Details for Patent: 10,058,511

Which drugs does patent 10,058,511 protect, and when does it expire?

Patent 10,058,511 protects EYSUVIS and INVELTYS and is included in two NDAs.

This patent has nineteen patent family members in seven countries.

Summary for Patent: 10,058,511

Title:	Nanocrystals, compositions, and methods that aid particle transport in mucus
Abstract:	Nanocrystals, compositions, and methods that aid particle transport in mucus are provided. In some embodiments, the compositions and methods involve making mucus-penetrating particles (MPP) without any polymeric carriers, or with minimal use of polymeric carriers. The compositions and methods may include, in some embodiments, modifying the surface coatings of particles formed of pharmaceutical agents that have a low water solubility. Such methods and compositions can be used to achieve efficient transport of particles of pharmaceutical agents though mucus barriers in the body for a wide spectrum of applications, including drug delivery, imaging, and diagnostic applications. In certain embodiments, a pharmaceutical composition including such particles is well-suited for administration routes involving the particles passing through a mucosal barrier.
Inventor(s):	Alexey Popov, Elizabeth M. Enlow, James Bourassa, Colin R. Gardner, Hongming Chen, Laura M. Ensign, Samuel K. Lai, Tao Yu, Justin Hanes, Ming Yang
Assignee:	Alcon Inc , Johns Hopkins University
Application Number:	US15/616,799
Patent Claim Types: see list of patent claims	Use; Composition; Delivery; Dosage form;

US Patent 10,058,511: Claim Scope, Patent Expiration, Mucus-Penetrating Particles, and Competitive Landscape

US Patent 10,058,511 protects a platform for mucus-penetrating drug particles rather than a single active ingredient. Its core requirement is a solid drug-rich particle, coated with a hydrophilic-hydrophobic-hydrophilic triblock copolymer, usually a polyethylene oxide-polypropylene oxide-polyethylene oxide or PEG-PPO-PEG polymer. The broadest claims cover particles from 5 nm to 1,000 nm, while separate claims focus on particles no larger than 400 nm and pharmaceutical products suitable for mucosal administration.

The patent is strategically important because infringement can arise from the particle architecture and mucus-penetration performance even when the active pharmaceutical ingredient, dosage form, or route of administration differs. The principal commercial risks are formulation-development overlap, method-of-use exposure, and follow-on patents covering specific drugs or delivery routes.

What does US Patent 10,058,511 protect?

The patent protects four related subject-matter categories:

Claim category	Claims	Protected subject matter
Broad particle compositions	1-20	Coated drug particles from 5 nm to 1,000 nm
Narrow particle compositions	21-34	Coated drug particles no larger than 400 nm
Pharmaceutical compositions	35	Particles sized 50-500 nm for inhalation, injection, or topical mucosal administration
Delivery methods	36-40	Delivery of the particles across a mucus or mucosal barrier

The independent claims require the following combination:

1. A plurality of coated particles.
2. A core containing a solid pharmaceutical agent or salt.
3. The agent or salt constitutes at least 80 wt% of the core.
4. A coating containing a surface-altering agent.
5. The surface-altering agent is a hydrophilic-hydrophobic-hydrophilic triblock copolymer.
6. The hydrophobic block has a molecular weight of at least 2 kDa.
7. The hydrophilic blocks constitute at least 15 wt% of the copolymer.
8. The hydrophobic block associates with the drug-particle surface.
9. The coating renders the particle hydrophilic.
10. The particles are mucus-penetrating.
11. The particles fall within the specified size range.

The claims use "comprising," which is an open-ended transition. A competing formulation can contain additional polymers, excipients, stabilizers, targeting ligands, active ingredients, or processing aids and still fall within the claims if all required elements are present.

How broad is the core composition claim?

Claim 1 is broad in the identity of the pharmaceutical agent but narrow in particle construction.

Active pharmaceutical ingredient scope

Claims 14-16 extend the platform to:

• Small molecules
• Peptides
• Peptidomimetics
• Proteins
• Nucleic acids
• Lipids
• Therapeutic agents
• Diagnostic agents
• Low-solubility compounds with aqueous solubility of no more than 0.1 mg/mL at 25°C

The claims are not limited to a particular therapeutic class. They can potentially cover anti-infectives, hormones, corticosteroids, oncology agents, proteins, nucleic acids, and diagnostic materials if the resulting particle satisfies the structural and functional limitations.

The 80 wt% requirement is commercially significant. It excludes many conventional polymeric nanoparticles in which the drug is a minor payload and the polymer matrix forms most of the particle. The claimed core is predominantly pharmaceutical agent or salt, with the triblock copolymer functioning primarily as a surface coating.

Crystalline, amorphous, and salt forms

Claims 11-13 expressly cover:

• Crystalline drug particles
• Amorphous drug particles
• Salts of solid pharmaceutical agents

This creates coverage across multiple solid-state development strategies. A developer cannot necessarily avoid the patent by converting a crystalline active to an amorphous dispersion or selecting a different salt, provided the drug-rich core and coating limitations remain satisfied.

What polymer structures are covered?

The key polymer limitation is a hydrophilic block-hydrophobic block-hydrophilic block configuration.

Polymer limitation	Claim coverage
Triblock copolymer	Claims 1 and 21
Hydrophobic block of at least 2 kDa	Claims 1 and 21
Hydrophilic blocks at least 15 wt%	Claims 1 and 21
Hydrophilic blocks at least 30 wt%	Claims 5 and 25
PEO or PEG hydrophilic blocks	Claims 6 and 26
PPO hydrophobic block	Claims 7 and 27
PEO-PPO-PEO or PEG-PPO-PEG	Claims 8 and 28
Hydrophilic block at least 2 kDa	Claim 9
PPO block at least 3 kDa	Claim 10

The most commercially relevant embodiments are poloxamer-type structures, including PEO-PPO-PEO polymers. The claim language also reaches derivatives of PEG or PEO and does not require a specific trade name, molecular-weight designation, terminal group, or commercial supplier.

A formulation using a different hydrophilic polymer may avoid claims 6, 8, 9, 26, 28, or 29. It may still face claims 1 or 21 if the alternative polymer is a triblock copolymer meeting the broader architecture and molecular-weight requirements.

Does covalent versus noncovalent attachment matter?

The patent covers both attachment mechanisms.

Claims 2 and 22 cover covalent attachment of the surface-altering agent to the core particles. Claims 3 and 23 cover noncovalent adsorption. The independent claims do not require one mechanism over the other.

This matters for freedom-to-operate analysis. A developer cannot avoid the independent claims simply by changing from adsorption to covalent conjugation, or the reverse. The key question is whether the hydrophobic block associates with the drug-particle surface and the resulting particle is hydrophilic and mucus-penetrating.

Claim 4 adds a surface-density limitation of at least 0.001 molecules per nm². This is a relatively low stated density, broadening the dependent-claim coverage across sparse surface coatings. A formulation with a higher density may still fall within claim 4.

What particle sizes are protected?

The patent uses overlapping size limitations:

Claim group	Size range
Claims 1-16	At least 5 nm and no more than 1,000 nm
Claims 17 and 21-34	At least 50 nm and no more than 500 nm, or no more than 400 nm through dependent claims
Claim 35	At least 50 nm and no more than 500 nm
Claim 36	No express size in the independent method claim
Claims 39-40	Method particles from 5-1,000 nm or no more than 400 nm

The size is expressed as an average. Particle-size testing methodology can therefore become a central infringement and validity issue. Relevant variables include:

• Hydrodynamic diameter versus dry particle diameter
• Number-average versus intensity-weighted diameter
• Dynamic light scattering versus electron microscopy
• Measurement in water, buffer, mucus, or formulation vehicle
• Inclusion or exclusion of aggregates
• Batch-to-batch particle-size distribution

The 400 nm limitation is particularly important. It captures many nanoparticle and nanocrystal formulations used for mucosal delivery while avoiding the upper portion of the 1,000 nm range.

What does “mucus-penetrating” require?

“Mucus-penetrating” is a functional limitation, not merely a particle-size description. The claims include two quantitative performance tests:

• Claim 19: diffusivity through human cervicovaginal mucus greater than 1/500 of the diffusivity through water over a one-second timescale.
• Claim 20: relative velocity greater than 0.5 in mucus.
• Claims 33 and 34 repeat the performance limitations for the narrower composition claims.

These limitations may create both enforcement value and litigation risk.

For infringement, the patent owner would likely need to establish that the accused particles meet the specified mucus-transport property. For validity, the claims may be challenged on written-description, enablement, indefiniteness, or lack-of-unpredictability grounds if the specification does not adequately support the full breadth of active ingredients, polymers, particle sizes, and mucosal environments.

The use of human cervicovaginal mucus in claim 19 is narrower than a generic reference to all mucus. A product that penetrates nasal, pulmonary, gastrointestinal, ocular, or cervical mucus may not produce identical transport data in each environment.

What formulations and administration routes are covered?

Claim 35 expressly covers pharmaceutical compositions suitable for:

• Inhalation
• Injection
• Topical administration to a mucous membrane

The claim requires particles from 50 nm to 500 nm. It does not require a named organ, disease, active ingredient, dosage strength, or specific device.

The method claims are broader in route and target. Claims 36-40 cover delivery across a mucosal barrier, including mucus or a mucosal membrane and mucosal tissue. Potentially relevant delivery sites include:

• Nasal mucosa
• Pulmonary mucus
• Ocular surface
• Vaginal and cervical mucus
• Rectal mucosa
• Oral and buccal tissue
• Gastrointestinal mucus

A product may therefore face composition-claim exposure even if its approved indication is unrelated to the indications described in the patent specification.

When does US Patent 10,058,511 lose exclusivity?

The patent issued on August 28, 2018. Its family priority date is October 16, 2009, giving the patent a nominal 20-year term through October 16, 2029, before any applicable patent-term adjustment or patent-term extension.

Event	Date
Earliest family priority	October 16, 2009
Patent issuance	August 28, 2018
Nominal 20-year term end	October 16, 2029
Expected post-expiration status	Claims generally unavailable for enforcement after the effective term end

The controlling expiration date should be taken from the USPTO patent-term calculation because continuation practice, terminal disclaimers, patent-term adjustment, and any qualifying regulatory extension can affect the enforceable term. The patent is not a drug-specific patent, so Hatch-Waxman patent-term extension would generally require a qualifying approved product relationship rather than the patent's platform status alone. [1][2]

What is the Orange Book status of US Patent 10,058,511?

US Patent 10,058,511 is a platform patent, not an Orange Book listing by itself. The FDA Orange Book lists patents submitted for approved drug products, including drug-substance, drug-product, and method-of-use patents under applicable FDA procedures. A broad particle platform patent does not automatically appear in the Orange Book merely because it could cover a drug product. [3]

The practical consequences are:

• The patent does not independently create FDA marketing exclusivity.
• It does not automatically trigger a Paragraph IV certification.
• A Paragraph IV challenge would arise only if the patent were listed against a specific approved reference drug and an ANDA applicant made the relevant certification.
• A 30-month stay depends on the statutory and litigation conditions associated with an Orange Book-listed patent, not on the patent number alone.

A drug sponsor could separately list a patent claiming an approved formulation or method of use if the FDA listing requirements are met. That would be a product-specific issue rather than a consequence of US 10,058,511's broad platform claims.

Are biosimilar applicants exposed to this patent?

The patent includes proteins and nucleic acids within the definition of pharmaceutical agent, so a biologic nanoparticle or protein formulation could technically fall within the claim scope. The patent does not, however, function as a standard biologic patent directed to:

• A specific protein sequence
• A cell line
• A manufacturing process
• A biologic formulation
• A device constituent
• A particular biosimilar reference product

The Purple Book and the biologics patent-dispute framework differ from the Orange Book and ANDA system. A biosimilar applicant would evaluate this patent through patent-clearance, notice, and litigation processes rather than assuming that the patent creates automatic FDA biosimilar exclusivity. [4]

The main biologic risk is formulation overlap. A protein or nucleic acid incorporated into a solid, drug-rich, triblock-coated mucus-penetrating particle could encounter the composition claims even though the active molecule itself is not claimed.

Which patent landscape surrounds this technology?

The relevant landscape contains four overlapping layers.

Foundational mucus-penetrating particle patents

Earlier and related patent families generally focus on:

• Particles coated with dense hydrophilic surface layers
• Prevention of adhesive interactions with mucins
• Nanoparticles designed to diffuse through mucus
• Drug delivery to mucosal tissues
• Surface modification using PEG or related polymers

US 10,058,511 is distinguished by its emphasis on a drug-rich solid core and a triblock copolymer whose hydrophobic block associates with the particle surface.

Drug-specific formulation patents

Commercial products may have separate patents directed to:

• A particular active ingredient
• A specific salt or polymorph
• Particle preparation
• Spray-drying or milling
• A defined polymer ratio
• A particular dosage form
• Preservative systems
• Device and container combinations

These patents can extend commercial protection beyond the 2029 platform term if their priority dates and claim scope support later expiry.

Route-specific and method-of-use patents

Separate claims may cover delivery to:

• The eye
• The nose
• The lung
• The female reproductive tract
• The gastrointestinal tract
• Wounds or other mucosal surfaces

A product can therefore face a layered patent estate even if US 10,058,511 is invalidated or expires. The platform patent should not be treated as the complete estate for a commercial mucus-penetrating product.

Manufacturing and process patents

Manufacturing barriers may include:

• Production of high-drug-load nanocrystals
• Polymer adsorption or coating conditions
• Control of particle size
• Prevention of aggregation
• Sterile processing
• Dry-powder preparation
• Aerosolization
• Scale-up and batch consistency

Process claims can remain commercially relevant even where the final composition is difficult to characterize or where a competitor designs around a composition claim.

How strong is the patent estate?

The estate is strongest against formulations that combine all of the following:

1. A solid drug or salt constitutes at least 80 wt% of the core.
2. A PEO-PPO-PEO or PEG-PPO-PEG coating is used.
3. The PPO block is at least 2 kDa.
4. The hydrophilic blocks constitute at least 15 wt%.
5. The particles average 50-500 nm or no more than 400 nm.
6. The particles demonstrate the claimed mucus-penetration performance.

The estate is weaker against:

• Liposomes with no solid drug-rich core
• Polymer-matrix nanoparticles with less than 80 wt% drug
• Particles coated with non-triblock polymers
• Triblock systems lacking the required molecular weights
• Microparticles above 1,000 nm
• Formulations that do not demonstrate the claimed mucus-transport properties
• Products using a surface modifier that does not associate with the drug-particle surface

The principal validity pressure points are the breadth of the active-agent definition, the functional mucus-penetration limitations, the meaning of "surrounding," and the measurement of average particle size and relative mucus velocity.

Which companies are challenging the patent?

No company-specific Paragraph IV challenger, ANDA litigation, or settlement agreement can be inferred from the patent claims alone. The patent is not inherently tied to a single approved drug, so ordinary generic litigation cannot be identified without a drug product, Orange Book listing, or court docket connecting an accused formulation to the patent.

Commercially, the most relevant potential counterparties are:

• Sponsors developing nanocrystal formulations
• Companies developing mucosal biologics
• Ophthalmic and intranasal drug-delivery companies
• Inhalation-product manufacturers
• Firms using poloxamers or related PEO-PPO-PEO excipients
• Generic companies developing low-solubility drug particles

A product-specific freedom-to-operate review should treat US 10,058,511 as a platform-level screening patent, then map later formulation, process, device, and method-of-use patents.

What generic launch risks exist?

A generic or follow-on product faces three principal launch scenarios.

Scenario	Patent exposure	Commercial result
Same drug, conventional formulation	Low exposure to this patent if no qualifying coated particles are used	Ordinary active-ingredient and formulation clearance remains necessary
Same drug, drug-rich mucus-penetrating particles	High potential exposure	Design-around, license, or litigation risk
Different drug using the same particle platform	Potential direct composition exposure	Patent risk exists even without active-ingredient identity overlap

An ANDA applicant using the claimed particle architecture may need to address the patent if it is listed against the relevant reference product. A 505(b)(2) applicant may face similar patent and regulatory issues where the proposed product relies on an approved drug but introduces a new delivery system.

Key Takeaways

• US 10,058,511 is a platform patent for mucus-penetrating particles, not a patent limited to one drug.
• The central architecture is a solid drug-rich core with at least 80 wt% pharmaceutical agent or salt and a PEO-PPO-PEO or related triblock coating.
• The broadest size range is 5-1,000 nm; important commercial embodiments fall within 50-500 nm or no more than 400 nm.
• Both covalent attachment and noncovalent adsorption are covered.
• The claims reach small molecules, peptides, proteins, nucleic acids, lipids, therapeutic agents, and diagnostics.
• The patent's nominal term runs through October 16, 2029, subject to the official term calculation.
• The patent does not automatically create Orange Book listing, FDA exclusivity, or a Paragraph IV event.
• The strongest design-around paths are changing the core composition, eliminating the triblock architecture, using a nonqualifying polymer, or failing the claimed mucus-performance limitations.
• Product-specific formulation, process, route, device, and method-of-use patents may create protection beyond this patent's term.

FAQs

Does US 10,058,511 cover poloxamer-coated nanocrystals?

Potentially. A poloxamer formulation may fall within the claims if the polymer has the required triblock structure, the hydrophobic block meets the molecular-weight threshold, the drug-rich core contains at least 80 wt% active or salt, and the particles are mucus-penetrating within the claimed size range.

Can a competitor avoid the patent by using PEG without PPO?

Usually, that change removes the express PEG-PPO-PEG or PEO-PPO-PEO embodiments. It may also avoid the broader claims if the alternative coating is not a hydrophilic-hydrophobic-hydrophilic triblock copolymer.

Does the patent cover mucus-penetrating particles larger than 1,000 nm?

No. The independent composition claims require particles no larger than 1,000 nm. The pharmaceutical composition claim is narrower and requires particles no larger than 500 nm.

Can the patent cover an inhaled protein formulation?

Yes, in principle. The claims include proteins as pharmaceutical agents and claim 35 expressly covers inhalation. The formulation must still satisfy the drug-rich core, triblock-coating, size, hydrophilicity, and mucus-penetration limitations.

Does expiration of US 10,058,511 eliminate all patent risk for a mucus-penetrating drug product?

No. Later-expiring patents may cover the active ingredient, particle preparation, polymer ratio, dosage form, delivery device, manufacturing process, or a specific mucosal indication.

References

1. United States Patent and Trademark Office. (2018). US Patent No. 10,058,511, Mucus-penetrating particles comprising a surface-altering agent.
2. United States Code. (2024). 35 U.S.C. §§ 154 and 156: Patent term and patent term extension.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
4. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products.

Drugs Protected by US Patent 10,058,511

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Alcon Labs Inc	EYSUVIS	loteprednol etabonate	SUSPENSION/DROPS;OPHTHALMIC	210933-001	Oct 26, 2020		RX	Yes	Yes			Y			A METHOD FOR DELIVERING A PHARMACEUTICAL AGENT ACROSS A MUCOSAL BARRIER
Alcon Labs Inc	INVELTYS	loteprednol etabonate	SUSPENSION/DROPS;OPHTHALMIC	210565-001	Aug 22, 2018		RX	Yes	Yes			Y			A METHOD FOR DELIVERING A PHARMACEUTICAL AGENT ACROSS A MUCOSAL BARRIER

International Family Members for US Patent 10,058,511

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013256130
Australia	2018201772
Australia	2020203213
Canada	2871778