For Drug Treatment Patents: Prior Art Must Show Efficacy

OSI Pharma v. Apotex Inc. (Fed. Cir. 2019)

New use of a known compound: This decision focuses on OSI’s U.S. Patent 6,900,221 — a method for treating non small cell lung cancer (NSCLC) with the drug erlotinib (sold by OSI as Tarceva).  In the US dosage is about $200 per day that continues “until disease progression or unacceptable toxicity.”

44. A method for the treatment of NSCLC … comprising administering to [a] mammal a therapeutically effective amount of a pharmaceutical composition comprised of at [erlotinib] and a carrier.

Apotex petitioned the USPTO to cancel several claims, including Claim 44 so that it could begin marketing a generic version.  The PTAB agreed to hear the case and eventually cancelled the claims — finding them obvious when laid next to a prior patent (Schnur) in view either of an academic review article on anticancer drug targets (Gibbs) or OSI’s own 10-K (OSI SEC filing).

Schnur lists Erlotinib as a preferred compound for treating cancer in mammals — and note that the class of drugs (erbB) is good for treating human tumors, including “renal, liver, kidney, bladder, breast, gastric, ovarian, colorectal, prostate, pancreatic, lung, vulval, thyroid, hepatic carcinomas, sarcomas, glioblastomas, various head and
neck tumors.” (Lung emphasized in the court decision, but not in the original prior art). Schnur discloses lung cancer treatment – but does not particularly discuss “non small cell lung cancer.”

Gibbs is a review of prior publications and makes the conclusion that erlotinib (and a parallel compound) “appear to have good anti-cancer activity in preclinical models … particularly in patients with non-small cell lung cancer.”  However, when the Federal Circuit looked-into the articles cited by Gibbs — none of them provided any “data regarding the use of erlotinib to treat NSCLC.”  OSI also hired Gibbs to provide a declaration that he was “not aware of any published abstracts or articles describing the clinical or preclinical response of a NSCLC tumor to [erlotinib] that were available as of the time my article was published, and I reviewed no such abstracts or articles in drafting my article.”

The SEC Filing by the patentee is a prior printed publication from more than 1 year before OSI’s filing date. The Filing states that the company is pursuing research on Erlotinib “which targets a variety of cancers including ovarian, pancreatic, non-small cell lung and head and neck. . . . [The drug] is a potent, selective and orally active inhibitor of . . . a key oncogene in these cancers.”  The SEC Filing also indicates that Phase I safety trials had been completed and Phase II clinical trials were ongoing.  The SEC filing does not include any “DATA.”

For the Board, the combination of these references rendered the broad claim 44 obvious — the claim just requires administration of “a therapeutically effective” of the drug and a carrier.

On appeal, however, the Federal Circuit has reversed — holding that the references did not create a “reasonable expectation of success.”  As such, the Board’s factual conclusion was not supported by substantial evidence.

Over the past several years, the Federal Circuit has been rebuilding its obviousness doctrine post-KSR.  The court now asks two key questions of fact: would a person of ordinary skill in the art (1) have been motivated to combine/modify the prior art teachings in order to make the invention; and (2) have had a reasonable expectation of success in doing so.

The combination of references state rather plainly that erlotinib is believed to has anti-cancer activity against non-small cell lung cancer and that the drug is safe (enough).  On appeal, however, the Federal Circuit rejected the obviousness claim because the prior art did not provide any evidence that the drug would work in humans. “These references thus contain no data or other promising information regarding erlotinib’s efficacy in treating NSCLC.” In its explanation, the court notes that this area is “highly unpredictable” — 99.5% failure rate of NSCLC treatments entering Phase II.

The court concludes with a caveat — attempting to cabin-in this ruling:

To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring “absolute predictability of success.” We conclude only that, on these particular facts, a reasonable fact finder could not find a reasonable expectation of success. The Board’s finding is thus not supported by substantial evidence, and accordingly we reverse its obviousness determination.

The decision here has a substantial amount of merit.

What gives me a lump in my throat is that the prior art discloses almost exactly what was claimed in these broad claims — with the addition of the functional language “therapeutically effective” amount.

50 thoughts on “For Drug Treatment Patents: Prior Art Must Show Efficacy

  1. 6

    Like in KSR, the Federal Circuit is again applying a doctrine too rigidly. 103 requires that a claim be not obvious to a PHOSITA; it is silent regarding a evidence of motivation to modify/combine teachings, and it is silent regarding evidence of a reasonable expectation of success.
    Like in KSR, the Federal Circuit could again be reaching a result that is not in agreement with the requirement of non-obvious to a PHOSITA set forth by Congress in 103 if the prior art would have made the invention easy to discover without undue experimentation.

  2. 5

    About time someone held the prior art to the same standard as the patent claim: if you haven’t shown the claimed invention is likely to work, you don’t get a patent, so why should you be denied a patent because the prior art – cobbled together in hindsight in view of your claim – suggests possibly doing what you claim (among many possible suggestions) but doesn’t make it seem like likely that that what you’re now claiming will work?

    Of course Judges Newman and Stoll were on the panel (not that Dennis told us that, he seems to think the panel composition isn’t worth mentioning). I’m surprised Judge Taranto agreed with them, but I’m not complaining.

    It’s too bad we don’t have more CAFC decisions like this one. But fear not, those of you who don’t like new drugs, I’m sure TC 1600 will continue to generally ignore decisions like this one.

  3. 4

    So … the President was widely known to be a path 0 logical li @r and a self-enriching criminal and scam artist, even before he landed the nomination for leader of his terminally diseased political party.

    What does it mean for Fraud Iancu and the credibility of his “leadership” at the PTO (where we has evidently decided to simply ignore the law to satisfy his preferred “customers” and friends)?

    Or do we pretend that there are “good” Re pu k k k es because it makes the c 0 cktail parties more fun?

    1. 4.1

      This thinly veiled rant is noted.

    2. 4.2

      MM brosef, did you hear? While you were talking about how good republicans are, your dem friends were proposing eating babies and aborting third world children to stop the climate catastrophe (which we all know is and was always only being caused by the ebil ones).

      link to twitter.com

  4. 3

    I will not make myself very popular among my pharma colleagues by saying this, but when I see “pharmaceutically effective amount” (or “therapeutically effective amount,” or “remission inducing dose,” or suchlike), I read these words as §112(f) limitations. If the spec discloses actual weights or concentrations that are shown to work (i.e., induce remission, dull pain, etc—whatever the application defines the end that the therapy seeks to effect), then the limitation reads on that weight or concentration (and equivalents). If no such weight or concentration is disclosed, then the claim simply fails as indefinite.

    1. 3.1

      Indefinite is the lesser issue.

      How about possession?
      How about utility?

      How about these things at the time of filing?

      What was that number, 99.5%…?

      1. 3.1.1

        … in other words, even if there are “definite” amounts/weights/concentrations etc, the 99.5% figure is DAMMING.

  5. 2

    If you want evidence….

    Prepare to HAVE evidence for when you file.

    You know, to show possession and utility, instead of a “research project.”

    Would it be a good time to quote that industry insider who was stating that 90% of items fail at the FDA trial stage (well,well, well, after possession/utility is mandated at the time of filing)…..?

    1. 2.1

      … looks like we don’t even have to go back to that industry insider (from the very article here):

      In its explanation, the court notes that this area is “highly unpredictable” — 99.5% failure rate of NSCLC treatments entering Phase II.

      I wonder how many of those 99.5% already had patents on file?

    2. 2.2

      Great advice for a change. It’s the same advice I give to all my clients.

      1. 2.2.1

        Did you want to take a shot at answering the question of:

        …how many of those 99.5% already had patents on file?

        1. 2.2.1.1

          I will. Probably most of them. Some will claim a treatment for a human disease, others will claim a mechanism of action implicated in that human disease.

          Below is my experience of the continuum of “possession” in the biotech arts.

          Because the art is unpredictable, there is a balance between what an expert in the field of science will attest to given the amount of pre-clinical (non-human) data available and the scope of the claim. For example, I think I have said this before, but if your drug restores memory in a rat T-maze (google it) and I try to claim with just this data a cure for Alzheimer’s, a group of neurological experts would not agree that this is sufficient data to support the claim. More data is needed because of the uncertain of the science and disease.

          In the other extreme, I know of a disease characterized by loss of production of a specific protein (call it “big toe” disease), and that inability to produce the protein is caused by a genetic mutation. I develop a human cell line with that mutation and I wash my drug over the cells. The cells start to produce the absent protein. I have a very good argument that i am in possession of a drug that treats human big toe disease. The idopathology of the disease is well-understood.

          1. 2.2.1.1.1

            Thanks xtian.

            I actually don’t have problems with Pharma if the claims are commensurate with what is possessed at the filing date (or with ANY art field for such).

            I am perplexed though that (clearly) there is a sizable number of people who don’t even “get” the issue with allowing filing prior to actual possession. And the funny thing is that MANY of these people are the same people so against innovation in the computing arts.

            It’s like a magic wand is waved over the heads of these people destroying any possibility of critical thinking.

    3. 2.3

      If you’re saying that patent applications need to have data from human trials, then you’ve got a great prescription for no new drugs. Human trials have NEVER been the standard for patent applications, b/c you have to file for a patent before you get anywhere near human trials. Some evidence suggesting it MAY work in people, like in vivo results against a particular cancer cell line, is required, and every good patent practitioner I know in this area tells his clients that. But just because it worked in a petri dish doesn’t mean a version that works in people is forthcoming – there may be problems with synthesizing it in pure enough form at sufficiently low cost, or in formulating it, or with dissolution or bioavailability, or toxicity…

      Has mooney been posting under your moniker? This is the kind of thing he would say.

      1. 2.3.1

        If you don’t have utility at the time of filing you don’t have it.

        Patents are not “research plans.”

        It is a fallacy to say “then you won’t have new drugs.”

        It is a fallacy because (like ALL other fields) the race is an even playing field for all comers.

        Malcolm would NOT be saying this, because this is eminently reasonable and based on clear foundations — unlike Malcolm who would base his point on feelings and nothing else (I just have never bought into the “but its medicine” waiver of possession at time of filing.

        And again note – this is the second time in short order that the
        F
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        at greater than 95% exposes the fallacy.

        Don’t whine about “no new drugs” and don’t file before you possess (like everyone else that PROPERLY files does so wait).

        It really isn’t too much to ask.

      2. 2.3.2

        To be clear,

        b/c you have to file for a patent before you get anywhere near human trials.

        IS

        the fallacy and is something NO other art field gets away with.

      3. 2.3.3

        “If you’re saying that patent applications need to have data from human trials…”

        Don’t expect him to say anything. He likes to make noises on this subject without specifically articulating a theory of how such claims fail on utility.

        1. 2.3.3.1

          Ben,

          Pretty sure that THAT 99.5%
          F
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          U
          R
          E
          rate speaks pretty clear all on its own.

          Or do you think that Pharma should have a pass on the actual utility possesses at the time of filing?

          Will YOU be the quiet one (while accusing others of being quiet)…?

          1. 2.3.3.1.1

            Do you recognize that you’re refusing to articulate the specific argument or are you too divorced from reality to see that?

            Anyways, Atari, 2.3.3.1 confirms what I said at 2.3.3: don’t expect anon to specifically articulate the deficiency he sees in these claims.

            1. 2.3.3.1.1.1

              Do you recognize that you’re refusing to articulate the specific argument or are you too divorced from reality to see that?

              YOU are the one that is divorced from reality.

              It is beyond clear what my position is: JUST LIKE ALL OTHER ART FIELDS, one must possess the utility of the claimed invention at the time of filing.

              The deficiency of ANY claims (and I of course am speaking globally, and NOT merely to “these claims”), occurs when the utility is not possessed at the time of filing.

              You (the royal you), want to ‘whine’ about unpredictability, or that it is SOOO hard to have the actual desired utility (as MUST be shown to the FDA)? then DON’T FILE until you actually possess THAT utility.

              As I noted at the start of this sub-thread</I patents are NOT for mere research projects with the “showing” years after filing.

              The articulation is there, it is definitely a YOU problem that you seem unable to grasp it.

              1. 2.3.3.1.1.1.1

                Since you refuse to articulate your position, let me help you with a prompt.

                Can you explain how an application’s utility is related to phase three clinical trials of the subject of the application?

                1. Ben,

                  Stop your fallacy. I have articulated the position and put a point to you that you have refused to engage.

                  The “help” that you should offer is to answer the question put to you. Don’t be looking for “prompts” or other excuses for you not to engage.

                  As for that “prompt:”

                  The failure at Phase III is a direct indicator that no utility was EVER possessed.

                  If you claim “an effective amount” and the test shows that you don’t have an effective amount, then you never had an effective amount, and certainly not at the preceding time of filing – that time of filing being the critical time at which point possession of the actual effective amount was required.

                2. “If you claim “an effective amount” and the test shows that you don’t have an effective amount, then you never had an effective amount, and certainly not at the preceding time of filing – that time of filing being the critical time at which point possession of the actual effective amount was required.”

                  But failing human trials is not necessarily indicative of “no effective amount”. Drugs can fail clinical trials because their efficacy is of limited statistical significance or because of side effects. Those findings do not speak to the pharmocological activity disclosed having no utility.

                3. The utility is not separable because “we cured the disease but the patient died.”

                  That is NOT possessing utility.

                4. Anyone reading this can see that you’re only addressing a limited subset of reasons why a drug may fail clinical trials.

                  Even within that subset, you’re wrong. A drug which eliminates all symptoms of late stage multiple sclerosis but which kills 100% of subjects in 2 months has a clear utility. I don’t think even you could disagree with that.

                  You appear to be using some sort of utility analysis which considers both the positives and negatives of an invention. Do you really want this applied in all fields? Should we question the utility of a fire hose nozzle which sprays better but weighs more? Should we question the utility of a GUI which requires fewer clicks but which confuses new users? I think not.

                5. Whether or not I am addressing a limited subset is a non-sequitur to the FACT that a
                  F
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                  shows that a claimed possession was not there AT THE TIME OF FILING.

                  You either have it or you do not have it. If you do not have it, then guess what – you do not have it (no matter the reason, no matter how “limited a subset”).

                6. I am more than sure that k illing the patient DOES NOT COUNT for utility.

                  This is NOT a matter of engineering trade-off of various features (put your strawman away).

                7. Why isn’t it just another trade-off? A drug which cures alzheimers but which kills 5% of patients has a plain utility and some downsides. You’re saying that the law requires the evaluation of that tradeoff to determine utility. If that’s true, the weight of the improved nozzle must be a factor in utility.

                8. Lol – do you really think human life is just a design variable like weight of an object?

                  Do you think about what you are posting?

                9. I’m unaware of any reason why it should be treated as “special” in the determination of utility, and you aren’t exactly helping by articulating a reason.

                  I think it is clear that there are human beings who would want to be able to take a pill to cure their M.S. even if there was a chance it would kill them. I think to act like such a pill has no utility is itself a devaluation of their humanity. But to each their own.

                  But fine, “death” is a special case for you.

                  Does the utility of an improved car engine depend on the chances it’ll explode and kill its operators? At what point does the danger override the improvement? If Ford won’t adopt the improved engine because it doesn’t meet Ford’s safety standards, does that demonstrate a lack of utility?

                10. Ben,

                  You need to move the goalposts back.

                  You accuse me of “You appear to be using some sort of utility analysis which considers both the positives and negatives of an invention.” and then YOU set your arguments to this edict.

                  My point is far simpler here: the claimed item (and extendable to most Pharma of the type that I am against) does NOT have the utility as per the claim AT THE TIME OF FILING as shown in subsequent testing.

                  Death IS a subset, but clearly, it is not the only determinative in that the specific and factual nature is that the claims DO NOT reach actually having the utility at point.

                  Do you know of ANY other art field that even remotely comes close to a Pharma
                  F
                  A
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                  rate of 99.5%?

                  Anything that comes to half of that?

                  Anything that comes to a tenth of that?

                  And yet for some odd reason, you persist in both challenging me AND not grasping the points provided to you.

                  For you, that “magic wand” must have been waved over your head with extra force.

                11. A drug which… but which kills 100% of subjects in 2 months has a clear utility.

                  What is the art unit for Dr. Kevorkian implements?

            2. 2.3.3.1.1.2

              Ben,

              Why don’t YOU articulate an answer to the direct question that I put to your “upvote” buddy at 2.2.1…?

              Maybe If you did, you wouldn’t be whining so much (and be able to see that my articulation is already there).

              1. 2.3.3.1.1.2.1

                Just answer the question, Bildo.

              2. 2.3.3.1.1.2.2

                I’m pretty sure now that you don’t have an answer to the question! Not going to waste my time further.

                1. But, no doubt, your head feels more clear now, for that gentle beating you just gave it against that brick wall…

                2. …and the inte11ectual chimes in on a matter he professes that he cannot even see….

                  Great job again, Greg.

              3. 2.3.3.1.1.2.3

                The two people asked to answer my question above BOTH don’t answer that question and whine that I haven’t answered a question (or to be more precise, have not articulated a position) that I have clearly articulated…

                Too funny.

                Malcolm and Malcolm-follower/up-voter Ben — maybe if you two actually stop playing the Accuse Others game and answer the question that I first put to you, you may be able to grasp the articulation already on the table.

                Give it a try (rather than whine and play your Accuse Others game).

  6. 1

    Well, Dennis, I think you identified the major shortcoming of this decision (which the panel goofed on).

    The patentee here is trying to have it both ways … because they failed to file their application in a timely manner. In a just system, you wouldn’t be able to make the statements in the SEC filing and then argue there was “no reasonable expectation of success” of a method that is as broadly claimed as the method here.

    Somebody isn’t telling the truth. Unfortunately one of those people is Judge Newman who really needs to retire as soon as President Warren is elected.

    1. 1.1

      I am surprised (not really) that Malcolm takes a shot at Judge Newman, with the “softball” slowly coming across the middle of the plate of:

      with the addition of the functional language “therapeutically effective” amount.

      Maybe for Pharma, this is “objective physical structure”

      1. 1.1.1

        Not sure what is so funny. You think based on the disclosure you can’t find agreement between skilled artisans regarding what mass ranges would satisfy the term?

        Contrast that with trying to find agreement between three programmers as to the structure of bits on a hard drive that correspond to “TV show preference values” (as opposed to, say, “medical information”).

        011011000011100011100010101011101101001

        What’s the meaning of the above, Bildo? Take an educated guess. I mean, you’re the expert. And then we’ll ask your bff NW for his deeply informed opinion.

        1. 1.1.1.1

          What I think is “funny” is your abject cognitive dissonance when it comes to a certain particular type of innovation — AND the fact that your behavior is so utterly Trump-like.

          The two really go together and explain your pathology so well.

          1. 1.1.1.1.1

            What does the term “Trump-like” mean to you, Bildo?

            Be specific and give examples of Spraytan R@perman’s own behavior to illustrate the different aspects.

            Have your glibertarian heroes called for his impeachment yet, by the way? LOL. Of course not.

            1. 1.1.1.1.1.1

              It matters far less “what it means to me” and far more that your behavior (especially in regards to how YOU view your own behavior) mirrors the psychopathy if the person that so obviously permeates your thinking.

              Perhaps it is that cognitive dissonance “finding a home”…

              1. 1.1.1.1.1.1.1

                Nobody cares what you think about anything, Bildo. We just like to watch you flop around like a disgusting dying fish on a hot dry beach.

                1. Says the one that is doing the flopping (and cannot see the similarity between his behavior and Trump)…

                  Classic.

                2. … plus, Malcolm, YOU were the one that advanced a “what do YOU think” question at post 1.1.1.1.1.

                  Of course, that post of yours was only a deflection, and I treated it as a deflection. It’s hilarious that after I dismissed YOUR deflection and brought you back on point that YOU attempt a denigration BASED on your attempted deflection.

                  I did not “bite” at the strawman you created and yet you still want to beat up that strawman.

                  Even your refusal to see the similarity of your behavior to Trump IS so very Trump-like.

      2. 1.1.2

        If therapeutically effective amount was “objective physical structure” that was known to one of ordinary skill in the art at the time of filing, then I struggle to see how it could also be the point of novelty. Do you want to die on the sword of 112 or on the sword of 103?

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