2010
DOI: 10.1007/s10529-010-0214-z
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Modulating the pharmacokinetics of therapeutic antibodies

Abstract: With the advent of antibody fragments and alternative binding scaffolds, that are devoid of Fc-regions, strategies to increase the half-life of small proteins are becoming increasingly important. Currently, the established method is chemical PEGylation, but more elaborate approaches are being described such as polysialylation, amino acid polymers and albumin-binding derivatives. This article reviews the main strategies for pharmacokinetic enhancement, primarily chemical conjugates and recombinant fusions that … Show more

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Cited by 53 publications
(33 citation statements)
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“…1) covalent conjugation of PEG to biologically active molecules, by a process called "PEGylation," is one of promising strategies being used to overcome these limitations. 10,11) Following the pioneering studies in the 1970s, 12,13) the procedure for PEGylation was extensively expanded and developed to prolong the half-life of bioactive PEGylated protein and peptide. In most of these studies, 3,6,10,14) attention was only paid to the immunogenicity of bioactive proteins and peptides, and not to the immunogenicity of PEG itself.…”
Section: Anti-peg Immunoglobulin M (Igm) Response To Pegylated Proteinsmentioning
confidence: 99%
“…1) covalent conjugation of PEG to biologically active molecules, by a process called "PEGylation," is one of promising strategies being used to overcome these limitations. 10,11) Following the pioneering studies in the 1970s, 12,13) the procedure for PEGylation was extensively expanded and developed to prolong the half-life of bioactive PEGylated protein and peptide. In most of these studies, 3,6,10,14) attention was only paid to the immunogenicity of bioactive proteins and peptides, and not to the immunogenicity of PEG itself.…”
Section: Anti-peg Immunoglobulin M (Igm) Response To Pegylated Proteinsmentioning
confidence: 99%
“…Biomedicines, such as protein drugs 1,2) and nucleic acid drugs, 3) have attracted considerable attention due to their high biological activity and specificity against target molecules. However, their application is sometimes limited due to their insufficient clinical effects as a result of susceptibility to destruction by proteolytic or nucleolytic enzymes, a short circulating half-life, low solubility, rapid kidney clearance and propensity to generate neutralizing antibodies.…”
mentioning
confidence: 99%
“…4) Covalent conjugation of polyethylene glycol (PEG) to the biological active molecules, by a process called "PEGylation," is one of the promising strategies being used to overcome these limitations. [1][2][3] PEG is one of the most versatile synthetic polymers and is widely believed to lack immunogenicity and toxicity and shows high solubility in water and in many organic solvents. 4,5) For instance, proteins modified with PEG have an increased solubility due to the hydrophilicity of grafted PEG; their destruction by protease and the immune system is decreased due to the steric hindrance of grafted PEG; and, glomerular filtration is decreased due to an increase in the apparent size or hydrodynamic volume of a given protein.…”
mentioning
confidence: 99%
“…EPO는 당쇄가 전체 분자량의 약 40% 정 도이며, 특히 N-linked 당쇄는 EPO의 생체 내 활성 및 안정성에 매우 중요한 역할을 한다. hEPO는 post-translational modification (PTM)의 glycosylation 과정 때문에 대장균에서는 제조가 불 가능하며 재조합 동물세포에서 생산할 경우에만 인체에서 와 같은 형태의 단백질이 만들어진다는 것이 밝혀졌다 [2].…”
Section: 서론unclassified