Procter & Gamble v. Teva Pharmaceuticals (CAFC 2008-1404, -1405, -1406) precedential

Risedronate, the subject of the contested claims, is a member of a group of compounds referred to as bisphosphonates. Bisphosphonates, in general, are active in inhibiting bone resorption. The first two promising bisphosphonates studied for the treatment of metabolic bone diseases, etidronate (EHDP) and clodronate, had clinical problems which prevented their commercialization. P&G conducted a significant amount of experimentation involving hundreds of different bisphosphonate compounds, but could not predict the efficacy or toxicity of the new compounds. Eventually, researchers at P&G identified risedronate as a promising drug candidate.

Risedronate is neither claimed nor disclosed in the '406 patent. Instead, the '406 patent, entitled "Regimen for Treating Osteoporosis," claims an intermittent dosing method for treating osteoporosis. As the trial court noted, the '406 patent "addresses the central problem seen in bisphosphonates at the time, namely that they inhibited bone mineralization, by teaching the use of a cyclic administrative regimen to achieve a separation of the benign effect of anti-resorption from the unwanted side effect of anti-mineralization in patients." Procter & Gamble, 536 F. Supp. 2d at 492. The '406 patent lists thirty-six polyphosphonate molecules as treatment candidates and eight preferred compounds for intermittent dosing, including 2-pyr EHDP. Teva contends that the structural similarities between risedronate and 2-pyr EHDP render the challenged claims of the '122 patent obvious.

From the testimony at trial, the district court concluded that the '406 patent would not have led a person of ordinary skill in the art to identify 2-pyr EHDP as the lead compound. In light of the extremely unpredictable nature of bisphosphonates at the time of the invention, the district court also found that a person of ordinary skill in the art would not have been motivated to make the specific molecular modifications to make risedronate. The district court concluded that unexpected results of risedronate's potency and toxicity rebut a claim of obviousness. The district court found that secondary considerations of non-obviousness supported its conclusions. Similarly, the court found that the '122 patent was not invalid for obviousness-type double patenting.

Hence the appeal by Teva.

Obviousness

The flavor of obviousness dished out here emphasizes a reason "to modify a known compound in a particular manner."

Under the U.S. Patent Act, an invention cannot be patented if "the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains." 35 U.S.C. § 103(a). Patents are presumed to be valid. Kao Corp. v. Unilever U.S., Inc., 441 F.3d 963, 968 (Fed. Cir. 2006). A party seeking to invalidate a patent based on obviousness must demonstrate "by clear and convincing evidence that a skilled artisan would have been motivated to combine the teachings of the prior art references to achieve the claimed invention, and that the skilled artisan would have had a reasonable expectation of success in doing so." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1361 (Fed. Cir. 2007). Clear and convincing evidence places in the fact finder "an abiding conviction that the truth of [the] factual contentions are highly probable." Colorado v. New Mexico, 467 U.S. 310, 316 (1984) (quotation marks omitted).

The obviousness determination turns on underlying factual inquiries involving: (1) the scope and content of prior art, (2) differences between claims and prior art, (3) the level of ordinary skill in pertinent art, and (4) secondary considerations such as commercial success and satisfaction of a long-felt need. Graham v. John Deere Co., 383 U.S. 1, 17 (1966). The Supreme Court has explained that the Federal Circuit's "teaching, suggestion or motivation" test provides helpful insight into the obviousness question as long as it is not applied rigidly. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 1741 (2007). Accordingly, under KSR, "it remains necessary to identify some reason that would have led a chemist to modify a known compound in a particular manner to establish prima facie obviousness of a new claimed compound." Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007).

If a patent challenger makes a prima facie showing of obviousness, the owner may rebut based on "unexpected results" by demonstrating "that the claimed invention exhibits some superior property or advantage that a person of ordinary skill in the relevant art would have found surprising or unexpected." In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995).

For combinatorial chemical cases, a lead compound lays a foundation stone for obviousness.

An obviousness argument based on structural similarity between claimed and prior art compounds "clearly depends on a preliminary finding that one of ordinary skill in the art would have selected [the prior art compound] as a lead compound." Takeda, 492 F.3d at 1359; see also Eisai Co. Ltd. v. Dr. Reddy's Labs., Ltd., 533 F.3d 1353, 1359 (Fed. Cir. 2008) (stating that "post-KSR, a prima facie case of obviousness for a chemical compound still, in general, begins with the reasoned identification of a lead compound" in the prior art).

Teva identified a lead compound, 2-pyr EHDP, which the district court resolved would not have been identified by "a person of ordinary skill in the art" as being such a lead. The CAFC topped that with a "so what, it still wouldn't have been obvious," because the CAFC found no motivation to combine.

The question of obviousness "often turns on the structural similarities and differences between the claimed compound and the prior art compound[]." Eisai Co. Ltd. v. Dr. Reddy's Labs., Ltd., 533 F.3d 1353, 1356-57 (Fed. Cir. 2008); see also Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1086 (Fed. Cir. 2008) ("Precedent establishes the analytical procedure whereby a close structural similarity between a new chemical compound and prior art compounds is generally deemed to create a prima facie case of obviousness . . . ."); In re Mayne, 104 F.3d 1339, 1343 (Fed. Cir. 1997) ("Structural relationships often provide the requisite motivation to modify known compounds to obtain new compounds."); In re Payne, 606 F.2d 303, 313-15 (CCPA 1979) (discussing the presumption of obviousness based on close structural similarity).

To successfully argue that a new compound is obvious, the challenger may show "that the prior art would have suggested making the specific molecular modifications necessary to achieve the claimed invention." Takeda, 492 F.3d at 1356 (quotation marks omitted). "In keeping with the flexible nature of the obviousness inquiry, the requisite motivation [to modify] can come from any number of sources." Eisai, 533 F.3d at 1357 (citation omitted). Thus, in addition to structural similarity between the compounds, a prima facie case of obviousness may be shown by "adequate support in the prior art" for the change in structure. In re Grabiak, 769 F.2d 729, 731-32 (Fed. Cir. 1985). As we noted in Takeda:

A known compound may suggest its homolog, analog, or isomer because such compounds often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. . . . [However,] it remains necessary to identify some reason that would have led a chemist to modify a known compound in a particular manner to establish prima facie obviousness of a new claimed compound.

492 F.3d at 1356-57 (citation omitted).

P&G expert witness was convincing that "a person having ordinary skill in the art realized that the properties of bisphosphonates could not be anticipated based on their structure." In other words, there appeared a lack of predictability.

In light of the Supreme Court's instruction in KSR, the Federal Circuit has stated that, "[t]o the extent an art is unpredictable, as the chemical arts often are, KSR's focus on [] 'identified, predictable solutions' may present a difficult hurdle because potential solutions are less likely to be genuinely predictable." Eisai, 533 F.3d 1353, 1359 (quoting KSR, 127 S. Ct. at 1742). The district court found that Teva failed to clear that hurdle, establishing insufficient motivation for a person of ordinary skill to synthesize and test risedronate. This finding was not clearly erroneous.

Then the issue of a "reasonable expectation of success," as indicated by the prior art.

Additionally, there was an insufficient showing that a person of ordinary skill in the art would have had a "reasonable expectation of success" in synthesizing and testing risedronate. PharmaStem, 491 F.3d at 1360. In KSR, the Supreme Court stated that when an obvious modification "leads to the anticipated success," the invention is likely the product of ordinary skill and is obvious under 35 U.S.C. § 103. 127 S. Ct. at 1742. "[O]bviousness cannot be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success." Pfizer, 480 F.3d at 1364 (citing In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985)). Here, the district court's findings indicate that there was no reasonable expectation in 1985 that risedronate would be a successful compound.

Cases following KSR have considered whether a given molecular modification would have been carried out as part of routine testing. See, e.g., Takeda, 492 F.3d at 1360 (discussing the district court's finding that a modification was not known to be beneficial and was not considered "routine"). When a person of ordinary skill is faced with "a finite number of identified, predictable solutions" to a problem and pursues "the known options within his or her technical grasp," the resulting discovery "is likely the product not of innovation but of ordinary skill and common sense." KSR, 127 S. Ct. at 1742. So too, "[g]ranting patent protection to advances that would occur in the ordinary course without real innovation retards progress." Id. at 1741. In other cases, though, researchers can only "vary all parameters or try each of numerous possible choices until one possibly arrive[s] at a successful result, where the prior art [gives] either no indication of which parameters [are] critical or no direction as to which of many possible choices is likely to be successful." In re O'Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988). In such cases, "courts should not succumb to hindsight claims of obviousness." In re Kubin, __ F.3d __, No. 2008-1184, slip op. at 14 (Fed. Cir. Apr. 3, 2009). Similarly, patents are not barred just because it was obvious "to explore a new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it." In re O'Farrell, 853 F.2d at 903.

In this case, there is no credible evidence that the structural modification was routine.

Further, "even if Teva could establish a prima facie case of obviousness, P&G had introduced sufficient evidence of unexpected results to rebut such a showing."

Then, a sometimes shiny secondary consideration of non-obviousness: commercial success in the face of a long-felt need, which, with a bit of intricate prior art history understood, the district court also found.

Secondary considerations of non-obviousness include the commercial success of the invention at issue and its satisfaction of a long-felt need. B.F. Goodrich Co. v. Aircraft Braking Sys. Corp., 72 F.3d 1577, 1582 (Fed. Cir. 1996). The district court found that secondary considerations supported a finding of non-obviousness. When present, such factors "may often be the most probative and cogent evidence [of non-obviousness] in the record." Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1538 (Fed. Cir. 1983).

Obviousness-Type Double Patenting

The '406 patent was found to be prior art to '122.

The double patenting doctrine is designed to prevent a patent owner from extending his exclusive rights to an invention through claims in a later-filed patent that are not patentably distinct from claims in the earlier filed patent. Geneva Pharm., Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373, 1378 (Fed. Cir. 2003.) In general, the obviousness analysis applies to double patenting, except for three distinctions. First, statutory obviousness compares claimed subject matter to the prior art, while non-statutory double patenting compares claims in an earlier patent to claims in a later patent or application. Id. at 1377 n.1. Second, double patenting does not require inquiry into a motivation to modify the prior art. Id. Finally, double patenting does not require inquiry into objective criteria suggesting non-obviousness. Id.

The CAFC panel agreed with the district court that "the claims of the '122 patent are distinct from the claims of the '406 patent."

'122 valid.

Affirmed.