RE:RE:RE:RE:RE:RE:On GLP-1 agonists US Senate passes anti-patent thicket billThe board's decision in Seagen is not surprising. Rather, it is consistent with the U.S. Patent and Trademark Office's guidelines for assessing enablement in utility applications and patents. The PTO guidelines were issued on Jan. 10 in view of the U.S. Supreme Court's May 2023 decision in Amgen Inc. v. Sanofi.
The guidelines provide for continued application of the Wands factors in assessing enablement after the Supreme Court's decision in Amgen v. Sanofi, which found claims directed to a genus of antibodies that bind specific amino acid residues on the PCSK9 protein and inhibit its binding to the low density lipoprotein receptor protein — i.e., a genus defined by function — invalid for lack of enablement.
The board found that the scope of the claims was extremely broad, encompassing ADCs composed of any antibody and any drug moiety, with the only limit being a smaller linker genus size — i.e., maleimidocaproyl group and Gly/Phe-only tetrapeptide limitations — and that the level of ordinary skill in the art was high. There were no working examples incorporating the claimed linkers containing a Gly/Pheonly tetrapeptide unit.
While the claims cover ADCs containing any drug, the board found that the specification does not provide guidance on the attachment of drugs other than dolastatin and auristatin and their derivatives to the recited linker. Although disclosing an extensive list of chemotherapeutic drugs and general reaction schemas for linker synthesis and attachment, the specification does not identify any specific heteroatoms or other "handles" for attachment of any other drugs to the linker or address how to place such handles on other drugs.
The board then turned to the state of the prior art and unpredictability of the art, rejecting Seagen's argument that the claims do not require any particular level of intracellular cleavage.
The board explained that the "[patent] statute and caselaw impose a 'use' requirement commensurate in scope with the claim which … requires sufficient 'intracellular cleavage in a patient' to function in the treatment of some disease or condition."
Nonetheless, the board found the prior art provided substantial details on methods for determining whether an ADC is cleaved intracellularly in vitro.
However, the board found significant unpredictability in attaching drugs to the claimed linker that the prior art does not resolve. The board pointed to references indicating that a certain type of linker worked for doxorubicin but was inapplicable to most other classes of drugs and explained that numerous attempts to target tumors with ADCs have met with limited success.
For most of the many drugs covered by the claims, no specific method of attachment to a linker was predictably provided in the prior art. Thus, "ADCs are not mix-and-match" and ADCs with certain drugs would be understood to have different properties that may make them incompatible with the claimed tetrapeptide linkers.
Finally, the board found that a large quantity of experimentation is required to create any particular ADC while retaining intracellular cleavage, let alone to enable the broad scope of the claims. It remains unknown how to attach many drug moieties to ADCs [ thus allowing for the attachment of ONCY's pelareorep, for example] .
No reference disclosed a toolkit for ADC preparation widely available to many drugs. References showed that many ADCs were less potent than non-conjugated drugs and had no selectivity for antigen-expressing cells. Also, the specification disclosed many more drugs than the four types of cancer drugs that the prior art disclosed in ADCs.
The board then analogized the facts to those in Amgen where the Supreme Court found lack of enablement, where the claimed class of antibodies included a vast number that were not described, noting that the '039 patent describes ADCs with two drug classes and no linkers in the scope of the claims while encompassing a vast number of additional drugs that were not described.
Furthermore, the board reasoned that as in Amgen, the specification leaves readers to "random trial-and-error discovery" where much of the selection of the optimal antibody, ideal linker-drug chemistry and optimal number of payload molecules are determined empirically.
The board then explained that considering the Wands factors as a whole, the large breadth of the claims, absence of working examples, limited amount of direction and guidance, unpredictability in synthesizing antibody-drug linker conjugates and extensive quantity of experimentation were balanced against the high level of skill in the art and predictability in testing intracellular cleavage.
Accordingly, the board found that undue experimentation was required to make and use the claimed invention.