Abstract
Executive Editor, Biotechnology Law Report
Partner, Dentons US LLP
M
CHRISTOPHER HOLMAN: What are the major differences between how biosimilars are covered by patent law vs. how generic drugs are covered?
DR. MICHAEL SAMARDZIJA: I assume you mean what are the major differences between how large molecules are covered by patent law vs. how small molecules are covered.
With the fallout from the Myriad decision and the still-pending U.S. Patent and Trademark Office guidelines based on it, a shadow has been cast on the patent eligibility of naturally occurring compounds. So unlike small molecules, for which claims to the compound are of the greatest value to the innovator, large-molecule patent protection must rely on method-of-making and method-of-treating claims. However, certain changes to the manufacturing processes invariably occur on scaling up of production of large molecules. Because even the smallest changes to manufacturing processes may cause changes in the immunogenicity, side effects, and efficacy of large molecules, most of these manufacturing processes are maintained as trade secrets rather than being covered by patents. With the changes to the best mode requirement in the America Invents Act and the pending federal trade secret legislation, it is likely that there will continue to be a shift in the protection of large molecules away from patents and toward trade secrets.
CHRISTOPHER HOLMAN: How might these differences impact the speed with which biosimilars receive FDA approval?
DR. MICHAEL SAMARDZIJA: A shift toward trade secret protection will increase the cost of R&D for a biosimilar applicant. There will be fewer and fewer publications and issued patents to rely on for guidance on how to make (and the most efficient way of making) the product.
CHRISTOPHER HOLMAN: Some IP lawyers think biosimilars will face greater patent litigation than generic drugs. Why might this be the case?
DR. MICHAEL SAMARDZIJA: There likely is a greater patent litigation risk for biosimilar applicants than for generic manufacturers because it is much clearer to a generic manufacturer what patents, if any, pose a problem for the product being developed. The Orange Book provides the generic manufacturer with the opportunity to evaluate and develop invalidity and noninfringing positions, as well as to determine the likelihood of success of a patent suit. A biosimilar applicant will not know with certainty what patents, if any, the branded biologic company may assert until that company provides its list to the biosimilar applicant during the “patent dance.” The time to develop invalidity and noninfringment positions is therefore short. As such, neither party may be in a position to make a thorough investigation and may be more likely to file suit and decide later.
CHRISTOPHER HOLMAN: What is the “Purple Book” for biosimilars? How will it be useful to biotechnology companies and patent lawyers?
DR. MICHAEL SAMARDZIJA: At the moment, the Purple Book is a work in progress. The first issue lists licensed biological products with the reference product exclusivity and the biosimilarity/interchangeability evaluations made by the FDA to date. Although this may change in the future, for now, no patents are listed therein. As such, in its current form, the Purple Book will be useful only to determine the end of the exclusivity period.
CHRISTOPHER HOLMAN: How do the various global agencies differ in how they regulate biosimilars?
DR. MICHAEL SAMARDZIJA: The regulatory agencies differ in several ways, such as in the amount of clinical and preclinical data they require both for approval and post-approval. Moreover, they differ in whether they provide a 1-year exclusivity period for a successful interchangeable drug applicant.
CHRISTOPHER HOLMAN: What are the main barriers to entry for developers of biosimilars?
DR. MICHAEL SAMARDZIJA: At present, the three key barriers to entry appear to be (1) manufacturing development (which includes safety, efficacy, and immunogenicity); (2) patent protection; and (3) lack of automatic substitution. The first barrier will ensure that only companies with the financial resources and the know-how will even begin the challenge of developing a biosimilar product. The second barrier will in time take care of itself. What happens with the last barrier may be the key to whether a biosimilar system is successful, in that it will not make business sense to invest such great resources and take on such a high risk if all a biosimilar can hope to get is 30% of the branded drug's market share.