Details for Patent: 8,178,582

Which drugs does patent 8,178,582 protect, and when does it expire?

Patent 8,178,582 protects IZBA and is included in one NDA.

This patent has thirty-nine patent family members in twenty-three countries.

Summary for Patent: 8,178,582

Title:	Pharmaceutical compositions having desirable bioavailability
Abstract:	The present invention is directed to the provision of pharmaceutical compositions. The compositions include a therapeutic agent and a relatively low amount of surfactant for providing higher bioavailability of the therapeutic agent. The compositions are particularly desirable as ophthalmic compositions in which the therapeutic agent is a prostaglandin such as travoprost and the surfactant is a vegetable oil such as castor oil.
Inventor(s):	Bhagwati P. Kabra
Assignee:	Novartis AG
Application Number:	US12/403,529
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,178,582
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

US Patent 8,178,582: Scope, Claims, Expiration and Ophthalmic Patent Landscape

US Patent 8,178,582 protects benzalkonium-chloride-free ophthalmic prostaglandin formulations for glaucoma that combine polyquaternium-1 or another polymeric quaternary ammonium preservative with a narrowly defined ethoxylated or hydrogenated vegetable-oil surfactant. The strongest commercial embodiment is a preserved, aqueous travoprost formulation containing Polyoxyl 40 Hydrogenated Castor Oil, with the surfactant as the only material surfactant.

The patent is primarily a formulation patent. It does not broadly cover travoprost, prostaglandin glaucoma therapy, or all preservative-free or BAK-free eye drops. Its scope depends on the combined presence of:

• An aqueous ophthalmic vehicle;
• A prostaglandin glaucoma agent;
• A polymeric quaternary ammonium preservative;
• An ethoxylated and/or hydrogenated vegetable-oil surfactant;
• Surfactant concentration within the claimed range;
• No benzalkonium chloride;
• Substantially no other surfactant.

What does US Patent 8,178,582 cover?

The patent covers a specific formulation architecture designed to solubilize and preserve poorly water-soluble prostaglandins while avoiding benzalkonium chloride, or BAK.

The independent claims are claims 1 and 14.

Claim	Core subject matter	Key concentration limitation	Prostaglandin limitation
1	Aqueous ophthalmic composition with prostaglandin, polymeric quaternary ammonium preservative and ethoxylated/hydrogenated vegetable-oil surfactant	At least 0.01% and less than 0.4% w/v	Any prostaglandin suitable for glaucoma
14	Narrower travoprost composition with the same formulation architecture	At least 0.01% and less than 0.3% w/v	Travoprost

Claim 1 is broader in drug identity and surfactant concentration. Claim 14 is narrower because it requires travoprost but has a tighter upper surfactant limit.

The claims use “comprising,” which generally makes them open-ended. A competing product may contain additional excipients and still fall within the claims if every required limitation is present. The “only surfactant” language materially narrows that principle. A formulation containing a second material surfactant would have a stronger non-infringement position, although the exact result would depend on whether that ingredient is legally characterized as a surfactant.

How do the dependent claims narrow the patent scope?

The dependent claims create several commercially relevant claim groups.

Travoprost claims

Claims 4 and 18 require travoprost. Claim 19 further requires Polyoxyl 40 Hydrogenated Castor Oil. These are the most relevant claims for a BAK-free travoprost product using the disclosed surfactant system.

A product meeting claim 19 would generally require:

1. Travoprost as the prostaglandin;
2. Polymeric quaternary ammonium preservation;
3. Polyoxyl 40 Hydrogenated Castor Oil as the surfactant;
4. Surfactant concentration within claim 1's range;
5. No BAK;
6. Water-based ophthalmic vehicle.

Polyoxyl 40 Hydrogenated Castor Oil claims

Claims 6 and 19 identify Polyoxyl 40 Hydrogenated Castor Oil, commonly associated with Kolliphor RH 40 or equivalent compendial material, as the surfactant.

Claim 5 instead refers to castor oil. Because the claim language distinguishes “castor oil” from “hydrogenated castor oil,” the chemical identity and commercial grade of the excipient may matter in an infringement analysis.

Polyquaternium-1 claim

Claim 20 requires the polymeric quaternary ammonium compound to be polyquaternium-1. This is an important limitation because polyquaternium-1 is the preservative used in several BAK-free ophthalmic systems, including the SofZia-related commercial formulation platform associated with Travatan Z.

A product using a different polymeric quaternary ammonium preservative could avoid claim 20 but may still fall within claim 1 or claim 14.

Concentration claims

Claims 1 and 14 provide the principal concentration boundaries:

• Claim 1: at least 0.01% and less than 0.4% w/v;
• Claim 14: at least 0.01% and less than 0.3% w/v.

Claims 16 and 17 narrow the surfactant range to 0.001% to 0.15% w/v. Because those claims depend on claims requiring a minimum of 0.01% w/v, the legally operative overlap is generally expected to be at least 0.01% and no more than 0.15% w/v. The lower 0.001% language does not ordinarily broaden the incorporated limitations of the parent claim.

Claims 10 and 11 require prostaglandin concentrations below 0.01% and below 0.006% w/v, respectively. These limitations are consistent with commercial prostaglandin ophthalmic products, where the active ingredient is present at a low concentration.

What formulation is most directly covered?

The highest-risk formulation profile is:

Attribute	Covered profile
Dosage form	Aqueous ophthalmic solution or similar topical eye formulation
Active ingredient	Travoprost
Prostaglandin concentration	Less than 0.01% w/v, including below 0.006% w/v
Preservative	Polyquaternium-1
Surfactant	Polyoxyl 40 Hydrogenated Castor Oil
Surfactant concentration	At least 0.01% and below 0.3% or 0.4% w/v, depending on claim
Vehicle	Water-containing
BAK	Absent
Other surfactants	Absent or present only in a legally insubstantial amount
Packaging	Eye dropper, under claim 15

This profile corresponds closely to the BAK-free travoprost formulation marketed as Travatan Z. The FDA-approved label identifies travoprost ophthalmic solution 0.004% and lists polyquaternium-1 as the preservative system for the BAK-free product [1].

When does US Patent 8,178,582 lose exclusivity?

US Patent 8,178,582 has a nominal 20-year patent term measured from its earliest effective nonprovisional filing date, subject to any patent-term adjustment or terminal-disclaimer effects. Public patent records place the ordinary expiration in December 2025 [2][3].

Event	Timing
Earliest priority period	2005
US patent grant	May 15, 2012
Nominal 20-year expiration	December 2025
Post-expiration position	Composition claims generally no longer block ordinary US manufacture or sale, absent another unexpired patent

The patent is not a biologic exclusivity right, pediatric exclusivity right, or regulatory exclusivity right. Patent expiration does not eliminate other patent risks covering travoprost, manufacturing processes, packaging, delivery devices, or separate formulation platforms.

The exact enforceable expiration date depends on the USPTO patent-term-adjustment calculation and any recorded terminal disclaimer. The Orange Book date, where listed, is the operative commercial reference for FDA-listed drug patents [4].

What is the Orange Book status of US Patent 8,178,582?

The patent has been associated with the FDA-listed patent estate for Travatan Z, the BAK-free travoprost product. FDA Orange Book listings identify patents submitted by the NDA holder and do not independently determine infringement or validity [4].

The relevant regulatory distinction is:

• Travatan, containing BAK, is a different formulation product;
• Travatan Z is the BAK-free formulation;
• US 8,178,582 is directed to the BAK-free prostaglandin formulation architecture rather than to travoprost as a molecule alone.

An abbreviated new drug application applicant challenging a listed patent may use a Paragraph IV certification. The certification would assert that the patent is invalid, unenforceable, or not infringed. A Paragraph IV notice can trigger a 45-day period for the patent owner or NDA holder to file suit and obtain a potential 30-month stay of FDA approval under the Hatch-Waxman Act [5].

Which companies are challenging the patent?

Publicly available regulatory and litigation records do not establish a single definitive, patent-specific Paragraph IV challenger that can be attributed to US 8,178,582 without matching the relevant ANDA, notice letter, and docket.

Generic travoprost products can be divided into two risk categories:

1. BAK-containing travoprost products, which may avoid the central BAK-free limitations;
2. BAK-free travoprost products, which face materially greater risk if they use polyquaternium-1 and Polyoxyl 40 Hydrogenated Castor Oil within the claimed concentration ranges.

A generic applicant can reduce literal infringement exposure by changing one or more required elements, including:

• Using BAK, where clinically and regulatorily acceptable;
• Using a preservative other than polyquaternium-1;
• Using no surfactant;
• Using a different surfactant class;
• Adding a second surfactant to challenge the “only surfactant” limitation;
• Moving the surfactant concentration outside the claimed ranges;
• Using a nonaqueous or materially different vehicle.

Those design-arounds may create separate safety, tolerability, stability, or FDA comparability issues.

What patent litigation affects Travatan Z and this formulation?

The principal litigation risk is an ANDA-based Hatch-Waxman dispute involving a proposed generic BAK-free travoprost product. The likely causes of action would involve:

• Literal infringement of claims 1 or 14;
• Infringement of travoprost-dependent claims 4, 18 and 19;
• Infringement of polyquaternium-1 claim 20;
• Validity challenges based on anticipation or obviousness;
• Claim-construction disputes over “only surfactant,” “substantially entirely,” “free of,” and “polymeric quaternary ammonium compound.”

The most vulnerable validity issue is obviousness. The prior-art record for ophthalmic prostaglandins includes BAK-preserved formulations, alternative preservatives, surfactants, solubilizers, and BAK-free delivery systems. The patent owner’s position would rely on the particular combination, concentration window, preservation performance, and tolerability results.

The most important infringement issue is formulation composition. FDA labeling discloses qualitative and quantitative ingredients, but not every manufacturing parameter or impurity profile. Laboratory testing, batch records, discovery, and expert analysis may be necessary to determine whether a generic product contains the claimed surfactant and whether any additional excipient is legally a second surfactant.

How strong is the patent estate?

The estate is strongest against a BAK-free travoprost solution that copies the commercial formulation strategy. Its strength is lower against products that change the preservative, surfactant, vehicle, or BAK status.

Risk factor	Assessment
Coverage of travoprost molecule alone	Weak
Coverage of BAK-containing travoprost	Limited
Coverage of BAK-free travoprost with polyquaternium-1	Stronger
Coverage of Polyoxyl 40 Hydrogenated Castor Oil formulations	Strong within concentration limits
Coverage of all preservative-free products	None based on these claims
Coverage of alternative surfactants	Limited
Ability to block nonaqueous products	Limited
Remaining term	Short, with nominal expiration in December 2025

The patent’s commercial value is therefore concentrated in a narrow formulation configuration rather than in the broader glaucoma market.

How does this patent compare with competing glaucoma-drug patent estates?

Product	Active ingredient	BAK-free strategy	Primary patent risk profile
Travatan Z	Travoprost	Polyquaternium-1-related system	US 8,178,582 formulation claims and related product patents
Xalatan	Latanoprost	Historically BAK-preserved	Latanoprost molecule and formulation patents, many expired or near expiry
Lumigan	Bimatoprost	BAK-preserved and BAK-free variants	Bimatoprost formulation and delivery patents
Zioptan	Tafluprost	Preservative-free single-dose container	Tafluprost, formulation and packaging patents
Vyzulta	Latanoprostene bunod	Preserved ophthalmic solution	Active ingredient, formulation and use patents
Rocklatan	Netarsudil/latanoprost	Preserved combination	Combination, formulation and use patents

US 8,178,582 is narrower than an active-ingredient patent but can be more commercially relevant to a BAK-free generic because it targets the product’s excipient system.

What manufacturing and IP barriers remain after patent expiry?

Patent expiration does not remove several practical barriers:

• FDA approval of the proposed generic formulation;
• Demonstration of pharmaceutical equivalence;
• Control of prostaglandin degradation and oxidation;
• Sterility assurance;
• Container-closure compatibility;
• Drop-size consistency;
• Preservative effectiveness;
• Control of surfactant grade and lot variability;
• Stability of the low-concentration prostaglandin;
• Nonclinical and clinical tolerability expectations for ocular excipients.

The formulation also may be protected by unexpired continuation patents, foreign counterparts, process patents, trade secrets, or device patents not captured by US 8,178,582.

Key Takeaways

• US 8,178,582 is a BAK-free ophthalmic formulation patent, not a broad travoprost patent.
• Its central combination is travoprost or another glaucoma prostaglandin, polyquaternium-1 or another polymeric quaternary ammonium preservative, and an ethoxylated or hydrogenated vegetable-oil surfactant.
• Polyoxyl 40 Hydrogenated Castor Oil is the most commercially important claimed surfactant.
• The claims require an aqueous vehicle and exclude benzalkonium chloride.
• The patent is strongest against BAK-free travoprost products that copy the Travatan Z-type excipient system.
• A product using BAK, a different preservative, a different surfactant, or no surfactant may present a stronger design-around position.
• The nominal US patent term ends in December 2025, subject to the official USPTO term calculation.
• Orange Book listing does not establish validity or infringement, but it can support Hatch-Waxman Paragraph IV litigation.
• Generic risk depends on the complete formulation, not on travoprost use alone.

FAQs

Does US 8,178,582 cover all travoprost eye drops?

No. The claims require a specific BAK-free formulation containing a polymeric quaternary ammonium preservative and a qualifying ethoxylated or hydrogenated vegetable-oil surfactant.

Can a generic use benzalkonium chloride and avoid the patent?

A formulation containing BAK would not satisfy the express “free of any benzalkonium chloride” limitation. It may still face separate patents or regulatory requirements.

Is Polyoxyl 40 Hydrogenated Castor Oil the same as castor oil?

No. They are chemically and functionally different excipient categories. The commercial grade and composition would matter when assessing claims 5, 6 and 19.

Does a preservative-free travoprost product infringe this patent?

Ordinarily, a genuinely preservative-free product would not contain the required polymeric quaternary ammonium preservative and therefore would not meet the asserted combination.

Can a generic avoid infringement by adding another surfactant?

Potentially, but the result depends on whether the added ingredient is legally a surfactant and whether the original surfactant remains “entirely or substantially entirely the only surfactant.” Adding an excipient does not automatically avoid infringement.

References

1. U.S. Food and Drug Administration. (2023). Travatan Z (travoprost ophthalmic solution) prescribing information. https://www.accessdata.fda.gov
2. United States Patent and Trademark Office. (2012). U.S. Patent No. 8,178,582, ophthalmic compositions containing a prostaglandin. https://patents.google.com/patent/US8178582
3. Google Patents. (n.d.). US8178582B2: Ophthalmic compositions containing a prostaglandin. https://patents.google.com/patent/US8178582B2
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
5. U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications. https://www.fda.gov/drugs/drug-approvals-and-databases/abbreviated-new-drug-application-anda-forms-and-submissions

Drugs Protected by US Patent 8,178,582

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	IZBA	travoprost	SOLUTION/DROPS;OPHTHALMIC	204822-001	May 15, 2014		DISCN	Yes	No	8,178,582		Y

International Family Members for US Patent 8,178,582

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	070888
Argentina	124058
Australia	2009225824
Brazil	PI0908717
Canada	2716994
Chile	2009000624
China	101977588