also people who were doing the process of trying to identify human antibodies did not use the fifteen mino acid that were then applied on the epitope to usually do anything in particular so it didn't after this they were using that c just knowing that there happened to be fifteen amino acids that make up the epitope doesn't help you find additional antibodies in any way so as a practical matter at this didn't this didn't disclose anything useful and of course the other problem of course with simply identifying the mino acid structure of the epitope is that's not the invention that's not what they claim with the claim is essentially the entire g canine inhibitors and the fundamental problem here is that when you describe even in some detail the epitope and then you provide two species that doesn't satisfy written description we say as a matter of law but the particularly acute problem in the way the trial proceeded is we weren't even able to put on the critical piece of evidence that this court use in abbey to determine that there wasn't sufficient representation among the species if you look at page twelve ninety three of the fed third in the abbey decision there's a big chart that shows essentially house the lera was very different from the disclosed an misconstrue a case law a whether or not it was just an evidentiary determination it would confuse the jury it was irrelevant to this cumulative so how do you see her determination are we sir see her determination as based fundamentally on a fundamental misconstruction about sort of rules of post priority evidence i'm happy to talk about what i think that is misguided to a fare thee well but just to be clear the suggestion that there was some sort of alternative rule for zero three alternative there is simply wrong and under third circuit case law that i think would govern this particular question it's reversible error for a district court to exclude on the basis of rule for a three without going through the balancing that's actually report i will for three so that that evidence you really can't stand on this sort of phantom alternative ground it stands on a fundamentally misguided idea that based i guess on this on this court hogan decision or improper court's decision that you just can't have this kind of evidence of the fused anti body and it wasn't just infused in a pot and wanted to show the jury we also wanted to show other antibiotics that were within the the genus and we want to show the jury how structurally diverse that are and of course as i as a limited to that was the critical evidence that this court relied on on page twelve ninety three of its decision and abdon and i think that that if we've been able to show that it would have fundamentally changed the determination because if you think about what the jury was asked to do here they're asked to decide whether or not the two specific anti bodies that are claimed you know and this debate whether two or twenty four but there are two that you actually have the x ray christology for new know exactly where they buy when they're asked to decide whether those two species are representative looking only at those two species so what's what is your view of what might be representative of what seems to me to say representative you need another property otherwise all you have this is i don't know how many i mean zero s as long these things are and every possible american combination which is an extremely large number nothing would be representative of anything else so what is the concept that might even theoretically lead you to say ok i've got the following thousand there representative of you know of the twenty to fourth or something or what's the concept what i think the concept that's supplied by area it is that they need to be representative of the structural diversity of the genus now i think is your question suggests that when you do as amgen did here and you claim a nearly infinite genus you're going to have an awful lot of trouble finding representative species but wasn't for dane that they claim again is that represented a structural diversity it seems to me i'm still not beyond the sheer number of you know twenty amino acids at possibilities at every one of of however many spaces what what is it representative of century every anti body that has ninety five percent of the same structure now if they'd done that then you could at least i think argue that it would be what they disclosed actually was representative of the genus that they can't because it would have that overlapping structure but when you claim every single thing that binds to an epitaph then i think you're setting yourself up for failure i mean you know but please don't blame me i didn't i didn't set forth the term of the genus engine came in and they wanted to claim everything that was that you know essentially that would block at the epitope and i think they set themselves up for failure because i don't think they can identify the common structural feature of anybody care about would they really evidence that traditionally people have cared about the amino acid sequences why because that's traditionally how you've claimed essentially ennahda these for years and years and that maps on to how you claim evidence to that effect i don't know that it's actually ultimately material in my view of the case may be material to you there is a whole dispute below about the blocking properties of the various antigens and you know we had you know essentially there was there was the issue that the to disclose antibodies are no allegedly edge blockers which is to say if you think about the fifteen amino acids that make up the epitope they sort of a century band on one edge or the other and we if we could  show the jury this which we could but you know our product accused product actually happens to block in the center and i believe that there was the testimony certainly we would have been happy to proffer it that there actually are some advantages to having a center blocker rather edgewater now honestly i don't think that's rough because i think what's relevant is the broader principle that you cannot claim everything that blocks on an epic tope simply by  that be their will that you have to specify the actual you know that the the chemical structure of the amino acids as opposed to if if truly every single one of the trillions and trillions structure and it only shares twenty six percent of the amino acid sequences in the cd ours that's what we want to show now that can have all sorts of differences and a great illustration of that is that pfizer also had an antibody  the party that had claimed the epitope would have been able to block everybody's antibody even very different chemical anti bodies even though they're at their body their species doesn't work as medicine now we wouldn't want that in  small molecule space it's a happy world that there are multiple statens on the market but they all operate in the same basic of otoh have we move on to a related question which deals with the jury instruction and yes i mean it's a look a little troubling or a little hard when the just record essentially in get reaching her jury instruction was plugging sentences from opinions that some of us have written including me to then turn around and say she's wrong now your answer to that is maybe correctly that that was all and so that we can now disassociate ourselves from those remarks and say the instruction was wrong but what would we have well i think you have more than judge prose to me first of all i do think and you know my friend on the other side describes this as nit picking in his brief but i don't think it is and i think it maps on directly to what the court said in footnote four senate core which is what even if you're going to assume for a second that the newly discovered new characterized antigen instruction is good law and i'd eventually like to tell you why it really is time to just and the madness and say it's not but if even if you assume that's generation of the claimed antibiotics and the what claim which i think is what is in this court's cases was not in the instructions and so if the question is and it may have matters a lot because you know the generation of antibodies that don't actually block at the site they don't have characteristics that is routine i suppose but to generate human antibodies that block at the desired citing that site that's not routine at all and indeed it's a process it's an arduous trial and error that my clients were in the involved in that amgen was involved in when engine came out with this invention it didn't change what they did as a practical matter they still had to engage in the same trial and error process that was additional evidence that went to in a moment in our view that we weren't able to put in front of the jury because this misguided priority ruling so that instruction doesn't follow this court's cases and the suspension isn't a nit pick it's absolutely critical and i think it actually  maps on to how i read this court's decision seneca or which is it said well that instruct doesn't apply here for among i think two reasons that are both leap likeable here one is the generation of antibiotics for human bodies was characterized it all everybody knew that was out there everybody was trying to do the same thing which was to come up with a human anti body that blocks the interaction between p c s canine in the receptor and both before and after th invention that was a trial and error process that required sensually you know well understood techniques but techniques that were arduous and require trial and error and the critical thing to understand here is just finding o i would like to just take a moment though to you know sort of say that you know i think this court in the senate court decision and you know i've reviewed the oral argument that case and i know it was a focus of the ork in that case i think there's an excellent argument that at least if you're trying to transfer the newly characterized energy and the so called antibody exception to the human anti bodies it just doesn't work it's based on a nine hundred seventy six textbook and it just the science just doesn't map on to the way the reality works today at least if you talk about human and i pods as this court said in the senate where this is maybe it makes a little bit of logic to say that if you discover a keyhole and that easily and routinely translates to one key you can claim the keyhole and the key but as this court put it in seneca work even if you have the keyhole there's a ring out there with a million consent and it really doesn't do you much good to simply describe the keyhole and so i think for that reason the science doesn't support it and i also like to make a humble point that the law doesn't support it means written description is a requirement that you describe the invention the invention that's claimed here is an entire genus of antibodies they don't claim that they invented the sweet spot where the epitope or the fifteen amino acids nor could they in a post myriad world so even and again this is another aspect in which what's going on here is actually not with this court has talked about its prior  this court talked about its prior cases a hypothetical possibility and we're somebody could claim the newly discovered antigen and the antibodies that went with it now in a post myriad world i think it's common between the parties describing from what the statute requires you to describe the statute requires you to describe your invention the target of your invention the problem you're trying to saw is not your invention and so no matter how much they describe in atomic level detail as they like to say the structure of the epitope it doesn't matter what they need to describe is their invention what they claim is this entire genus of antibiotics and they haven't adequately described that and just to go back to first principles what marion tells us is they have to show a common structure there is no common structure or they can show it by these representative species but as i alluded to earlier it's representative species of the full structure that makes up the genus and we don't think two can get that done we think we should prevail as a matter of law based on the four corners of the statute of before we set out about the matter of l i haven't been able to find do you have a case that says a complete non making of a fifty a motion just not a matter of interpretation a couple of words of a just you just never ever  the ready but i will tell you that the case law that they cite in response to that the dura last case doesn't help them at all mean girl asked i think it's actually drew exactly this distinction which is to say look you know if things were being handled in a relatively informal way and they were here in the sense that you know one page briefs and we're basically told don't worry about it i get your objection it's preserved when things are being done that way the law in the third circuit which is what's relevant here says that you can as long as you do something that sort of but everybody had that's right i tried to frame my question as i'm not sure you did anything on this boat but we didn't we we did we did we essentially objected to the sufficiency of the evidence we ma clear that that was our objection and we were essentially told by the district where judge yeah i got your i got your objection my point is that's not it there's no there's nothing that sort of says it has to rise like that this level of formality in them will take it the next step you just have to do something essentially to prize claims and then the court said well we can't stick it in there for you and i think in a way that that distinction actually makes some sense because the first certainly in terms of the role of the review in court the first one really flows sort of directly from the degree of formality that the district court wants to sort of run his or her court with and if they're doing this in a way that makes clear that everybody sort of gets the idea that the fundamental issue here is we don't think there's sufficient haven't see that's we've made this clear from the beginning and we continue to make that clear if the district court judge doesn't want formal motions on that mean so be it and i certainly think once she found in the jay momo sion that we preserved it and then went on and dressed the merits for sixteen pages that ought to be enough for this court on the x ray crystallography provided in the past this is one of the antibodies that at this is p c s canine and in terms of what was actually discovered when engine started its research all that was known was that p c s canine affected pieces of a three dimensional jigsaw puzzle so that for these to fit together there's a larger piece that goes here it's such as they're on the rolls over and at that point they come together very tightly tightly enough to allow the understood to have the characteristic y shaped structure of a monoclonal antibody with constant and variable regions almost all most almost all of any anti bias the same the main difference is here in the tips the business sense and that is where you get the structure from that because the claims reference the structure of the sweet spot and you then know if these two fit together that's close in the structure of this gives you all of the important common structural features of the that's how they fit together but how do same way or do they touch on part but not all of that structure there can be differences but they have to have the common structural features which history talking about but if we're talking about six common structural features they all have the common structural features to to even talk about it if if it does that if your position is that it doesn't have to match up hundred percent every single ad which i say that it is that they don't all work exactly the same way isn't it your duty to show that the structures are sufficiently similar that they don't have any other kinds of effects or the like are you to say anything that hooks up with that is sufficient to shove a written description now it's not just anything it's anything again there are multiple tasks for and description we could roll through them but on in terms of the say the middle one common structural features it doesn't mean that they're done it all means that the share of the comments that disclosed antibodies and the common structural features of others were right so what understand it let's assume that it's you you have a point at regions one two and three and that's the structure you can show based upon your particular suspicion whatever they're of that you have and they were preclude it from showing that there's all at thirteen fourteen and fifteen which are completely overlapping regions why is that the same structure sure i'm going to and forgive me if i get the three shows up in a couple places during the trial what the court explained in this is page eleven fifty seven to answer your question answer page twenty it starts around line seven as the court explained that they didn't need specific examples to prove the absence of fact their experts testified the this weak spot is this area that i just showed you and that they had an exam and they argued that exactly what you just said which is that the based on her conclusion that case law compelled her to exclude the at the end it was all a legal argument citing hogan and at the end some of the cases i guess the initial rush that and the  transcript whether or not what she what the she was talking about your evidence some time with their evidence right here our evidence was excluded before trial and when we along with law with their evidence with during trial when they kept fighting us and there be one example  thousand and one the very bottom of it when the court was then revisiting us she says but again this is an evidentiary question not the general question that was read by the federal circuit uses i said if including the advie case understand the princip the question is as i think you acknowledge it is or at least can be whether you have shown a sufficiently representative  number of examples covered your claim to class representative of something or other i'm not quite sure yet what why is it not important fore the other side to be able to walk in some detail through an example to show imho that it can be persuasive look at just how different at the molecular level this is from that now i'm no less you're going to tell me the molecular level is really really completely unimportant  that's why i keep asking about what it means to be representative because i'm not sure until i know the answer to that how to evaluate the significance of the evidence that they were barred from putting earth right we're talking about i mean generally speaking trial is that what's important is the three dimensional structure that's what affects finding else what effects blocking diversity in amino acid sequence beyond that is not important and because you can have vastly different you know acid sequences that have exactly the same same common structural features the reason is that if you write off the string of amino acids what's important is that how they fold into a three dimensional shape and only some of them you know houses have anything to do with how old into a three dimensional shape or with the chemical  which is why you can have two that are more than after friends but still have the same relevant characteristic of life shouldn't they have been able to show that their particular version or any other specific examples that they were able to d whether it was the accused one or anybody else's lilly's or somebody else's hold really really quite differently and yet buying to at least one of these fifteen amino acids  big difference between confusion and highly prejudicial right i mean confusing was because she said well you stipulated to intrenchments so it might confuse the confuse the jury to bring the seven and that's what the rational for confusing i believe the course understanding why it would be confusing is that the question is if it's in the sudan is that at the page twenty eight i think it combined with cumulative which is that  if you're looking at what happened after the fact after the fact after the fact it's normally not considered relevant u s steel for example held that it doesn't matter whether subsequent antibodies are discovered but that is wildly different properties because section wan because section wants well as the chairman at the time of the invention well that's her legal and that's the legal issue that's presented and that's the relevance but even then if you want to put in more evidence it's only q accusing it's also never was even handed because before trial they persuaded her to exclude engines that means that one of the management discretion that she couldn't let them put in contrary evidence having already excluded ours and especially under this rule for all three balancing just have to use the numbers for three hundred real balancing and gets cumulative and prejudicial if you know of first confusing and then also even now in terms of resembling the rule fifty a motion and that's that's the whole damn girl asked as a matter of law no fifty a motion no jam all very fundamental precept the protection of the things that are lost explained some of the men are going to challenge whether fact question goes for a jury after have twenty four record not just to twenty four representative antibiotics those lines it's just one of those across the sweet spot the talk about edge binders what that means is that each of them touches contrary edges but they also almost come together in the middle and you have these different these twenty four and you know acids that actually you can determine their representative because they all have the common structural features and they cover nearly the entire suite they also represent seven different gene families in the expert testimony is that there is considerable sequence diversity specific examples in description of how to go make many more and a comprehensive road map as dr reese testified for how to use those twenty four to go make it into to go make thousands of others then what you have is a situation where it point in time people can then disco and make others and it was also said that engine after the fact was still doing the same sort of this actually blind screening that was before not true at all here's what the patent actually discloses terms the conference of road they been with this one if they can both find at the same time if not then they have overlapping binding sites and that's shown in example ten of the patent then if you want to confirm that it really does find the sweet spot example three of the patent shows you how to then do a blocking formulas and algorithms in the patent where you can substitute cell take out amino acid and put in another one according the formula you know that will still work that would get you out of the claim scope this is all you can have there's also the c d r shuffling which essentially means you take two reference antibodies and mix and match the parts according to formulas to go there and have ideas that would work and then dr reese testified that doing that you can create thousands of other anti bodies and if any protection if that would get around a valid antibiotic patent specially  very issue the fact that they can bring in different types of structure sure they can point to they only have overlapping things and twenty percent versus ninety percent of the stuff is irrelevant yeah sorry i didn't see all of the point what they were trying to get at that kind of evidence i mean it would go one of the twenty over ninety percent they have evidence that they wanted to get and that they show this structure is so substantially structure of this was three more amino acid sites but i think the reason i want to keep these ads this isn't the invention it's fine that they describe three mino acid sites here that nobody knew about but this is it with their claim this isn't what they're claiming either at least not number of these go of things with pink on them because that's how many are in the genus they claim and they completely precluded us from showing that the structure which didn't is not function the fact that something has  mean it has the function of binding but the structure could be very different i mean they all have the basic y shape and everybody knows that we when they did we have precluded from having your expert testified that there were an infinite number of such structure merely merely precluded in saying here is an example that happens to be ours look at us we are experts we didn't have to have art experts say that there were a nearly infinite number of such a of anti bodies and that in the gen because that came from their expert dr pets were so so that was that was before the jury but this gets to this issue sort of cumulative and is where effect i mean this is being argued to a german a jury's being told that there's th spot and we have one species that we've disclosed the parts here and one that parts on the other side and to a jury that's not told that there's something else that looks pretty representative the fact that they're edge finder seems like a good thing because they're on both edges what could be more representative of course if we were allowed to come in and show that no actually there are multiple other anti bodies that have been indicted in a dependently developed that have very different structural characteristics and they think they may not have this exact y shape that if all the little different but in all events they find in a very different place and then if we were allowed to tell you what everybody in this field thinks of it's part of the structure which is the amino acid then i mean i love my friends phrase the business ends of these things because that's exactly what our testimony focused on and it showed that on the business and prevalent there was only twenty six percent overlap in  that's what we wanted to show the jury now in terms of what would be most effective for the jury would have been twenty six percent that would have been the fact that it parked right in the middle of the con the trial is set can tell you that most as of this question and i that would meet the claim limitation and that they would by and but they would look very very different and maybe even bind on different sides of the middle as opposed to the wings was were you not able to to put in evidence that many many different structures looking very different would satisfy the cli i mean our experts may have been able to say something about that constrained by the same post priority ruling which is fundamentally wrong and if i can address that for a second i mean you know we all know the sort of you know a false consistency is the hobgoblin except i mean you know harriet specifically says that there's a problem with an inventor putting in post priority evidence to make the written description something that it wasn't at the time but nothing in ad the or common sense suggests that if you have something that's in the claim that structurally looks completely different from the only to disclose species but you can't get that before the fact finder and in abby there was an unresolved issue about anticipation the court you know if there really were this cliff you fall off if it's post priority there's no way the court in every would have considered that made at the focal point of its decision a page twelve ninety three and the way i think about it is this which is if you had something that was in the claimed genus that was pre primary that would give you both an anticipation argument and a darned good argument that the disclosed species were not representative of the structure of the whole genes if you have one of those that comes into being afterwards no longer shows anticipation but it's every bit as relevant as showing that at the time of the priority date the written description showed something that they just didn't possess because they need to show structure structure is not function binding at the site it's the function that they've claimed it's not structural what structural in this context is amino acid sequence and we're not trying to limit them just to the amino acid sequence though that is how they principally claimed and that is how we principally claimed probably when as i pointed out in my opening argument you can claim a genus if it's a genus of thousands and that if it's face on what you disclose in ninety five percent homology will avoid all of the substitution my friend talked about innovation that's the way you can claim a genus where you actually have a species that's representative but you can't claim a nearly infinite genus based on a description of the epitope and to disclose species if i just make two other points in rebuttal my friend on the other side said  that you don't have to you know invoke the number for a three well the third circuit in the class decision says that you do and you have to do the balancing before you exclude the epts as the chief judge indicated i don't see how you could say that allow us to disclose a radically different structure would be unduly prejudicial and in the context of a trial where they have these two yellow things that represent they're too close this close species and we can't put on ours i mean that's hamlet without the prince that it's not cumulative that made a huge difference both in a court of law but especially in front of a jury the last point i want to make is i actually really would like to just invite you to read your last because so the point i wanted to end on is simply this you know this whole idea that there is an entire body exemption i think is fundamentally misconceived there isn't any anti body exemption in the relevant statue and the rule here should be the same for large molecules as it is for small molecules nobody thinks that one company gets to make every step just because they discovered the binding site nobody thinks that there should only be one aids protease inhibitor on the market just because one company described the binding so nobody thinks there should only be one cox two inhibitor on the market the rule should be any different in the end i buy context somebody whether it's an engine or pfizer based product ended up not working as medicine should not be able to quander the market on p c s canine inhibitors just because it ascribed an additional three mino assets on the binding site and came up with two species that aren't representative of the entire species genus can't thank you we thank