Preventing Aggregation of Recombinant Interferon beta-1b in Solution by Additives: Approach to an Albumin-Free Formulation

Mahjoubi, Najmeh; Fazeli, Mohammad Reza; Dinarvand, Rassoul; Khoshayand, Mohammad Reza; Fazeli, Ahmad; Taghavian, M; Rastegar, Hossein

doi:10.15171/apb.2015.068

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…Although the exact mechanism(s) governing UOX thermal inactivation remains unclear, it is mostly suggested that its tertiary and quaternary structure play a potential role in its susceptibility to environmental conditions. Moreover, several studies have emphasized the importance of osmolyte application for stabilization of proteins structures (Barnett et al 2016;Mahjoubi et al 2015). However, there is no special molecular mechanism by which osmolytes affect protein stability, but it is accordingly called preferential exclusion of an osmolyte from immediate vicinity of a protein or preferential hydration of water (Street et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies evaluated the effects of osmolytes on the stability of various proteins and enzymes such as catalase (Sepasi Tehrani et al 2013), monoclonal antibody (Barnett et al 2016), and recombinant interferon beta-1b (Mahjoubi et al 2015). However, the impact of osmolytes on uricase enzyme stability is not fully delineated (Caves et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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Recombinant production of Aspergillus Flavus uricase and investigation of its thermal stability in the presence of raffinose and lactose

Imani

Shahmohamadnejad

2017

3 Biotech

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Aspergillus flavus uricase (Rasburicase) with a molecular mass of 135 kDa is currently used for the treatment of gout and hyperuricemia occurring in tumor lysis syndrome. To characterize the effects of raffinose and lactose osmolytes on the uricase structure, its coding sequence was cloned, expressed in E. coli BL21, and purified by Ni-NTA agarose affinity chromatography. Thermal inactivation studies at 40 °C showed that nearly 15% of UOX activity was preserved, while the presence of raffinose and lactose reduced its activity to 35 and 45% of its original activity, respectively. Investigation of UOX thermal stability at 40 °C in the course of time showed that the enzyme relatively lost almost 60% of its original activity after 40 min, whereas more than 50% of UOX activity is preserved in the presence of lactose. Estimation of thermal inactivation rate constant, k , showed that the UOX k and UOX k in the presence of raffinose was unchanged (0.018 min), whereas for the presence of lactose, it was 0.015 min. Half-life and T analysis showed that UOX half-life is almost 38 min and addition of raffinose did not change the half-life, whereas the presence of lactose had remarkable impact on UOX half-life (46 min). The presence of raffinose increased UOX T to a lesser extent, whereas lactose notably enhanced the T from 27 to 37 °C. Overall, our findings show that lactose has protective effects on UOX stability, while for raffinose, it is relatively compromised.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recombinant production of Aspergillus Flavus uricase and investigation of its thermal stability in the presence of raffinose and lactose

Imani

Shahmohamadnejad

2017

3 Biotech

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“…The aggregation constitutes a pre-existing constraint for IFN-β-1b, with an aggregation rate of about 15% upon reconstitution (Barnard et al, 2013). Galenic optimization for protein nebulization is complex, and could be achieved by different excipients such as PEG 8000, n-Dodecyl-β-D-maltoside, l-arginine and trehalose (Mahjoubi et al, 2015;Sécher et al, 2019). The use of pegylated IFNs could also be considered to both increase stability and extend action at the local level (Mcleod et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Rationale for COVID-19 Treatment by Nebulized Interferon-β-1b–Literature Review and Personal Preliminary Experience

et al. 2020

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The inflammatory response to COVID-19 is specifically associated with an impaired type I interferon (IFN) response and complete blockade of IFN-β secretion. Clinically, nebulization of IFN-α-2b has been historically used in China to treat viral pneumonia associated with SARS-CoV. Very recent data show that the use of inhaled type I IFN is associated with decreased mortality in Chinese COVID-19 patients. However, IFN nebulization is currently not standard in Europe and the United States. Therefore, our group has set up a project aimed to evaluate the possibility to nebulize IFN-β-1b (a drug currently used in Europe to treat multiple sclerosis via subcutaneous injections) and to assess the safety of this new mode of administration in SARS-CoV-2 infected patients. We present here literature data that allowed us to build our hypothesis and to develop collaboration between clinical pharmacists, intensivists and nebulization engineers in order to gain first pre-clinical and clinical experience of IFN-β-1b nebulization. After validation of the nebulization method and verification of droplet size compatible with nebulization, the method has been applied to four intensive care patients treated at our university hospital, for whom none of the COVID-19 therapies initially used in France led to significant clinical improvement. All patients exhibited negative viral carriage and experienced clinical improvement 7–16 days after having initiated nebulized IFN-β-1b inhalation therapy. No side effects were observed. All patients were alive within a 90-days follow-up. Although it is not possible to draw firm conclusions on treatment efficacy based on this case report, our study shows that pulmonary IFN-β-1b administration is feasible, with a good safety profile. This procedure, which presents the advantage of directly targeting the lungs and reducing the risks of systemic side effects, may represent a promising therapeutic strategy for the care of patients with severe COVID-19. However, our preliminary observation requires confirmation by randomized controlled trials.

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“…Since h-interferon-β has been claimed as a cause of immunogenicity by all three paradigms: the epitope-based the mimetic-based [121] and IIRMI-based views (Chap. 7), it might be interesting from a manufacturing perspective to see if there is some relationship between the views.…”

Section: Are the Three Views Relatable?mentioning

confidence: 99%

The Biologics Revolution and Endotoxin Test Concerns

Williams

2019

Endotoxin Detection and Control in Pharma, Limulus, and Mammalian Systems

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The advent of "at will" production of biologics in lieu of harvesting animal proteins (i.e. insulin) or human cadaver proteins (i.e. growth hormone) has revolutionized the treatment of disease. While the fruits of the biotechnology revolution are widely acknowledged, the realization of the differences in the means of production and changes in the manner of control of potential impurities and contaminants in regard to the new versus the old are less widely appreciated. This chapter is an overview of the biologics revolution in terms of the rigors of manufacturing required to produce them, their mechanism of action, and caveats of endotoxin control. It is a continulation of the previous chapter that established a basic background knowledge of adaptive immune principles necessary to understand the mode of action of both disease causation and biologics therapeutic treatment via immune modulation.

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Preventing Aggregation of Recombinant Interferon beta-1b in Solution by Additives: Approach to an Albumin-Free Formulation

Cited by 5 publications

References 38 publications

Recombinant production of Aspergillus Flavus uricase and investigation of its thermal stability in the presence of raffinose and lactose

Recombinant production of Aspergillus Flavus uricase and investigation of its thermal stability in the presence of raffinose and lactose

Rationale for COVID-19 Treatment by Nebulized Interferon-β-1b–Literature Review and Personal Preliminary Experience

The Biologics Revolution and Endotoxin Test Concerns

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