Does an active CP with as yet no formal FDA response preclude approval? The CP does not have the power of an injunction. Are there precedents where the FDA has approved prior to a formal response to a CP? Thanks bp

Dew just saw that mouton supplied link for you, was working so I saw your request late in the day let me know your take after reading. bp

The amicus curare filed by the DOJ is yet another voice suggesting an eventual ruling in favor of MNTA/Sandoz upon remand thus making an at risk launch even less risky but still uncertain. The holdup is not a fear of successful TEVA litigation at this point IMO, but simply still is a direct reflection of the FDAs plodding analysis of something, who knows what? TEVA has done everything they can to delay including their genetic data which as Dew has pointed out may be the last hurdle. In any case given the likelyhood of ultimate success in the courts, now confirmed by the DOJ filing, I think Sandoz/MNTA will launch as soon as FDA approval occurs. Each day of delay is worth 9 million to TEVA. bp

Agreed but even if the respondents don't get a timely response (before the '808 actually expires), it appears that a favorable ruling after remand back to the court of appeals (should that occur) regardless of timing bodes well for the actual risk of (not) ever having to pay damages later on making an at risk launch a much lower risk proposition. The amicus brief seemed to indicate the likelihood the indefinite ness of the '808 would probably stand. Thanks to mouton and Dew for bird dodging this. bp

Reassessed on basis of new previously un reviewed info and a good nights sleep. I stated my reasons and provided some what I think are relevant quotes. You are entitled not to agree but how about some contributory discourse then? bp

To clarify: here is the quote from the Appeals Court dealing with the lack of definition of the type of molecular weight wording in the patent. It was TEVAs argument that they meant "peak" in the '808 but with out going back and reading the patent itself I am just forwarding for the board the language in the ruling that looks pretty favorable even if the case were remanded back to the Appeals court.
Sorry for not being more careful, here it is from the source:

<<copolymer-1 having a molecular weight of
about 5 to 9 kilodaltons. Pet. App. 5a (emphasis added by court of appeals).
Neither the patents’ claims nor their common specification identifies the type of “molecular weight” or “average molecular weight” used in the claims.>>

This from the article Dew cited:<<The Federal Circuit’s test, now unacceptable, would have found a claim indefinite only if it were “insolubly ambiguous.” In practice, this was a standard that was rarely, if ever, met.>>

This from the Court of Appeals ruling:<<It is undisputed that Group I claims contain an ambiguity because their plain language does not indicate which average molecular weight is intended>>

TEVA uses peak MW in the '808 but average MW in a related patent. This helps to add to the ambiguity according to Sandoz arguments.

So it comes back to what a "person skilled in the art" would interpret the patent(s) to mean. Dr. Grant was TEVAs paid expert and even his testimony had some ambiguities (thanks to mouton for providing the references). The MNTA case remains strong in my (very humble and non legal) opinion. Regards, bp

Opps sorry about the bold, I think that quote is actually from the TEVA response but basically the court of appeals quickly dealt with the '808 patent but a lot hangs on this and if the case is remanded back to the DC I suspect the clear error standard will be applied which is why I think trying to understand the arguments about indefiniteness are so important. bp

jmkobers, you are right its far from black and white and I may have been a bit too quick to "dis" the appellate court ruling. It was wording like the following ("cursory examination") from the court of appeals that I thought could have been developed and expanded upon to try to put this issue to rest:

<< For example, the panel placed crucial reliance on Figure 1 of the patent specification (as annotated in red by respondents’ counsel), Opp. 11, Pet. App. 10a-11a; respondents assert that a “cursory examination” of that figure was enough to undermine the district court’s claim construction. Opp. 20-21, 23. But Dr. Grant—who had far better than a “cursory” under- standing of the relevant science—specifically ad- dressed that very argument and explained why, giv- en the data conversions needed to produce Figure 1, Mp would not necessarily appear at the peak of that figure. Pet. App. 118a, 126a-27a.>>

This particular issue I think is of core importance and the TEVA team pounced on what was said to be a "cursory examination"--I wish Appellate court hadn't said it quite like that!

Re Mylan, I don't think they have the same credibility as MNTA would have taken nothing they say too seriously especially since it seems doubtful that have close to an exact copy of copax the way MNTA seems to. Mouton was kind enough to provide further reference information which I will review and try to incorporate into future discussions. It seemed the DC gave great credence to Dr. Grant and maybe less to MNTA/Sandoz, the latter information not clearly incorporated into the DC final decision. Looks like the jury is still out (so to speak) Regards, bp

<<This plan didn’t work, of course (except for the ‘808 non-Orange-Book patent). >>

True so far but I am not sure the '808 patent will hold up too for reasons mentioned earlier, (but at least having an Appellate ruling in hand as you have suggested will allow a "safer" market release even if they ultimately "fail")

<<No, IMO. Reverse-engineering a product as complex as Copaxone is a hugely difficult task—perhaps even more difficult than developing a de novo (non-infringing) process.>>

From my reading, the patents are very specific and would certainly provide a roadmap to a skilled company like Sandoz or Momenta should they deliberately choose to make a copy, rather than start with a gemish of a completely unknown substance and reverse engineer it. Not to say it was easy but basically they admitted to copying the patents so it might not have been as hard as you suggest especially since newer analytic and synthetic techniques were available (the history of copolymer 1 seems to go back a long way. ) The court proceeding suggested the early relationship between MNTA and Sandoz was based on a plan to develop a de novo non infringing process and that this was abandoned but since there was a contract in place to co develop the drug they went forward with a different plan, one that I am suggesting was not exactly what Sandoz, or Momenta might have wanted early on and one that might have influenced the development of their relationship in certain directions later on. bp

Dew, here is what I based my previous comments on from the District Court proceedings:

<<at 159:24 160:18.) Momenta stopped working on an alternative process in 2007, and decided to go forward with filing its ANDA, using Teva's patented process. (PTX 960 (Iyer Dep.) at 37:7-10, 41:6-13, 113:16-19, 127:24 128:3, 130:7-17, 138:5 13; PTX 957
(Brugger Dep.) at 78:16-79:23.) A May 2007 internal Momenta presentation explained
Momenta's reasoning for abandoning the development of an alternative, non-infringing process. Momenta decided to file its ANDA using Teva's patented process because it "[e]nable[d] a first to-file approach" and "[m]itigate[d] risk regarding chemical equivalence." (PTX 172 at MMT01287394.) In other words, as Dr. Iyer explained, Momenta decided to copy Teva's patented process for making copolyrner-1 instead of developing its own process because it provided the quickest route to a regulatory filing. (PTX 960>> Sorry this didn't copy completely but its around page 120 of the reference provided by mouton. My supposition was that since a work around would take to long or could not be done the value of Momenta to Sandoz may have diminished and so we did not see the marriage consummated the way we might have liked re other products. Let me know what you think bp

Have been wading through the District Court proceedings and have a few preliminary observations. First of all thank you Mouton for providing this link. The District Court ruling shows a careful and deep analysis of the issue and makes the Appellate ruling look almost childish. Sandoz admits that they abandoned a "work around" for copax production and their plan was basically to copy TEVA. Initially MNTA was to help with the work around but when this was abandoned so they could file early and wait for relief when the patents ran out. It became unclear to me (and probably Sandoz) as to what MNTAs role would ultimately be once they chose this route (where does MNTA unique technology come in here except to make a good copy)?. Hence the unexplained cooling off we saw a few years ago. The detailed ruling by the DC is basically a a tutorial by Dr. Grant the TEVA specialist in polymers. He ran circles around the Sandoz experts. When I asked my chemistry friend about the differences between average and peak molecular weights I came away thinking the Court of Appeals was right about the '808. Now it seems clear to me that the DC interpretation of "molecular weight" to be construed as "peak molecular weight" would be more correct in the context of one skilled in the art as interpreting the reference curves as the best to produce the product where most of the product comes off the SEC column, e.g. at the peak of the curve despite the wording of the patent which is admittedly unclear and indistinct. The indeterminate argument for '808 seems to weaken the more I read the ruling. Anyway, it is probable that MNTA will launch at risk and then pay for it later but have some market share and derail the TEVA strategy of 3x weekly dosing to some extent. Wheeler is starting to look more Marth like I am sorry to say. Very sorry. Someone else please read the DC court ruling and tell me I am wrong, I would welcome that. the only consolation is at lease in 2012 the NATCO product looks very different and its pretty clear that MNTA will have as exact a copy as possible. I think MNTA and Sandoz do not expect to win this case. Just to delay and launch at risk and have some long term market share despite the penalty. Good luck to all. bp

Thanks Mouton, this is exactly what I was looking for and a case of "be carful what you wish for" as it looks quite meaty and will take some time to wade through. The format is tough to read as you said. Please feel free to contact me, Dew has my email address since I don't have PM on this board. Thanks for the reference, it did not pop up in the usual Google searches and I sure will be very helpful to me. Regards, BP

Mouton, I am having no problem finding filings in the SCOTUS blog re appellate findings etc but just can't seem to access the district court ruling despite serious google searches. Any ideas? If Sandoz did not present the views of an expert as you suspect what could be gained by that? So much of TEVAs argument centers around their paid experts testimony. If the case is remanded back to the court of appeals can "new" testimony be sought e.g. that of a "master"? Or are they restricted to re reviewing what they already have. Thanks bp

Mouton, I am no hedge fund, just a little guy trying to do my own DD (with a little help from my friends, that is to say thank you mouton and Dew for your guidance and advice) . I am very willing to read through the court documents, maybe we could divide and conquer!) Issues of de novo or clear error standards aside, at some point the ruling will have to be reviewed and decided specifically related to '808. We know the outcome if a de novo standard is applied. But if the Appellate Court is instructed to apply the clear error standard in the future, I would think we should be able to get a sense for how they might rule based on how polymer scientists view this issue in the real world and how the USPO viewed it then and now (wrapper history). In my research so far including a conversation with a highly regarded chemist, there is no question as to the "fact" that peak molecular weight and average molecular weights yield different results. Period. To just say "molecular weight" and not specify which measurement was used is indeed hopelessly indefinite as different results accrue depending on the type of measurement used (and presumably not specified by TEVA in the '808. ) This is why I want to try to get at what the Sandoz experts said. We know from the TEVA filings what their (paid) expert said (with apparently conflicting information) but what did the Sandoz experts say? And if it was supportive why not include it in the court documents? (That part has me worried--why leave that out?) Is it just so obvious or is there a weakness in the clear error argument. So mouton how do I get at this info even if its just a few lines? I will pay for access if necessary and be happy to share my findings. Regards, bp

I would like to review the testimony at the District Court level from the expert witness in the Teva case but can't find a reference for the District Court proceedings (like some equivalent to SCOTUS blog). I am assuming Sandoz/MNTA also had expert testimony too, and I would like to evaluate this info first hand rather than read a biased distillation of it in the briefs filed in the Appellate court or the USSC. Is there a way to access this info (or recordings)? Thanks, bp

Just curious as to how TEVA might know what process Mylan/MNTA is using for production. I can see where MNTA would know about the bromine scavenger from a patent search re TEVA and plan a work around, but not the other way around. Looking at TEVAs devious strategies maybe they kept a bullet in the chamber? Or are we back to the as yet unsettled issue re process patents? bp

Y3maxx, I always wondered that too especially since they had a very up close and personal look, probably more than any outsider. I thought it was a red flag several years ago but stayed long. Maybe they didn't think AB interchangeability would be that important and that a "close" biosimiliar that had to undergo some measure of clinical testing would be cheaper for them? That is if they pursued it at all. bp

From the US Court of Appeals ruling re the family of '808 patents: <<It is undisputed that Group I claims contain an ambiguity because their plain language does not indicate which average molecular weight measure is intended.>> The ruling cites testimony from Dr. Grant (TEVA expert) and unnamed appellate experts (presumably from Sandoz) used to help arrive at this conclusion. Experts on both sides seemed to concur on the point of ambiguity and this was cited in the ruling. Admittedly the ruling is clear that a de novo standard was applied in arriving at this conclusion, not news to this board but if the case were remanded by the SC to the court of Appeals the language of the ruling seems to suggest to me that even if the standard of "clear error" were to be applied by the court of appeals doesn't it seem likely that they would arrive at the same conclusion? Also on the three judge panel there are two judges from the appellate court and one from a district Utah court sitting in. The court panel decision was unanimous. Not sure if that has any significance. All TEVA's maneuvering seemed designed to delay until Sept 2015 when '808 runs out anyway to allow deeper market penetration of the 3x weekly dose. It has not achieved this so far. I think Dr. Wheeler's decision to "take out an insurance policy" and sequester the income from generic copax is wise but don't see, given the language of the appeals court ruling that '808 status will be changed if a different standard is forced on the appellate court by the USSC. May your May 24th be a wonderful day. Comments?? Regards, bp

I found the following article interesting in helping me try to understand the differences referred to by mouton between law and fact. There is an in depth discussion of the standard for de novo determinations regarding PTO cases. I recommend it: Standards of Appellate Review in the Federal Circuit: Substance and Semantics
Kevin Casey,* Jade Camara** & Nancy Wright***

A quote by Judge Friendly regarding the "magic" of de novo determinations is interesting as is a discussion of the role of a "master" of the art in helping the appellate court make a ruling. The '808 patent cries out for a master to opine on the peak vs average molecular weight issue in trying to reach clarity regarding the indefiniteness argument. TEVA had their expert give an opinion in the briefs filed (referenced by mouton 4/3/14 posting.) Sandoz did not, suggesting that the argument for indefiniteness was so strong as to be obvious (see associated graphs provided in Sandoz brief). All three appellate judges appeared to agree and at least at the appellate level there was no master called upon. Was there at the district court level? Perhaps mouton read those briefs. Obviously I am not an attorney but want to try to understand what might happen if the SC remands back to the appellate court and requires a different standard (?clear error) to be applied in determining indefiniteness of the '808. While the SC will be undoubtedly be examining the ability of the circuit to try cases de novo, if they found for TEVA would it not diminish the authority of the circuit court of appeals? De novo examination appears to have strict criterion and is applied only in certain situations. It would seem the the circuit court judges should be arguing their own case before the SC to allow them to keep their authority! For those who have read this far, thanks for indulging me. bp

Thank you mouton, very interesting. And yet they signed an oath...This speaks to that elusive difference between truth and fact. Regards, bp

I know we have been over TEVA re filing re '808 patent and the recent denial by the USPO for re issue. In the Sandoz argument to SCOTUS, filed before the patent office ruling occurred, the following statement was made in the Sandoz legal brief regarding TEVA's (then pending) request to the USPO <<Reissue of patents to correct an error requires an oath by the applicant admitting the ex- istence of the error to be corrected. >> So, in essence hasn't TEVA admitted the '808 patent has an "error"? Clearly TEVA's strategy was to if not win, at least delay. They have failed in the latter. Regarding the former, even if SCOTUS remands to the circuit court and requires a different standard to be (re)applied in review of the '808 patent, hasn't TEVA is essence admitted the '808 has a hole in it? bp

It ain't over yet. bp

Maybe the same ones who say peak molecular weight and average molecular weight are the same thing? bp

Thanks Mouton, I was hoping to read the actual briefs so far have only found news stories. bp

Just curious, since SCOTUS blog does not yet have postings from the proceedings, how does the media know what was in the briefs? I assume there is no "argument" per se in front of justices as yet so right now its about the responses the SC requested from the participants. bp

For anyone interested, there is a page of definitions re polymer molecular weights (peak vs. weight average weight etc) that might help to understand the '808 patent and the arguments posted at the SCOTUS site referred to by mouton.

www.chem.agilent.com/Library/technicaloverviews/Public/5990-7890EN.pdf

bp

Dew, thanks for clarifying bp

Thanks Dew, I thought there was some issue with enforcing process patents under Hatch Waxman. Could you clarify? Thanks bp

Dew, I was typing while you were responding. My last post elaborates on my question re HW. Thanks, bp

Below is an excerpt from Teva's argument (a footnote) for cert of April 4th, the reference kindly and patiently provided by mouton. It acknowledges that:


<<The ’808 patent is not the type of patent for which Congress specifically authorized limited
injunctive relief as an infringement remedy because the ’808 patent claims a method of
manufacturing a drug, not the drug itself or the use of the drug. 35 U.S.C. § 271(e)(2), (e)(4).
Because the ’808 patent is the only patent-in-suit that will still be in force between May 2014 and
September 2015, respondents had the right—and every incentive—to raise in the District Court the
same arguments about the supposed lack of irreparable harm during that period that they now
advance in their opposition. They did not do so. >>

So while Sandoz did not make the lack irreparable harm argument as noted toward the end of the footnote, Teva itself acknowledges that the '808 patent is a process patent and not of the type Congress authorized as an exclusion beyond the expiring Orange Book patents, correct? Is this not a major weakness for Teva? Even if the SC deals with the indefinite question and even if it deals with the average vs. peak molecular weight issue, is it not still true that Hatch Waxman just doesn't allow for "limited injunctive relief as an infringement remedy because the '808 patent claims a method.." In other words its a process patent. Is it silly to be optimistic here? bp

Dew, would you please weigh in on what you are doing personally in this situation, holding or selling. I know you reduced your position previously. Also please comment on the bearing Hatch Waxman and the expiration of the Orange Book patents have on this situation and whether in the long run Hatch Waxman rules might supersede '808. Thanks, bp

<<So what TEVA is asking the Supreme Court to do is say that the Federal Circuit applied the wrong standard for evaluating the district court. >>


Is it possible for the SC to direct the Federal Circuit to apply a different standard (depending on what the new standard is ) and for the case to then still not be ruled in Teva's favor by the Federal Circuit? It seems to the outsider that the SC has taken this case in order to rule on a contentious point of law and the case itself is not that important to the SC per se. If they do reverse the Federal Court could all the cases that were affected by the Federal Court's position of stare decisis then be viewed as wrongly decided? It seems that Teva can "win" just by causing delay and thereby more firmly establish the thrice weekly dose in the market, even if they lose eventually.

If the Supreme Court decides in Teva's favor and upholds '808, does this still not go against the letter or the spirit of Hatch Waxman such that the earlier generic copax might still go forward, how might the court address that?

Mouton and Dew, I know these are kindergarden questions for you but it does help keep my gastric acid lower if I can understand some of this better, am assuming you have a lot on the line here as I do. TIA bp

Mouton, thank you for your kind guidance. Looks like I have a few hours of reading ahead of me. Couldn't TEVA' "win" in the SC and still lose to the USPO which has refused to extend the 808 patent in today's ruling? Anyway thanks for helping a doc try to make sense of your (very complex) legal world. If I can return the favor let me know. bp

Since the drug will be identical and just the dose different (unless I have this wrong) what prevents a physician from prescribing the generic three times a week in the 40mg dose? I suppose this would be off label but possible? Thanks bp

Mouton, thank you for keeping us up to date and for your legal insights. For Dew and the legal eagles, north, zip et al: Since the SC has agreed to review the case and since only a fraction of cases are granted cert, what does this mean regarding the "chances" of a reversal. In other words what percent of cases that get this far are actually reversed? The SC must feel there is merit to TEVAs argument since at least four of the justices agreed to allow the case to go forward. So can anyone 1. summarize the main remaining legal issue remaining (I looked on the RMF section but could not find an explanation of the patent in question) and or refer me to a place I can read about it and 2. Perhaps handicap the outcome, with no pulled punches as to how you think based on your knowledge and experience things are likely to go. Speculation welcome. Many thanks. I have held this stock for years and find it, well horrifying, to find myself a few months from presumed FDA approval for copax (enduring citizens petitions etc etc and now this!!) Can any share if they have modified their holdings based on recent events? Also going forward, for the unrelated biosimiliar program once they come off Orange Book will there be other land mines like this that will surface and therefore modify timelines that have been projected? Best Regards, bp

Dew Can you refresh my memory as to what Moments legal liability is (compared to Sandoz)if an at risk launch goes the wrong way? Thanks bp

Dew, as you know Geron's only product Imetelstat had their IND placed on full clinical hold because of LFT abnormalities noted in their ET trial and their MM trial (ongoing MF trial so far not affected but IND clearly is). None of these liver abnormalities bet Hy's law. Can you comment on how long these holds usually take to resolve and the severity of this FDA action and whether it carries a bad prognosis for the Imetelstat program in general which so far actually seems to be showing positive effects in MF (with unknown effect in AML and MP disease in small arms ongoing at Mayo Clinic) Thanks and regards, bp

jq, thanks for posting slide, I note the bilirubin elevation appears to be unconjugated does this not imply a cell lysis effect rather than hepatocellular failure? Also most lft abn classified as low grade and none met Hy's law. Also a board of expert hepatologists were said to have reviewed and passed on the data in question. Low grade lft abn seen w statins which usually resolve. FDA seems pretty concerned here even w hundreds of patients who have received drug (don't hold me to that number). Where's the red flag esp since patients have cancer some side effects might be outweighed by benefit esp if PR or CR achieved. TIA for the board's thoughts. Regards bp

Thanks Dew, thats a loooong timeline. bp