Details for Patent: 12,576,066

Which drugs does patent 12,576,066 protect, and when does it expire?

Patent 12,576,066 protects RYZUMVI and is included in one NDA.

This patent has twenty patent family members in fifteen countries.

Summary for Patent: 12,576,066

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:	US19/029,360
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

Scope and claims for US Drug Patent 12,576,066: phentolamine mesylate eye drops for reversing pharmacologically induced mydriasis after tropicamide/phenylephrine/hydroxyamphetamine

Answer in brief: US 12,576,066 is a method-of-treatment patent. It claims topical administration of phentolamine mesylate ophthalmic solution (including a 1% w/v drop) to treat mydriasis caused by prior administration of tropicamide, phenylephrine, or hydroxyamphetamine hydrobromide plus tropicamide, with claim coverage keyed to (i) timing of therapeutic benefit (within about 1 hour; assessments at 2 hours; in certain dependent claims at 24 hours), (ii) measurable pupil constriction (mm reduction and/or percent reduction), (iii) tolerability endpoints (eye redness grading by CCLRU scale), and (iv) formulation and product-quality constraints in a separate claim branch (dose range about 0.4–0.6 mg per eye drop; specific excipient and pH windows; stability defined as <10% degradation after cold storage). A sub-set of claims narrows to patients without ocular inflammation, including iritis excluded.

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US 12,576,066 claims overview: what exact methods and endpoints are covered?

What is the independent claim set?

The patent is structured around two largely parallel independent claim concepts, both method-of-treatment:

1. Core method (claims 1–20 and 21–30):
   Treat mydriasis in a human eye after the patient received a mydriatic drug (tropicamide, phenylephrine, or pharmaceutically acceptable salts; or hydroxyamphetamine hydrobromide + tropicamide). Treat with topical ocular phentolamine mesylate as one eye drop of a 1% (w/w) solution (claim 1) or one eye drop of a 1% (w/v) aqueous solution (claim 21).
   Coverage includes dependent refinements for: mechanism of mydriasis origin, pediatric patients, time-to-benefit, magnitude of pupil reduction, redness grading limits, and aqueous liquid ophthalmic formulation.

2. Pharmacologically induced mydriasis branch with dosing, formulation, and exclusion of inflammation (claims 31–54):
   Treat pharmacologically induced mydriasis where the patient received one or more of tropicamide/phenylephrine (or salt forms) or hydroxyamphetamine hydrobromide + tropicamide (or salts), and the patient does not have ocular inflammation. Administer phentolamine mesylate solution as an eye drop containing about 0.4 mg to about 0.6 mg. This branch adds:

   • exclusion of ocular inflammation (explicitly iritis in claim 32)
   • dosing schedule tied to completion of an eye exam (claim 37)
   • pupil reduction thresholds (including 1 mm at 2 hours)
   • detailed formulation composition ranges (claims 41–50) including phentolamine concentration, polyol excipients (mannitol/glycerol/propylene glycol), alkali metal acetate and pH ranges
   • stability specification (<10% degradation after storage at 2–8°C for 18/24/36 months) (claims 52–54)

How tightly does the patent key to “who” and “why”?

• “Who” is constrained to human patients with mydriasis requiring treatment; multiple claims expressly cover pediatric patients.
• “Why” is constrained to pharmacologically induced mydriasis caused by specific agents: tropicamide, phenylephrine, and hydroxyamphetamine hydrobromide + tropicamide.

What performance metrics define “treat the mydriasis” in claim language?

The claims translate “treatment” into measurable outcomes:

• Time windows

  • Within 1 hour (claims 5–7, 25)
  • At 2 hours (claims 12–14, 13–14 variants; 26, 28; 34–36)
  • At 24 hours in one specific branch (claim 51)

• Pupil size endpoints

  • At least a 2 mm reduction under photopic conditions vs baseline without the dosing (claim 11)
  • At least 1 mm reduction under photopic conditions at 2 hours (claims 12–14, 28; 34–36)
  • A dependent claim also uses percent-based reduction: “at two hours … at least a 30% reduction in pupil diameter” (claim 26)

• Tolerability endpoint

  • Eye redness increases limited to no more than two grades using the CCLRU Redness Grading Scale (claims 15–17, 29)

• Exam-timing operational constraint

  • Administer after completion of an eye exam where tropicamide/phenylephrine/hydroxyamphetamine+or tropicamide was administered (claim 37)

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What mydriasis causes are explicitly tied to US 12,576,066?

Which upstream mydriatics trigger infringement risk?

US 12,576,066 explicitly covers mydriasis “due to” exposure to:

• Tropicamide (claim 2, 22, 24?; plus claim 31’s list)
• Phenylephrine (claim 3, 23; plus claim 31’s list)
• Hydroxyamphetamine hydrobromide + tropicamide (claim 4, 24; plus claim 31’s list)

Does it cover combinations beyond those listed?

The claims are anchored to these specific mydriatics and salt forms, plus the defined hydroxyamphetamine+тropicamide combination. The claim text does not expand to other agents beyond that set.

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What formulations are protected by US 12,576,066?

1% ophthalmic solution claims: what is fixed vs flexible?

In the first claim family:

• Claim 1: 1% (w/w) phentolamine mesylate solution administered as one eye drop
• Claim 21: 1% (w/v) phentolamine mesylate aqueous solution administered as one eye drop
• Claim 8/9/10/27/28: the eye drop is a liquid aqueous ophthalmic formulation (dependent coverage)

This language emphasizes a specific strength (1%) and delivery format (one eye drop).

0.4 mg to 0.6 mg per eye drop and detailed composition: the second family

Claims 31–50 define a more drug-product-specific space:

• Dose per drop: about 0.4 mg to about 0.6 mg phentolamine mesylate
• Composition skeleton (claim 41):
  • phentolamine mesylate: about 0.1% to about 2% (w/v)
  • polyol: about 1% to about 6% (w/v) selected from mannitol, glycerol, propylene glycol
  • alkali metal acetate: about 1 mM to about 6 mM
  • water
  • pH about 4 to 6
• Dependent narrowing examples include:
  • claim 42: phentolamine about 0.5% to about 2%, polyol 1% to about 6%, acetate 1 mM to 6 mM, pH 4.5 to 5.5
  • claim 43: phentolamine 0.25% to 2%, mannitol 3% to 5%, sodium acetate 2–4 mM, pH 4.5 to 5.2
  • claim 44: phentolamine 0.5% to 2%, mannitol 3% to 5%, sodium acetate 2–4 mM, pH 4.6 to 5.2
  • claim 45: phentolamine 0.5% to 1%, mannitol 4%, sodium acetate 3 mM, pH 4.6 to 5.2
  • claim 49: includes a negative limitation: no chelating agent
  • claim 50: explicit restriction to no chelating agent

pH and excipient constraints drive freedom-to-operate

The second family’s claim structure makes formulation design a high-leverage variable:

• pH window: ~4.0–6.0 at the broad level, with multiple tighter windows
• acetate salt source: “alkali metal acetate” broadly; several dependents specify sodium acetate
• polyol role: can be multiple types, but certain dependent claims pin mannitol
• chelating agent exclusion: in claims 49–50

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What stability constraints are included in US 12,576,066?

The patent includes product stability limitations:

• Claims 52–54: phentolamine mesylate solution characterized by <10% by weight degradation after storage at 2–8°C for 18 months, 24 months, or 36 months.

This is a formulation-quality claim hook that can matter in litigation if accused products vary stability profile, packaging, or shelf-life support.

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When does US 12,576,066 require benefit to occur after dosing?

Timing gates

The claims incorporate multiple time points:

• Within 1 hour: claims 5–7 and 25
• At 2 hours: claims 12–14, 13–14 variants, 26, 28, and in claims 34–36 as “measured two hours after the dosage”
• At 24 hours: claim 51 includes a “statistically significant” baseline in mean pupil diameters at 1 hour for inflammatory exclusion branch and a “reduction at 24 hours” statement tied to iritis exclusion

Operational implication

To avoid infringement, a potential challenger would need to consider whether their clinical endpoints or timing measures do not align with the claim’s “therapeutic benefit observed” language. The claim language is endpoint-driven rather than merely pharmacologic.

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How does the patent treat tolerability and safety: what is the eye redness limit?

CCLRU Redness Grading Scale

The method includes a tolerability-dependent constraint:

• claims 15–17 (and 29): eye redness increase limited to no more than two grades on the CCLRU Redness Grading Scale vs untreated baseline.

This can be used as a claim qualifier in both validity and infringement analyses, particularly if accused products show different redness outcomes.

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Does US 12,576,066 cover pediatric patients?

Yes:

• claims 18–20: pediatric human patient
• claims 30: pediatric human patient in the second family

This expands enforceability against pediatric-specific labeling or off-label pediatric use where the claim conditions align.

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What is the “no ocular inflammation” limitation doing in the claims?

Exclusion of inflammation types

Claim 31 defines the method where the patient does not have ocular inflammation. Claim 32 narrows inflammation type to iritis.

This creates two litigation-relevant dimensions:

• If an accused use targets patients with ocular inflammation, the method-claim fit may narrow based on the “does not have ocular inflammation” limitation.
• If accused products are indicated/used after exams that include inflammatory findings, parties may dispute whether patients met the “no inflammation” condition at the time of dosing.

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What does “administer after completion of eye examination” mean legally and operationally?

Claim 37 requires administration “once the patient has completed an eye examination in which” the mydriatic(s were administered. This is a process/timing limitation tied to clinical workflow. If an accused dosing occurs earlier, after different clinical steps, or in a different workflow, infringement analysis can shift to whether the dosing step satisfies the claim.

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Scope comparison inside the patent: 1% drop vs mg-per-drop/formulation branch

Key differences that change infringement footprint

• First claim family (claims 1–30): anchors to 1% w/w or 1% w/v drop and supports mydriasis reversal with outcome endpoints at 1 and 2 hours and redness limits.
• Second claim family (claims 31–54): anchors to mg-per-drop range (0.4–0.6 mg) and adds explicit formulation composition, pH ranges, excipient constraints, chelating agent exclusions, and stability requirements, plus “no ocular inflammation.”

A product could satisfy the general therapeutic concept (phentolamine reversal after tropicamide/phenylephrine) yet not meet the 1% concentration limitation, or fail the mg/dose-per-drop window and specific formulation constraints.

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Patent landscape: what must be searched around US 12,576,066 to map real enforcement risk?

Core landscape question

US 12,576,066’s independent claim coverage is method-of-treatment with endpoint thresholds and formulation restrictions in a dependent branch. Real-world risk for competitors depends on whether they plan:

• to use phentolamine mesylate ophthalmically to reverse dilation from tropicamide/phenylephrine (method claim)
• to use a 1% solution specifically (first family)
• to match the specific mg-per-drop dosing and formulation/pH and chelator restrictions (second family)
• to use patient populations with ocular inflammation vs without (no ocular inflammation limitation)

How to structure an actionable freedom-to-operate (FTO) search

A business-grade search map typically branches into:

1. Same active + same target indication
   Patents and applications on “phentolamine mesylate” topical ocular reversal of pharmacologically induced mydriasis after tropicamide/phenylephrine/hydroxyamphetamine+topical tropicamide.
2. Same therapeutic endpoints but different dosing form
   Claims that recite pupil constriction thresholds (mm or percent) and photopic measurement timing.
3. Formulation and stability patents
   Claims covering pH buffers, mannitol-based tonicity, alkali metal acetate, and stability under 2–8°C.
4. Related ocular antagonism approaches
   If competitors use other alpha antagonists or different mechanisms, method claims may not cover them but product/formulation patents could.

Where landscape battles typically occur

Given the endpoint-heavy nature of US 12,576,066, disputes often center on:

• whether clinical endpoints align with claim thresholds (1-hour vs 2-hour; 1 mm vs 2 mm; percent reduction)
• whether patient selection met “no ocular inflammation”
• whether dosing meets the specific strength (1%) and dosing amount (0.4–0.6 mg per drop)
• whether accused formulations match pH and excipient composition windows
• whether stability and chelator exclusions are satisfied

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Key takeaways

• US 12,576,066 claims phentolamine mesylate eye drops for treating mydriasis induced by tropicamide, phenylephrine, or hydroxyamphetamine hydrobromide + tropicamide.
• Independent method coverage is built around topical administration as one eye drop of 1% solution (w/w or w/v).
• Dependent claims add endpoint qualifiers: photopic pupil constriction at 1 hour and 2 hours (and 24 hours in one inflammatory-exclusion context), and eye redness limited to ≤2 CCLRU grades.
• A second branch narrows to pharmacologically induced mydriasis in patients without ocular inflammation (including explicit iritis exclusion) and requires 0.4–0.6 mg per drop, plus detailed formulation/pH limits and a stability requirement (<10% degradation at 2–8°C over 18–36 months), including no chelating agent in certain dependents.
• Enforceability and risk analysis will hinge on whether an accused product and clinical protocol meet these tight dose, formulation, timing, and patient-selection claim constraints.

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FAQs

1) Does US 12,576,066 cover phentolamine mesylate for mydriasis not caused by tropicamide or phenylephrine?

The claim language ties mydriasis causation to tropicamide, phenylephrine, or hydroxyamphetamine hydrobromide + tropicamide, plus salts; coverage is limited to those enumerated causes.

2) Are the pupil reduction thresholds absolute, or can different measurement conditions avoid infringement?

The claims specify photopic conditions and set numeric thresholds (mm and percent) relative to a baseline without dosing; deviations from the specified measurement context can change whether the claim “therapeutic benefit” elements are met.

3) Can a product avoid the patent by using a phentolamine strength other than 1%?

The first claim family is anchored to a 1% (w/w or w/v) eye drop. A different strength can fall outside that claim set, though the second branch may still capture certain phentolamine concentration ranges within 0.1–2% depending on formulation and dose-per-drop.

4) How does the “no ocular inflammation” limitation affect use in real clinics?

Claim 31 requires that the patient does not have ocular inflammation; if dosing is done despite ocular inflammation findings (including iritis), that limitation can be a key infringement defense element.

5) What formulation changes are most likely to test the second-branch claims?

Changes affecting pH, acetate type/level (sodium acetate vs other alkali metal acetates), polyol selection and concentration, presence of chelating agents, and stability under 2–8°C can impact whether formulation-dependent claims are met.

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References

1. United States Patent No. 12,576,066.

Drugs Protected by US Patent 12,576,066

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						TREATMENT OF PHARMACOLOGICALLY-INDUCED MYDRIASIS

International Family Members for US Patent 12,576,066

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2019366451
Australia	2024219970
Brazil	112021007725