Sandoz, Inc. (“Sandoz”) entered into the battlefield over patents related to AbbVie’s Humira® (adalimumab).  On July 20, 2017, Sandoz filed petitions with the Patent Trial and Appeal Board (“PTAB”) for inter partes review (“IPR”) of two patents assigned to AbbVie, U.S. Patent No. 8,802,100 (“the ’100 patent”) entitled “Formulation of Human Antibodies for Treating TNF-Alpha Associated Disorders,” and U.S. Patent No. 9,512,216 (“the ’216 patent”) entitled “Use of  TNF- α Inhibitor.”

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.

The proceedings are IPR2017-01823 (involving the ‘100 patent) and IPR2017-01824 (involving the ’216 patent). The only real party-in-interest identified for Petitioner is Sandoz.

Several other companies including Coherus, Boehringer Ingelheim, and Amgen have previously filed IPR petitions on other patents related to Humira®.  A complete list of IPRs can be found in RFEM’s IPR Dashboard.  We will continue to provide updates as these cases progress.

On July 24, 2017, Samsung Bioepis and Merck & Co., Inc. announced the launch of Renflexis® (infliximab-abda) in the United States.  According to Merck’s press release, Renflexis® “will be introduced in the U.S. [at] . . . a 35 percent discount to the current list price” of the reference product.  Renflexis® is the second FDA-approved commercially available biosimilar to Jansen’s Remicade® (infliximab) available in the United States.  As we previously reported, the FDA approved Reflexis® in April of this year, and Janssen filed patent litigation (arising to the BPCIA) against Samsung in New Jersey in May 2017 based on the filing of the BLA.

The first FDA-approved infliximab biosimilar, Sandoz’s Zarxio®, was launched in September 2015.  Litigation related Sandoz’s infliximab is also currently pending in New Jersey, as discussed in RFEM’s Litigation Spotlight series here and here.

The approval dates and launch status of all FDA-approved biosimilars in the United States are shown in the table above.  Two additional biosimilars, Amgen and Allergan’s bevacizumab and Mylan and Biocon’s trastuzumab, have been recommended for approval by the FDA’s Advisory Committee but have not yet been formally approved and licensed.

The U.S. Senate passed S.934 – FDA Reauthorization Act of 2017 on Thursday, August 3, 2017, by a 94-1 vote after having been passed by the House last month, as reported here. The President immediately signed it into law.

As we previously reported, the Biosimilar User Fee Act “BsUFA II” portion of the FDA Reauthorization Act of 2017 creates important changes for biosimilar applicants, including new user fees and application timelines.  In particular, the bill would increase user fees from $508 million to $1.3 billion in 2018 and extend the application review timeline by two months, while empowering the FDA to collect $9 billion in user fees between 2018 and 2022. More complete details on the changes to the legislative authority can be found in our previous post here.

Since our prior article on the litigation between Amgen and Hospira over Hospira’s proposed biosimilar to Amgen’s Epogen®, there have been several developments, including those that occurred after the Supreme Court’s recent Amgen v. Sandoz decision.

The last major development we previously discussed was a motion for a preliminary injunction filed by Amgen 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).” Since then, the brief supporting the motion, which was initially sealed, was filed in redacted form on June 5, 2017.

In its original supporting brief, Amgen relied heavily on the Federal Circuit’s earlier holding in Amgen v. Sandoz to support its position that the notice of commercial marketing was required to be given after FDA approval. Amgen also cited to this holding in support of its arguments with respect to Hospira’s alleged failure to disclose manufacturing information. While compelling such disclosure was not a direct point of this motion (as this exact point is currently pending before the Federal Circuit in an interlocutory review), Amgen used this alleged failure of disclosure as a factor in support of the preliminary injunction, citing to a Federal Circuit statement that a party in Amgen’s position can “access the required [manufacturing] information through discovery” in a patent-infringement action.

Then, on June 12, 2017, the Supreme Court issued its decision reversing the portion of the Federal Circuit’s Amgen v. Sandoz decision regarding notice of commercial marketing on which Amgen had relied. Specifically, the Supreme Court held that the notice of commercial marketing may be provided before a biosimilar applicant obtains a license (e.g. FDA approval).

The Supreme Court also emphasized that federal law does not provide the right to an injunction to force compliance with the disclosure requirements of section (l)(2)(A) of the BPCIA.  However, the Court left open the issue of whether state laws may provide an alternative avenue for injunctive relief, as discussed in this article.

On June 12, 2017, the parties in the Epogen® litigation stipulated to an extension of time regarding the motion for a preliminary injunction to allow the parties to consider and address the impact of the Supreme Court decision. A week later on June 19, 2017, Amgen moved to file an amended brief in view of the decision, and following grant of the motion, a sealed amended brief was filed on June 20, 2017. Hospira’s sealed opposition brief was filed June 26, 2017.

Amgen’s amended brief (as seen in its redacted form filed on June 29, 2017) seems to focus on the argument that notice of commercial marketing is mandatory and that Hospira’s notice is ineffective. While much of the rationale as to why the notice was allegedly ineffective is currently redacted, the argument appears to be based on an assertion that because Hospira had received a complete response letter from the FDA requiring resubmission of its application, any notice provided prior to such resubmission was no longer effective.   Amgen’s position on the discovery of manufacturing information remained largely the same as in its original brief.

Hospira’s amended opposition brief (as seen in its redacted form filed on July 6, 2017) noted that there is no requirement for additional notice following receipt of and response to a complete response letter.  Hospira characterized Amgen’s argument as “a repackaged version of its argument in Sandoz, which was explicitly rejected by the Supreme Court” and argued that “Amgen now links its argument to the submission of additional data and information to the FDA, rather than the date of FDA approval.” Hospira did not address Amgen’s points regarding disclosure of manufacturing information and the pending interlocutory review.

The district court held oral argument on several motions, including the motion for preliminary injunction, on June 28, 2017.  Amgen requested and received an extended deadline to submit a reply in response to Hospira’s amended opposition brief.  Then, on July 12, 2017, Amgen filed a notice of withdrawal of its preliminary injunction motion.  Not only has there been a change in the law, as discussed above, but the pertinent facts have also changed since the filing of the motion seeking a preliminary injunction. When At the time the motion initially filed, the FDA’s Oncologic Drugs Advisory Committee had recommended approval of Hospira’s Epogen® biosimilar. Amgen cited this recommendation in support of its claim of imminent harm absent an injunction. However, as we previously discussed in this post, Pfizer/Hospira announced in late June that its pending application had received another complete response letter, thus delaying any approval. Such delay would make it more difficult to establish imminent irreparable harm for purposes of a preliminary injunction, and this may have also impacted Amgen’s decision.

Unfortunately, for those looking to the limited number of biosimilar litigations for guidance, this case has presented additional questions but has not yet provided an answer to the question of what exactly is required to provide sufficient notice of commercial marketing.  Perhaps the pending appeal will provide further answers regarding the disclosure of manufacturing information.

On July 20, 2017, the parties filed a joint stipulation regarding the case schedule.  The pretrial order is currently due on August 31, 2017, and a five day jury trial remains scheduled to begin on September 18, 2017.

Merck & Co., Inc. (“Merck”) announced last week that the FDA has granted tentative approval for its insulin glargine injection LusdunaTM NexvueTM,  a follow-on biologic to Sanofi’s Lantus®.  Because Merck’s application for insulin glargine was filed using the abbreviated 505(b)(2) regulatory pathway provided by the Hatch-Waxman Amendments (not a section (k) application under the BPCIA), the product is properly characterized as a follow-on biologic, not a biosimilar.

Insulin glargine is a long-acting human insulin analog indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.  According to Merck, LusdunaTM NexvueTM  is being developed with funding from Samsung Bioepis.

Sanofi and Merck are currently involved in patent litigation related to this application. Sanofi filed a suit against Merck in the United States District Court for the District of Delaware in September 2016.  See Sanofi v. Merck, Civ. No. (D.Del.).  As a result of the litigation, final approval of Merck’s application is subject to the automatic 30-month stay of approval provided by Hatch-Waxman.  This is not the first follow-on biologic for insulin glargine. In December 2015, the FDA granted final approval to Basaglar®, Eli Lilly’s follow-on insulin glargine product.

Several other companies are reportedly developing insulin glargine products.  In June of this year, Mylan filed IPR petitions on two of Sanofi’s patents related to insulin glargine, as reflected in RFEM’s IPR Dashboard.

As we previously reported here, earlier this year the Supreme Court agreed to hear its first case arising under the Biosimilars Price Competition and Innovation Act (“BPCIA”) in the cases of Sandoz v. Amgen and Amgen v. Sandoz.  Our earlier post provides the factual background on this case, which involves Sandoz’s application to market Zarxio®, a biosimilar to Amgen’s Neupogen® (filgrastim) product.

This case is very important in determining how two key provisions of the BPCIA will be interpreted: (1) Can a biosimilar applicant provide an effective 180-day notice of commercial marketing prior to FDA approval (licensure); and (2) Is an injunction available to require a biosimilar applicant to provide the reference product sponsor with a copy of its biologics license application and its manufacturing information (i.e., to take the first step of the “patent dance”)?

Briefing was completed on April 14, 2017, as discussed in this prior article, and we also provided a summary of oral argument in this article.

The Court issued its unanimous decision on June 12, 2017.  Sandoz Inc. v. Amgen, Inc., 137 S. Ct. 1664 (2017).  The Court provided clear guidance that biosmilar applicants may provide 180-day notice of commercial marketing prior to the FDA’s approval of the application.  This holding means that an applicant that provides early notice of its intent to commercially market a biosimilar product may be able to launch that product immediately upon receiving FDA approval (provided no injunction has been entered pending resolution of patent disputes).

The Court left some open questions, however, regarding whether the biosimilar applicant can unilaterally “opt out” of the BPCIA’s patent dance.  The Court held that Federal law does not provide for an injunction requiring a biosimilar applicant to start the patent dance by providing its application and manufacturing information to the reference product’s sponsor under 42 U.S.C. § 262(l)(2)(A).  The Court left open the possibility, however, that state law (e.g., California’s unfair competition statute) may provide a remedy for the biosimilar applicant’s failure to provide its application to the reference product’s sponsor.

1.Notice of Commercial Marketing Can Be Provided Before the FDA Approves the Application

The BPCIA requires that a biosimilar applicant “shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing of the biological product licensed under subsection (k).”  42 U.S.C. § 262(l)(8)(A).  The Federal Circuit had interpreted this provision as requiring 180-day notice to be provided following the FDA’s approval of the application, reasoning that phrase “the biological product licensed under subsection (k)”refers only to a product that has already received a license.  Amgen, Inc. v. Sandoz Inc., 794 F.3d 1347, 1357 (Fed. Cir. 2015), rev’d and remanded by Sandoz, 137 S. Ct. 1664.

The Supreme Court disagreed.  The Court held that “[t]he statute’s use of the word ‘licensed’ merely reflects the fact that, on the ‘date of the first commercial marketing,’ the product must be ‘licensed.’”  Slip Op. at 16.  The Court therefore held that “the applicant may provide notice either before or after receiving FDA approval.”  Id.

The Court dismissed both sides’ policy arguments, stating that “[t]he plausibility of the contentions on both sides illustrates why such disputes are appropriately addressed to Congress, not the courts.”  Id. at 18.  Interestingly, Justice Breyer’s short concurrence suggests that the FDA could later issue a rulemaking that departs from the Court’s interpretation of the BPCIA in the Sandoz case.  Justice Breyer states his view that “Congress implicitly delegated to the [FDA] authority to interpret [the statutory terms at issue].”  Therefore, Justice Breyer reasons that if, “after greater experience administering this statute,” the FDA “determines that a different interpretation would better serve the statute’s objectives, it may well have the authority to depart from, or modify, today’s interpretation.”

2.Federal Law Does Not Provide for an Injunction Requiring the Biosimilar Applicant to Provide its Application and Marketing Information (to begin the “Patent Dance”), But the Court Left Open the Question of Whether State Law May Provide Such a Remedy

A. The Patent Dance

The Sandoz v. Amgen decision also addresses whether a biosimilar applicant can “opt out” of the patent dance, as Sandoz elected to do in this case.  The patent dance involves a series of steps for the exchange of information between the biosimilar applicant and the sponsor of the reference product that is designed to narrow the issues for patent litigation.  As the Supreme Court explains, “[i]f the parties comply with each step outlined in the BPCIA, they will have the opportunity to litigate the relevant patents before the biosimilar is marketed.”  Sandoz, 137 S. Ct. 1664, Slip Op. at 7.

The steps of the patent dance, set forth in 42 U.S.C. §262(l), are summarized in the chart below.

Note that if the parties take the full time allotted for each step, 250 days will have passed from the FDA’s acceptance of the application until the litigation is filed.  A biosimilar applicant that anticipates receiving FDA approval relatively soon may seek to avoid this lengthy process, despite the various advantages of participating in the patent dance.  The question before the Supreme Court in this case was whether the reference product sponsor can obtain an injunction forcing the biosimilar applicant to provide the information required by § 262(l)(2)(A).

B. No Federal Injunction to Require Participation in the Dance

Although § 262(l)(2)(A) states that the biosimilar applicant “shall provide” the reference product sponsor with a copy of its application and manufacturing information to begin the patent dance, § 262(l)(9) expressly contemplates a situation in which the biosimilar applicant fails to provide its application and manufacturing information.  In that case, the sponsor of the reference product (but not the biosimilar applicant) may immediately bring an action “for a declaration of infringement, validity, or enforceability of any patent that claims the biological product or a use of the biological product.”  42 U.S.C. § 262(l)(9)(C).

The Supreme Court held that “[t]he remedy provided by §262(l)(9)(C) excludes all other federal remedies, including injunctive relief.”  Sandoz, Slip Op. at 12.  The Court found the BPCIA’s “carefully crafted and detailed enforcement scheme” evidences that Congress did not intend to authorize other remedies.  Id.

The Federal Circuit had reached the same conclusion that no injunctive relief was available, but under somewhat different reasoning.  The Federal Circuit relied on both 42 U.S.C. § 262(l)(9)(C) and 35 U.S.C. § 271(e), finding those statutes “expressly provide the only remedies for a violation of § 262(l)(2)(A).”  Amgen, 794 F.3d at 1357.  In reaching its conclusion, “the Federal Circuit relied primarily on § 271(e)(4), which states that it provides ‘the only remedies which may be granted by a court for an act of [artificial] infringement.’”  Sandoz, 137 S. Ct. 1664, Slip Op. at 11.

The Supreme Court explained that “[f]ailing to disclose the application and manufacturing information under §262(l)(2)(A)” does not itself constitute an artificial act of infringement under § 271(e)(2)(C)(ii).  Id.  Rather, it is the act of filing the application that constitutes an artificial act of infringement.   The Court explained that 35 U.S.C. 271(e)(2)(C)(ii) “facilitates [the § 262(l)((9)(C) declaratory judgment] action by making it an artificial act of infringement, with respect to any patent that could have been included on the §262(l)(3) lists, to submit a biosimilar application.”  Id. at 7, 11.

Accordingly, § 271(e)(4) does not provide the remedy for failure to disclose an application and manufacturing information under 42 U.S.C. § 262(l)(2)(A).  This is a potentially important distinction because of Amgen’s unfair competition claims under California state law.

C. State Law Claims Remanded

California’s unfair competition law prohibits “any unlawful … business act or practice.”  A practice is considered “unlawful” if it violates a rule in some other state or federal statute.  However, California’s unfair competition law does not provide a remedy when the underlying statute specifies an “expressly … exclusive” remedy.  The Federal Circuit thus rejected Amgen’s state law claims because § 271(e)(4) expressly states that it provides the exclusive remedy for artificial acts of infringement.  See Sandoz, Slip. Op. at 13-14.

The Supreme Court rejected the Federal Circuit’s reasoning, holding “[b]ecause §271(e)(4) provides remedies only for artificial infringement, it provides no remedy at all, much less an ‘expressly … exclusive’ one, for Sandoz’s failure to comply with §262(l)(2)(A).”  Id. at 14.

The Court also declined to rule on the Federal Circuit’s alternative basis for its holding: that Sandoz’s choice not to provide information under 42 U.S.C. § 262(l)(2)(A) was not “unlawful,” because it is a course expressly contemplated by the BPCIA.  The Court held that the issue of whether Sandoz’s conduct is “unlawful” is a state law question, and Federal Circuit had erred by trying to answer it solely by looking to the BPCIA.  Id. at 15.

The Court remanded to the Federal Circuit to determine “whether California law would treat noncompliance with § 262(l)(2)(A) as ‘unlawful,’” and, if so, whether Federal law nonetheless preempts the state law claims.  Id.  Alternatively, the Court noted that the Federal Circuit could first address the pre-emption issue by assuming that a remedy under state law exists.  Id.  The latter course might provide the Federal Circuit with the opportunity to clarify that there are no state law remedies available to require biosimilar applicants to participate in the patent dance—rather than limiting the holding to California law issues.  However, the Federal Circuit noted that “Sandoz did not argue preemption as a defense to Amgen’s state law claims,” so this case may not be the appropriate vehicle for the Federal Circuit to reach a broad preemption holding.

Sandoz has now asked the Federal Circuit to remand the state law claims to district court, rather than determining these questions in the first instance.  Appeal No. 2015-1499, ECF #174 (filed June 29, 2017).  The Federal Circuit has not yet issued an order determining how the remand will be handled.

We will continue to keep you apprised of further developments.

Novartis’ First CAR-T Cell Therapy Tisagenlecleucel (CTL019)

The FDA’s Oncologic Drug Advisory Committee (“ODAC”) held a public meeting on Wednesday, July 12, 2017, to consider Novartis’ biologic license application (BLA 125646) for tisagenlecleucel (CTL019), an investigational chimeric antigen receptor T cell (“CAR-T”) therapy.  Novartis is seeking approval of CTL019 for the treatment of patients from three to 25 years old with relapsed or refractory B-cell acute lymphoblastic leukemia.  Novartis announced last week that the committee unanimously recommended approval in a vote of 10-0.

Tisagenlecleucel is comprised of genetically-modified antigen-specific autologous T cells that have been reprogrammed to target cells that express CD19, an antigen that is expressed on the surface of B cells and tumors derived from B cells.  As explained in the FDA briefing document, available here, “[t]he tisagenlecleucel chimeric antigen receptor (CAR) protein consists of an extracellular portion that has a murine anti-CD19 single chain antibody fragment (scFv) and an intracellular portion that contains T cell signaling (CD3-ζ) and co-stimulatory (4-1BB) domains. These intracellular domains play critical roles in tisagenlecleucel’s functions, including T cell activation, persistence in vivo and anti-tumor activity.” Additional meeting materials are available on the FDA’s website here.

CTL019 was originally developed by the University of Pennsylvania, and Novartis entered into a global collaboration with the university in 2013 to further research, develop, and commercialize CAR-T cell therapies, including CTL019.  According to Novartis, if approved, CTL019 could become the first CAR-T cell therapy available.

Amgen and Allegan’s Proposed Bevacizumab Biosimilar (ABP 215)

On the morning of Thursday, July 13, 2017, FDA’s ODAC held a meeting to consider the approval of ABP 215, Amgen and Allergan’s proposed biosimilar to Roche/Genentech’s Avastin® (bevacizumab).  As we previously discussed in this post, the FDA established a public docket for comments in advance of this meeting, and a total of nine comments (available here) were submitted to the agency prior to the meeting.  The committee voted unanimously (17-0) in favor of approval.

Bevacizumab is an anti-vascular endothelial 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 cancers. Amgen and Allergan are seeking approval of ABP 215 for (1) metastatic colorectal cancer, with intravenous 5-fluorouracil–based chemotherapy for  first- or second-line treatment; (2) metastatic colorectal cancer, with fluoropyrimidine-irinotecan- or fluoropyrimidineoxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line Avastin-containing regimen; (3) non-squamous non-small cell lung cancer, with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease; (4) glioblastoma, as a single agent for adult patients with progressive disease following prior therapy; (5) metastatic renal cell carcinoma with interferon alfa; and (6) cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease.

The FDA meeting materials including, inter alia, the FDA’s and Amgen’s briefing documents as well as draft questions are available directly from the FDA’s website here.

Mylan and Biocon’s Proposed Trastuzumab Biosimilar (MYL-1401O)

In the afternoon of Thursday, July 13, 2017, FDA’s ODAC held a meeting to consider the approval of MYL-1401O, Mylan and Biocon’s proposed biosimilar to Roche/Genentech’s Herceptin® (trastuzumab).  A copy of the FDA briefing document for the proposed product is available from the FDA website here, and the other meeting materials, including a briefing document prepared by Mylan, are available here.  According to Mylan’s announcement that same day, the committee voted unanimously (16-0) in favor of approval.

Trastuzumab is a monoclonal antibody that interferes with the human epidermal growth factor receptor (HER2)/neu. Mylan and Biocon are seeking approval of their proposed trastuzumab for the same indications approved for Herceptin®, including treatment of adjuvant breast cancer, 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, and treatment of metastatic gastric cancer in combination with cisplatin and capecitabine or 5-fluorouracil.

Earlier this year, Mylan and Biocon announced that they entered into a global settlement and licensing agreement with Genentech and Roche regarding Mylan’s trastuzmab biosimilar, as we previously reported in this post. We will continue to keep you apprised of further developments with respect to all of these applications.

Boehringer Ingelheim International GMBH and Boehringer Ingelheim Pharmaceuticals, Inc. (“Boehringer Ingelheim”) have prevailed in two inter parts review trials against one of AbbVie’s patents related to Humira®.  In two final written decisions issued, the Patent Trial and Appeal Board (the “PTAB” or “Board”) found all claims of U.S. Patent No. 8,889,135 (the ’135 patent”) invalid.

The ’135 patent, entitled “Methods of Administering Anti-TNFα Antibodies,” issued on November 18, 2014.  According to the final written decision, the ’135 patent discloses methods of treating rheumatoid arthritis (“RA”) with a human anti-tumor necrosis factor α (“TNFα”) antibody.  The decision further explains that:

The methods of the claimed invention involve administering an anti-TNFα antibody having the six complementarity determining regions (“CDRs”) and heavy chain constant region of D2E7, a known recombinant human anti-TNFα antibody. The methods further include administering a total body dose of 40 mg of the anti-TNFα antibody subcutaneously every 13–15 days, i.e., biweekly, for a period of time sufficient to treat RA.

See IPR 2016-00408, Final Written Decision at p.4 (internal citations omitted).  After considering the parties arguments and evidence, the Board concluded that the Petitioner had satisfied its burden of demonstrating by a preponderance of the evidence that the subject matter of claims 1-5 of the ’135 patent would have been obvious in view of the prior art, and the claims are unpatentable.  Id. at pp. 45-49.

The proceedings are IPR2016-00408 and IPR2016-00409.  The decision also notes that the parties identified inter partes proceeding IPR2016-00172, in which Coherus BioSciences Inc. petitioned for review of claims 1–5 of the ’135 patent, as a related matter.  Id. at p. 3 citing Coherus BioSciences Inc. v. AbbVie Biotechnology Ltd., Case IPR2016-00172 (PTAB) (“the 172 IPR”).  According to the decision, the Board instituted inter partes review of claims 1–5 of the ’135 patent in the 172 IPR, and found claims 1–5 unpatentable in a final written decision issued May 16, 2017.  Id., citing Coherus, Case IPR2016-00172, slip op. at 44 (PTAB May 16, 2017) (Paper 60).

Litigation regarding Humira® is currently ongoing before Judge Robinson in the United States District Court of Delaware. That case involves ten of AbbVie’s patents and Amgen’s proposed biosimilar adalimumab product.  See AbbVie v. Amgen, Civ. No. 1:16-cv-666, (D. Del.)(SLR).  Several additional patents related to Humira® are currently being challenged in post-grant proceedings before the PTAB.  The final written decision in the proceedings discussed above, as well as a summary of the IPR proceedings on other patents related to Humira®, can be found in the RFEM IPR Dashboard.

H.R.2430 – FDA Reauthorization Act of 2017, a bill reauthorizing all of the U.S. Food and Drug Administration (“FDA”) user fee programs, including reauthorization of the Biosimilar User Fee Act (“BsUFA II”), was passed in the House of Representatives on July 12, 2017, with bipartisan support by voice vote.  The House bill comes as the current legislative authority is set to expire at the end of September 2017.

As discussed previously here, BsUFA II creates important changes for biosimilar applicants, including new user fees and application timelines.  In particular, the bill would increase user fees from $508 million to $1.3 billion in 2018 and extend the application review timeline by two months, while empowering the FDA to collect $9 billion in user fees between 2018 and 2022.  More complete details on the changes to the legislative authority can be found in our previous post located here.

The Senate’s version of the bill was passed by the Committee on Health, Education, Labor & Pensions (“HELP Committee”) on May 11, 2017, where it continues to await a floor debate and vote.

On June 30, 2017, Pfizer, Inc. (“Pfizer”) filed two new petitions for inter partes review (“IPR”) of U.S. Patent No. 8,591,897 (“the ’897 patent”) related to Genentech’s Herceptin® (trastuzumab).  Pfizer has a trastuzumab biosimilar in phase III development, but it has not yet announced the filing of an application for that product with the FDA.  The company announced positive results in a study in patients with HER2-positive metastatic breast cancer in November 2016.

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.

Pfizer and its subsidiary Hospira have previously filed several IPR petitions challenging certain claims of other patents related to Herceptin® (trastuzumab) as discussed here, here, here and here.  The new proceedings are IPR2017-01726 and IPR2017-01727. The only real party-in-interest identified for Petitioner is Pfizer.  The ’897 patent, entitled “ANTI-ERBB2 ANTIBODY ADJUVANT THERAPY,” issued on November 26, 2013.

Mylan and Biocon are also seeking approval of a trastuzumab biosimilar. In March 2017, they announced a global settlement and licensing agreement with Genentech and Roche regarding Mylan’s trastuzmab biosimilar, as discussed in this post.

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