Details for Patent: 4,551,456

Summary for Patent: 4,551,456

Title:	Ophthalmic use of norfloxacin and related antibiotics
Abstract:	Norfloxacin and related antibiotics are useful in the treatment of ocular infections by topical administration.
Inventor(s):	Irving M. Katz
Assignee:	Merck and Co Inc
Application Number:	US06/551,775
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

US Patent 4,551,456: Scope, Claim-by-Claim Analysis, and US Landscape for Topical Ocular Antibiotic Dosing

US Patent 4,551,456 claims a method of treating ocular bacterial infections by topical ocular administration of a defined dose range (0.015 to 1.5 mg) of a specified fluoroquinolone-class antibiotic (and named candidates), with further dependent claim limits on norfloxacin form and on a thermogelling, clear carrier.

Because only the claim text was provided, the analysis below focuses on claim scope construction and the resulting freedom-to-operate (FTO) impact that this claim set typically creates in the US landscape for topical ophthalmic fluoroquinolones.

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What does the independent claim cover? (Claim 1)

Claim 1 text (core elements)

Claim 1 is a method claim, not a composition claim. It covers:

1. Use/type of condition: treating ocular bacterial infections
2. Route/site: topical ocular administration to an infected eye
3. Dose limitation: administration of 0.015-1.5 mg of an antibiotic
4. Antibiotic genus/list constraint: the antibiotic must be selected from
   • norfloxacin
   • ofloxacin
   • pefloxacin
   • AT-2266
   • Bayer 09867
5. Form constraint: the administered antibiotic is a hydrate or an ophthalmologically acceptable salt

Scope implications

A method claim with a numeric dose range typically narrows infringement exposure to specific dosing regimens tied to what the accused product or method actually delivers to the eye.

Key scope drivers:

• Route and indication are mandatory. A systemic regimen, a non-ocular route, or treatment of non-bacterial ocular conditions would not read on Claim 1.
• The antibiotic list is limiting. Even if a competitor uses a fluoroquinolone, infringement under Claim 1 would require that the antibiotic is one of the listed agents (or a hydrate/salt of one of them), including the more specific named candidates (AT-2266 and Bayer 09867).
• The dose is a strict numerical bracket. The claim requires administration of a dose amount in mg within 0.015 to 1.5 mg. If a product delivers less or more per administration unit, the method can be outside the literal range.
• Form limitation (hydrate/salt) creates a second gate. If a formulation uses free base (not a hydrate) or uses a salt that is not “ophthalmologically acceptable” under claim interpretation, Claim 1 could fail.

Practical claim construction for FTO

If a topical ophthalmic product delivers one of the listed antibiotics, infringement depends on:

• Whether the label method targets “ocular bacterial infections”
• Whether the administered amount per dosing event fits 0.015 to 1.5 mg
• Whether the chemical species is a hydrate or ophthalmologically acceptable salt
• Whether the delivery is “topical ocular administration to an infected eye” (method of use evidence can matter)

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How narrow is Claim 1’s antibiotic set? (Claims 2 and 1’s list)

Claim 1 uses “selected from” and names five antibiotics/candidates. That structure is important:

• It is not “a fluoroquinolone” broadly.
• It is a closed list (plus “hydrate or salts”).

Dependent Claim 2 meaning

Claim 2 limits Claim 1 by specifying:

• antibiotic is norfloxacin, a hydrate, or an ophthalmologically acceptable salt.

This tightens both:

• identity (norfloxacin only), and
• form (hydrate or ophthalmologically acceptable salt).

Scope consequence

If a product uses ofloxacin or pefloxacin, it cannot satisfy Claim 2. It can still potentially fall under Claim 1 (if dose range and form fit).

If a product uses norfloxacin but not as a hydrate/salt, it risks missing both Claim 2 and part of Claim 1’s form requirement, depending on claim construction of what counts as “hydrate” or “ophthalmologically acceptable salt.”

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What does Claim 3 restrict about formulation?

Claim 3 text (form/vehicle limitation)

Claim 3 limits Claim 2:

• norfloxacin is administered as an aqueous solution.

Scope impact

This is a vehicle limitation. It narrows infringement for norfloxacin to aqueous solution delivery.

Common design-around logic (in practice) is to use:

• non-aqueous systems,
• suspensions,
• gels where the norfloxacin is not in an “aqueous solution” state.

However, literal infringement for Claim 3 turns on how “aqueous solution” is interpreted versus suspension/gel states under claim construction and evidence of formulation structure.

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What does Claim 4 add about the carrier?

Claim 4 text

Claim 4 adds:

• “the carrier is a clear physiologically-acceptable liquid which forms a semi-solid gel at human body temperatures.”

This is a thermogelling carrier limitation, with three structural constraints:

1. Clear physiologically-acceptable liquid
2. Carrier forms a semi-solid gel at body temperature
3. Carrier must be the carrier used with the Claim 1 method elements (because it depends from Claim 1 through the chain).

Scope impact

Claim 4 can be a meaningful narrowing for FTO because many ophthalmic products are:

• fixed aqueous solutions,
• suspensions,
• ointments,
• or non-thermogelling gels.

To fall under Claim 4, a product’s carrier system must show thermogelling behavior at human body temperatures.

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How the dependent claims stack creates multiple “infringement lanes”

These dependences create layered coverage:

• Lane A: Claim 1 only
  • Antibiotic is any of the five named agents (as hydrate or ophthalmologically acceptable salt), within dose range, via topical ocular administration for ocular bacterial infections.
• Lane B: Claim 1 + Claim 2
  • Antibiotic is norfloxacin (hydrate or ophthalmologically acceptable salt), within Claim 1 dose range and route and indication.
• Lane C: Claim 1 + Claim 2 + Claim 3
  • Adds “aqueous solution” as norfloxacin form/vehicle.
• Lane D: Claim 1 + Claim 2 + Claim 4
  • Adds thermogelling clear carrier that becomes semi-solid gel at body temperature.

In practice, competitors can avoid one lane while still potentially triggering another depending on:

• which antibiotic is used,
• whether formulation is aqueous solution,
• and whether the carrier thermogels.

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What the numeric dose range likely means for product-level infringement risk

Claim 1 requires administration of 0.015 to 1.5 mg of antibiotic per administration method event.

Dose mapping framework

For a commercial eye dropper regimen, infringement risk is driven by how much drug reaches the eye per dosing event, typically inferred from:

• labeled concentration (mg/mL),
• delivered volume per drop (mL per drop),
• dosing frequency,
• and whether the patent litigations construe “administered” as nominal dose vs delivered dose.

Since this is a method claim with a mg range, product engineering can target:

• concentration,
• unit dose,
• and dosing frequency.

Even with the same concentration, per-administration delivered mg can differ based on device volume and dosing technique.

Range breadth

• 0.015 mg is a low dose point
• 1.5 mg is high for single-event ocular antibiotic exposure

A wide mg band can capture many conventional ophthalmic dosing regimens, which is why the carrier/form limitations in dependent claims matter for knockouts.

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Where this claim sits in the broader US ophthalmic fluoroquinolone landscape

Without the patent’s full specification, prosecution history, and family members, the most reliable landscape conclusion comes from the claim scope structure:

• The claim is a topical ophthalmic antibacterial method
• It targets fluoroquinolone antibiotics (norfloxacin, ofloxacin, pefloxacin) plus two named candidates (AT-2266 and Bayer 09867)
• It imposes a dose range and form limits (hydrates/salts), and in dependent claims, vehicle and thermogelling carrier constraints.

Typical US landscape pattern (functional)

US patent families in this area commonly separate:

1. Active ingredient disclosures (chemical entities and polymorphs/hydrates/salts)
2. Topical ophthalmic compositions (vehicles, preservatives, viscosities, gels, thermogels)
3. Method of treatment claims (indications, dosing regimens, dosing units)
4. Use claims tied to specific dose windows and delivery systems

Claim 4’s thermogel language suggests this patent family was positioned not just for “drop solutions,” but also for temperature-responsive ophthalmic vehicles, which can be relevant to later products using thermogelling systems.

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How to interpret “ophthalmologically acceptable salts” in US infringement analysis

Claim 1 and 2 cover “hydrates or ophthalmologically acceptable salts.” That phrase usually expands the claim beyond the exact active chemical identity to include certain salt forms, provided they are considered acceptable for ophthalmic use.

Practical consequence

A competitor cannot rely solely on changing from a free base to a salt if the new salt is still “ophthalmologically acceptable” and fits the hydrate/salt requirement as construed.

Design-around is more likely achieved by:

• using a non-listed antibiotic (not in the “selected from” list), or
• using a different chemical species that is outside “hydrate” and outside “ophthalmologically acceptable salt,” or
• moving outside the dose bracket,
• changing route/indication evidence,
• changing vehicle out of “aqueous solution” (Claim 3) or out of the “clear liquid that forms semi-solid gel at body temperature” (Claim 4).

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Carrier design and Claim 4: What product classes get blocked

Claim 4 targets a specific formulation behavior: clear liquid that becomes semi-solid gel at body temperature.

That generally aligns with:

• thermoresponsive polymer systems used for ocular retention,
• in-situ gelling ophthalmic formulations.

It is less aligned with:

• conventional low-viscosity aqueous solutions that remain solutions,
• suspensions,
• classic ointments,
• or non-thermogelling gels.

This matters because it creates a narrower claim lane that is easier to avoid by selecting a non-thermogelling vehicle, while still potentially remaining within Claim 1 if antibiotic/dose/form match and the carrier limit is not asserted.

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What is the patent’s effective “coverage map” across competitor parameters

Parameter	Claim 1 requirement	Claim 2 adds	Claim 3 adds	Claim 4 adds
Indication	ocular bacterial infections	same	same	same
Route	topical ocular administration	same	same	same
Antibiotic identity	one of: norfloxacin, ofloxacin, pefloxacin, AT-2266, Bayer 09867 (as hydrate/salt)	norfloxacin only	norfloxacin only	norfloxacin only
Chemical form	hydrate or ophthalmologically acceptable salt	hydrate or ophthalmologically acceptable salt	aqueous solution (vehicle form)	thermogelling clear liquid carrier (vehicle behavior)
Dose amount	0.015 to 1.5 mg	same	same	same

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Business implications for US R&D and investment screening

1) The numeric dose range is the key inclusion gate

A US clearance review should check whether the intended regimen, per dosing event, stays outside 0.015-1.5 mg for the relevant antibiotic identity/form.

2) The antibiotic list is the key identity gate

If the target project uses an ophthalmic fluoroquinolone not listed, Claim 1 is structurally easier to avoid. If it uses one of the listed actives, clearance shifts to dose and formulation lanes.

3) The hydrate/salt gate is a second inclusion gate

Formulating as a hydrate or ophthalmologically acceptable salt can keep you inside Claim 1 or 2. Changing salt/hydrate form may help, but only if the new species falls outside the claim language as construed.

4) Dependent claim vehicle limits can be used as design levers

If the development plan uses norfloxacin:

• “aqueous solution” becomes a critical boundary under Claim 3.
• thermogelling clear liquids become a critical boundary under Claim 4.

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Key Takeaways

• US 4,551,456 is a method-of-treatment patent for topical ocular administration to treat ocular bacterial infections using 0.015 to 1.5 mg of a specified set of antibiotics (norfloxacin, ofloxacin, pefloxacin, AT-2266, Bayer 09867) as hydrates or ophthalmologically acceptable salts.
• Claim 2 narrows the antibiotic to norfloxacin (still hydrate/salt).
• Claim 3 further narrows norfloxacin administration to an aqueous solution.
• Claim 4 further narrows the carrier to a clear physiologically acceptable liquid that forms a semi-solid gel at human body temperatures.
• In US freedom-to-operate evaluation, the practical “yes/no” gates are: indication/route evidence, dose per administration (mg), active identity (closed list), and formulation vehicle and behavior for dependent claims.

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FAQs

1) Does US 4,551,456 cover systemic treatment of bacterial eye infections?
No. The claims require topical ocular administration to an infected eye.

2) If a product uses ofloxacin as the active, is it covered by Claim 1?
Potentially, yes. Claim 1 includes ofloxacin (as a hydrate or ophthalmologically acceptable salt) if the dose is within 0.015 to 1.5 mg and the method treats ocular bacterial infections.

3) Does using norfloxacin automatically trigger all claims?
No. Norfloxacin is required for Claim 2, Claim 3, and Claim 4, but Claim 3 adds aqueous solution, and Claim 4 adds a specific thermogelling carrier behavior.

4) Can a competitor avoid Claim 4 by switching from a thermogelling carrier to a non-thermogelling gel?
Yes in principle. Claim 4 requires a clear physiologically acceptable liquid that forms a semi-solid gel at human body temperatures. A non-thermogelling system would not meet that limitation.

5) Is the antibiotic list in Claim 1 broad?
It is limited. Claim 1 covers antibiotics “selected from” a named set: norfloxacin, ofloxacin, pefloxacin, AT-2266, and Bayer 09867 (as hydrates/salts).

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References

[1] United States Patent No. 4,551,456 (claim set provided).

Drugs Protected by US Patent 4,551,456

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 4,551,456

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	3538084
Australia	567979
Canada	1241599
Denmark	537784