Monday, November 26, 2012

Tuschl Patents Stage Remarkable Comeback in US

[please note the changes below after I discovered that I missed the last claim amendments, as correctly pointed out by a commenter]

Alnylam announced today that the US patent office had issued 3 Notices of Allowance in recent weeks pertaining to the Tuschl patent estate.  Before your eyes glace over, read on, it's actually one of the few important patent news.  

The granted composition-of-matter claims cover very broadly 19-25bp RNAi triggers, independent of structure.  This is a stark departure from the trend that had materialized in the Tuschl patent applications where Tuschl I seemed to get relegated to treating diseases of fly lysates and Tuschl II suffering from double-patenting issues over Tuschl I.

Claim 1 of allowed patent application 12/537602:

1. Isolated double-stranded RNA molecule, wherein each RNA strand has a length from 19-25 nucleotides, wherein said RNA molecule is capable of target-specific nucleic acid modifications.

1.  An isolated double-stranded RNA molecule, which is a non-enzymatically processed RNA molecule, wherein: (i) each RNA strand independently consists of 19-25 nucleotides in length, and (ii) at least one RNA strand forms a single-stranded 3'-overhang from 1 to 5 nucleotides, wherein said RNA molecule is capable of target-specific RNA interference.

The reason why such a comeback was possible can be traced back to the settlement over the Tuschl patents 'with Merck' in early 2011.  This allowed the Tuschl I and II prosecutions to be aligned such that the double-patenting issue for the 3' overhang claim could be overcome such that the broadness of the Tuschl I RNAi triggers could be rescued into the valuable human therapeutic uses. 

Among those without RNAi trigger licenses from Alnylam, Silence Therapeutics (and its partners, especially Quark) should be hit particularly hard by the latest development: 19bp RNAi triggers are no place to hide any more.   

There are thus two monsters of RNAi trigger patents that consequently co-exist in the commercially very important US market: Baulcombe for almost all types of therapeutically useful double-strand RNA lengths (20-24/30bp; see here) and Tuschl for the desirable 3' overhang feature of RNAi triggersIt is unclear to me how two patents can essentially claim the same.  Either the patent office is aware of this and is satisfied with ultra-fine semantics distinguishing the two, or this is an issue worth reconsidering.

Another indication that the last word might not have been spoken may be the multiple requests by Alnylam (i.e. their law firm) to expunge certain materials that were rendered during the Tuschl patent prosecutions (possibly relating to timing and nature of the claimed invention), but are deemed trade secrets by Alnylam (can’t help but smile, here). Has Utah taken notes in time?


Anonymous said...

How can Silence Therapeutics be affected at all when they were just awarded two patents from the USPTO on November 5th?

Anonymous said...

Silence won't be affected as they have one of the strongest patent portfolios in the RNAi industry. Over 200 granted and pending patents.

Anonymous said...

Allowed claim 1 of patent application 12/537602 reads: "1. An isolated double-stranded RNA molecule, which is a non-enzymatically processed RNA molecule, wherein: (i) each RNA strand independently consists of 19-25 nucleotides in length, and (ii) at least one RNA strand forms a single-stranded 3'-overhang from 1 to 5 nucleotides, wherein said RNA molecule is capable of target-specific RNA interference." The claim you cite is from an Exhibit within the '602 file history.

Anindependanyunlikeyou said...

These rae very strong claims against Silence and Quark Dirk.I hope that you haven't shot from the hip which you often appear to do.It is oh so easy to disrespect iothers without the full facts or undertsanding and the mud sticks all too often.In your position where you have an audience you have a special responsibility to be careful to fairly present the facts rather than idly speculate.One might note you wouldnt so idly make such claims against yuor pet tekmira would you?Ther are lots reading yuor blog that may wonder why you are so blindly positive about them and always so quick to cast aspersions on others.

Dirk Haussecker said...

Thank you for pointing out my mistake. I did not scroll down the July 3, 2012 claim set (last submitted claim set) and missed the amendment which, as you correctly point out, does not cover 19-25bp RNAi triggers in general, but only those with 3' overhangs. This also makes more sense in light of Baulcombe.

Apologies to Silence and Quark for my mistake. In light of the changes and Baulcombe, blunt-ended 19mers will still circumvent the new Tuschls and Baulcombes. Having said that, Atu027 (lead Silence candidate) I believe is a 23mer and should thus infringe on Baulcombe. I guess though that can be resolved with taking a simple license. On the other hand, it is a fundamental mistake to believe that having patents will give you any more does not.

Anonymous said...

Dirk, what do you make of the licensing agreement between Tekmira and Marina Biotech?

Dirk Haussecker said...

The data on the UNA benefits by Marina, Dicerna, and Merck seem to be concordant. This makes me optimistic that UNA has real benefits in their application to RNAi trigger chemistry...not just for IP reasons. I would assume that Tekmira has made similar findings and are now taking a license.

Anonymous said...

Dirk, give or take for rough estimate purposes, what is your guess at what an InterfRx option currently worth now?

Dirk Haussecker said...

The value of an InterfeRx pick? Tough to say. There are now more obvious workaround options, although 3' overhang feature desirable for may RNAi trigger designs. Plus, you need the Baulcombe in addition. Value therefore largely in the eye of the beholder (i.e. will differ according to various needs).

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