testified that he had to do experimentation to get to the pharmacokinetics properties there is nothing in the record record in this certainly no evidence or argument that there was any inherent see from any specific for max not in isolation but an early t max in a formulation that results and twelve hour efficacy now the prior art didn't disclose that and in fact six didn't work out with the patient gets what the patient gets out of the combination of pharmacokinetic and clinical property just asking about the team  the key to pharmacokinetics as they relate to pharmacodynamic as a clinical property is how that relationship follows and what the end inventors found in this scenario is that they were able to invent the first liquid product by using a pharmaco kinetic profile that was taught away from in the prior art to result in clinical benefits that were special and those clinical benefits are tied to the unique pharmacokinetics you know and that is you know why we've relied and cited the cycle bends a p and case because we think that precedent is particularly relevant here k profile to get these characteristics for prior art actually taught away from the specific profile that the inventors came up with and specifically the that's relatively or on site a team that's relatively early yet the story of the invention and you know him i'm just remembering something that's not incorrect you're out of but it's not completely the story of the invention to the extent it relates to whether the claims are obvious includes over three years of work towards getting a pharmacokinetic profile that resulted in the clinical didn't specifically say they were  why the f d a requires it is because it is unique and it works in this liquid formulation as you probably noticed in our record the f d a uniquely for this product requires the generic companies seeking to copy it to do different and additional pharmacokinetic testing to ensure that they have this profile that's unique now this is this is something going to have me around this is something that was not preset bright prior prior art and was and was surprising kind of what what the court we wait for something that we think is significant the court found based on the evidence that was presented by triss that it was that the prior art taught away from using this early t max early time to maximum print concentration to get  they were known in the prior art for products that didn't meet the clinical benefit didn't meet the twelve hour after we think it is clear legal letters are you talking about it's the references  that's less than twelve hours when it talks about a product that has a twelve hour duration it's a six to seven hours team and that's that's right in th and then it says for that range you can get a duration of eleven to twelve hours it goes on into virtually the next sentence when it's talking about a product that is more germane to this invention a product as early onset one of one and a half hours and that has twelve hour twelve to fourteen hour efficacy it says to use six to seven similar to humans an overlap from our brief as a hypothetical it's based on no data it was clearly a prophetic disclosure and patent it's a patent application never issued a patent and if that's clear rishon right it's not a solution it is a solid product and so it's been since the inventors could have just said anything they want about the properties of their product they only aspired to a product that had an pharmacokinetics of the solid products disclose because in ski could be applied to a liquid and there's nothing in there that says it could be even if you assume that and you had the formulator attempt the past well if you look at that the pharmacokinetics of what was known in the prior art was all over the place the pharmacokinetics of the products of reinvention are unique for any product but it's the first liquid formulation there was nothing out there on a liquid long acting formulation so to look at hindsight as we believe defendants did to say well let's pick the pharmacokinetics the t max from these two products let's choose the twelve hour efficacy from these other products and say well that was routine experimentation for someone to put it all together i think it's the definition of hindsight and again if you look at what court actually found based on the prior art that it that  activity and twelve hour onset how do you find that those same references lead to obviousness without clear persuasive evidence tying those particular references to the prior right just the connection between well it all depends on what you consider known in the prior art there is no product in the prior art that had the combination of forty five minute onset of activity in twelve hour efficacy you can look at all the prior art whether it's solid patch whatever it was nothing and of course none of these had been applied to a liquid for fifty years there was an acknowledged need for a long acting liquid product if it was so obvious was so clear from what was known about the  why wasn't done before and so when you look at the like that it's important to begin just there the idea that there is no product with a forty five minute onset and a long acting duration that's right in the teeth of the findings that the district court made and i think that as this court that's the challenge of being able to put together a rationale for why it would have been so obvious reasons like security success that all of these different features i'm certain sure i understand that i took judging human to be asking th question where my friend had just left off about the idea that there is no product with these with these actual clinical trials it sort of made you inclined with respect to the on sent or consider and there there is a dispute between the parties on that you say do with the fact that you're we can do the secondary considerations section of this if you know where and when you look at the front part of you know this it doesn't talk about your men just talks and wrong generalities of how i think that the reason that the district court doesn't make this finding on page forty seven instead of earlier is that it had the court had rejected the idea that a single peak product would teach away from early on entity which of course is not a commercial product so it doesn't start talking about the commercial products until it is talking about the secondary consideration but it certainly is making a finding based on the very other the very factual on expert dispute there's any way to read the district court's decision as my friends read it to as a finding of teaching a way based on single people which is where the discussion is or on t backs because the district court i think makes a couple of important teaching away all the district court said was that the just that the other had found some things persuasive about the other side's evidence about the commercial products the second generation products but it then goes on to discuss the remainder of the prior art and i how are you really going to expect to get all three of the clean features i e forty five minute early onset single peak with twelve hour groups and that was the concern i had in trying to understand this district court's opinion as to  why one would expect all of that when you now says that the single is really just a single be question in isolation without considering it in combination with the other two claimed elements sure now of course as your your arms questions to my friend have brought out  stipulated in this case there's a motivation to make the product with early onset and extended duration stipulated the findings i think show why there's there's no findings of motivation to  from there because the evidence shows that the m as my friend conceded this morning that shape of the curve for example has no therapeutic significance of well right and then after you require that her brain are these suitable options now once you have the motivation to combine the prior art because the t max has no therapeutic significance for example or the if you've achieved early onset and extended aeration because the number of all based on k this is like car like they are versus watson for example in which it doesn't matter whether the combination of achieved is the letter where there are multiple ways of achieving a combination it doesn't matter whether it is the k profiles and then it's just a matter of selecting one of the other but they're still at the bottom than has to be a reason like the practitioner of success that you could achieve in one of those p k profiles now the pattern of making argument that nobody would have expected that you could have been able to achieve a single profile given the requirements of them having twelve hours a ration and a very early onset and that is the question that i was looking for an answer to in the district court's opinion and that's my concern right now where would it have been where is the evidence for why x and to you one would have expected reasonably that you could have achieved a single peak the evidence evidence the evidence that was submitted on the question of acute tolerance or talk if a lock says which was the way the emphasis of the other that the other side placed on the p k profile in the district court the question was whether you could you would expect to see some falling off based on a single peak profile and they and the in other words so you wouldn't be able to achieve the long term efficacy over the twelve hours because you'd see some falling off and the other side's expert admitted when confronted with figures one inference swanson that what matters is not whether there's a single peak but whether there is a flat p k here we have let me drill down a little bit more my concern right it and then it seems you would just assume that if you can make a single peak then the forty five minute nonsense in a twelve hour duration would be unaffected by just doing a deed convolution or some kind of racial next to figure out a way to get a smooth single curve the forty five minute onset and the twelve hour direction would stick in place and not move and and i'm concerned about why that is so you might be able to dig through the appendix and show me some pieces of testimony that the support and not that kind of conclusion but i don't see it in the district court's opinion and that's what i'm afraid of and in terms of whether  firms it's based on the lack of addressing here tolerance and the lack of really explaining why you can get a single piece while still preserving forty five minutes and twelve hours of research right and i think that the the reason that you should not have any reservations about affirming that on their q tolerance point is because the on the key point there's an admission from the other side's expert which i believe he just record credits although i don't have the faith number right in front of me stated that the acute tolerance theory is based on a sustained flat plasma concentration so in other words the idea that a single that you would basing the teaching away argument on the idea that a single peak would leave to tackle axis would lead to acute tolerance which you know would prevent you from accomplishing that or efficacy over the course of the twelve hour day that is not that does not come from the single people on the accept the premise that the court made a teaching away finding and perhaps we do have to disagree about that but i'd like to try to convince you that was at the bottom of page thirty nine where the court refers to the the second generation commercial products and says that the some of the other side's evidence on that is persuasive i don't think that the court is there by making a finding that all of the things it is said to date are the arguments that trash was making ar accepted by the court and given the status of factual findings but that's not how we read page thirty nine of the appendix and we don't think that you can read it that way and just just to give you one example right trish said keech away but then that page forty six the court credited any particular argument about it certainly can't have granted any of the other this four or five and then says i find those to be persuasive i don't think that's what the court says your honor respectfully the court says well the court believes trista's evidence regarding those that can generation products is persuasive it's not dispositive and so two things about that one the court goes on for the next two paragraphs to discuss the since the reference which is not a second generation product because it was not commercialized but which is nonetheless in the prior art and the court obviously gave considerable weight he despite the other side's evident attempts to discredit it the court considers that and you know weighs the competing expert testimony and makes a factual finding that since he teaches toward not away from the single people because of the forty one and then you know again all throughout the pages forty five to forty six and i believe to fall on to forty seven where the court makes additional findings about the second generation products specifically thousand but the point that the expert was making as i read it is that there are four separate limitations and while the closest prior one limitation might be x it depends on which limitation you're talking about and which factor you're talking about to decide what the closest prior art is and so instead of saying ok well that that might go into the weight of his testimony he just rejects all of it out of hand i don't understand how he could do that well but of course you're out of the court and then in the next paragraph are all over the map and so you want to pick and choose findings they want us to pick and choose findings and yet what we need is a road near that has findings that are clear and lead in one direction well but respectfully i would submit your honor that in this case we've cited a number of findings that at that that go to specific pieces of prior art they go to specific disputes between experts all of which the district were resolved in our favor the other side his side is cited one finding that if we don't agree that it's a finding concede that it is difficult to understand if you look only at that paragraph but seen in context so if you're reading the next couple of paragraphs and reading all of the actual specific findings on which we've relied i don't think that you can read the district court to have you know abruptly stand in for duration no you want to do the other there are distinct but do you see that that the court goes on to discuss the team actually range and then the half life range separately and the argument as i understand it from the other side  control the onset or duration of effect and if you look at the two testimony pages that are cited there so he cites three eighty and three seventy seven and that translates into i believe twenty's twenty one sixty four twenty one seventy two what our expert d strawn the only p k p d expert to testify on invalidity what he says in this book on this subject is that for an extended release product it's the ratio the ratio of immediate release to extended release beads in the product that controls the duration of action not the t max so the t max is incidental immunity you once you have for when you formulated the product you can look at what you know what the curve looks like but the curve and the of that curve are a function of the ratio the ratio is what the formulators would have drawn from the prior art the ratio is drawn from the the range of you know the narrow band of identified by the experts from the prior art that's how you range is a suitable way of achieving the goal that's you know with the goal that everyone stipulates there's there's a motivation to pursue early onset and extend and extended duration you can read that there has to be a reasonable expectation of being who read yes and the court in that set in that sentence that i've read i think the court is agreeing with our experts conclusion that in the context of extended release it is the ratio and not the t max that determines how long the response last in the other side had been arguing that in general it's the t max that determines that and what the court says what our expert says this is a twenty one one is that that may be a rule of thumb for many products but for a standard extended release products do well but you respect it's not at all unusual to combine immediate and extended release that's how each of these prop prior art second generation products works each of them is an extended release that combines some immediate release and some extended and the way that our expert approach this is to look at the ratios which is from the for the relevant prior art products and to explain where a formulator would would put the ratio with the using the error that i think the court was led to by the way obviousness was argued there is a huge difference between finding a formulation that has a particular set of pharmaco kinetic parameters and evidence that a certain set of pharmaco kinetic parameters will provide a certain clinical profile now this question of ratios there was some testimony by activists as formulation expert that you could use a whole host of range of ratios to tailor your product to get certain t max values and he looked at products in the prior art including conservator and meditate now if you look at those products the p k profiles from those products with almost the same ratios they look very different and their properties are very different so it's not just a matter of ratios that will get you to the claimed invention what the adventure is found was that there was a particular set of pharmacokinetics properties w to its liquid formulation that resulted in a unique and beneficial set of clinical properties that's not in the prior art and there's no suggestion well i would have i would agree with you or rather that you don't really claim limitations that you have a problem meeting but an argument that they're not important hell important to this invention and that's why i made the actually that's not contested every every every expert agreed that you know generally later team x results in a later episode there is there is a disagreement as to this whether you know someone would go to a single could concert at an early onset concert concert or if you look at the clinical data for concert or that's in their package insert it says that the onset is a two hours now there is this one reference that says you know look for it from thirty to thirty minutes to two hours but the the actual data that's in the package insert for a concert or says the onset is two hours but let's assume that it's thirty minutes that's not the same as the claimed limitation of less than forty five out of the forty five minutes forty five minutes it's not just thirty minutes  minutes if it was if the reference said activity within thirty minutes i would agree with that it says thirty minutes to two hours the claim requires activity within forty five minutes that's not the same thing and there was nobody that testified that said it was now he said that it was thirty that was a reference was bitterman and that was the reference that our experts said was clearly day who have an early t max that don't have more than six or eight hours effect there are other products that have a late t max like focal length and conservative and don't have the early onset and have twelve hour efficacy that's the exact evidence that the court relied on to show teaching away on this very characteristics so the cites are some general testimony that says well second generation