United States Patent 5,149,693: Claim Scope, Expiration, and Ophthalmic Patent Landscape

U.S. Patent No. 5,149,693 covers a topical ophthalmic combination of fluorometholone or fluorometholone acetate with tobramycin for treating eye inflammation and infection. The patent is directed to methods of treatment, not to the manufacture or sale of the composition as a standalone product. Its principal commercial relevance was the tobramycin/fluorometholone acetate product Zylet. The patent expired on September 22, 2009, eliminating it as a current U.S. patent barrier to generic entry.[1][2]

What does U.S. Patent 5,149,693 protect?

The patent protects administering a specified steroid-antibiotic combination topically to an affected human eye. The claim set has two principal levels:

A broad treatment method using either fluorometholone or fluorometholone acetate with tobramycin.
A narrower aqueous-solution formulation defined by active-ingredient ratio, total concentration, and pH.

Claim	Subject matter	Key limitations
1	Broad method of treatment	Topical administration to an affected human eye; ophthalmic composition; fluorometholone or fluorometholone acetate; tobramycin; pharmaceutically acceptable carrier
2	Preferred steroid	Fluorometholone acetate
3	Active-ingredient ratio	Tobramycin-to-steroid ratio of 0.1:1.0 to 10.0:1.0
4	Narrow aqueous formulation	Aqueous solution; combined tobramycin and steroid concentration of 0.01% to 2.0% by weight; pH 4.5 to 8.0
5	Preferred species under claims 3 and 4	Fluorometholone acetate

The patent does not claim every ophthalmic product containing tobramycin and fluorometholone. It claims a treatment method requiring the claimed combination and administration to the affected eye of a human host.

How should the claims be construed?

Claim 1 is a combination-treatment claim

Claim 1 requires all of the following:

A human patient.
An affected eye.
Topical administration to that eye.
A therapeutically effective amount.
An ophthalmic pharmaceutical composition.
An anti-inflammatory effective amount of fluorometholone or fluorometholone acetate.
An anti-infective effective amount of tobramycin.
A pharmaceutically acceptable carrier.

The claim uses “comprising,” so additional excipients, preservatives, buffers, viscosity agents, suspending agents, and other formulation components generally would not avoid the claim if the required elements were present.

The claim also uses functional terms such as “anti-inflammatory effective amount” and “anti-infective effective amount.” Those terms focus on the intended pharmacological role of each active ingredient rather than requiring a single fixed dosage.

Claim 1 covers both fluorometholone and fluorometholone acetate

The “selected from the group consisting of” language identifies two alternatives:

Fluorometholone.
Fluorometholone acetate.

A product using fluorometholone acetate falls within the steroid limitation if the remaining claim elements are satisfied. Claim 2 narrows the scope to fluorometholone acetate but does not otherwise change the treatment method.

The carrier limitation is broad

The carrier must be pharmaceutically acceptable, but the claims do not require a specific preservative, buffer, surfactant, viscosity modifier, or delivery device. Depending on the formulation, the carrier could be an aqueous vehicle, suspension vehicle, or another ophthalmically acceptable excipient system.

Claim 1 is therefore broader than claim 4, which requires an aqueous solution and specific numerical parameters.

What formulations are protected by claims 3 through 5?

Claims 3 through 5 define a narrower formulation subset.

Tobramycin-to-steroid ratio

Claim 3 requires a tobramycin-to-steroid ratio from 0.1:1.0 through 10.0:1.0. On a weight basis, the permitted range is approximately:

0.1 parts tobramycin per 1 part steroid.
10 parts tobramycin per 1 part steroid.

A formulation outside that ratio may remain within claim 1 or claim 2, but it would not satisfy claim 3.

Combined concentration

Claim 4 requires the combined concentration of tobramycin and steroid to be between 0.01% and 2.0% by weight.

For a product containing 0.3% tobramycin and 0.1% fluorometholone acetate:

Combined concentration: 0.4% by weight.
Tobramycin-to-steroid ratio: 3:1.

That numerical profile falls within claims 3 and 4, assuming the product is an aqueous solution and has a pH from 4.5 to 8.0.

Solution versus suspension

The distinction between an aqueous solution and an aqueous suspension is material. Fluorometholone acetate has limited water solubility, and commercial ophthalmic products may use a suspension rather than a true solution. A product that is technically an aqueous suspension would not satisfy claim 4’s “aqueous solution” limitation, although it could still fall within claim 1, claim 2, or claim 3.

The label for Zylet identifies the product as an ophthalmic suspension containing tobramycin 0.3% and fluorometholone acetate 0.1%.[3] Its concentration and ratio align with the numerical limitations, but the formulation classification must be evaluated separately from the active-ingredient profile.

When did U.S. Patent 5,149,693 expire?

U.S. Patent 5,149,693 issued on September 22, 1992. Under the pre-Uruguay Round patent-term regime applicable to the patent, the ordinary term was 17 years from issuance. The resulting expiration date was September 22, 2009.[1]

Event	Date
U.S. patent issuance	September 22, 1992
Ordinary 17-year expiration	September 22, 2009
Current status	Expired
Current enforceability	No enforceable patent term remaining

The patent is therefore relevant to historical freedom-to-operate analysis, prior litigation, and prosecution history, but it is not a current U.S. exclusivity barrier.

A patent term extension under 35 U.S.C. § 156 could have changed the date only if granted and reflected in the relevant records. The public patent and FDA listing history identifies the patent as expired in 2009.[1][2]

What was the commercial product associated with the patent?

The principal commercial product associated with the claimed combination was Zylet, an ophthalmic suspension containing:

Tobramycin: 0.3%.
Fluorometholone acetate: 0.1%.

The product is indicated for steroid-responsive inflammatory ocular conditions in which a superficial bacterial ocular infection exists or bacterial infection is a risk.[3]

Product characteristic	Zylet profile
Active antibiotic	Tobramycin 0.3%
Active steroid	Fluorometholone acetate 0.1%
Combined active concentration	0.4%
Approximate active ratio	3:1 tobramycin-to-steroid
Dosage form	Ophthalmic suspension
Therapeutic category	Anti-infective and corticosteroid ophthalmic combination
Patent relevance	Within the principal combination disclosed and claimed by Patent 5,149,693

The patent claims are broader than the marketed product in some respects. Claim 1 covers either fluorometholone or fluorometholone acetate and does not impose the numerical limits in claims 3 and 4.

What is the Orange Book status of U.S. Patent 5,149,693?

The patent was listed in FDA Orange Book records for the relevant tobramycin/fluorometholone acetate drug product. Orange Book listings identify patents submitted by an NDA holder as claiming the drug substance, drug product, or approved method of use. They do not independently establish that every listed claim is valid or infringed.[2]

For this patent:

The listed patent term has expired.
The patent does not create a current Orange Book patent block.
A present-day ANDA applicant would not face a live Paragraph IV dispute based solely on Patent 5,149,693.
FDA regulatory exclusivity and patent protection are separate rights.

The product’s historical Orange Book status should not be confused with current protection. An expired listed patent can remain visible in historical regulatory records while imposing no remaining stay or launch prohibition.

When did FDA exclusivity for the product end?

FDA marketing exclusivity is distinct from patent term. The relevant product was approved after the patent issued, but any ordinary new-drug exclusivity associated with the approval would have expired years before the current date. The product is not protected today by an active period of new chemical entity exclusivity, orphan-drug exclusivity, or pediatric exclusivity based on the patent claims.

The patent’s 2009 expiration date is the operative date for assessing this patent as a U.S. barrier. FDA exclusivity would not revive or extend the expired patent.

Were there Paragraph IV challenges to this patent?

A Paragraph IV certification would have been relevant while the patent was listed and unexpired. It would assert that the patent was invalid, unenforceable, or not infringed. Under the Hatch-Waxman framework, an ANDA filing containing a Paragraph IV certification could have triggered patent litigation and, if suit was filed within the statutory period, a 30-month FDA approval stay.[4]

For Patent 5,149,693, the commercial significance of any historical Paragraph IV challenge ended with patent expiration. After September 22, 2009:

The patent could no longer support a 30-month stay.
The patent could no longer block an ANDA launch.
A later generic applicant would not need to overcome this patent as a live exclusion right.
Any dispute would be academic unless tied to historical damages or pre-expiration conduct.

No current Paragraph IV risk remains under this patent.

What patent litigation affects U.S. Patent 5,149,693?

The principal litigation risk existed before expiration and would have involved an ANDA applicant seeking approval for a tobramycin/fluorometholone product. The legal issues would have included:

Whether the proposed generic label induced infringement of the method claims.
Whether the generic formulation satisfied the steroid, antibiotic, carrier, and administration limitations.
Whether the claimed ranges were met.
Whether the patent claims were anticipated or obvious in view of earlier ophthalmic steroid-antibiotic combinations.
Whether the patent had adequate written description and enablement.
Whether the patent was enforceable.

Because the patent expired in 2009, it no longer creates prospective injunctive risk. Any historical litigation must be analyzed separately for damages periods, settlement terms, launch dates, and claim construction rulings. The patent number alone does not establish a current litigation constraint.

How strong was the patent estate?

Strengths

The patent had several commercially useful characteristics:

It claimed a specific antibiotic-steroid ophthalmic combination.
Claim 1 covered both fluorometholone and fluorometholone acetate.
The treatment claim did not depend on a narrow brand-specific excipient system.
The claims could reach use of a corresponding generic product where the label directed treatment of both inflammation and infection.
The claimed 0.3% tobramycin/0.1% steroid profile falls within the numerical ratio and concentration ranges.

Limitations

The estate also had structural weaknesses:

The claims were method claims rather than direct composition claims.
Product-sale infringement would require a theory based on induced or contributory infringement, rather than literal infringement of a composition claim.
Claim 4 is limited to an aqueous solution, while commercial ophthalmic products may be suspensions.
The claim required both anti-inflammatory and anti-infective therapeutic purposes.
Generic labeling could affect induced-infringement exposure.
The patent had a finite pre-2009 term and could not support a post-expiration barrier.

The patent was commercially meaningful during its term but is now legally exhausted.

How does this patent compare with competing ophthalmic combination patents?

Patent 5,149,693 should be separated from patents covering other corticosteroid-antibiotic combinations.

Combination	Steroid	Antibiotic	Relationship to Patent 5,149,693
Tobramycin/fluorometholone acetate	Fluorometholone acetate	Tobramycin	Directly aligned with the claimed combination
Tobramycin/dexamethasone	Dexamethasone	Tobramycin	Different steroid; generally outside the literal steroid limitation
Neomycin/polymyxin B/dexamethasone	Dexamethasone	Neomycin and polymyxin B	Different steroid and antibiotic combination
Loteprednol/tobramycin	Loteprednol	Tobramycin	Different corticosteroid
Fluorometholone alone	Fluorometholone	None	Does not satisfy the required tobramycin limitation

The patent does not cover all ophthalmic anti-infective/corticosteroid products. It is composition-specific at the active-ingredient level, even though claim 1 is broad as a method claim.

What generic entry risks existed, and what risks remain?

Before expiration, generic entry risk depended on formulation and labeling:

A generic using fluorometholone acetate and tobramycin could implicate claim 1.
A 0.3%/0.1% product could implicate claims 2 and 3.
A product satisfying the claimed pH and concentration range could implicate claim 4 if it was an aqueous solution.
A product labeled for simultaneous infection and inflammation presented greater method-claim exposure than a product with a restricted, non-infringing label.

After expiration, these risks no longer prevent U.S. launch. Current competitors may sell products using the same active ingredients without infringing this patent, subject to other unexpired patents, trademark rights, FDA requirements, manufacturing controls, and product-specific regulatory obligations.

Does biosimilar risk apply?

No. Biosimilar risk does not apply to this patent because the product is a small-molecule ophthalmic drug, not a biologic. The relevant competitive pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under section 351(k) of the Public Health Service Act.

The commercial barriers are therefore generic-drug substitution, formulation development, sterile ophthalmic manufacturing, FDA approval, and any separate unexpired patents. Patent 5,149,693 is not one of those current barriers.

What manufacturing and geographic barriers remain?

The expired patent does not remove non-patent barriers. A competing manufacturer still must address:

Sterile ophthalmic manufacturing.
Uniform dispersion of fluorometholone acetate.
Particle-size control.
Suspension stability.
Preservative effectiveness.
Container-closure integrity.
Drop-size and dosing consistency.
Microbial limits and aseptic processing.
Bioequivalence or equivalent therapeutic performance requirements.
U.S. labeling and facility compliance.

The patent was a U.S. right. Expiration in the United States did not automatically terminate corresponding foreign patents. Foreign freedom-to-operate analysis requires separate review of national patent records, assignments, term adjustments, supplementary protection rights, and local litigation. U.S. Patent 5,149,693 itself has no current geographic enforceability in the United States.

What licensing and ownership issues matter?

The relevant licensing question is historical ownership and commercialization, not current enforcement. Patent assignments, mergers, and product rights should be distinguished:

Patent ownership determines who could sue during the patent term.
A product license determines who could commercialize the ophthalmic product.
An NDA holder may differ from the original patent owner.
A later corporate successor may hold historical records without possessing a live patent right.

Because Patent 5,149,693 expired in 2009, any historical license cannot recreate patent exclusivity today. Contractual restrictions, royalty obligations, or trademark rights could survive independently, but they are not patent rights.

Key Takeaways

U.S. Patent 5,149,693 covers topical treatment of ophthalmic inflammation and infection with fluorometholone or fluorometholone acetate plus tobramycin.
Claim 1 is the broadest claim and is a method-of-treatment claim.
Claims 3 and 4 narrow the scope using a 0.1:1 to 10:1 ratio, 0.01% to 2.0% combined concentration, and pH 4.5 to 8.0.
The 0.3% tobramycin/0.1% fluorometholone acetate profile associated with Zylet falls within the numerical ranges.
The distinction between an aqueous solution and suspension is material to claim 4.
The patent expired on September 22, 2009.
No current Paragraph IV, Orange Book, biosimilar, or generic-launch barrier remains under this patent.
Current competition is governed by FDA approval requirements, sterile ophthalmic manufacturing, trademarks, and any separate unexpired rights.

FAQs

Is U.S. Patent 5,149,693 a composition patent or a method patent?

It is a method patent. The claims require topical administration of the combination to an affected human eye. They do not directly claim the composition as an isolated article.

Does a tobramycin/fluorometholone product automatically infringe every claim?

No. Claim 1 requires treatment of ophthalmic inflammation and infection in a human using the specified combination. Claims 3 through 5 add ratio, concentration, pH, solution, and steroid limitations.

Does a product containing fluorometholone acetate but no tobramycin infringe?

No. Tobramycin is a required element of every claim.

Could a tobramycin/dexamethasone product infringe this patent?

Not literally based on the disclosed claims because dexamethasone is not fluorometholone or fluorometholone acetate. A separate patent analysis would be required for tobramycin/dexamethasone products.

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

No. An expired patent cannot impose a current approval stay or prevent launch. A generic applicant must still satisfy applicable FDA requirements and evaluate other live patents.

References

United States Patent and Trademark Office. (1992). U.S. Patent No. 5,149,693.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (n.d.). Zylet (tobramycin and fluorometholone acetate ophthalmic suspension) prescribing information.
Hatch-Waxman Amendments, 21 U.S.C. § 355(j); 35 U.S.C. §§ 271(e), 156.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	122564	⤷ Start Trial
Australia	3347689	⤷ Start Trial
Australia	606515	⤷ Start Trial
Canada	1338554	⤷ Start Trial
Germany	365613	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,149,693

Summary for Patent: 5,149,693