Litigation on combination of sofosbuvir and ledipasvir reaches Switzerland

Case No. S2014_008 ¦ Decision of 28 October 2014 ¦ “Superprovisorische Anordnung einer Verfügungsbeschränkung im Patentregister (Registersperre)”

— THE DECISION IN A NUTSHELL —

Both Gilead Pharmasset LLC and AbbVie Inc. hold patent applications on the combination of the sofosbuvir and ledipasvir for the treatment of hepatitis C. This combination is marketed by Gilead under the tradename Harvoni™. Gilead has sued AbbVie for assignment of their Swiss patent applications. In first place, a block of the register for these patent application was ordered as an interim measure.

— THE DECISION IN MORE DETAIL —

This decision pertains to new pharmaceuticals for the treatment of hepatitis C.

1.  BACKGROUND

Undisputedly, sofosbuvir has been a breakthrough in the treatment of this widespread disease. It is a ribonucleotide analog inhibitor of the RNA-dependent RNA polymerase of hepatitis C virus (HCV).

Sofosbuvir
Sofosbuvir (PSI-7977)

Sofosbuvir causes chain termination by competing at the triphosphate level with natural nucleotides for incorporation into elongating RNA. The triphosphate serves as a defective substrate for the NS5B protein (which is the viral RNA polymerase), and thus acts as an inhibitor of viral RNA synthesis; see Antimicrob Agents Chemother. 2014 Jul; 58(7): 3636-45.

Way of acgtion of sofosbuvir
Way of action of sofosbuvir (by Anypodetos, via Wikimedia Commons); click on image to enlarge.

Sofosbuvir has received the FDA’s Breakthrough Therapy Designation and has been marketed since 2013. Compared to previous treatments, sofosbuvir-based regimens are reported to provide a higher cure rate, fewer side effects, and a two- to four-fold reduced duration of therapy.

In October 2014 a combination of sofosbuvir with the viral NS5A inhibitor ledipasvir was approved by the FDA.

Ledipasvir
Ledipasvir (GS-5885)

The combination of sofosbuvir and ledipasvir is marketed by Gilead under the tradename Harvoni™; see also the Harvoni™ patient information. It is reported to provide high cure rates in people infected with genotype 1 (the most common subtype in the U.S., Japan, and much of Europe).

Principal display panel of Harvoni™
Principal display panel of Harvoni™; click on image to enlarge.

Well, and here we are at the very core of this dispute: The rights in the invention of a combination of sofosbuvir and ledipasvir. Some indication of this issue is already contained in Thomson Reuters’ report to the WHO on the patent situation of sofosbuvir (see Patent 2, p. 16-17), the respective report on ledipasvir (see the Note in the Summary on p. 11) and newsfeeds such as e.g. Knowledge Ecology International or Biospace.

2.  WHO ACTUALLY INVENTED IT?

This question will be dealt with in co-pending main proceedings (O2014_013). Both parties had filed patent applications on this combination of drugs. The present decision only deals with a block on the register as an interim measure (see below). However, the plaintiff exhaustively argued on the merits of his rights in the invention, in order to get the block on the register issued. And, indeed, it was issued even without hearing the defendant beforehand.

The plaintiff essentially argued as follows:

As the legal successor of Gilead Sciences, Inc., Gilead Pharmasset LLC owns all rights and interest in this invention that is subject of patent applications (for the assignment see the request for a change under R. 92bis PCT and the corresponding notification issued by the WIPO). An outline of this patent family is shown below. Claim 3 of WO 2013/040492 A2 is directed to the combination of sofosbuvir (referred to as “compound 10”) and ledipasvir (referred to as “compound 6”).

Priority applications filed in the U.S.:
#1
Sep 16, 2011
61/535,885
#2
Nov 18, 2011
61/561,753
PCT application claiming these priorities:
filed
Sep 14, 2012
PCT/US2012/055621
pub’d
Mar 21, 2013
WO 2013/040492 A2

Gilead Sciences, Inc. had acquired Pharmasset LLC in January 2012, incl. the rights to sofosbuvir (PSI-7977). On the other hand, ledipasvir had been developed in-house at Gilead. Gilead’s first priority application had been filed on September 16, 2011 (at a time when a takeover bid for Pharmasset LLC had already been placed), and this application already included the combination of sofosbuvir and ledipasvir (GS-5885) for the treatment of HCV (in particular of genotype 1) for twelve weeks, with or without the further antiviral agent ribavirin, but in any case without interferon. Thus, the plaintiff had been in possession of the invention already on September 16, 2011.

The defendant’s patent applications are outlined below, in chronological order. The two Swiss patent applications that are litigated here are given in the last line. There are two series of applications, one with and one without the yet further antiviral agent ribavirin.

w ribavirin
w/o ribavirin
Priority applications filed in the U.S.:
#1
Oct 21, 2011
61/550,352
61/550,360
#2
Nov 21, 2011
61/562,181
61/562,176
#3
Jan 17, 2012
61/587,225
61/587,197
#4
Feb 17, 2012
61/600,276
61/600,468
#5
Apr 03, 2012
61/619,870
61/619,883
#6
Jun 06, 2012
61/656,251
61/656,253
#7
Oct 10, 2012
61/711,830
61/711,793
PCT applications claiming these priorities:
filed
Oct 19, 2012
PCT/US2012/061075
PCT/US2012/061085
pub’d
Apr 25, 2013
WO 2013/059630 A1
WO 2013/059638 A1
Nationalised in Switzerland:
nat’d
Jan 13, 2014
CH 707 029
CH 707 030

As can be seen, the defendant had filed the first priority application on October 21, 2011, i.e. only after the plaintiff’s first priority application of September 16, 2011. Ledipasvir as such is not referred to by the defendant in his first priority application, but rather only the identifier GS-5885. Neither the chemical structure is given, nor the specific combination of GS-5885 and sofosbuvir. The plaintiff points at two peculiarities in the subsequent time line of the defendant’s priority filings:

First, the plaintiff had mentioned the combination of GS-5885 and sofosbuvir for the first time in an investor phone conference on February 02, 2012. However, the structure of GS-5885 had not been made publicly available. About two weeks later, the fourth priority applications had been filed and disclose the specific combination of sofosbuvir and GS-5885 for the first time in the series of priority applications.

Second, only the sixth priority applications of the defendant (filed June 06, 2012) disclose the structure of ledipasvir / GS-5885. This is about six weeks after the plaintiff had made the structure of GS-5885 publicly available for the first time on April 18, 2012 at the 25th International Conference on Antiviral Research in Sapporo, Japan. The defendant does not rely on clinical data in the patent applications, but rather used computer models to predict the advantageous combinations of drugs.

3.  NOW, WHAT HAS BEEN DECIDED?

Both parties are domiciled in the U.S.; competency for interim measures is thus governed by Art. 10 IPRG. The requested interim measures aim to preserve the status quo for as long as the assignment suit has not yet been decided in co-pending main proceedings (O2014_013). In main proceedings, the courts of Switzerland have jurisdiction (Art. 109(1) IPRG; Art. 29 PatA). Moreover, the requested interim measures (block of the register) are to be executed in Switzerland. Competency of the FPC is thus given, and Swiss law is to be applied (Art. 110(1) IPRG).

Interim measures are ordered when the plaintiff credibly shows that a) a right to which he is entitled has been violated or a violation is anticipated; and the violation threatens to cause not easily reparable harm to the plaintiff (Art. 261(1) CPC). Prima facie evidence is sufficient. Further, a certain urgency must be given and the requested interim measures must be proportinate. The FPC held that all these prerequisites were fulfilled in the present matter. The block of the register was ordered without hearing the defendant beforehand, to prevent that the enforcement might be jeopardized.

It remains to be seen how the defendant defeats the allegations. The defendant will now belatedly be heard and the FPC will then finally decide on the requested interim measures (Art. 265(2) CPC).

Reported by Martin WILMING

— BIBLIOGRAPHY —

Case No. S2014_008 ¦ Decision of 28 October 2014 ¦ “Superprovisorische Anordnung einer Verfügungsbeschränkung im Patentregister (Registersperre)”

Gilead Pharmasset LLC ./. AbbVie Inc.

Subject(s):

  • Interim measures without hearing the defendant
  • Transfer of patent application

Composition of the Board of the FPC:

  • Dr. iur. Dieter BRÄNDLE (President)
  • Lic. iur. Susanne ANDERHALDEN (First Court Secretary)

Representative(s) of Plaintiff:

Representative(s) of Defendant:

  • none yet

— FULL TEXT OF THE DECISION —

Download (PDF, 210KB)

Print Friendly, PDF & Email

3 Replies to “Litigation on combination of sofosbuvir and ledipasvir reaches Switzerland”

  1. Well, you may easily dislike AbbVie’s approach. And one might doubt the story of a computer model that predicted the effective combination therapies. To me, all this is somewhat disturbing. But is it really a case for an assignment action under your Art. 29 PA? How to prove(!) that it’s not been an independent invention (Art. 3/3 PA)?

Leave a Reply

Your email address will not be published.