Federal Circuit Vacates Ultracet Obviousness Decision

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 Cir. 2009)(nonprecedential)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.

Comments

[Malcolm Mooney]

What a strange case, and thankfully a non-precedential one. It seems unlikely that the ultimate outcome will change on remand. The majority seems very concerned with the lack of unrebutted "expert" testimony". Meanwhile, the district court judge and Judge Mayer, capable of reading references themselves and seeing through the self-serving testimony, seem concerned with getting this lame case off their docket as quickly as possible.

[Federally Circuitous]

Let's see what happens on remand to the district court - Mayer's dissent certainly sets up the possibility for JMOL for the defendants if the jury decides for Ortho.

[Malcolm Mooney]

Did I miss the part where the remarkable "synergistic effects discovered by Ortho" are described in detail? Seems odd that these effects wouldn't be highlighted.

A scintilla of synergy (1 + 1 = 2.1) is rarely enough to overcome a prima facie case of obviousness (old compositions plus teaching that compositions could be combined to advantageous effect). What are we talking here? Two or three-fold improvement over the added effects of each drug?

[Kevin E. Noonan]

It seemed to me that the decision is completely procedural - to decide a summary judgment motion there must be no issue of material fact and all inferences must be decided in favor of the non-movant (here, Ortho).

So the majority sent it back because Teva didn't proffer an expert to rebut Ortho's.

And Mayer cut to the chase for the ultimate decision, which is probably correct on what was discussed in the opinion.

(Not sure "impassioned" isn't a better description than "eloquent", but Judge Mayer certainly got to the point.)

[6]

Yeah that's what I thought too kev. btw, been meaning to respond to your response the other day on your site, but I'm lazy.

[fortramadol]

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.

[EG]

As I see it Ortho's reissue patent is hanging by a thread and a weak one at that. Also, now that all of the original claims are essentially "dead" Ortho faces a significant "intervening rights" issue even if the remaining reissued claims survive.

[4 8 15 16 23 42]

Flick alone doesn't convince me that this is hands-down obvious. Whenever I have a reference disclose multiple embodiments, all of which are different from my claim, but have the Examiner rely on a sentence like "these are merely examples" or "all these examples can be varied as desired" to meet the claim, I at least want a dam good reasoning from the Examiner why the reference would have been varied to meet my specific claim. The German refs seem to do that here by teaching synergy of claim elements, such that Flick + German references seems pretty much textbook obvious. I wonder why the expert testimony went unrebutted at trial?

[hmm]

Although I haven't read the trial, it the case for obviousness would appear to hinge on how "complicated and unpredictable" (per the expert testimony) the drug interactions were and whether there were any counterveiling results (e.g., by changing the ratio of the two remaining active ingredients, by removing one of the two active ingredients removed by the formulation). If there were not, it seems pretty obvious to me...

[Kevin Outterson, BU Law]

My recent short law review essay on Ultracet is in the online version of the Texas Law Review: http://www.texaslrev.com/seealso/volume-87/roin/death-from-the-public-domain.html

I wrote the essay in response to Ben Roin's article (in Texas Law Review) arguing that obviousness should not be a barrier to drug patenting, citing the Ultracet litigation.

[Blimpy]

"A scintilla of synergy (1 + 1 = 2.1) is rarely enough to overcome a prima facie case of obviousness"

I am not familiar with this test... it must have been pulled out of the same place where search teams found that lubricious thermometer...

And besides, who is Mayer to make such off-the-cuff determinations that removing a couple of elements == obviousness? If I were an appeals judge, I would not feel that it was part of my job to play scientist. I agree that a statement such as "these are mere examples" does not amount to a teaching or even a suggestion.

[FirstInFirstOut]

Mayer's dissent has many good points, but doesn't directly address the pertinent claim limitations; the ratios. The issue is not about combining Tramadol and Acet., the issue is the ratio at which they are combined. Not saying Mayer is wrong or right, just noting that at least in the excerpt posted, only the obviousness of ingredient choices is addressed, not their ratio.

[Blimpy]

FirstInFirstOut:

Mayer alleges that example 23 teaches the claimed ratio but in combination with other agents. In reality, by having 4 agents, the total ratios are not the same as they would be with only 2 agents.

I guess that is my point about the science of it. Even if example teaches the ratios as between eachother, but with 2 other agents, as a judge, you can't just arbitrarily remove 2 agents from the teaching and say "there you have it." That is classic hindsight reconstruction (or, in this case deconstruction) of the prior art teachings. There is nothing to say that the 2 agents would behave as taught in Ortho's specification with 2 additional agents.

[Malcolm Mooney]

Blimptroll attempts to find a nut: "Even if example teaches the ratios as between each other, but with 2 other agents, as a judge, you can't just arbitrarily remove 2 agents from the teaching and say "there you have it."

It wasn't "arbitrary". Nice try, though. Maybe you should stick to defending methods for determining who gets to use the toilet next.

"I am not familiar with this test..."

That's because it's not a test, moran.

[Malcolm Mooney]

"I wrote the essay in response to Ben Roin's article (in Texas Law Review) arguing that obviousness should not be a barrier to drug patenting, citing the Ultracet litigation"

I'm sorry to hear it. Points for being honest, I guess.

[don't bother]

"I'm sorry to hear it. Points for being honest, I guess."

Uhm, Ben Roin is the one arguing that obviousness should not be a barrier to drug patenting.

The poster, Kevin Outterson, wrote an essaying disagreeing with Mr. Roin.

Your reading comprehension blows.

You've been working at the PTO too long, Mooney. Spending too much time conducting interviews with firms that hire former high-level PTO personnel to prosecute reexams. How's the dynamic during those interviews? I hear it's interesting, to say the least.

LOL

[Malcolm Mooney]

"Your reading comprehension blows."

No, it doesn't. The sentence wasn't clear.

"The poster, Kevin Outterson, wrote an essaying disagreeing with Mr. Roin."

I apologize to Mr. Outterson for adding to the confusion. My pity is properly directed at Mr. Roin.

[don't bother]

"No, it doesn't. The sentence wasn't clear."

It wasn't clear to those with poor reading comprehension.

Too many interviews with former high-up PTO personnel has addled your brain.

Let us know when you're eligible to retire from the PTO, Mooney. We'll throw you a party.

[Practitioner]

"It wasn't "arbitrary". Nice try, though. Maybe you should stick to defending methods for determining who gets to use the toilet next."

If it wasn't arbitrary, what was it? I'll give you a clue - it WAS arbitrary.

Mayer simply said the 2 claimed agents were present in the same ratio along with other agents (which really means the 2 claimed agents were NOT present in the claimed ratio), arbitrarily ignoring the presence of the other agents.

"That's because it's not a test, moran."

QED, its just typical Mooney hyperbole and garbage.

You provided absolutely no substance Mooney, just empty and argumentative garbage.

You are truly a sleazebag.

[Freud]

"who gets to use the toilet next."

There you go again with the perverse interest in toilets...

I'd say we need a toilet admission system because so many people are lined up to puke their guts out after reading your constant flow of garbage.

[Just Visiting]

Mayer simply said the 2 claimed agents were present in the same ratio along with other agents (which really means the 2 claimed agents were NOT present in the claimed ratio)"

Not if "ratio" means the ratio between the two claimed agents. Adding four tons of other stuff to a and b wouldn't change the ratio of a to b.

"arbitrarily ignoring the presence of the other agents."

Mayer described reasons to at least try removing the other two agents, and if "obvious to try" is the standard, then Mayer's at least on the right track. This case is probably strictly about the standard for summary judgment rather than about any weighing of the evidence.

[Paul F. Morgan]

This is not about this case in particular, but about the difficulty in getting summary judgments of invalidity in patent suits in general.
Notwithstanding the fact that the KSR decision itself came to the Supreme Court on a summary judgment of 103 obviousness, the CAFC's Chief Judge was quoted at the time as saying that summary judgment would be difficult to sustain with the usual disputed facts on that issue.
That is what happened here. This panel majority simply held that:
"The district court improperly resolved disputed questions of fact in reaching this conclusion. What a reference discloses is a question of fact. Para-Ordnance Mfg., Inc. v. SGS Imps. Int’l, Inc., 73 F.3d 1085, 1088 (Fed. Cir. 1995). The parties dispute ... The parties also dispute..."
However, there WERE some disputed facts in KSR, and if one more judge had joined the dissent here, this S.J. would have been sustained also. Thus, it seems somewhat optional, and certainly requires more work for CAFC judges, to seriously consider in each such case if the allegedly disputed facts are sufficiently immaterial to be able to sustain the S.J.? [Rather than to so easily reverse such S.J.'s to force a multi-million dollar patent trial on ALL possible issues.] What patent suit party is not able to hire an expert willing to testify to unobviousness or obviousness? Should that be nearly as relevant as the teaching contents of the prior art references themselves, which CAFC judges are supposed to have technical assistance to read and understand, unless there is some ambiguity in dispute? The ultimate question of obviousness may also be difficult, but it is a legal issue.

[Malcolm Mooney]

Superb commenting by Mr. Morgan.

[Paul F. Morgan]

Before being tarred and feathered for Mr. Mooney having unexpectedly liked something I said, let me make it clear that if a patent owner has presented comparative data evidence for the unexpected results for a particular specificly claimed ratio of prior known combinable ingredients, in the spec or by affidavit, that would of course be a material fact issue that does require discovery and trial court fact-finding. [It might be nice if that could be bifurcated and tried first in some cases, but that is very unlikely.]

[Anon E. Moose]

>This is not about this case in particular, but
>about the difficulty in getting summary
>judgments of invalidity in patent suits in
>general...

So the moral of the story is - no SJ for defendants sued on laughably obvious patents? Full employment for patent litigators!

[Nice Llama]

One problem is that showing ANY KIND "unexpected results" is almost a certainty because ALL of the properties of a new compounds cannot be accurately predicted. Any new compound will have an array of "unexpected results".

I have not seen a great deal of discussion about WHAT KIND of "unexpected results" are required to show non-obviousness. In my mind, the unexpected results should provide some sort of "unexpected utility", requiring that the unpredicted property yields an additional benefit along the same axis asserted for the invention's utility.

Here, if the ratio affords the patient some advantage *in pain reduction* beyond what one would expect by extrapolating the existing data for the components, then it is likely not obvious.

As Mr. Mooney points out, its not exactly clear what the fantastic results are in this case. I would imagine that if such results really existed then the patentee would have emphasized them more rather than jumping up and down about numerical boundaries that supposedly confine these results.

[Malcolm Mooney]

"I have not seen a great deal of discussion about WHAT KIND of "unexpected results" are required to show non-obviousness. In my mind, the unexpected results should provide some sort of "unexpected utility", requiring that the unpredicted property yields an additional benefit along the same axis asserted for the invention's utility."

Absolutely, because it is nearly always possible to come up with some "unexpected result" that nobody cared about before ("It tastes better to elderly dogs than the slightly lower ratio!"). In a field like this one, the unexpected result of the ratio must be profound to overcome the prima facie case.