Antibody formulation

a technology of anti-cd40 and pharmaceutical formulation, which is applied in the field of pharmaceutical formulations of anti-cd40 antibodies, can solve the problems of large unmet need for more efficacy, unfavorable alternative primary immunotherapy, and the risk of progressive multifocal leukoencephalopathy, and achieves low antibody aggregation and high concentration of anti-cd40 antibodies

Inactive Publication Date: 2015-03-26
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite the availability of several immunosuppressive treatments for autoimmune diseases, there remains a large unmet need for more efficacious and safer drugs in a large fraction of the patient population.
For example, despite the reported efficacy of B cell depleting / inhibiting therapies like Rituximab and Belimumab in rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and multiple sclerosis, these therapies are only effective in a portion of diseased individuals, and with Rituximab, with an accompanying risk of progressive multifocal leukoencephalopathy.
While nephrotoxicity and cardiovascular morbidity associated with CNIs is one of the drivers of chronic allograft nephropathy as well as patient death with a functioning graft, alternative primary immunosuppression have not been able to replace CNIs.
B-cell mediated immunological damage of transplanted kidneys may contribute to poor long-term outcomes and the need for new agents to target B-cell rejection is increasingly recognised by the medical community.
Formulations with high concentration of antibody may have short shelf lives and the formulated antibodies may lose biological activity resulting from chemical and physical instabilities during the storage.
In particular, aggregation can potentially lead to increased immune response in patients, leading to safety concerns.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

Preparing Anti-CD40 Antibodies

[0221]CHIR-12.12, and mAb1 (N297A CHIR-12.12), mAb2 (D265A CHIR-12.12), and mAb3 (CHIR-12.12 LALA) bind specifically to CD40. Tables 1 and 2 below summarise the sequence characteristics of these antibodies. These antibodies may be produced in mammalian host cells, such as, a CHO cell line transfected with expression vectors carrying heavy and light chain coding sequences under suitable expression promoters.

TABLE 1Brief description of the sequences listed in the sequence listing of Table 2SEQ IDNO:Description of the sequence1Amino acid sequence of the variable region (VH) of the heavy chain of CHIR-12.12, mAb1, mAb2 and mAb32Amino acid sequence of the variable region (VL) of the light chain of CHIR-12.12, mAb1, mAb2 and mAb33Amino acid sequence of HCDR1 of CHIR-12.12, mAb1, mAb2 and mAb34Amino acid sequence of HCDR2 of CHIR-12.12, mAb1, mAb2 and mAb35Amino acid sequence of HCDR3 of CHIR-12.12, mAb1, mAb2 and mAb36Amino acid sequence of LCDR1 of CHIR-12.1...

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Abstract

Anti-CD40 antibodies are formulated as lyophilisate or liquid formulation. The lyophilisates can be reconstituted to give a solution with a high concentration of the antibody active ingredient for delivery to a patient without high levels of antibody aggregation. The lyophilisate can be reconstituted with an aqueous reconstituent to provide an aqueous composition in which the antibody has a concentration of at least 50 mg / ml. The lyophilisate or aqueous pharmaceutical composition may include one or more of a sugar, a buffering agent, a surfactant, and / or a free amino acid.

Description

TECHNICAL FIELD[0001]The present invention relates to a pharmaceutical formulation of an antibody against CD40, a process for the preparation thereof and uses of the formulation.BACKGROUND[0002]Despite the availability of several immunosuppressive treatments for autoimmune diseases, there remains a large unmet need for more efficacious and safer drugs in a large fraction of the patient population. For example, despite the reported efficacy of B cell depleting / inhibiting therapies like Rituximab and Belimumab in rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and multiple sclerosis, these therapies are only effective in a portion of diseased individuals, and with Rituximab, with an accompanying risk of progressive multifocal leukoencephalopathy. Further, multiple other leukocyte cell types are often involved in the pathology of these autoimmune diseases such as macrophages, dendritic cells and T cells, therefore therapeutic intervention targeting additional ce...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/26A61K47/18A61K47/22A61K39/395C07K16/28
CPCA61K47/26A61K39/3955C07K16/2878A61K47/22C07K2317/76A61K2039/505C07K2317/94C07K2317/21A61K47/183A61K39/39591A61K9/19A61K47/20A61P17/00A61P19/02A61P29/00A61P37/00A61P37/02A61P37/06A61K39/395C07K16/28A61K39/39558
Inventor MUELLER, CLAUDIAWILLMANN, MATTHIAS
Owner NOVARTIS AG
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