United States Patent 7,323,463: Claim Scope, Patent Expiration, Orange Book Status, and Generic Entry Risk

U.S. Patent No. 7,323,463 covers a single ophthalmic composition containing approximately 0.2% timolol and 0.5% brimonidine as the only active ingredients. Dependent claims add benzalkonium chloride at approximately 0.005%. Separate article-of-manufacture claims cover packaging that identifies the composition for twice-daily topical treatment of glaucoma or ocular hypertension.

The patent’s practical scope is narrow. It is directed to a specific fixed-dose combination, preservative concentration, and labeled dosing regimen. It does not broadly cover all brimonidine-timolol combinations, all ophthalmic formulations, or the individual active ingredients. Based on the patent’s 2008 issue date and reported 2022 patent-term endpoint, the principal U.S. patent protection has expired.

What does U.S. Patent 7,323,463 protect?

The patent protects two related categories:

A composition containing approximately 0.2% timolol and approximately 0.5% brimonidine as the sole active agents.
An article of manufacture consisting of the composition in packaging that identifies the twice-daily treatment of glaucoma or ocular hypertension.

The claims supplied for analysis are:

Claim	Claim type	Required elements
1	Composition	About 0.2% timolol; about 0.5% brimonidine; sole active agents; single composition
2	Dependent composition	Claim 1 plus 0.001%-0.01% benzalkonium chloride
3	Dependent composition	Claim 2 plus about 0.005% benzalkonium chloride
4	Article of manufacture	Packaging, composition, stated concentrations, and packaging indication for twice-daily glaucoma or ocular-hypertension treatment
5	Dependent article	Claim 4 plus 0.001%-0.01% benzalkonium chloride
6	Dependent article	Claim 5 plus about 0.005% benzalkonium chloride

The composition claims are product claims. The article claims are combination claims that require both the product and packaging carrying a specified therapeutic indication.

How narrow are the composition claims?

The composition claims contain several cumulative limitations. A potentially infringing product would generally need to satisfy all of the following:

Timolol at approximately 0.2% by weight.
Brimonidine at approximately 0.5% by weight.
Both ingredients present in one composition.
No other active pharmaceutical ingredient.
For claims 2 and 3, benzalkonium chloride within the specified concentration range.
For claim 3, approximately 0.005% benzalkonium chloride.

The phrase “sole active agents” excludes a formulation containing another pharmacologically active ingredient. It does not necessarily exclude excipients, buffers, tonicity agents, stabilizers, viscosity modifiers, pH adjusters, or preservatives. Benzalkonium chloride is treated in the dependent claims as an excipient or preservative rather than an active therapeutic agent.

What does “about” mean in these claims?

“About” creates a tolerance around the stated concentration, but it does not make the claim unlimited. The scope would depend on intrinsic evidence in the patent, including examples, specification language, prosecution history, analytical measurement conventions, and any construction adopted by a court.

A formulation at exactly 0.2% timolol and 0.5% brimonidine presents the strongest literal infringement case. A material departure from either concentration creates a potential noninfringement position, although the Federal Circuit’s doctrine-of-equivalents analysis could remain relevant if the accused formulation performs substantially the same function in substantially the same way to achieve substantially the same result.

The claim language is also sensitive to how concentration is measured. A formulation expressed as the weight of the active moiety may differ from one expressed as the weight of a salt, such as timolol maleate or brimonidine tartrate. Regulatory labeling commonly identifies both the salt and the active-equivalent concentration. The patent specification and prosecution record would control the applicable calculation.

What formulations are protected by claims 2, 3, 5, and 6?

Claims 2 and 5 cover benzalkonium chloride concentrations from 0.001% through 0.01%. Claims 3 and 6 narrow that range to approximately 0.005%.

Formulation characteristic	Claim coverage
No benzalkonium chloride	Claim 1 or claim 4 may apply if all other limitations are met
0.001%-0.01% benzalkonium chloride	Claims 2 and 5
Approximately 0.005% benzalkonium chloride	Claims 3 and 6, as well as the broader claims 2 and 5
Preservative other than benzalkonium chloride	Not literally covered by the BAK limitations
Additional active ingredient	Conflicts with the “sole active agents” limitation
Separate bottles or sequential administration	Does not satisfy the “single composition” limitation

A formulation without benzalkonium chloride can still fall within independent claims 1 or 4. The preservative limitation is not required for the independent claims.

The use of a different preservative, such as polyquaternium-1, does not literally satisfy a benzalkonium-chloride limitation. A doctrine-of-equivalents theory would face claim-vitiation and prosecution-history issues, particularly if the patent distinguishes benzalkonium chloride from alternative preservatives.

Do the claims cover a method of treating glaucoma?

No. The supplied claims do not expressly recite a method of treatment. They cover:

A composition.
An article of manufacture.
Packaging that indicates a twice-daily use for glaucoma or ocular hypertension.

Claim 4 is therefore not a conventional method-of-use claim. The labeling requirement is a limitation of the article claim. A manufacturer could challenge infringement by arguing that its packaging does not contain the specified indication, although that defense would not avoid claims 1 through 3 if the formulation itself falls within their scope.

The twice-daily limitation is important for claim 4. Packaging that instructs once-daily, three-times-daily, or non-ocular use may not satisfy the express labeling limitation. It would not, however, change the scope of the composition claims.

When did U.S. Patent 7,323,463 expire?

The patent issued on January 29, 2008. Public patent-term records associate the patent with a 2022 expiration endpoint, commonly reported as October 15, 2022, based on the underlying U.S. patent-term calculation.[1]

Event	Date
U.S. patent issued	January 29, 2008
Reported patent expiration	October 15, 2022
Current status of original patent term	Expired

The applicable expiration date should be confirmed against the USPTO Patent Center record, including any patent-term adjustment or disclaimer information. Once the term expired, claims 1 through 6 ceased to provide enforceable exclusionary rights in the United States.

Patent expiration does not eliminate other possible barriers, including later patents, regulatory exclusivity, trade secrets, contractual restrictions, or state-law claims. It does eliminate the ability to enforce the expired claims against a new entrant.

What is the Orange Book status of U.S. Patent 7,323,463?

The patent was associated with the fixed-dose brimonidine-timolol ophthalmic product and was listed in FDA Orange Book materials during the product’s patent-protection period.[2] Orange Book listing is relevant to an approved drug application and to ANDA certification procedures. It does not extend the patent term.

After expiration, the patent no longer creates a live Orange Book patent barrier. An ANDA applicant filing after expiration would not face a continuing Paragraph IV dispute based solely on this patent. Earlier ANDA applicants may have filed Paragraph IV certifications before the patent expired, and those certifications could have generated litigation or a 30-month stay at an earlier time.

The Orange Book should be distinguished from FDA regulatory exclusivity:

Patent listing concerns enforceable patent rights linked to an approved product.
New-drug exclusivity is an FDA regulatory period.
Orphan-drug exclusivity applies only in the orphan-drug context.
Pediatric exclusivity can add six months to otherwise applicable exclusivity or patent protection.
None of these categories automatically revives an expired patent.

Were Paragraph IV challenges possible?

Yes. Before the reported expiration date, an ANDA applicant could submit a Paragraph IV certification asserting that the patent was invalid, unenforceable, or would not be infringed by the proposed generic product.[3]

A Paragraph IV challenge to this patent would likely focus on four issues:

Claim construction. The applicant could contest the meaning of “about,” “sole active agents,” and “single composition.”
Concentration design-around. A generic could use concentrations outside the claimed ranges, subject to regulatory requirements and any separate patent claims.
Obviousness. The applicant could argue that combining an alpha-2 adrenergic agonist with a beta blocker in an ophthalmic composition, including a preservative, would have been obvious.
Written description and enablement. The applicant could challenge whether the specification supports the full scope of the concentration and packaging claims.

The patent holder would likely respond that the claimed concentration pairing, compatibility, preservative system, and twice-daily labeling produced a specific combination not adequately disclosed or suggested by the prior art.

A Paragraph IV notice would not itself establish infringement. The patent owner would need to file an action within the statutory period to obtain the ANDA-related 30-month stay. After patent expiration, the commercial value of such a challenge would shift from blocking launch to accelerating market entry or resolving damages and settlement issues.

Which companies challenged the patent?

The supplied information identifies the patent claims but does not establish a complete historical list of ANDA filers, district-court defendants, Federal Circuit appeals, or settlement counterparties. A claim-specific litigation conclusion cannot be made from the claims alone.

The relevant search set includes:

ANDA litigation involving the branded brimonidine-timolol product.
Cases naming Allergan, Inc. or an affiliated patent owner.
Defendants seeking approval for a generic fixed-dose ophthalmic brimonidine-timolol product.
Paragraph IV notices concerning U.S. Patent 7,323,463.
District-court opinions construing the concentration or packaging limitations.

A later generic product may have entered after the patent’s reported expiration without needing to defeat the patent in court. That scenario is materially different from a pre-expiration launch following a successful Paragraph IV judgment or settlement.

How strong was the patent estate?

The patent was commercially useful but technically narrow.

Strengths

It targeted a fixed combination rather than an abstract therapeutic concept.
The “single composition” requirement addressed co-formulation.
The article claims connected the product to the twice-daily glaucoma or ocular-hypertension indication.
The dependent claims created fallback positions around benzalkonium chloride concentration.
Composition claims 1 through 3 did not depend on a particular package or label.

Weaknesses

The claims were concentration-specific.
“About” could create claim-construction disputes.
The patent did not broadly cover every brimonidine-timolol ratio.
The article claims required a particular packaging indication.
The claims did not expressly cover manufacturing processes, containers, delivery devices, particle size, viscosity, osmolarity, or alternative preservatives.
The “sole active agents” limitation could exclude combination products with a third active ingredient.

The estate’s blocking power depended heavily on whether a generic needed to match the claimed concentration. A product using a different ratio or preservative could create a design-around pathway, provided it complied with FDA requirements and did not infringe another patent.

How does this patent compare with later formulation patents?

U.S. Patent 7,323,463 is primarily a combination-composition patent. Later patents in the same product area may address narrower technical features, including:

Preservative-free ophthalmic formulations.
Container-closure systems.
Multidose delivery devices.
Improved stability.
Reduced ocular irritation.
Specific salt forms or active-equivalent concentrations.
Manufacturing and filling processes.
Alternative dosing schedules.
New therapeutic indications.

A later formulation patent can remain enforceable after the expiration of the ’463 patent if it has a later priority date and a valid, unexpired term. It cannot extend the term of the ’463 patent itself. A generic applicant therefore must conduct a separate patent-family analysis rather than rely solely on the expiration of U.S. Patent 7,323,463.

What generic entry risks existed?

The original patent presented three principal generic-entry risks before expiration:

Risk	Impact
Exact or near-exact concentration match	High risk under composition claims
Same formulation plus BAK near 0.005%	Higher risk under dependent claims
Same product with twice-daily glaucoma labeling	Potential exposure under article claims

After expiration, the patent-specific risk became low. The remaining exposure would arise from other unexpired patents, regulatory exclusivity, product-liability issues, or manufacturing constraints.

A generic launch could occur through several routes:

At-risk launch before final patent resolution. This creates potential damages if the patent is later upheld and found infringed.
Launch after expiration. This avoids infringement liability under the expired patent.
Formulation design-around. The generic uses a different concentration, preservative, package, or labeling structure.
Paragraph III certification. The applicant accepts that launch will not occur until patent expiration.
Paragraph IV certification. The applicant challenges validity, enforceability, or infringement before expiration.

What manufacturing and intellectual-property barriers remain?

The patent claims do not create a manufacturing-process monopoly. They do not require a particular mixing sequence, sterilization method, filling operation, container, or delivery device.

Practical barriers may still include:

Sterile ophthalmic manufacturing capacity.
Compatibility of the active ingredients in one aqueous vehicle.
Stability over the proposed shelf life.
Preservative effectiveness.
Container-closure integrity.
Extractables and leachables.
FDA bioequivalence and product-quality requirements.
Availability and qualification of brimonidine and timolol active ingredients.
Other unexpired formulation or device patents.

These are commercial and regulatory barriers rather than direct exclusions created by the expired ’463 claims.

What is the current commercial significance of the patent?

The patent’s direct revenue-protection value ended with expiration. During its term, the patent could support exclusivity for a fixed-dose ophthalmic combination and strengthen the originator’s position against ANDA products that matched the claimed formulation.

Revenue exposure would have depended on:

U.S. sales of the branded combination.
The number of ANDA applicants.
Whether generic products matched the claimed concentrations.
The existence of later Orange Book-listed patents.
The timing of generic approval and launch.
Reimbursement substitution and pharmacy-level switching.

The patent should therefore be treated as an expired historical barrier, not as a current standalone basis for U.S. market exclusivity.

Key Takeaways

U.S. Patent 7,323,463 covers a single ophthalmic composition containing approximately 0.2% timolol and 0.5% brimonidine as the sole active agents.
Claims 2, 3, 5, and 6 add benzalkonium chloride, with claim 3 and claim 6 centered on approximately 0.005%.
Claims 4 through 6 are article-of-manufacture claims and require packaging with a twice-daily glaucoma or ocular-hypertension indication.
The patent does not contain a conventional method-of-treatment claim in the supplied claim set.
The reported U.S. expiration date is October 15, 2022.
The patent’s term has expired, eliminating current enforcement rights under these claims.
The patent was narrow and concentration-dependent, leaving potential design-around strategies based on concentration, preservative, packaging, or labeling.
Later formulation, device, manufacturing, or method-of-use patents must be analyzed separately.
No current generic-entry prohibition can be based solely on U.S. Patent 7,323,463.

Frequently Asked Questions

Does U.S. Patent 7,323,463 cover separate timolol and brimonidine bottles?

No. The claims require the ingredients to be present in a “single composition.” Separate products administered sequentially would not literally satisfy that limitation.

Does the patent cover a formulation containing a third active ingredient?

Generally no. Claims 1 through 6 require timolol and brimonidine as the sole active agents. A third pharmacologically active ingredient would create a substantial noninfringement argument.

Does using a preservative other than benzalkonium chloride avoid the patent?

It may avoid the BAK-specific limitations in claims 2, 3, 5, and 6. It would not avoid claims 1 and 4 if the other limitations are satisfied.

Can an expired patent block FDA approval of a generic ophthalmic product?

No. An expired patent cannot provide a continuing patent-based bar to approval or commercial launch. Other unexpired patents or regulatory exclusivities may still matter.

Is a twice-daily label required for infringement of every claim?

No. The twice-daily packaging indication is expressly required by claims 4 through 6. Claims 1 through 3 are composition claims and do not contain that packaging limitation.

References

United States Patent and Trademark Office. (2008). U.S. Patent No. 7,323,463, compositions and methods for treating glaucoma. https://patents.google.com/patent/US7323463B2/en
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Patent certifications and notices. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/anda-submissions-refused-approve-respond-reference-listed-drug-patents-para-iv-certifications-and-gran-ndas-180-days-exclusivity- para-iv-notices

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2003228480	⤷ Start Trial
Brazil	0302584	⤷ Start Trial
Canada	2440764	⤷ Start Trial
China	100558364	⤷ Start Trial
China	101664414	⤷ Start Trial
China	112219061	⤷ Start Trial
China	1516588	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,323,463

Summary for Patent: 7,323,463