Hypothesis alone Does not Make the Results Obvious

by Dennis Crouch

My former bosses Paul Berghoff and Alison Baldwin (at MBHB) won an interesting case today on behalf of Genzyme and its corporate parent Sanofi-Aventis.

Genzyme Corp. v. Dr. Reddy’s Labs., Ltd. (Fed. Cir. 2017)

Genzyme’s patent No. 7,897,590 is an important part of modern stem-cell practice in the treatment of non-Hodgkin’s lymphoma and multiple myeloma.  The patented process stimulates mobilization of a donor’s bone marrow by administering both a “granulocyte-colony stimulating factor” and also plerixafor (See Claim 19).  The plerixafor drug (sold under the brand name Mozobil) is no longer patented, but the treatment protocol is patented.

In the ANDA lawsuit, the generic defendants argued that the asserted claim was obvious.  Following a bench trial (no right to jury trial in ANDA cases), the district court sided with the patentee — finding insufficient evidence of obviousness. On appeal, the Federal Circuit has also affirmed.

For obviousness analysis, the first consideration is typically the scope-and-content of the prior art.  Any reference used must qualify as prior art under Section 102 and must also be considered analogous or pertinent.  The key prior art reference – Hendrix discussed the pharmacokinetics and use of plerixafor – but was focused on use of the drug in HIV treatment.  The district court excluded Hendrix – finding that it was not analogous art since one of skill in the art would not have been looking for this type of drug in researching stem cell mobilization.  On appeal, the Federal Circuit did not review that particular holding – instead finding that even if considered pertinent to an obviousness analysis, it still would not be sufficient to render the claim invalid.

For the Federal Circuit, the basic dispute comes down to whether a person of skill would have a “reasonable expectation of success” – i.e., a reasonable expectation that combining Hendrix with the other references would lead to a treatment that mobilizes stem cells as claimed.

Here, the district court found that a skilled artisan would not have had a reasonable expectation of success that plerixafor would mobilize stem cells. DRL has not shown that this determination was clearly erroneous.

The basic difficulty is that the prior art stem-cell mobilization research focused on a “completely different family of receptors” than those triggered by plerixafor; and that stem cells exhibit “around one hundred different types of receptors.”  Thus, according to the court, it would have been a major leap to use plexifora as described in Hendrix for stem cell mobilization.

The one difficulty with the Federal Circuit and District Court analysis is that this key prior art reference “Hendrix” actually states that the drug may cause stem-cell mobilization.

These combined observations suggest that binding of [plexifora] to CXCR4 may inhibit the chemotactic effects of SDF-1α, causing release of WBCs from the endothelium and/or stem cells from bone marrow.

Hendrix. The Federal Circuit recognizes what’s happening here and does an interesting word dance – attempting to explain-away the statement:

Although Hendrix hypothesized in an isolated sentence, without explanation, that plerixafor may cause stem cell mobilization, the rest of the seven-page article focused on the elevation of WBC counts. . . .  A skilled artisan would have recognized that Hendrix never tested for the presence of stem cells. The primary speculation in Hendrix for the phenomenon associated with elevated WBC counts was “demargination,” which refers to the release of WBCs from the endothelium. This emphasis on demargination is consistent with how an independent group of contemporary researchers perceived Hendrix.

The district court’s finding that stem cell mobilization was highly unpredictable at the time of the invention also runs counter to an expectation of success. In particular, there was great uncertainty about the role of SDF-1 or CXCR-4, if any, in the process of stem cell mobilization. …

Holding of non-obviousness affirmed since there was no reasonable expectation of success.

Note here – Although MBHB does not exert any editorial control over Patently-O, they are the primary advertiser for the site, and my former employer. DC. 

29 thoughts on “Hypothesis alone Does not Make the Results Obvious

  1. 8

    Didn’t the Court in KSR reverse the general understanding and assert that obvious to try (rather than the higher standard: obvious to do) WAS sufficient for a finding of obviousness?

    If the reference says X might work for Y, doesn’t that make X obvious to try?

    Maybe the Fed. Cir. will find its way clear to start ignoring Alice and Mayo too.

    1. 8.1

      Didn’t the Court in KSR reverse the general understanding and assert that obvious to try (rather than the higher standard: obvious to do) WAS sufficient for a finding of obviousness?


      The decision was more subtle than that.

      Instead of an open invitation TO apply “obvious to try,” the Court simply added (that in some situations) “obvious to try” may be available.

      There is a HUGE difference between the situational “may” and the open-ended “WAS sufficient.”

      1. 8.1.1

        Did they give any guidance as to when obvious to try would not be “available.” For instance, did they give any indication that it would not be available when the cited document literally suggests it might work?


          they give any indication that it would not be available when the cited document literally suggests it might work

          Whether they did so (or not), that is not my argument or position.

          I can easily see where – as here – that a cited document literally suggests that something might work that indeed it may be “obvious to try.”

          This may very well be a particular instance (the situational) – as opposed to the open-ended. Maybe you should read my post again to see what I actually said…


          As the court in KSR said:

          “When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.”

          Might show that it was obvious. And the trying must lead to anticipated success (i.e. there still must be a reasonable expectation of success).

          As the court also explained:

          “For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill. ”

          The determination of obviousness requires the resolution of the factual inquiries into 1) the level of ordinary skill in the art; 2) whether there was an apparent reason with rational underpinning to modify/combine the prior art; and 3) whether there was a reasonable expectation of success for one of ordinary skill in so modifying/combining the prior art.

          A determination of obviousness cannot be made on a finding that there was a reason to (try to) modify/combine the prior art. That’s not sufficient.


            Thanks AAA JJ – that’s a fantastic addition of details.

            But let’s look at Les’s point here: I have to wonder why the “obvious to try” argument was not advanced.

            I take the point here that a one-line mention may not be sufficient to show “expectation of success,” but at least the one line should have engendered the attempt at “obvious to try,” which IS a “lower hurdle” than “pure” obviousness.

            If that path were taken, then perhaps the point below (by Malcolm if all people) that the “one line” was present for a reason, and perhaps then the additional support for that reason could have been brought forth.

  2. 7

    Dennis: no right to jury trial in ANDA cases…

    The Federal Circuit certainly has never so held. Oil States might have a lot to say on whether patent owners have a right to a jury trial on validity.

  3. 6

    Seems like the correct decision. The determination that there was an apparent reason to modify/combine the prior art and the determination that there was a reasonable expectation of success in so doing are separate factual inquiries. The objective evidence must support, by a preponderance, both conclusions. Too many examiners, and APJ’s, collapse both inquiries into one, meaning they conclude that because there is evidence that one of ordinary skill in the art would (at least try to) modify/combine the prior art, then that evidence also supports the conclusion that there was a reasonable expectation of success in doing so. Lots of PTAB decisions where the APJ’s conclude that appellant didn’t present any evidence that there wasn’t a reasonable expectation of success. Of course, the burden of proof on that issue is on the examiner, not the appellant.

    1. 6.1

      I love when examiners give as evidence of the separate factual inquiry that the benefits of the individual aspects are (both) the motivation to combine and the expectation of success (merely ‘because’ the individual items are “great,” so why not combine to get the individual benefits?)

      (one could cue Les on the cloth, rope and wood items that could be combined for what each ‘generically” or “conventionally” does of each on their own…)

    2. 6.2

      Mr. JJ, where did the court say that “[t]he objective evidence must support, by a preponderance, both conclusions.” What the court said is that patent invalidity must be established by clear and convincing evidence.

  4. 5

    Disclaimer: I don’t work in this art.
    That said, the reference clearly suggests that the process causes stem-cell mobilization. Forget Bilski, this is obvious under TSM.
    What am I missing?

      1. 5.1.1

        But, if I need to mobilize stem-cells, and the reference suggest that this drug does that, wouldn’t it be reasonable to expect that using the drug to mobile stem-cells would be successful in mobilizing stem-cells? That’s what the reference is suggesting!


              The “prior art suggests!!!!!!” the modification/combination is not the end of the inquiry.


                To your point here (and as an analogue to my post above), an attempt at “obvious to try” may have induced more information for WHY that rather direct and on point (but single sentence) was present, and THAT more developed record MAY have satisfied the additional point that you are (correctly) stressing here.

    1. 4.1

      BUT what about my normal practice of peppering my applications with science fiction and speculation as a good tool to pre-empt or block other applicants?

      In any case, why should “inventions” trump the innovation of my arbitrary speculative imaginations?

      1. 4.1.1

        Those are decent questions – and have been discussed recently between Greg and I.

        (One of the aspects presented is that claims of a granted patent ARE vetted – and even if one ‘goes back’ within two years for more, the “more” is also vetted.)

  5. 2

    The Fed. Cir. panel judges were MOORE, PLAGER, and CHEN (author).

    In hindsight, should the generic have used an IPR rather than an ANDA challenge? The several months of exclusivity isn’t worth much if you don’t win.

  6. 1

    hypothesized in an isolated sentence, without explanation

    I’m curious about this “without explanation” business. Presumably the observations that led to the hypothesis form part of “the explanation” for the hypothesis that stem cells would be mobilized by the drug. Another part of “the explanation” seems to be right there in Hendrix’ observation that, by binding to CXR4, the drug “may inhibit the chemotactic effects of SDF-1α” which appears to be part of a pathway that culminates in the release of stem cells from bone marrow …?

    Maybe this case should be filed right next to that recent CAFC case where the court held that the FDA’s suggestion to a researcher to remove an additive wasn’t enough to show that the resulting mixture was non-obvious.

    1. 1.2

      Well, we both know that the affirmative statement (even if one mere sentence) certainly was not “teaching away.”

    2. 1.3

      MM, I sense that you are right. Someone at the Federal Circuit was carrying water for the patentee for some reason. Perhaps they like the patentee’s attorneys?

      1. 1.3.1

        I wonder if the CAFC is really the party to whom you ought be directing your disappointment? Is it not really the trial judge whom you should accuse of “carrying water” for the patentee?

        The appellant was contesting the “reasonable expectation of success.” Reasonable expectation of success is a question of fact, reviewed for clear error. Cumberland Pharma. v. Mylan LLC, 846 F.3d 1213, 1222 (Fed. Cir. 2017). So, if the appellant wanted a reversal, they needed to show that it was clearly erroneous for the trial court to find that there was no reasonable expectation of success. Sure, the appellant had one line in one paper in their favor, but there were other lines in other papers going the other way. It is not crazy for the CAFC to look at that and say “we cannot say, on this record, that the trial judge committed a clear error.”

        In other words, maybe the trial judge got this wrong (I take no strong position one way or another), but the CAFC almost certainly did all that it was supposed to do on this record, no more, no less.

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