United States Patent 11,400,077: Claims, Scope, Expiration and Patent Landscape for Phentolamine Mydriasis Treatment

U.S. Patent No. 11,400,077 protects a post-examination method for reversing pharmacologically induced mydriasis with topical phentolamine mesylate. The broadest independent claim requires five elements: prior administration of tropicamide and/or phenylephrine, an ophthalmic phentolamine mesylate dose of about 0.4 to 0.6 mg, administration as an eye drop, treatment of the resulting mydriasis, and at least a 30% pupil-diameter reduction two hours after dosing under photopic conditions.[1]

The patent is commercially relevant to Ryzumvi, the FDA-approved phentolamine ophthalmic product marketed for reversal of pharmacologically induced mydriasis.[2] The strongest practical coverage is directed to a 0.5 mg aqueous eye drop administered after an examination involving phenylephrine, tropicamide, or both.

What patent does U.S. Patent 11,400,077 protect?

The patent protects a method of treating mydriasis after a patient has received an adrenergic or anticholinergic mydriatic agent.

Claim element	Requirement
Patient	Human patient
Condition	Mydriasis caused by tropicamide, phenylephrine, or both
Active ingredient	Phentolamine mesylate
Route	Topical administration to the eye
Dosage form	Eye drop
Dose	About 0.4 to about 0.6 mg
Efficacy threshold	At least 30% pupil-diameter reduction at two hours
Measurement condition	Photopic conditions
Additional timing limitation in claim 24	Administration after completion of the eye examination

Claim 1 is the principal method claim. It uses “comprising,” which generally leaves the claim open to additional treatment steps, excipients, or associated products, provided the listed elements are present.

The claim is narrower than a claim covering every use of phentolamine in the eye. It does not expressly cover:

Systemic phentolamine administration.
A formulation used without a prior mydriatic.
A dose outside approximately 0.4 to 0.6 mg.
A treatment that does not achieve the stated two-hour pupil-reduction result.
A non-drop delivery system, unless the product is legally characterized as an eye drop.
Reversal of mydriasis caused by drugs other than tropicamide or phenylephrine.

How do claims 1 through 24 differ?

Claims 2 through 24 create narrower species and performance limitations.

Triggering mydriatic agent

Claims 2 and 3 narrow the cause of mydriasis:

Claim 2 covers phenylephrine-induced mydriasis.
Claim 3 covers combined tropicamide and phenylephrine-induced mydriasis.

Claim 1 already reaches those scenarios because it covers one or more of tropicamide and phenylephrine. Claims 2 and 3 provide fallback positions if the broader language is challenged.

Pupil-reduction limitations

Claims 4 through 9 require specified absolute reductions in pupil diameter.

Claims	Required reduction
4 and 5	At least 1 mm under photopic conditions
6 and 7	At least 2 mm under photopic conditions
8 and 9	At least 2 mm at two hours after dosing

Claims 8 and 9 are commercially important because they combine the 2 mm result with a specific two-hour measurement point. A product or treatment protocol that routinely produces a smaller response could avoid these dependent claims but may still implicate claim 1 if it achieves the 30% reduction threshold.

Tolerability and accommodation

Claims 10 through 15 add safety and functional-performance requirements:

Eye redness increases by no more than two grades on the CCLRU Redness Grading Scale.
The patient experiences no burning sensation.
Change in accommodation is at least -1 diopter relative to baseline at two hours.

These limitations are difficult to assess solely from a product label. They generally require clinical data, protocol-specific measurements, or evidence that the claimed tolerability outcome is inherent in the accused method.

Onset and dose

Claims 16 and 17 require a therapeutic benefit within one hour. Claims 18 through 20 narrow the dose to approximately 0.5 mg.

The 0.5 mg limitation is commercially significant because it maps the patent more closely to a defined marketed dose rather than to the full claimed range.

Formulation limitations

Claims 21 through 23 narrow the method to an aqueous ophthalmic product and, in claim 23, identify a specific excipient combination:

Water
Mannitol
Sodium acetate
Approximately 0.5 mg phentolamine mesylate

Claim 23 is the most formulation-specific claim. It is less vulnerable to a challenge based on broad functional language but can be avoided by changing the composition, concentration, dose volume, or excipient system, subject to potential doctrine-of-equivalents arguments.

Post-examination administration

Claim 24 requires administration after the patient has completed an eye examination during which tropicamide, phenylephrine, or both were administered.

This claim ties the patented method to the clinical workflow used in optometry and ophthalmology offices. It may be particularly relevant to physician-administered or office-dispensed products.

What is the patent expiration date for U.S. Patent 11,400,077?

The patent issued on August 9, 2022. Its enforceable term is governed by the earliest effective nonprovisional filing date in the priority chain, not by the issue date.[1,3]

The publicly reported priority chain places nominal expiration in approximately 2038, before any patent-term adjustment. The final expiration date depends on:

The earliest nonprovisional or international application that supports the claimed subject matter.
Patent-term adjustment.
Any terminal disclaimer.
Whether a patent-term extension is available and granted.

The practical exclusivity window therefore extends into 2038 or later if patent-term adjustment applies. FDA regulatory exclusivity is separate from this patent term. A generic applicant could face patent-based barriers after regulatory exclusivity expires if the patent remains enforceable.

What is the Orange Book status of U.S. Patent 11,400,077?

The relevant reference product is Ryzumvi, phentolamine ophthalmic solution, approved by the FDA for reversal of pharmacologically induced mydriasis.[2]

The Orange Book analysis should distinguish three categories:

Protection type	Relevance
Listed patent	May support a Paragraph IV certification by an ANDA applicant
FDA regulatory exclusivity	Blocks certain abbreviated approvals for the applicable period
Unlisted method or formulation patent	May still support infringement litigation but may not automatically delay ANDA approval

U.S. Patent 11,400,077 is a method-of-use patent. Its commercial effect depends on whether it is listed against the approved Ryzumvi labeling and whether the approved labeling contains the patented use. If listed, an ANDA applicant would generally need to submit a Paragraph IV certification to challenge the patent or a Section viii statement to omit the protected use, depending on the proposed labeling and FDA’s treatment of the indication.[4]

A Paragraph IV certification is not itself a finding of infringement. It is a statutory assertion that the patent is invalid, unenforceable, or will not be infringed. The patent owner can bring an action under 35 U.S.C. § 271(e)(2), potentially triggering a 30-month stay of FDA approval under the Hatch-Waxman framework.[5]

What FDA regulatory exclusivity applies to Ryzumvi?

Ryzumvi was approved in 2023 for reversal of pharmacologically induced mydriasis produced by phenylephrine and/or tropicamide.[2] The product is a small-molecule ophthalmic drug, not a biologic. Biosimilar regulation under the Biologics Price Competition and Innovation Act does not apply.

The main regulatory routes are:

NDA approval for the reference product.
ANDA approval for a therapeutically equivalent generic, if the applicant can satisfy product, labeling, patent, and bioequivalence requirements.
Potential 505(b)(2) approval for a modified phentolamine ophthalmic product that relies in part on FDA findings for the reference drug but differs in formulation, dose, delivery system, or clinical use.

Regulatory exclusivity and patent protection should be modeled separately. A 505(b)(2) applicant may face different patent-certification obligations from an ANDA applicant, particularly for method-of-use and formulation patents.

Which companies are challenging U.S. Patent 11,400,077?

No publicly established Paragraph IV litigation or final court judgment against U.S. Patent 11,400,077 is identified in the supplied record. A definitive competitive challenge assessment requires current FDA Orange Book records, FDA Paragraph IV notifications, Patent Center prosecution data, and PACER litigation records.

The most likely challengers would be:

Generic ophthalmic manufacturers seeking an ANDA for phentolamine ophthalmic solution.
505(b)(2) developers pursuing a different concentration, dose volume, excipient system, or administration protocol.
Companies developing alternative reversal agents that do not contain phentolamine.
Compounding pharmacies or office-dispensing channels, although compounded products raise separate federal and state regulatory issues.

A generic applicant could attempt to avoid the claims by using a dose below 0.4 mg or above 0.6 mg, omitting phenylephrine or tropicamide from the labeled use, or adopting a method that does not require the claimed post-dose efficacy result. Those approaches carry commercial and regulatory tradeoffs.

How strong is the patent estate for phentolamine mydriasis treatment?

U.S. Patent 11,400,077 has meaningful product-level strength because claim 1 combines the drug, dose, route, indication, timing, and objective efficacy result. A commercial product that follows the Ryzumvi clinical workflow may satisfy most of those elements simultaneously.

Its principal vulnerabilities are claim-specific:

Functional-result vulnerability

The 30% pupil-reduction requirement is an objective limitation. The patentee would need to prove that the accused method produces the required result under photopic conditions. Variability in baseline pupil size, illumination, measurement equipment, and patient response may create factual disputes.

Dose-range vulnerability

The core range of approximately 0.4 to 0.6 mg is relatively narrow. A competitor may attempt dose selection outside the range. The practical viability of that strategy depends on whether the alternative dose retains efficacy and whether the doctrine of equivalents becomes relevant.

Method-of-use vulnerability

The patent does not prevent manufacture or sale of phentolamine mesylate by itself. Liability generally depends on use, induced use, labeling, instructions, or evidence that a manufacturer encourages the patented administration protocol.

Measurement vulnerability

“Photopic conditions,” pupil diameter, the CCLRU redness scale, accommodation, and therapeutic benefit require defined testing methods. Differences between clinical protocols can affect both infringement and validity analyses.

Formulation vulnerability

Claim 23 is narrow because it recites a particular excipient combination. A competing aqueous formulation using a different buffer, tonicity agent, preservative, or delivery volume may avoid literal infringement of that claim while remaining exposed to broader claims.

What manufacturing and intellectual-property barriers exist?

The active ingredient, phentolamine mesylate, is not itself a novel molecule. The commercial barriers are more likely to arise from ophthalmic formulation, sterility, stability, dose uniformity, container closure, and clinical performance.

Key barriers include:

Sterile aqueous manufacturing under current good manufacturing practice requirements.
Consistent delivery of approximately 0.5 mg per administered eye drop.
Stability of phentolamine mesylate in the selected pH and excipient system.
Microbial control and preservative strategy.
Dose-volume control in multidose or unit-dose containers.
Demonstration of pharmacodynamic reversal under photopic conditions.
Labeling that avoids or addresses patented method-of-use language.

A manufacturer could face patent risk even if it uses a different bottle or excipient system, because claims 1 and 18 are directed primarily to the treatment method and dose rather than to the container.

How does this patent compare with competing mydriasis products?

Ryzumvi is a reversal product. Mydcombi, by contrast, contains tropicamide and phenylephrine and is used to produce mydriasis for ophthalmic examinations. The products occupy opposite positions in the examination workflow.[2,6]

Product or technology	Active ingredients	Clinical role	Relationship to U.S. 11,400,077
Ryzumvi	Phentolamine ophthalmic solution	Reverses pharmacologically induced mydriasis	Directly aligned
Mydcombi	Tropicamide and phenylephrine	Produces mydriasis	Supplies the triggering condition
Generic phentolamine ophthalmic product	Phentolamine mesylate	Potential reversal product	May face method claims
Alternative reversal agent	Non-phentolamine active	Reverses dilation by another mechanism	Potentially outside literal scope

The patent does not claim the use of tropicamide or phenylephrine to dilate the pupil. It claims the subsequent use of phentolamine to reverse that effect.

What generic launch scenarios exist?

Scenario 1: Paragraph IV challenge

A generic applicant files an ANDA with a Paragraph IV certification against listed patents. Litigation could delay approval for up to 30 months, subject to statutory exceptions and court outcomes.[5]

Scenario 2: Section viii carve-out

The applicant removes the patented reversal indication from its labeling. This route is more difficult if the product’s commercial purpose is the patented use or if the remaining labeling would effectively encourage that use.

Scenario 3: 505(b)(2) product

A sponsor develops a different concentration, dose, formulation, or delivery system. This may reduce exposure to the exact claims but can create new clinical, formulation, and patent issues.

Scenario 4: Post-expiration entry

A company waits for patent expiration and pursues an ANDA or 505(b)(2) approval without a Paragraph IV litigation strategy. This minimizes litigation risk but delays market entry.

What revenue exposure does the patent create?

The patent creates exposure across the entire branded reversal market because the claimed method is closely tied to the standard office-based use of phentolamine after pharmacologic dilation. The highest-risk commercial activities are:

Selling a phentolamine eye drop with instructions to administer after tropicamide or phenylephrine.
Promoting a 0.5 mg dose.
Promoting reversal within one or two hours.
Reporting at least 30% or 2 mm pupil reduction.
Using the same aqueous formulation and clinical workflow described in the patent.

The patent is less likely to block non-phentolamine reversal products, diagnostic technologies, or products used for unrelated ophthalmic indications.

Key Takeaways

U.S. Patent 11,400,077 is a method-of-treatment patent covering topical phentolamine mesylate for reversing tropicamide- or phenylephrine-induced mydriasis.
Claim 1 requires an approximately 0.4 to 0.6 mg eye-drop dose and at least a 30% pupil-diameter reduction at two hours under photopic conditions.
Claims 18 through 23 provide commercially relevant protection around a 0.5 mg aqueous formulation and specified excipients.
Claim 24 protects the post-eye-examination administration workflow.
The nominal patent term extends into approximately 2038, subject to patent-term adjustment and the complete priority record.
Ryzumvi is the principal commercial product aligned with the claimed method.
Generic entry would likely require a Paragraph IV challenge, a labeling carve-out, a 505(b)(2) strategy, or a post-expiration launch.
The patent is strongest against a product that copies the branded dose, indication, clinical timing, and post-examination administration sequence.

FAQs

Can a generic phentolamine eye drop avoid U.S. Patent 11,400,077 by changing the excipients?

Potentially, but changing excipients would not avoid the broader method claims if the product still administers approximately 0.4 to 0.6 mg topically to reverse tropicamide- or phenylephrine-induced mydriasis and achieves the claimed pupil-reduction result.

Does U.S. Patent 11,400,077 cover phentolamine use for presbyopia?

Not based on the supplied claims. The claims are directed to reversal of mydriasis caused by tropicamide, phenylephrine, or both. Presbyopia treatment would require separate claim language and may be covered by different patents.

Can a physician infringe the patent by administering phentolamine after an eye examination?

A physician’s administration could satisfy direct method infringement if every claim element is met. Commercial liability for a manufacturer or distributor would require a separate analysis of induced or contributory infringement, labeling, and the facts of the supply relationship.

Does biosimilar competition threaten phentolamine ophthalmic exclusivity?

No. Phentolamine ophthalmic solution is a small-molecule drug. The relevant competitors are ANDA generics, 505(b)(2) products, alternative reversal agents, and compounded products, not biosimilars.

What clinical data are most important in a validity or infringement dispute?

The critical data are dose delivered, baseline and post-dose pupil diameter, photopic measurement conditions, timing at two hours, prior use of tropicamide or phenylephrine, accommodation results, redness grading, and evidence of burning or other tolerability outcomes.

References

United States Patent and Trademark Office. (2022). U.S. Patent No. 11,400,077, Methods of treating mydriasis.
U.S. Food and Drug Administration. (2023). Ryzumvi (phentolamine ophthalmic solution) prescribing information and approval materials.
United States Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation guidance.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355(j); 35 U.S.C. § 271(e).
U.S. Food and Drug Administration. (2023). Mydcombi (tropicamide and phenylephrine hydrochloride ophthalmic spray) prescribing information.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Famygen Life Sci	RYZUMVI	phentolamine mesylate	SOLUTION;OPHTHALMIC	217064-001	Sep 25, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				TREATMENT OF PHARMACOLOGICALLY-INDUCED MYDRIASIS	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2019366451	⤷ Start Trial
Australia	2024219970	⤷ Start Trial
Brazil	112021007725	⤷ Start Trial
Canada	3116589	⤷ Start Trial
China	113164452	⤷ Start Trial
Denmark	3870170	⤷ Start Trial
European Patent Office	3870170	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 11,400,077