Exploring open innovation with a patient focus in drug discovery: an evolving paradigm of patient engagement.

It is suggested in this article that patient engagement should occur further upstream during the drug discovery stage. 'Lead patients', namely those patients who are proactive with respect to their health, possess knowledge of their disease and resulting symptoms. They are also well informed about the conventional as well as non-conventional treatments for disease management; and so can provide a nuanced perspective to drug design. Understanding how patients view the management of their diseases and how they view the use of conventional versus non-conventional interventions is of imperative importance to researchers. Indeed, this can provide insight into how conventional treatments might be designed from the outset to encourage compliance and positive health outcomes. Consequently, a continuum of lead patient engagement is employed that focuses on drug discovery processes ranging from participative, informative to collaborative engagement. This article looks at a variety of open innovation models that are currently employed across this engagement spectrum. It is no longer sufficient for industry stakeholders to consider conventional therapies as the only mechanisms being sought after by patients. Without patient engagement, the industry risks being re-prioritized in terms of its role in the patient journey towards not only recovery of health, but also sustained health and wellness before disease onset.

The successes and challenges of open-source biopharmaceutical innovation.

INTRODUCTION: Increasingly, open-source-based alliances seek to provide broad access to data, research-based tools, preclinical samples and downstream compounds. The challenge is how to create value from open-source biopharmaceutical innovation. This value creation may occur via transparency and usage of data across the biopharmaceutical value chain as stakeholders move dynamically between open source and open innovation. AREAS COVERED: In this article, several examples are used to trace the evolution of biopharmaceutical open-source initiatives. The article specifically discusses the technological challenges associated with the integration and standardization of big data; the human capacity development challenges associated with skill development around big data usage; and the data-material access challenge associated with data and material access and usage rights, particularly as the boundary between open source and open innovation becomes more fluid. EXPERT OPINION: It is the author's opinion that the assessment of when and how value creation will occur, through open-source biopharmaceutical innovation, is paramount. The key is to determine the metrics of value creation and the necessary technological, educational and legal frameworks to support the downstream outcomes of now big data-based open-source initiatives. The continued focus on the early-stage value creation is not advisable. Instead, it would be more advisable to adopt an approach where stakeholders transform open-source initiatives into open-source discovery, crowdsourcing and open product development partnerships on the same platform.

Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases.

Repurposing has the objective of targeting existing drugs and failed, abandoned, or yet-to-be-pursued clinical candidates to new disease areas. The open-source model permits for the sharing of data, resources, compounds, clinical molecules, small libraries, and screening platforms to cost-effectively advance old drugs and/or candidates into clinical re-development. Clearly, at the core of drug-repurposing activities is collaboration, in many cases progressing beyond the open sharing of resources, technology, and intellectual property, to the sharing of facilities and joint program development to foster drug-repurposing human-capacity development. A variety of initiatives under way for drug repurposing, including those targeting rare and neglected diseases, are discussed in this review and provide insight into the stakeholders engaged in drug-repurposing discovery, the models of collaboration used, the intellectual property-management policies crafted, and human capacity developed. In the case of neglected tropical diseases, it is suggested that the development of human capital be a central aspect of drug-repurposing programs. Open-source models can support human-capital development through collaborative data generation, open compound access, open and collaborative screening, preclinical and possibly clinical studies. Given the urgency of drug development for neglected tropical diseases, the review suggests elements from current repurposing programs be extended to the neglected tropical diseases arena.

Understanding and creating value from open source drug discovery for neglected tropical diseases.

INTRODUCTION: The health commons (known as open source) refers to knowledge-based assets that are shared or owned in common by stakeholders found across the health value chain. The unique challenges presented to drug discovery and development including biological, chemical and economic are particularly salient for neglected tropical diseases (NTDs), warranting new networks and models of open collaboration between scientists from the public and private sectors. AREAS COVERED: The goal of this paper is to progress beyond the review of open source strategies NTDs to a discussion of an assessment of these strategies. The authors discuss the notion of evolving openness across the pharmaceutical value chain and discuss and develop a framework for assessing the value and outcomes of open source drug discovery for NTDs, based on the available literature. EXPERT OPINION: Collectively, open source programs for NTDs, beyond the actual deposits themselves, should foster linkages between experts in key disease arenas, encourage collaborations through such linkages and most urgently enable human capacity development. Quantifying their value in absolute terms is not an easy task since exchange markets do not always exist for deposited and shared assets. From the perspective of capacity development, the potential and benefits certainly exist for program development involving NTD initiatives, institutions and students in disease-endemic countries. Here, stakeholders such as public grant agencies and private sector sponsors can play a role in encouraging initiatives that link open and broad knowledge dissemination to the development of local human and technological capacity in NTD-endemic countries.

Developing a framework for understanding and enabling open source drug discovery.

Open source drug discovery is increasingly being sought as a solution for managing product development complexities. Three drivers encouraging the use of the open source strategy include: upstream knowledge-based complexities associated with complementary assets, technological complexities given the scale of research and interdependencies between disciplines and downstream commercialization complexities. While literature currently discusses the need for open source strategies and their outcomes, we have reached a critical stage for a framework to cohesively understand how the drivers affect the open source models chosen as well as the governance strategies to ensure a successful outcome both in terms of knowledge access and product development. In this paper, an initial framework is designed with a focus on the type of participant as impacting the motivation to participate in an open source initiative, the objective of any open source strategy as impacting the structural model adopted and the structure of knowledge produced as impacting its management. It is anticipated that this framework should then provide an opportunity to develop governance rules for open source drug discovery initiatives.

Recent patents on cell signaling systems.

A new biological paradigm, Systems Biology, has emerged with the completion of the Human Genome Project. The Human Genome Project has advanced the view that biological information operates on multiple hierarchical levels and is processed in complex networks. In this paradigm, cumulative knowledge will be used to build models, providing positive externalities to researchers who can use this knowledge to generate new products. As systems biology is likely to become the dominant paradigm in biology, central to the development of medically viable products is ensuring accessibility to systems-based knowledge for multiple researchers. In this paper, we have selected seven systems based on their biological significance including: the Akt (Protein Kinase B), BCR-ABL, GPCR (G-Protein-Coupled Receptor), JAK/STAT (Janus Kinase/Signal Transducers and Activators of Transcription), MAP Kinase, NF-kappaB (Nuclear Factor Kappa B), and Phospholipase C signaling pathways. For each system we provide a complete list of patents, including categorization and institutional ownership; we also review specific patents for each system from the perspective of type of assignee, breadth of claims, and focus-namely whether the focus of the patent is on upstream knowledge regarding the signaling pathway or downstream on pharmaceutical or biological drug development, screening assays, or diagnostics.

Innovation and intellectual property rights in systems biology.

A framework for characterizing systems-based knowledge is needed to understand the new complexities arising from the assignment of IP rights to biological information.

Identification of a cis-element that determines autonomous DNA replication in eukaryotic cells.

A 36-bp human consensus sequence (CCTMDAWKSGBYTSMAAWTWBCMYTTRSCAAATTCC) is capable of supporting autonomous replication of a plasmid after transfection into eukaryotic cells. After transfection and in vitro DNA replication, replicated plasmid DNA containing a mixture of oligonucleotides of this consensus was found to reiterate the consensus. Initiation of DNA replication in vitro occurs within the consensus. One version, A3/4, in pYACneo, could be maintained under selection in HeLa cells, unrearranged and replicating continuously for >170 cell doublings. Stability of plasmid without selection was high (> or =0.9/cell/generation). Homologs of the consensus are found consistently at mammalian chromosomal sites of initiation and within CpG islands. Versions of the consensus function as origins of DNA replication in normal and malignant human cells, immortalized monkey and mouse cells, and normal cow, chicken, and fruit fly cells. Random mutagenesis studies suggest an internal 20-bp consensus sequence of the 36 bp may be sufficient to act as a core origin element. This cis-element consensus sequence is an opportunity for focused analyses of core origin elements and the regulation of initiation of DNA replication.