By Kevin E. Noonan –

The Federal Circuit affirmed a District Court determination that method claims reciting administration of a modification of an established antibiotic by adding magnesium to the composition were infringed and not invalid in Melinta Therapeutics, LLC v. Nexus Pharmaceuticals, Inc.

The case arose as ANDA litigation over Nexus Pharma’s generic version of Melinta’s antibiotic formulations comprising magnesium cations used in a claimed method for treating bacterial infections that reduced hemolysis of red blood cells at the injection site, compared with such methods using antibiotics without the addition of magnesium, as claimed in U.S. Patent Nos. 9,084,802 and 9,278,105.  Claim 1 of the ‘805 patent and claim 1 of the ‘105 patent are reproduced in the opinion as being representative:

The ‘802 patent:

1.  A method of treating a bacterial infection in a subject, wherein the method consists of:

administering a therapeutically effective amount of a composition to a subject in need thereof via an intravenous route of administration,

wherein the composition consists of an aqueous solution consisting of minocycline or a salt thereof, a salt that comprises a magnesium cation, and a base,

wherein the molar ratio of magnesium cation to minocycline is greater than about 4:1, and

wherein the composition has a pH that is no less than 4 and no greater than 6,

whereby injection site hemolysis of red blood cells is reduced relative to intravenous administration of a composition that does not include magnesium.

The ‘105 patent:

1.  A method of treating a bacterial infection in a subject, wherein the method comprises administering a therapeutically effective amount of a composition to a subject in need thereof via an intravenous route of administration, wherein the composition comprises an aqueous solution of a 7-dimethylamino-tetracycline antibiotic and a magnesium cation, wherein the molar ratio of magnesium cation to 7-dimethylamino-tetracycline antibiotic is greater than 3:1 and wherein the solution does not comprise a pharmaceutically acceptable oil, has a pH greater than 4 and less than 7, and has an osmolality less than about 500 mOsmol/kg.

Melinta’s product, Minocin, is an aqueous solution of minocycline and magnesium and, as the opinion notes, had been marketed since 1972 but had been reformulated to include magnesium, as well as having an increase pH and a reduced six of the administered dose.

The District Court found that Nexus Pharma’s generic formulation would infringe the patented method claims of the ‘802 and ‘105 patents and issued a permanent injunction.  The District Court also held that Nexus had failed to establish invalidity of the claims on “obviousness, indefiniteness, inadequate description, or lack of enablement” grounds.  This appeal followed.

The Federal Circuit affirmed with regard to the asserted claims of the ‘802 patent and did not reach the issues raised for the ‘105 patent, in an opinion by Judge Bryson, joined by Judges Prost and Reyna.  With regard to the District Court’s findings concerning the ‘802 patent Nexus raised two arguments on appeal.  First, Nexus argued that the District Court erred in construction of the terms “composition” and “administering.”  Regarding the “composition” term, District Court construed the term to mean (as recited in the claim) the combination of minocycline, magnesium, and a base prior to the addition of the diluent needed to produce the formulation (the “admixture” as recited in the claim) actually administered to a patient in need thereof.  The construction of the term “administering” by the District Court referred to the diluted composition given to the patient.

Nexus argued that the phrase as a whole in the claim (“administering . . . a composition”) required the administered composition not to include a diluent, because claim 1 recites that the composition “consists of” the three listed named ingredients and did not include a diluent (“wherein the composition consists of an aqueous solution consisting of minocycline or a salt thereof, a salt that comprises a magnesium cation, and a base”).  Because Nexus Pharma’s composition does contain a diluent administration thereof is not infringing according to their argument.  Melinta argued that the term “composition” should be construed to the “”concentrated, reconstituted solution prior to further dilution” and that what was administered was the composition after the diluent was added.

The District Court construed these terms consistent with Melinta’s argument and the Federal Circuit affirmed based on the intrinsic and extrinsic evidence.  This included a description in the specification that the three-component composition was diluted prior to administration; the testimony of three expert witnesses to the same effect; and the prescribing information that instructs reconstitution and further dilution.  Nexus Pharma’s proposed construction was inconsistent with this evidence, according to the opinion, and a person having ordinary skill in the art would know adding a diluent to the composition was necessary.  The panel affirmed the District Court’s finding that Nexus Pharma’s generic, diluent- and magnesium-containing antibiotic composition would infringe.

The second basis for Nexus Pharma’s challenge to the District Court’s decision was that the specification did not satisfy the disclosure requirements under 35 U.S.C. § 112(a) because the relevant claim limitation (“injection site hemolysis of red blood cells is reduced relative to intravenous administration of a composition that does not include magnesium”) did not make clear that the comparison would be made against compositions that contained no divalent cations or ones containing a different divalent cation (such as calcium, for example).  Nexus contended that to be consistent with satisfaction of the written description requirement the comparison must be between compositions having magnesium and that do not.  The inventors failed to show that they had possession of reduced hemolysis when the comparison was made with compositions having calcium cations.

Melinta first argued that Nexus had waived this argument because it had appeared in only a single sentence of Nexus Pharma’s post-trial brief (which the Court rejected based on, inter alia, expert trial testimony by the parties on this issue).  Melinta also argued that the correct comparison would be between compositions with magnesium and those without.  Regarding this argument the Federal Circuit held that the District Court did not err and considered it to be the most natural comparison” between the same composition with and without magnesium (wherein the latter was Melinta’s prior formulation).  The specification sets forth comparisons between formulations having divalent cations (including those with magnesium or calcium) and those without (i.e., lacking any metal cations).  However, “[n]othing in the specification is directed to comparing the effect of magnesium with that of calcium [but r]ather, the focus of the specification is the reduction of hemolysis resulting from the inclusion of magnesium or calcium, as compared to prior art formulations, which did not include metal cations at all.”

The panel conceded that the District Court’s construction “does not expressly exclude a formulation that lacks magnesium but includes a different cation, such as calcium, in place of the absent magnesium.”  Nevertheless, the panel opined that the construction argued by Nexus Pharma “would be contrary to the overwhelming evidence that the invention of the ‘802 patent was directed to the advantage of adding magnesium to a minocycline formulation lacking divalent cations, and not to any advantage magnesium might have compared to other metal cations.”  It did not escape the panel’s notice that the prior art Minocin product included a warning against administering formulation including a calcium-containing diluent which may form a precipitate.

 Having affirmed the District Court’s decisions on infringement and non-invalidity, the opinion explains that the parties had stipulated that the district court’s infringement finding would be upheld if either the ‘802 or ‘105 patents were found not invalid and thus the Court did not address validity of the ‘105 patent.

The outcome in this case is somewhat in contrast to that in Enanta Pharmaceuticals inc. v. Pfizer Inc.  In that case, the patentee lost priority to its earliest-filed provisional application (U.S. Patent Application No. 63/054,048) for reciting alternatives for a substituent as being “NHC(O)—C₂-C₁₂-alkyl” whereas U.S. Patent No. 11,358,953 at issue before the Court recited “NHC(O)—C₁-C₁₂-alkyl.”  The District Court’s decision was affirmed by the Federal Circuit, but it is just as easy to see that the decision could also have readily rested on a finding that the lack of disclosure in the ‘048 provisional precluded Enanta from a finding that Pfizer infringed by including a species (nirmatrelvir) in its product Paxlovid^Ò) that had a C₁ substituent (-CH₃), and permitting Enanta to retain the scope of the C₂-C₈ alkyl species disclosed in the provisional application to which they were arguably entitled.  Here the District Court and the Federal Circuit somewhat overlooked Nexus Pharma’s distinction that although the specification disclosed the need to add a diluent to the magnesium-containing composition prior to administration that wasn’t what was recited in the asserted claims of either patent-in-suit.  Maybe that is because the asserted claims were method claims and the “invention” was inclusion of magnesium to a well-known antibiotic that reduced an important drawback, injection site hemolysis of red blood cells, rather than the composition of matter claims in Enanta. But it seems prudent to recognize the distinctions.

Melinta Therapeutics, LLC v. Nexus Pharmaceuticals, Inc. (Fed. Cir. 2026)
Nonprecedential disposition
Panel:  Circuit Judges Prost, Bryson, and Reyna
Opinion by Circuit Judge Bryson