C3 fusion protein and methods of making and using thereof
Inventors
BORJAS, Ricardo • Fleming, Mark • Huang, Mei • Jain, Mayur • Sanghvi, Tapan • Saxena, Kumkum • TORRES-DELGADO, Amaris • Yin, Ping • McKerracher, Lisa • RYU, Elizabeth
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11324802-B2
Publication Date
2022-05-10
Expiration Date
Abstract
The present invention provides, among other things, improved therapeutic compositions comprising a C3 fusion protein and methods of making and using the same. In particular, the present invention provides improved methods for the treatment of spinal cord injury and other CNS trauma and/or facilitate axon growth or other tissue repair.
Core Innovation
The invention relates to improved pharmaceutical composition and formulation of an ADP-ribosyl transferase C3 fusion polypeptide for spinal cord injury and CNS trauma. The compositions include a population of polypeptides having a total of 231 amino acid residues and an amino acid sequence at least 95% identical to SEQ ID NO:1. A key defining characteristic is that the first amino acid is not a methionine, and the polypeptide population constitutes greater than 85% of the total amount of polypeptides in the composition.
The invention further distinguishes between two polypeptide forms based on the presence or absence of an N-terminal methionine. A first polypeptide is otherwise identical to a second polypeptide but does not contain a methionine at the N-terminus in the first polypeptide, while the second polypeptide contains a methionine at the N-terminus. The composition requires a specific weight ratio of the first polypeptide to the second polypeptide, with at least 6:1.
The invention also defines pharmaceutical compositions with measurable and constrained quality parameters. These include a polypeptide concentration ranging from 1.0 mg/mL to 40 mg/mL as determined by UV spectrometry at 280 nm, host cell protein less than 100 ng/mg, endotoxin less than 2.9×10^4 EU/mg, and a buffer having a pH ranging from 5.5 to 7.5 at 25 °C. In addition, the concentration is further refined to 27–33 mg/mL based on UV spectrometry at 280 nm.
Claims Coverage
The independent claims cover three main inventive feature themes: polypeptide population composition, form ratio between N-terminal methionine present/absent polypeptides, and specified QC/parameter constraints tied to UV concentration, HCP/endotoxin limits, and pH.
High-fraction N-terminal methionine-absent SEQ ID NO:1 polypeptide population
A pharmaceutical composition comprising a population of polypeptides, each having a total of 231 amino acid residues and an amino acid sequence at least 95% identical to SEQ ID NO:1, wherein the first amino acid is not a methionine, and wherein the population constitutes greater than 85% of the total amount of polypeptides.
First and second N-terminal methionine-defined polypeptide forms with required weight ratio
A pharmaceutical composition comprising a first polypeptide and a second polypeptide, wherein the first polypeptide has a total of 231 amino acid residues and has an amino acid sequence at least 95% identical to SEQ ID NO:1 but does not contain a methionine at the N-terminus, the second polypeptide is otherwise identical to the first polypeptide but contains a methionine at the N-terminus, and the weight ratio of the first polypeptide to the second polypeptide is at least 6:1.
QC-parameter constrained N-terminal methionine-absent SEQ ID NO:1 polypeptide concentration with impurity and pH limits
A pharmaceutical composition comprising a polypeptide having a total of 231 amino acid and an amino acid sequence at least 95% identical to SEQ ID NO:1, wherein the polypeptide does not contain a methionine at the N-terminus, and wherein the polypeptide is present at a concentration ranging from 1.0 mg/mL to 40 mg/mL as determined by UV spectrometry at 280 nm, or wherein the composition contains less than 100 ng/mg host cell protein (HCP), or wherein the composition contains less than 2.9×10^4 EU/mg endotoxin, or wherein the pharmaceutical composition comprises a buffer and has a pH ranging from 5.5-7.5 at 25 °C.
Overall, the claim set defines pharmaceutical compositions built around a 231-residue SEQ ID NO:1-based C3 fusion polypeptide enriched in a form lacking an N-terminal methionine, optionally framed by the ratio of N-terminal methionine-present versus -absent forms. Additional independent-claim scope includes concentration specified by UV spectrometry at 280 nm and explicit QC limits for HCP, endotoxin, and buffer pH constraints.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Spinal cord injury therapy using a C3 fusion polypeptide pharmaceutical composition for CNS trauma.
Interested in licensing this patent?