Month: May 2020

The Scripps Research Molecular Screening Center (SRMSC) was founded in 2004 and comprises more than $22 million of specialized automation. As part of the Translational Research Institute (TRI), it comprises early drug discovery labs and medicinal chemistry.

Together with Scripps Research at the La Jolla, California, campus, this represents one of the most competitive academic industrial screening centers worldwide. The SRMSC uses automated platforms, one a screening cell and the other a cherry-picking platform. Matched technologies are available throughout Scripps to allow scientists to develop assays and prepare them for automated screening. The library comprises more than 1 million drug-like compounds, including a proprietary collection of >665,000 molecules. Internal chemistry has included ~40,000 unique compounds that are not found elsewhere.

These collections are screened against a myriad of disease targets, including cell-based and biochemical assays that are provided by Scripps faculty or from global investigators. Scripps has proven competence in all detection formats, including high-content analysis, fluorescence, bioluminescence resonance energy transfer (BRET), time-resolved fluorescence resonance energy transfer (TR-FRET), fluorescence polarization (FP), luminescence, absorbance, AlphaScreen, and Ca++ signaling. These technologies are applied to NIH-derived collaborations as well as biotech and pharma initiatives.

The SRMSC and TRI are recognized for discovering multiple leads, including Ozanimod.

The prevailing philosophy in biological testing has been to focus on simple tests with easy to interpret information such as ELISA or lateral flow assays.

At the same time, there has been a decades long understanding in device physics and nanotechnology that electrical approaches have the potential to drastically improve the quality, speed, and cost of biological testing provided that computational resources are available to analyze the resulting complex data.

This concept can be conceived of as “the internet of biology” in the same way miniaturized electronic sensors have enabled “the internet of things.” It is well established in the nanotechnology literature that techniques such as field effect biosensing are capable of rapid and flexible biological testing.

Until now, access to this new technology has been limited to academic researchers focused on bioelectronic devices and their collaborators. Here we show that this capability is retained in an industrially manufactured device, opening access to this technology generally.

Access to this type of production opens the door for rapid deployment of nanoelectronic sensors outside the research space. The low power and resource usage of these biosensors enables biotech engineers to gain immediate control over precise biological and environmental data.

The discovery of new medicines has become increasingly more challenging and requires significant collaboration between pharma, biotech, academia, and technology to be successful.

These partnerships necessitate the streamlined exchange of samples while adhering to the increasingly complex set of legal and proprietary restrictions, government legislation, and ethical considerations associated with samples. There is a significant volume of literature published on clinical sample compliance but little describing compliance aspects of discovery sample management.

This paper describes some of the key compliance activities and challenges and shares GlaxoSmithKline’s experiences and current practices.

Synthetic biology is an established but ever-growing interdisciplinary field of research currently revolutionizing biomedicine studies and the biotech industry.

The engineering of synthetic circuitry in bacterial, yeast, and animal systems prompted considerable advances for the understanding and manipulation of genetic and metabolic networks; however, their implementation in the plant field lags behind.

Here, we review theoretical-experimental approaches to the engineering of synthetic chemical- and light-regulated (optogenetic) switches for the targeted interrogation and control of cellular processes, including existing applications in the plant field.

We highlight the strategies for the modular assembly of genetic parts into synthetic circuits of different complexity, ranging from Boolean logic gates and oscillatory devices up to semi- and fully synthetic open- and closed-loop molecular and cellular circuits.

Finally, we explore potential applications of these approaches for the engineering of novel functionalities in plants, including understanding complex signaling networks, improving crop productivity, and the production of biopharmaceuticals.

Adeno-associated virus (AAV) vectors currently represent the most attractive platform for viral gene therapy and are also valuable research tools to study gene function or establish disease models.

Consequently, many academic labs, core facilities, and biotech/pharma companies meanwhile produce AAVs for research and early clinical development. Whereas fast, universal protocols for vector purification (downstream processing) are available, AAV production using adherent HEK-293 cells still requires time-consuming passaging and extensive culture expansion before transfection.

Moreover, most scalable culture platforms require special equipment or extensive method development. To tackle these limitations in upstream processing, this study evaluated frozen high-density cell stocks as a ready-to-seed source of producer cells, and further investigated the multilayered CELLdisc culture system for upscaling.

The results demonstrate equal AAV productivity using frozen cell stock-derived cultures compared to conventionally cultured cells, as well as scalability using CELLdiscs.

Thus, by directly seeding freshly thawed cells into CELLdiscs, AAV production can be easily upscaled and efficiently standardized to low-passage, high-viability cells in a timely flexible manner, potentially dismissing time-consuming routine cell culture work. In conjunction with a further optimized iodixanol protocol, this process enabled supply to a large-animal study with two high-yield AAV2 capsid variant batches (0.6-1.2 × 10¹⁵ vector genomes) in as little as 4 weeks.

The cost of treating cancer patients is high and rising in the United States. Payers are exposed to cost through doctor visits, laboratory tests, imaging tests, radiation treatment, drugs, hospital stays, surgery, home care, transportation and travel, and caregiving.

This study focuses on the cost of medication from the viewpoint of U.S. payers. Although new tools for managing these costs have been gaining attention, prices continue to rise, and challenges to managing costs remain high. Innovative tools are necessary for controlling the cost of care in oncology, but their effectiveness is still unclear.

To (a) gauge payer perceptions of current and future cost management of innovative oncology drugs and (b) predict which management tools will increase in prevalence by 2020-2022.A literature search of cost and management of oncology created the foundation for developing a survey for U.S. payers. The mobile survey was completed on devices such as smart phones or tablets.

Payers were asked about general oncology product management, use of specific management tools today, management challenges, and expected use of specific management tools in 2020-2022. Management tools were segmented into traditional (used across many therapeutic categories), oncology-specific (used in oncology but not routinely used in other disease areas), and systemic (not product-specific but that affect the way services are provided and funded).

Specific questions for managing the cost of care in non-small cell lung cancer (NSCLC) and chronic lymphocytic leukemia (CLL) were included in the survey. NSCLC and CLL were chosen because of their diverse clinical characteristics and the level of innovation in these disease areas.

The survey was fielded from May 31, 2017, to June 15, 2017. Results consisted of simple descriptive statistical analysis weighted by the payer’s reported organizational covered lives.Payers were concerned with the high cost and budget impact of oncology drugs and considered these a high priority for management.

However, they continue to use traditional management tools such as manage to FDA label, quantity limits, step edits, and reauthorizations, which are ineffective in controlling cost.

More innovative management tools such as pathways of care are available but are not yet widely adopted. Payers hope to better control oncology cost in the future; however, specific questions pertaining to the management of NSCLC and CLL indicate that minimal changes in cost management will occur by 2020-2022.Despite an increasing number of innovative cost management tools, challenges remain for managing oncology medication costs.

New incentives are being generated, but barriers to their implementation will continue to restrict use through 2020-2022.No outside funding supported this study. The authors are employed by MKO Global Partners, which is a consulting firm that focuses on payer strategy and market access in the pharmaceutical and biotech markets. Some initial results from this research were published as part of a comparative poster at ISPOR European Conference; November 4-8, 2017; Glasgow, Scotland, UK.