Ortho-McNeil Pharmaceutical, Inc. v. Teva Pharmaceuticals (Fed. Cir. 2009)(nonprecedential)
Ultracet is the brand name for Ortho's combination pill of the popular drug acetaminophen with light opioid tramadol. The current patent rights are found in Ortho's reissued patent RE 39,221. A prior Federal Circuit decision found that certain generic versions of the drug combination do not infringe the narrowed reissue patent. Link. In the present case involving Teva, the district court issued a summary judgment invalidating the asserted claims as obvious. On appeal, the Federal Circuit vacated and reversed holding that, although the elements of the claim are all "familiar" and were combined "according to known methods," the resulting combination "yield[s more than] predictable results."
A single tablet containing only tramadol and acetaminophen in a fixed dose ratio within the claimed range is not disclosed in the cited prior art. . . . The expert testified that [the Prior Art] Flick's broad statement that tramadol "often" displays synergistic affects when combined with other analgesics would not be enough give one of ordinary skill any expectations whether tramadol combined only with acetaminophen in a 1:5 to 1:19 ratio [as claimed] would exhibit the synergistic effects discovered by Ortho. . . . Ortho's proffered reading of Flick and the German references, as well as expert testimony regarding the understanding of one skilled in the art, raises material questions of fact as to whether a skilled artisan would have found the claimed combination of tramadol and acetaminophen to be obvious.
The majority opinion distinguished Claim 6, and agreed with the lower court that it was obvious. [Claims 1-5 were cancelled in the reissue, so claim 6 is the broadest independent claim.] The prior art taught a 1:10 ratio of tramadol to acetaminophen while the claim 6 required an about 1:5 ratio. In a prior decision, the Federal Circuit interpreted "about" to create a range "from 1:3.6 to 1:7.1." In its obviousness analysis, the court agreed that "the difference between 1:7.1 and 1:10 is so slight" and that the patentee provided no evidence of a "perceptible difference in synergy" between the different ratios. Therefore, that claim remains invalid.
Dissent: Judge Mayer wrote an eloquent dissent, which is partially reproduced below:
The claimed invention does nothing more than combine two well-known pain relievers—acetaminophen and tramadol—in a single tablet. Since the prior art clearly and unequivocally taught that these two analgesics could be combined for effective pain relief, the claimed invention is the epitome of obviousness. I therefore respectfully dissent.
Ortho-McNeil Pharmaceutical, Inc. ("Ortho") did not invent acetaminophen and it did not invent tramadol. Long before the critical date for U.S. Patent No. RE39,221 (the "RE221 patent"), acetaminophen had been combined with other pain relievers, including opioid pain medications such as tramadol. Such compositions include Tylenol® with Codeine, Tylox® (acetaminophen with oxycodone), and Vicodin® (acetaminophen with hydrocone bitartrate). Prior to the effective date of the RE221 patent, it was widely recognized that the combination of a peripherally-acting non-opioid analgesic, such as acetaminophen, and a centrally-acting opioid analgesic, such as tramadol, was an effective way to treat pain that did not respond to the use of non-opioid pain relievers alone.
In fact, a patent issued in 1972 specifically discloses the use of tramadol in combination drugs including phenacetin—which metabolizes into acetaminophen in the human body—to achieve synergistic effects. U.S. Patent No. 3,652,589 (the "Flick patent") teaches that acetaminophen can be combined with other analgesics including phenacetin, and instructs that such combinations are "proven to be of considerable therapeutic value." Example 23 of the Flick patent discloses a combination of phenacetin and acetaminophen in a ratio that falls squarely within that claimed in the RE221 patent. The only alleged difference between the tablet disclosed in the asserted claims of the RE221 patent and the tablet disclosed in example 23 is that the latter also contains two additional ingredients, pentobarbital sodium and ethoxy benzamide. Given that ethoxy benzamide was a known carcinogen and pentobarbital sodium was known to have antagonistic interactions with analgesics, it would have been obvious to remove these two drugs from Flick's formulation.
Indeed, Flick teaches that its four-agent tablet was merely an example of a possible combination tablet, stating that example 23 "illustrates the composition" of a combination tablet "without, however, limiting the same thereto." Flick also teaches that ingredients can be varied as desired. The patent states: "Of course, by variation and calculation of the ingredients tablets and other compositions are prepared containing lower or higher amounts of the essential active agents as desired." Nowhere does Flick state that pentobarbital sodium and ethoxy benzamide are required components in a tramadol/acetaminophen tablet. "If a person of ordinary skill can implement a predictable variation [of the prior art], § 103 likely bars its patentability." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). Here, the removal of pentobarbital sodium and ethoxy benzamide was a predictable and simple variation on the Flick formulation….
In addition to the Flick patent, several other prior art references (the "German references") explicitly teach that tramadol can be combined with acetaminophen to provide effective pain relief. Most of these references discuss combining tramadol and acetaminophen without any additional ingredients. Although the German references involve the administration of two separate tablets and adhere to an individualized, rather than fixed, dosing regimen, these differences are insufficient to preclude a finding of obviousness….
Combining acetaminophen with tramadol was such an expected and logical step that one of Ortho's own research fellows, Fred Minn, M.D., Ph.D., testified that acetaminophen was the "obvious" drug to combine with tramadol and that he could not "think of anybody who didn't think of it." Minn further explained that it was a "natural phenomenon" for Ortho to combine tramadol with acetaminophen since Ortho had a long history "of combining [acetaminophen] with everything in the world."
The situation presented here parallels that presented in Richardson-Vicks Inc. v. Upjohn Co., 122 F.3d 1476, 1480 (Fed. Cir. 1997). There we held that it would have been obvious to combine two drugs, the analgesic ibuprofen and the decongestant pseudoephedrine, in a single tablet since the drugs had been co-administered in the past. There, as here, it was manifestly obvious to combine two well-known drugs—which had previously been administered together—in a single tablet. See In re Diamond, 360 F.2d 214, 217-18 (C.C.P.A. 1966) (concluding that a combination of two therapeutic agents for inflammatory disease was obvious).
Simply put, there is nothing even arguably new about what Ortho claims to have invented. I would affirm.