Prepopik® – USA

On Jul 11, 2017 Delaware court issued its opinion in Prepopik ANDA case. Plaintiffs Ferring Pharmaceutical brought this patent infringement action against Par Pharmaceutical, Inc. on February 20, 2015. Defendant filed an Abbreviated New Drug Application ("ANDA"), seeking to engage in the commercial manufacture, use, and sale of a generic version of Ferring's Prepopik (sodium picosulfate, magnesium oxide, and citric acid) product. Plaintiffs allege that Defendant's submission of this ANDA infringes U.S. Patent Nos. 8,450,338 ("the '338 patent") and 8,481,083 ("the '083 patent"). The Delaware court held a bench trial on November 8-9, 2016. Prior to trial, Defendants dismissed all invalidity defenses with prejudice. Therefore, the only issue addressed at trial was whether Defendant's proposed ANDA product and process infringe the '338 and '083 patents.

Plaintiffs assert claims 1, 4-6, 8, 9-12, and 17-18 of the '338 patent and claims 1 and 7-11 of the '083 patent. The parties agree that if Defendant's ANDA product meets all limitations of claim 1 of the '338 patent and if the process by which it makes its ANDA product meets all limitations of claim 8 of the '338 patent, then all limitations of the asserted dependent claims of the '338 patent are met.

Claim 1 is a composition claim and reads as follows:

1. A composition comprising sodium picosulphate coated granules having a spray-coated layer of sodium picosulphate coating a potassium bicarbonate core.

Claim 8 is a process claim and reads as follows:

8. A process for the preparation of a composition according to claim 1 wherein said process comprises steps of: (a) spray coating a solution of sodium picosulfate on to potassium bicarbonate; and (b) drying the sodium picosulfate and potassium bicarbonate thereby obtaining sodium picosulphate coated granules, Wherein the sodium picosulfate coated granules have a layer of sodium picosulfate coating a potassium bicarbonate core.

There is no dispute that Defendant's ANDA product is a composition comprising sodium picosulfate and potassium bicarbonate. There is also no dispute that Defendant's ANDA product contains granules.

The parties also agree that if Defendant's ANDA product meets all limitations of claim 1 of the '083 patent, then all limitations of the asserted claims of the '083 patent are met.

Claim 1 is a composition claim and reads as follows:

1. A pharmaceutical composition comprising: (a) magnesium oxide coated granules which have a layer of magnesium oxide coated on a core of citric acid; and (b) sodium picosulphate coated granules having a spray-coated layer of sodium picosulphate coating a potassium bicarbonate core.

There is no dispute that Defendant's ANDA product is a pharmaceutical composition comprising magnesium oxide coated granules which have a layer of magnesium oxide coated on a core of citric acid. The only disputed issue, therefore, is whether Defendant's ANDA product comprises a "spray-coated layer of sodium picosulfate coating a potassium bicarbonate core."

The essence of the parties' disputes as to both limitations revolves around the plain and ordinary meaning of the terms "coated," "coating," and "layer." Plaintiffs' expert, Dr. Davies, opined that "coated" and "coating" mean "a layer of a substance, which is on the outer surface of another substance or material." Defendant's expert, Dr. Augsburger, disagreed, opining that these terms mean a "process resulting in the production of a layer of sodium picosulfate substantially evenly surrounding the potassium bicarbonate core." Dr. Augsburger further opined that a "layer" is "a structural component of the sodium picosulfate/potassium bicarbonate granules that substantially evenly surrounds the potassium bicarbonate core."

Defendant argues that the term "coated" is used in the claims as an adjective while the term "coating" is used as a verb. (Id. at 9). This means, according to Defendant, that Plaintiffs' proposed plain and ordinary meaning "cannot be correct" because Plaintiffs' meaning requires these terms to be nouns. Judge disagreed and said that rather the dispute is whether the sodium picosulfate layer must "substantially evenly surround" the core, as Defendant contends. Judge cast doubts on Dr. Augsburger's purported reliance on scientific literature for arriving at his plain and ordinary meaning. Furthermore, none of Defendant's citations support Dr. Augsburger's proposal that the layer must "substantially evenly surround" the core. Judge agreed with Plaintiffs that Dr. Augsberger' s opinion amounts to an attempt to reargue claim construction. Plaintiff’s expert Dr. Davies explained that a person of ordinary skill in the art would expect the magnesium oxide layer coated on the citric acid core to be continuous because of the relative proportions of the two compounds given in the patent. On the other hand, because of the relative proportions of potassium bicarbonate and sodium picosulfate, a person of ordinary skill would expect the sodium picosulfate layer to be discontinuous. Dr. Davies further explained that it would be impossible to create a layer of sodium picosulfate "substantially evenly surrounding" the core because of the random nature of the spray-coating process.

The parties dispute whether Defendant's process involves spray-coating or wet granulation. While both processes can be performed using the same equipment, they are distinct processes that produce different sized particles. Plaintiffs' expert, Dr. Johnson, opined that Defendant's ANDA product is made using a spray-coating process. Dr. Johnson evaluated Defendant's process conditions and equipment configuration in arriving at his opinion. Defendant argues in response that its product is manufactured by "agglomeration via a wet granulation process." Judge said that he process must be considered as a whole, as Dr. Johnson persuasively opined during direct examination. Furthermore, while Defendant sometimes refers to the process as wet granulation, Plaintiffs pointed out at trial that some of Defendant's own lab notebooks reference using a spray-coating process.

Defendant next argues that its manufacturing equipment is configured for agglomeration via wet granulation, and that this configuration is not appropriate for spray-coating. Defendant further argues that its process parameters, including temperature and humidity, indicate that the process is wet granulation. Defendant further argues that the separate drying step it employs is evidence that its process is wet granulation. Defendant also criticizes Dr. Johnson for failing to cite to scientific literature that would show how a person of skill in the art would distinguish between spray-coating and wet granulation. Judge denied all arguments & said that I find Dr. Johnson's detailed testimony about Defendant's ANDA manufacturing process persuasive and more credible than Dr. Augsburger's. I hold that Defendant's process employs spray-coating.

CONCLUSION: Plaintiffs have met their burden of proving by a preponderance of the evidence that Defendant's proposed ANDA product infringes claims 1, 4-6, 8, 9-12, and 17-18 of the '338 patent and claims 1 and 7-11 of the '083 patent.