complex environment such as drug carry out excels in in vitro test tube experiments that argument presuppose that we agree with you that there's not enough evidence for the board to reach a conclusion based on the documents alone that they cited that there was in fact that motivation i don't know that it presupposes i think that it's a separate error but they are related your honor because what we what we read the board opinion as saying that the applicants had not come forward with the evidence to prove that link which indicated to me that the board expected us the evidence to prove that link and then to follow up on your question there isn't fact in our view no evidence of record that the board pointed to to prove that link purpose was obvious based on other studies that had used progeria in vitro experiments and had used different types of integration and the key fact that was missing from the analysis is evidence showing why someone skilled in the art would expect the success in the complex you carry out of environment a very much different environment than a pro carry out itself as a nucleus it has or complex d n a simply based doing at that point was looking to see if there was any profit and invest the that's the argument that the p t o makes in its brief on page thirty five i think we think that's wrong for two two reasons first if you look at the board's opinion there's nothing in the opinion where references t fish case or the fact that the examiner had made out the privatisation case the second i think is more fundamental and it confuses the two birds here there's a burden of production and a burden of persuasion i think that's being confused by the p t o here the case if it hadn't fact been made out which we'd all agree that it had been a don't see that the board found that it had it doesn't matter the burden of persuasion what we would for to it the burden of proof globally always rests on the examiner at all times to prove invalidity including by proving that one skilled in the art would reasonably expect success in one environment based on demonstrated results in another environment and the board clearly felt that that was an important concern because it is in the at the part that we just mentioned placed on the applicants the burden to disprove that link rather than time placing the burden on the examiner to prove that the link exists yes the examiner said there was a reasonable expectation of success but what is missing is any evidence from which one might conclude that one skilled in the art would in fact extrapolate the results from those other environments into the more complex you carry out environment so you're saying that even if we accept that chris that is what examiner thought it time that they're still not enough to put together chris jack with the with the yes but i think in the carry out environment it had the broad claim and what we would view as overbroad claim to the use of many different any graces in many different cells but there's no experimental data here that would indicate anyone skilled in the ar burden of proof the burden of persuasion always exists on the examiner at all times including to prove this likelihood of success and that's the error that we think was made here and just that to get at what the ford and the p t o are talking about with the cruise a reference  there they're using a presumption that the patent would would be unable we're not making an enabler and argument here and i think that presumption might work well in anticipation rejection which is where the presumption of liberty that attaches the patents that patents presumed valid and therefore that's all the examiner needs to do but in that obviousness rejection there isn't any reference that contains all of that elements of the claim and the inquiry is always what one skilled in the art would understand from the reference not simply that there are claims in the reference what one would understand and how to be applied to another area and people skilled in the art don't deal with presumptions they deal with actual evidence actual results actual screen results none of which proves a has in it and in fact i think that the p t o brief in our view is telling on this point of page twenty three of the footnote in their brief they actually say well presumably lambda integrate into the cell you would have to have some way of adding to it and integration host factor because the wild type only works with integration host factor and they say presumably you would have to do that recently so presumably if there's nothing i disclosing wild interest in you terry on excels and you're right it doesn't give working examples but why don't we presume want to kill me or would no help to do that since it is an issue patent and especially in light of the fact that you offered no evidence to the nicolai and so he said that now i think yes it's not as clear as the point directed to to the cruise a reference but what he's saying and that is that one skill in the art based on their own work by the way the christ and drove publication would have thought that you needed additional work in the new environment that they were using why didn't why didn't you offer a neutral declaration from somebody other than an interested party with respect to what one skilled in there would understand at the time i was not in prosecution i can't really speculate why we didn't do one thing or the other we did after the droege declaration where he's says here's what once killed me are you myself understood i don't think that the fact that he was the inventor should give that any less weight when i was looking at what skilled  art would understand and again i want to get back to what i think is the fundamental issue here and that is the burden is on the examiner to prove that one skilled the art would necessarily have a reasonable expectation and that's the key evidence that's missing you but ok so you've got two references and between the two of them they disclose all the elements the motivations the combined is the modified intends a greater affinity which provides a clear advantage over using the wild so why isn't that enough there's a motivation to combine haven't experimented beacher isn't enough we have an experiment prokaryotic isn't enough and the reason is not enough that those are very different environments so we have a case from this court which they don't by the way even to dress in their briefs that indicate that it's not enough and  these mutant races it says it doesn't really explain it i mean you have to concede there's no real explanation and and as your friend on the other side argues and able meant i and then it goes down further down that same column to describe that integrates the wild type land into great system so it's apparent that there's been a lot of work a lot of study done in this very important field but here we have one of the world's experts in this field grows and he writes a very even handed declaration which he says pretty much yes has been a lot going on  medicine we've been thinking about it but what he also says is in to you do it and find out whether it can be done or not you don't know who's a didn't do it he's got a catch all that i would think any and so the also says well it was obvious to do it and find out if it works i think that moves the standard a bit too far from as to what's of use to try and what was not obvious not and just relied on obviousness but for others since that's where i'm having trouble with this poor decision how can it be obvious unless you really have indicators that this is what you should do and it will work i have to well three things one is i want to talk about the enable rejection made by the examiner just quickly state that enable rejection with based upon broader claims that encompass looking like the old fashioned cord a telephone that i think we've all grown up with that's really very much what the d n a helix looks like if you turn it to the right so that it mutant integrate this works equally fine in either setting so it's not enough to say hey we don't know if that was work and you care about excel now moving into the dark trying to reason it's not enough to say hey we don't know if  both of those both of those reasons and length incited language stuff and both of those reasons are we submit erroneous and those actual signs were adopted by the board hoped but we didn't know until we actually did it whether it would work or how it would work and they then proceeded over what looks from the record like many years of research it wasn't something we were  just so you know that we have that test to really priority in there it is but at this this is not easy sons and the technology and the applications which they were evolving  incredibly complex where the office draws a lot it just looks to me a good deal to use given perhaps as to where the lines are drawn between the basic science and their applications but to show that this was straight forward or whatever the reason why i don't is racism and one question i would disagree with that people were modifying lambda to make and i think it's in the record somewhere there were over four hundred lamb debate that there is at this time it wasn't that that were you know many of which were being used and you cereal it wasn't it that it was too difficult to get to this point it was as if there were you know many alternatives that you could  it really gets a cannot be the the law that for a certain class of infections you absolutely have to reduce it to practice in order to to show obvious that it just it maybe is sort of the most well known and basic starting point for id so while the area might be unpredictable to the degree that there's more certainty it would be in the exacting with that issue here right i think  unpredictable and this court found that with unpredictable on that was merely obvious to try and that that what we were talking about in that case that that was  it progressed to the point where this facet of biotechnology is no longer that unpredictable which is examiner has to do to to satisfy the burden of establishing that there is a reasonable likelihood of success in other words you can't just assume that we take things that are done entirely different environments and things never say ok because it was done here it was done here it would be obvious to put them together i mean obviously there's more than that in our case makes a clear that there's more than add and we and you're putting this correct that more stringent it has more requirements and if you're moving this to the you you know and those that would carry the wild type in a grace has more requirements than them you and i were talking about them you know those they don't have those same sorts of requirements so there's more of an expectation that the newtons would work and you carry out then the wild type reasons why we would expect that this would work that these mutants would work in a new carry out excess and we have scientific reasons to believe that the wild type that the answer just moore's point on the bacteria phages lambda the worst of the part of the bacterial page means bacteria it's a bacterial product and it had been studied for many years in bacteria where it where it is native virus that infects bacteria what these people were doing was taking it into a different environment that you carry out environment and that's important because it's a big advance in the heart if you can do this re terminations inside you carry out excel you have the potential for gene therapy which is the alteration of genes in an actual living you carry out a being and you have the potential to create pharmaceutical products that are more tailored towards actual human beings because they're created in you carry out excel now engineered prokaryotic cells so that they didn't have a didn't produce a they made a mutant form of a pro carry out a still it didn't have a chance to test out the combination they did not work and you carry out excel and what creates and roche does say also and this is a page seven seventy five of the appendix and figure seven and as well as seven seventy six what they were speculating was that they did know why it worked in pro carriers and what they speculated was of their work e coli proteins speculating in their own work was that they needed they thought at that time that there might need to be e coli proteins that help this you can do with reaction and that's what dr gross repeated in his declaration at the time when we're doing this we're arc we didn't know what was going to work because we thought as it turned out probably wrongly we thought that they needed to be additionally cold like back tears and that's not surprising given that bacteria phages land comes from e coli is a virus that predictable but it wasn't shown in this case and the examiner had the burden to show it in this case is that a court case where where where somebody is coming in and have the burden overcome examiner the burden of an examiner to show that once  art would in fact predict success in one environment based on success and the other i would like to one correction if i might i know certainly is not really before the court and i agree with your honor on that but we have explained that hartley did not involve the use of these integrators you know if you carry out excel when she's referring to the host receiving the product what that means is that the host can receive a reconfirmation product that's already been created somewhere else there's nothing in hartley and it's in our briefs don't want to repeat what we