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June 20, 2023 - Biotech, Pharma, Intellectual Property, Litigation, Cell + Gene Therapy

Practical Strategies for Protecting Innovations Under the Doctrine of Equivalents

Recent Digital Health-Related FDA Announcements

Recent case law highlights enablement and written description challenges for genus claims.[1] Given the challenges of enforcing genus claims, the doctrine of equivalents (DOE) may become a more important tool for patentees when literal infringement is unavailable.

As discussed below, the outlook for successful application of DOE to biologics remains uncertain. But with careful prosecution strategies, patentees can better preserve their DOE arguments to block design-arounds with insubstantial differences and/or those that perform substantially the same function in substantially the same way.

DOE for Biologics

Ajinomoto Co., Inc. v. ITC provides a rare example of successful DOE application to protein sequences.[2] There—applying the “function-way-result” (FWR) test for analyzing equivalence—the Federal Circuit concluded that a bacterial strain engineered to express a particular amino acid sequence was equivalent to a strain engineered to express a different amino sequence of a related protein.[3] In finding that the proteins functioned in substantially the same way, the court relied on the facts that the two proteins were 95% identical in primary amino acid sequence and were predicted to be 85% identical in structure.[4] Thus, when applying the FWR test to large biomolecules, sequence similarity will likely be an important consideration as it was in the Ajinomoto decision.

A more recent case, Teva Pharmaceuticals International GmbH v. Eli Lilly & Co., illustrates that relying on DOE to broaden the scope of claims reciting biological sequences (e.g., antibody sequences) can be challenging.[5] There, Teva asserted two claims reciting antibody CDR sequences and variable region sequences against Lilly under DOE. The antibodies at issue shared only 29.9% sequence similarity in the CDRs, and the heavy chain of the closest variant disclosed in Teva’s patent shared only 52.5% similarity with Lilly’s antibody.[6] In this case, the court said that application of DOE would be “a bridge too far” and would effectively read the amino acid sequence limitation out of the claims.[7] Thus, DOE arguments that essentially vitiate the sequence limitations would not be likely to succeed.

It is worth noting that the court in Teva decided on the DOE issue using the “insubstantial differences” test, which the court viewed as more appropriate for evaluating equivalents in chemical compounds. Although it is clear from Teva that application of DOE to biologics likely requires “insubstantial differences” between the claimed and accused products, how much sequence identity or similarity in primary amino acid or nucleic acid sequence amounts to insubstantial difference is far from being clear. Moreover, large biological molecules having low sequence identity in primary sequences may nevertheless assume highly similar three-dimensional structures and/or functions – in such cases, would the difference be insubstantial?

Despite these uncertainties and the paucity of examples successfully applying DOE to biological drugs and particularly antibodies in district court litigation or before the Federal Circuit, DOE may be an important tool in view of genus claim vulnerabilities. Patent applicants looking to apply DOE in any field must take care during prosecution to avoid estoppel, as discussed below.

DOE Prosecution Strategies

  • Consider initially pursuing narrow claims with a high likelihood of patentability without amendments to the claims during prosecution to avoid estoppel issues.[8] Fewer written arguments during prosecution may help reduce the risk of estoppel issues. Consider making greater use of examiner interviews to help focus amendments and arguments.
  • Remember that preliminary amendments can also create prosecution history estoppel.[9]
  • Take care to avoid new matter or written description rejections when introducing dependent claims. Dependent claim cancellations can also invoke prosecution history estoppel.[10]
  • The “disclosure dedication” rule may bar application of DOE for equivalents that are disclosed in the specification.[11] Rather than relying on DOE in such cases, applicants should consider pursuing a continuation application to cover specific competitor products disclosed in the specification but not initially claimed.

[1] Amgen Inc. v. Sanofi, No. 21-757, 2023 WL 3511533 (U.S. May 18, 2023).

[2] See, generally, 932 F.3d 1342 (Fed. Cir. 2019).

[3] Id. at 1356-1357.

[4] Id. at 1357.

[5] No. 18-CV-12029-ADB, 2022 WL 4824318, at *18 (D. Mass. Oct. 3, 2022).

[6] Id. At *16.

[7] Id. at *18.

[8] Narrowing amendments made during prosecution create a rebuttable presumption that the patentee has surrendered the broader claim scope, typically referred to as “prosecution history estoppel.” This presumption is rebuttable if (1) the equivalent would have been unforeseeable at the time of the amendment; (2) the rationale underlying the amendment is only tangentially related to the equivalent in question; or (3) “there [is] some other reason suggesting that the patentee could not reasonably be expected to have described the insubstantial substitute in question.” Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 344 F.3d 1359, 1365 (Fed. Cir. 2003.

[9] In Amgen Inc. v. Hoechst Marion Roussel, Inc., for example, the Federal Circuit found that a preliminary amendment limiting the claims to a 166-amino acid sequence of human erythropoietin (EPO) surrendered coverage of EPO with a 165-amino acid sequence (the mature, cleaved form of the protein). 457 F.3d 1293, 1297 (Fed. Cir. 2006).

[10] Consider UCB, Inc. v. Yeda Research & Development Co., Ltd., 117 F. Supp. 3d 755 (E.D. Va. 2015). There, Yeda added dependent claims reciting “chimeric” claims, which Yeda explained encompassed humanized antibodies. Yeda canceled these dependent claims after the examiner rejected them for lack of written description. Although the independent claim reciting “monoclonal antibodies” had not been amended, the court held that the main claim could not be construed to cover humanized antibodies literally or under DOE in view of the claim cancellation in response to a rejection.

[11] In Morphosys AG v. Janssen Biotech, Inc., for example, disclosure of human or humanized anti-CD38 antibodies precluded the patentee from asserting that a claim limited to human antibodies also covered humanized antibodies under DOE. 358 F. Supp. 3d 354 (D. Del. 2019).