Praxair Distribution Inc v. Mallinckrodt Hospital Products IP Ltd

1. Case Identification

• Case #: IPR2016-00780
• Patent #: 8,795,741
• Filed: March 23, 2016
• Petitioner(s): Praxair Distribution, Inc. and NOxBOX Limited
• Patent Owner(s): Mallinckrodt Hospital Products IP LTD., and INO Therapeutics, Inc. d/b/a IKARIA, INC.
• Challenged Claims: 1-44

2. Patent Overview

• Title: Method of Reducing Risk of Pulmonary Edema in Neonatal Patients with Hypoxic Respiratory Failure
• Brief Description: The ’741 patent discloses methods for reducing the risk of pulmonary edema when treating neonatal patients with inhaled nitric oxide (iNO). The methods involve identifying patients with pre-existing left ventricular dysfunction (LVD) and excluding them from iNO treatment.

3. Grounds for Unpatentability

Ground 1: Obviousness over Greenough and Jaypee - Claims 1-2, 4, 6-14, 17-23, 31-32, 34-35, 37-40, and 42-44 are obvious over Greenough in view of Jaypee.

• Prior Art Relied Upon: Greenough (a 2003 textbook on neonatal respiratory disorders) and Jaypee (a 2006 textbook on pediatric and neonatal mechanical ventilation).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the combination of Greenough and Jaypee taught all limitations of the independent claims. Both references described treating term or near-term neonates suffering from hypoxic respiratory failure with 20 ppm iNO. Both also disclosed using standard diagnostic procedures, such as echocardiography, to assess cardiac function. Crucially, Petitioner asserted that Greenough explicitly taught that LVD is an “absolute contraindication” for iNO treatment due to the increased risk of pulmonary edema. Jaypee allegedly confirmed this risk, teaching that iNO treatment in patients with LVD can elevate pulmonary capillary wedge pressure (PCWP), leading to pulmonary edema. Therefore, the combination rendered it obvious to identify a patient population, use known diagnostic methods to determine which patients have LVD, administer iNO to those without LVD, and exclude those with LVD from treatment to avoid a known adverse event.
  • Motivation to Combine: A person of ordinary skill in the art (POSA) would combine the teachings of these authoritative textbooks to develop a safe and effective iNO treatment protocol. The known problem of adverse events associated with iNO, identified in the product's own labeling (INOmax), would motivate a POSA to consult comprehensive literature like Greenough and Jaypee, which specifically address contraindications and patient safety. The fact that Jaypee cites works by the author of Greenough further supported the motivation to consider their teachings in combination.
  • Expectation of Success: A POSA would have a reasonable expectation of success in combining the references. The combination involved applying known diagnostic techniques to stratify patients and avoid a well-documented risk, which is a predictable application of established medical principles.

Ground 2: Obviousness over Greenough, Jaypee, and Widlitz - Claims 3, 5, 15, 16, 28, 36, and 41 are obvious over Greenough and Jaypee in view of Widlitz.

• Prior Art Relied Upon: Greenough, Jaypee, and Widlitz (a 2003 review article on pulmonary hypertension in children).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon the combination in Ground 1 to address dependent claims that specifically recite LVD being attributable to congenital heart disease. Petitioner argued that while Greenough and Jaypee established the obviousness of excluding patients with LVD generally, Widlitz provided the explicit link to congenital heart disease. Widlitz taught that congenital heart disease is the most common cause of pulmonary venous hypertension and severe left ventricular failure in children.
  • Motivation to Combine: A POSA, having already been motivated to combine Greenough and Jaypee to understand the risks of iNO treatment in patients with LVD, would be further motivated to consult a reference like Widlitz to understand the common underlying causes of LVD. Identifying the etiology of the contraindication, such as congenital heart disease, was a logical next step in refining patient selection criteria to ensure treatment safety and efficacy.
  • Expectation of Success: Incorporating Widlitz's teaching on the cause of LVD into the treatment protocol established by Greenough and Jaypee was a predictable step. It represented a straightforward application of knowledge to better characterize at-risk patients, with a high expectation of successfully identifying them.

4. Key Claim Construction Positions

• Petitioner accepted, for the purpose of judicial efficiency, claim constructions for "child" and "term or near-term neonate" that the Board had previously adopted in a related, denied inter partes review (IPR) proceeding (IPR2015-00526).
• "Child" was construed as "humans from birth until 18 years of age."
• "Term or near-term neonate" was construed as "an infant aged 1 month or younger born between around 37 and 40 weeks gestation or greater than around 34 weeks gestation."

5. Arguments Regarding Discretionary Denial

• Petitioner argued that the Board should not exercise its discretion under 35 U.S.C. §325(d) to deny institution, despite having previously denied a petition challenging the same patent.
• The core argument was that this petition was based on entirely new prior art (Greenough and Jaypee) and a new invalidity theory not previously considered by the Board or the Examiner.
• Petitioner asserted these references were discovered only after diligent searches conducted for a district court litigation that commenced after the first IPR was filed. The new art allegedly addressed the specific deficiencies the Board identified in its prior denial by explicitly teaching that LVD was an "absolute contraindication" for iNO therapy in children, a direct teaching the previous art combination lacked.

6. Relief Requested

• Petitioner requested institution of an IPR and cancellation of claims 1-44 of Patent 8,795,741 as unpatentable.