Mumbai-based pharmaceutical manufacturer Lupin recently received FDA approval for its generic version of Roche’s Tamiflu® (oseltamivir phosphate), one of the most popular antivirals prescribed for relief from the influenza virus. The active ingredient is indicated for the treatment of acute, uncomplicated influenza A and B in patients two weeks of age or older who have been symptomatic for no more than forty-eight hours. The drug comes in capsule form in strength amounts of 30 mg, 45 mg, and 75 mg.[1]

This FDA approval comes near the end of a particularly dangerous flu season, which scientists consider to rival the swine flu pandemic of 2009.[2] The latest report from the Centers for Disease Control and Prevention (“CDC”) in the first week of February notes that 7.7% of reported patients visiting hospitals nationwide -nearly 1 out of every 13 hospital patients- have come in with flu-like symptoms, including a temperature of 100°F or greater and cough and/or sore throat.[3] This is well above the national baseline of 2.2%.[4] The report further explains how there has been a significant increase in deaths resulting from the virus, especially in vulnerable populations such as children and the elderly, with over 60 reported pediatric deaths thus far across the country.[5]

As the flu vaccine has only proven to be about 30% effective against this year’s most prevalent virus strain, prescriptions of treatments like Tamiflu® are on the rise.[6] In a market currently worth over $500 million a year in U.S. sales, Lupin is right on time for the party, joining pharmaceutical competitors Natco, Macleods, Nesher, Alvogen, and Amneal, who also received FDA approvals for generic oseltamivir phosphate capsules and/or oral suspensions in 2016 and 2017.[7] This new competition is finally leveling the playing field with Roche, who has dominated the market since obtaining FDA approval for the Tamiflu® oral capsules and suspensions in 1999 and 2000, respectively.[8]

Notably, Lupin should face little to no opposition from Roche in bringing the generic to market. While Roche, in addition to Genentech and Gilead Sciences, the collective owners of U.S. Patent No. 5,763,483 for Tamiflu®, sued Lupin in a Maryland federal court in 2015 for patent infringement based on an intent to market the drug before the patent expires in 2021, the parties were able to come to a settlement agreement and the case was dismissed in May of 2016.[9]

 

[1] FDA Drug Approval for ANDA 208348, available at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=208348 (last accessed on February 12, 2018).

[2] Mike Stobbe, This Year’s Flu is Now as Bad as the 2009 Sine Flu Epidemic, CDC Says, TIME, available at http://time.com/5143232/cdc-flu-epidemic/ (last accessed on February 12, 2018).

[3] Centers for Disease Control and Prevention, 2017-2018 Influenza Season Week 5 ending February 3, 2018, available at  https://www.cdc.gov/flu/weekly/#S6 (last accessed on February 12, 2018).

[4] Id.

[5] Id.

[6] Centers for Disease Control and Prevention, Vaccine Effectiveness- How Well Does the Flu Vaccine Work, available at https://www.cdc.gov/flu/about/qa/vaccineeffect.htm (last accessed on February 12, 2018).

[7] FDA Approvals for Oseltamivir Phosphate, available at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process (last accessed on February 12, 2018).

[8] Id.

[9] Gilead Sciences, Inc. et al. v. Lupin Pharmaceuticals, Inc., No. 1-15-cv-02793 (D. MD May 12, 2016).

Last week, the Federal Circuit affirmed a lower court’s dismissal of AbbVie’s complaint seeking declaratory judgment of invalidity of U.S. Patent No. 6,248,516 (“the ’516 patent”) owned by Astra Zeneca subsidiary MedImmune.  AbbVie brought this declaratory judgment action in June 2016 in the hopes of ending its royalty obligations to MedImmune.

The Fed. Circuit’s decision on appeal from the U.S. District Court for the Eastern District of Virginia establishes that a party may not seek declaratory judgment to obtain piecemeal adjudication of subsidiary issues that do not resolve the overall dispute.

The declaratory judgment action is related to a development and licensing agreement initiated in 1995 that led to the antibody known as adalimumab.  Adalimumab is the active ingredient in the blockbuster drug Humira®.  As we reported previously, Humira® generated over $16 billion USD in 2016, becoming the world’s best-selling drug.  The agreement allowed AbbVie to practice a number of patents, including the ’516 patent, but required AbbVie to pay royalties on related sales until the later of fifteen years from the date of First Commercial Sale or the expiration date of the last patent to expire amongst the specified patents under the agreement (i.e. the expiration of the ’516 patent).  Therefore, under the agreement, royalties would be paid to MedImmune until January 2018 or June 2018, respectively.  AbbVie asserted that a declaration of the ’516 patent’s invalidity would be an expiration of the patent for the purpose of the agreement, thereby ending its royalty obligations.

The district court dismissed AbbVie’s complaint for two reasons: (1) AbbVie did not practice the ’516 patent, and therefore lacked standing since it could not be subject to patent infringement; and (2) even in the event AbbVie had standing, the court declined to use its discretionary declaratory judgment jurisdiction since the British government jointly owns the patent and the agreement is governed by British contract law.  Accordingly, the invalidity question would not likely resolve the parties’ underlying dispute in view of concerns about foreign law and sovereign immunity.

The Fed. Circuit disagreed with the district court over its holding that it lacked declaratory judgment jurisdiction.  The court reasoned that even in the absence of patent infringement, it should look to the “‘character of the threatened action’ that the declaratory judgment defendant ‘might have brought.’”  Specifically, the contractual obligations under the 1995 agreement would turn on the expiration and/or validity of the ’516 patent.  The court opined that “[i]f properly presented, such a contractual dispute could confer declaratory judgment jurisdiction.”

However, in the instant case, AbbVie sought out declaratory judgment of invalidity in regard to the ’516 patent, rather than its contractual obligations.  The court noted that AbbVie has no other pending litigation in American or British courts that could resolve the contractual dispute.  Accordingly, the court held that AbbVie cannot establish declaratory judgment jurisdiction over invalidity, reasoning that it is an open question as to how the British courts would view the invalidity of ’516 patent in relation to patent expiry under the agreement.

On February 2, 2018, U.S. District Judge George H. Wu granted Genentech’s motion to dismiss a complaint brought by Amgen in the Central District of California seeking a declaratory judgment of non-infringement, invalidity, and unenforceability of twenty-seven patents related to Genentech’s cancer treatment biologic, Avastin® (bevacizumab).[i]

Judge Wu issued a tentative decision on January 11, 2018, stating he would grant the motion to dismiss, but stayed that decision until a determination was made in two related Delaware cases on Amgen’s motions to transfer venue to the Central District of California.[ii] The Delaware court denied Amgen’s motions to transfer venue on January 22, 2018.[iii]

Judge Wu granted the motion to dismiss based on the court’s “broad discretion under the Declaratory Judgment Act, including [his] concerns that Amgen’s suit in [the Central District of California] was anticipatory and that the concurrent proceedings in Delaware would lead to duplicative litigation.” He also based his decision on the reasons provided in the tentative decision, where he noted that he was declining to hear Amgen’s case because Amgen had not properly completed the negotiation process required by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”). He stated that he would decline “to hear a case where Amgen effectively attempted to bypass the BPCIA’s scheme for negotiations and eventual litigation.”

The dispute arose over Amgen’s attempts to seek approval from the FDA to market a biosimilar of Avastin®. The FDA approved Amgen’s Mvasi™ (bevacizumab-awwb) as a biosimilar to Genentech’s Avastin® on September 14, 2017.[iv] On October 6, 2017, Amgen provided its notice of commercial marketing to Genentech and immediately filed the declaratory judgment action in the Central District of California. That same day, Amgen reached out to Genentech to continue the final patent exchange procedures as required for the first phase of patent litigation under the BPCIA. Genentech learned of Amgen’s declaratory judgment action and immediately filed a lawsuit in Delaware alleging infringement of twenty-four of the twenty-seven Avastin®-related patents at issue in the declaratory judgment action. The parties completed the BPCIA’s required negotiation process on October 13, 2017, and Genentech brought its “first phase” lawsuit in Delaware on October 18, 2017, asserting infringement of twenty-five of the twenty-seven patents and alleging that Amgen failed to comply with its statutory obligations under the BPCIA. Genentech’s two Delaware cases have been consolidated. Amgen filed a motion to dismiss for failure to state a claim and for lack of subject matter jurisdiction, which is currently pending before the Delaware court.

 

[i] Amgen Inc. v. Genentech, Inc., Case No. 2:17-cv-07349 (C.D. Cal. Feb. 2, 2018) (Docket No. 63).

[ii] Amgen Inc. v. Genentech, Inc., Case No. 2:17-cv-07349 (C.D. Cal. Feb. 2, 2018) (Docket No. 56).

[iii] See Genentech, Inc. v. Amgen Inc., Civ. No. 17-1407-GMS (D. Del. Jan 22, 2017) (Docket Nos. 58 & 59) and Genentech, Inc. v. Amgen Inc., Civ. No. 17-1471-GMS (D. Del. Jan 22, 2017) (Docket No. 57).

[iv] https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm576112.htm

This is our second update on the litigation (you can see the prior analyses here and here, in addition to a parallel post on our companion blog concerning patent office practice) involving Janssen Biotech, Inc. (“Janssen”), Celltrion Healthcare Co. and Celltrion, Inc. (“Celltrion”), and Hospira Inc. (“Hospira”); but, judging by the course of things, it will not be the last.  There have been several developments since our last post, detailed below.  Most recently, the parties submitted a joint status report detailing the various pending motions.

Our last update occurred shortly after Janssen had filed a new lawsuit against Celltrion and Hospira alleging infringement of U.S. Patent No. 7,598,083 (“the ’083 patent”) under 35 U.S.C. §§ 271(a) and (b), as well as a claim for artificial infringement under 271(e)(2)(C).  Shortly thereafter, the parties agreed to a stipulation that was entered by the Court which, among other things, consolidated the claims for infringement of the ’083 patent into Case No. 17-cv-11008, the “2017 Action.”

Standing Resolved

In January 2017, Defendants alleged for the first time (in what was already at that time a long-running litigation) that Janssen lacked standing to bring suit on the ’083 patent.  See this post.  Specifically, the Defendants argued that the inventors had assigned their rights to a host of Johnson & Johnson companies, and not just Centocor (Janssen’s predecessor).  As such, those entities would be necessary parties, dooming Janssen’s lawsuit.  The Court resolved that question in its October 31, 2017 opinion, ruling that Janssen alone held the rights to the ’083 patent and therefore had standing to bring suit.  The Court began its analysis with the language of the relevant contracts—the inventors’ employment agreements with Centocor, each of which assigned rights in inventions to the “Company.”  But, as Defendants argued, the agreements defined “Company” to include not only Centocor, but also Johnson & Johnson and its other subsidiaries.  The Court was blunt in its view of the agreements, finding them “poorly drafted” and therefore ambiguous.

The Court therefore turned to the parties’ “intent” and the “surrounding circumstances” to determine whether the assignment was to Centocor alone or to the entire Johnson & Johnson family.  Specifically, the Court examined extrinsic evidence, including Janssen’s patent database and several other assignment documents executed between the inventors and Janssen.  Ultimately, the Court found that there was no evidence to rebut the understanding that the agreement was solely between the inventors and Janssen, and therefore found that Janssen alone had standing to bring the lawsuit.  The case continued.

But More Disputes Remain

Although the question of standing has been resolved, there still remain several open motions, including a summary judgment motion that would dismiss Hospira from the case.  To summarize, Celltrion and Hospira have partnered in the marketing of the biosimilar product.  Celltrion has contracted out the manufacture of the allegedly infringing cell culture media.  Janssen alleges that Hospira has joined with Celltrion in a “joint enterprise” and in the process has directly and indirectly infringed the ’083 patent.  Hospira disagrees, contending the theory is unfounded both legally and factually.  Nonetheless, there is no question that the case will proceed with or without Hospira as a defendant.

In addition to the summary judgment motion, the Defendants have moved to strike (what they claim) is a procedurally improper and legally unfounded counterclaim by Janssen.  Specifically, Janssen added a counterclaim under 35 U.S.C. § 271(f)(1), arguing that Defendants have “caused to be supplied” all or a portion of the allegedly infringing cell culture media from the U.S. to Singapore.  That is, whereas the Defendants had purchased the allegedly infringing cell culture media in the U.S., operations changed such that the product is now made (and purchased) in Singapore.  Janssen contends that in the process of moving the operation from the U.S. to Singapore, Defendants committed infringement pursuant to § 271(f)(1).  The Defendants argue that the claim is lacking (on both the facts and the law) and that Janssen raised it in an improper manner.  Therefore, they argue the counterclaim should be stricken.

Finally, the court is set to hear a series of pending Daubert motions and several motions addressing third-party discovery.

***

While the infliximab litigation began in 2014, a final resolution appears unlikely in the near future.

  • U.S. Food & Drug Administration and European Medicines Agency approve first trastuzumab biosimilars
  • U.S. Food & Drug Administration approves a second infliximab biosimilar

As pharmaceutical drug costs attract increasing media attention and political scrutiny, a growing number of biosimilar drugs are set to enter the U.S. and European markets in the coming years.  Global sales for the top nine branded biologic drugs were estimated to total $63 billion in 2016[1].  Competition in the heavily regulated marketplace for these blockbuster therapeutics is expected to substantially impact the pharmaceutical industry and national health systems.  To date, the U.S. has considerably lagged behind Europe’s expansion of biosimilar drug options.  The RAND Corporation estimates that biosimilar products can save the U.S. health system approximately $54 billion over the next decade, as discussed here.

Since 2005, the biosimilar regulatory framework in Europe has been implemented through the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMA).  The CHMP provides initial assessments for marketing authorization of new medicines that are ultimately approved centrally by the EMA.  Since Sandoz’s somatotropin biosimilar Omnitrope® was first authorized on April 12, 2006, an additional 37 out of 42 applications have been approved in Europe.  Three of the authorizations have been withdrawn post-approval by the marketing authorization holders (Table 1).

The U.S. did not implement a regulatory framework for biosimilar evaluation until after enactment of the Biologics Price Competition and Innovation Act (BPCIA) of 2009.  Given that the first U.S. biosimilar drug was approved almost a decade after the first in Europe, the number of authorized biosimilar drugs in Europe far exceeds the number of biosimilars approved in the United States.  Sandoz’s filgrastim biosimilar Zarxio® received the first U.S. approval in 2015, whereas nine filgrastim biosimilars have been approved in Europe dating back to multiple authorizations in 2008.  Zarxio® (in the U.S.) and Zarzio® (in Europe) are biosimilar to the reference product Neupogen® marketed by Amgen and originally licensed in 1991.   Subsequent to Zarxio®’s approval, only eight other biosimilar drugs have gained U.S. approval to date (Table 2).  As illustrated in the following graph, the EU’s significant head start led to the existent imbalance in the number of biosimilar drugs available in the respective markets.

Currently, sixteen biosimilar applications are under review by the EMA for marketing authorization (Table 3).  As an increasing number of U.S. patents expire on blockbuster biologic drugs, the number of abbreviated biologics license applications is also increasing.  Biosimilars for at least eleven different original biologics are currently navigating the FDA’s biosimilar pathway or are in late stage development (Table 4).

On December 1, 2017, Mylan and Biocon announced that the FDA approved OgivriTM, a trastuzumab biosimilar to Roche’s Herceptin®.  This is the first Herceptin® biosimilar approved by the FDA, and it follows the EMA’s approval of the first Herceptin® biosimilar (Ontruzant®) in November 2017.  No launch date has been set for OgivriTM in the United States.

On December 13, 2017, Pfizer announced that the FDA approved IxifiTM, a infliximab biosimilar to Pfizer’s Remicade®.  This is the second infliximab biosimilar approved by the FDA after Inflectra®’s approval in 2016.  Pfizer currently has no plans to launch IfixiTMin the United States, according to Pfizer spokesperson Thomas Biegi, because Pfizer already markets Inflectra® in the U.S.

On January 15, 2018, the EMA approved MvasiTM, the first bevacizumab biosimilar to Roche’s Avastin in Europe.  The FDA previously approved MvasiTM in September 2017.  MvasiTM is the first product from Allergan’s collaboration with Amgen to receive authorization from the European Commission according to David Nicholson, chief research and development officer at Allergan.

Given biosimilar applicant experience in navigating the EMA process and the EMA’s high authorization rate, the FDA will need to continue to provide useful guidance and streamline the approval process in order to reduce the imbalance.

Table 1. European Medicines Agency List of Approved Biosimilar Drugs (updated January 24, 2018).

Table 2. U.S. Food and Drug Administration List of Approved Biosimilar Drugs (CDER list of licensed biologics updated on December 13, 2017).

Table 3. European Medicines Agency List of Biosimilars Under Evaluation for Marketing Approval (Source: EMA list of applications for new human medicines updated on January 4, 2018).

Table 4. Biologics with recent or nearing primary patent expiry in the U.S. that have biosimilars in the regulatory pipeline.

[1] Mullard, Asher. “Bracing for the biosimilar wave.” Nature Reviews Drug Discovery 16.3 (2017): 152-154.

On December 20, 2017, Bristol Myers Squibb Company, Bavarian Nordic, and Enzo Biochem, Inc. filed an amicus brief in support of Amgen’s petition for rehearing en banc. We reported previously that on November 6, 2017, Amgen filed a petition for rehearing en banc of a Federal Circuit panel’s decision vacating a permanent injunction against Sanofi and Regeneron’s Praluent® and remanding the appeal to the district court for a new trial on the defendants’ written description and enablement defenses.

As “innovator biopharmaceutical companies that research targeted treatments for human diseases,” amici expressed concern that the panel’s decision alters existing law under 35 U.S.C. §112 such that it “undermines a reasonable scope of patent coverage” and will cause them to lose their previously-held patent protection.[1] Amici requested that the Court vacate the previous panel’s decision and reconsider the issues.

As previously reported, in its petition Amgen asserted two grounds for rehearing. The amicus brief discussed both of these grounds.

Amici argued that the Federal Circuit panel’s undermining of the “newly characterized antigen rule” set out in Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004) is incorrect because the decision is sound and may only be overturned en banc. Although the panel did not outright overrule Noelle, amici argued that its criticisms and dismissal of the decision leads to the conclusion that it did overturn the decision. Amici also argued that the panel erred by viewing the “newly-characterized antigen rule” as an “antibody exception” to the written description requirement.[2] Instead, the rule is based on antibody science where an antibody genus may be described by the antigen’s structure without the need to describe the multiple representative antibody sequences. Amici asserted that to hold “that a person of ordinary skill in the art does not have possession of the genus of antibodies that bind a well-characterized antigen until she has provided detailed sequence information of multiple representative CDS sequences is an unwarranted extrapolation from organic chemistry.”[3]

Amici then asserted that forty years of precedent demonstrates that an analysis using after-arising embodiments to determine validity based on written description is impermissible. They argued that the rule in In re Hogan, 559 F.2d 595 (C.C.P.A. 1977) makes it clear that an inventor cannot be expected to enable embodiments that were unknown as of the priority date. They further argued that they have relied on this precedent and have operated under this presumption when prosecuting and enforcing their patents.

In addition to addressing the two grounds raised in Amgen’s petition, the brief also emphasized that the panel’s decision will have profound impacts on companies in the molecular medicine field. When researchers seek to obtain genus protection for antibodies, they will now face the burden of having to include a list of the sequences that bind to the antigen. This burden in turn will lead to “never-ending pre-filing actual reductions to practice,” a requirement that small businesses and non-profit organizations cannot afford.[4] Amici argue that even larger companies who can afford the costs will be forced to expend time and resources to create actual reductions to practice when those resources could otherwise go towards other development efforts.

We will continue to provide updates as the case continues.

 

[1] Brief for Bristol-Myers Squibb Co. et al. as Amicus Curiae Supporting Appellees’ Petition for En Banc, Amgen Inc. v. Sanofi, No. 17-1470 (Dec. 20, 2017).

[2] Id. at 5.

[3] Id. at 7.

[4] Id. at 12.

On January 3, 2018, Momenta and Mylan announced their development plan for a proposed biosimilar to Regeneron’s Eylea® whose active ingredient is aflibercept, a recombinant fusion protein. Eylea® was first approved as an intravitreal injection indicted for the treatment of patients with neovascular (wet) age-related macular degeneration. Eylea® is now also indicated for macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in patients with diabetic macular edema.

Momenta and Mylan’s announcement indicated that a pivotal clinical trial — a comparative study of the biosimilar and Eylea for diabetic macular edema — is planned to begin in the first half of 2018. While at least one other company, Formycon, has indicated that it is in the process of developing an Eylea® biosimilar, that product appears to still be in a preclinical phase. As such, Momenta and Mylan’s pivotal trial indicates that their development is much further along, and as such, their product is likely to be the spearhead in any attacks on Regeneron’s patent protections.

As of the writing of this article, there have not yet been any challenges, either through litigation or through the PTAB, to Regeneron’s patents that may cover aflibercept. Assuming that Momenta and Mylan’s clinical trial goes smoothly, this may not be the case for long.

Regeneron holds several active patents that could prevent the entry of a biosimilar to Eylea® through 2023. For example, U.S. Patent No. 7,070,959, “Modified Chimeric Polypeptides with Improved Pharmacokinetic Properties,” contains claims covering nucleic acid molecules encoding fusion proteins for binding vascular endothelial growth factor (VEGF) which may read on aflibercept. This patent was filed May 23, 2000, and has received 1,119 days of extension time under 35 USC § 156, pushing the expiration date into June 2023.[1]

Several other patents, including U.S. Patent Nos. 7,303,746; 7,303,747; and 7,306,799 expire slightly earlier due to not being extended under § 156. These specifically named patents cover methods of treating eye disorders by administering VEGF-binding fusion polypeptides, which may read on aflibercept, but other patents with similar early 2020s expiration dates cover the actual fusion protein and methods of inhibiting tumor growth by administering the protein.

Beyond the above patents, which may require attempts at invalidation in order for a biosimilar to Eylea® to come to the market prior to 2023, Regeneron holds more specific patents which read on the currently approved Eylea® formulation. For example, claim 1 of U.S. Patent No. 7,608,261 covers formulations of a certain concentration of VEGF antagonist with certain concentrations of compounds including polysorbate, sodium phosphate, and sodium or potassium chloride. All of the compounds and ranges required in the claim are found in the approved product. Further claims require sucrose or pH, also at levels in the approved product. U.S. Patent No. 8,092,803 similarly claims the ingredients of the Eylea® product, further claiming a stability requirement. These claims, compared to the method of treatment claims or those claiming the protein or its method of production, potentially present more opportunity for pharmaceutical companies to design around them.

Ultimately, without invalidating or designing around claims, a biosimilar to Eylea® is likely still more than 5 years away. The patent landscape covering the product will require careful consideration for any potential biosimilar, and with Mylan and Momenta soon to initiate a pivotal clinical trial, they have almost certainly already been thoroughly reviewed. With U.S. net sales of Eylea® of more than $3 billion in 2016 and reported increases in quarterly figures in 2017, Regeneron is sure to vigorously defend its patent portfolio covering the product.

 

[1] This patent is also subject to a terminal disclaimer to a patent with the same pre-extension expiration date, which does not impact the expiration date of the patent receiving the term extension.

We previously reported that on January 11, 2018, Celltrion, Inc., Celltrion Healthcare, Co. Ltd. (collectively “Celltrion”), Teva Pharmaceuticals International GmbH, and Teva Pharmaceuticals USA (collectively “Teva”) filed suit seeking declaratory judgment that thirty-eight patents relating to Herceptin® (trastuzumab) are non-infringed, invalid, or unenforceable.  That same day, Celltrion and Teva also filed a suit seeking declaratory judgment that thirty-seven patents relating to Rituxan® (rituximab) are non-infringed and invalid.  Many of the patents named in this suit overlap with those named in the Herceptin®-related action.

Celltrion and Teva’s rituximab suit names Genentech, Inc., Biogen Inc., Hoffmann-La Roche Inc., and City of Hope as defendants.  According to Celltrion and Teva, a substantial controversy of “sufficient immediacy and reality to warrant the issuance of a declaratory judgment” exists between the parties due to Celltrion’s filing of an application under the BPCIA that seeks approval to market a rituximab biosimilar product.  Teva is Celltrion’s exclusive partner for the selling and distribution of the rituximab biosimilar in the United States.

According to the complaint, the FDA accepted Celltrion’s biosimilar application on June 27, 2017, and since that time the parties have been engaged in the so-called “patent dance” portion of the BPCIA.  In particular, on July 17, 2017, Celltrion produced its biosimilar application to Genentech as well as “other detailed information regarding the manufacturing processes used to make [the rituximab biosimilar].”  On September 14, 2017, Genentech then provided a list of forty patents that it believed could be reasonably asserted against Celltrion’s proposed biosimilar. The parties exchanged detailed statements asserting the factual and legal basis for their respective positions on infringement and validity of the patents identified by Genentech.  On January 11, 2018, Celltrion notified Genentech that it wished to litigate all of the patents Genentech identified on its list, and filed a declaratory judgment action.

A summary chart identifying the patents-in-suit, the patents that overlap with the previously reported Herceptin®-related suit, and Celltrion’s requested relief for each patent is provided below:

As we previously reported, Celltrion filed a petition for inter partes review (“IPR”) of the ʼ838 patent, but institution was denied.  Similarly, institution of review of the ʼ172 patent, the ʼ244 patent, the ʼ612 patent, and the ʼ711 patent was also denied.  However, review of the ʼ161 patent and the ʼ821 patent was instituted by the PTAB.

Rituximab is an anti-CD20 chimeric murine/human monoclonal antibody approved for the treatment of non-Hodgkin’s lymphoma, chronic lyphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangitis, and microscopic polyangitis.

We will continue to keep you updated on future developments.

On January 11, 2018, Celltrion, Inc., Celltrion Healthcare, Co. Ltd. (collectively “Celltrion”), Teva Pharmaceuticals International GmbH, and Teva Pharmaceuticals USA (collectively “Teva”) filed suit against Genentech, Inc., Hoffmann-La Roche Inc., and City of Hope seeking declaratory judgment that thirty-eight patents relating to Herceptin® (trastuzumab) are non-infringed, invalid, and/or unforceable. According to Celltrion and Teva, a substantial controversy of “sufficient immediacy and reality to warrant the issuance of a declaratory judgment” exists between the parties due to Celltrion’s filing of an application under the BPCIA that seeks approval to market a trastuzumab biosimilar product.  Teva is Celltrion’s exclusive partner for the selling and distribution of the trastuzumab biosimilar in the United States.

According to the complaint, the FDA accepted Celltrion’s biosimilar application on July 28, 2017, and since that time the parties have been engaged in the so-called “patent dance” portion of the BPCIA.  In particular, on August 11, 2017, Celltrion produced its biosimilar application to Genentech as well as “other detailed information regarding the manufacturing processes used to make [the trastuzumab biosimilar].”  On October 10, 2017, Genentech then provided a list of forty patents that it believed could be reasonably asserted against Celltrion’s proposed biosimilar. The parties exchanged detailed statements asserting the factual and legal basis for their respective positions on infringement and validity of the patents identified by Genentech.  On January 11, 2018, Celltrion notified Genentech that it wished to litigate all of the patents Genentech identified on its list, and filed a declaratory judgment action.

A summary chart identifying the patents-in-suit, and Celltrion’s requested relief for each patent is provided below:

As we previously reported, Celltrion filed two petitions for inter partes review (“IPR”) of the ʼ213 patent, and review on both petitions was instituted on December 1, 2017.  In addition, review has been instituted on the ʼ441 patent, the ʼ549 patent, the ʼ196 patent, and the ʼ379 patent.

Herceptin® is a monoclonal antibody that interferes with human epidermal growth factor receptor (HER2)/neu.  The produce 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.

We will continue to keep you updated on future developments.

On December 5, 2017, the Federal Circuit held oral argument in Momenta Pharmaceuticals, Inc. v. Bristol-Myers Squibb Company, 17-1694. The case comes on appeal from an IPR decision where the Board declined to find U.S. Patent No. 8,476,239 (“the ʼ239 patent”) unpatentable as obvious. The ʼ239 patent covers Bristol-Myers Squibb’s (“BMS”) Orencia® product, a CTLA4Ig protein formulation, also known as abatacept, that is used in treating autoimmune diseases such as rheumatoid arthritis. Judge Newman, Judge Dyk, and Judge Chen made up the panel.

Two issues were raised on appeal: (1) whether Momenta has standing under Article III of the Constitution to pursue its appeal; and (2) whether the Board correctly held that there was no reasonable expectation of success in formulating the liquid protein formulations in the ʼ239 patent claims.

The only issue raised during the oral argument was with respect to Momenta’s standing and right to appeal the Board’s decision. The judges’ questions and comments specifically addressed where the line should be drawn for standing and what the current remedy should be.

What Constitutes a Concrete Injury-in-Fact

Momenta argued that if the Federal Circuit were to affirm the Board’s decision, it would cause concrete immediate harm. Momenta argued that it is at a “fork in the road” in the development process and if it cannot appeal the Board’s decision, it would be forced to change the direction of its research efforts and spend millions of dollars. Momenta also emphasized that the Board’s decision is blocking its freedom to operate. Judge Chen expressed concern over the extent to which Momenta’s alleged injury is speculative, noting that Momenta is not yet a competitor in the market so speculation remains as to whether the product will make it all the way to market and as such, whether the expenditure of money is enough to create concrete harm. Judge Chen further questioned whether the actual reason for Momenta not being able to move forward is not the Board’s decision but rather the failure of Momenta’s Phase 1 trial.

BMS asserted that Momenta lacks standing to assert an appeal, arguing that Momenta has not suffered a concrete injury because Momenta is years away from being able to file an FDA application for its product and the product is not yet marketed. BMS argued the “artificial act of infringement” by filing an FDA application would be the concrete injury-in-fact and that Momenta “jumped in early” so currently it only has a future injury, which is the speculation that it may be sued for infringement. Judge Dyk raised concerns of this argument being inconsistent with years of Supreme Court precedent about what concrete injury is sufficient to have standing. He further noted that there are legal restrictions placed on Momenta by the USPTO upholding the validity of the patent because it could be sued for infringement.

Judge Dyk characterized BMS’ position as being only advantageous for them because it suggests patent owners could own invalid patents that would have no chance of being challenged until a competitor files an FDA application, which would require them to spend millions of dollars at risk before getting a determination of whether the patent bars their product. He voiced concerns about how a company cannot, before spending millions of dollars, secure a determination as to whether it is all for nothing if its product is covered by the patent.

Judge Chen stated that the BPCIA provides that the filing of an FDA application is an act of infringement, and he questioned whether before that a party can have the right to appeal an adverse agency decision. BMS argued that the “artificial” act of infringement is what creates the risk of harm.

If Momenta Lacks Standing, Whether Vacatur is Appropriate

BMS argued that should the Federal Circuit find that Momenta lacks standing to appeal, the only appropriate remedy is dismissal. It also argued that vacatur is an extraordinary remedy that is only appropriate where events render the controversy moot or where the prevailing party deprives the party of its right to appeal. Rather, here, the case is moot due to Momenta’s voluntary act to file an IPR too early.

Momenta argued that the Federal Circuit should vacate the decision to take away any estoppel that would occur through the Board’s decision.

Judge Dyk appeared unpersuaded by the argument that the Federal Circuit should dismiss rather than vacate the Board’s decision. He noted that Momenta did not take some voluntary act to deprive them of the right to appeal or to moot the case, but instead he questioned whether Momenta had standing in the first place.

Conclusions

It is difficult to predict exactly how the Federal Circuit will rule based on oral argument. However, the concerns voiced by Judge Chen and Judge Dyk suggest that they may be leaning towards finding that Momenta satisfied the requirements for standing. Both expressed concerns about a party having the ability to challenge an agency action before spending millions of dollars on filing an application with the FDA. Judge Newman’s minor comments do not appear to suggest where she may be leaning on these issues.

While the requirements for standing are more relaxed when a party is challenging an agency action, the question still remains as to where to draw the line with respect to a concrete injury-in-fact. The issue here is whether the mere investment of millions of dollars, coupled with the impending consequence of being sued for infringement, is enough to constitute an immediate injury-in-fact. The Federal Circuit’s decision here could have a major impact on the biosimilar industry.