Orange Book Blog

OBB News Briefs

• Earlier this week, FDA Law Blog provided an update on Teva's suit against the FDA, seeking relisting of Janssen's patent on Risperdal (risperidone) and confirmation of Teva's 180-day exclusivity on a generic version of the drug.
• Last week, FDA Law Blog reported on a recent FDA determination that Watson Labs forfeited its 180-day exclusivity on generic Camptosar (irinotecan HCl) because it failed to obtain tentative approval of its ANDA within 30 months of filing, as required by the MMA.
• Pharmalot and the WSJ Health Blog recently ran posts on a series of articles in the Los Angeles Times examining whether generic drugs are as good as brand-name drugs.
• Eighteen states recently sued Abbott Labs for antitrust violations, alleging that Abbott made trivial changes to the formulation of its TriCor cholesterol drug, thereby delaying generic competition.  Statements were released by the Attorneys General from Florida and Iowa.
• William Kovacic was appointed the new Chairman of the Federal Trade Commission this week, succeeding Deborah Platt Majoris.  The Wall St. Journal reported that Mr. Kovacic has been a strong proponent of FTC action against "reverse payment" settlements.

OBB News Briefs

• Last Friday, Rep. Anna G. Eshoo (D-CA) announced that she and Rep. Joe Barton (R-TX) introduced H.R. 5629, the "Pathway for Biosimilars Act" (click here for summary; click here for text of bill).  BIO immediately applauded the bill, while GPhA immediately denounced it.  For more, visit FDA Law Blog; Pharmalot; or the WSJ Health Blog.
• Barr Labs and Teva are two of the world's largest, and most litigious, generic drug companies.  Their CEO's gave extensive interviews to separate newspapers last week: Barr's CEO Bruce Downey to Investor's Business Daily and Teva's CEO Shlomo Yanai to Globes.
• We reported in January that Teva filed a citizen petition asking FDA to relist J&J's patent on Risperdal and to grant it 180-day exclusivity on the generic.  Recently, FDA law blog and Patent Baristas reported that FDA denied Teva's petition on February 26, and Teva responded by filing suit against FDA on March 4.  Also see: Reuters and Teva press release.
• The Wall St. Journal reported last week that Thailand is poised to disregard patents on several cancer drugs.  The WSJ Health Blog has a summary of the article.
• Teva announced last month that it received approval for the first biosimilar G-CSF in Europe.

Teva Seeks Relisting of J&J's Risperdal Patent and Asserts Right to 180-Day Exclusivity

A reader recently e-mailed me about an interesting citizen petition that Teva filed last August.  In the petition, Teva requests that FDA:  (1) relist U.S. Patent No. 5,158,952 in the Orange Book for Risperdal (risperidone) tablets; (2) confirm Teva's right to 180-day exclusivity for risperidone tablets; and (3) refrain from approving any other ANDAs for risperidone tablets until Teva's exclusivity expires.  Risperdal is Johnson & Johnson's blockbuster treatment for schizophrenia and other neurological disorders.

Teva filed its ANDA for risperidone tablets on August 28, 2001, with a paragraph III certification to U.S. Patent No. 4,804,663 and a paragraph IV certification to the '952 patent.  At the time, both patents were listed in the Orange Book for Risperdal.  On October 12, 2001, FDA notified Teva that it had delisted the '952 patent from the Orange Book and informed Teva that it would not accept Teva's ANDA for filing unless Teva amended its paragraph IV certification to reflect the fact that the '952 patent had been delisted.  Teva complied by amending its ANDA.

Five years later, in Ranbaxy v. Leavitt, the D.C. Circuit ruled that FDA had improperly delisted two patents on Zocor because the effect of delisting would be to deny the first ANDA filer of 180-day exclusivity on simvastatin tablets.  According to Teva's citizen petition, following that decision "Teva began reviewing its portfolio of pending ANDAs to determine whether FDA's unlawful delisting practices had deprived Teva of its entitlement to 180-day exclusivity for any other generic product."

In its risperidone petition, Teva contends that because the '952 patent was listed in the Orange Book when it filed its ANDA for risperidone tablets, it had no choice but to certify as to the '952 patent.  "Teva thus did precisely what it was obligated to do under the plain text of the governing statute and Agency regulations, and it therefore earned its exclusivity as the first applicant to file a paragraph IV certification to a patent listed as claiming the reference listed drug."  Teva argues that the Ranbaxy decision compels FDA to relist the '952 patent and restore Teva's right to 180-day exclusivity.  Teva further argues that "the fact that FDA never accepted Teva's paragraph IV ANDA for filing has no bearing on the fact that FDA must relist the '952 patent."

The '663 patent (whose validity was affirmed in a Federal Circuit decision last year) expired on December 29, 2007.  Pediatric exclusivity on Risperdal extends to June 29, 2008.  Thus, FDA must decide the issues presented in Teva's citizen petition before then.  FDA will post its decision in the docket established for Teva's petition.

Dismissal of Invalidity Counterclaims Thwarts Apotex's Attempt to Trigger 180-Day Exclusivity on Cosopt

Merck v. Apotex, No. 06-5789 (D.N.J. 2007)

Merck has sold Cosopt (dorzolamide hydrochloride/timolol maleate), an opthalmic drug indicated for the treatment of ocular hypertension and open-angle glaucoma, since 1998.  In October 2005, Hi-Tech Pharmacal filed the first ANDA for a generic version of Cosopt with paragraph IV certifications to the Orange Book-listed patents: U.S. Patent Nos. 4,797,413; 6,248,735; and 6,316,443.

In January 2006, Merck sued Hi-Tech, asserting infringement of the '413 patent but not the '735 or '443 patents.  On April 18, 2006, Merck filed a statutory disclaimer of the '735 and '443 patents with the USPTO, effectively dedicating its rights under the patents to the public.  Shortly thereafter, on April 25, Merck wrote to the FDA and requested that the agency delist those two patents from the Orange Book.  The FDA, however, did not delist the patents--indeed the patents remain listed today.

In October 2006, Apotex sent Merck a letter notifying it that Apotex had filed an ANDA for a generic version of Cosopt with paragraph IV certifications to all three Orange Book-listed patents.  In response, Merck sued Apotex in December 2006, again asserting infringement of the '413 patent but not the '735 or '443 patents.  Apotex agreed to be bound by the court decision on the '413 patent in the Hi-Tech case, but pursued declaratory judgment counterclaims of invalidity of the disclaimed patents.  On March 29, 2007, the Federal Circuit affirmed the patent term of the '413 patent, leaving only Apotex's counterclaims on the disclaimed '735 and '443 patents in the case.  The '413 patent will expire in April 2008, with pediatric exclusivity extending to October 2008.

Shortly after the Federal Circuit decision on the '413 patent, Merck moved under Fed. R. Civ. P. 12(b)(1) to dismiss Apotex's counterclaims of invalidity of the '735 and '443 patents for lack of subject matter jurisdiction.  In an opinion released earlier this month, the district court granted Merck's motion to dismiss, concluding: "because Merck has formally disclaimed the '735 and '443 patents, and can no longer enforce any claims as to these patents, there is no justiciable case or controversy to support jurisdiction in an action for a declaratory judgment here."  Apotex has appealed the decision to the Federal Circuit.

BRIEFS:

• Merck brief in support of motion to dismiss
• Apotex brief in opposition to motion
• Merck reply brief

ADDENDUM:
In a separate case, relating to Precose (acarbose), Cobalt Pharmaceuticals recently filed a complaint seeking a declaratory judgment of invalidity or noninfringement with respect to another statutorily-disclaimed patent, U.S. Patent No. 4,904,769.  In that case, Cobalt is the first ANDA filer, and the '769 patent is the only Orange Book-listed patent for Precose.  For more information, see this FDA Law Blog post.

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.