Glycerol phenylbutyrate, sold under the brand name Ravicti, is a nitrogen-binding agent medication used for chronic management of certain urea cycle disorders. The medication reduces the harmful buildup of ammonia in the body.[4] It functions as a prodrug of phenylbutyric acid, which conjugates with glutamine to form phenylacetylglutamine, facilitating ammonia excretion via the kidneys
Glycerol phenylbutyrate is indicated for chronic management of people with urea cycle disorders who cannot be managed by dietary protein restriction and/or amino acid supplementation alone.[2]
Patents
While GPB is the subject of several patents related to its synthesis, formulation, and therapeutic monitoring, the core patent covering its composition and use in treating UCDs is US 5,968,979. Subsequent patents build on this foundation, focusing on manufacturing improvements, dosing methods, and related applications. Below is a summary of key issued US patents explicitly addressing GPB's use in UCDs, based on patent database records. Note that patents often cover broader nitrogen retention disorders, including UCDs as a primary indication.
Issued US Patents
Patent Number
Title
Issue date
Assignee/Inventor
Summary of Relevance to UCD Treatment
US 5,968,979
Glycerol ester derivatives
October 19, 1999
Children's Medical Center Corp. (Boston, MA); Saul W. Brusilow, Marshall L. Summar
Foundational patent for GPB (glyceryl tri-(4-phenylbutyrate) or HPN-100) as a nitrogen-scavenging agent. Claims methods for treating UCDs by administering GPB to reduce hyperammonemia, with dosages of 5–10 g/m²/day. Enabled FDA approval in 2013.US 5968979,Brusilow, Saul W.; Summar, Marshall L.,"Glycerol ester derivatives""Ravicti Label"(PDF). U.S. Food and Drug Administration. Retrieved 14 October 2025.
US 9,914,692
Procedure for the preparation of 4-phenyl butyrate and uses thereof
March 13, 2018
Horizon Therapeutics Ireland DAC; Bruce A. Bloom, Mitchell L. Chan
Describes synthesis of 4-phenylbutyric acid (GPB precursor) via oxidation of 4-phenyl-1-butanol. Claims use of GPB in treating UCDs and hepatic encephalopathy, emphasizing >99% purity for ammonia control.US 9914692,Bloom, Bruce A.; Chan, Mitchell L.,"Procedure for the preparation of 4-phenyl butyrate and uses thereof"
US 10,045,959
Methods of therapeutic monitoring of nitrogen scavenging drugs
August 14, 2018
Horizon Therapeutics USA, Inc.; Jeffrey L. Gelfand, Bruce A. Bloom
Covers methods to monitor and adjust GPB dosing in UCD patients using fasting ammonia levels. Includes dose titration algorithms to maintain ammonia <0.5 mmol/L, improving long-term management.US 10045959,Gelfand, Jeffrey L.; Bloom, Bruce A.,"Methods of therapeutic monitoring of nitrogen scavenging drugs"
US 9,999,608
Methods of therapeutic monitoring of nitrogen scavenging drugs
June 19, 2018
Horizon Therapeutics USA, Inc.; Jeffrey L. Gelfand, Bruce A. Bloom
Continuation of US 10,045,959, focusing on predictive modeling of ammonia exposure to prevent hyperammonemic crises in UCD patients, with clinical data from pediatric and adult cohorts.US 9999608,Gelfand, Jeffrey L.; Bloom, Bruce A.,"Methods of therapeutic monitoring of nitrogen scavenging drugs"
Additional Notes Patent Expiry: US 5,968,979 expired in 2018, potentially allowing generic GPB formulations by late 2025. Later patents (e.g., US 9,914,692) extend protection for synthesis methods until ~2035–2038. "Ravicti Patent Expirations". DrugPatentWatch. Retrieved 14 October 2025. Related Patents: International patents (e.g., WO 2015/063659) and pending US applications (e.g., US 2021/0114996 for RNA-modulating therapies) mention GPB but are not issued US patents.WO 2015063659,"Process for preparation of glycerol phenylbutyrate" Clinical Context: These patents supported trials showing GPB reduces ammonia by ~30% compared to sodium phenylbutyrate, leading to FDA approval for patients ≥2 months.
Additional Notes
Scope and Expiry: US 5,968,979 expired in 2018, aligning with the entry of generic GPB formulations expected by late 2025. Later patents (e.g., US 9,914,692) extend protection for manufacturing processes, potentially affecting generics until around 2035-2038. Related but Non-US or Pending: International equivalents (e.g., WO 2015/063659 for GPB synthesis) and US applications (e.g., US 2021/0114996 for RNA-modulating therapies in UCDs mentioning GPB) exist but are not issued US patents. Clinical Context: These patents supported pivotal trials (e.g., phase 3 studies showing GPB reduces ammonia by 30% vs. sodium phenylbutyrate) leading to FDA approval for all ages ≥2 months.
Society and culture
Economics
Hyperion has been criticized for setting a high price for the drug. The price was set at US$250,000–290,000. In 2014, the drug generated $30.8 million in net sales, far behind the older and less expensive Buphenyl ($113.6 million in sales).[7]
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