In Allergan, Inc. v. Sandoz, Inc., the Federal Circuit reversed the district court in part, finding that Allergan’s composition claims and most of its method claims are invalid as obvious, but upholding one method claim because it recites a non-obvious result. Some of the court’s reasoning in this opinion is troubling, and the non-obvious result may be difficult to extrapolate to other cases, but this case illustrates the value of including a variety of claims that focus on different aspects of the same invention.

The Patents At Issue

The patents at issue are four patents listed in the Orange Book for Allergan’s Combigan® product: U.S. Patent 7,642,258, U.S. Patent 7,320,976, U.S. Patent 7,323,463, and U.S. Patent 7,030,149.

The Federal Circuit identified claim 1 of the ’463 patent as representative of the claims that it held invalid:

1. A composition comprising about 0.2% timolol by weight and about 0.5% brimonidine by weight as the sole active agents, in a single composition.

Other claims recite methods of treating glaucoma or ocular hypertension by administering such a composition twice daily, or articles of manufacture comprising packaging material indicating that twice daily administration of the composition is useful for treating glaucoma or ocular hypertension.

The District Court Litigation

The district court litigation was brought under the Hatch-Waxman ANDA litigation framework, after the defendants filed Abbreviated New Drug Applications seeking approval to market generic version of Combigan®, with Paragraph IV certifications against the Allergan patents.

Before trial, the district court granted summary judgment of non-infringement of claims 1-3 of the ’149 patent, and the parties stipulated to infringement of the other asserted claims. Thus, the only issue before the district court was invalidity.

The Federal Circuit summarized the evidence of obviousness as follows:

  • Both timolol and brimonidine were commercially available drugs used for opthamalic conditions at the time of the invention. Moreover, they were available in their claimed concentrations, contained the preservative BAK, and the commercially available form of brimonidine—Alphagan®—contained BAK in the claimed concentration.
  • At the time of the invention, it was known that the serial administration of brimonidine and timolol reduced intraocular pressure greater than either timolol or brimonidine alone.
  • DeSantis expressly provided a motivation to formulate fixed combinations of alpha2-agonists and beta blockers, including timolol, in order to increase patient compliance.

Nevertheless, the district court upheld the claims based on the following findings:

  • [T]here would be no motivation to create the combination product because the FDA did not view patient compliance as a factor for approval.
  • [T]he formulation arts are unpredictable.
  • [T]here were some teachings in the prior art that taught away from the claimed invention.
  • [T]here were secondary considerations that support the finding of nonobviousness including long-felt need and unexpected results.

The Federal Circuit Decision

For all but one of Allergan’s claims, the Federal Circuit rejected each of the findings that supported the district court’s non-obviousness determination, or found the finding insufficient to overcome the evidence supporting obviousness.

The Federal Circuit’s comments on FDA-related motivation are interesting.

FDA approval may be relevant to the obviousness inquiry …. [but] [t]here is no requirement in patent law that the person of ordinary skill be motivated to develop the claimed invention based on a rationale that forms the basis for FDA approval. Motivation to combine may be found in many different places and forms; it cannot be limited to those reasons the FDA sees fit to consider in approving drug applications.

The Federal Circuit’s comments on unexpected results are more troubling.

[The district] court found that there was increased efficacy of the drug and a reduction in side-effects. The court found that previous attempts to treat patients twice per day with brimonidine resulted in a loss of efficacy eight to nine hours post administration. This loss of efficacy is referred to as the “afternoon trough.” The court found that a twice per day dosage regimen of Combigan® unexpectedly did not suffer from the afternoon trough issue.

We agree with the court’s finding that this result was unexpected. However, we do not find that these unexpected results are sufficient to outweigh the other evidence of obviousness as to these formulation claims. While the unexpected benefits of twice a day dosing of the combination formula are relevant to Sandoz’s attack on the validity of the method claims, we do not find it similarly meaningful to our analysis of the formulation claims. There is extensive evidence in the prior art showing the concomitant administration of brimonidine and timolol multiple times per day, that the combination had benefits over the administration of either alone, and that there was a motivation to combine the two to achieve better patient compliance. …. Whether or not that combination also solved problems associated with the afternoon trough, we find the motivation to make the combination was real. Accordingly, we conclude that the claims of the ’463 patent are invalid as obvious.

I am troubled by the court’s conclusion that the claims are obvious despite the unexpected results, particularly because the court does not discredit the evidence of unexpected results or find that the results were not actually unexpected. I also am troubled by the line the court draws between composition claims and method claims, as other Federal Circuit jurisprudence plainly holds that unexpected results achieved when a composition is used in a particular method support non-obviousness of composition claims.

The Federal Circuit reached a different conclusion with regard to method claim 4 of the ’149 patent:

4. A method of reducing the number of daily topical ophthalmic doses of brimondine administered topically to an eye of a person in need thereof for the treatment of glaucoma or ocular hypertension from 3 to 2 times a day without loss of efficacy, wherein the concentration of brimonidine is 0.2% by weight, said method comprising administering said 0.2% brimonidine by weight and 0.5% timolol by weight in a single composition.

The Federal Circuit found no evidence that the claimed method would have been expected to achieve the recited result of twice daily dosing without loss of efficacy. To the contrary,

The record firmly establishes that when brimonidine is dosed twice per day as opposed to three times per day, there is a loss of efficacy in the afternoon—the so called, afternoon trough.

I am concerned with this caveat in the Federal Circuit opinion:

At the outset, we note that Sandoz does not argue that this efficacy limitation is inherent to fixed combination products containing timolol and brimonidine, nor that a dose reduction without loss of efficacy would inherently flow from the obvious fixed-combination of timolol and brimonidine.

*****

The evidence of record does not establish that the dose reduction “from 3 to 2 times a day without loss of efficacy” limitation is an inherent property or a necessary result of the administration of 0.2% brimonidine and 0.5% timolol in a single composition. Of course, it may be true that the mere administration of 0.2% brimonidine and 0.5% timolol twice daily in any fixed combination formulation inherently produces the claimed result. Alternatively, it may also be true that only certain fixed combination formulations produce this result. On the present record, we cannot draw a conclusion in favor of either proposition.

Does this rationale place claim 4 between a rock and a hard place? If the recited result is not inherent to the recited compositions, is the claim adequately described and enabled?

Judge Dyk’s Concurrence-In-Part And Dissent-In-Part

Judge Dyk concurred in the majority decision invalidating most of Allergan’s claims, but dissented from the decision upholding claim 4 of the ’149 patent.

While a new and nonobvious method of using an existing (or obvious) composition may itself be patentable … a newly-discovered result or property of an existing (or obvious) method of use is not patentable. …. In this case, the method of claim 4 consists of a single step: applying a fixed combination of 0.2% brimonidine and 0.5% timolol twice a day. …. Avoiding a “loss of efficacy” is not a separate step, but rather a result of the claimed method. … We should recognize in this case, as we did in Bristol-Myers Squibb [v. Ben Venue Labs (Fed. Cir. 2001)], that “[n]ewly discovered results of known processes directed to the same purpose are not patentable.”

Judge Dyk also criticized the line the majority’s discussion of “inherency.”

The majority appears not to dispute that claiming the result of an otherwise unpatentable process cannot render the process patentable, but suggests that this rule should not apply here because there may exist specific and 0.5% timolol that do not inherently achieve this result. … . Claim 4, however, is not limited to any particular formulation. ….The majority’s argument therefore only suggests that the claim would have been even more clearly obvious, since it would cover the use of compositions that do not even achieve the allegedly unexpected result. “Claims [that] are broad enough to read on obvious subject matter are unpatentable even though they also read on nonobvious subject matter.”

 Building A Wall Around An Invention

This case illustrates the potential value of pursuing a variety of claims that focus on different aspects of the same invention. Allergan asserted several claims from four different patents against the defendants. Although the Federal Circuit invalidated most of Allergan’s claims, it only takes one relevant claim to keep would-be competitors off the market. Here, because the claim 4 of the ’149 patent was upheld, the defendants will not be able to enter the market until that patent expires on April 19, 2022.