Off patent drugs (OFP)
ChemDiv’s library of off-patent drugs (OFP) contains 996 entries.
Drug repositioning aims to reuse “old” drugs to treat diseases outside their approved indications. Composition-of-matter patents and FDA exclusivities can hinder the immediate availability of some drugs to be repositioned (repurposed). Working on this collection, we analyzed data from the FDA Orange Book and used current on-market patent validity and exclusivities to classify drugs into on-patent (ONP), off-patent (OFP), and off-market (OFM) sets. In the absence of a unanimously accepted definition for small molecules, these sets include organic molecules and peptides with molecular weights between 100 and 1250 Da, resulting in 237 ONP drugs, 320 OFM drugs, and 996 OFP drugs.
We discuss the differences between the three categories in terms of primary molecular properties, chemical diversity, mechanism-of-action target classes, and therapeutic areas. ONP drugs, protected by active patents and exclusivities, often represent the most recent advancements in pharmaceutical innovation, possessing high specificity and efficacy, but are less accessible for repositioning due to intellectual property restrictions. OFM drugs, although no longer on the market, retain their safety and efficacy profiles, providing a potentially rich but underexplored resource for repurposing. OFP drugs, no longer under patent protection, offer the most immediate opportunity for repositioning, as they are widely available and free from legal constraints, making them prime candidates for repurposing efforts.
Given the intellectual property landscape and the absence of specific property rights, we suggest that drugs should be prioritized as follows to improve the repositioning strategy:
(i) OFP, due to their immediate availability and lack of patent restrictions,
(ii) OFM, as they provide a valuable reservoir of compounds with established safety profiles, albeit requiring more extensive re-evaluation,
(iii) ONP, which, while currently less accessible, could be considered in future repositioning efforts once their patents expire.
By systematically categorizing and prioritizing these drugs, we can more effectively leverage existing pharmaceuticals to address unmet medical needs and accelerate the development of new therapeutic options.
Drugs from the OFP library can be used for drug discovery by leveraging their established safety and efficacy profiles to explore new therapeutic indications. Researchers can screen these compounds against novel biological targets associated with various diseases, particularly those that are neglected or rare, where traditional drug development is less commercially viable. By repurposing these off-patent drugs, scientists can rapidly advance from preclinical studies to clinical trials, significantly reducing the time and cost associated with bringing new treatments to market. This strategic approach not only maximizes the utility of existing drugs but also accelerates the availability of innovative therapies for patients with unmet medical needs.
By leveraging the OFP library, researchers can significantly enhance their ability to discover and develop new treatments, ultimately benefiting both the scientific community and patients due to the following beneficial aspects:
● Established Safety Profiles.
○ Since OFP drugs have already undergone extensive safety and efficacy testing, researchers can bypass many early-stage toxicology assessments. This reduces the risk of adverse effects, making the drug development process more predictable and safer.
● Cost-Effectiveness:
○ Utilizing existing drugs for new indications can significantly lower the financial burden associated with drug discovery. The costs of synthesizing new compounds and conducting initial safety studies are minimized.
● Accelerated Development Timelines:
○ With known pharmacokinetics and pharmacodynamics, OFP drugs allow researchers to expedite the preclinical and early clinical phases, moving more quickly to later stages of development and market approval.
● Expanded Research Opportunities:
○ Researchers can explore a broader range of therapeutic areas and disease targets, particularly for neglected and rare diseases, by repurposing drugs that are already available and have demonstrated biological activity.
● Enhanced Funding and Support:
○ Repurposing efforts often attract funding from government grants, non-profit organizations, and other entities interested in maximizing existing resources to address urgent medical needs, providing additional financial and institutional support for researchers.
● Innovative Insights:
○ Investigating new uses for existing drugs can lead to novel insights into disease mechanisms and drug actions, potentially uncovering new biological pathways and targets for therapeutic intervention.
● Collaborative Opportunities:
The use of OFP libraries fosters collaboration between academia, industry, and regulatory bodies, encouraging a shared approach to tackling pressing health challenges through innovative drug repurposing strategies.