High purity oritavancin and method of producing same

Inventors

Rafai Far, Adel • Krishna, Gopal • Ding, Min • Chemburkar, Sanjay R. • Knable, Carl M. • Petzel, James P. • Pruyne, Julie J. • Reamer, Douglas M.

Assignees

Melinta Subsidiary Corp • Melinta Therapeutics LLC

Abstract

Drug substance preparations of oritavancin having high purity are disclosed, along with pharmaceutical compositions comprising such oritavancin drug substance preparations, and drug products or dosage forms comprising such pharmaceutical compositions.

Core Innovation

The disclosure relates to high-purity oritavancin drug substance preparations and to pharmaceutical compositions and drug products comprising an oritavancin drug substance preparation and one or more pharmaceutically acceptable excipients. A central aspect is specifying impurity or purity criteria for the oritavancin drug substance preparation using HPLC-defined impurity peaks, including impurities 2-16 defined by peaks B-P of FIG. 2, and maximum impurity levels for impurity 2 (DEV A) and impurity 10 (oritavancin CR) defined by peaks B and J of FIG. 2.

The pharmaceutical composition is prepared by forming an excipient solution in water having a pH of 2.5 to 3.5, dissolving the oritavancin drug substance preparation in that excipient solution, and adjusting the pH of the resulting solution to 3.5 to 4.0. The method includes filtering the solution and lyophilizing the filtered solution, and the disclosure describes measured purity and stability over storage.

The disclosed preparation and formulation also include control approaches tied to impurity formation and the properties of the final lyophilized composition, including lyophilized moisture control and defined pharmaceutically acceptable excipients such as mannitol, sorbitol, sucrose, and trehalose. The disclosure further specifies how purity and impurities are determined by HPLC, including an HPLC method using a C18 reverse-phase stationary phase and mobile phases/gradient defined using phosphoric acid, water, acetonitrile, and tetrahydrofuran.

Claims Coverage

The document provides two independent method claims. Across these independent claims, the inventive features focus on meeting defined HPLC-based purity/impurity thresholds for an oritavancin drug substance preparation and using a defined formulation workflow with excipients in acidic water, pH adjustment, filtering, and lyophilization.

Overall, the independent claims are directed to producing a pharmaceutical composition by dissolving defined pharmaceutically acceptable excipients in acidic water, adding the oritavancin drug substance preparation with pH adjustment to 3.5 to 4.0, then filtering and lyophilizing, while meeting specific HPLC-defined purity/impurity criteria based on impurity peaks in FIG. 2.

Stated Advantages

Documented Applications