Direct mass spectrometric analysis of aggregates of...

Chemistry: analytical and immunological testing – Peptide – protein or amino acid

Reexamination Certificate

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C436S002000, C436S008000, C436S063000, C436S173000, C436S176000

Reexamination Certificate

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07943387

ABSTRACT:
The invention relates to a method of using high-mass matrix assisted laser desorption-ionization (MALDI) mass spectrometry for the quantitative analysis of the amount of aggregation (dimers, trimers or multimers) of antibodies or other therapeutic proteins in purified pharmaceutical samples or complex biological matrices, as well as to the use of this method for characterization of antibodies, drug development and quality control of therapeutic proteins, including automated high throughput applications.

REFERENCES:
patent: 2006/0271306 (2006-11-01), Dobson et al.
patent: 2005/045442 (2005-05-01), None
patent: 2006/116893 (2006-11-01), None
Cleland, Jeffrey L. et al. “A specific molar ratio of stablizer to protein is required for storage stability of a lyophilized monoclonal antibody.” Journal of Pharmaceutical Sciences (2001) 90 310-321.
“Monoclonal Antibody Production.” A Report of the Committee on Methods of Producing Monoclonal Antibodies by the Institute for Laboratory Animal Research, National Research Council, Washington, DC 1999.
Nazabal, Alexis et al. “Immunoassays with direct mass spectrometric detection.” Analytical Chemistry (2006) 78 3562-3570.
Wenzel, Ryan J. et al. “Comparison of sensitivity and saturation of MALDI-ToF detectors for high mass ions.” Proceedings of the 54th ASMS Conference on Mass Spectrometry; Seattle, May 2006.
International Search Report issued Mar. 10, 2008 in PCT/EP2007/064056 of which the present application is the U.S. National State.
PCT Written Opinion issued Mar. 10, 2008 in PCT/EP2007/064056.
Farmer et al., “Assessing the Multimeric States of Proteins: Studies Using Laser Desorption Mass Spectrometry”, Biological Mass Spectrometry, vol. 20, pp. 796-800 (1991).
Farmer et al., “Mass Discrimination in Matrix-assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry: a Study Using Cross-linked Oligomeric Complexes”, Journal of Mass Spectrometry, vol. 30, pp. 1245-1254 (1995).
Gerard Bolbach, “Matrix-Assisted Laser Desorption/Ionization Analysis of Non-Covalent Complexes: Fundamentals and Applications”, Current Pharmaceutical Design, vol. 11, pp. 2535-2557 (2005).

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