honor i think you know the answer to that question so what we're talking about today is an invention of the first drug that was ever approved for one month that does t treat any disease worse the patents covering that dosing regimen were found obvious into summary judgment the issues that i'd like to talk about today focusing material to the different courts determination of audiences and in particular i'd like to focus on whether there would have been a reasonable expectation of succeeding with a once monthly dosing regimen let me ask you a he's launched at rest and started to cause damage to rove we inform dish or for that we want to stick our damages in a trial that we in fact won a jury trial so there are damages that issue in the case there will be if you send it back because  several of the penalties watch the rest of generic products that infringe the pat but then you would have to amend your complaint presumably to it to include those claims if you send it back down but as the case now stands it would not tribally on the basis of the first complaint on the basis of the first complaint a believe that's correct we would need to amend the contents but i did point out one of the appeal is requested a jury trial and we haven't resolved the issue of whether or that which we interpret asked reliance on defend an argument you know that we we reviewed decisions not opinions and you've got this certainly it is simpler to take a medication once a month and then rather than every day and so obvious to try to let me answer that question i was going to yes or there are a finite number of predictable solutions and that's a very good issue in that case was the result of taking a one month supply of drugs all of one day at a predictable solution to the problem and that's where roche's expert testimony says no it wasn't for several different reasons so the question is did the court overlook evidence create a contested issues of fact on that very point that milligram dose did not have positive results because as the dose finding study and grab the included the dose response peaked at two and a half milligrams going that's another way of saying that it was roughly equally effective which is a positive result for the two point five and the five if i recall grab and that was fragments conclusion rather this conclusion was that the two point five and f whether if they both are under pressure and drug but why wasn't five a positive result because rather than also observe that the g i gastrointestinal side effects were higher with the five milligram dos rather than the convenience of the drug and remember that the effort in this area in this area of art was to have post menopausal women take continuous chronic therapy so that they would get protection against fractures and what ravin found with the five milligram dose was that it didn't give a better back and it caused higher the number of dropouts from the study meeting the patients in the clinical study didn't like taking the drug in the conclusion stated that the two and a half milligram provided maximal left the city and at the lowest affected so when you say more affective you're considering the side effects in the overall determination of the effect will correct because if you can't get a patient to stay on drugs then you can treat them with the drug basic basic premise and and what the court was spoke to stay on in this case and this is on spewed was that patients needed chronic therapy in order to have protection against fractures without being treated thirty five percent but also there's damage to the bone that leads to increased risk fractures the issue with that roche i v trial and rector as discussion schnitzer was it did increase bone density but that didn't have an effect on reducing fracture it was a failure the f d a record at a not statistically significant reduction i think was the conclusion correct if i recall correctly there was a twenty five percent reduction in the actual numbers order to conduct clinical testing on human beings you have to define the parameters to find success and because this is in water to test this doesn't even have the numbers they used they have to have three thousand women in that study for three years so our experts as we cited in our group all talked about the fact that was a failure if you don't demonstrate in effect beyond mere chance you haven't demonstrated that the drug works also point out the runner at eight o two one of the f b i records the f b i indicates that that trial was terminated prematurely due to lack of efficacy meaning the results were so bad they wouldn't so in the case of local local described i don't put a tablet's up to two hundred fifty milligrams the claims were limited during prosecution to a maximum of one hundred milligrams the statements  not refer to specific clinical trials and all of the experts in the case testified they were unaware of any testing of that drug published in the literature at those above twenty milligrams in postmenopausal  which was in reese fifty milligrams in the coleman cancer study and there was a very preliminary test of a hundred milligrams single dose in normal young healthy male volunteers the issue again if you go back to the toler ability issue is can you get post menopausal us to your precious patients which would be women typically in their seventy's to to find the drug collar bone up with a dose of your ministry so that they'll stay on  fifty milligrams oral once monthly dosing of a band or nate was already known and fought in the prior art so the only question a person of ordinary skills is going to confront is what  patent from actually doing that experimental work are understanding use a direct connect permit experimental work without infringed but that doesn't necessarily mean that the that the person of ordinary answering it doesn't necessarily mean that a party could have gone forward to commercialize the product because it would still covered by roche's patent all the way through two thousand and twelve ok so would you answer the question i asked you right so you said why didn't somebody else commercialize somebody else you know why didn't someone else make the discovery someone didn't make the discovery it was reported in the prior art it was reported in this country impressive milligram thirty for thirty days  anticipation analysis but the fact the matter remains is that selecting a dose is something that their experts and the prior are both recognized is something that was a matter of routine skill for the person of ordinary skill in the art so they focus ninety if you hadn't expressly said this is really something that the person foreigners on the air can do and is routine and their own expert admitted that once you have identified the drug you want to for multiple reasons first there's no requirement there's no threshold requirement of achieving anti fracture efficacy in the claims under roche's infringement else's for example they took the position that if any one woman take one single one hundred fifty milligram dose of their infringing the claims you're not going to achieve an a fracture efficacy with just that single one mill one dose but nevertheless that's the same type of activity that they would say infringes even though that particular woman doesn't achieve efficacy in fact mr dell just acknowledged that maybe only about thirty percent of women are actually going to potentially experience an anti fracture risk reduction benefit so i think the district court was correct and not saying that you advocacy not a part of the claims that you don't need to have that proof in the prior art again for reasonable expectation of success and i think that what the district court also relied on was the admission by their own experts that that bone mineral density which is the testing that was one of the test markers that was used in the reese paper discussing the total those concepts won't be the only mineral density is one of the most powerful surrogate markers we have in medicine today in the context of the field of drugs so when the restate for points out that under the total of those concepts you can hit the same bone mineral expectation of success likewise let's not forget roche has never tested the one hundred fifty milligram dose in an anti fracture efficacies study all roche did is they did a b c bone mineral density test to correlate it and also if i'm able to give the court an additional citation to one of roche's experts this is it a eighty four thirty one harris transcript of three or four lines eight to fifteen within any given bisphosphonate compound i think that one of ordinary skill would argue that a bigger bone mineral density change is likely to provide better fracture protection than a smaller change so it was recognised by those in the art that if you could have an improvement in bone mineral density it was reasonable to expect that would lead to better anti fracture efficacy so i think the district court was absolutely correct in finding that roche's anti fracture efficacies theory was really not material to the legal test which is is there a reasonable expectation of success with ways the first theory is that it somehow would dissuade the person of ordinary skill in the arts from following the total those concepts but the problem is that it can't serve as a teaching that way  about it it can't teach away from a flying little those concepts now the other argument that roche's ignorance mid ignorance is not the total relevant well for the way in which russia is trying to use that data article away from the total dose concept can't work because if you want to have a teaching away it has to actually be in the prior art if it's not in the prior art it can't teach away from anything because it's not known now the other way they've just say oh you know it's here with before this court is they're trying to say the secondary consideration is an unexpected result but in the ninety five seven summary judgment briefing and this is a one two two three four they specifically said quote roche is not arguing that non linear drug absorption is per se an unexpected result so having made that representation to the district court i don't think it's appropriate for them to raise or suggest for the first time here that it should count as some sort of independent standalone unexpected result so you're saying that that information should not be considered it's not like all of the cases to say that you have to consider the pharmaceutical context such as mcneil vs upjohn neal the pair go there have been many instances even where there has been evidence of secondary consideration that was undisputed certainly stronger evidence of commercial success as compared to the type that we had here and the court said that when there is nevertheless a strong reason or motivation to prepare whatever it is playing then that's not going to outweigh obviousness certainly a secondary consideration should be considered but as this court said in they are versus watson they are versus watson case reciting briefs the fact that you may try to put forth some evidence of secondary considerations doesn't mean it's going to change the ultimate outcome and i think that was actually one of the but how can you predict the ultimate outcome we're told that no drug has ever been approved before this for once a month  one that those patients with two point five milligrams a day and then dosed the patients with much larger versions of the doses and then let the patients not take the drug for the rest of a two month interval and what reese reported is that when you looked at the bone mineral density results with a two point five daily those versus the longer nine week off interval those those patients wound up in the same place in terms of the the very powerful surrogate marker that their own experts agree is the strongest predictor of anti fracture efficacy so with that teaching for this field and because the bisphosphonates the way in which they were is they get into the bone they humiliate their over time and because bone turnover is a much slower process then the drug is there to actually do its work and slowly over time builds up the bone mineral density that's why release was a very important paper in this field because it didn't give that assurance that now you can go for these longer doses and i think it's commercial success success standpoint once monthly didn't actually take the market by storm it actually didn't displace the ones weekly dosing so while it was out there was proposed it was suggested teaching that's one of the things they pointed out as they said if we're going to look at the preferred doses for these sites at this fascinates they had the narrow range and then they went to more preferred range of the five and ten milligram  the scofield publication also by the application of the title dos concept and approach has not shown any error in that in that undisputed material fact so when you get down to it what are the undisputed doses that worked two point five and five daily doses and when you plug those numbers into the total those concepts you reach a seventy five milligram in a one hundred fifty milligram dose it's a limited number of options and the district co concluded that for all of the other things that roche tried to raise they didn't change the undisputed fact and they did in their so called secondary considerations that this didn't really sway that how you actually calculate which the patent specifications here themselves relied on as the written description supported that certain hundred fifty milligrams it's two hundred fifty milligrams further the die so this is one thing explicitly said no significant side effects well is there specification doesn't give any safety assurances this port said it would be error to try to rely on that as a point of distinction versus the prior art but i would also say that does focus ninety three to patent which also well it didn't include clinical reasonable expectation that it was going to happen and i think that you might find some helpful testimony from dr harris to my point eight four two two there he testifies about those findings studies and he says dad we had to use surrogate markers to to do them but they didn't tell us whether we were really going to succeed or not he said most of the most of the trials a and intermittent dosing trial the fracture trial with the banter that it raised be ended but it failed to reduce bracket it was terminated prematurely due to lack of effort to see it and he says that this changed after this failure which is reported in the shitter paper this caused people in new york to focus on gee do we need to continuously suppress abnormal bone resorption in order to as the abnormal bone resorption destroys bump of course bone density goes down that's why diagnostic of the disease but in order to treat the disease you not only have to raise bone density back you have to fix the broken structure think of a bridge with the beams of rusted away you could well new steel on the beans but if you don't we stored the connectivity of the structure it's not going to hold up and that's what was unknown in treating fracture would be strong and what dr harris talked about a quarter to two we have the surrogate workers that we can use to try and find doses that we can then use in these three thousand patient multi year studies infringement there was a misstatement fine my friends i did not say only thirty five percent of women in french what i said is that if on treated thirty five percent of women will suffer a broken back or broken hip in their lifetime if they suffer from osteoporosis the aim of treatment is the tree or all women who are susceptible to the disease give them chronic treatment and give them protections against that potential like changing events