Sequence Identity and the Doctrine of Equivalents in Biotechnology Claims

 The biological activity of proteins and nucleic acids often does not depend upon their having one exact nucleotide or amino-acid sequence. Many changes may be made to a sequence without materially affecting its biological function. An enzyme, for example, may tolerate numerous amino-acid substitutions while retaining essentially the same catalytic activity. Similarly, a nucleic acid may contain sequence variations yet still encode a protein having substantially the same biological properties.

This presents an important problem in patent drafting. If a patent claim protects only one precisely recited sequence, an alleged infringer might attempt to avoid literal infringement simply by making one or more relatively minor sequence changes. A claim directed only to “a protein having the amino-acid sequence of SEQ ID NO:1” ordinarily does not literally cover a protein having a different sequence, even if the difference has little or no practical effect on its function.

There are, however, several ways in which patent protection may extend beyond the exact sequence recited in a claim.

One is the doctrine of equivalents. Under this doctrine, a patent claim may sometimes be infringed even though the accused product or process does not literally satisfy every claim limitation. An accused element may be treated as equivalent to a claimed element when the differences between them are insubstantial. Courts have frequently expressed this inquiry by asking whether the accused element performs substantially the same function, in substantially the same way, to obtain substantially the same result.

The doctrine of equivalents can therefore be particularly important in biotechnology, where a minor structural change may have little biological significance. But reliance on the doctrine has definite limitations. Its application is highly fact specific and  depends on the prior art, the language of the claims, and amendments or arguments made during prosecution. Prosecution-history estoppel, for example, may prevent a patentee from recapturing through equivalents subject matter that was surrendered in obtaining the patent. The doctrine also cannot simply be used to erase or disregard a limitation that the patentee chose to include in the claim. As a result, infringement under the doctrine of equivalents is generally less predictable than literal infringement.

A second and more direct approach is to draft the claim itself so that it expressly encompasses sequence variants. For example, rather than claiming only one enzyme sequence, a claim might recite:

“An enzyme comprising an amino-acid sequence having at least 95% sequence identity to SEQ ID NO:1, wherein the enzyme catalyzes reaction X.”

Such a claim does not merely protect the precise sequence appearing as SEQ ID NO:1. Its literal scope potentially includes many different sequences, provided that they satisfy the stated degree of sequence identity and retain the required biological function. Thus, a protein differing at several amino-acid positions may still literally infringe the claim, without any need to invoke the doctrine of equivalents.

Sequence-identity limitations can therefore be extremely useful in biotechnology patent claims. They recognize an important biological reality: molecules need not be structurally identical to be functionally equivalent.

There is, however, a corresponding patent-drafting problem. The broader the range of variants encompassed by the claim, the greater the need for the patent specification to demonstrate that the inventor possessed and enabled the claimed range. A claim covering every sequence having 90%, 95%, or even 98% identity to a disclosed protein may encompass an enormous number of possible molecules, some of which may not retain the desired activity. Adding a functional limitation can help define the relevant class, but it does not automatically eliminate written-description or enablement concerns.

For this reason, choosing a sequence-identity percentage is not simply a matter of making the claim as broad as possible. The percentage, the required biological activity, the amount of experimental support in the specification, and the predictability of the relationship between sequence and function should all be considered together.

In biotechnology patents, therefore, sequence identity provides an important bridge between two extremes: a claim so narrow that trivial sequence changes may avoid literal infringement, and a claim so broad that it may be difficult to support. Carefully drafted sequence-identity claims can provide meaningful literal protection for biologically equivalent variants while reducing the need to depend exclusively on the less predictable doctrine of equivalents.

 Disclaimer: This piece is provided for general informational purposes only and does not constitute legal advice. Patent issues are often complex and highly fact-specific, and no one should act on general information of this kind without consulting qualified patent counsel regarding the particular circumstances involved.