Antibody Glycosylation and Its Impact on the Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies and Fc-Fusion Proteins

2015 ◽  
Vol 104 (6) ◽  
pp. 1866-1884 ◽  
Author(s):  
Liming Liu
Keyword(s):  
Monoclonal Antibodies ◽  
Fusion Proteins ◽  
Pharmacokinetics And Pharmacodynamics

Use of recombinant fusion proteins for generation and rapid characterization of monoclonal antibodies

1992 ◽  
Vol 147 (1) ◽  
pp. 1-11 ◽  
Author(s):  
D. Wunderlich ◽  
A. Lee ◽  
R.P. Fracasso ◽  
D.V. Mierz ◽  
R.M. Bayney ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Fusion Proteins ◽  
Recombinant Fusion Proteins ◽  
Rapid Characterization

scholarly journals The Instability of Dimeric Fc-Fusions Expressed in Plants Can Be Solved by Monomeric Fc Technology

2021 ◽  
Vol 12 ◽  
Author(s):  
Pia Gattinger ◽  
Shiva Izadi ◽  
Clemens Grünwald-Gruber ◽  
Somanath Kallolimath ◽  
Alexandra Castilho
Keyword(s):  
Monoclonal Antibodies ◽  
Fusion Proteins ◽  
Degradation Products ◽  
Therapeutic Proteins ◽  
Cost Effective ◽  
Full Length ◽  
Peptide Sequence ◽  
Reporter Protein ◽  
The Stability

The potential therapeutic value of many proteins is ultimately limited by their rapid in vivo clearance. One strategy to limit clearance by metabolism and excretion, and improving the stability of therapeutic proteins, is their fusion to the immunoglobulin fragment crystallizable region (Fc). The Fc region plays multiple roles in (i) dimerization for the formation of “Y”-shaped structure of Ig, (ii) Fc-mediated effector functions, (iii) extension of serum half-life, and (iv) a cost-effective purification tag. Plants and in particular Nicotiana benthamiana have proven to be suitable expression platforms for several recombinant therapeutic proteins. Despite the enormous success of their use for the production of full-length monoclonal antibodies, the expression of Fc-fused therapeutic proteins in plants has shown limitations. Many Fc-fusion proteins expressed in plants show different degrees of instability resulting in high amounts of Fc-derived degradation products. To address this issue, we used erythropoietin (EPO) as a reporter protein and evaluated the efforts to enhance the expression of full-length EPO-Fc targeted to the apoplast of N. benthamiana. Our results show that the instability of the fusion protein is independent from the Fc origin or IgG subclass and from the peptide sequence used to link the two domains. We also show that a similar instability occurs upon the expression of individual heavy chains of monoclonal antibodies and ScFv-Fc that mimic the “Y”-shape of antibodies but lack the light chain. We propose that in this configuration, steric hindrance between the protein domains leads to physical instability. Indeed, mutations of critical residues located on the Fc dimerization interface allowed the expression of fully stable EPO monomeric Fc-fusion proteins. We discuss the limitations of Fc-fusion technology in N. benthamiana transient expression systems and suggest strategies to optimize the Fc-based scaffolds on their folding and aggregation resistance in order to improve the stability.

Monoclonal antibodies and fusion proteins

2008 ◽  
pp. 1405-1416
Author(s):  
Susan J. Lee ◽  
Arthur F. Kavanaugh
Keyword(s):  
Monoclonal Antibodies ◽  
Fusion Proteins

Clinical Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies Approved to Treat Rheumatoid Arthritis

2015 ◽  
Vol 54 (11) ◽  
pp. 1107-1123 ◽  
Author(s):  
David Ternant ◽  
Theodora Bejan-Angoulvant ◽  
Christophe Passot ◽  
Denis Mulleman ◽  
Gilles Paintaud
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibodies ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Clinical Pharmacokinetics

Ultrafiltration behavior of monoclonal antibodies and Fc-fusion proteins: Effects of physical properties

2017 ◽  
Vol 114 (9) ◽  
pp. 2057-2065 ◽  
Author(s):  
Youngbin Baek ◽  
Nripen Singh ◽  
Abhiram Arunkumar ◽  
Michael Borys ◽  
Zheng J. Li ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Physical Properties ◽  
Fusion Proteins
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