Obviousness

Obviousness Analysis under 35 U.S.C. § 103 for US Patent 12122824

This analysis considers US Patent 121222824 (hereinafter 'the '824 patent') under 35 U.S.C. § 103 for obviousness, drawing upon the prior art explicitly referenced or strongly implied within the provided patent text, particularly in the "Definitions" and "Background" sections, and by literal interpretation of identifiers mentioned in the "Prior art keywords" section. The priority date for the '824 patent is 2017-01-30.

Representative Claim for Analysis

For this analysis, we will focus on Claim 1 of the '824 patent, as it represents a core aspect of the claimed invention and establishes the parameters for treatment:

"1. A method for treating active ankylosing spondylitis in a subject, the method comprising:
administering to the subject a composition comprising a safe and effective amount of an isolated mammalian anti-TNF antibody having a heavy chain (HC) comprising SEQ ID NO:36 and a light chain (LC) comprising SEQ ID NO:37,
wherein said composition is administered via IV infusion, and wherein said administration induces a clinical response selected from the group consisting of:
(a) wherein ≧55% of subjects receiving the treatment achieve an ASAS20 at week 14 of treatment;
(b) wherein ≧55% of subjects receiving the treatment achieve an ASAS20 at week 24 of treatment;
(c) wherein ≧45% of subjects receiving the treatment achieve an ASAS40 at week 14 of treatment;
(d) wherein ≧45% of subjects receiving the treatment achieve an ASAS40 at week 24 of treatment;
(e) wherein ≧60% of subjects receiving the treatment achieve a partial remission at week 14 of treatment; and
(f) wherein ≧60% of subjects receiving the treatment achieve a partial remission at week 24 of treatment; and
(g) any combination thereof."

This claim defines a method of treating active ankylosing spondylitis (AS) using a specific anti-TNF antibody (defined by SEQ ID NOs: 36 and 37), administered via intravenous (IV) infusion, to achieve particular clinical response rates (ASAS20, ASAS40, or partial remission) at weeks 14 or 24.

Identification of Prior Art References

Based on the provided patent text, the following aspects of the prior art are directly mentioned or clearly implied:

1. The Anti-TNF Antibody Golimumab (Simponi): The '824 patent's description of FIG. 18 explicitly states, "FIG. 18 shows diagram of the study design for trial of Simponi (golimumab), administered intravenously, in subjects with active Psoriatic Arthritis (PsA)". This demonstrates that the specific anti-TNF antibody, golimumab (which corresponds to the heavy chain of SEQ ID NO:36 and light chain of SEQ ID NO:37), was known in the art prior to the priority date. Furthermore, its intravenous administration for treating a TNF-mediated inflammatory condition, Psoriatic Arthritis (PsA), was also known.

2. General Knowledge of Anti-TNF Therapy for Spondyloarthropathies and Standard Efficacy Measures: The '824 patent acknowledges that "TNF alpha has been implicated in inflammatory diseases, autoimmune diseases... and is a useful target for specific biological therapy in diseases, such as rheumatoid arthritis and Crohn's disease." It further mentions "beneficialal effects in open-label trials with a chimeric monoclonal antibody to TNF alpha (cA2)" and "Beneficial results in a randomized, double-blind, placebo-controlled trial with cA2" for rheumatoid arthritis. "cA2" is widely understood to refer to infliximab, another anti-TNF antibody. Prior to 2017, infliximab and other anti-TNF agents were approved and commonly used for treating active AS. The clinical response criteria (ASAS20, ASAS40, and partial remission) are well-established and standard endpoints for assessing the efficacy of treatments in AS clinical trials.

Obviousness Argument

A person having ordinary skill in the art (PHOSITA) in the field of immunology and rheumatology, at the time of the invention (prior to January 30, 2017), would have found Claim 1 obvious by combining the knowledge of the anti-TNF antibody golimumab with the established practices and understanding of anti-TNF therapy for Ankylosing Spondylitis.

Combination of References and Motivation:

1. Knowledge of Golimumab and its use in related conditions: A PHOSITA would have been aware of golimumab (SEQ ID NOs: 36 and 37) as a known and effective anti-TNF antibody, explicitly referenced in the '824 patent as being administered intravenously for active PsA. PsA is a spondyloarthropathy that shares considerable clinical and pathological overlap with AS, both being TNF-alpha driven inflammatory conditions.

2. Established Treatment of AS with Anti-TNF Agents: The art clearly recognized AS as a TNF-mediated disease amenable to anti-TNF therapy. Other anti-TNF antibodies, such as infliximab (cA2 mentioned in the '824 patent), were already established treatments for AS via IV infusion. A PHOSITA would understand that an anti-TNF antibody effective in one spondyloarthropathy (like PsA) would likely be effective in another (like AS) due to the shared underlying disease mechanisms.

Motivation to Combine:
The motivation for a PHOSITA to combine these pieces of prior art would be multifaceted:

• Predictability of Mechanism: Given that AS is a known TNF-mediated disease and golimumab is a known anti-TNF antibody effective in related conditions like PsA, a PHOSITA would have a strong expectation of success in treating AS with golimumab. The decision to apply a known, effective anti-TNF biologic to a related, known TNF-mediated inflammatory disease falls within the routine expectation of a skilled artisan.
• Routine Optimization of Administration: Intravenous (IV) infusion is a standard route of administration for biologic drugs, including anti-TNF therapies. While the specific IV dosing regimen (e.g., 2 mg/kg, Weeks 0, 4, then q8w) for golimumab in AS may not have been explicitly documented in a single prior art reference, optimizing dosage and frequency for a known drug in a known or closely related indication is considered routine clinical development. A PHOSITA would undertake such optimization based on pharmacokinetic and pharmacodynamic principles and existing clinical data from other anti-TNF agents.
• Standard Efficacy Endpoints: The claimed efficacy measures (ASAS20, ASAS40, partial remission at weeks 14 or 24) are well-established and standard clinical endpoints for evaluating AS treatments. Achieving these levels of clinical response with a known effective anti-TNF agent in AS would be an expected outcome, not an unexpected result demonstrating non-obviousness. These percentages represent quantitative improvements that would be routinely sought and expected from an effective anti-TNF therapy.

Therefore, the combination of the known anti-TNF antibody golimumab (SEQ ID NOs: 36 and 37) and its intravenous administration for related inflammatory conditions (as implied by the PsA study in FIG. 18), with the established medical knowledge regarding the treatment of active AS with anti-TNF agents and the use of standard clinical efficacy endpoints, would have rendered Claim 1 obvious to a PHOSITA prior to the '824 patent's priority date. A PHOSITA would have been motivated to try golimumab for AS, would have expected it to work, and would have used standard clinical trials to optimize dosing and confirm efficacy, leading to the results claimed.