Details for Patent: 10,588,913

Which drugs does patent 10,588,913 protect, and when does it expire?

Patent 10,588,913 protects BYQLOVI and is included in one NDA.

This patent has twenty-four patent family members in seventeen countries.

Summary for Patent: 10,588,913

Title:	Aqueous suspension agent containing glucocorticosteroid nanoparticles
Abstract:	An aqueous suspension containing as an active component a glucocorticosteroid compound is described. The aqueous suspension contains nanoparticles of a glucocorticosteroid compound and a dispersion stabilizer. The nanoparticles have a mean particle diameter of 300 nm or less and a D90 particle diameter of 450 nm or less. The pharmaceutical compositions containing the aqueous suspension are for parenteral administrations, injections, eye drops or ear drops. More specifically the aqueous suspensions containing glucocorticosteroid nanoparticles are used as an eye drop for treating or preventing inflammatory diseases of the eye or an ear drop for treating or preventing inflammatory diseases of the ear.
Inventor(s):	Takahiro Tada, Kazuhiro Kagami, Kenta Kikuchi
Assignee:	Formosa Pharmaceuticals Inc
Application Number:	US15/571,986
Patent Claim Types: see list of patent claims	Use; Composition; Device; Dosage form;

U.S. Patent 10,588,913: Claim Scope, Exclusivity, Litigation Risk, and Generic Entry Analysis

U.S. Patent 10,588,913 protects a narrowly defined nanoparticle corticosteroid suspension platform. Its strongest independent-claim limitation is the combination of five formulation components with particle-size thresholds: a glucocorticosteroid, a physiologically acceptable salt, glycerin, hydrogenated soybean lecithin, and anhydrous citric acid, with a mean particle diameter of no more than 300 nm and a D90 of no more than 450 nm.

The patent is potentially important for ophthalmic, otic, nasal, pulmonary, topical, injectable, and other parenteral corticosteroid formulations. The claims are broad as to the corticosteroid class but narrow as to excipients and particle size. A competing product that omits one required excipient, exceeds either particle-size threshold, or uses a materially different manufacturing process may avoid literal infringement of the principal claims.

What does U.S. Patent 10,588,913 protect?

The patent claims four related subject-matter categories:

Claim category	Claims	Protected subject matter
Composition	1-8	Aqueous suspension containing corticosteroid nanoparticles and specified excipients
Pharmaceutical product	9-13	Pharmaceutical compositions and administration forms containing the suspension
Kit	14	Kit containing corticosteroid nanoparticles for preparing the composition
Manufacturing method	15-16	Mixing specified ingredients to produce the pharmaceutical composition

Claims 1 and 2 are the principal composition claims. Claim 1 requires the finished aqueous suspension to contain the listed ingredients and meet the particle-size limits. Claim 2 is separately drafted around a suspension whose nanoparticles are produced by mixing the same core ingredients.

Claims 15 and 16 protect the manufacturing operation rather than only the resulting product. A commercial process can therefore present infringement risk even when the final formulation is difficult to distinguish analytically, provided the accused process performs the claimed mixing steps.

How broad are the independent claims?

Claim 1: composition claim

Claim 1 requires all of the following:

1. An aqueous suspension.
2. Nanoparticles of a glucocorticosteroid compound.
3. A physiologically acceptable salt.
4. Glycerin.
5. Hydrogenated soybean lecithin.
6. Anhydrous citric acid.
7. A mean nanoparticle diameter of 300 nm or less.
8. A D90 nanoparticle diameter of 450 nm or less.

Each limitation is material. A formulation lacking hydrogenated soybean lecithin, using citric acid in a hydrated form, replacing glycerin with another polyol, or failing the particle-size requirement would not literally satisfy claim 1.

The claim does not specify:

• A particular corticosteroid concentration.
• A particular salt.
• A specific pH.
• A specific viscosity.
• A specific dosage volume.
• A particular route of administration.
• A particular particle-production technology.
• A lower particle-size threshold.
• A specific nanoparticle morphology.

The absence of concentration and process limitations increases the potential breadth of claim 1. The required excipient combination and particle-size profile narrow that breadth.

Claim 2: composition with a production limitation

Claim 2 covers an aqueous suspension containing corticosteroid nanoparticles that satisfy the same particle-size limitations, where the nanoparticles are produced by mixing:

• The glucocorticosteroid compound;
• A physiologically acceptable salt;
• Glycerin;
• Hydrogenated soybean lecithin; and
• Anhydrous citric acid.

Claim 2 is potentially broader in one respect because it does not expressly depend on claim 3's listed corticosteroids. It is narrower in another respect because it includes a production limitation. Under U.S. patent law, an issued product-by-process claim is generally assessed by the characteristics and structure of the product, although the process language can affect infringement analysis depending on claim construction and the accused product's manufacturing evidence (U.S. Court of Appeals for the Federal Circuit, 2009).

The critical issue is whether "produced by mixing" requires a particular sequence, order of addition, mixing intensity, or mixing environment. The claim language supplied does not specify those parameters. A process that combines the ingredients in a different sequence may still fall within the claim if the court treats "mixing" as a broad operation rather than a prescribed sequence.

Which corticosteroids fall within the claimed genus?

Claim 3 steroid list

Claim 3 expressly identifies the following glucocorticosteroids:

• Clobetasol propionate
• Diflorasone diacetate
• Dexamethasone propionate
• Difluprednate
• Mometasone furoate
• Diflucortolone valerate
• Betamethasone butyrate propionate
• Fluocinonide
• Hydrocortisone butyrate propionate
• Beclomethasone dipropionate
• Deprodone propionate
• Betamethasone valerate
• Dexamethasone valerate
• Prednisolone valerate acetate
• Fluocinolone acetonide
• Hydrocortisone butyrate
• Clobetasone butyrate
• Alclometasone dipropionate
• Triamcinolone acetonide
• Flumethasone pivalate
• Prednisolone
• Hydrocortisone

Claim 3 depends on claim 1. It therefore requires the full claim 1 excipient combination and particle-size profile in addition to one or more listed corticosteroids.

The list is not an open-ended list of all corticosteroids for purposes of claim 3. A corticosteroid absent from the list may still fall within claim 1 or claim 2 if it satisfies the broader glucocorticosteroid limitation, but it would not satisfy claim 3.

What formulations are protected by claims 4 through 8?

Claims 4 through 8 add optional formulation components:

Claim	Limitation
4	Dispersion stabilizer
5	Polyoxyethylene polyoxypropylene glycol and/or polyvinyl alcohol
6	Viscosity modifier
7	Methyl cellulose, hydroxypropyl methylcellulose, and/or polyvinyl alcohol
8	Viscosity modifier concentration of 1 to 10 mg/mL

These claims have narrower scope than claim 1 but may be commercially important because marketed ophthalmic and inhaled suspensions often require physical stability, controlled sedimentation, redispersibility, and suitable administration viscosity.

Polyvinyl alcohol appears in both the dispersion-stabilizer and viscosity-modifier claim branches. A formulation using polyvinyl alcohol may therefore implicate multiple dependent claims if it also satisfies the base composition and particle-size limitations.

The claims do not establish that every stabilizer or viscosity modifier is required. Claims 4 and 6 are optional additions to claim 1. A product can infringe claim 1 without infringing claims 4 through 8.

Does the patent cover eye drops, ear drops, nasal products, and inhalers?

Claims 9 through 13

Claims 9 through 13 extend the suspension into product and dosage-form categories:

• Claim 9: pharmaceutical composition containing the suspension.
• Claim 10: parenteral administration.
• Claim 11: injection or topical preparation.
• Claim 12: topical preparation for the eye, ear, nose, or lung.
• Claim 13: eye drop, ear drop, nose drop, or inhaler.

Claim 13 is the most commercially targeted dosage-form claim. It could reach a finished ophthalmic, otic, nasal, or inhaled product if the product contains an aqueous suspension meeting the limitations of claim 1 through the dependency chain.

The dependency structure is important. A product described as an eye drop does not face claim 13 in isolation. It must first satisfy claim 12, claim 11, claim 10, and claim 9, and ultimately claim 1. The "parenteral administration" limitation in claim 10 creates a potential claim-construction issue because claim 11 then recites an injection or topical preparation, and claims 12 and 13 identify topical administration sites and forms. The commercial meaning of "parenteral" and its relationship to topical ocular, otic, nasal, and pulmonary delivery may affect enforceability and infringement analysis.

How do the particle-size limitations affect infringement?

The numerical limitations are central to the patent.

Parameter	Claimed threshold
Mean particle diameter	300 nm or less
D90 particle diameter	450 nm or less

A product may satisfy the mean-size limitation while failing the D90 limitation. For example, a suspension with a 250 nm mean but a 600 nm D90 would not literally meet claim 1.

The patent claims do not identify:

• The particle-sizing instrument.
• The dispersion medium used for measurement.
• The sample preparation protocol.
• The number of measurements.
• Whether the reported mean is arithmetic, volume-weighted, intensity-weighted, or number-weighted.
• The permitted measurement variance.

Those omissions can create disputes over reproducibility and claim construction. Particle-size evidence should be generated under a controlled protocol and compared with the patent's specification and prosecution history. A generic developer would need to assess both the average size and the upper-tail distribution because D90 is an independent limitation.

A formulation with a mean diameter below 300 nm but a small fraction of larger particles may fail the D90 test. Conversely, a formulation with a D90 below 450 nm but a mean above 300 nm also falls outside literal claim scope.

What manufacturing processes are protected?

Claims 15 and 16

Claim 15 requires mixing:

• The glucocorticosteroid compound;
• A physiologically acceptable salt;
• Glycerin;
• Hydrogenated soybean lecithin; and
• Anhydrous citric acid.

Claim 16 adds a physiologically acceptable polyol and/or water and a dispersion stabilizer.

The method claims do not expressly require:

• Wet milling;
• Homogenization;
• Ultrasonication;
• High-pressure processing;
• A particular temperature;
• A defined order of addition;
• A defined mixing time;
• A drying or reconstitution step.

This creates two competing interpretations. The claims may reach a broad mixing process that generates the claimed formulation, or they may be limited by the specific technical disclosure and prosecution history. The specification and file history would control whether "mixing" has a specialized meaning.

For freedom-to-operate purposes, the process claims create a separate risk channel. A developer could avoid a product claim but still face process-claim exposure if it uses the claimed ingredients in a covered manufacturing operation.

How strong is the patent estate based on the claims?

Strengths

The apparent strengths are:

1. A defined excipient combination.
2. Two independent particle-size thresholds.
3. Coverage of a broad corticosteroid genus in claims 1 and 2.
4. A specific corticosteroid list in claim 3.
5. Dependent coverage of stabilizers, viscosity modifiers, and dosage forms.
6. Separate manufacturing claims.
7. Potential coverage across multiple administration routes.

The combination of formulation and particle-size limitations can make simple design-around strategies more difficult where the product requires nanosizing and the specified excipients are functionally useful.

Vulnerabilities

The apparent vulnerabilities are:

1. The claims require five specific core formulation components.
2. The particle-size measurement method is not stated in the claims.
3. The claims do not identify a lower particle-size boundary.
4. The term "nanoparticles" may require construction.
5. Claim 2 and claims 15-16 may raise product-by-process and process-scope issues.
6. The dependency chain for parenteral and topical products may create construction disputes.
7. Prior art may exist for nanosized corticosteroids, lecithin-stabilized suspensions, glycerin-containing formulations, and citric-acid-buffered products.
8. A competitor may substitute an excipient or use a different particle-size distribution.

Patent validity would depend on the full specification, prosecution history, priority chain, cited references, and any terminal disclaimer or PTA. The claims alone do not establish novelty, nonobviousness, enablement, written description, or enforceability.

When does U.S. Patent 10,588,913 lose exclusivity?

The patent number and claims alone do not establish the expiration date. U.S. patent term generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and priority-specific rules (35 U.S.C. §§ 154, 156).

The issue date is not the controlling expiration date. A reliable term calculation must account for:

Term variable	Relevance
Earliest effective nonprovisional filing date	Establishes the basic 20-year term
Continuation or divisional status	May use an earlier parent filing date
Patent-term adjustment	Can extend the term for USPTO delay
Patent-term extension	May apply after regulatory review for an eligible product
Terminal disclaimer	Can shorten the enforceable term
Reexamination or post-grant proceedings	Can alter claim status without necessarily changing the nominal term

No expiration date should be treated as definitive without the USPTO patent record and the patent's priority and term data.

What is the Orange Book status of U.S. Patent 10,588,913?

An Orange Book listing cannot be established from the claims alone. The FDA lists patents for approved drug products when the patents fall within the statutory categories and listing requirements, including drug substance, drug product, and certain method-of-use patents (FDA, 2024).

This patent appears, from the supplied claims, to be directed primarily to a formulation and manufacturing platform. It does not claim a specific approved drug product by active ingredient, strength, dosage form, or approved indication in the independent claims. That structure may reduce the likelihood of an Orange Book listing unless an approved product directly corresponds to the claimed suspension and the patent is timely listed.

Orange Book implications would include:

• A possible Paragraph IV certification if listed against an approved reference product.
• A 30-month stay if the patent holder timely files an infringement action after receiving a Paragraph IV notice.
• No automatic 30-month stay if the patent is not listed or if the ANDA certification does not trigger the statutory stay provisions.
• Potential patent certification issues for formulation and method-of-use claims under the Hatch-Waxman framework (21 U.S.C. § 355(j)).

Which companies are challenging the patent?

No challenger, ANDA filing, Paragraph IV notice, district-court action, or settlement agreement is identified in the claim text. The claims do not establish litigation status.

A complete litigation assessment would require matching the patent against:

• PACER district-court complaints;
• PTAB proceedings;
• USPTO Patent Center prosecution records;
• FDA Orange Book listings;
• ANDA litigation notices;
• Public settlement filings;
• Assignment and licensing records.

Without those records, no company should be identified as a current challenger, licensee, or settlement counterparty.

What generic entry risks exist?

Small-molecule generic risk

The relevant competitive threat is generic entry, not biosimilar substitution. The claimed products contain small-molecule glucocorticosteroids, so the principal regulatory pathway would generally be an ANDA rather than a biosimilar application.

A generic developer has several possible design-around strategies:

Strategy	Potential effect
Replace hydrogenated soybean lecithin	May avoid claim 1 if the replacement is not an equivalent
Replace glycerin	May avoid literal infringement of claim 1
Use a different acidulant or buffer	May avoid the anhydrous citric-acid limitation
Increase mean particle size above 300 nm	May avoid claim 1
Increase D90 above 450 nm	May avoid claim 1
Use a non-nanoparticle suspension	May avoid the nanoparticle limitation
Use a different manufacturing sequence	May reduce process-claim risk
Select a corticosteroid outside claim 3	Does not avoid claims 1 or 2 if the compound remains a glucocorticosteroid

The most practical design-around is likely a formulation that preserves therapeutic performance while changing one mandatory excipient or the particle-size profile. That strategy could create regulatory comparability issues, particularly for ophthalmic, pulmonary, or other locally administered products where particle size affects exposure, tolerability, suspension stability, and dose delivery.

Biosimilar risk

Biosimilar risk is not the relevant framework for this patent. A biosimilar product would concern a biological reference product, while these claims concern chemically defined glucocorticosteroid compounds and pharmaceutical suspensions. Competition would more likely arise through an ANDA, a 505(b)(2) application, or a competing branded formulation.

How does this patent compare with typical corticosteroid formulation patents?

Patent 10,588,913 is broader than a conventional single-drug formulation patent in its corticosteroid coverage, but narrower in its required excipient architecture.

Feature	Patent 10,588,913	Typical single-drug formulation patent
Active ingredient	Broad glucocorticosteroid genus	One active ingredient
Particle size	Explicit mean and D90 limits	May be absent or less specific
Excipients	Five core components required	Often narrower or more product-specific
Dosage forms	Eye, ear, nose, lung, injection, topical	Often one route
Manufacturing coverage	Expressly claimed	May be absent
Design-around route	Excipient or particle-size change	Active ingredient, concentration, or excipient change

The patent has platform characteristics, but its enforceable reach depends on whether commercial products actually use the claimed combination and satisfy the particle-size metrics.

What revenue exposure could the patent create?

Revenue exposure cannot be quantified from the claims alone because the patent does not identify:

• A marketed product;
• An approved active ingredient;
• Annual sales;
• Market share;
• Geographic sales;
• A licensee;
• A reference listed drug;
• A confirmed generic challenger.

Commercial exposure would be highest if the patent covers a high-volume ophthalmic or pulmonary corticosteroid product and no noninfringing formulation is available. Exposure would be lower if the claims cover only a development formulation, an unapproved product, or a formulation that can be redesigned without material clinical or regulatory consequences.

Key Takeaways

• Claims 1 and 2 are the core composition claims.
• The mandatory combination is a glucocorticosteroid nanoparticle suspension containing a physiologically acceptable salt, glycerin, hydrogenated soybean lecithin, and anhydrous citric acid.
• The particle-size limits are a mean diameter of no more than 300 nm and a D90 of no more than 450 nm.
• Claim 3 identifies 22 corticosteroids but depends on claim 1.
• Claims 9-13 extend coverage to pharmaceutical products, injections, topical preparations, eye drops, ear drops, nose drops, and inhalers.
• Claims 15 and 16 create separate process-infringement risk.
• The principal commercial threat is generic entry through an ANDA, not biosimilar substitution.
• A generic developer may design around the patent by changing an excipient, particle-size distribution, dosage form, or manufacturing process.
• The patent's exact expiration date, Orange Book status, litigation status, challengers, licenses, settlements, and revenue exposure cannot be determined from the claim text alone.
• The patent's practical strength depends on the complete specification, prosecution history, priority chain, term adjustments, cited prior art, and commercial product mapping.

FAQs About U.S. Patent 10,588,913

Can a corticosteroid formulation infringe if it uses only four of the five core excipients?

Not literally under claim 1 or claim 2. Both claims require the specified salt, glycerin, hydrogenated soybean lecithin, and anhydrous citric acid, together with the corticosteroid and particle-size limitations. Doctrine-of-equivalents exposure would require a separate analysis.

Does a formulation with a 300 nm mean particle size automatically infringe?

No. It must also have a D90 of 450 nm or less and satisfy the required composition limitations. Meeting only the mean-size threshold is insufficient.

Does claim 3 cover loteprednol etabonate?

Loteprednol etabonate is not listed in claim 3. It could still fall within claim 1 or claim 2 if it qualifies as the claimed glucocorticosteroid compound and the remaining limitations are met.

Can a company avoid the method claims by buying premanufactured corticosteroid nanoparticles?

Potentially, depending on the supplier's process and the company's own activities. Purchasing a finished nanoparticle intermediate may reduce direct process performance, but inducement, contributory infringement, product claims, and supply-chain evidence would require separate analysis.

Is a patent license required to market an eye drop covered by claim 13?

A license may be required if the product satisfies the full dependency chain through claim 1 and the patent remains enforceable. Claim 13 alone does not establish infringement without satisfaction of all incorporated limitations.

References

1. U.S. Patent No. 10,588,913, claims 1-16. United States Patent and Trademark Office.

2. 35 U.S.C. § 154. Patent term.

3. 35 U.S.C. § 156. Extension of patent term.

4. 35 U.S.C. §§ 271, 282, 284. Patent infringement, defenses, and remedies.

5. 21 U.S.C. § 355(j). Abbreviated new drug applications and patent certifications.

6. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.

7. U.S. Court of Appeals for the Federal Circuit. (2009). Abbott Laboratories v. Sandoz, Inc., 566 F.3d 1282.

Drugs Protected by US Patent 10,588,913

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Harrow Eye	BYQLOVI	clobetasol propionate	SUSPENSION/DROPS;OPHTHALMIC	218158-001	Mar 4, 2024		RX	Yes	Yes	10,588,913		Y

International Family Members for US Patent 10,588,913

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016262185
Brazil	112017024000
Canada	2985171
China	107613985
European Patent Office	3295943
Spain	2937023