4GB is a little over the top! Thumbs up to Brian, the SymDiag tool is able to resolve a great many issues.
As a shortcut, the below article shows how to clear out corrupt defs:
http://www.symantec.com/docs/HOWTO59193
NOTE: As you've named the IPSDefs folder in particular, this sounds like a an issue with the SEP Client on the server, rather than the SEP Manager that you mention.