On June 14, 2018, Senator Orrin Hatch of Utah, the co-author of the Hatch-Waxman Act, filed an amendment to the Hatch-Waxman Act in an effort to further incentivize generic drug development. The language of the amendment, known as the Hatch-Waxman Integrity Act of 2018, states that its purpose is “to prevent the inter partes review process for challenging patents from diminishing competition in the pharmaceutical industry and with respect to drug innovation.” Senator Hatch has indicated that while he strongly supports the inter partes review (“IPR”) process, he feels that it is producing unintended consequences in the pharmaceutical industry by allowing two separate pathways for attacking a brand patent, and that it has upset the brand-generic balance put in place by the Hatch-Waxman Act. In a statement made at a Senate Judiciary Committee hearing, Senator Hatch stated that the amendment would preserve the ANDA/biosimilar process as the standard pathway for companies to challenge brand patents, and that “it would prevent companies from using IPR to put added litigation pressure on innovators above and beyond what Hatch-Waxman already provides. And it would prevent a company that rightfully loses a Hatch-Waxman suit from getting a second bite at the apple.”[1]

Changes Proposed by the Hatch-Waxman Integrity Act

The act provides amendments to Section 505 of the Federal Food, Drug, and Cosmetic Act for generic and brand drug makers and to Section 351(k) of the Public Health Service Act for biosimilar drug makers. For biosimilar applications, the proposed amendment would require an applicant to submit an application including “with respect to any patent that is, or that could be, included on a list of patents under subsection 18 (l)(3)(A)(i), … a certification that neither the applicant nor any party in privity with the applicant has filed, or will file, a petition to institute inter partes review or post grant review of that patent under chapter 31 or 32, respectively, of title 35, United States Code.’’[2]  Similar amendments were proposed for ANDA applicants.

The Hatch-Waxman Integrity Act essentially would require an ANDA or biosimilar applicant to choose between engaging in the ANDA/biosimilar approval pathway or challenging a patent in an IPR or PGR proceeding.  As noted by Senator Hatch, engaging in the ANDA/biosimilar process, a company may “rely on the brand company’s safety and efficacy studies for FDA approval,” whereas a party who files an IPR proceeding would have to develop its own safety and efficacy data.[3]

Potential Impacts for Biosimilar Applicants

Currently, under the Biologics Price Competition and Innovation Act (“BPCIA”), a biosimilar applicant is not required to disclose any patents when submitting its application. Thus, at the outset, the amendment would require more work and costs to be expended by a biosimilar applicant in preparing an application. Furthermore, it may be difficult for a biosimilar applicant to identify all the patents applicable for the proposed certification. There is no FDA listing of the patent exclusivities for biologics similar to the Orange Book. Thus, a biosimilar applicant may not be able to identify the necessary patents, or may be forced to identify the entire patent portfolio related to the biologic whether it would actually apply to its product or not.

Conclusions

In addition to the specific impacts it may have for biosimilar applicants, the Hatch-Waxman Integrity Act may cause significant impacts to ANDA and biosimilar applicants generally. For ANDA/biosimilar applicants, what was originally seen as a quick and cost-effective alternative to engaging in lengthy patent litigation may no longer be a feasible or favorable option. IPR and PGR proceedings are quicker and cheaper than filing a patent litigation lawsuit. However, the added costs and time ANDA/biosimilar applicants would need to spend to develop new safety and efficacy studies would likely far outweigh any potential savings to be had by challenging patents through the IPR process. Therefore, despite recently being upheld to be constitutional, IPR and PGR proceedings may be effectively eliminated in the pharmaceutical industry if the Hatch-Waxman Integrity Act is enacted.

 

[1] “Hatch Amendment to Incentive Generic Drug Development”, Senator Hatch Press Release, (June 14, 2018) https://www.hatch.senate.gov/public/index.cfm/2018/6/hatch-amendment-to-incentivize-generic-drug-development

[2] S. 974, 115th Cong. (2018).

[3] See supra note 1.

Earlier this month, the U.S. FDA announced approval of Mylan’s Fulphila biosimilar to Neulasta® (pegfilgrastim).  Neulasta® was developed by Amgen and first approved in the U.S. and Europe in 2002.  Following the approval announced on June 4, 2018, Fulphila, which was co-developed with Biocon, becomes the first biosimilar to pegfilgrastim approved in the U.S.

The FDA approved Fulphila to treat cancer patients with non-myeloid cancers receiving myelosuppressive chemotherapy that have clinically significant incidence of febrile neutropenia.  As we reported previously, Neulasta® (pegfilgrastim) biosimilars have failed to gain approval in Europe and in the United States despite numerous attempts.  The FDA previously rejected several pegfilgrastim applications, including the first Biologics License Application filed by Mylan/Biocon, and there are currently eight applications for pegfilgrastim pending in Europe.

Nevertheless, the FDA explained in their announcement that the review of evidence showed “extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Fulphila is biosimilar to Neulasta.”  The announcement marks another major win for Mylan and Biocon following the December 2017 approval of their co-developed Ogivri biosimilar to Herceptin® (traztuzumab).

The patents covering Neulasta® expired in October 2015 in the U.S. and August 2017 in Europe.  Mylan and Biocon also submitted an application for their pegfilgrastim candidate biosimilar product (MYL-1401H) to the European Medicines Agency (EMA).  However, Europe has yet to approve a pegfilgrastim biosimilar.

The FDA Commissioner, Scott Gottlieb, stressed that the U.S. agency will continue to prioritize review of biosimilar products.  As a result, the U.S. may start to gain some ground on the European markets, which have seen biosimilar approvals rapidly increase over the last three years. Click here to learn more about how the U.S. compares to Europe in biosimilars approvals and products in the pipeline.

The Patent Trial and Appeal Board (“PTAB”) recently denied Sandoz’s petition for inter partes review (“IPR”) of claims 1-30 of AbbVie’s patent, U.S. Patent No. 9,187,559 (“the ’559 patent”). The ’559 patent is directed towards a multiple-variable dose regimen for treating idiopathic inflammatory bowel disease. The patent discloses administering a high dose of a TNFα inhibitor in an induction phase and following up with a second administration of the inhibitor during a maintenance or treatment phase. Claim 1 specifically recites administering a first dose of 160 mg of adalimumab and two weeks after administration of the first dose, administering a second dose of 80mg of adalimumab. In its petition, Sandoz asserted that the ’559 patent claims were unpatentable under 35 U.S.C. §103(A) over the combination of a 2003 Humira Package Insert, WO 02/100330 A2 (“WO ’330”), Goodman & Gilman’s The Pharmaceutical Basis of Therapeutics, a 2002 Remicade Package Insert, and Hanauer’s Evolving Treatment Strategies for Inflammatory Bowel Disease. The PTAB denied institution, concluding that Sandoz failed to demonstrate that the 160mg/80mg dosing regimen of the ’559 patent claims would have been obvious. See Sandoz Inc. v. AbbVie Biotechnology LTD., IPR2018-00156 (PTAB June 5, 2018) (Paper 11).

Sandoz argued that the asserted prior art references disclosed all of the elements of the claims except the 160mg/80mg induction dosing regimen. Id. at 17. However, Sandoz argued that the dosing regimen would have been obvious because WO ’330 disclosed using higher doses of adalimumab, such as 80 mg every other week, to treat TNFα related disorders. Id. at 18. Sandoz argued that a person of ordinary skill in the art (“POSITA”) would have expected an 80 mg every other week dosing regimen to serve as good baseline for determining an induction or loading dose. Id. at 18. Sandoz also argued that a POSITA would have modified the 80mg every other week induction dose to arrive at the claimed 160mg/80mg dosing scheme based on several teachings in the prior art. Id. at 18. For example, Sandoz argued that the prior art taught that an “80 mg dose administered 2 weeks after the 160 mg dose would maintain heightened blood levels for 4 weeks, at which time the 40 mg every other week maintenance dosing would begin.” Id. at 18-19 (citing Petition at 22-23).

The PTAB held that Sandoz failed to show, without the use of hindsight, that a POSITA would have been motivated to use 160 mg as an induction dose or to select an intermediate dose to serve as a base for determining an induction dose. The PTAB agreed with Sandoz that the prior art disclosed that an induction/loading dose “is twice the size of the maintenance dose, if the maintenance dosing interval corresponds to the biological half-life of the drug.” Id. at 19. However, the PTAB concluded that “[a]pplying the general rules for determining an appropriate loading dose…results in an adalimumab loading dose of 80mg (i.e. a doubling of the 40 mg dose that Petitioner identifies as the maintenance dose), not a dose of 160 mg as recited in the claims.” Id. at 20. The PTAB stated that the prior art does not show how a POSITA would thus have arrived at the recited dosing regimen.

The PTAB also rejected Sandoz’s argument that the prior art discloses using a baseline dose to select an induction dose for a dosing regimen. The PTAB stated that instead, an induction dose is determined based on the maintenance dose. Thus, the PTAB denied institution of Sandoz’s petition, finding that the claims of the ’559 patent were not obvious over the cited prior art.

This is not the first time the PTAB has denied Sandoz’s petitions for IPR of AbbVie’s patents relating to the treatment of diseases using adalimumab. As discussed in a previous blog post, the PTAB recently denied Sandoz’s petition for IPR of AbbVie’s patent, U.S. Patent No. 9,512,216, directed towards a method of treating moderate to severe chronic plaque psoriasis using adalimumab.

On March 8, 2018, Amgen Inc. (“Amgen”) filed suit against Adello Biologics, LLC (“Adello”) in the District of New Jersey, alleging infringement of seventeen patents:  U.S. Patent Nos. 6,180,391; 7,083,948; 7,118,884; 7,384,765; 7,427,659; 7,662,930; 7,735,525; 7,781,395; 8,191,566; 8,273,707; 8,940,878; 8,952,138; 9,418,416; 9,632,095; 9,643,997; 9,704,239; and 9,856,287.  The case is assigned to Judge Claire C. Cecchi and Magistrate Judge Mark Falk, and is Civil Action No. 18-cv-3347.

According to the complaint, in a letter dated September 11, 2017, Adello “purported to provide notice, pursuant to 42 U.S.C. § 262(l)(8)(A), of its intent to commercially market a proposed biosimilar to NEUPOGEN® ” and “informed Amgen that Adello took advantage of the abbreviated subsection (k) pathway in submitting its aBLA.”  Complaint ¶12.

However, the complaint also asserts that Adello’s September 11, 2017 letter explained that Adello did not intend to participate in the patent dance, stating that “Adello ‘is not required to and does not intend to provide Amgen with [the Adello aBLA] or manufacturing information contemplated by 42 U.S.C. § 262(l)(2)(A).’”  Id. ¶13.  As a result of not having this information, Amgen has stated in each count of infringement that it is “thus unable to provide a more detailed infringement analysis for the Adello Filgrastim Product or the process(es) of its manufacture at this time without discovery, including the Adello aBLA and other information that describes the process or processes used to manufacture the Adello Filgrastim Product.”  Complaint ¶¶95, 106, 117, 128, 139, 150, 161, 172, 183, 194, 205, 216, 227, 238, 249, 260, and 271.  The Complaint alleges infringement under 35 U.S.C. § 271(e)(2)(C)(ii) based on Adello’s aBLA submission to FDA, Id. ¶18, and alleges that “[u]nless enjoined by this Court, upon information and belief, Adello will infringe one or more claims of each of the Asserted Patents under 35 U.S.C. §§ 271(a) and 271(g) by making, using, offering to sell or selling within the United States, or importing into the United States the Adello Filgrastim Product which Adello makes by a process covered by the Asserted Patents, before the expiration of Asserted Patents.”  Id. at ¶20.

Adello recently answered the complaint on May 17, 2018, denying infringement and asserting counterclaims of non-infringement and invalidity for all seventeen patents.  Relying on the Supreme Court’s Sandoz, Inc. v. Amgen, Inc. decision (137 S. Ct. 1664, 1674-75 (2017)), Adello admitted “that it was not required to, and did not, provide Amgen with a copy of its aBLA or manufacturing information prior to Amgen filing this lawsuit.”  Answer ¶13.  In its counterclaims, Adello points out that two of the patents-in-suit, U.S. Patent Nos. 8,940,878 and 8,952,138, were the subject of prior district court litigations where the biosimilar applicants, Sandoz and Apotex, respectively, were found not to infringe.  Counterclaim ¶¶15-16.  Adello also alleges in its counterclaims that “[n]one of the Patents-in-Suit specifically claim G-CSF or methods of treatment using G-CSF. Nor are any of the Patents-in-Suit identified on the label for NEUPOGEN® as covering that product. Upon information and belief, Amgen does not practice any of the Patents-in-Suit in its manufacture of NEUPOGEN®.”  Id. ¶19.

A scheduling conference is set for June 19, 2018.

Last week, Eli Lilly and Company (“Lilly”) announced that galcanezumab met its primary endpoint in a Phase 3 study of patients with episodic cluster headaches. Lilly previously announced that galcanezumab met its primary endpoints in three different Phase 3 studies evaluating its effectiveness in preventing episodic and chronic migraine.

The episodic cluster headache study was a two-month Phase 3, randomized, double-blind, placebo-controlled, global trial evaluating the safety and efficacy of galcanezumab (300 mg once-monthly) administered subcutaneously compared with placebo in 106 patients.  According to Lilly, patients treated with galcanezumab experienced statistically significant differences in the reduction of weekly cluster headache attacks compared to patients treated with placebo across weeks one to three of the study.  The safety and tolerability profile was consistent with previous studies evaluating galcanezumab for the prevention of migraine.

Galcanezumab is a monoclonal antibody that is designed to bind to and inhibit the activity of calcitonin gene-related peptide (“CGRP”).  Increased levels of CGRP have been reported in patients during migraine and cluster headache episodes.  Based on the results of the migraine Phase 3 trials, Lilly submitted galcanezumab to the FDA for review, and a decision is expected in the third quarter of this year.  Based on the results of the cluster headache trial, Lilly will no doubt seek to add the treatment of episodic cluster headaches as an indication for galcanezumab.

CGRP antagonists such as galcanezumab have been a focus for a number of companies seeking to develop migraine treatments.  In addition to Lilly’s galcanezumab, two other anti-CGRP antibodies are in late-stage development.  In fact, Teva has already submitted an application for its fremanezumab to the FDA (although manufacturing concerns have delayed FDA approval until at least September), and Alder Biopharmaceuticals is expected to submit an application for its eptinezumab later this year.  In addition, as we previously reported, Amgen and Novartis recently announced that the FDA approved its Aimovig™ (erenumab) product for the preventive treatment of migraine, although erenumab targets the CGRP-receptor instead of CGRP itself.

Last week, Novartis and Amgen announced the FDA approved Aimovig™ (erenumab) for the preventive treatment of migraine in adults.  The FDA granted approval to Amgen; however, Amgen and Novartis have entered into a global collaboration to develop and commercialize treatments in the field of migraine. As part of this agreement, the two companies will co-commercialize Aimovig™ in the U.S.  Amgen retains exclusive commercialization rights in Japan, and Novartis has exclusive commercialization rights in Europe, Canada, and the rest of the world.

Aimovig™ is a monoclonal antibody that targets the calcitonin gene-related peptide receptor.  According to the FDA,“Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that work by blocking the activity of calcitonin gene-related peptide, a molecule that is involved in migraine attacks.”  Aimovig™ is self-administered via a subcutaneous injection at a dose of 70 mg once monthly, although some patients may be prescribed a dosage of 140 mg once monthly.

Novartis and Amgen expect that Aimovig™ will be available as soon as this week.  The two companies have also announced that Aimovig™ is expected to cost $575 per month, or $6,900 annually.

According to some experts, the global market for migraine drug sales is around $4 billion per year and is expected to grow to $8.7 billion by 2026.  Thus, it is not surprising that although Amgen is the first to obtain approval for a product that interferes with CGRP signaling, it is not the only company pursing this avenue.  Indeed, Eli Lilly and Company, Teva, and Alder Biopharmaceuticals all have similar products that are either currently under review by the FDA or are expected to be shortly.

As we recently covered, May 15, 2018, saw the FDA granting approval to Hospira (now a Pfizer subsidiary) for its Retacrit injection, a biosimilar to Amgen’s Epogen®. The approval, based on a Biologics License Application dated December 16, 2014, came after Hospira resubmitted its application twice after receiving Complete Response Letters from the FDA, most recently in November 2017.

In addition to the regulatory barriers Hospira has overcome in reaching approval, Hospira has faced legal challenges from Amgen in the form of one of the earliest litigations filed under the Biologics Price Competition and Innovation Act (“BPCIA”). We previously covered that litigation here and here.

Since our last update in early August 2017, there have been several developments in the litigation, including the Federal Circuit dismissing Amgen’s appeal regarding its denied discovery of Hospira manufacturing information on jurisdictional grounds and failure to satisfy the prerequisites for mandamus. However, the most significant development was the five day trial which took place in September 2017.

At the conclusion of trial, the jury found that Hospira had not infringed any claim of U.S. Patent 5,756,349 (“the ’349 patent”), while it did infringe two asserted claims of U.S. Patent No. 5,856,298 (“the ’298 patent”). The jury found those two claims to not be invalid for anticipation or obviousness, and further held that only a portion of the lots manufactured by Hospira fell into the BPCIA’s Safe Harbor Defense. Ultimately, the jury found that Amgen had proven $70 million in damages as a result of Hospira’s pre-approval manufacturing activities.

On September 25, 2017, the Court entered its judgment, awarding $70 million and holding the ’298 patent valid and infringed, and the ’349 patent not infringed. Soon after, the first of several post-trial motions were filed. On October 12, as both parties agreed that several counts by both parties had not yet been ruled on, a stipulated agreement was entered into the case that the judgment was not final and was not immediately appealable or executable, and it additionally stipulated a schedule for briefing post-trial motions.

Both parties then filed their initial Motions for Judgment as a Matter of Law or of New Trial on October 23, 2017. Answering briefs were filed by both parties on November 20, and reply briefs on December 8. The most recent filing in the case took place on December 15, 2017, requesting oral argument regarding the motions. Hospira’s motion requests findings that 1) its 21 manufacturing batches are protected under the Safe Harbor Defense, 2) it did not infringe the claims of the ’298 patent, 3) the claims of the ’298 patent are invalid, and 4) damages should be limited to no more than $1.5 million per batch. Amgen’s motion, meanwhile, requests a finding of infringement of the ’349 patent.

If the judgment at issue currently stands, Hospira will be on the hook for $70 million for its pre-approval manufacturing activities. However, as both the ’298 and ’349 patents are currently expired, none of the current judgment or rulings in favor of either party on their motions will prevent Hospira from bringing its now-approved Retacrit to market, and only modifications or removal of the damages award may occur.

What may remain a difficulty for Hospira, however, is that the court still has not entered judgment as to Count 1 of Amgen’s complaint regarding Hospira’s allegedly giving ineffective Notice of Commercial Marketing as required under the BPCIA. While the latest stipulation entered on October 31, 2017, indicates that the parties recognize that as time goes on, this may become, or already has become, a moot issue,  it is still a factor that Hospira considers in the timing of its launch into the U.S. market.

Earlier this month, Celltrion, Inc. (“Celltrion”) filed a copycat IPR petition directed against U.S. Patent No. 7,976,838 (“the ʼ838 patent”) that is essentially identical to a petition filed by Pfizer, Inc. (“Pfizer”).  The PTAB recently instituted review of the ʼ838 patent based on Pfizer’s petition in IPR2017-01923.  Celltrion’s copycat petition was accompanied by a motion for joinder with the currently pending Pfizer IPR.

Celltrion’s motion for joinder asserts that it contains identical grounds to those presented in the Pfizer petition, and thus would not create any additional burdens on the parties or impact the trial schedule.  Celltrion further explains that it conferred with Pfizer’s counsel and agreed to proceed in a limited “understudy” role, unless Pfizer is terminated from the proceedings.  As part of this understudy role, Celltrion agreed to not produce its own testifying witnesses, file any substantive papers (unless those papers do not affect Pfizer), or participate in the oral hearing.

This is the third time Celltrion has challenged the ʼ838 patent in an IPR.  Celltrion’s first challenge to the ʼ838 patent was via another copycat petition based on Boehringer Ingelheim’s (“Boehringer”) petition filed in IPR2015-00417.  Celltrion filed a motion for joinder in that case but while the motion was pending, Boehringer requested adverse judgment and the IPR was terminated.  Celltrion then requested dismissal of its copycat petition without prejudice, which the PTAB granted.  Celltrion subsequently filed its own IPR challenging the patentability of the ʼ838 patent, but the PTAB declined to institute review.

In Celltrion’s first copycat petition in the Boehringer IPR, Celltrion did not retain an expert of its own to support its petition.  Rather, Celltrion relied on the same exhibits and expert declaration that Boehringer submitted.  However, once Boehringer requested adverse judgment, Celltrion was no longer able to work with that expert.  Without an expert of its own, Celltrion could not proceed in the IPR.  Celltrion apparently learned from this experience, and supported its most recent copycat petition with expert declarations submitted by experts independent of those relied on by Pfizer.

The lesson here for parties filing copycat petitions is that they should consider submitting independent expert declaration(s), even if those declaration(s) are essentially identical to those supporting the petition being copied, to avoid any problem with continuing in the IPR if the first-filing party drops out of the proceeding.

Earlier this month, the Patent Trial and Appeal Board (“PTAB” or “the Board”) denied institution of Sandoz’s petition for inter partes review of Abbvie’s patent, U.S. Patent No. 9,512,216 (“the ’216 patent”), directed to methods for treating moderate to severe chronic plaque psoriasis with a human anti-tumor necrosis factor α (TNFα) antibody.[1] The petition, filed on October 2, 2017, asserted that claims 1-16 of the ’216 patent were unpatentable under 35 U.S.C. § 103(a) as obvious over a Humira 2003 Label and a Humira 2002 Label, in combination with other references. The institution decision ultimately hinged on whether the labels constituted prior art “printed publications” under 35 U.S.C. § 102(b).

As the Board explained in its decision, the petitioner has the burden to establish a reasonable likelihood that it will prevail on the merits, which, inter alia, includes putting forth sufficient arguments and evidence to show that the petitioner would establish public accessibility of the reference by a preponderance of the evidence over the course of the trial.[2] Whether a reference qualifies as a “printed publication” is a case-specific inquiry, with the key factor being a satisfactory showing that the reference was “sufficiently accessible to the public interested in the art” before the filing date.[3] A reference is considered “publicly accessible” if it was “disseminated or otherwise made available to the extent that persons interested and ordinarily skilled in the subject matter or art exercising reasonable diligence can locate it.”[4]

In its petition, Sandoz identified the Humira 2002 Label and Humira 2003 Label as prior art under § 102(b), asserting merely that the labels were “prior art FDA-approval label[s]” and that the drugs were approved by the FDA in December 2002 and January 2003, respectively.[5] In the preliminary patent owner response, Abbvie argued that this showing was insufficient. Specifically, Abbvie pointed out that the issue dates on the face of the labels do not establish “public accessibility,” and although Sandoz attached exhibits which could support an argument that the labels were publicly accessible, including a screenshot of the Humira 2003 label from the WayBack Machine and affidavit from the Office Manager at the Internet Archive, neither was cited or discussed in the petition itself.

In response to the preliminary patent owner response, Sandoz sent an email to the Board requesting, in part, authorization to file a reply to address Abbvie’s arguments regarding the public availability of the Humira labels. The PTAB denied this request, explaining that Petitioner could have reasonably foreseen arguments regarding whether the Humira labels were publicly available before the priority date of the ʼ216 patent, given that a petitioner bears the initial burden of production to establish the existence of prior art that renders the claims unpatentable. The Board did, however, grant Sandoz’s request to file a reply in response to the Patent Owner’s arguments regarding §§ 314(a) and 325(d).

Despite the Board’s limited authorization regarding the scope of the reply, the background section of Sandoz’s reply included arguments addressing the public availability and “printed publication” status of the Humira labels, citing to the WayBack Machines screenshot and the affidavit of Christopher Butler, Office Manager at the Internet Archive, affirming that the 2003 Humira Label was publicly accessible and archived from www.fda.gov on March 31, 2003. This appears to have rubbed the Board the wrong way. In the decision denying institution, the PTAB noted that “Petitioner’s attempt in the Reply to meet its threshold showing that Humira 2003 Label is a printed publication is not only untimely, but also appears to circumvent our Order (Paper 11) denying Petitioner’s request to file a reply on that very issue.”[6]

The PTAB ultimately agreed with Abbvie’s arguments that the Humira labels were insufficient to establish public availability, such that the labels did not qualify as prior art under § 102(b), and the petition was thus denied. While this decision illustrates a hard lesson learned under the old adage “don’t bite the hand that feeds you,” it is also a testament to the need for petitioners to put forth sufficient evidence to establish that a reference relied upon is indeed a prior art “printed publication” in the petition itself. Merely including supporting evidence as an exhibit, without a citation or explanation in the petition, just won’t cut it for meeting the threshold showing of prior art status.

 

[1] Sandoz Inc. v. Abbvie Biotechnology Ltd., IPR2018-00002, Paper No. 13 (PTAB May 3, 2018).

[2] Id. at 6-8.

[3] Id. at 7 (citing In re Lister, 583 F.3d 1307, 1311 (Fed. Cir. 2009)).

[4] Id. (citing Kyocera Wireless Corp. v. ITC, 545 F.3d 1340, 1350 (Fed. Cir. 2008) (citation and internal quotations marks omitted)).

[5] Petition at 24.

[6] Sandoz Inc. v. Abbvie Biotechnology Ltd., IPR2018-00002, Paper No. 13 at 12 (PTAB May 3, 2018).

 

Today, the FDA announced that it approved Retacrit (epoetin alfa-epbx) as a biosimilar to Epogen® for the treatment of anemia caused by chronic kidney disease, chemotherapy, or use of zidovudine in patients with HIV infection.  The FDA also approved Retacrit for use before and after surgery to reduce the chance that red blood cell transfusions will be necessary due to blood loss during surgery. The FDA’s approval was granted to Hospira, which is now a Pfizer company by virtue of Pfizer’s acquisition of Hospira in 2015.

According to the FDA, approval “is based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Retacrit is biosimilar to Epogen/Procrit.”  The FDA further noted that although Retacrit has been approved as a biosimilar, it has not been approved as interchangeable with Epogen®.

Retacrit is the first epoetin alfa biosimilar to be approved by the FDA, and just the tenth biosimilar approved overall.  In announcing the approval, Pfizer stated that “[a]s the first approved epoetin alfa biosimilar in the U.S., RETACRIT may provide patients and their physicians with increased access to a high-quality, lower-cost alternative treatment option for anemia and the reduction of allogeneic red blood cell (RBC) transfusions in certain patients.”  Pfizer also stated that “RETACRIT is expected to be available in the U.S. at a significant discount to the current wholesaler acquisition cost (WAC) of Epogen and Procrit.”

The FDA’s approval of Retacrit comes nearly a year after it issued a complete response letter (“CRL”) to Pfizer regarding the then pending application.  As we previously reported, Pfizer stated that the CRL did not specifically relate to the manufacture of Retacrit, but was in response to matters noted in a Warning Letter following a routine inspection of a manufacturing facility that was identified as a potential manufacturing site for its epoetin biosimilar.

Hospira and Amgen are currently involved in litigation over patents that Amgen has asserted over this biosimilar.  Last September, a jury in the District of Delaware found Hospira liable for infringing one of the two patents at issue and awarded Amgen 70 million dollars in damages.  However, post-trial motions filed by both Hospira and Amgen are still pending, and so the judgment is not final.  In addition, the patent that Hospira was found to infringe has now expired.