Sound Prediction & The Case For Xalatan®

Sound Prediction & The Case For Xalatan®

Lena Vartanian is a JD candidate at Osgoode Hall Law School and is enrolled in Professor Mgbeoji’s Patents class in Fall 2011. As part of the course requirements, students are asked to write a blog on a topic of their choice.

On October 11, 2011, Apotex Inc. announced its latest successful patent challenge, resulting in the removal of an Order of Prohibition for the production and sale of a generic alternative to Xalatan®, in the Canadian market.  After the ruling of the Federal Court of Appeal (FCA), Apo-Latanoprost was released to the Canadian market on October 3, 2011, nearly three years prior to the expiry of the patent held by Pfizer Canada Inc. and Atkiebolag (together known as Pfizer). Although, this decision was clearly a victory for Apotex, Apotex held that the real winner was the Healthcare system, stating in its press release that the “savings to the Healthcare system will be approximately $30 million which the provinces can then reinvest into critical areas of healthcare.” Jack Kay, Apotex president stated,

We are proud that our legal victory and launch will deliver needed savings to the healthcare system…It's only through the support of pharmacy as well as the public and private drug plans, that Apotex can continue to take on patent challenges to deliver cost saving medications to market sooner.

Application Court

On September 12, 1989, Pfizer Canada Inc. and Pharmacia Atkiebolag filed the ‘132 patent. This patent addressed certain prostaglandin derivatives and their use for the treatment of glaucoma or ocular hypertension. Prostaglandins are naturally occurring substances, which can be found in human and animal tissues. Lantanoprost was the compound claimed in the ‘132 patent and is a prostoglandin derivative. The ‘132 patent contains 38 claims.

Prior to the introduction of latanoprost, other drugs were used to treat glaucoma and ocular hypertension. There were, however, various adverse side-effects ranging from tingling to death. Latanoprost was claimed to reduce intraocular pressure, without causing substantial ocular irritation.

Pfizer made an application to the court, for an order prohibiting the Minister of Health from issuing a Notice of Compliance to Apotex, for the production and sale of latanoprost, for which Pfizer held a patent (the ‘132 patent). The application was made subsequent to Apotex filing a Notice of Allegation claiming the ‘132 patent was invalid, and in producing its version of the drug it would not be infringing the patent. Further, Apotex held that the compound was based on chronic use and was invalid for double patenting, anticipation, obviousness, lack of utility, lack of sound prediction and over breath. These claims failed and the Order of Prohibition was granted in favour of Pfizer.

Federal Court of Appeal: Apotex Inc. v. Pfizer Canada Inc., 2011 FCA 236

The appeal by Apotex was from the Order of Prohibition which precluded the Minister of Health from issuing a Notice of Compliance to Apotex. Consequently, Apotex was barred from the production and sale of latanoprost for which Pfizer held a patent (the ‘132 patent). Apotex argued, at the time of filing the ‘132 patent inventors had only conducted “single dose” studies, yet claimed that the compounds could be used chronically without causing any of the adverse side effects of the predecessor drugs. Consequently, Apotex argued that the ‘132 patent was not based on a demonstrated utility, rather, the patent was based on a prediction of chronic treatment without significant side effects. Further, Apotex argued that as a result of the ‘132 patents “failure to disclose a sound line of reasoning to bridge the gap between the factual basis of the patent (the one dose studies) and its promise, it must fail.”

The court applied the three-part test for sound prediction set out in the Supreme Court of Canada decision, Apotex Inc. v. Wellcome 2002 FCC 77 (at paragraph 70). All parts of the test must be met for a patent to survive:

  1. There must be factual underpinnings for the prediction;
  2. There must be an articulable and “sound” line of reasoning from which the desired result can be inferred from the factual basis; and
  3. There must be proper disclosure.

Factual Underpinnings and Proper Disclosure

Trudel JA held that the Application Judge erred in dismissing Apotex’s argument about the soundness of the patent, holding that there was “strong and convincing evidence on record” supporting Apotex’s claim. Trudel JA agreed with Apotex, holding that the Application Judge had discounted Pfizer’s own evidence that glaucoma at the time of filing would have been known by the person skilled in the art (POSITA) to be a chronic condition that required chronic treatment. Consequently, Pfizer had failed to satisfy the factual underpinnings of the promise of the patent, as it was “clearly not a chronic use study.” Trudel JA held on the issue of demonstrated utility and sound prediction that the promise of the patent is chronic use of a compound for a chronic medical condition.

Articulable and Sound Line of Reasoning and Proper Disclosure

The court held that there was no requirement to prove demonstrated utility in the disclosure of the patent, only that the disclosure refer to a study which demonstrates that the patent does what it claims it can do. At the time the ‘132 patent was filed, only “single dose” studies had been conducted on animals and healthy humans. The studies had not been conducted on patients with glaucoma, nor had they been tested for chronic use.  Fatal to Pfizer’s position was the fact that none of Pfizer’s experts had as Trudel JA held, demonstrated “an articulable and sound line of reasoning bridging the gap between the factual basis and the promise of the patent.” Consequently, Trudel JA held the patent invalid as Pfizer had failed to “bridge the gap” between the single doses studies and the claimed chronic use. Trudel JA held the patent invalid on the principle that the patent was not based on demonstrated utility rather it was based on a prediction which in this case was not sound.

Case Analysis

In attempting to distinguish this decision from the seminal decision of the Supreme Court in Apotex Inc. v. Wellcome, 2002 SCC 77, the court held that there was a “factual foundation” for the claims in the patent, and thus the patent was valid and infringed. The drug AZT had been tested on human cells in vitro as well as on mouse cells. Consequently, the court held that the data provided by these tests, was sufficient to ground a factual foundation for a sound prediction of the claims. The court in Pfizer seemed rather to focus on the intended use of the drug for a chronic condition as a basis to invalidate the patent. The court held that the disclosure must refer to a study that demonstrates that the patent does what it claims it can do. The court held that Pfizer had failed to meet this test, as the drug had not been used or tested on any patients suffering from glaucoma. Consequently, the court held that the basis of the patent was a prediction, which was not sound.

Pfizer argued that the treatment and use of the drug itself was a matter to be left to physicians to determine and not a matter for the Court to decide in its determination of the construction of the claims. Pfizer also argued that adopting the position that the drug would be used for the treatment of a chronic condition, would amount to “reading in” a chronic element into the claims. However, Pfizer’s own expert Dr. Rechtner, had testified that “implicit in the treatment of glaucoma or ocular hypertension, is chronic treatment.”

It seems that this decision may limit the scope for claims of sound prediction. However, it seems that the threshold remains the same namely, the courts require “an articulable and sound line of reasoning bridging the gap between the factual basis and the promise of the patent.” In this decision, it seems that the seminal finding was that the factual foundation could extend to the intended therapeutic use implicit in a drug.

On October 17, 2011, Pfizer Canada Inc. filed an application to the Supreme Court of Canada to appeal the decision for Xalatan®.

In recent news, Pfizer has entered into the generics marketplace through the creation of the division GenMed, who is expected to produce generic versions of drugs. Could this have been a strategic way for Pfizer to neutralize the economic effects of orders by courts invalidating their patents? It is interesting to note that in this circumstance, a loss of a patent may not necessarily equal a loss in profits.

Judicial Treatment After the Decision

The decision Astrazeneca Canada Inc. v. Mylan Pharmaceuticals ULC 2011 FC 1023 came just days after this ruling and in that decision the Justice agreed that the disclosure requirement can be satisfied by simply making reference to a test or study that demonstrates utility.