Pharmaceutical composition comprising bispecific antibody constructs for improved storage and administration
A bispecific antibody and composition technology, which is applied in drug combination, antibody, drug delivery, etc., can solve problems such as yield loss
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[0116] For the production of monoclonal antibodies, any technique that provides antibodies produced by continuous cell line cultures can be used. For example, monoclonal antibodies to be used can be prepared by the hybridoma method first described by Koehler et al., Nature, 256:495 (1975), or can be prepared by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567). Examples of additional techniques for producing human monoclonal antibodies include tripleoma technology, human B-cell hybridoma technology (Kozbor, Immunology Today [Today Immunology] 4 (1983), 72) and EBV-hybridoma technology (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss Company (1985), 77-96).
[0117] Standard methods such as enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (BIACORE TM ) assay) hybridomas are screened to identify one or more hybridomas that produce an antibody that specifically binds to a given antigen. Any form of the relevant antigen can b...
example 1
[0457] Example 1: To investigate the compatibility of known preservatives with representative bispecific antibody constructs according to the invention, CD19xCD3 bispecifics were formulated in the presence of the respective known preservatives with the parameters listed in Table 4 Antibody constructs.
[0458] Table 4: Formulation parameters used to test the compatibility of preservatives with CD19xCD3 bispecific antibody constructs.
[0459]
[0460] The formulation parameters used were previously found to be effective in stabilizing the bispecific antibody constructs. Therefore, any differences should become even more pronounced compared to the preservative-free negative control (G4SuT). The preservative concentrations chosen reflect standard concentrations used in the art. The respective formulations were stored at 25°C for 14 days and checked by size exclusion chromatography (SEC-HPLC) on days 0, 1, 3, 7 and 14. From figure 1 It can be seen that some of the formulat...
example 2
[0461] Example 2: As another known preservative, benzyl alcohol was tested for compatibility with a representative bispecific antibody construct according to the invention, the CD19xCD3 bispecific antibody construct. Physiological pH 7 was chosen as a challenging environment in order to better mimic clinical application situations, since typically bispecific antibody constructs as described herein are less affected by aggregation in a pH 7 environment compared to a pH 4 environment. A general trend towards aggregation would be expected. In detail, dilution lines of the CD19xCD3 antibody construct were prepared from 4.5 to 800 μg / ml, reflecting typical clinical application concentrations and concentrations that may be exceeded. The 0.9% benzyl alcohol concentration was chosen according to the commercially and regulatory approved 0.9% sodium chloride USP with 0.9% benzyl alcohol. Compatibility was checked by size exclusion chromatography (SEC-HPLC) to determine the percentage o...
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