may please the court the district court eroni asli invalidated the three five eight patent which claims a method of treating type two diabetes using a novel an unprecedented combination of two drugs that exhibited the combination with her pagla not the examiner and a district court analyzed this one of the two stretch steps obvious to try for it and we don't argue here that it would not agree that a skilled artisan would not have been motivated to try the combination but there is no evidence up here no evidence whatsoever that the magnitude of result actually achieved would have been expected by a skilled artisan and that was the burden that character of carried a trial had to carry out to cement that because it seems to me that you one correct that's correct right but in so far as i can tell the only evidence in the record comparing the results of those two compositions shows that the repaired home in the form in combination is not as effect as the earlier case your honor that's incorrect let me let me explain why first the evidence in the record shows the evidence the prior art for the critical date showed that rick had been not standing alone this is the wolf separate out what you say is attributable to to one aspect become what but you agreed that when you compare the two combinations that the result of your supposed invention is in fact less than the prior are absolutely not around or there's no comparison between those two there is no you may not like the comparison but if you make a comparison it shows what i said that's right your honor if you the absolute results are true knight one of the two compounds at issue and the district court didn't even mention it because it is in hireling inconsistent with the conclusion reached by the district court there is no way the caricature can carry its burden in light of the will to get a reference in the district courts failure to consider the most provocative evidence is clearly error prone but it's not a study of the combination when it comes is a study of one of the two comp ponens of the combination your honor and this court has made clear in many cases including the posen case most recently that wary combination therapy is claimed the monotherapy test must be considered in determining unexpected results that a black letter law that goes back to past and o'farrell that is the way a combination is established the way that  the unexpectedness is take the two compounds in monotherapy look at what we would expect them to do if the combination result is different as it clearly was here as it indisputably was here jericho's expert agrees that this would have been an unexpected result your honor in light of that evidence you can't ignore the evidence of one of the two compounds in monotherapy that is error you can ignore the evidence of the earlier comment if you compared it later and they didn't your honor when you asked about head to head comparison dr chil testify that the closest prior art was different to the front so clearly shows added foundations and the head to head to paris in the scientifically head to head comparison was made in the engine of moto opposition this was all testified about a trial that was submitted t examiner and she decided that it was still unexpected over that combination it is not absolute level of reduction too much reduction is harmful to a patient around or if you make them the blood sugar crash you're going to kill the patient your honor the the obvious to try framework grew up in the prosecution context where the after an initial rejection of the base the basis of obvious to try the applicant has the burden of showing unexpected results translated over into district court he didn't conclude as happened in your rant of one of these cases whatever where the conclusion of obviousness of the ultimate conclusion before secondary considerations were considered it seems to me precisely what is just as to what was wrong with this and by putting forth the record that was before the examiner and the persuaded the examiner of the factual matter that these results were unexpected it then became characters burden to show that a reasonable artisan would have expected these results the magnitude of result actually observed in th supreme court opinion which is a good start uses a different term it doesn't use the term overcome it uses the term just law is there in your view of that and a world of difference between the word dislodge and the word overcome your honor argues that it is never the pa even if everything mr perry just argued about unexpected results were correct and i'll just as arguments in a second there is one very simple reason while firm and moscow whether must be in a permit in this case and this reason percent confidence and ninety four percent is not the difference between high day or black or white well i i think that statisticians generally agree that you have to have to ninety five percent confident  general term ninety four percent confidence is does not disprove any relationship let me say that a different way you're talking about the right study so i'm trying to understand what you just said about soon the price that there's so many pay there's no not at all what your case doesn't depend on that life my case does not depend on proving the absence of synergy because this combination is obvious regardless of how somebody views the synergy issue but just to get to my first point unexpected results have to be reasonably commensurate with the scope of the claims the district court here held as follows the scope of claims for substantially exceeds the scope of the evidence of alleged unexpected results and went on and the record clearly and convincing convincingly precludes extending the probative value of those results beyond the small type two diabetes patients a population that experienced them their experts said their evidence of an expected result literally for fifty years article after article taught combining metformin with secreted gods because they have different mechanisms of action therefore attack the disease from different directions to achieve an additive so what is the burden on the other side what is the nature of the burden then the burden of production to show legally sufficient unexpected results but the burden of persuasion overall unclear recommitting evidence always remains with the challenge always expected unexplainable page sixty one clear this is a quote from the district court this was a finding a clear and convincing evidence that's our evidence we carry the burden clear and convincing evidence establishes  results of the claim combination therapy said by novo to be unexpected and unexplainable were to the contrary expected and explainable in light of the state of the art as of the critical day so the district court found by clear convincing evidence that the results they claimed were unexpected were both expected and explainable and that's fine it was certainly not clear air because there was a wealth of prior art that taught these two combinations could give you synergy under certain circumstances type two diabetes well you always have that meaning for any new drugs in regards what you expect to have the status of the f d a says satisfaction that your drug actually works so they had a tough they had to actually conduct a test but the prior art taught to that when you combine these two different kinds of drugs you're going to achieve even the synergistic results by different prior art articles bosses who expected whether they have to go through all these expensive clinical trials this is clear well i mean you always have to do the test to prove it up of course but if you have to prove it if it's no it is predicted to use we without any possibility of error while nobody's saying there's no possible things can go wrong that's why the f d a requires clinical studies to ensure the drugs are safe and effective but the the prior touch of this is expected to be a combination that would produce synergistic results that's what the prior thought and what authority talking about i think despite what you say that even with a ninety four percent probability some was an additive attack was shown however the right setting still to get i as i recall there's no numbers associated no synergy numbers associates human trials because they didn't run that kind of study so they didn't they don't have any evidence that it synergistic in humans and even in rats that cherry pick one data point because the overall erin of the cur to conduct very briefly knoebels lead argument lead argument unelectable conduct is that the district court failed to apply that there are some standards but that's exactly what the district court applies to but for materiality standard the most single for this particular dispute on this particular drug my client wouldn't have an interest in the unit will conduct interim issue because we need only win one of those two defenses so it only rests we don't have to decided what it will come i mean normally there's a reason for  meet in this case in fact the way they argued in their briefs they never identify particular factual findings as clearer they argue it as if it's a turnover review by this court where the real arguing all the facts the district court was there for three weeks said this to the folks internally at novo at the same time he submitted an affidavit to the patent office saying now we have clear evidence of synergy here's what he said i don't think he used the term  patent office his opinion they never got this patent for rejections in a row due in part to a lack of sufficient evidence of synergy and that's how they finally got over the top and here's what he says not possible to assess whether so we're being accused of infringement on this point explain that because as i understand it as a result of the earlier case yes the results here is that the use code has been corrected in the orange  capitol when people had diabetes to give them a pussy to placebo so that's why they didn't do the placebo and as a result they couldn't actually conduct any statistical analysis of synergy and that's why they thought maybe it's suggestive of synergy which is after with the prior art showed for the form that that's basically what's going on here right almost or on what they want to compare is the total results not the component results we want to compare the inventive combination to the closest parent which is a lot of very clear and unexpected real results you have to compare the invention say you want to compare it to the two the two compounds see their effect in the prior are considered individual rather than combined no your honor either considered individually we clearly when they're a things that is correct that is not correct or i don't think the greater drop in blood glucose levels that doesn't mean more effective this drug has huge advantages for example you can take this drug with meals you can't take the so funny areas with meals you can take this drug multiple times a day those drug you can do you  am a problem i am trying to answer what you want to talk about and i understand why you want to talk about other things other things may be relevant but i'm trying to focus you on making a comparison between the prior combination and this combination in terms of  and terms of glucose reduction that combination in the fryer are more effective no your honor and that is shown very clearly in the engine of moto opposition which were submitted to the examiner in detail to an extremely complicated all the tables all the charts are all there explaining exactly the comparison we cross examine dr chilly on that and he agreed with that so that was done a trial your honor and that doesn't appear anywhere in judge tones opinion for a very good reason because there is no evidence that that comparison holds true because when you correct for the different populations the different study periods a different dosages and so forth you know when you take out the apples to oranges problem because paris in doesn't hold and that is why you have to look at what was known in the prior art in the there was no evidence other than this additive effect and mr kerr said over and over again the prior art but synergism there are five articles he cites for that and they all use the word synergy which dr chili said was mushy to mean not antagonistic synergy in biochemistry does not always mean greater than additive every dictionary will tell you that and induct garber the author of through those three articles said on the stand and testify that he meant not antagonistic and there is this is an obvious this case your it was their burden to show th magnitude was expected there was no greater than additive prior art there is not to this day there is no trump how no combination works anything like this this is been a tremendously successful product did you know a few times prescribed is a hundreds of millions of dollars product they want to copy it recycling because it is so good for some patients with type two diabetics it is improve their lives dramatically it was a breakthrough invention a breakthrough combination and the patent office allowed it for that reason this challenge time it had only just been approved in united states today repack united well known to every diabetes practitioner at the time it had just been characterized and had never been approved in any country for in use so so all that's going on here is a bunch of hindsight twenty twenty reflection that we know today is a powerful popular successful clinically useful treatment at the time dr rackrent the only other study of a pattern i'd question whether it had any clinical benefit whatsoever the australian researchers said we shouldn't even test fasting plasma glucose because we know this drug has no effect on that and so you know we have skepticism for masters we have commercial success we have unexpected results where the finding of the examiner and against all of that we have nothing we have no evidence of obviousness this is a problem this judgment needs to be reversed and judged pros thank you