CORvus Pharmaceuticals Inc v. United States

1. Case Identification

• Case #: PGR2016-00042
• Patent #: 9,415,105
• Filed: September 12, 2016
• Petitioner(s): Corvus Pharmaceuticals, Inc.
• Patent Owner(s): The United States of America, as represented by The Secretary, Department of Health and Human Services
• Challenged Claims: 1-12 and 14-25

2. Patent Overview

• Title: Methods for Using Extracellular Adenosine Inhibitors and Adenosine Receptor Inhibitors to Enhance Immune Response and Inflammation
• Brief Description: The ’105 patent discloses methods for reducing tumor volume or size in a subject. The methods involve administering a combination of an anti-neoplastic agent with either an adenosine A2a receptor (A2aR) antagonist or an agent that inhibits the accumulation of extracellular adenosine.

3. Grounds for Unpatentability

Ground 1: Lack of Written Description and Enablement - Claims 1-12 and 14-25 are unpatentable under 35 U.S.C. §112

• Core Argument for this Ground: Petitioner argued that the challenged claims are not entitled to their pre-AIA priority date (December 2, 2011) and are therefore eligible for Post-Grant Review (PGR). This argument was based on the assertion that the priority applications, like the ’105 patent itself, failed to meet the written description and enablement requirements of §112 for the full scope of the claims.
  • Written Description: The claims allegedly used broad functional language to define key elements, such as "an adenosine A2a receptor antagonist" and "an anti-neoplastic agent," encompassing vast and structurally diverse genera of compounds. Petitioner contended the specification failed to describe a representative number of species or common structural features to demonstrate possession of these genera. For example, it was argued that while the claims covered thousands of potential small-molecule A2aR antagonists across over 90 known chemotype families (as of 2011), the specification disclosed species from only 35 of those families, leaving 80% of known families structurally distant and undescribed.
  • Enablement: Petitioner asserted that a person of ordinary skill in the art (POSA) would require undue experimentation to practice the full scope of the claims. The technology was described as nascent, requiring heightened enablement. The specification provided only two working examples using one type of anti-neoplastic agent (adoptive T-cell therapy with CTLs) in mice, which was not representative of the myriad other claimed anti-neoplastic agents (e.g., hormones, antibiotics, enzymes) or subjects (any vertebrate). The provided in vitro screening methods were alleged to be too general to identify suitable therapeutic candidates for in vivo use without a significant, multi-step research program.

Ground 2: Anticipation over Tsuchiya - Claims 1, 4, 5, 7, 16, 17, 19, and 21 are anticipated by Tsuchiya

• Prior Art Relied Upon: Tsuchiya et al., "Caffeine-Potentiated Radiochemotherapy and Function-Saving Surgery for High-Grade Soft Tissue Sarcoma," Anticancer Research (2000) ("Tsuchiya").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued Tsuchiya disclosed every element of the challenged claims. Tsuchiya described a clinical study treating human patients with high-grade soft tissue sarcomas (a cancer) by administering a combination therapy. This therapy included caffeine, which a POSA would have recognized as an A2aR antagonist, and anti-neoplastic agents such as cisplatin and doxorubicin. The study explicitly measured and reported "marked tumor shrinkage," including "complete disappearance of a tumor" in some patients, directly teaching a method for reducing tumor volume and/or size in a subject.
  • Key Aspects: Tsuchiya’s disclosure of a practiced clinical method in humans with specific agents and dosages was argued to be a complete and enabling disclosure that anticipated the functionally-defined claims of the ’105 patent.

Ground 3: Obviousness over Tsuchiya in view of Powell - Claims 1, 4-10, 16, 17, and 19-25 are obvious over Tsuchiya in view of Powell

• Prior Art Relied Upon: Tsuchiya (2000 journal article) and Powell (WO 2009/033161).
• Core Argument for this Ground:
  • Prior Art Mapping: Tsuchiya disclosed a method of reducing tumor size using chemotherapy and caffeine, a non-selective A2aR antagonist. Powell described using potent and selective A2aR antagonists, such as ZM 241385, in combination with anti-cancer agents to reduce tumor size and metastases. Petitioner argued that combining these references rendered the challenged claims obvious.
  • Motivation to Combine: A POSA would combine the teachings to improve upon Tsuchiya's method. The motivation would be to replace Tsuchiya's non-selective and less potent antagonist (caffeine) with Powell's more potent and selective A2aR antagonist (ZM 241385). This substitution would be expected to increase therapeutic efficacy while reducing off-target side effects, potentially allowing for the elimination of the harsh radiation therapy component of Tsuchiya's protocol.
  • Expectation of Success: A POSA would have had a reasonable expectation of success because both references taught the same general principle: combining an A2aR antagonist with an anti-neoplastic agent to treat cancer. Tsuchiya demonstrated success in humans, and Powell demonstrated that a more selective antagonist was effective. Therefore, substituting a better, more selective component into a known, effective protocol was a predictable path to an improved therapy.
• Additional Grounds: Petitioner asserted additional challenges including that claims 1-12, 14-16, 18, 19, and 21-23 are anticipated by Sitkovsky 2010 (Application # 2010/0178299), and that claims 1-12 and 14-25 are obvious over Sitkovsky 2010.

4. Key Claim Construction Positions

• "an adenosine A2a receptor antagonist": Petitioner argued this term should be construed broadly according to its functional definition in the specification as any agent that nullifies the action of adenosine on the A2aR. This construction was central to the argument that the claims covered a vast, structurally diverse genus of compounds, including small molecules, peptides, and nucleic acids, many of which were not described or exemplified in the patent.
• "an anti-neoplastic agent": Petitioner argued this term, defined by its function of preventing, curing, or alleviating a tumor, was exceptionally broad. The petition noted that claimed examples included disparate categories such as alkylating drugs, hormones, enzymes, and antibodies. This broad functional definition was key to Petitioner's arguments regarding lack of written description and enablement for the full scope of the claimed methods.

5. Relief Requested

• Petitioner requests institution of post-grant review and cancellation of claims 1-12 and 14-25 as unpatentable.