Actonel Patent Validity Affirmed: Nonobviousness of Positional Isomer

Procter & Gamble (P&G) v. Teva Pharmaceuticals (Fed. Cir. 2009)

P&G’s osteoporosis drug Actonel reportedly has $1.5 billion in annual sales. Hoping to manufacture a generic version, Teva challenged P&G’s patent – arguing obviousness in light of a prior P&G patent (the ’406 patent) and obviousness-type double patenting. The district court rejected those challenges, and on appeal the Federal Circuit affirmed the patent’s validity. The patent is set to expire in 2013.

New Compound is Nonobvious: The claimed active compound – risedronate – is a bisphosphonate. In arguing obviousness, Teva pointed to P&G’s ’406 patent which listed “central problems” in using bisphosphonates to treat osteoporosis. Although the prior art patent does not list risedronate, it does suggest the use of thirty-six similar molecules in the same class including one a positional isomer of the claimed risedronate. The positional isomer (2-pyr EHDP) includes the same atoms as risedronate, but those atoms are arranged in a somewhat different order.

In risedronate, the hydroxy-ethane-diphosphonate group is connected to the #3 carbon of a pyridine ring, while in 2-pyr EHDP, the hydroxy-ethane-diphosphonate group is connected to the #2 carbon. Because the nitrogen atom is in a different position in the two molecules, they differ in three dimensional shape, charge distribution and hydrogen bonding properties.

In addition to these structural differences, P&G pointed to “contemporaneous writings from Herbert Fleisch, the preeminent authority on bisphosphonates during the relevant time period.” Fleisch wrote that “every … bisphosphonate, exhibits its own physical-chemical, biological and therapeutic characteristics, so that each bisphosphonate has to be considered on its own. To infer from one compound the effects in another is dangerous and can be misleading.”

On appeal, the Federal Circuit agreed that these differences were sufficient to push development of the new compound beyond the obvious – additionally noting that Teva had not shown that a PHOSITA would have had a “‘reasonable expectation of success’ in synthesizing and testing risedronate.” Here, the court quoted its 1988 O’Farrell decision: “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.’”

This holding further supports the conventional wisdom that the KSR case will have much less impact in the area of pharmaceutical research.

Secondary Factors: In arguing secondary considerations of nonobviousness, TEVA argued that the element of long-felt but unmet need could not be proven because another drug (aledronate) was available prior to risedronate. The Federal Circuit rejected that argument – holding that the need may still have existed because the P&G patent application was filed before the other drug was on the market. “Under Monarch, we look to the filing date of the challenged invention to assess the presence of a long-felt and unmet need.”

Swearing Behind Not Allowed: P&G’s researcher had evidence that it had invented risedronate prior to the filing of the ’406 patent. In particular, the inventor submitted a lab notebook with detailing the structure of risedronate and the procedure for its synthesis. However, the Federal Circuit rejected the evidence because the entry “was unwitnessed and was not corroborated by any other evidence.”

Double Patenting: “Having concluded that risedronate was not obvious under 35 U.S.C. § 103, we similarly conclude that the [risedronate] patent is not invalid for obviousness-type double patenting … [because] the claims of the [risedronate] patent are distinct from the claims of the ’406 patent.”

Further Discussion:

19 thoughts on “Actonel Patent Validity Affirmed: Nonobviousness of Positional Isomer

  1. Understood. The EPO requires a written description of the claimed invention (what technical problem was addressed and solved, and how) by the filing date but recognises that more relevant art can emerge later. In such a case, you can file late-generated evidence to demonstrate unexpected effects, relative to that art, but they have to be effects you had already foreshadowed, in the app as filed. I think that’s pragmatic and fair but, of course, others will differ.

  2. Max,

    Thank you for the note. I limited my comments to the U.S. because the case was a U.S. case. I don’t doubt that the U.S. and the E.P.O. are reasonably consistent in their jurisprudence. I do question whether it is wise to permit considering data generated post-filing as a means for demonstrating nonobviousness at filing. Again, I only claim to have the question here–certainly not the answer.

  3. Don’t know about the US jurisdiction, Llama, but there has been plenty published, about the EPO jurisdiction, on the extent you can use experimental evidence of unexpected effects, created after the filing date. Hesitate before dismissing it as mere PTO stuff. It’s jurisprudence generated over thousands of inter partes, fully contested oppositions, over 25 years, for a 600 million inhabitant jurisdiction, in which the EPO is the final instance. I think Chris Mercer read a Paper on it, to a recent AIPLA Meeting. I think the jurisprudence is relatively clear, and getting clearer.

  4. Breadcrumbs,

    Thanks for the link. This is exactly what I was curious about. The OTDP analysis quite clearly includes post-filing data. Do you know if this is also true for an analysis under section 103– during prosecution, at the time of litigation?

    From what I can tell, the case that you cite (Takeda) appears to allow evidence up to the filing of the application that “triggers” the OTDP analysis. As statutory obviousness (under 103) compares the prior art (not claims in another application), the “trigger” exception would not apply. Accordingly, I would think that (based only on Takeda) evidence of nonobviousness should be limited to that before filing.

    Again, the Court’s quoting of In re Soni in P&G v. Teva does not make this clear. I remain curious as to whether post-filing evidence has been used to rebut obviousness under 103.

    Thanks again for the link Breadcrumbs.

  5. “Is there a clearly stated rule that data showing unexpected results must be at/before filing? Alternatively, is there a case that says it can come after filing?”

    reminds me of a similar issue recently explored at
    link to patentlyo.com

    Your thoughts on that case Nice Llama?

  6. On page 5 of the slip. op., the court discusses rebutting a case of obviousness by showing unexpected results:

    “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).

    Here, the court quotes In re Soni, where that decision uses the present tense “exhibits”. In the Soni case, the evidence of “unexpected results” was from the specification. See In re Soni at 750. Thus, In re Soni appears to only focus on evidence that was present at filing: “the PTO must consider comparative data in the specification….” Id.

    I am not sure whether the data used in this case were AT FILING data or POST-FILING data. In any event, this somewhat loose quoting of In re Soni certainly expands the scope In re Soni’s facts.

    Is there a clearly stated rule that data showing unexpected results must be at/before filing? Alternatively, is there a case that says it can come after filing?

    My concern with allowing the later is that a patent applicant may dramatically extend the time that s/he has to experiment with the invention. This may result in what the SCOTUS has once called a “hunting license”. If post-filing data suffices to show unexpected results, then a patentee could, in theory, wait for litigation to provided objective support for the invention patented.

  7. On page 14 of the slip op., the court notes that an obviousness-type double patenting (“OTDP”) rejection differs from the analysis under 103 in three ways (citing Geneva Pharm., Inc. V. GSK, 349 F.3d 1373, 1378 (Fed. Cir. 2003) in all instances; my paragraph breaks):

    “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.”

    Considering point #1 (compare claim to claim), what’s the point of point #2 (no reason to modify PRIOR ART)? Should we consider whether OTDP requires considering a reason to modify the CLAIM notwithstanding the lack of any requirement to compare the claim to the prior art (see point #1)?

  8. “Looks like EG returned to earth and forgot that he ever left.”

    MM,

    My feet are firmly planted in logic and reason, unlike you who is constantly up in the clouds, spouting “moon law” (like your name suggests).

  9. “Perhaps I have led an isolated life, but quite frankly it never occurred to me that the First Amendment is in “tension” with Title 35, that “gene patents” are deemed outside the classes of subject matter addressed by 101, and that persons who apparently have no reasonable apprehension of being sued as infringers of the patents are named as plaintiffs.”

    Michael,

    You haven’t led an “isolated life” but a logical one which obviously the ACLU has not. These unconstitutionality counts should be tossed quickly under FRCP 12(b)(6)/summary judgment. And the unrepetant, two-faced, fork-tongued ACLU should be sanctioned under FRCP 11 for urging such drivel.

  10. How “sure” are you, GP? Might it not depend on what you have disclosed in your app, about what ETOH does, whether your claim gets rejected or not?

  11. Seems like the correct decision.

    I often get OAs in which the Examiner argues – “Compound Z, in the PA, is like yours, except for the ———.” The blank, of course, is the critical distinction.

    Methanol – kills you.
    Ethanol – just makes you sick.

    But I’m sure if the you applied for a patent on ETOH you’d get a rejection over the wood alcohol if it was in the PA.

  12. “Perhaps the ACLU should ask for input from physicians and scientists…”

    James, perhaps you’re new here, but the majority opinion of at least the most vociferous posters on this blog is that the only input that matters is from patent prosecutors.

  13. “Contrary to populat, uninformed belief (and consistent with SCOTUS’ KSR opinion), the TSM test is still alive and well, at least in the “unpredictable” pharmaceutical area.”

    Looks like EG returned to earth and forgot that he ever left.

  14. Slight typo in paragraph 2 – it’s a “bisphosphonate” (singular).

    @Michael: Even as a non-lawyer, I agree that Amendment I is probably not a fruitful line of argumentation. That said, I agree with the ACLU that patents on genes that are merely discovered, not created, should not stand. I would probably pursue the non-invention angle more heavily. Perhaps the ACLU should ask for input from physicians and scientists…

  15. EG,

    The following has been asserted as being a copy of the ACLU complaint:

    link to graphics8.nytimes.com

    Perhaps I have led an isolated life, but quite frankly it never occurred to me that the First Amendment is in “tension” with Title 35, that “gene patents” are deemed outside the classes of subject matter addressed by 101, and that persons who apparently have no reasonable apprehension of being sued as infringers of the patents are named as plaintiffs.

    Merely as an aside, these inventions appear to have arisen under federal grants to the University of Utah. It is quite interesting to peruse the names of the assignees, one of whom is the USG itself.

  16. Curious,

    Ah yes, more silliness from our friends at the ACLU and PatPub who appear to have nothing better to do than to make it even more difficult to keep American research and innovation here and to create American jobs in an awful economy. Once more the Crichton/Becerra illogic rears its ugly head, and will hopefully be chopped off quickly by a district court judge who has the sense to realize that this suit is “frivolous rhetorical nonsense” that the plaintiffs should have known better not to file.

    Dennis: This suit was reported on the Patent Docs blog.

  17. Contrary to populat, uninformed belief (and consistent with SCOTUS’ KSR opinion), the TSM test is still alive and well, at least in the “unpredictable” pharmaceutical area.

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