possesses the necessary qualifications it when this has been a year since you come and join my chamber and i'm sure that time has gone by pretty fast for you because that's what happens when when you work hard as to the the claim because it's important to understand the specific aspects of the claims in the five hundred and fifty nine patent i did as i think all of you know other than the claim for a claim three the claims plasma ammonia level that's between the upper limit of normal and half the upper limit of normal that's what the claims are about how the claims require certain specific steps measuring st the fasting plasma ammonia level comparing that to the upper limit of normal and then administering an increased dose of h b n one hundred if that ammonia level is greater than half the upper limit of normal that's what's required by the claims those are all of the key aspects that you must find when you look at the prior art in order to find obvious horizons view is that the prior it's really deployed absolutely devoid of any teaching or reason that would motivate a force in ordinary skill in the art to increase the dose of h p n one hundred if the patient's fasting blood ammonia it was already below the us in and i have to say i have found the finding of obviousness to be puzzling puzzling from the standpoint what's the key june of last year not the eight hundred and fifty nine publication and using that as a as a key basis for finding obviousness i find it puzzling because of many factors but among others if you look at what  which became which came from it or the publication itself the fifty one publication says when you're dealing with using plasma ammonia level in order to determine how to treat a patient how to do it doesn't seem change if you did baseline that by the probability of a spike can certainly be present depending upon the individual patient that's involved but that has been my story i was wondering the reason why i was asking was i was wondering about it was a situation where a patient well i was saying is that your initial explication of what the plan was doing seem to me to didn't take into account the possibility of a person who is within the normal range we measured nationally in the morning or spiking certainly was recognized to occur i mean it's recognized all we back in one thousand nine hundred and sixty that that could occur the use of nitrogen scavenging drugs has been out there for forty years in this purpose was to  counteract the spike why are the number bringing the number down so to speak yeah well it was always recognize a spike in could occur but that was never used as a motivation to increase the dose of nitrogen  was it sixty years old and the fact that nitrogen scavenging agents could be used as a method for reducing the level here of they could be of a problem is not an issue that was considered to be of such a nature that you needed to continue to take the level down the law short of anticipation here it's obviously absolutely and obvious is has to be looked at from the standpoint of a person very very skilled in the art and those of ordinary skill in the art who look at this over a forty year period never said we need to continue to dose to take it the level down below normal that  fact that you could go off of normal in a spike throughout the period has been recognized over this huge period of time of over forty years and no one said you should even treat once it's above partially above the upper limit diagnosis and straightforward diagnosis and then known treatment well we have more than that in this case you are what we what we have is a recognition that comes from the five  patent it's not just looking for something out there it's looking for a problem finding the problem and finding the solution to that problem we have affirmative steps that say once you determine that the patient is in this range of between half and the upper limit of normal there is a need at that point the treatment and that's what the patent says to increase a dose at that point but it's not an issue that simply says don't do anything other than determine that there is a problem it's got an affirmative step that says treated treat it how by making sure that if it's above half a below the upper limit of normal you increase docs that's not to be found anywhere that's not a an issue of prior art it's also not and internal issue in your body it's that at this point in time it's the physician taking affirmative steps to change that so i think it found the obviousness decision based upon their expert and their expert specifically said that there was a motive the reason that they found the way they did their experts that is there was a motivation to continue to increase the dose in order to get the level down below the upper limit of normal and that's where the board turned to and said why in order to prevent spiking and so forth a poster would have done that because there are spiking sick and curry very day at but there fonte their finding is not based on any art and it's also not based and from the standpoint of their expert their expert had nothing to support that position either because again if you look at what was out there available from a prior art standpoint the only thing you have articles that talk about treatment but treatment from the standpoint of is a need maybe if you're up at about three times that you want to increase it dose but no motivation to take an affirmative action if the patient's already within the normal range that's what it that's not there it doesn't know  found in any prior art that would say that patient is not in good condition that's the point because they were exposed excepting at that time much much higher levels to be ok two and three times the upper limit of normal so sure spikes occurred but there was no motivation once you were in that happy zone at around or slightly below or above the ul n position so that's good they never said there's a problem that's what was found by dr sharp schmidt and the research that he did looking at this for the st ever sixty five patients that at u c d and determined that there was a reason why you needed to lower that level and if you look at the data that's in there it shows that there is a vastly increased probability that the average during the day is going to be normal and that the amount of spiking that occurs is going to be a low one and a half times the upper limit of normal that was never seen before and that's where the motivation wrong i thought there was an understanding in and there are that there was a goal to that if someone is at a lower range medicated going to have a spiking of men who know about you know if you have a little bit more of the pharmaceutical you counteract the effect of the additional protein in order to bring the evidence about the goal was a piece of the puzzle of why it was that one more in there is going on there or would find a reason to do the piece of the puzzle that was needed was really the testing that was done that for sixty five patients that resulted in the data source that was then used by dr george smith to determine that there was a problem that went because they said you have to look at obviousness from the standpoint of posa and there was no article ever out there no one ever went to a conference no one ever said if there's a range that's above the upper limit of or at from below the upper limit of normal we should still increase the dose nobody did that and you can look at it from the standpoint too you're treating a patient and that patient has u c and it's very very hard to maintain for a patient level that is good for them as fact that's one of the big issues if you if you look at the history here and why dr sharp smith did the work that he did that the numbers are devastating you can on articles for example that that show that the  children mean we drilled and that level had numerous problems they had cognitive problems and they had other life threatening problems because the treatment wasn't good but one wasn't good it wasn't because there was no recognition that there was a need to make this and to find that between half in the upper limb of normal was really a problem because no cosa is out there they had that feeling or wrote a book about  is a fundamental issue we appreciate the statute authorizes the director to intervene but i don't see that it authorizes the director to substitute itself and what would be are reasonable one hundred there were any problems with side effects is that evidence is in the eight hundred and fifty nine which had nothing to do with increasing doses whatsoever and that's one of the littlest defying things is that there is a position taken that somehow the eight hundred and fifty nine and was dealing with those increases it wasn't the eight  pattern when it was looking at the data that resulted from the small clinical study it was done at that time it was a comparison between professional and h p and one hundred dollars and all they did in that case is they took the same amount of active that would come and it would be administered then to the individual patient and found in some instances when they'd been one hundred dollars was given yeah there was a change but it wasn't necessarily do there's no indication as to the reason why there was a change if you look at the table twelve and the eight hundred and fifty nine cat and you'll see some of the changes are actually kind of massive but there was nothing that said that there was any control that was put on those patients when those  levels were taken those levels that were taken were not designed to be nor were they said to be fasting blood ammonia levels and all it shows is when you changed the the dose in for some of the patients there was  nine if you look at the eight hundred and fifty nine publication when it comes to dealing and this is what i find puzzling using plasma monia levels it says eight hundred and fifty nine says plasma monia levels are less reliable and provide no direct information reliable as a direct measure of the nitrogen scavenges effect so as of the eight hundred and fifty nine timeframe what did what did your principal run reference say it said don't look at the that that you have g n and because of that i can i just can't envision how there was any motivation for a poster to do that and there's no indication that the osa would have relied on