By Andrew Williams --
On Monday, the Federal Circuit issued its decision in Amgen, Inc. v. Ariad Pharmaceuticals, Inc., dealing another blow to Ariad Pharmaceuticals and U.S. Patent No. 6,410,516, directed to certain aspects of the NF-κB transcription factor pathway. Previously, on April 3, the Federal Circuit held that four of the claims of the '516 patent were invalid because of a failure to satisfy the written description requirement. At that time, Patent Docs provided a detailed report of that case. In the present case, the Court affirmed a Delaware District Court's grant of Amgen's motion for summary judgment of non-infringement related to Amgen's Enbrel® (etanercept, a TNF blocker) product.
The technology of the '516 patent relates to gene regulation, and specifically the transcription factor NF-κB. The technology was described in detail in the Ariad v. Lilly opinion, as well as our post regarding that case. Briefly, NF-κB exists in an inactive state in the cytoplasm of a cell when it is bound to its natural inhibitor, IκB. NF-κB is activated when various stimuli external to the cell cause the NF-κB-IκB complex to dissociate, resulting in the transcription factor traveling into the nucleus and binding NF-κB recognition sites found in various promoters. This binding results in the production of many different proteins. When the external stimulus is eventually removed, the cell returns to a state in which NF-κB is inactive. This natural cycle of NF-κB control can become disrupted, resulting in the continual production of protein, often to the detriment of the cell, and can result in various diseases and conditions, ranging from sepsis, cancer, and AIDS.
The '516 patent issued with 203 claims -- 197 of which contain the single step of either "reducing" or "altering" NF-κB activity in cells. In fact, all of the claims at issue in the present case contain the limitation "reducing NF-κB activity in [the] cells." For example, claim 6 reads:
6. A method for diminishing induced NF-κB-mediated intracellular signaling comprising reducing NF-κB activity in cells such that NF-κB-mediated intracellular signaling is diminished.
As another example, claim 18 reads:
18. A method for reducing Interleukin-1 or Tumor Necrosis Factor-α activity in mammalian cells comprising reducing NF-κB activity in the cells so as to reduce intracellular signaling caused by Interleukin-1 or Tumor Necrosis Factor-α in the cells.
The District Court construed this phrase to mean "taking action inside cells to directly inhibit (interfere or block) an NF-κB activity." However, Amgen's Enbrel works outside the cells by binding to free TNF-α, thereby interfering with TNF-α's ability to reach the receptors on the cell surface, resulting in an interference of inducing NF-κB activity. Therefore, because Enbrel works outside the cell, it could not infringe these claims, and the District Court granted Amgen's summary judgment motion of non-infringement.
Ariad argued that the District Court's claim construction was wrong, and that under the proper construction, Enbrel infringes. Judge Moore authored the opinion for the Court, reviewing support for the construction of this claim term in the language of the claims, the context of the entire patent, including the specification, and the prosecution history of the patent. The Court first noted that the ordinary meaning of "reducing NF-κB activity in cells" was unclear. In fact, a simple conclusion that the term means that NF-κB activity must occur in cells would be redundant, because NF-κB activity already only occurs in cells. Ariad took the position that the method must be performed on cells in which NF-κB is present, regardless of where the reducing agent is situated. The Court then reviewed the specification and found that the '516 patent differentiates external influences (such as TNF-α) from intercellular transducers (such as NF-κB), and that the dividing line between these two is the cell membrane. The specification provides hypothetical agents for carrying out this step, including inhibitors, decoy molecules, and dominantly interfering molecules. However, all of these examples act within the cell to reduce NF-κB activity. The specification does not provide any example of agents that could work outside the cell to block external influences from reaching the cell. And, this is exactly what Enbrel does, blocking TNF-α from reaching the cells and interacting with receptors found in the cell membrane.
Most damaging for Ariad was a position that they took in the prosecution history, not of the original patent, but one taken during the currently pending reexamination of the '516 patent. One of the class of prior art molecules asserted as inherently anticipating the '516 claims was antibiotics. Antibiotics work outside the cell by killing bacteria, which subsequently reduces the amount of TNF-α released by cells in response to the bacterial infection with a concomitant reduction in NF-κB activity. As a result, Ariad was in the tenuous position of placing a boundary for where the reducing activity could occur somewhere outside of the cell, to cover Enbrel, but not anywhere outside a cell, in order to leave antibiotics outside of the scope of the claims. The Federal Circuit picked up on a distinction Ariad made in the reexam between two types of claims found in the patent: (a) methods that reduce the induced NF-κB activity by intervening intracellularly at a specific segment within the signaling pathway, and (b) methods that prevent the external inducing stimuli from inducing the intercellular signaling pathway in the first place. Clearly, decoy molecules and dominantly interfering molecules belong to category (a), while antibiotics belong to category (b). Tellingly, however, Ariad lacked any basis in the specification to distinguish Enbrel from antibiotics in this scheme. And, because the patent creates a category of agents that impact "external influences," both Enbrel and antibiotics must be found in this category. Therefore, because the specification and prosecution history, albeit of the reexamination of the '516 patent, "unequivocally point" to a construction whereby the reduction of NF-κB activity occurs within the cells, the Court concluded that the District Court's claim construction was correct. And, as a result, the Federal Circuit affirmed that Enbrel does not infringe the claims at issue.
Finally, in light of the Ariad v. Lilly decision, Amgen moved the Court for affirmance on the alternative ground of collateral estoppel. The Court, however, declined to reach this issue.
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