determination that ground attack so i guess the root of the argument we've got it right is lisa many many cases whether or not there is a motivation to combine whatever motivation combined into the question that yes you're right it's a question of fact because it's doctor calls testimony appendix one thousand one hundred and twenty five dollars they said that they would want to see that it too treatment combination was better than that single treatment before adding a rd treatment not one of the five references provide any clinical data results comparing two treatments to one in patients over sixty with d l c this is undisputed that would be a one or two reference that we're we're dealing with one of three well they combine five references so none right the claim doesn't isn't written that way the claim is not written that way but when you want a basic combined from the perspective a person skill in the art and what they've stoled us here in this case then in order to act before adding a rd treatment to a very sensitive skilled artisan be motivated here when we have a link that actually combined did a test on humans combining chopped with or whatever it's called and then we have another one mcneil that says i am going to run a clinical human clinical trial on on patients over sixty using me i mean there's a question of whether and i prefer to go skilled artisan would have been motivated but then we have evidence of people actually doing it i mean that seems age was forty nine over there but when you have mcneil which is specifically talking about this looks good for people who are over sixty this is what i'm going to do i mcneil am motivated and am going to do this particular human clinical trial so that sounds like pretty strong evidence that when you actually have someone saying they're going to do it as evidence that people would be motivated because there was at least one person mcneil who was going to do it well make a deal does not disclose any study design any details or any were dealt in fact mcneil says that patients over sixty have been excluded from clinical trials so we need to conduct this pilot study more all on its face board doesn't explain why a person skilled the art would nonetheless rely on link when patients over sixty weren't included in that study and it's also undisputed that elderly patients react to treatment differently than younger deal solve d l c all patients that come in to re thank you yes it matters because linked in is not a study of patients or sixty and mcneil says we need to have a study for patients over sixty because they've been excluded they actually identify a presidential panel that criticizes just that there should be a study and make no actually goes further to say that there should be a top alone compared to the top and a nd treatment mcneil does not disclose of the study done design it doesn't disclos link eight hundred and fourteen patients had great three toxicities eight had great four that's over sixty five percent of younger patients experiencing toxicities and that experts have confirmed that elderly patients are more prone to t design for patients over sixty because they respond to treatment differently so the experts have to testify consistently with each other that deals all t l c all patients over sixty had worse response to treatment and was worse taleb realty treatment talks expectation of success from the person skill no art and so what the experts had testify consistently with each other here is that a reasonable expectation success meant to them an improved prognosis for patients over sixty and even printed the sest meant to them and improve prognosis and patients over sixty for example dr sophy or in his deposition at seven hundred and eighty six so that we just talk about patients over the age of sixty successful treatment would mean improving the prognosis of patients over sixty it's suggest that there are going to be an improved prognosis in patients over sixty with a two treatment combination and the lack of clinical data here is even more significant because we have that person skilled are telling us what they what reasonable expectation of success meant to them it meant an improved prognosis and in fact position as in their original petition for i p r to appendix one hundred and twenty they acknowledge that the general problem confronted by the inventor before the invention was made was whether new therapies would have improved the prognosis for patients over sixty there's no evidence in the rhetoric that i was too good factual questions but when you're talking about improved prognosis so if you take two particular therapies  individually it's improvement over one of them individually so if you take top of a toxin they said that they want to see that toxin which of reflection is better than top alone before adding a rd treatment for patients over there doesn't disclose treatment of elderly patients with bone marrow involvement so what the board did is they really conflated and collapse a claim form to claim one rather than looking at claim for requirement that it doesn't say the director has the right to take sides when the other side has dropped out and i think this is a curious situation and here we have  the winning party refuses to do so while your i'm in this court has already decided the nose of the director does have the statutory authority to step in in this situation and we are here to defend the board's decision just like we do in ex part cases as part of the agency defending the agency's decision and i think that it helps the court and to really understand the merits of the case to actually have two parties disputing i think we're trying to understand the ro agency activity right and we're here to try and help your honor stand to make the best decision based on what our understanding of the board's decision and to give you the other side of the i'm looking at the combination right so morrow teaches all the limitations of the claim your honor except the addition of the cd twenty antibody reflects a med we can just call it the antibody that might be easier for everyone and morrow already has  has a successful treatment for the exact patient population that's claimed older patients that have d l c l and the question then the motivation question that your honor is getting at is the motivation then to add the antibody to that method that's how the board is from either of the motivation to combine and what the board looks at with the other prior art is in fact that there is explicit statements in the prior art to make the combination link is a study that combines for toxin med and chop in the l c l patients and has a night shows an increased efficacy over chop alone and ninety six percent efficacy without any increase in toxicity which is suggesting to someone that you can get a better africa see with adding or toxin and without extra toxicity and the older patients are the exact patient population that have this problem the toxicity of the chop that what mcneil says is this clinical trials and finding that they're getting success in that they're having responses from patients with d l c l and including people who are older patients with  sure what the regular agency has said about clinical trials for this particular combination that's not in the record but this court has repeatedly said whatever the standard is for an f d a trial it's not what the standard is for obvious the board there is substantial evidence for the board the motivation to combine finding we haven't even talked about mahoney which money is a study of a toxin mad and pellet correct that all the experts in this case agreed that reasonable expectation of success would hinge on and improve prognosis as compared to an individual truck that you wouldn't add a rd treatment until you knew anything to was better than just any one of them by themselves eighty five the seven hundred and eighty six but i agree with what you're saying that there are more generalized statements but given that all of the experts seem to have said and no experts contradicted the notion that in general you wouldn't think about adding a rd drug in with this patient population given the toxicity concerns unless you were sure that the two you were already working with was better than either one of them individually so to answer to that st the claims don't require any improved prognosis so for reasonable expectation of success it has to be a reasonable expectation of what is claimed and that is treating d l c out and the experts can't change what the claim say through their expert testimony interrelated yes so why would somebody be motivated to add a rd treatment and given the toxicity concerns in this picture population if they weren't sure that two treatments taken together are any better than why it is that those two concepts are intertwined for me ok it's so i think when pfizer's expert said that they was not saying it in the context of the specific facts of this case and i believe pfizer's expert understood this case based on the prior art there was reading that chop therapy as part of chemotherapy part of cell stem cell transplantation was already one conventional therapy for a certain population of patients with aggressive on so the motivation to combine issue was adding the antibody to what morrow or says is already the treatment of choice for a particular patient population and the toxicity concerns are laid because you don't city as chop alone but is it the same toxicity as what morrow discloses which is chop plus the transplantation so both proport not significant toxicity there is no toxic  no organ toxicity people do fail the trial with disease progression but i think the point is i don't i don't seem to understand i don't think the record includes but please correct me and articulation of toxicity for just chop versus toxicity for stem cell versus toxicity for the two of them together and when you need to know that before you're going to add a rd in which could further exacerbate the toxicity respond to chop you not to go on to treat the transplant patient of the cells the harvesting and all that and the toxicity associated with that entire therapy is what neuro says is actually tolerable in the exact patient population that's claimed d l c all patients who are older population so the toxicity concern is about adding or toxin med to that combination whatever it has some toxicity yes but not no toxic d tolerable right could be like just borderline on the edge of oh my god don't do it again you know we don't know where that tower i don't understand from morrow precisely where something would cross the line there seems to be no doubt that the additional treatment would increase toxicity the question is by how much i don't think they're i mean i don't think people do think adding rituximab would increase taxes because it increases type it causes toxicity in and of itself by itself the toxicity is we we know chop is probably the large cause of the toxicity concern morose says it added in the stem cell and then it was tolerable but it doesn't tell you whether it be increased toxicity above what chop alone would have had we only know it's tolerable tolerable to me seems like borderline tolerable doesn't seem like what you want to hear if you're hoping for you know  it's just you know tolerable means ok this is going to suck but i'm not going to die you know and so then then you're talking about adding something which has been established by this record to increase toxicity even if it's only in a minor way and i guess my concern is when you're in this patient population which is is definitely sensitive and you're talking about such a large number of references combining in such an unpredictable area i am sort of not confident in what you've done right two answers one in the end i think reading the tolerable therapy we are talking about a very aggressive disease that these patients have and fifty percent of them are surviving which is what moros to saying this is a treatment of choice for salvage therapy for a certain group of patients who don't have a good prognosis the review in the record says that chop therapy alone is the standard of care for people with poor prognosis with good prognosis and people have poor prognosis we're going to intensify with stem cell transplantation because they're not going to respond to chop alone so yes there's some toxicity associate and definitely with the transplant patient but the problem is this is the therapy we have for these patients the chop chemotherapy is part of all the stages you're going to do it will never sell it that's the thing i mean you've got the one level with this chopping up the stem cell which a more and then you say we should add a rd but the only reason to add a rd is because there are some study out there that says number one and number three might be a good idea to add together but what it doesn't suggest is one dollar and two dollars with the already more vulnerable population already with the increased toxicity is a good idea to at least three and that's i think i think you understand my concern yeah i understand your concern i will note that mahoney does suggest once with the toxin med to combine it with chemotherapy and stem cell transplant patient and you already have that therapy working in the exact patient population claimed the idea is you're having the toxin at the same time reducing the trial there that's it a moros therapy reduces the six cycles to three cycles at the induction phase and the idea is older patients can't handle the six cycles we reduce chop if we advertise the med link tells us we are looking at a high love all of  oftentimes oncologists would be motivated to add a new drug in this case for a toxin for a regiment that you've established and you think it's safe to improve outcomes dr o's are similarly in his deposition at appendix ninety the claimed invention and i can tell that testimony is linked to trying to understand or to the words of the claim treating deal still patients that are over sixty well in the context find you know the next solution but i'm also you know in a court of law where i have to give deference to the fact findings made by the fact finder below and then also understand how to apply the law here on obviousness and specifically reasonable expectation of success of the claimed invention out of all of that within what these witnesses were testifying to so treatment is some quantum better than prior art treatment i don't think there's any bright line rule or if there's any case all eyes a matter of law that this should be the standard we're talking about in the about run out yourself like tons of questions i mean you're obviously a much smarter and well understood on all these technology things that i am and you've done a great job in that regard today explaining it to me but my issues which i think you may have heard in my dialogue with the putting helpful i don't think haynes on me having to agree with you that a reasonable expectation of success i prognosis as opposed to any individual therapy i think i can still conclude a reasonable expectation of success in this case it's just over no treatment at all theoretically but i think whether it's through the mechanism of motivation  reasonable expectation of success which are intertwined did you understand my argument do you think i have to agree with you on this question you have about reasonable expectation of success in order to have the concern i do because i don't think i do i think i can conclude you're wrong about that but actually still maybe finding your favor because i think reasonable expectation of success may not have been at all reasonable in light of the toxicity concern think that's independent of this argument that you're discussing now on rebuttal but am i wrong is it not independent of that can you tell me are these things intertwined in short i'm way that i don't understand right so we take the position that a reason says the person is going art we don't think the board should come in and say what i understand what your position is but do you understand the question i have with great i don't know why a skilled artist and would add a rd in this patient population when the st two together were only tolerable and the rd definitely increases toxicity they don't know that i don't think that's the same as the argument you're making i mean i  just the combination with this antibody is going to have a worst toxicity well that's that's the problem there's there's no references that right but it says what it's about when you combine these two with those patients average age forty nine and i get that but if i could just step aside from that on its face it says there's no worse adverse there that your argument is that because link only deals with younger patients the fact that they didn't have a worse adverse effect doesn't mean that wouldn't be true for older people