Legal Case Summary

. There isn't sufficient Description to enable the production, but that's not to say that there isn't in the specification Indications of directions to go Methods technologies to use that would point you in the direction the only question is how much of a leap right between what's in the spec and what Ultimately is obtained. That's correct. Let me break it down into the two different legal principles because I think the distinctions important For the written description issue a wish or a plan is not enough Pointing someone in the right direction is not enough for enablement. It's slightly different analysis But try let's focus on what Senna Corset to the jury on enablement their argument was it's all out there It's all out there in the prior way we disclosed a couple of things 19 words in column 18 and Affinity Modulation in column 33 we disclose a couple things and when you combine it with everything that's out there That's enough this court said in Genentech the obligation of the patent key on enablement is to enable novel aspects of the invention particularly where you have Disclined as with true and Genentech and as is true here Or you identified a problem that should now put forwarding to solve the I'm sorry. No good

. Okay. The it's all out there Isn't sufficient as a matter of law and that's what this court said in Genentech So I agree with the distaste your honor is drawing. I think there are two different analytical disciplines We have to engage in written description the area of requirement of structure chemical properties physical properties Representative number is to communicate I've got it. I've invented it Camerican anybody the C a2 is adequately described isn't it the American body's adequately described it right? Anastatically it's adequately in a right and so in the process of Manufacturing the C a2 you're gonna get to get some human right into the Region because it's it's a mixture of human and you're right, right? No, you are actually that's placed where I think the records undisputed and if I can go to that issue The key area is the complimentary determining region. It's referred to in a Lily grave is the hyper variable region Those are the keys and both of us agree that those are the keys They're different I'm sorry what I was trying to get at is it look to me like the argument that your opposition is making you as look we've described and enabled the C a2 and The C a2 is this blend of human and non human in the Gravel region for the binding and it's not a big deal As a matter of science

. It's not a big deal to go from there to the fully human At a well and they say you know and the tools are here Well, they're three answers to that your honor. The first is in the regular big step in science Yes, it was it was a big step your honor It's the reason that their witness described Humera as a dramatic innovation and it was because there's not a progression between Mureen to Chimeric to humanize to fully human fully human as the record demonstrates was the Holy Grave It was if you go back to the 91 application your honor that they filed they said a Full human antibody would be ideal, but you can't do it So we're gonna do the primary didn't know how to do it from this particular Well, they didn't know how to do it for this to go to the energy and in 19 Sepsis hadn't they had a fully human antibody perception. Yep, but you're on a by 1994. They still didn't have it and Let me to go to your honors question really explaining me why I mean look to me like like the big deal was to go to these people at cat And it takes them about six months to be able to come up with a Reutomatory totally human antibody and then they have to tinker whether for a few months You know you're out of it. There are three answers to your question first is in the record at a 579 to 580 and 2020 1920 You will find the amino acid sequence of the variable regions of CA2 and humera as the lowly wave Demonstrates those different by more than 60% and those are the key The second thing your honor is send a court self-sit with the disclosures that your honor has just described We didn't have the Exproperience to make a fully human antibody the third thing your honor is The undisputed record is not that someone just had six months in it popped out you had the best scientists in the world working over period of years making innovations and inventions Innovations and inventions and phase display guided selection affinity modulation all with the end result That added invented the first fully human antibody Got a patent on it a patent for the issue two years before these claims were ever fine Now to go to judge Bryson's question that Recication collapses a little bit the written description and enablement issues, right? but if you take this court decision in area ad and you take this court's decision in Genentech They both decide these issues as a matter of law area ad in fact there was a jury verdict Their in fact was competing expert test That's what I was going to get you to backing away from the science and getting back to the law because as you well know It's a question of fact

. We've got a jury verdict here. We can assume the jury didn't credit Dr. Mark's your principal witness So where are we left on the question of fact or we only to look at the for the you know Four corners of the document and decide for our set elves you and judge Clement They were talking about whether it was a big step or not a big step How are we supposed to as a question of that devaluated? You're I think in the same way that the court did an area ad the same way the court did an an escape decision Which the Supreme Court denied served on yesterday it looked at the Specification and looked at the record and what in both cases this court looked at were the fundamentally Undisputed facts the fact and matter is they didn't call an expert But if you took Dr. Mark's and we pretended or we assumed from it he had never testified Never testified at all Let's just assume that for a second and we look at this tent in the specification and we're looking at what they claim to have done as of 1994 There is no disclosure that satisfies an area ad even if this were a species claim Where is the written description of the precise definition of physical properties chemical structure or formula? There is not for the genus there certainly is not For enablement to go to judge bison's second question on enablement I don't think anybody disputes that the argument that it's all out there is not good enough before this court You have to enable the novel portions of your invention and again if you go to that Issue There's no dispute you don't need Dr. Mark's and you're on it here's the best indication that they haven't enabled the novel portions of their invention What did they say they said jury and they said you it's all out there? Well by saying it's all out there

. They're saying to you. It's not in here And if it's not in the specification you haven't enabled it To be fair when I my understanding of the context of that statement is that what they're saying is the technology is available And we describe the technology in the in the specification and it is out there and in that sense Available for ready implementation by persons of skill in the art now I understand that you disagree with that, but isn't that in itself a question of fact? No, your honor. Okay, guys Let me interrupt you before you answer it just to make sure that part is in it We're gonna not hold everybody to the strictly to the time limits here So we'll make sure that we will at least make an effort to try to keep the amount of time equal So don't worry about time the answer is no your honor and here's the reason why their argument has two components to it The first part would actually fall within which your honor just described in 1994 there was material added to the specifications there are nine marks is article for one thing Dr. Marx's article a 1993 article in a peer review journal right and then I mentioned a affinity modulation in column 30 phrase display But the argument was not that that was enough there were five other references None of which were identified in the specification at all That were the basis for it's enabled and we cite those to your we cite those to the court in our brief But there were five other references none of which were cited so If you step back from this honor and you think about the progression that's been presented to the court and judge Post to go to your question about what you can decide as a legal matter Here's the progression the first stopping point is the fully Characters and agent of Tina Falfell was out there and we identified the binding site. That's not enough That's enough But if that's not enough then those two things plus identifying Dr

. Marx's article plus referring to fit affinity modulation is enough But if that's not enough there these five other articles out there now at the end of the day It's critical to distinguish the two concepts these other articles that were out there Or pointing in the right direction if that's what they did isn't sufficient for written description Right actually honored that's no different than area edit that's no different than Nintendo that's no The opposition starts off with a presumption of validity, right? So this this patent is presumed to be described and enabled and your honor over your problem is to knock it down You put Mr. Marx on the stand Right and he's your guy and if they don't believe Mr. Marx then what's left of your? What actually your honor you still have a burden actually your honor we can sustain that burden Just says the defendant did an area head just as the defendant did in Nintendo By pointing the court to the undisputed facts. That's why I think an answer to judge Post Just I don't want to rub to the club and it was that in enablement there's an do experimentation I think it's harder to get over that the jury Disbelieved Marx under cross examination Dr. Marx under cross examination I think on the question of under experimentation

. I see it is slightly different than the area model Which was exclusively on written description? That's true area and Nintendo are both on written description and the answer to judge Pfevitors question is it's the reason we have J. M. Well is the reason we have appeals is to look at what it's fundamental The undisputed evidence if we're gonna just defer to any jury verdict and I've been here before both defending them and attacking them But then but you're still got the problem on undo experimentation your witness who says well, you know You these tools were out there yet, but the honor is judge process correct that has nothing to do with the written description I'm still talking about a label. Okay, and I think that judge post Statement is right. We have to distinguish between the two

. You feel more I well this may not be a fair question But I'm not limited to fair questions You seem to feel that you're on somewhat firmer ground with the written description with respect to this issue of the Problem that the jury verdict presents you is that a fair characterization your honor if I were I think it's a fair question and a question we've thought about I think if I were to rank them for your honor under this court's area decision in Nintendo, Toronto The easiest way to get it to jury verdict is written description because the standard is clear The Rochester case says you can answer it to go up judge Clevver's question on the basis of what's disclosed in the specification As a matter of law now yet you like the genentech case in the enablement case the area because it is In some respects pretty close it the genentech case is actually very close to honor and so if I were to say which is The most easily dealt with as a matter of law on undisputed facts written description is it Enablement on the specific facts of this case compared to the genentech case You get very close and the reason is this Genentech you recall was a preliminary junction in case but the court decided to address the question of the validity of the patent as a matter of law So you did well that procedural context different you do address it as a matter of law and I think you're Hard time you keep on saying they're under written description. They're undisputed facts, but written description is entirely a question of fact We're here you're just we're disputing what the specification whether the specification adequately describes it So I don't see that there are undisputed facts I think there's to the extent written description is a question of fact. There's an entire Actual dispute I don't think there's any dispute on the following there is no example of a fully human antibody disclosed There is no There is no to go to judge Bryson's question. There is no teaching As to how to make a fully human antibody with the claimed characteristics There is no amino acid sequence or DNA sequencing coding the hybrid variable or complementary determining region There is no identification at identification of the structure of that hyper variable region There's no dispute as it's just like the area and Just like fears and lily And you can take that and then the question solely is this if we believe if we apply area precise definition chemical structure formula physical properties What is there and the answer is there is nothing and The best indication that your honors. What do they point to they say to you the following? They say that disclosing the fully characterized antigen and And the binding site is enough That's wrong for five reasons The first is they don't claim just one binding site to go to judge the cleventer's question They claim multiple binding sites and epitope or epitopes so they're claiming a genius The second is the disclosure at column 13 of the patent Basically, it doesn't say here's a locking key

. It says here's the general region five or more will do If we're using the locking key analogy, this is closer to what here's the door the locks somewhere on there And you find the lock maybe you can find the key the third thing your honor is the case the if they were correct If they were correct The language in and noelle that's in the case that both are you seem to be dancing around and not actually fully embracing but isn't that the language there that if you If you have the the antigen That's the law you get the key well Let me address Noel and the pq training materials at the same time because no well is dick because Noel is holding is No, I'm sorry. Go ahead. Well, I was just gonna say that you know Saying that it's dipped him maybe true But it isn't a terribly warm endorsement of a path for us to follow in design in the case So so any other help that you can give us with the noelle case would be would we welcome other than to simply say well It's dick to me. You could ignore it. No, I actually was gonna move on okay Okay, but what I was gonna say your honor is it's dick to end the whole thing is that the disclosure of a muring Antibody or anogen is not sufficient to disclose the human antibody

. That's the holding now The pq guidelines or training materials are noelle collapse. So let me address both of them together because noelle is Commenting upon what thinks he's sitting is an example 13 16 is it depends what we're dealing with the 99 version of the later version, but it's it's the same example So let's start with the guidelines because noelle follows noelle chronologically follows the guidelines the pq training materials don't apply for these reasons first the claim is different If you look at the claim it's any energy and it's capable of binding Any antibody capable of binding to the engine so it's a very different claim than the claim here that requires high affinity Neutralization and competitive innovation the second is the time of the guidelines is 1999 That's when they're first promulgated not 1994 when we're dealing with Our claim priority date the third is the technology is different the technology is a non-full human murine Hybridoma it's a different area of technology But the fourth and key distinction because it goes to fears and lily is this The words youth in example 13 or 16 are routine Convention the presumption of the example is that there's a well-established correlation between function and structure There is none here so the time was different the claim was different the technology was different and the presumption that there's a well-established correlation is different well is that is what you are saying are suggesting that in Some instances are perhaps many instances there is such a correlation that they're just doesn't I mean I'm talking about antigens and antibodies now, but they're just doesn't happen to be here or are you saying That that's just wrong Grievously wrong is a matter of science because with no antigen is there a corresponding antibody? You can't simply look at the endogen and boom you've got the antibody right it seems to me What you've just been saying is saying well, you know this and maybe this is an effort to respond to my Question about what beyond dictum you can say about the well, but It seems to me in your brief you were saying that that's just wrong as a matter of basic antibody science You're I think these two things We have sighted to the court in a law review article that came out shortly after the example 13 or 16 and it said It's just wrong as a matter of antibody science the You know I was written by Lily's counsel and Lily's an amicus in this case That's so much sort of like saying well, we're citing our amicus brief, right? I mean that well, but you know compliant with the courts rules that was their amicus brief not I understand not ours But you're on a here's the here's the best indication In no well picking up on that if you read the dicta that Santa Corvallize upon it almost presumes that there's one antibody for one antigen But we know that's not true No one contends that's true at all. So actually I don't you know we've talked about this question Scientifically do we think it's likely incorrect? Yes, if you build upon the Example though and you take it into no well Let me just say these things about no well because I was trying first again the claim is different Right the claim is just binds to the antigen any antibody the binds in the antigen doesn't have any of the additional requirements we have Here, right, but that presumably would be even broader class, right? Right, you're on a but remember we're the written description requirement There if you apply the written description requirement and you have a broader class But then you claim a narrow reclass you're going to have to show that you have possession of the narrow class If I invent the airplane and I describe to my specification the propeller airplane But then I have a dependent claim it says I have a jet airplane and I assert the jet airplane Again the subsequent inventor of the jet airplane that I need a written description of that Dependent claim that subgenius jet airplanes in my specification and It's in some ways it's almost counterintuitive But it's correct if you're going to have additional requirements of high affinity neutralizing right and competitive inhibition you need to describe that because the fact the matter is your honor the Well, those are all the functional components, but there were some structural Components in the specification as well, right? Not not for insights not for fully human antibody. Here's what Senna court has done in its briefing Here's what Senna court did in its brief and here's what it did with jury In 1994 in two locations it put the word human antibodies in Kyron says that's not enough. That's like the perpetual time machine in area It's like the automobile in the 19th century in Rochester They then pointed to the jury and you and said oh, but see all of this over here about high affinity neutralizing competitive inhibition that was all the chimeric antibody They had no information About those properties for the fully human antibody So to go back to Noel and finish your honor. It's a different claim Right it is at the end of the day the holding is one that we actually embrace I think to the extent and and this is the best indication it is dick I think in some ways if you take what they're doing and taking the training materials and building it into a suggestion that there is And antibody for each and a gin We do know that is not true Let me add just two other thoughts and then I'm well by on my time that I'll preserve whatever time you'll give me for Rebuttal um One of the thing I want to go back to this question of whether disclosure of the fully characterized and a gin and the binding site is enough and to go back to the samples Your honor in the examples It is the patentee who was disclosing the fully characterized and a gin and then making a claim based upon In this case the fully characterized and a gin was disclosed in 1984 By someone else it was fully characterized in its crystal structure in 1989 by someone else The binding site was in the prior It follows her on the logic of Letterman the the the keys belong to whoever invented the energy The energy and predates here, right, but this is not a case where the night where the patent ensued in bed of the energy Yeah, and you're on I think that there is no case where this court has gone so far as to hold That if you fully characterized the anagen you have the antibody But if your honor is correct and you follow through that logic the claims invalid That's I think what yeah I'm sure clients is too. I mean all the antibody claims are in valve. Yeah, that's exactly right I mean if that's the big difference. There's something wrong with no I'll guess Letterman when you read if you try to read it literally They say that if you invent you know if you have the antigen you invent the antigen And you know the binding site then you're going to get all the antibody that that's exactly right and and the difference in no well Those of the ad antigen in note the no well case was not Unlite in contrast to TNF here what you say was in the art long before right and and the key difference between the statement in no well And the pto training materials are that they presume that it's the patentate Who's disclosing this full characterization and then claiming invention This is judge clementary points out as a situation in which it was out there for a decade Right and after that decade they're now claiming Right that was enough to demonstrate they had possession of the invention that would render the claim Inval and I'll say the rest of my time for both Let's see Mr. Williams could you add Let me say 15 so if you could add Why don't you say 20 minutes To Miss elderkins time and will that'll probably bring us up to about parody and we will reserve some time for mr

. It's a different claim Right it is at the end of the day the holding is one that we actually embrace I think to the extent and and this is the best indication it is dick I think in some ways if you take what they're doing and taking the training materials and building it into a suggestion that there is And antibody for each and a gin We do know that is not true Let me add just two other thoughts and then I'm well by on my time that I'll preserve whatever time you'll give me for Rebuttal um One of the thing I want to go back to this question of whether disclosure of the fully characterized and a gin and the binding site is enough and to go back to the samples Your honor in the examples It is the patentee who was disclosing the fully characterized and a gin and then making a claim based upon In this case the fully characterized and a gin was disclosed in 1984 By someone else it was fully characterized in its crystal structure in 1989 by someone else The binding site was in the prior It follows her on the logic of Letterman the the the keys belong to whoever invented the energy The energy and predates here, right, but this is not a case where the night where the patent ensued in bed of the energy Yeah, and you're on I think that there is no case where this court has gone so far as to hold That if you fully characterized the anagen you have the antibody But if your honor is correct and you follow through that logic the claims invalid That's I think what yeah I'm sure clients is too. I mean all the antibody claims are in valve. Yeah, that's exactly right I mean if that's the big difference. There's something wrong with no I'll guess Letterman when you read if you try to read it literally They say that if you invent you know if you have the antigen you invent the antigen And you know the binding site then you're going to get all the antibody that that's exactly right and and the difference in no well Those of the ad antigen in note the no well case was not Unlite in contrast to TNF here what you say was in the art long before right and and the key difference between the statement in no well And the pto training materials are that they presume that it's the patentate Who's disclosing this full characterization and then claiming invention This is judge clementary points out as a situation in which it was out there for a decade Right and after that decade they're now claiming Right that was enough to demonstrate they had possession of the invention that would render the claim Inval and I'll say the rest of my time for both Let's see Mr. Williams could you add Let me say 15 so if you could add Why don't you say 20 minutes To Miss elderkins time and will that'll probably bring us up to about parody and we will reserve some time for mr. Lee for rebuttal Thank you may it please the court The inventors of the 775 patent made a substantial and significant advancement in size and the jury verdict Which rejected Abbott's position that this specification does not provide a written description or enablement Is correct and supported by substantial evidence And this is not a case where the invention is trying to preempt all TNF antibodies This is really a narrow invention. There were three witnesses at trial Dr. Graham send a question to the inventor Dr. Southveld one of Abbott's inventors and Dr. Marks their expert who all testified That's what's critical is to find an antibody that binds the TNF in the right place To make the TNF stop working to neutralize it Now anti TNF antibodies were known human anti TNF antibodies were known Dr

. Lee for rebuttal Thank you may it please the court The inventors of the 775 patent made a substantial and significant advancement in size and the jury verdict Which rejected Abbott's position that this specification does not provide a written description or enablement Is correct and supported by substantial evidence And this is not a case where the invention is trying to preempt all TNF antibodies This is really a narrow invention. There were three witnesses at trial Dr. Graham send a question to the inventor Dr. Southveld one of Abbott's inventors and Dr. Marks their expert who all testified That's what's critical is to find an antibody that binds the TNF in the right place To make the TNF stop working to neutralize it Now anti TNF antibodies were known human anti TNF antibodies were known Dr. Marks their expert had made one in the early 90s and we don't have there's no obviousness challenge to these claims before us Because what was invented here was the specific class of antibodies when you say human TNF alpha antibodies were known not with the high affinity and Exactly not until these inventors made their invention Was it known how to make these anti TNF antibodies work? These are the inventors who decide who discovered that if the TNF if the antibody buys the TNF in the right place So they compete with a2 it works But how does it bind it in the right place if they identified the human variable region? Where is that in the path the right place on the on the TNF is identified in the patent as in two ways by The competition with a2 if an antibody competes with a2 for binding to TNF That means they bind in the same or similar region And that is one way of defining the structure and the the patent even talks about the particular anti amino acid residues on the TNF antigen which are implicated in as the patent discloses the regions of the TNF molecule Where the a2 antibody or a2 specific antibodies bind So this was a this is a narrow invention and it has Several flavors as we know the claim languages performing a written description task Yes, yes, just as it would in a chemical compound claim if I had a chemical compound claim to benzene with lots of substituents on it That's defining the invention and hear the a2 specificity that's recited in the patent I heard you to be saying it's the a2 specificity that's beginning to describe for you the human human That is describing the structure of the antibody Effectively a purely functional limitation right and to say that it competes with a2 doesn't tell me anything about what its Sequences it doesn't tell me about what its structure is it doesn't tell me anything about Where specifically it binds where the epitope is right it just tells me something about its function No, I would argue that it is a structural definition Because the we had witnesses a trial who talked about the lock and key analogy for antibodies and antigen interacting The antigen is the lock the antibody is the key and doctor Works or doctor self-added said if you know the lock that helps to define the key Well, what we have to find with these patents what the patent defines here is the lock is the keyhole This is the keyhole So that you can turn the antibody turn this TNF off and neutralize it My analogy is that the keyhole is very large and the and the key is a little smaller so just on the basis of the Top competing with a2 the key is rattling around the lock isn't hitting the tumours You need to have more specificity right? There's no evidence of that the evidence of record is that a2 specific antibodies and there are two of them that we know about one Is Abbott's umira and one is Santa Cours Remicade are very effective at turning off TNF now there may be other antibodies as well But there's no evidence of their on record that that is not a sufficient description We had a long discussion with mr. Lee about the noel case and the whole if you've got the antigen then you've got the antibody notion You don't you're you're pretty certainly can sort of mentions that concept but then Seems this may not be a fair characterization But seems not certainly not to fully embrace it and perhaps even to walk away from it You don't really believe that that's correct as a matter of science do you? No, we're not walking away from we're being very careful not to characterize it as a holding because I know I'm here let me sort of take to the chase here and and setting aside holding in dictum and so forth You don't believe that if you have the antigen you've got the antibody correct Well, there could be many antibodies to an antigen which sort of answers the question right because they're You don't have if you have many you don't have any one You have a category and then we're into the problem of deciding how you how well you've defined the categories right and the particular category here Are the antibodies that are a two specific that compete with a two that is some genius In noel To the effect of If you've got the antigen you have the anybody is just wrong. I do not and I and there's no basis on this record to change that I mean for over a decade the expectations of the industry have been based on the patent office written description guidelines And this courts guidance in cases like no well and ends though that's the expectation of the industry and that's Those these are the experts at the patent office talking about the Recognized correlation between structure and function of antibodies and there's nothing nothing on this record That would in our in would do respect allow this court to overturn that because there's nothing in this record Patent on anticipation if that's the case because TNF was known back in the 80s I don't think you dispute mr Lee statement in that regard so if just knowing TNF the antigen gets you Or is sufficient written description for the antibodies then everybody's invention here is anticipated But there is no wrong about that that analysis. Oh, yes, you are your honor the issue was not whether the TNF antigen was novel or not There are many with them. There's a ration at if the theory is that if you own if you if you own the antigen you own the antibodies I have problem is that your client doesn't know the antigen somebody else sounds yeah So somebody else owns the antibodies with all the respect I don't believe that was the the underlying basis for no well that well There's a sentence in no well and since we've been talking about so much I'm just leaving it so it's on the on the floor I believe this is the right sentence if no well It's sufficiently described the human form of CD 40 CR antigen He could have claimed its antibody by simply stating its binding affinity for the fully characterized antigen Which sounds pretty much like saying it's my shorthand in some cumbersome fashion If you've got the antigen you've got the antibody you can claim it But of course the consequence of that position would be if somebody else has the antigen They got the antibody and you don't so why do you let me put it this way you agree with that sentence as a statement of Science science is that scientifically correct? I have no basis not to disagree with that based on the record and based on what the path of the experts at the patent office Is it not to disagree me you have no basis to disagree? I have no basis to disagree with that

. Marks their expert had made one in the early 90s and we don't have there's no obviousness challenge to these claims before us Because what was invented here was the specific class of antibodies when you say human TNF alpha antibodies were known not with the high affinity and Exactly not until these inventors made their invention Was it known how to make these anti TNF antibodies work? These are the inventors who decide who discovered that if the TNF if the antibody buys the TNF in the right place So they compete with a2 it works But how does it bind it in the right place if they identified the human variable region? Where is that in the path the right place on the on the TNF is identified in the patent as in two ways by The competition with a2 if an antibody competes with a2 for binding to TNF That means they bind in the same or similar region And that is one way of defining the structure and the the patent even talks about the particular anti amino acid residues on the TNF antigen which are implicated in as the patent discloses the regions of the TNF molecule Where the a2 antibody or a2 specific antibodies bind So this was a this is a narrow invention and it has Several flavors as we know the claim languages performing a written description task Yes, yes, just as it would in a chemical compound claim if I had a chemical compound claim to benzene with lots of substituents on it That's defining the invention and hear the a2 specificity that's recited in the patent I heard you to be saying it's the a2 specificity that's beginning to describe for you the human human That is describing the structure of the antibody Effectively a purely functional limitation right and to say that it competes with a2 doesn't tell me anything about what its Sequences it doesn't tell me about what its structure is it doesn't tell me anything about Where specifically it binds where the epitope is right it just tells me something about its function No, I would argue that it is a structural definition Because the we had witnesses a trial who talked about the lock and key analogy for antibodies and antigen interacting The antigen is the lock the antibody is the key and doctor Works or doctor self-added said if you know the lock that helps to define the key Well, what we have to find with these patents what the patent defines here is the lock is the keyhole This is the keyhole So that you can turn the antibody turn this TNF off and neutralize it My analogy is that the keyhole is very large and the and the key is a little smaller so just on the basis of the Top competing with a2 the key is rattling around the lock isn't hitting the tumours You need to have more specificity right? There's no evidence of that the evidence of record is that a2 specific antibodies and there are two of them that we know about one Is Abbott's umira and one is Santa Cours Remicade are very effective at turning off TNF now there may be other antibodies as well But there's no evidence of their on record that that is not a sufficient description We had a long discussion with mr. Lee about the noel case and the whole if you've got the antigen then you've got the antibody notion You don't you're you're pretty certainly can sort of mentions that concept but then Seems this may not be a fair characterization But seems not certainly not to fully embrace it and perhaps even to walk away from it You don't really believe that that's correct as a matter of science do you? No, we're not walking away from we're being very careful not to characterize it as a holding because I know I'm here let me sort of take to the chase here and and setting aside holding in dictum and so forth You don't believe that if you have the antigen you've got the antibody correct Well, there could be many antibodies to an antigen which sort of answers the question right because they're You don't have if you have many you don't have any one You have a category and then we're into the problem of deciding how you how well you've defined the categories right and the particular category here Are the antibodies that are a two specific that compete with a two that is some genius In noel To the effect of If you've got the antigen you have the anybody is just wrong. I do not and I and there's no basis on this record to change that I mean for over a decade the expectations of the industry have been based on the patent office written description guidelines And this courts guidance in cases like no well and ends though that's the expectation of the industry and that's Those these are the experts at the patent office talking about the Recognized correlation between structure and function of antibodies and there's nothing nothing on this record That would in our in would do respect allow this court to overturn that because there's nothing in this record Patent on anticipation if that's the case because TNF was known back in the 80s I don't think you dispute mr Lee statement in that regard so if just knowing TNF the antigen gets you Or is sufficient written description for the antibodies then everybody's invention here is anticipated But there is no wrong about that that analysis. Oh, yes, you are your honor the issue was not whether the TNF antigen was novel or not There are many with them. There's a ration at if the theory is that if you own if you if you own the antigen you own the antibodies I have problem is that your client doesn't know the antigen somebody else sounds yeah So somebody else owns the antibodies with all the respect I don't believe that was the the underlying basis for no well that well There's a sentence in no well and since we've been talking about so much I'm just leaving it so it's on the on the floor I believe this is the right sentence if no well It's sufficiently described the human form of CD 40 CR antigen He could have claimed its antibody by simply stating its binding affinity for the fully characterized antigen Which sounds pretty much like saying it's my shorthand in some cumbersome fashion If you've got the antigen you've got the antibody you can claim it But of course the consequence of that position would be if somebody else has the antigen They got the antibody and you don't so why do you let me put it this way you agree with that sentence as a statement of Science science is that scientifically correct? I have no basis not to disagree with that based on the record and based on what the path of the experts at the patent office Is it not to disagree me you have no basis to disagree? I have no basis to disagree with that. It's true then why doesn't possession of TNF alpha Give possession To the antibody or antibodies all of the antibodies of TNF alpha Under that sentence that seems and that's I'm just reading it that seems to be what it's saying I I think that maybe we read that sentence differently. Okay. That's what I want from you Tell me how you read it right see if that seems to make it sure I respectfully disagree with counsel's Representation of what the new L holding was I believe he said it's a holding is a disclosure of the murine antigen was not a description of the human antibody to it And that's that's not the issue the issue in no well was that they were trying to claim All antibodies to both human and murine Antigens the cd40 which would be analogous to the TNF that we have here so that's the thing that the antibody is binding to and they had Disclosed the sequence of the murine CD40 they had not disclosed the sequence of the human cd40 so it wasn't an issue about who owned it or who discovered cd40 It what the issue was did you disclose the sequence of the antigen because Based on what the patent office has done in its guidelines which this court has accepted in a number of cases The issue is whether you have a fully characterized antigen not who owns it But did you fully characterize it and if you did that according to the guidelines and you can claim antibodies based on their affinity They're binding affinity to that antigen, but noelle hadn't disclosed the human antigen sequence here Which with reasons to that sentence which burns and and you're reading of that sentence that differs From the one that I suggested is exactly what I want to make sure I have exactly what your view of that It's not that noelle didn't own or discover the human cd40 sequence is that they didn't disclose the sequence never mind what happened in noelle This is I think everybody agrees this is is is a piece of dictum which isn't tied directly to The holding of that case, but what the court is saying there is I understand it is again If you've got the antigen If you have sufficiently described the human form of the antigen you can claim the antibody without more presumably at least there is If it says by by its binding affinity to the antibody and that's precisely What we've done here except we've gone much farther than that we have disclosed the human tnf structure We we invented a class of antibodies You didn't fit the antigen And that is not the basis of the noelle decision the basis of the noelle decision is it regardless of who invented cd40 maybe nobody invented it It exists naturally did you characterize it? Did is there a characterization of it either in your patent or somewhere in the other state you care You're the novelty of your invention is that you characterize the tnf Yeah, the novelty of our invention is all the things in the claims But part of the written description of our invention according to the guidelines and again with this court has said is if you have a fully characterized antigen Which we do here tnf You can claim antibodies to it based on their binding affinity to that Based on their binding affinity what I was reading that language to mean is if you have something that binds Then you've got the antibody that you can fully claim all you have to show is that it binds to the energy I understand binding affinity to mean by a certain that it binds to a certain extent as in our claims We require that the antibodies have a particular affinity I think it's one time send to the aid to the way of measuring the strength of the bond to the antigen which is purely functional correct that particular part is functional Yes, so you've not described You can't point us to any structure you're just saying that there's efficient description because we describe the tnf Which was not novel and then we've listed the function Under the pto guidelines that's all that would be required, but we do go farther than that We go farther because we describe the antibodies as being a true specific and that is a structural definition of the antibodies Well, let me ask what else because we got into this discussion because For my purposes at page 44 in your brief you're saying you're not relying on the structure of the antigen as the only evidence of compliance So that's where I thought you're kind of walking gently retreating from the no-elterth and you say to the contrary The there are many facts which evidence the addictions closure So what what's beyond the a2 specific? Well the a2 specific Let's just take off of the playing field entirely the whole argument about knowing the specific characters is the antigen Okay, taking off one of the data points And in the fact that the show you've described the fully human Anybody the fact that we are limiting ourselves and define them as a2 specific But these are antibodies that bind to tnf in the same way as a2 at the same or similar place as a2 and the patent defines Where that is on the tnf molecule? It says these particular amino acid residues are implicated in this binding and because of the known correlation between structure and function of antibodies and antigens On which pto guidelines are based that is a structural definition You have to you have to be a little more specific with this second point the known correlation Well again the the pto guidelines are because the pto guidelines don't say that you have to have an actual amino acid structure for an antibody They had to claim to it they recognize that there's a known correlation between the way antibodies and antibodies and antigen bind And the function of the antibody to put the problem here nobody actually knew That very information with regard to an entirely human antibody Not at all the again the key here is that by finding this particular class of antibodies that are a2 specific that bind like a2 Unlike all the other tnf antibodies that might be out there that aren't Effective in neutralizing tnf like dr. Marx is antibody the ones that are specific to a2 Turn off the or neutralize tnf and that is a structural Description because of the lock and key analogy that happens witnesses use in describing antibodies and antigens. I suppose Well, you may disagree, but I'll put this proposition out on the floor for you That it is at the time that the 94 application was filed it was entirely possible that No one would ever find A fully humanized antibody that competitively bound a2 at the 10 to the eighth Litter's per mole affinity level correct It's entirely possible that nobody would ever find one a that no one would ever find one and be that there isn't one right I mean that There's no way you can tell me that there I take it that there was definitely one out there or more but This was the best we could do to describe it right? No, the patent it's and it's been established again through through the evidence of what Of abits own infringing antibody that a human antibody it what we know now But in the 94 could you have been if we were standing here having this conversation in 1994 Would you be able to tell me with dead certainty that there is An antibody that satisfies the requirements of claims 2 and 3 Yes, and Dr

. It's true then why doesn't possession of TNF alpha Give possession To the antibody or antibodies all of the antibodies of TNF alpha Under that sentence that seems and that's I'm just reading it that seems to be what it's saying I I think that maybe we read that sentence differently. Okay. That's what I want from you Tell me how you read it right see if that seems to make it sure I respectfully disagree with counsel's Representation of what the new L holding was I believe he said it's a holding is a disclosure of the murine antigen was not a description of the human antibody to it And that's that's not the issue the issue in no well was that they were trying to claim All antibodies to both human and murine Antigens the cd40 which would be analogous to the TNF that we have here so that's the thing that the antibody is binding to and they had Disclosed the sequence of the murine CD40 they had not disclosed the sequence of the human cd40 so it wasn't an issue about who owned it or who discovered cd40 It what the issue was did you disclose the sequence of the antigen because Based on what the patent office has done in its guidelines which this court has accepted in a number of cases The issue is whether you have a fully characterized antigen not who owns it But did you fully characterize it and if you did that according to the guidelines and you can claim antibodies based on their affinity They're binding affinity to that antigen, but noelle hadn't disclosed the human antigen sequence here Which with reasons to that sentence which burns and and you're reading of that sentence that differs From the one that I suggested is exactly what I want to make sure I have exactly what your view of that It's not that noelle didn't own or discover the human cd40 sequence is that they didn't disclose the sequence never mind what happened in noelle This is I think everybody agrees this is is is a piece of dictum which isn't tied directly to The holding of that case, but what the court is saying there is I understand it is again If you've got the antigen If you have sufficiently described the human form of the antigen you can claim the antibody without more presumably at least there is If it says by by its binding affinity to the antibody and that's precisely What we've done here except we've gone much farther than that we have disclosed the human tnf structure We we invented a class of antibodies You didn't fit the antigen And that is not the basis of the noelle decision the basis of the noelle decision is it regardless of who invented cd40 maybe nobody invented it It exists naturally did you characterize it? Did is there a characterization of it either in your patent or somewhere in the other state you care You're the novelty of your invention is that you characterize the tnf Yeah, the novelty of our invention is all the things in the claims But part of the written description of our invention according to the guidelines and again with this court has said is if you have a fully characterized antigen Which we do here tnf You can claim antibodies to it based on their binding affinity to that Based on their binding affinity what I was reading that language to mean is if you have something that binds Then you've got the antibody that you can fully claim all you have to show is that it binds to the energy I understand binding affinity to mean by a certain that it binds to a certain extent as in our claims We require that the antibodies have a particular affinity I think it's one time send to the aid to the way of measuring the strength of the bond to the antigen which is purely functional correct that particular part is functional Yes, so you've not described You can't point us to any structure you're just saying that there's efficient description because we describe the tnf Which was not novel and then we've listed the function Under the pto guidelines that's all that would be required, but we do go farther than that We go farther because we describe the antibodies as being a true specific and that is a structural definition of the antibodies Well, let me ask what else because we got into this discussion because For my purposes at page 44 in your brief you're saying you're not relying on the structure of the antigen as the only evidence of compliance So that's where I thought you're kind of walking gently retreating from the no-elterth and you say to the contrary The there are many facts which evidence the addictions closure So what what's beyond the a2 specific? Well the a2 specific Let's just take off of the playing field entirely the whole argument about knowing the specific characters is the antigen Okay, taking off one of the data points And in the fact that the show you've described the fully human Anybody the fact that we are limiting ourselves and define them as a2 specific But these are antibodies that bind to tnf in the same way as a2 at the same or similar place as a2 and the patent defines Where that is on the tnf molecule? It says these particular amino acid residues are implicated in this binding and because of the known correlation between structure and function of antibodies and antigens On which pto guidelines are based that is a structural definition You have to you have to be a little more specific with this second point the known correlation Well again the the pto guidelines are because the pto guidelines don't say that you have to have an actual amino acid structure for an antibody They had to claim to it they recognize that there's a known correlation between the way antibodies and antibodies and antigen bind And the function of the antibody to put the problem here nobody actually knew That very information with regard to an entirely human antibody Not at all the again the key here is that by finding this particular class of antibodies that are a2 specific that bind like a2 Unlike all the other tnf antibodies that might be out there that aren't Effective in neutralizing tnf like dr. Marx is antibody the ones that are specific to a2 Turn off the or neutralize tnf and that is a structural Description because of the lock and key analogy that happens witnesses use in describing antibodies and antigens. I suppose Well, you may disagree, but I'll put this proposition out on the floor for you That it is at the time that the 94 application was filed it was entirely possible that No one would ever find A fully humanized antibody that competitively bound a2 at the 10 to the eighth Litter's per mole affinity level correct It's entirely possible that nobody would ever find one a that no one would ever find one and be that there isn't one right I mean that There's no way you can tell me that there I take it that there was definitely one out there or more but This was the best we could do to describe it right? No, the patent it's and it's been established again through through the evidence of what Of abits own infringing antibody that a human antibody it what we know now But in the 94 could you have been if we were standing here having this conversation in 1994 Would you be able to tell me with dead certainty that there is An antibody that satisfies the requirements of claims 2 and 3 Yes, and Dr. Graham explained that you could do that. How would you know that? It was already there How would you know it was not it was not already there no but it but Dr. Grave explained that if you find antibodies that bind the same ways you If you can if you when you make one and yes you make one though, right? You might be able to make one You might be saying you would know it when you found it But the question is would you find it and if you didn't find it is it because it's not out there I mean what is it about it? I mean it well that that logic Go to the ultimate conclusion that you can't possibly claim anything until you've actually made it Which is contradictory to decades of this court's jurisprudence? It's contrary to decades of this court's jurisprudence is as you don't need to have an actual example Well, I'm not leaping to that. I just want to know before we get to that question Whether there's anything that would that you can point to that would satisfy me that yes The 1994 application tells us that there is such an animal We just can't give it we can't describe it with any more specificity in other words if I make some something in the lab silly putty or something whatever you know something that he makes by accident I know how I made it but I have absolutely no idea what the structure is but I've got it And so I know it exists and I characterize it by function and smell and a few other things a pretty cumbersome characterization But I put it in a patent application because I don't want to wait to get the thing sorted out chemically I'm fine now the question is is this that case? Did you know that there was such and that anybody or were you saying if anybody comes up with this antibody? we get it The invention here was the specific class of antibodies that bind to TNF like H2 and did you demonstrate that There was at least one member not that you'd made it but that there was at least one member of that class out there In the chimeric antibodies? Yes The human in the human antibodies there is not a specific example No, there was not a specific example, but again, that's not required by this court's jurisprudence And you know mr. Blea has argued that the only way this could have been a Satisfying the this this specification could have satisfied the written description is having an actual example amino acid sequence by amino acid sequence of the antibody and again That is Contrary to what this court has said in other antibody cases

. Graham explained that you could do that. How would you know that? It was already there How would you know it was not it was not already there no but it but Dr. Grave explained that if you find antibodies that bind the same ways you If you can if you when you make one and yes you make one though, right? You might be able to make one You might be saying you would know it when you found it But the question is would you find it and if you didn't find it is it because it's not out there I mean what is it about it? I mean it well that that logic Go to the ultimate conclusion that you can't possibly claim anything until you've actually made it Which is contradictory to decades of this court's jurisprudence? It's contrary to decades of this court's jurisprudence is as you don't need to have an actual example Well, I'm not leaping to that. I just want to know before we get to that question Whether there's anything that would that you can point to that would satisfy me that yes The 1994 application tells us that there is such an animal We just can't give it we can't describe it with any more specificity in other words if I make some something in the lab silly putty or something whatever you know something that he makes by accident I know how I made it but I have absolutely no idea what the structure is but I've got it And so I know it exists and I characterize it by function and smell and a few other things a pretty cumbersome characterization But I put it in a patent application because I don't want to wait to get the thing sorted out chemically I'm fine now the question is is this that case? Did you know that there was such and that anybody or were you saying if anybody comes up with this antibody? we get it The invention here was the specific class of antibodies that bind to TNF like H2 and did you demonstrate that There was at least one member not that you'd made it but that there was at least one member of that class out there In the chimeric antibodies? Yes The human in the human antibodies there is not a specific example No, there was not a specific example, but again, that's not required by this court's jurisprudence And you know mr. Blea has argued that the only way this could have been a Satisfying the this this specification could have satisfied the written description is having an actual example amino acid sequence by amino acid sequence of the antibody and again That is Contrary to what this court has said in other antibody cases. It's contrary to the the statement in no well It's contrary to the pto-guidelines and there is nothing in this record To support the necessity for that Come back to your brief when I started in 1445 where you said you're not reliant exclusively on the existence of the of the engine You said there are many facts that evidence the attitude disclosure I got one on the list your a-two argument right well. There are also functional attributes of the antibodies that are described And listed in the claims the fact that it binds to a neutralizing epitope the fact that it has particular affinity the fact that the constant region Of the of the human antibody is it sequence is provided anything out Those are the things that come to mind on standing in the patent The Judgment know the fact that you know you added the words human antibodies that one place you added human and another place adding those words Right, what's the word significant? Well, certainly the words are significant I we recognize that the words alone may not be so may not be sufficient But certainly the fact that human antibodies are called out as one of the antibodies one of the classes of antibodies It's not what you is significant. I mean for example if I rejected your a-two argument in your functional attributes argument You wouldn't have a written description as a matter of law, right? I'm sorry. Could you say it again? If I what I'm trying to get at is that the The the application got decorated in 94 There had been some decoration event a couple of references in a human the human human in the 92 application So you've got to serve a decoration aspect and what I'm trying to do is to decide whether if If your argument that you're making based saying that the a-two and the functional attributes actually Helping to describe the invention As opposed to just being over here what's left? Well, what's left then are these references human in the tertiary places and the path What what what what happens to your case if I don't buy your argument that the a-two and the functional attributes are helping to describe the invention Isn't your application too thin then? Again not according to the patent office guidelines and what was said in no well because there's a fully characterized antigen tnf And the claim recites antibodies Again, I you're on a respectfully disagree with that position. It's not about owning the antigen It's about whether the antigen has been fully characterized Whether you own it or not, but it had been fully characterized and in our case tnf Right, right, which which is which is not the rule of law that you're suggesting Though by by saying well, that's that under no well

. It's contrary to the the statement in no well It's contrary to the pto-guidelines and there is nothing in this record To support the necessity for that Come back to your brief when I started in 1445 where you said you're not reliant exclusively on the existence of the of the engine You said there are many facts that evidence the attitude disclosure I got one on the list your a-two argument right well. There are also functional attributes of the antibodies that are described And listed in the claims the fact that it binds to a neutralizing epitope the fact that it has particular affinity the fact that the constant region Of the of the human antibody is it sequence is provided anything out Those are the things that come to mind on standing in the patent The Judgment know the fact that you know you added the words human antibodies that one place you added human and another place adding those words Right, what's the word significant? Well, certainly the words are significant I we recognize that the words alone may not be so may not be sufficient But certainly the fact that human antibodies are called out as one of the antibodies one of the classes of antibodies It's not what you is significant. I mean for example if I rejected your a-two argument in your functional attributes argument You wouldn't have a written description as a matter of law, right? I'm sorry. Could you say it again? If I what I'm trying to get at is that the The the application got decorated in 94 There had been some decoration event a couple of references in a human the human human in the 92 application So you've got to serve a decoration aspect and what I'm trying to do is to decide whether if If your argument that you're making based saying that the a-two and the functional attributes actually Helping to describe the invention As opposed to just being over here what's left? Well, what's left then are these references human in the tertiary places and the path What what what what happens to your case if I don't buy your argument that the a-two and the functional attributes are helping to describe the invention Isn't your application too thin then? Again not according to the patent office guidelines and what was said in no well because there's a fully characterized antigen tnf And the claim recites antibodies Again, I you're on a respectfully disagree with that position. It's not about owning the antigen It's about whether the antigen has been fully characterized Whether you own it or not, but it had been fully characterized and in our case tnf Right, right, which which is which is not the rule of law that you're suggesting Though by by saying well, that's that under no well. That would be sufficient Would be seemed to me to be self-defeating Well, if we were just claiming antibodies to tnf that might be self-defeating But we're not claiming this antibody satin f we're claiming a very narrow class of antibodies That have at least a human constant region human variable region that are a-two specific that bind to neutralizing epitope and then have a particular affinity So we're not claiming trying to pre-empt the whole field of antitnf antibodies We're claiming this very narrow case class and this is not like Ariad where they just said hey go out and find a compound that'll inhibit NF cap of B Our inventors told you These are the antibodies that are going to neutralize tnf the ones that bind The same way as a two that are that compete with a two so this was a Contribution decides and declaims or commensurate in scope with the contribution of these inventors may it seems to me that competing with a two is just really another way of saying well, you know, we don't know What out there is going to work But we do know that a two works and therefore if this competes with a two Then it has the same functionality as a two and it seems to me that the affinity is just a way of picking a number and saying we'd really like to have Affinity that's high enough to be therapeutic and 10 to the eighth Leaders per mole sounds like a you know from everything we know a pretty good affinity But those are just ways of saying it seems to me correct me if this is wrong just ways of saying We're not going to ask for all of the antigens. We're just going to ask for the ones that we know will work But then describing them in a functional way No, well, I would agree that the affinity might be functional But the a two specificity is not functional because you have to it's it's a description of the structure because we know that there's a correlation Between the structure of the antibody and the antigen. It's the locking key analogy We now know where on tnf this antibody has to bind to be effective to be neutralizing and and we're only claiming the Antibodies that bind to that same or similar region and there's nothing in this record to suggest That there are a two specific antibodies that don't work To the contrary the evidence of the record is at the two and the two a two specific antibodies That had been manufactured are wildly successful drugs that have changed the lives of Because even there were some that some a two specific antibodies that didn't work in You know the the mice have told us that a two is a a very effective sort of Anybody so you know why not copy the mice and Your claim says it has to compete with a two which is to say that that's we know that that is going to work There may be others that work, but you're taking your chances out there in the in the wilderness of all the other potential Epitops right right and and there are many tnf antibody patents out there not ours is not the only one I assure you but we're not trying to claim antibodies that might bind to a different region of tnf We're claiming the ones that bind to this particular region Which is a very successful invention and It may have a different amino acid structure but the tertiary structure the 3d structure which is effective for this lock to fit the key Is going to have to be somewhat similar to fit into that same lock and antibodies have a relevant 3d structure That's described in the patent it comes 33 and 34 So it's a description of the three-dimensional structure When you talk about the lock and the key analogy in the fact that these antibodies that are claimed in this narrow class Have to bind to the same or similar place as a two And if I may I'd like to go back bring this back down to the record because we've had a lot of talk here about Scientific theory but we are here from a jury verdict And I invite you to look in the record to see exactly what was presented by Abbott in terms of written description There experts opinion for for why the patent allegedly didn't meet the written description part was based on two things One there was no specific example And as I buy as I've argued there's nothing in the law of this court or in the patent office guidelines it requires a Particular amino acid sequence and his other point was and he didn't enable it if you look through His discussion of his written description requirement he goes on and on about well you couldn't make human antibodies And that was rebuffed That was his enablement opinion it was rebutting the jury rightfully disregarded His testimony because he was discredited time and again The one part that they cite to in their reply brief. It's it's a one sentence from dr. Marks At 18475 that they cite and truncated form in their reply brief where he says we wouldn't be able to model the antibody from knowing the antigen If you look at that in context of what he was saying He was commenting on the affinity maturation section in our patent Where it talks about you know that the three-dimensional structure you can you can make Modifications and mutations of the amino acid sequence to improve the affinity and he said We didn't even know how to model TNF So sure we couldn't model the antigen based on the TNF He was sadly discredited on that because TNF had been modeled and on his cross examination It came out but not only had the three-dimensional structure of TNF been modeled and disclosed It was cited in a publication right in the path now you said a moment ago

. That would be sufficient Would be seemed to me to be self-defeating Well, if we were just claiming antibodies to tnf that might be self-defeating But we're not claiming this antibody satin f we're claiming a very narrow class of antibodies That have at least a human constant region human variable region that are a-two specific that bind to neutralizing epitope and then have a particular affinity So we're not claiming trying to pre-empt the whole field of antitnf antibodies We're claiming this very narrow case class and this is not like Ariad where they just said hey go out and find a compound that'll inhibit NF cap of B Our inventors told you These are the antibodies that are going to neutralize tnf the ones that bind The same way as a two that are that compete with a two so this was a Contribution decides and declaims or commensurate in scope with the contribution of these inventors may it seems to me that competing with a two is just really another way of saying well, you know, we don't know What out there is going to work But we do know that a two works and therefore if this competes with a two Then it has the same functionality as a two and it seems to me that the affinity is just a way of picking a number and saying we'd really like to have Affinity that's high enough to be therapeutic and 10 to the eighth Leaders per mole sounds like a you know from everything we know a pretty good affinity But those are just ways of saying it seems to me correct me if this is wrong just ways of saying We're not going to ask for all of the antigens. We're just going to ask for the ones that we know will work But then describing them in a functional way No, well, I would agree that the affinity might be functional But the a two specificity is not functional because you have to it's it's a description of the structure because we know that there's a correlation Between the structure of the antibody and the antigen. It's the locking key analogy We now know where on tnf this antibody has to bind to be effective to be neutralizing and and we're only claiming the Antibodies that bind to that same or similar region and there's nothing in this record to suggest That there are a two specific antibodies that don't work To the contrary the evidence of the record is at the two and the two a two specific antibodies That had been manufactured are wildly successful drugs that have changed the lives of Because even there were some that some a two specific antibodies that didn't work in You know the the mice have told us that a two is a a very effective sort of Anybody so you know why not copy the mice and Your claim says it has to compete with a two which is to say that that's we know that that is going to work There may be others that work, but you're taking your chances out there in the in the wilderness of all the other potential Epitops right right and and there are many tnf antibody patents out there not ours is not the only one I assure you but we're not trying to claim antibodies that might bind to a different region of tnf We're claiming the ones that bind to this particular region Which is a very successful invention and It may have a different amino acid structure but the tertiary structure the 3d structure which is effective for this lock to fit the key Is going to have to be somewhat similar to fit into that same lock and antibodies have a relevant 3d structure That's described in the patent it comes 33 and 34 So it's a description of the three-dimensional structure When you talk about the lock and the key analogy in the fact that these antibodies that are claimed in this narrow class Have to bind to the same or similar place as a two And if I may I'd like to go back bring this back down to the record because we've had a lot of talk here about Scientific theory but we are here from a jury verdict And I invite you to look in the record to see exactly what was presented by Abbott in terms of written description There experts opinion for for why the patent allegedly didn't meet the written description part was based on two things One there was no specific example And as I buy as I've argued there's nothing in the law of this court or in the patent office guidelines it requires a Particular amino acid sequence and his other point was and he didn't enable it if you look through His discussion of his written description requirement he goes on and on about well you couldn't make human antibodies And that was rebuffed That was his enablement opinion it was rebutting the jury rightfully disregarded His testimony because he was discredited time and again The one part that they cite to in their reply brief. It's it's a one sentence from dr. Marks At 18475 that they cite and truncated form in their reply brief where he says we wouldn't be able to model the antibody from knowing the antigen If you look at that in context of what he was saying He was commenting on the affinity maturation section in our patent Where it talks about you know that the three-dimensional structure you can you can make Modifications and mutations of the amino acid sequence to improve the affinity and he said We didn't even know how to model TNF So sure we couldn't model the antigen based on the TNF He was sadly discredited on that because TNF had been modeled and on his cross examination It came out but not only had the three-dimensional structure of TNF been modeled and disclosed It was cited in a publication right in the path now you said a moment ago. I think and and I correct me if this is not What you said, but I thought you said that Dr. Marks testified that No one had made any form of fully human antibody I thought it was at the 10 to the 8 affinity level Is that right? I mean you I think you didn't add that right right Because his own paper I take it right 10 to the 6th 7th right in his enablement discussion discussion I was talking about his written description opinion and his enablement opinion He starts out and on the very first page of that transcript He's asked in three different ways why isn't this enabling? He says because it doesn't disclose how to make human antibodies period Later on when he's asked about well, what's your opinion on undue experimentation? Then he does say because there's nothing to just to disclose how to make A high affinity neutralizing antibody and of course that was soundly discredited as well now am I am I correct and I Through it out and I'm not sure it's right now that I think about it am I correct in saying that that 1993 paper did disclose and fully human antibody, but it'll lower Affinity level and Below therapeutic level His his doctor work prior Dr. March testifying that in 1991 he had made 91 a human and a human anti-tNF antibody with low affinity He also testified though that in February of 1994 The winter lab which was the lab from cat right had made a higher affinity Anti-tNF human anti-tNF antibody, but that's later in 94 that's in February 1994 and our priority date is February But February early February right every four I don't know that I don't know if the date is in I Begin there's nothing in this record we hear a lot about we need the amino acid sequence of the antibody There's nothing in this record to suggest That the patent office guidelines and the long-time Commentary from this court on those guidelines should be overturned if that's going to be done This is not the record to do it on because there's no scientific basis to do so based on this record I'd like to turn quickly to enable them if I may We've counsel talked about the genitech case There is enabling disclosure in the 775 patent That the jury rightfully accepted Dr. Graham who is one of the inventors painfully took the jury through the specification of a patent He pointed them to the discussion in column 18 about how the variable region of a human antibody could be obtained You refer to phage display. He explained how that could be used to get the human variable region of the antibody Then he talked about the affinity maturation section in columns 33 and 34 He said this could be used to enhance the affinity even further that is an enabling disclosure that is in the patent Now there was a lot of other evidence that used to trial much of it through cross-examining at Abbott witnesses That is supplementary to that and is very relevant Because it goes to issues such as was there was undue experimentation required how nascent was the artist? But there was enabling disclosure in the patent as required by genitech this other evidence It's very valid and very helpful it supplements that But the the disclosure does meet the requirements of genitech So the argument that we just said hey, it's all out there is frankly Not correct enough and the specifications for what I'm worried I was telling the art to be able to Use the invention and enable him to do it There's there is testimony from dr

. I think and and I correct me if this is not What you said, but I thought you said that Dr. Marks testified that No one had made any form of fully human antibody I thought it was at the 10 to the 8 affinity level Is that right? I mean you I think you didn't add that right right Because his own paper I take it right 10 to the 6th 7th right in his enablement discussion discussion I was talking about his written description opinion and his enablement opinion He starts out and on the very first page of that transcript He's asked in three different ways why isn't this enabling? He says because it doesn't disclose how to make human antibodies period Later on when he's asked about well, what's your opinion on undue experimentation? Then he does say because there's nothing to just to disclose how to make A high affinity neutralizing antibody and of course that was soundly discredited as well now am I am I correct and I Through it out and I'm not sure it's right now that I think about it am I correct in saying that that 1993 paper did disclose and fully human antibody, but it'll lower Affinity level and Below therapeutic level His his doctor work prior Dr. March testifying that in 1991 he had made 91 a human and a human anti-tNF antibody with low affinity He also testified though that in February of 1994 The winter lab which was the lab from cat right had made a higher affinity Anti-tNF human anti-tNF antibody, but that's later in 94 that's in February 1994 and our priority date is February But February early February right every four I don't know that I don't know if the date is in I Begin there's nothing in this record we hear a lot about we need the amino acid sequence of the antibody There's nothing in this record to suggest That the patent office guidelines and the long-time Commentary from this court on those guidelines should be overturned if that's going to be done This is not the record to do it on because there's no scientific basis to do so based on this record I'd like to turn quickly to enable them if I may We've counsel talked about the genitech case There is enabling disclosure in the 775 patent That the jury rightfully accepted Dr. Graham who is one of the inventors painfully took the jury through the specification of a patent He pointed them to the discussion in column 18 about how the variable region of a human antibody could be obtained You refer to phage display. He explained how that could be used to get the human variable region of the antibody Then he talked about the affinity maturation section in columns 33 and 34 He said this could be used to enhance the affinity even further that is an enabling disclosure that is in the patent Now there was a lot of other evidence that used to trial much of it through cross-examining at Abbott witnesses That is supplementary to that and is very relevant Because it goes to issues such as was there was undue experimentation required how nascent was the artist? But there was enabling disclosure in the patent as required by genitech this other evidence It's very valid and very helpful it supplements that But the the disclosure does meet the requirements of genitech So the argument that we just said hey, it's all out there is frankly Not correct enough and the specifications for what I'm worried I was telling the art to be able to Use the invention and enable him to do it There's there is testimony from dr. Graham that you could use What's in the patent to get the variable region of the antibody now? I said he took x unspeakable to export folks more than there is still in the rough enough doubt Which is related to five Is obviously saying that there's Undue experimentation required here because you require a real expert novel or there is In the art to be able to run the library to be able to get to the end Well the evidence of that came in through dr. Marks who again was severely discredited one of his Basis for saying that undue experimentation was required he said well we had to make a lot of innovation We had to learn how to increase the size of these phage display libraries. They were too small Well, dr. Southfield their inventor had said in his 1992 memo that the phage display libraries the cat had were of unprecedented size 10 to the 2300 even know how you how you say that number but that was how big their libraries was work That's undisputed dr. Marks's testimony and undue experimentation just sound discredited and the jury rightfully disregarded them I'd like to close By just commenting on on one last thing This verdict got a lot of attention because of the size of the damages award And that damages award was as large as it was because the infringing product humerus is successful as it is There were over 8

.7 billion dollars worth of infringing sales and the jury's verdict was understandably large in view of those infringing sales But all the issues we've discussed here today and that we discussed in the brief were hotly contested below The jury was properly instructed you haven't heard one word one argument with the way the jury was instructed they did their job They did the right thing and that should not be overturned. Thank you We have Rebellum Mr. Lee You're all be brief and let me address a couple points at the outset and go to the issue that was the focus of your questions and mezel Again, which is what structure is disclosed in the pen because I think judge pros to close your question of can you decide this as an issue of law But let me hit a few points first um The case is not about overturning the pto guidelines The pto guidelines were complicated for the first time in 1999. That's five years after the priority here The question is what guidance to the pto guidelines provide us in reaching the correct result as a matter of law here We've suggested the answer is none Second point on the article the 1993 article it is a low affinity antibody the present status of magnitude below the 10 that's exactly right and on the only other document Miss elder convention the saw-filled memo which is I think is it 2870 to 872 It's describing the work of people of extraordinary skill in the art and the only antibody described in 871 is one that is non-neutralizing So it doesn't satisfy the claims Judge clevenger asked whether the claim language can perform the written description function and the answer is there's been some debate at the court about That but doesn't matter here because this claim language wasn't in the 94 specification or application it wasn't added till 2002 That claim language they're lying upon to cover a fully human antibody wasn't there So let me go to the written description issue and the question of what structure was disclosed because each of you asked Is elder can what structure was disclosed and there were Yes, and you've discussed and I discussed with you the characterization of the energy Here are the simple answer to the a2 argument the first is if you read the claim limitation it's functional It's describing competitive inhibition it couldn't be more functional is describing a result But here's the second most important thing The prior date we're talking about is 1994 As a result of that being the prior date the late 1992 application was in the prior art as of 92 the competitive binding site of a2 was in the prior art So there are two answers to their argument the first is The energy was characterized by someone else and competitive inhibition of a2 is purely functional The second is whether it is or it isn't That was in the prior art to for purposes of this case because 94 is a priority date So if you take their argument based upon the pcho guidelines and you take their argument based upon noel to its logical conclusion This claim is invalid now the truth of the matter is All of its described is the characterization of the energy and the crystal structure by someone else 26 examples of a murine and chimeric antibody There was no description of a structure by chemical formula physical properties or Otherwise of the fully human antibody they now claim At the end of the day Your honor I think actually in the best I can do in this room I I would say that you can't say if you said flatly you could never describe an invention I silly case You could describe silly buddy even though you don't know the chemical formula So there there might be circumstances I would say this in 1994 I'm just pressing you to see whether you're standing on the real life the early way you're up You say really you're gonna have example, but I The answer I think is in 1994 for a fully human antibody with these claim characteristics You should be able to provide an example because you should be able to have it This is a lot like kairan and the statement of this court at 363 fed second at 12 55 and they're basically the court said What doesn't make any sense that you're claiming a chimeric antibody chimeric antibodies didn't exist at the time And this goes to judge brystman's question in 1994 and there is no dispute about this On the record in 1994 No one Anywhere on the face of the earth had a fully human antibody that was high affinity neutralizing Of any kind to TNF alpha Not center core not us not cat Also undisputed is lots of people had tried and they had failed And those people had the same information in 1994 about the fully characterized antigen and a2 As center core now says describes their invention and you would say I take it to My further question in jellicin was is there any reason To believe or to believe with confidence that there would be such An antibody Discovered or that it even existed and I take it your answer would be no no And so your written description then becomes potentially written description to the null set That's exactly how can you have a written description that says to the one of ordinary scale in the art That you have possession of something that you don't even know exists Which is a point made in chiron and in fact there are two fully human antibodies To TNF alpha with the claim characteristics r Resulting in our patent and theirs which they began working on in 1997 with the technology that didn't even exist in 1994 At the end of the day we step back from all the details. We're almost there. Yes, we are We're at the end of this day for sure At the end of the day the written description requirement You know has its groundings in the supreme courts 1854 decision in morse And the supreme court said if you haven't invented and described it You can't claim it Senacord did not invent the full human antibody It's not a coincidence that they couldn't describe the structure by chemical formula or otherwise It's not a coincidence. I couldn't enable it. I agree with Miss Altaquin the number is big It's a $2 billion jury verdict and they've represented to the district court. They want $2 billion more For post verdict damages Should someone be able to recover that amount or any amount When they filed an application at a time when they did not have could no