[发明专利]水性抗PD-L1抗体制剂

说明书

本发明涉及新型抗PD‑L1抗体制剂。特别地，本发明涉及抗PD‑L抗体Avelumab的水性药物制剂。

技术领域

本发明涉及新型抗PD-L1抗体制剂。特别地，本发明涉及抗PD-L1抗体Avelumab的水性药物制剂。

背景技术

程序性死亡1(PD-1)受体和PD-1配体1和2(PD-L1、PD-L2)在免疫调节中发挥不可或缺的作用。在活化的T细胞上表达的PD-1，被基质细胞、肿瘤细胞或两者表达的PD-L1和PD-L2激活，引发T细胞死亡和局部免疫抑制(Dong H,Zhu G,Tamada K,Chen L.B7-H1,athird member of the B7 family,co-stimulates T-cell proliferation andinterleukin-10secretion.Nat Med 1999；5:1365-69；Freeman GJ,Long AJ,Iwai Y等，Engagement of the PD-1immunoinhibitory receptor by a novel B7 family memberleads to negative regulation of lymphocyte activation.J Exp Med 2000；192:1027-34；Dong H,Strome SE,Salomao DR等，Tumor-associated B7-H1 promotes T-cellapoptosis:a potential mechanism of immune evasion.Nat Med 2002；8:793-800；Erratum,Nat Med 2002；8:1039；Topalian SL,Drake CG,Pardoll DM.Targeting the PD-1/B7-H1(PD-L1)pathway to activate anti-tumor immunity.Curr Opin Immunol 2012；24:207-12)，潜在地为肿瘤发展和生长提供免疫耐受性环境。相反地，抑制这种相互作用可增强局部T细胞应答，并且在非临床动物模型中介导抗肿瘤活性(Dong H,Strome SE,Salomao DR等，Nat Med 2002；8:793-800；Erratum,Nat Med 2002；8:1039；Iwai Y,IshidaM,Tanaka Y等，Involvement of PD-L1 on tumor cells in the escape from hostimmune system and tumor immunotherapy by PD-L1blockade.Proc Natl Acad Sci USA2002；99:12293-97)。在临床环境中，已经报道使用阻断PD-1-PD-L1相互作用的抗体的治疗在晚期或转移性实体瘤的患者中产生7％至38％的客观缓解率，并具有可接受的安全性谱(Hamid O,Robert C,Daud A等，Safety and tumor responses with lambrolizumab(Anti-PD-1)in melanoma.N Engl J Med 2013；369:134-44；Brahmer JR,Tykodi SS,ChowLQ等，Safety and activity of anti-PD-L1 antibody in patients with advancedcancer.N Engl J Med2012；366(26):2455-65；Topalian SL,Hodi FS,Brahmer JR等，Safety,activity,and immune correlates of anti-PD-1antibody in cancer.N Engl JMed 2012；366(26):2443-54；Herbst RS,Soria J-C,Kowanetz M等，Predictivecorrelates of response to the anti-PD-L1 antibody MPDL3280A in cancerpatients.Nature 2014；515:563-67)。值得注意的是，对于大多数患者而言，应答看起来延长，其持续时间为1年或更长时间。