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In Silico Devices May Improve Drug Manufacturability

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Using in silico tools to augment physical experiments can help identify manufacturability issues early in development. That’s according to an AI technology company that spoke on a recent panel.

BigHat Biosciences, which was among the companies presenting at PEGS Boston, explained that developing in silico models of antibody yields using a cell-free expression system allows the exploration of a wider range of mutations.

And this, in turn, lets companies better optimize their product for manufacturability.

“There’s only so many experiments you can do by putting an antibody into CHO [Chinese Hamster Ovary] cells,” explains Hunter Elliott, PhD, vice president of machine learning at BigHat Biosciences.

“With in silico tools augmenting that exploration side, we can build models that make predictions for improved sequences, screening many more antibodies in silico than we need to send to the lab.”

Elliott’s talk came alongside a panelist who argued it was important for preclinical researchers to communicate with the manufacturing departments of their companies to make a success of the latest generation of harder-to-manufacture drugs.

Speaking about his own products, Elliott argues that using in silico tools to explore a wider range of possible antibody mutations means it’s possible to select the handful with the highest possible yields as well as other improved biophysical properties.

“You’re derisking your processes because you’re combining your experiments with the in silico tools you’re using,” he says.

Talking about the panel, Elliott adds that discussion around the limitations of models included the lack of publicly available data on manufacturability and developability, especially for potential products that have failed to make it to the clinic.

Some have expressed concern that using in silico tools might also accidentally screen out the best-performing antibodies. Although, he says, “my personal opinion is that the ability to predict properties of sequences without sending them into the lab makes it easier for us to optimize from a suboptimal starting sequence.”

“With these models, we can keep this imperfect antibody in the loop and take it forward through several rounds of optimization, and then, instead of a candidate molecule being killed early on, it might be engineered into manufacturability.”

The post <i>In Silico</i> Devices May Improve Drug Manufacturability appeared first on GEN – Genetic Engineering and Biotechnology News.

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New webinar: Tackling drug discovery challenges in cancer research

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Cancer cells

Hosted by Drug Discovery World and supported by Sartorius and BioIVT, this webinar will explore the opportunities and challenges that exist within cancer research drug discovery and development.

You will hear from Dr Sudha Rao, Chief Scientific Officer of Kazia Therapeutics, Karol Budzik, PhD, Business Development Associate at Vyriad Therapeutics and Lars van der Veen, Chief Scientific Officer at iOnctura.

Presentations will cover how cancer treatments have shifted towards reprogramming the biology driving tumour growth, immune escape and treatment resistance, the trajectory that in vivo CAR-T treatments are taking, and how challenging tumours burdened by stroma and immune-mediated resistance can be tackled.

Q&A with the speakers follows the presentations.

Register for free now.

The post New webinar: Tackling drug discovery challenges in cancer research appeared first on Drug Discovery World (DDW).

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Psilocybin proves promising in neuropathic pain mouse study

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Amid the rise of psychedelics in the mental health space, researchers have begun to explore psilocybin as a treatment for chemotherapy-induced peripheral neuropathy.

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New Spectrometry Technique Could Aid Formulation Development

New Spectrometry Technique Could Aid Formulation Development

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A new technique combining two forms of spectrometry could help biopharmaceutical companies improve their choice of formulation buffer for antibody manufacturing by revealing how molecular forms and three-dimensional shapes of complex biologics respond to their environment. That’s the view of Christian Bleiholder, PhD, a professor at Florida State University who helped develop the technique.

According to Bleiholder, what happens structurally when a complex biological molecule, such as an antibody or viral spike protein, binds to its target is currently poorly understood.

“This is where [this approach] can help with the bioprocessing and formulation,” he says, as structural changes “can affect the lifespan [of the product] and lead to issues, such as aggregation.”

Because antibodies are complex, existing techniques tend to be powerful at different levels of complexity, he explains. Mass spectrometry is particularly powerful for distinguishing molecular composition, while structural approaches such as X-ray crystallography and cryo-electron microscopy can provide high-resolution structural information.

The challenge is understanding the link between these things within a heterogeneous sample, he says.

To overcome this, Bleiholder and his team worked with Bruker Daltonics to develop Tandem-Trapped Ion Mobility Spectrometry (Tandem-TIMS). This combines tandem ion mobility spectrometry with tandem mass spectrometry to disentangle three overlapping layers of molecular complexity: molecular form, three-dimensional shape, and binding or assembly state, he says.

He explains that, if the proteins have different structures, they can be characterized with tandem ion mobility spectrometry, and then mass spectrometry can be used to look at their molecular forms and binding states.

Going forward, Bleiholder hopes the technique can be used for formulation development but also earlier, during drug discovery of new products, such as multi-specific antibodies, to determine which molecular states are important and how those change when a biologic engages its target. He also plans to look at automating the technique.

Bleiholder spoke about using Tandem-TIMS at the Bioprocessing Summit in Boston earlier this year.

The post New Spectrometry Technique Could Aid Formulation Development appeared first on GEN – Genetic Engineering and Biotechnology News.

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