Many readers of this blog will remember one of the first pharmacokinetic (“PK”) patents to be granted and successfully asserted in litigation. The patent was for an extended release formulation of guaifenesin marketed under the brand name Mucinex®. Even though guaifenesin was a very old cold medicine, no one had previously formulated guaifenesin for extended release. The product was a huge success, and the patent created a huge barrier to generic entry because generics had to copy Mucinex’s PK profile, and thereby infringe the patent, to be approved by FDA. See Adams Respiratory Therapeutics, Inc. v. Perrigo Co., 616 F.3d 1283 (Fed. Cir. 2010).
A similar patent strategy was employed Pozen, a North Carolina company that developed several new combination drug products using esomeprazole. Esomeprozole is a well-established proton pump inhibitor used to prevent stomach ulcers. Prior to Pozen’s work, it was well known that non-steroidal anti-inflammatory drugs (“NSAIDs”) caused ulcers and other gastrointestinal problems, and that esomeprazole could prevent those ulcers when administered along with the NSAIDs. Pozen decided to combine naproxen – a well-known NSAID – with esomeprazole into a single tablet, in an extended release dosage form for longer pain relief. It called its new drug Vimovo® and secured several PK patents covering the drug.
One of Pozen’s patents -- U.S. 9,220,698 (the '698 patent) – covered the combination of naproxen and esomeprazole in an extended release dosage form, and described the combination by its PK profile. Claim 1 of the ‘698 patent recited:
1. A method for treating osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis comprising orally administering to a patient in need thereof an AM unit dose form and, 10 hours (+/- 20%) later, a PM unit dose form, wherein: the AM and PM unit dose forms each comprises: naproxen, or a pharmaceutically acceptable salt thereof, in an amount to provide 500 mg of naproxen, and esomeprazole, or a pharmaceutically acceptable salt thereof, in an amount to provide 20 mg of esomeprazole; said esomeprazole, or pharmaceutically acceptable salt thereof, is released from said AM and PM unit dose forms at a pH of 0 or greater,
the AM and PM unit dose forms target:
i) a pharmacokinetic (pk) profile for naproxen where: a) for the AM dose of naproxen, the mean Cmax is 86.2 μg/mL (+/- 20%) and the median Tmax is 3.0 hours (+/- 20%); and b) for the PM dose of naproxen, the mean Cmax is 76.8 μg/mL (+/- 20%) and the median Tmax is 10 hours (+/- 20%); and
ii) a pharmacokinetic (pk) profile for esomeprazole where: a) for the AM dose of esomeprazole, the mean area under the plasma concentration-time curve from when the AM dose is administered to 10 hours (+/- 20%) after the AM dose is administered (AUC0-10,am) is 1216 hr*μg/mL (+/- 20%), b) for the PM dose of esomeprazole, the mean area under the plasma concentration-time curve from when the PM dose is administered to 14 hours (+/- 20%) after the PM dose is administered (AUC0-14,pm) is 919 hr*μg/mL (+/- 20%), and c) the total mean area under the plasma concentration-time curve for esomeprazole from when the AM dose is administered to 24 hours (+/- 20%) after the AM dose is administered (AUC0-24) is 2000 hr*μg/mL (+/- 20%);
and the AM and PM unit dose forms further target a mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period after reaching steady state that is at least about 60%.
The Federal Circuit considered the validity of these claims recently in Horizon Pharma, Inc. v. Reddy's Labs. Inc., 2021 U.S. App. LEXIS 296 (Fed. Cir. Jan. 6, 2021). Of particular note, the Federal Circuit did not question whether Dr. Reddy’s infringed the claims, or whether the claimed combination was obvious.
The sole question on appeal was whether the term “target” rendered the claims indefinite. The Court asked whether it was even possible for a pill to “target” the claimed PK profile and if not, should the claim instead be interpreted to cover a pill that “produces” the claimed PK profile?
Unfortunately for the patent owner, the Federal Circuit had to look only to the dictionary to answer both questions against it. The literal meaning of “to target” is “to set a goal” and, as the District Court held, “pills cannot be said to set goals.”
The patent owner relied heavily on Federal Circuit statements in previous cases that ambiguous claims should be construed to preserve their validity. However, according to the Federal Circuit, there was nothing ambiguous in the meaning of the term “target.” It means to set a goal, and pills cannot set goals. As stated by the Court:
“As the district court explained, both clauses [where “target” appears in the claim] are incomprehensible. Reading the claim literally, a dose form, which is an inanimate object, cannot set a goal. That the proper construction of the claims is nonsensical does not warrant judicial redrafting of the claims.”
The drafter’s choice of words was obviously unfortunate. At a minimum, the drafter should have better explained in the body of the application what was meant by the term “target.” The case teaches us to be very careful in the words we use to describe an invention, and never to use colloquial terms that cannot find support in the dictionary.
