This article provides an update on our prior analysis of the infliximab litigation involving Janssen Biotech, Inc. (“Janssen”), Celltrion Healthcare Co. and Celltrion, Inc. (“Celltrion”), and Hospira Inc. (“Hospira”).

Briefly, when we last addressed this case, the litigation had already been narrowed to one patent, U.S. Patent No. 7,598,083 (“the ’083 patent”).  Further, there were two important developments with respect to the ’083 patent.  First, Celltrion alleged that Janssen did not have standing to bring suit on that patent because Janssen had failed to join all of the co-owners of the ’083 patent to the action.  Second, and relatedly, the Court provided “guidance” indicating that because the parties had never completed the ‘patent dance,’ 35 U.S.C § 271(e)(6) would not limit Janssen’s damages to a reasonable royalty in the event a future lawsuit was filed.

The parties proceeded to brief the questions of standing, with the Defendants filing a motion to compel evidence allegedly relevant to that question.  The case took a twist on May 31, 2017 (Dkt. 562), when Janssen informed the Court that it had filed a new lawsuit against Defendants, once again alleging infringement of the ’083 patent.  This was something that the Court had previously suggested.  Janssen contended that it was forced to file this lawsuit to preserve its rights because Celltrion had attempted to invoke the ‘patent dance’ with respect to the ’083 patent, triggering the deadline for filing a suit and preserving remedies under Section 271(e)(6).  Needless to say, Janssen contended that Defendants’ position was meritless, but stated it filed the lawsuit to eliminate any issue concerning its potential rights to future damages.  Moreover, Janssen explained that it executed a further assignment of the patent, mooting any standing issues.  Finally, Janssen stated that in light of these developments, it intended to dismiss the existing claims without prejudice to litigate the new lawsuit.

The following day, June 1, 2017, the Court held a telephone conference.  The docket indicates that the parties are to update the Court by June 16 in advance of a June 21, 2017 hearing.

Janssen’s new lawsuit is limited solely to the ’083 patent, with claims for infringement under Sections 271(a) and (b), as well as a claim for artificial infringement under 271(e)(2)(C).

Finally, the venue of the new lawsuit presents another potential quagmire, as Hospira is a Delaware corporation with a principal place of business in Illinois.  As such, in view of TC Heartland, Hospira may be able to argue that venue is improper in the new lawsuit.  Indeed, the new complaint goes out of its way to state that the defendants “did not contest venue in the 2015 action and the 2016 action,” perhaps setting up an argument that any such arguments are now waived.  Ultimately, this lawsuit will surely continue, regardless of any unique procedural developments.

We will continue to keep you apprised of further updates.

Fujifilm Kyowa Kirin Biologics announced that its Medical Marketing Application (“MMA”) for FKB327, a biosimilar to AbbVie’s Humira® (adalimumab), has been accepted for review by the European Medicines Agency (“EMA”).  Adalimumab is a TNF (tumor necrosis factor) inhibitor that binds to TNF-alpha (TNF-α), preventing it from activating TNF receptors, which cause the inflammatory reactions associated with autoimmune diseases. Humira® is indicated for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis, and ulcerative colitis.

Fujifilm Kiowa Kirin, Samsung Bioepis, and Biogen prevailed in patent litigation involving two patents related to adalimumab in the UK earlier this year, as we reported here. Fujifilm Kiowa Kirin is also developing FKB238, a bevacizumab biosimilar, jointly with AstraZeneca.  Bevacizumab is an anti-vascular endothelia growth factor A (Anti-VEGF) specific monoclonal antibody that inhibits formation of new blood vessels and is used to slow the growth of tumors related to several types of cancer.  Genentech’s Avastin® (bevacizumab) is indicated for the treatment of conditions related to metastatic colon cancer, lung cancer, glioblastoma, ovarian cancer, and cervical cancer.

The FDA announced yesterday that the Oncologic Drug Advisory Committee (“ODAC”) has scheduled a public meeting to review ABP 215, Amgen’s proposed biosimilar to Genentech’s Avastin (bevacizumab), on July 13, 2017.  According to the announcement, the proposed indications and uses for ABP 215 include:

  1. first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil-based chemotherapy;
  2. use in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line ABP 215-containing regimen;
  3. the first-line treatment of unresectable, locally advanced, recurrent, or metastatic non-squamous, non-small cell lung cancer in combination with carboplatin and paclitaxel;
  4. the treatment of glioblastoma with progressive disease in adult patients following prior therapy as a single agent;
  5. the treatment of metastatic renal cell carcinoma in combination with interferon alfa; and
  6. use in combination with paclitaxel and cisplatin or paclitaxel and topotecan for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix.

The FDA has established a public docket for comment on this meeting.  The docket number is FDA 2017-N-2732, and the comment period closes on July 10, 2017.

Amgen and Allergan announced that they submitted an application for ABP 215 to the FDA in November 2016, and according to Amgen, the BSUFA date (FDA’s target goal) for action on the application is September 14, 2017.  Amgen and Allergan also have an application for ABP 215 pending in Europe that was submitted in December 2016.

Introduction

The Amgen, Inc. and Amgen Manufacturing, Limited (“Amgen”) litigation against Hospira, Inc. (“Hospira”), filed in September 2015, was one of the earliest cases filed under the Biologics Price Competition and Innovation Act (“BPCIA”).  The case involves Hospira’s proposed biosimilar to Amgen’s Epogen®/Procrit® (epoetin alfa).  The procedural posture is somewhat complicated, as there are district court proceedings and an interlocutory appeal to the Federal Circuit underway simultaneously.  Furthermore, several issues raised in the dispute will be directly affected by the outcome of the decision in the consolidated Sandoz v. Amgen and Amgen v. Sandoz cases that are currently under consideration by the Supreme Court.

Epoetin alfa is a human erythropoietin that stimulates the production of red blood cells (erythropoiesis).  Epoetin alfa is produced in cell cultures using recombinant DNA technology.  The product is manufactured by Amgen and sold in the United States by Amgen as Epogen® and by Janssen, a subsidiary of Johnson & Johnson, as Procrit®.  Epoetin alfa is approved in the United States for treating anemia due to chronic kidney disease, anemia due to the use of zidovudine in HIV-infected patients, and the effects of concomitant myelosuppressive chemotherapy treatment. Epoetin alfa is also indicated to reduce the need for blood transfusions in certain patients undergoing certain types of elective surgery.

Epogen® first received FDA approval in 1989. Amgen prevailed in legal battles in the early 1990’s regarding patent ownership, and epoetin alfa has gone on to become a  blockbuster biologic, with yearly revenues consistently reaching over $1 billion annually since the mid-1990s, peaking at $2.6 billion in 2004, with around $1.3 billion in 2016.

Hospira, Inc. (“Hospira”) submitted an abbreviated biologics license application (“BLA”) seeking to market a proposed biosimilar (referred to by FDA as “Epoetin Hospira”) to Amgen’s Epogen® (epoetin alfa) in December 2014. Hospira publicly announced the submission of the application (BLA 125545) in January 2015, and the application was acquired by Pfizer when it purchased Hospira in 2015.  The original BSUFA date (target goal for FDA action) on the application was November 2015, but the FDA initially rejected the application.  Pfizer and Hospira resubmitted the application in December 2016. As we previously reported here, the FDA’s Oncologic Drugs Advisory Committee (ODAC) reviewed the application at a public meeting on May 25, 2017, and recommended approval across all indications.  Pfizer has publicly stated that, once approved, the product will be commercialized pursuant to an agreement between Pfizer and Vifor Pharma, Inc.

Hospira’s Retacrit® was approved in the EU in 2007, and according to Pfizer, its product is the first biosimilar erythropoiesis-stimulating agent (“ESA”) recommended for approval by an FDA Advisory Committee.  The FDA will take the ODAC’s recommendation into consideration before taking final action on the application, and although a specific date has not been announced, based on the date of the ODAC recommendation, a final decision on “Epoetin Hospira” could come as early as this summer.

The “Patent Dance” Between the Parties

In the Complaint, Amgen noted that this case was one of the first BPCIA infringement cases generally, and that it was also one of the first actions seeking to specifically enforce the application disclosure provision of section (l)(2)(A) and commercial notice provision of section (8)(A) of the BPCIA.  While this is a substantive patent infringement case, the disclosure and notice provisions of the BPCIA have taken center stage in the litigation thus far.  As previously discussed here, here, and here, at the time of this writing, the Supreme Court is considering the issues of: (1) whether a biosimilar applicant is required to provide the reference product sponsor with a copy of its biologics license application and related manufacturing information or whether the “patent dance” is optional; and (2) whether a biosimilar product must be “licensed” (meaning FDA-approved) before a biosimilar applicant can provide an effective 180-day  notice of commercial marketing (“NCM”) to the reference product sponsor (“RPS”), or whether such notice can be provided any time after the FDA has accepted the application for review.  The outcome of the Supreme Court’s decision will impact the issues surrounding these same questions in the Amgen v. Hospira litigation.

Hospira filed its application in December 2014, and the application was accepted for review by FDA in February 2015. This acceptance kicked off the complex series of deadlines for the exchange of information related to patent infringement, validity, and enforceability, affectionately known as the “patent dance.” One of Congress’s stated goals of the BPCIA’s “patent dance” is to potentially streamline and narrow patent litigation for biosimilar products.  According to the Compliant, Hospira notified Amgen when the FDA had accepted its BLA.  Although Hospira provided a copy of its BLA to Amgen on February 23, 2015, Amgen alleges that Hospira did not satisfy the disclosure requirements of section (l)(2)(A) of the BPCIA because Hospira did not provide any manufacturing information in addition to its BLA.

Following receipt of Hospira’s BLA, Amgen provided Hospira with a 3A list of patents which it believes could be asserted against Hospira. According to the pleadings submitted to the Court, Hospira’s 3A list identified only two patents.  The parties exchanged detailed statements, but Amgen has alleged that Hospira’s statement was deficient.  In the next step of the information exchange, section 4(a) of the BPCIA says that the RPS and the applicant “shall engage in good faith negotiations to agree on which, if any, patents” identified on their respective 3A and 3B lists “shall be the subject of an action for patent infringement.” According to Hospira’s Answer filed in the litigation, “Hospira advised Amgen that it accepted the patents” identified on Amgen’s 3A list and that litigation could proceed without further negotiations. Amgen’s Complaint, however, accuses Hospira of violating section (l)(4) of the BPCIA and contends that such acceptance did not amount to good-faith negotiations.

Hospira provided a notice of commercial marketing to Amgen on April 8, 2014.  Amgen objected to the notice as ineffective because it was provided before Hospira received approval (“licensure”) of its proposed product from the FDA.  The pleadings indicate that Hospira responded that it would rely on the April 8, 2015 notice and would not provide any further notice because in its view, further notice is not required.

The Litigation Begins

The Disclosure of Manufacturing Information Under (l)(2)(A)

On September 18, 2015, Amgen filed a Complaint against Hospira alleging infringement of U.S. Patent No. 5,856,298 (“the ’298 patent”), which Amgen identified in its initial list during the Patent Dance, and U.S. Patent No. 5,756,349 (“the ’349 patent”). In addition to counts based on infringement of these patents, Amgen’s complaint also included counts asserting that Hospira had violated the BPCIA by: 1) not providing manufacturing information along with its BLA in its initial notice to Amgen (Section (l)(2)); and 2) refusing to give NCM following the application’s approval.

In October 2015, Hospira moved to dismiss the count charging a violation of section (l)(2) regarding the disclosure requirements of the BPCIA, arguing that there is no private right of action for the enforcement of provisions of the BPCIA. Instead, Hospira argued that when an applicant elects not to disclose its application and manufacturing information pursuant to section (l)(2)(A) of the BPCIA, a reference product sponsor has a statutory remedy in the form of an immediately available declaratory judgment action, as expressly provided in section 9 of the BPCIA.

Following the Federal Circuit’s denial of a request for en banc review of the split majority panel’s decision in Amgen v. Sandoz which held that the BPCIA did not grant the right to compel compliance with the disclosure requirement of section (2)(A) and that the statute provided the only remedy in the form of a declaratory judgment action pursuant to section 9, Amgen filed an Amended Complaint dropping the section (2)(A) disclosure issue as a separate count. However, as the litigation progressed, Amgen has maintained its position that it requires manufacturing information, particularly to determine whether it may reasonably assert method patents directed to the cell culture in which Hospira’s product would be manufactured. In April 2015, the Court entered a scheduling order and the case was set for trial beginning in September 2017.

During discovery, Amgen sought manufacturing information and FDA correspondence from Hospira.  Hospira objected and sought to limit discovery to issues related to the two patents identified and asserted by Amgen.  In April 2015, the parties submitted letter briefings to the court, and Amgen sought to compel the production of manufacturing information and FDA correspondence.  The district court (Judge Andrews) denied the motion to compel, finding that the information sought was not relevant to the two patents which were asserted in the litigation.

Amgen appealed the decision to the Federal Circuit, and Hospira filed a motion to dismiss Amgen’s appeal for lack of jurisdiction, arguing that the Court’s ruling on the discovery dispute is not a final appealable order subject to the Appeals Court’s jurisdiction.  Hospira further argued that the order does not fall within the scope of the collateral order doctrine.  The Court requested briefing on the issue of jurisdiction as well as the denial of the motion to compel.  Briefing in the appeal was completed in November 2016, and the Federal Circuit heard oral argument on April 3, 2017. In that argument, the panel noted that the Sandoz opinion was still binding on the panel pending Supreme Court review.  The Court asked counsel for both sides what was stopping Amgen from filing new infringement suits on its cell culture patents. Amgen’s position is that it does not have enough information to reasonably file suits under the standards of Rule 11.

Notice of Commercial Marketing

Amgen’s complaint contained a count for declaratory judgment that Hospira’s refusal to provide a post-approval NCM violated the BPCIA, and Amgen sought an injunction prohibiting Hospira from marketing the product until 180 days after a post-approval NCM was provided to Amgen.

In October 2015, Hospira moved to dismiss the count regarding the NCM. Hospira argued that under its reading of the BPCIA, the 180-day NCM is only necessary for applicants who were not participating in the patent dance, and that Hospira had participated by providing its BLA to Amgen following its acceptance for review by the FDA.

In August 2016, the district court denied Hospira’s motion to dismiss the count regarding the NCM.  The Court recognized that the Federal Circuit’s Sandoz v. Amgen decision held that NCM is only effective after the FDA has “licensed” (approved) a product, and that the Federal Circuit’s Apotex v. Amgen case also concluded that the 180-day delay between NCM and entering the market was a mandatory requirement enforceable by injunction. As such, the district court held that it was presented with the same question that had been answered by the Federal Circuit, and under current law, Hospira’s motion should be denied.

Under current Federal Circuit precedent, a notice of commercial marketing is a “stand alone” requirement, meaning that it must be provided regardless of whether the parties complete the patent dance, and such notice can only be provided once the biosimilar has been approved by the FDA.  See Amgen, Inc. v. Sandoz, Inc., 794 F.3d 1347 (Fed. Cir. 2015). However, as discussed above, that specific issue is currently under review by the Supreme Court.  The Supreme Court heard oral arguments on April 26, 2017, and a decision is expected in late June.

The Status of the Substantive Patent Infringement Case

The ’298 patent, entitled “Erythropoietin Isoforms,” issued on January 5, 1999, from an application filed on November 3, 1994, and claims priority through a series of applications to October 13, 1989. The ’298 patent is assigned on its face to Amgen Inc. The ’349 patent, entitled “Production of Erythropoietin,” issued on May 26, 1998, from an application filed on June 6, 1995, and claims priority through a series of applications to December 13, 1983. The ’349 patent is assigned on its face to Amgen Inc.

Both of these patents are currently expired. As such, even if Amgen were to prevail on its claims of infringement, the two patents in suit would not prevent Hospira from launching its product upon approval (and effective NCM), but could subject Hospira to potential damages.  Amgen has taken the position that if additional patents are identified based on discovery, or if new patents issue that might be infringed, claims based on those patents could be asserted, which could prevent Hospira from entering the market.  On the other hand, Hospira has taken the position that Amgen is precluded by the BPCIA from asserting any existing patents that were not identified on Amgen’s original 3A patent list.

Infringement and invalidity contentions regarding the two patents were exchanged in April and May 2016. A Markman hearing was held in September 2016, and the district court issued an opinion construing the disputed claim terms and of the ’298 patent in November 2016.  In August 2016, Amgen filed a sealed motion for leave to file an amended complaint adding three additional defendants. As discussed in an October 2016 order granting the motion in part, the court noted that adding defendants so close to trial (scheduled for September 2017) would be prejudicial to the defendant and denied the motion as to that point.  However, the court noted that the proposed amended complaint also added two new theories of infringement based largely on the existing facts of the case, and the court allowed these theories to be added with respect to Hospira. One of these two new theories appears to be that Hospira directed and controlled an unidentified Hospira agent to infringe the patent. An additional count of infringement of the ’349 patent under 35 U.S.C. § 271(b) was added as well. This count alleged induced infringement as a result of Hospira directing two (redacted) companies to infringe claims of the ’349 patent.

Expert discovery closed on May 5, 2017, and dispositive motions were due by May 12, 2017.  Amgen did not file any dispositive motions. Hospira filed a motion for summary judgment that:

  1. all of Hospira’s accused erythropoietin drug substance batches are protected by the safe harbor provisions of 35 U.S.C. § 271(e)(1) and thus do not infringe U.S. Patent Nos. 5,756,349 and 5,856,298; and
  2. that Hospira does not infringe the asserted claims of U.S. Patent No. 5,856,298 either literally or under the doctrine of equivalents.

Briefing on Hospira’s summary judgment motion should be completed in early June, along with any briefing on Daubert motions. On May 26, 2017, Amgen filed a motion for a preliminary injunction seeking “to enjoin [Hospira] from launching a biosimilar version of Amgen’s EPOGEN® (epoetin alfa) product until Hospira has complied with the [notice of commercial marketing] requirement of 42 U.S.C. § 262(l)(8)(A).” Hospira has not yet responded to the motion for preliminary injunction.

A pretrial conference is currently scheduled for September 8, 2017, and a five-day jury trial will begin on September 18, 2017.  As noted above, a final decision on FDA approval of “Epoetin Hospira” could come as early as this summer.  We will continue to keep you apprised of further developments.

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.