Inventors
Arnon Rosenthal, Michael Leviten, Beth Stevens, Soyon Hong, and Daniel Wilton
Assignees
- ANNEXON, INC.[US/US}; P.O. Box 2931, South San Francisco, CA 94083-2931 (US).
- BOSTON CHILDREN’S HOSPITAL [US/US]; 300 Longwood Avenue, Boston, MA 02115 (US)
Abstract
This invention relates generally to methods of treatment for neurodegenerative diseases such as Alzheimer’s disease, Alzheimer’s-related diseases, and Huntington’s disease, and more specifically to methods involving the inhibition of the classical pathway of complement activation. Certain aspects of the present disclosure are directed to methods and kits for treating or preventing Alzheimer’s disease and/or Huntington’s disease that include inhibiting the classical pathway of complement activation by neutralizing complement factor C1q, e.g., through the administration of antibodies, such as monoclonal, chimeric, humanized antibodies, antibody fragments, etc., which bind to C1q.
CovalX Technology Used
Outcomes
In order to determine whether or not the CIq peptides that had been generated by proteolysis competed for binding of CIq to the antibody, analysis was performed. 25 µi of the CIq antigen (10 μM) was digested with immobilized pepsin (5 µiM) and incubated at room temperature for 30 minutes. The incubated sample was centrifuged and the supernatant was removed by pipetting. To control the completion of proteolysis and optimize it to the 1000 to 3500 Da range, a MALDI mass spectrometer was used in linear mode. 5 µi of antigen peptides that were generated from the proteolysis were mixed with 5 µi of ANN-001 or ANN-005 (5 μM) before being incubated for 6 hours at 37 °C. 5 µi of the incubated mixture was mixed with 5 µi of the C1Q antigen (4 μM). This mixture contained either 2 μM/2 μM/2.5 μM of C1QA antigen/4A4B11 or MI/C1Q antigen peptides. The mixture was spotted on a MALDI plate and analyzed using a mass spectrometer that had been modified with a CovalX HM3 detection system. The data was smoothed and subtracted using the CovalX Complex Tracker software.
Patent Number
WO2015/006507 A1