United States Patent 5,212,196: Scope, Claims, Expiration, and Patent Landscape for Laser-Surgery IOP Control

U.S. Patent No. 5,212,196 covers topical use of substituted phenylimino-imidazoline compounds to control or prevent acute intraocular-pressure elevation associated with ophthalmic laser surgery. The patent is a method-of-use patent, not a composition-of-matter or manufacturing patent. It issued May 18, 1993, and its ordinary 17-year term from issuance expired May 18, 2010, subject to any patent-term adjustment or terminal disclaimer reflected in the official prosecution record. It is therefore no longer an enforceable U.S. patent.

The principal commercial relevance was the use of apraclonidine and related alpha-adrenergic imidazoline compounds around laser procedures such as laser iridotomy and laser trabeculoplasty. Current commercial risk from this patent is effectively limited to historical infringement analysis, damages disputes, validity research, or assessment of continuation and foreign-family rights.

What does U.S. Patent 5,212,196 protect?

The patent protects a treatment protocol rather than a particular bottle, formulation, manufacturing process, or active ingredient as such.

The central claimed method requires:

An ophthalmic laser surgical procedure.
An acute postoperative rise in intraocular pressure associated with that procedure.
Topical application to the involved eye.
Application both before and after the procedure.
An amount of a substituted phenylimino-imidazoline compound effective to control or prevent the pressure rise.

Independent claim 1 defines a broad imidazoline genus using substituent variables R1, R2, X, and Y. Independent claim 17 defines a second genus in which at least one of X and Y is alkyl. Independent claim 22 uses functional and structural language for a substituted phenylimino-imidazoline without reproducing the full formula.

Claim group	Subject matter	Principal limitation
Claim 1	Broad imidazoline method	Pretreatment and post-treatment around ophthalmic laser surgery
Claims 2-5	Specific compounds under claim 1	Defined R1/R2 and ring-substituent combinations
Claim 6	Restricted compound genus	R1/R2 limited principally to H and NH2
Claims 7-15	Species under claim 6	Specific methyl, ethyl, chloro and mixed substitution patterns
Claim 16	Concentration limitation	Approximately 0.05% to 5% by weight
Claim 17	Second broad genus	At least one of X and Y is alkyl
Claims 18-20	Species under claim 17	Diethyl, ethyl-methyl and chloro-ethyl substitution
Claim 21	Concentration limitation	Approximately 0.05% to 5% by weight
Claim 22	Functional genus	Substituted phenylimino-imidazoline applied before and after surgery

The practical claim center is the perioperative administration schedule. A product used only after surgery, or only for chronic glaucoma control, would not meet the express before-and-after limitation of the independent claims.

How broad are the independent claims?

Claim 1

Claim 1 has both structural and use limitations. The compound must fall within the stated imidazoline formula, and the use must address an acute postoperative IOP rise linked to ophthalmic laser surgery.

The claim covers:

Free-base compounds.
Pharmaceutically acceptable acid salts.
R1 and R2 substituents selected from hydrogen, hydroxyl, and amino or alkylamino groups.
X and Y selected from bromine, chlorine, methyl, and ethyl.
Topical administration before and after the laser procedure.

The requirement that one of R1 and R2 is always hydrogen narrows the genus. The claim does not cover every substituted imidazoline or every alpha-adrenergic ophthalmic drug.

Claim 17

Claim 17 is structurally different. It covers a formula II compound with X and Y selected from bromine, chlorine, methyl, and ethyl, provided at least one is alkyl. Claims 18-20 then identify particular ethyl, methyl, and chloro combinations.

This limitation excludes compounds in which both X and Y are halogen unless another claim independently captures them. The claim is potentially broader in relation to R1 and R2 because those substituents are not expressly recited in the supplied text.

Claim 22

Claim 22 is the most functionally framed independent claim. It requires topical application of a substituted phenylimino-imidazoline before and after an ophthalmic laser procedure to control or prevent acute postoperative IOP elevation.

Its breadth would depend heavily on the specification's definition of "substituted phenylimino-imidazoline," the prosecution history, and the written-description support for compounds not expressly listed in the claims. The claim is potentially vulnerable to:

Written-description challenges if construed to cover compounds outside the disclosed examples.
Enablement challenges if the genus is read broadly.
Indefiniteness arguments concerning the boundaries of "effective" treatment and "acute" postoperative pressure rise.
Prosecution-history limitations imposed during examination.

Which compounds are specifically covered?

The supplied claim text identifies several substitution patterns. The claims refer to imidazoline derivatives with combinations of amino, alkylamino, hydrogen, hydroxyl, methyl, ethyl, chlorine, and bromine substituents.

The most commercially relevant compound associated with this therapeutic area is apraclonidine hydrochloride, the active ingredient in Iopidine. Apraclonidine is an alpha-adrenergic agonist derived from clonidine and is used ophthalmically to reduce short-term IOP elevations, including pressure increases after laser procedures. The exact mapping of apraclonidine to the numbered species requires the patent drawings and the patent's chemical nomenclature, which are not reproduced in the supplied claim text.

The claim text also contains apparent transcription problems. Claim 4 recites "NH2 CH3," which is chemically ambiguous and may represent an OCR or source-formatting error. Claims 13-15 duplicate claims 7-9 in substance, and claims 14 and 15 duplicate earlier species. These defects affect claim interpretation but do not change the patent's expired status.

What formulations are protected by U.S. Patent 5,212,196?

Claims 16 and 21 recite topical concentrations of approximately 0.05% to 5% by weight. Those claims do not claim a formulation as a composition. They claim use of the relevant compound at the stated concentration.

The patent therefore does not, on its face, require:

A particular preservative.
A particular buffer.
A specific pH.
A specific viscosity.
A particular container or dropper.
A defined dosing volume.
A particular salt concentration.
A specific formulation excipient.

A commercial ophthalmic solution could fall within the concentration claims if it used a qualifying compound in the claimed range and followed the claimed perioperative administration protocol. A formulation containing the same active ingredient at a different concentration could still implicate claims 1, 17, or 22 if all other claim elements were met.

Does the patent cover chronic glaucoma treatment?

No. The claims are directed to acute postoperative IOP elevation associated with ophthalmic laser surgery.

The patent does not expressly claim:

Long-term glaucoma treatment.
Chronic ocular hypertension treatment.
Standalone reduction of baseline IOP.
Oral administration.
Intravenous administration.
Intracameral administration.
Use unrelated to laser surgery.

A chronic glaucoma indication could involve separate method-of-use patents, regulatory exclusivity, or product-label restrictions. Those rights would need to be analyzed independently from U.S. Patent 5,212,196.

When did U.S. Patent 5,212,196 expire?

Event	Date or status
U.S. patent number	5,212,196
Issue date	May 18, 1993
Statutory term for a pre-June 8, 1995 application	Generally 17 years from issue
Ordinary calculated expiration	May 18, 2010
Present enforceability	Expired
U.S. generic blocking effect	None from this patent

Because the patent issued before the Uruguay Round Agreements Act transition rules took full effect, its baseline term was generally calculated from issuance rather than the modern 20-year-from-earliest-effective-filing-date rule. The official USPTO record controls for patent-term adjustment, terminal disclaimers, reexamination certificates, and any other term-affecting event.[1]

No current U.S. infringement claim can ordinarily be based on an expired patent. The patent may still matter in prior commercial disputes, validity analyses, freedom-to-operate reports covering historical periods, and interpretation of related family members.

What was the FDA and Orange Book status?

Apraclonidine ophthalmic solution was approved by FDA and marketed as Iopidine. FDA labeling identifies apraclonidine hydrochloride as an alpha-adrenergic agonist used to prevent or reduce IOP elevation associated with anterior-segment laser procedures.[2]

The relevant regulatory distinction is:

FDA approval concerns safety, efficacy, labeling, and product quality.
The Orange Book identifies patents and exclusivity associated with approved drug products.
A patent's presence in the Orange Book does not extend the patent term.
Expired patents do not create a current U.S. launch bar.

Iopidine's commercial protection depended on a combination of FDA approval, brand market position, formulation and labeling rights, and any listed patents applicable to the approved product. U.S. Patent 5,212,196, having expired in 2010, does not currently block an ANDA applicant.

Were there Paragraph IV challenges?

A Paragraph IV certification would have been relevant while the patent was listed and unexpired. A generic applicant could have asserted that the patent was invalid, unenforceable, or not infringed.

For an expired patent, a Paragraph IV challenge generally has no present commercial function because the patent no longer delays approval or launch. Historical ANDA records, litigation dockets, and settlement terms would be required to identify the particular applicants, certification dates, and any court decisions.

The claim architecture would have created several possible non-infringement positions:

The product was not used in an ophthalmic laser procedure.
The drug was administered only after surgery.
The drug was not administered topically.
The active ingredient did not fall within the claimed chemical genus.
The procedure did not produce the claimed acute postoperative IOP rise.
The concentration was outside claims 16 and 21.
The use was for chronic IOP management rather than perioperative control.

Potential validity positions included lack of novelty, obviousness over prior imidazoline ophthalmic use, lack of enablement across the genus, written-description deficiencies, and indefiniteness of functional terms.

What patent litigation affected the patent?

The patent's business significance was linked to the commercial use of apraclonidine and related ophthalmic products. The supplied information does not identify a particular infringement action, ANDA defendant, district-court docket, settlement, or Federal Circuit decision involving U.S. Patent 5,212,196.

The patent should therefore be treated as an expired historical right rather than a current litigation barrier. Any assertion that a particular company challenged, settled, licensed, or litigated this patent would require confirmation from PACER, district-court filings, USPTO Patent Center, or an authenticated prosecution and litigation database.

How strong was the patent estate?

Strengths

The independent claims tied the compound to a specific clinical problem.
The before-and-after dosing limitation created a defined perioperative protocol.
The claims covered multiple substituted imidazoline species.
Salt forms were included in claim 1.
Concentration-dependent dependent claims added a formulation-use layer.
Claim 22 potentially captured compounds not individually listed in the narrower dependent claims.

Weaknesses

The patent claimed therapeutic use rather than the active molecule itself.
Infringement required proof of the actual perioperative use.
"Effective" amount and "acute" postoperative IOP rise introduced factual and construction issues.
The chemical formulae are essential, but they are absent from the supplied text.
Several dependent claims appear duplicative or contain notation errors.
Prior art concerning alpha-adrenergic imidazolines and ophthalmic IOP control would have been central to obviousness analysis.
The patent expired more than a decade ago.

Overall, the patent was commercially meaningful when enforceable but had a narrower enforcement profile than a composition-of-matter patent covering apraclonidine itself.

How does this patent compare with other protection for apraclonidine?

Protection type	Scope	Current relevance
U.S. Patent 5,212,196	Perioperative topical use around ophthalmic laser surgery	Expired
Composition-of-matter patent	Chemical identity of apraclonidine or related compounds	Depends on separate family and expiration
Formulation patent	Solution, salt, preservative, pH, container or stability features	Depends on separate patent family
Method-of-use patent	Glaucoma, ocular hypertension, or laser-procedure indications	Depends on claim language and expiration
FDA orphan or pediatric exclusivity	Regulatory approval timing	Does not apply based on the supplied record
Trade secret	Manufacturing or formulation know-how	May remain relevant if not publicly disclosed

The key business point is that U.S. Patent 5,212,196 did not establish a continuing monopoly over apraclonidine. A current entrant would need to review separate active patents, FDA-listed rights, formulation patents, trademark rights, and regulatory requirements.

What generic entry risks exist today?

For the specific expired patent, no current U.S. generic-entry risk remains because the patent cannot ordinarily be enforced.

A modern entrant could still face:

FDA approval requirements for an ANDA or other abbreviated pathway.
Reference-product exclusivity or regulatory exclusivity, if any remains.
Active formulation or manufacturing patents.
Patent litigation involving later patents.
Labeling restrictions if the proposed product includes or omits the laser-surgery indication.
Product-liability and ophthalmic manufacturing requirements.
Commercial barriers from limited market size and established ophthalmic suppliers.

The lack of a current bar from Patent 5,212,196 does not establish that every apraclonidine product is free of all other intellectual-property constraints.

Does the patent create biosimilar risk?

No. Apraclonidine is a small-molecule drug, not a biologic. Biosimilar statutes and the BPCIA do not govern an apraclonidine product. The relevant pathway is generally an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, subject to product-specific FDA requirements.

What is the geographic coverage?

The patent covered the United States only. Foreign counterparts, if any, required separate prosecution and had separate terms, claim scope, validity, and lapse histories.

A global freedom-to-operate review would need to distinguish:

U.S. Patent 5,212,196.
Foreign national-phase or priority-family patents.
European, Canadian, Japanese, and other jurisdictional rights.
Patent term extensions or supplementary protection certificates.
Local regulatory exclusivities.
National litigation and settlement records.

Expiration of the U.S. patent does not establish expiration of foreign family members.

What manufacturing and IP barriers remain?

Patent 5,212,196 does not claim a manufacturing process. It does not prevent synthesis of a covered imidazoline after expiration, and it does not create a current barrier to contract manufacturing.

Remaining barriers may include:

Process patents in other families.
Crystalline or polymorphic-form patents.
Salt or impurity-control patents.
Sterile ophthalmic manufacturing capability.
Container-closure compatibility.
Preservative and multidose-delivery technology.
FDA inspection and quality-system requirements.
Commercial sourcing of qualified active pharmaceutical ingredient.

Key Takeaways

U.S. Patent 5,212,196 claims topical perioperative use of substituted phenylimino-imidazolines to prevent acute IOP elevation after ophthalmic laser surgery.
It is a method-of-use patent, not a composition-of-matter patent.
The core requirement is topical administration both before and after the laser procedure.
Claims 16 and 21 add a 0.05% to 5% concentration range.
Apraclonidine is the principal commercial compound associated with this therapeutic area, although exact claim-species mapping requires the patent drawings and specification.
The patent issued May 18, 1993, and its ordinary 17-year term expired May 18, 2010.
It creates no current U.S. generic-launch blocking right.
It does not create biosimilar risk because apraclonidine is a small molecule.
Separate formulation, process, composition, regulatory, and foreign patents must be reviewed independently.
The supplied claim transcription contains apparent chemical notation and duplication errors.

FAQs

Is U.S. Patent 5,212,196 still enforceable?

No. Its ordinary patent term expired in 2010, absent an unusual term event not reflected in the supplied record.

Does Patent 5,212,196 cover Iopidine as a product?

No. The claims cover a method of using qualifying imidazoline compounds. They do not claim Iopidine as a composition.

Can a generic use apraclonidine before and after laser surgery?

The expired patent does not prevent that use. A generic applicant must still assess active patents, FDA requirements, labeling strategy, and any later-listed rights.

Does the patent cover brimonidine?

The supplied claims do not establish that brimonidine falls within the claimed phenylimino-imidazoline structures. Brimonidine has a distinct quinoxaline-based structure and requires separate claim-chart analysis against the actual patent formulae.

What is the most important limitation for infringement?

The strongest narrowing limitation is the requirement that the drug be applied topically both prior and subsequent to an ophthalmic laser surgical procedure to control or prevent an acute postoperative IOP rise.

References

United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term expiration guidance. https://www.uspto.gov/patents/laws/patent-term-adjustment
U.S. Food and Drug Administration. (n.d.). Iopidine label: Apraclonidine hydrochloride ophthalmic solution. https://www.accessdata.fda.gov/drugsatfda_docs/label/
United States Patent and Trademark Office. (1993). U.S. Patent No. 5,212,196. Patent Center. https://patentcenter.uspto.gov/
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application pathway. https://www.fda.gov/drugs/types-applications/abbreviated-new-drug-application-anda

Details for Patent: 5,212,196

Summary for Patent: 5,212,196