Amgen Reply Brief Addresses Mischaracterizations by Sanofi, U.S. Government on Proper Enablement Inquiry for Genus Claims

“Only when ‘the number of inoperative combinations becomes significant, and in effect forces’ skilled artisans ‘to experiment unduly’ to find ones that do exist or operate, does that suggest ‘the claims might indeed be invalid.” – Reply Brief of Amgen

ReplyOn March 6, biotechnology developer Amgen filed a reply brief with the U.S. Supreme Court in its appeal of the invalidation of its patent claims covering antibodies effective at blocking low-density lipoprotein (LDL) cholesterol receptors. The brief responds to arguments raised both by rival pharmaceutical firm Sanofi and the U.S. federal government in Amgen’s appeal of the invalidation of its patent claims as a matter of law under 35 U.S.C. § 112, which the district court entered on judgment as a matter of law (JMOL) after a jury verdict upheld the validity of Amgen’s patent claims.

Amgen v. Sanofi has had an incredibly active docket at the Supreme Court, with a few dozen amicus filings submitted since the Court granted Amgen’s petition for writ of certiorari last November. More than a dozen amicus filings were submitted to the Court on January 3 of this year, many of which supported reversal of the U.S. Court of Appeals for the Federal Circuit’s decision to affirm Section 112 invalidity under a heightened legal standard requiring patentees to disclose the entire scope of a claimed invention, a standard highly detrimental to genus claims. On February 10, another batch of amicus briefs was filed, many supporting Sanofi’s decision that genus claims like Amgen’s are overbroad as a matter of law.

Sanofi Asked For ‘Cumulative-Effort Standard’ it Now Decries as ‘Straw-Man Argument’

Amgen’s recent reply brief begins by pushing back on Sanofi’s contentions that the Federal Circuit did not adopt a higher standard for Section 112 enablement. Despite Sanofi’s February 3 response brief, in which Sanofi said Amgen was raising a “straw-man argument” about a supposed “cumulative-effort standard” being applied by the Federal Circuit, several U.S. federal court cases and U.S. Patent and Trademark Office administrative decisions since the 2021 ruling for Sanofi have interpreted the decision as raising the enablement standard under Section 112. As Amgen notes, Sanofi had argued multiple times to the Federal Circuit that Amgen’s patent claims should be invalid due to the cumulative effort required to find all antibodies covered by Amgen’s genus claim, so Sanofi should not now disclaim that it hasn’t been requesting a standard that many commentators have found to be a significant change from the status quo.

Instead of the Federal Circuit’s novel “reach the full scope” test for enablement, Amgen asks the Supreme Court to return to Section 112’s statutory language, which requires a patentee to enable others skilled in the art to “make and use” the claimed invention based on the disclosure in the patent’s specification. “If the patent’s instructions are ‘sufficiently definite to guide’ skilled artisans to ‘successful application’ across the scope of the ‘invention,’ the claims are enabled,” under the Supreme Court’s 1916 decision in Minerals Separation, Ltd. v. Hyde. “But cataloging every embodiment is a task for ‘the mechanic, not the inventor,’” Amgen asserts.

‘Specific Undisclosed Embodiments’ Standard is Not Supported by Legal Precedent

Amgen notes that several cases cited in Sanofi’s briefing show how the “make and use” standard for enablement has led federal courts to uphold the validity of challenged patent claims even when the patent’s disclosed a roadmap to making inventions across a certain genus even when every embodiment in the genus could not be properly described in the specification. On the other hand, Amgen argues that Sanofi has identified no case precedent for its proposed standard requiring a patent to teach skilled artisans to “predictably produce specific undisclosed embodiments of the claimed invention.”

Citing to the Federal Circuit’s 1984 decision in Atlas Powder Co. v. E.I. du Pont De Nemours & Co., Amgen contends that the proper legal standard recognizes that inoperative embodiments within a genus do not invalidate the claim. “Only when ‘the number of inoperative combinations becomes significant, and in effect forces’ skilled artisans ‘to experiment unduly’ to find ones that do exist or operate, does that suggest ‘the claims might indeed be invalid,’” Amgen’s reply brief argues. The present case highlights the issues with Sanofi’s proposed standard, Amgen indicates, as Sanofi has argued that certain antibodies within Amgen’s genus claim are somehow more desirable than other effective antibodies that can be created by Amgen’s roadmap.

“That insinuation is unsupported by any evidence. Sanofi-Regeneron’s own expert said the opposite, testifying that ‘there’s no correlation between the number of amino acids that are bound and the [antibody’s] blocking’ of PCSK9’s interaction with LDL receptors… The undisputed testimony was that, ‘if an antibody has a structure that allows it to bind to one or more residues on the sweet spot’—no matter which ones or how many—’it will block’ PCSK9’s interaction with LDL receptors.” – Amgen’s reply brief

Sanofi’s invocation of the “specific undisclosed embodiments” standard is ironic, Amgen argues, because Sanofi, the district court and the Federal Circuit never identified any antibodies within the genus that could not be made by following Amgen’s roadmap. This includes the four antibodies Sanofi created in developing its cholesterol treatment Praluent. While only 26 example antibodies are disclosed by amino acid sequence, Amgen’s patents disclosed that Amgen had actually created 384 antibodies within the genus by following the claimed roadmap. This total includes 20 antibodies within a “middle binders” class, refuting Sanofi’s earlier contentions that no such “middle binders” antibodies were disclosed by Amgen.

Section 112 Enablement Does Not Require Structurally Representative Disclosures

Similar arguments by the U.S. government about the lack of enablement due to Amgen’s meager patent disclosures should also fail, Amgen counters. Along with the fact that the patents actually disclose the creation of hundreds of antibodies within the claimed genus, not just the 26 antibodies identified by amino acid sequence, Amgen asserts that the government is erroneously urging the Court to require that Amgen’s disclosed amino acid sequences be structurally representative of the entire genus, which isn’t required by the traditional test for enablement.

While the U.S. government argued that federal courts have required that a patent claiming a genus disclose within the specification “‘some general quality, running through the whole’ genus,” Amgen notes that this standard is not the only way for a patent claim describing an invention in functional rather than structural terms to survive an enablement challenge. Indeed, the seminal Supreme Court decision in Diamond v. Chakrabarty (1980) paved the way for the modern day U.S. biotech industry by upholding the validity of a patent claiming an invention implemented by functional biological generation instead of structural assembly, Amgen contends.

Further, while Sanofi and the U.S. government have portrayed Amgen’s disclosed roadmap as “little different from [Amgen’s] initial research plan,” Amgen notes that the roadmap allows skilled artisans to start where Amgen’s research ended. The roadmap disclosed by Amgen includes several techniques and teachings that were previously unknown, including assays identifying antibodies that bind the antigenic “sweet spot” of PCSK9, and the precise three-dimensional structure and biochemical properties of the sweet spot region that binds LDL receptors.

Heightened Enablement Standard Would Promote Infringement in Biological Inventions

Finally, Amgen responded to contentions raised by several amicus filings in February, many of which were filed by other pharmaceutical firms, that genus claims do not contribute to innovation. As has been reported here on IPWatchdog, and cited in the Amgen reply brief, Sanofi and several of the pharmaceutical amici making such claims themselves have obtained patents relying on genus claims. While disclosure of amino acid sequences is one way to claim a biological discovery, it is not the only way that courts have recognized over years, and current legal doctrines would make it difficult to address infringement if a heightened patenting standard requires such sequences to be disclosed.

“The doctrine of equivalents hardly ‘address[es] th[e] risk’ of copyists avoiding infringement by making minor changes to amino-acid sequences. That doctrine does not apply where ‘even one limitation of a claim * * * is not present in the accused [product].’ Courts thus have refused to apply ‘the equivalence argument’ because it ‘would read the amino acid sequence limitation out of’ the claim and ‘effectively expand’ the claim’s scope to encompass any ‘antibody that has the [claimed] effect.’ No company would invest billions in researching and developing new antibodies in hopes that the doctrine of equivalents will prevent competitors from evading an amino-acid-sequence claim.” – Amgen’s reply brief



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Join the Discussion

One comment so far.

  • [Avatar for Anon]
    March 12, 2023 08:22 pm

    Both sides argue poorly – in my humble opinion.

    One can fully exchange the gist of the arguments with the actual use of case law and still be at the same point.

    It looks like pedantic semantics.

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