please the court steve sallust and for duke university and its prior decision in this case this court identified two errors in the board's original decision invalidating claim not st the board applied an improper claim construction and treated the claim element that the ga the enzyme in question quote is a precursor as if it needed to only include or be part of a mixture of precursor and non precursor forms that was error number one the nd error was as the court pointed out you know footnote number two in its original decision that the presumption of nexus had not been properly applied by the two errors st it read prior art disclosures and expert declarations that refer to quote precursor as though they addressed ga that is exclusively a precursor when in fact those  cookoo ci and b zhu away and a number of other prior art preclinical studies had used the proof of the precursor form they refer to it when in fact it was a mixture and coochie is a mixture although it is predominantly over ninety percent most of the other prior art references for example the van bre patent which comes up quite a bit it was prefer really predominantly namely where than fifty percent no more than fifty rival more than ninety is quite a bit different in that particular animal model that's what was described but there is no disclosure or teaching there and no testimony from anybody in the record that a person of  with at least some basis in the record that was the priority date it was pretty well understood that the mechanism by which  no teaching in either of the asserted references or in the testimony that you could get surely precursor no reference discloses that nd although you are correct that for there are a variety of prior art references that state that for a fission uptake into the cells the precursor has the proper glycol solution and other markers to be recognized by the receptors there is also teaching of the prior art that in the license omes the other forms the mature forms are water active and we are talking about a disease that affects the entire body skeleton muscle heart muscle liver kidney spleen etc etc and in the studies what the data showed is that the mature form of the non precursor form was taken up by these other organs now those other organs are affected in the disease so it is not intuitively obvious and necessarily the right conclusion that you would want to exclusively precursor you might well want a mixture which is what all of the other prior art references taught before the chen patent taught and claim exclusively precursor as the as the preferred and body image to be administered to treat the disease and in regard to the good some of what you just said about and of ferment of benefit from having some at least of the mature for form get testified to by the experts there were there was no testimony by either party's experts on that subject what we have is the prior art references which which teach a mixture and we have i would say a failure of proof on the part of the challenger here were in challenging the patent to demonstrate that a exclusively precursor version of the enzyme was taught or suggested by the prior art and that there would be a reasonable expectation of success in achieving the claimed invention namely an effective treatment for the disease using that form of the enzyme did the parties have an opportunity on re man to submit anything yes the opportunity exists because even before the adoption of the standard operating procedure and the for ready the permits of that type of submission on agreement and the board was permitting that the board issued its decision on remand neither party requested the opportunity to submit additional evidence by a marine having relied on business the board did not do that it went about its business and one day a decision came in the mail the last thing i want to point out on the references here on earth is that it is demonstrably clear and this is set forth in detail in our papers that when bio marines experts were testifying about quote the precursor form they were not referring to exclusively the precursor but rather a mixture of precursor and non precursor forms for example  and who by the way you admitted he is not a person of ordinary skill and did not view the evidence through that lens said royce or one of the two references that the ga quote produced in the examples only way these experts could have made statements like they did is by construing references to precursor as though they meant exclusively precursor which is not in fact what the references say or what they teach turning then to the or the nd error or the treatment or mistreatment of the objective in d c not obviousness the evidence in this case candidly is off the charts this invention provides  ever say to the board you should apply a presumption of nexus we did not your honor and that's why isn't it a little hard to follow the board for not doing that notably duke's objection to the board's treatment of its evidence of objective in d c of non obviousness including its failure to apply a presumption of nexus appear well taken so that i don't understand the fuss without the presumption would would not be found so the law on this says as i understand it this is from the elect sam case and the center cut case that where the patent owner proves that the commercial and body men quote is the patented invention and we prove that with undisputed evidence that the the drugs myozyme lumizyme that are marketed for the purpose of treating the disease with  exclusively precursor enzymes are the invention in clay nine and they are administered by doctors according to the instructions in claim one of which is from which claim nine depends that this is the st teaching in the prior art of treating the disease with exclusively a precursor readily and as i me just against framing that the question that's in in my mind and why in this case a presumption might make a difference there is remarkably little evidence from either side about whether there would have been comparable success from let's say van bree which is just before this and the only difference between then and this is exclusivity if there is no evidence on that question the presumption may decide it but if there is no presumption and you have to show that nexus of exclusivity to success that is only because of the excellence of it he was there success where is ninety percent wouldn't have been successful now isn't really sound that plausible on its face without some evidence saying why exclusivity mate would make a giant difference in whether there was going to be a successful product then the presumption mean might make all the difference that the marketed form of the drug the only approved version of the drug anywhere in the world and the only one that's ever been successfully given to a patient to treat the disease is the has been three in its in its quiver and it has this in says let's do this one let's not pursue ventry but the next question is maybe somebody else had their own van would have pursued van breach and gotten f d a approval and that unknown because the record is remarkably thin fair enough it is an unknown and that's what the board said they can't conclude on the record whether the commercial success is truly attributable to the exclusively precursor feature or bend bree that's the one they explicitly cited that your honor is a failure of proof on by over in this part they had the burden we established as the law required us to do that the the prior art teaches a mixture the i think there's a word game going on here i think some of the prior art that had actually been used in certain currently experiments you know early i'm talking had at that time and they hadn't necessarily all purified it to the level that they might need to get f d a approval which is basically highly pure product they were to research articles they hadn't necessarily quit to put it in humans yet but  the whole idea of purifying this active compound it was all over the place and in terms of specific teachings the two main references all just point to what they actually teach  tissue culture medium so it isolated doesn't say the words of the plane construction exclusively but it's certainly isolated and there's been a lot of discussion about van hoven i want to go over it again it's important that of you know what you would call impurities as opposed to getting only the precursor and not the mature and nd even if you purify why would you necessarily use only the purified four maybe you get a nice pure batch of precursor and you decide i'm going to use that mix with ten percent of mature so that you know the heart gets gets the benefit of what we think a mature one is doing well all of the evidence teaches i mean all of the evidence teaches that the active form is the precursor for the fact that once it gets to work supposed to be it's broken down into the miniature what's what but that's not what's the best you basically up to about five percent can be tolerated in the current batch as are greater than ninety five percent sure so danbury itself actually talks about purity of greater than ninety five percent that's  to any form of the ga that will do anybody any good is the precursor for as opposed to it will do more good to have more every every study that that cited in our brief they used a form that they didn't realize at the time was the mature form and nothing happened there was no benefit to the patient and the patient probably die this is back in the sixty's so there was a long felt need but by and ninety there was a seminal article i don't remember which one it is right now but we have in our brief they said aap we now we know why those earlier studies failed because they were using the they were using the mature led to our form was missing something yeah it's missing a piece off the end it's got it's an incomplete molecule it's like you have this great drug and if you cut the end of it off this protein it doesn't work anymore and they didn't realise that back in the sixty's but that was reported in the early ninety's and then all of a sudden about ninety five dollars there was article after article after article came out saying hey this is it this is where we're going to go we're going to go with producing it mean i think everything says he is the purified molecule and our witnesses testified to that and we argued that at the board purified which precursor yeah purified precursor all by itself that's that's where everybody was going so that's to me that's i think that's on the reef so there's there's no there's not one scintilla of evidence that says the mature form might give some benefit all the evidence says the precursors where you get your benefit and that's where they were going but nobody actually did produce to put it through the system yet had got to have the right i mean it was all in the art it was all in the prior art you know this is this is the this is because you're the st one to get f d a approval doesn't mean you should it's a pat little invention where it's all over the prior art if somebody has got to get the approval st it was hard to tell because the f d a instructions in all the rest have a good deal to that's important one thing i'd also like to point out is that the more said that they didn't feel that do even prove at least need to show that your claims cover your product and i'm going to point to the board's statement experts of jews ever talked about it ministering substantially the language here on the planes instruction it was like exclusively the precursor none of those three witnesses said that in their declarations and none of them had firsthand knowledge of i mean they basically said oh it's cover the claims to cover the product ok so what does that mean i mean i think there wasn't really any real proof there that what the what is the approved product ducats knows what the approved product is they never came in and even showed it they didn't have their witnesses say there were they criticize our witnesses for not talking about the plane construction when they gave their opinions and gave their testimony what the ark teaches their witnesses didn't either they just said the plane all the planes cover it and then there was no discussion of claim nine and what that means in terms party so i don't think it was it was covered in cross examination when i think there how can you criticize this is being somehow unsupported and rejected i'm saying the board said padna does not adequately does not show adequately that my as i'm a limousine are the invention disclosed and claimed in plan nine as it was you know right right i don't think that they showed it but even if they did but there's four patents that covered it that were based on earlier filed work that are all listed as covering it and there's no attempt to break down claim nine and show why claim nine is important and there's there's no attempt by any of their remit one challenge to why do they have to do it ok let's with the boys yeah i would say it is yeah the claim interpretations legal but the whether or not they prove that that it actually falls within the claim that would be fact finding is the f d a label or other f d a information in a the record be the joint appendix yes and so i do that does that say whether all of the arrays in the product is precursor the answer is no it doesn't appendix yes i can give you the page numbers  quote that it's there they didn't try to say well you know you use the language of the claim and i looked for it i didn't see it it's not does not point it out anywhere so and i think you said you made a reference to the material do and thirty one maybe a page before or after that ok and it's not it's not there there's no statement that it's homogeneous but we're only the precursor it's just not there thank you your honor let me start where we just left off the evidence that you put forward as to whether the claim claim nine is practiced consists of declarations by doctors wasserstein and  cummings which are so can be found at page eight hundred and eighty eight through eighty nine of the appendix in the case of wasserstein and two thousand and nine of the appendix in the case of cummings and what they both said is that both went through all the claims that were in dispute and said every one of these claims except claims five through seven which deal with particular dosages that clinical practice showed were not high enough to provide the desired benefit so all the other claims are practice program their expert for example said that purification refer to quote removing contaminants such as choke proteins d n a and dodginess retrovirus as well as adventitious virus from the finished product that's a good seven hundred and thirteen through fourteen of the appendix when when there's a description of purified to homo to navy there is nothing in the reference and certainly in the testimony that says that that means purifying the precursor janay the as opposed to isolating the ga enzyme in whatever form from the medium in which it's produced whether it's rabbit milk in the case of the transgenic mammals or cho coles cell culture medium in the case of cho cells finally with respect to judge newman's questions about f d a approval and what have you this is the long felt neat story in a nutshell no one had discovered  or proved an effective treatment for this disease until dr chen did it with exclusively precursor material in the clinic and that is a revolutionary invention in the treatment of this previously fatal disease for infants and children that no there is no teaching of the prior art that pointed to or suggested that and certainly no testimony from bio marines experts but a person of ordinary skill in the art would have come to that invention by combining rois are seven hundred and seventy one with van one thousand nine hundred and seven neither of those references contains the teaching of exclusively precursor and or suggests it and there's no evidence that a person of ordinary skill would have and there and so on that record just like there was no sufficient evidence on clay nineteen the one that this court reinstated the last time this case was before you claim nine should be reinstated there is no evidence from which a the court