PTAB

PGR2023-00014

Forte BioSciences Inc v. University Of Massachusetts

Log In

1. Case Identification

2. Patent Overview

  • Title: Diagnosis and treatment of vitiligo
  • Brief Description: The ’505 patent discloses methods for treating vitiligo, a localized autoimmune skin disorder, by administering a therapeutically effective amount of an inhibitor of interleukin-15 (IL-15) or the IL-15 receptor (IL-15R). The claimed method aims to treat depigmentation lesions caused by the autoimmune destruction of melanocytes.

3. Grounds for Unpatentability

Ground 1: Lack of Written Description - Claims 1-5 are invalid under 35 U.S.C. §112

  • Core Argument: Petitioner argued that the claims lack written description because their scope is far broader than the invention disclosed in the specification. The claims functionally recite treating vitiligo with any inhibitor of IL-15 or its receptor (IL-15R), in any subject. However, the specification provides only a single working example: the use of a specific, Fc-diminished chimeric antibody (ChMBC7) targeting the IL-15Rβ subunit (CD122) in a specific, induced-lesion mouse model. Petitioner contended that this single example is insufficient to demonstrate possession of the vast and unpredictable genus of claimed inhibitors, which includes different molecular structures (small molecules, peptides, nucleic acids), different targets (IL-15, IL-15Rα, CD122, CD132), and different inhibition mechanisms. Furthermore, the induced-lesion mouse model was argued to be unrepresentative of naturally occurring vitiligo in humans, making the results non-extrapolatable to the full scope of claimed subjects.

Ground 2: Lack of Enablement - Claims 1-5 are invalid under 35 U.S.C. §112

  • Core Argument: Petitioner asserted that the specification fails to enable a person of ordinary skill in the art (POSA) to practice the full scope of the claimed invention without undue experimentation. The argument parallels the written description challenge, focusing on the highly complex and unpredictable nature of cytokine signaling. Given the nascent state of the art, a POSA would not be able to determine which of the incalculable number of potential inhibitors would be effective for treating vitiligo based on the patent’s sparse guidance. The specification allegedly provides only a "starting point for further research" rather than an enabled method. Petitioner contended that identifying effective inhibitors for the various targets (IL-15, IL-15Rα, CD122, CD132) and subjects (e.g., humans) would require an extensive, iterative trial-and-error process, constituting undue experimentation.

Ground 3: Obviousness over Xing and Harris - Claims 1-5 are obvious over Xing in view of Harris under 35 U.S.C. §103

  • Prior Art Relied Upon: Xing (a 2014 journal article on alopecia areata) and Harris (a 2012 journal article on a vitiligo mouse model).
  • Core Argument:
    • Prior Art Mapping: Petitioner argued that Harris disclosed the exact same induced-lesion mouse model for vitiligo later used in the ’505 patent, where the disease is caused by autoreactive CD8+ T cells. Harris explicitly suggested that preventing the accumulation of these cells has "therapeutic potential" for treating vitiligo. Xing taught that systemic administration of a CD122 antibody (an IL-15Rβ inhibitor) successfully depleted autoreactive CD8+ T cells and prevented hair loss in a mouse model of alopecia areata, a closely related autoimmune skin disease also driven by CD8+ T cells.
    • Motivation to Combine: A POSA would combine these references because Harris identified the problem (vitiligo caused by CD8+ T cells) and suggested a therapeutic path (depleting those cells), while Xing provided a specific solution (using a CD122 antibody to deplete CD8+ T cells) in a highly analogous context. The motivation would be to apply Xing's proven method to treat the disease described in Harris.
    • Expectation of Success: A POSA would have had a reasonable expectation of success. Since both vitiligo (in Harris) and alopecia areata (in Xing) were known to be driven by autoreactive CD8+ T cells, and Xing demonstrated that a CD122 antibody effectively depleted these cells and treated the condition, it would be expected that the same antibody would work in the vitiligo model by the same mechanism. The dependent claims (3-5) for local administration were also argued to be obvious, as Xing taught local administration of downstream inhibitors.

4. Key Technical Contentions (Beyond Claim Construction)

  • Complexity of Cytokine Signaling: Petitioner’s arguments for §112 relied heavily on the technical assertion that the IL-15 signaling pathway is highly complex and shares components (e.g., the CD122 and CD132 receptor subunits) with other cytokine pathways like IL-2. The biological effect of any inhibitor was argued to be highly unpredictable, depending on which subunit, binding interaction (cis- or trans-presentation), and pathway it targets. Therefore, the effect of the patent’s single exemplified antibody (ChMBC7) could not be extrapolated to other inhibitors.
  • Mouse Model Unrepresentative of Human Disease: Petitioner contended that the patent’s sole working example, using a mouse model where vitiligo is artificially induced by transferring a specific cell population, is not representative of treating natural or spontaneous vitiligo in humans. The biological causes of human vitiligo are far more complex, and cytokine-blocking experiments in mice are not reliably predictive of efficacy or safety in humans.

5. Arguments Regarding Discretionary Denial

  • Material Error in Prosecution: The petition argued that institution is warranted due to material error during the original prosecution. Petitioner asserted that the examiner never considered any challenges under §112 for lack of written description or enablement, which are central to the petition.
  • New Prior Art and Arguments: The primary obviousness reference, Xing, was not before the examiner. The patent owner allegedly overcame a rejection over a different reference by arguing a "surprising discovery." Petitioner contended that Xing provides the very evidence the examiner found lacking, demonstrating that depleting CD8+ T cells with a CD122 antibody was a known and obvious therapeutic strategy, thus negating any claim of surprise.

6. Relief Requested

  • Petitioner requested institution of a post-grant review and cancellation of claims 1-5 of Patent 11,278,505 as unpatentable.