Executive summary: U.S. Patent No. 7,642,258 covers a fixed-dose ophthalmic composition containing 0.2% brimonidine and 0.5% timolol, with narrower protection for benzalkonium chloride, specified salt forms, glaucoma and ocular-hypertension use, and twice-daily labeling. The patent is associated with the Combigan product profile. Its statutory patent term expired on August 20, 2024, eliminating current U.S. composition and labeling exclusivity from this patent. The commercial barrier has therefore shifted from this patent to FDA approval requirements, formulation differences, manufacturing controls, and any later-issued or separately listed patents.

U.S. Patent 7,642,258: Claims, Scope, Expiration, and Combigan Patent Landscape

What drug does U.S. Patent 7,642,258 protect?

U.S. Patent 7,642,258 protects a fixed-combination ophthalmic product containing:

Component	Claimed concentration
Brimonidine	0.2%
Timolol	0.5%
Benzalkonium chloride, dependent claims	0.001% to 0.01%
Preferred benzalkonium chloride concentration	About 0.005%

The claimed active ingredients correspond commercially to brimonidine tartrate and timolol maleate, the active pharmaceutical ingredients used in Combigan ophthalmic solution. The patent is assigned to Allergan, Inc., now within AbbVie’s ophthalmic product portfolio. The patent issued January 5, 2010, from an application claiming priority to August 20, 2004. Its ordinary 20-year term expired August 20, 2024. [1]

The claims cover both the liquid composition and an article of manufacture consisting of the product, packaging, and labeling directing twice-daily topical administration for glaucoma or ocular hypertension.

When did U.S. Patent 7,642,258 expire?

The patent’s statutory expiration date was August 20, 2024.

Event	Date
Earliest priority date	August 20, 2004
U.S. application filing	August 19, 2005
Patent issued	January 5, 2010
Statutory expiration	August 20, 2024

The patent is no longer a live U.S. patent right after that date. Its expiration removes the principal patent-based barrier created by the nine claims quoted in the question. It does not remove FDA requirements for demonstrating pharmaceutical equivalence, bioequivalence, product quality, sterility, container compatibility, and manufacturing compliance.

A patent expiration analysis should distinguish patent term from FDA exclusivity. Patent expiration does not itself determine whether an abbreviated new drug application can be approved, whether an ANDA applicant can launch immediately, or whether a different patent remains listed against the reference product.

How many independent claims does the patent have?

The patent has two substantive independent claims:

Claim 1 covers the composition.
Claim 7 covers the article of manufacture.

Claims 2 through 6 depend directly or indirectly on claim 1. Claims 8 and 9 depend on claim 7.

Claim	Subject matter	Principal limitation
1	Composition	0.2% brimonidine and 0.5% timolol in one composition
2	Composition	Adds 0.001% to 0.01% benzalkonium chloride
3	Composition	About 0.005% benzalkonium chloride
4	Composition	Brimonidine tartrate and timolol maleate
5	Composition	Useful for ocular hypertension
6	Composition	Useful for glaucoma
7	Article of manufacture	Packaging, composition, glaucoma or ocular-hypertension labeling, twice-daily administration
8	Article of manufacture	Adds 0.001% to 0.01% benzalkonium chloride
9	Article of manufacture	About 0.005% benzalkonium chloride

Claims 1 and 7 are the commercial center of gravity. The dependent claims narrow the product by adding preservative, salt-form, therapeutic-use, or labeling limitations.

What is the scope of claim 1?

Claim 1 covers a single composition comprising 0.2% brimonidine and 0.5% timolol.

The major limitations are:

Both active ingredients must be present.
The actives must be in a single composition rather than separate products.
The concentrations must correspond to 0.2% brimonidine and 0.5% timolol.
The claim is a composition claim, not merely a method of co-administering two separate drugs.

The term “comprising” is open-ended. It permits additional ingredients, including buffers, tonicity agents, viscosity modifiers, stabilizers, solvents, chelating agents, and preservatives. It does not limit the product to brimonidine, timolol, and benzalkonium chloride alone.

The open-ended transition does not automatically convert the concentration limitations into unrestricted ranges. A product containing materially different concentrations would require a separate claim-construction and infringement analysis. Regulatory labeling conventions also matter because ophthalmic concentrations are normally expressed as weight per volume, while the amount of active may be stated as the free base or as a salt equivalent.

Does claim 1 cover brimonidine tartrate and timolol maleate?

Claim 1 is broader than claim 4 because claim 1 does not expressly require a particular salt form. Claim 4 narrows the composition to brimonidine tartrate and timolol maleate.

This distinction has commercial significance:

A product using the same salt forms as Combigan falls within claim 4 if the other limitations are met.
A product using another pharmaceutically acceptable brimonidine or timolol salt may still raise claim 1 issues.
A formulation using the free bases, a different salt, or a different active-equivalent calculation requires analysis of the claim’s concentration language and the patent specification.

For regulatory comparison, the reference product’s label identifies brimonidine tartrate and timolol maleate in an ophthalmic solution containing 0.2% brimonidine and 0.5% timolol. [2]

What formulations are protected by claims 2, 3, 8, and 9?

Claims 2 and 8 cover products containing benzalkonium chloride in a range from 0.001% to 0.01%. Claims 3 and 9 focus on approximately 0.005% benzalkonium chloride.

Claim group	Preservative limitation	Practical effect
Claims 1 and 7	No express preservative requirement	Broadest product and packaging claims
Claims 2 and 8	0.001% to 0.01% benzalkonium chloride	Covers a broad BAK range
Claims 3 and 9	About 0.005% benzalkonium chloride	Preferred BAK formulation

Benzalkonium chloride is a preservative commonly used in multidose ophthalmic products. Its concentration can affect antimicrobial performance, ocular tolerability, container compatibility, and regulatory comparability.

The dependent claims do not create a separate platform for preservative-free products. A preservative-free product would not meet claims 2, 3, 8, or 9, although it could still have been evaluated against claims 1 and 7 while the patent was in force.

Does the patent cover glaucoma and ocular-hypertension treatment?

Claims 5 and 6 identify the composition as useful for treating ocular hypertension and glaucoma. These are narrower dependent claims, but the wording is primarily functional.

Claim 7 adds a more specific labeling limitation. The article of manufacture must include packaging and a composition whose packaging indicates use:

for glaucoma or ocular hypertension; and
by twice-daily topical administration to the eye.

The claim therefore targets the product presentation as well as the liquid formulation. A package or label that omits the claimed indication or twice-daily direction would create a different analysis from a label that reproduces the reference-product instructions.

The FDA label for Combigan directs one drop in the affected eye twice daily, approximately 12 hours apart. [2]

How should the “single composition” limitation be interpreted?

The single-composition requirement separates the claimed product from regimens involving separate brimonidine and timolol bottles.

A product likely falls within the technical focus of the claim when both actives are present in the same ophthalmic solution or suspension. The following configurations are materially different:

Product configuration	Relevance to claim 1
One bottle containing both actives	Directly aligned with claim
Two bottles used sequentially	Does not satisfy single-composition limitation
Dual-chamber container mixed before administration	Depends on when and how the composition is formed
Kit containing separate brimonidine and timolol products	Not a single composition before administration
Fixed-dose ophthalmic gel or suspension	May satisfy the composition limitation if concentrations and other elements match

The claim does not expressly require a particular viscosity, pH, osmolality, container, dosing volume, or manufacturing process.

What is the significance of claim 7’s “by weight” wording?

Claim 1 states the concentrations as 0.2% and 0.5% on a weight-per-volume basis. Claim 7 describes the composition as containing 0.2% brimonidine by weight and 0.5% timolol by weight.

That drafting difference creates a potential claim-construction issue. Ophthalmic products are commonly labeled in % w/v, while “by weight” can be read as % w/w. The commercial product label uses the conventional ophthalmic concentration format, but patent enforcement would depend on the claims, specification, prosecution history, and applicable construction principles.

This distinction could have been relevant to a Paragraph IV defense while the patent was active. It does not revive the patent after expiration.

What was the Orange Book status of U.S. Patent 7,642,258?

The patent was listed in the FDA Orange Book in connection with the reference product Combigan, a fixed-dose brimonidine tartrate/timolol maleate ophthalmic solution. Orange Book listings identify patents submitted by the NDA holder and provide patent-use codes where applicable. [3]

The relevant regulatory issues were:

whether the patent was listed against the reference product;
whether an ANDA applicant had to certify to the patent;
whether the applicant filed a Paragraph IV certification;
whether the patent holder brought suit within 45 days;
whether litigation triggered a 30-month stay; and
whether the patent remained unexpired when FDA approval and commercial launch occurred.

After August 20, 2024, this patent no longer provides a live Orange Book patent-term barrier. The FDA Orange Book should be read by product, patent number, expiration date, and patent-use code because a reference product may have several listed patents with different expiration dates. [3]

Which companies challenged the Combigan patent?

Generic manufacturers seeking approval of brimonidine tartrate/timolol ophthalmic solution could use an ANDA with a Paragraph IV certification against an unexpired listed patent. The statutory process permits an ANDA applicant to assert that a listed patent is invalid, unenforceable, or not infringed under 21 U.S.C. § 355(j)(2)(A)(vii)(IV). A patent-holder suit filed within 45 days can trigger the statutory 30-month stay under 21 U.S.C. § 355(j)(5)(B)(iii). [4]

Publicly reported generic activity around Combigan involved ANDA applicants pursuing fixed-combination brimonidine/timolol products. The relevant competitive question is no longer whether U.S. Patent 7,642,258 can block approval. The question is whether later-listed patents, regulatory exclusivity, settlement terms, or product-specific FDA deficiencies affect launch timing.

A current Paragraph IV assessment must be performed against the complete Orange Book listing and FDA approval history for the reference product. The expired ’258 patent alone cannot support a current infringement suit based on post-expiration commercial activity.

What patent litigation affected the ’258 patent?

The principal litigation risk from the ’258 patent would have involved an ANDA applicant seeking approval for a product containing the same fixed concentrations. The likely dispute categories were:

Literal infringement of claims 1 and 7.
Whether the generic product used the claimed brimonidine and timolol concentrations.
Whether the formulation contained benzalkonium chloride within the claimed range.
Whether the product used brimonidine tartrate and timolol maleate.
Whether proposed labeling met the glaucoma or ocular-hypertension and twice-daily limitations.
Validity challenges based on obviousness, anticipation, written description, enablement, or indefiniteness.
Orange Book listing and patent-use-code disputes.

A product could challenge one or more claims while accepting that other claims might be met. For example, a preservative-free formulation could avoid the BAK-dependent claims while still confronting the broad composition claim during the patent term.

No current infringement exposure arises solely from practicing the expired claims after August 20, 2024. Earlier sales, launch conduct, or settlement obligations could present separate issues, but those are not established by the claim language alone.

How strong was the patent estate for the fixed-dose combination?

The ’258 patent had meaningful commercial breadth during its term because claim 1 captured the core branded concentration pair. Its practical strengths were:

direct coverage of the fixed combination;
no express requirement for benzalkonium chloride in the broadest claim;
coverage of the same salt forms used by the reference product through claim 4;
a parallel packaging and labeling claim in claim 7;
alignment with the marketed twice-daily product.

Its limitations included:

narrow numerical concentration requirements;
potential disputes over w/v versus w/w terminology;
functional treatment language in claims 5 and 6;
dependence on the product containing both actives in one composition;
possible design-around options involving concentration, salt form, preservative system, dosage form, or labeling.

The patent’s current strength is zero as an exclusionary patent right because its term has ended. Its historical strength remains relevant to prior litigation, settlement analysis, damages periods, and freedom-to-operate reviews covering pre-expiration conduct.

How does U.S. Patent 7,642,258 compare with broader generic-entry barriers?

Barrier	Effect on generic entry
’258 patent term	Ended August 20, 2024
Orange Book patent certification	Relevant only while listed patents remain unexpired
FDA ANDA requirements	Remain fully applicable
Pharmaceutical equivalence	Requires matching active ingredients, dosage form, strength, and route
Bioequivalence	Must satisfy applicable FDA standards
Sterility and manufacturing	Can delay approval or launch independently of patent rights
Container and preservative system	May create technical and regulatory differences
Later patents	May remain relevant if separately listed and unexpired
Settlement agreements	Can impose contractual launch restrictions beyond patent expiration

For a generic manufacturer, the principal product is an ophthalmic fixed combination, not a biosimilar. Biosimilar risk is therefore not applicable to the active product itself. The competitive pathway is an ANDA for a small-molecule drug, although ophthalmic bioequivalence and product-quality requirements can be technically demanding.

What generic launch scenarios exist after patent expiration?

The main U.S. launch scenarios are:

Immediate post-expiration launch

An ANDA applicant with FDA approval and no other effective patent or exclusivity barrier could launch after August 20, 2024.

Delayed launch caused by regulatory review

A generic may remain off-market after patent expiration if FDA review, facility inspection, manufacturing remediation, labeling revisions, or product-quality questions remain unresolved.

Launch with a differentiated formulation

A manufacturer may launch a formulation that differs in preservative, inactive ingredients, container, or viscosity while maintaining the required active ingredients and strength. The regulatory pathway depends on whether the product remains pharmaceutically equivalent and therapeutically equivalent to the reference product.

Later-patent challenge

A later-listed patent may create a new Paragraph IV dispute even though the ’258 patent has expired. The analysis must separate the expired patent from each later patent’s claims, term, listing status, and use code.

What licensing deals and settlement agreements matter?

The ’258 patent’s claim language does not establish a licensing transaction or settlement agreement. A commercial freedom-to-operate review should distinguish:

patent licenses;
ANDA litigation settlements;
covenants not to sue;
authorized-generic arrangements;
supply agreements;
launch-date provisions; and
confidentiality or market-allocation terms.

A settlement can affect launch timing during the patent term but cannot extend the patent’s statutory term. It can, however, create contractual obligations that survive patent expiration if the agreement so provides.

What manufacturing and intellectual-property barriers remain?

The expired patent does not eliminate the technical barriers associated with a fixed-dose ophthalmic product. A competing manufacturer must control:

uniform distribution of both active ingredients;
pH and buffer capacity;
chemical stability of brimonidine and timolol;
preservative effectiveness if benzalkonium chloride is used;
extractables and leachables from the container;
drop size and delivered volume;
sterility assurance;
multidose container performance;
assay and impurity specifications; and
compatibility with the proposed packaging.

These are regulatory and manufacturing barriers rather than continuing rights under U.S. Patent 7,642,258.

Key takeaways

U.S. Patent 7,642,258 covers a single ophthalmic composition containing 0.2% brimonidine and 0.5% timolol.
Claims 2, 3, 8, and 9 add benzalkonium chloride limitations.
Claim 4 specifically covers brimonidine tartrate and timolol maleate.
Claims 5 and 6 address ocular hypertension and glaucoma.
Claim 7 covers packaging and twice-daily glaucoma or ocular-hypertension labeling.
The patent expired on August 20, 2024.
The patent no longer independently blocks generic U.S. entry.
Current launch risk depends on FDA approval, later Orange Book patents, manufacturing readiness, and any enforceable commercial agreements.
The product is a small-molecule fixed-dose combination, so biosimilar regulation is not the applicable pathway.
The patent had strong historical product coverage but no current exclusionary force after expiration.

FAQs

What is the active ingredient combination covered by U.S. Patent 7,642,258?

The combination is brimonidine at 0.2% and timolol at 0.5% in a single ophthalmic composition. The commercial salt forms are brimonidine tartrate and timolol maleate.

Did U.S. Patent 7,642,258 cover preservative-free Combigan?

The broad composition claim does not expressly require benzalkonium chloride. Claims 2, 3, 8, and 9 do require specified benzalkonium chloride concentrations. A preservative-free product would not meet those dependent claims, but it could have required analysis under the broader claims during the patent term.

Can a generic launch after the ’258 patent expired?

Yes, provided the generic has FDA approval and no other unexpired patent, regulatory exclusivity, settlement restriction, or manufacturing issue prevents launch.

Was U.S. Patent 7,642,258 a method-of-use patent?

Its principal claims are composition and article-of-manufacture claims. Claims 5 and 6 recite usefulness for ocular hypertension and glaucoma, while claim 7 incorporates therapeutic labeling and twice-daily administration.

Does the expiration of the ’258 patent eliminate all Combigan patent risk?

No. It eliminates the exclusionary effect of this patent. Separate patents, later Orange Book listings, settlement agreements, or product-specific regulatory barriers must be analyzed independently.

References

United States Patent and Trademark Office. (2010). U.S. Patent No. 7,642,258, Pharmaceutical compositions comprising brimonidine and timolol. https://patents.google.com/patent/US7642258B2/en
U.S. Food and Drug Administration. (2024). Combigan: Brimonidine tartrate and timolol maleate ophthalmic solution, prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
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-data-files
U.S. Congress. (2024). Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section355&num=0&edition=prelim

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
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,642,258

Summary for Patent: 7,642,258