Analyzing Biologics Under the Doctrine of Equivalents and Prosecution History Estoppel

In a recent decision, Ajinomoto v. ITC, the Federal Circuit addressed the issues of doctrine of equivalents and prosecution history estoppel as applied to patent claims reciting specific amino acid sequence of a biologic. On appeal, the Federal Circuit affirmed the decision by the United States International Trade Commission that a protein having 85% to 95% identity infringed a claim reciting specific amino acid sequences under the doctrine of equivalents.

The doctrine of equivalents is used to find infringement of products or processes that do not fall within the literal scope of patent claims. The function-way-result test is frequently used to determine equivalents.[1] Prosecution history estoppel limits the reach of equivalents based on claim amendments during prosecution of a patent. Specifically, a narrowing amendment gives rise to the presumption that the territory between the original claim and the amended claim has been surrendered. This presumption can be rebutted, however, if 1) the equivalent was unforeseeable at the time of amendment; 2) the rationale underlying the amendment bears no more than a tangential relationship to the equivalent in question; or 3) there is some other reason suggesting that the patentee could not reasonably be expected to have claimed the equivalent. [2]

The Ajinomoto case involved an unusual file history. During prosecution of the asserted patent, Ajinomoto presented a claim that recited two alternatives for the claimed protein:

(A) a protein that comprises the amino acid sequence of SEQ ID NO:2; or

(B) a protein that comprises an amino acid sequence including deletion, substitution, insertion, or addition of one or several amino acids in the amino acid sequence shown in SEQ ID NO:2.

SEQ ID NO:2 corresponds to the amino acid sequence of the E. Coli YddG protein. Facing anticipatory prior art which disclosed an E. Coli protein with a similar sequence, Ajinomoto kept alternative (A) and replaced alternative (B) with “a protein which comprises an amino acid sequence that is encoded by a nucleotide sequence that hybridizes with the nucleotide sequence of SEQ ID NO:1 under stringent conditions.” Ultimately, claims 9 and 15 issued, each reciting one of the alternatives. The asserted claim (claim 20) depends from both claims and recites:

A method for producing an aromatic L-amino acid, which comprises cultivating the bacterium according to any one of claims 9-12, 13, 14, 15-18, or 19.

The accused bacterial strain expressed a codon-randomized non-E. Coli YddG gene that codes for a protein having 85% – 95% identity with the amino acid sequence of SEQ ID NO:2.[3] The issue before the Court was whether the accused bacterial strain met the protein limitation (A) under the doctrine of equivalents.

Although a narrowing claim amendment was made during prosecution, the Court held that prosecution history estoppel did not preclude a finding of equivalents. The Court reasoned that prosecution history applies under unusual circumstances, because the infringement determination rested on finding equivalents of the protein limitation (A), which was not altered during prosecution.[4] The Court found that the amendment to the claim limitation (B) bore no more than a tangential relationship to the accused product because “the objectively evident rationale for the amendment was to limit the set of proteins within the claim’s scope so that it no longer included the prior art E. Coli YfiK protein and, more generally, no longer allowed as wide a range of amino acid alterations. The reason for the amendment had nothing to do with choosing among several DNA sequences in the redundant genetic code that correspond to the same protein.”[5]

The Federal Circuit then applied the function-way-result test set forth by the Supreme Court in Graver Tank to determine equivalents.[6] The Federal Circuit found that the accused equivalent performed the same function, namely exporting aromatic L-amino acids out of bacterial cells. The Court found that the accused equivalent performed the function in the same way because the equivalent had 85 – 95% identity with the sequence recited in the claim. The Court further determined that the recited protein and the accused equivalent produced the same result of increasing the ability of the bacteria to produce and accumulate L-tryptophan. The Court consequently concluded that the accused strain infringed the asserted claim under the doctrine of equivalents.

Judge Dyk, in dissent, disagreed with the majority’s prosecution history estoppel analysis. In Judge Dyk’s view, the equivalent was directly related to the reason for the claim amendment, namely to exclude those proteins made by an encoding nucleotide that does not hybridize with SEQ ID NO:1.[7]

The Ajinomoto decision sheds light on how patents reciting specific sequences of a biologic are analyzed under the existing prosecution history estoppel and doctrine of equivalents frameworks. However, many questions remain unanswered. For example, as noted by the decision, this was an unusual case where the amendment that may have given rise to prosecution history estoppel was not made with respect to the particular limitation at issue. It is unclear whether similar reasoning would apply if the original claim did not list the protein and its variants as alternatives on separate tracks and/or if the narrowing amendment were made to the limitation at issue.

The doctrine of equivalents and prosecution history estoppel involve fact-intensive inquiries and detailed analysis of the prosecution history of a patent. Practitioners analyzing infringement of biologics on a patent should go beyond the claimed sequences and consider whether related proteins or nucleic acids may be infringing under the doctrine of equivalents, even if the claims are narrowed during prosecution. In addition, patent applicants should consider the option of starting prosecution with narrow claims when prosecuting a biologics patent application to limit potential prosecution history estoppel arguments down the line during litigation.

[1]Graver Tank v. Linde Air Products, 339 U.S. 605, 608 (1950).

[2] Festo v. Shoketsu Kinzoku Kogyo Kabushiki, 535 U.S. 722, 740 (2002).

[3] Although it is unclear from the opinion, it appears that the Court may be referring to 85% identity with respect to predicted secondary structure based upon the reference cited in the opinion.  

[4] Ajinomoto V. ITC, Federal Circuit (2018-1590, 2018-1629), slip opinion at p. 18.

[5] Slip opinion at p. 21.

[6] Graver Tank at 608.

[7] Slip opinion Dissent at p. 7.