Exelixis and MSN are about to go to trial over Cabometyx. Will MSN launch at risk?

Zachary Silbersher

Exelixis is on the eve of trial against MSN over its prospective generic for Cabometyx.  Yet, there are now two separate patent litigations between the companies related to Cabometyx.  Exelixis succeeded in slowing down MSN’s entry by keeping the cases separate, but an MSN victor in the upcoming trial may increase the odds of an at-risk launch.  I have previously blogged about Exelixis’ patent dispute with MSN here, here and here, and these prior posts provide much background on the lawsuits to date.

The new case

In late February 2022, Exelixis commenced a new Hatch-Waxman patent lawsuit against MSN that asserts three new patents, including, U.S. Patent Nos. 11,091,439, 11,091,440, and 11,098,015.  That means MSN must now contend with three new patents before gaining freedom to launch its prospective generic without the risk of patent liability.  

In my post earlier this year, I discussed how the parties were disputing whether the new patents should be added to the older suit.  At stake was whether this entire dispute could go to trial this year, or would have to be delayed until next year.

Exelixis won that skirmish.  And it was an important one.  The new patents have not been consolidated into the older case.  That means the older case is still scheduled to go to trial in May 2022.  But that also means that the new case is not scheduled to go to trial until next year, at the earliest.

Accordingly, regardless of the outcome of the upcoming trial, MSN will still face patent risk if it launches before resolution of the second suit.  The second suit is currently scheduled to go to a three-day trial beginning on May 22, 2023 (i.e., more than a year from now).  The court will likely require months after that to issue its decision.  That will be followed by an appeal to the Federal Circuit that will likely to take approximately one year to resolve.

Will MSN launch at risk?  The 30-month stay is scheduled to expire in November 2022.  Assuming MSN’s generic receives FDA approval, its decision to launch at risk is a business one, rather than legal one.  

Yet, MSN may take a lot from how the court reacts to its infringement challenge to the ‘776 patent in the upcoming trial this May.  The three new patents asserted in the second lawsuit (‘439, ‘091 and ‘440 patents) are similar to the ‘776 patent.  They each share the same patent specification as the ‘776 patent, and are also directed to malate salts of cabozantinib.  Thus, the court’s findings with respect to the ‘776 patent may read through to the ‘439, ‘091 and ‘440 patents.  Thus, if MSN knocks it out of the park in the upcoming trial, that may embolden its appetite to launch at risk. 

The old case

Meanwhile, the existing litigation is going to trial.  The trial is scheduled to commence on May 16, 2022 and last for three days.  

To date, numerous patents have been asserted in this case.  Yet, the parties have now streamlined their respective contentions and each has dropped many claims and defenses.  Accordingly, the upcoming trial will focus on the following two discrete issues.  

·      First, whether MSN’s prospective generic will infringe claims 1 and 2 of the ‘776 patent.  (MSN has dropped its invalidity challenge to the ‘776 patent.).  

·      Second, whether claim 5 of the ‘473 patent invalid?  (MSN has stipulated to infringement of this claim.  In addition, Exelixis has dropped its assertion of the ‘284 patent.)

Starting with the ’776 patent, since the issue at trial will concern only infringement, then the burden of proof will rest with Exelixis.  The ‘776 patent is a polymorph patent, and Exelixis’ arguments to prove infringement are likely to be very technical, rather than legal.  My previous blog post explored some of the infringement issues around Exelixis’ burden of proving infringement of a polymorph patent.

The ‘776 patent is directed to a specific crystalline form of the (L)-malate salt of cabozantinib.  Exelixis will have to prove at trial that MSN’s generic comprises a crystalline (L)-malate in Form N-2, as disclosed in the ‘776 patent.  Exelixis will likely introduce evidence of powder x-ray diffraction to show diffraction patterns satisfying the Form N-2 embodiment from the patent.  In particular, this will likely require showing that MSN’s generic matches the pattern shown in FIG. 8 of the patent.  

Turning to the ‘473 patent, since the issue at trial will concern invalidity, then the burden of proof will rest with MSN.  The arguments on this issue are also likely to be very technical.  

The ‘473 covers the chemical compound of cabozantinib.  MSN has identified a prior art compound within Example 5 of patent WO 03/000660.  MSN’s principle invalidity argument is that it would have been obvious to start with the Example 5 compound in the ‘660 patent, and modify it to include a geminal-cyclopropyl ring at the position of the malonamide methylene.  MSN further argues that such a modified compound would be reasonably expected to inhibit c-Met tyrosine kinase.  

The following is an illustration of MSN’s invalidity argument for the ‘473 patent, starting with the lead compound identified in Example 5 of the ‘660 patent.  (This illustration was taken from 1:19-cv-2017-RGA-SRF, D. Del., Dkt. 275, Ex. 3 at 4). Settlement is always a possibility, but at this stage the trial in May is looking more and more likely to occur.  I will follow up with more posts around the trial.