Details for Patent: 9,604,028

Which drugs does patent 9,604,028 protect, and when does it expire?

Patent 9,604,028 protects GENOSYL and is included in one NDA.

This patent has eight patent family members in five countries.

Summary for Patent: 9,604,028

Title:	Systems and devices for generating nitric oxide
Abstract:	Various systems and devices for generating nitric oxide are disclosed herein. According to one embodiment, the device includes a body having an inlet, an outlet, and a porous solid matrix positioned with the body. The porous solid matrix is coated with an aqueous solution of an antioxidant, wherein the inlet is configured to receive a gas flow and fluidly communicate the gas flow to the outlet through the solid matrix to convert nitrogen dioxide in the gas flow into nitric oxide. The porous solid matrix allows the device to be used in any orientation. Additionally, the porous solid matrix provides a rigid structure suitable to withstand vibrations and abuse without compromising device functionality.
Inventor(s):	David H. Fine, Bryan Johnson, Gregory Vasquez
Assignee:	Vero Biotech Inc
Application Number:	US14/612,266
Patent Claim Types: see list of patent claims	Use; Delivery; Device;

United States Patent 9,604,028: Claim Scope, Patent Strength, Exclusivity and Competitive Landscape

U.S. Patent No. 9,604,028 protects a nitric-oxide delivery method that converts nitrogen dioxide into nitric oxide through a porous antioxidant-containing matrix positioned inside a gas-flow device. The patent is strongest against systems using the claimed diverter, variable-width bypass space, porous matrix, and patient-interface configuration together. It does not broadly cover every nitric oxide generator, nitric oxide cylinder, delivery circuit, humidifier, or patient treatment using inhaled nitric oxide.

The patent issued on March 28, 2017, under the title "Nitric Oxide Delivery System." The disclosed architecture is associated with GeNO LLC and its nitric oxide delivery technology. The claims are method claims, even though claim 1 uses the phrase "providing a system." [1]

What technology does U.S. Patent 9,604,028 protect?

The patent covers a chemical conversion and delivery architecture:

1. A gas source containing nitrogen dioxide, dinitrogen tetroxide, or nitric oxide.
2. A first receptacle with an inlet, outlet, and diverter.
3. A porous solid matrix containing an antioxidant.
4. A variable-width space between the matrix and receptacle wall.
5. Gas flow directed through the space and then through the porous matrix.
6. Conversion of nitrogen dioxide into nitric oxide.
7. Delivery through a patient interface.

The core commercial concept is the controlled conversion of nitrogen dioxide to nitric oxide immediately before patient administration. The porous antioxidant matrix appears intended to reduce nitrogen dioxide concentration while preserving or generating nitric oxide in a usable delivery stream.

The claim does not require a particular antioxidant, porous-material chemistry, receptacle shape, gas-flow rate, or patient-interface type. Those omissions broaden the claim, but only within the structural architecture expressly recited.

What are the independent claim limitations?

Claim 1 is the principal independent claim. Each limitation must be satisfied for literal infringement.

Limitation	Scope and legal significance
Method of delivering nitric oxide	Requires an act of delivery to a patient, not merely manufacture or sale of a component
Gas source	Covers nitrogen dioxide, dinitrogen tetroxide, or nitric oxide
First device	Requires a receptacle, inlet, outlet, and diverter
Porous solid matrix	The matrix must be porous and contain an antioxidant
Variable-width space	The distance between the matrix and receptacle must vary along the receptacle length
Diverter	Must direct incoming gas to the space surrounding the matrix
Gas path	Gas must move from the space through the porous matrix to the outlet
Conversion	The system must convert nitrogen dioxide into nitric oxide
Patient interface	The outlet must be coupled to a patient interface
Delivery	Nitric oxide must be delivered to the patient

The combination of the variable annular space and diverter is a material narrowing feature. A conventional inline filter with a uniform clearance, without a diverter directing gas around the matrix, is less likely to fall within the literal scope of claim 1.

How do dependent claims 2 through 7 expand the patent scope?

Claims 2 through 7 add humidification arrangements and temperature limitations.

Claim	Added limitation	Commercial relevance
2	Humidifier between gas source and first device	Covers upstream humidification
3	Humidifier is integral with first device	Targets integrated cartridges or delivery modules
4	Upstream humidifier temperature of 18°C to 23°C	Narrows the claim to near-room-temperature operation
5	Second humidifier and second conversion device after the first device	Covers staged conversion and humidification
6	Humidifier before patient interface	Covers downstream humidification
7	Downstream humidifier temperature of 32°C to 37°C	Targets near-body-temperature gas conditioning

Claim 5 is materially narrower than claim 1 because it requires two conversion devices and a specific sequence:

gas source → first device → second humidifier → second device → patient interface.

A competing system with only one converter cannot infringe claim 5. A system with two converters but a different humidifier position may avoid literal infringement of this claim while remaining exposed under claim 1.

Claims 4 and 7 are temperature-limited. A system operating outside those ranges would not literally meet the respective claim, although measurement conditions and claim construction could affect the analysis.

What diseases and concentrations are covered by claims 8 and 9?

Claim 8 adds a broad disease and clinical-condition limitation. It lists pulmonary hypertension, acute respiratory distress syndrome, pulmonary edema, hypoxia, asthma, sepsis, neonatal conditions, pulmonary embolism, acidosis, inhalation injury, and related conditions.

Because the claim uses "one or more," a patient satisfying any listed condition may meet the limitation. The claim does not require a particular disease severity, treatment duration, dose schedule, or clinical endpoint.

Claim 9 covers nitric oxide concentrations greater than any of the listed thresholds, including:

• Greater than 10 ppm
• Greater than 40 ppm
• Greater than 80 ppm
• Greater than 100 ppm
• Greater than 150 ppm
• Greater than 200 ppm
• Greater than 250 ppm
• Greater than 300 ppm
• Greater than 350 ppm
• Greater than 400 ppm
• Greater than 450 ppm
• Greater than 500 ppm
• Greater than 550 ppm
• Greater than 600 ppm
• Greater than 650 ppm
• Greater than 700 ppm
• Greater than 750 ppm
• Greater than 800 ppm
• Greater than 850 ppm
• Greater than 900 ppm
• Greater than 950 ppm
• Greater than 1,000 ppm

The drafting structure creates alternative concentration thresholds rather than a single continuous range. A device delivering 20 ppm could satisfy the "greater than 10 ppm" alternative, while a device delivering 1,200 ppm could satisfy every listed alternative.

What is the likely claim construction of the variable-width space?

The "width" is expressly defined as the distance from the outer surface of the porous solid matrix to the receptacle. The width must vary along the length of the receptacle.

This limitation likely requires a nonuniform clearance. Examples could include:

• A tapered matrix inside a cylindrical receptacle.
• A cylindrical matrix inside a tapered receptacle.
• A stepped or contoured matrix.
• An eccentric matrix producing different radial clearances along the flow path.

A uniform annular gap would present a substantial noninfringement position. The patent does not appear, based on the supplied claims, to require a particular rate of change, minimum width, maximum width, or geometric profile.

The phrase "variable along a length" may cover gradual or discrete changes. The prosecution record would be important if the applicant distinguished prior art based on a specific taper or flow profile.

How strong is the patent estate for nitric oxide delivery?

The patent has meaningful but concentrated strength.

Strengths

• The claim combines chemical conversion, fluid mechanics, device geometry, and patient delivery.
• The antioxidant matrix is defined functionally and structurally, without limiting the claim to one named antioxidant.
• The variable-width space can capture nonuniform flow-control designs.
• Claims 2 through 7 create fallback positions for humidified delivery systems.
• Claim 8 gives broad clinical-use coverage across adult, pediatric, neonatal, acute, and chronic conditions.

Weaknesses

• Claim 1 requires conversion of nitrogen dioxide into nitric oxide. A system supplied with pharmaceutical-grade nitric oxide that performs no conversion may avoid the central limitation.
• The claim requires the specific receptacle, diverter, porous matrix, and variable-width space combination.
• The claims are method claims. Manufacturing or selling a converter alone may not directly infringe unless the required delivery method is performed or infringement theories such as inducement apply.
• Claim 1 refers to a gas source of nitric oxide even though the device is described as converting nitrogen dioxide into nitric oxide. A nitric-oxide-only system may raise a claim-construction issue over whether conversion is required for every listed gas-source alternative.
• Clinical-use claims are vulnerable if the accused product is not directed to the listed condition or concentration.

What patents protect competing nitric oxide delivery approaches?

The relevant patent landscape divides into four technology groups.

Technology group	Typical product architecture	Exposure to U.S. 9,604,028
Compressed nitric oxide	Cylinder containing nitric oxide in nitrogen, connected to a delivery system	Generally lower exposure if no nitrogen-dioxide conversion matrix is used
Nitric oxide generation	On-demand generation from nitrogen and oxygen, often using plasma or electrical energy	Usually outside the literal matrix-conversion limitations
Nitrogen-dioxide conversion	Chemical conversion using antioxidant or catalytic media	Highest potential overlap
Portable pulsed delivery	Small portable source with demand-triggered or pulsed administration	Depends on whether the system includes the claimed converter and geometry

Mallinckrodt's INOmax platform is primarily associated with compressed nitric oxide delivery and monitoring. Vero Biotech's GENOSYL Delivery System is an FDA-approved nitric oxide delivery platform. Bellerophon has developed INOpulse, a portable pulsed nitric oxide delivery system. These products should be analyzed by actual device configuration, not by product category alone. [2-4]

A system may compete commercially with the patented technology while avoiding infringement if it uses a different nitric oxide source or conversion mechanism.

What is the Orange Book status of U.S. Patent 9,604,028?

The patent is not an Orange Book listing merely because it relates to a drug-delivery system. Orange Book listing depends on FDA-approved drug-product identification and whether the patent claims the approved drug, a formulation, or an approved method of use under FDA listing rules.

The supplied claims are directed to a delivery method and device architecture. They do not claim a nitric oxide composition, a drug formulation, or a conventional product composition. On that basis, the patent would not be expected to function as a standard composition-patent barrier to an abbreviated new drug application.

An Orange Book analysis must distinguish:

• Patent listed against the approved nitric oxide drug product.
• Patent listed against an approved method of use.
• Device or delivery-system patent not listed for the drug product.
• Patent relevant to a combination product but not listed in the Orange Book.

FDA approved INOmax for inhaled nitric oxide therapy in 1999, and later approved additional nitric oxide delivery products, including GENOSYL. FDA labeling identifies approved uses, dosing, administration, warnings, and delivery-system requirements. [2, 3]

When does U.S. Patent 9,604,028 lose exclusivity?

The patent issued on March 28, 2017. Its enforceable term is generally determined from the earliest effective nonprovisional U.S. filing date, subject to patent-term adjustment, terminal disclaimers, patent-term extension, and other statutory adjustments. The issue date alone does not establish the expiration date. [1, 5]

For commercial diligence, the following dates must be separated:

Date category	Relevance
Earliest priority date	Establishes priority and prior-art position
Earliest effective nonprovisional filing date	Usually controls the 20-year patent term
Patent issue date	Marks grant, not ordinary expiration
Patent-term adjustment	Can extend the term for USPTO delay
Terminal disclaimer	Can shorten the term to match another patent
Patent-term extension	May extend certain FDA-regulated product patents
Maintenance-fee status	Determines whether the patent remains enforceable

The patent's remaining commercial value therefore depends on the recorded term calculation and current maintenance status, not on the 2017 grant date alone.

Are Paragraph IV challenges relevant to this patent?

A Paragraph IV certification is relevant when a generic applicant challenges a patent listed in the Orange Book for an approved drug product. This patent's claims are principally directed to a delivery method and device configuration, so a Paragraph IV challenge would depend on whether the patent was listed against the relevant approved product.

If listed, an ANDA applicant could assert that:

• The proposed product does not use the claimed nitrogen-dioxide conversion pathway.
• The proposed device lacks a variable-width space.
• The proposed device lacks the claimed diverter.
• The porous matrix does not contain an antioxidant.
• The proposed use does not satisfy the patient-condition or concentration limitations.
• The claims are invalid for anticipation, obviousness, indefiniteness, or lack of written description.

If the patent is not listed, the patent may still create infringement risk after commercial launch, but the statutory Paragraph IV pathway would not necessarily be the operative mechanism.

What generic launch scenarios exist?

Scenario 1: Compressed nitric oxide replacement

A generic or competing product uses nitric oxide supplied in a cylinder and a delivery circuit without a nitrogen-dioxide conversion cartridge. This is the clearest design-around path for avoiding claim 1.

Scenario 2: Alternative chemical converter

A competitor uses a catalyst, scrubber, membrane, or nonporous reactive bed. Risk depends on whether the device still has a porous antioxidant-containing matrix and the claimed variable-width geometry.

Scenario 3: Uniform-bed converter

A competitor uses a porous antioxidant matrix but places it in a receptacle with a uniform space. This directly targets the variable-width limitation.

Scenario 4: Generator-based system

A system generates nitric oxide electrically or through another chemical process without converting nitrogen dioxide through the claimed matrix. Literal claim exposure is likely lower.

Scenario 5: Same converter architecture with altered humidification

Changing humidifier location may avoid claims 2 through 7 but will not necessarily avoid claim 1. The core converter architecture remains the principal risk.

What manufacturing and intellectual-property barriers exist?

The central manufacturing barriers are likely:

• Producing a reproducible porous matrix with stable antioxidant loading.
• Controlling nitrogen-dioxide conversion across changing flow rates.
• Maintaining conversion performance under humidified conditions.
• Preventing excessive nitrogen dioxide or other toxic byproducts.
• Ensuring consistent clearance between the matrix and receptacle.
• Validating the flow path and concentration at the patient interface.
• Meeting FDA combination-product and medical-device quality requirements.

A design-around must be evaluated at both the patent and regulatory levels. Eliminating the porous antioxidant matrix may reduce patent risk but create new validation requirements for nitrogen-dioxide control, dose accuracy, and patient safety.

What litigation and licensing issues affect the patent?

The supplied claim text does not establish a litigation judgment, settlement, license, covenant not to sue, or assignment history. Patent ownership and enforcement rights must be determined from the current USPTO assignment and maintenance records, while litigation status must be checked against federal court and Patent Trial and Appeal Board records.

A license covering the patent may materially change market risk. A commercial agreement could grant field-of-use rights, geographic restrictions, sublicensing rights, or a covenant covering only specified products. Those terms cannot be inferred from the patent claims.

Key Takeaways

• U.S. Patent 9,604,028 is directed to a nitric oxide delivery method using nitrogen-dioxide conversion through an antioxidant-containing porous matrix.
• The most important limitations are the diverter, variable-width space, porous matrix, and patient-interface delivery.
• A compressed nitric oxide system without nitrogen-dioxide conversion is a relatively strong design-around candidate.
• Claims 2 through 7 protect specific humidification arrangements, including upstream, integrated, staged, and downstream configurations.
• Claim 8 broadly covers listed pulmonary and critical-care conditions.
• Claim 9 creates multiple alternative concentration thresholds, beginning at greater than 10 ppm.
• The patent is not equivalent to an Orange Book composition patent and may not block every generic nitric oxide product.
• Patent expiration must be calculated from the effective filing date and adjusted for terminal disclaimers, patent-term adjustment, and other statutory factors.
• Competitor exposure depends on actual device structure, not merely on whether the product is marketed for inhaled nitric oxide therapy.

FAQs About U.S. Patent 9,604,028

Does U.S. Patent 9,604,028 cover INOmax?

Not automatically. INOmax is primarily a compressed nitric oxide product and delivery platform. Infringement would depend on whether the accused system includes every required element of the asserted claim, including the nitrogen-dioxide conversion architecture, porous antioxidant matrix, diverter, and variable-width space.

Does the patent cover portable nitric oxide generators?

Only if the portable generator also uses the claimed conversion and delivery structure. Portability, battery operation, and pulsed delivery alone do not satisfy the patent's limitations.

Can a competitor avoid the patent by changing the antioxidant?

Possibly. The claims do not identify one specific antioxidant, so substituting another antioxidant may not avoid infringement. A stronger design-around would alter the claimed matrix, flow path, diverter, or variable-width-space architecture.

Does a humidifier have to be present for claim 1 infringement?

No. Claim 1 does not require a humidifier. Humidification is added by claims 2 through 7. A system without a humidifier may still infringe claim 1 if all core converter and delivery limitations are present.

Does delivering nitric oxide at 20 ppm satisfy claim 9?

Yes, on the supplied claim language, 20 ppm is greater than 10 ppm. It would not be greater than the higher listed thresholds, but the claim is drafted with alternative thresholds.

References

1. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,604,028, Nitric oxide delivery system.
2. U.S. Food and Drug Administration. (1999). INOmax nitric oxide for inhalation prescribing information.
3. U.S. Food and Drug Administration. (2019). GENOSYL nitric oxide for inhalation prescribing information.
4. Bellerophon Therapeutics, Inc. (n.d.). INOpulse nitric oxide delivery system.
5. United States Code. (2023). 35 U.S.C. §§ 154 and 156: Patent term and patent-term extension.

Drugs Protected by US Patent 9,604,028

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vero Biotech Inc	GENOSYL	nitric oxide	GAS;INHALATION	202860-001	Dec 20, 2019		RX	Yes	Yes	9,604,028					A METHOD FOR DELIVERING NITRIC OXIDE TO A PATIENT WITH PULMONARY HYPERTENSION OR HYPOXIA

International Family Members for US Patent 9,604,028

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2009282986
Canada	2734788
European Patent Office	2328592
Japan	2012500091
Japan	2014166557