By: Katie Rubino
Molecules used as drug products are often categorized into two classes: small molecule drugs or biological drugs. Small molecule drugs are often synthesized from organic and inorganic compounds, and have a low molecular weight, typically less than 1000 Daltons. Identical copies of small molecules are easy to reproduce, as small molecule compounds are typically composed of a single molecule. Small molecule compounds are often small enough to be dosed into an oral dosage form such as a capsule or tablet.
Biological drugs include any virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or arsphenamine derivative that is applicable to the prevention, treatment or cure of disease or conditions in humans. Biologics are drugs sourced from proteins and frequently consist of heterogenous mixtures. Generally, biologics have a high molecular weight greater than 10,000 Daltons and can be as heavy as 150,000 Daltons. One classic example of biologics are monoclonal antibodies that are used in cancer therapy to fight abnormal cells. Biologics are typically administered by injection or infusion and are produced in genetically modified cells of microorganisms such as bacteria or yeast.
|Small Molecule Drugs||Biological Drugs|
-Molecular weight less than 1000 Daltons
|-Mixture of molecules
-Molecular weight between 10,000-150,000 Daltons
|Synthesis||-Produced by chemical synthesis||-Produced in microorganisms|
|Route of Administration||-Oral||-Intravenous or subcutaneous|
|Manufacturing||-Identical copy can be made||-Impossible to ensure identical copy|
|Targeted Disease States||-Psychiatry, acid reflux, hyperlipidemia, COPD, pain, heat disease, thrombocytopenia,||-Cancer, cystic fibrosis, diabetes, hemophilia, hepatitis, autoimmune disorders|
|Average Daily Cost||$1/day||$22/day|
Patent strategies for small molecule drugs include identifying potential drug candidates early and filing a patent quickly as multiple companies could be working on similar products. Further into development and synthesis of a leading compound, an international filing strategy can take place to file applications in targeted countries that align with business strategies.
Recently international patent offices have emphasized that inventors of small molecules need to show evidence of unexpected results of the small molecule in clinical trials, as the small molecule space has become more crowded. Frequently, getting over this hurdle can be difficult. Often, showing some type of unexpected benefit outside what the class has already demonstrated can be critical to success. Due to the uncertainty as to what small molecules will become blockbusters later on, filing early is imperative. Identifying new compounds early, protecting products early, and bringing products to market early is critical to success. Furthermore, working with patent counsel to create an international filing strategy that aligns with business goals is of utmost importance.
Patent prosecution techniques for biologics are often more complex than small molecules, as further complexities can muddy the waters in this area. In 2009, Congress passed the Biologics Price Competition and Innovation Act (BPCIA) of 2009, which amended the public health service act (PHS Act), to create an abbreviated approval pathway for biological products shown to be biosimilar with an FDA-licensed referenced biological product. The legislative intent behind the BPCIA was to increase access and affordability to biologics for consumers, similar to what the Hatch-Waxman Amendments did for small molecule drugs in the 1980’s.
The BPCIA defines a biosimilar as “a biological product that is highly similar to an approved biological reference product notwithstanding minor differences in clinically meaningful differences in terms of safety, purity, and potency.” In mere laymen’s terms, a biosimilar is a generic version of a biologic drug. The approval of biosimilars in the United States has slowly been on the rise since the first biosimilar was approved in 2015 by the Food and Drug Administration (FDA). In 2017, five biosimilars were approved by the FDA and in 2018 that number increased to seven biosimilars being approved by the FDA. The first ever biosimilar drug product was approved by the European Medicine Agency (EMA) in 2013, for a monoclonal antibody biosimilar of the reference product Remicade produced by Johnson and Johnson.
In developing a patent strategy, reference products must consider kinds of modifications that could be made to the reference product and clinical differences made during manufacturing. The goal of a patent for a reference product is to have patent claims that capture the reference product and the entire biosimilar marketplace for that particular biological product. Frequently, additional patents such as continuations are needed to cover potential variations in the reference product, such as new formulations, additional routes of administration, new manufacturing methods such as manufacturing in different cell lines, and the like. For example, modifications to certain amino acid sequences may yield a highly similar product that is not clinically different. Successful patent prosecution strategies surrounding biosimilars include disclosure that supports modifications to reference products and to different methods of manufacturing reference products. Such disclosure can help adequately support claims that provide enablement for such modifications to the reference product. With regard to biologic products, working with patent counsel to build a moat of intellectual property around the reference product is of utmost importance.
Further, working with counsel to identify potential trade secrets used in the manufacturing of the biological product can be helpful. Generally, methods of manufacturing a biologic such as DNA cell lines used to synthesize a biologic as well as cell lines that biologics are produced within may be kept as trade secrets. Further down the road, these trade secrets can be turned into subsequent patents when necessary.
To summarize, developing a patent strategy for small molecule drug products and biological drug products is imperative. Working with patent counsel to build strong monetizable patent portfolios is critical to success in the life sciences landscape.
Caldwell Intellectual Property Law