Friday, August 22, 2014

Dicerna and Arrowhead Gain Broad Dicer-Substrate Patent Rights

A day after Alnylam claimed ownership over Dicerna’s Dicer-substrate technology, Dicerna shot back with the announcement of a newly allowed US patent that gives it and most likely its co-licensee Arrowhead Research (via mdRNA/Marina Biotech and then Roche) broad control over the Dicer-substrate RNAi trigger space.  Specifically, claims from the Rossi-Kim invention were awarded that broadly cover ~25-30bp dsRNAs with essentially no other structural limitations.

Below 25bp, Dicer does not effectively recognize dsRNAs for processing into small siRNAs; above 30bp, the risk of inducing immune responses is thought to increase considerably as do manufacturing costs.

If you are wondering how Dicerna and Alnylam could be claiming possession over the same trigger structures, it is worth noting that while Dicerna’s patent cover 25-30bp in general, Alnylam is limited to 25bp dsRNAs that further contain a 3’ overhang.  Moreover, it is expected that since the invention by Tuschl explicitly aimed at using dsRNAs downstream of Dicer for RNAi gene silencing purposes, Alnylam’s 25bp claim is unlikely to prevail if the company should file an infringement suit against Dicerna (or Arrowhead Research should it adopt Dicer substrates).  

A simple way to get around all the uncertainty is to simply use RNAi triggers of 26bp and more.  Of course, for Dicerna’s lead candidate DCR-MYC, a 25/27 design, this train has already left the station and I am not sure whether Dicerna was forward-thinking enough to consider 26bp and longer for the orphan PH1 indication, its next clinical candidate.

Assuming that Arrowhead Research has access to the same patent, the adoption of 26bp and longer Dicer-substrate RNAi triggers could be a relatively simple strategy to remove the IP uncertainty lingering around usiRNAs: is a UNA a 'nucleotide analogue' or not?  Moreover, there is a scientific argument for Arrowhead considering Dicer substrates given that they should synergize with a conjugate approach like DPC.



Should we care about all this IP stuff?

Yesterday, I read a comment on InvestorVillage that investors would do best to ignore all the IP noise, including on my blog :(.  I agree that as long as the capital markets are a valid source of capital for small biotech companies, the issues around fundamental RNAi trigger IP, which will largely expire in 2019-2021, will be mute by the time products have come to the market and/or a court decision has been rendered. 

However, the outcome from the lawsuit by ISIS against Roche/Santaris where ISIS accused Santaris (now part of Roche) of monetizing ISIS IP by entering into partnerships with Big Pharma, could remove a lot of business development from Safe Harbor protection.  From there, challenging capital raises on similar grounds is only one step away. Personally, I don't think it will come to this since essentially all business development deals and capital raises in this industry ultimately aim at helping get drugs onto the FDA-regulated market.

And at the end of the day, as is also illustrated by mega-blockbuster Sovaldi, as long as the scientific data is compelling, none of this will prevent a drug from reaching the market and biotech companies making deals.  

13 comments:

Anonymous said...

Do the readers at the gumshoe site realize that their vaunted Dr. KSS, the blogger who has to be anonymous due to his problems with the medical boards of Texas and ND, know that he had offered his services to Benitec and that PF said no thanks. Perhaps that is the reason for his constant attacks of mgmt. Opinions disguised as facts are his MO and they just keep following him over the cliff with his latest picks. Ouch, there have been some doozies recently....Novabay, Regado and who can forget qrxpy?

Anonymous said...

To the author of the previous comment (or anyone else), please explain the point of this post. I've been reading this blog for a while now but have been unable to understand exactly what is behind these and similarly veiled comments. Other posts seem to insinuate that DH was somehow professionally rejected by Benitec and this "fact" explains his negative view of that company. If so, what is the proof of this assertion? If something else is being asserted, please state exactly what the claim is and why anyone should believe it and care.

Anonymous said...

It is a strange thing but there is an army of internet vigilantes who police the airways dogmatically hunting down anyone who says something bad about BLT.

BLT has to be one of the greatest failures in the RNAi space in a commercial context. But any observance of this fact soons sees one being attacked and belittled by this army.

One could blame the failure of BLT on the inability of the market to understand its phenomenal science and its dominant IP position and they could be right. But when you see the gratuitous,self enriching and deceptive mismanagement going on over so many years mixed with the disdain and disregard for those who have supported them then it is not so much the market at fault for shunning them but their own.

If Dirk was rejeected by BLT, which I doubt, it was probably the most reputation and career destroying move he was fortunate enough to miss.

Like you, I have no idea what these people are trying to assert except for they know better and BLT is a path to untold riches for them and those who listen to them.

For their sake I hope they are right, but experience tells me Dirk is right when he says, BLT will end in tears before bedtime for some.

Anonymous said...

It has nothing to do with Dirk, i think, it is the guy over at Stock Gumsho who has picked some doozies. Don't know why it is here other than he and Dirk have had at it.

Anonymous said...

If the story going round the traps is true, something going down on Sept. 1st, then this is the make or break for BLT.

They are either in or out.

Given they have just missed another target in their HCV program, along with their abysmal history of mismanagement and egregious self serving, my money is long on them being out.

Perhaps this is the weekend where Dirk is finally and fully vindicated for his position on BLT.

Don't expect any apologies though Dirk. These people are some of the most graceless you will ever come across.

Anonymous said...

What's the word going around the traps? These Benitec loving Dirk bashers need a reality check.

Would love to know more.

Anonymous said...

Events to be completed by Sept
1st are preparatory on nature. They are not the event.

Anonymous said...

The curious thing is, the first comment is not a reference to Dirk at all. It is about KSS as referenced by the medical boards, obviously not Dirk.

Anonymous said...

DRNA has been around for seven years and spent millions. What data do they have to show? Have they ever run a primate trial? Where's the data?

Anonymous said...

I can't see how the ISIS lawsuit against Roche/Santaris will go ahead. Roche is ISIS's partner on its HD program.

Anonymous said...

Benitec still mired in its patent lawsuits according to release today. Gives grist to the above comments about ALNY, ssRNA and Patent Secrecy Act.

The fact that we know about it shows us BLT isn't worth knowing about. If it were, everything would be hush hush.

Anonymous said...

See this slide show for details of ARWR's endosomal escape hatch technology. If not the same must be very similar as this company has it patented.

No disclosure as to what the payload is but I suspect Dirk was on the right trail in his piece entitled, Co-delivering Antisense and RNAi for Cancer dated Monday, November 10, 2014.

That part of the presentation that covers their breast program looks like its got Avastin written all over it. Might explain why Genetech came to terms with them the other week.

Leaves the question, where is PFE and MRK?

http://phylogica.com/media/2015-_PYC-Biotech-Showcase.pdf

Anonymous said...

What are the Rothschilds doing being involved with this company? Would prefer if Soros were involved. The fact that he isn't suggests there is no money to be had.

By Dirk Haussecker. All rights reserved.

Disclaimer: This blog is not intended for distribution to or use by any person or entity who is a citizen or resident of, or located in any locality, state, country or other jurisdiction where such distribution, publication, availability or use would be contrary to law or regulation or which would subject the author or any of his collaborators and contributors to any registration or licensing requirement within such jurisdiction. This blog expresses only my opinions, they may be flawed and are for entertainment purposes only. Opinions expressed are a direct result of information which may or may not be accurate, and I do not assume any responsibility for material errors or to provide updates should circumstances change. Opinions expressed in this blog may have been disseminated before to others. This blog should not be taken as investment, legal or tax advice. The investments referred to herein may not be suitable for you. Investments particularly in the field of RNAi Therapeutics and biotechnology carry a high risk of total loss. You, the reader must make your own investment decisions in consultation with your professional advisors in light of your specific circumstances. I reserve the right to buy, sell, or short any security including those that may or may not be discussed on my blog.