Last month, Abbott Laboratories was sued by Bayer AG's HealthCare unit, alleging that drugmaker Abbott Laboratories' best-selling drug, the arthritis drug Humira, infringes on a Bayer patent. Bayer claims that Humira, a recombinant human IgG1 monoclonal antibody specific for human TNF used to treat severe types of arthritis and other immune disorders, infringes on US Pat. No. 5,654,407, issued Aug. 5, 1997.
Bayer's lawsuit was filed six years after Humira was approved for sale in the U.S. in the District Court for the Eastern District of Texas, a venue considered to be very favorable for patent-holders. The lawsuit seeks triple damages for past and future patent infringement, attorney fees and other relief, but does not seek an injunction against sales of Humira. Bayer does not sell any products of its own that compete with Humira.
One issue that may come into play here is the Doctrine of Laches, an equitable defense that arises from a delay in taking action. Laches defenses have been successful in cases in which a patent owner knows about an infringement and then delays many years before bringing suit. Laches typically bars the recovery of any past damages but allows for the recovery of damages arising after the filing of the lawsuit. Once the laches defense has been raised, the plaintiff may still offer evidence that the delay either was reasonable or not prejudicial to the defendant.
Ultimately, the burden of proving laches rests with the defendant, who must prove that there was an unreasonable delay in bringing suit and that this delay prejudiced the defense. However, a rebuttable presumption of laches arises when the patentee waits more than six years from the time when he or she discovered (or reasonably should have discovered) the infringement to file a lawsuit.
The '407 patent, set to expire in 2014, very broadly covers human monoclonal antibodies that bind specifically to human tumor necrosis factor alpha. It is doubtful Bayer suddenly realized that it held the '407 patent. The filing of a lawsuit at this late stage may instead have been prompted by Humira sales, which increased 50 percent to $1.2 billion in the third quarter of 2008 after Abbott received regulatory approval to sell the drug for treatment of psoriasis and juvenile rheumatoid arthritis. In October, the company boosted its forecast for full-year sales to $4.4 billion.
Humira (adalimumab) is the third tumor necrosis factor (TNF) inhibitor, after infliximab and etanercept, to be approved in the U.S. and is used to treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis and plaque psoriasis. It is also used to treat Crohn's disease after other drugs have been tried without successful treatment of symptoms. Humira competes with the drug Remicade, made by Johnson & Johnson's Centocor unit. That company and New York University filed a patent infringement suit against Abbott in April 2007, also in the Eastern District of Texas.
In one new twist, Abbott Labs has now turned around and sued Bayer AG's HealthCare unit, claiming the Bayer patent is invalid, not infringed or unenforceable. The competing lawsuits could set up a dispute over where the case will be heard. Abbott, in its complaint, said the case should be heard in Boston because some of its research and manufacturing of Humira is done at the company's Worcester facility.
It could be that Abbott feels that Humira can be distinguished from the claims of the '407 patent since its monoclonal antibodies were created using phage display technology resulting in an antibody with human-derived heavy and light chain variable regions and human IgG1: constant regions. However, it appears that Humira antibodies are still fully human monoclonal antibodies. So, we could see a detailed battle over the definition of "human" antibodies.
Theoretically, Bayer could go after other producers of anti-TNF-alpha drugs as well such as Enbrel (etanercept), co-marketed by Amgen and Wyeth, and Remicade (infliximab), sold by Schering-Plough and Johnson & Johnson. However, Bayer HealthCare has noted in its complaint that its lawsuit against Abbott is "an exceptional case," whatever that means. Infliximab is actually a chimeric antibody, so it could fall outside of the scope of the "human" claim in the Bayer patent. Likewise, etanercept is not really an antibody, but rather a receptor-Fc fusion protein, which also could fall outside of the scope of Bayer's claims.
Generally, it is possible to make mouse-human hybrid antibodies including chimeric antibodies, where the antibody combines the antigen-binding parts (variable regions) of the mouse antibody with the effector parts (constant regions) of a human antibody, and humanized antibodies, where the antibody combines only the amino acids responsible for making the antigen binding site (the hypervariable regions) of a mouse (or rat) antibody with the rest of a human antibody molecule, thus replacing its own hypervariable regions.
However, you can make transgenic mice that have had human antibody gene loci inserted into their bodies so that they produce fully human, not mouse, antibodies against the antigen and can yield cells that can be fused with myeloma cells to manufacture all-human monoclonal antibodies. Unlike some related technologies that create chimeric or partly humanized proteins, the antibodies produced by these mice are 100 percent human protein. DDN
Stephen Albainy-Jenei is a patent attorney at Frost Brown Todd LLC, serving up chat at PatentBaristas.com. Write him with comments or questions at stephen@patentbaristas.com. Stephen doesn't own shares of companies mentioned in this article.
