Orange Book Blog

Federal Circuit grapples with scope of Orange Book listings

As readers of this blog surely known, parties seeking to launch a generic drug must address the patents listed in the Orange Book for the reference listed drug. Listing of a patent in the Orange Book is a powerful tool for pharmaceutical patent owners, as it gives the right to an automatic 30 month stay against generic competition without meeting the stringent requirements for a preliminary injunction (an "extraordinary remedy"). Moreover, unlike a typical preliminary injunction which requires the patentee to post a bond allowing the enjoined party to seek compensation for its losses during the enjoined period if the patent is determined to be invalid or not infringed, there is no effective recourse for lost sales of a generic during during the automatic 30-month stay (at least that I am aware of).

Understandably then, much attention has been given to what patents may be listed in the Orange Book. The senate passed the Orange Book Transparency Act of 2020 (unanimously!), which in part sought to clarify the scope of patents that could be listed in the Orange Book, limiting them to “claims the drug for which the applicant submitted the application and is a drug substance (active ingredient) patent or a drug product (formulation or composition) patent” or "claims a method of using such drug for which approval is sought or has been granted in the application." 21 U.S.C. § 355(b)(1)(A)(viii)(I). The OBTA replaced language that allowed listing of "any patent which claims the drug for which the applicant submitted the application" which was introduced in response to a concern that companies may be “submitting patents potentially for the purpose of blocking generic competition.” H.R. Rep. No. 116-47 at 4 (2019).

In Teva et al. v. Amneal et al., Teva sued Amneal for filing an ANDA to a generic version of ProAir HFA, which Teva describes as being regulated “single-entity combination products,” meaning a drug and a device “combined or mixed and produced as a single entity, asserting claims reciting the inhaler portion (but as best I can tell, not claiming even a genus of the active ingredient). Amneal counterclaimed for an injunction requiring Teva to delist the patents. The district court granted Amneal's motion for judgment on the pleadings and ordered delisting. Teva appealed, and the Federal Circuit recently heard oral argument. See https://oralarguments.cafc.uscourts.gov/default.aspx?fl=24-1936_11082024.mp3. 

On appeal, Teva focused on the definition of "drug" in the FDCA, which it argued broadly covers "not just the active ingredient, but the entirety—specifically including any 'component'—of any article' used for the 'treatment' or prevention of disease' or to 'affect … any function of the body,' for example." Citing 21 U.S.C. § 321(g)(1). Thus, Teva argued a patent need not "recite the active ingredient by name in order to claim the drug" because "a patent claiming a genus of compounds reads on a drug whose active ingredient is one species within the genus." Teva thus argued that "the scope of what a patent 'claims' must be determined through an infringement-type analysis," i.e., that if the claims would cover the drug product, they claim the drug product. 

Amneal defended the district court's judgment, arguing that to qualify for listing, a "drug product" patent "must satisfy three criteria": (1) a claim of infringement can be reasonably asserted (citing 21 U.S.C. § 355(b)(1)(A)(viii)); (2) the patent is a “drug product” patent, i.e., claims a drug product (citing 21 U.S.C. § 355(b)(1)(A)(viii)(I)) and (3) “claims the drug for which the applicant submitted the application.” (again citing 21 U.S.C. § 355(b)(1)(A)(viii)(I)). Amneal argued that the "second and third requirements work in tandem to require a drug product patent to claim not just any 'drug product,' but the specific NDA 'drug product,' as that term is defined by the FDA" which requires the drug product to "contain a drug substance" or "active ingredient." Citing 21 C.F.R. § 314.3. Amneal argued that Teva's argument would render the "claims the drug" requirement superfluous, and that the statute cannot be read to treat a device as if it is a drug.

The briefing of both parties is heavy on statutory and regulatory citations which I have not exhaustively reviewed, but the Federal Circuit panel seemed to struggle with a more simple issue - what does it mean to claim a "drug product." The panel used the hypothetical of a steering wheel and a car. Does a claim to a steering wheel cover a car? the panel asked. According to Teva, the answer was yes, a claim to a steering wheel claims a Ford Bronco. Judge Taranto seemed skeptical, saying "nobody, nobody, would think that if I have a patent, which I claim as my invention the steering wheel, that I'm claiming the car that it is in." But Teva responded that if the claim recited a "car comprising a steering wheel" it would claim a car. Judges Taranto and Prost seemed skeptical. Teva argued that Amneal's construction would require a claim to cover every component of a drug product to claim the drug product and would threaten listings for inactive ingredient and genus claims.

The panel seemed more interested in this concern, and asked Amneal to address it. Amneal argued that Teva can still assert the inhaler patents, they simply don't get the "superpower" effect of Orange Book listing given under the statute. Amneal argued that if the statute allowed Orange Book listing for any patent that "claims a drug" then Teva would win, but the statute does not. 

Like the panel, I am skeptical of Teva's position broadly that any claim to any component of a drug product is sufficient, regardless of whether it claims the specific drug substance. Surely a claim to an excipient used in the NDA product does not "claim" the drug product, even though it would read on the product. But Teva's argument about genus claims is a bit more interesting. For example, the active ingredient in the drug product is albuterol sulfate, a class of bronchodilators. It seems clear a claim to an "inhaler comprising albuterol sulfate" would claim the "drug product" (even though it doesn't claim every single component or excipient). Presumably too, a claim to an "inhaler comprising albuterol" would suffice. But would a claim to "an inhaler comprising a bronchodilator"? How broad can the genus be and still claim the "drug product"? Would "an inhaler comprising a drug substance" be sufficient? 

While Teva argued that Amneal's construction would exclude claims to genuses, it didn't appear to make any argument that any of its claims included a limitation to a genus (and the claim it identified on the front cover of its brief does not claim any genus of active ingredients). I am thus skeptical the Court will need to grapple with this line drawing or that Teva will prevail on a genus argument. 

An interesting issue is what tools to generics have to combat improper Orange Book listings? While Amneal was apparently able to get a relatively rapid ruling from the district court, Teva still obtained roughly a quarter of the 30 month automatic stay. It will be interesting to see if Congress attempts to make any sort of recourse available for generics who are found to be improperly stayed. Or will courts consider this a ground for awarding attorneys fees? Time will tell.

Obviousness-Type Double Patenting for Patent-Term-Adjusted Patents post-Allergan and In re Cellect (2/2)

  by: Rocco J. Screnci

This is the second post in a two-part series on obviousness-type double patenting (“ODP”). Part one summarized the two recent precedential Federal Circuit decisions in this area.

To sum up where last post left off: The Federal Circuit’s decision in Cellect initially seemed to drastically expand the application of ODP, and the Allergan decision limited the broadest readings of Cellect by explaining that later-filed, later-issued patents cannot be used as ODP references against the “first” patent in the family even if patent-term adjustment (“PTA”) awarded for Patent Office delays during prosecution means that the “first” patent expires later. At the same time, Allergan seemingly reaffirmed its earlier ODP cases, including Cellect, in which expiration date controlled the outcome. This leaves a few important takeaways.

First, Allergan did not disturb past cases applying ODP to invalidate later-filed and later-expiring patents. Indeed, Allergan contrasted its facts with those in past cases, like Abbvie Inc. v. Mathilda & Terence Kennedy Inst. of Rheumatology Tr., 764 F.3d 1366 (Fed. Cir. 2014), in which the patentee secured a second, later-expiring patent by filing a continuation that received 750 days more PTA than the first patent in the family, and Gilead Scis., Inc. v. Natco Pharma Ltd., 753 F.3d 1208 (Fed. Cir. 2014), in which the patentee secured a second, later-expiring patent by beginning a new application chain with a later priority date. With that in mind, it is important for defendants to always keep an eye on a plaintiff’s earlier-filed, earlier-expiring patents as potential grounds for invalidity against later-filed, later-expiring patents. And plaintiffs will need to keep its earlier-filed, earlier-patents in mind when developing their prosecution and Orange Book-listing strategies.

Second, Allergan left intact Cellect’s central holding: that the PTA-added expiration date is the expiration date that matters for ODP purposes. It will thus be important for ANDA filers to keep track of not just when Orange Book-listed patents expire, but also when the NDA holder’s other patents expire. What’s more, given that PTE and PTA are treated differently for ODP purposes, ANDA filers will want to account for both PTE- and PTA-added expiration dates when planning their filing strategies. On the flipside, NDA holders will want to consider revisiting their Orange Book-listed patents to see if any terminal disclaimers are necessary for later-filed patents with PTA.

Third, Allergan clarified that issuance date matters in the ODP analysis. This limits the available references that can be asserted to support an ODP defense. Defendants now know that they cannot simply invoke PTA-added expiration dates when arguing invalidity on ODP grounds. That said, the precise contours of Allergan’s holding on that point are a bit unclear.

On one hand, Allergan seems to shut the door on the idea that a later-filed, later-issued “child” patent without PTA can invalidate a “first” or “parent” patent. But that only invites the question of what it means to be a “first” or “parent” patent. Recall that the ODP reference patents in Allergan were not the immediate descendants of the challenged “first” patent in the family. The ODP reference 011 and 709 patents in Allergan were the metaphoric grandchild and great-grandchild, respectively, of the 356 patent. The 011 patent issued on a divisional of an application that itself was a continuation of the 356 patent’s application, and the 709 patent was a continuation of the 011 patent’s application. Indeed, the 356 patent issued before the applications leading to the 011 and 709 patent were filed. And the Federal Circuit emphasized those facts when explaining why the facts in Allergan exemplified why ODP did not apply. As a result, some may construe Allergan as narrowly applying to the precise fact pattern there: The patent issuing from the first nonprovisional application in the family cannot be invalidated by later-issued patents that were applied for only after the first patent issued. This could mean that patents issuing from continuations are still susceptible to attack, or that a different rule applies if the reference patent’s application was copending.

On the other hand, some may read Allergan as foreclosing ODP whenever the later-expiring patent was earlier filed and earlier issued than the would-be reference patents, even if the patents were copending and have different priority chains. This broad reading stems from Allergan’s favorably citing past cases in which the Federal Circuit declined to extend ODP to similar situations. See 111 F.4th at 1370. But those cases were limited to distinct scenarios or expressed their narrow views on ODP only in dicta. See Cellect, 81 F.4th at 1230 (“We do, however, note that the non-asserted claims in the challenged patents are entitled to their full term, including the duly granted PTA, unless they are found to be later-filed obvious variations of earlier-filed, commonly owned claims.”); Novartis AG v. Ezra Ventures LLC, 909 F.3d 1367, 1374 (Fed. Cir. 2018) (“[T]he traditional concern with obviousness-type double patenting” is not raised where “it is the earlier-filed, earlier issued ... patent, not the later-filed, later-issued ... patent, that has the later expiration date”); Novartis Pharms. Corp. v. Breckenridge Pharm. Inc., 909 F.3d 1355, 1366 (Fed. Cir. 2018), (declining to invalidate patent on ODP grounds “[i]n th[e] particular situation where we have an earlier-filed, earlier-issued. . . patent that expires after the later-filed, later-issued . . . patent due to a change in statutory patent term law”).

Of course, the real impact of Allergan is yet to be seen and likely lies somewhere between the narrowest and broadest possible readings. One can imagine a middle-ground approach that forecloses ODP as a form of patent patricide. In other words, the rule from Allergan would bar defendants from pitting later-filed, later-issued patents against the earlier-filed, earlier-issued patents in the same priority chain. This rule would potentially balance the Federal Circuit’s policy concerns about depriving patentees of their original patent terms while leaving room for the courts to curb any gamesmanship that may arise when patentees try to stagger priority chains to secure longer patent terms.

In any event, perhaps the most important takeaway from Allergan is that the Federal Circuit continues to develop its view on ODP case-by-case. In its latest cases addressing ODP, the Federal Circuit has carefully parsed its ODP jurisprudence to determine how ODP ought to apply to the issues on appeal. Allergan continues this trend by limiting earlier ODP cases to their particular facts and by narrowing Cellect to the issue framed by the appellant about how PTA interacts with ODP. This trend is important for two key reasons. First, it shows how critical it is for defendants to continue to identify and raise potential ODP defenses as the law in this area continues to develop, and for plaintiffs to anticipate these arguments when preparing for litigation. Second, it reminds all litigants to consider how they frame arguments. Given some of the Federal Circuit’s concerns in Allergan, perhaps the fact pattern in Cellect could have played out differently had the appellant taken a more moderate approach in urging to reverse the ODP determinations by the Patent Trial and Appeals Board.

Obviousness-Type Double Patenting for Patent-Term-Adjusted Patents post-Allergan and In re Cellect (1/2)

    by: Rocco J. Screnci

This post is the first in a two-part series about recent developments in the law of double patenting. This post provides relevant background and summarizes the Federal Circuit’s recent decisions in In re Cellect, 81 F.4th 1216 (Fed. Cir. 2023) and Allergan USA, Inc. v. MSN Laboratories Priv. Ltd., 111 F.4th 1358 (Fed. Cir. 2024). For those already familiar with the decisions, please feel free to move on to the next post in this series, which discusses the potential implications of these cases for Orange Book patents.

The doctrine of obviousness-type double patenting (“ODP”) is judge made and bars a patentee from securing multiple patents with different expirations for patentably indistinct (i.e., obvious) variants of the same invention. The doctrine developed to address gamesmanship that arose under earlier versions of the patent act when patent applications were not published and when expiration dates were determined by the issuance dates. ODP was thus needed to combat “submarine” patents, a practice by which patentees maintained a chain of secret applications before drafting patentably indistinct claims on a competing product long after the original patent had expired. But submarine patents are now a relic of the past. This is because applications are published and because filing date—not issuance date—determines patent term. Even so, ODP still persists as an invalidity defense when two patents claiming patentably indistinct subject matter expire at different times.

In fact, the law on ODP is dynamic as ever. Last year, in In re Cellect, the Federal Circuit explained for the first time how ODP interacts with patents that have received a patent-term adjustment (“PTA”) for delays during prosecution. The patentee in Cellect had secured a web of patents with a shared priority date, but having different PTAs and thus different expiration dates as depicted in the following timeline. Several patents were challenged on ODP grounds in petitions for ex parte reexamination. Because each of the challenged patents were patentably indistinct from the reference patents (as shown in the table below), the sole issue was what expiration date mattered when analyzing ODP.

Challenged Patent	ODP Reference Patent
742	369
369	036
626	369
621	626

The patentee relied on earlier decisions that had held that ODP challenges to patents with patent-term extensions (“PTE”)—additional patent term awarded to certain drug or medical device patents due to time spent awaiting FDA approval—must use the expiration date before accounting for any PTE. In other words, if there are no ODP concerns for a patent’s original patent term, it can enjoy its full original patent term plus PTE. The patentee in Cellect argued that the same rule should apply for PTA, but the Federal Circuit disagreed. As a result, each patents was held invalid on ODP grounds.

Many saw Cellect as a drastic expansion of ODP. While some took issue with the disparate treatment of PTE and PTA when evaluating ODP, the bigger concern was the Cellect seemingly stood for the premise that PTA-added expiration date—and that expiration date alone—is all that matters for ODP purposes. This would mean that later-filed, later-issued patents could invalidate earlier-filed, earlier-issued patents simply because the earlier patent received PTA and the later patents did not. That rule would be surprising because it would create an invalidity defense that escapes prosecution. Usually, the Patent Office catches ODP concerns during examination of later-filed patent that claim obvious variants of previously issued patents. To overcome an ODP rejection, the applicant must file a terminal disclaimer, which ties expiration date of the later-filed claims to those of the earlier-filed claims. But a broad reading of Cellect would flip that scenario on its head, meaning that issued patents could have their patent terms truncated if later continuations received less PTA. And because earlier Federal Circuit decisions prevent patentees from terminally disclaiming to already-expired patents, that broad reading would mean that it was too late to save some otherwise valid patents. This reading would be even more impactful given that Cellect arose from ex parte reexaminations.

Ex parte reexamination is a post-grant proceeding in which the Patent Office reopens patent prosecution if a petition for reexamination identifies a "substantial new question of patentability." While the petitioner in an ex parte reexamination has less involvement in proceedings than its counterpart in inter partes review ("IPR"), ex parte reexamination has some noteworthy advantages over IPR. For one, IPR has tighter filing deadlines and limits challenges to novelty and obviousness based on printed prior art (i.e., patents and publications). A petition for ex parte reexamination, by contrast may be filed any time before the patent expires and also may raise ODP as an invalidity ground. The generous filing deadline makes ex parte reexamination a particularly powerful tool in the ODP context because it means that a party can wait until after the reference patents expire to challenge a patent on ODP grounds, leaving the patentee no time to file a terminal disclaimer to overcome ODP. With that in mind, a broad interpretation of Cellect would empower defendants to invalidate an entire patent simply by waiting until it is too late to cure ODP with a terminal disclaimer.

At least one district court endorsed that broad reading of Cellect. In Allergan v. MSN Laboratories, the district court applied ODP to invalidate Allergan’s Orange Book-listed 356 patent covering eluxadoline, a drug used to treat IBS-D sold under the brand name Viberzi®. The district court found that the 356 patent was patentably indistinct from Allergan’s two earlier-expiring patents in the same patent family that also claimed eluxadoline. Relying on Cellect, the district court said it was irrelevant that the 011 and 709 patents were later-filed, later-issued descendants of the 356 patent. The district court read Cellect for the broad proposition that “[w]hen analyzing ODP, a court compares patent expiration dates, rather than filing or issuance dates…[N]o exception[s].” Allergan USA, Inc. v. MSN Laboratories Priv. Ltd., 694 F. Supp. 3d 511, 540 (D. Del. 2023).

But in late-August, the Federal Circuit explained that Cellect is not so broad. In a precedential decision, the Federal Circuit reversed the district court in Allergan v. MSN Laboratories, 111 F.4th 1358 (Fed. Cir. 2024). The court explained that Cellect addressed only the narrow issue about how ODP interacts with PTA. “Cellect does not address,” the court continued, the threshold issue about when a patent “can properly serve as an ODP reference.” Allergan, 111 F.4th at 1368. The court then concluded that the 011 and 709 patents could not be asserted as ODP references against the 356 patent because the 356 patent was the “first” patent to cover eluxadoline. There was thus no concern that Allergan tried to prolong its monopoly on eluxadoline beyond the original patent term because the first-issued, first-filed 356 patent—not the later-filed, later-issued 011 and 709 patents—dictated that patent term. Put another way, the Federal Circuit declined to let a “second” patent truncate the effective patent term of the “first” patent.

The Federal Circuit also took time to address pre-Cellect cases that seemingly stood for the proposition that patent filing dates are irrelevant when analyzing ODP. The court distinguished those cases by explaining that they confronted different scenarios. Those cases, the court explained, each involved later-expiring patents that, at a minimum, were filed after the ODP reference patents. According to the court, those cases presented the opportunities for gamesmanship that ODP seeks to prevent. By contrast, the facts in Allergan presented, as the court put it, “‘a prime example’ of when ODP does not apply.” 111 F.4th at 1371. Because the 011 and 709 patents did not exist when the 356 patent issued, the 356 patent in no way “result[ed] in an extension of patent term of the invention[s] claimed in the [011 and 709] patent[s].” Id. In other words, the court recognized that letting the later-filed, later-issued patents invalidate the "first" patent would defy the rationale underlying ODP, which is to prevent a patentee from using serial continuations to prolong a patent monopoly. If later-filed, later-issued patents could serve as ODP reference patents, patentees would effectively be forced to forgo PTA or cease filing continuations altogether.

While Allergan seems to have reined in Cellect’s impact, the Federal Circuit still left intact most pre-Cellect caselaw. Part two of this post explores what this means for Orange Book patents. It also identifies a few ambiguities in Allergan and their potential implications.

Novo Nordisk Requests FDA Advisory Opinion Concerning Orange Book Listing of Patents on Pre-Filled Drug Delivery Devices

    by Aaron F. Barkoff

Novo Nordisk recently became the fourth company to ask FDA for guidance concerning whether patents on pre-filled drug delivery devices should be listed in the Orange Book.  Novo markets several drug products as pre-filled pen-injector systems, including insulin and growth hormone products.

In a Request for Advisory Opinion dated November 26, 2012, Novo raised two specific questions:

1. What constitutes an approved pre-filled drug delivery system for purposes of determining whether information on patents relating to that system should be submitted to FDA for Orange Book listing; and
2. Whether information on patents relating to approved pre-filled drug delivery systems should be submitted to FDA for Orange Book listing if such patents neither disclose nor claim the active ingredient or formulation of the approved drug product.

Novo Nordisk's request follows similar requests submitted by GlaxoSmith Kline in 2005; AstraZeneca in 2006 and 2007; and Forest Laboratories in 2011.  According to Novo, "To date, FDA has not substantively answered the advisory opinion requests or otherwise publicly addressed the patent listing issues they raise."

The Federal Food, Drug, and Cosmetic Act requires the sponsor of a New Drug Application to submit for listing in the Orange Book "any patent which claims the drug for which the applicant submitted the application or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug."

Novo's request states that in June 2003, "FDA sought to clarify the types of patents that must and must not be submitted for listing in the Orange Book," and clarified "that if the patent claims the drug product as defined in 21 CFR 314.3, the patent must be submitted for listing."  The term "drug product" is defined by FDA as "a finished dosage form, for example, tablet, capsule, or solution, that contains a drug substance."  According to Novo:

FDA stated that a key factor in determining whether to list a patent, therefore, is whether the patent claims the finished dosage form of the approved drug product.  FDA noted that these finished dosage forms include "metered aerosols, capsules, metered sprays, gels, and pre-filled drug delivery systems" but do not include "bottles or containers and other packaging."

FDA's distinction between pre-filled drug delivery systems and product packaging remains unclear, however, because the term "pre-filled drug delivery system" is not defined.  The Orange Book does not list "pre-filled drug delivery systems" as a dosage form in Appendix C (Uniform Terms); nor does FDA's Data Standards Manual Dosage Form Monograph (C-DRG-00201) provide any useful guidance.

Novo's request notes that in at least one instance a defendant in a Hatch-Waxman case filed a "delisting counterclaim" seeking the removal of a device-related patent.  That case, King Pharms. v. Intelliject (D. Del.), was dismissed before the court ruled on the counterclaim.  Novo argues that an advisory opinion from FDA addressing Novo's questions "could reduce the likelihood of patent delisting litigation and is in the interest of judicial economy."  Novo also argues that the "patent notice" and "early patent challenge" functions of the Hatch-Waxman Act would be advanced if FDA were to issue such an advisory opinion.

Novo concludes its request by informing FDA--just as GSK, AstraZeneca, and Forest previously informed FDA--that in the absence of guidance from FDA that the listing of patents on pre-filled drug delivery devices is improper, Novo will submit such patents for listing in the Orange Book.

RELATED READING:

• GSK Request for Advisory Opinion dated Jan. 10, 2005
• AstraZeneca Request for Advisory Opinion dated Aug. 10, 2006
• AstraZeneca Request for Advisory Opinion dated June 21, 2007
• Forest Labs Request for Advisory Opinion dated May 12, 2011

Obama Administration Urges Supreme Court to Grant Certiorari in Case on Orange Book Patent Use Codes

Caraco Pharm. Labs. v. Novo Nordisk, No. 10-844 (U.S. 2011)

Last week, in response to the Supreme Court’s request for its views, the Solicitor General’s office filed an amicus brief in Caraco v. Novo Nordisk and urged the Court to take the case.  At issue is the “patent delisting counterclaim” provision of the 2003 Medicare Modernization Act.  The case is an appeal from a Federal Circuit decision last year holding that the provision is not available to compel a change to a patent use code in the Orange Book.

Patent use codes relate specifically to method-of-use patents.  FDA regulations require an NDA holder submitting a method-of-use patent for Orange Book listing to also submit a patent use code for the patent.  The purpose of the use code is to indicate “the approved indications or other conditions of use covered by [the] patent.”  21 C.F.R. 314.53(e).

When a company files an ANDA with a section viii statement, asserting that it does not seek approval of its drug for a patented use, FDA compares the ANDA applicant’s proposed drug labeling to the patent use code to determine whether the section viii statement is acceptable.  If there is any overlap between the proposed labeling and the use code, FDA will reject the section viii statement and require the ANDA applicant to file a Paragraph IV certification instead.

In this case, Novo’s U.S. Patent No. 6,677,358 claimed a method for treating diabetes comprising administering repaglinide in combination with metformin and its use code for the ‘358 patent was “a method for improving glycemic control in adults with type 2 diabetes mellitus.”  Caraco filed an ANDA for a generic version of PRANDIN (repaglinide) and included a section viii statement, asserting that it sought approval for repaglinide used alone—not in combination with metformin.  In other words, Caraco sought to “carve out” the patented use from its labeling, thereby trying to avoid inducing infringement of the ‘358 patent.

Because Caraco’s proposed use overlapped with Novo’s use code, however, FDA rejected Caraco’s section viii statement, rejected Caraco’s carve-out labeling, required Caraco to file a Paragraph IV certification, and required Caraco to copy Novo’s PRANDIN labeling.  It did not matter that Caraco’s proposed use did not overlap with Novo’s patent claim—the FDA only checks the use code.  In the Paragraph IV litigation, Caraco filed a counterclaim seeking to compel Novo to revise the use code for the ‘358 patent to more narrowly tailor the use code to the method claimed in the ‘358 patent: administering repaglinide in combination with metformin.  The district court sided with Caraco and ordered Novo to change the use code, but the Federal Circuit reversed.  Caraco then appealed to the Supreme Court.

The Federal Circuit’s decision has caused a great deal of concern to the generic drug industry, as seen in the five amicus briefs filed in support of Caraco’s cert petition (and none opposed).  Briefs in support were filed by Apotex; the Consumer Federation of America and U.S. PIRG; the Generic Pharmaceutical Association (GPhA); Mylan; and Teva.  In March, the Supreme Court asked the Solicitor General’s office for its views on the case, which many in the generic pharmaceutical industry took as a positive sign.  After the Solicitor General filed its brief last week, urging the Court to grant certiorari, the generic industry was even more encouraged, as reflected in GPhA’s press release.

According to the Solicitor General:

Under the Federal Circuit's decision, a brand-name manufacturer can effectively preclude generic competition by submitting an overbroad description of its method-of-use patent to FDA.  Congress enacted the counterclaim provision at issue here to combat precisely that sort of manipulation.  The court's ruling significantly impairs ANDA applicants' ability to secure FDA approval for their products, and hence deprives consumers the full benefit of generic competition.

Despite the complex regulatory background and policy arguments, this case presents a relatively straightforward question of statutory interpretation: does the term "patent information" in the counterclaim provision encompass patent use codes or not?  By the end of June, the Supreme Court will announce whether it has decided to take up the case.

RELATED READING:

• SCOTUSblog, with links to all briefs

Federal Circuit Vacates Injunction that Directed Novo Nordisk to Revise Patent Use Code for Prandin

Novo Nordisk v. Caraco Pharm. Labs. et al., No. 2010-1001 (Fed. Cir. 2010)

In the Medicare Modernization Act of 2003, Congress gave ANDA applicants who have been sued for patent infringement the statutory right to file a counterclaim seeking the delisting of the patent from the Orange Book:

If an owner of the patent or the holder of the [NDA] for the drug that is claimed by the patent or a use of which is claimed by the patent brings a patent infringement action against the [ANDA] applicant, the applicant may assert a counterclaim seeking an order requiring the holder to correct or delete the patent information submitted by the holder . . . on the ground that the patent does not claim either—(aa) the drug for which the application was approved; or (bb) an approved method of using the drug.  21 USC 355(j)(5)(C)(ii).

Pursuant to this provision, after Novo Nordisk sued Caraco for infringement of U.S. Patent No. 6,677,358 based on Caraco’s paragraph IV certification, Caraco filed a counterclaim requesting an order directing Novo to change the Orange Book patent use code for the ‘358 patent, and thereby “correct the patent information” for the ‘358 patent.

Prandin (repaglinide) is FDA-approved for three uses:  (1) repaglinide by itself (i.e., monotherapy); (2) repaglinide in combination with metformin; and (3) repaglinide in combination with thiazolidinediones.  The ‘358 patent, which is the only patent listed in the Orange Book for Prandin, claims, “A method for treating non-insulin dependent diabetes mellitus (NIDDM) comprising administering to a patient in need of such treatment repaglinide in combination with metformin.”  Accordingly, the original patent use code for Prandin was “Use of repaglinide in combination with metformin to lower blood glucose.”

Caraco’s ANDA contained a paragraph IV certification to the ‘358 patent and a section viii statement declaring that Caraco was not seeking approval for the repaglinide-metformin combination therapy.  Because there was no overlap between Caraco’s proposed carve-out label and the repaglinide-metformin use code, FDA accepted the proposed label.

Thereafter, Novo changed the use code for the ‘358 patent to broaden it from the repaglinide-metformin combination therapy to “A method for improving glycemic control in adults with type 2 diabetes mellitus.”  The new use code covered all three approved uses for Prandin, even though the ‘358 patent covered only one approved use.  Caraco’s carve-out label now overlapped with the use code, and therefore FDA retracted its approval of Caraco’s proposed label and section viii statement.  As a result, Caraco’s current label now includes the repaglinide-metformin combination therapy, which is stipulated to infringe claim 4 of the ‘358 patent.  This prompted Caraco’s counterclaim seeking an order directing Novo to replace the new use code with the former listing.

On September 24, 2009, the U.S. District Court for the Eastern District of Michigan ruled that Caraco was entitled to the requested injunction.  The court stated, “Novo, by the change in the use code narrative is attempting to extend the life of an expired patent”—namely, U.S. patent RE37,035, which broadly claims repaglinide.  According to the court, “the clear legislative intent behind the 2003 amendments to Hatch-Waxman that added the counterclaim provision, section 355(j)(5)(C)(ii), [was] to curb Orange Book abuses arising from misinformation regarding listed patents.”  The next day, the court issued an order granting the injunction sought by Caraco.

On Wednesday, in a 2-1 decision—over a 28–page dissent from Judge Dyk—the Federal Circuit reversed and vacated the injunction.  The majority reasoned that the statutory language is clear on its face:  “an approved method of using the drug” means “any approved method” (as Novo urged) rather than “all approved methods” (as Caraco argued).  Further, according to the majority, its decision to vacate the injunction is consistent with the legislative intent:  the counterclaim provision in the 2003 Act “sought to correct the specific issue raised in Mylan v. Thompson (Fed. Cir. 2002), i.e., to deter pioneering manufacturers from listing patents that were not related at all to the patented product or method.”  In addition, the majority concluded that “the patent information” referred to in the counterclaim provision meant “the patent number and the expiration date”—not also the use code narrative.

In dissent, Judge Dyk expressed strong disagreement with the majority.  He wrote:

In 2003, Congress enacted the counterclaim provision of the Hatch-Waxman Act in order to prevent manipulative practices by patent holders with respect to the Orange Book listings.  These practices were designed to delay the onset of competition from generic drug manufacturers.  In my view, the majority, in reversing the district court, now construes the statute contrary to its manifest purpose and allows the same manipulative practices to continue in the context of method patents.

Judge Clevenger, in a short concurring opinion, stated that, in his view, “Novo did nothing that was illegal or forbidden.”  He acknowledged that FDA “may have inadvertently upset the careful balance of interests represented by the efficient dispute resolution mechanism Congress created in the Hatch-Waxman Act.”  But, he concluded, “Congress is the appropriate entity to readjust, if necessary, the delicate balance it has struck between original drug manufacturers and their generic counterparts.”

Perhaps Congress will "readjust" the Act--time will tell.  Caraco and Novo Nordisk have not yet commented on the Federal Circuit’s decision.

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:

• Janssen press release, announcing launch of authorized generic
• Motley Fool article
• April 11 FDA Law Blog post
• January 17 OBB post

OBB News Briefs

• As reported by FDA Law Blog, FDA determined on May 7 that Cobalt forfeited its 180-day exclusivity on acarbose and Cobalt sued FDA on May 8 for injunctive relief.  Last Friday, for some reason, Cobalt voluntarily dismissed its suit against FDA.
• Also last Friday, FDA appealed the D.C. district court's decision requiring relisting of Janssen's patent on Risperdal (risperidone).
• Ivax recently filed a declaratory judgment complaint against AstraZeneca, reportedly seeking to trigger Ranbaxy's 180-day exclusivity on esomeprazole.  AstraZeneca and Ranbaxy settled their esomeprazole litigation last month.
• The district court in Washington, D.C. recently transfered the FTC v. Cephalon "reverse payment" antitrust case to the Eastern District of Pennsylvania, Reuters reported, possibly throwing a wrench into the FTC's plans to get a "reverse payment" case before the Supreme Court.
• Pharmalot had an interesting post last week on the coming wave of generic drugs from Chinese generic drug companies.

OBB News Briefs

• Last Monday, the Federal Circuit affirmed a district court decision in McNeil-PPC v. Perrigo, concerning a generic version of Pepcid Complete.  The decision was affirmed without an opinion, under Rule 36.
• Tuesday, AstraZeneca and Ranbaxy announced a settlement of their patent litigation over generic Nexium (esomeprazole), with Astra granting Ranbaxy exclusive rights to sell a generic version of Nexium in 2014, six months before the first patent expires.  Teva and Dr. Reddy's plan to continue challenging Astra's patents.  Astra press release; Ranbaxy press release; AP; Bloomberg; Pharmalot; WSJ Health Blog.
• In a very surprising decision, a D.C. district court recently ruled in favor of Teva in a case in which Teva alleged that the FDA wrongfully delisted a patent on Risperdal (risperidone) from the Orange Book, depriving Teva of 180-day exclusivity.  FDA Law Blog has a full report.
• Earlier this month, Depomed announced a settlement of patent litigation against Teva over generic Glumetza (metformin HCl).  Depomed press release; AP story.
• Pharmalot recently had two interesting posts about biosimilars: the first suggested, based on a report about the Food and Drug Law Institute's annual meeting, that biosimilars legislation may actually be passed this year; the second reported on lobbying for a biosimilars bill.
• FDA Law Blog recently updated their coverage of the generic Depakote (divalproex sodium) litigation between Nu-Pharm (a former subsidiary of Apotex) and FDA, in which Nu-Pharm is seeking an injunction requiring FDA to grant final approval to its divalproex ANDA.
• Pharmalot posted a summary of a recent article in the Seattle Post-Intelligencer about a citizen petition that has stymied Nastech Pharmaceutical's bid to market a generic version of Miacalcin (calcitonin), a treatment for postmenopausal osteoporosis.
• Takeda announced earlier this month that on March 31, the Supreme Court denied Alphapharm's cert petition from the Federal Circuit's decision last year in the Actos (pioglitazone) litigation.

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.