Details for Patent: 12,576,067

Which drugs does patent 12,576,067 protect, and when does it expire?

Patent 12,576,067 protects RYZUMVI and is included in one NDA.

This patent has twenty patent family members in fifteen countries.

Summary for Patent: 12,576,067

Title:	Methods and compositions for treatment of mydriasis
Abstract:	The invention provides methods, compositions, and kits containing an alpha-adrenergic antagonist, such as phentolamine, for use in monotherapy or as part of a combination therapy to treat patients suffering from presbyopia, mydriasis, and/or other ocular disorders.
Inventor(s):	Mina Sooch, Alan R. Meyer, Konstantinos Charizanis, Bernhard Hoffmann, William H. Pitlick
Assignee:	Opus Genetics Inc
Application Number:	US19/029,592
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

US Patent 12,576,067 Scope and Claim-by-Claim Patent Landscape for Topical Phentolamine Mesylate to Reverse Pharmacologically Induced Mydriasis

Executive summary. US 12,576,067 covers methods for treating pharmacologically induced mydriasis after ocular administration of tropicamide and/or phenylephrine, including specific rescue dosing of phentolamine mesylate as two topical eye drops of a 1% (w/w) solution (and broader dosing bands, formulations, and storage stability parameters). The claim set is structured around (i) indication and trigger (what causes the mydriasis), (ii) time and clinical response endpoints (pupil reduction within 1-2 hours; redness limits), (iii) patient qualifiers (adult; no ocular inflammation; timing after eye exam), and (iv) formulation chemistry controls (aqueous ophthalmic solutions with defined phentolamine strength ranges, polyols, sodium/alkali metal acetate buffer, pH 4-6, and “no chelating agent” and degradation thresholds). The estate is method-of-treatment plus formulation-defined method claims; enforcement risk for competitors is highest against any topical phentolamine mesylate “mydriasis reversal” product that matches the dosing regimen, timing, and response thresholds, and against formulations that fall within the recited composition and stability windows.

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What patents protect topical phentolamine mesylate to reverse tropicamide and phenylephrine-induced mydriasis under US 12,576,067?

Core protection theme. US 12,576,067 is directed to counteracting drug-induced mydriasis using phentolamine mesylate administered topically as eye drops, with explicit alignment to common dilation agents:

• Tropicamide (antimuscarinic)
• Phenylephrine (alpha-adrenergic agonist)
• Hydroxyamphetamine hydrobromide in combination with tropicamide

Claim architecture in plain scope terms.

1. Method claims tied to the mydriasis cause (claims 1-4, 21-24, 31-40).
2. Dose regimen and dosage form (two drops; 1% solution; and/or 0.4–0.6 mg per drop; and/or concentration ranges).
3. Efficacy endpoints using measurable pupil size change under photopic conditions at 1 hour and/or 2 hours (claims 5-7, 11-14, 25, 26, 28, 34-36).
4. Safety/clinical tolerability endpoint measured via CCLRU redness grading (claims 15-17, 29).
5. Patient qualifiers: adults; no ocular inflammation; timing “after completion of an eye examination” (claims 18-20, 31, 37).
6. Formulation-defined method limits: aqueous, specific excipient classes (polyols), acetate buffers, pH windows, “no chelating agent” limitation, and storage degradation thresholds (claims 8, 21, 31, 41-51, 52-54).

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What are the key independent claims and what does each cover in US 12,576,067?

Claim 1 (phentolamine 1% as two eye drops after tropicamide/phenylephrine/hydroxyamphetamine+tropicamide)

Read as: Treat mydriasis in humans caused by receiving tropicamide, phenylephrine, or hydroxyamphetamine+tropicamide (or salts) by topically administering phentolamine mesylate as two eye drops of 1% (w/w) phentolamine mesylate solution.

Important scope levers:

• Causation trigger: restricts mydriasis to the listed inducing agents.
• Dosing specificity: “two eye drops” and 1% concentration (w/w).
• Route and target: topical to the eye, administering to an eye.

Claim 21 (same but expressly “two eye drops of a 1% (w/v) phentolamine mesylate aqueous solution”)

Read as: Same overall concept as claim 1 but pinned to:

• 1% (w/v) and explicit aqueous ophthalmic solution language.

This matters for competitors because formulation and labeling can be tuned between w/w and w/v conventions, and claim 21 tightens the “aqueous solution” framing.

Claim 31 (pharmacologically-induced mydriasis; excludes ocular inflammation; dose band per drop)

Read as: Treat pharmacologically induced mydriasis in a human patient after receiving one or more of tropicamide/phenylephrine (and/or hydroxyamphetamine+tropicamide), where the patient does not have ocular inflammation, by administering a phentolamine mesylate solution topically as two eye drops, where each drop contains about 0.4 mg to about 0.6 mg.

Key differences from claims 1/21:

• Exclusion: “patient does not have ocular inflammation,” narrowing covered subjects but adding enforceability constraints for challenged methods.
• Dose quantification: per-drop mg range, not only concentration.
• Maintains the same trigger drugs.

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How do the dependent claims expand scope on timing, pupil diameter reductions, and redness limits?

Time-to-response and pupil reduction endpoints

• Within 1 hour benefit: claims 5-7 and 25.
• Photopic pupil reduction thresholds
  • At least 2 mm reduction: claim 11
  • At 2 hours, at least 1 mm reduction: claims 12-14 and 13-14 via different trigger sub-clauses
  • At 2 hours, at least 1 mm reduction under photopic conditions also reflected in claim 28
  • Additional phrasing: claim 34-36 tie pupil reduction “measured two hours after” to specific earlier-dependent framing (including inflammation exclusion).

Safety/tolerability endpoint

• CCLRU redness grading increase limited to no more than two grades:
  • claims 15-17 and 29

This creates a relatively concrete clinical performance window that can be used both to support infringement and to design around by exceeding the redness threshold (a risky and likely unacceptable clinical strategy for an innovator or competitor).

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What formulation and composition elements are claimed, and which ones create the strongest design-around pressure?

US 12,576,067 has significant formulation constraints embedded into method-of-treatment claims, which is a typical enforcement strategy for ophthalmic products. The more a competitor’s product mirrors the claimed composition and pH/excipient system, the more difficult design-around becomes.

Aqueous solution characterization

• “liquid aqueous ophthalmic formulation” is stated in claims 8, 21, 27.

Defined ophthalmic solution composition with pH control

Claims 41-50 recite detailed solution parameters:

• Phentolamine mesylate concentration range
  • claim 41: 0.1% to 2% (w/v)
  • claim 42: 0.5% to 2% (w/v)
  • claim 43: 0.25% to 2% (w/v)
  • claim 44: 0.5% to 2% (w/v)
  • claim 45: 0.5% to 1% (w/v)
  • claim 46: 0.25% to 2% (w/v)
  • claim 47: ~1% (w/v) (single point)
  • claim 48: 0.25% to 2% (w/v)
  • claim 49-50: similar ranges with additional “no chelating agent” constraint
• Polyol excipient range
  • claims 41-50: polyol compound(s) from mannitol, glycerol, propylene glycol; specific examples:
    • claim 43: mannitol 3% to 5% (w/v)
    • claim 44: mannitol 3% to 5% (w/v)
    • claim 45: mannitol 4%
    • claim 47-50: mannitol 3% to 5% (or 4% in claim 50)
• Buffer system
  • “alkali metal acetate” including explicit sodium acetate:
    • claim 41: 1 mM to 6 mM alkali metal acetate
    • claims 43-48: specific acetate ranges like 2 mM to 4 mM sodium acetate
    • claim 45: 3 mM sodium acetate
• pH window
  • claim 41: pH 4 to 6
  • claim 42-44: tighter, e.g., 4.5 to 5.5 or 4.6 to 5.2
  • claim 43: 4.5 to 5.2
  • claim 49-50: typically 4.6 to 5.2
• Chelator exclusion (design-around pressure)
  • claim 49-50: explicitly “does not contain any additional component that is a chelating agent”

This is one of the clearest “switches” a competitor might flip (removing or avoiding any chelator-like component). But note the claims require the rest of the excipient and buffer architecture to remain within the listed ranges.

Storage stability and degradation thresholds

• claim 52: < 10% by weight degradation after storage at 2-8°C for 18, 24, or 36 months
• claim 53: similar but tied to “phentolamine mesylate aqueous solution”
• claim 54: similar to claim 52 but tied to “phentolamine mesylate solution”

These create compliance risk for products whose stability profile deviates, even if composition and dosing match.

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When does US 12,576,067 risk generic entry for a topical phentolamine mesylate “mydriasis reversal” product?

Exclusive impact timing is driven by patent term and enforceable boundaries, not by the clinical timing language. The “within 1 hour” and “2 hours” endpoints describe efficacy and are not exclusivity periods themselves. For commercial entry strategy, the practical implication is:

• During patent live term, competitors face method infringement risk if their labeling, instructions, and real-world administration patterns fall within the claimed triggers, dosing regimen, and endpoints.
• Product timing in a trial does not avoid infringement unless the method steps and outcomes fall outside the claimed ranges.

Because the prompt supplies claim language but not filing date, priority, prosecution history, or maintenance status, exclusivity date calculations cannot be produced here without risking inaccuracy.

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How would a Paragraph IV challenge be framed for US 12,576,067?

A typical Paragraph IV attack against this type of patent would aim at the elements that are easiest to contest in claim construction and evidence:

1. Trigger drug mismatch: design a product or label so that it is not “for mydriasis due to” tropicamide and/or phenylephrine and/or hydroxyamphetamine+tropicamide.
2. Dosing regimen mismatch: avoid “two eye drops” or move outside the recited concentration or mg-per-drop windows (claims 1, 21, 31).
3. Outcome mismatch: do not claim or instruct performance within “within 1 hour” or “at 2 hours at least X mm reduction under photopic conditions,” and ensure clinical data are not consistent with the claimed thresholds (claims 5-7, 11-14, 25-28, 34-36).
4. Redness endpoint mismatch: ensure marketed protocols do not demonstrate “increase in redness of no more than two grades” (claims 15-17, 29).
5. Formulation mismatch: move outside the claimed polyol/acetate/pH system or add chelator components while staying within clinical acceptability (but note claim 49-50 explicitly exclude chelators; flipping that could be a design-around lever if it doesn’t re-enter other constraints).
6. Stability mismatch: show degradation above 10% under 2-8°C conditions over the claimed months.

Without the cited prior art list and without the patent’s prosecution record, an invalidity map (for example, which specific references anticipate each dependent limitation) cannot be stated without fabricating.

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What does the claim set imply about the likely “product form” that the patent is aiming to monopolize?

The independent claims and composition-dependent clauses point to a very specific development target:

• Two-drop topical regimen
• Strength around 1% phentolamine mesylate (claims 1 and 21) or 0.4-0.6 mg per drop (claim 31)
• Aqueous ophthalmic solution with
  • polyol such as mannitol
  • acetate buffer at low mM levels
  • acidic-ish pH around mid-4 to low-5
• Low degradation under refrigerated storage
• Outcome measures aligned with photopic pupil diameter reduction and CCLRU redness scale

This combination suggests that the patent is not just on “phentolamine for reversing mydriasis,” but on a particular dosing and formulation system that reliably produces measurable pupil constriction while managing hyperemia risk.

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How broad is the landscape risk: which design changes are most likely to avoid US 12,576,067?

Lowest-effort avoidance vectors

• Avoid the “two eye drops” regimen or instruction cadence so it is not literally met.
• Avoid the phentolamine strength/mass windows (1% w/w in claim 1; 1% w/v aqueous in claim 21; 0.4–0.6 mg per drop in claim 31).
• Avoid the claimed mydriasis triggers in labeled use (tropicamide, phenylephrine, hydroxyamphetamine+tropicamide).

Medium-effort avoidance vectors

• Shift formulation outside claimed pH/buffer/polyol ranges and/or add any chelating agent if the competitor is prepared to manage formulation consequences (claim 49-50’s “no chelating agent” is a clear carve signal).
• Shift stability profile so that <10% degradation over the claimed refrigerated period is not met.

High-effort avoidance vectors

• Achieving full separation from the claim by altering patient outcomes so that the method is not practiced “with a therapeutic benefit observed within 1 hour” or not meeting the “at least X mm” reductions at 2 hours under photopic conditions, while also maintaining a viable clinical product.

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How does US 12,576,067 compare with typical ophthalmic “reversal of dilation” patent strategies?

This patent looks like a hybrid of:

• Method-of-use protection tied to specific initiating agents (tropicamide, phenylephrine, hydroxyamphetamine+tropicamide)
• Formulation-dependent method claims (defined excipient and pH system embedded into the method steps)
• Performance-based endpoints (pupil diameter change and redness grading scale)

Many “reversal” patents focus only on active therapy or general indication. Here, the claim set adds practical controllables (dose, timing, endpoints, and stability), which tends to broaden infringement coverage through multiple claim surfaces and narrows design-around latitude.

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Key takeaways

• US 12,576,067 protects topical phentolamine mesylate as a two-drop therapy for tropicamide/phenylephrine (and hydroxyamphetamine+tropicamide) induced mydriasis, with claimed efficacy measured in photopic pupil diameter reduction and tolerability assessed via CCLRU redness grading.
• Claim breadth is split across:
  • Trigger-based indication (mydriasis caused by specific dilation agents),
  • Dose regimen (1% solutions and/or 0.4–0.6 mg per drop),
  • Measured clinical endpoints (within 1 hour and at 2 hours),
  • Formulation-controlled method claims (polyols, acetate buffer, pH, aqueous system, chelator absence),
  • Storage stability under 2-8°C with <10% degradation over up to 36 months.
• Design-around is most plausible by changing at least one of the hard claim “switches”: (i) dose regimen/mass-concentration, (ii) labeled trigger agents, (iii) formulation pH/buffer/excipient boundaries, (iv) chelator presence, (v) refrigerated stability profile.

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FAQs

1) Does US 12,576,067 require the mydriasis to be caused by tropicamide or phenylephrine?
Yes. Multiple claims require the mydriasis is “due to” administration of tropicamide and/or phenylephrine and/or hydroxyamphetamine hydrobromide plus tropicamide (or their salts).

2) Is the timing of treatment an element of infringement in US 12,576,067?
The claims include efficacy timing (“therapeutic benefit within 1 hour” and pupil reduction at 2 hours) and at least one patient-timing qualifier (administer once the patient completes the eye exam). That makes timing part of the claim performance structure.

3) What dosing format is explicitly required?
Claims require topically administering to the eye as two eye drops, with the independent claim set covering 1% (w/w) or 1% (w/v) solutions and a separate independent path specifying 0.4–0.6 mg per drop.

4) Does the patent include formulation-level limitations beyond “phentolamine mesylate solution”?
Yes. Multiple dependent claims specify aqueous formulation composition: polyol selection and amounts, acetate buffer concentration, pH range, and in some claims the absence of chelating agents. Storage degradation limits are also claimed.

5) What clinical endpoints are used to define “success” in the claims?
Pupil diameter reduction under photopic conditions at 1-2 hour timepoints, plus a redness tolerability limit using the CCLRU Redness Grading Scale.

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References (APA)

1. US Patent 12,576,067. “Method of treating mydriasis using phentolamine mesylate eye drops.” Claimed subject matter and limitations as provided in the prompt.

Drugs Protected by US Patent 12,576,067

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	12,576,067					TREATMENT OF PHARMACOLOGICALLY-INDUCED MYDRIASIS

International Family Members for US Patent 12,576,067

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2019366451
Australia	2024219970
Brazil	112021007725
Canada	3116589
China	113164452