United States Patent 9,233,068: Claim Scope, Exclusivity, and Otic Drug Patent Landscape

U.S. Patent No. 9,233,068 protects a sterile, preservative-free or preservative-containing aqueous otic depot using a thermoreversible gel, micronized non-microencapsulated antimicrobial, injectable room-temperature viscosity, body-temperature gelation, and at least five days of antimicrobial release.[1] The broadest independent claim is formulation-based and is not limited to ciprofloxacin, Poloxamer 407, otitis media, or any single dosage strength.

The patent’s commercial relevance is highest for injectable or intratympanic otic products that form an in-ear depot after administration. The claims reach multiple antibiotic and antifungal classes, but infringement depends on satisfying every limitation in claim 1, including the quantitative viscosity ranges and sustained-release requirement.

What does U.S. Patent 9,233,068 protect?

The patent protects a sterile aqueous pharmaceutical composition for treating an otic disease or condition. Claim 1 requires all of the following:

Claim element	Scope
Dosage form	Sterile aqueous pharmaceutical composition
Therapeutic use	Treatment of an otic disease or condition
Delivery vehicle	Thermoreversible gel
Active ingredient	Micronized, non-microencapsulated antimicrobial agent
Gelation temperature	Between approximately room temperature and body temperature
Administration property	Injectable at or about room temperature
Needle compatibility	Needle gauge from 18 through 31
Non-gelation viscosity	Must permit injection at room temperature; no numerical range is stated
Gelation viscosity	Approximately 15,000 to 1,000,000 cP
Release profile	Sustained antimicrobial release into the ear for at least five days

The claim is drafted using “comprising.” That term generally permits additional excipients, active ingredients, buffers, surfactants, tonicity agents, or other formulation components unless another claim or specification limitation excludes them.

The patent does not require a named commercial antibiotic in claim 1. The antimicrobial may be an antibiotic or antifungal, subject to the micronized and non-microencapsulated limitations.

How broad is claim 1 of U.S. Patent 9,233,068?

Claim 1 is technically broad in active-ingredient selection but narrower in formulation performance.

It covers a platform rather than a single molecule. A composition could potentially fall within claim 1 even if it uses an antimicrobial not expressly listed in claims 7, 8, 9, 10, 11, or 13, provided the antimicrobial satisfies the claim’s structural and functional requirements.

The principal narrowing limitations are:

The antimicrobial must be micronized.
The antimicrobial must not be microencapsulated.
The gel must be thermoreversible.
The formulation must be injectable at approximately room temperature through an 18- to 31-gauge needle.
The gel must reach a viscosity of approximately 15,000 to 1,000,000 cP after gelation.
The formulation must provide at least five days of sustained release into the ear.

A competing formulation that uses nanoparticles, microspheres, liposomes, a nonthermoreversible hydrogel, or a liquid suspension without gelation may avoid one or more express limitations. That conclusion would depend on product composition, test methods, and claim construction.

What does “micronized and non-microencapsulated” mean?

“Micronized” generally indicates that the antimicrobial is present as particles reduced to a micrometer-scale size. “Non-microencapsulated” excludes an antimicrobial enclosed within a microcapsule or similar discrete coating structure.

The claim therefore targets direct incorporation of fine antimicrobial particles into the thermoreversible gel. It does not, on its face, require the active ingredient to be dissolved. A suspension of micronized particles in the gel may satisfy the limitation if the other requirements are met.

This limitation creates design-around opportunities through:

Dissolved antimicrobial formulations
Molecular complexes
Liposomal or nanoparticle systems
Microencapsulated particles
Drug-loaded microspheres
Covalent prodrugs
Nonparticulate active forms

Whether a nanoparticle system is “microencapsulated” would depend on the particle architecture and the intrinsic meaning assigned to the claim term.

What formulations are protected by claims 2 through 4?

Poloxamer 407 formulations

Claim 2 narrows claim 1 to a thermoreversible gel containing a copolymer of polyoxyethylene and polyoxypropylene. Claim 3 narrows the composition further to Poloxamer 407.

Poloxamer 407 is a triblock copolymer commonly used in temperature-responsive pharmaceutical gels. It is liquid or relatively low-viscosity at lower temperatures and forms a more viscous gel near physiological temperature.

A Poloxamer 407 product is not automatically infringing. It must also satisfy the claim 1 requirements, including:

Micronized, non-microencapsulated antimicrobial
Room-temperature injection through the specified needle gauge
Gelation viscosity of approximately 15,000 to 1,000,000 cP
At least five days of sustained release into the ear
Sterility and aqueous composition requirements

Preservative-free formulations

Claim 4 covers a composition that is free of preservatives. This claim is commercially relevant to single-dose otic products, especially formulations intended for intratympanic or middle-ear administration.

A preservative-free composition that satisfies claim 1 may fall within claim 4. Claim 4 does not require Poloxamer 407, a specific antibiotic, or otitis media. It depends on claim 1 and therefore inherits all of claim 1’s limitations.

Which antimicrobial drugs fall within the patent?

Claims 5 through 13 identify broad antimicrobial categories and specific compounds.

Claim group	Covered class or examples
Claim 5	Antibiotics
Claim 6	Sulfonamides, penicillins, quinolones, cephalosporins, macrolides
Claim 7	Sulfacetamide, sulfisoxazole, trimethoprim, cotrimoxazole and other sulfonamides
Claim 8	Amoxicillin, ampicillin, nafcillin, oxacillin, ticarcillin and other penicillins
Claim 9	Ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin and other quinolones
Claim 10	Cefuroxime, cefixime, cefdinir, ceftriaxone, cefepime and other cephalosporins
Claim 11	Azithromycin, clarithromycin, erythromycin and other macrolides
Claim 12	Antifungal agents
Claim 13	Azoles, polyenes, echinocandins, allylamines and other antifungals

The listed compounds are claim-dependent examples, not independent alternatives to claim 1. For example, a ciprofloxacin formulation must still be sterile, aqueous, thermoreversible, injectable within the specified parameters, sustained-release for at least five days, and formulated with micronized non-microencapsulated ciprofloxacin.

The list also contains apparent spelling or nomenclature errors, including “amrolfine,” “nystastin,” “peperacillin,” and “ceftobirprole.” The legal effect of those entries would depend on the issued patent record, prosecution history, specification, and how a court construes each term.

What otic diseases are covered?

Claims 14 and 15 narrow the invention to:

Otitis media
Otitis media with effusion

Claim 15 is narrower than claim 14 because otitis media with effusion is a specific subtype or clinical presentation within the broader otitis media field.

The claims are not limited to external ear infections. The wording “into the ear” and the inclusion of otitis media and otitis media with effusion support relevance to middle-ear delivery. A product intended for otitis externa could still fall within claim 1 if it satisfies the claimed formulation and release properties.

The patent does not expressly require:

Intratympanic injection
Transtympanic administration
Myringotomy
Tympanostomy-tube delivery
A particular ear compartment
A particular administration volume
A particular dosing frequency

Those factors may be relevant to infringement analysis but are not express limitations in the supplied claims.

How does the patent compare with conventional otic antibiotics?

Product architecture	Likely relationship to claim 1
Conventional aqueous ear drops	Usually lacks thermoreversible gel and five-day depot release
Oil-based otic formulation	May fail the aqueous-composition limitation
Immediate-release suspension	May fail sustained-release limitation
Thermosensitive Poloxamer gel	Higher relevance; requires testing against all claim limitations
Microencapsulated antimicrobial depot	May fail the non-microencapsulated limitation
Liposomal antimicrobial	May avoid the claimed direct micronized-particle architecture
Injectable intratympanic depot	High technical relevance
Nonsterile veterinary ear gel	Fails the sterile pharmaceutical composition limitation
Solid implant	May fail the aqueous composition and injectable viscosity limitations

The patent is strongest against products that reproduce the same delivery concept: a sterile thermoreversible aqueous gel containing micronized antimicrobial particles that is injected while fluid and gels after reaching body temperature.

When does U.S. Patent 9,233,068 lose exclusivity?

The patent issued on January 12, 2016.[1] U.S. patent term generally runs for 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments.[2]

The issue date alone does not establish the expiration date. The operative term must be calculated from the patent’s priority and filing history and confirmed against the USPTO patent record. A patent-term extension under 35 U.S.C. § 156 could be relevant if the patented product and regulatory history satisfy the statutory requirements.

A patent expiration analysis should distinguish:

Exclusivity type	Relevance
Patent term	Determines enforceable exclusion rights
FDA new-drug exclusivity	Restricts certain abbreviated applications for a defined period
Pediatric exclusivity	Adds six months to qualifying regulatory exclusivities and listed patents
Orphan-drug exclusivity	May restrict approval for the same orphan indication
Patent-term adjustment	Adds time for qualifying USPTO delays
Patent-term extension	May restore part of regulatory-review time for an approved product

The patent claims provided do not establish any FDA exclusivity period, Orange Book listing, or patent-term adjustment.

What is the Orange Book status of this patent?

Orange Book listing is product-specific. A patent is listed only if it is submitted for an approved drug product and meets FDA listing requirements.[3]

The claims are formulation and method-of-use oriented. A listing analysis would require comparison of the patent claims with the approved product’s:

Active ingredient
Dosage form
Route of administration
Formulation
Approved indication
Labeling

If the patent is listed for an approved otic product, an ANDA applicant could face a Paragraph IV certification. If it is not listed, the patent may still be enforceable against commercial conduct, but it would not necessarily create the same ANDA litigation pathway.

A patent listing would be particularly relevant where the approved product uses:

A sterile aqueous depot
Poloxamer 407
Micronized ciprofloxacin or another listed antimicrobial
Preservative-free single-dose packaging
Otitis media or otitis media with effusion labeling

What Paragraph IV challenges and litigation risks exist?

A Paragraph IV challenge would likely attack one or more of the following limitations:

Lack of thermoreversibility

The accused product may remain a liquid at body temperature or use a gel that does not undergo the claimed temperature-dependent transition.

Viscosity outside the claimed range

A formulation may be injectable but have a gelation viscosity below 15,000 cP or above 1,000,000 cP. Measurement conditions would matter, including temperature, shear rate, equilibration time, and instrument geometry.

Failure to meet the five-day release period

A generic or follow-on product may release most of the antimicrobial within hours or one to four days. Conversely, a product with a longer release profile could still satisfy “at least 5 days.”

Microencapsulation or alternative particle engineering

A product using coated particles, microspheres, liposomes, or nanoparticles could dispute whether its antimicrobial is micronized and non-microencapsulated.

Non-otic labeling

A product labeled only for an indication outside the patent’s otic-use limitations may reduce method-of-use risk, but a formulation claim remains potentially relevant independent of labeling.

Invalidity defenses

Potential validity issues include:

Obviousness based on thermoreversible gels, Poloxamer systems, and otic antibiotics
Written-description support for the full range of antimicrobial agents
Enablement across the viscosity, temperature, and release ranges
Indefiniteness of terms such as “about,” “room temperature,” “body temperature,” and “sustained release”
Anticipation by prior otic depot formulations

The strength of these defenses depends heavily on the specification, prosecution amendments, cited prior art, and expert testing.

How strong is the patent estate?

Based on the supplied claims, the estate appears strongest as a platform patent if the patent family includes corresponding claims covering:

Specific ciprofloxacin or quinolone formulations
Poloxamer 407 concentrations
Intratympanic administration
Specific release testing methods
Otitis media treatment
Preservative-free single-dose packaging
Manufacturing and sterilization processes

Claim 1 has substantial breadth across antimicrobial classes but also contains multiple objective performance constraints. Those constraints improve technical specificity and may help distinguish prior art. They also create several noninfringement paths.

The dependent claims provide fallback positions, particularly claims 3, 4, 9, 14, and 15. A composition using Poloxamer 407, ciprofloxacin, no preservative, and treatment for otitis media with effusion would implicate the densest cluster of dependent limitations.

What generic launch scenarios exist?

Launch scenario	Patent exposure
Conventional ciprofloxacin ear drops	Lower exposure to the formulation claims
Immediate-release ciprofloxacin suspension	Potential defense based on release duration
Injectable Poloxamer 407 ciprofloxacin depot	Highest exposure
Microencapsulated ciprofloxacin depot	Possible defense to non-microencapsulation limitation
Dissolved ciprofloxacin thermogel	Possible defense to micronized-particle limitation
Non-Poloxamer thermogel	Avoids claims 2 and 3 but not necessarily claim 1
Product for otitis externa only	May reduce claims 14 and 15 exposure but not claim 1
Nonsterile or preservative-containing product	Does not meet claim 4, but may still meet claim 1

A generic applicant would need to assess both literal infringement and the doctrine of equivalents. The most important technical evidence would be formulation microscopy, particle-size distribution, gel-transition data, viscosity testing, needle-force testing, sterility records, and in-ear release studies.

What manufacturing and IP barriers are relevant?

Manufacturing barriers include:

Maintaining antimicrobial particle-size distribution
Preventing aggregation during sterilization and storage
Achieving reproducible gelation temperature
Controlling viscosity across temperature ranges
Demonstrating injection through the claimed needle gauges
Preserving sterility in a low-temperature or aseptic process
Producing a stable suspension without microencapsulation
Validating at least five days of release in a relevant ear model

A competitor may avoid the patent through a different delivery architecture, but that can create new regulatory and manufacturing risks. A dissolved drug, nanoparticle system, implant, or alternative polymer may require separate stability, toxicology, device, and clinical-development work.

Key Takeaways

U.S. Patent 9,233,068 is a formulation-platform patent for sustained-release antimicrobial otic depots.
Claim 1 is not limited to ciprofloxacin, Poloxamer 407, otitis media, or any stated concentration.
The central technical combination is a sterile aqueous thermoreversible gel with micronized, non-microencapsulated antimicrobial particles.
The quantitative gelation-viscosity range is 15,000 to 1,000,000 cP.
The formulation must be injectable at approximately room temperature through an 18- to 31-gauge needle.
Sustained release must continue into the ear for at least five days.
Claims 3, 4, 9, 14, and 15 create the most commercially relevant fallback positions for a Poloxamer 407, ciprofloxacin, preservative-free otitis media product.
Conventional ear drops and immediate-release suspensions are structurally differentiated from the claimed depot system.
The issue date was January 12, 2016, but the precise expiration date requires the patent’s filing history, patent-term adjustment, terminal-disclaimer status, and any patent-term extension.
A Paragraph IV strategy would likely focus on viscosity, gelation, particle form, release duration, and claim validity.

FAQs About U.S. Patent 9,233,068

Does the patent cover ciprofloxacin ear drops?

Not all ciprofloxacin ear drops. Coverage requires the full claim 1 combination, including a thermoreversible gel, micronized non-microencapsulated antimicrobial, specified injectable and gelation properties, and at least five days of sustained release.

Does using Poloxamer 407 automatically infringe the patent?

No. Poloxamer 407 is specifically recited in claim 3, but infringement still requires satisfaction of claim 1 and the other applicable limitations.

Can a microencapsulated antibiotic avoid the patent?

It may avoid the express “non-microencapsulated” limitation, subject to the product’s actual structure and the possible application of the doctrine of equivalents.

Are antifungal otic depots covered?

Yes, claims 12 and 13 extend the dependent-claim coverage to antifungal agents, including azoles, polyenes, echinocandins, allylamines, and other listed compounds.

Is the patent relevant to otitis externa?

Potentially. Claim 1 covers treatment of an otic disease or condition without limiting the disease to otitis media. Claims 14 and 15 specifically narrow coverage to otitis media and otitis media with effusion.

References

United States Patent and Trademark Office. (2016). U.S. Patent No. 9,233,068.
35 U.S.C. §§ 154, 156 (2024).
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Alk Abello	OTIPRIO	ciprofloxacin	INJECTABLE, SUSPENSION;OTIC	207986-001	Dec 10, 2015		DISCN	Yes	No	9,233,068	⤷ 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	071388	⤷ Start Trial
Argentina	072253	⤷ Start Trial
Argentina	072828	⤷ Start Trial
Australia	2009239429	⤷ Start Trial
Australia	2009246870	⤷ Start Trial
Australia	2009271129	⤷ Start Trial
Australia	2009274137	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,233,068

Which drugs does patent 9,233,068 protect, and when does it expire?

Summary for Patent: 9,233,068