On May 25, 2017, Pfizer, Inc. (“Pfizer”) filed two new petitions for inter partes review (“IPR”) of U.S. Patent No. 6,407,213 (“the ’213 patent”).  The ‘213 patent, entitled “Method for Making Humanized Antibodies,” issued on June 18, 2002.  Although the IPR petitions do not identify a particular biologic, Genentech has publicly stated that the technology claimed by the ’213 was used in the development of Herceptin® (trastuzumab), as well as several other products.  Genetech applied for a patent term extension of the ’213 patent under the Drug Price Competition and Patent Term Restoration Act of 1984 based on the regulatory review period of its biologic license application for Lucentis® (ranibizumab), and Genentech applied for a patent terms extension of a different patent in the same patent family based on the regulatory review period for Avastin® (bevacizumab).

The new proceedings are IPR2017-01488 and IPR2017-01489. Hospira, a Pfizer company, has filed IPR petitions challenging claims of other patents related to Herceptin® (trastuzumab), as we reported earlier this year here and here.  In those cases, Hospira was identified as the real party in interest and Pfizer was also identified as a party having interest.  The only real party-in-interest identified for Petitioner in these two new IPR filings is Pfizer.  The fact that Hospira was not also identified as interested party in the petitions could possibly indicate that these petitions were filed as part of a patent strategy related to other products in Pfizer’s development pipeline, in addition to trastuzumab.

Celltrion has also filed IPR petitions challenging several patents related to Herceptin® (trastuzumab), including the ’213 patent, as discussed here, here, and here.  Mylan is also seeking approval of a trastuzumab biosimilar and had filed two IPR petitions challenging the ’213 patent.  Those petitions were withdrawn, as we reported in this post in March 2017, as part of a global settlement agreement that Mylan and Biocon entered into with Genentech and Roche related to Mylan’s proposed trastuzumab biosimilar.  A complete list of IPRs related to trastuzumab and other proposed biosimilar products can be found in RFEM’s IPR Dashboard.

Pfizer announced last week that the FDA’s Oncologic Drug Advisory Committee (ODAC) recommended its proposed biosimilar to Amgen’s Epogen®/Procrit® for approval across all indications after a public meeting held on May 25, 2017.  The meeting materials are available from the FDA’s website here.

The history of this application is interesting.  The original biologics application (BLA 125545) was submitted by Hospira in December 2014 and was subsequently acquired by Pfizer when it purchased Hospira in 2015.  The initial BSUFA date (FDA’s target goal for action) was in November 2015.  The application was rejected after the FDA’s first review, and Pfizer publicly stated in October 2015 that it received a complete response letter from FDA that would delay the anticipated release of the product.  At that time, Pfizer indicated “that it was working closely with the agency to address the concerns of the letter” and expected to resubmit the application.  Since then, few details have been available on the status of the application, although under current performance goals, the FDA aims to take action within approximately six months of resubmission of an application.

Epoetin alfa is a human erythropoietin that stimulates the production of red blood cells (erythropoiesis). Epoetin alfa is produced in cell culture using recombinant DNA technology. The proposed indications for Pfizer’s proposed biosimilar include: (1) the treatment of anemia due to chronic kidney disease; (2) the treatment of anemia due to zidovudine in HIV-infected patients; (3) the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppresive chemotherapy; and (4) reducing the need for allogeneic RBC transfusions among patients with perioperative hemoglobin who are at high risk for perioperative blood loss from elective, noncardiac, and nonvascular surgery.

Hospira’s Retacrit® was approved in the EU in 2007, and according to Pfizer’s announcement, this product is the first biosimilar erythropoiesis-stimulating agent (“ESA”) recommended for approval by an FDA Advisory Committee.  The announcement notes that the FDA will take the ODAC’s recommendation into consideration before taking final action on the application, and indicates that once approved, the product will be commercialized pursuant to an agreement between Pfizer and Vifor Pharma, Inc.

Amgen filed a Complaint for patent infringement under the BPCIA against Hospira regarding this product in the United States District Court for the District of Delaware in September 2015.  The Complaint alleges infringement of two patents (U.S. Patent Nos. 5,856,298 and 5,756,349) and contains separate claims for alleged violations of sections (l)(2)(A) and (l)(8) of the BPCIA.  Stay tuned for an in-depth discussion of the erythropoietin litigation, coming soon in the Litigation Spotlight series.

Earlier this month, Janssen Biotech, Inc., a subsidiary of Johnson and Johnson,   (“Janssen” or “Plaintiff”) filed a Complaint in the United States District Court for the District of New Jersey against Samsung Bioepis Co., Ltd. (“Samsung Bioepis” or “Defendant”),  a joint venture between Samsung Biologics and Biogen.  The patent infringement litigation relates to Samsung Bioepis’s Renflexis® (infliximab-abda), a biosimilar to Janssen’s Remicade®.

Infliximab is an anti-Tumor Necrosis Factor (anti-TNF) monoclonal antibody that was first approved in the United States in 1998.  Samsung Bioepis announced in May 2016 that the FDA had accepted its application for SB2, a proposed infliximab biosimilar, for the treatment of rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis.  In April 2017, Samsung Bioepis announced that the FDA had approved Renflexis® (infliximab-abda) across all eligible indications, as we reported here.  The approval of this product marks the fifth biosimilar approval by the FDA and is Samsung Bioepis’s first biosimilar approval in the United States.  It was also notable because infliximab is now the only product for which the FDA has approved more than one biosimilar.  The FDA previously approved Celltrion’s Inflectra® (infliximab-dyyb) on April 5, 2016, and Inflectra® was launched in the United States in November 2016 under a marketing agreement with Pfizer.  Samsung Bioepis has publicly announced that Renflexis® will be marketed in the United States by Merck & Co., Inc. (known as MSD outside of the U.S. and Canada), pursuant to a commercialization agreement entered into in 2013. Samsung Bioepis’s infliximab has been approved previously in the EU, Norway, Lichtenstein, Iceland, Australia, and Korea.

The Complaint filed on May 17, 2017, alleges that Samsung Bioepis’s filing of a biologics license application (“BLA”) for infliximab under the abbreviated section (k) pathway of the BPCIA constitutes an artificial action of patent infringement, pursuant to 35 U.S.C. §271(e)(2)(C), of three patents: U.S. Patent No. 7,598,083 (“the ’083 patent”); Patent No. 6,900,056 (“the ’056 patent”); and Patent No. 6,773,600 (“the ’600 patent”).  According to the Complaint, the claims of the ’083 and ’056 patents are directed generally to “cell growth media for use in growing biological products, including infliximab,” and the claims of the ’600 patent cover “methods of purifying biological products such as infliximab.”

The Complaint also contains a separate count seeking a declaratory judgment that Samsung Bioepis violated the requirements of section (l)(2)(A) of the BPCIA by refusing to disclose its abbreviated biologics license application and manufacturing information to Janssen.  In a letter to Janssen dated March 26, 2016, a copy of which is attached to the Compliant, Samsung Bioepis advised Janssen that:

On May 20, 2016, the FDA provided notice … that Bioepis BLA No. 761054 has been accepted for review by the FDA. The reference product for Bioepis BLA No. 761054 is Remicade® infliximab … Bioepis will not provide Janssen Biotech, Inc. with a copy of BLA No. 761054 or any information that describes the process or processes used to manufacture the biological product that is the subject of BLA No. 761054. Janssen Biotech, Inc. is hereby notified that Bioepis will forego the exchange of information as described in 42 U.S.C. §§ 262(1)(2)-(1)(6). Thus, pursuant to 35 U.S.C. § 271 (e)(2)(c)(ii) and 42 U.S.C. § 262(1)(9)(C), Janssen Biotech, Inc. may bring an action against Bioepis under 28 U.S.C. § 2201 for a declaration of infringement, validity, or enforceability of any patent that claims the biological product or its use or its manufacture

Janssen acknowledges in the Complaint that under current law, the Federal Circuit has not interpreted the disclosures requirements of section (l)(2)(A) as mandatory; however, Janssen included the Count because the Supreme Court has granted certiorari on this precise issue.  We have previously discussed the issues pending before the Supreme Court here, here, and here.  The Complaint also includes a separate count alleging violation of the BPCIA related to the notice of commercial marketing provision.  According to the Complaint, Samsung Bioepis submitted two letters providing notice of commercial marketing, the first after FDA acceptance of the application, and the second after FDA approval.  It appears that Janssen included this Count because Samsung Bioepis refused to withdraw its initial notice of commercial marketing, which is not effective under current law, but could be effective if the Supreme Court were to reverse the Federal Circuit’s interpretation of section (l)(8) of the BPCIA.

This case is not the first litigation involving infliximab.  As we previously reported, Janssen and NYU have also filed an infringement suit against Celltrion and Hospira related to their FDA-approved infliximab product Inflectra®, as discussed in detail in this post.

The Janssen v. Samsung Bioepis litigation is Civ. No. 17-cv-03524, in the District of New Jersey, and the case has been assigned to Judge Madeline Cox Arleo and Magistrate Steven C. Mannion.  We will continue to keep you apprised as the case develops.

Partner Nikki Gifford gave a presentation entitled “Intellectual Property – Recent Developments and Implications,” at the World Biosimilar Congress in San Diego, California, on Wednesday, May 24, 2017. The 30-minute session covered: (1) the BPCIA’s “patent dance”; (2) what’s at stake in Sandoz v. Amgen, and the potential outcomes and practical implications of the Supreme Court’s decision; and (3) how IPRs can provide a strategic alternative to litigation for key patents.

The slides presented can be found here. To learn more about Nikki and her practice, please find her bio here. To contact Nikki with any questions, she can be reached at ngifford@rfem.com.

Last week, Celltrion, Inc. (“Celltrion”) filed two new petitions for inter partes review (“IPR”) of U.S. Patent No. 6,407,213 (“the ’213 patent”) related to Genentech’s Herceptin® (trastuzumab).  Celltrion has announced that it plans to submit an application for a trastuzumab biosimilar product to the FDA this year (possibly as early as next month), as reported in this post.  Celltrion has filed IPR petitions challenging certain claims of other patents related to Herceptin® (trastuzumab) as discussed here and here.

Trastuzumab is a monoclonal antibody that interferes with the human epidermal growth factor receptor (HER2)/neu. Herceptin® is indicated for the treatment of patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens for their metastatic disease.

The new proceedings are IPR2017-01373 and IPR2017-01374. The real parties-in-interest identified for Petitioner are Celltrion, Inc., Celltrion Healthcare Co. Ltd., and Teva Pharmaceuticals International GmbH.  The ’213 patent, entitled “Method for Making Humanized Antibodies” issued on June 18, 2002.  Genentech has publicly stated that the technology claimed by the ’213 was used in the development of Herceptin® (trastuzumab), as well as several other products.

Hospira has also filed IPR petitions challenging patents related to Herceptin®, as we reported earlier this year here and here. A complete list of IPRs related to trastuzumab and other proposed biosimilar products can be found in RFEM’s IPR Dashboard.

Mylan is also seeking approval of a trastuzumab biosimilar. In March, Mylan and Biocon announced that they had entered into a global settlement and licensing agreement with Genentech and Roche regarding Mylan’s trastuzmab biosimilar, as discussed in this post.

Baxalta Incorporated and Baxalta GmbH (collectively “Baxalta” or “Plaintiffs”) filed a Complaint in the United States District Court for the District of Delaware on May 4, 2017, against Genentech, Inc. (“Genentech”) and Chugai Pharmaceutical Co. Ltd., (“Chugai,” and collectively with Genentech “Defendants”) alleging that Defendants’ bispecific monoclonal antibody emicizumab infringes claims 1, 4, 15, 17 and 19 of U.S. Patent No. 7,033,590 (“the ’590 patent”) under 35 U.S.C. § 271(a), (b), (c) or (g).  The Complaint contains a separate count seeking a declaratory judgement that Defendants will directly infringe, or will actively induce and/or contribute to infringement of valid and enforceable claims of the ’590 before its expiration in violation of 35 U.S.C. § 271(a), (b), (c) or (g).

The ’590 patent, entitled “Factor IX/Factor IXa Activating Antibodies and Antibody Derivatives,” issued on April 25, 2006 from an application filed on September 14, 2000, claims priority to a foreign application filed on September 14, 1999.  According to the Complaint, the ’590 patent was assigned to Plaintiffs in March 2016. Plaintiffs are wholly-owned subsidiaries of Shire plc.

Emicizumab (ACE910) is an investigational bispecific monoclonal antibody designed to bring together factors IXa and X to activate the natural coagulation cascade and restore the blood clotting process. Emicizumab was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche, and Genentech. Genentech announced in September 2015 that FDA granted breakthrough therapy designation to emicizumab based on the results of a Phase I study in people with severe hemophilia A.  Breakthrough therapy status gives an application priority at the FDA and typically reduces the target goal for approval (BSUFA date) from the standard ten months after submission to just six months.  In December 2016, Genentech reported positive results from a Phase III study, indicating that emicizumab met its primary endpoint.  The Complaint does not affirmatively allege that Genentech has already filed its emicizumab application with FDA, but rather alleges that “on information and belief, the filing of Defendants’ BLA for emicizumab with the FDA to obtain licensure is either ongoing or is imminent.”  The Complaint further alleges that Defendants stated in publicly available information that they expect to launch emicizumab in the United States in the fourth quarter of 2017.

The Delaware litigation is Civ. No. 17-cv-00509, and the case has been assigned to Judge Sleet.  Defendants have not yet filed an Answer or otherwise responded to the Complaint.

Baxalta previously filed a suit against Chugai in Japan in May 2016, alleging patent infringement based on, inter alia, the use of emicizumab in clinical trials there.  Chugai has denied the allegations of infringement in Japan as reported here.

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.