two thousand and fifteen eleven twenty three twelve forty three this  good morning your honor may please the court the board erred in its obvious analyses in both cases by focusing on the dice all fired linkage limitation in isolation and it's the dice all fired that connects the label to the base and this error is particularly apparent with respect to the issue of motivation to come by well the die so fide link that was what it was added to the claims it was the original particular connection points for the three prime protecting groups now in making that change the original rejection by the board was one of anticipation and the rejection that was sustained was an obvious rejection so they carefully they say right bonnie teaches a dice off by the linkage to attach a label to a base church teaches a dice all five linkage to attach a label to a big nobody disagrees with the church teachings of those two references what the board doesn't then do is give you any reason to use that link or in combination with the three prime protecting group and to make them cleave a ball under identical conditions and importantly the church method didn't have three prime protected nucleotides so there was no reason to combine the two from church the rabbani reference teaches a three prime protecting group it separately teaches a deisel five linkage connecting the label to the base but it doesn't give you any reason to put those two together in fact none of the nucleotides and rabbani despite disclosing each piece combine those two and the board's opinion is bereft of any re actually put them together and then when you look at what one of skill in the art would have known there was actually a reason not to combine them these nucleotides have one use and that  of references the board never said it's a limited universe the board with the direction of hindsight said none was you picking on the language in the reasoning rather than really the basics of the of the two references no there was no reason to pick the i saw five linkage in the first instance from the myriad of other linkages that were available maria is another thing the only reason we're focused on the dice all five linkage is because that's what was added by amendment and if you look at the record there are three facts that are fundamental the first one is you need to cleave the three prime protecting group with greater than ninety percent efficiency ninety percent is insufficient and that fact was undisputed it comes from rabbani but i guess an expert dr branch out reference for the ninety percent figure on the claims do not contain an efficiency requirement but when you look at a reason to motivate to combine the prior art you're looking at a sensually and although the board doesn't say it we have to assume hundred percent removal of the three prime protecting groups and so you wouldn't modify those references in a way that's going to make them worse the only proffered motivation from i d s for modifying the prior art is to improve the process a way that made the existing art less efficient with the didn't work for its intended purpose of s b s what about on pages j forty three forty one here the board has a section titled reason to use  at the one to a case which is the first appeal yes ok but on page forty and forty one if you look at what the board is doing they're giving you a reason to use a face all five linkage that come straight out of rabbani and straight out of church what they don't give you with any reason to use it in combination with the three prime protected nucleotide where you make the dice often linkage and the three prime group cleave a ball under identical conditions which is what you would get if you combined i take it to him using the label cleavage and using the cleavage of the three primal age group protecting group under simon simultaneously which in effect  using reductive cleavage luck but as just exactly a very tense and it does identify d d t as one potential cleavage right but that was all over the prior yes right so there's nothing there so give me my problem is that you're identifying for march as having achieved this close to one hundred percent efficiency but with a cleavage agent that isn't in the patent so we're in the patent is there anything that  something some increased efficiency of of what the prior art to achieve or in a cleavage agent that would achieve that and the patent doesn't teach you an expectation of better cleavage right what the patent tells you is and once you picked i saw five as your linker you can have the conditions that give you the cleavage with the three protecting group that that's not disputed that picking them to clean under identical conditions would have been within the skill the ark the problem is there's nothing that tells you to pick the i saw fight in the first instance and as for your difference in solvents if you look at shape a thirty twenty one paragraph fifty three it's dr bran s expert he says that you should be able to get a fission cleavage with the t t which is what disclosed in the prior art and so the choice of solvent shouldn't make a difference and i b s never challenge before the board the choice of solving there's no argument from any expert that the choice of solvent should make a difference and one of the lumina was able to show with their unexpected result is that in one hundred and fifty cycles you get eight point four three percent error which is far better than had been achieved in the arc but i would like to go back to the efficiency argument for one moment it was undisputed that ninety percent was insufficient for cleaving the three prime protecting  expert never said you would expect to get better three prime cleavages would expect to cleave them at different rates and so once you have those two unchallenged wrongs and then the efficiency of the dice off a linkage which was eighty six or eighty seven percent based on ruby or herman and then herman does additional work where he gets about half you just have wild variability with di sulfide and the rigorous article say there was  variability we didn't proceed i saw five linkage with linkages rigorously so there was no reason to pick this linker that gave you variable cleavage and unpredictable results pair it with a three prime group and cleave them under identical conditions in a serial scheme where the efficiency of each round builds on the next one it simply would have made or chen less efficient than they already were and the board doesn't give you any reason to put those together and you allude to this in your brief but the the focus of the deisel fight of course is on the linking with the label not the link wit have to sleep with a particular efficiency the problem is on this record we it's undisputed they do need at least ninety percent and that ninety percent for the three prime group is probably insufficient like ninety percent for the three prime group isn't driven by the person i don't think unless you mean you may argue to the contrary but i'd be interested in hearing what the argument is but i my understanding was that that's not driven by the percentage  of accuracy the percentage of cleavage of the sulfide bond to the label correct and or am i am i wrong about that well and and here's the issue and that they are a luminous expert he said that the person of skill in the art wouldn't have expected the three prank group to cleave with any greater efficiency than the dice all five winter attaching the label to the base in view of ruby herman short i b s never challenge that so you do have a direct link between the efficiency of di some fight cleavage and the efficiency of the three prime protecting to produce a higher rate of cleavage right it's not directly it's not addressed in the record the the answer was apparently the positioning of the three private group makes it such that you would expect the dice all five took to be the limiting step as if as explained but but that statement is not in the record of what is in the record is you wouldn't expect the three prime group to cleave with any better efficiency than the could you repeat that because it's thirty seven zero one two zero five and the paragraph numbers are fifty to fifty five fifty eight and sixty and this is from the eleven twenty six really a part of it i have it if you want to from the efficiency mattered you could increase the efficiency of a dice off i'd like it and that is unsupported by substantial evidence on this record but about the expert testimony the expert testimony is simply a statement from dr branch out it's a paragraph it's joint appendix thirty sixteen paragraph thirty seven and if it's a naked statement the only support for it is ruby and her load which she relies on and the ruby reference the board said it teaches you all of these things and that could get you increase cleavage but ruby actually did the experiments ruby change the concentration and the cleavage a and the best ruby did was eighty six percent after one hundred minutes there's nothing in the record to suggest you could do better than that the eyes are man you're into your rebuttal time i think  the court my name drug baron i represent intelligent biosystems judge larry i want to turn to something you notice in the beginning of this and i think it's exactly right that it's important to understand the context which is that the nucleotide as originally hydroxyl to be used among other things in an s p s process known so they react to that by saying ok we're going to cancel our claims that it's and we're going to instead add the deisel five so one the one hand art that ship top point to die itself and i think that's where the board was found the art was was very substantial in that they and obviously as you said judge stole that they actually have a headache and he points to ruby and and the eighty seven percent for a very different experiment and he says this is an exact example of someone link using adults i'd like to connect a label to a nucleotide including it  now i think that the crux of their argument is and of course the church shows it being incorporated in an s p s process so the crux of their argument is they try to take the ninety percent will will live with the purpose argument i think that the board rightly put a lot of skepticism on the ninety percent for many different reasons that they articulate pretty well in that particularly the three four six decision but even if you do have a ninety percent  adams and he says i encourage you to look at other things so that the five fits right within that and so there's all these examples of being used successfully including an s p s their point is a person of skill  because of the three prime age cleaving efficiency requirement ninety percent would use that as a litmus test for the i felt like link or when they would look at the reported efficiencies of rubin and herman and i and i think that's incorrect theories incorrect in a couple ways in the board noted them and first as as you said such dollars in your discussion there is no evidence that a person skill me or look at those numbers and think that they they're not motivated to keep on experimenting till they get to ninety some magical ninety and then you're right judged that ninety is not in that and i think we need to remember that ninety percent find that not only is it not in the claims on the specification which is important  it's emotion from and so that so a person's going to really look at ruby and herman which is looking at aleutian percentages of connecting something to a column and seeing how much dropped out and ruby in fact says the percentages on reporting do not are not dependent only pleading the deisel side linkers there are other things in what i'm doing that could affect that negatively so they would look at that and they would say i could get better at the ruby teaches by optimizing conditions such as ph such as temperature the concentration the cleaning  dr ruby and his team was not doing s p s number one they were they didn't have to keep on experimenting to hit ninety that's number one number two there's no evidence in ruby if you look at that eighty six is a limit he just reports it he says he actually one point says we didn't get a chance to try to milam all ors of concentration it was working for its purpose was to which was to not not s b s and so it worked for a purpose with the board said it was dr rover which said i don't think you can get any higher than that he didn't have anything else other than his opinion to back him up that's what the cleave under greater efficiency than the title fight later it's so carefully crafted in those paragraphs that it's clear that all he is really testifying to is those references do not provide anticipation but he does and he had certainly had the opportunity to do make that testimony he did not so there is i think that what you see the board doing is on this what are public property point that the ninety percent that they would be the same to your point is this if they were the same material and they're not the claims don't require that and i also want to be talking about the board construed that to the point that they said it's not required that the linkage for the protected group in the linker be the same be dice all side so just the act of construction is which is him and said the board same chemical conditions for the other so we construe it so they're obviously paying attention to it as a whole and actually interestingly in the secondary considerations point one of the many reasons that the board found that there was no evidence of unexpected results was they said you didn't provide evidence that it was the nucleotide that gave the result versus the deisel five and so the board actually to cleavage right they made to put they made several you're right your honor first they said there's nothing on kind of a nexus argument there's nothing that on the next starting this is the primary observation they said there's nothing here that would prove that it was this one photon expected result was due to the the bond as opposed to depleting agent because they use a different season agent than has been used previously that's exactly right and that and that is totally supported by the records of the substantial evidence but they also towards the end they made what i call an inherent seer latency observation and rate baxter where they said and they called out loon for saying look for it to be you didn't provide any evidence that the nucleotide with all of this plume of patients is what created this you just focus on the bond and therefore the deisel five linkage this  known so i think that you're just talking about to the extent it's you know was unexpected that it was something that was inherent property of an already known thing i mean that the fact is since the i'd just like to make three quick points the first one is that the characterization of dr rome's birds testimony in paragraphs fifty two fifty five fifty eight and sixty as carefully crafted he looks at each reference that was before the board and says this reference wouldn't give a person of skill in the art the expectation that you would cleave that i saw fight and the three private texting group under identical conditions and get above ninety for the three private the testimony was straightforward if there were any ambiguity that this was carefully crafted or that a person of skill in the art would have said no no no the expectation is different i sue their expert would have said it somewhere the statements from dr room for are completely unchallenged on this record the second point goes to judge sauls discussion about could you improve concentration varied the cleavage agent and he got eighty six percent after one hundred minutes we're talking about if you use this for s b s a serial scheme that hundred minutes means to do five bases you're talking five hundred minutes there's no expectation that you could improve this and the board didn't give us any then on the herman references the original cleavage of herman was eighty seven percent two years later they said we got virtually all of it but there's no data in the paper two years after that they provide the data and it's fifty percent there's no basis for the board to say you could routinely enhanced cleavage efficiency with an expectation of success there just isn't substantial evidence to support that point and for the board to say wildly variable cleavage gives you an expectation of success we think was erroneous linkage with a three prime protecting group and you cleave them under identical conditions if you read both boards opinions there is not a statement anywhere in there that says you put them together because and so at the end of the day you are left with what is the motivation to combine these and all that we can all try to come up with one there isn't one in the board's opinion and therefore it's insufficient