Orange Book Blog

Novartis Pharms. v. Teva Pharms. USA, No. 05-1887 (D.N.J. 2007)

Novartis and Teva have been in litigation over Teva’s ANDA for generic Famvir (famciclovir), Novartis’s antiviral treatment for herpes, since 2005.  Teva was prepared to launch its generic famciclovir product on August 24, 2007–the day the 30-month stay expired.  To prevent such an at-risk launch, Novartis filed a motion for a preliminary injunction, claiming that Teva infringes U.S. Patent No. 5,246,937.

Last Wednesday, following a one-and-a-half hour oral argument, the district court denied Novartis’s motion.  On Thursday, the court released its opinion, in which it concluded that Novartis was unlikely to succeed on the merits of its case and that Novartis would not suffer irreparable harm from denial of the injunction.  Specifically, the court ruled that Novartis failed to show that Teva’s obviousness and inequitable conduct defenses lack substantial merit.  The court further ruled that any economic harm to Novartis is not irreparable since Teva is able to pay whatever damages may arise and that Novartis’s research activities would not be disrupted by a temporary reduction in Famvir sales revenue.

On Thursday afternoon, Novartis filed an Emergency Motion for an Injunction Pending Appeal with the Federal Circuit.  Friday morning, Teva announced that it had "commenced shipment of Famciclovir Tablets" and that it is the 180-day exclusivity holder.  Friday afternoon, the Federal Circuit ordered that Teva "is temporarily enjoined from selling its generic famciclovir product, pending the court’s receipt of Teva’s response and the court’s consideration of the papers submitted."  Teva filed its opposition brief this past Tuesday, and Novartis filed its reply brief on Wednesday.  The Federal Circuit is still considering the parties’ submissions.

The primary issue on appeal is whether the claims of the ‘937 patent are invalid as obvious.  The district court ruled that it would have been obvious to select penciclovir as a lead compound from which to design famciclovir because it was "one of only five known acyclic nucleosides to have strong activity and low toxicity."  On this basis, the court distinguished the case from Takeda Chemical.  Quoting KSR, the district court stated that "selecting penciclovir was a matter of ‘ordinary skill and common sense.’"  Further, the court ruled that it would have been obvious to modify penciclovir into an effective orally-absorbed prodrug (famciclovir).  Both of these questions are hotly contested on appeal.  The inequitable conduct and irreparable harm issues are secondary.

Famvir is a relatively minor product for Novartis, with about $200 million in annual U.S. sales.  Nevertheless, the case is important to the parties, especially since Teva’s 180-day exclusivity is running while it is enjoined from marketing its product.  A decision from the Federal Circuit on Novartis’s motion is expected next week.

RELATED READING:

• Motley Fool article
• Reuters article

Aventis Pharma and King Pharms. v. Lupin, No. 2006-1530 (Fed. Cir. 2007)

The Court of Appeals for the Federal Circuit today reversed a district court trial verdict that held the asserted claims of Aventis's patent on Altace not invalid, finding instead that the claimed invention would have been obvious.  The patent in suit was U.S. Patent No. 5,061,722, which covers ramipril, the active ingredient in Altace.  Aventis owns the '722 patent and King Pharmaceuticals markets Altace under an exclusive license.

Ramipril is a stereoisomer belonging to a family of compounds that includes 25 stereoisomers.  Additionally, ramipril is one of a family of drugs known as Angiotensin-Converting Enzyme inhibitors, or "ACE inhibitors," which are useful for treating high blood pressure.  The prior art asserted by Lupin included structurally similar ACE inhibitors, including enalapril, as well as publications describing how to separate stereoisomers from each other.

The Supreme Court's recent decision in KSR v. Teleflex appears to have been a key to the Federal Circuit's decision today:

The district court held that Lupin failed to meet its burden of proof by clear and convincing evidence that a person of ordinary skill in the art would have been motivated to purify 5(S) ramipril into a composition substantially free of other isomers.  The district court saw this as a close case based principally on the absence of a clear and convincing showing of motivation.  Since the date of that decision, however, the Supreme Court decided KSR Int'l Co. v. Teleflex Inc. . . . .  Requiring an explicit teaching to purify the 5(S) stereoisomer from a mixture in which it is the active ingredient is precisely the sort of rigid application of the TSM test that was criticized in KSR.

Another interesting aspect of today's decision is that just six days ago, in Forest Labs v. Ivax Pharms., the Federal Circuit upheld the validity of another patent on a stereoisomer pharmaceutical compound: Lexapro (escitalopram).  The Federal Circuit held today that ramipril is prima facie obvious (based, in part, on its structural similarity to prior art compounds) and that Aventis and King "failed to show unexpected results that would tend to rebut a prima facie case of obviousness."  In contrast, according to today's opinion, in the Lexapro case "prima facie obviousness of a claim to a particular stereoisomer over a racemic mixture was rebutted where the particular stereoisomer showed unexpected benefits and evidence indicated that the isomers would have been difficult for a person of ordinary skill in the art to separate."

Given the amount of revenue at stake (about $700 million in annual U.S. sales), I would expect Aventis and King to file a petition for rehearing or rehearing en banc with the Federal Circuit.

RELATED READING:

• AP story
• Reuters article
• TheStreet.com article
• Patently-O

Altana Pharma AG and Wyeth v. Teva Pharms. USA, No. 04-2355 (D.N.J. 2007)

Last Thursday, a federal district court denied Wyeth’s motion for a preliminary injunction that would have prevented generic drug manufacturer Teva from launching its generic version of Protonix.  The opinion denying Wyeth's motion was filed under seal; only the order is publicly available currently.

Wyeth amassed $2.5 billion in sales of the heartburn medication for the sales year ending on June 30, 2007.  Last month, the FDA gave Teva the go-ahead to launch 20 mg and 40 mg versions of generic Protonix.  But since the district court has not yet held a trial on the merits of the case, Teva must decide whether to launch at risk or to wait for a favorable verdict.  At this point, Teva has not begun shipment of generic Protonix. 

Wyeth’s stock price has already taken a hit from the ruling.  After the court decision was announced on Thursday, Wyeth’s stock fell by $1.82/share in late-day trading.

UPDATE:  In a research note Monday, pharma analyst Joe Tooley of A.G. Edwards said he expects Sun Pharma to receive final FDA approval today.  Additionally, he stated that if both Teva and Sun decide to launch at-risk, the branded market for Protonix could contract as much as $500 million in the remaining months of this year.

RELATED READING:

• Bloomberg story
• Reuters article
• Teva press release
• WSJ Health Blog post

Forest Labs. v. Ivax Pharms. and Cipla, No. 2007-1059 (Fed. Cir. 2007)

In an opinion released today, the Court of Appeals for the Federal Circuit affirmed a district court decision that upheld the validity of Forest Labs’ U.S. Reissue Patent 34,712, which covers (+)-citalopram, the active ingredient in Lexapro.  Teva, seeking to market a generic version of Lexapro before the ‘712 patent expires in 2012, challenged the patent’s validity in a paragraph IV filing.

Teva’s lead argument (which took up the entire 30-minute oral argument in May) was that the claims of the ‘712 patent were anticipated by a prior art reference that predicted that one enantiomer of the racemate, citalopram, would be more active than the other.  The Federal Circuit affirmed the district court’s conclusion that the prior art reference was not enabled, and therefore not anticipating.

Teva’s second argument was that the claims of the ‘712 patent were obvious in light of racemic citalopram and known techniques of separating enantiomers from their racemates.  The Federal Circuit dismissed this argument in less than a paragraph, stating: " As with their arguments on anticipation, Ivax and Cipla mainly emphasize the evidence that is favorable to their desired outcome without addressing the evidence favorable to Forest."

Forest earns more than $2 billion annually on U.S. sales of Lexapro.  If today’s decision sticks, Teva won’t be able to sell a generic version until 2013, when Forest’s pediatric exclusivity on the drug expires.

RELATED READING:

• Reuters story
• Patent Docs post
• Patently-O: part 1; part 2
• July 16, 2006 OBB post on the district court decision

As The Wall Street Journal reported last week, the U.S. Patent and Trademark Office has issued an initial rejection of Pfizer’s application for a reissue patent of U.S. Patent No. 5,273,995–one of two Pfizer patents covering Lipitor.

In a decision last August, the Court of Appeals for the Federal Circuit upheld one Pfizer patent on Lipitor (U.S. Patent No. 4,681,893) and invalidated another (the ‘995 patent).  Specifically, the court invalidated claim 6 of the ‘995 patent, covering the hemicalcium salt of atorvastatin acid (the active ingredient in Lipitor), because it failed to specify a further limitation to the claim from which it depended.  Pfizer sells about $12 billion worth of Lipitor annually.  The ‘995 patent (if valid) was set to expire more than a year later than the ‘893 patent will expire, so naturally Pfizer filed a reissue patent application to try to correct the ‘995 patent.

In a preliminary amendment filed as part of its reissue application in January, Pfizer amended claim 6 of the ‘995 patent to be an independent claim, and indicated that "this was one of the options . . . approved by the Federal Circuit in its decision."

Ranbaxy–the first ANDA filer for generic Lipitor and the defendant in the patent litigation decided by the Federal Circuit–filed a protest against Pfizer’s reissue application in May.  Among Ranbaxy’s arguments was that the defect in claim 6 is not correctable through a reissue patent.

The Patent Office mailed a first Office Action on Pfizer’s reissue application last Thursday.  While the Patent Office stated that the defect in claim 6 is in fact correctable through a reissue application, the Office rejected all 14 claims of Pfizer’s reissue application on grounds of anticipation, obviousness, or obviousness-type double patenting.  In particular, the Office rejected claim 6 for obviousness-type double patenting in view of U.S. Patent Nos. 6,605,729 and 5,969,156.

The proceedings over Pfizer’s reissue patent application are far from over.  Pfizer will certainly file a response to last week’s Office Action, after which the Patent Office might issue a final Office Action.  If Pfizer is unsatisfied at that point, it might request continued examination or file an appeal to the Patent Office Board of Appeals.  If rebuffed there, Pfizer could appeal to the Federal Circuit.  Given how much money is at stake, Pfizer is likely to pursue all its options before giving up on the reissue application.

RELATED READING:

• Bloomberg News
• CNNMoney.com
• India Business Standard
• Pharmalot
• Reuters
• Earlier OBB posts on Lipitor litigation: 29 Jan 07; 23 Oct 06; 31 Aug 06