Emerging methods for identifying monoclonal antibodies with low propensity to self-associate during the early discovery process

Tessier, Peter M.; Wu, Jugang; Dickinson, Craig D.

doi:10.1517/17425247.2014.876989

Cited by 23 publications

(19 citation statements)

References 31 publications

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“…Besides thermal stability, colloidal stability is an important factor to be addressed during developability assessment . Colloidal interactions can be the common cause for low solubility, high viscosity, phase separation, off‐target binding, and fast antibody clearance .…”

Section: Desired Molecular Features and Test Methods Used During Devementioning

confidence: 99%

“…Colloidal stability is to a large extent dependent on the formulation conditions, where ionic strength, the type of ions present in the solution, effective charge, and molecule‐specific interactions with cosolutes play a role . On the contrary, colloidal stability is also a molecule‐inherent feature that can be probed for with small‐scale methods during molecule selection …”

Section: Desired Molecular Features and Test Methods Used During Devementioning

confidence: 99%

“…Besides thermal stability, colloidal stability is an important factor to be addressed during developability assessment. 98,111,112 Colloidal interactions can be the common cause for low solubility, high viscosity, phase separation, off-target binding, and fast antibody clearance. 45,46,111,113 For some biotherapeutics, high protein concentrations of up to 200 mg/mL and above are desired, for example, if subcutaneous or intravitreous injection is the intended administration route.…”

Section: Colloidal Stability Protein-protein Self-interaction Aggrementioning

confidence: 99%

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Developability Assessment During the Selection of Novel Therapeutic Antibodies

Jarasch

Koll

Regula

et al. 2015

Journal of Pharmaceutical Sciences

207

191

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Section: Desired Molecular Features and Test Methods Used During Devementioning

confidence: 99%

Section: Desired Molecular Features and Test Methods Used During Devementioning

confidence: 99%

Section: Colloidal Stability Protein-protein Self-interaction Aggrementioning

confidence: 99%

See 1 more Smart Citation

Developability Assessment During the Selection of Novel Therapeutic Antibodies

Jarasch

Koll

Regula

et al. 2015

Journal of Pharmaceutical Sciences

207

191

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“…One of the most challenging parts of antibody production is to manufacture antibodies in higher yields and formulate them stably in liquid form. Proteins are prone to self‐interaction at higher concentrations which brings along the risk of aggregation; therefore, it is critical to determine aggregation tendency at the earlier stages . There are many factors affecting the protein aggregation such as hydrophobicity, electrical charge, and propensity .…”

Section: Introductionmentioning

confidence: 99%

Phage display derived therapeutic antibodies have enriched aliphatic content: Insights for developability issues

2019

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Phage display is one of the most widely used technology for antibody discovery and engineering. Number of therapeutic antibodies derived from phage display increases rapidly due to its ease of use and ability to control antibody sequence information. Although there are numerous antibody candidates as promising therapeutics, most of them fail at later stages of development due to undesired biophysical properties. Antibody candidates with poor properties should be prevented or improved in early development phases to minimize enormous loss of time and resources. In this study, we showed that phage display derived therapeutic antibodies show higher self‐interaction and polyspecificity compared to non‐phage display derived ones. To identify molecular determinants behind this, physicochemical properties of CDR regions of 137 therapeutic antibodies were analyzed. We found multiple significant differences in both heavy and light chain CDR regions. Most profoundly, aliphatic content of HCDR3, HCDR2, and LCDR3 regions were enriched in phage display derived antibodies compared to non‐phage display derived ones. Physicochemical determinants documented here seem to play important roles in polyspecific and aggregation‐prone natures of antibodies which should be avoided in early development phases.

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“…2,3 It is an indirect diagnostic of protein interactions and aggregation of the protein monomer. [4][5][6][7][8][9] Although there is not a clearly established relationship between viscosity and protein selfassociation and/or aggregation, considerable work is aimed at this goal. 10 Despite the maturity of viscometry, there remains a need for a rheometer that meets the following three needs of the biopharamaceutical industry: small volume; large dynamic range of shear rates; and no air-sample interface.…”

Section: Introductionmentioning

confidence: 99%