Schofield, Darren J Percival-Alwyn, Jennifer Rytelewski, Mateusz Hood, John Rothstein, Raymond Wetzel, Leslie McGlinchey, Kelly Adjei, Grace Watkins, Amanda Machiesky, LeeAnn
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mAbs
Preclinical studies of PD-L1 and CTLA-4 blockade have relied heavily on mouse syngeneic tumor models with intact immune systems, which facilitate dissection of immunosuppressive mechanisms in the tumor microenvironment. Commercially developed monoclonal antibodies (mAbs) targeting human PD-L1, PD-1, and CTLA-4 may not demonstrate cross-reactive bin...
Gong, Danyang Riley, Timothy P Bzymek, Krzysztof P Correia, Ana R Li, Danqing Spahr, Christopher Robinson, John H Case, Ryan B Wang, Zhulun Garces, Fernando
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mAbs
Bispecific antibodies, engineered to recognize two targets simultaneously, demonstrate exceptional clinical potential for the therapeutic intervention of complex diseases. However, these molecules are often composed of multiple polypeptide chains of differing sequences. To meet industrial scale productivity, enforcing the correct quaternary assembl...
Valente, Delphine Mauriac, Christine Schmidt, Thorsten Focken, Ingo Beninga, Jochen Mackness, Brian Qiu, Huawei Vicat, Pascale Kandira, Abdullah Radošević, Katarina
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mAbs
Monoclonal antibodies (mAbs) are among the fastest growing and most effective therapies for myriad diseases. Multispecific antibodies are an emerging class of novel therapeutics that can target more than one tumor- or immune-associated modulators per molecule. The combination of different binding affinities and target classes, such as soluble or me...
Sepp, Armin Bergström, Mats Davies, Marie
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mAbs
Two-pore physiologically-based pharmacokinetics (PBPK) for biologics describes the tissue distribution and elimination kinetics of soluble proteins as a function of their hydrodynamic radius and the physiological properties of the organs. Whilst many studies have been performed in rodents to parameterize the PBPK framework in terms of organ-specifi...
Chen, Zhiqiang Qian, Yueming Song, Yuanli Xu, Xuankuo Tao, Li Mussa, Nesredin Ghose, Sanchayita Li, Zheng Jian
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mAbs
Manufacturability of immunoglobulin G4 (IgG4) antibodies from the Chemistry, Manufacture, and Controls (CMC) perspective has received little attention during early drug discovery. Despite the success of protein engineering in improving antibody biophysical properties, a clear gap still exists between rational design of IgG4 candidates and their man...
Tang, Peifeng Tan, Zhijun Ehamparanathan, Vivekh Ren, Tingwei Hoffman, Laurel Du, Cheng Song, Yuanli Tao, Li Lewandowski, Angela Ghose, Sanchayita
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mAbs
Disulfide bonds play a crucial role in folding and structural stabilization of monoclonal antibodies (mAbs). Disulfide bond reduction may happen during the mAb manufacturing process, resulting in low molecular weight species and possible failure to meet product specifications. Although many mitigation strategies have been developed to prevent disul...
Low, Benjamin E. Christianson, Gregory J. Lowell, Emily Qin, Wenning Wiles, Michael V.
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mAbs
A major asset of many monoclonal antibody (mAb)-based biologics is their persistence in circulation. The MHC class I family Fc receptor, FCGRT, is primarily responsible for this extended pharmacokinetic behavior. Engagement of FCGRT with the crystallizable fragment (Fc) domain protects IgG from catabolic elimination, thereby extending the persisten...
Tan, Zhijun Ehamparanathan, Vivekh Ren, Tingwei Tang, Peifeng Hoffman, Laurel Kuang, June Liu, Peiran Huang, Chao Du, Cheng Tao, Li
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mAbs
Disulfide bond reduction, which commonly occurs during monoclonal antibody (mAb) manufacturing processes, can result in a drug substance with high levels of low molecular weight (LMW) species that may fail release specifications because the drug's safety and the efficiency may be affected by the presence of this material. We previously studied disu...
Zheng, Songmao Niu, Jin Geist, Brian Fink, Damien Xu, Zhenhua Zhou, Honghui Wang, Weirong
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mAbs
Biotherapeutic drugs against tumor necrosis factor (TNF) are effective treatments for moderate to severe inflammatory bowel disease (IBD). Here, we evaluated CNTO 5048, an antimurine TNF surrogate monoclonal antibody (mAb), in a CD45RBhigh adoptive T cell transfer mouse colitis model, which allows examination of the early immunological events assoc...
Kopp, Marie R G Wolf Pérez, Adriana-Michelle Zucca, Marta Virginia Capasso Palmiero, Umberto Friedrichsen, Brigitte Lorenzen, Nikolai Arosio, Paolo
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mAbs
High physical stability is required for the development of monoclonal antibodies (mAbs) into successful therapeutic products. Developability assays are used to predict physical stability issues such as high viscosity and poor conformational stability, but protein aggregation remains a challenging property to predict. Among different types of stress...