Orange Book Blog

At the intersection of Patent and FDA Law

Recent Posts

  • C5 “Biotech Patenting” Conference, London, September 23-24

    C5 will be bringing its popular “Biotech Patenting” conference to London on September 23-24.

    According to C5, the conference “provides updates on the latest developments in biotech patenting, including recent case law and regulatory developments.”  The conference is unique in offering an international perspective on biotechnology patent law:  experts from Europe, Asia and the United States will be speaking.  One of the highlights will be a keynote address by Judge Randall Rader of the U.S. Court of Appeals for the Federal Circuit.

    The agenda includes numerous talks and panel discussions that should be of interest to Orange Book Blog readers, such as:

    • “Critical Update on Legislative and Policy Developments at the UK-IPO and EPO,” presented by officials from the UK-IPO and the EPO
    • “Review of Recent EPO and EU National Court Biotech Decisions”
    • “Impact of the EPC 2000 on Medical Use Claims”
    • “Analysis of the Latest Decisions of the U.S. Courts and Their Implications”
    • “Obviousness Determinations After KSR v. Teleflex”
    • “How to Successfully Obtain and Enforce Your Biotech Patents in China and India”
    • “Comparison of the U.S. and European Legal Issues Surrounding Biosimilars:  Legislation, Case Law and Approvals to Date”
    • “Managing Your Biotech Patent Litigation: In-House and Outside Counsel Perspectives”

    In addition, two pre-conference workshops are offered on September 22:  “How to Conduct Effective IP Due Diligence” and “Successfully Evaluating Freedom to Operate.”

    Orange Book Blog readers can receive a 10% discount off the registration fee with the following code:  789L09.OBB.

    For more information or to register, please visit the conference website.

  • Federal Circuit Vacates Dismissal of Delaratory Judgment Counterclaims in Fosamax Case as Moot

    Merck & Co. v. Apotex, No. 2007-1362 (Fed. Cir. 2008)

    Fosamax (alendronate sodium) is one of the all-time best-selling drugs for the treatment and prevention of osteoporosis, with over $3 billion in U.S. sales last year.  Merck listed ten patents in the Orange Book for Fosamax:  U.S. Patent No. 4,621,077, which claims a method of inhibiting bone resorption by administering alendronate sodium; U.S. Patent No. 5,994,329, which claims other methods of use; and eight other patents on formulations and methods.

    In 1999, Teva filed an ANDA for a generic version of Fosamax, with paragraph IV certifications to all ten Orange Book-listed patents.  Teva was the first ANDA filer, earning 180-day exclusivity.  According to Teva’s approval letter, a district court upheld the validity of the ‘077 and ‘329 patents and dismissed the cases with respect to the other patents-in-suit.  The Federal Circuit affirmed the validity of the ‘077, but, in a January 2005 opinion, held two claims of the ‘329 patent to be invalid for obviousness.

    Apotex filed an ANDA for generic Fosamax sometime later, with a paragraph III certification to the ‘077 patent and paragraph IV certifications to the other nine Orange Book-listed patents.  Merck sued Apotex for infringement and Apotex counterclaimed for invalidity and noninfringement.  Following discovery, Merck granted Apotex a covenant not to sue and moved to dismiss the case.

    Apotex opposed the motion, arguing that as long as it was blocked by Teva’s 180-day exclusivity, there was an Article III case or controversy and thus it should be allowed to pursue its counterclaims.  Apparently, Apotex aimed to trigger Teva’s exclusivity by obtaining an early “court decision.”  Apotex further argued that dismissal might not lift the automatic 30-month stay of FDA approval of Apotex’s ANDA.  However, the district court granted Merck’s motion to dismiss (click here for opinion), based largely on the covenant not to sue.  Apotex appealed to the Federal Circuit.

    The Federal Circuit issued its opinion this morning.  The court began its analysis by noting that “depending on the circumstances, a justiciable Article III controversy may continue to exist between a patentee drug company and a Paragraph IV ANDA filer in the context of the Hatch-Waxman Act even after the patentee drug company has granted the Paragraph IV ANDA filer a covenant not to sue,” citing its decision in Caraco v. Forest earlier this year.  The court continued:

    This case, however, has been rendered moot by two factual developments that were brought to this court’s attention after oral argument.  First, the FDA decided to treat the thirty-month stay on Apotex’s ANDA as dissolved once the district court dismissed this case.  Second, the first Paragraph IV filer (i.e., Teva) triggered its 180-day exclusivity period . . . by marketing its generic drug on or about February 6, 2008.  As a result, Apotex no longer suffers a delay in entering the market under either the thirty-month stay provision or the 180-day exclusivity provision that is traceable to Merck and redressible by a court judgment.  Indeed, Apotex’s only remaining delay in entering the market is the balance of Teva’s 180-day exclusivity period, which expires on or about August 5, 2008.

    Thus, the Federal Circuit vacated the district court’s dismissal of Apotex’s counterclaims as moot.

  • AstraZeneca Wins Seroquel Case on Summary Judgment; Teva and Sandoz to Appeal

    AstraZeneca v. Teva Pharms. USA and Sandoz, No. 05-5333 (D.N.J. 2008)

    On July 1st, the U.S. District Court for the District of New Jersey granted AstraZeneca’s motion for summary judgment that its patent on quetiapine fumarate, the active ingredient in Seroquel, is not unenforceable for inequitable conduct.  The decision disposed of the last remaining issue in the case, as Teva and Sandoz, which are challenging the patent, had already conceded infringement and validity.

    The district court’s opinion explains that Seroquel, which is indicated for the treatment of schizophrenia and bipolar disorder, is in a class of drugs known as “atypical antipsychotics.”  According to the opinion, early (“typical”) antipsychotic medications were plagued by undesirable side effects, including acute dyskinesias (uncontrollable muscle movements).  In 1985, Astra scientists discovered quetiapine, which showed reduced potential to cause dyskinesias, and in 1989 Astra was issued U.S. Patent No. 4,879,288 on the compound.

    Teva and Sandoz offered four arguments for the unenforceability of the ‘288 patent:

    • Astra misrepresented and/or omitted material information concerning certain prior art compounds in its prosecution of the ‘288 patent;
    • In response to a request by the patent examiner, Astra falsely asserted that generating data regarding a particular prior art compound would have been “very expensive”;
    • Astra deceived the PTO by representing that a record reference taught that a particular compound was a typical antipsychotic; and
    • Astra failed to disclose to the PTO the death of a cebus monkey during testing of quetiapine.

    The district court rejected each of these arguments, concluding that the information allegedly withheld or misrepresented by Astra during prosecution of the ‘288 patent was not sufficiently material to support a finding of inequitable conduct.

    In addition, the court rejected as a “facile argument” the defendants’ suggestion that a trial is necessary “in order for the parties to present expert testimony and to allow the court to make credibility determinations with respect to fact witnesses.”  According to the court, “there are no credibility determinations to be made here; the prosecution record speaks for itself.  Moreover, experts engaging in hindsight cannot change the facts and circumstances of the patent application process that occurred two decades ago.”

    Seroquel is Astra’s best-selling drug, with global sales of $4 billion last year (accounting for 10% of Astra’s revenues) and annual U.S. sales of $3.5 billion.  Teva and Sandoz have announced their intention to appeal the district court’s decision to the Federal Circuit.  The ‘288 patent is currently set to expire in 2011, though pediatric exclusivity could extend Astra’s protection until 2012.

    RELATED READING:

  • Federal Circuit Affirms Acular LS Decision in Favor of Roche and Allergan, and Against Apotex

    Roche Palo Alto and Allergan v. Apotex, No. 2008-1021 (Fed. Cir. 2008)

    In an opinion released today , the Federal Circuit affirmed a district court decision granting summary judgment that Roche’s U.S. Patent No. 5,110,493 is valid and infringed by Apotex’s ANDA for a generic version of Acular LS (ketorolac tromethamine opthalmic solution).  Acular LS, marketed by Allergan, is indicated to reduce pain, burning and stinging following corneal refractive surgery.

    The ‘493 patent is directed to a formulation comprising a non-steroidal anti-inflammatory drug, such as ketorolac tromethamine (“KT”); a quaternary ammonium preservative, such as benzalkonium chloride (“BC”); and the nonionic surfactant, octoxynol 40 (“O40”).  Apotex did not dispute that its formulation falls within the literal scope of claim 1 of the ‘493 patent.  Instead, Apotex argued that the district court erred in failing to find noninfringement under the reverse doctrine of equivalents.

    The Federal Circuit explained that the reverse doctrine of equivalents (“RDOE”) “is an equitable doctrine designed to prevent unwarranted extension of the claims beyond a fair scope of the patentee’s invention.”  The court applied the Supreme Court’s RDOE test, set forth in the Graver Tank case:

    Where a device is so far changed in principle from a patented article that it performs the same or a similar function in a substantially different way, but nevertheless falls within the literal words of the claim, the reverse doctrine of equivalents may be used to restrict the claim and defeat the patentee’s action for infringement.

    Apotex argued that the “principle” of the ‘493 patent is “the use of O40 in an amount sufficient to cause the formation of micelles and thereby provide robust stability to the formulation by preventing interactions between KT and BAC.”  The Federal Circuit, however, found no support for this principle in the specification, prosecution history or the prior art (where such support must be found).  Rather, according to the Federal Circuit, Apotex relied exclusively on the declaration of its expert.  Thus, the court agreed that Apotex failed to make out a prima facie case of noninfringement under the reverse doctrine of equivalents, and therefore summary judgment of infringement was proper.

    Next, the Federal Circuit agreed with the district court that Apotex’s invalidity arguments were barred by claim preclusion (i.e., res judicata).  Claim preclusion applies where (1) the same parties were involved in the prior litigation; (2) the prior litigation involved the same claim or cause of action as the later suit; and (3) the prior litigation was terminated by a final judgment on the merits.  Here, Apotex conceded that a prior case (involving Apotex’s ANDA for a generic version of Acular–not Acular LS) ended in a final judgment that the ‘493 patent is valid and involved the same parties, but disputed that it involved the same claim or cause of action.

    According to the Federal Circuit, an infringement claim in a second suit is the “same claim” as in an earlier infringement suit if the accused products in the two suits are “essentially the same.”  Apotex argued that its formulation for Acular (in the prior case) was not “essentially the same” as its formulation for Acular LS (in this case) because the two formulations are stabilized by completely different ingredients and mechanisms.  The Federal Circuit rejected this argument, however, stating that the point “is irrelevant because both formulations are encompassed by the claims of the ‘493 patent.  Thus, any difference in composition between the two formulations is merely colorable and the two formulations are ‘essentially the same.’”

    Apotex argued in the alternative that “principles of fairness should prevent application of claim preclusion given the change in the law of obviousness following the Supreme Court’s opinion in KSR.”  Again, however, the Federal Circuit disagreed, concluding that the district court “correctly recognized that there is no ‘change of law’ or fairness exception to prevent application of claim preclusion.”  Accordingly, the Federal Circuit found no error in the district court’s grant of summary judgment of validity.

    RELATED READING:

  • Book Review: Generic Pharmaceutical Patent and FDA Law

    Shashank Upadhye has written a new text, Generic Pharmaceutical Patent and FDA Law, that anyone reading Orange Book Blog will certainly find useful.  Mr. Upadhye is Vice President & Global Head of Intellectual Property for Apotex.

    The book provides a nice overview of patent law–especially as applied to pharmaceuticals–and the drug approval process.  In addition, it includes detailed chapters on issues that arise from the Hatch-Waxman Act, including Orange Book patent certifications and notice letters, the 30-month stay, 180-day exclusivity and forfeiture, and declaratory judgment.  A complete list of the book’s chapters appears below.

    Generic Pharmaceutical Patent and FDA Law is incredibly current, citing not only cases that were decided this year, but also FDA decisions made this year and even numerous pending cases.  The book also excels by offering countless practice tips.  It is not simply a legal treatise.  Moreover, despite its focus on generic drugs, those who work with brand-name drug companies will also find the book helpful because it describes the issues facing generic drug companies.

    Generic Pharmaceutical Patent and FDA Law is published by Thomson/West and is available to purchase from their website.  To receive a 10% discount on the book, use promo code 571793 or click here.

    Chapter Listing:

    1. Basics of Patent Law
    2. Patent Infringement Rules and Procedures
    3. Foundations of Patent Invalidity
    4. Inequitable Conduct and Unenforceability
    5. Equitable Defenses to Patent Infringement
    6. Basics of Brand Drug Approval Process and Orange Book Listings
    7. Abbreviated New Drug Application (ANDA) Approval Process
    8. “Paper NDA” and 505(b)(2) Applications
    9. Patent Infringement Safe Harbor Exemptions
    10. Mechanics of Orange Book Patent Certifications and Notice Letters
    11. The 30-Month Injunction/Stay
    12. Brand Side Exclusivities
    13. The 180-Day Exclusivity
    14. Forfeiture of the 180-Day Exclusivity
    15. Declaratory Judgment
    16. Patent Infringement Damages and Remedies

  • OBB News Briefs

    • On June 25, the Congressional Budget Office released a cost estimate for the Biologics Price Competition and Innovation Act of 2007 (S. 1695), concluding that the biosimilars bill would save American consumers $25 billion on prescription drug costs over the next ten years.  For more: statements from BIO and PhRMA; FDA Legislative Watch; Pharmalot; The Hill’s Congress Blog.
    • Bayer and Barr announced on June 24 that they signed a deal licensing Barr to market authorized generic versions of Bayer’s Yasmin and Yaz oral contraceptives.  Under the agreement, Bayer will continue to appeal the March 3rd district court decision on Yasmin and will receive higher royalties from Barr if it succeeds.  More: Reuters.
    • On June 23, FDA Law Blog reported that Rep. William Delahunt (D-MA) introduced a bill specifically meant to allow The Medicines Company, a Massachusetts company, to obtain a patent term extension for its patent covering Angiomax (bivalirudin)–for $65 million.
    • FDA Law Blog reported on June 19 that the House Commerce Committee posted the responses to its April 3rd letter soliciting feedback on how to establish a pathway for FDA approval of biosimilar products.
    • On June 18, Pfizer and Ranbaxy announced a comprehensive settlement of patent litigation over generic Lipitor.  Under the agreement, Ranbaxy will have a license to sell generic versions of Lipitor (atorvastatin) and Caduet (atorvastatin/amlodipine) effective Nov. 30, 2011.  For more: NYT; Pharmalot; Reuters; WSJ; WSJ Health Blog.
    • On June 17, the Federal Circuit affirmed the district court findings of inequitable conduct and exceptional case in Synthon IP v. Pfizer, in which Synthon unsuccessfully alleged that Pfizer infringed its patent on a process for making amlodipine, the active ingredient in Norvasc.
    • The AP reported on June 5th that Abbott and Mylan settled their patent litigation over Mylan’s generic version of Depakote ER, with the parties agreeing that Mylan may launch its generic no later than Jan. 1, 2009.
    • The Lewis & Clark Law Review recently published a special issue devoted entirely to the patent law doctrine of obviousness.  One of the articles is of particular interest:  Pharma’s Nonobvious Problem, by Prof. Rebecca S. Eisenberg.

  • In a “Surprising” Victory, Barr and Mylan Invalidate Boehringer Ingelheim’s Patent on Mirapex

    Boehringer Ingelheim v. Barr and Mylan, No. 05-700-JJF (D. Del. 2008)

    Last week, following a bench trial held in March, the U.S. District Court for the District of Delaware held that Boehringer Ingelheim’s patent on Mirapex (pramipexole dihydrochloride) is invalid for obviousness-type double patenting.  Mirapex, indicated for the treatment of Parkinson’s disease and Restless Leg Syndrome, has annual U.S. sales of approximately $380 million.

    Barr Labs filed its ANDA for a generic version of Mirapex in 2005 with paragraph IV certifications to Boehringer’s U.S. Patent Nos. 4,843,086 and 4,886,812.  Mylan filed its ANDA, with paragraph IV certifications to the same patents, shortly thereafter.  Barr’s approval letter confirms that Barr was the first to file, and therefore is entitled to 180-day exclusivity.

    Boehringer responded by filing suit against Barr and Mylan, and the cases were consolidated for trial.  The ‘086 patent expired while the litigation was pending, leaving only the ‘812 patent in suit.

    The district court’s opinion explains that the “basic premise of double patenting is that the same invention cannot be patented twice.”  Here, the ‘086 patent claimed methods of treating certain diseases by administering tetrahydrobenzthiazoles, while the ‘812 patent claims the tetrahydrobenzthiazole compounds themselves, including the active ingredient in Mirapex, pramipexole dihydrochloride.  The court concluded that “although there are differences between the ‘812 patent and the ‘086 patent, . . . those differences are insufficient to support the patentability of the ‘812 patent in light of the ‘086 patent.”

    Of course, obviousness-type double patenting can be avoided by a terminal disclaimer.  Interestingly, Boehringer filed a terminal disclaimer of the ‘812 patent on the second day of trial of the case, on March 12, 2008.  Boehringer terminally disclaimed:

    only the terminal part of the statutory term of the ‘812 patent which would extend beyond the 1,564 days after the full statutory term of the ‘086 patent as that term is defined in 35 U.S.C. § 154, so that by virtue of this disclaimer, the ‘812 patent will expire on October 8, 2010.

    Boehringer received a 1,564-day extension under 35 USC § 156 due to FDA regulatory review of Boehringer’s New Drug Application for Mirapex.  As a result of this patent term extension, the original expiration date of the ‘812 patent, December 12, 2006, was extended to March 25, 2011.  Thus, by its terminal disclaimer, Boehringer disclaimed five and a half months of patent term–the period of time between the expiration date of the ‘086 patent and the original expiration date of the ‘112 patent.

    Boehringer argued that the terminal disclaimer obviated Barr and Mylan’s double-patenting argument.  However, the court noted that “a dual problem is presented in that the terminal disclaimer was not only filed at or near the conclusion of trial in this action, but it was also filed after the expiration of the earlier ‘086 patent.”  Citing two cases, the court observed that “the Federal Circuit has at least suggested in dicta that for a terminal disclaimer to be effective, the earlier filed patent must not have expired at the time of the filing of the disclaimer.”  Boehringer tried to distinguish these cases “because neither case involved a terminal disclaimer in the context of a Section 156 patent term extension,” but the court was not persuaded.  The district court held that Boehringer’s terminal disclaimer was ineffective to moot the double patenting issue because it was filed after the ‘086 patent had expired.

    According to an investor note from Bernstein Research, the decision was surprising because the district court was not expected to “make a controversial opinion on what is likely to be a precedent-setting ruling by the appellate court on patent extensions and terminal disclaimers.”  In addition, the note indicates that Bernstein expects Barr to “maximize the value of the challenge through settlement.”  According to Bernstein, “the most likely settlement is that Barr would have a date-certain launch of generic Mirapex in 2010 with an agreement protecting it from both an authorized generic and a potential Boehringer win on appeal.”

    The “failure to market” forfeiture provisions, however, will likely complicate any settlement discussions.  Under the MMA, the 180-day exclusivity period may be forfeited if the first applicant does not launch its generic drug product within 75 days after “a court enters a final decision from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the patent is invalid or not infringed.”  If Boehringer and Barr settle the case, for example, with an agreement that Boehringer will not appeal, Barr’s 180-day exclusivity would be forfeited later this summer.  For at least this reason, Boehringer is expect to appeal the district court decision.

    RELATED READING:

  • After Court Victory over FDA, Teva Receives Final Approval of Risperidone ANDA and Launches With 180-Day Exclusivity

    Teva announced yesterday that the FDA granted final approval to its ANDA for generic Risperdal (risperidone) tablets, that it was awarded 180-day exclusivity as the first paragraph IV filer for risperidone, and that it immediately commenced a commercial launch.  FDA confirmed the final approval in a press release.  Risperdal is a schizophrenia drug marketed by Janssen, a unit of Johnson & Johnson, with annual U.S. sales of $2.8 billion.

    FDA’s decision to grant 180-day exclusivity to Teva follows an April 11, 2008, order of the U.S. District Court for the District of Columbia, granting Teva’s request to require FDA to relist Janssen’s U.S. Patent No. 5,158,952 in the Orange Book and enjoin FDA from approving any other risperidone ANDAs until Teva’s 180-day exclusivity period expires.

    Teva was the first ANDA applicant to file a paragraph IV certification on the ‘952 patent, but FDA delisted the patent in 2001, in response to a request from Janssen.  FDA argued to the district court that the ‘952 patent was delisted before Teva filed its ANDA.  Teva argued that the delisting “did not become effective until January 2002, when the official Orange Book reflected the delisting of that patent.”

    FDA has appealed the district court’s decision to the U.S. Court of Appeals for the D.C. Circuit, and oral argument is scheduled for September 12, 2008.  Meanwhile, according to the FDA website, risperidone ANDAs filed by Mylan and Pliva (a subsidiary of Barr Labs) have tentative approval.  Thus, if the D.C. Circuit reverses the district court, Teva’s 180-day exclusivity period would be cut short.

    RELATED READING:

  • Mutual Pharmaceutical Jumps the Gun By Sending Paragraph IV Notice Letter Before Acceptance of ANDA

    GlaxoSmithKline v. Mutual Pharm., No. 08-549 (E.D. Pa. 2008)

    The U.S. District Court for the Eastern District of Pennsylvania recently granted a motion for judgment on the pleadings in a paragraph IV case because the ANDA filer sent its notice letter prematurely, before FDA had accepted the ANDA for filing.  The case concerns Mutual Pharmaceutical’s generic version of GlaxoSmithKline’s heart medication Coreg CR (carvedilol phosphate).

    Mutual submitted its ANDA for carvedilol phosphate 80 mg capsules on November 19, 2007.  On December 21, Mutual filed an amendment to its ANDA, with a paragraph IV certification with respect to Glaxo’s U.S. Patent No. 7,268,156.  At the same time, Mutual sent Glaxo a paragraph IV notice letter, but FDA had not yet accepted Mutual’s ANDA at the time.

    On February 4, 2008 (the 45th day after receiving Mutual’s notice letter), Glaxo filed a complaint for declaratory judgment that, among other things, Mutual’s paragraph IV notice letter was “improper, null, void, and without legal effect.”  Mutual counterclaimed for a declaratory judgment that the ‘156 patent is invalid.  On March 17, following FDA’s acceptance of Mutual’s ANDA for filing, Mutual sent Glaxo a second notice letter.  The following day, Glaxo filed a motion for judgment on the pleadings.

    In opposition to Glaxo’s motion, Mutual argued that the relevant statute “says nothing that prohibits giving voluntary notice before the FDA has issued filing acceptance.”  According to the court, Mutual “seems to suggest that an ANDA applicant may send a Paragraph IV notice letter and thus trigger patent litigation, at any time it chooses.”

    In a decision on April 28th, however, the court concluded that “under the statute and regulations, the sending of a notice of a Paragraph IV certification is expressly predicated upon the ANDA applicant receiving its own notice and acknowledgment from the FDA that the submitted ANDA has been received.”  The court noted that the “Paragraph IV notice sequence ensures that the statutory litigation triggers do not result in unnecessary patent infringement litigation initiated by incomplete ANDAs.”  The court cited legislative history and FDA’s interpretation of the statute in support of its decision.

    Furthermore, the court rejected Mutual’s argument that even if the court dismissed Glaxo’s patent infringement claim without prejudice, it retained subject matter jurisdiction over Mutual’s counterclaim for a declaratory judgment of patent invalidity.  Here, the court contrasted the facts of the case with those of the Teva v. Novartis and Caraco v. Forest cases.  Additionally, the court reasoned that “due to the unfiled status of the ANDA, Defendants were not alleged infringers at the time this case was brought.”

    On April 30, Glaxo filed a second suit against Mutual, within the 45-day period from receipt of Mutual’s second notice letter.  Interestingly, on May 27, Mutual filed a Notice of Appeal of the district court’s decision on the first lawsuit.

  • FDA Denies King Pharma’s Citizen Petition Concerning Altace, Approves Ramipril ANDAs

    We reported last month that King Pharmaceuticals filed a citizen petition that could delay final approval of numerous ANDAs for generic versions of Altace (ramipril), which were set to earn final approval on June 7.  King's citizen petition asked FDA to require ANDA applicants for ramipril to file patent certifications with respect to newly-issued U.S. Patent No. 7,368,469, a method-of-use patent.

    On June 18, FDA denied King's citizen petition, concluding that the ANDAs may be approved with section viii "carve out" statements and that patent certifications are not necessary.  The same day, FDA granted final approval to the ANDAs.

    FDA's letter decision explains that King sought for FDA to

    confirm that label information describing cardiovascular outcomes from the Heart Outcomes Prevention Evaluation (HOPE) trial and the related indication may not be omitted from the labeling of any [ANDA or 505(b)(2) application] that relies upon an Altace product and seeks approval for treatment of hypertension.  Accordingly, the Petition seeks to confirm that ANDAs and 505(b)(2) applications that reference an Altace product must contain an appropriate patent certification to [the '469 patent] and may not contain a statement pursuant to section 505(b)(2)(B) or 505(j)(2)(A)(viii) of the Act explaining that the patent does not claim a use for which the applicant is seeking approval.

    FDA's letter concludes

    that ANDA and 505(b)(2) applicants seeking approval of ramipril products can omit from the product labeling the information from Altace labeling related to a reduction in risk of myocardial infarction, stroke, and death from cardiovascular causes (the HOPE indication) without rendering the proposed drug product less safe or effective than Altace products for the remaining conditions of use (treatment of hypertension and use in heart failure post-myocardial infarction).

    If FDA had reached the opposite conclusion and required ANDA applicants to include the HOPE indication in their labeling, the applicants would have had to file a paragraph III or IV certification to the '469 patent.  Although a paragraph IV certification would not have led to a 30-month stay of FDA approval (because the ANDAs had already been filed when King submitted the patent for listing in the Orange Book), such a certification would have allowed King to sue the applicant under 35 USC 271(e)(2) for infringement of the '469 patent.  Thus, the applicant would have had to decide whether to launch their generic ramipril product at-risk of liability for patent infringement.

    FDA's website shows that seven ramipril ANDAs were granted final approval immediately after FDA denied King's citizen petition and that Cobalt and Lupin also have final approval, for a total of nine generic ramipril products currently on the market.