US Patent 9,463,161: Glycopyrrolate HFA Co-Suspension Claims, Exclusivity and Generic Risk
US Patent 9,463,161 protects selected glycopyrrolate metered-dose inhaler formulations and their use in treating pulmonary disease. The patent is directed to a HFA-propellant co-suspension containing crystalline glycopyrrolate particles and separate respirable phospholipid particles, with defined particle-size, concentration, weight-ratio and clinical-response limitations. Its broadest practical commercial relevance is to low-dose glycopyrrolate MDI products, particularly glycopyrrolate/formoterol products using Pearl Therapeutics' co-suspension platform.
The patent does not cover every glycopyrrolate inhaler. Infringement generally requires the accused product or use to satisfy the claimed HFA vehicle, crystalline glycopyrrolate, separate phospholipid suspending particles, and, for the composition claims, the specified DSPC, particle-size, concentration and ratio limitations.
What does US Patent 9,463,161 protect?
US 9,463,161 contains two principal claim groups:
- Method-of-treatment claims, principally claims 1-13 and 21-23.
- Pharmaceutical-composition claims, principally claims 14-20 and 24-31.
The patent's technical center is a co-suspension rather than a conventional suspension of active pharmaceutical ingredient alone.
| Claim element |
Method claims |
Composition claims |
| Metered-dose inhaler |
Required |
Required as delivery context |
| HFA propellant |
Required |
Required |
| Crystalline glycopyrrolate |
Required |
Required |
| Separate suspending particles |
Required |
Required |
| Dry particulate phospholipid |
Required |
Required |
| DSPC specifically |
Not expressly required in claim 1 |
Required by claim 14 |
| Suspending-particle diameter of 1.5-10 μm |
Not expressly required in claim 1 |
Required by claim 14 |
| Suspending-particle concentration up to 30 mg/mL |
Not expressly required in claim 1 |
Required by claim 14 |
| Suspender-to-drug ratio of 10:1-200:1 |
Added by claims 21-22 |
Required by claim 14 |
| Glycopyrrolate dose of 80 μg or less |
Required |
Not required in claim 14 |
| FEV1 increase of at least 70 mL |
Required |
Not required |
| FEV1 increase of at least 100 mL within one hour or less |
Added in dependent claims |
Not required |
| COPD |
Dependent claims 2 and 23 |
Not required |
The claims combine formulation structure with performance outcomes. That combination can narrow infringement analysis but also create validity questions if the clinical-response limitations are difficult to reproduce consistently or were inadequately supported by the specification.
What is the scope of independent claim 1?
Claim 1 is a method claim requiring all of the following:
- Treatment of one of the listed pulmonary diseases or conditions.
- A metered-dose inhaler.
- A pharmaceutically acceptable co-suspension.
- An HFA propellant as the suspension medium.
- Crystalline glycopyrrolate, or a pharmaceutically acceptable salt, ester or isomer.
- Separate respirable suspending particles.
- Suspending particles made from dry particulate phospholipid.
- The phospholipid particles are substantially insoluble in the HFA medium.
- Administration of 80 μg or less glycopyrrolate per actuation.
- An increase in FEV1 of at least 70 mL.
The listed diseases include asthma, COPD, allergic rhinitis, sinusitis, pulmonary vasoconstriction, allergies, respiratory distress syndrome, pulmonary hypertension and pulmonary conditions associated with cystic fibrosis.
Claim 1 does not expressly require DSPC, a 1.5-10 μm particle diameter, a specific phospholipid concentration or a 10:1-200:1 mass ratio. Those limitations appear in the composition claims and in claims 21-25. A product could therefore fall outside the express wording of the composition claims while still raising a method-claim issue if it uses the claimed treatment conditions and achieves the claimed FEV1 response.
The phrase "consisting essentially of" limits the suspension medium. It permits components that do not materially affect the basic and novel characteristics of the claimed co-suspension, but it creates a fact-intensive question for products containing cosolvents, surfactants, stabilizers or other excipients.
What do the glycopyrrolate dose and FEV1 limitations require?
The method claims establish a dose-response and onset-of-action hierarchy.
| Claim |
Dose limitation |
Clinical limitation |
| 1 |
80 μg or less per actuation |
FEV1 increase of at least 70 mL |
| 3 |
No more than 40 μg delivered dose |
Claim 1 response |
| 4 |
No more than 10 μg or up to 20 μg |
Claim 1 response |
| 5 |
Claim 1 dose |
At least 100 mL within one hour or less |
| 7 |
No more than 40 μg |
At least 100 mL within one hour or less |
| 8 |
No more than 20 μg |
Claim 1 response |
| 9 |
No more than 20 μg |
At least 100 mL within one hour or less |
| 10 |
No more than 10 μg |
At least 100 mL within one hour or less |
| 11 |
Claim 1 dose |
At least 100 mL within 30 minutes or less |
| 13 |
No more than 20 μg |
At least 100 mL within 30 minutes or less |
These limitations make the patent relevant to low-dose products. They also create several enforcement issues:
- Delivered dose must be distinguished from nominal label dose.
- FEV1 must be measured using a reproducible protocol.
- The response threshold may require clinical or pharmacodynamic evidence.
- A method claim generally requires performance of the claimed treatment method, not merely possession or sale of a formulation.
- A product that contains the same formulation but is labeled for a different use may still present inducement issues if its labeling or promotional activity encourages the claimed use.
What do composition claims 14-31 cover?
Claim 14 is the principal composition claim. It requires:
- An HFA propellant suspension medium.
- Crystalline glycopyrrolate particles.
- Separate suspending particles.
- Suspending particles with a volume median optical diameter of about 1.5-10 μm.
- Substantial insolubility in the HFA medium.
- DSPC as the phospholipid.
- Suspender concentration of up to about 30 mg/mL.
- A total suspending-particle-to-active-particle mass ratio of 10:1-200:1.
The ratio is central. The claimed formulation contains a substantially greater mass of phospholipid suspending material than glycopyrrolate. That ratio is designed to reduce sedimentation and improve dose uniformity in a pressurized MDI.
Dependent claims narrow or expand the technical definition:
- Claims 15 and 16 address lower suspender concentrations and suspender density.
- Claims 17 and 18 address density differences and perforated microstructures.
- Claim 19 adds crystalline formoterol particles.
- Claim 20 specifies glycopyrrolate concentration of about 0.04-2.25 mg/mL.
- Claims 24 and 25 narrow the mass ratio to 15:1-60:1.
- Claims 26-31 cover specified glycopyrrolate salts, including glycopyrrolate bromide.
The supplied claim text contains apparent dependency inconsistencies in claims 15 and 16, which refer to claims 4 and 5 even though those claims are method claims. The issued patent and official USPTO file history control the legal dependency. A claim chart should use the issued patent PDF rather than a transcription.
What formulations are protected by US 9,463,161?
The strongest literal formulation target is a product with the following profile:
- Glycopyrrolate bromide in crystalline form.
- HFA-134a, HFA-227 or another pharmaceutically acceptable HFA propellant.
- DSPC particles manufactured separately from glycopyrrolate particles.
- DSPC particles that remain substantially insoluble in the propellant.
- Suspender particle diameter between approximately 1.5 and 10 μm.
- DSPC concentration no greater than approximately 30 mg/mL.
- Suspender-to-glycopyrrolate mass ratio between 10:1 and 200:1, preferably 15:1-60:1.
- Optional formoterol particles.
- Delivery through a pressurized metered-dose inhaler.
The patent is narrower than a general claim to glycopyrrolate in an HFA MDI. Products using dissolved glycopyrrolate, a different suspending excipient, a single co-processed particle population, a non-HFA propellant or a dry-powder inhaler may avoid literal infringement of claim 14.
The doctrine of equivalents could create residual risk where a substitute phospholipid or particle architecture performs substantially the same stabilizing function in substantially the same way. Equivalence would be limited by prosecution history, claim amendments and any disclosed distinction between DSPC and alternative materials.
How does US 9,463,161 compare with Bevespi Aerosphere and Breztri Aerosphere?
| Product |
Active ingredients |
Device |
Relevance to patent |
| Bevespi Aerosphere |
Glycopyrrolate/formoterol fumarate |
HFA MDI |
Directly aligned with the glycopyrrolate/formoterol co-suspension technology |
| Breztri Aerosphere |
Budesonide/glycopyrrolate/formoterol fumarate |
HFA MDI |
Uses the same broad co-suspension platform but has additional formulation and combination-product patent issues |
| Seebri Neohaler |
Glycopyrrolate |
Dry-powder inhaler |
Different delivery technology; lower literal risk under the HFA MDI claims |
| Lonhala Magnair |
Glycopyrrolate |
Nebulizer |
Different device and formulation route |
| Generic glycopyrrolate inhalation products |
Product-specific |
DPI, nebulizer or MDI depending on product |
Risk depends on device, propellant, excipient and label |
Bevespi is the most direct commercial comparator because it combines glycopyrrolate and formoterol in a pressurized HFA inhaler. Breztri adds an inhaled corticosteroid but may rely on overlapping co-suspension technology. The presence of formoterol is not required by claim 14, so adding formoterol does not by itself avoid the patent.
When does US 9,463,161 lose exclusivity?
The patent issued on October 11, 2016. Its nominal patent term is generally measured from the applicable earliest nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers and any other USPTO-recorded term adjustment. Public patent records associate the patent family with Pearl Therapeutics' glycopyrrolate co-suspension technology. A nominal expiration in the early 2030s is expected, but the controlling date is the term shown in the USPTO Patent Center record.
The patent does not receive biologic exclusivity. Glycopyrrolate is a small-molecule active ingredient, so the relevant regulatory routes are abbreviated new drug applications under section 505(j) and, for certain products, 505(b)(2) applications. The 12-year biosimilar exclusivity framework does not apply.
FDA product exclusivity is separate from patent term. Bevespi received FDA approval in 2016, while Breztri received FDA approval in 2020. Any NCE, pediatric, orphan or other regulatory exclusivity must be analyzed independently from US 9,463,161 and the Orange Book patent listing.
What is the Orange Book status of US 9,463,161?
Orange Book relevance depends on whether the patent is listed against a specific approved drug product and whether the listed claims cover the approved formulation or method of use. A patent number alone does not establish current listing status.
For an Orange Book-listed product, a generic applicant may certify under Paragraph I, II, III or IV. A Paragraph IV certification asserts that the listed patent is invalid, unenforceable or will not be infringed. The patent's method and composition claims create different certification questions:
- Composition claims may be challenged through a formulation-based noninfringement position.
- Method claims may be addressed through a label carve-out under section viii, if the patented use can be omitted.
- A generic MDI using the same co-suspension architecture may face greater Paragraph IV exposure than a DPI or nebulizer product.
- A product using a different active-particle or suspender architecture may have a stronger noninfringement position.
The Orange Book should be reviewed by product, strength, dosage form and patent-use code. The patent's presence or absence in the Orange Book does not determine validity.
Which companies face the greatest patent risk?
A competitor faces the highest risk when it uses the same commercial architecture:
- Glycopyrrolate bromide in crystalline form.
- HFA pressurized MDI.
- DSPC respirable suspending particles.
- Separate active and suspender particle populations.
- Suspender-to-drug ratio within 10:1-200:1.
- Low delivered glycopyrrolate dose.
- Labeling that promotes rapid bronchodilation in COPD.
A competitor using a dry-powder inhaler, nebulizer, non-DSPC suspender, dissolved active ingredient or a materially different particle system has a clearer design-around path. That design-around may still encounter other Pearl, AstraZeneca or third-party patents covering the active ingredient, combination, device, manufacturing process or therapeutic indication.
What manufacturing and IP barriers does the patent create?
The patent creates process-control requirements beyond ordinary glycopyrrolate formulation work:
- Separate manufacture of active and suspending particles.
- Control of crystalline glycopyrrolate morphology.
- Control of DSPC particle size and density.
- Maintenance of suspension uniformity in HFA.
- Control of sedimentation and redispersion.
- Accurate delivered-dose testing at low microgram strengths.
- Compatibility between formulation, metering valve and actuator.
- Demonstration of aerodynamic and optical particle-size parameters.
These requirements can create practical barriers even where a competitor disputes literal claim coverage. Process patents, device patents and confidential manufacturing know-how may provide additional protection not visible from the asserted composition claims.
What patent litigation and settlement activity affects US 9,463,161?
The supplied patent and claim text establish no litigation, Paragraph IV notice or settlement agreement. A definitive litigation assessment requires the USPTO file history, PACER docket records, FDA Orange Book updates and company disclosures. The key litigation questions would be whether a generic applicant challenges the composition claims, whether the innovator asserts method claims, and whether a court construes "separate," "different particles," "substantially insoluble" and "consisting essentially of" narrowly.
Validity challenges would likely focus on:
- Anticipation by earlier HFA glycopyrrolate formulations.
- Obviousness based on known phospholipid suspension systems.
- Written-description support for the claimed ratios and performance outcomes.
- Enablement of the full disease, dose and FEV1 scope.
- Indefiniteness of functional terms and approximate numerical ranges.
Key Takeaways
- US 9,463,161 is a glycopyrrolate HFA co-suspension patent.
- Its strongest composition claim requires crystalline glycopyrrolate, separate DSPC suspending particles, 1.5-10 μm suspender particles, up to 30 mg/mL suspender concentration and a 10:1-200:1 mass ratio.
- Its method claims add low delivered doses and FEV1 response thresholds.
- Bevespi Aerosphere is the most direct commercial product comparator; Breztri Aerosphere presents related combination-product risk.
- DPI and nebulizer glycopyrrolate products generally present less literal risk under the HFA MDI claims.
- Glycopyrrolate is a small molecule, so biosimilar analysis does not apply.
- The patent's effective expiration date must be confirmed from the USPTO term record, including patent-term adjustment and any terminal disclaimer.
- Claims 15 and 16 in the supplied text contain apparent dependency errors that require confirmation against the issued patent.
- A Paragraph IV strategy would likely combine a formulation noninfringement position with validity challenges to the particle, ratio and functional-response limitations.
FAQs
Does US 9,463,161 cover glycopyrrolate dry-powder inhalers?
Generally, no. The independent claims require an HFA suspension medium and a metered-dose inhaler. A dry-powder inhaler would require separate analysis under other patents.
Does adding formoterol avoid US 9,463,161?
No. Claim 14 does not require formoterol, and claim 19 expressly covers a composition that also contains formoterol.
Is glycopyrrolate bromide required?
The independent claims permit a pharmaceutically acceptable salt, ester or isomer. Dependent claims narrow the salt to glycopyrrolate bromide and other specified salts.
Can a competitor avoid the patent by changing DSPC particle size?
Potentially, if the product falls outside the claimed 1.5-10 μm range and does not satisfy another asserted claim. The effect of approximate-language construction and equivalents would require claim-specific analysis.
Does a Paragraph IV certification automatically invalidate US 9,463,161?
No. Paragraph IV is an applicant's statutory position that the patent is invalid, unenforceable or not infringed. The patent remains enforceable unless invalidated, disclaimed, expired or otherwise rendered unenforceable.
References
- U.S. Patent and Trademark Office. (2016). U.S. Patent No. 9,463,161, Glycopyrrolate compositions and methods of use thereof.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
- U.S. Food and Drug Administration. (2016). Bevespi Aerosphere prescribing information. AstraZeneca Pharmaceuticals LP.
- U.S. Food and Drug Administration. (2020). Breztri Aerosphere prescribing information. AstraZeneca Pharmaceuticals LP.
- United States Code. (2024). 35 U.S.C. §§ 154, 271 and 282.
- United States Code. (2024). 21 U.S.C. § 355(j).
