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An immunogenic serotype 35b pneumococcal polysaccharide-protein conjugate and conjugation process for making the same

A protein conjugate, Streptococcus pneumoniae technology, applied in the direction of antigen-carrier connection, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve problems such as the increase in the prevalence of pneumococcus

Pending Publication Date: 2022-02-08
MERCK SHARP & DOHME BV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the evasion described above, the prevalence of pneumococci expressing serotypes not present in the vaccine is increasing

Method used

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  • An immunogenic serotype 35b pneumococcal polysaccharide-protein conjugate and conjugation process for making the same
  • An immunogenic serotype 35b pneumococcal polysaccharide-protein conjugate and conjugation process for making the same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0179] Example 1: Streptococcus pneumoniae 35B Preparation of capsular polysaccharide

[0180] fermentation

[0181] Methods of culturing pneumococci are well known in the art. See, eg, Chase, 1967, Methods of Immunology and Immunochemistry 1:52. Methods of preparing pneumococcal capsular polysaccharides are also well known in the art. See eg European Patent No. EP 0 497 524 B1. The method described below generally follows that described in European Patent No. EP0497 524 B1 and is generally applicable to all pneumococcal serotypes unless specifically modified.

[0182] Isolates of pneumococcal subtype 35B were obtained from the Merck Culture Collection. Subtypes can be differentiated based on the Quelling reaction using specific antisera if desired. See, eg, US Patent No. 5,847,112. The isolated isolates were further cloned by serial plating in two stages on agar plates consisting of an animal component-free medium containing soy peptone, yeast extract and glucose ...

Embodiment 2

[0189] Example 2: Activation of Streptococcus pneumoniae serotype 35B polysaccharide

[0190] The purified pneumococcal capsular Ps powder was dissolved in water and subjected to 0.45 micron filtration. Homogenize the dissolved polysaccharides to reduce the Ps solution viscosity. The homogenization pressure and the number of passes through the homogenizer were controlled to 100 bar / 5 passes. The homogenized polysaccharides were concentrated and diafiltered against water using a 5 kDa NMWCO tangential flow ultrafiltration membrane.

[0191] The polysaccharide solution was adjusted to 22 °C and pH 5 with sodium acetate buffer. Polysaccharide activation was initiated by the addition of 100 mM sodium metaperiodate solution. The amount of sodium metaperiodate added was 0.01, 0.03, 0.05, 0.07, 0.09, or 0.11 moles of sodium metaperiodate per mole of polysaccharide repeat unit to achieve the target level of polysaccharide activation (moles of aldehyde per mole of polysaccharide r...

Embodiment 3

[0195] Example 3: Conjugation of Streptococcus pneumoniae serotype 35B polysaccharide to CRM197

[0196] polysaccharide activation

[0197] The polysaccharide was activated and purified as described in Example 2.

[0198] Conjugation of polysaccharides to CRM197

[0199] Purified CRM197 obtained by expression in Pseudomonas fluorescens as previously described (WO2012 / 173876A1) was diafiltered against 2 mM phosphate (pH 7.2) buffer using a 5 kDa NMWCO tangential flow ultrafiltration membrane, and 0.2 micron filter.

[0200] The activated polysaccharide was formulated for lyophilization at a concentration of 6 mg Ps / mL and 5% w / v sucrose. CRM197 was formulated for lyophilization at a concentration of 6 mg Pr / mL and 1% w / v sucrose.

[0201] The prepared Ps and CRM197 solutions were lyophilized separately. Freeze-dried Ps and CRM197 material were redissolved separately in an equal volume of DMSO. For the saline group, NaCl was spiked into dissolved Ps to a concentratio...

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Abstract

The present invention provides a process improvement related to the conjugation of capsular polysaccharides from Streptococcus pneumoniae (S. pneumoniae) serotype 35B to a carrier protein. The serotype 35B polysaccharide-protein conjugate, prepared by the disclosed process, is, among other things, more immunogenic than similar conjugates made by prior art methods. S. pneumoniae serotype 35B polysaccharide-protein conjugates prepared using the processes of the invention can be included in multivalent pneumococcal conjugate vaccine compositions.

Description

[0001] field of invention [0002] The present invention provides related information from Streptococcus pneumoniae ( S. pneumoniae ) Process improvement for conjugation of capsular polysaccharide of serotype 35B to carrier protein. In particular, serotype 35B polysaccharide-carrier protein conjugates prepared by the methods of the present disclosure are more immunogenic than similar conjugates prepared by prior art methods. The S. pneumoniae serotype 35B polysaccharide-carrier protein conjugate prepared using the method of the present invention can be included in a multivalent pneumococcal conjugate vaccine composition. [0003] Background of the invention [0004] As an example of an encapsulated bacterium, Streptococcus pneumoniae is an important cause of severe disease worldwide. In 1997, the Centers for Disease Control and Prevention (CDC) estimated that there were 3,000 cases of pneumococcal meningitis, 50,000 cases of pneumococcal bacteremia, 7,000,000 cases of pneumoc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/02A61K47/64A61P31/04C12P19/04
CPCA61P31/04A61K47/646A61K47/6415A61K39/092A61K2039/6037A61K2039/55505A61K39/385A61K2039/62
Inventor J·何P·麦休K·M·菲利普斯A·N·圣地亚哥-米兰达
Owner MERCK SHARP & DOHME BV
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