Introduction and Background

The Apotex filgrastim/pegfilgrastim biosimilar litigation was the first biosimilar litigation where the parties participated in the patent dance.  As a result, important issues regarding the interpretation of the Biologics Price Competition and Innovation Act (the “BPCIA”) were raised, including whether a biosimilar applicant (“(k) applicant”) must give 180-days’ notice to the reference product sponsor (“RPS”) before its first commercial marketing in accordance with 42 U.S.C. § 262(l)(8)(A).  The district court (Southern District of Florida) and the Federal Circuit both concluded that such notice was mandatory even when the (k) applicant participates in the patent dance.

Filgrastim and pegfilgrastim have been some of the most-targeted biologics for biosimilars to date.  Sandoz’s Zarxio® (filgrastim) was the first biosimilar approved by FDA, and several applications for pegfilgrastim biosimilars are currently under review by FDA, including at least applications filed by Sandoz, Coherus, and Mylan, in addition to Apotex.

Neupogen® (filgrastim) is indicated to:  (1) decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever; (2) reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia; (3) reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation; (4) mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis; and (5) reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia. Neulasta® (pegfilgrastim) is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Apotex seeks to market and sell its filgrastim product under the name GrastofilTM.  Its BLA was accepted by FDA on February 13, 2015.  Apotex seeks to market and sell its pegfilgrastim product under the name LapelgaTM, and that BLA was accepted by FDA in December 2014.  Neither application has yet been approved.

Litigation:  Round 1 (BPCIA Interpretation)

District Court

On August 6, 2015, Amgen filed its Complaint for patent infringement regarding Apotex’s pegfilgrastim BLA in the Southern District of Florida alleging infringement of two patents, U.S. Patent Nos. 8,952,138 (“the ’138 Patent”) and 5,824,784 (“the ’784 Patent”), and the case was assigned to Judge Cohn (Civil Action No. 15-cv-61631).  According to the Complaint, the inclusion of the ’138 and ’784 Patents is the result of the parties’ participation in the patent dance.  In its October 5, 2015 Answer, Apotex sought not only a declaration of non-infringement and invalidity of the ’138 Patent, but it also asserted that Amgen violated the Sherman Act.  Apotex asserted that Amgen engaged in sham litigation because Apotex told Amgen during the patent dance that it would not begin commercial marketing prior to the expiration date of the ’784 Patent (which expired October 20, 2015) as well as the ’933 Patent (which was not included in the action and was also expired).  Apotex also alleged that it provided irrefutable proof that it would not infringe the ’138 Patent during the patent dance.  Similarly, Apotex included a patent misuse counterclaim—alleging that the litigation was filed to delay Apotex’s market entry—stating that Amgen failed to carry out a good faith investigation based on Apotex’s BLA documents.  Most important to BPCIA interpretation issues, Apotex also sought a declaration that an RPS’s remedy against a (k) applicant that participates in the patent dance but elects not to provide notice of commercial marketing under section (8)(A) is a declaratory judgment suit pursuant to section (9)(B), and not an injunction.

On October 2, 2015, Amgen filed a separate Complaint for patent infringement regarding Apotex’s filgrastim BLA in the same court (Civil Action No. 15-cv-62081).  Apotex again alleged infringement of the ’138 Patent and also asserted infringement of U.S. Patent No. 6,162,427 (“the ’427 Patent”).   The two cases were consolidated in November 2015.

Shortly thereafter, Amgen moved for a preliminary injunction (October 16, 2015), and a hearing was held on December 7, 2015.  The only dispute was the likelihood of success on the merits regarding whether a (k) applicant must give 180-days’ notice before commercial marketing.  The district court granted the preliminary injunction on December 9, 2015.  It relied heavily on the Federal Circuit’s decision in Amgen v. Sandoz, which explains that “the word ‘shall’ in the context of § 262(l)(8)(A) does mean ‘mandatory.’”  Amgen, Inc. v. Apotex Inc., No. 15-cv-61631, 2015 U.S. Dist. LEXIS 183036, at *11 (S.D. Fla. Dec. 9, 2015) (citation omitted).  The district court recognized, however, that because Sandoz did not participate in the patent dance, the Federal Circuit had not directly addressed whether the (8)(A) notice of commercial marketing is also required for a (k) applicant that participates in the patent dance.  Id.  The district court concluded that there is no basis to treat the two applicants differently stating:  “Nothing in the statute or the Sandoz decision leads to or supports such a result; neither the statute nor the Sandoz decision condition the 180 day notice provision of section 262(l)(8)(A) upon a subsection (k) applicant’s compliance with § 262(l)(2).”  Id. at *12.  The district court also countered Apotex’s argument that such a result would give the RPS an extra 180 days of exclusivity by relying on the Federal Circuit’s statement in Amgen v. Sandoz, and that this would not be the “usual case” as applications begin to be filed during the 12-year exclusivity period.[1]  Id. at *13.  In addition, the district court found no basis for a section (l)(9) declaratory judgment action to be the exclusive remedy for failure to comply with the notice of commercial marketing provision.  The district court enjoined Apotex from any commercial marketing until it provided Amgen with notice after FDA licensure and at least 180 days before its first commercial marketing.

Apotex appealed the preliminary injunction on December 10, 2015.

The Federal Circuit Appeal

On July 5, 2016, the Federal Circuit affirmed the district court’s holding that the commercial-marketing provision is mandatory and enforceable by injunction even for (k) applicants that participate in the patent dance.  Amgen Inc. v. Apotex Inc., 827 F.3d 1052 (Fed. Cir. 2016). The Federal Circuit panel was Taranto (opinion author), Wallach, and Bryson, and Apotex’s appeal of the preliminary injunction is Appeal No. 16-1308.

Relying on its Amgen v. Sandoz decision, the Federal Circuit explained that “the notice starting the 180-day clock must follow, not precede, the licensure.”  Id. at 1056.  It reiterated its statements from Amgen v. Sandoz, that the (8)(A) notice requirement is “a standalone notice provision.”  Id. at 1059.  However, given the difference between the two cases, i.e., that Sandoz had not participated in the patent dance whereas Apotex had participated, the Federal Circuit further explained that the notice provision “contains no words that make the applicability of its notice rule turn on whether the applicant took the earlier step of giving the (2)(A) notice that begins the § 262(l) information-exchange process.”  Id. at 1061.  It further concluded that, unlike with (2)(A)’s use of “shall” to initiate the patent dance, there was no statutory basis to give the use of “shall” in the notice provision any meaning other than its usual mandatory meaning.  Id.

The Federal Circuit also made two observations to rebut Apotex’s argument that (8)(A) was not intended to extend the 12-year exclusivity period by an additional 180 days.  First, it relied on its reasoning from Amgen v. Sandoz that delay beyond 12 years will occur less as time goes by and that (k) applicants can seek approval before the 12-year exclusivity period has expired.  Id. at 1061-62.  Second, and perhaps as further explanation for its first point, it stated that “we have been pointed to no reason that the FDA may not issue a license before the 11.5-year mark and deem the license to take effect on the 12-year date—a possibility suggested by § 262(k)(7)(A)’s language about when the FDA approval may ‘be made effective.’”  Id. at 1062.  It explained that (8)(A) would allow “the 180-day notice of commercial marketing to be sent as soon as the license issues, even if it is not yet effective, because it is at the time of the license that ‘the product, its therapeutic uses, and its manufacturing processes are fixed.’”  Id. (citation omitted).

The Federal Circuit also rejected Apotex’s final argument that a declaratory judgment action pursuant to (9)(B) is the exclusive remedy for violating (8)(A).  It found no such exclusivity in the statute, specifically noting that other remedies were not excluded.  Id. at 1064.  It also relied on the monetary and injunctive relief provided by 35 U.S.C. § 271(e)(4) as support for its position that a declaratory judgment action is not intended as the exclusive remedy for (8)(A) violations.  Id.  The Federal Circuit further relied on what it viewed as the likelihood that an RPS would not know “that the applicant will fail to provide the actual 180-day commercial-marketing notice required by (8)(A) until the applicant begins commercial marketing or, at least, declares that it may begin such marketing at any moment.”  Id. at 1065.  It stated that such late notice would result in precisely the rushed decision-making that (8)(A) was designed to prevent.  Id.

The Supreme Court Declines Review

Apotex petitioned for a writ of certiorari of the Federal Circuit’s decision in Case No. 16-1308, which was filed on September 9, 2016.  Two questions were presented:

  1. Whether the Federal Circuit erred in holding that biosimilar applicants that make all disclosures necessary under the BPCIA for the resolution of patent disputes (viz. 42 U.S.C. § 262(l)(2)(A)) must also provide the RPS with a notice of commercial marketing under 42 U.S.C. § 262(l)(8)(A).
  2. Whether the Federal Circuit improperly extended the statutory 12-year exclusivity period to 12 1/2 years by holding that a biosimilar applicant cannot give effective notice of commercial marketing under 42 U.S.C. § 262(l)(8)(A) for its biosimilar product until it receives an FDA license and therefore may not commercially market its biosimilar product for 180 days after receiving its license.

The Biosimilars Council and Mylan Pharmaceuticals filed amici curiae briefs in support of Apotex’s petition on October 14, 2016.  Amgen filed its opposition brief on November 8, 2016.

The Supreme Court denied Apotex’s petition on December 12, 2016.[2]

Litigation:  Round 2 (Infringement and Invalidity)

District Court

On December 11, 2015, two days after the district court granted Amgen’s preliminary injunction, the parties began claim construction briefing in the consolidated action.  The claim construction hearing was held on February 5, 2016, and the district court issued its claim construction order on April 7, 2016.

The parties also filed two separate joint stipulations of dismissal on May 31, 2016.  The first sought dismissal (without prejudice) of Apotex’s Sherman Act counterclaim.  The second sought dismissal (without prejudice) of all claims and counterclaims related to the ’427 and ’784 patents.  The district court granted both on June 14, 2016.

A bench trial was held July 11-15 and 18, 2016.  On July 14, 2016, and at the conclusion of Apotex’s presentation of evidence, the district court entered partial findings that the ’138 Patent was not anticipated, did not lack adequate written description, was not indefinite, and was not obvious.[3]

On September 6, 2016, the district court issued its decision finding that Apotex did not infringe the ’138 Patent.  The district court found that Amgen had not established that Apotex’s process had:  “(1) a ‘high protein concentration’ at or above about 1 g/L; and (2) a redox component having a redox buffer strength of 2 to 100 mM.” Dkt. No. 267 at 10.  The district court noted that with respect to the first point, Amgen had only alleged literal infringement and not infringement under the doctrine of equivalents, and that Apotex’s refold mixture was well below “at or above about 1 g/L.”  Id. at 10-11.  For the second point, even though Amgen alleged infringement under the doctrine of equivalents and even assuming that “the combination of Apotex’s Cysteine and Cystine Solutions in a hypothetical volume” satisfied the hypothetical redox component, the district court found that the redox buffer strength would be from 214 to 340 mM with a volume two to three times greater than the hypothetical redox component.  Id. at 17-18.  In other words, “Apotex’s process uses a smaller volume of more concentrated redox component than is claimed in the ’138 Patent to achieve its desired redox conditions.”  Id. at 18.  Given its non-infringement finding, the district court declined to rule on invalidity for lack of enablement and dismissed that counterclaim without prejudice.  Id. at 28.  The district court also declined to award attorneys’ fees.  Id. at 29.

Amgen appealed the non-infringement decision on October 3, 2016.

Appeal of Non-Infringement Decision to the Federal Circuit

Amgen appealed the district court’s non-infringement decision in Appeal No. 17-1010.  Briefing was complete on February 2, 2017, but oral argument has not been scheduled for upcoming court dates through June 2017.

Therefore, at this time, the only remaining issue in the Apotex action is the decision on appeal of infringement.  Because the ’138 Patent was asserted in both Apotex actions, the decision will impact the future of its filgrastim and pegfilgrastim products.  It remains to be seen what impact the Supreme Court’s decision in Sandoz v. Amgen will have on the Apotex case because Apotex participated in the patent dance.  However, the Supreme Court’s decision will likely impact at least the notice of commercial marketing issue in Apotex.

***

[1] This statement by the Federal Circuit has been subject to substantial scrutiny and was addressed in briefing and at oral argument before the Supreme Court in Sandoz Inc. v. Amgen Inc. (Nos. 15-1039, 15-1195).

[2] As indicated above, however, the Supreme Court granted certiorari in Sandoz Inc. v. Amgen Inc., which also addressed the notice of commercial marketing issue.

[3] Apotex filed a petition for Inter Partes Review of the ’138 Patent on August 5, 2016.  The IPR was instituted on February 17, 2017.

The battle over the proper forum for patent infringement litigation regarding Dupixent® (Dupilumab) appears to have been resolved.  Last week, on May 1, 2017, Sanofi, Genzyme, and Regeneron voluntarily dismissed their Declaratory Judgment Complaint in the District of Massachusetts (Civ. No. 17-cv-10465).  The dismissal, however, does not resolve the underlying patent infringement dispute, which is still the subject of a separate pending litigation in the Central District of California (Civ. No.  17-cv-01623).  Nor does the dismissal resolve the substantive dispute over patent validity, which is the subject of an IPR petition pending at the PTAB (IPR2017-01129).

The dispute began on March 20, 2017, when Sanofi-Aventis U.S. LLC, Genzyme Corporation, and Regeneron Pharmaceuticals, Inc. filed a Complaint against Amgen, Inc. and Immunex Corp. in the United States District Court for the District of Massachusetts seeking a declaratory judgment that their Dupixent® (dupilumab) does not infringe U.S. Patent No. 8,679,487 (“the ’487 patent”) as we reported in this post.  Just a few days later, Sanofi, Genzyme, and Regeneron file a petition for inter partes review of the ’487 patent, as discussed here.  At that time, Dupixent® had not yet been approved, but Regeneron and Sanofi announced that the FDA had granted final approval to the product on March 28, 2017.

The following week, on April 5, 2017, Immunex filed  a separate Complaint in the United States District Court for the Central District of California alleging infringement of the ’487 patent.  Then, on April 11, 2017, Immunex filed a motion to dismiss the Massachusetts case or to transfer the case to California, setting up a battle over the litigation forum, as we reported in this post.   Meanwhile, in the California case, on April 19, 2017, the parties filed a joint stipulation extending Sanofi, Genzyme, and Regeneron’s time to file an Answer from May 5, 2017 to May 26, 2017.

Rather than file an opposition to the motion to dismiss, Sanofi, Genzyme, and Regeneron filed an Amended Complaint in the Massachusetts case on April 24, 2017.  The Amended Complaint set forth additional facts in support of personal and subject matter jurisdiction in the Massachusetts Court.  The following day, on April 25, 2017, Judge Gorton entered an Order in the Massachusetts case denying Immunex’s motion to dismiss or transfer as moot (in view of the Amended Complaint).  A discussion of the Plaintiffs’ reasons for dismissing the suit after having defeated the initial motion to dismiss or transfer would be speculation.

The time for Sanofi, Genzyme, and Regeneron to Answer or otherwise respond to the Complaint in the California district court litigation is still a few weeks away, and a scheduling order has not yet been entered.  However, given that there is only one patent at issue in the litigation, and that same patent is the subject of a petition for IPR, it is possible that the district court litigation will be stayed if the IPR proceeding is instituted.  Immunex’s preliminary response in the IPR petition is currently due no later than July 6, 2017, and the PTAB should issue a decision on institution three months later, in early October of this year.  Stay tuned for future developments.

Over the last two weeks, Pfizer, Inc. (“Pfizer”) has filed petitions for inter partes review (“IPR”) of three additional patents related to Biogen and Genentech’s Rituxan® (rituximab) at the Patent Trial and Appeal Board (“PTAB”).  The proceedings are: IPR2017-01166, filed on April 21, 2017, regarding U.S. Patent No. 8,329,172 (“the ’172 patent”); IPR2017-1167, filed on April 27, 2017, regarding U.S. Patent No. 8,557,244 (“the ’244 patent”); and IPR 2017-1168, filed on April 28, 2017, regarding U.S. Patent No. 8,821,873 (“the ’873 patent”). Biogen is identified as the Patent Owner and Pfizer, Inc. is the sole real party-in-interest identified for Petitioner in all three petitions.

Rituximab is an anti-CD20 monoclonal antibody approved for the treatment of non-Hodgkin’s lymphoma, chronic lyphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangitis, and microscopic polyangitis.  Pfizer announced in January 2017 that its proposed biosimilar rituximab (PF 05280586) is in Phase 3 development.

The sole claim of the ’172 patent is directed to a method of treating low-grade B-cell non-Hodgkin’s lymphoma (“NHL”) by administering a well-known chemotherapy regimen of cyclophosphamide, vincristine, and prednisone (“CVP”), followed by rituximab maintenance therapy administered in four weekly doses of 375 mg/m2 every six months for two years.  The ’244 patent has two claims.  Claim 1 of the ’244 patent is directed to a method of treating a patient with diffuse large cell lymphoma (a subset of NHL) by administering a combination of an unlabeled chimeric anti-CD20 antibody and chemotherapy, the chemotherapy consisting of cyclophosphamide, hydroxydaunorubicin/doxorubicin, vincristine, and prednisone/prednisolone (“CHOP”).  The treatment claimed in the ’244 patent is specific to a patient who is greater than 60 years old, has bulky disease, and has a tumor greater than 10 cm in diameter. Claim 2 of the ’244 patent further limits the chimeric anti-CD20 antibody to rituximab.  The ’873 patent has five claims that are generally directed to methods of treating a patient with diffuse large cell lymphoma by administering a combination of an anti-CD20 antibody and CHOP chemotherapy, whereby the antibody is administered to the patient in combination with a stem cell transplantation regimen. The treatment claimed in the ’873 patent is also specific to a patient who is greater than 60 years old, and claim 3 of the ’873 specifically limits the anti-CD20 antibody to rituximab.

Earlier this year, Pfizer filed a petition with the PTAB for IPR of U.S. Patent No. 7,820,161 (“the ’161 patent”), which is also related to Biogen and Genentech’s Rituxan® (rituximab), as we reported in this post.  Prior to the filing of that petition, in February 2017, the PTAB instituted an IPR for certain claims of the ’161 patent on a petition filed by Celltrion (as we reported here), and Pfizer has requested that its petition be joined with that proceeding.  Celltrion currently has petitions pending for review of three other patents related to rituximab as reported here, and the PTAB denied Celltrion’s petition related to U.S. Patent No. 7,976,838 as reported here.  Boehringer Ingelheim and Celltrion had previously filed petitions at the PTAB for patents related to this same product that were voluntarily dismissed in 2015.

A complete list of IPRs related to rituximab and other proposed biosimilars can be found in RFEM’s IPR Dashboard.  We will continue to provide updates as these cases progress.

Celltrion announced last week that it has submitted an application for approval of Herzuma, its proposed trastuzumab biosimilar (CT-P6), in Japan.  Trastuzumab is a monoclonal antibody indicated for the treatment of patients with metastactic breast cancer whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens.  Celltrion’s Herzuma (trastuzumab) is a biosimilar to Roche/Genentech’s Herceptin®.   According to the announcement, the application was submitted on April 11, 2017, and once approved, Herzuma will be marketed and distributed in Japan by Nippon Kayaku, pursuant to an agreement with Celltrion.  Celltrion’s Remsima, an infliximab biosimilar, is already approved in Japan.

Celltrion’s Truxima (rituximab) was approved in Europe on February 22, 2017, as we reported here, and the Company also announced last week that it has now officially launched the product in Europe, making actual sales in the UK.  Rituximab is an anti-CD20 monoclonal antibody approved for the treatment of non-Hodgkin’s lymphoma, chronic lyphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangitis, and microscopic polyangitis. Truxima, a biosimilar to Biogen and Roche/Genentech’s Rituxan®, was the first biosimilar product for the treatment of cancer approved in Europe.  Truxima was also approved in South Korea in November 2016.

The company has stated that it plans to submit applications for Herzuma and Truxima to the FDA during the first half of 2017.

The Supreme Court heard oral arguments on Wednesday in its first biosimilar case.  On a petition filed in Sandoz, Inc. v. Amgen, Inc., et al. No. Case No. 2015-1039, and a cross-petition filed in Amgen Inc., et al. v. Sandoz, Inc., Case No. 2015-1195, the Court was asked to interpret two provisions of the Biologics Price Competition and Innovation Act (“BPCIA”).  Parties submitting amici briefs are discussed in this earlier post.  A transcript of the oral argument is available here, and an audio recording of the oral argument will be available after conferences this afternoon here on the Supreme Court’s website.

The questions presented to the Court, as discussed in detail in our prior article, are: (1) whether a biosimilar applicant is required by the term “shall” in section (l)(2)(A) of the statute to provide the reference product sponsor with a copy of its biologics license application and related manufacturing information, and if the applicant fails to provide that information, whether a declaratory judgment action under section (l)(9)(C) and/or a patent-infringement action under 35 U.S.C. § 271(e)(2)(C)(ii) are the only remedies available to the reference product sponsor; and (2)  whether notice of commercial marketing can only be effective after approval by the Food and Drug Administration, and whether notice of commercial marketing set forth in section (l)(8)(A) of the BPCIA is a stand-alone provision that permits an injunction to delay commercial launch of all biosimilars by an additional 180 days after FDA approval.

Below at the Federal Circuit, the majority of a split-panel (Judge Lourie and Judge Chen) held that when an applicant fails to comply with the disclosure requirement of section (l)(2)(A), the BPCIA permits the filing of a declaratory judgment suit for patent infringement, and that such suits, pursuant to 42 U.S.C. § 262(l)(9) and 35 U.S.C. § 271(e), are the only remedies available.  In other words, the biosimilar applicant has the choice to opt-out of the “patent dance,” and the remedy provided to the reference product sponsor is the ability to file an immediate declaratory judgment action on any patent that claims the biological product or a use of the biological product.  The Federal Circuit’s majority decision also includes a footnote recognizing that while the language of (l)(9)(c) does not expressly include process patents, 35 U.S.C. § 271(e)(2)(C)(ii) does not exclude process patents and “allows the [reference product sponsor] to assert process patents, ‘if the [subsection (k)] applicant. . . fails to provide the application and information’ and ‘the purpose of [the subsection (k)] submission is to obtain approval . . . to engage in the commercial manufacture, use, or sale of a . . . biological product claimed in a patent or the use of which is claimed in a patent before the expiration of such patent.’ 35 U.S.C. § 271(e)(2).”

With respect to the second issue, a different majority of the panel (Judge Lourie and Judge Newman) held that the notice of commercial marketing under section (l)(8) is a “stand alone” provision of the statute that requires the biosimilar applicant to provide notice of commercial marketing after the product is “licensed,” meaning that such notice is only effective after FDA approval and is required regardless of whether there are outstanding patent infringement issues remaining at the time of the notice.  The Court reasoned that providing notice only after approval of a license allows the reference sponsor to definitively determine the patents involved and the scope of potential injunctive relief.  The result of that decision, however, is that approval of every biosimilar product is delayed an additional six months (180 days) beyond the 12 year exclusivity period provided by the BPCIA.  Judge Chen provided a strong well-reasoned dissent on this issue explaining why the extra six month “windfall” of exclusivity is improper and why the majority was wrong to interpret (l)(8) as a stand-alone requirement.

It is the opinion of this author that Judge Chen was correct on both issues. Prior to oral arguments, I expected that the Supreme Court would readily affirm the Federal Circuit’s decision that the BPCIA allows the applicant to elect not to disclose information pursuant to (l)(2)(A) and that it provides the only remedy available to the reference product sponsor in the form of an immediate declaratory judgement action on any patent.  I also expected the Supreme Court to reverse the Federal Circuit on the notice of commercial marketing issue and to allow the biosimilar applicant to provide notice at any time after its application is accepted for review by the FDA (and at least 180 days prior to the date of first commercial marketing).  The questions posed by the Court during oral argument make it difficult to predict if the actual outcome will match my expectations.

Although this was first case on the docket for the day, Chief Justice Roberts announced before arguments began that the Court had decided to grant each side five extra minutes. Counsel for Petitioner, Sandoz, argued first, followed by Counsel for the United States, then Counsel for Respondent and Cross-Petitioner, Amgen, concluding with rebuttal reserved by Sandoz.

Counsel for Sandoz opened by saying that “The Biosimilars Act created a comprehensive and self-contained scheme for the early resolution of patent disputes. Regardless of the actions an applicant or sponsor take along the way, the end result is the same, patent litigation.” She argued that “Courts should apply that comprehensive scheme as written. They shouldn’t look elsewhere for consequences.”

Justice Kennedy asked the first few questions of the day seeking clarification on the timing of FDA’s decision to approve a biosimilar product compared to the actual grant of a license, in light of the exclusivity provisions of the BPCIA.  Justice Sotomayor inquired how long it takes for the FDA to approve a biosimilar, and Justice Kennedy asked if the applicant was apprised of the approval prior expiration of the exclusivity.  He commented that it seems the “180 day notice has to run from the time that the product is licensed.”  Counsel for Sandoz responded that such a reading is foreclosed by the language of the statute because the only timing element of the statute is tied to the date of first commercial marketing, not licensure of the product.

Justice Breyer questioned how one could provide notice of commercial marketing without knowing what the final licensed product is, and noted that the FDA has a lot of “power over what is licensed.” Then, he clarified that “maybe that isn’t what notice means. Maybe it just means notice that you will commercially market X, or maybe it means some combination thereof.” Justice Breyer characterized this as a “crucial ambiguity” that has to do with arguments on both sides.  Justice Breyer suggested several times that perhaps agency rulemaking would help the Court, saying:

We are being asked to interpret very technical provisions that I find somewhat ambiguous and am operating in a field I know nothing about. But it’s going to have huge implications for the future. So why isn’t the way to go about this case to ask the agency to issue some regulations? Then when we see their interpretation, you all will be able to argue that their interpretation exceeds the statutory delegation. And by doing that, we would have a better picture.

Justice Breyer came back to the idea of agency rulemaking, which was a consistent theme of his questions and comments, throughout the argument.  Counsel for Sandoz explained that neither the FDA nor the PTO has rule-making authority to interpret the BPCIA, urging the Court that this is an issue of statutory interpretation.  Later, when counsel for the United States presented his arguments (in support of Sandoz), he affirmed that although FDA is involved in licensure, Congress separated the FDA from the patent litigation process provided by the BPCIA.  The Court asked counsel for the United States to confirm that neither the FDA nor the PTO had rulemaking authority, which he did, agreeing with Sandoz that the issues presented are ones of statutory interpretation.

Justice Sotomayor asked counsel for Sandoz to address the issue of how the reference product sponsor would know exactly what the biosimilar product will be and have enough information to form a good faith belief of infringement for purposes of litigation if the applicant, like Sandoz here, does not provide the reference product sponsor with access to the biosimilar application.  Counsel for Sandoz first pointed to the artificial act of infringement created by the statute and based solely on the filing of an application as evidence of Congress’ intent to allow litigation to proceed early — before product approval or licensure. Second, Sandoz’s counsel argued that because the reference product and the proposed biosimilar are “highly similar,” under the statute, the reference product sponsor would have “a good faith basis to bring suit on any patent that covers its own product or any patent that covers a use of its own product.”  Justice Roberts seemed skeptical of that argument, pointing out that the reference product and the biosimilar are not identical.

It was clear from the questions being asked that the Court was trying to understand both the litigation process and remedies that Congress envisioned under the BPCIA.  Justice Kagan asked counsel for Sandoz if the reference product sponsor would always sue if they have a valid patent. Justice Ginsberg asked counsel to explain the difference between the two phases of the litigation, phase I and phase II.

Justice Gorsuch questioned counsel for the United States about the position that a declaratory judgment suit is the exclusive remedy for failure to comply with the disclosure requirements of (l)(2), raising issues of preemption and potential inconsistencies under state and federal law.  Justice Roberts also expressed concern that “in terms of the preemption question, . . . it’s very hard to give a comprehensive answer to the questions presented without considering whether . . . [under] state law, you can get the same injunction. It’s really asking us to put together a puzzle where a big piece is missing.”  Counsel for the government explained that the questions being presented in the appeal rest entirely on federal law, and the state law claims were found moot.  He also noted that while strong arguments would exist in favor of preemption, the issue was not part of the appeal and had not been briefed, suggesting that the Court should simply decide is what’s required under the statute, leaving open any other questions of state law and preemption.

Justice Breyer raised concerns about whether allowing the applicant to provide notice of commercial marketing early in the process, for example the day after the application is accepted for review by the FDA (“day 2”), would upset the negotiation process envisioned by Congress under the statutory scheme.  Specifically, Justice Breyer noted that the statute sets up a “system, where you’ve put tremendous incentives on people to negotiate and to work it out in an orderly way,” and questioned whether “you can just gut it by simply filing your commercial notice on day 2?” At the end of his discourse with counsel for the government, Justice Breyer pointed to this question as another example of why he believes “this would work out a lot better if you could somehow get this to a rule making.”

When counsel for Amgen began his argument he noted it was “tempting” to just stand up and give a “tutorial on this extremely complicated situation,” but indicated that instead his presentation would be guided by the Court’s earlier questions. The questioning, however, again began immediately.  Justice Sotomayor asked several questions about Amgen’s argument that notice must be given only after the product is approved by FDA and whether this would always force the phase II litigation to start after the reference product sponsor’s 12 year exclusivity period has expired. She also inquired whether Amgen assumes that the commercial launch has to be 12 ½ years rather than 12.

Justice Gorsuch and Justice Sotomayor both posed questions to counsel for Amgen about the remedies provided by the statute, even assuming that the Court agrees “shall” means “shall.”  Justice Breyer asked whether the Court should simply answer the question of whether shall means shall and just stop because the statute “doesn’t say that’s the only remedy or that there are others.”  Justice Roberts followed up with additional questions on preemption and how state law comes into play under the federal statute.  Counsel for Amgen argued that “California law is not incorporating into state law, federal remedies. It says it is a violation of our state law, fair commercial practices law, to violate a command of another sovereign’s law.”  He recognized however, that the remedy under state law was an injunction, not damages or anything else.

Justice Sotomayor then questioned whether, under Amgen’s theory of the case, state law would in effect “force a biosimilar to invoke Phase I” because in the event that the biosimilar applicant elects to opt out of any stage, the reference product sponsor could go to court under state law seeking to force compliance with an injunction.  This raises the question of whether the Court will ultimately deem it necessary to consider the issue of preemption as part of determining whether a declaratory judgment suit is an exclusive remedy.

The questions presented make it clear that the Court has a lot to consider before reaching a conclusion on the issues presented, and suggest that perhaps the decision could be broader in scope (if the Court deems it appropriate to addresses preemption) or narrower in scope (if the Court simply defines “shall” and stops) than many people anticipated.

The Supreme Court’s decision is expected to issue in June 2017.

FDA approved Samsung Bioepis’s Renflexis® (SB2, infliximab-abda) on Friday, April 21, 2017.  Renflexis® is the fifth biosimilar approved by the FDA and the second infliximab biosimilar to Janssen’s Remicade®.  Infliximab is an Anti-Tumor Necrosis Factor (Anti-TNF) monoclonal antibody approved in the U.S. for treating rheumatoid arthritis, ulcerative colitis, Crohn’s disease, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.  FDA previously approved Celltrion’s Inflectra® (infliximab-dyyb), the first biosimilar to Remicade®, on April 5, 2016, and that product was launched in the United States in November 2016 under a marketing agreement with Pfizer.

Samsung Bioepis announced that the FDA had accepted its biologics license application for SB2, its infliximab biosimilar, in May 2016.  The company has publicly stated that when launched, marketing and distribution of Renflexis® will be handled by Merck in the United States.  Renflexis® is Samsung Bioepis’s first biosimilar approved by the FDA, but the product was approved earlier in South Korea (in December 2015), Europe (in May 2016), and Australia (in November 2015).

Genentech filed suit against Amgen this past February when a dispute arose between the parties during the first step of the “patent dance” for Amgen’s bevacizumab product (ABP 215), a proposed biosimilar to Genentech’s Avastin®.  Genentech accused Amgen of violating sections (l)(2)(A) and (l)(1)(c) of the Biologics Price Competition and Innovation Act (“BPCIA”), 42 U.S.C. § 262, as previously discussed in this post.

The lawsuit came to a swift end when the Court dismissed the Complaint for lack of subject matter jurisdiction, only two weeks after it was filed, in light of the Federal Circuit’s decision in Amgen v. Sandoz, 794 F.3d 1347 (Fed. Cir. 2015).[1] As we previously reported, Judge Sleet dismissed Genentech’s complaint without prejudice and expressly provided Genentech forty-five days, until April 14, 2017, to amend the Complaint to seek declaratory judgment of patent infringement.

Last week Genentech submitted a letter to the Court indicating that it will not be filing an amended Complaint prior to the expiration of the 45-day period provided by the Court’s Order.  In the letter to Judge Sleet, dated April 14, 2017, Genentech states that it believes it would be “more efficient for the Court and the parties to address both the patent merits and Amgen’s continued noncompliance with its statutory production obligations. . . . after the Supreme Court’s expected decision in June in Amgen v. Sandoz.”  Genentech also provided a Proposed Judgment dismissing the case and requested that the Court enter the Judgement.

Before the next business day, Amgen submitted a responsive letter to the Court advising Judge Sleet that “Genentech failed to inform the Court in its April 14 letter that it elected to provide its disclosure under § 262(l)(3)(A) and continue with the “patent dance” instead of amending its Complaint within the 45 day window it requested.” According to Amgen’s April 16, 2017 letter, Genentech provided its section 3A patent list (see 42 U.S.C. § 262(l)(3)(A)) on March 24, 2017, and  “the parties are moving through the ‘patent dance’ as contemplated under the BPCIA.”  Amgen further suggested that in light of the Court’s prior order of dismissal on March 1, 2017, “there is nothing left for the Court to do and it need not entertain Genentech’s request to again dismiss this action.”  Yesterday, on April 19, 2017, Judge Sleet issued an oral order indicating that the court agrees with Amgen’s position set forth in its April 16 letter, and the Court declined to enter the proposed judgment provided with Genentech’s April 14 letter.

In view of Genentech’s decision not to amend its Complaint and the subsequent Court Order, the case is completed.   But, we can expect to see a new patent infringement case after the parties complete the patent dance, if not before.  We will continue to provide updates on any future litigation over bevacizumab.

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[1] In Amgen v. Sandoz, the majority of a split panel of the Federal Circuit held that when an applicant fails to comply with the disclosure requirement of section (l)(2)(A), the BPCIA permits the filing of a declaratory judgment suit for patent infringement, and that such suits, pursuant to 42 U.S.C. § 262(l)(9) and 35 U.S.C. § 271(e), are the only remedies available.  The Federal Circuit’s majority decision recognizes that “the BPCIA has no other provision that grants a procedural right to compel compliance with the disclosure requirement of paragraph (l)(2)(A).” However, that decision is currently on appeal to the Supreme Court, and a decision from the high court is expected early this summer as discussed in this post.

Editors’ Note: Although the BPCIA was enacted seven years ago, to date, only four biosimilar products have been approved by the FDA, and only two of those products are commercially available to patients in the United States – Sandoz’s Zarxio® (a filgrastim biosimilar to Amgen’s Neupogen®) and Celltrion and Hospira’s Inflectra® (an infliximab biosimilar to Janssen’s Remicade®) now marketed by Pfizer.  Given the number of biologics license applications that have been filed using the BPCIA’s abbreviated approval pathway and the highly complex nature of the statute, the number of litigations also remains quite small.  So far, district court litigation related to or arising under the BPCIA has been filed with respect to only seven reference products.  This week, we begin a new series of articles that we are calling the “Litigation Spotlight.” The articles in this series will provide a summary of the factual background, legal issues, and current status of each biosimilar litigation, grouped by reference product.  We will continue to provide updates as the cases continue.  

Introduction and Background

The infliximab litigations demonstrate the complexities of the Biologics Price Competition and Innovation Act (the “BPCIA”) and the unanswered questions that remain on the statute’s procedural and substantive requirements.  Perhaps just as importantly, the litigations demonstrate that all of the normal challenges present in a patent litigation remain.  Indeed, in an Order issued in December 2014, Judge Crotty observed that “the pursuit of FDA approval for a biosimilar version of the rheumatoid arthritis treatment Remicade has triggered a lot of litigation.”  As a result, it is critical to have counsel that is both experienced in tackling the normal hurdles of a patent litigation, but also willing and capable to delve into the biosimilar statute.

Infliximab is an Anti-Tumor Necrosis Factor (Anti-TNF) monoclonal antibody, approved in the United States for treating rheumatoid arthritis, ulcerative colitis, Crohn’s disease, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.  The antibody was developed by Centocor (a predecessor to Janssen Biotech, Inc. (“Janssen”)) and scientists at New York University (“NYU”).  Janssen introduced infliximab to the U.S. market in 1998 under the brand name Remicade®.  The product has been successful, with more than $6.9 billion in worldwide sales in 2016 alone.

Celltrion Healthcare Co. and Celltrion, Inc. (“Celltrion”) have introduced a biosimilar to Janssen’s Remicade®.  Celltrion has partnered with Hospira, a subsidiary of Pfizer, to market and sell infliximab under the name Inflectra® in the United States.  The U.S. regulatory process began with the submission of an Investigational New Drug application in October 2013, an abbreviated biologics license application in August 2014, and finally FDA approval on April 5, 2016.  Inflectra® launched in the U.S. shortly thereafter, in November 2016.

The Early Declaratory Judgment Actions

Litigation over infliximab began with Celltrion and Hospira filing suits for declaratory judgment of non-infringement, invalidity, and unenforceability in 2014.  Specifically, Celltrion filed suit in the United States District Court for the District of Massachusetts in March 2014 (Civ. No. 14-cv-11613), and the Southern District of New York (Civ. No. 14-cv-2256), while Hospira filed suit in August 2014 in the Southern District of New York (Civ. No. 14-cv-7059).  Importantly, however, these suits were filed before Celltrion or Hospira had submitted an abbreviated biologics license application (“aBLA”) to the FDA, placing the suits outside the framework of the BPCIA and making them premature.  Judge Crotty in the Southern District of New York dismissed the lawsuit there, explaining that Celltrion sought to “reap the benefits” of the BPCIA’s approval process while ignoring the dispute resolution procedures.  Following the December 2014 Orders dismissing the New York lawsuits for a lack of jurisdiction, Celltrion voluntarily withdrew its Massachusetts lawsuit as well.

Janssen Goes on the Offensive

Janssen and NYU (“Janssen”) made the next move, filing suit against Celltrion and Hospira (hereinafter, “Defendants”) in Massachusetts in March of 2015 (Civ. 15-cv-10698).  The complaint alleged two types of claims.  First, Janssen alleged that the Defendants violated the BPCIA by failing to provide, along with their aBLA, “such other information that describes the process or processes used to manufacture the biological product that is the subject of such application.” Janssen interpreted section (l)(2)(A) of the BPCIA to require the production of manufacturing information in addition to the applicant’s BLA.  See 42 U.S.C. 262(l)(2)(A)(“the subsection (k) applicant— (A) shall provide to the reference product sponsor a copy of the application submitted to the Secretary under subsection (k), and such other information that describes the process or processes used to manufacture the biological product that is the subject of such application”).  Janssen therefore alleged that the Defendants were not forthcoming with additional manufacturing information, thus frustrating its ability to identify all patents that could potentially be asserted against Defendants on its 3A list as part of the BPCIA’s contemplated exchange of patent information.[1]  In a separate BPCIA claim, Janssen further alleged that Celltrion’s notice of commercial marketing was premature.  Section (l)(8)(A) of the BPCIA states that “[t]he subsection (k) applicant shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing of the biological product licensed under subsection (k).”  See 42 U.S.C. 262(l)(8)(A). Janssen alleges that reference to a “licensed product” in this section of the BPCIA requires the applicant to obtain FDA approval (licensure) before it can provide an effective notice of commercial marketing.  Specifically, because the Defendants did not yet have a licensed product, Janssen stated that they could not provide notice of an intent to market a licensed product.  (This issue is currently the subject of a pending petition for certiorari and will be considered by the Supreme Court later this term).  Ultimately, Janssen complained that the Defendants were not engaging in good faith negotiations, forcing Janssen to file a lawsuit that it believed was premature.

Second, Janssen alleged that the Defendants committed an act of infringement pursuant to 35 U.S.C. § 271(e)(2)(C)(i) by submitting its aBLA.  Specifically, Plaintiffs alleged infringement based on U.S. Patent Nos. 6,284,471; 7,223,396; 5,807,715; 7,598,083; 6,900,056; and 6,773,600.   (Several of these patents were voluntarily dismissed after additional discovery, and only two patents remain in active litigation—the ’471 patent and the ’083 patent.)  The ’471 patent contains claims directed to the infliximab cA2 monoclonal antibody, and expires on September 4, 2018.  The ’083 patent, by contrast, contains claims generally directed to cell culture media for use in growing biological products and expires on February 7, 2027.

Finally, on June 14, 2016, Janssen filed another lawsuit (Civ. No. 16-cv-11117) against the same parties asserting infringement of the ’083 patent based on alleged “actual acts of infringement.”  That is, unlike the earlier filed action based on “technical” infringement, this lawsuit concerns alleged acts of actual infringement based on the production of cell culture media.  Specifically, Janssen alleged that Celltrion’s agent and supplier (HyClone) manufactured a cell culture media in the United States in violation of the ’083 patent, and media was used to manufacture the infliximab product approved for sale in the United States.  (Janssen also filed suit against the supplier, HyClone, in Utah (Civ. No. 16-cv-71), but that case has been stayed in light of the Massachusetts litigation.)  According to publicly available information, the supplier had previously worked with Janssen’s predecessor, Centocor, and allegedly was given access to the confidential formulation for a cell culture media later allegedly claimed in the ’083 patent.  Because of the substantial overlap between the two cases, the parties submitted a stipulation consolidating the two cases and bifurcating the issue damages.

The ’471 Patent and Invalidity

In February 2016, Defendants moved for summary judgment of invalidity of the ’471 patent based on obviousness type double patenting in view of several prior art references.  In August 2016, the Court granted Celltrion’s motion for summary judgment of invalidity, further narrowing the issues in the case. The Court concluded that the ’471 patent was invalid for obviousness-type double patenting in view of U.S. Patent No. 6,790,444 based on the Federal Circuit’s decision in Gilead Sciences, Inc. v. Natco Pharma Limited, 753 F.3d 1208 (Fed. Cir. 2014).  In Gilead, the Federal Circuit held that a later-issuing, earlier-expiring patent may act as a double-patenting reference for an earlier-issuing, later-expiring patent.

The Court also granted summary judgment of invalidity based on obviousness type double patenting in view of U.S. Patent Nos. 5,656,272 and 5,698,195, two patents that also descended from the same parent application as the ’471 patent.  The decision involved three subsidiary determinations.  First, the Court concluded that the Plaintiffs were not subject to the § 121 safe harbor provision; second, the court found that the one-way test for obviousness applied (as opposed to the two-way test); and third, the court found that even if the two-way test did apply, the ’471 was still invalid.  With respect to the first determination, the Court found that even though the ’471 patent had been re-labeled as a divisional in an ongoing reexamination, that amendment was not final.  Moreover, the Court concluded it did not have the power to re-label the ’471 patent as a divisional.  Next, the Court concluded that the one-way test for obviousness applied.  That is, the only question was whether the ’471 patent claims were obvious in view of the reference patent.  Janssen argued that an exception to this rule applied, the so-called “two-way” test, which also considers whether the reference claims would be obvious.  The “two-way” test applies where the “PTO is solely responsible for the delay in causing the second-filed application to issue prior to the first.”  The two-way test is designed to allow for a “later-filed improvement patent” that issues before the earlier filed basic patent.  The Court found that the one way test applied, and Janssen conceded that under the one way test, the patents were invalid.  Finally, the Court concluded that even if the two-way test applied, the claims were still invalid.[2]

While Janssen lost the summary judgment motions regarding the ’471 patent’s validity, it was Celltrion that pushed for entry of a final judgment pursuant to Federal Rule of Civil Procedure 54(b).  The Court recognized that Janssen had a “financial incentive to try to delay the appeal,” but concluded that the BPCIA’s “primary purpose” was to “expedite patent litigation” in order to maximize certainty.  Interestingly, the Court used Janssen’s own press announcement that it intended to appeal the ruling in support of the Rule 54(b) certification.  Therefore, the Court ultimately granted certification for immediate appeal.

The ’083 Patent and Infringement

The parties also dispute whether the Defendants infringe the only remaining patent in the district court litigation—the ’083 patent.  The Court and the parties sometimes refer to the ’083 patent as the “soup patent” because it is not directed to the infliximab antibody itself.  Rather, the patent is generally directed to a cell culture media that can be used to produce antibodies.  Moreover, a third party, HyClone, is the entity that is alleged to actually manufacture the cell culture media.  Finally, that cell culture is created in the U.S., sent to Korea, and then allegedly used to create  infliximab that is (and will be) sent back to the U.S. as the final product.

Nonetheless, Janssen contends that the Defendants infringe the ’083 Patent, both directly and indirectly through inducement, points which Defendants dispute.  Janssen’s claim for direct infringement is premised on the theory that Defendants direct and control HyClone and/or that HyClone acts as Defendants’ agent in creating the cell culture.  Defendants moved for summary judgment of non-infringement, but the Court denied the motion with respect to Celltrion at an oral hearing in December.  This infringement theory therefore appears to be one to be determined at trial.

The Parties Proceed Toward Trial – But Standing Gets in the Way

With only the ’083 patent remaining, the parties proceeded towards a trial that was scheduled to begin in February 2017.  However, after issues were raised at a scheduling conference in January 2017, the Court issued an order instructing the parties to submit briefing to address the appropriate measure of damages and the Plaintiffs’ right to a permanent injunction if defendants are found to infringe the ’083.  Then, in a brief filed on January 25, 2017, Defendants argued for the first time that the Plaintiffs did not have standing because they had failed to join all of the co-owners of the ’083 patent to the action, which Defendants alleged would require a dismissal for lack of subject matter jurisdiction.  After further briefing and oral argument, the court found that the issue of standing raised serious questions concerning the court’s jurisdiction that required the postponement of trial to permit briefing on a motion to dismiss for lack of jurisdiction and possibly additional limited discovery.

While a lack of standing would be problematic in any case, this was particularly concerning in a case arising under BPCIA.  This is because, “[s]ection 271 (e)(6) limits a patentee’s damages to a reasonable royalty if it proves infringement of a patent identified under 42 U.S.C. §§262(1)(4) and (5)(B) in a suit filed more than 30 days after the end of the process prescribed by the BPCIA.”  Defendants argued that because the “patent dance” had been completed more than 30 days prior to January 2017, any new lawsuit would necessarily be limited to a reasonable royalty.  On the other hand, Janssen alleges that because Defendants refused to complete the negotiation process, the 30-day period under the BPCIA never began.

The Court provided guidance on the issue of damages in a March 3, 2017 Order.  The Court concluded that “on the present record,” it could not conclude that Celltrion had engaged in good faith negotiations under the BPCIA sufficient to trigger the reasonable royalty limitation.  Therefore, Janssen would not be limited to a reasonable royalty.  In the same Order, the Court found that Janssen could recover lost profits from sales of Inflectra sold in the United States made from “the infringing media powders in the United States.”  Therefore, despite the fact that Inflectra itself was manufactured in Korea, because the allegedly infringing cell culture media was produced in the U.S., Plaintiffs could recover lost profits for sales of Inflectra made using that allegedly infringing cell culture.

A Summary of Where Things Stand (Pun Intended)

The District Court Litigation

Trial in the district court trial has been postponed until after the parties briefing on the issue of whether Plaintiffs lacked standing to bring suit on the ’083 patent.  Defendants have raised two arguments—first, that one of the named inventors did not assign his rights in the patent to Janssen in the first place; and second, that the other named inventors actually assigned their rights to the entire Johnson & Johnson family of companies, and not just the Janssen corporate entity.  This dispute has also resulted in new discovery surrounding standing, as well as disputes regarding the extent of this discovery.  The Court has entered a notice setting a hearing on the issue for June 21, 2017.

Assuming the case proceeds to trial, there are still a myriad of disputes to be decided.  Plaintiffs are alleging infringement solely under the doctrine of equivalents, and Defendants challenge its application, both on the law and the facts.  In addition, although HyClone manufactured the allegedly infringing cell culture, Janssen contends that Celltrion is directly liable for infringement because Celltrion directs and controls HyClone, and/or HyClone acted as Celltrion’s agent.  Again, Defendants dispute these allegations.  Finally, Janssen contends that Defendants have induced infringement, and Defendants again disagree.  Defendants, in turn, contend that the ’083 patent is invalid as obvious and invalid for lacking a sufficient written description.

In addition to its claims for “traditional” infringement, Janssen is also pursuing claims that Defendants failed to comply with the provisions of the BPCIA.  Defendants have responded that any claim for “artificial infringement” is moot in light of the Federal Circuit’s holding in Amgen that there is no private right of action to enforce BPCIA’s so-called “patent dance.”  Defendants also argue that this issue is moot in any event based on the actual allegation of infringement.  Finally, the parties disagree as to whether Janssen would be entitled to an injunction.

The Invalidity Appeal

The district court’s summary judgment determinations with respect to the ’471 patent were appealed, and the parties are currently briefing the dispute in the Federal Circuit (Case No. 17-1120).  At this time, Janssen’s reply brief is due on April 20, 2017, and oral argument will presumably be scheduled sometime thereafter.

The Ex Parte Reexamination Appeal

As noted above, while the district court litigation was ongoing, the ’471 was undergoing ex parte reexamination.  Ultimately, the PTAB issued a decision affirming a rejection for obviousness-type double patenting, and that decision was appealed to the Federal Circuit as well (Case No. 17-1257).  The Federal Circuit has designated this appeal as a “companion” case to the summary judgment ruling, meaning the cases will be assigned to the same merits panel for oral argument.  Briefing is scheduled to be completed by April 24, 2017.

We will continue to keep you apprised of further developments.

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[1]   For the sake of completeness, we further note that Janssen provided a list of patents to Defendants pursuant to Section 3A of the BPCIA.  After receiving the 3A list, Defendants informed Janssen that they “agree” to Janssen’s list of patents, in their view, making the further exchange of information or negotiations unnecessary.  Defendants’ provided a detailed statement to Janssen and asserted that Janssen was required to file suit within 30 days of receipt of the detailed statement.  Janssen disputed Defendants’ interpretation but filed suit.

[2] At the time Janssen filed its first Complaint, the ‘471 patent was undergoing ex parte reexamination at the PTO.  The proceeding had been underway for 2 years and the claims stood finally rejected.  On November 14, 2016, the Patent Trial and Appeal Board (“PTAB”) issued a decision affirming a USPTO examiner’s final rejection of the claims of the ’471 patent for obviousness-type double patenting in an ex parte reexamination. Janssen had moved to stay the district proceeding as it relates to the ’471 patent pending that appeal, which was denied.  The appeal of the PTAB decision has been assigned Fed. Cir. Appeal No.17-1257 and designated as a related case to the appeal of the summary judgment decision on the ’471 patent.  Briefing on the appeal of the reexam decision will be completed on April 24, 2017.  Oral argument has not yet been scheduled.

As we previously reported in this post, the Supreme Court granted certiorari in its first biosimilar case on Sandoz’s petition in Sandoz, Inc. v. Amgen, Inc., et al., Case No. 2015-1039 and on Amgen’s cross-petition in Amgen Inc., et al. v. Sandoz, Inc., Case No. 2015-1195.  On January 25, 2017, the Supreme Court issued a briefing schedule and briefing for the consolidated cases is now completed.

Sandoz filed its opening brief on the merits in 15-1039 on February 10, 2017, and several industry organizations, trade associations, and pharmaceutical companies filed amici curiae briefs in support of Sandoz on February 17, 2017, including: Adello Biologics LLC; Apotex Inc. and Apotex Corp.; Coherus Biosciences, Inc.; Mylan, Inc.; AARP and AARP Foundation; Citizens Against Government Waste, The UAW Retiree Medical Benefits Trust, The National Health Law Program, and The Coalition to Protect Patient Choice; America’s Health Insurance Plans; The Biosimilars Council; Pharmaceutical Care Management Association, National Association of Chain Drug Stores, and Healthcare Supply Chain Association. The Solicitor General filed an amicus brief on behalf of the United States in support of Sandoz and also filed a motion seeking leave to participate in the oral argument.

Amgen filed its consolidated opening brief on the merits in case 15-1195 and responsive brief on the merits in 15-1039 on March 17, 2017.  AbbeVie Inc., Janssen Biotech, Inc., The Biotechnology Innovation Association, Eleven Professors (who teach and write on patent law and policy), and Genentech, Inc. each filed an amici brief in support of Amgen.

Sandoz filed its consolidated response in 15-1195 and reply in case 15-1039 on March 31, 2017.  Today, Amgen submitted its reply brief in 15-1195 to complete all of the briefing in the case. Oral argument is scheduled for Wednesday, April 26, 2017.

As we previously reported, Sanofi-Aventis U.S. LLC, Genzyme Corporation, and Regeneron Pharmaceuticals, Inc. filed a Declaratory Judgment Complaint against Amgen, Inc. and Immunex Corporation in the United States District Court for the District of Massachusetts on March 20, 2017, preemptively seeking a determination that Sanofi and Regeneron’s Dupixent® (dupilumab) product does not infringe U.S. Patent No. 8,679,487 (“the ’487 patent”).  Sanofi and Regeneron also filed a petition for inter partes review of the ’487 patent with the Patent Trial and Appeal Board just a few days later, as we reported here.  The FDA approved Dupixent on March 28, 2017.

Returning fire, Immunex filed a separate Complaint in the United States District Court for the Central District of California on April 5, 2017, accusing Sanofi, Genzyme, and Regeneron of infringing the ’487 patent.  Yesterday, Immunex filed a motion seeking to dismiss the Complaint in the Massachusetts case, or in the alternative, to transfer the case to the Central District of California where Immunex’s later-filed case is now pending.

Amgen and Immunex argue in the motion to dismiss that the Massachusetts court lacks subject matter jurisdiction over Amgen (because Immunex is the sole owner of the ’487 patent and Amgen, the parent company, has no rights in the patent).  They further argue that the Complaint should be dismissed because neither Immunex nor Amgen are subject to personal jurisdiction in Massachusetts, and because the venue is improper in Massachusetts.

Alternatively, even if the Massachusetts court determines that it has sufficient jurisdiction and proper venue, Amgen and Immunex seek to transfer the Massachusetts litigation to the Central District of California, which they allege is the more proper forum, and to have the case consolidated with Immunex’s later-filed litigation.   The California case is Civ. No. 17-cv-02613 and has been assigned to Judge Otero.

The filing of a second litigation and the related motion to dismiss or transfer creates a battle over which court will hear the patent infringement case.   We will continue to provide updates as the litigation continues.