JP-2026076187-A - Anti-sclerostin antibody preparations

Abstract

[Problem] To provide an optimized pharmaceutical composition that enhances the stabilization of therapeutic proteins to avoid aggregation, which is a major phenomenon of physical instability of proteins, and prevents loss of function and harmful immunogenic reactions by reducing aggregation, denaturation, or degradation during formulation, filling, transport, storage, and administration. [Solution] (a) Anti-sclerostin antibody; (b) A buffering agent comprising glutamic acid, histidine, or succinic acid; and (c) A pharmaceutical composition comprising a polyol, wherein the pharmaceutical composition has a pH of 4 to 7. [Selection Diagram] None

Inventors

• クリスチャン，トゥインクル，アール．

Assignees

• アムジエン・インコーポレーテツド

Dates

Publication Date

20260511

Application Date

20251226

Priority Date

20190812

Claims (20)

1. (a) Anti-sclerostin antibody; (b) Buffering agents containing glutamic acid, histidine, or succinic acid; and (c) a pharmaceutical composition comprising a polyol, The aforementioned pharmaceutical composition has a pH of 4 to 7. Pharmaceutical composition.
2. The pharmaceutical composition according to claim 1, wherein the buffering agent is present in an amount of approximately 10 mM to approximately 50 mM.
3. The pharmaceutical composition according to claim 1, wherein the polyol is present in an approximate concentration of about 1% to about 10% w/v.
4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the polyol is sorbitol.
5. The pharmaceutical composition according to claim 4, wherein sorbitol is present in an amount of approximately 5% to approximately 10% w/v.
6. The pharmaceutical composition according to claim 4, wherein the sorbitol is present in an amount of approximately 5% w/v.
7. A pharmaceutical composition according to any one of claims 1 to 6, further comprising glycerol.
8. The pharmaceutical composition according to claim 7, wherein the glycerol is present at a concentration of approximately 1% to approximately 5% w/v.
9. The pharmaceutical composition according to claim 8, wherein the glycerol is present at a concentration of approximately 1% w/v.
10. The pharmaceutical composition according to claim 8, wherein the glycerol is present at a concentration of approximately 2.5% w/v.
11. A pharmaceutical composition according to any one of claims 1 to 10, further comprising sucrose.
12. The pharmaceutical composition according to claim 11, wherein the sucrose is present at a concentration of approximately 1% to approximately 10% w/v.
13. The pharmaceutical composition according to claim 12, wherein the sucrose is present at a concentration of approximately 9%.
14. A pharmaceutical composition according to any one of claims 1 to 13, further comprising an amino acid other than histidine.
15. The pharmaceutical composition according to claim 14, wherein the amino acid is arginine.
16. The pharmaceutical composition according to claim 15, wherein arginine is present in an amount of approximately 10 mM to approximately 250 mM.
17. The pharmaceutical composition according to claim 16, wherein arginine is present in an amount of approximately 100 mM.
18. A pharmaceutical composition according to any one of claims 1 to 6, 11, and 12, further comprising methionine.
19. The pharmaceutical composition according to claim 18, wherein methionine is present in an amount of approximately 10 mM to approximately 100 mM.
20. The pharmaceutical composition according to claim 19, wherein the methionine is present in an amount of approximately 20 mM.

Description

Cross-reference of related applications: This application claims priority to U.S. Provisional Patent Application No. 62/885,672, filed on 12 August 2019, which is incorporated herein by reference in its entirety. This application concerns pharmaceutical formulations containing anti-sclerostin antibodies. Incorporation by reference of electronically submitted materials: The computer-readable nucleotide/amino acid sequence listings submitted concurrently with this specification are incorporated in their entirety by reference and identified as follows: a 17,909-byte ASCII (text) file named "53956_Seqlisting.txt" created on 7 August 2020. Incorporation by Reference The following applications are incorporated herein by reference in their entirety: International Patent Application PCT/U.S. Patent Application Publication No. 2012/049331 filed August 2, 2012 (claiming priority to U.S. Provisional Patent Application No. 61/515,191 filed August 4, 2011), U.S. Patent Application No. 11/410,540 filed April 25, 2006 (U.S. Provisional Patent Application No. 60/792,645 filed April 17, 2006, U.S. Provisional Patent Application No. 60/782,244 filed March 13, 2006, U.S. Provisional Patent Application No. 60/776,847 filed February 24, 2006, and 20 (claiming priority to U.S. Provisional Patent Application No. 60/677,583 filed May 3, 2005); and U.S. Patent Application No. 11/411,003 filed April 25, 2006 (registered as U.S. Patent No. 7,592,429) (claiming priority to U.S. Provisional Patent Application No. 60/792,645 filed April 17, 2006, U.S. Provisional Patent Application No. 60/782,244 filed March 13, 2006, U.S. Provisional Patent Application No. 60/776,847 filed February 24, 2006, and U.S. Provisional Patent Application No. 60/677,583 filed May 3, 2005). The following applications are also incorporated herein by reference: U.S. Patent Application No. 12/212,327, filed September 17, 2008 (claiming priority to U.S. Provisional Patent Application No. 60/973,024, filed September 17, 2007), and U.S. Patent Application No. 12/811,171, filed June 29, 2010 (a U.S. National Phase Entry application under Section 371 of the U.S. Patent Act for International Patent Application No. PCT/US08/86864, filed December 15, 2008, claiming priority to U.S. Provisional Patent Application No. 61/013,917, filed December 14, 2007). Protein-based drugs are among the fastest-growing therapeutics in (pre)clinical development and as marketed products. Compared to small molecule chemical agents, protein-based drugs exhibit high specificity and activity at relatively low concentrations and typically provide treatment for various cancers, autoimmune diseases, and metabolic disorders with significant impact (Roberts, Trends Biotechnol. 2014 Jul; 32(7): 372-80, Wang, Int J Pharma. 1999 Aug 20; 185(2): 129-88). Advances in commercial-scale purification processes now allow for the acquisition of high-purity recombinant proteins and other protein-based pharmaceuticals during initial production. However, proteins are only slightly stable and are highly susceptible to both chemical and physical degradation. Chemical degradation refers to modifications involving covalent bonds, such as deamide, oxidation, cleavage or formation of new disulfide crosslinks, hydrolysis, isomerization, or deglycosylation. Physical degradation includes protein unfolding, undesirable surface adsorption, and aggregation. Addressing these physical and chemical instabilities is one of the most challenging aspects of protein-based pharmaceutical development (Chi et al., Pharma Res, Vol. 20, No. 9, Sept 2003, pp. 1325-1336; Roberts, Trends Biotechnol. 2014 Jul; 32(7): 372-80). Protein aggregation is a major phenomenon of protein physical instability and arises from an inherent tendency to minimize thermodynamically unfavorable interactions between the solvent and hydrophobic protein residues. Protein aggregation can be particularly problematic because it occurs during processes such as refolding, purification, sterilization, transport, and storage. Aggregation can occur even under thermodynamically favorable solution conditions for the protein's native state (e.g., neutral pH and 37°C) and in the absence of stress (Chi et al., Pharm Res, Vol. 20, No. 9, Sept 2003, pp. 1325-1336; Roberts, Trends Biotechnol. 2014 Jul; 32(7): 372-80; Wang, Int J Pharm. 1999 Aug 20; 185(2): 129-88; Mahler J Pharm Sci. 2009 Sep; 98(9): 2909-34). Maintaining the stability and activity of proteins in biological and biotechnological applications presents a serious challenge. Optimized pharmaceutical compositions that enhance the stability of therapeutic proteins and reduce aggregation, denaturation, or degradation during formulation, filling, transport, storage, and administration, thereby preventing loss of function and adverse immunogenic reactions, are needed in the art. In one embodiment, the pharmaceutical composition described herein comprises an anti-sclerostin antibody; a buffer containing glutamic acid, hist