If you are using a proxy through to the internet, check that the proxy filtering policies allow access to
and that is is not classified as "Uncategorised". Direct access to this URL through Internet Explorer shouldn't fail.
Review the FCS Exchange Program Log and you will also see C:\Program Files (x86)\Microsoft Forefront Security\Exchange Server\Data.
Open Regedit and navigate to the following key: HKLM\SOFTWARE\Microsoft\Forefront Server Security\SharePoint. Click New DWORD Value, type EngineDownloadTimeout, and then press Enter. Right-click the new value and select Modify. Select Decimal as the base, enter 600 in the Value data box, and then click OK. This setting causes the scan engine download process to time out after 600 seconds (10 minutes, instead of 5 minutes). See the link to “Fix for Forefront Update Timeout Errors“ for details.
Generic engine update error from Antigen for Exchange. In my case this error was caused by an expired evaluation version of the software.