Details for Patent: 8,323,630

Which drugs does patent 8,323,630 protect, and when does it expire?

Patent 8,323,630 protects TRAVATAN Z and is included in one NDA.

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

Summary for Patent: 8,323,630

Title:	Self-preserved aqueous pharmaceutical compositions
Abstract:	The present invention is directed to the provision of multi-dose, self-preserved ophthalmic compositions. The compositions possess sufficient antimicrobial activity to satisfy USP preservative efficacy requirements, as well as similar preservative standards (e.g., EP and JP), without requiring the presence of conventional anti-microbial preservative agents, such as benzalkonium chloride. The compositions are effectively preserved by a balanced ionic buffer system containing zinc ions at a concentration of 0.04 to 0.9 mM, preferably 0.04 to 0.4 mM. One aspect of the balanced buffer system is limitation of the amount of buffering anions present to a concentration of 15 mM or less, preferably 5 mM or less. In a preferred embodiment, the compositions also contain borate or, most preferably, one or more borate/polyol complexes. The use of propylene glycol as the polyol in such complexes is strongly preferred. Limiting the amount of divalent metals other than zinc and the amount of ionized salts present has also been determined to be important to maximize the antimicrobial activity of the balanced buffer systems.
Inventor(s):	Bhagwati P. Kabra, Masood A. Chowhan, L. Wayne Schneider, Wesley Wehsin Han
Assignee:	Novartis AG
Application Number:	US13/086,950
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,323,630
Patent Claim Types: see list of patent claims	Formulation; Compound;

U.S. Patent 8,323,630: Claim Scope, Travoprost Formulation Coverage, and Patent Landscape

U.S. Patent 8,323,630 protects self-preserved, multi-dose ophthalmic solutions that combine zinc, borate, propylene glycol, and sorbitol within narrow concentration ranges. Its strongest commercial coverage is directed to travoprost formulations that use zinc chloride, boric acid, polyoxyl 40 hydrogenated castor oil, propylene glycol, and sorbitol at concentrations corresponding to the marketed Travatan Z formulation.

The patent is formulation-focused. It does not broadly claim travoprost as a molecule, the treatment of glaucoma generally, or every preservative-free ophthalmic product. The principal infringement risk arises when a competing product reproduces the claimed excipient system and passes the USP 27 antimicrobial-preservation requirement without a conventional preservative.

What does U.S. Patent 8,323,630 protect?

The patent protects multi-dose ophthalmic solutions that are self-preserved through the combined effects of formulation components and pH rather than through a conventional antimicrobial preservative such as benzalkonium chloride.

The independent claim architecture is:

Claim	Claim type	Principal subject matter
1	Broad composition claim	Therapeutic agent, zinc ions, borate, propylene glycol, sorbitol, low anionic content, low multivalent-ion content, and USP 27 antimicrobial performance
8	Travoprost-specific composition claim	Travoprost, nonionic surfactant, zinc chloride, boric acid, propylene glycol, sorbitol, pH 5.5-5.9, and self-preservation
10	Narrow formulation claim	Exact or near-exact Travatan Z-type composition using specified excipients and concentrations

The claims use different transition language:

• Claim 1 uses “comprising,” making it an open claim.
• Claim 8 also uses “comprising,” allowing additional ingredients unless they create a separate claim limitation problem.
• Claim 10 uses “consisting essentially of,” which is materially narrower. Additional components may be permitted only if they do not materially affect the basic and novel characteristics of the claimed formulation.

The patent’s basic inventive concept is the use of a low-ionic-strength ophthalmic formulation in which zinc and the selected polyol and borate system provide sufficient antimicrobial activity for multi-dose use.

How broad is claim 1 of U.S. Patent 8,323,630?

Claim 1 is the broadest composition claim and does not require travoprost. It covers a therapeutically effective amount of any “ophthalmically acceptable therapeutic agent,” provided the formulation includes all of the following:

Component or limitation	Claimed range or requirement
Zinc ions	0.1-0.4 mM
Borate	0.5-1.2% w/v
Propylene glycol	0.25-1.25%
Sorbitol	0.05-0.5% w/v
Anionic species	Less than 15 mM
Multivalent buffering anions	Less than 5 mM
Multivalent metal cations other than zinc	Less than 5 mM
Antimicrobial performance	USP 27 preservative efficacy requirements
Dosage form	Multi-dose ophthalmic solution

The claim therefore reaches beyond prostaglandin analogs. Potentially relevant agents could include other ophthalmic drugs, subject to the requirement that the full excipient and ionic profile fall within the claimed limits.

The claim is not limited to a particular container, bottle design, pump, dispensing mechanism, or manufacturing process. A product can therefore fall within claim 1 regardless of whether it uses a conventional ophthalmic dropper, a multidose dispensing closure, or another delivery format.

What does claim 2 add regarding zinc chloride?

Claim 2 specifies zinc chloride at 0.001-0.005% w/v as the source of zinc.

This range corresponds to:

Zinc chloride concentration	Approximate mass concentration
0.001% w/v	10 mg/L
0.005% w/v	50 mg/L

The zinc-ion limitation in claim 1 is expressed as elemental zinc concentration, while claim 2 is expressed as zinc chloride concentration. That distinction matters because a product can satisfy the zinc-ion range only if the amount of elemental zinc contributed by the selected zinc salt falls within 0.1-0.4 mM.

A formulation using zinc acetate, zinc sulfate, or another zinc salt could potentially satisfy claim 1 without satisfying claim 2, assuming the elemental zinc concentration and all remaining limitations are met.

How do claims 3 through 7 narrow the patent?

Claims 3 through 7 progressively narrow claim 1:

• Claim 3 requires boric acid as the borate source.
• Claim 4 requires a pH of 5.5-5.9.
• Claim 5 requires a nonionic surfactant.
• Claim 6 limits the therapeutic agent to a prostaglandin analog.
• Claim 7 specifically identifies travoprost.

These claims create multiple infringement routes. A competing product could avoid claim 7 by using a different therapeutic agent but still face claims 1, 3, 4, or 5. Conversely, a travoprost formulation could avoid claim 7 by omitting one of the incorporated limitations, such as the specified pH or nonionic surfactant, while still requiring a separate analysis under claim 1.

The claim dependency language is important. Claims 6 and 7 depend on “any one of claim 1, 3, 4 or 5.” A product assessed against those claims must satisfy the incorporated limitations of the selected parent claim.

What is the commercial significance of claim 8?

Claim 8 is the central travoprost formulation claim. It requires:

• Travoprost;
• A nonionic surfactant;
• Zinc chloride at 0.001-0.005% w/v;
• Boric acid at 0.5-1.2% w/v;
• Propylene glycol at 0.25-1.25% w/v;
• Sorbitol at 0.05-0.5% w/v;
• pH of 5.5-5.9;
• Anionic species below 10 mM;
• Multivalent buffering anions below 5 mM;
• Multivalent metal cations other than zinc below 5 mM; and
• USP 27 antimicrobial performance based solely on the specified components and pH.

The “solely” limitation has practical importance. A formulation that depends on benzalkonium chloride, polyquaternium-1, chlorobutanol, or another separate antimicrobial preservative would have a stronger non-infringement position against claim 8, assuming that preservative is not otherwise included within the claimed component set.

The claim does not require a particular nonionic surfactant. A product using polysorbate, poloxamer, polyoxyl castor oil, or another nonionic surfactant could fall within the claim if the remaining limitations are met.

What formulation is covered by claims 10 and 11?

Claim 10 is the most commercially specific claim. It recites:

Ingredient	Claimed concentration or condition
Travoprost	0.004% w/v
Zinc chloride	0.0025% w/v
Polyoxyl 40 hydrogenated castor oil	0.5% w/v
Boric acid	1.0% w/v
Propylene glycol	0.75% w/v
Sorbitol	0.25% w/v
Sodium hydroxide and/or hydrochloric acid	Amount sufficient to produce pH 5.5-5.9
Water	Required solvent
Multivalent buffering anions	None
Multivalent cations other than zinc	None

Claim 11 adds the self-preservation requirement based solely on the antimicrobial properties of components (a)-(f) and the pH.

This claim set closely tracks the recognized SofZia-type travoprost formulation associated with Travatan Z. The concentration profile is unusually specific:

• Travoprost: 0.004%;
• Zinc chloride: 0.0025%;
• Boric acid: 1.0%;
• Propylene glycol: 0.75%;
• Sorbitol: 0.25%; and
• Polyoxyl 40 hydrogenated castor oil: 0.5%.

A competing product that changes one or more of these concentrations may avoid literal infringement of claim 10 while remaining exposed to the broader ranges in claims 1 or 8.

Which elements create the principal infringement risk?

The most important limitations are the formulation combination, not any individual excipient.

Multi-dose presentation

The claims require a multi-dose ophthalmic solution. A single-use vial or unit-dose package would have a potential defense against the multi-dose limitation, although packaging alone does not resolve whether a product is commercially equivalent or whether another patent applies.

Zinc concentration

The zinc range is narrow enough to create a meaningful design-around opportunity. A formulation with no zinc, or with zinc outside the claimed range, may avoid literal infringement. The risk remains if the concentration varies by lot, falls within the range after accounting for formulation tolerances, or is covered under a doctrine-of-equivalents theory.

Borate concentration

Claims 1, 8, and 10 require substantial borate content. Replacing boric acid with a different buffer may avoid claims 3, 8, or 10, but claim 1 covers borate more generally.

Low ionic content

The limitations on anionic species, multivalent buffering anions, and multivalent cations are central to the patent’s mechanism. Phosphate, citrate, sulfate, calcium, magnesium, and similar excipients can materially affect the analysis.

Claim 8 sets a stricter anionic-species ceiling than claim 1:

• Claim 1: less than 15 mM;
• Claim 8: less than 10 mM.

A product that contains phosphate or another multivalent buffering system may fall outside claims 8 and 10, even if it retains travoprost, zinc, borate, propylene glycol, and sorbitol.

USP 27 preservative efficacy

Antimicrobial performance is a claim limitation, not merely a product-quality characteristic. The product must satisfy the applicable USP 27 preservative efficacy requirements. A formulation that contains the claimed ingredients but fails the antimicrobial test would have a potential non-infringement position.

When does U.S. Patent 8,323,630 lose exclusivity?

The patent’s term is governed by the filing and priority history, any applicable patent-term adjustment, and any patent-term extension. A definitive expiration date must be taken from the USPTO’s official Patent Center record and the patent’s front-page term information.

Based on the patent’s grant-era chronology, the ordinary 20-year term would be expected to fall in the late 2020s rather than the 2030s, subject to adjustment. The patent should be evaluated separately from:

• FDA regulatory exclusivity;
• The underlying travoprost compound or use patents;
• Other formulation patents;
• Any continuation or divisional applications; and
• Foreign counterparts.

A patent expiration date does not automatically establish generic market entry. FDA approval, ANDA litigation, pediatric exclusivity, other listed patents, and settlement restrictions can affect actual launch timing.

What is the Orange Book status of the patent?

The Orange Book analysis must distinguish between the patent and the approved product.

The relevant FDA product is Travatan Z, an ophthalmic solution containing travoprost 0.004%. The product’s formulation and labeling history are separate from the patent’s claim scope. A patent may be:

1. Listed in the Orange Book for an NDA;
2. Not listed despite covering a formulation;
3. Listed for a method of use rather than formulation;
4. Listed for a later-approved product or supplemental application; or
5. Relevant to litigation without being listed.

U.S. Patent 8,323,630 should therefore be checked against the FDA Orange Book patent listing for the applicable Travatan Z NDA and against any later FDA patent-listing updates. The patent number alone does not establish that it was listed, that it remains listed, or that an ANDA applicant must certify to it.

What Paragraph IV challenges and generic entry risks exist?

A generic travoprost applicant has several potential design-around strategies.

Generic strategy	Likely risk under Patent 8,323,630
Use benzalkonium chloride	Lower risk against claims requiring self-preservation based solely on the claimed components and pH
Omit zinc	Strong design-around position against claims 1, 8, and 10
Use a different surfactant	May avoid claim 10 but not necessarily claim 8
Use phosphate or citrate buffer	May exceed ionic limitations or introduce prohibited multivalent buffering anions
Alter boric acid concentration	May avoid narrow claims while requiring analysis under claim 1
Use a unit-dose package	Potentially avoids multi-dose limitations
Retain all excipients but change pH	May avoid claims requiring pH 5.5-5.9
Use a different zinc salt	May avoid claim 2 but not claim 1

A Paragraph IV certification would be material only if the patent were listed for the relevant NDA and remained an enforceable barrier. The applicant would need to challenge validity, enforceability, or infringement, or rely on a non-infringing formulation. A Paragraph III certification would defer approval until patent expiration.

The most vulnerable validity issues would likely involve:

• Anticipation by earlier ophthalmic formulations containing zinc, borate, polyols, and surfactants;
• Obviousness based on known antimicrobial effects of zinc and low-ionic-strength formulations;
• Written-description or enablement challenges concerning the breadth of “therapeutic agent” and the USP 27 performance limitation; and
• Definiteness or proof issues surrounding “sufficient antimicrobial activity” and the calculation of anionic species.

The patent’s narrower claims 8 and 10 are generally more difficult to invalidate for lack of written description because they recite a defined travoprost formulation. Their vulnerability may instead depend on prior-art disclosure of the same or substantially similar excipient system.

Which companies are challenging the patent?

The claim set alone does not identify an ANDA challenger, Paragraph IV notice, settlement agreement, or active infringement case. Patent litigation cannot be inferred from the existence of a formulation patent.

A complete challenger analysis would require matching the patent against:

• FDA Orange Book records;
• ANDA litigation filed under the Hatch-Waxman statute;
• District court and Federal Circuit dockets;
• Patent Trial and Appeal Board proceedings; and
• Public settlement or license disclosures.

No biosimilar pathway applies. Travoprost is a chemically synthesized small molecule, not a biologic. Competing products would generally use the ANDA pathway rather than a biosimilar application under the Public Health Service Act.

How does the patent compare with the broader travoprost patent estate?

Patent 8,323,630 occupies the formulation and antimicrobial-preservation segment of the travoprost estate.

Patent category	Relevance to a travoprost competitor
Travoprost compound patents	May have protected the active ingredient or prostaglandin analog chemistry
Therapeutic-use patents	May cover glaucoma, ocular hypertension, or dosing methods
Formulation patents	Cover excipient combinations, pH, concentration, solubility, stability, or preservation
Device and container patents	Cover multidose dispensing systems and contamination control
Manufacturing patents	Cover synthesis, purification, sterilization, filling, or scale-up
Regulatory exclusivity	May delay approval independently of patent enforceability

Patent 8,323,630 is most relevant to a generic seeking to reproduce the Travatan Z formulation rather than a generic using a conventional preserved travoprost formulation.

The strongest commercial design-around is a product that uses travoprost with a different preservation system, different ionic composition, or a non-multi-dose presentation. The strongest infringement risk is a product that reproduces the SofZia-type ingredient profile and pH.

What manufacturing and formulation barriers remain after patent expiry?

Patent expiry would remove the principal legal barrier created by this patent, but it would not eliminate technical barriers.

A competing manufacturer must still address:

• Travoprost solubility and chemical stability;
• Uniform low-dose filling at 0.004% w/v;
• Zinc and borate control;
• Container compatibility;
• Microbial control during repeated use;
• USP preservative-efficacy performance;
• Drop-size consistency;
• Ocular tolerability;
• Sterility assurance; and
• FDA equivalence requirements for an ophthalmic solution.

For an ANDA, a formulation that differs from Travatan Z may need to establish pharmaceutical equivalence and bioequivalence through the FDA’s ophthalmic-product requirements. A formulation that uses a different preservative can create a separate clinical or tolerability profile even if it avoids the patent.

What revenue exposure is associated with the patent?

The patent’s economic exposure is concentrated in products using the claimed self-preserved travoprost formulation. It does not control the entire travoprost market.

Revenue exposure depends on:

• Sales of Travatan Z and related branded products;
• The number of approved generic travoprost products;
• Whether generics reproduce the zinc-borate-polyol system;
• The patent’s actual expiration date;
• Any Orange Book listing;
• ANDA litigation outcomes; and
• The availability of alternative preserved formulations.

Public company filings generally report ophthalmology revenue at broader segment levels rather than isolating revenue attributable to one formulation patent. Patent 8,323,630 should therefore be treated as a product-specific barrier rather than a basis for assigning the full revenue of a company’s glaucoma franchise to one patent.

How strong is the patent estate?

Patent 8,323,630 has a layered claim structure:

• Claim 1 provides broad composition coverage.
• Claims 2-7 create narrower fallback positions.
• Claim 8 targets the travoprost formulation.
• Claims 9-11 narrow the ionic profile and exact formulation further.

Its practical strength is highest against a formulation that copies the complete excipient system. Its practical strength is lower against:

• Benzalkonium-preserved travoprost;
• Unit-dose travoprost;
• Formulations without zinc;
• Formulations using materially different buffers;
• Products outside the claimed pH range; and
• Products that fail the multi-dose or self-preservation limitations.

The patent is therefore a strong blocking patent for the specific self-preserved travoprost architecture, but not a broad monopoly over travoprost ophthalmic products.

Key Takeaways

• U.S. Patent 8,323,630 is a formulation patent covering self-preserved, multi-dose ophthalmic solutions.
• Claim 1 is broad and can cover therapeutic agents other than travoprost.
• Claims 8 and 10 focus on travoprost and a SofZia-type excipient system.
• Claim 10 is the most commercially specific claim, requiring exact concentrations of travoprost, zinc chloride, boric acid, propylene glycol, sorbitol, and polyoxyl 40 hydrogenated castor oil.
• The low-anionic and low-multivalent-ion requirements are central limitations.
• A conventional benzalkonium-preserved travoprost product has a stronger design-around position.
• A biosimilar challenge is not relevant because travoprost is a small-molecule drug.
• Orange Book listing, Paragraph IV activity, litigation, and the precise expiration date must be determined from current FDA and USPTO records.
• The patent’s commercial value is concentrated in Travatan Z-type formulations, not the entire travoprost market.

FAQs

Does U.S. Patent 8,323,630 cover all travoprost eye drops?

No. It covers travoprost products only when the formulation satisfies the claimed zinc, borate, propylene glycol, sorbitol, surfactant, ionic-content, pH, multi-dose, and antimicrobial-performance limitations.

Can a generic avoid the patent by using benzalkonium chloride?

Potentially. A benzalkonium-preserved product may avoid claims requiring antimicrobial activity based solely on the claimed formulation components and pH. It must still be assessed against the broader composition limitations and other patents.

Does changing zinc chloride to another zinc salt avoid infringement?

It may avoid claim 2, which specifically recites zinc chloride. It would not necessarily avoid claim 1, which is directed to zinc ions generally.

Is claim 10 limited to the exact Travatan Z commercial formulation?

Claim 10 is highly specific and recites exact concentrations, but infringement analysis also considers formulation tolerances, “consisting essentially of” interpretation, and whether additional ingredients materially alter the claimed formulation.

Does patent expiry automatically permit immediate generic launch?

No. Launch timing also depends on FDA approval, Orange Book status, other unexpired patents, regulatory exclusivity, litigation outcomes, and any settlement restrictions.

References

1. U.S. Patent No. 8,323,630. (2012). Self-preserved ophthalmic compositions. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (n.d.). Travatan Z (travoprost ophthalmic solution) prescribing information. FDA.

3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.

4. United States Pharmacopeial Convention. (2004). United States Pharmacopeia 27: Antimicrobial effectiveness testing. United States Pharmacopeial Convention.

5. United States Patent and Trademark Office. (n.d.). Patent Center. USPTO.

Drugs Protected by US Patent 8,323,630

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Sandoz	TRAVATAN Z	travoprost	SOLUTION/DROPS;OPHTHALMIC	021994-001	Sep 21, 2006	AT2	RX	Yes	Yes	8,323,630		Y

International Family Members for US Patent 8,323,630

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	062929
Austria	E531358
Australia	2007299727
Brazil	PI0717067
Canada	2606370