three reasons isn't there some some support in the spec that is the use of the word substitution that is in the family embody that's correct your honor there used the word substitution which is an example or which is  promoter or the out the word is replace or substitute the object that the word is the whole promoter is either either being generally used to refer to the entire nucleotide sequence making up the promoter or just you start with one promoter and you end up with another even if all you've done is we've placed a component so i believe neither one of those terms was expressly defined in the extreme to government what was disclosed in the extrinsic evidence of record is that those of skill in the art knew of numerous methods of replacing or changing promoter sequences such as mutagenesis or we've called kind of wholesale cut and replace evidence about how about the linguistic usage from the linguistic usage that's correct but we do get from the external evidence that those of skill in the art those genetic engineers with a tool box of have to change promoters knew that mutagenesis was a very well known way to do that for decades and substitution was a different way to do it and there were other methods of increasing expression that were well known in the art so the dialogue between the examiner and the applicant here makes very clear that the issue was not with how to change these promoters it was with what were the changes to enhance expression occurred and that's clear both from examiner statements and applicants there on the examiner side every single time the examiner identified an issue with the claim he always tethered that issue to the expression regulation which has huge chains well language from offering to replacing well it may not appear to me that it was necessary based on the exchange exam her but you still did it and you put the public on notice of change so why shouldn't that change be interpreted exactly the way it was interpreted a law by the i t c you want me to say that change w irrelevant i don't think any change during prosecution should be treated as irrelevant people have a weak right to believe because they're put on notice that you made this change for a reason so our position is not that it's irrelevant it's that you can't be so narrowed to just the preferred environment an example for and that's clear because the example or the examiner noted that there was mutagenesis well known are well known methods mutagenesis in the record but there are there are lots of cases we have where it wasn't necessary for an applicant to limit their claims the way they did but they nonetheless limited and the question is what were you what could you have been allowed to claim the question is what would the world reading those of skill and we said that's consistent with your your recognition we didn't say it equates to recognition and indeed consistent with does not equal equates does not mean equates and if we had wanted to equate the term replacement with the term substitution we would have just used the term substitution there was no need to not to try a different term unless we were trying to get something else and not limit ourselves that sort of if you're suggesting that basically by choosing a different word you plain meaning that absolutely entitles you to something you don't have that here you don't have a plain meaning the absolutely entitles you to what you're asking or you have some ambiguous language where we're not sure what you're entitled to so disclaimer only comes into play when you're taking something out of what is an otherwise plain m below that the application considered broad methods of changing expression within the scope of its and that is the broad methods that we're talking about and there must be something the prosecution history that makes it very clear that you're giving up those broad methods now you know it's your claim language which dictates what you consider there are lots of suspects that disclose a million different things that will claim their own only one aspect a particular invention or continuations hiding in the w waiting with other aspects but it's not the breadth of what you contemplated that would get coverage or it's what you claim in our position is that the term replacement is not so narrow a substitution and it has been has been used in other art of record that's not part but discusses age old mutagenesis techniques as a replacement single nucleotide as a result we have to assume that it means something different from alteration you don't have to but you can and if it does mean something different i just don't think it means if you deleted a promoter you would decrease expression that would not make sense so to the extent there are some differences in the context there could be we just don't think it goes to the level of defining the invention only by substitution we also think that other extrinsic evidence of record supports that because c j is expert has admitted that whether you change the nucleotide sequence a single nucleotide sequence by mutagenesis or whether you cut and paste according to the method of example or what you get is a new promoter there is a more potent promoter there and it doesn't matter whether you've done the replacement or the substitut skull so if as i understand the prosecution history examiner said to think most you've been able substitution of promoters you haven't been able alteration of why if why would there have even been unable to conserve if with taking a promoter say six nuclear tied promoter using any technique you felt like to change the first letter resulting in a new promoter when the chemical mutagenesis to change the first letter was i think by everybody's different two different arguments here one is that what the examiner said more or less drove them into the choice they made but the softer argument is that what the examiner said actually left room for them to do several different things but the thing that they did they think the choice they made was in fact i'm going it was to do the extremely safe thing of simply adopting a small variant  the language examiner had himself articulated as suffic i think what's happening here is that engine a motor was attempting to divide the term replacing the native promoted with a more potent promoter into the first part of that term which is replacing what the commission did in the promoter by substituting with a more potent promoter now when they talk about alterations they're saying let's look at just the replacing there they're forgetting that you also have to do something with a new promoter coming in there just saying replace and replace or alter a nucleotide and that's specifically as means raja said what the examiner said was not enabled you can't make specific changes and expect them to have a function of increasing say you started with six nucleotide promoter and you ended with the same six nucleotides except the first one first nucleotide was different is there anything any reason to think that the potential effect perfect production or whatever would be affected at all by how you made that first letter change you would know whether it would go up down or have no effect and that's the point you made so that so that the effect on the cellular production of the identical six nucleotides might be different according to how you got to them section promoter is is more like forty or or ninety whatever i feel what six you make one change and you don't know what the effect of that changes there's no argument that you can make a change but you have no idea what the effect of that change will be will it decreased the promoter will it increase the promoter only do nothing you just don't know and that's why they examine a said you haven't enabled making specific alterations to improve production why the which is the whole point of using a more potent among motors in terms of potency but they didn't know what the effect of changing a particular sequence was correct you could take one out and put a new one in but you couldn't just change one and expect to be better or worse you just wouldn't know as i say when interim intermodal quoted the rejection they left out the portion that said you can't enable specific changes the other thing one of the questions to us was to read anything else in the specification that talked about  substitution and if you look in the specification at volume one appendix one nine zero to one nine one it starts out on one nine zero saying the present inventions are as follows and then it lists amp examiner interpreted it and where the commission interpreted it in terms of replacing a promoter with something else not changing something which had maybe no effect at all promoter now the commission found below that there is a clear link between what's called the consensus sequence and promoters strengths and here there is testimony that those are still new york looking at the sequence id number nine and looking at that promoter would know as they move individual nucleotides towards consensus that would make the promoter stronger so you could affect the motor strength based on the seque and we think the entirety of the record indicates that there was no narrowing of the claim such that was to the preferred embodiment of example for to this very specific substitution method and to the exclusion of decades old methods of mu court today i'm going to address two issues that are in our appeal and both of the part dispositive with respect to strain or the one hundred one the first is the commission your law in disregarding the festival instructions that in order to find a rebuttal on the ten general prong the reason for the amendment must be apparent from the from the specification and from the prosecution's gives me and that the really invoked it is very narrow secondly i want to address written description he of the commission ignored areas or principle that you need to have a representative number of species and on the commission pointed to for th and find an objective lee apparent reason for the amendment here the commission found nothing they cited nothing from the prosecution and if you look at the can that's the commission's decision volume one forty three to forty four nothing in the prosecution gave a reason for the amendment and if you look for that it's volume one and tics five six one seven what the prosecution said and this is it one one five six also five six enough to allow tangential or bottle second in jem's narrowing amendment took a claim that was business big covering any protein that had one or more changes compared the sequence id to theirs and one of  more was there some sort of several limit it was just one or several changes that are correct but one and more could be changed everybody one of them right that's true and so the claim was this big now they said the claim is this big sequence ninety two and public notice the public is allowed to rely on what engineer moto chose to make the men maybe they could have made a different amend but i think his judgment was set on the replacing side they didn't this is what they chose to do and c j is allowed to do that and it's not disputed assumption if it were apparent that the reason for the amendment was to bring the claim down to waikiki for proteins to and to avoid was it lipshitz was why if i k or something if if in the amendment which obviously didn't happen the patentee the of the op kind of the time that said my amendment is designed to only cover y d d g proteins then we might have a different case but that's not what they said they said my amendment gets rid of the prior rot and nothing else so my saying about it is being less than that ok so now take the opposite as an assumption let's assume that they say we are trying to get to one hundred eighty proteins then we think about the tangential nature question then they would have to show i think that if the function where result would the tangential question i think would be a more difficult case for us because they could legitimately say you know why d t g protein falls within the claim by the doctor equivalents because we didn't mean to exclude that but that's not the case here decision cannot stand on the area and for three reasons one the four promoters to which it points are not representative of this genus in fact they are representative of three call i and one viral promoter secondly testing known promoters to see which one of the maybe more potent than the y t d promoter when the white e g promoted was not known and its strength was not known is not written description doesn't show a recognition of more potent promoters and finally there's no common structure that links more potent promoters tourney's the first representative species as dr robi said it's a virtually representative of the entire class of anybodies because they differed in structure just like the promote is in this case in more potent promoters different structure second finding that the person skilled on the out could actually go off and test the promoters that were known in the art to see which one wants what but which ones were more potent that's an annulment that's not written description in an area it specifically says at three thirteen fifty six an invitation to further research does not constitute written description of a class of compounds used in a method and when you look at the various written description cases when there is no known promote as in the art known compounds in the art the known to have the specific activity that's required in the claim that's a different story this is not that here promoters were known in the art but not which ones were more potent so that doesn't allow the skilled worker to finding of ability to make and used runs of fall of what is perhaps the court room ruling of area so you can't go off and just test that's a research plan that's not written description and finally the solution at forty six knowledge that the consensus sequence did not apply to the cola and one example of that is the johnson textbook from one thousand nine hundred eighty eight of volume four a nine one four nine statements made about what was going on fifteen years earlier that's not substantial evidence you have to look at what the skilled worker knew at the priority date and here at the priority date the skilled worker knew that the consensus rule did not link ico i promote is which is the specific  to end up with the same protein that somehow the amendment has to engender where's it seems to me that the amendment was designed to define the end result in terms of the process by which it was made as though it's sort of a product by a product by process life and that the fact the change in the up with the same thing by a different process i'm not sure that i understand why that makes it right but when you look at to do reason and it's incorrect to say that the commission did not look at the prosecution history because appendix forty four the commission stated that what the amendment was meant to do was to  protein i don't think that's really responsive to the suggestion that they chose to make an amendment which define things in terms of the process will by which it was made and it seems to me that by the what the commission did is say that doesn't to hybridize is intonated form and codes for the exact same protein protein as the code on randomized version of to cheat and when you look at the reason because that's what the law says is what is the rationale behind him and if and it's only you only surrender with the russian now is not the sort of will from the prosecution history record and we think the rationale for the amendment is manifest throughout the prosecutor's examiner said you've got this term that properly inserted are interpreted virtually read on any protein and we identify this one that happened to be from one of our inventors called y if i can in so your terminal of the growing interest if you make an amendment you're even if the it's tangential if it covers more than was necessary to avoid the rejection or tangential argument is that the amendment was made to define the claims go to y d t g proteins variants there of my species or by how they're coded by d n a what we gave up was totally unrelated why if i keep proteins and proteins in between other proteins that mind things that literally infringe which is the definition of the use a doctrine of well if you chose to define what was corny by the amendment in terms of how the protein w code on randomized versions of those sequences it was a totally unrelated wife like a protein that had nothing to do with this protein at all on the one twelve issue of the commission made specific findings on the representative species including identifying the four examples that are in the patent the patent described as four examples and also described and the like pacifically discloses other examples that were well known in the arctic dorsal oracle there are numerous prior articles on the front of the patent but also disclose other promoters and there are hundreds of examples of more potent promoters that are in the ar and that at the time of the patent thing the promoter efficiency cannot be predicted entirely from conformity to consensus sequence the beginning of that quote says occasional exceptions to this rule show and that's not in want just a couple of points you want to first of all there's been a lot of discussion about what the amendment said in terms of tangential and what is clear from appendix page forty four of the decision the commission never pointed to anything in the prosecution second on the discussion of examples of more potent promoters in the art there's no examples of more potent promoters in the us is examples of promoters in the art to determine if it's more protein was which is a comparison you need to compare it to the strength of the white gene promoter and that was not known at the filing at the priority date sequence id nine in the specification is one hundred sixty base pair sequence it