Category Archives: ANDA

Reasonable Expectation of Success Made Claims Obvious

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In Salix Pharmaceuticals. Ltd v. Norwich Pharmaceuticals Inc., [2022-2153, 2023-1952] (April 11, 2024), the Federal Circuit affirmed the district court determination that Norwich infringed claim 8 of U.S. Patent 8,624,573, claim 6 of U.S. Patent 9,421,195, and claims 11
and 12 of U.S. Patent 10,335,397 and had failed to prove that those claims were invalid.

Rifaximin, the active ingredient in Salix’s commercial product Xifaxan®, has been widely used as an antibiotic for decades, having been first synthesized in the early 1980s
in Italy and approved there as an antibiotic in 1985. The FDA approved Xifaxan nearly 20
years later, in 2004, as 200 mg tablets for the treatment of travelers’ diarrhea. The FDA subsequently approved 550 mg tablets for hepatic encephalopathy in 2010 and for irritable bowel syndrome with diarrhea (“IBS-D”) in 2015.

Norwich sought to market a generic version of rifaximin and, in 2019, filed an ANDA for 550 mg tablets with the same indications as Xifaxan, certifying pursuant to 21 U.S.C. § 355(j)(2)(vii)(IV) that Salix’s rifaximin patents were invalid. Salix timely sued, asserting that Norwich’s
ANDA infringed dozens of valid, Orange Book-listed patents. By the time of trial, the case had been streamlined to three groups of patents:

  1. the ’573, ’195, and ’397 patents, directed to treating hepatic encephalopathy
  2. the ’569 and ’667 patents, directed to treating irritable bowel syndrome with diarrhea with 550 mg rifaximin three times a day (1,650 mg/day) for 14 days; and,
  3. the ’199 and ’206 patents, directed to rifaximin form β

Following a bench trial, the district court held that Norwich infringed the hepatic encephalopathy patents’ claims and had failed to establish their invalidity. Norwich did not appeal those holdings. The court also held that Norwich’s ANDA infringed the irritable bowel syndrome and polymorph patents, but that those patents’ claims would have been obvious
over the prior art. Salix appealed those invalidity holdings.

Norwich then amended its ANDA in an attempt to remove the infringing hepatic encephalopathy indication and moved to modify the judgment under Federal Rule of Civil Procedure 60(b), asserting that the amendment negated any possible infringement. The court denied Norwich’s motion, and Norwich cross-appealed.

Validity of the Irritable Bowel Syndrome Claims

The key limitation on appeal is the dosage amount that appears in the claims: 550 mg, three times per day (“TID”), for a total of 1,650 mg/day. Norwich challenged the IBS-D claims’ validity by asserting as prior art references a clinical trial protocol that had been published and a 2006 journal article by Pimentel. The Protocol described a Phase II study evaluating
twice-daily doses of 550 mg (1,100 mg/day) and 1,100 mg (2,200 mg/day) for 14 and 28 days for the treatment of irritable bowel syndrome. Pimentel taught administering 400 mg, TID (1,200 mg/day), for the treatment of irritable bowel syndrome but further opines that the “optimal dosage of rifaximin may, in fact, be higher than that used in our study.” The district court found that those two references disclose each and every limitation of the challenged irritable bowel syndrome claims, and further found that a skilled artisan would have been motivated to combine those two references to arrive at what is claimed with a reasonable expectation of success.

Salix appealed, asserting that the court erred in finding that a skilled artisan would have had a reasonable expectation of success in using the claimed 1,650 mg/day dosage to treat irritable bowel syndrome. According to Salix, the highest prior art dosage amount
that could have been supported with a reasonable expectation of success was the 1,200 mg/day dose evaluated by Pimentel. The Federal Circuit disagreed, noting that while the Protocol alone might not support the reasonable expectation of success, in combination with Pimentel, which taught that “[r]ecent data suggest that the optimal dosage of rifaximin may, in fact, be higher than that used in our study,” it was not error for the district court to conclude that there was a reasonable expectation of success as to the efficacy of 550 mg TID dosing.

Validity of the rifaximin form β Claims

Norwich challenged the polymorph claims’ validity by asserting, inter alia, Cannata, which discloses that rifaximin exists in crystalline form with “outstanding antibacterial properties.”

The district court held that expert testimony supported a conclusion that, in view of the prior art, (1) a skilled artisan would have had good reason to characterize the crystalline
rifaximin obtained by following the Cannata protocols, (2) that such characterization was routine and could have been performed “in one day,” and (3) that doing so would have led the skilled artisan to have “detected rifaximin β.”

The Federal Circuit noted that the scope and content of the prior art here includes preparations of crystalline rifaximin, which expert testimony supports would have yielded the β form of rifaximin. The difference between the prior art and the claims is thus effectively nothing more than the performance of routine characterization to identify the polymorphic forms that result from the known Cannata processes.

Salix argued that the rifaximin’s β form nonetheless constituted a non-obvious invention because, although skilled artisans actually succeeded in producing and characterizing it, they would not have expected to succeed because, as of the critical date, the polymorphic nature of rifaximin had not yet been reported and the identity of the β form remained undisclosed. Salix further argues that there could have been no expectation of success because the skilled artisan would not have been able to predict what polymorphic forms might result from following the preparation protocols disclosed in the prior art. The Federal Circuit disagreed, noting that Salix has done no more than combine known elements of the prior art to verify readily accessible information concerning a compound already in the hands of those of ordinary skill in the art, and such routine efforts do not justify removing this polymorph from the public domain.

The Federal Circuit noted that it was not holding that there is always a reasonable expectation of success in accessing or characterizing polymorphs. It was simply reviewing the district court’s decision before it as to its factual finding of a reasonable expectation of success, and in so doing, have not been left with a definite and firm conviction that a mistake was made in reaching that finding.

Norwich’s Cross Appeal

On cross-appeal, Norwich raises two related but distinct arguments that arose after the district court held that Norwich infringed the HE patents and failed to establish invalidity. Norwich first argues that the district court misinterpreted 35 U.S.C. § 271(e)(4)(A), which directs a court, following a finding of infringement, to order the FDA to defer final approval of an ANDA until the expiration of the infringed patent. According to Norwich, that statute precludes delaying final approval of an entire ANDA, and instead requires delaying only the approval of the infringing use.

The Federal Circuit said Section 271(e)(4)(A) instructs that, following a finding of infringement, “the court shall order the effective date of any approval of the drug or veterinary biological product involved in the infringement to be a date which is not earlier than the date of the expiration of the patent which has been infringed.” Norwich argued that the language of § 271(e)(4) requires courts to tie the restriction on FDA approval to the
indication for which the ANDA seeks approval when that indication was the source of infringement. The district court order concerned only the specific ANDA in question that included an infringing use, referred to the ANDA by its number, and enjoined the approval
of that ANDA.

Since the FDA does not approve drugs in the abstract, but rather approves drugs for particular uses (indications) of that drug, the statute is appropriately construed as directed to approval of particular infringing uses of the drug, not all uses of the drug including non-infringing uses. The statutory scheme makes clear that the relevant infringement is the submission of the ANDA that included an infringing use. That the ANDA further recited a non-patent-protected indication does not negate the infringement resulting from the ANDA’s submission. The order thus appropriately delayed the effective final approval date of “this
infringing ANDA” submission.

Norwich’s second argument arises from its decision to amend its ANDA to carve out the infringing HE use after final judgment. Following that amendment, Norwich filed a motion to modify the final judgment to allow for prompt approval of the amended ANDA that purportedly no longer sought approval for the infringing HE use. The district court denied that motion, holding that Norwich “fully litigated the merits of its non-infringement and invalidity case, lost, and now seeks a way around the final judgment through Rule 60(b).

The Federal Circuit said that a district court may reconsider its own finding of infringement
in light of an amended ANDA, but the court need not do so, and the Federal Circuit said that the court reasonably held that consideration of the amended ANDA would be inequitable
and inappropriate. The court noted that it is not a simple matter to determine whether an
ANDA applicant has successfully carved out language from a label to turn infringement into non-infringement” and that what Norwich sought in its Rule 60(b) motion would essentially be a second litigation” following final judgment.

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Filing an ANDA is not Infringement, Unless the Specified Use is Claimed in the Patent

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In H. Lundbeck A/S v. Lupin Ltd., [2022-1194, 2022-1208, 2022-1246] (December 7, 2023), the Federal Circuit affirmed the judgment of non-infringement of U.S. Patent Nos.

9,278,096 and 9,125,910, and the determination that Lupin infringed claim 12 of U.S. Patent No. 9,101,626.

The Federal Circuit agreed with the district court that filing an ANDA is not infringement, unless the specified use is claimed in the patent.  The defendants solely seek approval to market the drug for the treatment of MDD pursuant to the methods of expiring patents—that is the “purpose” of the ANDA submissions. Thus, the patented uses are not those for which ANDA approval is sought. The Federal Circuit found that Plaintiffs have failed to establish that section 271(e)(2)(A) provides an independent basis of infringement.

The Federal Circuit also rejected the argument that the ANDA induced infringement, noting that the label in question is not a label that induces infringement of the ’096 patent. It was the label FDA required for the sale of the drug to treat MDD—a label that the patentee itself proposed for that purpose in connection with its NDA for treating MDD and that preexisted the issuance of the ’096 patent.  It cannot be, as plaintiffs suggest, that a patentee can bar the sale of a drug for a use covered only by patents that will have expired simply by securing a new patent for an additional, narrower use.

On its cross appeal, argued that the district court erred in construing “reacting” in the ’626 patent to mean “the changing of a reactant(s) to product(s)” and in finding infringement under that construction. The Federal Circuit disagreed.  Lupin contended that “reacting” meant “the specified chemicals are added to the reaction vessel at the beginning of the process as starting material,” and Lupin’s process does not use one of the compounds as a starting material.  The Federal Circuit said that it was true that the specification only refers to using the compound as starting materials, but nothing in the claims, specification, or file history requires Lupin’s narrower reading.

The Federal Circuit noted that the district court’s definition was consistent with the dictionary definition, that the prosecution did not support Lupin’s definition, nor did Lupin’s arguments about claim differentiation.  Based upon what the Federal Circuit found was the correct definition of reacting, the Federal Circuit affirmed the finding of infringement.

A System is Not a Method (Unless §101 is Involved)

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In Jazz Pharmaceuticals, Inc., v. Avadel CNS Pharmaceuticals, LLC, [2023-1186] (February 24, 2023) the Federal Circuit lifted its stay on an injunction directing Jazz to take measures to delist U.S. Patent 8,731,963 from the FDA’s orange book, and affirmed the district court’s decision.

Claim 1 of the ‘963 patent was directed to “A computer-implemented system for treatment of a narcoleptic patient with a prescription drug that has a potential for misuse, abuse or diversion.”  Claim 6, the other claim at issue, was dependent on claim 1.  Under the Hatch-Waxman Act (21 U.S.C. § 355(b)(1)(A)(viii)), when a drug developer files an NDA, information on each patent “for which a claim of patent infringement could reasonably be asserted” must be submitted to the FDA if the patent claims either (i) the drug submitted for approval, or a formulation or composition thereof, or (ii) “a method of using such drug for which approval is sought or has been granted in the application.”

Avadel responded to Jazz’s infringement assertions with a counterclaim seeking delisting of the ’963 patent for failure to claim a drug or method of use. In evaluating the counterclaim, the district court found that, as a matter of claim construction, the ’963 patent claims a system and thus does not claim an approved method of use. The district court subsequently ordered Jazz to ask the FDA to delist the ’963 patent.  Jazz filed a notice of appeal and moved the district court to stay the injunction pending appeal, when the district court denied the stay, the Federal Circuit extended the stay until it could evaluate the issue on the merits.

The district court determined that the ’963 patent claims recited systems, not methods. Jazz contends that the word “system” as it appears in the ’963 patent claims is, essentially, a synonym for “method.” But, the Federal Circuit noted, method claims require the performance of steps; claims that describe physical components of a whole are system, or apparatus, claims.  The Federal Circuit said that the fact that the claimed systems can be used in the course of treating patients suffering from narcolepsy did not alter the fact that these are system claims.  It therefore found that the claims of the ’963 patent were properly construed by the district court as system claims, not method claims.

Jazz contended that FDA regulations which describes listing patents that “claim conditions of use,” yields a broader definition of “method” than permitted by the language of patent law and that this broader definition encompasses the claims of the ’963 patent.  Jazz argued that since prescribers were bound to follow the system in treating patients with narcolepsy. The Federal Circuit said that Jazz misread the

regulation describing method-of-use patents. The regulations do not broaden the term “method” such that reciting a condition of use turns a system patent into a listable method-of-use patent. Rather, this regulation narrows that category of listable patents to those that (1) claim methods of use, wherein (2) those methods of use are directly relevant to the NDA in question.

The Federal Circuit thus affirmed the district court, and lifted the stay, restarting the 14-day period for compliance prescribed by 21 C.F.R. § 314.53(f)(2)(i) to be within 14 days of its

decision. Although not directly relevant, it is interesting to note that the Federal Circuit approves treating apparatus claims like method claims in §101 eligibility analysis.  Too bad that that reasoning didn’t work for Jazz.

Patent Venue Construed Strictly, Even in ANDA Litigation

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In Celgene Corp. v. Mylan Pharmaceutics Inc., [2021-1154] (November 5, 2021) the Federal Circuit affirmed the dismissal of a patent infringement action against defendants, MPI and Mylan Inc. for improper venue, and against defendant Mylan N.V. for failure to state claim upon which relief can be granted.

After an giving an excellent summary of Hatch-Waxman Act litigation, the Federal Circuit recounted the history of the action. Celgene filed its first case in May 2017. The defendants-
appellees moved to dismiss for improper venue and failure to state a claim in August 2017. That motion was denied in March 2018 without prejudice so that the parties could engage in venue-related discovery.

After two years of that discovery, the defendants renewed their motion to dismiss. The district court concluded that venue was improper. Namely, the thin set of facts that Celgene had gathered after those two years—the presence of affiliated entities and employees in New Jersey—failed to show a “regular and established place of business” of the defendants in the district under 28 U.S.C. § 1400(b).

The Federal Circuit found that neither MPI nor Mylan had “committed acts of infringement” in New Jersey. The court noted that in Valeant, it said that “venue in Hatch-Waxman cases must be predicated on past acts of infringement.” For the purposes of the Hatch-Waxman Act, “it is the submission of the ANDA, and only the submission, that constitutes an act of infringement
in this context.” The question, then is where the submission occurred, and what acts it includes.

The Federal Circuit rejected the argument that the submission extends to whereever the generic drug woudl be marketed and sold. The Federal Circuit also rejected the argument that the submission included the act of sending the mandatory ANDA Notice, reiterating that it is the submission of the ANDA, and only the submission, that constitutes an act of infringement in this context.

The Federal Circuit also found that neither MPI nor Mylan had a regular and established place of business in New Jersey. There are three requirements for a regular and established palace of business: (1) there must be a physical place in the district; (2) it must be a regular and established place of business; and (3) it must be the place of the defendant. The third requirement was the relevant one in this case. The place of business must be “of the defendant, not solely . . . of the defendant’s employee.” Accordingly, “the defendant must establish or ratify the place of business,” and it is “not enough that the employee does so on his or her own.”

As to the third requirement, the Federal Circuit noted that it has discussed four non-exhaustive relvant factors:

(1) “whether the defendant owns or leases the place, or exercises other attributes of possession or control over the place”; (2) “whether the defendant conditioned employment on” “an employee’s continued residence in the district” or “the storing of materials at a place in the district so that they can be distributed or sold from that place”; (3) “a defendant’s representations” about that place, including advertisements; and (4) “the nature and activity of
the alleged place of business of the defendant in the district in comparison with that of other places of business of the defendant in other venues.”

17 of MPI’s and Mylan’s tens of thousands of employees live in New Jersey, but MPI and Mylan showed that it did not require or instruct those employees to live in New Jersey, or pay for their homes, or require employees to store materials in their homes, or pay for secretarial or support staff. The Court found that a roster of employees who live in the state, a handful of business cards with employee names and New Jersey home addresses, and two LinkedIn
profiles mentioning New Jersey were all too speculative to show ratification of those addresses by MPI and Mylan.

The Federal Circuit also found that two small storage lockers rented by MPI sales or marketing employees to store product samples are not places “of the defendant.” Nor do they bolster that the employees’ homes were such places. Those lockers are rented in the employees’ own names. They are used to intermittently store and access product samples. There is no evidence, in contrast, that they are used like warehouses—for order fulfillment, wholesaling, retail, or the like.

Overall, the Federal Circuit concluded that the employee-associated locations are not
a regular and established place of business of the defendants under § 1400(b).

The district court also concluded that, for Mylan N.V., Celgene had failed to state a claim upon which relief could be granted. That is, the ANDA that Celgene itself included with its complaint sought approval only on behalf of MPI. And Celgene’s pleadings with respect to the involvement of Mylan N.V. in that submission were simply too speculative and conclusory.

The Federal Circuit noted that MPI, not Mylan N.V., was the entity that signed and physically submitted the ANDA. Thus the question was whether Celgene sufficiently plead that (1) Mylan N.V. was actively involved in and directly benefited from the ANDA (including in the agent–principal sense) or (2) MPI acted as Mylan N.V.’s alter ego in derogation of the corporate form.
The Federal Circuit found that Celgene’s pleadings fail under either theory.

As to the denial of leave to amend the Complaint, the Federal Circuit said that Celgene’s allegations in its complaint were conclusory and insufficient. It knew the basis for their deficiency for years, as the district court correctly concluded, yet made no attempt to amend them in a timely manner. Nor has Celgene argued on appeal that it showed good cause. In
our view, then, the district court did not abuse its discretion in denying Celgene’s request for leave to amend its complaint.

The Scope of Patent Term Extension under 35 USC §156 Only Includes the Active Ingredient of an Approved Product

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In Biogen International GmbH v. Banner Live Sciences, LLC, [2020-1373] (April 21, 2020), the Federal Circuit affirmed the district court’s determination that Banner does not infringe the extended portion of U.S. Patent No. 7,691,001.

The ‘001 patent covers the administration of dimethyl fumarate, methyl hydrogen fumarate, or combinations thereof , and cover both the dimethyl ester and monomethyl ester forms are covered by this claim.

Biogen asserted the ’001 patent in an infringement action against Banner in the District of Delaware. Banner immediately moved for a judgment of
noninfringement, arguing that § 156(b)(2) limits the scope of the ’001 patent’s extension to methods of using the approved product as defined in § 156(f)—in this case, DMF, its salts, or its esters—and that MMF is none of those. Biogen responded that § 156(b)(2) does not limit extension of a method of treatment patent to uses of the approved product, but instead only to uses of any product within the original scope of the claims. Biogen further argued that, in any event, “product” in § 156 has a broader meaning encompassing any compound that shares with the approved product an “active moiety.”


The district court agreed with Banner’s interpretation of § 156 in both respects and rendered a judgment of noninfringement. It rejected Biogen’s argument that extension of a method of treatment patent under § 156(b)(2) is not limited to uses of the approved product.

The Federal Circuit explained that under § 156, an NDA holder is entitled to extend the term of only one patent for the corresponding approved product. Subsection (a) places several conditions on term extension for an NDA holder, including that the applicant’s approved NDA must be “the first permitted commercial marketing or use of the product. Subsection (b) limits the scope of the patent extension to “any use approved for the product,” and further, for method of treatment patents, to uses also “claimed by the patent.” The Federal Circuit said that citically, for the purposes of the appeal, subsection (f) defines “product” as “the active
ingredient of . . . a new drug . . . including any salt or ester
of the active ingredient.” § 156(f)(2)(A).

The Federal circuit said that “Active ingredient” is a term of art, defined by the FDA as “any component that is intended to furnish pharmacological activity or other direct effect,” 21 C.F.R. § 210.3(b)(7), and it “must be present in the drug product when administered.” The active ingredient
of a given drug product is defined by what is approved and is specified on the drug’s label. The Federal Circuit noted that MMF is not the approved product, nor is it specified as the active ingredient on the Tecfidera® label. Esters are included in the statutory definition of what can be extended, but MMF is the de-esterified form of DMF, not an ester of DMF. Thus, it is
not the same product under § 156(f) and does not fall within the scope of the ’001 patent’s term extension under § 156(b)(2).

Federal Circuit Affirms Non-obvious Holding in “Close” Case, Declining to Disturb Factual Findings on Motiviation

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In Impax Laboratories Inc. v. Lannett Holdings Inc., [2017-2020] (June 28, 2018), the Federal Circuit affirmed the district court decision that claims 4, 11, 12, and 14 of U.S. Patent 6,760,237 and claims 6 and 14–
16 of U.S. Patent 7,220,767 were not shown to be invalid and entering an injunction.

The claims at issue are directed to pharmaceutical formulations, intranasal administration devices, or aqueous solutions, of zolmitriptan.  The Federal Circuit noted that all of the claims at issue rise and fall together with the issue of whether it would have been obvious to make zolmitriptan into a nasal spray.

In considering the asserted obviousness of the claimed invention, the Federal Circuit noted that while the reference mentioned the possible nasal administration of zolmitriptan (just once, and not in a claim or an example), the reference was not about administering zolmitriptan, but about the nasal administration of active ingredients generally.  The Federal Circuit also noted evidence in the record that a skilled artisan would have expected delayed or lower therapeutic effectiveness from
zolmitriptan if administered nasally because it would have been “absolutely counterintuitive to make a nasal spray when you have an active metabolite which is more potent . . . than the drug itself.”

The Federal Circuit said that:

In view of the totality of the record evidence of the state of the prior art, we cannot find that the district court clearly erred in its findings. Far from disregarding the prior art’s discussion of zolmitriptan, the court specifically considered and acknowledged that zolmitriptan was mentioned in connection with nasal formulations and
sprays. However, the court also properly considered additional record evidence to make findings on the state of the prior art as a whole.

The Federal Circuit noted that the presence or absence of a motivation to combine references in an obviousness determination is a pure  question of fact, as is what a reference teaches and whether it teaches toward or away from the claimed invention.  Based on the record before it, the Federal Circuit could not find that the court clearly erred in concluding that at the time, zolmitriptan’s known significant reliance on its active metabolite would have, on balance, dissuaded a person of
skill in the art from making nasal formulations of zolmitriptan.  The Federal Circuit said that it does not and should not reweigh evidence or make factual findings anew on appeal.