Stable anti-OSMR antibody formulation
Inventors
Manning, Mark Cornell • Shahrokh, Zahra • Nichols, Dave • Levesque, Phillip M • Holcomb, Ryan Erik
Assignees
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Publication Number
US-10391170-B2
Publication Date
2019-08-27
Expiration Date
Abstract
The present invention provides, among other things, stable formulations comprising an anti-oncostatin M receptor (OSMR) antibody and having a pH ranging from approximately 6.0-7.6, wherein less than approximately 5% of the anti-OSMR antibody exists as high molecular weight (HMW) species in the formulation.
Core Innovation
The invention relates to a stable formulation comprising an anti-oncostatin M receptor (OSMR) antibody at a concentration of 100 mg/ml-250 mg/ml and having a pH ranging from approximately 6.0-7.6. The anti-OSMR antibody comprises a light chain having an amino acid sequence set forth in SEQ ID NO: 2 and a heavy chain having an amino acid sequence set forth in SEQ ID NO: 1.
The formulation addresses stability by limiting high molecular weight (HMW) species, including aggregates, relative to monomeric IgG, and by maintaining at least 97% of the antibody as monomer. The composition is characterized by stable performance across storage and stress conditions, with a defined increase of the relative amount of HMW species after storage at 25°C for 4 weeks, and with NaCl as the salt used.
Analytical characterization is used to monitor HMW species and/or monomer, including SEC, AUC, FFF, and light scattering, and to characterize charge variants using cIEF/icIEF. The disclosed stability and robustness include temperature stability and impacts from freeze-thaw and agitation, together with low viscosity suitable for syringeability/injectability and isotonic osmolarity.
Claims Coverage
The independent claim is directed to a stable anti-OSMR antibody formulation defined by antibody concentration, pH range, and specific light- and heavy-chain amino acid sequences (SEQ ID NO: 2 and SEQ ID NO: 1). The claim set also includes dependent features that refine monomer/HMW stability metrics, specify NaCl, define a liquid formulation reconstitutable from lyophilized powder, and identify analytical characterization methods; in total, the claims emphasize several inventive features that define stability, composition, and quality control.
Stable formulation with anti-OSMR antibody concentration and pH
A stable formulation comprising an anti-oncostatin M receptor (OSMR) antibody at a concentration of 100 mg/ml-250 mg/ml and having a pH ranging from approximately 6.0-7.6, wherein the anti-OSMR antibody comprises a light chain having an amino acid sequence set forth in SEQ ID NO: 2 and a heavy chain having an amino acid sequence set forth in SEQ ID NO: 1.
High monomer existence requirement
A stable formulation in which at least 97% of the antibody exists as monomer.
HMW species increase constraint after storage at 25°C
A stable formulation characterized by the increase of the relative amount of HMW species after storage at 25°C for 4 weeks, rising by approximately between 0.3% and 0.7%.
NaCl as the defined salt component
A stable formulation characterized in that the salt used is NaCl.
Liquid formulation reconstitutable from lyophilized powder
A stable formulation characterized in that the formulation is a liquid formulation that can be reconstituted from a lyophilized powder.
Analytical characterization of HMW species and monomer using specified methods
A stable formulation in which the high molecular weight (HMW) species and/or the monomer are characterized by one or more of SEC, AUC, FFF, or light scattering.
Overall, the claims coverage centers on a stable anti-OSMR antibody formulation defined by concentration, pH, and specific SEQ ID-defined light/heavy chains, with dependent refinements that constrain monomer/HMW stability metrics, specify NaCl, define a liquid formulation reconstitutable from lyophilized powder, and specify analytical characterization methods for HMW species and/or monomer.
Stated Advantages
Provides a stable formulation with controlled pH for an anti-OSMR antibody.
Limits the relative amount of HMW species and supports monomer integrity (e.g., at least 97% monomer).
Maintains antigen binding activity while keeping formulation attributes suitable for injection.
Supports low viscosity for syringeability/injectability.
Provides isotonic osmolarity suitable for injectable use.
Enables analytical characterization of HMW species/monomer and charge variants using specified analytical methods.
Documented Applications
Disease-treatment context is described, notably pruritus.
Kit/delivery considerations and injectable delivery context are described.
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