University of Colorado

Travere Therapeutics Switzerland Gmbh

Jan P Kraus

Tomas Majtan

Erez Bublil

Marcia Sellos-Moura

Frank Glavin

Richard Carrillo

David Naveh

Jana Oliveriusova

Vladimir Kery

Randy Wanner

Orhan Causevic

Richard G Carrillo

The present disclosure provides formulations for a drug product comprising a PEGylated CBS protein having the amino acid sequence of SEQ ID NO: 1. Dosages and dosing regimens are provided for treatment of homocystinuria in a subject in need thereof. Additionally, the dosages and dosing regimens are also provided to reduce the level of homocysteine (Hcy) or increase the levels of cysteine (Cys) and/or cystathionine (Cth) in a subject in need thereof.

Pegylated cystathionine beta synthase for enzyme therapy for treatment of homocystinuria

Provided are compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.

Compositions and methods for treatment of homocystinuria

The present invention provides a method of PEGylating a human truncated cystathionine β-synthase protein containing a mutation of a cysteine to a serine at amino acid position 15 (htCBS C15S). The htCBS C15S was PEGylated with one of 5 kDa, 10 kDa, or 20 kDa NHS ester PEG molecules. In-process monitoring of the PEGylation process was used in the method to reduce levels of unPEGylated htCBS C15S and htCBS C15S with insufficient PEGylation. Administration of the PEGylated htCBS C15S had efficacy throughout the course of treatment for homocystinuria.

Optimization of enzyme replacement therapy for treatment of homocystinuria

Provided herein are improved compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.

The present invention provides a method of PEGylating a human truncated cystathionine &#x3b2;-synthase protein containing a mutation of a cysteine to a serine at amino acid position 15 (htCBS C15S). The htCBS C15S was PEGylated with one of 5 kDa, 10 kDa, or 20 kDa NHS ester PEG molecules. In-process monitoring of the PEGylation process was used in the method to reduce levels of unPEGylated htCBS C15S and htCBS C15S with insufficient PEGylation. Administration of the PEGylated htCBS C15S had efficacy throughout the course of treatment for homocystinuria.

This invention provides chromatographic methods for the purification of a cystathionine &#x3b2;-Synthase (CBS) protein, particularly truncated variants thereof and compositions and pharmaceutical compositions prepared therefrom.

Purification of cystathionine beta-synthase

The invention provides reagents and methods for enzyme replacement therapy using chemically modified species of human cystathionine &#x3b2;-synthase (CBS) to treat homocystinuria and other related diseases and disorders.

Chemically modified cystathionine beta-synthase enzyme for treatment of homocystinuria

This invention provides compositions of human propionyl-CoA carboxylase (PCC) and pharmaceutical compositions of human PCC and methods for treating conditions such as propionic acidemia (PA), propionic aciduria, propionyl-CoA carboxylase deficiency and ketotic glycinemia.

Propionyl-CoA carboxylase compositions and uses thereof

Human cystathionine &#x3b2;-synthase variants are disclosed, as well as a method to produce recombinant human cystathionine &#x3b2;-synthase and variants thereof. More particularly, the role of both the N-terminal and C-terminal regions of human CBS has been studied, and a variety of truncation mutants and modified CBS homologs are described. In addition, a method to express and purify recombinant human cystathionine &#x3b2;-synthase (CBS) and variants thereof which have only one or two additional amino acid residues at the N-terminus are described.

Growing community of inventors

Littleton, CO, United States of America

Jan P Kraus