Redefining Protein Products – When is a Tail a Leg?
This is a guest post from Susan K Finston, President of Finston Consulting. Do you have a response to Susan’s post? Respond in the comments section below.
Over the past decade, peptide therapies have crossed over into the mainstream with over 60 approved products, 140 therapies in the clinic and an estimated 500 – 600 in preclinical development. Indications for peptide drugs also are broadening, ranging from infectious disease, to metabolic disorders and advanced cancer therapies. With less toxicity and fewer side effects, naturally occurring peptide drugs have an approval rate that is double that of small molecules (new chemical entities or NCEs).
Why are peptide drugs so important?
“Evolution has been honing the specificity of polypeptides for millions of years. Amino Acid sequences – whether in peptides or proteins – control and direct all aspects of cellular functioning and coordinate most intercellular communication. No other class of biological molecules offers the range of chemical diversity … they are nature’s toolkit and the more we can use native peptides or closely related analogs , the safe and more specific the drugs at the physician’s disposal.” (Source: Rodney Lax)
With emerging nanotechnologies, we are seeing breakthrough products like oral insulin, along with a range of critical new therapeutic approaches including peptide cancer therapies for oral delivery and on an out-patient basis, up to and including anticipation of effective cancer prophylaxis for patients with BRCA mutations. Convergence of nanotechnologies with increased understanding of peptides makes everything possible.
Understanding the greater development and manufacturing challenges associated with biologics, the FDA’s understandable preference is for shorter, truncated, peptides that can be manufactured through chemical synthesis. This entails a time-consuming and painstaking process of optimizing and abbreviating peptide drugs to reduce the size from 50, 40, or 30 peptides to a smaller size can be synthesized chemically for hospital use (IV delivery) or as oral formulations (nanotechnology).
So while avoiding the risks and challenges of biologics, peptide therapies are inherently more complex than typical small chemical entities. Months or even years of additional development time may be needed to fully optimize a truncated peptide that will retain safety and effectiveness as a drug, comprising smallest possible amino acid chain for submission to the FDA.
Given lengthier product development cycles, increased patent litigation, greater complexity of clinical trial requirements and the new regulatory pathway for biosimilars, the U.S. Government mandated an increased data exclusivity period for biotech drugs generally. The BCPI Act included a 12 year period of exclusivity for regulatory dossiers associated with biologicals and protein products.
You may think that this includes peptide drugs – that would be logical. In fact, the opposite is true. Based on the (revised) definition and FDA guidance to the BPCI Act, peptide drugs that navigate the Scylla and Charybdus of biologics and small molecule development and gain FDA approval expressly are excluded from the 12 year period of exclusivity available for biologics.
This brings to mind President Lincoln’s famous riddle:
“If you call the tail a leg, how many legs does a horse have?
Four – calling a tail a leg does not make it a leg.”
As the building blocks of proteins, technology-intensive peptide therapies are essentially biologic in nature – and well deserving of 12 years of data exclusivity.
About the author:
President of Finston Consulting LLC since 2005, Susan works with innovative biotechnology and other clients ranging from start-up to Fortune-100, providing support for legal, transactional, policy and “doing business” issues. Susan has extensive background and special expertise relating to intellectual property and knowledge-economy issues in advanced developing countries including India and South Asia, Latin America and the Middle East North Africa (MENA) region. She also works with governments, and NGOs on capacity building and related educational programs through BayhDole25. Together with biotechnology pioneer Ananda Chakrabarty, she also is co-founder of Amrita Therapeutics Ltd., an emerging biopharmaceutical company based in India with cancer peptide drugs entering in vivo research. Previous experience includes 11 years in the U.S Foreign Service with overseas tours in London, Tel Aviv, and Manila and at the Department of State in Washington DC. For more information on latest presentations and publications please visit finstonconsulting.com.
Yes, peptides appear to be slighted as a class of biologic products, with even recombinant ones treated more as drugs.
But in terms of real-world utility and impact, 12 years U.S. biologic reference product data exclusivity is rather meaningless. In my studies of ref. product patent and data and market (orphan) exclusivity expirations (see published article at http://www.biosimilarspipeline.com/pipeline.pdf), patents for nearly 90% of potential ref. products extend longer than any other exclusivity (and this is just the known and more easily identified patents, with many, including exclusively licensed patents, likely remaining unidentified so far).
Related to this, shortening of U.S. ref. product data exclusivity, such as to 5 years, as called for by some politicians and activists, is meaningless, a waste of time. No proponent of this (or anyone else), as far as I am aware, has yet ever cited even a single product where 5 vs. 12 years would make any difference in timing of U.S. market entry, with patents the real block to marketing.
Hi Ron, Where you stand depends on where you sit! As co-founder and Managing Director of Amrita Therapeutics, I am looking at this issue through the eyes of a start-up, not a global bio-pharma company with deep pockets for litigation to prevent or stop patent infringement. In this context, a 12-year DE period provides a kind of absolute protection that patent protection cannot, where the government is the gatekeeper.