PTAB

PGR2021-00115

KymEra Therapeutics Inc v. Dana Farber Cancer Institute Inc

Key Events

Petition

petition

Title: Compounds and Methods for the Targeted Degradation of Proteins
Brief Description: The ’980 patent describes hetero-bifunctional compounds designed for targeted protein degradation (TPD). These compounds comprise three components: a cereblon-binding moiety (based on thalidomide), a linker, and a targeting ligand that binds to a target protein implicated in a disease, thereby recruiting an E3 Ubiquitin Ligase to mark the target protein for destruction.

Prior Art Relied Upon: Not applicable (challenge based on patent specification).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner argued that the ’980 patent fails to demonstrate possession of the claimed invention. The claims recite a vast genus of compounds defined by function—specifically, a targeting ligand that binds to a target protein from an extensive list. However, the specification allegedly fails to disclose a single working example of a degrader compound that meets all the structural and functional limitations of independent claims 1 or 24.
- Motivation to Combine (for §103 grounds): Not applicable.
- Expectation of Success (for §103 grounds): Not applicable.
- Key Aspects: The core of the argument was the disconnect between the broad, functional claim scope and the limited, non-representative examples provided. Petitioner contended that for a nascent and unpredictable field like TPD, the specification must provide a representative number of species or common structural features, which it failed to do for the claimed targeting ligands and linkers. The patent allegedly does not provide a structure-function correlation to guide a person of ordinary skill in the art (POSA) across the full scope of the claims.

Prior Art Relied Upon: Not applicable (challenge based on patent specification).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner argued that practicing the full scope of claims 1-45 would require undue experimentation. The claims cover an incalculable number of compounds across more than 150 target proteins in a highly unpredictable technological field. A POSA would have to engage in an iterative, trial-and-error process with no reasonable expectation of success.
- Motivation to Combine (for §103 grounds): Not applicable.
- Expectation of Success (for §103 grounds): Not applicable.
- Key Aspects: The argument focused on the multiple layers of unpredictability. A POSA would first need to determine if a given target is even degradable by a cereblon-based system. Then, they would need to screen millions of potential targeting ligands, as binding affinity does not predict degradation efficacy. Finally, they would have to design and test innumerable linkers, as minor structural changes to a linker can have unpredictable effects on a degrader’s performance. The patent provides insufficient guidance to navigate this process.

Prior Art Relied Upon: Liu et al. (a 2013 journal article, Ex. 1005).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner asserted that the Liu reference discloses Compound 3, a hybrid molecule that anticipates the claimed invention. Liu’s Compound 3 consists of curcumin covalently linked to thalidomide via a carbonyl linker. Petitioner mapped these components to the elements of claim 24: thalidomide is the claimed cereblon-binding moiety, curcumin is the "Targeting Ligand," and the carbonyl group is the "Linker."
- Motivation to Combine (for §103 grounds): Not applicable.
- Expectation of Success (for §103 grounds): Not applicable.
- Key Aspects: Petitioner argued that curcumin, the targeting ligand in Liu's compound, is known to bind several target proteins recited in claim 24, including ERBB2, GSK3beta, and PAK1. Furthermore, Liu’s disclosure of Compound 3 being active in multiple myeloma cell lines meets the functional requirement that the target protein is a "mediator of abnormal cellular proliferation" (as multiple myeloma is a cancer).
Additional Grounds: Petitioner asserted that claims 1-45 are indefinite under §112(b) because key functional terms are not defined with reasonable certainty.

"the Targeting Ligand is a moiety that binds to a Target Protein": Petitioner argued this term is indefinite because the specification fails to provide a consistent standard for determining "binding." It is unclear whether binding must be measured on an attached or unattached ligand, or whether mere binding affinity is sufficient versus binding that leads to degradation. The patent’s own examples allegedly present conflicting data, showing a compound with measurable binding affinity but describing it as lacking binding because it was inactive as a degrader.
"the Target Protein is a mediator of abnormal cellular proliferation": Petitioner contended this term is indefinite because the specification provides no guidance on how to determine if a protein is a "mediator." It is unclear if a mediator must be a protein that causes abnormal proliferation or merely one that participates in both normal and abnormal cellular proliferation machinery. This ambiguity allegedly prevents a POSA from discerning the scope of the claims with reasonable certainty.

Petitioner argued against discretionary denial under §325(d), asserting that the grounds presented in the petition are not the same as, nor substantially the same as, arguments previously considered by the USPTO. The core §112 written description and enablement challenges were never raised during prosecution. Furthermore, while the anticipating Liu reference was cited in an Information Disclosure Statement (IDS), it was part of a list of over one hundred references and was never substantively addressed by the Examiner.

Petitioner requested institution of a Post-Grant Review and cancellation of claims 1-45 of the ’980 patent as unpatentable.