US Patent 9,421,265: Ophthalmic Suspension Claims, Patent Scope and Competitive Landscape

US Patent 9,421,265 covers multi-dose ophthalmic suspensions that combine low concentrations of benzalkonium chloride, borate, two defined polyols, and a carboxyvinyl polymer suspending system. The strongest commercial claim set is directed to suspensions containing brinzolamide, brimonidine, or both, with controlled viscosity, pH, tear-buffering resistance, and redispersion performance.

The patent is formulation-focused. It does not broadly claim every ophthalmic product containing brinzolamide or brimonidine. Infringement requires a product to satisfy the required ingredient, concentration, physical-performance, and use limitations of at least one asserted claim.

What patents protect the ophthalmic formulations in US 9,421,265?

US 9,421,265 claims a multi-dose ophthalmic suspension with the following core architecture:

Claim element	Claimed limitation
First polyol	Mannitol, sorbitol, or a combination
Second polyol	Propylene glycol, glycerine, or a combination
Borate	Less than about 0.5% w/v
Preservative	Benzalkonium chloride, or BAC
BAC concentration	Greater than 0.00001% w/v and less than 0.0035% w/v
Therapeutic agent	Broad in independent claims; brinzolamide and brimonidine in dependent or narrower claims
Suspending agent	Carboxyvinyl polymer
Dosage form	Multi-dose ophthalmic suspension
Solvent	Water

The patent’s claim strategy combines composition-of-matter limitations with measurable product-performance requirements. Those requirements include pH, viscosity, resistance to tear-pH normalization, and redispersion after shaking.

The principal independent claims are claims 1, 13, and 20.

Claim 1: broad formulation platform

Claim 1 requires:

a first polyol selected from mannitol or sorbitol;
a second polyol selected from propylene glycol or glycerine;
borate below approximately 0.5% w/v;
BAC within a narrow concentration range;
a therapeutic agent;
water; and
a suspension containing the therapeutic agent and carboxyvinyl polymer.

Claims 2 through 12 narrow claim 1 by adding pharmacopoeial preservative testing, concentration limits, pH, therapeutic-agent identity, redispersion time, and tear-pH behavior.

Claim 1 is potentially broad because the therapeutic agent is not limited to brinzolamide or brimonidine. Its practical reach is narrower because the product must also contain the specified polyol combination, borate, BAC range, and carboxyvinyl polymer suspension system.

Claim 13: narrower concentration and preservative platform

Claim 13 adds several limitations:

first polyol concentration of at least 0.01% and no greater than 0.5% w/v;
second polyol concentration of at least approximately 0.1% and less than approximately 5% w/v;
BAC within the claim 1 range;
substantial absence of preservatives other than BAC; and
carboxyvinyl polymer as the suspending agent.

Claims 14 through 19 add:

tear-pH resistance below 15 microliters of 1 M sodium hydroxide per milliliter;
viscosity above 20 cP and below 500 cP at 120 sec-1 and room temperature;
redispersion within 15 seconds of vigorous shaking;
chronic administration;
treatment of elevated intraocular pressure.

Claim 13 is commercially important because it links the formulation to measurable physical characteristics that may be present in marketed glaucoma suspensions.

Claim 20: brinzolamide and brimonidine formulation claim

Claim 20 is the most product-specific claim. It requires:

mannitol;
propylene glycol;
borate below approximately 0.5% w/v;
brinzolamide, brimonidine, or both;
carboxyvinyl polymer between approximately 0.1% and less than 1.2% w/v;
BAC within the stated range;
no material preservative other than BAC;
tear-pH resistance below 15 microliters of 1 M sodium hydroxide per milliliter;
suspension viscosity above 20 cP and below 500 cP;
no quinolone anti-infective or antibiotic therapeutic agent;
pH from approximately 6.2 to 7.7; and
brinzolamide suspended with the carboxyvinyl polymer.

Claim 20 is substantially narrower than claim 1. It is also more vulnerable to non-infringing design-around because a competitor can target one of several independent numerical or structural limitations.

The text supplied for claim 20 states the concentration limitation after “propylene glycol” using the word “mannitol.” That appears to be a drafting or transcription issue. The limitation should be analyzed against the issued patent text and prosecution history before relying on it in litigation or freedom-to-operate work.

How many patents cover the claimed glaucoma suspension technology?

The supplied claims establish one patent family or claim set, but they do not establish the full patent estate surrounding a commercial product. A complete landscape normally separates:

active-ingredient patents;
fixed-combination patents;
suspension and preservative-system patents;
formulation-process patents;
method-of-use patents;
manufacturing patents;
regulatory exclusivity; and
Orange Book-listed patents.

US 9,421,265 is principally a formulation patent. It does not claim the chemical structure of brinzolamide or brimonidine. It also does not, based on the supplied claims, claim a particular manufacturing process, container, dispenser, or ophthalmic indication in every claim.

The patent’s commercial relevance is highest where the marketed product uses:

brinzolamide or brimonidine;
mannitol and propylene glycol;
BAC at approximately 0.003% w/v;
borate;
a carbomer or other carboxyvinyl polymer;
a suspension dosage form; and
a pH near the claimed range.

What formulations are protected by US 9,421,265?

Brinzolamide suspensions

Claims 10 and 20 expressly identify brinzolamide. A brinzolamide suspension may fall within the patent if it also meets the required BAC, borate, polyol, polymer, pH, viscosity, and tear-pH limitations.

A brinzolamide product that uses a different suspending agent, omits borate, uses a BAC concentration outside the claimed range, or has a viscosity outside the claimed range may avoid at least some claims.

Brimonidine suspensions

Claim 20 identifies brimonidine as an eligible therapeutic agent. The claim therefore reaches certain brimonidine-containing suspensions even though the commercially relevant formulation may be a fixed combination with brinzolamide.

A brimonidine product must still satisfy the other claim 20 limitations. The presence of brimonidine alone is insufficient.

Brinzolamide-brimonidine fixed combinations

The fixed-combination formulation is the most commercially significant target. The claim language permits brinzolamide, brimonidine, or a combination of the two. A product containing both active ingredients can therefore fall within claim 20 without requiring a separate claim directed only to the combination.

The product must be assessed by finished-product testing, not by ingredient labels alone. Relevant tests include:

BAC assay;
borate concentration;
mannitol and propylene glycol concentration;
carbomer or carboxyvinyl polymer concentration;
viscosity at the specified shear rate;
pH;
redispersion time; and
tear-pH buffering resistance.

How strong is the patent estate for US 9,421,265?

The patent has a mixed strength profile.

Strength factor	Assessment
Commercial specificity	Strongest in claim 20 because it identifies brinzolamide and brimonidine
Numerical limitations	Can improve enforceability but create design-around opportunities
Formulation evidence	Potentially strong if examples demonstrate the claimed ranges and performance
Functional limitations	Useful against copycat products, but testing methodology may be disputed
Broad claim 1	Broader therapeutic-agent coverage, but more potential prior-art exposure
Claim 13	Intermediate scope, with added preservative and concentration limitations
Claim 20	Narrower but more closely aligned with a commercial glaucoma suspension
Design-around risk	Material because concentration and physical-property ranges are central
Validity risk	Focused on prior-art combinations, written description, enablement, and claim construction

Potential validity pressure points

A challenger would likely examine prior-art ophthalmic suspensions containing:

polyols;
borate buffers;
BAC;
carbomer or carboxyvinyl polymers;
brinzolamide or brimonidine; and
pH-controlled ophthalmic formulations.

The numerical ranges may be attacked through anticipation if a prior-art reference discloses the same ranges, or through obviousness if the ranges represent routine optimization. Functional limitations such as rapid redispersion and tear-pH resistance may create additional validity issues if the specification does not adequately define testing conditions or provide sufficient representative examples.

The “substantially free” limitation may also create claim-construction questions. It generally does not necessarily mean absolute absence of every other preservative, but its scope depends on the patent specification, prosecution history, and the materiality of residual or incidental substances.

When does US 9,421,265 lose exclusivity?

The patent issued on August 23, 2016. Its expiration date cannot be determined from the claim text alone because the statutory term depends on the earliest effective nonprovisional filing date, patent-term adjustment, terminal disclaimers, and any applicable patent-term extension.

The normal US patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments. Patent expiration is separate from FDA regulatory exclusivity and from the date on which an ANDA applicant may obtain approval.

Exclusivity issue	Relevance
Patent term	Controls enforceable patent rights
Patent-term adjustment	May extend the nominal term
Patent-term extension	May apply only if statutory requirements are met
FDA approval exclusivity	May delay approval independently of patent expiry
Orange Book listing	Determines notice and Paragraph IV litigation consequences
Settlement agreement	May establish an earlier or later generic entry date

A reliable expiration analysis requires the patent’s continuity data and USPTO term records. The claims alone do not provide that information.

What is the Orange Book status of US 9,421,265?

The claim text does not establish whether US 9,421,265 is currently listed in the FDA Orange Book, whether it was listed for a particular reference-listed drug, or whether the listing remains active.

If listed for a drug product, the patent could support a Paragraph IV certification and related Hatch-Waxman litigation. The relevance would depend on:

the reference-listed drug;
the NDA holder;
the listed patent use code, if any;
whether the patent is product, formulation, or method-of-use listed;
the ANDA applicant’s proposed labeling; and
the timing of notice and litigation.

Because US 9,421,265 claims compositions rather than only a therapeutic method, its primary Orange Book relevance would ordinarily be as a formulation or drug-product patent.

Which companies are challenging the patent?

The supplied information identifies no litigation party, ANDA applicant, Paragraph IV notice, district-court case, Federal Circuit appeal, or settlement involving US 9,421,265.

The principal competitive threat would come from generic manufacturers seeking approval for:

brinzolamide ophthalmic suspension;
brimonidine ophthalmic suspension; or
a brinzolamide-brimonidine fixed-combination suspension.

A generic applicant could challenge the patent through:

Paragraph IV certification;
a declaratory-judgment action;
an invalidity defense after infringement litigation; or
a non-infringement position based on formulation differences.

No litigation conclusion follows from the claims themselves.

What generic launch risks exist?

At-risk launch

An ANDA applicant may launch before patent expiry after making a Paragraph IV certification if litigation does not trigger or sustain a statutory approval stay, or if the applicant prevails.

Design-around launch

A non-infringing formulation could alter one or more of the following:

replace mannitol with another tonicity agent;
replace propylene glycol with another excipient;
omit borate;
use a preservative other than BAC;
use BAC outside the claimed concentration range;
use a non-carboxyvinyl suspending system;
change pH outside 6.2 to 7.7;
formulate a solution rather than a suspension; or
alter viscosity or redispersion characteristics.

The difficulty is that changes must preserve ophthalmic stability, comfort, antimicrobial protection, suspension uniformity, and regulatory comparability.

Biosimilar risk

Biosimilar risk is not applicable to this patent’s claimed technology. Brinzolamide and brimonidine are small-molecule active ingredients, and competing products would generally proceed through the ANDA pathway rather than the biologics license application and biosimilar pathway.

How does US 9,421,265 compare with active-ingredient patents?

US 9,421,265 differs from an active-ingredient patent in both scope and vulnerability.

Patent type	Typical protection	Relevance to this patent
Active-ingredient patent	Chemical compound or salt	Not the principal subject of the supplied claims
Combination patent	Two or more active ingredients	Claim 20 reaches brinzolamide, brimonidine, or both through formulation limitations
Formulation patent	Excipients, concentrations, dosage form	Primary scope of US 9,421,265
Method-of-use patent	Treatment of glaucoma or ocular hypertension	Claims 18 and 19 add chronic-use and elevated-pressure limitations
Manufacturing patent	Mixing, sterilization, filling, or suspension processing	Not expressly covered by the supplied claims
Device patent	Container, dropper, or delivery mechanism	Not covered by the supplied claims

The patent may remain commercially relevant after active-ingredient patents expire if its formulation claims remain enforceable. Conversely, a formulation patent does not prevent a competitor from selling the active ingredient in a technically distinct formulation.

What manufacturing and intellectual-property barriers apply?

The principal manufacturing barrier is reproducibility. A competing manufacturer must control:

polymer hydration and dispersion;
particle-size distribution of suspended drug;
uniformity during filling;
preservative concentration;
pH adjustment;
viscosity under defined shear conditions;
microbial-preservation performance; and
redispersion after storage.

The patent converts several of those product attributes into claim limitations. A manufacturer may avoid infringement by changing the process or formulation, but the alternative must still meet FDA quality requirements for a multi-dose ophthalmic suspension.

Key Takeaways

US 9,421,265 is a formulation patent covering multi-dose ophthalmic suspensions.
Its core combination is mannitol or sorbitol, propylene glycol or glycerine, low borate, BAC, water, and a carboxyvinyl polymer.
Claim 20 is the most commercially targeted claim because it expressly covers brinzolamide, brimonidine, or both.
The patent’s strongest infringement case would involve a product with matching excipients, BAC concentration, pH, viscosity, and suspension behavior.
The numerical and performance limitations create meaningful design-around options.
Brinzolamide and brimonidine are small molecules, so biosimilar analysis is not applicable.
The claim text does not establish current Orange Book listing, litigation, settlement, patent-term adjustment, or exact expiration.
Generic risk depends on the reference-listed drug, Orange Book records, ANDA certifications, formulation testing, and the patent’s live legal status.

FAQs About US Patent 9,421,265

Does US 9,421,265 cover all brinzolamide eye drops?

No. The claims require a defined suspension system, excipient combination, BAC range, borate, and other limitations. A brinzolamide solution or a suspension using different excipients may fall outside the claims.

Can a product avoid the patent by removing benzalkonium chloride?

Potentially, because BAC is required by the independent claims. The product would still require analysis against other patent claims, continuation patents, and separate regulatory requirements for multi-dose antimicrobial preservation.

Does the patent cover Simbrinza?

The claimed combination of brinzolamide, brimonidine, mannitol, propylene glycol, borate, BAC, and a carboxyvinyl polymer is technically relevant to a Simbrinza-type product. Actual infringement or Orange Book coverage requires comparison with the approved product formulation and the patent’s legal status.

Are claims 18 and 19 independent method-of-use claims?

No. They depend on claim 13 and inherit its composition limitations. The chronic-administration and elevated-intraocular-pressure limitations narrow the composition claims rather than create a standalone method claim.

What is the most important non-infringement strategy?

The most direct strategies are changing the preservative system, replacing the polyol combination, using a different suspending polymer, or moving outside the claimed pH and viscosity ranges while maintaining regulatory product performance.

References

United States Patent No. 9,421,265, claims 1-20. U.S. Patent and Trademark Office, 2016.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term expiration information. USPTO.

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	SIMBRINZA	brimonidine tartrate; brinzolamide	SUSPENSION/DROPS;OPHTHALMIC	204251-001	Apr 19, 2013		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	077126	⤷ Start Trial
Argentina	122017	⤷ Start Trial
Australia	2010262898	⤷ Start Trial
Brazil	PI1015996	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,421,265

Which drugs does patent 9,421,265 protect, and when does it expire?

Summary for Patent: 9,421,265