Written Description of Therapeutic Efficacy

Fenwick & West LLP

Fenwick & West LLP

Inventors are generally counseled to file a patent application as soon as they have a patentable invention to avoid potential forfeiture of important rights in today’s first inventor-to-file system. However, inventors—particularly those in drug development—should be wary of potential risks associated with racing to the U.S. Patent and Trademark Office and filing too early. As one example of additional considerations to take into account prior to filing, we look at two recent cases in which the U.S. Court of Appeals for the Federal Circuit invoked the “written description requirement” of 35 U.S.C. § 112 to require evidentiary support for efficacy—a twist the U.S. Supreme Court was asked to consider but denied.

Although demonstration of human clinical efficacy of a drug is not required for patentability, the claimed invention has to have a specific, substantial and credible use under the “utility requirement” of 35 U.S.C. § 101 and the specification must teach those in the art how to use the invention without undue experimentation under the “enablement requirement” of 35 U.S.C. § 112. Given that human clinical efficacy is unpredictable, as evidenced by the percentage of failures in Phase 3 clinical trials, heightened standards have been applied and evidentiary support for therapeutic efficacy has been required, often based on experimental data, to support utility and enablement.

Recently, the Federal Circuit invoked the written description requirement of 35 U.S.C. § 112, separate from the enablement requirement, to require evidentiary support for efficacy in Idenix Pharmaceuticals v. Gilead Sciences and Nuvo Pharmaceuticals v. Dr. Reddy’s Laboratories. In both opinions, the court held claims invalid for failing to meet the written description requirement, failing to demonstrate that the inventor was in possession of the claimed invention at the time of filing the patent application.

This article reviews these Federal Circuit decisions and a recent petition for writ of certiorari.

Idenix v. Gilead

Idenix v. Gilead involved a patent related to a method of treating the hepatitis C virus (HCV) by administering nucleoside compounds. The relevant claim recited:

  1. A method for the treatment of a hepatitis C virus infection, comprising administering an effective amount of a purine or pyrimidine β-D-2’-methyl-ribofuranosyl nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.

The “method for the treatment” preamble, in combination with the requirement to administer an “effective amount,” led the U.S. District Court for the District of Delaware to construe the claim to require “use of some set of compounds that are effective for treatment of HCV.”

The Federal Circuit first assessed whether the claim meets enablement requirement, asking “whether a person of ordinary skill in the art would know, without undue experimentation, which 2’-methyl-up nucleosides would be effective for treating HCV.” The Federal Circuit found that “the claims … encompass at least many, many thousands of 2’-methyl-up nucleosides which need to be screened for HCV efficacy, the quantity of experimentation needed is large.” Although the specification contained some data showing working examples, it found that the “working examples are exceedingly narrow relative to the claim scope.” In addition, the Federal Circuit determined that “[d]ue to the unpredictability of the art … each of these compounds would need to be screened” and “the immense breadth of screening required” to determine the effectiveness is undue experimentation. Therefore, the Federal Circuit found the patent invalid for lack of enablement.

Separately, the Federal Circuit addressed the issue of written description. It asked whether the inventor was in possession of 2’-methyl-up nucleosides that fall within the scope of the claim but that are not encompassed by the explicit formulas or examples in the specification. In other words, whether the patent demonstrated that such 2’-methyl-up nucleosides are effective against HCV.

It noted that for genus claims, the written description inquiry is whether there are “‘blaze marks which single out particular trees’ in a forest, rather than simply ‘pointing to trees.’” (Here, it cited a 1996 Federal Circuit ruling, Fujikawa v. Wattanasin.) In such a Ruschig inquiry, “a genus can be sufficiently disclosed by ‘either a representative number of species falling within the scope of the genus or structural features common to the members of the genus.’”

The Federal Circuit then held that the claims were invalid for lack of written description, as the specification “fails to provide sufficient blaze marks to direct a person of ordinary skill in the art (POSA) to the specific subset of 2’-methyl-up nucleosides that are effective in treating HCV.” It explained that “the specification provides no indication that any nucleosides outside of those disclosed in its formulas could be effective to treat HCV” and “no method of distinguishing effective from ineffective compounds for the compounds reaching beyond the formulas disclosed in the ‘597 patent.”

The patentee argued that the application provided “‘abundant traditional blaze marks for the claims—working examples, formulas, data, synthesis routes, and the target.’” The Federal Circuit disagreed, explaining that “[t]hey provide lists or examples of supposedly effective nucleosides, but do not explain what makes them effective, or why. As a result, a POSA is deprived of any meaningful guidance into what compounds beyond the examples and formulas, if any, would provide the same result.”

Nuvo v. Dr. Reddy

Nuvo v. Dr. Reddy involved a patent related to a new drug dosage form that coordinates the release of an acid secretion inhibitor (PPI) and a nonsteroidal anti-inflammatory drug (NSAID). The dosage form contains a core of NSAID, a coating that prevents release of the NSAID until the PPI reduces the acid level (raises the pH) in the stomach, and PPI outside of the coating, which can act immediately to increase pH to the desired level.

The representative claim reads:

  1. A pharmaceutical composition …, comprising:
  • (a) an acid inhibitor present in an amount effective to raise the gastric pH of said patient to at least 3.5 …;
  • (b) a non-steroidal anti-inflammatory drug (NSAID) …;

and wherein said unit dosage form provides for coordinated release such that:

  • i) said NSAID is surrounded by a coating that, …, prevents the release of essentially any NSAID … unless the pH of the surrounding medium is 3.5 or higher;
  • ii) at least a portion of said acid inhibitor is not surrounded by an enteric coating and, …, is released regardless of whether the pH of the surrounding medium is below 3.5 or above 3.5.

Based on the limitations underlined above, the claim was construed to require “a therapeutically effective amount of uncoated PPI that can raise the gastric pH to at least 3.5.”

The U.S. District Court for the District of New Jersey found the claims to be valid, with the specification meeting both the enablement and written description requirements. The defendant generic companies appealed the written description decision to the Federal Circuit, but not the enablement decision. Specifically, the defendants argued the claims lacked written description support for the claimed effectiveness of uncoated PPI.

It was undisputed that there was no experimental data in the specification demonstrating the therapeutic effectiveness of any amount of uncoated PPI. The patentee argued, however, that the specification’s statements, such as “an acid inhibitor present in an amount effective to raise the gastric pH of a patient to at least 3.5,” and that an acid inhibitor “will typically be present at about 5 milligrams to 600 milligrams per dose,” provide written description support for amounts of uncoated PPI effective to raise the gastric pH to at least 3.5.

The Federal Circuit rejected the arguments, stating that “simply calling generally for effective amounts of uncoated PPI … is not enough.” It explained that “a [POSA] would not have known or understood that uncoated PPI is effective. … There must be some description, such as a constructive reduction to practice, establishing that the inventor ‘was in possession of the ... claimed invention, including all of the elements and limitations.’”

With the District of New Jersey’s holding of enablement unchallenged on appeal, the patentee further argued that the enabling disclosure in the specification sufficed to meet the written description requirement.

The Federal Circuit disagreed. It distinguished the written description requirement from the enablement requirement, stating that “the fact that an invention may be enabled does not mean it is adequately described. … The focus of the written description requirement is instead on whether the specification notifies the public about the boundaries and scope of the claimed invention and shows that the inventor possessed all the aspects of the claimed invention.”

The Federal Circuit decided that the claim was invalid for lack of written description sufficient to support the “efficacy” limitation in the challenged claims.

Idenix and Nuvo: Key Takeaways

The Idenix and Nuvo courts clarified that even if an invention is enabled, that finding does not mean that the claims are adequately described; the patent has to show that the inventor possessed all limitations of the claimed invention. For claims requiring therapeutic efficacy, the courts required experimental data proving efficacy, or sufficient data and a detailed theory of why the claimed subject would be effective. For genus claims, the Idenix court required that the patent provide guidance into what species would provide the same therapeutic effects beyond specific examples in the specification.

The Supreme Court Decided Not to Weigh in

The patentee in Idenix filed a petition for certiorari on September 21, 2020, challenging the application of the separate written description requirement, specifically:

Whether, as the Federal Circuit has held, § 112(a) contains a separate ‘possession’ requirement—or whether, as the statute provides, § 112(a) sets forth a single substantive requirement of ‘a written description of the invention’ sufficient ‘to enable any person skilled in the art … to make and use the same.’

Idenix argues that § 112(a) demands a single inquiry, which turns on enablement. This assertion was previously rejected by the Federal Circuit in its en banc decision in Ariad Pharmaceuticals v. Eli Lilly.

Although this is an important question that would affect the scope of patent protection available to drug developers, the Supreme Court denied the petition on January 19, 2021. As a result, the written description requirement will continue to present a third hurdle, in addition to the utility and enablement requirements, for claims that recite therapeutic efficacy. Accordingly, extra precaution is required when drafting claims requiring therapeutic effects, e.g., claims reciting “effective amount.”

Although written description is a matter of fact and written description analyses are therefore fact specific, such claims would likely require experimental evidence of efficacy or at least description of a theory of effectiveness of the claimed invention in its entire scope to meet the written description requirement. It is also recommended to consider how to use or define the term “effectiveness” in the specification and how to relate evidentiary support in the specification to the “effectiveness” so that it can provide written description support.

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

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