Details for Patent: 11,202,767

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Which drugs does patent 11,202,767 protect, and when does it expire?

Patent 11,202,767 protects OLPRUVA and is included in one NDA.

This patent has thirty-five patent family members in twenty-two countries.

Summary for Patent: 11,202,767

Title:	Methods of treating urea cycle disorders and maple syrup urine disease
Abstract:	The present invention provides methods for the treatment of urea cycle disorders and Maple Syrup Urine Disease.
Inventor(s):	Leah E. Appel, Joshua R. Shockey, D. Christopher SCHELLING
Assignee:	Green Ridge Consulting , Acer Therapeutics Inc
Application Number:	US17/196,599
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

US Patent 11,202,767: Scope, Claim Construction, Patent Strength, and Competitive Landscape for Sodium Phenylbutyrate

US Patent 11,202,767 is directed to taste-masked, layered sodium phenylbutyrate particles and their use in treating urea cycle disorders and maple syrup urine disease. The patent does not broadly cover all sodium phenylbutyrate products. Its commercial scope depends on the combination of particle architecture, coating chemistry, particle-size distribution, formulation percentages, and method of treatment.

The principal enforcement risk is directed to an oral sodium phenylbutyrate product using drug-loaded seed particles coated with a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate. Conventional sodium phenylbutyrate tablets, powders, and formulations lacking that layered-particle architecture generally fall outside literal infringement of independent claim 1.

What does US Patent 11,202,767 protect?

The patent protects two primary method categories:

1. Treatment of a urea cycle disorder using a specified taste-masked sodium phenylbutyrate formulation.
2. Treatment of maple syrup urine disease using substantially the same formulation.

Claims 1 and 15 are the independent claims. Both require the same core formulation limitations:

Required limitation	Claim requirement
Active ingredient	Sodium phenylbutyrate
Administration	Oral administration
Particle structure	Seed core, drug layer, and taste-mask coating
Particle size	At least 90% of particles smaller than 500 micrometers by volume
Seed-core content	About 10% to 20% by total weight
Taste-mask coating	About 5% to 25% by total weight
Sodium phenylbutyrate content	More than 60% by total weight
Coating chemistry	Polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate
Therapeutic use	Urea cycle disorder or maple syrup urine disease

The patent is therefore a formulation-plus-use patent. A product must practice both the specified dosage form and the claimed therapeutic method to create a direct infringement theory under the independent claims.

How should independent claim 1 be construed?

Claim 1 requires more than a taste-masked sodium phenylbutyrate product. It requires a multilayer particle.

Seed core

The seed core is the internal particulate substrate on which the drug layer is formed. The claim requires that seed cores account for approximately 10% to 20% of the total composition by weight.

A formulation using sodium phenylbutyrate compressed directly into tablets, blended into a powder, or encapsulated without a seed-core drug-layer arrangement would not ordinarily satisfy this limitation.

Drug layer

The sodium phenylbutyrate must be present in a drug layer on the seed core. This language distinguishes coated-particle systems from simple physical mixtures.

The claim does not specify every excipient in the drug layer. That creates some flexibility for formulation development, but the product must retain the claimed layered structure.

Taste-mask coating

The outer coating must mask the taste of sodium phenylbutyrate and account for approximately 5% to 25% of the composition by total weight.

The coating limitation is central to the patent’s commercial value. Sodium phenylbutyrate is associated with poor taste and palatability problems, particularly in pediatric patients. A coating that changes release characteristics, uses a different polymer system, or falls outside the claimed weight range may provide a design-around opportunity.

Polymer composition

The coating must comprise a polymer formed from:

• Dimethylaminoethyl methacrylate;
• Butyl methacrylate; and
• Methyl methacrylate.

This combination corresponds to the type of acrylic copolymer chemistry commonly used in taste masking and pH-responsive pharmaceutical coatings. The claim is not limited by expressly reciting a commercial trade name. A coating supplier or generic manufacturer could face infringement risk if its product documentation identifies the same monomer-derived polymer, even under a different product name.

The phrase “formed from” may cover a copolymer containing the specified monomers without requiring the exact commercial polymer grade. The strength of that interpretation would depend on the specification, prosecution history, and analytical evidence concerning the accused coating.

What do the dependent claims add?

The dependent claims narrow the methods by adding dosing, patient, disease, vehicle, and outcome limitations.

Claims	Added subject matter
2	Bioequivalence to an uncoated sodium phenylbutyrate formulation
3-5	Administration with a dosing vehicle containing modified food starch or maltodextrin; modified corn starch is specified
6	Dose of 450-600 mg/kg/day for subjects below 20 kg, or 9.9-13.0 g/m²/day for larger subjects
7	Protein-restricted diet
8	Co-administration of essential amino acids
9-10	Dosing with meals or feedings, three to six times daily
11	Specific urea-cycle enzyme deficiencies
12-14	Particle-size limitation, human subject, and ammonia removal
16-18	Dosing vehicles for the maple syrup urine disease claims
19-21	Dose and administration frequency for maple syrup urine disease
22-23	Particle size and human subject
24-27	Lowering plasma branched-chain amino acids, including specified leucine, isoleucine, and valine ranges

Claims 12 and 22 repeat the particle-size limitation already present in the corresponding independent claims. That repetition does not materially expand the patent.

Claim 2 contains the phrase “bioequivalent to compared to,” which appears grammatically defective. Courts generally construe claims in light of the specification and prosecution record rather than disregard them automatically. The defect could still create an indefiniteness or construction dispute if the claim is asserted.

Which diseases and patient populations are covered?

Urea cycle disorders

Claim 11 identifies disorders caused by mutations in:

• N-acetylglutamate synthetase;
• Carbamoyl phosphate synthetase I;
• Ornithine transcarbamylase;
• Argininosuccinic acid synthetase;
• Argininosuccinic acid lyase; and
• Arginase.

The claims therefore target the established urea cycle disorder population, including pediatric and adult patients. Claims 6, 9, and 10 track dosing patterns commonly used for nitrogen-scavenging therapy.

BUPHENYL sodium phenylbutyrate is FDA-approved for adjunctive treatment of chronic management of patients with urea cycle disorders involving deficiencies of carbamoyl phosphate synthetase, ornithine transcarbamylase, or argininosuccinate synthetase, subject to the product labeling conditions. [2]

Maple syrup urine disease

Claim 15 separately covers treatment of maple syrup urine disease. Claims 24 through 27 add biochemical response limitations based on reductions in branched-chain amino acids:

Biomarker	Claimed target
Leucine	200-500 micromoles/L
Isoleucine	100-200 micromoles/L
Valine	100-300 micromoles/L

These claims may be harder to enforce in practice because they require proof of the claimed therapeutic result. A manufacturer could sell a product without promoting the claimed BCAA-lowering outcome, although direct infringement may still be established if the product is used according to the patented method.

What is the scope of the particle-size limitation?

The claims require a volume-based particle-size distribution in which at least 90% of the layered particles are smaller than 500 micrometers. This is effectively a D90 limitation.

Particle-size testing would likely become a central issue in any infringement dispute. The following variables matter:

• Whether “particle” refers to the complete coated particle rather than the seed core;
• The analytical instrument and dispersion method;
• Whether agglomerates are included;
• Whether the measurement is performed before or after mixing with the dosing vehicle;
• Whether the 500-micrometer threshold is measured by volume, mass, or number.

The claim expressly requires a volume-based distribution. A manufacturer cannot rely on a particle-size specification based only on number distribution if the product would satisfy the volume-based D90 limitation.

How strong is the patent estate?

The issued claim set is commercially targeted but technically narrow.

Strengths

The patent has several enforcement advantages:

1. It claims the complete product-use combination rather than an isolated excipient.
2. The coating monomer combination provides a relatively specific chemical fingerprint.
3. The particle-size limitation is measurable.
4. The composition ranges are broad enough to cover practical product formulations.
5. The claims address pediatric administration, dosing vehicles, and meal-based dosing.
6. The claims cover both urea cycle disorders and maple syrup urine disease.

Weaknesses

The main vulnerabilities are:

1. A competing product can avoid the claims by using a different taste-mask polymer.
2. A non-layered formulation can avoid the seed-core and drug-layer limitations.
3. A product with a D90 of 500 micrometers or greater may avoid the particle-size limitation.
4. A formulation outside the claimed seed-core or coating percentages may avoid literal infringement.
5. Claims 24-27 may raise proof issues because they require specified BCAA outcomes.
6. Claim 2 has drafting ambiguity regarding bioequivalence.
7. Method claims require proof of the claimed administration and therapeutic use.

The patent is stronger against a copy of the claimed formulation than against a conventional sodium phenylbutyrate generic.

What products compete with the claimed technology?

BUPHENYL sodium phenylbutyrate

BUPHENYL is the principal established sodium phenylbutyrate reference product in the United States. It is available as tablets and oral powder for treatment of urea cycle disorders. The product is not the same as the claimed layered, taste-masked particle system. [2]

A generic or follow-on product based on BUPHENYL tablets or powder would not necessarily infringe US Patent 11,202,767 unless it also used the claimed particle architecture and polymer coating.

Pheburane

Pheburane is a taste-masked sodium phenylbutyrate product using coated granules and has been marketed outside the United States. Its relevance to this patent depends on the exact coating polymer, particle-size profile, and composition percentages used in the commercial product.

A product name or general description such as “taste-masked granules” is insufficient to determine infringement. The critical comparison is the formulation’s actual polymer composition and particle architecture.

RAVICTI glycerol phenylbutyrate

RAVICTI contains glycerol phenylbutyrate, a different nitrogen-scavenging active ingredient and prodrug. It is not sodium phenylbutyrate and does not ordinarily implicate the claims of US Patent 11,202,767. [3]

RAVICTI competes commercially in urea cycle disorders but presents a different patent and regulatory landscape, including prodrug, formulation, and method-of-use claims.

Carglumic acid

Carglumic acid is used in selected urea cycle disorders, particularly N-acetylglutamate synthase deficiency. It is pharmacologically distinct from sodium phenylbutyrate and does not fall within the patent’s claimed active ingredient.

What is the FDA and Orange Book status?

BUPHENYL has FDA approval for urea cycle disorder management. RAVICTI also has FDA approval for chronic management of urea cycle disorders. [2,3]

The Orange Book status of US Patent 11,202,767 cannot be established from the claim text. Patent listing depends on the relationship between the patent, an approved NDA, the NDA holder, and the FDA’s listing determination. A patent directed to an investigational or non-approved taste-masked product would not automatically be listed against BUPHENYL or RAVICTI.

A patent covering a different formulation can be relevant to market entry without being listed in the Orange Book for the reference product. Conversely, Orange Book listing would create a potential Paragraph IV pathway for an ANDA applicant, while an unlisted patent would generally require separate enforcement under ordinary patent litigation procedures.

When does US Patent 11,202,767 lose exclusivity?

The patent issued on December 21, 2021. The enforceable term is generally calculated under 35 U.S.C. § 154 from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable patent-term extension. [1,4]

The issue date alone does not determine expiration. The claims supplied do not identify:

• The earliest nonprovisional filing date;
• Any continuation or divisional relationship;
• Patent-term adjustment;
• A terminal disclaimer; or
• Patent-term extension.

Accordingly, an expiration date should not be inferred from the December 21, 2021 issue date. For due-diligence purposes, the controlling term data is the USPTO patent record and the face of the issued patent.

Are there Paragraph IV challenges or generic launch risks?

The patent creates three different generic-entry scenarios.

Conventional sodium phenylbutyrate generic

A conventional tablet or powder generic has a comparatively low risk of literal infringement if it lacks:

• Layered particles;
• The specified acrylic coating;
• The seed-core and coating weight ranges; and
• The sub-500-micrometer D90 profile.

Its principal regulatory pathway would relate to the approved reference product, not necessarily this formulation patent.

Taste-masked granule generic

A taste-masked granule product presents a higher risk. The sponsor would need to compare:

• Polymer identity;
• Coating weight;
• Seed-core proportion;
• Sodium phenylbutyrate loading;
• Particle-size distribution; and
• The proposed labeling and method of use.

A Paragraph IV certification would be commercially significant only if the patent is listed against the relevant reference product and the ANDA applicant certifies that the patent is invalid, unenforceable, or not infringed.

Alternative polymer or dosage form

A formulation using a different coating polymer, a matrix system, a tablet, a capsule, or a non-layered suspension may offer a more defensible design-around position. The principal residual risk would be a doctrine-of-equivalents argument, which would depend heavily on prosecution history and the degree to which the alternative polymer performs the same taste-masking function in substantially the same way.

What patent litigation or settlement issues matter?

The supplied claim set does not establish a litigation, Paragraph IV settlement, or license agreement. The relevant legal questions are:

1. Whether the patent is listed in the Orange Book against an approved product;
2. Whether the patent owner has asserted the claims against a formulation developer;
3. Whether a defendant’s product contains the specified acrylic copolymer;
4. Whether the product meets the D90 and composition limitations;
5. Whether any settlement includes a licensed launch date or formulation restrictions.

A commercial agreement involving the patent owner would be material if it granted rights to the claimed coating technology, authorized a generic launch, or transferred rights to the sodium phenylbutyrate product candidate. Patent ownership and licensing should be distinguished. An assignment or acquisition does not itself establish a field-of-use license.

What is the geographic coverage?

US Patent 11,202,767 provides protection only in the United States. International protection would require corresponding applications or granted patents in jurisdictions such as:

• European Patent Office;
• Canada;
• Japan;
• China;
• Australia; and
• Other national patent systems.

The existence, status, and expiration of foreign counterparts cannot be determined from the US claims alone. For global launch planning, the key distinction is between jurisdictions where the same formulation claims are pending or granted and jurisdictions where only broader sodium phenylbutyrate or method-of-use claims remain active.

What manufacturing and IP barriers affect market entry?

The patent’s manufacturing barriers are moderate. The claimed technology requires a reproducible multiparticulate process, likely involving:

1. Seed-core preparation;
2. Drug-layer deposition;
3. Polymer-coating application;
4. Particle-size classification; and
5. Final blending with a dosing vehicle.

The coating process may create regulatory comparability challenges even where patent infringement is avoided. A different polymer can change taste, dissolution, stability, and bioequivalence. A different particle-size distribution can affect mouthfeel and dose uniformity.

The strongest design-around strategy is likely a different taste-mask polymer combined with a distinct particle architecture. Merely changing trade names, excipient suppliers, or manufacturing equipment would not reliably avoid infringement if the resulting product still contains the claimed structural elements.

What revenue exposure is associated with the patent?

Revenue exposure depends on the product attached to the patent. The claims are most valuable if they cover a commercially approved or launch-ready pediatric sodium phenylbutyrate product. They are less valuable if the covered product remains investigational or lacks a US regulatory pathway.

The patent does not block the entire sodium phenylbutyrate market. Its exposure is concentrated in:

• Pediatric urea cycle disorder therapy;
• Palatable oral granules;
• Dosing with food or modified starch;
• Products intended to improve adherence;
• Potential off-label or specialty use in maple syrup urine disease.

RAVICTI and conventional BUPHENYL products remain outside the patent’s core formulation scope unless they use the claimed layered-particle technology.

Key Takeaways

• US Patent 11,202,767 is a narrow, formulation-specific method patent.
• Its independent claims require layered sodium phenylbutyrate particles with a seed core, drug layer, taste-mask coating, specified polymer chemistry, weight percentages, and a D90 below 500 micrometers.
• Conventional sodium phenylbutyrate tablets and powders are less likely to infringe literally.
• Taste-masked granules using the specified acrylic polymer present the highest infringement risk.
• Claims 1-14 target urea cycle disorders; claims 15-27 separately target maple syrup urine disease.
• Claims 24-27 add BCAA outcome limitations that may complicate enforcement.
• The patent’s issue date is December 21, 2021, but the expiration date requires the earliest effective filing date and patent-term adjustment data.
• Orange Book listing, Paragraph IV activity, litigation, and settlement status cannot be inferred from the claims.
• The most practical design-around routes are a different coating polymer, a non-layered dosage form, or a particle-size and composition profile outside the claimed ranges.
• The patent is strongest against a direct copy of the claimed multiparticulate formulation and weaker against established sodium phenylbutyrate products using different dosage forms.

Frequently Asked Questions

Does US Patent 11,202,767 cover all sodium phenylbutyrate products?

No. It requires a specific taste-masked layered-particle formulation and a claimed therapeutic method.

Does BUPHENYL automatically infringe this patent?

No. BUPHENYL’s approved tablets and oral powder do not automatically satisfy the seed-core, drug-layer, acrylic-coating, composition, and particle-size limitations.

Can a generic avoid the patent by using a different taste-masking polymer?

Potentially. A different polymer can avoid literal infringement if the product also avoids the other claimed limitations. The doctrine of equivalents and prosecution history would remain relevant.

Does the patent cover glycerol phenylbutyrate in RAVICTI?

No. The claims require sodium phenylbutyrate. Glycerol phenylbutyrate is a different active ingredient.

Are maple syrup urine disease claims commercially important?

They can be important for a product marketed or used for BCAA reduction, but claims 24-27 may require evidence that the treatment achieves the specified plasma amino-acid ranges.

What is the most important technical test in an infringement analysis?

The highest-value tests are polymer identification, particle morphology, D90 measurement, seed-core percentage, coating percentage, and sodium phenylbutyrate loading.

References

1. United States Patent and Trademark Office. (2021). United States Patent No. 11,202,767.
2. U.S. Food and Drug Administration. (n.d.). BUPHENYL (sodium phenylbutyrate) prescribing information.
3. U.S. Food and Drug Administration. (n.d.). RAVICTI (glycerol phenylbutyrate) prescribing information.
4. 35 U.S.C. § 154. Contents and term of patent; provisional rights.

Drugs Protected by US Patent 11,202,767

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Acer	OLPRUVA	sodium phenylbutyrate	FOR SUSPENSION;ORAL	214860-007	Oct 10, 2025		RX	Yes	No						TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
Acer	OLPRUVA	sodium phenylbutyrate	FOR SUSPENSION;ORAL	214860-008	Oct 10, 2025		RX	Yes	No						TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
Acer	OLPRUVA	sodium phenylbutyrate	FOR SUSPENSION;ORAL	214860-001	Dec 22, 2022		RX	Yes	No						TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
Acer	OLPRUVA	sodium phenylbutyrate	FOR SUSPENSION;ORAL	214860-002	Dec 22, 2022		RX	Yes	No						TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
Acer	OLPRUVA	sodium phenylbutyrate	FOR SUSPENSION;ORAL	214860-003	Dec 22, 2022		RX	Yes	No						TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE

International Family Members for US Patent 11,202,767

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016398029
Brazil	112018068665
Canada	3017573
Cyprus	1125450
Denmark	3429559