morning yet this court i'd like to focus and three legal issues that the district court three legal heirs that just quote made i mean in deciding this case against the defendants and one sixty seven had in the eight hundred  dispute that there were substantial not infringing uses in this case for the for the product as labeled and the only issue is whether or not that the instead label itself induces infringement based on what it says and the label itself doesn't contain an explicit instruction to administer the drug to the patients with the risk factor what the district court would do you could buy its corruption i mean the pharmaceutical company doesn't instruct the doctors to be something it's gives information it supplies a product and then it provides information that the doctor who used to decide which patients to use  then here you dick ations for you says it's for reduced cockle hospitalization and then it's as if you want to know which patients we think that will occur c section fourteen most of which clinical studies section it's not referring to an instruction only to administer to the patients with the risk factor why should it have to be why should why shouldn't because the inducement for all of the indications that the label says this is a good product a and for be induced by b because under the case law for example the vitamin scase and an instruction that is it results in ambiguity  or results and could result in infringing uses or could not result infringing uses is is not enough to to demonstrate specific intent to induce infringement in in this case so  for for a because you also say you can use it for in another way it's probably a little more subtle than that your honor in that the instruction itself doesn't say you can use it for a or you can use it for b the instruction just self indication is the patient population in europe as in the dance so at all it does this refer you to a clinical trials section that also contains information about your it as an adonis so it's the instruction itself is ambiguous as to what it's telling you to do it's with taylor i'm trying to do anything all it's doing is providing doctors information about what this massive set of scientific studies do and i've just instructed you that's not what goes on in in this world or in general the you don't need that for inducement for encouraging right now that i agree with that i think you do though in a circumstance where there is a where the in the the actual instruction or the what is being described in the label is not is ambiguous here there is there is an a t m so for example if you're with him up to what patients over seventy and with certain risk for years correct so that's one of the that section forty points to potentially maybe more than one population to which the struggle should be administered but that population and the being a study is that least one of the right that's correct so if you're inducement never are not able to be available if you have something that points and encourages this can be used for a or b and you're just in the camps that still be indecent it could be as long as there's enough evidence of intent for b so it could be the vitamin k says it's not enough just that it's not enough there has to be something that you know that i don't miss if that's were a little differently and there were i mean that what we were dealing with in the blender was a little different and but other than section fourteen none of the every occasions or instructions refer to a particular population then we should ignore what's in section fourteen or pay much less attention to it or  was to titrate down there was a there was a positive instead affirmative instruction to titrate down to the lower dose which would lead to infringement it's a little different than here where the instruction would case you get to a point two five mil leader file you use it and if you're a patriot and down to the lower dose you're going to only do it once a day so that's where the extra kind of instruction is is  and here's why the court found that there was no difference as far as obviousness was concerned and there was no in a footnote the court mentioned that that in might have less of a reasonable expectation couple couple of things that you can look at the first issue is the disclosures so there are two disclosures the hormones are two thousand and eight disclosure in the clinical trials act of disclosure both of which lay out every element of this every element was you can't if they are guides you directly to the method if you can't say you can claim you've got an invention by just proving what the art told you it was going to do so reasonable expectation is used as a measure to guard against hindsight and to guard against grabbing elements from multiple different sources when there's no guidance as to how how do you use those elements to get the result in this case that that's not that's not the circumstance here here the method was taught in two prior art publications the entire method was taught with the exception of one thing that is in sufficient case you probably wouldn't be talking about reasonable expectancy that's correct that's we probably wouldn't be talking about it and i think that the issue here then it becomes with that statement and contemporaneous statements in the earth said we expect this to work every can every single one in that case every single one i think maybe i'm just remembering i guess i was remembering to th poorly formulated statement of the hypothesis being tested and no more why it is and judge andrew said i'm persuaded by that why is that clear because i have had the sense under the law would be enough that i would i would add that not only the m p p says that we will presume that it's reasonably expected to succeed if you have an f d a approved protocol because when you're giving the drug to patients the f says i want to make sure that i'm not going to even answer even taking that as a presumption that doesn't mean that a finding to the contrary in a particular case is clear correct which is why i think the  that the way the opinion reads it reads like he ignored them by saying it's just a hypothesis i'm not sure it's just a hypothesis answers the question of whether it's a reasonable expectation well here's what i understood that the district court concluded having heard all the evidence which is yes this is kind of quite a strong statement but we've got the other experts saying this is nothing more than a hypothesis this is how we write hypothesis and the only thing in this article analysis doesn't give me anything it doesn't give me anything if anything and he he used a word like inconsistency so whenever so he looked at the under what appears to be the underlying basis for the for the hypothesis reached us and   i think the error is because because none of the contemporaneous evidence of the times courts there is no none of the statements at the time support that conclusion well how did we supposed to know i mean one of the big fights and one expert says no no no no this is the real deal how we supposed to have value it that you're supposed to evaluate it on a bean and a basis of reasonableness and i think that's where the the clear error problem comes discarded it when he evaluated the post hack analysis and determined that he wouldn't what he did was he determined that that wouldn't get you to a reasonable expectation of success i don't think he he didn't analysis was wrong it just didn't get you where you needed to go that that's how that's how i read his his opinion it wasn't that i would think that this is completely wrong i on and putting it i mean i understand that there are that that some of the statements by santa feely were not public but they are evidence of what someone would expect at the time so it's a what the f d a did was we said we took a look at your it as an s and then we took a look at it in drama and said we want we think you need to do one more study that's what the f d a concluded we think you need to do one more study which is how we know when you know they said we think you need to know because it's so problematic because of the because they were concerned about the andromeda study because it well did i think there's a lot here and i've just found parts of it appendix results and he goes on to i almost read this is almost he was kind of arguing this comes to teaching the way his analysis is evaluation of the study and he bought everything the other side's expert said about those studies completely  what the district court did here as far as how it and that analyzed the studies but with respect to what the court is to the standard is for recently expectation of success the issue is whether or not if you're viewing this as a personal skill in the earth in two thousand and eight or two thousand and nine would you expect when you're given the rumors or are you would you expect this is going to work and yes there were some question isn't quite right i where there whether the person would expect by some probability in the neighborhood of fifty percent maybe a little bit more and have a scientifically reasonable basis for the expectation is that lots of people  assume scientists are among them have expectations that this soon is that they would immediately follow the explanation but this is just kind of a scientific intuition based on past things and now could i tell you what the scientifically reliable basis for that expectation is and i don't think there is a standard for scientific expectation i think there is a reasonable scientific explanation or expectation used in patients by the time homo's or was actually published it are already had then that study had been going on for a while so under those circuits if your question is that does the standard require scientific evidence or some sort of before i have not seen a clinical study protocol or patient information i'm not saying it doesn't happen but i've never seen it done and these cases a long time i've never seen that before and again this is one of those circumstances where they're telling the f d a we expect this to work they're telling patients we expect this to work and now they're standing you're saying we no one expected this to work when they publicly announced that they expected it to work so it's a little bit questionable when you're going to i'm happy to hear what you have to say but if you could just include in that analysis i mean we have don't have that many cases but it seems to me that what they are we agree or disagree with you this goes beyond what it where our cases  investment stuff so could you just address the cases i will just the cases ago but in terms of the factual findings the court found that this prop this product according to the current label is prescribed eighty percent of the time in an infringer manner it found that these are under scrutiny facts and found that when the defendant's product is sold with their labels it will be infringed eighty percent of the time can i ask about that because i have some question of that i thought the number was seventy seven a percent it's time but the question i had about that number was there something in the record just says that the label initially was more specific and included the athena study and then that was taken up so i guess my question was d those prescriptions that comprise the seventy seven to eighty percent could it be that those prescriptions or given at the time were in the instructions in the education clearly pointed you towards the athena study no your honor they have not changed in doctor's us n the defendant's witness said that it did not change the prescribe ing patterns of the drug ok and the last fact that the judge found with respect to intent was that the defendants were aware of the patent and that they spectrum there are those cases where there is no question that the product is going to be used in an infringing manner in those cases you are entitled to presume intent and i think the m g m case from the supreme court at that point clearly and you very rarely see those cases because that's not something that's often litigator on the other end of the spectrum is where the label does not and say anything about the infringing use that's the general amer case i contend that's the vita mix case and then there are cases in between where the label says something about infringing use and at the same time as a substantial non infringing use for example the astra zeneca case where the primary use of the product was not infringing it was twice a day  physician was presented with a patient let's say a seventy five year old patient that was on that had diabetes and directly and wanted to keep that patient out of the hospital the physician would know if you think first of all based on the prior art no other anti growth make drug ever treated that condition to keep the patient out of the hospital never shown to do that fact all of them were shown not to have that effect second also kill yes that's right it kill people and then so he would consider never own label and you can see right in the indication that it is meant for the prevention of cardiovascular hospitalization reduces the risk of cardiovascular hospitalization right in the indications and it says that in the indication s clinical studies fourteen the doctor would then go to the clinical studies and the first thing he would see most prominently is the athena study if in a study as a judge found is the only study that reasonably because it had nothing to do with the endpoints and so what the post talking alice was used for in dr holos was paper was to design athena to figure out how many patients do we have to enroll it's a guess you never know how many patients you have to enroll unless you make some estimate as to what the effect size is going to be and remember again the primary thing that they were looking for in the athena study was no difference on mortality neutrality or mortal it was a total surprise that reduced cardiovascular hospitalizations that finding was was commented on the art as a breakthrough and as remarkable a total surprise that that happened and that's what they were able to seek f d a approval on that particular indication but the paragraph talks about giving it that the patient population is those over seventy at over seventy and then three paragraphs later it talks about patients raging from twenty three to ninety seven yes so how are we getting to twenty three when i thought the eight over and over seventy with at least one risk that if in the study it was modified at some point in the in the the original protocol halfway through because they were not seeing enough frankly enough deaths in the exact type of patient is the one in which to measure on was shown to reduce the risk of cardiovascular hospitalization and what the judge found was that based on that evidence that the physician would be encouraged to give that drug to a patient according to the label and as this court has found it is not an instruction that's necessary it's encourage recommend or promote and promotion or recommendation is similar to what the supreme court has said about inducement in the m g m case that into the study you should think it's going to work ok so the there's a couple things to say about that document first of all there was no evidence that was ever promulgated to anybody and with fact a subtext that no no in fact that document that was referred to and entered into the record might have been a draft it was contained within sanity's files and that most was given to physicians at their hospitals that were going to run the study now what physicians did at their hospitals and there's clear evidence of this in the record because this is what doctors usman did they have a negotiation with the institutional review board which governs the in the administration of that in their hospital and in his instance he rewrote that section he rewrote it to take all the expectation language out of it and that you can find on at the record an appendix to thirty six page three thirty eight by starting at about one five through three forty one for today so at his institution he wrote  don't know that this is a factual finding i think he's pointing out that that's what doctors usman said i'm not sure that rises have little finding that he needs of the court i think what he's saying is it didn't matter in his in his analysis just like the homos are statement that's in the prior art publication and like the post hoc analyses that they didn't they didn't overcome the overwhelming evidence of uncertainty that he found both based on the prior administration that can be read two way that is the initial one consideration of that evidence when he looked at the homos or statement in the in the article he said the judge said you have to look at that in the context of two or three different sets of evidence of and they were found in each and every case to either worsen or to not not better cardiovascular hospitalizations they didn't show reduction in cardiovascular hospitalizations and sometimes they  what would the defendant say as well all those are relevant because they're different drugs but that's that's not the case imagine if the opposite were true imagine if every other entity arrhythmic drugs were tested and in every single instance it reduced the risk of hospitalization i think that would be the primary argument in terms of obviousness of this patent the fact that every single other anti rhythmic drug something which had better that had better anti rhythmic properties internet around failed to reduce the hospitalization i think is very important it is the written subject and right ok so that's a page seventy nine seventy seven if and if so perhaps the ones with the it is that that's right he says that those two pages two thirty six and two thirty seven of the transcript yes i'm with you which is what judge andrew cites at age appendix thirty nine if this was in fact given to patients so patients are being told o at line sixteen for he shown question this is what the patients got yes so now we're talking about what the patients actually received only evidence in a trial as to what the patient recei testimony besides the testimony that we've been talking about other witnesses about how x twenty four posed patient information was or was not given to patients was this the record on or i believe dr rachel also testified that the that his institution changed it and i believe one of the in the witnesses that i sort of expected to come from the other side is you know i'm not that i'm aware of the only testimony i'm aware says you know what it means in the scientific community it's really it's context in particular and so one of the difficulties i had and i guess it's appendix three sixty nine and it went in and just kind of goes to what he was talking about when he was talking about hypothesis when he was evaluating what a reasonable expectation of success is what that all meant to him and he says something like it may be worth testing prospectively the hypothesis derived from it i would make no other statements about i would not use that to alter my clinical care question i understand that let me just make sure i understand what standard here flip you're saying  know a little troubling or would it lead you to question his evaluation and this is the context of whether or not this was a hypothesis that was meaningful and if he thinks the only meaningful measure for reasonable expectation of success is three his own you know personal view that when you look at the well this is a scientific view that when you look at those prior studies you saw patients being killed when you look at the end drama study which overlap substantially with the population was always testifying from the point of view of what a poster would think so i find if if i'm using he thinks i meant by he thinks to put a post with thing i don't know that he was involved in he certainly wasn't involved in writing any of the sanity documents not dr if he had no involvement wit the uncertainty that at best what dr holmes or was saying was a hypothesis and in his view to test that particular hypothesis you needed a phase three clinical study because of the of the risk of mortality that in andromeda and and the modest effects on the on cart anti arrhythmia that you saw in phoenix given those very modest effects and given the mortality you saw in the other other drugs and the fact that no other eighty had ever been shown to do this that's the type of study that he thought you would need could there be another study is the law that you need f d a approval or a phase three clinical study no it is not the law you use one could conceive of a large phase two study that would enter this particular question that didn't happen in the priority here and in fact many companies run a phase two study before they do a phase three to reduce the risk of a phase  study that did not happen here so what the only evidence that this drug ever actually reduced cardiovascular house was a she came from the phase three study and he thought to answer that question expectation about them yes if i could take you in the appendix to page two thirty one and this this is the protocol that we're talking about here this is the protocol for the end so remember this is the one that failed in the prior art and had to be stopped early because of greater mortality so one picked appendix two thirty one on page three twenty the question says who is the what is that this would be dr this is the this is the authors of the andromeda protocol we anticipated internet or own would reduce to the rate of hospitalization and that was disappointed that yes actually your honor that's not the protocol that is the was stated for andromeda so that's a similar type language we anticipate and i realize this is a transcript yes i understand you know are they is that language that was in the andromeda you're on i don't have it in front of you i believe that's the way that i would re expectation of success and what was examined here by the district court and how the district court went about analyzing the issue the district court didn't look at reasonable expectation at  time in two thousand and eight that it's apparent from the from the analysis that what what the court did was take it back and take it from from not expecting success and then backward and back  i'm sorry the word i'm looking for is is escaping me but looking at it from the from a backwards angle instead of saying what is a reasonable expectation of success he looked at whether or not the art at the time taught that you would expect it concretely to work and that's why he discount with that's why the court discounted the statement in homeless or as a as a hypothesis do you have any more information about whether or not this written instruction was given or not given you heard the with that was a statement to the f d a we expect this to work so it's not just patients that they they wanted to tell that they would expect it to work but it was also the f d a in order to get approval for a protocol that they published as prior expectation analysis instead of looking at what would a person scale what a person recently expected based on kind of what the the law was at that what the law is which is when you publish something with almost all of the elements you you you have more of an expectation then when you're trying to pull elements from a multiple different story sources and  when the court analyzed the recently expectational instead of looking at it from a reasoned perspective he started knocking down all the evidence that was in the art at the time in two thousand and eight person would have had a reasonable expectation of success doesn't that person in fact look at the body of evidence existing at that time and that includes suddenly the new two thousand and eight cation of the basically the protocol in a new englander medicine with dr homeowners characterization but it also includes the other stuff some of which points in the other direction and as long as the t so you do have to have some kind of retrospective look and judge andrew says somebody looking at all of that would could conclude what if you get one of them one of the publications said that this was sort of confusing and uncertain certainly the word was confusing as was was in there confusing and severely each severely challenged so far namely that the clinical day so i don't think the clinical data was actually confusing the clinical data in this is where i think that the district court erred in this strictly the stringency of the the expectation requirement when you look at that body of evidence at the time the body of evidence mother said you would expect to work it might have caused someone to not have a concrete expectation of success but that is not the standard that is not the legal standard for reasonable expectation  said the two thousand and eight promos your article represents i have half a cyst that requires future testing requires future testing rather than a concrete expectation sets so as i interpret that phrase that is requiring something more than just reasonable if you have to do testing in order to prove it which to me suggests an actual success you have to demonstrate an actual success and there are other elements there are other parts of the opinion where he does that as well he uses the term concrete multiple times and discussing and that he uses it he did when he uses it at least the primary way he juxtaposes it against a hypothesis so i think that supports kind judge toronto's that we're not talking about concrete versus reasonable we're talking about a concrete expectation of success as opposed to hypothesis he jacks to pose those two terms he did it sometimes and sometimes he did year and conclude that it was obvious that the trials would successfully hit their primary end point that is not the standard that's not the standard doctor's usman applied and that's not the standard in this court for reasonable expectation of success showing