Translating Molecules into Medicines

Bhattachar, Shobha; Morrison, J. S.; Mudra, Daniel R.; Bender, David M.

doi:10.1007/978-3-319-50042-3

Cited by 4 publications

(1 citation statement)

References 22 publications

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“…In early phase of drug discovery, proper tool molecules (drug like molecules) that are potent in vitro and can be produced in sufficient quantities are usually selected for in vivo experiments. They are utilized to understand the extent and duration of in vivo target engagement required for efficacy, this is first step to design a potent drug molecule [257]. For preparation of LAI, not only a drug candidate needs to be potent but also needs to be loaded into a carrier system (e.g., PLGA MPs and implants) with high loading capacity to supply the dose required for an extended period (i.e., weeks to months), since the volume of injection is often limited depending on the site of injection.…”

Section: Drug Substance Attributes For Lai Developmentmentioning

confidence: 99%

Clinically established biodegradable long acting injectables: An industry perspective

Nkanga

Fisch

Rad‐Malekshahi

et al. 2020

Advanced Drug Delivery Reviews

104

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Section: Drug Substance Attributes For Lai Developmentmentioning

confidence: 99%

Clinically established biodegradable long acting injectables: An industry perspective

Nkanga

Fisch

Rad‐Malekshahi

et al. 2020

Advanced Drug Delivery Reviews

104

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Minimal purification method enables developability assessment of recombinant proteins

Rodriguez-Aponte

Naranjo

Johnston

et al. 2023

Biotech & Bioengineering

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Analytical characterization of proteins is a critical task for developing therapeutics and subunit vaccine candidates. Assessing candidates with a battery of biophysical assays can inform the selection of one that exhibits properties consistent with a given target product profile (TPP). Such assessments, however, require several milligrams of purified protein, and ideal assessments of the physicochemical attributes of the proteins should not include unnatural modifications like peptide tags for purification. Here, we describe a fast two‐stage minimal purification process for recombinant proteins secreted by the yeast host Komagataella phaffii from a 20 mL culture supernatant. This method comprises a buffer exchange and filtration with a Q‐membrane filter and we demonstrate sufficient removal of key supernatant impurities including host‐cell proteins (HCPs) and DNA with yields of 1–2 mg and >60% purity. This degree of purity enables characterizing the resulting proteins using affinity binding, mass spectrometry, and differential scanning calorimetry. We first evaluated this method to purify an engineered SARS‐CoV‐2 subunit protein antigen and compared the purified protein to a conventional two‐step chromatographic process. We then applied this method to compare several SARS‐CoV‐2 RBD sequences. Finally, we show this simple process can be applied to a range of other proteins, including a single‐domain antibody, a rotavirus protein subunit, and a human growth hormone. This simple and fast developability methodology obviates the need for genetic tagging or full chromatographic development when assessing and comparing early‐stage protein therapeutics and vaccine candidates produced in K. phaffii.

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Biodegradable Long-Acting Injectables: Platform Technology and Industrial Challenges

Duvnjak

Villois

Ramazani

2023

Handbook of Experimental Pharmacology

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Translating Molecules into Medicines

Cited by 4 publications

References 22 publications

Clinically established biodegradable long acting injectables: An industry perspective

Clinically established biodegradable long acting injectables: An industry perspective

Minimal purification method enables developability assessment of recombinant proteins

Biodegradable Long-Acting Injectables: Platform Technology and Industrial Challenges

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