Stable igg4 based binding agent formulations
a technology of igg4 and binding agent, which is applied in the field of stable can solve problems such as dimerization of binding agents, and achieve the effect of reducing the amount of unwanted byproducts and high-stable igg4 binding agent formulations
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Benefits of technology
Problems solved by technology
Method used
Image
Examples
example 1
Characterization of a Phosphate Buffered Saline (PBS) Formulation and Disadvantages Associated Therewith
[0305]In this example, the Reference Lot was characterized. As stated in the Materials section above, the Reference Lot contains the Lead LIGHT Antibody formulated in phosphate buffered saline (PBS) at a concentration of 5.5 mg / mL and at a pH of 7.3, and produced in research solutions Vitry (BioSCP).
[0306]Isoelectric focusing (IEF) was used to determine the isoelectric point (pI) of the Lead Antibody. The pI of the Lead LIGHT Antibody was theoretically calculated as 6.28, and then measured by denaturated isoelectric focusing standard methods known in the art. As shown in FIG. 1, the main bands show that the pI of the Lead LIGHT Antibody was 6.8-7.2.
[0307]SDS-PAGE was used to identify the molecular weight of the antibody monomer, potential aggregates, or the presence of half-molecules. FIG. 2 shows an SDS-PAGE gel that compared different Reference Lot batches under reducing and non...
example 2
Development of Citrate-Buffered Formulations, and Advantages Associated Therewith
[0312]The original buffer, phosphate buffered saline (PBS) at a pH of 7.3, was, in terms of pH, very close to the isoelectric point (pI) of the Lead Antibody (see Example 1). In addition, the Original Formulation exhibited aggregates; half-molecules; degradation products; low molecular weight proteins (LMWPs); high molecular weight proteins (HMWPs); and rearrangements of acidic, basic, and neutral antibody isoforms (see Example 1). Thus, there was a need for an improved formulation that does not suffer from these disadvantages.
[0313]Formulations of the Lead LIGHT Antibody (a fully human IgG4 anti-LIGHT antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 7 and a light chain comprising the amino acid sequence of SEQ ID NO: 8) containing 10 mM citrate buffer at a pH of 5, 5.5, and 6, with and without polysorbate 20 were tested. Table 3 shows the analytical results of the firs...
example 3
Development of High-Concentration Antibody Formulations
[0315]In view of the improvements provided by the Citrate-Buffered Antibody Formulation of Example 2, the citrate buffer components were optimized for increased concentrations of Lead LIGHT Antibody. Table 6 shows the analytical results of the first batch of high concentration (about 40 mg / ml) antibody formulations: high phosphate buffered saline (PBS) at a pH of 7.3 (Formulation 2) or citrate at a pH of 5.5 with polysorbate 20 (Formulation 4).
TABLE 6Analytical results of Formulations 2 & 4SampleTm1Tm2Tm3ZAveConcentrationnumber[° C.][° C.][° C.]pH[nm][mg / mL]BufferReference67.9475.0077.377.310.055.5PBSLotFormulation67.8774.8777.287.312.8942.1PBS2Formulation61.5572.0076.485.516.7139.97Citrate410 mMPS200.01%
[0316]Slightly reduced monomer content was observed after concentrating the protein solution in citrate buffer. Moreover, dimer concentration was reduced and high molecular weight proteins (HMWPs) could be significantly reduced ...
PUM
| Property | Measurement | Unit |
|---|---|---|
| pH | aaaaa | aaaaa |
| concentration | aaaaa | aaaaa |
| pH | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More