After scanning the 1000's of pages of court documents and evidence yesterday I see 2 issues for the PBA patents that are a bit of a problem. I think there are excellent answers to the concerns from AVNR's side...I only mention them because they could be the relative sticking points as compared to the wall of PK garbage the defendants' experts tried to throw out which will be obliterated as nonsense.
1. Prior art "Yakatan Poster" has a table showing doses of Q that convert patients to "poor metabolizers" of DM. In that table it shows that 6 of 7 subjects converted to PM by the 13th dose
2. One prior patent application includes 20mg/d of Q in it's (very wide) range of targeted dosages
I think there are very good answers to each of these and when the full picture is taken they will be trivial. That being said, they weaken AVNR's case somewhat. Please add any other issues seen as weakening the case to my short list.
Also, if anyone can summarize the '115 prospects/issues I'd appreciate it.
I did a little research from a legal stand point on the "Yakatan" thing and I agree that it could possible be a problem for Avanir. Unfortunately, I know next to nothing about medical science, so I have no way to begin to evaluate the validity of the patents from a scientific or medical standpoint. I did read about a case, which even with my lack of knowlege about these things, I could tell wasn't exactly on point, but it had similaritiesfi and the plaintiff lost because of a situation like the "Yakatan" thing. I read about it a few weeks ago. It was a recent case from maybe 2010 about some kind of heart drug. The plaintiff actually won, but lost on appeal. If I was a little younger, my memory would be better and I could tell you exactly what case I am referring to, but if you happen to know about it maybe you could post your take on how much this may endanger Avanir's patent.
I only read a newspaper article about it, but someone just gave me access to Westlaw, so I may be able to look it up and let you know exactly what I am talking about at some future point when I have a chance to try to check it out. There is another legal factor though, which is easy enough to understand. If, per chance, the former Avanir employees who had input into Westlaw signed non-disclosure agreements and produced the "Yakatan" papers in violation of that agreement, then the "Yakatan" papers couldn't be used to invalidate the patent. Obviously, I have no idea, whether they signed non-disclosure agreements or not, but it would make a difference if they did.
Follow up note on the "poor metabolizer" conversion concern.
I made the mistake of thinking poor metabolizers are something akin to non-metabolizers. Instead, they have just somewhat reduced activity and you would NOT be able to give them DM alone and expect a therapeutic response. After a 30mg dose of DM their maximum blood level of DM is 12-19 ng/ml vs. over 100 ng/ml when maximal quinidine is given with 30mg DM.
Thus there shouldn't really be a patent concern regarding the poster showing 6 of 7 converting to the "PM" status on 10mg of Q. It just means their blood level of DM was somewhere around 20ng/ml by the 13th dose. Pretty much irrelevant.
I truly appreciate your unbiased analysis, OFP, and once again urge you to call Ian Clements, IR for Avanir, such that your thoughts can perhaps be alluded to in the briefs to be filed by Avanir's counsel. You are very bright and if long the stock, why not offer your fine brain and services to the company..
Sentiment: Strong Buy
This talk about doses and prior art is a little over my head...I can follow it, but I don't know how to interpret the law that is connected with it. I appreciate everyone's contributions to understand it better. In the end, does it matter? From a layman's perspective, Avanir HAD to go back to the drawing board because of the FDA not allowing higher levels of Q...this was in 2006. So isn't all prior art irrelevant as they had to reformulate the recipe and get new patents?
This is from BioFierce:
August 11, 2009 | By John Carroll
Nearly three years ago the FDA told Avanir Pharmaceuticals to take its application for Zenvia and go back to the drawing board, requiring the developer to reformulate the drug and test it in a new clinical trial to satisfy regulators of the drug's safety. This morning the company said that the reformulated therapy hit its primary endpoint-significantly cutting down on the number of emotional outbursts linked to a neurological disorder-and Avanir's stock almost immediately doubled in value.
Wanna million, you're right, the main problem we have here is we don't know how patent law applies to what was obvious from Avanir's 1999 pharmacology presentation, i.e. that 10 mg of quinidine twice per day was likely to be shown to be effective when combined with dex 30 mg per day.
Avanir even had a 20 mg dex arm in the STAR study.
Does patent law require for "obviousness" that a dose (10 mg of quinidine) that could "obviously" be predicted as likely to succeed must be shown to succeed with a clinical study?
I think "prior art" does not have anything to do with the FDA's strong desire for Avanir to find a dose closer to the mininmum effective dose. I think "prior art" has to do with the concept that "low dose quinidine" works to make dex effective for PBA.
I think "low dose quinidine" is defined by the patents as 150 mg of quinidine or less every 12 hours. This was the new concept that arose in the mid to late 1980's and which got the original patents.
Then I think the unknown patent law question, is if lowering the dose further deserves new patents or not.
Then I think the question becomes, how low does the dose have to get to warrant a new patent?
Clearly by 1999 it was known that 50 mg twice per day would provide complete inhibition and Avanir had already published what was probably their Phase 2 study of 30 mg of quinidine twice per day in 1995. And Avanir presented the data that 10 mg of quinidine twice per day provides 70% of enzyme inhibition in 1999 and that 25 mg twice per day provides almost 100% inhibition .
Further, a clinical effect was seen in many patients before 100% inhibition was achieved.
Knowing that, it was obvious that a reasonable amount of dex with 10 mg of quinidine was likely to be shown to be safe, effective, and FDA approved, whether it had to be 40 or 45 mg of dex, whether the drug had to be given three or even four times per day some acceptable 10 mg formulation could likely be found. (cont'd)
And here is news of the NEW PATENT related to this reformulation. For those who do not know Nuedexta is the new name for Zenvia:
Avanir shares boosted by news of Zenvia patent
October 7, 2009 | By John Carroll
Shares of Avanir Pharmaceuticals got a boost this morning after the developer announced that it had obtained a new patent on its late-stage therapy Zenvia, which is intended to prevent uncontrollable bursts of crying and laughing. The patent will extends Zenvia's commercial exclusivity period until well into 2025.
Investors liked the sound of that, and bid up Avanir's shares by seven percent. Last August Avanir reported that Zenvia had successfully hit the primary endpoint in a late-stage trial.
"We were little bit surprised that they got it (new patent) this early. I was expecting it later," said Summer Street Research analyst Carol Werther.
Hello Onlyfacts – Just wanted to thank your good self and all the others over there that have provided information and debated the subject matter in a cordial manner.
Very much appreciated.
Very best regards.
You are most welcome and your input is also much appreciated.
As for the "concerns" above...there are good answers and I'll try to weigh in a bit more with Ray/Places interchange below.
Teaching away from the prior art...doctrine of non-obviousness, no enablement, commercial success, copying, clear and convincing standard of proof needed to invalidate a patent, with an even higher level of proof, as per the decisions of the Federal Circuit, for patents vetted and approved by the USPTO...all these concepts and many more will be in the post-trial brief of Avanir...I discussed the case with someone who attended the trial...the generics are going to lose...
Sentiment: Strong Buy