Orange Book Blog

Pharma News Briefs

• The Supreme Court this morning denied Pfizer's cert petition in the Norvasc case (AP story).  Although the Federal Circuit's March 22 decision is controversial, the denial of Pfizer's cert petition is not surprising, given that the Court had previously denied Pfizer's motions for an emergency stay and for an expedited appeal.
• Late last Friday the Court of Appeals for the Federal Circuit denied Novartis's emergency motion to enjoin Teva from selling generic Famvir (Teva press release; Globes article).  Three weeks ago, the Federal Circuit temporarily enjoined Teva, apparently costing Teva three weeks of its 180-day exclusivity.
• President Bush signed the FDA Amendments Act of 2007 into law last Thursday (AP story).  FDA put out this press release.  PhRMA released this statement.
• Also Thursday, the Federal Circuit denied Alphapharm's petition for rehearing en banc of Takeda v. Alphapharm, in which the court previously upheld Takeda's patent on Actos.  No opinion was issued.
• The Federal Trade Commission announced in a press release Thursday that it is challenging Mylan's proposed acquisition of E. Merck oHG, which is Merck KgAA's generic subsidiary.  See also this Reuters article.
• FDA Law Blog had a very interesting post last Wednesday on FDA's recent letter requesting comment on certain 180-day exclusivity forfeiture and Orange Book patent delisting issues.

Pharma News Briefs

• The Federal Circuit reissued its July 11 opinion in Daiichi Sankyo v. Apotex as a precedential opinion, one day after denying Daiichi's petition for rehearing.  According to Hal Wegner, a major reason for making the decision precedential was Prof. Joseph Scott Miller's Rule 47.6(c) filing.
• Biosimilars legislation is "off the table" for now.  The FDA bill is moving forward without it.  (Bloomberg; Pharmalot).
• Novartis is set to launch its biosimilar Epoetin in Europe.  (msnbc.com).
• Cubist Pharmaceuticals has asked the FDA to delist a patent on its lead product, Cubicin, from the Orange Book.  (The Street.com).
• FDA issued final guidance on commercially distributed Analyte Specific Reagents, such as antibodies and nucleic acids.  (FDA Law Blog).
• Dr. Reddy's and Teva settled their patent dispute over generic Zoloft.  Teva had alleged that Dr. Reddy's infringed its sertraline HCl polymorph patents.  (TMCnet.com).
• Imclone and Repligen/MIT settled their patent dispute over Erbitux.  (Patent Prospector).
• Ranbaxy vs. Pfizer worldwide Lipitor patent litigation scorecard: mixed results.  (MarketWatch.com).
• Feroz Ali Khader has written a new book on Indian patent law, particularly as it relates to pharmaceuticals.  (Generic Pharmaceuticals & IP blog).
• Mr. Kapil Sibal, Honorable Minister for Science and Technology in India, will be speaking tomorrow, September 17 at 4 pm at the George Washington University Law School.  (Flyer; Program).

Pharma News Briefs

• The House of Representatives passed an omnibus FDA bill on Wednesday.  The Senate passed its own FDA bill in May.  Differences between the two bills will be hammered out in conference committee, where follow-on biologics provisions may be tacked on.  See coverage at: FDA Law Blog; Pharmalot;  PhRMA press release; WSJ Health Blog.
• Business Standard magazine had this story Monday on reaction by Indian generic drug companies to authorized generics.
• FDA Law Blog had an interesting post last week on a recent request for information on FDA's policy for Orange Book listings of patents that cover drug delivery systems but that do not recite an active ingredient or drug formulation.
• More generic Norvasc approvals: Lupin; Ranbaxy; Roxane.

Pharma News Briefs

• Last week, the U.S. District Court for the District of Columbia denied Mylan's emergency motion for a temporary restraining order that would have forced FDA to relist Pfizer's Norvasc patent in the Orange Book.  Until June 22, when FDA delisted Pfizer's patent, Mylan and Apotex had the only approved ANDAs for generic Norvasc.
• Bloomberg reported Thursday that Pfizer and Sandoz have settled their litigation over Sandoz's ANDA for generic Zithromax.  The district court entered an order dismissing the case on June 25.
• Also Thursday, The Wall St. Journal Health Blog reported that the government of Brazil and Abbott Labs stepped back from the brink and agreed on a price for Kaletra, Abbott's AIDS drug.
• The National Law Journal had this article Friday on alleged abuse of the citizen petition process by pharmaceutical companies.
• FDA released a new final guidance document entitled "ANDAs: Pharmaceutical Solid Polymorphism -- Chemistry, Manufacturing, and Controls Information."  The guidance provides recommendations on assessing sameness when a drug substance exists in polymorphic forms.

D.C. Circuit Agrees That FDA Improperly Delisted Merck's Zocor Patents From Orange Book, Unlawfully Denying Teva and Ranbaxy of Simvastatin Exclusivity

The Court of Appeals for the D.C. Circuit today affirmed a district court decision finding that the FDA wrongly delisted two Merck patents on Zocor (simvastatin), which in turn unlawfully denied Teva and Ranbaxy from 180 days of marketing exclusivity on generic simvastatin.  FDA appealed the district court decision but did not request a stay.  FDA then granted final approval of Teva and Ranbaxy's ANDAs in June, after which the two companies launched their generic simvastatin products.

In today's D.C. Circuit opinion, written by Judge Ginsburg for a unanimous panel, the court upheld the district court's finding that FDA's interpretation of the statue was contrary to the clear intent of Congress.  FDA's policy was to allow delisting when a generic drug maker had filed an ANDA containing a paragraph IV certification and the NDA holder had not filed a lawsuit to contest the certification, as occured in the Zocor case.

The appeals court framed the question at issue as "whether the FDA may delist a patent upon the request of the NDA holder after a generic manufaturer has filed an ANDA containing a paragraph IV certification so that the effect of delisting is to deprive the applicant of a period of marketing exclusivity."  In striking down FDA's policy, the court reasoned:

Not only does the statute not require litigation to preserve a generic applicant's eligibility for exclusivity . . . such a requirement is inconsistent with the structure of the statute because, if the patent is delisted before a pending ANDA is approved, then the generic manufacturer may not initiate a period of marketing exclusivity.

By thus reducing the certainty of receiving a period of marketing exclusivity, the FDA's delisting policy diminishes the incentive for a manufacturer of generic drugs to challenge a patent listed in the Orange Book in the hope of bringing to market a generic competitor for an approved drug without waiting for the patent to expire.  The FDA may not, however, change the incentive structure adopted by the Congress.

This case appears to require FDA to set a new policy, whereby it should refuse to delist a patent if a generic manufacturer has filed an ANDA containing a paragraph IV certification with respect to the patent.

RELATED READING:

• November 14, 2006 Reuters article
• May 17, 2006 post, including link to district court decision

KV Pharma Files Citizen Petition Requesting Relisting of Astra Zeneca's Toprol XL Patent

KV Pharmaceutical Company recently filed a citizen petition asking the FDA to relist U.S. Patent No. 5,246,714 for 100 mg and 200 mg Toprol XL in the Orange Book.  In the same petition, KV asked the FDA to refrain from approving any ANDA for 100 mg and 200 mg Toprol XL filed after KV's ANDA No. 76-640 and to confirm that KV's right to 180 days of exclusivity based on its ANDA has not been affected by FDA's delisting of the '714 patent.  Toprol XL is Astra Zeneca's extended release formulation of metoprolol succinate, a beta blocker approved for treating hypertension, angina, and heart failure.  Sales of Toprol XL reached $1.3 billion last year.

According to KV's petition, its ANDA included paragraph IV certifications for each of the five patents listed in the Orange Book for Toprol XL:  the '714 patent and U.S. Patent Nos. 4,927,640; 4,957,745; 5,001,161; and 5,081,154.  While Astra brought suit in the Eastern District of Missouri based on KV's certifications with respect to the '154, '161, and '745 patents, it did not bring suit based on the '714 and '640 patent certifications.  KV subsequently filed declaratory judgment counterclaims of non-infringement with respect to the '640 and '714 patents, which apparently have been dismissed in view of Astra's covenant not to sue on the patents.

KV argues in its citizen petition that FDA's delisting of the '714 patent was in error because delisting occurred after (1) KV filed its paragraph IV certification, and (2) the '714 patent had been subject to a lawsuit.  Based on its belief that it was the first ANDA applicant to file a paragraph IV certification on the '714 patent, KV further argues that it is entitled to 180 days of marketing exclusivity for generic Toprol XL.  KV's petition relies extensively on the recent Ranbaxy v. Leavitt case from the U.S. District Court for the District of Columbia, in which Ivax and Ranbaxy successfully appealed FDA's delisting of Merck's Zocor patents.

Previously, Astra sued KV, Andrx Pharmaceuticals, and Eon Laboratories based on ANDA filings for Toprol XL generics.  The suits were consolidated, and in a ruling last January from the U.S. District Court for the Eastern District of Missouri, both patents were held invalid for double patenting and anticipation, and Astra was found to have engaged in inequitable conduct during prosecution of the patents.  Astra has appealed the decision to the Federal Circuit.

RELATED READING:

May 17, 2006 Orange Book Blog post on Ranbaxy v. Leavitt

NOTE:  thanks to Kurt Karst for sending us a copy of the citizen petition.

Astra Zeneca Lists Device Patents In Orange Book

AstraZeneca recently filed a Request for Advisory Opinion with the FDA, asking for a determination "whether patents on drug delivery systems, such as inhalation devices, that do not recite the approved active ingredient or formation," should be listed in the Orange Book.  GlaxoSmithKline submitted a request to the FDA in January, 2005, asking the very same question, which AstraZeneca attached to its filing.

Interestingly, AstraZeneca reveals toward the end of its request, "Because AstraZeneca believes that such patents should be listed, AstraZeneca will continue to list them unless it receives guidance from  FDA that such listings are improper."  Of course, Orange Book listing is a predicate to a 30-month stay of FDA approval of any generic equivalents, as well as to 6-month marketing exclusivity after any successful generic patent challenge.

NOTE:  Thanks very much to Kurt Karst for bringing this FDA filing to my attention.

FDA Updates Status of Its Response to Zocor Citizen Petitions

The FDA recently published a letter to attorneys representing generic drug companies who filed citizen petitions relating to their ANDAs for generic Zocor.

The three-page letter essentially ties up some loose ends that remained after the District of Columbia's April 30, 2006 decision holding that it was unlawful for the FDA to deny IVAX and Ranbaxy's citizen petitions to relist in the Orange Book two Merck patents covering Zocor.  While the FDA has appealed that decision to the Court of Appeals for the District of Columbia, and the appeal has been granted expedited review, in the meantime the FDA relisted the two Merck patents and granted 180 day market exclusivity to the first ANDA filers, IVAX and Ranbaxy.

IVAX, a division of Teva, and Ranbaxy launched their generic Zocor products last month when Merck's last patent on Zocor expired and they were granted final approval by the FDA.

Sandoz's Motion for Preliminary Injunction to Delay FDA Approval of Generic Zocor is Denied

The District Court for the District of Columbia today denied Sandoz's motion for a preliminary injunction, filed June 22, 2006, to delay final FDA approval of Teva and Ranbaxy's generic versions of Zocor.  Previously, the same court denied Sandoz's request for a temporary restraining order.  The FDA granted final approval to Teva and Ranbaxy on June 23, 2006, and the companies launched their products shortly thereafter.

In today's opinion, the district court wrote that Sandoz's motion failed on each of the four factors:  likelihood of success on the merits, irreparable harm, balance of interests, and the public interest.

Earlier this year, the FDA appealed a separate decision by the same district court that required the FDA to grant final approval to Teva and Ranbaxy upon expiration of Merck's final orange book listed patent on Zocor.

NOTE:  thanks to Kurt Karst for sending us a copy of today's opinion.

FDA Grants Final Approval to Ivax and Ranbaxy for Generic Zocor

The FDA today granted final approval to Ivax and Ranbaxy to market generic versions of Zocor (simvastatin).  Additionally, it appears the FDA has granted generic marketing exclusivity to Ivax and Ranbaxy for the next 180 days.

The FDA approval comes despite a last-ditch effort by Novartis subsidiary Sandoz to prevent the FDA from granting final approval and marketing exclusivity to Ivax and Ranbaxy.  Earlier today, the U.S. District Court for the District of Columbia refused to grant Sandoz's request for a temporary restraining order against the FDA.

In a press release announcing the approval, the FDA stated, "This approval is another example of our agency's efforts to increase access to safe and effective generic alternatives as soon as the law permits."  The FDA has appealed a district court ruling that required the FDA to grant final approval to Ivax and Ranbaxy today, the day Merck's final patent on Zocor expired.  That appeal is still pending before the D.C. Circuit.

RELATED READING:

• 23 June 06 MarketWatch.com story
• 23 June 06 Reuters article

UPDATES:

• 24 June 06 Bloomberg story:  Insurance Companies Push Generic Zocor
• Dr. Reddy's launches authorized generic Zocor