Source: Natlawreview by:Lisa L. Mueller
This post will examine recent patent litigation between Genentech (a U.S. subsidiary of Hoffmann-La Roche Ltd. (Roche)) and the Russian company, Biocad JSC (Biocad). Because of the significance of this litigation for the biopharmaceutical industry in Russia, a detailed analysis of the litigation and its implications is provided below.
MabThera® and Biocad’s biosimilar version
In 2006, Roche/Genentech (Roche) launched MabThera® (rituximab) in Russia. Rituximab is a chimeric monoclonal antibody against the protein CD20, which is found primarily on the surface of B-cells. Rituximab destroys B cells and is used to treat diseases characterized by excessive numbers of B cells, overactive B cells or dysfunctional B cells. Examples of such diseases include non-Hodgkin’s lymphoma, leukemia and autoimmune disorders. As a result, rituximab is on the World Health Organization’s List of Essential Medicines. In 2014, worldwide sales of rituximab exceeded $7 billion U.S. dollars.
Rituximab was initially developed by Biogen Idec and is protected by patents throughout the world. A Russian patent, RU 2139731 (the ‘731 patent), entitled “Method of treatment, antibodies, hybridoma”, claims the use of rituximab in treating lymphomas. The ‘731 patent expired in 2013. An Eurasian patent, EA 004107 (the ‘107 patent), entitled “Combinational therapy of B-cell lymphomas with the use of anti-CD20 antibodies”, also claims the use of rituximab to treat lymphomas. The ‘107 patent expires on November 8, 2019. Both the ‘731 and ‘107 patents claim methods of medical treatment which are excluded from patentability in many countries. However, such claims are permitted in the Russian and Eurasian patent systems.
Following the development of the Russian biotechnology industry in late 2000’s, several local biopharmaceutical companies began producing biologics and biosimilars. One such company, Biocad (www.biocad.ru), described itself as a “full cycle Russian biopharmaceutical company, holding the leading position for investment attractiveness among leading pharmaceutical companies”.
Not surprisingly, in 2012, at the beginning of the patent-cliff era, many local Russian companies directed their focus towards developing biosimilar versions of “blockbuster” biologics (such as, for example, Embrel®, Neulasta®, etc.). From the Russian authorities’ point of view, rituximab was one of the key targets for import substitution due to the fact that it was included in the essential drugs list and the Federal “7 Nosology” program (which is the Russian federal reimbursement program which pays for the treatment of many high costs diseases). However at the time, Roche was the only supplier of rituximab in Russia. As a result, in 2013, state-procurement of rituximab accounted for about $217 million (U.S.) dollars of the Russian federal budget.
In 2014, despite encountering administrative hurdles during state registration, Biocad launched a rituximab biosimilar called “AcellBia”, for the treatment of blood cancers. At that time, the ‘731 patent was expired. Shortly thereafter, Biocad received a $240 million (U.S.) dollar state procurement contract for the supply of rituximab, essentially eliminating Roche from the marketplace.
Ensuing patent litigation
In 2015, Roche filed a lawsuit against Biocad alleging infringement of the ‘107 patent. The ‘107 patent contains three claims:
A method for treating an individual with B-cell lymphoma comprising administration of a synergistic therapeutic combination of at least one anti-CD20 antibody and at least one cytokine, wherein said method has a better therapeutic effect over other methods of therapeutic treatment carried out separately.
A method for treating an individual with B-cell lymphoma comprising administration of a synergistic combination of a therapeutically effective amount of the anti-CD20 antibody and at least one chemotherapeutic agent; wherein the method enables destruction of cells of B-cell lymphoma with a synergistic effect greater than that achieved using anti-CD20 antibody or chemotherapeutic agent alone.
A method for reducing the risk of relapse of B-cell disease in a patient receiving a bone marrow or tissue grafts of peripheral blood stem cells after myeloablative chemotherapy, comprising the step of administering the amount of anti-CD20 antibody to effectively reduce the number of disease-causing CD20 antigen-expressive cells and to reduce the risk of recurrence of said B-cell disease in a patient.
The product insert provided with AcellBia partially mirrored the rituximab product insert (the AcellBia product insert mirrored the rituximab product insert regarding use in blood cancers; use in rheumatoid arthritis was not recited since this use was covered by another patent in Russia). Specifically, both inserts described the use of an anti-CD20 antibody either alone or in combination with at least one cytokine or chemotherapeutic agent for use in treating blood cancers. As a result, Roche argued that Biocad infringed independent claims 1 and 2 of the ‘107 patent when it began selling its AcellBia biosimilar in Russia.
The trial court held that none of Biocad’s actions could be considered to be an infringement of the claims of the ‘107 patent. According to the court, the claims of the ‘107 patent provided legal protection for a method of treatment. The production and marketing of a medicine did not necessarily lead to the use of the medicine as a treatment. Because Biocad was not a medical organization and was not licensed to perform any medical activities, it could not offer or provide services for the use of the patented method of treatment. As a result, Roche was unable to prove infringement.
In addition, Biocad was able to prove that it had not induced infringement of the ‘107 patent. Specifically, Biocad argued that the independent claims of the ‘107 patent assumed the co-administration of rituximab with a cytokine or chemotherapeutic agent (such as INF-α, INF-γ, IL-2, GM-CSF, G-CSF, fludarabine, cyclophosphamide, doxorubicin, vincristine and prednisone), each of which was available by prescription only. Because Biocad did not produce any of these cytokine or chemotherapeutic agents, it argued that its production and marketing of AcellBia did not infringe the ‘107 patent in the absence of these agents which were required to achieve the claimed synergistic effect.
Based on these findings, the trial court rejected Roche’s claim of infringement. Roche did not appeal and voluntarily abandoned the ‘107 patent.
What does this decision mean to the Russian pharmaceutical industry?
The litigation between Roche and Biocad is the first patent infringement case in Russia involving method of treatment claims. As a result, the decision raises questions about whether method of treatment claims will be enforceable in the future. Certainly, this decision highlights that method of treatment claims are less reliable than claims claiming compositions of matter or methods of use.
After its victory against Roche, Biocad went public and challenged the unfavorable aspects of Russian intellectual property law, arguing that certain types of patents violate the principles of fair competition. Specifically, according to Biocad’s Legal and Administrative Affairs Director, Alexey Katkov:
…There are substantial patents when a company really protects its new products, and there are instruments for holding monopoly on the market. When a deadline is due for patent protection of a molecule, manufacturers start making continuing patent applications for methods of treatment, use, etc., thus, extending the patent life of the drug…
Among the numerous state bodies of the Russian Federation, the Federal Antimonopoly Service (FAS) took an interest in preventing the scenario mentioned by Mr. Katkov. Very quickly, FAS released an official communication in which it stated that it was considering the possibility of banning divisional patent applications. Specifically, FAS stated that the “artificial extension of the monopoly by certain pharmaceutical companies” prevented other fair competitors from entering the market, thereby delaying the emergence of affordable generics and biosimilars.
Additionally, according to the information published in Russian newspaper “Vedomosti” on March 1, 2016, the FAS has begun discussing amendments to Russian patent law which will allow Russian companies to use inventions claiming medicines and medical devices without the consent of the patent holder. If such amendments are passed, the end result would be the compulsory licensing of pharmaceutical patents in Russia (see here)
Even though FAS has no legal power to “ban” divisional patent applications or implement compulsory licensing, the question is now being discussed by various stakeholders, including local businesses and ministries. While still too early to know the outcome, the overall political trend of such a discussion fits with strong government support of local industry players, most of which are still only able to produce generic medicines.