US Patent 10,772,829: Phentolamine Ophthalmic Solution Claims, Expiration, and Competitive Patent Landscape

US Patent No. 10,772,829 protects a defined aqueous ophthalmic formulation containing phentolamine, a specified polyol, a low-concentration buffer, water, and a controlled acidic-to-neutral pH. The patent is directly relevant to Ryzumvi, the phentolamine ophthalmic solution approved by the FDA for reversal of pharmacologically induced mydriasis.

The central commercial embodiment is a formulation containing approximately 0.75% phentolamine mesylate, mannitol, sodium acetate buffer at approximately 3 mM, water, and a pH around 5.0. The patent has a nominal expiration date of April 26, 2038. FDA regulatory exclusivity for Ryzumvi is separate from the patent term and expires earlier.

What does US Patent 10,772,829 protect?

US 10,772,829 protects an aqueous ophthalmic composition rather than a method of treatment, dosing regimen, device, or manufacturing process. Claim 1 is the only independent claim. Claims 2 through 35 narrow the formulation by specifying concentration ranges, excipients, buffer identity, and pH.

Claim element	Scope of claim 1
Phentolamine or pharmaceutically acceptable salt	About 0.1% to about 4% w/v
Polyol	About 1% to about 6% w/v
Permitted polyols	Mannitol, glycerol, propylene glycol, ethylene glycol, sorbitol, or xylitol
Buffer	About 0.1 mM to about 10 mM
Water	Required
Alkali or alkaline-earth metal halide	Optional
pH	4.0 to 7.5
Composition format	Aqueous ophthalmic solution

The claim requires the formulation to contain all required elements. A competing product that contains phentolamine but lacks the claimed polyol, falls outside the stated concentration ranges, or uses a pH outside the claimed range would have a stronger non-infringement position against literal infringement of claim 1.

How do claims 2 through 35 narrow the patent scope?

The dependent claims progressively target the commercial formulation. The most important claim group is the combination of approximately 1% phentolamine mesylate, approximately 4% mannitol, approximately 3 mM buffer, sodium acetate, and a pH of 4.5 to 5.5.

Concentration claims

Claims 2 through 4 cover phentolamine mesylate concentrations of:

About 0.25% to about 2%;
About 0.25% to about 1%; and
About 1%.

Claims 5 through 7 add approximately 4% polyol, with claims 6 and 7 tying that concentration to narrower phentolamine mesylate embodiments.

The use of “about” creates a factual infringement issue around measurement precision and acceptable formulation tolerances. The patent does not define a single exact numerical cutoff in the claim language. A court would evaluate the intrinsic record, analytical method, formulation variability, and ordinary meaning of “about.”

Polyol claims

Claims 8 through 10 specify mannitol as the polyol. Mannitol is commercially important because it is the polyol associated with the narrow formulation branch that most closely tracks Ryzumvi’s disclosed composition.

Claims 8, 9, and 10 cover:

A broader phentolamine formulation with mannitol;
A formulation containing approximately 1% phentolamine mesylate and mannitol; and
A formulation containing approximately 1% phentolamine mesylate, approximately 4% mannitol, and the limitations inherited through claim 7.

Buffer claims

Claims 11 through 18 narrow the buffer concentration to:

About 2 mM to about 4 mM; or
About 3 mM.

Claims 19 through 23 specify an alkali metal acetate, while claims 24 through 28 specifically identify sodium acetate.

The most commercially significant buffer chain is:

Claim 10 → claim 14 or 15 → claim 18 → claim 23 → claim 28

This chain captures a formulation with approximately 1% phentolamine mesylate, approximately 4% mannitol, approximately 3 mM buffer, and an alkali metal acetate or sodium acetate.

pH claims

Claims 29 through 35 narrow the pH to 4.5 to 5.5. The narrowest commercially relevant combination is claim 35, which incorporates:

About 1% phentolamine mesylate;
About 4% mannitol;
Approximately 3 mM buffer;
An alkali metal acetate;
Sodium acetate; and
A pH from 4.5 to 5.5.

These claims create substantial overlap among the dependent claims. The claim set uses multiple paths to protect substantially similar formulations, which can complicate invalidity and design-around analysis.

Does US 10,772,829 cover Ryzumvi?

US 10,772,829 covers the formulation profile publicly associated with Ryzumvi, subject to comparison against the product’s approved composition and the claim construction applied in a particular enforcement proceeding.

Ryzumvi contains phentolamine mesylate as the active ingredient. FDA product information identifies mannitol and sodium acetate among the inactive formulation components and describes an ophthalmic solution with an acidic pH consistent with the patent’s narrower pH claims (FDA, 2024).

The relevant formulation comparison is:

Formulation feature	Patent claims	Ryzumvi public product profile
Active ingredient	Phentolamine or salt	Phentolamine mesylate
Phentolamine concentration	0.1% to 4% in claim 1	Approximately 0.75%
Polyol	1% to 6% of listed polyols	Mannitol
Buffer	0.1 mM to 10 mM	Sodium acetate disclosed
pH	4.0 to 7.5	Acidic pH, within the claimed range
Dosage form	Aqueous ophthalmic solution	Aqueous ophthalmic solution

The principal question is not whether the patent covers the general concept of a phentolamine eye drop. It does. The key question is whether the approved product satisfies every limitation of one or more asserted claims, including the precise excipient composition and the “consisting of” transition.

What is the Orange Book status of US 10,772,829?

US 10,772,829 is listed in FDA Orange Book materials for the Ryzumvi NDA, according to FDA patent-listing records. The listed patent protects the drug product formulation rather than a treatment method.

Regulatory item	Status
Product	Ryzumvi
Active ingredient	Phentolamine ophthalmic solution
NDA pathway	505(b)(2)
NDA holder	Vyluma, Inc.
Patent	US 10,772,829
Patent category	Drug-product formulation
Nominal patent expiration	April 26, 2038
FDA approval	2024
Regulatory exclusivity	Three-year exclusivity associated with the approval
Biosimilar pathway	Not applicable

The patent expiry date is based on the recorded priority and patent-term framework. Patent term adjustment, terminal disclaimers, patent-term extension, or later Orange Book corrections can affect the operative date. The patent’s commercial protection is therefore longer than the FDA’s three-year approval-related exclusivity.

When does Ryzumvi lose FDA exclusivity and patent protection?

Ryzumvi received FDA approval in 2024 under a 505(b)(2) application. Because phentolamine is an established active ingredient, Ryzumvi does not receive five-year new chemical entity exclusivity. Its relevant FDA exclusivity is the three-year exclusivity available for a drug supported by new clinical investigations essential to approval.

The principal timeline is:

Date	Event
April 26, 2018	Earliest priority date associated with the formulation patent family
September 15, 2020	US 10,772,829 issued
2024	FDA approved Ryzumvi
August 2027	Approximate end of three-year FDA exclusivity
April 26, 2038	Nominal expiration of US 10,772,829

After FDA exclusivity ends, an ANDA or other abbreviated pathway may become commercially relevant, subject to patent certification, litigation, regulatory approval, and any applicable pediatric or other exclusivity.

The 2038 patent date remains the principal barrier to an unlicensed generic launch if the generic formulation falls within an asserted claim.

What Paragraph IV challenges could affect Ryzumvi?

A generic applicant seeking approval before expiration of US 10,772,829 could submit a Paragraph IV certification alleging that the patent is invalid, unenforceable, or not infringed. The likely litigation issues would differ from those arising with a conventional single-active-ingredient patent.

Likely infringement issues

A Paragraph IV dispute could focus on:

Whether the applicant’s phentolamine concentration falls within the claimed range;
Whether the applicant uses one of the six listed polyols;
Whether the polyol concentration is within 1% to 6%;
Whether the buffer concentration is within 0.1 mM to 10 mM;
Whether sodium acetate is present;
Whether the final pH is within the claimed range; and
Whether the “consisting of” language excludes additional formulation components.

A generic applicant could attempt to design around the claims by using a non-listed tonicity agent, a different buffer system, a different pH, or concentrations outside the claimed ranges. Such changes would require pharmaceutical development work and regulatory comparability analysis.

Likely validity issues

Potential invalidity theories would include:

Obviousness based on known phentolamine ophthalmic formulations;
Lack of written description for the full numerical ranges;
Lack of enablement across the full combination of polyols, buffer concentrations, and pH values;
Anticipation by earlier ophthalmic formulation disclosures; and
Indefiniteness involving “about,” “at least one,” and the composition’s closed-transition language.

The patent’s strongest position is likely against products that copy the specific Ryzumvi-like combination. Its vulnerability would be greater if prior art disclosed phentolamine ophthalmic solutions containing mannitol, acetate buffer, and an overlapping pH and concentration range.

Which companies are challenging US 10,772,829?

No publicly identified Paragraph IV litigation or settlement involving US 10,772,829 and Ryzumvi is established in the cited FDA and patent materials. No approved generic phentolamine ophthalmic product is identified in the FDA product records reviewed for this analysis.

The absence of public litigation does not eliminate future challenge risk. Ryzumvi’s short commercial history and the patent’s 2038 expiry create an incentive for early formulation development, but a challenger would need to address both regulatory requirements and the patent’s composition limitations.

Are biosimilars a risk for Ryzumvi?

No. Ryzumvi is a small-molecule phentolamine ophthalmic solution, not a biologic. Biosimilar approval under the Public Health Service Act does not apply.

The relevant competitive pathway is an ANDA for a generic ophthalmic solution or, depending on product differences, a 505(b)(2) application. Generic applicants would need to establish pharmaceutical equivalence and bioequivalence or otherwise satisfy FDA requirements for ophthalmic products.

What formulation patents protect phentolamine ophthalmic products?

US 10,772,829 is a formulation patent directed to the combination of:

Phentolamine;
Polyol-based stabilization or tonicity control;
Low-strength buffering;
Water; and
A pH from 4.0 to 7.5.

The patent does not claim every phentolamine ophthalmic formulation. Its scope depends on the intersection of the listed ingredients, concentrations, and pH limits.

A formulation containing phentolamine hydrochloride rather than phentolamine mesylate may still fall within claim 1 because the claim covers phentolamine or a pharmaceutically acceptable salt. Changing the salt alone therefore may not avoid the independent claim.

A formulation using glycerol, propylene glycol, sorbitol, or xylitol may also remain within claim 1 if all other limitations are satisfied. Substituting a polyol not listed in the claim may present a stronger design-around argument, although the resulting product would need to meet stability, tolerability, sterility, and regulatory specifications.

How strong is the patent estate for Ryzumvi?

The identified estate has a strong product-specific position but a narrower platform position.

Strengths

Claim 1 covers a broad concentration range for phentolamine.
The claim covers multiple pharmaceutically acceptable salts.
Six polyols are expressly listed.
The pH range is broad enough to capture many ophthalmic formulations.
Dependent claims target the likely commercial composition.
Formulation infringement can be assessed from product labels, specifications, and discovery records.
The patent expires materially later than FDA regulatory exclusivity.

Limitations

The patent is composition-specific and does not independently claim all methods of using phentolamine.
A formulation using a different excipient architecture may avoid literal infringement.
“Consisting of” language may create disputes over unrecited excipients.
Broad numerical ranges may face obviousness or written-description attacks.
The active ingredient is an old molecule, increasing the importance of formulation prior art.
The patent does not create biosimilar-style barriers because Ryzumvi is not biologic.

The estate is strongest against a direct copy of the approved product and weaker against materially reformulated products.

What generic launch scenarios exist for Ryzumvi?

Launch scenario	Timing	Risk profile
No challenge; launch after patent expiry	After April 2038	Lowest litigation exposure
Paragraph IV challenge with copied formulation	Before 2038	High infringement risk, but meaningful invalidity leverage
Design-around ANDA	After regulatory approval and before 2038	Technical and regulatory risk
505(b)(2) reformulation	Potentially before 2038	Requires separate clinical and patent strategy
Authorized generic or license	Contract-dependent	Depends on Vyluma commercial strategy
Post-exclusivity ANDA	After approximately August 2027, subject to patent	Regulatory exclusivity falls away, patent remains

The most plausible early competitive strategy is a design-around formulation rather than a direct copy. The patent’s use of a closed composition format gives a challenger potential room to examine alternative excipient combinations, but ophthalmic tolerability and stability constraints may narrow practical options.

What patent litigation and licensing issues affect the product?

No cited record identifies a public settlement agreement, patent license, or active litigation involving US 10,772,829. Vyluma’s commercial rights and any upstream arrangements are separate from the patent’s recorded ownership and should not be inferred from the FDA label.

For transaction diligence, the relevant issues are:

Ownership and assignment history;
Whether the Orange Book listing matches the approved formulation;
Any terminal disclaimer or patent-term adjustment;
Patent maintenance-fee status;
The scope of Vyluma’s license rights;
Royalty obligations;
Existing development or commercialization agreements; and
Any confidential patent settlement not reflected in public FDA materials.

Key Takeaways

US 10,772,829 is a formulation patent for aqueous phentolamine ophthalmic solutions.
Claim 1 requires phentolamine, one of six listed polyols, a low-concentration buffer, water, and a pH of 4.0 to 7.5.
Claims 24 through 35 focus on sodium acetate, approximately 3 mM buffer, approximately 4% mannitol, approximately 1% phentolamine mesylate, and pH 4.5 to 5.5.
The claim set closely tracks the commercial Ryzumvi formulation.
The nominal patent expiration date is April 26, 2038.
Ryzumvi’s three-year FDA exclusivity expires materially earlier, in approximately August 2027.
Biosimilar competition is irrelevant because phentolamine is a small molecule.
Generic competition would proceed through an ANDA or potentially a 505(b)(2) route.
A copied formulation would face substantial infringement risk.
The principal patent vulnerabilities are obviousness, written description, enablement, and construction of “about” and “consisting of.”
No publicly identified Paragraph IV litigation or settlement is established in the cited materials.

FAQs About US Patent 10,772,829 and Ryzumvi

Does changing phentolamine mesylate to another salt avoid US 10,772,829?

Not necessarily. Claim 1 covers phentolamine and pharmaceutically acceptable salts generally. A salt substitution alone may remain within the independent claim.

Does using glycerol instead of mannitol avoid the patent?

No. Glycerol is one of the expressly listed polyols. A glycerol formulation could still infringe if it meets the remaining concentration, buffer, water, and pH limitations.

Is the Ryzumvi 0.75% concentration outside the patent’s dependent claims?

It is within claim 1’s 0.1% to 4% range and within claims covering approximately 0.25% to 2% and approximately 0.25% to 1%, subject to the legal meaning of “about” and the complete formulation composition.

Can a generic launch after FDA exclusivity ends in 2027?

FDA exclusivity and patent protection are separate. A generic may seek approval after regulatory exclusivity ends, but a launch before the asserted patent expires could trigger Paragraph IV litigation or require a non-infringing design.

Does US 10,772,829 claim treatment of presbyopia?

No. The patent claims an aqueous ophthalmic solution. It does not, based on the supplied claims, independently claim a method of treating presbyopia, reversing mydriasis, or improving near vision.

References

U.S. Patent and Trademark Office. (2020). U.S. Patent No. 10,772,829, ophthalmic compositions comprising phentolamine.
U.S. Food and Drug Administration. (2024). Ryzumvi (phentolamine ophthalmic solution) prescribing information. Vyluma, Inc.
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2024). Ryzumvi NDA approval materials.
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Patent and exclusivity 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	10,772,829	⤷ Start Trial	Y				⤷ 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	2014212274	⤷ Start Trial
Australia	2018200566	⤷ Start Trial
Canada	2899339	⤷ Start Trial
Denmark	2950648	⤷ Start Trial
European Patent Office	2950648	⤷ Start Trial
Spain	2762153	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,772,829

Which drugs does patent 10,772,829 protect, and when does it expire?

Summary for Patent: 10,772,829