | 2022-04-13 | 2023-10-19 | Genentech, Inc. | Pharmaceutical compositions of mosunetuzumab and methods of use |
WO2023211889A1 (en) | 2022-04-25 | 2023-11-02 | Ikena Oncology, Inc. | Polymorphic compounds and uses thereof |
WO2023214325A1 (en) | 2022-05-05 | 2023-11-09 | Novartis Ag | Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors |
WO2023219613A1 (en) | 2022-05-11 | 2023-11-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023220703A1 (en) | 2022-05-12 | 2023-11-16 | Genentech, Inc. | Methods and compositions comprising a shp2 inhibitor and a pd-l1 binding antagonist |
WO2023222854A1 (en) | 2022-05-18 | 2023-11-23 | Kymab Limited | Uses of anti-icos antibodies |
WO2023228095A1 (en) | 2022-05-24 | 2023-11-30 | Daiichi Sankyo Company, Limited | Dosage regimen of an anti-cdh6 antibody-drug conjugate |
WO2023230205A1 (en) | 2022-05-25 | 2023-11-30 | Ikena Oncology, Inc. | Mek inhibitors and uses thereof |
WO2023230541A1 (en) | 2022-05-27 | 2023-11-30 | Viiv Healthcare Company | Piperazine derivatives useful in hiv therapy |
WO2023235847A1 (en) | 2022-06-02 | 2023-12-07 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
WO2023240058A2 (en) | 2022-06-07 | 2023-12-14 | Genentech, Inc. | Prognostic and therapeutic methods for cancer |
WO2023240156A1 (en) | 2022-06-08 | 2023-12-14 | Tidal Therapeutics, Inc. | Ionizable cationic lipids and lipid nanoparticles, and methods of synthesis and use thereof |
TW202402279A (zh) | 2022-06-08 | 2024-01-16 | 美商英塞特公司 | 作為dgk抑制劑之三環三唑并化合物 |
WO2023242351A1 (en) | 2022-06-16 | 2023-12-21 | Lamkap Bio Beta Ag | Combination therapy of bispecific antibodies against ceacam5 and cd47 and bispecific antibodies against ceacam5 and cd3 |
WO2023250430A1 (en) | 2022-06-22 | 2023-12-28 | Incyte Corporation | Bicyclic amine cdk12 inhibitors |
WO2023250400A1 (en) | 2022-06-22 | 2023-12-28 | Juno Therapeutics, Inc. | Treatment methods for second line therapy of cd19-targeted car t cells |
WO2024015731A1 (en) | 2022-07-11 | 2024-01-18 | Incyte Corporation | Fused tricyclic compounds as inhibitors of kras g12v mutants |
WO2024015803A2 (en) | 2022-07-11 | 2024-01-18 | Autonomous Therapeutics, Inc. | Encrypted rna and methods of its use |
WO2024015897A1 (en) | 2022-07-13 | 2024-01-18 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024015372A1 (en) | 2022-07-14 | 2024-01-18 | Teon Therapeutics, Inc. | Adenosine receptor antagonists and uses thereof |
WO2024020432A1 (en) | 2022-07-19 | 2024-01-25 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024023740A1 (en) | 2022-07-27 | 2024-02-01 | Astrazeneca Ab | Combinations of recombinant virus expressing interleukin-12 with pd-1/pd-l1 inhibitors |
WO2024023750A1 (en) | 2022-07-28 | 2024-02-01 | Astrazeneca Uk Limited | Combination of antibody-drug conjugate and bispecific checkpoint inhibitor |
WO2024028364A1 (en) | 2022-08-02 | 2024-02-08 | Liminal Biosciences Limited | Aryl-triazolyl and related gpr84 antagonists and uses thereof |
WO2024028365A1 (en) | 2022-08-02 | 2024-02-08 | Liminal Biosciences Limited | Substituted pyridone gpr84 antagonists and uses thereof |
WO2024028363A1 (en) | 2022-08-02 | 2024-02-08 | Liminal Biosciences Limited | Heteroaryl carboxamide and related gpr84 antagonists and uses thereof |
US20240041929A1 (en) | 2022-08-05 | 2024-02-08 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for gprc5d and bcma |
WO2024036100A1 (en) | 2022-08-08 | 2024-02-15 | Bristol-Myers Squibb Company | Substituted tetrazolyl compounds useful as t cell activators |
WO2024036101A1 (en) | 2022-08-09 | 2024-02-15 | Bristol-Myers Squibb Company | Tertiary amine substituted bicyclic compounds useful as t cell activators |
WO2024033400A1 (en) | 2022-08-10 | 2024-02-15 | Institut National de la Santé et de la Recherche Médicale | Sk2 inhibitor for the treatment of pancreatic cancer |
WO2024033399A1 (en) | 2022-08-10 | 2024-02-15 | Institut National de la Santé et de la Recherche Médicale | Sigmar1 ligand for the treatment of pancreatic cancer |
WO2024033458A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives |
WO2024033389A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033388A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033457A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024049949A1 (en) | 2022-09-01 | 2024-03-07 | Genentech, Inc. | Therapeutic and diagnostic methods for bladder cancer |
WO2024052356A1 (en) | 2022-09-06 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Inhibitors of the ceramide metabolic pathway for overcoming immunotherapy resistance in cancer |
WO2024054992A1 (en) | 2022-09-09 | 2024-03-14 | Bristol-Myers Squibb Company | Methods of separating chelator |
WO2024056716A1 (en) | 2022-09-14 | 2024-03-21 | Institut National de la Santé et de la Recherche Médicale | Methods and pharmaceutical compositions for the treatment of dilated cardiomyopathy |
WO2024069009A1 (en) | 2022-09-30 | 2024-04-04 | Alentis Therapeutics Ag | Treatment of drug-resistant hepatocellular carcinoma |
WO2024077166A1 (en) | 2022-10-05 | 2024-04-11 | Genentech, Inc. | Methods and compositions for classifying and treating lung cancer |
WO2024077191A1 (en) | 2022-10-05 | 2024-04-11 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additionalpolypeptides and their use in treating cancer |
WO2024077095A1 (en) | 2022-10-05 | 2024-04-11 | Genentech, Inc. | Methods and compositions for classifying and treating bladder cancer |
CN116444675B (zh) * | 2023-05-11 | 2023-12-22 | 亲和(武汉)生命科技有限责任公司 | 一种Pfu DNA聚合酶纳米抗体及其制备方法和应用 |
Family Cites Families (421)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US30985A (en) | 1860-12-18 | Thomas l | ||
US5432A (en) | 1848-02-01 | Improvement in machinery for knitting | ||
US18A (en) | 1836-08-31 | Thomas blanchard | ||
USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
US4275149A (en) | 1978-11-24 | 1981-06-23 | Syva Company | Macromolecular environment control in specific receptor assays |
US4657760A (en) | 1979-03-20 | 1987-04-14 | Ortho Pharmaceutical Corporation | Methods and compositions using monoclonal antibody to human T cells |
WO1981001145A1 (en) | 1979-10-18 | 1981-04-30 | Univ Illinois | Hydrolytic enzyme-activatible pro-drugs |
US4419446A (en) | 1980-12-31 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant DNA process utilizing a papilloma virus DNA as a vector |
US4601978A (en) | 1982-11-24 | 1986-07-22 | The Regents Of The University Of California | Mammalian metallothionein promoter system |
US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
EP0138854B1 (en) | 1983-03-08 | 1992-11-04 | Chiron Mimotopes Pty. Ltd. | Antigenically active amino acid sequences |
NZ207394A (en) | 1983-03-08 | 1987-03-06 | Commw Serum Lab Commission | Detecting or determining sequence of amino acids |
WO1984003506A1 (en) | 1983-03-08 | 1984-09-13 | Commw Serum Lab Commission | Antigenically active amino acid sequences |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
US4965199A (en) | 1984-04-20 | 1990-10-23 | Genentech, Inc. | Preparation of functional human factor VIII in mammalian cells using methotrexate based selection |
NZ215865A (en) | 1985-04-22 | 1988-10-28 | Commw Serum Lab Commission | Method of determining the active site of a receptor-binding analogue |
US5206344A (en) | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
US5567610A (en) | 1986-09-04 | 1996-10-22 | Bioinvent International Ab | Method of producing human monoclonal antibodies and kit therefor |
IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
GB8705477D0 (en) | 1987-03-09 | 1987-04-15 | Carlton Med Prod | Drug delivery systems |
US4975278A (en) | 1988-02-26 | 1990-12-04 | Bristol-Myers Company | Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells |
IL87737A (en) | 1987-09-11 | 1993-08-18 | Genentech Inc | Method for culturing polypeptide factor dependent vertebrate recombinant cells |
ES2058199T3 (es) | 1987-09-23 | 1994-11-01 | Bristol Myers Squibb Co | Heteroconjugados de anticuerpos para la eliminacion de celulas infectadas por el vih. |
US5571689A (en) | 1988-06-16 | 1996-11-05 | Washington University | Method of N-acylating peptide and proteins with diheteroatom substituted analogs of myristic acid |
US5663143A (en) | 1988-09-02 | 1997-09-02 | Dyax Corp. | Engineered human-derived kunitz domains that inhibit human neutrophil elastase |
US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
EP0435911B1 (en) | 1988-09-23 | 1996-03-13 | Cetus Oncology Corporation | Cell culture medium for enhanced cell growth, culture longevity and product expression |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
CA2062795A1 (en) | 1989-06-29 | 1990-12-30 | Michael W. Fanger | Bispecific reagents for aids therapy |
US5225212A (en) | 1989-10-20 | 1993-07-06 | Liposome Technology, Inc. | Microreservoir liposome composition and method |
US5859205A (en) * | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
CA2050918A1 (en) | 1990-01-12 | 1991-07-13 | Raju Kucherlapati | Generation of xenogeneic antibodies |
US5229275A (en) | 1990-04-26 | 1993-07-20 | Akzo N.V. | In-vitro method for producing antigen-specific human monoclonal antibodies |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
US5723286A (en) | 1990-06-20 | 1998-03-03 | Affymax Technologies N.V. | Peptide library and screening systems |
WO1992000373A1 (en) | 1990-06-29 | 1992-01-09 | Biosource Genetics Corporation | Melanin production by transformed microorganisms |
US6172197B1 (en) | 1991-07-10 | 2001-01-09 | Medical Research Council | Methods for producing members of specific binding pairs |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
ES2108048T3 (es) | 1990-08-29 | 1997-12-16 | Genpharm Int | Produccion y utilizacion de animales inferiores transgenicos capaces de producir anticuerpos heterologos. |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
US5264365A (en) | 1990-11-09 | 1993-11-23 | Board Of Regents, The University Of Texas System | Protease-deficient bacterial strains for production of proteolytically sensitive polypeptides |
US5508192A (en) | 1990-11-09 | 1996-04-16 | Board Of Regents, The University Of Texas System | Bacterial host strains for producing proteolytically sensitive polypeptides |
DE69130831T2 (de) | 1990-11-21 | 1999-09-16 | Iterex Pharma Lp | Synthese äquimolarer mischungen vielzähliger oligomere, speziell oligopeptidmischungen |
DE69129154T2 (de) | 1990-12-03 | 1998-08-20 | Genentech Inc | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
AU662148B2 (en) | 1991-04-10 | 1995-08-24 | Scripps Research Institute, The | Heterodimeric receptor libraries using phagemids |
JPH06507398A (ja) | 1991-05-14 | 1994-08-25 | リプリジェン コーポレーション | Hiv感染治療のための異種複合抗体 |
EP0590058B1 (en) | 1991-06-14 | 2003-11-26 | Genentech, Inc. | HUMANIZED Heregulin ANTIBODy |
JP3951062B2 (ja) | 1991-09-19 | 2007-08-01 | ジェネンテック・インコーポレーテッド | 少なくとも遊離のチオールとして存在するシステインを有する抗体フラグメントの大腸菌での発現、2官能性F(ab’)2抗体の産生のための使用 |
ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
US5587458A (en) | 1991-10-07 | 1996-12-24 | Aronex Pharmaceuticals, Inc. | Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof |
US5270170A (en) | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
AU3178993A (en) | 1991-11-25 | 1993-06-28 | Enzon, Inc. | Multivalent antigen-binding proteins |
ATE419355T1 (de) | 1992-02-06 | 2009-01-15 | Novartis Vaccines & Diagnostic | Marker für krebs und biosynthetisches bindeprotein dafür |
US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
JPH08500017A (ja) | 1992-08-17 | 1996-01-09 | ジェネンテク,インコーポレイテッド | 二特異的免疫アドヘジン |
DK0669836T3 (da) | 1992-11-13 | 1996-10-14 | Idec Pharma Corp | Terapeutisk anvendelse af kimære og radioaktivt mærkede antistoffer og humant B-lymfocytbegrænset differentieringsantigen til behandling af B-cellelymfom |
EP0672142B1 (en) | 1992-12-04 | 2001-02-28 | Medical Research Council | Multivalent and multispecific binding proteins, their manufacture and use |
CA2143491C (en) * | 1994-03-01 | 2011-02-22 | Yasumasa Ishida | A novel peptide related to human programmed cell death and dna encoding it |
US5639635A (en) | 1994-11-03 | 1997-06-17 | Genentech, Inc. | Process for bacterial production of polypeptides |
EP1241264A1 (en) | 1994-12-02 | 2002-09-18 | Chiron Corporation | Monoclonal antibodies to colon cancer antigen |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US5840523A (en) | 1995-03-01 | 1998-11-24 | Genetech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
US5739277A (en) | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
KR100654645B1 (ko) | 1995-04-27 | 2007-04-04 | 아브게닉스, 인크. | 면역화된 제노마우스 유래의 인간 항체 |
EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
US5837234A (en) | 1995-06-07 | 1998-11-17 | Cytotherapeutics, Inc. | Bioartificial organ containing cells encapsulated in a permselective polyether suflfone membrane |
DE19544393A1 (de) | 1995-11-15 | 1997-05-22 | Hoechst Schering Agrevo Gmbh | Synergistische herbizide Mischungen |
AU2660397A (en) | 1996-04-05 | 1997-10-29 | Board Of Regents, The University Of Texas System | Methods for producing soluble, biologically-active disulfide bond-containing eukaryotic proteins in bacterial cells |
ATE549918T1 (de) | 1996-12-03 | 2012-04-15 | Amgen Fremont Inc | Menschliche antikörper, die ausdrücklich menschliches tnf alpha binden |
WO2001034629A1 (en) | 1999-11-12 | 2001-05-17 | Human Genome Sciences, Inc. | 21 human secreted proteins |
US6083715A (en) | 1997-06-09 | 2000-07-04 | Board Of Regents, The University Of Texas System | Methods for producing heterologous disulfide bond-containing polypeptides in bacterial cells |
PT1034298E (pt) | 1997-12-05 | 2012-02-03 | Scripps Research Inst | Humanização de anticorpo murino |
DE69937291T2 (de) | 1998-04-02 | 2008-07-10 | Genentech, Inc., South San Francisco | Antikörpervarianten und fragmente davon |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
US6335155B1 (en) | 1998-06-26 | 2002-01-01 | Sunesis Pharmaceuticals, Inc. | Methods for rapidly identifying small organic molecule ligands for binding to biological target molecules |
WO2000026227A1 (en) | 1998-10-30 | 2000-05-11 | Millennium Pharmaceuticals, Inc. | Ldl related protein and uses thereof |
US6406884B1 (en) | 1999-06-18 | 2002-06-18 | Millennium Pharmaceuticals, Inc. | Secreted proteins and uses thereof |
US20030027998A1 (en) | 1998-10-30 | 2003-02-06 | Holtzman Douglas A. | Novel genes encoding proteins having prognostic, diagnostic, preventive, therapeutic, and other uses |
US20060205034A1 (en) | 1998-10-30 | 2006-09-14 | Millennium Pharmaceuticals, Inc. | Novel genes encoding proteins having prognostic, diagnostic, preventive, therapeutic, and other uses |
EP1141708A1 (en) | 1998-12-28 | 2001-10-10 | Sunesis Pharmaceuticals Inc. | Identifying small organic molecule ligands for binding |
US20080213778A1 (en) | 1998-12-30 | 2008-09-04 | Millennium Pharmaceuticals, Inc. | Novel genes encoding proteins having prognostic, diagnostic, preventive, therapeutic, and other uses |
EP1710299A3 (en) | 1998-12-30 | 2007-01-10 | Millennium Pharmaceuticals, Inc. | Secreted proteins and nucleic acids encoding them |
EP1140976A4 (en) | 1998-12-30 | 2003-05-21 | Millennium Pharm Inc | SECRETED PROTEINS AND THEIR USES |
US7041474B2 (en) * | 1998-12-30 | 2006-05-09 | Millennium Pharmaceuticals, Inc. | Nucleic acid encoding human tango 509 |
AU2396700A (en) | 1998-12-30 | 2000-07-31 | Millennium Pharmaceuticals, Inc. | Secreted proteins and uses thereof |
US20120270219A1 (en) | 1998-12-30 | 2012-10-25 | Millennium Pharmaceuticals, Inc. | Novel genes encoding proteins having prognostic, diagnostic, preventive, therapeutic, and other uses |
WO2000050442A2 (en) | 1999-02-26 | 2000-08-31 | Millennium Pharmaceuticals, Inc. | Secreted proteins and uses thereof |
EP1173456A4 (en) | 1999-03-01 | 2005-10-12 | Millennium Pharm Inc | SECRETED PROTEINS AND NUCLEIC ACIDS ENCODING THEM |
EP1444260A4 (en) | 1999-05-14 | 2004-08-25 | Millennium Pharm Inc | SECRETED PROTEINS AND THEIR USE |
WO2001000672A1 (en) | 1999-06-29 | 2001-01-04 | Millennium Pharmaceuticals, Inc. | Secreted proteins and uses thereof |
WO2001000673A1 (en) | 1999-06-30 | 2001-01-04 | Millennium Pharmaceuticals, Inc. | Membrane-associated and secreted proteins and uses thereof |
EP1074617A3 (en) | 1999-07-29 | 2004-04-21 | Research Association for Biotechnology | Primers for synthesising full-length cDNA and their use |
JP2002171977A (ja) | 1999-07-29 | 2002-06-18 | Herikkusu Kenkyusho:Kk | 新規なヒトsh2蛋白質 |
JP2002191363A (ja) | 1999-07-29 | 2002-07-09 | Herikkusu Kenkyusho:Kk | 全長cDNA合成用プライマー、およびその用途 |
US6908748B2 (en) | 1999-07-29 | 2005-06-21 | Kenji Sobue | Genes associated with the maintenance of differentiation of smooth muscle cells |
AU6180900A (en) | 1999-07-29 | 2001-02-19 | Chugai Seiyaku Kabushiki Kaisha | Novel genes encoding protein kinase/protein phosphatase |
WO2001009346A1 (fr) | 1999-07-29 | 2001-02-08 | Ota, Toshio | Gene codant pour une nouvelle proteine de type adenylate kinase 3 (ak3) |
AU6181000A (en) | 1999-07-29 | 2001-02-19 | Chugai Research Institute For Molecular Medicine, Inc. | Novel genes encoding protein kinase/protein phosphatase |
WO2001009317A1 (fr) | 1999-07-29 | 2001-02-08 | Helix Research Institute | Gene associe au cancer de l'estomac |
WO2001009319A1 (fr) | 1999-07-29 | 2001-02-08 | Helix Research Institute | Gene exprime specifiquement dans le muscle cardiaque foetal humain |
WO2001009349A1 (fr) | 1999-07-29 | 2001-02-08 | Helix Research Institute | Nouveaux genes codant pour une proteine de type serine protease |
AU6394400A (en) | 1999-07-30 | 2001-02-19 | Millennium Pharmaceuticals, Inc. | Secreted proteins and uses thereof |
JP4896327B2 (ja) * | 1999-08-23 | 2012-03-14 | ダナ−ファーバー キャンサー インスティテュート,インコーポレイテッド | Pd−1、b7−4の受容体、およびその使用 |
WO2001014556A1 (en) * | 1999-08-23 | 2001-03-01 | Dana-Farber Cancer Institute, Inc. | Novel b7-4 molecules and uses therefor |
EP1218411A4 (en) | 1999-09-20 | 2004-09-01 | Millennium Pharm Inc | SECRETED PROTEINS AND THEIR USES |
WO2001023523A2 (en) | 1999-09-30 | 2001-04-05 | Millennium Pharmaceuticals, Inc. | Secreted proteins and uses thereof |
US20070219125A1 (en) | 1999-11-17 | 2007-09-20 | Cojocaru Gad S | Novel thrombospondin-1 polynucleotides encoding variant thrombospondin-1 polypeptides and methods using same |
WO2001036632A2 (en) | 1999-11-17 | 2001-05-25 | Compugen Ltd. | Variants of alternative splicing |
WO2001039722A2 (en) | 1999-11-30 | 2001-06-07 | Mayo Foundation For Medical Education And Research | B7-h1, a novel immunoregulatory molecule |
US6803192B1 (en) * | 1999-11-30 | 2004-10-12 | Mayo Foundation For Medical Education And Research | B7-H1, a novel immunoregulatory molecule |
EP1908780B1 (en) * | 2000-01-03 | 2012-08-15 | The Trustees Of The University Of Pennsylvania | Novel chimeric proteins and methods for using the same |
WO2001068134A2 (en) * | 2000-03-14 | 2001-09-20 | Genetics Institute, Inc. | Therapies that improve graft survival, using antibodies against a b7 antigen |
NZ522045A (en) | 2000-03-30 | 2007-05-31 | Whitehead Biomedical Inst | RNA sequence-specific mediators of RNA interference |
JP2003530839A (ja) * | 2000-04-12 | 2003-10-21 | プリンシピア ファーマスーティカル コーポレイション | アルブミン融合タンパク質 |
US6936450B2 (en) | 2000-04-12 | 2005-08-30 | Compugen Ltd. | Variants of protein kinases |
US7030219B2 (en) * | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
US20030031675A1 (en) | 2000-06-06 | 2003-02-13 | Mikesell Glen E. | B7-related nucleic acids and polypeptides useful for immunomodulation |
EP1292619B1 (en) | 2000-06-06 | 2008-02-06 | Bristol-Myers Squibb Company | B7-related nucleic acids and polypeptides and their uses for immunomodulation |
US7323174B1 (en) * | 2000-06-12 | 2008-01-29 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Modulation of immune response and methods based thereon |
NZ522844A (en) | 2000-06-28 | 2005-02-25 | Brigham & Womens Hospital | PD-L2 molecules: novel PD-1 ligands and methods to identify compounds to modulate T cell activation |
US6635750B1 (en) * | 2000-07-20 | 2003-10-21 | Millennium Pharmaceuticals, Inc. | B7-H2 nucleic acids, members of the B7 family |
EP1328624B1 (en) | 2000-09-20 | 2011-11-09 | Amgen Inc. | B7-like molecules and uses thereof |
WO2002039813A1 (fr) * | 2000-11-15 | 2002-05-23 | Ono Pharmaceutical Co., Ltd. | Souris sans pd-1 et utilisation de celle-ci |
US20060014166A1 (en) | 2004-01-27 | 2006-01-19 | Yossi Cohen | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of endometriosis |
US7601692B2 (en) | 2000-11-28 | 2009-10-13 | Compugen Ltd. | MCP-1 splice variants and methods of using same |
JP3523245B1 (ja) | 2000-11-30 | 2004-04-26 | メダレックス,インコーポレーテッド | ヒト抗体作製用トランスジェニック染色体導入齧歯動物 |
ES2728168T3 (es) | 2000-12-01 | 2019-10-22 | Max Planck Gesellschaft | Moléculas pequeñas de ARN que median en la interferencia de ARN |
US9249229B2 (en) | 2000-12-08 | 2016-02-02 | Alexion Pharmaceuticals, Inc. | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
US20060057651A1 (en) | 2000-12-08 | 2006-03-16 | Bowdish Katherine S | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
AU2002246632B2 (en) | 2000-12-08 | 2007-04-05 | Alexion Pharmaceuticals, Inc. | Chronic lymphocytic leukemia cell line and its use for producing an antibody |
US7408041B2 (en) | 2000-12-08 | 2008-08-05 | Alexion Pharmaceuticals, Inc. | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
US20040198661A1 (en) | 2000-12-08 | 2004-10-07 | Bowdish Katherine S. | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
US20030180309A1 (en) | 2001-01-08 | 2003-09-25 | Baum Peter R. | Human B7 polypeptides |
US20040005557A1 (en) | 2001-01-16 | 2004-01-08 | Muralidhara Padigaru | Proteins, polynucleotides encoding them and methods of using the same |
WO2002068647A2 (en) | 2001-01-16 | 2002-09-06 | Curagen Corporation | Proteins, polynucleotides encoding them and methods of using the same |
US7754208B2 (en) * | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
AU2002240818C1 (en) | 2001-03-14 | 2008-11-06 | Agilent Technologies, Inc. | MHC molecule constructs and their uses for diagnosis and therapy |
WO2002077208A1 (de) | 2001-03-27 | 2002-10-03 | Genethor Gmbh | Antigen-abhängige reduktion von spezifischen immunreaktionen durch beeinflussung der co-stimulation |
AR036993A1 (es) * | 2001-04-02 | 2004-10-20 | Wyeth Corp | Uso de agentes que modulan la interaccion entre pd-1 y sus ligandos en la submodulacion de respuestas inmunologicas |
WO2002079499A1 (en) | 2001-04-02 | 2002-10-10 | Wyeth | Pd-1, a receptor for b7-4, and uses therefor |
WO2002080952A2 (en) | 2001-04-09 | 2002-10-17 | Lorantis Limited | Therapeutic use and identification of modulators of a hedgehog signalling pathway or one of its target pathways |
AU2002258941A1 (en) * | 2001-04-20 | 2002-11-05 | Mayo Foundation For Medical Education And Research | Methods of enhancing cell responsiveness |
FR2824567B1 (fr) * | 2001-05-11 | 2003-08-08 | Inst Nat Sante Rech Med | Procede d'obtention de lymphocytes tr1 regulateurs specifiques d'antigene |
WO2002092792A2 (de) | 2001-05-16 | 2002-11-21 | Genethor Gmbh | Antigen-abhängige reduktion von spezifischen immunreaktionen durch beeinflussung der co-stimulation |
US20060276422A1 (en) * | 2001-05-18 | 2006-12-07 | Nassim Usman | RNA interference mediated inhibition of B7-H1 gene expression using short interfering nucleic acid (siNA) |
US20030003953A1 (en) * | 2001-06-18 | 2003-01-02 | Comverse Network Systems Ltd. | Multi-user chat service in a cellular network |
ATE524495T1 (de) | 2001-07-31 | 2011-09-15 | Ono Pharmaceutical Co | Pd-1-spezifische substanz |
US20040033497A1 (en) * | 2002-08-13 | 2004-02-19 | Alarcon-Riquelme Marta E. | Polymorphisms of PD-1 |
US20040101876A1 (en) | 2002-05-31 | 2004-05-27 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
US7678769B2 (en) | 2001-09-14 | 2010-03-16 | Compugen, Ltd. | Hepatocyte growth factor receptor splice variants and methods of using same |
US20040248157A1 (en) | 2001-09-14 | 2004-12-09 | Michal Ayalon-Soffer | Novel polynucleotides encoding soluble polypeptides and methods using same |
US20100183573A1 (en) | 2001-09-14 | 2010-07-22 | Compugen Ltd. | Hepatocyte growth factor receptor splice variants and methods of using same |
US20040142325A1 (en) | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
CA2842429A1 (en) | 2001-10-19 | 2003-05-01 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of inflammatory bowel disorders |
WO2003042402A2 (en) * | 2001-11-13 | 2003-05-22 | Dana-Farber Cancer Institute, Inc. | Agents that modulate immune cell activation and methods of use thereof |
GB0130955D0 (en) | 2001-12-24 | 2002-02-13 | Cancer Res Ventures | Expression system |
US7638326B2 (en) * | 2002-01-03 | 2009-12-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform |
US20030166282A1 (en) | 2002-02-01 | 2003-09-04 | David Brown | High potency siRNAS for reducing the expression of target genes |
AR038568A1 (es) | 2002-02-20 | 2005-01-19 | Hoffmann La Roche | Anticuerpos anti-a beta y su uso |
EP2865688A1 (en) | 2002-03-01 | 2015-04-29 | Immunomedics, Inc. | Internalizing anti-CD74 antibodies and methods of use |
IL148993A0 (en) | 2002-04-04 | 2002-11-10 | Yissum Res Dev Co | Broad-spectrum in-vivo effective superantigen toxin antagonists based on the interaction between cd28 and the superantigen and uses thereof |
US8535672B2 (en) * | 2002-04-04 | 2013-09-17 | Yissum Research Development Of The Hebrew University Of Jerusalem | Broad-spectrum in-vivo effective superantigen toxin antagonists based on the interaction between CD28 and the superantigen and uses thereof |
EP2305710A3 (en) * | 2002-06-03 | 2013-05-29 | Genentech, Inc. | Synthetic antibody phage libraries |
CA2388441A1 (en) * | 2002-06-10 | 2003-12-10 | Wei-Ping Min | Immunomodulation using rna interference |
US7595048B2 (en) * | 2002-07-03 | 2009-09-29 | Ono Pharmaceutical Co., Ltd. | Method for treatment of cancer by inhibiting the immunosuppressive signal induced by PD-1 |
JP2004121218A (ja) * | 2002-08-06 | 2004-04-22 | Jenokkusu Soyaku Kenkyusho:Kk | 気管支喘息または慢性閉塞性肺疾患の検査方法 |
US7217797B2 (en) | 2002-10-15 | 2007-05-15 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
CA2502413A1 (en) | 2002-11-01 | 2004-05-21 | 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 |
US7449300B2 (en) * | 2002-11-21 | 2008-11-11 | Mayo Foundation For Medical Education And Research | Detection of antibodies specific for B7-H1 in subjects with diseases or pathological conditions mediated by activated T cells |
US7439042B2 (en) * | 2002-12-16 | 2008-10-21 | Globeimmune, Inc. | Yeast-based therapeutic for chronic hepatitis C infection |
CN1753912B (zh) | 2002-12-23 | 2011-11-02 | 惠氏公司 | 抗pd-1抗体及其用途 |
US6808748B2 (en) | 2003-01-23 | 2004-10-26 | Applied Materials, Inc. | Hydrogen assisted HDP-CVD deposition process for aggressive gap-fill technology |
JP4532409B2 (ja) * | 2003-01-23 | 2010-08-25 | 小野薬品工業株式会社 | ヒトpd−1に対し特異性を有する物質 |
KR20120084343A (ko) | 2003-03-04 | 2012-07-27 | 알렉시온 파마슈티칼스, 인코포레이티드 | 만성 림프성 백혈병 세포로부터 유래된 폴리펩티드와 항체 및 이들의 용도 |
AU2003272065A1 (en) | 2003-04-03 | 2004-10-25 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Broad-spectrum in-vivo effective superantigen toxin antagonists based on the interaction between cd28 and the superantigen and uses thereof |
US20040248205A1 (en) * | 2003-04-16 | 2004-12-09 | Stern Lawrence J. | Major histocompatibility complex (MHC)-peptide arrays |
PT1698642E (pt) * | 2003-12-26 | 2009-01-13 | Shinetsu Chemical Co | Processo para a produção de polímero de cloreto de vinilo |
US20090075257A1 (en) | 2004-01-27 | 2009-03-19 | Compugen Ltd. | Novel nucleic acid sequences and methods of use thereof for diagnosis |
US20090215046A1 (en) | 2004-01-27 | 2009-08-27 | Compugen Ltd. | Novel nucleotide and amino acid sequences, and assays methods of use thereof for diagnosis of colon cancer |
US20060040278A1 (en) | 2004-01-27 | 2006-02-23 | Cojocaru Gad S | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of ovarian cancer |
US20060183131A1 (en) | 2004-01-27 | 2006-08-17 | Amir Toporik | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of breast cancer |
US20080182299A1 (en) | 2004-01-27 | 2008-07-31 | Compugent Ltd. | Novel brain natriuretic peptide variants and methods of use thereof |
US7569662B2 (en) | 2004-01-27 | 2009-08-04 | Compugen Ltd | Nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of lung cancer |
US7368548B2 (en) | 2004-01-27 | 2008-05-06 | Compugen Ltd. | Nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of prostate cancer |
EP1749025A2 (en) | 2004-01-27 | 2007-02-07 | Compugen Ltd. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of colon cancer |
AU2005206389A1 (en) | 2004-01-27 | 2005-08-04 | Compugen Ltd. | Methods of identifying putative gene products by interspecies sequence comparison and biomolecular sequences uncovered thereby |
WO2005072055A2 (en) | 2004-01-27 | 2005-08-11 | Compugen Usa, Inc. | Novel brain natriuretic peptide variants and methods of use thereof |
US7345142B2 (en) | 2004-01-27 | 2008-03-18 | Compugen Ltd. | Nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of cardiac disease |
WO2005072340A2 (en) | 2004-01-27 | 2005-08-11 | Compugen Ltd. | Novel polynucleotides encoding polypeptides and methods using same |
EP1735342A2 (en) | 2004-01-27 | 2006-12-27 | Compugen USA, Inc. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis |
EP1713900A4 (en) | 2004-01-27 | 2009-06-17 | Compugen Ltd | METHOD AND SYSTEMS FOR COMMENTING BIOMOLECULAR SEQUENCES |
AU2005248530A1 (en) | 2004-01-27 | 2005-12-08 | Compugen Ltd. | Differential expression of markers in ovarian cancer |
US7667001B1 (en) | 2004-01-27 | 2010-02-23 | Compugen Ltd. | Nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of lung cancer |
WO2006035273A2 (en) | 2004-01-27 | 2006-04-06 | Compugen Usa, Inc. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis |
WO2006021874A2 (en) | 2004-01-27 | 2006-03-02 | Compugen Usa, Inc. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of prostate cancer |
CA2555509A1 (en) | 2004-01-27 | 2005-07-27 | Compugen Usa, Inc. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of lung cancer |
US7842459B2 (en) | 2004-01-27 | 2010-11-30 | Compugen Ltd. | Nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis |
US20060263786A1 (en) | 2004-01-27 | 2006-11-23 | Rotem Sorek | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of colon cancer |
US7332569B2 (en) | 2004-01-27 | 2008-02-19 | Compugen Ltd. | Brain natriuretic peptide spliced variant |
WO2005072050A2 (en) | 2004-01-27 | 2005-08-11 | Compugen Usa, Inc. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of breast cancer |
US7714100B2 (en) | 2004-01-27 | 2010-05-11 | Compugen Ltd | Nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of cardiac disease |
EP1713827A2 (en) | 2004-01-27 | 2006-10-25 | Compugen Ltd. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of cardiac disease |
KR20050082389A (ko) * | 2004-02-18 | 2005-08-23 | 메덱스젠 주식회사 | 직렬 연쇄체를 갖는 면역접합체를 포함하는 장기이식합병증 치료용 약제학적 조성물 |
AU2005250408B2 (en) * | 2004-05-27 | 2010-09-23 | The Trustees Of The University Of Pennsylvania | Novel artificial antigen presenting cells and uses therefor |
EP2481750A1 (en) | 2004-06-30 | 2012-08-01 | Mayo Foundation for Medical Education and Research | B7-DC binding antibody |
US20060099203A1 (en) | 2004-11-05 | 2006-05-11 | Pease Larry R | B7-DC binding antibody |
US7501119B2 (en) | 2004-06-30 | 2009-03-10 | Mayo Foundation For Medical Education And Research | Methods and molecules for modulating an immune response |
US20060003452A1 (en) * | 2004-07-01 | 2006-01-05 | Virxsys Corporation | Vector packaging cell line |
PT1810026T (pt) * | 2004-10-06 | 2018-06-11 | Mayo Found Medical Education & Res | B7-h1 e pd-1 no tratamento do carcinona de células renais |
WO2006043271A1 (en) | 2004-10-22 | 2006-04-27 | Compugen Ltd. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis |
WO2006054297A2 (en) | 2004-11-17 | 2006-05-26 | Compugen Ltd. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis |
KR20070086218A (ko) * | 2004-12-17 | 2007-08-27 | 제넨테크, 인크. | 자가면역 질환에 대한 이전 요법에 실패했던 환자에서의,자가면역 질환의 항-혈관신생 요법 |
AU2005323025A1 (en) * | 2004-12-31 | 2006-07-13 | Biogen Idec Ma Inc. | Polypeptides that bind BR3 and uses thereof |
WO2006072954A2 (en) | 2005-01-05 | 2006-07-13 | Compugen Ltd. | Novel il-6 polynucleotides encoding variant il-6 polypeptides and methods using same |
US7906635B2 (en) | 2005-01-27 | 2011-03-15 | Compugen Ltd. | Nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of ovarian cancer |
EP1851543A2 (en) | 2005-02-24 | 2007-11-07 | Compugen Ltd. | Novel diagnostic markers, especially for in vivo imaging, and assays and methods of use thereof |
CN105315373B (zh) | 2005-05-09 | 2018-11-09 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及使用抗pd-1抗体来治疗癌症的方法 |
ES2609429T3 (es) * | 2005-05-12 | 2017-04-20 | Zymogenetics, Inc. | Composiciones y métodos para modular respuestas inmunitarias |
CA2545557A1 (en) * | 2005-05-31 | 2006-11-30 | Mcgill University | Stromal antigen-presenting cells and use thereof |
PL2397156T3 (pl) | 2005-06-08 | 2017-07-31 | Dana-Farber Cancer Institute, Inc. | Sposoby i kompozycje do leczenia uporczywych infekcji i nowotworu poprzez hamowanie ścieżki zaprogramowanej śmierci komórki 1 (PD-1) |
EP1891218A2 (en) | 2005-06-08 | 2008-02-27 | Compugen Ltd. | Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis |
JP2006345852A (ja) * | 2005-06-16 | 2006-12-28 | Virxsys Corp | 抗体複合体 |
KR101607288B1 (ko) | 2005-07-01 | 2016-04-05 | 이. 알. 스퀴부 앤드 선즈, 엘.엘.씨. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날 항체 |
CA2624535A1 (en) | 2005-09-30 | 2007-04-05 | Compugen Ltd. | Hepatocyte growth factor receptor splice variants and methods of using same |
EP1777523A1 (en) | 2005-10-19 | 2007-04-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | An in vitro method for the prognosis of progression of a cancer and of the outcome in a patient and means for performing said method |
ES2618543T3 (es) * | 2005-11-23 | 2017-06-21 | Genentech, Inc. | Métodos y composiciones relacionados con ensayos de linfocitos B |
AU2006321888A1 (en) * | 2005-12-08 | 2007-06-14 | University Of Louisville Research Foundation, Inc. | Immunostimulatory compositions and methods |
WO2007082154A2 (en) | 2006-01-05 | 2007-07-19 | Mayo Foundation For Medical Education And Research | B7-h1 and b7-h4 in cancer |
US20100015642A1 (en) | 2006-01-05 | 2010-01-21 | Kwon Eugene D | B7-h1 and survivin in cancer |
US20100015143A1 (en) | 2006-03-22 | 2010-01-21 | Tracy Hussell | Compositions and Methods Relating to Modulation of Immune System Components |
US20070243548A1 (en) * | 2006-03-28 | 2007-10-18 | Elias Georges | Calumenin-directed diagnostics and therapeutics for cancer and chemotherapeutic drug resistance |
WO2007124361A2 (en) | 2006-04-20 | 2007-11-01 | Mayo Foundation For Medical Education And Research | Soluble b7-h1 |
US20100166741A1 (en) | 2006-07-13 | 2010-07-01 | Genentech , Inc. | Altered br-3 binding polypeptides |
WO2008011344A2 (en) | 2006-07-17 | 2008-01-24 | Nationwide Children's Hospital Inc. | Disruption of programmed death-1 (pd-1) ligands to adjuvant adeno-associated virus vector vaccines |
GB0615662D0 (en) * | 2006-08-07 | 2006-09-13 | Affitech As | Antibody |
WO2008034076A2 (en) | 2006-09-15 | 2008-03-20 | The Johns Hopkins University | Cyclophosphamide in combination with immune therapeutics |
WO2008085562A2 (en) * | 2006-09-20 | 2008-07-17 | The Johns Hopkins University | Combinatorieal therapy of cancer and infectious diseases with anti-b7-h1 antibodies |
WO2008057632A1 (en) | 2006-11-09 | 2008-05-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Differential gene expression in physiological and pathological angiogenesis |
AU2007325283B2 (en) | 2006-11-27 | 2012-08-30 | Diadexus, Inc. | Ovr110 antibody compositions and methods of use |
CA2672595A1 (en) | 2006-12-15 | 2008-06-19 | Guy Hermans | Amino acid sequences that modulate the interaction between cells of the immune system |
NZ629273A (en) | 2006-12-27 | 2015-02-27 | Harvard College | Compositions and methods for the treatment of infections and tumors |
WO2008091643A2 (en) | 2007-01-23 | 2008-07-31 | Altarex Medical Corp. | In vitro culture system to evaluate synergy in targeting immune suppressive pathways concurrent to immunotherapy |
JP2010516786A (ja) | 2007-01-26 | 2010-05-20 | ユニバーシティー オブ ルイヴィル リサーチ ファウンデーション,インコーポレーテッド | ワクチンとしての使用のためのエキソソーム成分の改変 |
KR20090114443A (ko) | 2007-02-09 | 2009-11-03 | 제넨테크, 인크. | 항-Robo4 항체 및 그의 용도 |
WO2008116468A2 (en) | 2007-03-26 | 2008-10-02 | Dako Denmark A/S | Mhc peptide complexes and uses thereof in infectious diseases |
EP3023436A1 (en) | 2007-07-03 | 2016-05-25 | Dako Denmark A/S | Improved methods for generation, labeling and use of mhc multimers |
US9243052B2 (en) | 2007-08-17 | 2016-01-26 | Daniel Olive | Method for treating and diagnosing hematologic malignancies |
EP2195342A1 (en) | 2007-09-07 | 2010-06-16 | Ablynx N.V. | Binding molecules with multiple binding sites, compositions comprising the same and uses thereof |
US8062852B2 (en) | 2007-10-01 | 2011-11-22 | The Children's Hospital And Regional Medical Center | Detection and treatment of autoimmune disorders |
BRPI0819349B1 (pt) | 2007-10-31 | 2018-05-08 | Idexx Lab Inc | métodos de distinguir entre animais que foram ou não infectados com e. canis, e de determinar a presença de um anticorpo ou fragmentos de ligação de antígeno, composição e kit |
CA2742926A1 (en) | 2007-11-28 | 2009-06-04 | Universite De Montreal | Pd-1 modulation and uses thereof |
US20100285039A1 (en) | 2008-01-03 | 2010-11-11 | The Johns Hopkins University | B7-H1 (CD274) Antagonists Induce Apoptosis of Tumor Cells |
WO2009108341A1 (en) | 2008-02-28 | 2009-09-03 | Argos Therapeutics, Inc. | Transient expression of immunomodulatory polypeptides for the prevention and treatment of autoimmune disease, allergy and transplant rejection |
US20110020325A1 (en) | 2008-02-29 | 2011-01-27 | Kwon Eugene D | Methods for reducing granulomatous inflammation |
WO2009114335A2 (en) | 2008-03-12 | 2009-09-17 | Merck & Co., Inc. | Pd-1 binding proteins |
US8246016B2 (en) | 2008-07-18 | 2012-08-21 | Uop Llc | Downcomer for a gas-liquid contacting device |
WO2010014784A2 (en) | 2008-08-01 | 2010-02-04 | Bristol-Myers Squibb Company | Combination of anti-ctla4 antibody with diverse therapeutic regimens for the synergistic treatment of proliferative diseases |
PL2350129T3 (pl) | 2008-08-25 | 2015-12-31 | Amplimmune Inc | Kompozycje antagonistów PD-1 i sposoby stosowania |
WO2010027828A2 (en) | 2008-08-25 | 2010-03-11 | Amplimmune, Inc. | Pd-1 antagonists and methods of use thereof |
KR101050829B1 (ko) | 2008-10-02 | 2011-07-20 | 서울대학교산학협력단 | 항 pd-1 항체 또는 항 pd-l1 항체를 포함하는 항암제 |
WO2010056735A1 (en) | 2008-11-11 | 2010-05-20 | The Trustees Of The University Of Pennsylvania | Compositions and methods for inhibiting an oncogenic protein to enhance immunogenicity |
US20110229411A1 (en) | 2008-11-27 | 2011-09-22 | Institut Gustave Roussy | Use of p2x7 pathway for assessing the sensitivity of a subject to a cancer treatment |
CA2744449C (en) | 2008-11-28 | 2019-01-29 | Emory University | Methods for the treatment of infections and tumors |
SG196798A1 (en) * | 2008-12-09 | 2014-02-13 | Genentech Inc | Anti-pd-l1 antibodies and their use to enhance t-cell function |
LT2769737T (lt) | 2009-07-20 | 2017-06-26 | Bristol-Myers Squibb Company | Anti-ctla4 antikūno derinys su etopozidu, skirtas sinerginiam proliferacinių ligų gydymui |
CA2778714C (en) | 2009-11-24 | 2018-02-27 | Medimmune Limited | Targeted binding agents against b7-h1 |
EP2504028A4 (en) | 2009-11-24 | 2014-04-09 | Amplimmune Inc | SIMULTANEOUS INHIBITION OF PD-L1 / PD-L2 |
PL2542590T5 (pl) | 2010-03-05 | 2020-08-10 | The Johns Hopkins University | Kompozycje i sposoby dla ukierunkowanych immunomodulatorowych przeciwciał i białek fuzyjnych |
EP2571577A1 (en) | 2010-05-17 | 2013-03-27 | Bristol-Myers Squibb Company | Improved immunotherapeutic dosing regimens and combinations thereof |
WO2012037551A2 (en) | 2010-09-17 | 2012-03-22 | Irx Therapeutics, Inc. | Primary cell-derived biologic and wt1 synthetic long peptide vaccine |
HUE051674T2 (hu) | 2010-09-24 | 2021-03-29 | Niels Grabe | Eszközök és eljárások rákos beteg kezelésére adott válaszának elõrejelzésére |
ES2669310T3 (es) | 2011-04-20 | 2018-05-24 | Medimmune, Llc | Anticuerpos y otras moléculas que se unen con B7-H1 y PD-1 |
JP6238459B2 (ja) | 2011-08-01 | 2017-11-29 | ジェネンテック, インコーポレイテッド | Pd−1軸結合アンタゴニストとmek阻害剤を使用する癌の治療方法 |
PT2785375T (pt) | 2011-11-28 | 2020-10-29 | Merck Patent Gmbh | Anticorpos anti-pd-l1 e usos destes |
WO2013085893A1 (en) | 2011-12-05 | 2013-06-13 | Immunomedics, Inc. | Therapeutic use of anti-cd22 antibodies for inducing trogocytosis |
US9757458B2 (en) | 2011-12-05 | 2017-09-12 | Immunomedics, Inc. | Crosslinking of CD22 by epratuzumab triggers BCR signaling and caspase-dependent apoptosis in hematopoietic cancer cells |
US20140212425A1 (en) | 2011-12-05 | 2014-07-31 | Immunomedics, Inc. | Therapeutic use of anti-cd22 antibodies for inducing trogocytosis |
US20150004175A1 (en) | 2011-12-13 | 2015-01-01 | Yale University | Compositions and Methods for Reducing CTL Exhaustion |
CA2862390A1 (en) | 2012-01-25 | 2013-08-01 | Dnatrix, Inc. | Biomarkers and combination therapies using oncolytic virus and immunomodulation |
WO2013164754A2 (en) | 2012-05-04 | 2013-11-07 | Pfizer Inc. | Prostate-associated antigens and vaccine-based immunotherapy regimens |
WO2013172926A1 (en) | 2012-05-14 | 2013-11-21 | Yale University | Immune biomarkers and assays predictive of clinical response to immunotherapy for cancer |
SG10201700698WA (en) | 2012-05-15 | 2017-02-27 | Bristol Myers Squibb Co | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
AU2013262655A1 (en) | 2012-05-16 | 2014-12-04 | John Wayne Cancer Institute | Immunological markers for adjuvant therapy in melanoma |
EP2854843A4 (en) | 2012-05-31 | 2016-06-01 | Sorrento Therapeutics Inc | ANTIGEN BINDING PROTEINS THAT BIND PD-L1 |
ES2742379T3 (es) | 2012-05-31 | 2020-02-14 | Hoffmann La Roche | Procedimientos de tratamiento del cáncer usando antagonistas de unión al eje de PD-1 y antagonistas de VEGF |
US9845356B2 (en) | 2012-08-03 | 2017-12-19 | Dana-Farber Cancer Institute, Inc. | Single agent anti-PD-L1 and PD-L2 dual binding antibodies and methods of use |
JP6559566B2 (ja) | 2012-08-06 | 2019-08-14 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 癌患者をスクリーニングするための方法及びキット |
WO2014028560A2 (en) | 2012-08-14 | 2014-02-20 | Ibc Pharmaceuticals, Inc. | T-cell redirecting bispecific antibodies for treatment of disease |
US9682143B2 (en) | 2012-08-14 | 2017-06-20 | Ibc Pharmaceuticals, Inc. | Combination therapy for inducing immune response to disease |
US9382329B2 (en) | 2012-08-14 | 2016-07-05 | Ibc Pharmaceuticals, Inc. | Disease therapy by inducing immune response to Trop-2 expressing cells |
US20150231241A1 (en) | 2012-08-14 | 2015-08-20 | Ibc Pharmaceuticals, Inc. | Combination therapy for inducing immune response to disease |
WO2014083178A1 (en) | 2012-11-30 | 2014-06-05 | F. Hoffmann-La Roche Ag | Identification of patients in need of pd-l1 inhibitor cotherapy |
AR093984A1 (es) | 2012-12-21 | 2015-07-01 | Merck Sharp & Dohme | Anticuerpos que se unen a ligando 1 de muerte programada (pd-l1) humano |
CA2896797A1 (en) | 2013-01-11 | 2014-07-17 | Dingfu Biotarget Co., Ltd | Agents for treating tumours, use and method thereof |
WO2014122271A1 (en) | 2013-02-07 | 2014-08-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of patients suffering from diffuse large b-cell lymphomas |
EP2958571B1 (en) | 2013-02-21 | 2024-04-10 | Michele Maio | Dna hypomethylating agents for cancer therapy |
WO2014165082A2 (en) | 2013-03-13 | 2014-10-09 | Medimmune, Llc | Antibodies and methods of detection |
EP2971128B1 (en) | 2013-03-15 | 2023-03-01 | Veracyte, Inc. | Biomarkers for diagnosis of lung diseases and methods of use thereof |
KR20230070054A (ko) | 2013-03-15 | 2023-05-19 | 제넨테크, 인크. | Pd-1 및 pd-l1 관련 상태를 치료하기 위한 바이오마커 및 방법 |
US20160084839A1 (en) | 2013-04-02 | 2016-03-24 | Marisa Dolled-Filhart | Immunohistochemical assay for detecting expression of programmed death ligand 1 (pd-l1) in tumor tissue |
JP6361039B2 (ja) | 2013-04-03 | 2018-07-25 | アイビーシー ファーマスーティカルズ,インコーポレイテッド | 疾患に対する免疫反応を誘導するための併用療法 |
WO2014194293A1 (en) | 2013-05-30 | 2014-12-04 | Amplimmune, Inc. | Improved methods for the selection of patients for pd-1 or b7-h4 targeted therapies, and combination therapies thereof |
EP3003316B1 (en) | 2013-05-31 | 2020-07-22 | Merck Sharp & Dohme Corp. | Combination therapies for cancer |
EP3004877A4 (en) | 2013-06-06 | 2017-04-19 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification, assessment prevention, and treatment of cancer using pd-l1 isoforms |
WO2015035112A1 (en) | 2013-09-05 | 2015-03-12 | The Johns Hopkins University | Cancer therapy via a combination of epigenetic modulation and immune modulation |
GB201316024D0 (en) | 2013-09-09 | 2013-10-23 | Almac Diagnostics Ltd | Molecular diagnostic test for lung cancer |
WO2015035365A1 (en) | 2013-09-09 | 2015-03-12 | The Nohns Hopkins University | Targeting the m2-tumor associated macrophage for cancer therapy |
WO2015038538A1 (en) | 2013-09-10 | 2015-03-19 | Medimmune, Llc | Compositions and methods for treating sepsis |
EP3626742A1 (en) | 2013-09-27 | 2020-03-25 | F. Hoffmann-La Roche AG | Anti-pdl1 antibody formulations |
WO2015050663A1 (en) | 2013-10-01 | 2015-04-09 | Mayo Foundation For Medical Education And Research | Methods for treating cancer in patients with elevated levels of bim |
CA2926690A1 (en) | 2013-10-11 | 2015-04-16 | Sloan-Kettering Institute For Cancer Research | Methods and compositions for regulatory t-cell ablation |
EP3060919A4 (en) | 2013-10-25 | 2018-02-14 | Nodality, Inc. | Methods and compositions for immunomodulation |
CN104558177B (zh) | 2013-10-25 | 2020-02-18 | 苏州思坦维生物技术股份有限公司 | 拮抗抑制程序性死亡受体pd-1与其配体结合的单克隆抗体及其编码序列与用途 |
CA2926856A1 (en) | 2013-10-25 | 2015-04-30 | Dana-Farber Cancer Institute, Inc. | Anti-pd-l1 monoclonal antibodies and fragments thereof |
WO2015069770A1 (en) | 2013-11-05 | 2015-05-14 | Cognate Bioservices, Inc. | Combinations of checkpoint inhibitors and therapeutics to treat cancer |
US20160299146A1 (en) | 2013-11-20 | 2016-10-13 | Dana-Farber Cancer Institute, Inc. | Kynurenine Pathway Biomarkers Predictive of Anti-Immune Checkpoint Inhibitor Response |
WO2015081158A1 (en) | 2013-11-26 | 2015-06-04 | Bristol-Myers Squibb Company | Method of treating hiv by disrupting pd-1/pd-l1 signaling |
WO2015088930A1 (en) | 2013-12-10 | 2015-06-18 | Merck Sharp & Dohme Corp. | Immunohistochemical proximity assay for pd-1 positive cells and pd-ligand positive cells in tumor tissue |
WO2015088847A1 (en) | 2013-12-11 | 2015-06-18 | Glaxosmithkline Llc | Treating cancer with a combination of a pd-1 antagonist and a vegfr inhibitor |
RS59480B1 (sr) | 2013-12-12 | 2019-12-31 | Shanghai hengrui pharmaceutical co ltd | Pd-1 antitelo, njegov fragment koji se vezuje na antigen, i njegova medicinska primena |
US8986691B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
US9045548B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment |
AU2014364606A1 (en) | 2013-12-17 | 2016-07-07 | Genentech, Inc. | Combination therapy comprising OX40 binding agonists and PD-1 axis binding antagonists |
US9067998B1 (en) | 2014-07-15 | 2015-06-30 | Kymab Limited | Targeting PD-1 variants for treatment of cancer |
US8945560B1 (en) | 2014-07-15 | 2015-02-03 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
US9017678B1 (en) | 2014-07-15 | 2015-04-28 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
US8992927B1 (en) | 2014-07-15 | 2015-03-31 | Kymab Limited | Targeting human NAV1.7 variants for treatment of pain |
EP2886558A1 (en) | 2013-12-17 | 2015-06-24 | Kymab Limited | Antibodies for use in treating conditions related to specific PCSK9 variants in specific patient populations |
US9045545B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision medicine by targeting PD-L1 variants for treatment of cancer |
US9914769B2 (en) | 2014-07-15 | 2018-03-13 | Kymab Limited | Precision medicine for cholesterol treatment |
EP2975058A1 (en) | 2014-07-15 | 2016-01-20 | Kymab Limited | Antibodies for use in treating conditions related to specific PCSK9 variants in specific patient populations |
CN105934253A (zh) | 2013-12-17 | 2016-09-07 | 豪夫迈·罗氏有限公司 | 使用pd-1轴结合拮抗剂和抗her2抗体治疗her2阳性癌症的方法 |
US9051378B1 (en) | 2014-07-15 | 2015-06-09 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US8883157B1 (en) | 2013-12-17 | 2014-11-11 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US20150210772A1 (en) | 2013-12-17 | 2015-07-30 | Genentech, Inc. | Methods of treating cancer using pd-1 axis binding antagonists and an anti-cd20 antibody |
US9034332B1 (en) | 2014-07-15 | 2015-05-19 | Kymab Limited | Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment |
US9023359B1 (en) | 2014-07-15 | 2015-05-05 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US8986694B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Targeting human nav1.7 variants for treatment of pain |
WO2015092393A2 (en) | 2013-12-17 | 2015-06-25 | Kymab Limited | Human targets |
WO2015095868A1 (en) | 2013-12-20 | 2015-06-25 | Wake Forest University Health Sciences | Methods and compositions for increasing protective antibody levels induced by pneumococcal polysaccharide vaccines |
GB201322725D0 (en) | 2013-12-20 | 2014-02-05 | Immodulon Therapeutics Ltd | Cancer therapy |
US20160340407A1 (en) | 2014-01-14 | 2016-11-24 | Dana-Farber Camcer Institute, Inc. | Compositions and methods for identification, assessment, prevention, and treatment of melanoma using pd-l1 isoforms |
CA3193936A1 (en) | 2014-01-15 | 2015-07-23 | Kadmon Corporation, Llc | Immunomodulatory agents |
TWI680138B (zh) | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗pd-l1之人類抗體 |
TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
US20170175197A1 (en) | 2014-01-29 | 2017-06-22 | Caris Mpi, Inc. | Molecular profiling of immune modulators |
WO2015117164A1 (en) | 2014-02-03 | 2015-08-06 | Memorial Sloan-Kettering Cancer Center | Tumor-associated macrophages and methods and compositions for targeting cancer therapy and identifying potential responders |
WO2015114146A1 (en) | 2014-02-03 | 2015-08-06 | Sividon Diagnostics Gmbh | Method for predicting the response to an anti-her2 containing therapy and/or chemotherapy in patients with breast cancer |
EP3102233A4 (en) | 2014-02-05 | 2017-11-22 | Cedars-Sinai Medical Center | Methods and compositions for treating cancer and infectious diseases |
US10619210B2 (en) | 2014-02-07 | 2020-04-14 | The Johns Hopkins University | Predicting response to epigenetic drug therapy |
CA2937236C (en) | 2014-02-21 | 2023-03-07 | Ibc Pharmaceuticals, Inc. | Disease therapy by inducing immune response to trop-2 expressing cells |
US20170107577A1 (en) | 2014-03-11 | 2017-04-20 | The Council Of The Queensland Institute Of Medical Research | Determining Cancer Aggressiveness, Prognosis and Responsiveness to Treatment |
CN114081946A (zh) | 2014-03-12 | 2022-02-25 | 耶达研究与开发有限公司 | 降低系统性调节性t细胞水平或活性来治疗cns疾病和损伤 |
WO2015157623A1 (en) | 2014-04-11 | 2015-10-15 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Immune gene signatures in urothelial carcinoma (uc) |
WO2015164743A2 (en) | 2014-04-24 | 2015-10-29 | Dana-Farber Cancer Institute, Inc. | Tumor suppressor and oncogene biomarkers predictive of anti-immune checkpoint inhibitor response |
WO2015162596A1 (en) | 2014-04-25 | 2015-10-29 | Immunid | Use of immune diversity as a predictive marker for identifying patients likely to respond to an anti-ctla4 treatment |
US10302653B2 (en) | 2014-05-22 | 2019-05-28 | Mayo Foundation For Medical Education And Research | Distinguishing antagonistic and agonistic anti B7-H1 antibodies |
WO2015178746A1 (ko) | 2014-05-23 | 2015-11-26 | 주식회사 제넥신 | Pd-l1 융합 단백질 및 이의 용도 |
US20170115291A1 (en) | 2014-05-28 | 2017-04-27 | Dana-Farber Cancer Institute, Inc. | Activating JAK Kinase Biomarkers Predictive of Anti-Immune Checkpoint Inhibitor Response |
US20160031990A1 (en) | 2014-05-29 | 2016-02-04 | Medlmmune, Llc | Antagonists of pdl-1 and pd-1 for the treatment of hpv-negative cancers |
JP6666905B2 (ja) | 2014-05-29 | 2020-03-18 | スプリング バイオサイエンス コーポレーション | Pd−l1抗体及びその使用 |
CA2951278A1 (en) | 2014-06-19 | 2015-12-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized programmed cell death 1 gene |
KR102130600B1 (ko) | 2014-07-03 | 2020-07-08 | 베이진 엘티디 | Pd-l1 항체와 이를 이용한 치료 및 진단 |
DK3166976T3 (da) | 2014-07-09 | 2022-04-11 | Birdie Biopharmaceuticals Inc | Anti-pd-l1-kombinationer til behandling af tumorer |
JP6279733B2 (ja) | 2014-07-09 | 2018-02-14 | 日本全薬工業株式会社 | 抗イヌpd−1抗体又は抗イヌpd−l1抗体 |
CN112546230A (zh) | 2014-07-09 | 2021-03-26 | 博笛生物科技有限公司 | 用于治疗癌症的联合治疗组合物和联合治疗方法 |
US9150660B1 (en) | 2014-07-15 | 2015-10-06 | Kymab Limited | Precision Medicine by targeting human NAV1.8 variants for treatment of pain |
US9139648B1 (en) | 2014-07-15 | 2015-09-22 | Kymab Limited | Precision medicine by targeting human NAV1.9 variants for treatment of pain |
DE202015008974U1 (de) | 2014-07-15 | 2016-06-30 | Kymab Limited | Targeting von humaner PCSK9 zur Cholesterinbehandlung |
EP3332790A1 (en) | 2014-07-15 | 2018-06-13 | Kymab Limited | Antibodies for use in treating conditions related to specific pcsk9 variants in specific patients populations |
GB201413162D0 (en) | 2014-07-24 | 2014-09-10 | Immusmol Sas | Prediction of cancer treatment based on determination of enzymes or metabolites of the kynurenine pathway |
US11186640B2 (en) | 2014-07-31 | 2021-11-30 | The University Of Western Australia | Method for the identification of immunotherapy-drug combinations using a network approach |
ES2847311T3 (es) | 2014-08-05 | 2021-08-02 | MabQuest SA | Reactivos inmunológicos que se unen a PD-1 |
JP6909153B2 (ja) | 2014-08-05 | 2021-07-28 | アポロミクス インコーポレイテッド | 抗pd−l1抗体 |
CN106794246B (zh) | 2014-08-08 | 2021-10-15 | OncoQuest制药有限公司 | 肿瘤抗原特异性抗体和tlr3刺激以增强检查点干扰癌症疗法的性能 |
WO2016023916A1 (en) | 2014-08-12 | 2016-02-18 | Kymab Limited | Treatment of disease using ligand binding to targets of interest |
AU2015303239A1 (en) | 2014-08-14 | 2016-12-15 | F. Hoffmann-La Roche Ag | Combination therapy of antibodies activating human CD40 and antibodies against human PD-L1 |
WO2016027273A1 (en) | 2014-08-19 | 2016-02-25 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd | Methods for predicting and monitoring cancer patients' response to treatment by measuring myeloid derived suppressor cells (mdscs) |
DK3186283T3 (da) | 2014-08-29 | 2020-03-02 | Hoffmann La Roche | Kombinationsbehandling med tumormålrettede IL-2- immuncytokinervarianter og antistoffer mod humant PD-L1 |
CN112546238A (zh) | 2014-09-01 | 2021-03-26 | 博笛生物科技有限公司 | 用于治疗肿瘤的抗-pd-l1结合物 |
WO2016034718A1 (en) | 2014-09-05 | 2016-03-10 | Medimmune Limited | Methods for identifying patients responsive to anti-pd-l1 antibody therapy using markers (cxcl9, krt8.trim29, and ifngamma) |
US9535074B2 (en) | 2014-09-08 | 2017-01-03 | Merck Sharp & Dohme Corp. | Immunoassay for soluble PD-L1 |
EP3659621A1 (en) | 2014-09-13 | 2020-06-03 | Novartis AG | Combination therapies for cancer |
WO2016044736A1 (en) | 2014-09-18 | 2016-03-24 | Cell Signaling Technology, Inc. | Altered antibodies and methods of making the same |
WO2016049385A1 (en) | 2014-09-24 | 2016-03-31 | Apellis Pharmaceuticals, Inc. | Methods and compositions for cancer treatment and treatment selection |
AU2015326996B2 (en) | 2014-09-30 | 2021-05-20 | Intervet International B.V. | PD-L1 antibodies binding canine PD-L1 |
US20170209574A1 (en) | 2014-10-03 | 2017-07-27 | Novartis Ag | Combination therapies |
WO2016057933A1 (en) | 2014-10-10 | 2016-04-14 | Global Biopharma, Inc. | Methods for treating and/or preventing a tumor growth, invasion and/or metastasis |
WO2016061256A1 (en) | 2014-10-14 | 2016-04-21 | The University Of Chicago | Nanoparticles for photodynamic therapy, x-ray induced photodynamic therapy, radiotherapy, chemotherapy, immunotherapy, and any combination thereof |
PE20171067A1 (es) | 2014-10-14 | 2017-07-24 | Novartis Ag | Moleculas de anticuerpo que se unen a pd-l1 y usos de las mismas |
US20170242016A1 (en) | 2014-10-15 | 2017-08-24 | Epic Sciences, Inc. | Circulating tumor cell diagnostics for therapy targeting pd-l1 |
WO2016059602A2 (en) | 2014-10-16 | 2016-04-21 | Glaxo Group Limited | Methods of treating cancer and related compositions |
AU2015343425A1 (en) | 2014-11-04 | 2017-05-25 | Dana-Farber Cancer Institute, Inc. | Anti-galectin antibody biomarkers predictive of anti-immune checkpoint and anti-angiogenesis responses |
WO2016073760A1 (en) | 2014-11-05 | 2016-05-12 | The Regents Of The University Of California | Methods for stratifying non-responders to therapies that block pd1/pdl1 axis |
WO2016071701A1 (en) | 2014-11-07 | 2016-05-12 | Kymab Limited | Treatment of disease using ligand binding to targets of interest |
US20190076452A1 (en) | 2014-11-11 | 2019-03-14 | Medimmune Limited | Therapeutic combinations for treating neoplasia |
CN106999583A (zh) | 2014-11-17 | 2017-08-01 | 豪夫迈·罗氏有限公司 | 包含ox40结合激动剂和pd‑1轴结合拮抗剂的组合疗法 |
MA40737A (fr) | 2014-11-21 | 2017-07-04 | Memorial Sloan Kettering Cancer Center | Déterminants de la réponse d'un cancer à une immunothérapie par blocage de pd-1 |
WO2016089873A1 (en) | 2014-12-02 | 2016-06-09 | Celgene Corporation | Combination therapies |
AU2016274584A1 (en) | 2015-06-08 | 2018-01-04 | Genentech, Inc. | Methods of treating cancer using anti-OX40 antibodies and PD-1 axis binding antagonists |
JP6996983B2 (ja) | 2015-06-16 | 2022-02-21 | ジェネンテック, インコーポレイテッド | 抗cll-1抗体及び使用方法 |
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