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As more biosimilar applications are filed, courts will inevitably face the novel and complex issues posed by the BPCIA with increasing frequency.
I. INTRODUCTION
Pharmaceutical biologics are complex creatures. They are among the most cutting-edge and innovative medical technologies available and include a diverse array of biological agents, such as vaccines, blood, blood components, and allergenics, among others.1 To encourage the development of these products, the Biologics Price Competition and Innovation Act of 2009 (the "BPCIA")grants biologic producers 12 years of marketing exclusivity.2 Perhaps predictably in light of the nature of biologics themselves, one federal appeals court recently described the BPCIA as a "riddle wrapped in a mystery inside an enigma."3
Like the Drug Price Competition and Patent Term Restoration Act (commonly known as the "Hatch-Waxman Act"),4 which provides a track for market entry by less expensive generic alternatives to brand name pharmaceuticals, the BPCIA provides an entry pathway for "biosimilars," or versions of biologic products that are "highly similar."5 Under the BPCIA, a pharmaceutical company may file an abbreviated Biologic License Application ("aBLA"), which relies on the pioneer (or reference) product sponsor's clinical studies to demonstrate that the biosimilar will be safe and effective. The biosimilar, if approved by the FDA, can then be considered "interchangeable" with its reference biologic product, thus allowing the developer to market and sell it in competition with the reference product.6
Due to their complicated development and testing requirements, biosimilars generally are priced less aggressively against pioneer biologics than are generic drugs to brand drugs. Nevertheless, biosimilar competition will likely generate significant savings to the public.7 One biosimilar developer projected that biosimilars could generate U.S. $250 billion in savings to consumers over ten years.8 Further, while sales of biosimilars in the United States currently are relatively small, it is only a matter of time before they occupy a larger share of the biologics market. Indeed, in anticipation of the rapid growth of biosimilars, many states have passed legislation that permits pharmacists to substitute biosimilars for their reference biologic products.9
Although enacted in March 2010, it was not until June 2013 that the BPCIA became the subject of litigation.10 There has been a flurry of litigation since then, however, particularly with respect to two key elements of the BPCIA: (1) the necessity of the complex patent information exchange procedure, also known as the "patent dance;" and (2) the necessity of obtaining FDA approval of an aBLA prior to issuing the 180-day notice of commercial marketing.
This article examines the recent litigation on these two issues, which includes an appellate decision from the Federal Circuit. However, these cases are just the beginning. As more biosimilar applications are filed, courts will inevitably face the novel and complex issues posed by the BPCIA with increasing frequency. The law's competitive impact on the marketplace for biologic products is still to come.
II. THE BPCIA AND THE "PATENT DANCE"
Under the BPCIA, biosimilar manufacturers may submit an aBLA for FDA review and approval. To receive approval, the applicant must demonstrate its product is biosimilar, which may be shown by presenting, among other things, "analytical studies that demonstrate that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components."11
First-filing biosimilar applicants are entitled to a statutory exclusivity period that bars the FDA from approving a subsequent aBLA. However, the BPCIA's exclusivity provision was not enacted without significant debate as to its effects on spurring competition in the biologics market. As Congress was considering whether to include an exclusivity provision for first-filing biosimilar applicants in the BPCIA, the U.S. Federal Trade Commission ("FTC") petitioned Congress not to do so because of, among other things, the likelihood that pay-for-delay agreements would be repeated in the biologics market.12 The FTC wrote:
[P]ioneer manufacturers and [biosimilars] could settle patent litigation such that a payment is made to the first interchangeable [biosimilar] entrant to settle the patent dispute and defer its entry. This settlement could create a bottleneck that blocks subsequent interchangeable [biosimilar] from obtaining FDA approval because the first-approved product's exclusivity period has not run.13
However, Congress was unmoved and ultimately included a biosimilar exclusivity provision that provided the first-filing biosimilar applicant freedom from additional generic competition until the earlier of: (i) 12 months after first commercial marketing of the first-filed aBLA product; (ii) 18 months after a "final court decision" in any litigation over patents that are the subject of the aBLA product, or the dismissal of such an action; (iii) 18 months after submitting aBLA to the biologic manufacturer and the biologic manufacturer fails to sue the biosimilar applicant; and (iv) 42 months after the approval of the aBLA product that is still the subject of litigation.14
While there are certain similarities between the BPCIA and the Hatch-Waxman Act, the mechanism for resolving patent disputes under BPCIA is more complicated. Indeed, unlike the Hatch-Waxman Act, section 262( l) of the BPCIA sets forth a multi-faceted " patent dance."15
First, under the patent dance, a biosimilar applicant must submit a copy of its application to the producer of the reference biologic product.16 The failure of a biosimilar applicant to comply with this provision provides the biologic manufacturer with an automatic right to bring a declaratory patent infringement action.17
Next, within 60 days after receiving the application, the maker of the reference biologic product must provide the applicant with a list of patents that cover the referenced biologic product, including a list of patents that the reference product sponsor would be prepared to license to the applicant.18 Upon receipt of this list, the biosimilar applicant may, within 60 days, provide a written description of those patents that the biosimilar product might infringe or a description of how the patents at issue are unenforceable, invalid, or not infringed by the biosimilar.19 If there is a claim of non-infringement, the biologic producer shall then provide the applicant with a statement that describes the basis for infringement, on a claim-by-claim basis.20
The biosimilar applicant and the biologic producer must then engage in "good faith negotiations to agree on which, if any, patents listed... by the [biosimilar] applicant or the reference product sponsor shall be the subject of an action for patent infringement."21 If there is no agreement, the parties shall exchange a list of patents that they believe would be the subject of an infringement suit.22 Regardless of whether there is an agreement about the relevant patents at issue, within 30 days of these negotiations the maker of the biologic may bring a patent infringement suit on each patent identified through the above process.23 A biosimilar applicant's failure to comply with these patent dance provisions gives the biologic manufacturer the right to bring a declaratory patent infringement action.24
In addition to these patent information exchanges, the biosimilar applicant "shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing" of the biosimilar.25 Upon receiving the notice, the biologic manufacturer may bring a preliminary injunction action against the biosimilar applicant.26 However, barring an injunction, once the biosimilar applicant's product is approved by the FDA, the applicant may begin marketing and selling its biosimilar.
These provisions of the BPCIA have proven to be fertile grounds for litigation between biologic producers and biosimilar applicants. Two issues in particular have been the subject of recent litigation: (1) the necessity of the patent dance, and (2) the necessity of the 180-day notice of commercial marketing.
III. Recent Litigation Involving the BPCIA's Patent Dance and Notice of Commercial Marketing
A. Amgen v. Sandoz District Court Litigation
In October 2014, Amgen filed suit against Sandoz for patent infringement, conversion, and unfair competition under California law for attempting to obtain marketing approval of a biosimilar version of Amgen 's Neupogen® (filgrastim), a biologic which helps stimulate the production of white blood cells for those undergoing cancer treatment.27 Amgen alleged that after Sandoz filed an aBLA for a biosimilar version of Neupogen,28 Sandoz "refused to provide Amgen with the [a]BLA and manufacturing information in a timely manner . . . and to otherwise comply with what the [BPCIA] requires them to do."29
Sandoz's lack of compliance included the tendering of a notice of commercial marketing on July 8, 2014, which Amgen considered premature and defective in light of Sandoz's failure to obtain FDA approval of its aBLA.30 Sandoz answered and asserted counterclaims for declaratory relief, stating that BPCIA 's patent dance and notice of commercial marketing were not mandatory and that the Neupogen patents were invalid and not infringed.
Amgen moved and Sandoz cross-moved for judgment on the BPCIA claims. Amgen argued that Sandoz 's failure to comply with the BPCIA 's disclosure and negotiation procedures and its premature issuance of a noncompliant notice each comprised unlawful practices for purposes of California's Unfair Competition Law. Amgen also argued that Sandoz 's use of Amgen 's FDA license for Neupogen in its aBLA without adhering to BPCIA 's patent dance procedures was an act of conversion.31 Further, Amgen-upon learning that Sandoz intended to launch its product on or around March 8, 2015-moved for preliminary injunction to stop Sandoz 's sale of its biosimilar product in the event it received FDA approval.32
In its cross motion, Sandoz argued that biosimilar applicants may elect not to provide their aBLA 's to the biologic manufacturer, subject to an infringement action provided under the statute. In addition, Sandoz argued that the 180-day notice is not predicated on FDA approval, and that, as a result, its notice was compliant. Sandoz also argued that the BPCIA does not permit actions for injunctive relief, restitution, or damages for the biosimilar 's failure to tender its aBLA, and that Amgen's state law claims were preempted by the BPCIA.33
The Court denied Amgen 's motions, finding Sandoz 's "overall interpretation of [BPCIA] 's plain language is more persuasive."34 Despite the repeated use of the word "shall" in patent dance and notice provisions, the Court found it did not imply a mandatory obligation on the part of the biosimilar applicant.
The Court held that subsection 262( l) of the BPCIA gives biosimilar applicants two options: (1) to engage in the patent dance; or (2) forgo it entirely and force the biologic manufacturer to sue for patent infringement. While compliance with subsection 262( l) 's patent dance provisions "allows the [biosimilar] applicant to preview which patents the reference product sponsor believes are valid and infringed, assess related factual and legal support, and exercise some control over which patents are litigated and when," a biosimilar applicant "who values expedience over risk mitigation may believe that the disclosure and negotiation process would introduce needless communications and delay. Such an applicant may have good reason to believe that no unexpired relevant patents relate to its biosimilar, and that it is likely to prevail if challenged with an infringement suit."35
Indeed, the Court found that Congress 's concurrent amending of the patent law via the BPCIA-codified as 35 U.S.C. § 271(e)-demonstrates that the exchanges are not per se mandatory. This provision of the patent law permits a biologics manufacturer to bring a patent infringement action in the event the biosimilar applicant fails to comply with the patent information exchanges.36
Similarly, the Court found that Sandoz was not required to wait until it receives FDA approval before sending the 180-day notice of commercial marketing to Amgen. The Court found that to read this provision as requiring otherwise would "tack an unconditional extra six months of market exclusivity onto the twelve years reference product sponsors already enjoy...."37 As a result, the Court found no basis to prevent Sandoz from marketing its biosimilar for failure to comply with BPCIA mandates. In fact, Amgen 's only option-even if Sandoz failed to give 180 days ' notice-would be to sue Sandoz for declaratory patent infringement.38
Because the Court found that Sandoz did not violate the mandates of the BPCIA, it dismissed the unfair competition law and conversion claims.
B. Federal Circuit Review of the BPCIA's Patent Dance and Notice Provisions
Amgen appealed the decision to the Federal Circuit, which granted the appeal on an expedited basis. On July 21, 2015, the Court issued an opinion (1) affirming the district court 's ruling that Sandoz was not required engage in the patent dance under the BPCIA, but (2) reversing on the issue of notice, holding that a biosimilar applicant cannot provide the 180-day notice of commercial marketing prior to receiving FDA approval of its aBLA.39
There was clear disagreement among the judges on the panel. The majority opinion was delivered by Judge Alan Lourie and supported by Judges Pauline Newman and Raymond Chen, albeit separately: Judge Newman provided the support for the holding that the 180-day notice period was mandatory; Judge Chen provided the support for holding that the patent dance was optional. In addition, both Judge Newman and Judge Chen wrote dissenting opinions, with Judge Newman disagreeing that the patent dance was optional, and Judge Chen disagreeing that it was mandatory to obtain FDA approval prior to issuing the 180-day notice.
1. The Majority Opinion: Split Decision for Both Amgen and Sandoz
With respect to the necessity of the patent dance procedures, the majority found that the despite the mandatory nature of the word "shall" in subsection 262( l)(2)(A), that provision cannot be read in isolation from the rest of the BPCIA.40 It reasoned that reading "shall" as "must" would render other BPCIA provisions meaningless.41 For example, the majority found that to read 262 ( l)(2)(A) as mandatory would make superfluous other BPCIA provisions that provide the biologic manufacturer a remedy in the form of a patent infringement lawsuit for a biosimilar applicant's failure to comply with subsection 262( l)(2)(A).42
Thus, the Court found that Sandoz did not violate the BPCIA for its failure to disclose its aBLA by the statutory deadline. Accordingly, the majority affirmed the district court 's dismissal of Amgen 's unfair competition law and conversion claims, each of which were predicated on this alleged violation of the BPCIA.43
But Sandoz was not so fortunate with respect to Amgen 's contention that Sandoz's notice was defective. On this point, the majority reversed the district court 's ruling that the BPCIA does not mandate a biosimilar applicant to wait until it receives FDA approval before giving the statutorily required notice of commercial marketing to the biologic manufacturer. Rather, the Court "agree[d] with Amgen that, under paragraph ( l)(8)(A), a [biosimilar] applicant may only give effective notice of commercial marketing after the FDA has licensed its product."44 It found that:
While it is true that only a licensed product may be commercially marketed, it does not follow that whenever the future commercial marketing of a yet-to-be licensed product is discussed, it is the "licensed" product. It is not yet "the licensed product" Congress could have used the phrase "the biological product that is the subject of" the application in paragraph ( l)(8)(A), as it did in other provisions, but it did not do so.45
The majority reasoned that this outcome is proper because it is only after FDA licensure-a process through which the FDA could require changes to the biosimilar product or approve for some, but not all, uses of it-that the biologic manufacturer can "effectively determine whether, and on which patents, to seek a preliminary injunction from the court."46
The majority further agreed with Amgen that holding the BPCIA to require actual FDA approval of an aBLA prior to disseminating notice of commercial marketing would not conflict with the 12-year exclusivity provided to biologics makers under the BPCIA. While conceding that Amgen would be afforded an additional 180 days of exclusivity under this interpretation of the BPCIA, the majority found that in most cases "aBLAs will often be filed during the 12-year exclusivity for other products."47 However, while the majority found Sandoz's July 8, 2014 notice defective, it found that Sandoz's notice after receipt of FDA approval was compliant. As a result, the majority only extended the injunction against Sandoz's sale of Zarxio to September 2, 2015.48
While the majority effectively split-the-baby with respect to the issues before it, two judges on the Federal Circuit believed that no splitting was necessary: Judge Newman believed that Sandoz should have lost on all grounds, while Judge Chen believed that Amgen should have lost on all grounds.
2. Judge Newman's Concurrence in Part and Dissent in Part: Victory to Amgen
Judge Newman took the position that the patent dance provisions of the BPCIA were mandatory, in light of Congress 's use of the word "shall" in subsection 262( l)(2). Reading subsections 262(k) and 262( l) as a cohesive unit, Judge Newman reasoned that the mandatory "shall" in subsection 262( l)(2)(A) governed the obligation of the biosimilar applicant with respect to the disclosure of its aBLA and manufacturing processes. To Judge Newman, the failure to include more permissive language was fatal because Congress knew how to, and, in fact, did include such language in other provisions of the BPCIA- e.g., in subsection 262( l)(2)(B), which states that a biosimilar applicant " may provide... additional information requested by...the reference product sponsor."49
Further, she found the majority 's reliance on the language of subsection 262( l)(9)(C)-which provides the biologic manufacturer a remedy in the event the biosimilar applicant fails to tender information required by 262( l)(2)(A), and thus supported the notion that 262( l)(2)(A) 's required disclosure to be permissive-misplaced because it only provides the biologic manufacturer a right of suit on declaratory patent infringement on "product" and "use" claims, as opposed to manufacturing-related patents, which appeared to be primarily at issue in the Amgen-Sandoz litigation.50
Therefore, even assuming that the majority 's view could be accepted-a view with which she did not agree-subsection 262( l)(2)(A) would still leave Amgen helpless in the face of Sandoz 's non-compliance. Accordingly, she deemed that compliance with the patent dance provisions was mandatory and unavoidable.
3. Judge Chen's Concurrence in Part and Dissent in Part: Victory to Sandoz
Judge Chen believed that total victory was in order as well, but to Sandoz. Judge Chen found that FDA approval of a biosimilar 's aBLA was not required prior to tendering the 180-day notice of commercial marketing, reasoning that just as the "shall" language in subsection 262( l)(2)(A) could not be read to mean "must," the "shall" language in subsection 262( l)(8)(A) should be read to be permissive as well.51
Finding that subsection 262( l) of the BPCIA "created a comprehensive, integrated litigation management system," Judge Chen concluded that "[r]ather than forcing the [biosimilar] applicant...to engage in the subsection ( l) process, or conditioning the [aBLA] 's approval on the [biosimilar] applicant fulfilling the requirements set forth in subsection ( l), Congress instead authorized the [reference product sponsor] in this situation to immediately file an infringement action."52
Turning to the 180-day notice of commercial marketing (subsection 262( l)(8)), Judge Chen reasoned that while 262( l)(8)(A) makes no reference to other provisions of 262( l), it cannot be divorced from 262( l)(8)(B), which does.53 Thus, to Judge Chen, the 180-day notice provision "is part and parcel to, and contingent upon, the preceding steps in ( l)(2)-( l )(8) litigation management regime."54
Judge Chen also takes the majority to task for justifying the mandatory nature of the 180-day notice because subsection 262( l)(9) lacks a remedial provision. To the contrary, Judge Chen believed there is a remedy: A patent infringement action under subsections 262( l)(9)(B) or (C)-the former in the event that biosimilar applicant complies with 262( l)(2) procedures, and the latter if the applicant does not.55
Lastly, Judge Chen found the implications of forced compliance with the 180-day notice provision to be contrary to congressional intent. To him, the majority 's reading of the provision would, in effect, create a Hatch-Waxman-like automatic stay.56 Judge Chen concluded "[i]f Congress intended to create a 180-day automatic stay it understood how to do so."57
Further, he found that accepting the majority 's position would potentially create scenarios in which certain applicants would be subjected to mandatory compliance with the 180-day notice, while others would not. For example, under the majority's ruling, biosimilar applicants who fail to comply with subsection 262( l)(2)-(7) requirements would be required to provide notice of commercial marketing upon FDA licensure and be subjected to a mandatory 180-day injunction. However, biosimilar applicants who do comply with these provisions would not be mandated to provide such notice because the biologic manufacturer would have a right to sue for patent infringement under subsection 262( l)(9)(B).58 Judge Chen found nothing in the BPCIA's structure or underlying purpose that would suggest Congress intended these two different outcomes when applying the law.
IV. IMPLICATIONS OF RECENT BPCIA RULINGS ON COMPETITION IN THE MARKET FOR BIOLOGICS
The Federal Circuit's decision provides some early insight and analysis as to the mandatory nature of the BPCIA's patent dance procedures. Amgen's holding that the patent dance is optional is a potential boon for competition in the biologics market because, as noted by the FTC, requiring "a pre-approval patent resolution process . . . is likely to lead to consumer harm, including the facilitation of anticompetitive conduct that defeats the purpose of starting patent litigation early."59 Following the Federal Circuit's ruling, Sandoz began marketing Zarxio on September 2, 2015, selling it at a 15 percent discount to Neupogen.60
However, Amgen II also held that the 180-day notice of commercial marketing was mandatory and could only be submitted upon receiving FDA approval of the biosimilar. This may have the effect of slowing entry of less expensive biosimilars into the market.
In any event, this decision may face further scrutiny. Both Amgen and Sandoz have requested en banc review of Amgen II, and several stakeholders have already submitted amici briefs in support of both Amgen and Sandoz61 On October 16, 2015, the Federal Circuit denied en banc proceedings, making certiorari review in the Supreme Court the only remaining appellate path.62
The Federal Circuit's opinion, however, is not a magnum opus on all aspects of the BPCIA. Several issues regarding the application of the BPCIA and its effects on the burgeoning market for biosimilars remain. First, as explained by Judge Chen in his dissenting opinion, under the majority's reasoning, the 180-day notice provision may not be mandatory for those biosimilar applicants who undertake some part of the patent dance. Instead, biologics manufacturers may have to sue for patent infringement and seek a court order enjoining the sale of the biosimilar's aBLA product. Whether the Federal Circuit will rule that the 180-day notice is mandatory under this scenario- i.e., compliance with some or all of the patent dance procedures-is uncertain, but the Court may have an opportunity to address this relatively soon.
On August 6, 2015, Amgen filed suit against Apotex for patent infringement and declaratory judgment for the biologic Neulasta® (pefilgrastim).63 According to Amgen's complaint, in December 2014, Apotex provided Amgen with notice that it had filed an aBLA for a Neulasta biosimilar. Amgen and Apotex began patent dance exchanges that same month. These exchanges continued through July 7, 2015. However, on April 17, 2015, Apotex issued a letter, purportedly serving as its notice of commercial marketing to Amgen-likely a decision made in light of the ruling in Amgen I just a few days earlier.64 Amgen moved for preliminary injunction, requesting an order requiring Apotex to provide Amgen with notice of FDA approval of Apotex's biosimilar and to refrain from marketing its biosimilar for 180 days after issuing a compliant notice of commercial marketing.
On December 9, 2015, the Neulasta Court granted Amgen's motion for preliminary injunction.65 While the Court acknowledged the issues raised in Judge Chen's dissent, it found that even when the biosimilar applicant engages in some portion of the patent dance, notice of commercial marketing is still mandatory and the biosimilar applicant can provide such notice only when it obtains FDA approval.66 Whether the majority that decided Amgen II will agree with this construction remains to be seen.
Second, the Federal Circuit in Amgen II had no opportunity to address the competitive effects of settlements arising from patent infringement actions triggered by the BPCIA. Amgen II did not address any aspect of the underlying patent infringement claims or counterclaims of invalidity and non-infringement. Indeed, the Federal Circuit remanded these issues to the district court.67
Undoubtedly, the patent litigation between Amgen and Sandoz will continue, and may at some point in the future result in a settlement. It remains to be seen whether a settlement in the context of biologics patent litigation will ultimately trigger the same competitive concerns that patent settlements in the Hatch-Waxman context have often triggered. There is good reason to believe they may.
There are aspects of the BPCIA that suggest such settlements could arise. Just as in the Hatch-Waxman Act, the first biosimilar applicant to file an aBLA receives a statutory grant of exclusivity that forbids the FDA from approving a subsequent aBLA. Thus, as has been observed in Hatch-Waxman cases, a biologic manufacturer could offer a biosimilar applicant valuable consideration-in the form of straight cash payment68 forgiveness of contingent liability,69 co-promotion and other side deals,70 or licenses to other biological or pharmaceutical products71 in exchange for dropping its patent challenge and agreeing to delay entry into the market.
Biologics manufacturers, like brand drug manufacturers, have every incentive to protect the exclusionary rights conferred to them by their patents, so a payment to a biosimilar manufacturer to delay entry may well be worth avoiding the prospect of impending competition. Thus, so long as these elements exist, there is always the potential that biologic and biosimilar manufacturers will enter agreements that may restrict competition for particular biologic products.
V. CONCLUSION
As biologic and biosimilar manufacturers continue to navigate the scope of the BPCIA, more litigation is inevitable.72 Patent litigation arising from the BPCIA will likely lead to settlements, which in turn may spawn additional litigation regarding those settlements' competitive effects on the biologics market. Courts will ultimately be asked to resolve these issues and, in doing so, they will likely borrow from existing case law concerning Hatch-Waxman settlements to guide their decisions. Further, industry stakeholders, the FDA, and FTC will also continue adding their input on these competitive issues as more biosimilar applicants trigger the application of the BPCIA.
[1] Food & Drug Administration ("FDA"), What Are "Biologics" Questions and Answers, (Aug. 8, 2015), http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm133077.htm.
[2] 42 U.S.C. § 262(k)(7)(A). The BPCIA, Pub. L. No. 111-148, 124 Stat. 804 (2010), was enacted as part of the Patient Protection and Affordable Care Act and amended the Public Health Services Act, 42 U.S.C. §§ 201, et seq.
[3] Amgen Inc. v. Sandoz Inc., 794 F.3d 1347, 1351 n.1 (Fed. Cir. 2015) (" Amgen II")(quoting Winston Churchill , The Russian Enigma (BBC radio broadcast Oct. 1, 1939), http://www.churchill-societylondon.org.uk/RusnEnig.html).
[4] Data Supplied by the U.S. Department of Justice, Pub. L. No. 98-417, 98 Stat. 1585 (1984).
[5] 42 U.S.C. § 262(i)(2)(A)-(B).
[6] Interchangeability means that the "biological product may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product." 42 U.S.C. § 262(i)(3). The FDA publishes a list of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations, known as the "Purple Book."
[7] Federal Trade Comm'n, Emerging Health Care Issues: Follow-On Biologic Drug Competition; A Federal Trade Commission Report 47, 53 (June 2009) ("FTC Report"), https://www.ftc.gov/reports/emerging-health-care-issues-follow-biologic-drug-competition-federal-trade-commission-report (anticipating biosimilar pricing to be between 10-30 percent lower than pioneer biologics).
[8] See Sumant Ramachandra, Senior V.P., Hospira, Presentation, Lessons for the United States: Biosimilar Market Development Worldwide (Feb. 4, 2014), https://www.ftc.gov/news-events/events-calendar/2014/02/follow-biologics-workshop-impact-recent-legislative-regulatory, then follow Event Speakers. In Europe, where several countries have passed legislation permitting the licensing of biosimilars, the entry of biosimilars has had a positive competitive impact on the prices of biologic products. For example, brand manufacturers of a first-generation EPO biologic product reduced their prices by about 15 percent upon market entry of biosimilars, with the biosimilars themselves being sold at a 25 percent discount. See Remarks of Paul Heldman, Senior Health Policy Analyst with Potomac Research Group, FTC Roundtable on Follow-on Biologic Drugs: Framework for Competition and Continued Innovation, Tr. at 27 (Nov. 21, 2008), https://www.ftc.gov/sites/default/files/documents/publicevents/emerging_health_care_competition_and_consumer_issu
[9] See, e.g., Del. S. 118, Ch. 238 (signed May 28, 2014); Fla. H.R. 365, Ch. 2013-102 (signed Jun. 3, 2013); Ind. S. 262, Ch. 96 (signed Mar. 31, 2014); Mass. H.R. 3734, Ch. 143 (signed Jun. 23, 2014); N.D. S. 2190, Ch. 181 (signed Jun. 25, 2013); Or. S. 460, Ch. 342 (signed Jun. 6, 2013); Utah S. 78, Ch. 423 (signed Apr. 26, 2013); Va. H.R., Ch. 412 (signed Mar. 16, 2013); Va. S. 1285, Ch. 544 (signed Mar. 18, 2013). Other states have legislation pending. See National Conference of State Legislatures, State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars (Nov. 9, 2015), http://www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx#2013-14.
[10] The first cases involving the BPCIA were declaratory judgment actions brought by prospective biosimilar applicants. The courts dismissed these actions as premature in light of the fact that none of the biosimilar applicants bringing suit had submitted applications for FDA approval of their biosimilar products. See Sandoz Inc. v. Amgen Inc., No. C-13-2904, 2013 WL 6000069 (N.D. Cal. Nov. 12, 2013), aff'd, 773 F.3d 1274 (Fed. Cir. 2014); Hospira, Inc. v. Janssen Biotech, Inc., No. 14-cv-7049, 2014 WL 6766263 (S.D.N.Y. Dec. 1, 2014); Celltrion Healthcare Co., Ltd. v. Kennedy Tr. for Rheumatology Research, No. 14-cv-2256, 2014 WL 6765996 (S.D.N.Y. Dec. 1, 2014).
[11] 42 U.S.C. § 262(k)(2)(A)(i).
[12] See FTC Report at 70-71.
[13] Id. at 71. The FTC also noted that the inclusion of a marketing exclusivity provision "will inevitably generate lawsuits against the FDA regarding award, timing, scope, and termination of the marketing exclusivity periods has occurred regarding the 180-day provision of the Hatch-Waxman Amendments." Id. at 71-72. This may be particularly acute with the BPCIA, where exclusivities vary depending on the circumstances. See 42 U.S.C. § 262(k)(6).
[14] 42 U.S.C. § 262(k)(6)(A)-(C). A final court decision means "a final decision of a court from which no appeal (other than a petition to the United States Supreme Court for a writ of certiorari) has been or can be taken." Id.
[15] See Amanda Potter, Interpreting the BPCIA - Is the " Patent Dance " Mandatory? , Colum. Sci. & Tech. L. Rev. Blog, (Mar. 31, 2015), http://stlr.org/2015/03/31/interpreting-the-bpcia-is-the-patent-dance-mandatory/.
[16] 42 U.S.C. § 262( l)(2).
[17] 42 U.S.C. § 262( l)(9)(C); 35 U.S.C. § 271(e)(2)(C)(ii) (action for patent infringement for failing to provide aBLA).
[18] 42 U.S.C. § 262( l)(3)(A)(i)-(ii).
[19] 42 U.S.C. § 262( l)(3)(B)(i)-(ii).
[20] 42 U.S.C. § 262( l)(3)(C).
[21] 42 U.S.C. § 262( l)(4).
[22] 42 U.S.C. § 262( l)(5).
[23] 42 U.S.C. § 262( l)(6). See also 35 U.S.C. § 271(e)(2)(C)(i) (action for infringement for listed patents that are the subject of an aBLA).
[24] 42 U.S.C. § 262( l)(9(B).
[25] 42 U.S.C. § 262( l)(8)(A).
[26] 42 U.S.C. § 262( l)(8)(B).
[27] Compl. at ¶ 2, Amgen Inc. v. Sandoz Inc., No. 14-cv-4741 (N.D. Cal., Oct. 24, 2014) (" Amgen I Compl. ").
[28] Sandoz's biosimilar was to be marketed under the trade name "Zarxio." The FDA approved Zarxio on March 6, 2015, as the first-and, to date, the only-biosimilar product approved in the United States. See Press Release, FDA, FDA approves first biosimilar product Zarxio (Mar. 6, 2015), http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm.
[29] Amgen I Compl. at ¶ 6.
[30]Although Sandoz maintained that the July 8, 2014 notice was effective under the BPCIA, upon receiving FDA approval for Zarxio, Sandoz provided "further notice of commercial marketing" to Amgen.
[31] Amgen Inc. v. Sandoz Inc., No. 14-cv-4741, 2015 WL 1264756, at *4 (N.D. Cal. Mar. 19, 2015) (Seeborg, J.) (" Amgen I"), aff'd in part, vacated in part, 794 F.3d 1347 (Fed. Cir. 2015).
[32] Sandoz and Amgen entered into a stipulation whereby Sandoz agreed not to launch its product until the earlier of either a partial judgment on the pleadings in its favor, or April 10, 2015. See id. at *1 n.3.
[33] Id . at *4.
[34] Id. at *6.
[35] Id. at *7.
[36] Id. at *6-7.
[37] Id. at *8.
[38] Id. at *8 n.8 (citing 42 U.S.C. § 262( l)(9)(B)).
[39] See Amgen II.
[40] Amgen II, 794 F.3d at 1355.
[41] Id. at 1356.
[42] Id. at 1356 (referring to 42 U.S.C. § 262( l)(9)(C) and 35 U.S.C. § 271(e)(2)(C)(ii)) .
[43] Id. at 1360-61.
[44] Id. at 1357 (emphasis added).
[45] Id. at 1357-58.
[46] Id. at 1358.
[47] Id. The Court found the facts in the Amgen case to be " untypical" because Sandoz's aBLA was filed more than 12 years after Amgen received FDA approval of Neupogen.
[48] Id. at 1360. As explained above, Amgen based part of its unfair competition law claim on Sandoz's defective notice of commercial marketing. However, the Court deemed Amgen's appeal on this basis moot because it had already enjoined Sandoz's sale of Zarxio until September 2, 2015. Id. at 1361.
[49] Id. at 1365 (Newman, J., dissenting in part, concurring in part).
[50] Id. at 1366.
[51] Id. at 1367.
[52] Id. at 1368.
[53] Id. at 1369-70.
[54] Id. at 1370.
[55] Id.
[56] Id. at 1370-71.
[57] Id. Cf. id. at 1358 (majority holding the 180-day marketing provision was mandatory because "Congress could have used the phrase 'the biological product that is the subject of ' the application in paragraph ( l)(8)(A), as it did in other provisions, but it did not do so.").
[58] Id.
[59] FTC Report at 48. Notably, the Biotechnology Industry Organization ("BIO"), a trade group representing biologics manufacturers, found the FTC's objection to pre-approval patent resolution procedures of the BPCIA to be "fundamentally flawed" because "without it, biosimilars 'would systematically have to enter the market under a cloud of patent uncertainty,' resulting in confusion 'about the long-term availability' of particular biosimilars." Krista Hessler Carver, et al., An Unofficial Legislative History of the Biologics Price Competition and Innovation Act of 2009, 65 Food & Drug L.J. 671, 790 (2010) (quoting BIO, FTC Biosimilars Rebuttal, at 1 (2009)).
[60] See Ben Hirschler & Michael Shields, Novartis Launches First U.S. 'Biosimilar' Drug at 15 Percent Discount, Reuters (Sept. 3, 2015), http://tinyurl.com/oelnjsg. Amgen petitioned the Federal Circuit to continue the injunction during the pendency of the en banc review, but the Federal Circuit denied the request. See Amgen Inc. v. Sandoz Inc., No. 2015-1499, slip op. (Fed. Cir. Sept. 2, 2015) ( per curiam); See also Aron Fischer, Both Parties Seek En Banc Intervention in Amgen v. Sandoz, Biologics Blog (Aug. 28, 2015), http://www.biologicsblog.com/blog/both-parties-seek-en-banc-intervention-in-amgen-v-sandoz/.
[61] Biosimilar manufacturers Celltrion Inc., Hospira Inc., and Mylan, Inc. and a biosimilar trade association, the Biosimilars Council, have filed amici curiae in support of Sandoz. Janssen Biotech, Inc., who is embroiled in litigation with Celltrion over its biologic Remicade®, has filed an amicus in favor of Amgen. See Kurt R. Karst, Multiple Parties Chime in as the Federal Circuit Gears Up for a Rehearing in the ZARXIO Biosimilar Patent Dance/180-Day Notice Appeal, FDA Law Blog (Sept. 9, 2015), http://t.co/TUUyXbiBcC.
[62] Amgen Inc. v. Sandoz Inc., No. 2015-1499, slip op. (Fed. Cir. Oct. 16, 2015).
[63] See Compl., Amgen Inc. v. Apotex Inc., No. 15-cv-61631 (S.D. Fla. Aug. 6, 2015) (" Amgen Neulasta Compl."). See also James C. Shehan, You're Better Than My Last Dance Partner But Still Not Perfect: Amgen Alleges that an Otherwise Complete Patent Dance Was Ruined by Pre-Approval Notice of Marketing, FDA Law Blog (Aug. 17, 2015), http://tinyurl.com/o384o5d.
[64] See Amgen Neulasta Compl. at ¶¶ 44-51.
[65] Amgen Inc. v. Apotex Inc., No. 15-cv-61631, slip op. (S.D. Fla. Dec. 9, 2015).
[66] Id. at 5.
[67] Amgen II, 794 F.3d at 1362 .
[68] See, e.g., In re Cardizem CD Antitrust Litig., 105 F. Supp. 2d 618, 623 (E.D. Mich. 2000) (brand paid generic $40 million per year in exchange for generic's promise not (1) to launch until an agreed upon entry date or (2) assign its first-filer exclusivity to another company), aff'd, 332 F.3d 896 (6th Cir. 2003); In re Ciprofloxacin Hydrochloride Antitrust Litig., 363 F. Supp. 2d 514, 519 (E.D.N.Y. 2005) (cash payment of $398 million over six years from Bayer to prospective generic competitors), aff'd in part, 544 F.3d 1323 (Fed. Cir. 2008).
[69] See In re Nexium (Esomerprazole) Antitrust Litig., 968 F. Supp. 2d 367 (D. Mass. 2013) (brand's forgiveness of contingent liability of a generic competitor).
[70] See Federal Trade Commission v. Actavis, Inc., 133 S. Ct. 2223 (2013) (co-promotion agreement between brand and generic companies).
[71] See In re Nexium (Esomerprazole) Antitrust Litig., 42 F. Supp. 3d 231 (D. Mass. 2014) (payment in the form of authorized generic distribution agreements for drugs unrelated to drug that the primary subject of the reverse payment); Compl., Federal Trade Commission v. AbbVie Inc., No. 14-cv-5151 (E.D. Pa., filed Sept. 8, 2014) (alleging that AbbVie gave Teva access to Tricor intellectual property in exchange for delaying entry on Androgel).
[72] In addition to the Neulasta action, see supra note 64, Amgen filed suit against Hospira over Hospira's aBLA for a biosimilar version of Epogen®, a biologic used to treat anemia caused by chronic kidney disease. See Compl., Amgen Inc. v. Hospira, Inc., No. 1:15-cv-839 (D. Del., Sept. 18, 2015). Amgen alleges that Hospira failed to produce information Amgen requested under the patent dance procedures and that Hospira issued ineffective notice of commercial marketing. See also Kurt R. Karst, Amgen Wants Patent Dance Redo and a Halt to Hospira's EPOGEN Biosimilar, FDA Law Blog (Sept. 24, 2015), http://t.co/CsK0p9HbCl.
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