Blog Big Molecule Watch October 27, 2022

Biogen Seeks a Preliminary Injunction in Natalizumab BPCIA Case Against Sandoz

Biogen seeks a preliminary injunction in its BPCIA case against Sandoz related to Sandoz’s proposed biosimilar of TYSABRI (natalizumab).  On October 20, 2022, the Court issued a sealed order on the parties’ joint stipulation and proposed schedule for a preliminary injunction motion.  A redacted version of the parties’ proposed schedule provides that briefing on Biogen’s motion shall be completed by April 7, 2023, with a hearing to be scheduled thereafter at the Court’s convenience.  The joint proposal also requires that Biogen elect, by November 18, 2022, up to 5 patents and up to 10 claims to be asserted as part of the preliminary injunction.

Biogen has also recently field a redacted version of its 107-page sealed complaint against Sandoz.  Biogen alleges infringement of twenty-eight patents under the BPCIA based on Sandoz’s submission of an aBLA for PB006, a proposed biosimilar of TYSABRI (natilizumab).  According to Biogen, “[t]he claims for patent infringement brought in this action are necessitated by Defendants’ development and stated intent to import, market, and sell in Delaware and throughout the United States a biosimilar version of Biogen’s groundbreaking biologic product, Tysabri® (natalizumab) (“Tysabri”)—which aids over 200,000 patients in their fights against chronic, painful, and life-threatening autoimmune diseases—by improperly exploiting Biogen’s intellectual property.”  Biogen seeks a judgment that Sandoz and Polpharma have infringed or will infringe the asserted patents, and preliminary and permanent injunctive relief.

TYSABRI is indicated for the treatment of multiple sclerosis and Crohn’s disease.  TYSABRI is a humanized monoclonal antibody that targets the alpha-4 integrin component of adhesion molecules found on many white blood cells and, according to Biogen, “was designed to selectively inhibit immune cells in the blood stream, preventing them from passing from the blood into the [central nervous system] where they can damage nerves.”

According to Biogen, the asserted patents are directed to “inventions relating to Tysabri, including regarding therapeutic uses of Tysabri, ways of making treatment with Tysabri safer for patients and Biogen’s innovative methods of manufacturing antibodies, such as Tysabri.”  Biogen alleges that “[i]n February 2005, after Tysabri was on the market, it was discovered that two individuals who had received Tysabri during clinical trials developed progressive multifocal leukoencephalopathy (PML),” causing Biogen to “voluntarily withdrawal Tysabri from the market.”  About a year later, “Tysabri was approved for re-entry to the market[ with] a warning on the label regarding the potential risk of PML.”  According to the Complaint, “Biogen worked hard to develop an innovative risk-management plan to give early warning of cases of PML,” including a Risk Evaluation and Mitigation Strategy (REMS) program to “mitigate the potential risk of PML in patients receiving treatment with Tysabri.”

Biogen also alleges that its efforts lead to “the FDA’s approval of the first and only clinically and analytically validated anti-JCV antibody assay, the Stratify JCV Antibody Enzyme-Linked Immunosorbent Assay (“ELISA”) Test (“Stratify” or the “Stratify assay”).”  JCV is a “human polyomavirus” that “can remain in the latest state in the body, typically with no apparent clinical symptoms,” but “JCV reactivation can lead to PML.”  According to Biogen, it’s “innovative approaches to safely administering Tysabri and managing PML risk were recognized by the U.S. Patent Office.”

Biogen also alleges infringement of patents directed to manufacturing antibodies, including methods for producing CHO cells with “enhanced growth characteristics”; methods for preventing and removing trisulfide bonds; methods for control of glycosylation in cell culture processes; and methods for depth filtration to clarify mammalian cell culture.  According to Biogen, “[o]ne of the key challenges in the manufacturing of therapeutic antibodies is that the production is limited to cell-based expression systems which are costly and inefficient, can have varied yields depending on the product and expression system, and require downstream processing to remove biological contaminants introduced from the expression system.”  Biogen asserts that it has “developed specialized cell-based expression systems that can be used to generate high yield therapeutic antibodies, as well as specialized methods for culturing mammalian cells to improve the yield of therapeutic antibodies.”   

Stay tuned to Big Molecule Watch for further development on this BPCIA case.

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