Pfizer, Inc. v. Apotex, Inc. (Fed. Cir. 2007)

    By Donald Zuhn --

On Monday, the Federal Circuit denied a combined petition for panel rehearing and rehearing en banc filed by Plaintiff-Appellee Pfizer, Inc.  The Federal Circuit's denial of Pfizer's petition for rehearing en banc was not unanimous, with Judges Newman, Lourie, and Rader each writing their own dissent.

Pfizer had been seeking a rehearing of the Federal Circuit's earlier determination that U.S. Patent No. 4,879,303 (the '303 patent) was obvious in view of U.S. Patent No. 4,572,909 (the '909 patent) and Berge, 1977, "Pharmaceutical Salts," J. Pharm. Sci., 66:1-19 (Berge) (as previously reported by Patent Docs).  Pfizer's '303 patent relates to amlodipine besylate, an acid addition salt of amlodipine that does not exhibit the instability and stickiness in tablet form of amlodipine maleate (an acid addition salt of amlodipine disclosed in Pfizer's '909 patent).

The District Court determined that amlodipine besylate was nonobvious, concluding that "[t]here is no reliable way of predicting the influence of a particular salt species on the behavior of a parent compound," and further, that amlodipine besylate "clearly and unexpectedly illustrates a superior combination of properties when compared to [amlodipine maleate]."  On appeal, a panel consisting of Chief Judge Michel and Judges Mayer and Linn reversed, stating that "[a]t most . . . Pfizer engaged in routine, verification testing to optimize selection of one of several known and clearly suggested pharmaceutically-acceptable salts to ease its commercial manufacturing and marketing of the tablet form of the therapeutic amlodipine."

In dissenting from the denial of a rehearing en banc, Judge Newman stated that a rehearing en banc was necessary because "the panel's statement of the applicable law and its application to the facts of this case are inconsistent with the court's precedent."  In particular, Judge Newman concluded that the panel, in reaching its decision, had (1) applied "the long-discredited 'obvious to try' standard . . . in direct conflict with precedent," (2) declined to give weight to "acknowledged 'secondary considerations' of unexpected results" - namely the stability and lack of stickiness of the besylate salt, and (3) improperly "change[d] the criteria as well as the analysis of patentability."

Because "the panel erred in its legal determinations, and . . . those errors will confuse the law relating to rebuttal of a prima facie case of obviousness of a chemical compound," Judge Lourie concluded that "an en banc hearing is warranted . . . in order to maintain uniformity of the court's decisions and because it presents questions of exceptional importance."  In Judge Lourie's view, the panel erred when it (1) "failed to defer to fact-findings made by the district court that were not clearly erroneous regarding the unexpected properties of amlodipine besylate" and the expectation of success that existed in the art, (2) "improperly placed greater importance on the therapeutic value of a claimed compound over the value of its physical properties" by "conclud[ing] that the improvement of the invention, which related to drug formulation . . . was 'insufficient' to meet the standards of patentability," and (3) contravened the statutory requirement that "[p]atentability shall not be negatived by the manner in which the invention was made" by finding that the invention was the result of routine experimentation, and therefore not patentable.

In the final dissent, Judge Rader noted that "[t]hree separate district courts held trials involving the '303 patent [and] each of those three different district court judges came to the same factual conclusion regarding the nonobviousness of amlodipine besylate."  Agreeing with Judge Lourie, Judge Rader concluded that the District Court's factual determinations were not clearly erroneous, and therefore, that the panel should have deferred to those factual findings.  With regard to the panel's "obvious to try" analysis, Judge Rader felt that "[w]ith unpredictable pharmaceutical inventions, this court more wisely employs a reasonable expectation of success analysis," and since salt selection is unpredictable, there would be no reasonable expectation of success in this case (as three District Court judges had found).  Finally, Judge Rader, like Judge Lourie, believed that the panel had placed far too much emphasis on therapeutic value, essentially disregarding the compound's other beneficial properties.

Pfizer, Inc. v. Apotex, Inc. (Fed. Cir. 2007)
Before: Chief Judge Michel and Circuit Judges Newman, Mayer, Lourie, Rader, Schall, Bryson, Gajarsa, Linn, Dyk, Prost, and Moore
Circuit Judges Newman, Lourie, and Rader each dissenting in a separate opinion

Additional information regarding this case can be found at the Orange Book Blog.

Comments

[Brad Crawford]

If you have a patent on a particular pharmaceutrical salt, formulation, or enantiomer, this case should make you very nervous.

[Nena Neener]

"If you have a patent on a particular pharmaceutrical salt, formulation, or enantiomer, this case should make you very nervous."

Of course, one should have been nervous about such narrow patents that are grounded solely in the alleged "unpredictability" of the chemical arts long before this decision.

The likelihood of such patents crashing in litigation has always been high, i.e., one skilled in the art of litigating would "reasonably expect" them to be found invalid.

[Kevin E, Noonan]

Dear Neener:

"Alleged?" Not so - it is the nature of biology and chemistry to be unpredictable compared with mechanical and electrical arts. It is no coincidence that KSR was an electromechanical case, because the type of "common sense" expectation occurs in these arts. If we ignore the fact that making salts etc. can be (not has to be) unexpected we lose the advantages of further development of new formulations of old drugs.

And, if you are worried about the types of activities characterized by Nexium, or (fill in the blank)-SR type drugs, remember that people used Prilosec for years, and when it went off patent there was the Schwarz Pharma generic and then the OTC, so no one was forced to take Nexium. The Pfizer case is an anomaly since the District Court found non-obviousness. Provided there is a patentable advantage to a new formulation it should be patentable, unless (as the CAFC found in Apotex), the resulting salt worked precisely as it was expected to.