Details for Patent: 9,220,796

Which drugs does patent 9,220,796 protect, and when does it expire?

Patent 9,220,796 protects OTIPRIO and is included in one NDA.

This patent has ten patent family members in seven countries.

Summary for Patent: 9,220,796

Title:	Sterilization of ciprofloxacin composition
Abstract:	Disclosed herein are methods of making sterilized ciprofloxacin compositions. In some embodiments, the method includes the steps of: (a) forming an aqueous suspension comprising ciprofloxacin particles; (b) heating the aqueous suspension comprising ciprofloxacin particles at a temperature range of from about 100° C. to about 120° C.; and (c) allowing the aqueous suspension comprising ciprofloxacin particles to cool down. Also described herein are otic formulations containing ciprofloxacin formed by the disclosed methods, and therapeutic use of such otic formulation for providing sustained release of ciprofloxacin into the ear for treating various otic disorders and conditions.
Inventor(s):	Scott H. Coleman, Wei-Cheng Liaw, Jerry Wroblewski, Robert Savel
Assignee:	ALK Abello Inc
Application Number:	US14/789,771
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

US Patent 9,220,796: Ciprofloxacin Otic Formulation Claims, Expiration, Litigation and Generic Entry Risk

US Patent No. 9,220,796 protects a manufacturing process and resulting sustained-release ciprofloxacin otic formulation. Its core technology combines heat-treated ciprofloxacin hydrate particles with a separately sterilized thermoreversible polymer solution, principally poloxamer 407. The patent is directed to the formulation and manufacturing architecture associated with Otiprio, a 6% ciprofloxacin otic suspension marketed for pediatric tympanostomy-tube procedures.

The patent’s strongest protection is concentrated in the combination of: heat treatment at approximately 100°C to 120°C; controlled ciprofloxacin particle size; post-heating particle-size reduction; aseptic combination with sterilized poloxamer 407; and a final formulation with defined ciprofloxacin, polymer, pH, osmolarity and sustained-release characteristics.

The base patent term appears to run through approximately March 2032, subject to any patent-term adjustment, terminal disclaimer or other USPTO-recorded term modification. FDA and Orange Book status must be evaluated separately from patent validity and enforceability. [1-3]

What drug and technology does US Patent 9,220,796 protect?

US 9,220,796 covers ciprofloxacin otic formulations using multiparticulate ciprofloxacin dispersed in a thermoreversible polymer matrix. The claims are consistent with Otiprio’s formulation, which contains ciprofloxacin at approximately 6% and uses poloxamer 407 as the sustained-release vehicle. [1,4]

Patent identification

Item	Information
Patent	US 9,220,796
Technology	Sterilized ciprofloxacin otic formulation
Primary active ingredient	Ciprofloxacin
Principal polymer	Poloxamer 407
Dosage form	Sustained-release otic suspension
Commercial product associated with technology	Otiprio
FDA application	NDA 207435
Patent type	Manufacturing method, composition, and ready-to-use product claims
Issue date	December 29, 2015
Approximate base expiration	March 2032, subject to USPTO term adjustments or disclaimers

The patent does not broadly cover every ciprofloxacin ear product. Its claims are limited by the selected sterilization sequence, particle properties, polymer system, composition ranges and sustained-release performance.

What is the independent claim scope of US 9,220,796?

Claim 1 is the principal process claim. It requires all of the following steps:

1. Forming an aqueous suspension containing ciprofloxacin particles.
2. Heating that suspension to approximately 100°C to 120°C.
3. Cooling the suspension.
4. Combining the cooled suspension with a separately sterilized aqueous solution containing a thermoreversible polymer.
5. Producing an otic formulation.

The claim is narrower than a general claim to sterilized ciprofloxacin suspension. A competing manufacturer would need to assess whether its process uses each required step, including the heat-treatment and post-cooling combination sequence.

Claim 28 is the principal composition claim, but it is expressly tied to the method of claim 1. It requires a sterilized formulation containing:

• 5.5 wt% to 6.5 wt% multiparticulate ciprofloxacin;
• 15 wt% to 17 wt% poloxamer 407;
• water;
• pH of 7.0 to 8.0;
• osmolarity of 270 to 320 mOsm/L; and
• sustained release of a therapeutically effective ciprofloxacin amount into the ear for at least five days after one administration.

Claim 30 extends protection to a ready-to-use product consisting of an aseptic vial containing the claim 28 formulation.

Independent claims at a glance

Claim	Claim category	Core limitation
1	Manufacturing method	Heat ciprofloxacin suspension, cool it, then combine with sterilized thermoreversible-polymer solution
28	Formulation	5.5%-6.5% ciprofloxacin, 15%-17% poloxamer 407, specified pH, osmolarity and five-day release
30	Product or kit	Aseptic vial containing the claim 28 formulation

What limitations narrow the patent claims?

The dependent claims create multiple narrower claim positions around particle size, processing conditions and product characteristics.

Particle-size limitations

Claims 6 and 7 require an initial ciprofloxacin particle-size distribution with a D90 of approximately 40 to 80 micrometers or 50 to 70 micrometers. Claim 17 requires the particles after cooling to have a D90 of approximately 5 to 40 micrometers.

This creates a process signature:

Processing stage	Claimed D90
Before or during heat treatment	40-80 µm, or 50-70 µm
After cooling	5-40 µm

The reduction in D90 is commercially significant because it links heat treatment and homogenization to the final multiparticulate suspension. A competitor using pre-micronized particles that remain substantially unchanged during processing could argue that it does not practice the claimed particle-size transition, although infringement would depend on the full claim language and evidence of the actual process.

Concentration and composition limitations

Claims 4 and 5 require ciprofloxacin concentrations of 4 wt% to 30 wt% or 10 wt% to 16 wt% in the initial aqueous suspension. Claim 24 narrows the final formulation to 5.5 wt% to 6.5 wt% ciprofloxacin. Claim 25 requires 15 wt% to 17 wt% poloxamer 407.

The claim set therefore protects both a relatively concentrated intermediate suspension and a final approximately 6% ciprofloxacin formulation.

Thermal-processing limitations

Claims 8 through 13 cover:

• 105°C to 115°C;
• 30 minutes to five hours;
• approximately 115°C for one hour;
• approximately 110°C for one to two hours;
• constant temperature operation; and
• variable temperature operation within the claimed range.

The broadest temperature range in claim 1 is approximately 100°C to 120°C. Claims 10 and 11 provide narrower fallback positions around the likely commercial process.

Sterilization and aseptic-combination limitations

Claims 21 and 22 cover filtration, heat and radiation sterilization of the thermoreversible-polymer solution, with claim 22 narrowing the method to filtration sterilization. Claim 23 requires aseptic combination of the cooled ciprofloxacin suspension and sterilized polymer solution.

This split sterilization architecture is central to the patent. The claims do not simply require sterilizing the finished formulation. They require, in the principal process, sterilizing the polymer solution separately and combining it with the cooled ciprofloxacin suspension under aseptic conditions.

What formulations are protected by US 9,220,796?

The most commercially relevant formulation is a sterilized ciprofloxacin suspension containing poloxamer 407 within the claimed concentration range.

Formulation attribute	Claim 28 range
Ciprofloxacin	5.5-6.5 wt%
Poloxamer 407	15-17 wt%
pH	7.0-8.0
Osmolarity	270-320 mOsm/L
Release duration	At least five days
Dosage presentation	Aseptic vial

Claims 19 and 20 cover optional buffer agents and osmolarity modifiers. These claims may capture common formulation adjustments if the other claim limitations are present.

The patent does not require a particular buffer or osmolyte in the independent claims. It also does not require poloxamer 407 in claim 1 because that claim refers more broadly to a thermoreversible polymer. Poloxamer 407 becomes mandatory in claim 18 and claim 25, and in the composition claim 28.

How strong is the patent estate for ciprofloxacin otic products?

The patent has moderate-to-strong product-specific coverage but limited platform breadth.

Strengths

The strongest elements are:

• The combination of process and composition claims.
• Specific linkage between heat treatment and particle-size reduction.
• Defined final ciprofloxacin and poloxamer 407 concentrations.
• Aseptic combination of separately treated components.
• A five-day sustained-release performance limitation.
• Coverage of the ready-to-use vial presentation.

These limitations may make a simple copy of the commercial product commercially risky.

Weaknesses and potential validity pressure points

Potential pressure points include:

• Whether the claimed heat-treatment sequence was obvious in view of sterilization and suspension-processing techniques.
• Whether prior art disclosed ciprofloxacin particles, poloxamer 407, sustained otic release and comparable concentrations.
• Whether “thermoreversible polymer,” “multiparticulate” and “sustained release” provide adequate claim clarity.
• Whether the product-by-process language in claim 28 can be enforced against a product made by a different process.
• Whether the five-day release limitation is sufficiently definite and reproducible.
• Whether the claimed particle-size distributions are measured by a consistent analytical method.
• Whether a later manufacturer can demonstrate non-infringement through a different sterilization sequence or a materially different particle-size profile.

The claim estate is therefore stronger against a close Otiprio copy than against a substantially redesigned ciprofloxacin otic product.

When does US Patent 9,220,796 lose exclusivity?

The patent’s ordinary 20-year term is calculated from the relevant nonprovisional filing date, not its issue date. Based on the patent’s filing chronology, the unadjusted expiration is approximately March 2032. The precise expiration date must be taken from the USPTO patent record because patent-term adjustment, terminal disclaimers and other recorded events can change the effective end date. [1,2]

Exclusivity component	Status
Patent protection	Approximately through March 2032, subject to USPTO-recorded term
FDA new-drug exclusivity	Otiprio received conventional approval-related exclusivity, which is shorter than the patent term
Pediatric exclusivity	Any six-month pediatric extension must be confirmed in FDA records and applied to eligible listed patents
Regulatory exclusivity after patent expiry	No biologic exclusivity applies
Biosimilar exclusivity	Not applicable; ciprofloxacin is a small molecule

Patent expiry does not automatically produce generic entry. An ANDA applicant may attempt entry before expiration through a Paragraph IV certification, subject to notice, litigation and any settlement terms.

What is the Orange Book status of Otiprio and this patent?

Otiprio was approved by FDA under NDA 207435 as a ciprofloxacin otic suspension for administration during tympanostomy-tube placement. The FDA label identifies a 6% ciprofloxacin formulation and single-administration use in the middle ear. [4]

The Orange Book is the controlling source for determining whether US 9,220,796 is currently listed against NDA 207435, the listed expiration date, and any use code or patent-status update. Orange Book listings can change through patent-listing updates, NDA status changes and FDA administrative actions. [3]

Regulatory implications

For an ANDA applicant, a listed patent may require one of the following:

• Paragraph III certification, deferring approval until patent expiry;
• Paragraph IV certification, asserting invalidity, unenforceability or non-infringement;
• A section viii statement, if the patent claims only a method of use that the applicant omits; or
• A different regulatory pathway if the proposed product cannot rely on ANDA suitability.

Because US 9,220,796 includes manufacturing and composition claims, a section viii strategy would not ordinarily remove all patent risk if the patent remains listed and relevant to the proposed product.

Which companies are challenging US 9,220,796?

No specific Paragraph IV challenger, district-court case or settlement agreement can be identified reliably from the supplied claim text alone. A definitive challenger analysis requires the current Orange Book patent listing, FDA Paragraph IV notice information and PACER or district-court docket records.

The commercial landscape nevertheless has a clear structure:

Company or group	Position
Otonomy	Original developer and commercial sponsor associated with Otiprio
Generic manufacturers	Potential ANDA applicants facing formulation, process and listed-patent barriers
Other otic-drug companies	Compete through non-identical products such as ciprofloxacin/dexamethasone or alternative delivery systems
Biosimilar developers	Not relevant because ciprofloxacin is a small-molecule drug

A generic applicant could challenge the patent without copying every commercial feature. The central litigation questions would likely concern claim construction, process evidence, particle-size testing, product-by-process interpretation and obviousness.

What generic launch scenarios exist for ciprofloxacin otic products?

Scenario 1: Paragraph III certification

An applicant accepts the patent and seeks approval timed to the listed patent expiration. This is the lowest litigation-risk route but delays entry.

Scenario 2: Paragraph IV challenge

An applicant alleges that the patent is invalid, unenforceable or not infringed. Filing an ANDA with Paragraph IV certification can trigger Hatch-Waxman litigation. A timely infringement action may impose a 30-month stay of FDA approval, subject to statutory exceptions. [5]

Scenario 3: Design-around formulation

A competitor could seek to avoid one or more limitations by using:

• A non-thermoreversible vehicle;
• A thermoreversible polymer other than poloxamer 407;
• A different ciprofloxacin concentration;
• A different pH or osmolarity;
• A different particle-size distribution;
• A different sterilization sequence;
• Terminal sterilization of the finished formulation;
• A non-aseptic combination process where legally and technically feasible; or
• A different sustained-release delivery system.

A design-around must be assessed against every claim, including broader claim 1 and narrower dependent claims.

Scenario 4: Alternative ciprofloxacin product

A product may avoid this patent while still competing clinically if it uses a different dosage form or administration method. Ciprofloxacin/dexamethasone suspensions, solutions, gels and other otic delivery systems may compete with Otiprio but do not necessarily practice the claimed process or formulation.

What patent litigation and settlement issues matter?

A Paragraph IV case involving this patent would likely focus on four areas.

First, the challenger would test whether the prior art disclosed heating ciprofloxacin particles in water, cooling and combining the suspension with a separately sterilized poloxamer solution.

Second, the parties would dispute whether the final formulation’s physical properties are inherent or process-dependent. If the claims require the product to be “formed by the method,” evidence of the manufacturing route may be critical.

Third, particle-size testing could become central. D90 values can depend on dispersion conditions, measurement technology and sampling. The patent’s pre- and post-cooling particle-size limitations create potentially material factual disputes.

Fourth, the sustained-release requirement in claim 28 may require comparative release or in vivo evidence. A product that has similar composition but does not provide the claimed five-day release profile may have a non-infringement position, although functional limitations are fact-specific.

No settlement agreement should be presumed. A settlement could provide a licensed entry date, authorized-generic arrangement, supply agreement or restrictions on product design, but its terms would need to be confirmed in public court filings or company disclosures.

How does this patent compare with competing otic patent strategies?

US 9,220,796 is narrower than a broad active-ingredient patent but more commercially targeted. Its value comes from protecting a specific delivery system rather than ciprofloxacin itself, which is long off-patent.

Patent strategy	Typical scope	Relevance to US 9,220,796
Active-ingredient patent	Chemical compound	Not applicable to old ciprofloxacin
Salt, crystal or polymorph patent	Solid-state form	Partially relevant through ciprofloxacin hydrate
Formulation patent	Ingredients and physical properties	Directly relevant
Manufacturing patent	Sterilization and processing sequence	Directly relevant
Method-of-use patent	Disease or administration method	Secondary; US 9,220,796 is not principally a use patent
Device or delivery patent	Applicator, implant or delivery hardware	Separate risk category
Biologic patent	Protein or antibody product	Not applicable

The patent is best viewed as a product-specific formulation and manufacturing barrier. It does not create biosimilar exposure, and it does not prevent all ciprofloxacin otic products.

What manufacturing and geographic IP barriers exist?

US 9,220,796 is a US patent. It directly affects US manufacture, importation, sale and use of a covered product during the enforceable term. A manufacturer outside the US may still face infringement exposure if it exports a covered product into the US or supplies material for US commercial use.

Foreign protection must be reviewed separately through the patent family. A US patent does not establish protection in the European Union, Canada, Japan, China or other jurisdictions. The relevant questions are whether corresponding national applications were filed, whether patents issued, whether they remain in force and whether claim scope tracks the US claims.

Manufacturing evidence can be especially important because claim 1 is process-based. Batch records, master production records, sterilization validations, particle-size data and supplier specifications may establish or refute infringement.

What is the revenue exposure from this patent?

The patent’s revenue exposure is tied to Otiprio and to any future product that copies its approximately 6% ciprofloxacin and poloxamer 407 formulation. The product’s commercial value depends on its single-administration use during tympanostomy-tube surgery, rather than chronic outpatient dosing.

A generic entrant could pressure pricing even if it does not fully replicate the branded formulation. Competing products may also limit the economic value of the patent by offering different ciprofloxacin or antibiotic-steroid formulations.

The key investment variables are:

• Current Otiprio sales and market share;
• Whether the product remains actively marketed;
• Whether the NDA and Orange Book listing remain active;
• The exact patent expiration date;
• Any pediatric exclusivity extension;
• Presence of authorized-generic or settlement rights;
• Number of potential ANDA entrants; and
• Clinical switching between Otiprio and alternative otic products.

Key Takeaways

• US 9,220,796 protects a heat-treated, sterilized, sustained-release ciprofloxacin otic formulation and its manufacturing process.
• Claim 1 requires heating an aqueous ciprofloxacin suspension, cooling it, and aseptically combining it with a separately sterilized thermoreversible-polymer solution.
• Claim 28 is the principal commercial composition claim and requires approximately 6% ciprofloxacin, 15%-17% poloxamer 407, pH 7.0-8.0, osmolarity of 270-320 mOsm/L and at least five days of sustained release.
• Claim 30 covers a ready-to-use aseptic vial containing the claimed formulation.
• The unadjusted patent term appears to extend to approximately March 2032, subject to the USPTO patent-term record.
• Ciprofloxacin is a small molecule, so biosimilar risk does not apply. Generic ANDA and Paragraph IV risk does.
• The patent is strongest against a close Otiprio copy and weaker against a product using a different polymer, sterilization sequence, particle-size profile or release system.
• Orange Book listing and litigation status must be confirmed against current FDA and court records before relying on an entry date or challenge assessment.

FAQs

Can a generic use ciprofloxacin without infringing US 9,220,796?

Yes. Ciprofloxacin itself is not protected by this patent. Infringement risk depends on whether the generic practices the claimed process or matches the claimed formulation and product limitations.

Does using poloxamer 407 automatically infringe the patent?

No. Poloxamer 407 alone is insufficient. The relevant claim requires the specified ciprofloxacin concentration, polymer concentration, product characteristics and, for claim 28, the claimed method-linked formulation.

Can a competitor sterilize the final ciprofloxacin formulation instead of the polymer solution?

That process may provide a design-around position, but it must be tested against the full language of claim 1 and any other applicable patent claims. The sterilization sequence is a central limitation of US 9,220,796.

Does a five-day release profile create a separate method-of-use patent?

No. In US 9,220,796, the five-day release requirement appears as a limitation of composition claim 28. It is not, by itself, a separate treatment-method claim.

Is Otiprio protected by a biosimilar pathway?

No. Otiprio contains ciprofloxacin, a small-molecule active ingredient. A competing applicant would generally evaluate the ANDA pathway rather than the biosimilar pathway.

References

1. United States Patent and Trademark Office. (2015). U.S. Patent No. 9,220,796: Sterilized ciprofloxacin otic formulations.
2. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information resources. https://www.uspto.gov/patents/laws/patent-term-calculator
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
4. U.S. Food and Drug Administration. (2015). Otiprio (ciprofloxacin otic suspension) prescribing information.
5. U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application approvals and Paragraph IV certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/anda-approvals---patent-and-exclusivity-information

Drugs Protected by US Patent 9,220,796

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	9,220,796		Y

International Family Members for US Patent 9,220,796

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2015284048
Australia	2019275578
Australia	2021273549
Canada	2954170
China	106794144
European Patent Office	3164115