As we previously reported here and here, Celltrion filed suit against Genentech seeking declaratory judgment that a number of patents relating to Herceptin® (trastuzumab) and Rituxan® (rituximab) are non-infringed, invalid, and/or unenforceable.  In response, Genentech filed a motion to dismiss in both cases arguing that the case was statutorily barred under the BPCIA.  On May 9, 2018, the Court granted both of the motions.

To better understand the parties’ positions and the Court’s ruling, a brief recap of the patent dance portion of the BPCIA is helpful.  Following the FDA’s acceptance of an abbreviated Biologic Licensing Application, the applicant (here, Celltrion) provides the reference product sponsor (here, Genentech) with a copy of that application.  After receipt of the application, the reference product sponsor provides the applicant with a list of patents that it believes to be infringed.  The applicant then sends the reference product sponsor a claim-by-claim analysis of why it believes the asserted patents are not infringed by the biosimilar product, are invalid, or are otherwise not enforceable.  The reference product sponsor then responds to the applicants arguments.  Once those exchanges are complete, the parties must negotiate in good faith to identify the patents that will be subject of immediate patent infringement litigation.  The parties have 15 days to complete these negotiations.  If an agreement cannot be reached, the applicant must identify the number of patents that it wishes to litigate, and that number sets the limit on the patents-in-suit.  The parties then exchange the lists of patents that each party believes should be litigated and the reference product sponsor may then bring suit.

The BPCIA also sets limits on the remedies available to an applicant in the event it does not comply with any of the various steps in the patent dance. For example, if the applicant does not provide a copy of its application to the reference product sponsor, then the applicant cannot bring a declaratory judgment action.  Similarly, the applicant is barred from bringing a declaratory judgment action if it does not serve the various required disclosures, e.g., the number of patents it wishes to litigate or the list of patents it believes should be litigated, on the reference product sponsor.

Returning to Genentech’s motion(s) to dismiss, the thrust of the motions was that Celltrion’s declaratory judgment actions were barred due to Celltrion failing to comply with its obligations during the “patent dance” portion of the BPCIA.  According to Genentech, Celltrion failed to engage in the required good faith negotiations that must occur following Genentech’s initial disclosure of the patents it believed Celltrion’s product would infringe.  Genentech alleged that although it initially identified 40 patents, it subsequently proposed reducing the number of patents it would assert based on Celltrion’s responses.  Genentech asserted that Celltrion responded by stating it wished to litigate all 40 patents and filing the declaratory judgment action.

Celltrion counters that although Genentech proposed narrowing the number of patents in suit, it purported to reserve its right to assert infringement of the other identified patents.  According to Celltrion, this “created unacceptable legal uncertainty” and for this reason, it wished to litigate all 40 patents.  Celltrion also explained that it provided Genentech with a notice of commercial marketing when it brought the declaratory judgment action.  According to Celltrion, service of a notice of commercial marketing triggers a new wave of the patent dance that allows either party to bring a declaratory judgment action to settle any patent disputes remaining at the time of the notice.

The Court disagreed with Celltrion, and found that the declaratory judgment suits were clearly barred by the BPCIA. In both suits, the Court noted that Celltrion failed to identify the number of patents it wished to litigate and failed to exchange a list of patents that it believed should have been in the suit with Genentech.  The Court found Celltrion’s explanation for its actions unavailing.  Celltrion argued that it notified Genentech that it wished to litigate all of the patents originally identified, and thereby simultaneously fulfilled its obligation to negotiate, set the number of the patents in dispute, and rendered a subsequent list exchange redundant.  However, the Court found that because the requirement to negotiate in good faith is in one section of the statute and the identification of the number of patents-in-suit/list of patents exchange is in another, “no single statement or gesture can satisfy the requirements of both sections simultaneously.”  The Court thus concluded that Celltrion had improperly conflated a number of discrete steps and exchanges that are mandated by the statutory framework.  The Court also found that even assuming Celltrion’s interpretation of the statute was correct, Celltrion had erred by presupposing disagreement during the negotiation phase gave it the power to unilaterally terminate the patent dance.  Moreover, the Court concluded that even if negotiations had not been fruitful, the statute requires the list exchange and empowers Genentech, and not Celltrion, to file suit.

The Court also disagreed that Celltrion’s service of a notice of commercial marketing permitted Celltrion to bring the declaratory judgment action.  According to the Court, the BPCIA contains three distinct statutory bars that each apply to a different factual circumstance where an applicant fails to comply with the statute.  Service of a notice of commercial marketing only lifts one of those statutory bars, i.e., where the parties have fully complied with all of the statutory steps.  If the list exchange step (among others spelled out in the statute) is not completed, then a separate bar applies, and the filing of a notice of commercial marketing cannot lift it.

In its order dismissing the case, the Court permitted Celltrion to file an amendment complaint.  However, the basis for the Court’s dismissal was that Celltrion did not comply with certain steps in the statute, and, notwithstanding Celltrion’s explanation of its actions, there does not appear to be a dispute between the parties as to what actions did and did not occur. Meanwhile, Genentech has filed patent infringement suits based on the same Celltrion abbreviated Biologic Licensing Applications in New Jersey and Delaware.

We will continue to keep you updated on future developments.

The Patent Trial and Appeal Board (“the Board”) has decided not to institute inter partes review (“IPR”) on two patents owned by Biogen and Genentech.  Pfizer, Inc. (“Pfizer”) filed two petitions asserting that the patents, U.S. Patent Nos. 8,206,711 (“the ’711 patent”) and 7,682,612 (“the ’612 patent”), were invalid as obvious in view of prior art. Both of these patents relate to Rituxan® (rituximab) and its use in the treatment of chronic lymphocytic leukemia (“CLL”).

Last month, the Board denied Pfizer’s IPR petition for the ’711 patent, finding that all of the claims were not obvious over the cited prior art. Pfizer, Inc. v. Biogen, Inc., IPR2017-02127 (PTAB Apr. 19, 2018) (Paper 10). The Board held that the cited prior art failed “to provide guidance concerning clinical endpoints, treatment parameters, or other information relating to how one would treat CLL with rituximab, or why one would reasonably expect such treatment to be successful.” Id.at 23.

This past week, the Board denied Pfizer’s other petition for the ’612 patent, again finding that the claims were not obvious over the prior art. Pfizer, Inc. v. Biogen, Inc., IPR2017-02126 (PTAB Apr. 30, 2018) (Paper 10). Pfizer argued that the prior art “would have provided an ordinarily skilled artisan with a reasonable expectation of success for methods of using rituximab to treat CLL patients at the claimed doses.” Id.at 11. However, the Board disagreed that the prior art demonstrated that “an ordinarily skilled artisan would have had a reasonable expectation of success in using any dosage of rituximab to treat CLL.” Id. at 10. Rather, the prior art suggested “a rationale for exploring the possibility of treating CLL with rituximab,” but such suggestion amounted “to no more than an invitation to experiment.” Id. at 10.

This is not the first challenge to these two Rituxan® patents. Celltrion, Inc. previously filed three IPR petitions challenging both patents, all of which were denied by the Board. See Celltrion, Inc. v. Biogen, Inc., IPR2017- 01227 (PTAB Oct. 23, 2017) (Paper 10); Celltrion, Inc. v. Biogen, Inc., IPR2017-01230 (PTAB Oct. 12, 2017) (Paper 12); Celltrion, Inc. v. Biogen, Inc., IPR2017-01229 (PTAB Oct. 23, 2017) (Paper 10).

Sandoz announced last week that the FDA issued a complete response letter for its proposed biosimilar to rituximab.  In the announcement, Sandoz stated that it “stands behind the robust body of evidence included in the regulatory submission and is currently evaluating the content of the letter.”  Sandoz further indicated that although disappointed, it “remains committed to further discussions with the FDA to bring this important medicine to US patients as soon as possible.”

Sandoz initially announced that the FDA accepted its application for its proposed rituximab biosimilar on September 12, 2017.  Sandoz’s licensing application to the United States FDA followed the approval of its rituximab biosimilar for all indications in Europe.

Rituximab is an anti-CD20 monoclonal antibody approved for the treatment of non-Hodgkin’s lymphoma (follicular lymphoma and diffuse large B-cell lymphoma) and chronic lymphocytic leukemia, as well as immunological diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

We will continue to keep you updated on further developments.

  • European Medicines Agency approves second trastuzumab and third insulin glargine biosimilars
  • FDA has not approved any biosimilar drug in 2018
  • Only three of nine approved biosimilars have launched in the United States

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 39 out of 44 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 twelve different original biologics are currently navigating the FDA’s biosimilar pathway or are in late stage development (Table 4).  Interestingly, Neulasta® (pegfilgrastin) biosimilars have failed to gain approval in Europe and in the United States despite numerous attempts.  The FDA has rejected pegfilgrastim applications filed by Coherus, Mylan/Biocon, and Sandoz, and there are currently eight pending applications for pegfilgrastim pending in Europe.

On February 9, 2018, the EMA approved HerzumaTM, the second trastuzumab biosimilar to Roche’s Herceptin® in Europe.  The EMA previously approved Samsung Bioepis’ Ontruzant TM in November 2017.  Herzuma is the third biosimilar from Celltrion’s portfolio approved by the European Commission.

On April 23, 2018, Pfizer announced that the FDA had issued a Complete Response Letter (CRL) highlighting the need for additional information for its trastuzumab biosimilar referencing Herceptin®.   On April 5, 2018, Celltrion announced that the FDA had issued CRLs for 2 of its products, CT-P10, a proposed rituximab biosimilar referencing Rituxan®, and CT-P6, a proposed trastuzumab biosimilar referencing Herceptin®.  The FDA has not approved any biosimilars in 2018.

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 May 1, 2018).

Table 2. U.S. Food and Drug Administration List of Approved Biosimilar Drugs (CDER list of licensed biologics updated on April 17, 2018).

Table 3. European Medicines Agency List of Biosimilars Under Evaluation for Marketing Approval (Source: EMA list of applications for new human medicines updated on April 10, 2018).

Table 4. Biologics having already expired 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.

Last week, on April 18, 2018, Judge Stark in the District of Delaware entered the Final Judgment and Order dismissing the patent infringement case brought by Amgen Inc. and Amgen Manufacturing, Limited (collectively “Amgen”) against Coherus Biosciences, Inc. (“Coherus”). Judge Stark previously issued a Memorandum Order on March 26, 2018, adopting Magistrate Judge Burke’s Report and Recommendation (issued December 7, 2017) to grant Coherus’s motion to dismiss.

Amgen’s Complaint was filed on May 10, 2017, alleging infringement under the BPCIA due to Coherus’s submission of an abbreviated Biologic License Application seeking approval to market a biosimilar version of Amgen’s Neulasta® (pegfilgrastim) product.  In particular, Amgen alleged infringement of a single patent, U.S. Patent No. 8,273,707 (“the ʼ707 patent”), directed to a process for purifying proteins. Of particular relevance, the claimed process requires a combination of a first and second salt selected from the group consisting of citrate and sulfate, citrate and acetate, and sulfate and acetate.  Each salt must also be present within a particular concentration range.  In its Complaint, Amgen alleged that the Coherus process met this limitation through the use of a first and second salt that is the equivalent of one or more of the specified salt pairs.

On June 1, 2017, Coherus filed a motion to dismiss for failure to state a claim.  Coherus contended that it was entitled to dismissal because, as a matter of law, its accused manufacturing process does not infringe the ʼ707 patent.  In particular, Coherus argued that its process does not utilize one of the claimed salt pair, and does not utilize salts within the claimed concentration range.  Because the Court concluded that Coherus did not infringe based on the use of one of the claimed salt pairs, it did not address the second argument.

The Court initially noted that Amgen’s Complaint did not allege sufficient facts to support equivalence between the claimed salt pairs and the Coherus manufacturing process.  Instead, the Court explained that Amgen’s Complaint simply makes the legal conclusion that there is equivalence. Normally, Amgen would likely be permitted an opportunity to amend its Complaint to include facts sufficient to support its doctrine of equivalents theory.  However, Coherus argued there was no reason to allow Amgen to amend in this case because prosecution history estoppel barred Amgen’s theory of infringement.  Specifically, Coherus argued that during prosecution Amgen distinguished its claims from the cited prior art by emphasizing that the prior art did not teach or suggest the particular combinations of salts that were being claimed.  Accordingly, Coherus asserted that Amgen was estopped from asserting a different salt combination infringes the ʼ707 patent claims.

Following review of the prosecution history, the Court concluded that Amgen had clearly and unmistakably surrendered processes using a combination of salts that was different from the claimed combinations.  In particular, the Court took note of Amgen’s repeated emphasis that the cited reference did not teach that the “particular combination” of salts would increase the dynamic capacity of the column as required by the then pending claims.  Interestingly, the Court noted that if the prosecution history focused only on the fact that the pending claims required a combination of salts instead of the single salt disclosed in the prior art, there would not be an estoppel issue.

The Court also found it telling that Amgen did not substantively address the prosecution history argument made by Coherus.  Instead, it made three “peripheral” arguments that the Court did not find persuasive. First, Amgen argued that Coherus’s argument regarding the salt pair limitation should be taken up after claim construction and discovery.  However, the Court faulted Amgen for not explaining how either would “shed light on the objective inquiry regarding whether argument-based prosecution history estoppel applies here.”  Second, Amgen argued that prosecution history does not apply to so-called clarifying amendments.  Although the Court agreed with that principle, it noted that Amgen had not explained how the prosecution history statements Coherus relied on were clarifications as opposed to claim scope surrender.  Third, Amgen argued Coherus had not met the stringent standard for applying argument-based estoppel.  However, the Court dismissed this argument as being based on “wordplay [that] ignores the meat of Coherus’s position.”

It remains to be seen whether Amgen will appeal this ruling, although that seems likely.  In related news, Coherus recently announced that it anticipates a U.S. commercial launch of its pegfilgrastim product in the second half of 2018.

Fujifilm Kyowa Kirin Biologics Co., Ltd. (“Fujifilm”) recently announced that it will partner with Mylan N.V. (“Mylan”) to commercialize a biosimilar to adalimumab developed by Fujifilm.  Under the terms of the agreement, Fujifilm grants Mylan an exclusive license to commercialize the biosimilar in Europe, and will receive an up-front fee in return.  In addition, Fujifilm is eligible to receive commercialization milestone payments and sales royalties.  Mylan is responsible for all sales activity of the product in Europe.  The parties are continuing to negotiate commercialization rights in other territories.

As we previously reported, Fujifilm’s medical marketing application for its adalimumab biosimilar was accepted for review by the European Medical Agency on May 18, 2017.  A decision from the EMA is expected in the second half of 2018.

We will continue to keep you updated on future developments.

On the same day that the PTAB instituted review of an AbbVie Biotechnology Ltd. (“AbbVie”) patent covering a method of using adalimumab to treat psoriatic arthritis, it also instituted review of a second AbbVie patent directed to the use of adalimumab to treat chronic plaque psoriasis. More specifically, and once again at the urging of Sandoz Inc. (“Sandoz”), the PTAB instituted review of claims 1, 4, 7, 10, 13, 16, and 19 of U.S. Patent No. 9,090,689 (“the ʼ689 patent”), which is entitled “Use of TNFα Inhibitor for Treatment of Psoriasis.”

The challenged claims of the ʼ689 patent are directed to methods of administering adalimumab for the treatment of moderate to severe chronic plaque psoriasis.  The claims require filling adalimumab into vessels (syringes) and subcutaneously administering 40 mg of adalimumab to a patient every other week. Certain dependent claims also recite various efficacy limitations, e.g., achieving a score reduction for a particular psoriasis severity measurement.

The only claim construction dispute at issue in the Petition was whether the preambles of the independent claims (1 and 7) are statements of intended use.  If so, then Sandoz argued they are non-limiting. AbbVie did not respond to that position in its Preliminary Response, but reserved the right to do so if trial was instituted.  However, the PTAB determined that it was unnecessary to determine if the preambles are limiting at this stage.

Sandoz proposed two Grounds of unpatentability in its Petition, although both Grounds are substantively similar.  AbbVie did not contest that the cited references collectively disclose the claim limitations.  Instead, AbbVie disputed that a person of ordinary skill would have had a reasonable expectation of success in using adalimumab to treat chronic plaque psoriasis, or a reasonable expectation of success in using the claimed dosing regimen, i.e., 40 mg adalimumab administered every other week.

AbbVie’s arguments in this IPR were very similar to those it made in arguing that trial should not be instituted in the companion ʼ992 patent. Briefly, Sandoz asserted there was a reasonable expectation of success in using adalimumab (a TNF-α inhibitor) to treat chronic plaque psoriasis because the disease was known to be mediated by TNF-α, and other TNF-α inhibitors had been successfully used to treat it. Because of this known link, Sandoz alleged a prior art disclosure  in which adalimumab had been successfully used to treat rheumatoid arthritis (another TNF-α related disease) would have led a person of ordinary skill to believe it would also be effective to treat chronic plaque psoriasis.  AbbVie countered that none of the cited references actually disclose using adalimumab to treat chronic plaque psoriasis, and a disclosure that adalimumab can treat rheumatoid arthritis is not predictive of its ability to treat psoriasis. However, much like in the ʼ992 IPR, the PTAB was not persuaded by this argument based on the record currently before it.

AbbVie also asserted that two of the relied upon references do not teach treating chronic plaque psoriasis at all; rather, they teach treating “psoriasis.”  AbbVie contended that Sandoz did not establish that a disclosure of “psoriasis” teaches or suggests chronic plaque psoriasis. These arguments are part of a larger argument that AbbVie made regarding Sandoz’s failure to set forth an express construction of the term “moderate to severe chronic plaque psoriasis.”  However, the PTAB was once again not persuaded by this argument, and pointed out that Sandoz’s experts offered uncontested testimony that the term “psoriasis” is most commonly associated with chronic plaque psoriasis. Regardless, the PTAB pointed out that another reference that is common to both Grounds does teach treating chronic plaque psoriasis.

With respect to the claimed dosage regimen, Sandoz argued that numerous prior art references demonstrate the same dosage of a TNF-α inhibitor was successful in treating both rheumatoid arthritis and psoriasis. Thus, Sandoz alleged that the prior art disclosure of dosing adalimumab at 40 mg every other week to successfully treat rheumatoid arthritis would have provided a person of ordinary skill a reasonable expectation of success in using the same dosage to treat psoriasis. AbbVie responded by arguing that Sandoz’s cited prior art references used higher doses than those approved for rheumatoid arthritis to treat chronic plaque psoriasis. Thus, AbbVie contended that the prior art would have led a person of ordinary skill to use a higher dosage of adalimumab than what is claimed.  The PTAB disagreed, and pointed out that AbbVie assumed the FDA approved dosage is the only dosage relevant to the obviousness inquiry. The PTAB also found that Sandoz had submitted sufficient evidence showing that the same dose of adalimumab would have been effective to treat both rheumatoid arthritis and chronic plaque psoriasis.

With respect to the dependent claims, AbbVie contested only Sandoz’s allegations that the claimed efficacy requirements are the inherent result of administering the treatment.  The PTAB noted that AbbVie’s contentions implicate a claim interpretation for the clinical endpoints that neither party addressed in its papers to date. Consequently, the PTAB determined the best course was to institute and let the parties resolve the dispute during trial.

We will continue to keep you updated on future developments.

At the urging of Sandoz Inc. (“Sandoz”), the PTAB instituted review of claims 1, 2, and 5-7 of U.S. Patent No. 9,067,992 (“the ʼ992 patent”) on April 3, 2018.  The ʼ992 patent is entitled “Use of TNFα Inhibitor for Treatment of Psoriatic Arthritis,” and is assigned to AbbVie Biotechnology Ltd. (“AbbVie”).  The claims of the ʼ992 patent are generally directed to treating psoriatic arthritis comprising subcutaneous administration of 40 mg of adalimumab every other week. The claims also recite various outcomes associated with the treatment.  In its Petition, Sandoz presented four separate Grounds for unpatentability, and the PTAB instituted review on all four grounds.

Before reaching the Grounds presented by Sandoz, the PTAB first addressed the parties’ respective claim construction positions.  First, Sandoz argued that the preambles to independent claims 1 and 2 are statements of intended use, and therefore are non-limiting.  AbbVie countered that the preambles are limiting because they provide antecedent basis for the claims and are the only parts of the claims that recite psoriatic arthritis and refer to the “said patient,” which is further limited by a dependent claim.  However, the PTAB declined to reach a decision on whether the preambles are limiting, instead concluding that such a determination was unnecessary at this stage.

Although not presented as a claim construction dispute in Sandoz’s petition, Sandoz also asserted that the outcome limitations recited in the various claims are simply statements of intended results that do not convey patentability. Unsurprisingly, AbbVie disagreed.  AbbVie pointed out that the outcome limitations in the claims expressly require particular ACR scores to be achieved following treatment for at least 24 weeks.  Thus, according to AbbVie, the claims require a particular treatment term and a heighted efficacy requirement.  The PTAB agreed with AbbVie and concluded each of the outcome limitations is entitled to patentable weight.

Turning to Ground 1, Sandoz alleged that claims 1, 5, and 6 are anticipated by a publication (Mease 2004) disclosing the results of a clinical trial that evaluated the safety and efficacy of administering 40 mg of adalimumab subcutaneously every other week.  According to Sandoz, the publication describes the same clinical study that was added as an example to the ʼ992 patent specification in a continuation-in-part application.  As a result, the limitations of claim 1, which are based on the patient population and results of the clinical study, are expressly disclosed.  Sandoz further asserted that claims 5 and 6 are anticipated because they recite the clinical outcomes of that study. AbbVie did not contest the Mease 2004 disclosure in its preliminary response.  Instead, AbbVie asserted Ground 1 should be denied because it is irreconcilable with Sandoz’s position regarding the effect of the ACR outcome language. More specifically, AbbVie argued that Sandoz’s position that the outcome language is non-limiting means that Sandoz cannot then rely on those limitations to establish a later effective filing date that makes the Mease 2004 publication available as prior art.  The PTAB sided with Sandoz on this dispute and concluded that Sandoz’s arguments are permissible alternative arguments based on different asserted priority dates.  Moreover, the PTAB also concluded that the limitations are entitled to patentable weight.

Grounds 2-3 alleged the claims are unpatentable as obvious over various combinations of references. Grounds 2 and 3 are substantively similar, and, in fact, have two references in common. In its Preliminary Response, AbbVie did not contest that the references relied on in the Grounds collectively teach the claim limitations.  Instead, AbbVie argued there was no reasonable expectation of success in (1) using adalimumab to treat psoriatic arthritis, or (2) using 40 mg of adalimumab every other week to treat that condition.

In its Petition, Sandoz asserted that psoriatic arthritis and rheumatoid arthritis are closely related diseases that are both mediated by TNF-α.  Sandoz further asserted that both diseases can be treated with the same drugs using the same or similar dosing regimen.  Accordingly, Sandoz argued that prior art disclosing the use of a 40 mg every other week adalimumab dosing regimen for the treatment of rheumatoid arthritis would have rendered use of the same regimen and drug to treat psoriatic arthritis obvious.  AbbVie countered by arguing none of the cited prior art references disclose the use of adalimumab to treat psoriatic arthritis, and, in fact, none of the cited references even discuss a possible connection between adalimumab and psoriatic arthritis. AbbVie similarly argued that disclosures in the cited references regarding the use of other TNF-α inhibitors to treat psoriatic arthritis ignore both the complexities of the disease and the differences between other inhibitors and adalimumab.  According to AbbVie, without this discussion there cannot be a reasonable expectation of success.

The PTAB disagreed by explaining the record indicates that (1) TNF-α was implicated in rheumatoid arthritis and psoriatic arthritis, (2) other TNF-α inhibitors were successfully used to treat both diseases, and (3) based on the success of the other inhibitors, a person of ordinary skill  would have reasonably expected adalimumab to also be successful. Accordingly, the PTAB found a person of ordinary skill would have a reasonable expectation of success in using adalimumab to treat psoriatic arthritis.

Regarding the claimed dosing regimen, Sandoz asserted that a person of ordinary skill would have had a reason to use 40 mg every other week because the prior art discloses that other TNF-α inhibitors were used to treat both rheumatoid and psoriatic arthritis with the same dose and dosing regimen. Consequently, according to Sandoz, a person of ordinary skill would have reasonably expected success in using adalimumab at 40 mg every other week to treat psoriatic arthritis because the prior art taught using adalimumab at the same dose and dosing regimen to treat rheumatoid arthritis. AbbVie argued that Sandoz’s citation to various references describing dosing regimens for other TNF-α inhibitors confirm the uncertainty of dosing.  However, the PTAB found AbbVie’s arguments assumed that the FDA approved dose is the information that would have been relevant to a person of ordinary skill, but that this assumption was counter to the relevant obviousness inquiry.  Accordingly, the PTAB agreed with Sandoz that a person of ordinary skill would have had a reasonable expectation of success in using the claimed dosing regimen based on the current record.

Ground 4 utilizes the same references as Ground 3, but adds a fourth for purposes of claim 7, which depends from claim 2 and adds the limitation that the symptoms reduced by treatment are “progression of structural damage assessed by radiograph.”  Sandoz argued that this limitation is the inherent result of practicing the claimed method or, alternatively, the prior art taught that treating patients with TNF-α inhibitors led to the claimed result.  AbbVie asserted that Sandoz did not put on a sufficient case under either theory and, in particular, Sandoz’s inherency theory was entirely conclusory because it did not cite any data showing that a patient treated with the claimed method would necessarily achieve the claimed result.  However, the PTAB agreed with Sandoz that the claimed result was the inherent outcome of the claimed method based on the current record.  Consequently, the PTAB did not address Sandoz’s alternative theory that the prior art taught the claimed limitation.

We will continue to keep you updated on further developments.

Lately, it has been very difficult to get diagnostic claims allowed without limiting the method steps to very specific components (e.g. reagents, devices, assays, samples, etc.). However, a recent Federal Circuit case suggests that there may be hope for broader diagnostic claims in the future.  In Exergen Corp. v. Kaz USA, Inc., Appeal No. 2016-2315, 2016-2341 (March 8, 2018), the Federal Circuit upheld the district court decision that the claimed diagnostic technique was patent eligible under 35 USC §101.  While the decision is nonprecedential, it shows that not all diagnostic claims are invalid as directed to a natural correlation or law of nature.

Claims 7, 14, and 17 of US Patent No. 6,292,685 (“the ’685 patent”) and claims 17, 24, 33, 39, 40, 46, 49, 60, and 66 of US Patent No. 7,787,938 (“the ’938 patent”) were at issue in Exergen. Claim 14 is representative of the method claims in the ’685 patent and reads as follows:

  1. A method of detecting human body temperature comprising:
    detecting temperature at a forehead through a lateral scan across the
    temporal artery; and
    computing an internal body temperature of the body as a function of
    ambient temperature and sensed surface temperature.

Claim 14 is representative of the method claims in the ’983 patent and reads as follows:

  1. A method of detecting human body temperature comprising making at least
    three radiation readings per second while moving a radiation detector to scan
    across a region of skin over an artery to electronically determine a body
    temperature approximation, distinct from skin surface temperature.

The Federal Circuit considered the two prong test under Alice (Alice Corp. V. CLS Bank Int’l, 132 S. Ct. 2347 (2014) and Mayo (Mayo Collaborative Servs v. Prometheus Labs, Inc., 132 S.Ct. 1298 (2012).  The two prongs are 1) whether the claims at issue contain a patent ineligible concept (law of nature) and 2) whether they contain an “inventive concept” sufficient to transform the claimed abstract idea into a patent eligible application. In other words, if the claims recite only well understood, routine, and conventional activity, they do not constitute an inventive concept.  There was no disagreement that the claims utilized a natural law (correlation between temperature readings from the forehead skin and core body temperature and the calculations used to determine the core temperature based on ambient and skin temperature). The question was whether the additional claimed steps were directed to a novel technique or added an inventive concept so that the claims were transformed into patent-eligible subject matter.  The asserted claims recited at least one of the following steps: 1) moving while laterally scanning across the temporal artery, 2) obtaining a peak temperature reading, and 3) obtaining at least three readings per second.  Though these claim elements were known in the art, they were previously used to detect hot spots indicating injury or tumors or surface temperature differentials.  They were not used to detect arterial temperature beneath the skin.  In addition, the prior art methods did not use the newly determined coefficient for translating measurements taken at the forehead into core body temperature readings. The district court found that there was no evidence that the claimed methods were well understood, routine, and conventional prior to Exergen’s invention. The Federal Circuit agreed, stating that “the inventor determined for the first time the coefficient representing the relationship between temporal-arterial temperature and core body temperature and incorporated that discovery into an unconventional method of temperature measurement” and thus, the method was found patent eligible.

The dissenting opinion stated that the claimed invention measures air temperature and the temperature of forehead skin directly over the temporal artery and then inputs these temperatures into a “heat balance equation,” which is a mathematical representation of the law of nature that governs the relationship between skin, air, and core temperatures.  Devices for measuring temperature while laterally scanning an area were known in the art. Though the specific coefficient was not previously known, the inventors identified this coefficient through empirical testing of the coefficient that governs the relationship between core temperature and the temperature of the skin above the temporal artery.  The dissent concluded that the calculations merely reflect the natural relationship between forehead and core body temperature, and thus the claims lack an inventive concept sufficient to transform them into patent eligible inventions.

It is clear from the dissent that there is still disagreement as to what makes a diagnostic claim patent eligible.  Hopefully this will be cleared up as the Federal Circuit hears more challenges to patent eligibility decisions.  In the meantime, it may be helpful to clearly indicate in the specification why the claimed combination of detection steps is not conventional, and to emphasize any transformations that occur as a result of the diagnostic method.  Specific components used in the method steps should still be disclosed in the specification so that the claims can be limited to these components if the claims continue to be rejected as abstract ideas or natural correlations.

Last week, Mylan N.V. and Biocon Ltd. announced that their jointly-developed insulin glargine biosimilar, Semglee™, received marketing approval from both the European Commission (which applies to all 28 European Union member states) and the European Economic Area member states of Norway, Iceland, and Liechtenstein.[1] Additionally, the Therapeutic Goods Administration approved the biosimilar for use in Australia. While the pharmaceutical partners received U.S. approval for their breast cancer drug Ogivri (the biosimilar Trastuzumab) in December 2017, this is their first co-developed biosimilar to be approved in Europe.[2]

Insulin glargine is a biosimilar of Sanofi’s Lantus™, in which the amino acid sequence of natural human insulin has been genetically modified to improve its absorption, distribution, metabolism, and excretion characteristics in patients with either type 1 or type 2 diabetes.[3] This insulin analog thus provides a drug that is more readily and quickly accepted by the body, with a prolonged duration of activity such that patients may control their blood sugar with just a single dose per day. The approval in Europe and Australia is for a 100 unit/mL 3 mL prefilled disposable pen of the insulin glargine, for application by subcutaneous injection.

While Semglee™ is the third insulin glargine biosimilar to hit the European market (behind Eli Lilly’s Abasaglar™ and Merck’s Lusduna™) and second in Australia (again behind Eli Lilly’s Abasaglar™), the manufacturers hope that the drug will provide an affordable and high quality option for patients and expand the diabetes market on a global scale. The number of people with diabetes in Europe is expected to reach 38 million over the next ten to twelve years and there are nearly 2 million people, and counting, currently living with diabetes in Australia.[4] Thus, as the diabetes pandemic continues to grow at an alarming rate, Mylan and Biocon are entering the lucrative $6 billion global market at the perfect time.[5] The duo plans to launch the product in both Europe and Australia by the end of 2018.

In the same week that Mylan and Biocon announced their success with their insulin glargine biosimilar abroad, the U.S. Food and Drug Administration approved Sanofi’s 900-unit, or 300 unit/mL 3mL, insulin glargine pen, the highest capacity long-acting insulin pen currently on the U.S. market.[6] Sanofi hopes that the new disposable prefilled pen (named Toujeo Max SoloStar), which includes double the dosage of its original SoloStar pen, will ultimately reduce the number of injections needed for some adults with diabetes. With its higher capacity, the pharmaceutical company also expects that the Max SoloStar pen will allow for fewer refills and related copays, depending on the individual’s insurance coverage.[7]

 

[1] Mylan, Biocon Get Approval for Glargine Insulin in Europe, Australia, RTTNews (March 28, 2018), available at http://www.rttnews.com/2876753/mylan-biocon-get-approval-for-glargine-insulin-in-europe-australia.aspx (last accessed April 2, 2018).

[2] Id.

[3] Ambika Basa, Efforts to Develop Generic Versions of Insulin Glargine an Exciting Evolutionary Trend in Diabetes Treatment (March 28, 2018), available at http://www.editiontruth.com/efforts-develop-generic-versions-insulin-glargine-exciting-evolutionary-trend-diabetes-treatment/ (last accessed April 2, 2018).

[4] Viswanath Pilla, We expect roll out of insulin glargine in Europe to start in second half of 2018, says Biocon (March 29, 2018), available at https://www.moneycontrol.com/news/business/companies/we-expect-roll-out-of-insulin-glargine-in-europe-in-second-half-of-2018-says-biocon-2539125.html (last accessed April 2, 2018).

[5] Id.

[6] See Labeling-Package Insert for NDA 206538, Toujeo SoloStar Insulin Glargine Recombinant, available at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=206538 (last accessed April 2, 2018).

[7] FDA Approves High-Capacity Insulin Glargine Pen, Healio Endocrinology (March 27, 2018), available at https://www.healio.com/endocrinology/diabetes/news/online/%7Bcec71f19-7d1e-4b27-b4b9-dd7df673ff74%7D/fda-approves-high-capacity-insulin-glargine-pen (last accessed April 2, 2018).