Baylor College Of Medicine v. Board Of Regents Of University Of Texas System

1. Case Identification

• Case #: Unassigned
• Patent #: 8,728,806
• Filed: April 18, 2018
• Petitioner(s): Baylor College of Medicine, Diakonos Research, Ltd.
• Patent Owner(s): The Board of Regents of the University of Texas System, Gensetix, Inc.
• Challenged Claims: 1-30

2. Patent Overview

• Title: Methods for Inducing an Immunologic Response Using Dendritic Cells
• Brief Description: The ’806 patent is directed to methods for inducing an immunologic response in a patient. The method involves "double-loading" immature dendritic cells (DCs) by transfecting them with a nucleic acid encoding tumor antigens and simultaneously contacting them with a tumor antigen composition (e.g., lysate) containing epitopes that overlap with, but are not identical to, the epitopes encoded by the nucleic acid.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1, 11, 14-15, and 26-28 under 35 U.S.C. §102

• Prior Art Relied Upon: Decker et al., "Double loading of dendritic cell MHC class I and MHC class II with an AML antigen repertoire enhances correlates of T-cell community in vitro via amplification of T-cell help," Vaccine (2006) ("Decker").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Decker expressly or inherently discloses every limitation of independent claim 1. Decker describes a method of preparing a DC vaccine by obtaining monocytic DC precursors, culturing them into immature DCs, and then "double-loading" them with both total tumor mRNA (the nucleic acid composition) and tumor lysate (the tumor antigen composition) derived from the same Acute Myeloid Leukemia (AML) tumor cells. Petitioner contended the key limitation—an epitope in the antigen composition that overlaps by at least 5 amino acids with an epitope encoded by the nucleic acid but is not identical—is inherently disclosed. Because both the mRNA and lysate come from the same tumor source, they necessarily contain a coextensive pool of antigens (e.g., Proteinase 3), which would naturally generate different but overlapping MHC-I and MHC-II binding epitopes, thus fulfilling the claim limitation.
  • Key Aspects: Petitioner asserted that Example 1 of the ’806 patent is copied nearly verbatim from Decker. During prosecution, the Patent Owner allegedly used the results from Decker (as presented in Example 1) to argue for patentability based on "surprising results," which Petitioner characterized as an admission that Decker's methods practice the claimed invention.

Ground 2: Obviousness of Claims 2 and 3 under 35 U.S.C. §103

• Prior Art Relied Upon: Decker, in view of Tedder et al., "Isolation and generation of human dendritic cells," Current Protocols in Immunology (1997) (“Tedder”).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground addressed dependent claims 2 and 3, which require selecting mature DCs with increased CD83 expression. Decker’s method produced a non-homogenous population where only 80-95% of mature DCs expressed the maturation marker CD83. Tedder taught that isolating a homogenous population of CD83+ mature DCs is beneficial for developing effective anti-tumor vaccines. Petitioner argued that the claimed increase in CD83 expression (10-40% higher) in double-loaded cells is an inherent result of Decker’s method, as admitted by the Patent Owner in Example 2 of the ’806 patent, which is based on Decker's work.
  • Motivation to Combine: A person of ordinary skill in the art (POSA) would have been motivated to apply the selection techniques taught by Tedder to Decker’s DC population to enrich for the most potent CD83+ cells, thereby improving the vaccine's efficacy as suggested by Tedder.
  • Expectation of Success: A POSA would have a high expectation of success, as Tedder provided well-established protocols for isolating specific DC populations using known markers like CD83.

Ground 3: Obviousness of Claims 4-9 under 35 U.S.C. §103

• Prior Art Relied Upon: Decker, in view of Eggert et al., "Generation of human and murine dendritic cells," in Cell Biology: A Laboratory Handbook (2006) (“Eggert”).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground targeted claims 4-9, which relate to the negative and positive selection of immature DCs using agents that bind to non-target or target cells (e.g., based on HLA alleles). While Decker provided the core double-loading method, Eggert, a standard laboratory textbook, provided detailed, routine protocols for preparing and isolating DC subpopulations using both positive and negative selection with antibody-conjugated magnetic beads.
  • Motivation to Combine: A POSA implementing the vaccine preparation method of Decker would have been motivated to consult a standard reference like Eggert to find established protocols for purifying the starting immature DC population. The methods are complementary, with Eggert providing the specific purification steps to improve the starting material for Decker's functional method.
  • Expectation of Success: Combining the references would have been straightforward, as Eggert provided well-understood, routine techniques for cell purification that were directly applicable to the cells used in Decker.

• Additional Grounds: Petitioner asserted additional obviousness challenges, including combinations of Decker with: (1) Cezayirli (Patent 6,645,487) to teach using total nucleic acid and simultaneous loading; (2) Reyes (Patent 6,107,023) to teach enriching for tumor-specific mRNA via subtraction; (3) Wang (Patent 6,960,449) to teach selecting tumor source cells; (4) Renner (Patent 7,264,810) to teach enriching lysate with protein arrays; (5) Lotem (a 2006 journal article) to teach using expression constructs for specific antigens like gp100; and (6) a combination of Decker, Wang, and Lotem to teach screening patients for a tumor antigen and then preparing a corresponding vaccine.

4. Key Claim Construction Positions

• Petitioner argued that several key terms should be given constructions based on express definitions in the ’806 patent’s specification.
• Antigen: "a molecule capable of being bound by an antibody or T-cell receptor."
• Epitope: "those parts of an antigen that are recognized by antibodies, or in the context of an MHC, by T-cell receptors."
• Negative/Positive Selection: The terms "negative selection" and "positive selection" were defined according to their express definitions in the specification as, respectively, the "elimination, removal, or reduction" of a non-target component and the "retention, enrichment, or increase" of a target component.

5. Key Technical Contentions (Beyond Claim Construction)

• A central technical contention was the inherency of the "overlapping but not identical epitope" limitation in the Decker reference. Petitioner argued, with support from an expert declaration, that the process described by Decker—using both mRNA and protein lysate derived from the same population of tumor cells—necessarily results in the creation of a diverse pool of related epitopes. This pool would inherently include epitopes that satisfy the claim limitation (e.g., distinct MHC-I and MHC-II binding peptides from the same protein), even though Decker does not explicitly state this molecular-level detail.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that the Board should not exercise its discretion to deny institution under §325(d), even though the Decker reference was before the Examiner during prosecution.
• The core reasons given were that Decker was never substantively examined or used as the basis for a rejection. Petitioner contended the Examiner erred by relying on the Patent Owner's mischaracterization of Decker and that the current petition provided new evidence (an expert declaration) and arguments regarding inherency that the Examiner never considered.

7. Relief Requested

• Petitioner requested that the Board institute an inter partes review and cancel claims 1-30 of the ’806 patent as unpatentable.