Reasonable Expectation of Success as the Post-KSR Nonobviousness Hook

Tris Pharma v. Actavis Labs (Fed. Cir. 2022) (non-precedential opinion)

One quirk of the Patent Act is Section 271(e), which creates infringement liability for simply seeking FDA approval to market a generic version of an already approved drug. 35 USC 271(e).  Here, Actavis filed an Abbreviated New Drug Application (ANDA) seeking FDA approval to market a “liquid methylphenidate (MPH) oral suspension.”  This is the same drug found in Ritalin and used to treat ADHD and other neurological concerns.  This particular formulation is in liquid form and the active ingredient is designed for slow release. (Tris sells under the brand “Quillivant XR”).  Tris responded to the Actavis ANDA by suing under 271(e) and asserting three separate patents.

271(e) actions are seen as a form of declaratory action similar to those taken by courts of equity prior to the merger of law and equity.  As such, there is no Constitutional right to a jury trial in these cases and instead all issues of fact and law are typically determined by a federal district court judge.

The usual jury verdict just requires the ticking of an [X] invalidity box. Likewise, the Federal Circuit regularly decides its cases with by ticking the [X] affirmed without opinion box.  The trick with bench trials though, is that the judge is required to explain its factual and legal conclusions.  Fed. R. Civ. Pro. 52(a).

In an action tried on the facts without a jury or with an advisory jury, the court must find the facts specially and state its conclusions of law separately.

Id.  Here, Judge Connolly (D.Del.) held a bench trial and original sided with the generic manufacturer–finding the asserted claims obvious.  That original decision though was vacated by the Federal Circuit back in 2018 (the also panel slightly amended its decision in a 2019 rehearing order). In its decision, the Federal Circuit found that the district court had failed to explicitly and specifically consider a number of factual disputes and thus remanded for further findings:

[T]he district court failed to make the necessary factual findings and provide sufficient analysis of the parties’ arguments to permit effective appellate review. Specifically, the district court’s opinion merely recites the parties’ arguments but fails to explain or identify which arguments it credits or rejects. We thus cannot reach the merits of whether the Quillivant XR® formulation would have been obvious over the prior art. Rather, we identify gaps in the district court’s opinion and remand for the district court to conduct further factfindings and detailed analysis consistent with this opinion.

Tris Pharma, Inc. v. Actavis Lab’ys FL, Inc., 755 F. App’x 983 (Fed. Cir. 2018) (Tris I).

On remand, the district court accepted further briefing on the merits and then flipped the outcome–this time siding with the patentee.  In particular, the district court held that “Actavis failed to prove by clear and convincing evidence that a person of ordinary skill in the art would have been motivated to combine the prior art references with a reasonable expectation of success.”  On appeal here, the Federal Circuit has affirmed.

Claim 1 of Tris Pharma’s U.S. Patent Nos. 8,465,765 reads as follows:

1. A methylphenidate aqueous extended release oral suspension comprising (1) an immediate release methylphenidate component, (2) a sustained release methylphenidate component, and (3) water, said suspension having a pH of about 3.5 to about 5,

wherein said suspension provides a single mean average plasma concentration peak and a therapeutically effective plasma profile for about 12 hours for methylphenidate, and

wherein the suspension has a pharmacokinetic profile in which the single mean plasma concentration peak for methylphenidate has

  • an area under the curve (AUC)0->∞ of about 114 to about 180 ng-hr/mL,
  • Cmax of about 11 to about 17 ng/mL,
  • Tmax of about 4 to about 5.25 hours, and
  • T1/2 of about 5 to about 7 hours

following a single oral administration of said suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults.

By the time Tris filed its patent application, several other methylphenidate oral formulations & extended release versions were already on the market, including Concerta, Daytrana, Focalin XR, Metadate CD, and Ritalin LA. As with most obviousness cases, the prior art taught all the claim limitations in various subsets, but no single reference disclosed an embodiment with all the limitations.  And, the Federal Circuit agreed with the district court that the patent challenger had failed to show that PHOSITA would have a reasonable expectation of success when attempting to make any of the proffered combinations.

Without delving into the merits here, I only want to note the court’s focus on motivation-to-combine that is now regularly coupled with the requirement that the combination be based upon a “reasonable expectation of success.”   The Federal Circuit (as well as lower courts and the USPTO) have increasingly used the “reasonable expectation of success” as a prong in the obviousness analysis.   The chart below shows the number of Precedential Federal Circuit decisions that discuss a the Reasonable Expectation of Success test as part in the context of an Obviousness determination. As you can see, there was a substantial rise in its use beginning in 2006 during the lead-up to KSR (2007).

I’ll note also that this appears to be a case where forcing the tribunal to fully explain its decision ended up shifting the ultimate result.

17 thoughts on “Reasonable Expectation of Success as the Post-KSR Nonobviousness Hook

  1. 5

    Are there any objective measures for determining if reasonable expectation of success exists? PTAB decisions just seem to state a conclusion rather than analysis .

    1. 5.1

      No.

      Jurisprudence IS a bit shoddy — that’s why I was hoping for an additional tidbit from George.

      1. 5.1.1

        Shoddy is an understatement.

  2. 4

    Of the typical defenses to obviousness addressed in KSR, reasonable expectation of success was one of a few things that survived. For many years, I have trained patent practitioners to make this argument if at all reasonably possible. Those same practitioners noticed a significant increase in allowance of claims after they started to make the argument (lack of reasonable expectation of success). Thus, we see the same trend with the USPTO.

    1. 4.1

      Alright George – you have my attention – care to share any tidbits?

    2. 4.2

      Is rendering the primary reference unsuitable for its intended use a sub-argument of reasonable expectation of success?

      1. 4.2.1

        I tend to view them as separate items — but not a major deal if you do otherwise.

  3. 3

    Reasonable Expectation of Success
    … as to what?

    That’s always been my question. Success as to what? Success as to the combination? Success as to some particular benefit? What are we being successful about?

    I can combine anything with a reasonable expectation of success as to the combination. Put a frog, a chicken egg, and a circuit board into an industrial-strength blender, and I can combine them quite nicely. If all one is looking for is a success as to a combination, then that isn’t much of a test.

    If one is looking as to a particular benefit, can that benefit be recognized in hindsight or must it be in foresight? In KSR, the Supreme Court wrote “rejections on obviousness grounds cannot be sustained by merely conclusory statements; instead there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.” Is “reasonable expectation of success” merely a rewording of this? In other words, does the “rational underpinning” relate to some reasonable expectation success of a particular benefit?

    It would be nice for the Federal Circuit to elucidate on what “reasonable expectation of success” actually refers to when it talks about “success.”

    1. 3.1

      Well stated — mere combination is ALWAYS possible (given then claims being mapped to).

      As such, only providing for such would be akin to a blank check for hindsight reasoning (read that as fulfilling the (apocryphal) Charles H Duell quote).

    2. 3.2

      Exactly. In the art I’m most focused on, “reasonable expectation of success” is always a conclusion that the references can be combined and provide some entirely hindsight benefit. When I point that out, examiners say that it’s ok to have SOME hindsight (the limit of “some” appears to be 100%). I wish I could argue that, if it takes 8 references to find my first claim obvious, it might not be obvious. (And yes, in my art, 6+ references is the common base 103 rejection.)

      1. 3.2.1

        [I]n my art, 6+ references is the common base 103 rejection.

        I am always surprised when litigators and examiners in the software arts tell me that it is impossible to win an obviousness challenge based on more than a 3-way combination. Like yourself, I see 6-, 7-, 8-, or even 10-way combinations on a daily basis.

      2. 3.2.2

        Would love to have George wander back around these parts.

        One of the aspects that I have found helpful in the “very large sets” type of piecemeal puzzle piece approach is that the sum total of everything a reference teaches cannot be violated by any of the other “piece parts” from the large set.

        If one aspect (say, X’Y”) is garnered from a single reference, but that same reference states that AB’C is absolutely necessary, then another reference provided another aspect (say, XY’) that depends on an absence of AB’C cannot be combined because of BOTH: a lack of expectation of success (all of the references must each lead to that expectation), AND a reference cannot be combined if its mode of operation would be destroyed in the operation.

        What you often see (in the method you describe) is a lack of appreciation by examiners that 103 references are NOT merely a collection of 102 references for individual elements — that is just not how 103 works.

        1. 3.2.2.1

          “AND a reference cannot be combined if its mode of operation would be destroyed in the operation.”

          Yeah. Except that the examiner’s response is nuh-uh, and then you have to go through the time and expense of appeal (and don’t bother with a PABRR). And in many cases, the Board affirms.

          1. 3.2.2.1.1

            An answer of “nuh-uh” does not answer the substance of the argument provided.

            Aiming for the correct argument (and there well may be more than one — but INCLUDE the requirement that the Office MUST answer the substance of ALL arguments provided — WILL carry the day at the PTAB [if only to obtain a remand and direction for the Examiner to do their F N job]).

            As to the PABRR, I tend to agree, as attention to the merits of that program has GREATLY slipped by the Office.

            Mayhap a word with the New Director could revive that program’s efficacy.

  4. 2

    So, the reasonable expectation of success should hinge on whether a person can make this composition”:

    A methylphenidate aqueous extended release oral suspension comprising (1) an immediate release methylphenidate component, (2) a sustained release methylphenidate component, and (3) water, said suspension having a pH of about 3.5 to about 5,

    …. and then have a reasonable expectation that the properties of the resulting combination will have the properties recited in what comes after …about 5,”

    The variable seems to be pH, so, we do some routine experimentation and make up several samples in the pH range recited, then look to see if the properties recited are found in any of the mixtures. If so, you’re done, if not, likely you will have an indication that you’re really close. Looking to the prior for guidance, would it be likely to be able to produce a composition having the recited inherent properties ? Probably, IMO. These are crowded arts, suspensions, emulsions, etc.

  5. 1

    “wherein said suspension provides a single mean average plasma concentration peak and a therapeutically effective plasma profile for about 12 hours for methylphenidate, and

    wherein the suspension has a pharmacokinetic profile in which the single mean plasma concentration peak for methylphenidate has

    an area under the curve (AUC)0->∞ of about 114 to about 180 ng-hr/mL,
    Cmax of about 11 to about 17 ng/mL,
    Tmax of about 4 to about 5.25 hours, and
    T1/2 of about 5 to about 7 hours
    following a single oral administration of said suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults.”

    Appears to be claiming a result and a mere recitation of properties inherent in the material.

    Saw this in the polymers area too, a later patent filer takes what is known, and runs new analytical tests, crystallinity, melt flow rate, etc. and puts those analytical results in a claim and gets granted a patent. hahahaha

    1. 1.1

      Re: “Appears to be claiming a result and a mere recitation of properties inherent in the material” [found by later tests of the patented products].
      That’s up to the defendant to prove by clear and convincing evidence obtained from doing such tests. [That may be expensive, but worth it to provide generics with lower cost drugs.]

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