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Immunoconjugate formulations

A technology for immunoconjugates and dosage forms, which can be used in immunoglobulins, antibody medical components, peptides, etc., to solve problems such as insufficient treatment of particles and aggregates

Inactive Publication Date: 2008-08-06
IMMUNOGEN INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these compositions do not adequately address particles and aggregates formed in immunoconjugate pharmaceutical compositions

Method used

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  • Immunoconjugate formulations
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0149] This example shows the effect of the following dosage form excipients on the appearance of the formed MAb-DM1 conjugate sample.

[0150] A sample containing 1.0 mg / mL of huN901-SPP-DM1 in a phosphate buffer solution was prepared. The phosphate buffer solution was 10 mM, pH 6.5, 140 mM NaCl and each excipient listed in the following table. The excipient was directly added to the huN901-SPP-DM1 sample in units of w / w% (weight of excipient / weight of solution). Immediately after the addition of excipients, the dosage form mixture is filtered, and then the appearance and particle count tests are performed. The samples were then stored at 40°C for the duration of the study, and then tested again at 2 weeks and 1 month. As for the appearance, the sample is tested by checking the clarity of at least 1.0 mL of the solution on a white background and whether it has visible particles in white light relative to a black background. Record the results regarding the presence or absence of ...

Embodiment 2

[0168] This example shows the effect of amino acids on the stability of huN901-SPP-DM1 in terms of conjugate aggregates.

[0169] A 5.0 mg / mL huN901-SPP-DM1 sample was prepared in the following buffer, and then stored at 2-8°C and 25°C for 12 months. The content of conjugate aggregates was tested by chromatographic analysis at 1, 3, 6 and 12 months.

[0170] (1) 10mM sodium phosphate, 140mM NaCl, pH 6.5.

[0171] (2) 10mM sodium citrate, 135mM NaCl, 0.01% polysorbate 20, pH 5.5.

[0172] (3) 10 mM sodium citrate, 130 mM histidine, 0.01% polysorbate 20, pH 5.5.

[0173] (4) 10mM sodium citrate, 110mM glycine, 80mM NaCl, 0.01% polysorbate 20, pH 5.5.

[0174] 2-8℃

[0175] Example 1 shows that histidine improves the dosage form in terms of inhibiting the formation of coupling aggregates. Glycine also has this advantage.

Embodiment 3

[0177] This example shows the effect of histidine on the stability of the huMy9-6-SPDB-DM4 conjugate in terms of conjugate aggregates.

[0178] A 5.0 mg / mL huMy9-6-SPDB-DM4 conjugate was formed in the following solution:

[0179] (1) 10mM sodium citrate, 135mM NaCl, pH5.5

[0180] (2) 150mM histidine / histidine chloride, pH5.5

[0181] The samples were kept at 2-8°C and 25°C for 6 months, and then the aggregation of the conjugate was tested by chromatographic analysis.

[0182] Dosage form

[0183] The data shows that histidine has the beneficial effect of preventing aggregate formation.

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Abstract

The present invention provides an immunoconjugate formulation that is substantially free of particles, the immunoconjugate formulation comprising: an immunoconjugate and one or more excipients selected from the group consisting of: sucrose, polysorbate 20, polysorbate 80, cyclodextrin, dextrose, glycerol, polyethylene glycol, mannitol, sodium chloride, and an amino acid, wherein the formulation is a buffered aqueous solution having a pH of 4.5 to 7.6. The present invention also provides an immunoconjugate formulation that is substantially free of aggregates, the immunoconjugate formulation comprising: an immunoconjugate and one or more excipients selected from the group consisting of histidine, sucrose, glycine and sodium chloride, wherein the formulation is a buffered aqueous solution having a pH of 4.5 to 7.6. The present invention further provides an immunoconjugate formulation that is substantially free of both particles and aggregates.

Description

[0001] This application requires U.S. application No. 60 / 704,902 with the filing date of August 3, 2005 and U.S. application No. 60 / 707,162 with the filing date of August 11, 2005 in accordance with U.S. Patent Law 35U.SC§119(e) The priority of U.S. Application No. 60 / 746,454 with the filing date of May 4, 2006 and U.S. Application No. 60 / 746,456 with the filing date of May 4, 2006, the contents of which are incorporated herein by reference. Technical field [0002] The invention relates to a method for preparing a stable dosage form of an immunoconjugate, which is a drug compound composed of an antibody and one or several drug molecules connected by covalent bonds. Background technique [0003] Immunoconjugates have been developed as highly effective and specific agents for the treatment of cancer and other conditions. Immunoconjugates include antibodies that specifically recognize target cell antigens, such as tumor cell antigens, and drug molecules linked to one or more covalen...

Claims

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Application Information

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IPC IPC(8): A61K39/00C07K16/00
CPCA61K47/48561A61K47/48384A61K47/6849A61K47/68033
Inventor 张伟迈克尔·S·弗莱明戈弗雷·阿姆弗雷特亨-伟·吉伊丽莎白·巴特利特
Owner IMMUNOGEN INC
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