Meloxicam – USA

Meloxicam – USA

On Feb 01, 2018, Judge Marvin J. Garbis of District of Maryland granted Lupin’s Motion for Summary Judgment in VIVLODEX® (meloxicam) Hatch-Waxman litigation.

In 2015, Co-Plaintiff Iroko Pharmaceuticals, LLC (“Iroko”) gained approval from USFDA for its New Drug Application (“NDA”) for 5 milligram (“mg”) and 10 mg formulations of the drug meloxicam which it markets under the VIVLODEX®. The NDA lists United States Patent Nos. 9,526,734 (“the ‘734 patent”) and 9,649,318 (“the ‘318 patent”) in Orange Book. The alleged invention in patents pertains to formulations of meloxicam (5 mg and 10 mg formulations) that are milled to meet a specified nanoparticulate size distribution profile. The Patents-in-Suit are owned by the Co-Plaintiff iCeutica Pty Ltd. (“iCeutica”) which exclusively licenses the patents to Iroko (Iroko and iCeutica collectively referred to as “Plaintiffs”).
On August 4, 2016, Defendant Lupin filed an Abbreviated New Drug Application (“ANDA”) with P-IV certification seeking FDA approval for a generic version of VIVLODEX®. Plaintiffs filed suit & contended that Lupin’s product directly infringes on all claims of the ‘734 and ‘318 patent—either literally or through the doctrine of equivalents—and that the prosecution history does not estop it from arguing doctrine of equivalents. In its ANDA application, Lupin specifies that the generic products it intends to market will have a D(0.9) of less than 800 nm.

Independent Claim 1 of ‘734 patent:
1. A capsule form of a pharmaceutical composition comprising 5 mg of meloxicam having a median particle size, on a volume basis, between 100 nm and 500 nm and a D(0.9) that is between 1200 nm and 3000 nm, wherein a single capsule, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞) of 7500-20000 h*ng/ml and a mean plasma Cmax of 350-950 ng/ml, wherein the dissolution rate is such that, when the capsule is tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 500 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37° C.+0.5° C., at least 80% of the meloxicam dissolves in 10 minutes or less, wherein a single capsule is effective for treating osteoarthritis pain.

Independent Claim 1 of ‘318 patent:
1. A capsule form of a pharmaceutical composition comprising 5 mg of meloxicam having a median particle size, on a volume basis, between 100nm and 1000 nm, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞) of 7500-20000 h*ng/ml and a mean plasma Cmax of 350-950 ng/ml, wherein the D(0.9) of the particles of meloxicam is less than 4000 nm and greater than 1200 nm, and wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 500 mL of pH 6.1 phosphate buffer with 0.1% sodium laurel sulfate (SLS) at 37° C.±0.5° C., at least 80% of the meloxicam dissolves in 10 minutes or less.

Plaintiffs contended that Lupin infringes on the ‘734 and ‘318 patents through the doctrine of equivalents (for particle size limitations) and literally (for all other limitations). In its Motion for Summary Judgment, Lupin contended that its ANDA products do not literally infringe on Plaintiffs’ patents, that Plaintiffs are estopped from arguing the doctrine of equivalents in light of the prosecution history, and that it is entitled to summary judgment as a matter of law.
On literal infringement, Court held that Lupin’s ANDA products would not literally infringe on the ‘734 and ‘318 claims because the product’s particle size distribution would not fall within the claimed ranges. The ‘734 patent claims a D(0.5) of 100-500 nm and a D(0.9) of 1200-3000 nm. The ‘318 patent claims a D(0.5) of 100-1000 nm and a D(0.9) of 1200-4000 nm. Lupin’s ANDA product needs a D(0.9) of less than 800 nm for FDA approval. Any D(0.9) value below 800 nm will fall outside of the minimum claimed value of 1200 nm. Because the D(0.9) of Lupin’s products does not fall within the claimed range of 1200-3000 nm (or 1200-4000 nm), the Court holds that a reasonable fact finder could not find that Lupin’s products will contain every limitation in the ‘734 and ‘318 patent claims.

With respect to Doctrine of Equivalents, Court held that that Plaintiffs are estopped from arguing that Lupin’s ANDA products would infringe on the ‘734 and ‘318 patent claims through the doctrine of equivalents because the applicant surrendered any particle size distributions with a D(0.9) below 1200 nm during prosecution through both amendment-based and argument-based estoppel.
The prosecution history shows that the ‘734 patent claimed a D(0.9) value of “less than 3000 nm” in the original application, indicating a range of 0-3000 nm. In a Response to the Examiner’s rejection, the applicant amended the D(0.5) to 100-3000 nm and the D(0.9) to 900-3000 nm. The Examiner still upheld the rejection over Cooper in a second Non-Final Office Action. Finally, the claims were further amended to a D(0.5) of 100-500 nm and a D(0.9) of 1200-3000 nm. In an Examiner Interview Summary, the Examiner noted that the amended ranges would “still adequately describe a broader particle size distribution, wherein the D(0.9) is distinct from the median particle size, which was not taught or contemplated by the prior art teachings of Cooper” and would be “commensurate in scope with the data provided in the specification.”

The ‘318 patent underwent a similar prosecution as the ‘734 patent. However, the examiner allowed the claims with a D(0.5) of 100-1000 nm and a D(0.9) of 1200-4000 nm. The upper bounds for the D(0.5) and D(0.9) are higher than those of the ‘734 patent. The prosecution history does not reveal a reason for why the upper bounds of the D(0.5) were allowed to remain at 1000 nm (as opposed to 500 nm as amended in the ‘734 patent).

Court further held that the Plaintiffs clearly narrowed its D(0.5) and D(0.9) valuesthrough amendments during prosecution. These amendments were made to overcome a § 103 rejection over Cooper. Therefore, a presumption is raised that bars a DOE argument for any product with a D(0.5) greater than 500 nm and a D(0.9) below 1200 nm. The equivalent in question (Lupin’s ANDA product) would have a D(0.5) of roughly 200 nm and a D(0.9) of less than 800 nm, falling below the claimed 1200 nm threshold. The Court also concluded that Plaintiffs have not rebutted the presumption (through the tangential relation exception) that Plaintiffs have surrendered D(0.9) values of less than 1200 nm, and Plaintiffs are thus barred from arguing that Lupin’s products will infringe through doctrine of equivalents for the ‘734 patent. Finally Court held that because the Plaintiffs cannot prove literal infringement of the ‘734 and ‘318 patents and are barred from proving infringement through the doctrine of equivalents, the Court found that there are no remaining genuine issues of material fact, and Lupin is entitled to judgment as a matter of law.

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