Pegfilgrastim – USA

On Jul 29, 2019, Federal Circuit affirmed district court & found Coherus' biosimilar non-infringing under Doctrine of Equivalents (DOE) because of prosecution history estoppel (PHE).

Coherus filed aBLA with USFDA which sought approval of biosimilar version of Amgen’s pegfilgrastim product, Neulasta®. Amgen sued Coherus over US 8,273,707 which claims methods of purifying proteins using hydrophobic interaction chromatography (“HIC”). All of the ’707 claims require a salt combination chosen from one of three pairs: citrate and sulfate, citrate and acetate, or sulfate and acetate for effective purification.

Claim 1 recites:

1. A process for purifying a protein on a hydrophobic interaction chromatography column such that the dynamic capacity of the column is increased for the protein comprising

mixing a preparation containing the protein with a combination of a first salt and a second salt,

loading the mixture onto a hydrophobic interaction chromatography column, and eluting the protein,

wherein the first and second salts are selected from the group consisting of citrate and sulfate, citrate and acetate, and sulfate and acetate, respectively, and

wherein the concentration of each of the first salt and the second salt in the mixture is between about 0.1 M and about 1.0.

Amgen during prosecution argued that prior art did not teach or suggest the claimed particular combination of salts. It supported this arguments with Declaration from inventor.  Amgen further argued that the claimed invention is directed to increasing dynamic capacity of a HIC column and prior art does not teach dynamic capacity at all. Examiner first rejected the arguments but finally allowed the claims as Amgen pointed out that choosing a working salt combination was a “lengthy development path” and that “merely adding a second salt” would not result in the invention.

During litigation, Delaware Court dismissed Amgen's infringement claim under DOE for failure to state the claim based on PHE. Amgen appealed. During appeal Federal Circuit sided with district court & said that argument based prosecution history estoppel prohibits Amgen from asserting infringement under DOE. Amgen clearly and unmistakably surrendered salt combinations other than the particular combinations recited in the claims. Notably, Amgen’s response to the examiner’s office action quotes the Declaration’s conclusion that “use of this particular combination of salts greatly improves the cost-effectiveness of commercial manufacturing by reducing the number of cycles required for each harvest and reducing the processing time for each harvest.”

Amgen argued that its statement regarding the “particular combinations” of salts “simply observes (correctly) as a factual matter that prior art does not disclose using combinations of salts in the first instance,” and thus does not clearly and unmistakably surrender unclaimed salt pairs. Amgen argued that PHE does not apply because it made three bases/statements along with the one which states that prior art failed to teach particular salt combination. But Federal Circuit said that PHE can apply to single statement or base also unless the combine effect is argued. Amgen did not rely on the combination of its asserted grounds to distinguish prior art, so prosecution history estoppel applies to the “particular combinations” ground regardless of the other two arguments Amgen made. Therefore, single statement or base can give rise to estoppel.

Amgen next argued that the statements made during prosecution were not final ones which resulted in notice of allowance. Court again disregarded this & held that it is not necessary that to apply the PHE only final response is taken into consideration. Any response made against the rejection at any stage can give rise to estoppel. Federal Circuit thus held that the district court did not err in determining that prosecution history estoppel bars Amgen from succeeding on its infringement claim under the doctrine of equivalents.