Will Exelixis’s Cabometyx face generic competition when the 30-month stay ends in November?

Zachary Silbersher

I previously blogged (here and here) about the pending Hatch-Waxman lawsuit between Exelixis ($EXEL) and MSN Pharmaceuticals in connection with MSN’s prospective generic for Cabometyx®.  The case has been barreling towards trial in May of this year, which would theoretically provide insight into how soon Cabometyx® may face generic competition.  This trial date is important because the 30-month stay is scheduled to expire in November 2022.  However, a current dispute over scheduling has called into doubt if the trial in May will proceed, and even if it does, if it will provide certainty on MSN’s entry.

Exelixis originally sued MSN for only one patent, U.S. Patent No. 8,877,776.  Several months later, MSN amended its ANDA to allege that two additional Orange Book listed patents for Cabometyx® were either not infringed or invalid.  That forced Exelixis to add those two patents to its suit against MSN.  Those patents include U.S. Patent Nos. 7,579,473 and 8,497,284.  Soon after that, MSN added a declaratory judgment counterclaim that its prospective generic would not infringe an additional patent that was owned by Exelixis, but not listed in the Orange Book for Cabometyx®.  That patent is U.S. Patent No. 9,809,549.

In October 2021, MSN appears to have conceded that it will infringe at least some of the claims of the ‘473 and ‘284 patents.  As a result, the parties stipulated to infringement of these two patents.  That does not mean that Exelixis automatically wins on these two patents.  Rather, MSN reserved the right to prove either patent is invalid.  If that defense is successful, then those patents cannot bar MSN’s generic entry despite MSN’s concession that those patents would otherwise be infringed by its generic. 

At the same time, MSN also dropped its claims for declaratory relief related to the ‘549 patent.  (More specifically, MSN agreed to drop its claim of non-infringement “with prejudice,” but its claim for invalidity “without prejudice”).  Yet, MSN’s declaratory relief claim was essentially preemptive.  Because Exelixis had never formally asserted this patent against MSN, then it could not have formally barred MSN’s generic entry until Exelixis did so. 

Despite all of this pruning of the case, the litigation between Exelixis and MSN has in fact continued to balloon.  In August 2021, Exelixis added new patents to the Orange Book covering Cabometyx®.  That prompted MSN, on January 11, 2022, to filed Paragraph IV certifications against three new patents: U.S. Patent Nos. 11,091,439, 11,091,440, and 11,098,015.  The parties are now disputing whether the upcoming trial should move forward, or whether the trial should be delayed pending Exelixis’ decision whether to assert any of these new patents against MSN. 

There are currently two major dates hanging over this case.  First, trial is currently scheduled to commence on May 16, 2022, and second, and perhaps more importantly, the 30-month stay is scheduled to expire on November 5, 2022.

The ‘776 patent is directed to specific crystalline form of the (L)-malate salt of cabozantinib.  The ‘473 patent covers the chemical compound of cabozantinib.  The ‘284 patent an indication patent that directed to methods of treating certain types of cancer with cabozantinib.  The three new patents in the case (‘439, ‘440 and ‘015) are more similar to the ‘776 patent than to the ‘473 or ‘284 patents.  They each share the same patent specification as the ‘776 patent, and are also directed to malate salts of cabozantinib.  These distinctions are important because MSN argues that litigating the new patents will be a breeze, whereas Exelixis claims, despite the similarities to the ‘776 patent, litigating the new patents cannot likely happen in under six months.

Then there is a fourth patent, U.S. Patent No. 11,141,413.  This is also an indication patent directed to treating kidney cancer in patients having received prior anti-angiogenic therapy.  MSN has not submitted a Paragraph IV certification against this patent.  Rather, MSN has claimed that, if Exelixis asserts this patent against MSN’s proposed generic, then MSN intends to carve out the indication covered by this patent from its generic label, thus obviating the need to try the question of whether MSN infringes the patent.

The current scheduling dispute centers around whether to move ahead with the trial scheduled in May—even though it will be only on the patents currently asserted (the ‘776, ‘473 and ‘284)—or whether to give the parties time to add the new patents to the case, and then reschedule a single trial covering all of the patents later in the year.  MSN has suggested that the trial could occur within November of this year.  

Complicating this issue is the outstanding question of whether Exelixis will assert any of its new patents against MSN or not.  MSN has filed a Paragraph IV letter against three of the new patents—the ‘439, ‘440 and ‘015—but Exelixis has not yet responded with a Hatch-Waxman lawsuit.  Technically, Exelixis has until February 22, 2022 to make that decision.  MSN attempted to force the issue by seeking leave to file declaratory judgment counterclaims against the new patents—thereby injecting them into the case asap—but the Court denied that request, and told MSN it would essentially have to wait until after Exelixis’s deadline to formally assert the patents in litigation has expired. 

All of these machinations over scheduling are likely a play for time.  Because time is money.  Or rather, when it comes to brand pharmaceutical drugs, delaying generic competition is money.  On the one hand, it is slightly counterintuitive that the brand owner is pushing for immediate trial, whereas the generic is asking to delay the trial.  Yet, MSN may really be trying to speed the case up, whereas Exelixis may be trying to slow it down.  

MSN understands that if three new patents are added to the case, that could slow down its generic entry by months, if not years.  Thus, MSN is attempting to cram the patents into the case as soon as possible, and push for a trial covering all patents before the end of the year.  By contrast, Exelixis’ attempt to move ahead with the May trial, but leave for another day the trial of the three new patents, is likely to result in a final resolution of entire this case being pushed out into 2023.  That would be good news for Exelixis given that the 30-month stay is due to expire later this year.

Apart from its litigation against MSN, Exelixis has also brought a Hatch-Waxman lawsuit against Teva, which is also seeking license to distribute a generic version of Cabometyx®. Teva is not, however, biting at the heels of Exelixis in the same way that MSN is.  Exelixis’s lawsuit against Teva asserts three entirely different patents, namely, U.S. Patent No. 9,724,342, 10,039,757, and 10,034,873.  These patents do not expire until at least 2031 or 2033.  

 All of this may mean—although it is not confirmed—that Teva has, for the time being, conceded that it will not seek to enter with a generic version of Cabometyx® until at least the ‘473, ‘284 and ‘776 patents expire—in other words, not until at least 2030.  At the same time, Teva is likely hoping to piggy-back on the efforts of MSN.  If MSN can invalidate the ‘473, ‘284 and ‘776 patents, then Teva may seek to enter earlier.  But there are a lot “if’s” in that sentence.

 Either way, on February 8, 2022, Exelixis and Teva stipulated to stay their litigation.  The typical reason that a patent litigation is stayed is because the defendant has filed a petition for inter partes review at the Patent Office against the asserted patents (otherwise known as “IPRs”).  Yet, here, Teva has not filed any IPRs.  The stipulation is itself sealed, and therefore, the basis for the stipulation is not available to the public.  For the time being, that likely means that whether or not Cabometyx® faces generic competition anytime soon likely depends upon the outcome of Exelixis’ litigation against MSN.