is not whether doctors freeman and would collaborated with dr honcho or whether they made value valuable scientific discoveries the question here is whether they made significant contributions to the definit and permanent idea of dr hondros past breaking methods for treating cancer that is a question of law and even accepting all of judge harris's findings of fact the answer is respectfully no let me let me start st with the four hundred and seventy four patent and dr freeman where i think the court's legal errors seem particularly clear i think there were three errors  and it's very clear that dr one joe started out working on auto immune diseases and there was one doctor who would dr freeman got involved and they certainly work together and  mean your question goes to the chronology of who did what when and i think it's important to understand and i'll refer the court to pages fourteen to sixteen of the joint appendix that b both mouse and human p d one using knockout mice they proved that this receptor was a negative regulator of immune response and they had the idea that blocking p d could have therapeutic effect for cancer now everybody agrees that that didn't amount to conception that was an idea but that conception occurred only after dr e y and dr completed their in vivo experiments in the fall of two thousand that allowed them to form the definite and permanent idea of the full scope of the invention everything that happened in between and i'm including both dr freeman and dr wood but i do hope that the court will focus on each individually everything that happened in between explains the biological helps explain the biological mechanism for why dr honcho was right but you didn't need to know that biological mechanism certainly for the four hundred and seventy four patent which he never mentions in the claims p d l one or it conceived to be effective as a therapy immunotherapy for cancer against tumors regardless of whether the tumors themselves expressed alive again and as he explained the the light hand itself anything that activates the receptor has ace down regulates in human response there as all agree there are many many cells in the body including immune cells as dr manado explained that expressed p d l one or perhaps some other like in the presence of that whether it's coming from the tumor or not if blocked following the forty eight patent but i think the court's case law is clear that joint inventor ship is determined on a patent by patent basis and indeed you know in some respects  could be correct judge laurie with all with all due respect inventor ship is clearly determined i mean you've said it over and over again on a patent by patent basis there is no question divisional is or no patents employed you know the same specification the same background of invention what's different is the claim but it is the claim that determines the invention and it has to be against the invention that joint  inventor ship is determined it cannot be and for reasons that we stated in our brief and that i can explicate here even leaving aside dr freeman and the four hundred and seventy four patent we we don't think that either dr freeman or doctor would qualify as having made a significant contribution to the definite and permanent idea of any of the inventions that are claimed in the different patents but it cannot be that because you have to p d l one or any other lighting and blocking p d one to treat cancer it directly follows from dr honchos pre collaboration discovery that blocking this  before the collaboration ever began they swam the collaboration began and they sent that antibody and their discoveries that were soon to be published in unity the immunity journal and ninety two was a live band for p d one and it was dr wood who confirmed using dr hondros antibody that the light and activated in fact activated inventor ship number two as judge it as as judge terrace found the dr freeman and dr wood did not establish by clear and convincing evidence that they were the ones who conceived of the idea of treating cancer by means of blocking the p d one receptor she found on page fifteen of her opinion that prior to this collaboration ever beginning once they conducted their knockout mouse experiments dr manado and dr honchos specifically discussed the potential for that discovery to provide a possible immuno therapeutic response to cancer and finally the point here is  that what we're talking about here adjusting immune response is utterly idiosyncratic there are dozens of receptor is on a t cell there are hundreds much less to a complex of cells like a tumor that are produced by one's own body it's it's and that's why knowing the specific chemistry of a particular pathway didn't amount to does not amount to a significant contribution to conception i think it's it's it's highly regulatory if you look for example were i was about to make a point on that provisional a different point which is it had to do with the unpredictability of how you how you use the knowledge about this pathway in order to provide it have it i ok i understand  l one law again and nine months before conception and then the publication by dr honcho dr wood and dr freeman of the article that was published i believe on october st two thousand and to give quite a bit of credit to doctors freeman and would there's you know what dr hondros remarks on the nobel lecture are public record and he acknowledged that they were valuable collaborators and there's no they are they are technically prior art but what those disclosures and more were published by doctors would freeman and time joe in an article that was available to of st principles the key to inventor ship is the mental act of conception even if you provided earlier assistance to the what ultimately became a conceived invention if you choose to put those disclosures into the public domain before conception they'd become free for all to use because with respect we think the district court erred but as to this point i'm not making a point at all about the you know the statutory one year grace period or any other grace period for prior art disclosure before the filing of a patent application this has to do with conception which in this case occurred on october th two thousand the patent applications here were filed until two thousand and three and so the public disclosure in this case occur well beyond outside the one year grace period the fundamental talking point we're talking about a conception of ultimately going that's i totally agree with you judge laurie and i as a thought experiment imagine that you have an invention to the combination of a b and c you might disclose you might disclose a to somebody else in confidence and that person might be thinking about a while looking for b and c but when that person figures out b and c and the time comes to put it sea the fact that a was published earlier by one of the intended to see the the the the conclusion that these people together worked on a b and c well i would what i guess what i would say judge laurie with respect is even for even let's just take a case of a soul inventor if the soul inventor conceived if the if the conception was the combination of a and b and a b and c were all essential components if the inventor prior to conception had put in the public domain that broke the chain he broke the chain before by publishing a before the i've always thought the law is so it would be helpful i think to take a couple of more minutes i know we're running over to explain the other reasons it seems to me that there is a strong argument that this is could be used as a method for treason curing cancer i was struck by the fact some very strong claims and we've got there's going to contributions where the line get drawn so i think that this this court case law has  recognized a distinction between but for causation and that including contributions as this court set in the lilly that help realize an invention on the one hand and on the other hand the test for joint inventor ship which is significant contributions to the definite and permanent conception of an operative invention in all of it aspects and your your honour's reference to the november nine hundred and ninety nine provisional i think is is a good illustration of just how far the discovery of a particular molecular pathway is from the mental conception of something that had never even been thought to be true that is that the immune system of a complex identity is alive and they disclose their research on the pathway they disclose the concept that antibodies can block interaction but in terms and they they posited that exist discovery granted over all of these disclosures which are also referenced in the background of the invention portion of the application and we've cited the court to the decision of the british pat and what to what british patent court said on the very last page of its summary in conclusion i i don't see i don't believe i have a public citation for it and i'm quoting and this is talking about the earlier dana farber would freeman application the court said quote while it's disclosure may be enough to support the general idea of using an agent which acts somehow on the p blockade against a tumor in a mouse would not have a fair expectation of success and that's that's again just the demonstration of the l response to the conceived invention that all agree had to could only have been done after dr experimentation using real organisms that in fact down regulate blocking p d one was both a safe and effective way of treating cancer  opponents are making is that this is a question of law that the court committed reversible error it's a question of law the significance of the contributions that's the ultimate conclusion but factual the subsidiary factual question they say is a question of law and in case after case this court has said that while the ultimate determination of inventor ship is a question of law it is premised on underlying questions of fact such as the existence of collaboration communication of the contributions and the significance of the contributions to conception this principle was articulated st in the house case in one thousand nine hundred and seven issue in that case was when  correct so there are several factors that enter into the ultimately bhushan several factual questions one of which is where they collaborating were they working towards the same and that's part of the proof that's part of the burden of proof and of course in this case judge ferr i know i think collaboration is a separate separate issue wasn't appealed the issue is the significance of the contributions whether they made significant contributions along the way to conception not whether nor do they claim as a separate patent as a separate claim they don't claim p d one r p g one antibodies which has been known in the art for years what they are claiming is a method of treating cancer by of administering either p d one or p d l one antibodies both required knowledge of p d l one's molecular structure and inhibitory function point being that you can't treat cancer and you can't claim a me anybody will find to be one it's will it block the interaction with p d l one and this is you see this throughout the patent what the patent describes as the invention is stopping the interaction between p t one  l one and you can't have a claim to that you don't have one hundred and twelve support for that if you don't know what p d l one is if you don't know its identity and its molecular structure i think it's notable also that not expressly refer to expression of one on tumor cells but the conception in this case was based upon knowing that the that tumors that human tumors expressed p d l one which came since we're on the four hundred and seventy four i just like to take one minute to make a comment on the dependent claims which are directed to specific kinds of tumors the appellant's argue  to up regulate the immune response to a tumor so these ideas were in the in the in that patent application what was not in that patent application contrary to mr waxman statement is that it did not talk over over that provisional application it was important to work but nobody suggests that the work was done at that point in the work continued oh well  pathway is inhibitory that had been shown in vitro i'm sorry what did you say they got there in it was removed from a claim what do you mean by that what i mean what is is simply said that the experiment antibody and of course it was in mice so it was so we agree it was an important contribution but it was one of many important contributions that ultimately led to the conception  i don't have time i don't think to really get into the prior art for argument but i would just would like to say that the principle that this court has long applied concerns whether a putative inventor has done nothing more than explain the current state of the art that is when the contribution is made and thus in the cardiac case the court said we can't identify any case in which we barred coat owner inventor ship as a matter of law just because the contribution later appeared in the public domain when the ideas were not contemporaneously available and in fact the principle that is being argued by  the new was still an inventor because he attributed he contributed his ideas to a total inventive concept as part of a collaborative enterprise and so as publication of the contribution more than a year before the collaboration starts does does not preclude inventor ship and certainly there can be no bright line rule precluding inventor ship where the publication is nearly a year after the parties again collaboration indeed was the publication they're referring to now was only three weeks before the the author of the disclosed portions now that's that's wrong and in this case just emphasizes all of the tumor expression data that dr freeman contributed at the collaboration meeting in september two thousand  just weeks before the alleged conception date that work was not even published until two thousand and three and the significance of the p d l one expression and tumors runs throughout the patent it is the key to  whether somebody who is a named inventor on one patent must be unnamed inventor on the other i just want to point the court to seven c f r section one dollar which says that a condition continuation or divisional application that names as inventors the same or fewer than all of the inventors named in the prior application may be filed under this paragraph the inventor ship in the divisional application must include at least one inventor in the prior application prior filed application i'll make just respond briefly to mr ware's point about the four hundred and seventy four patent and it's his assertion that would down regulate immune response confirming something that dr hunch over had already discovered and published the point about antibodies and the fact that i think mr ware was pointing out the fact that the in vivo experiments didn't even use antibodies just underscores the point that you don't need antibodies for conception they use the knockout mouse in the use of antibodies to block receptor as was well known in the art and judge terrace correctly concluded that the development of particular antibodies and all of the antibodies in the specification were developed by h is just reduction to practice the the wooden freeman in their november ninety nine provisional made reference to the fact that asserted that the antibodies blocking this pathway would affect the immune response that they didn't have any antibodies at the time other than the the p d one antibody that dr honshu had provided them on this question about prior art you know we've we have explained why we think pundit who doesn't stand in the way of what we think is a st principles point judge jury i know you offer ted opinion and it probably doesn't do me any good to explain recognized that it's an unpublished decision and maybe this is an appropriate case to really clarify this court's case law the the point here that mr ware was making which is well even if that's true with respect to the public to the disclosures that were published in the october one article it's not true with respect to the results of the staining experiments  did which showed that p d l one was expressed on a number of different tumors and many many different healthy cells judge at page one hundred and three of her opinion judge there is correctly