Details for Patent: 10,716,753

Which drugs does patent 10,716,753 protect, and when does it expire?

Patent 10,716,753 protects BEVESPI AEROSPHERE, BREZTRI AEROSPHERE, and SYMBICORT AEROSPHERE, and is included in three NDAs.

This patent has one hundred and ninety-four patent family members in thirty-two countries.

Summary for Patent: 10,716,753

Title:	Compositions for pulmonary delivery of long-acting muscarinic antagonists or long-acting B2 adrenergic receptor agonists and associated methods and systems
Abstract:	Compositions, methods and systems are provided for pulmonary delivery of long-acting muscarinic antagonists and long-acting β2 adrenergic receptor agonists via a metered dose inhaler. In particular embodiments, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.
Inventor(s):	Reinhard Vehring, Michael Steven Hartman, Adrian Edward Smith, Vidya B. Joshi, Sarvajna Kumar Dwivedi
Assignee:	Pearl Therapeutics Inc
Application Number:	US16/179,712
Patent Claim Types: see list of patent claims	Use; Composition; Delivery;

US Patent 10,716,753: Claim Scope, Exclusivity, and Inhaled LAMA/LABA Patent Landscape

US Patent No. 10,716,753 protects a pressurized metered-dose inhaler formulation in which micronized LAMA or LABA particles are suspended with separately manufactured, respirable phospholipid particles. The principal limitation is the particle architecture: the active-agent particles must be distinct from the phospholipid suspending particles, and the suspending-particle-to-active-particle mass ratio must exceed 1:1 and reach as high as 200:1.

The patent is technically broad across LAMA and LABA classes but narrower in commercial application because infringement requires the claimed dry particulate phospholipid suspending system, not merely an HFA inhaler containing glycopyrrolate, formoterol, or another long-acting bronchodilator.

What does US Patent 10,716,753 protect?

The independent composition claim protects five elements:

Claim element	Scope
Delivery device	Metered-dose inhaler
Suspension medium	Pharmaceutically acceptable propellant
Active particles	Particles containing a LAMA or LABA
Suspending particles	Separate, different respirable particles made from dry particulate phospholipid
Mass ratio	More than 1:1 and up to 200:1 suspending particles to active particles

The independent method claim, claim 26, repeats the same formulation architecture and adds treatment of pulmonary diseases and disorders.

The patent therefore covers a formulation platform rather than a single chemical entity. Its technical center is the use of a relatively large mass of respirable phospholipid particles to suspend and disperse a much smaller mass of crystalline bronchodilator particles in a propellant.

What is the core inventive concept?

The core concept is a two-population suspension:

1. Active-agent particles containing a LAMA or LABA.
2. Separately formed respirable phospholipid particles that act as suspending or carrier particles.

The active agent is not required to be incorporated into, coated by, or chemically associated with the phospholipid particle. Claims 1 and 26 expressly require that the two particle populations be formed separately and remain different particles.

That distinction creates a potentially important infringement boundary. A formulation containing porous phospholipid particles with the active ingredient embedded inside the same spray-dried particle may fall outside the literal scope of claims 1 and 26, depending on the product structure and claim construction.

How broad are the composition claims?

Claims 1 through 25 form a descending composition-claim hierarchy. Claim 1 is the commercially important broad claim. Claims 2 through 25 add particle morphology, manufacturing method, particle-size parameters, propellants, drug classes, chemical forms, and dose levels.

Independent claim 1

Claim 1 does not require:

• A particular LAMA or LABA molecule.
• A particular phospholipid.
• A particular propellant.
• Spray drying.
• Perforated particles.
• A specific particle diameter.
• A specific delivered dose.
• A particular disease indication.

It does require a phospholipid material that is substantially insoluble in the suspension medium. The insolubility limitation is directed to retaining the suspending particles as discrete solid particles in the propellant.

The ratio limitation is material. A formulation with a suspending-particle-to-active-particle ratio of exactly 1:1 is outside the literal range because the claim requires a ratio greater than 1:1. A ratio above 200:1 is also outside the literal range.

Dependent composition claims

Claims	Added limitation	Commercial significance
2-4	Perforated microstructures; spray drying; PFOB/DSPC/calcium chloride composition	Narrows the claim toward porous spray-dried particles
5	Aerodynamic particle-size ranges	Targets respirable particle performance
6	Optical particle-size ranges	Adds geometric-size limitations distinct from MMAD
7	HFA, PFC, or combined propellants	Covers conventional HFA and fluorocarbon systems
8	Specific particle-mass ratios up to 200:1	Provides fallback positions around the broad ratio
9-10	Crystalline or micronized crystalline active	Relevant to conventional API processing
11-18	LAMA compounds, especially glycopyrrolate bromide	Narrows toward glycopyrrolate products
19-25	LABA compounds, especially formoterol fumarate	Narrows toward formoterol products

The dependent claims are cumulative. For example, claim 18 requires the composition of claim 17, which depends on the glycopyrrolate limitations in claims 11 and 12 and ultimately includes the formulation architecture of claim 1.

Which drugs fall within the claimed LAMA and LABA classes?

The patent expressly identifies the following LAMA candidates:

• Glycopyrrolate
• Dexpirronium
• Tiotropium
• Trospium
• Aclidinium
• Darotropium

The expressly identified LABA candidates include:

• Bambuterol
• Clenbuterol
• Formoterol
• Salmeterol
• Carmoterol
• Milveterol
• Indacaterol
• Certain saligenin-containing, indole-containing, and adamantyl-derived beta-2 agonists

The claims do not require that the active agent be an approved product. A molecule may fall within the genus if it meets the structural and formulation limitations, even if the molecule is investigational or commercially inactive.

Glycopyrrolate-specific scope

Claims 12 through 18 narrow the LAMA genus to glycopyrrolate and then to specified salts. Claim 18 identifies glycopyrrolate bromide as:

3-[(cyclopentyl-hydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide.

Claims 15 through 18 also address concentrations, delivered dose, and salt identity. These limitations may be important for a low-dose glycopyrrolate HFA product, but they do not independently cover glycopyrrolate as an API or every glycopyrrolate inhaler.

A product containing glycopyrrolate but using a different carrier system, a dissolved formulation, or a single composite particle may avoid claims 12 through 18 even if it is therapeutically equivalent.

Formoterol-specific scope

Claims 20 through 25 narrow the LABA genus to formoterol and formoterol fumarate. They require crystalline or micronized crystalline formoterol in the relevant dependent claims.

The formoterol claims are potentially relevant to low-dose HFA formulations, but they do not cover all formoterol products. Dry-powder inhalers, nebulized solutions, and formulations that lack the claimed separate phospholipid suspending particles are materially different claim targets.

What particle technology is protected?

Claims 2 through 6 define a particle-engineering sublandscape.

Perforated microstructures

Claim 2 requires perforated microstructures. The term points to particles with internal voids or surface openings that reduce density and improve aerosolization. The claim does not, on its face, require a specific pore size, porosity percentage, or particle morphology beyond the perforated-microstructure limitation.

Claim 3 requires spray drying. Claim 4 is narrower and identifies a spray-dried emulsion containing:

• Perfluorooctyl bromide, or PFOB
• DSPC, or 1,2-distearoyl-sn-glycero-3-phosphocholine
• Calcium chloride
• Water

A formulation using DSPC and PFOB but manufactured by a different process may avoid claim 3, but could still raise issues under claim 2 or claim 1 if the resulting particles satisfy the composition and particle-identity requirements.

Particle-size limitations

Claim 5 lists alternative MMAD ranges:

• Approximately 10 micrometers to 500 nanometers
• Approximately 5 micrometers to 750 nanometers
• Approximately 1 to 3 micrometers

The ranges overlap substantially. The practical target is the respirable range of approximately 1 to 3 micrometers.

Claim 6 separately addresses volume median optical diameter, with ranges extending from submicron values to approximately 50 micrometers. MMAD and optical diameter are different measurements. A formulation can satisfy one metric without satisfying another, which may create both infringement and validity disputes over measurement method, sampling conditions, and batch variability.

Propellant limitations

Claim 7 covers:

• HFA propellants
• PFC propellants
• Combinations of HFA and PFC propellants

The claim is not limited to one HFA such as HFA-134a or HFA-227ea. A product using a different pharmaceutically acceptable HFA could remain within the claim if the other limitations are satisfied.

What method-of-use protection does US 10,716,753 provide?

Claims 26 through 41 cover treatment methods using the claimed formulation architecture. The disease list includes:

• Asthma
• COPD
• Allergic rhinitis
• Sinusitis
• Pulmonary vasoconstriction
• Inflammation and allergies
• Impeded respiration
• Respiratory distress syndrome
• Pulmonary hypertension
• Pulmonary disease associated with cystic fibrosis

The method claims are narrower than a general claim to treating a disease with a LAMA or LABA. The method must use a metered-dose inhaler composition containing the separate dry particulate phospholipid suspending particles and the claimed mass ratio.

Glycopyrrolate method claims

Claims 31 through 36 address delivered glycopyrrolate doses and clinical outcomes:

Claim	Limitation
31	Delivered glycopyrrolate dose of no more than 150 micrograms
35	Clinically significant increase in inspiratory capacity
36	Dose of no more than 80 micrograms and FEV1 increase of at least 150 mL within 0.5 hour or less

These claims introduce outcome-based infringement questions. The product must both use the claimed formulation and produce the specified clinical result. The FEV1 limitation may be difficult to assess from product labeling alone and could require clinical or pharmacodynamic evidence.

Formoterol method claims

Claims 37 through 41 cover formoterol doses of 10 micrograms or less per actuation, including crystalline micronized formoterol and formoterol fumarate. Claim 41 adds a clinically significant FEV1 increase.

These claims may be relevant to low-dose formoterol HFA development, but a competitor would need to assess delivered dose, not merely nominal canister concentration.

What is the likely patent term and expiration date?

US Patent 10,716,753 issued on July 21, 2020. A standard US utility patent generally expires 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and applicable transitional rules.[1]

The patent’s exact expiration date cannot be determined from the claims alone. The controlling analysis requires the patent’s front-page priority and filing data, terminal-disclaimer status, and USPTO patent-term calculation. The issue date does not determine the expiration date.

The patent should be evaluated against:

• Earliest claimed priority application
• Nonprovisional filing date
• International application status, if any
• Patent-term adjustment
• Patent-term extension
• Continuation or divisional relationship
• Terminal disclaimer
• Any post-grant correction affecting the term

A patent-term calculation based only on the grant date would be unreliable.

What is the Orange Book status of US 10,716,753?

US Patent 10,716,753 is a formulation and method-of-use patent. Its Orange Book relevance depends on whether the patent is listed by an NDA holder for a specific approved drug and whether FDA accepts the listing as timely and properly tied to the approved labeling.[2]

The patent number alone does not establish Orange Book listing status. A patent can be technically relevant to an inhaled LAMA or LABA without being listed for that product.

For an Orange Book-listed product, the practical consequences would include:

• A Paragraph IV certification by an ANDA applicant.
• Potential 30-month stay following a timely infringement suit.
• FDA review of the patent certification and litigation status.
• Possible settlement or launch-date restrictions.

If the patent is not listed for the relevant reference drug, it would not ordinarily create a statutory Orange Book-based ANDA stay, although it could still support separate patent litigation.

How does a Paragraph IV challenge apply?

A generic applicant would need to determine whether the reference product is protected by this patent and whether the patent is listed for that product. The relevant certification could be:

• Paragraph I, if no patent information is listed.
• Paragraph II, if the patent has expired.
• Paragraph III, if the applicant will wait until expiration.
• Paragraph IV, if the applicant asserts that the patent is invalid, unenforceable, or will not be infringed.

For this patent, a strong Paragraph IV noninfringement position could focus on the following formulation differences:

1. The product does not contain separate phospholipid suspending particles.
2. The phospholipid is dissolved or molecularly dispersed rather than present as dry particulate material.
3. The active agent is encapsulated in the same particle as the phospholipid.
4. The mass ratio is 1:1 or less.
5. The mass ratio exceeds 200:1.
6. The propellant is outside the claimed propellant categories.
7. The product is a dry-powder inhaler or nebulized solution rather than a metered-dose inhaler.
8. The active agent is neither a claimed LAMA nor a claimed LABA.

A validity challenge could target written description, enablement, indefiniteness, anticipation, and obviousness. The broad genus covering multiple LAMAs, LABAs, phospholipid materials, particle sizes, propellants, and ratios is more exposed than the narrow PFOB/DSPC/calcium chloride embodiment.

How strong is the patent estate?

The patent appears strongest when asserted against a product that closely matches the following profile:

• HFA or PFC metered-dose inhaler
• Micronized crystalline glycopyrrolate or formoterol fumarate
• Separate spray-dried phospholipid particles
• Perforated or porous particle morphology
• Respiratory aerodynamic size of approximately 1 to 3 micrometers
• Suspending-particle-to-active-particle ratio between 1:1 and 200:1

The patent is weaker against products using conventional suspension technologies without separate phospholipid carrier particles.

Claim-strength assessment

Issue	Assessment
Core particle architecture	Strong if product structure is documented
LAMA/LABA genus	Broad, but potentially exposed to prior-art and enablement arguments
Glycopyrrolate and formoterol species	More commercially focused and easier to map
PFOB/DSPC embodiment	Narrower but technically concrete
Mass-ratio limitation	Clear numerical boundary, subject to measurement disputes
MMAD and optical diameter	Potentially useful but vulnerable to testing-method disputes
Clinical-outcome claims	Narrow and evidence-intensive
Device requirement	Limits claims to metered-dose inhaler products
Manufacturing limitation	Spray-drying limitation applies only to narrower dependent claims

What prior-art areas are most relevant?

The relevant patent landscape includes four overlapping technology groups.

Porous phospholipid particles

Earlier patents concerning spray-dried phospholipid particles, porous particles, and large porous particles may be relevant to novelty and obviousness. The most important prior-art questions are whether earlier references disclose:

• Separate active and carrier particles.
• Dry particulate phospholipid material.
• Insolubility in the propellant.
• A suspending-particle-to-active-particle ratio above 1:1.
• LAMA or LABA actives.
• Metered-dose inhaler delivery.

A reference disclosing porous phospholipid particles alone may not anticipate claim 1 unless it also discloses the claimed separate active particles and ratio.

HFA suspension formulations

The HFA formulation field contains extensive prior art on micronized crystalline bronchodilators, surfactants, suspension stabilizers, and metered-dose inhalers. Such references may supply individual claim elements but may not disclose the claimed two-particle system.

LAMA and LABA inhalers

Patents covering glycopyrrolate, tiotropium, aclidinium, formoterol, salmeterol, and indacaterol generally focus on:

• Chemical compounds and salts
• Crystalline forms
• Device dose delivery
• Combination therapies
• COPD or asthma treatment
• Dry-powder or nebulized formulations

Those patents may overlap commercially without anticipating the specific phospholipid-particle architecture.

Pulmonary delivery manufacturing

Spray-drying, emulsion processing, PFOB-containing particles, DSPC particles, calcium chloride stabilization, and particle-size control are separate landscape clusters. A competitor may avoid the narrow manufacturing claims while still facing claim 1 if it produces an equivalent particle population.

Which companies could face competitive or freedom-to-operate risk?

Potentially affected developers include companies commercializing or developing inhaled LAMA/LABA products in HFA metered-dose inhalers, particularly products based on:

• Glycopyrrolate
• Formoterol fumarate
• Glycopyrrolate/formoterol combinations
• Other long-acting bronchodilator combinations

The principal commercial exposure is not the API market alone. It is the intersection of API, particle engineering, and device platform. A company using a conventional HFA suspension with a surfactant may have lower exposure than a company using spray-dried porous phospholipid carrier particles.

Biosimilar risk is limited. LAMAs and LABAs are small molecules, so the relevant competition is generic or hybrid drug-device competition rather than biosimilar substitution. FDA approval may proceed through an ANDA, 505(b)(2) application, or another pathway depending on the reference product and formulation differences.[3]

What generic launch scenarios exist?

Scenario 1: Same formulation architecture

A generic or follow-on product copies the separate phospholipid-particle system. This creates the highest infringement risk and is the most likely scenario for a Paragraph IV dispute if the patent is listed.

Scenario 2: Conventional HFA suspension

The competitor uses micronized API with conventional surfactants or excipients but no separate phospholipid suspending particles. This is the clearest design-around path.

Scenario 3: Single-particle spray-dried formulation

The active agent and phospholipid are incorporated into one composite particle. This may avoid the express requirement that the particles be separately formed and different, although the doctrine of equivalents could become relevant.

Scenario 4: Non-HFA dosage form

A dry-powder inhaler, nebulized solution, soft-mist inhaler, or other delivery system generally avoids the metered-dose-inhaler limitation, subject to product-specific analysis.

Scenario 5: Ratio-based design-around

A formulation with a suspending-particle-to-active-particle ratio of 1:1 or less, or above 200:1, may avoid literal infringement of claim 1. This approach must account for batch-to-batch variation and the measurement method used to calculate total mass.

What litigation and settlement issues should be reviewed?

A complete litigation assessment requires the patent’s current USPTO and PACER records, FDA listing data, and any terminal-disclaimer or continuation-family information. The claim set itself does not establish whether US 10,716,753 has been asserted, challenged, settled, licensed, disclaimed, or adjudicated.

The key litigation questions are:

• Whether the patent is listed in the Orange Book for a specific NDA.
• Whether an ANDA applicant has filed a Paragraph IV certification.
• Whether the patent owner sued within the statutory 45-day period.
• Whether a 30-month stay applies.
• Whether a court construed "formed separately" and "different particles."
• Whether "substantially insoluble" is indefinite or technically measurable.
• Whether MMAD and optical diameter are sufficiently definite.
• Whether the broad LAMA/LABA genus is enabled across its full scope.
• Whether prior art disclosed phospholipid carrier particles with inhaled bronchodilators.
• Whether any settlement permits an authorized generic or licensed launch.

No licensing or settlement right should be inferred from the existence of the patent or from its claim breadth.

How does US 10,716,753 compare with conventional inhaled bronchodilator patents?

Patent focus	Typical protected subject matter	Relationship to US 10,716,753
API composition patent	Chemical compound or salt	Separate from the formulation-platform claims
Crystalline-form patent	Solid-state form of LAMA/LABA	May overlap with claims requiring crystalline API
Conventional HFA formulation patent	API, propellant, surfactant, concentration	May overlap at the product level but lacks the claimed particle architecture
Dry-powder inhaler patent	Carrier powder, device, or DPI formulation	Generally outside the MDI requirement
Spray-dried porous-particle patent	Particle morphology and manufacture	May overlap with claims 2-4
US 10,716,753	Separate active and phospholipid respirable particles in an MDI	Targets the combination of particle platform and long-acting bronchodilator

What is the geographic coverage?

US Patent 10,716,753 provides rights only in the United States. Parallel protection, if any, would require corresponding patents or applications in other jurisdictions.

A global freedom-to-operate review should separately examine:

• PCT publications and national-phase filings
• European Patent Office records
• UK, Canadian, Australian, and Japanese family members
• National patent-term calculations
• Local supplementary protection certificates
• Local claim scope and prosecution amendments
• Litigation and opposition records

US claim language cannot be assumed to apply in Europe or other markets.

Key Takeaways

• US 10,716,753 is a formulation-platform patent for LAMA/LABA metered-dose inhalers.
• Claim 1 requires separate active-agent particles and dry particulate phospholipid suspending particles.
• The claimed mass ratio is greater than 1:1 and up to 200:1.
• Glycopyrrolate, glycopyrrolate bromide, formoterol, and formoterol fumarate are expressly covered in dependent claims.
• Spray-dried perforated particles and the PFOB/DSPC/calcium chloride system are narrower embodiments.
• Conventional HFA suspensions, dry-powder inhalers, nebulized solutions, and single composite particles may provide design-around routes.
• The method claims add pulmonary-disease indications, delivered-dose limits, and, in some claims, FEV1 or inspiratory-capacity outcomes.
• Orange Book status, Paragraph IV exposure, litigation, settlement, licensing, and exact patent expiration cannot be established from the claim text alone.
• The patent is most commercially relevant where a product combines a low-dose LAMA or LABA with a separate spray-dried phospholipid carrier platform.

References

1. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term expiration guidance. https://www.uspto.gov
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov
3. U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application submissions: Patent certifications and the 30-month stay. https://www.fda.gov
4. United States Patent and Trademark Office. (2020). U.S. Patent No. 10,716,753. U.S. Department of Commerce.

Drugs Protected by US Patent 10,716,753

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astrazeneca	BEVESPI AEROSPHERE	formoterol fumarate; glycopyrrolate	AEROSOL, METERED;INHALATION	208294-001	Apr 25, 2016		RX	Yes	Yes	10,716,753		Y			USE FOR THE MAINTENANCE TREATMENT OF PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
Astrazeneca Ab	BREZTRI AEROSPHERE	budesonide; formoterol fumarate; glycopyrrolate	AEROSOL, METERED;INHALATION	212122-001	Jul 23, 2020		RX	Yes	Yes	10,716,753		Y			USE FOR THE MAINTENANCE TREATMENT OF PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
Astrazeneca Ab	BREZTRI AEROSPHERE	budesonide; formoterol fumarate; glycopyrrolate	AEROSOL, METERED;INHALATION	212122-002	Apr 27, 2026		RX	Yes	Yes	10,716,753		Y			USE FOR THE MAINTENANCE TREATMENT OF ASTHMA IN PATIENTS 12 YEARS OF AGE OR OLDER

International Family Members for US Patent 10,716,753

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2435025		300995	Netherlands
European Patent Office	2435025		PA2019014	Lithuania
European Patent Office	2435025		122019000068	Germany