Saturday, January 23, 2010

The RNAi Trigger Marketplace in the Post-Tuschl World

This entry is the second of a 2-part series on the upcoming decision of who will control key intellectual property for therapeutic applications of RNAi. In the first part, I tried to provide an outline of the developments causing ownership of certain data in the Tuschl patent applications to become such an important issue. Here, I will try and delve more into the technical details of the scientific milestones that made RNAi a conceivable new class of human therapeutics, and based on that understanding make an educated guess about the outcome of the Tuschl Tussle and how this could shape the RNAi trigger IP marketplace in the future.

Back to Science.

Could RNAi be used as a therapeutic? That was the sort of topic of wild speculation in the lab where I worked as an undergrad in 2001 on a plant gene silencing project. Hey, Fire and Mello reported this cool stuff in worms 3 years ago and as we can see double-stranded RNAs can trigger the same process so beautifully also in plants thanks to some nice work by the Baulcombe group and another one in Australia. But humans? Well, unfortunately vertebrates seem to represent the exception when it comes to the existence of RNAi. That darn interferon response system...All this would change in a watershed moment when Tuschl and colleagues at the Max Planck reported in Nature the very existence of RNAi in human cells and taught a captivatingly simple technology to induce it there: siRNAs. The story therefore seemed quite simple until then. First it was Fire-Mello, then Tuschl's siRNAs.


Fire-Mello coins RNAi. The critical contribution by Fire and Mello in 1998 was their realization that it was in fact double-stranded RNA that was the effective inducer behind a variety of strange gene silencing phenomena in worm genetics and quite likely beyond (e.g. variegated Petunia flower color). While it was not necessarily obvious at the time that this would be applicable to humans as it was still very much doubted that RNAi existed in humans, the deeply influential nature of this eureka moment of the field of gene silencing and the non-exclusive licensing approach taken by the Carnegie Institution, the owner of Fire-Mello, established it as a widely respected patent. Add to this the endorsement by the scientific community as evidenced by the Nobel Prize in Physiology and Medicine this work entailed, there should be little doubt in the mind of patent examiners about the therapeutic relevance of that work. Prohhhhbably a fundamental patent.

Biochemical work in fly cell extracts by the inventors behind Tuschl I (Tuschl, Zamore, Bartel, Sharp) and involving the MIT, the Whitehead, UMass, and Max Planck on the same gene silencing phenomenon in flies aimed at the elucidation of the molecular fate of these long dsRNA RNAi triggers. Their main finding was that during RNAi, long dsRNA gave rise to 21-23 nucleotide small RNAs and that target RNA was cleaved at 21-23 nucleotide intervals also. This strongly indicated that it was the 21-23 nucleotide RNAs that were guiding the destruction of the target RNA. This, however, is different from demonstrating that the 21-23 nucleotide small RNAs are able to trigger RNAi themselves, something one would think would be important for claims to this effect to be considered enabled. To test this hypothesis, they therefore isolated and then reintroduced the 21-23 nucleotide mix of RNAs into fresh fly cell extract and asked whether those were able to induce RNAi gene silencing, too.

What may come as a surprise to a few: the silencing with these purified 21-23nt RNAs was actually quite mediocre, about 50% silencing compared to >>95% silencing with the long dsRNA (Figure 12 of US Tuschl I application). Similarly, when the dsRNA length dependency of RNAi was tested, the shorter the dsRNA, the worse the silencing. Together, these types of findings described in Tuschl I seriously calls into question claims that Tuschl I technically enabled human RNAi. Some may even cite such data as proof to the opposite, namely that this work made it even less likely that short RNAs would be useful RNAi triggers.

What is the explanation for this somewhat surprising finding? In retrospect, it is most likely the fact that when the 21-23nt small RNAs were introduced they were single-stranded and not double-stranded and demonstrates that at that time, the authors did not know about the requirement for double-strandedness also of the small RNA intermediates for triggering RNAi . Consequently, the patent contemplates both single-stranded and double-stranded RNAs as candidate RNAi triggers. Thus, while an important piece of the puzzle of RNAi molecular biology history with ~1600 citations to the underlying Year 2000 paper, it by no means was the catalyst leading to the adoption of RNAi in humans. I would not even be surprised if the authors did test the hypothesis of whether such isolated 21-23nt small RNAs were able to silence genes in humans cells (not very difficult to do) and came up short. It is also worth noting that their discovery of small RNAs during RNAi was not entirely new to gene silencing scientists then, a year after Hamilton and Baulcombe reported such an observation in Science, something that also has not escaped the patent examiner.

Tuschl II

Tuschl II coins ‘siRNA’. The critical insight that, first of all, proved the existence of RNAi in Man and even more importantly in terms of enablement, taught a straightforward method for triggering this process in humans, came from very elegant work led by Tom Tuschl at the Max Planck in Goettingen and forms the basis for Tuschl II.

The spark of ingenuity by the people at Max Planck, not involving those at the MIT, Whitehead, or UMass, was that the small RNAs had to be in double-stranded form to serve as useful triggers of RNAi. To prove this, they generated short dsRNAs, which they coined siRNAs, through chemical synthesis, also a first, and found them to be potent triggers of gene silencing not only in fly lysates, but subsequently also in human cells. The fact that the fly lysate work was reported separately by the Max Planck group and temporally between the Tuschl I 21-23 nucleotide RNA paper and the human RNAi findings, further illustrates the temporal, geographic, and intellectual separation of Tuschl's work in Massachussetts and then as a group leader in Germany.

Importantly, these siRNAs allowed for gene silencing that was specific and independent of the interferon response, again something speculated about, but not clearly proven in Tuschl I. The Tuschl siRNA-template is now used by thousands of laboratories around the world, with an amazing 6000 citations to the underlying paper further illustrating its importance.

In the Max Planck vs Whitehead case, the Whitehead argues that 3’ overhang siRNAs that are at the core of the Tuschl II patent application were already part of Tuschl I. On the surface this is true. This is because for some strange reason and that is the biggest mystery to me in all of this and that I hope the next months will shed some light on, the human siRNA data miraculously appear at the end of the Tuschl I application, as does the term ‘siRNA’ emerge without prior definition. If this data were to remain part of Tuschl I, there is the real possibility that Tuschl II could be declared invalid on a technical basis because of Tuschl I’s priority status (in a temporal sense) and double-patenting laws. Not good for Alnylam!

The two related questions of which the answer will rock the RNAi Therapeutics universe are therefore: a) Has the human siRNA data that in light of the weak activity of the ’21-23 nucleotide RNA’ in fly lysates and very uncertain translation of those results into humans now form the inventive basis for the broad human RNAi claims in Tuschl I, been rightfully included? b) In doing so, has the Whitehead, responsible for prosecuting Tuschl I also on behalf of Max Planck, fulfilled its fiduciary duty towards all its partners?

First of all, as I explained in my previous post, the data critical for the siRNA claims of Tuschl I had been generated by the inventors behind Tuschl II (most importantly, in addition to Tuschl, Elbashir and Lendeckel; both of them also at the Max Planck then), but who are not named as inventors on Tuschl I. On this technical ground already, Tuschl I in its present form is invalid. Beyond that, there appears to be early communication in which Max Planck confirmed with the Whitehead that the human siRNA data were the domain of Tuschl II. So even if Max Planck and the inventors of Tuschl I had been wrongly convinced by the Whitehead and their hired patent attorneys that this should not pose a problem for the approval of both patents, any patent attorney worth his salt should have known this to be a fundamental omission. It would therefore seem to be wise to remedy this deficiency either by including the inventors on the Tuschl I patent or by leaving out the data as stipulated by Max Planck, before the specter of 'malpractice' was raised. And obviously, Whitehead now is clearly not acting on Max Planck’s behalf and this should be sufficient cause to give back Max Planck de facto veto power in Tuschl I by confirming that the Whitehead does not have Max Planck's power of attorney any more.

Because some of these issues are civil ones that are not the domain of the USPTO, it is important to sort them out before it goes back to the patent office and can cause lasting damage to the patents. For the stated reasons, I am quite confident that Max Planck and Alnylam will prevail and regain control of the human RNAi data and some sort of declaratory judgement that the way that data had been used in Tuschl I cannot be construed to contest the validity of Tuschl II in the future.

Before I consider the ramnifications of the two main outcomes of the Tuschl Tussle for the RNAi Therapeutics RNAi trigger IP space, it should be noted that Tuschl II already disclosed the observation that blunt-ended siRNAs can silence, too, just not as efficiently as 3' overhung siRNAs on average. 3' overhangs were therefore taught to be a preferred characteristic of siRNAs when used for mammalian RNAi applications. Hence, with many more reports confirming that RNAi in fact is so robust that all sorts of exogenously introduced small dsRNAs can efficiently induce RNAi in humans, it will become more and more difficult to convince the patent offices of a proprietary nature of not only overhung siRNAs, but also those without overhangs. One exception may be Silence Therapeutics’ blunt ‘Atu-siRNAs’ which because it was a relatively early disclosure Silence/Atugen was able to convince the US and European patent offices of their arguably surprising stability, an important feature for most RNAi Therapeutics approaches.

Outcome 1: Tuschl II becomes dominant, Tuschl I essentially irrelevant

The most likely outcome. This will confirm Alnylam to be the most desirable partner based on RNAi trigger IP alone and leave Merck and RXi Pharmaceuticals empty-handed. Clear freedom-to-operate and exclusivity for the most efficient RNAi trigger that is also highly competitive with regards to other challenges such as innate immune activation. However, since Tuschl II does not claim blunt siRNAs, something I believe should have been done at least initially and maybe wasn’t because of an integrated Tuschl I-II strategy that now clearly has fallen apart, there remains scope for plenty of blunt-ended workarounds in the important 19-24 base-pair range. These workarounds, however, are not very attractive for licensing purposes if they cannot be protected by patents. Again, the exception here is Silence Therapeutics which, assuming that Kreutzer-Limmer's staying power is questionable, would be a beneficiary of such an outcome since it would now free Atu-siRNAs from the Tuschl I threat. There are, however, some significant limitations with Atu-siRNAs, since the scope of the patents is quite narrow in terms of allowed siRNA patterns and chemical modifications. Thus, while Tuschl II will offer a platform that should be applicable to RNAi Therapeutics for many years to come, Atu-siRNAs may not be able to adapt to the evolution in cutting-edge siRNA modification technology and hence its value should decline over time relatively quickly.

The IP position of Dicerna is probably least affected by the Tuschl outcome among the synthetic siRNA Therapeutics companies. There may be some uncertainties with whether and how the Tuschl patents may be applicable to Dicer substrates, but unless there will be a messy outcome in which both Tuschl’s go up in fire (highly unlikely), neither outcome 1 or 2 should change this much.

Under outcome 1, the market would have to balance the luxuries that Tuschl II offers, namely patent protection and overhangs, with the lower price, but added liabilities of the Silence Therapeutics and Dicerna platforms or even non-patented siRNA workaround designs. Last but not least, due to its use of overhangs, mdRNA’s overhung ‘usiRNAs’ would be a loser under this scenario.

Outcome 2: Tuschl I becomes (almost) gate-keeping, supersedes Tuschl II

If Tuschl I were allowed in the US in the form now proposed by Whitehead, then Tuschl II may go up in flames with Tuschl I covering blunt and overhang siRNAs comprising RNA strands of 21-23 nucleotides. Under this, albeit very unlikely scenario, Alnylam would have to share gate-keeper privileges for the most direct route to RNAi Therapeutics with Merck and RXi. Further risking to put pressure on price would be RXi selling such rights for a pittance as well as uncertainty about UMass’s ability and willingness to further grant rights to Tuschl I. Not all would be lost for the rest of the field even under this scenario. Silence Therapeutics, for example, would still be able to operate in the 15-20 base-pair range, with maybe 19 and 20 base-pair offering quite good opportunities of discovering efficacious and non-immunostimulatory siRNAs with acceptable efficiency. Similarly, 19 to 20 base-pair siRNAs may also become the preferred space for other non-patented siRNA designs, though all of this is dependent on what happens to Kreutzer-Limmer. Again, Dicerna would be little affected by all of this, and mdRNA may be well advised to try its luck with ‘usiRNAs’ outside the 21-23 nucleotides range, although I still feel chances are slim that one or two supposedly ‘non-nucleotide’ nucleotides will allow them to call what look and behave like siRNAs by another name.

Where does Big Pharma stand in all of this? Those interested in taking broad platform licenses to RNAi trigger IP can probably be classified into into two categories: 1) those like Pfizer and GSK that have diligently done their homework and will already have made up their minds about what type of RNAi triggers are required, including whether they consider overhangs to be an essential feature or not. Such companies can simply await the outcome of the trial and then choose the most economical option everything else (e.g. access to delivery and other know-how) being equal; 2) those companies that have shied away from heavy investments thus far and would prefer to get started with a pure-play RNAi Therapeutics partner providing patent-protected siRNAs and other basic RNAi capabilities. These companies may be most swayed by the outcome of the Tuschl Tussle, since they may be more relaxed in terms of what they consider acceptable siRNA designs.

Tekmira is a pure-play RNAi Therapeutics company that should be uniquely affected by the outcome, because it does not tout having invented unique siRNA triggers, although it certainly could make up such claims to the same degree that others do in the space, and because of its complex relationship with Alnylam. For one, it may determine whether potential partners consider it to be necessary to access SNALP delivery via Alnylam or whether they can go directly to Tekmira and get the same for probably considerably less. Moreover, in the unlikely case of a Max Planck/Alnylam loss, it may become even more difficult to insist on controlling SNALP delivery for RNAi Therapeutics all the while it is obvious that Alnylam is intent on minimizing the importance of Tekmira for their delivery efforts (the whole issue of what is called a SNALP which clearly differs between Alnylam and Tekmira). If SNALP is old and first-generation where is the harm in letting Tekmira fully exploit this technology by partnering it out ex-ALNY instead of letting it wither on the vine? I guess something ought to be worked out here to the satisfaction of both companies.

After 8 years of spending enormous efforts on confusing the investor world with what is valuable RNAi trigger IP, it looks like everything will come down to basic science. The collective scientific community based on the number of citations a paper gets and how it has recognized critical inventions for example in the form of scientific awards, would have been a much more straight-forward, fairer, and infinitely cheaper way of determining ‘good’ RNAi IP. Who else was better suited to spot critical contributions in technically demanding areas such as RNAi than scientists themselves? One would hope that the judge will concur, also in the interest of what RNAi Therapeutics could do for society.

Disclaimer: The above are my own interpretations of the case, based on publicly available documents from the USPTO and court sites, interviews, and press releases. Accuracy cannot be guaranteed as I may have overlooked critical elements of the case, and am neither trained in intellectual property nor contract law. Information provided herein cannot be relied upon for making investment decisions. Investments in RNAi Therapeutics are very risky and not suited for most. Consult with your own professional advisor before doing so.


Anonymous said...

What do you think about CSIRO/Benitec patents....any chance, or are they outta luck since they maybe didn't understand what they were seeing (Fire/Mello issue)?

Anonymous said...

What about the decision last year by a judge in Massachusetts that denied the motion by Alnylam and Max Planck to (basically) kill the prosecution of Tuschl I on the grounds that they did not have a "significant chance" of prevailing in their case? In the decision, the judge seemed to indicate that, in her mind, the fact that Max Planck signed off on the inclusion of Tuschl II data trumped everything else. What makes you so certain that the legal system will consider arguments of scientific merit over the technical points of contract law? Isn't the very opposite likely to be the case, when you consider what lawyers and judges are primarily trained in?

Dirk Haussecker said...

Benitec...yes, it looks like they are fighting an uphill battle against Fire-Mello, but without having done more detailed research the fact that the Benitec/CSIRO patents are about DNA-directed RNAi and CSIRO's work on DNA-directed RNAi (in plants) was considered leading at the time (in fact, I worked on an 'improved' version of such vectors as an undergrad), may leave them with some wiggle room.

RE technicalities vs is certainly a concern and my question is whether Max Planck could have acted earlier. Also in light that motifs have likely changed for the parties as the Tuschl patents made their way through the patent offices. I, however, like to think that it was the ultimate responsibility of the Whitehead attorneys to know whether they could include the human siRNA data, not whether it was the wrong judgement by the Tuschl I inventors and Max Planck to sign off on the data. And even if Max Planck were to be declared responsible for any actions, Tuschl I would still be invalid due to the omission of some inventors. But that would probably be something for the USPTO to decide.

John said...


Thanks for your great analysis. Presumably Tuschl will testify in support of the plaintiffs. How do you think the defendants will be able to overcome this?

Dirk Haussecker said...

Just imagine the headlines and photos if the defendants got their way in the end (very doubtful). It would be a very sad day for science and Tuschl the face of it if not martyr.

John said...

I'm thinking of attending the trial and reporting the daily testimony. Sort of an siRNA Court TV. Would you be interested in this.

Dirk Haussecker said...

Sure, if you can sponsor trip around the world plus accommodation, any time :)

John said...

I'll send you a ticket :-) ....No, I mean my reporting of the testimony. I will suggest to Nerac that it be reported at their website, and/or yours.

Anonymous said...


if you could report from the trial, that would be most welcome and appreciated by many.

Be sure to let the readers of this blog know if and where you are going to report.

Many thanks,


John said...

I'll followup on this in a few weeks.

Anonymous said...

Maybe CSIRO/Benitec knew exactly what they were seeing in animal cells before Fire/Mello understood the application beyond worms ...

Maybe the first complete vision of the therapeutic application of RNAi has an Australian "accent".

Dirk Haussecker said...

John- will wait for your follow-up.

Person from Down Under- when did Benitec/CSIRO experimentally observe RNAi in mammalian cells and how was this disclosed?

Anonymous said...

Go to the USPTO PAIR site

Look up 90/007,247

Read the affidavit filed by Michael Graham on 11/28/2007 - 202 pages

Page 5 forward, marked as about para 10 forward.

Dirk Haussecker said...

Person from Down Under- Thanks, interesting read. It addresses both the priority and animal RNAi issues, and you have to give it to Graham: he recognized very early on that the plant co-suppression mechanisms may be more widespread, that is also occur in mammals/Man, and that patents in this area could become very valuable. History would prove him right.

You are apparently more familiar with this particular patent prosecution, so I wonder how the examiner responded specifically to this affidavit/attempt to overcome Fire?

Anonymous said...

The examiner has dealt with the affidavit the traditional way ... by ignoring it.

The affidavit was filed to support the claims of the Graham '099 - which the examiner rejects based on Fire '599. Since Graham has established both conception and diligence prior to Fire '599 - you would think that the reasonable request to grant the '099 claims would be upheld.

If you think the Tuschl I vs II stouch is big news - imagine what would happen if CSIRO are backed into a corner and prosecute the claims of the Graham '099 by claiming interference OVER Fire '599.

This would rock the foundations of the RNAi IP domain.

I would also imply the Fire/Mello Nobel was for Physiology and not Medicine!

The Graham lab notebook extracts are in the public domain. CSIRO also has the Peter Waterhouse and Ming-Bo Wang lab notes. These could be more explosive:

Dirk Haussecker said...

What are CSIRO/Benitec's claims RE non-DNA-directed RNAi triggers?

Siddharth said...

Hey Dirk! Another great read. I just wanted to ask you about Rana's claims on 16-bp dsRNAs being the most efficient ones in their RNAi potency. Which patent does that come under, if any?

Dirk Haussecker said...

Haven't heard that 16bp dsRNAs are the most potent triggers. What is the precise structure of the siRNAs you are talking about, and in which context are they used?

Anonymous said...

I know that CSIRO have some significant endogenous RNAi IP - based on their extensive hairpin RNA work (as opposed to synthetic RNAi based on siRNAs).

Remember, Waterhouse claims "invention" of RNAi induction from 1994 and demonstration in tobacco plants in 1995! I think they called it "hairpin gene silencing", rather than RNAi (obviously).

I am not greatly familiar with the Waterhouse/Wang claims to invention. However, I would suggest that the recent CSIRO-Benitec agreement is of great significance in terms of the coherence of their vast IP estate.

After all, they have two important "firsts" - demonstration of "hairpin silencing" in any organism and demonstration in animal cells.

Anonymous said...

Waterhouse examination 11/364,183 on USPTO pairs : Miscellaneous incoming letter 04/15/2009 (83pp) claims Suggestion of Interference against Fire '599.

Latest 11/04/2009 (8pp) Non Final shows examiner has dropped all previous Fire '599 prior art rejections

Siddharth said...

Hey Dirk, this is the article I was talking about regarding the 16 bp RNAi triggers.

Dirk Haussecker said...

RE Waterhouse patent. Do I understand the current proceedings correctly in that at this stage it is a matter of determining the priority of Fire vs Waterhouse, and that a hypothetical loss of Fire e.g. would mean that the subject matter part of the interference proceedings would be lost forever?

And how does Waterhouse tie in with Graham/'099? Is the move now to consolidate the two such that Graham gets afforded the same priority as Waterhouse?

Dirk Haussecker said...

RE 16bp triggers. I had a look at the paper. While there were some interesting results there, I consider the claim that, bsaed on this one example, 16bp siRNAs are more potent RNAi triggers than more conventional siRNAs a slight overstatement.

It speaks to the robustness of RNAi that so many structures do induce the process, and as RXi shows this includes 14bp and less when you look hard enough.

Anonymous said...

I understand Waterhouse is co-named inventor on '099. Furthermore the 11/364,183 interference claim is on record for all graham applications and the '099 re-exam

also as i understand it the interference claim goes before BPAI, so all Fire related objections have been set aside by exmainer. Double patenting rejections to be dealt with first -then when they are clear onto BPAI for interference claim to be ruled upon.

Dirk Haussecker said...

Thanks. What would be the priority date of a '099 patent that is aligned with original Waterhouse patent as you describe?

Anonymous said...


Bit of an update re CSIRO / Fire.
BPAI have declared an interference. they advise approx 6 month proceeding to determine priority. (image file wrapper on USPTO PAIRS for 10/283,267)

Dirk Haussecker said...

Thanks for letting me know. Overcoming Fire-Mello through priority seems like an obvious strategy, and if successful could indeed have a little ripple effect on the RNAi trigger IP space. Do you believe the patent examiners of the Waterhouse and Graham patents had made a mistake when determining priority? And also, do you have an idea how many crop companies already commercialize ddRNAi plants and the size of the market?

Anonymous said...

im sure no patent guru - but my take is the examiners appear to have deferred to the BPAI judges when it comes to priority with waterhouse / graham work and fire.
infact in the waterhouse filing, they've gone as far as stating the interference is for BPAI judges to sort, not examiners.

not aware of any data on ddrnai crop market. following link gives interesting guidance on existing and potential markets, but less of an attempt at figures (probably wisely)

Anonymous said...

parallel to USPTO interference proceeding, the European Patent Office is current looking at same issue between Fire and CSIRO work.

An observation by third party of a CSIRO paper (DeFeyter) was filed in 2009. As of today EPO has dispatched a communication with 4month time limit. This doc yet online - but should be shortly.

Reference No. on EPO site is EP98964202

Site address:

Anonymous said...

Hi Dirk,

USPTO BPAI Judges have just put put their finding on the Graham '099 patent re-exam. They have reversed all of the examiner's rejections.

Dirk Haussecker said...

Thanks for the heads-up. This is somewhat new territory for me, so tell me if I am missing something here:

I went to the BPAI website and typed in interference number 105,754. I believe that's the one you are referring to. The last file posted was an Order on 9/15 on motions filed by Carnegie. This order does not seem to be it. Any other way of accessing the information, or do I just have to wait?

So if CSIRO prevails, then Fire-Mello does not apply to ddRNAi in the US- correct? Fire and Mello, however, would continue to be fundamental to the introduction of dsRNAs to induce gene silencing.?

Anonymous said...


with the Graham 099 patent ruling Fire / Mello still holds - however the judges found that Examiner's argument of Fire combined with antisense references did not make the Graham ddRNAi method obvious to invent.

Best place to check is under PAIRS, application number 90/007247

The interference proceeding is a totally separate application by Waterhouse (also from the CSIRO 'stable')

Anonymous said...

proper format for application number is 90/007,247

then click on image file wrapper

and the judges decision document is latest entry. looks like they didn't have too much trouble deconstructing the examiner's over use of antisense as prior art

Patent lawyer said...

Benitec has all human theraputic rights to Waterhouse and other CSIRO patents, if the Fire interference is successful where do SIRNA and Alnylam stand on IP , what else do they have? Does it mean anyone who needs to work in the space needs a CSIRO (Benitec ) license? Or is Fire irrelevent?

Anonymous said...

Tuscl 1 vs 2 , Waterhouse vs Fire, Nucleonics vs Benitec. The RNAi IP landscape is changing dramatically , is anyone taking notice?

Dirk Haussecker said...

To be clear, Fire is not worthless and no question that work deserved the Nobel Prize. However, it is evident that the plant community critically contributed to the discovery and development of RNAi technology and a Waterhouse patent covering also animal RNAi is not out of the question. As such, it would affect the claims and strategic importance of a revised Fire patent.

Anonymous said...

If Waterhouse interference succeeds and Graham is reissued is Tuschl 2 the only foundation patent outside CSIRO ? Does Waterhouse cover any of Tuschl as well? as some comments seem to indicate , are there any public postings I can examine?

Dirk Haussecker said...

IMO, a successful interference by Waterhouse wouldn't invalidate patents that claim specific features of RNAi triggers that make them more advantageous, but you might still need a license to Waterhouse.

Anonymous said...

Hi Dirk,

It appears Carnegie have abandoned the Fire application with the EPO.

They failed to respond to a Communication from EPO to respond to a third party observation citing the CSIRO's de Feyter paper (1996) as prior art.

maybe they lost interest - it was originally filed in 1998...


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