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Improving biophysical properties of a bispecific antibody scaffold to aid developability
| Content Provider | Scilit |
|---|---|
| Author | D’Angelo, Igor Kreudenstein, Thomas Spreter Von Escobar-Carbrera, Eric Lario, Paula I. Brault, Karine Kelly, John F. Durocher, Yves Baardsnes, Jason Woods, R. Jeremy Xie, Michael Hongwei Girod, Pierre-Alain Suits, Michael D. L. Boulanger, Martin J. Poon, David K. Y. Ng, Gordon Y. K. Dixit, Surjit B. |
| Copyright Year | 2013 |
| Description | While the concept of Quality-by-Design is addressed at the upstream and downstream process development stages, we questioned whether there are advantages to addressing the issues of biologics quality early in the design of the molecule based on fundamental biophysical characterization, and thereby reduce complexities in the product development stages. Although limited number of bispecific therapeutics are in clinic, these developments have been plagued with difficulty in producing materials of sufficient quality and quantity for both preclinical and clinical studies. The engineered heterodimeric Fc is an industry-wide favorite scaffold for the design of bispecific protein therapeutics because of its structural, and potentially pharmacokinetic, similarity to the natural antibody. Development of molecules based on this concept, however, is challenged by the presence of potential homodimer contamination and stability loss relative to the natural Fc. We engineered a heterodimeric Fc with high heterodimeric specificity that also retains natural Fclike biophysical properties, and demonstrate here that use of engineered Fc domains that mirror the natural system translates into an efficient and robust upstream stable cell line selection process as a first step toward a more developable therapeutic. \ua9 2013 Landes Bioscience.Peer reviewed: YesNRC publication: Ye |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/mabs.25632?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851217/pdf https://www.landesbioscience.com/journals/mabs/2013MABS0382R.pdf |
| Ending Page | 654 |
| Page Count | 9 |
| Starting Page | 646 |
| ISSN | 19420862 |
| e-ISSN | 19420870 |
| DOI | 10.4161/mabs.25632 |
| Journal | mAbs |
| Issue Number | 5 |
| Volume Number | 5 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2013-09-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Mabs Biotechnology and Microbiology Fc Engineering Lc-ms of Antibody Antibody Engineering Antibody Stability Biophysical Characterization of Antibody Bispecific Antibody Heterodimeric Antibody Quality By Design |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
