Obviousness

Obviousness Analysis of US Patent 9,522,163 Under 35 U.S.C. § 103

This analysis assesses the obviousness of US Patent 9,522,163 (hereinafter '163 patent) by considering combinations of the identified prior art references through the lens of a Person Having Ordinary Skill in the Art (PHOSITA) at the time of the '163 patent's priority date (May 17, 2002). A PHOSITA in this field would likely possess expertise in medical research, liver diseases, inflammatory processes, and gaseous signaling molecules, particularly nitric oxide and carbon monoxide.

Identified Prior Art References:

1. US 6,297,262 B1 (Choi et al.): Issued October 2, 2001, this patent describes methods for treating or preventing inflammation, tissue injury, or organ dysfunction by administering carbon monoxide (CO), with a mechanism involving heme oxygenase-1 (HO-1) induction.
2. US 6,613,793 B2 (Snyder et al.): Issued September 2, 2003 (with a filing date of February 2, 2001, making its contents prior art for obviousness), this patent focuses on methods and compositions for increasing HO-1 expression for protective effects against various cellular injuries.
3. US 7,208,485 B2 (Otterbein et al.): Issued April 24, 2007 (with a priority date tracing back to March 28, 2000, through its parent US6297262B1, making its contents prior art for obviousness), this patent details methods for treating or preventing inflammatory conditions or ischemia-reperfusion injury by administering CO and explicitly mentions modulating an inflammatory response.

Obviousness Combinations and Rationale:

Combination 1: US 6,297,262 B1 (Choi et al.) and General Knowledge of Hepatitis

• US 6,297,262 B1 teaches the therapeutic application of carbon monoxide to treat "diseases involving cellular inflammation," "tissue injury," or "organ dysfunction."
• The '163 patent itself defines "hepatitis" as "a disease characterized by inflammation of the liver," which involves "diffuse or patchy necrosis affecting acini." This description explicitly places hepatitis within the scope of both "diseases involving cellular inflammation" and "tissue injury" to an "organ dysfunction" (the liver).
• Motivation for a PHOSITA: A PHOSITA, at the time of the invention, would have been well aware that hepatitis is fundamentally an inflammatory condition affecting the liver. Given the broad teaching in US 6,297,262 B1 that CO has anti-inflammatory properties and can treat inflammatory diseases and organ injury, it would have been highly obvious for a PHOSITA to try or apply the CO treatment described in US 6,297,262 B1 to the specific inflammatory organ condition of hepatitis. The common inventors between US 6,297,262 B1 and the '163 patent (Choi and Otterbein) further suggest that this therapeutic connection would have been readily apparent and a natural extension of their existing work.
• Claims Rendered Obvious: This combination would render obvious broad method claims like Claim 1 of the '163 patent, which describes a method of treating, preventing, or reducing the risk of hepatitis by administering a pharmaceutical composition comprising an amount of carbon monoxide effective to treat hepatitis. Similarly, dependent claims relating to various known methods of administering gases or liquids (e.g., inhalation, insufflation, infusion, injection, ingestion) would also be obvious as these are standard medical practices, as noted in the '163 patent's detailed description: "The pharmaceutical composition can be administered to the patient by any method known in the art for administering gases and/or liquids to patients".

Combination 2: US 6,297,262 B1 (Choi et al.) and US 6,613,793 B2 (Snyder et al.)

• US 6,297,262 B1 discusses that the mechanism of CO's anti-inflammatory effects involves inducing HO-1 expression.
• US 6,613,793 B2 provides methods and compositions for specifically increasing HO-1 expression to protect against cellular injury.
• Motivation for a PHOSITA: Recognizing that CO's therapeutic effect is mediated, at least in part, by HO-1 induction (as taught by US 6,297,262 B1 and confirmed in the '163 patent's own experimental data, e.g., FIG. 1, FIG. 15), a PHOSITA would be motivated to enhance or augment this beneficial pathway. Therefore, combining CO administration with other known methods or compositions for inducing HO-1 (as taught by US 6,613,793 B2) or administering the downstream products of HO-1 (such as bilirubin, biliverdin, or ferritin, which are mentioned as co-treatments in the '163 patent) to treat an inflammatory condition like hepatitis would be a logical and obvious synergistic approach. The '163 patent itself states, "induction or expression of hemeoxygenase-1 (HO-1) in conjunction with administration of CO can be induced in a patient suffering from or at risk for hepatitis."
• Claims Rendered Obvious: This combination would make obvious claims of the '163 patent that include administering CO alongside treatments that induce HO-1, express recombinant HO-1 or ferritin, or administer HO-1, bilirubin, biliverdin, ferritin, apoferritin, iron, desferoxamine, or iron dextran.

Combination 3: US 7,208,485 B2 (Otterbein et al.) and General Knowledge of Hepatitis

• US 7,208,485 B2 explicitly describes methods for treating or preventing "inflammatory conditions" and "ischemia-reperfusion injury" by administering carbon monoxide. Given its common inventors and a priority date preceding the '163 patent, it represents a highly relevant disclosure.
• As established, hepatitis is an inflammatory condition of the liver.
• Motivation for a PHOSITA: Similar to Combination 1, the explicit teaching of CO for "inflammatory conditions" in US 7,208,485 B2 would directly motivate a PHOSITA to apply this known anti-inflammatory therapy to hepatitis. The shared inventorship further underscores the apparent nature of this application.
• Claims Rendered Obvious: This combination would render obvious the broad method claims of the '163 patent, including Claim 1, relating to using CO to treat hepatitis.

Obviousness Considerations for Specific Claim Types:

• Claims related to specific causes of hepatitis (e.g., viral, alcoholic, drug-induced, autoimmune, post-surgical, Claim 15, Claim 17): Once the general principle of using CO for hepatitis (an inflammatory liver condition) is established as obvious from the prior art (e.g., US 6,297,262 B1), extending this treatment to different etiological subtypes of hepatitis would be an obvious variation. A PHOSITA understands that inflammation can arise from various causes (viruses, alcohol, drugs, autoimmune responses, surgical trauma). Applying a general anti-inflammatory therapy like CO, known to treat "cellular inflammation" or "tissue injury," to these different inflammatory scenarios would be an expected and obvious clinical application, rather than a novel invention. For example, administering CO in conjunction with a hepatotoxic drug (Claim 17) to prevent or treat associated hepatitis would be an obvious prophylactic or therapeutic extension of using CO for drug-induced liver inflammation, especially given the prior art's broad teaching on tissue injury and organ dysfunction.
• Claims related to abdominal surgery/liver transplantation (Claim 13): US 6,297,262 B1 and US 7,208,485 B2 explicitly mention treating or preventing "organ transplant rejection" and "ischemia-reperfusion injury" with CO. Liver transplantation inherently involves both ischemia-reperfusion injury and a significant risk of post-operative inflammation and hepatitis. A PHOSITA would have been highly motivated to apply CO treatment, already taught for these related conditions, to liver transplantation patients to mitigate these known risks.
• Claims related to a vessel with a label (Claim 19, Claim 20): If the underlying method of treating hepatitis with CO (or co-administering with hepatotoxic drugs) is deemed obvious, then the creation of a commercial product (a vessel containing medical-grade compressed CO gas) with a label instructing or indicating that obvious use would also be obvious. The label merely communicates a known or obvious therapeutic application.

Conclusion on Obviousness:

Based on the analysis, a significant portion of the claims of US 9,522,163, particularly those related to the core inventive concept of using carbon monoxide to treat hepatitis, appear to be obvious under 35 U.S.C. § 103. The clear teaching in US 6,297,262 B1 and US 7,208,485 B2 regarding CO's role in treating inflammatory conditions and organ injury provides strong motivation for a PHOSITA to apply this therapy to hepatitis, which is characterized by liver inflammation. Furthermore, the combination of US 6,297,262 B1 and US 6,613,793 B2 would render obvious the co-administration of CO with HO-1 modulators or its products, given the known mechanistic link between CO and HO-1. The specific causes of hepatitis, methods of administration, and labeling of CO vessels represent predictable applications or minor variations of the primary obvious therapeutic use.