Please have a look at this link it may be helpful

http://forums.asp.net/p/1206468/3044068.aspx#3044068

Here's another post which talks about a similar error: http://forums.asp.net/t/1206468.aspx

Iam getting the same error when i use Telerik RadScriptManager. Just to document this, iam placing here.

Try this:

protected override void OnPreRenderComplete(EventArgs e)
{
   //My Code
}

MUST be:

Mr Blue Coat:

ScriptResource.axd handles the ScriptManager control that AJAX requires.  WebResource.axd handles embedded resources (such as embedded css files, embedded images, etc.)  SiteMinder intercepts all page calls and verifies any referenced file or resource exists before allowing the associated code to run.  ScriptResource.axd is referenced on your page (view the source code when running to see for yourself) but the ScriptResource.axd file only exists in memory (.NET 2.0 creates it dynamically).  Thus, SiteMinder sees a reference to a file that "supposedly" doesn't exist and therefore blocks the creation of the 'Sys' object (hence, 'Sys' not defined).  Likewise, the WebResource.axd file "supposedly" doesn't exist so SiteMinder blocks built-in css styles (i.e. ajax__calendar) and your toolkit controls will appear without any formatting.

This one is a bit old, but it still applies to those who use SiteMinder (CA Netegrity) if you are having this problem. If this is already answered elsewhere in this thread sorry for the repeat in advance.

Our problem manifested not as a "Sys" problem, but just that everything that was AJAX based didnt appear which, in our case, was about 70% of the information provided by our site. Not a good thing. A check of the weblogs showed every single call to an .axd file was returned as a 404 error. We turned off Siteminder and tried again and everything worked fine.

What Blue Coat wrote is correct, but you don't need to add the two empty files. As stated elsewhere it does work but it doesn't address the root of the problem. To make Siteminder stop blocking it:

1. Go into your IIS Manager and right-click the root of your site and select Properties.
2. Under Home Directory, click Configuration. 
3. There should be a Wildcard entry for ISAPI6WebAgentDLL there (we are using CA Siteminder v6.xx so its there for us). Highlight it and click Edit.
4. Make sure the checkbox for Verify that file exists is unchecked.
5. Click through on OK.

I was pulling my hair out trying to figure this one out, we are standing up a new server and everything mirrored the old one yet SSO worked on the old and not on the new. After a couple days of working with the helpdesk found out that the updated installation documentation we were provided omitted that fact to ensure you uncheck that checkbox, the older documentation we used to install on the old server had it. By default, when adding a Wildcard Mapping that checkbox is checked.

No guarantees this will work 100% of the time but as soon as I unchecked the box everything on my new server site worked, menu bars, tabs, all the AJAX just suddenly appeared. Oh Happy Day...heh heh. Hope this helps.

I found that running aspnet_regiis.exe - i from the v2.0x Microsoft.Net folder (under Windows) solved my problem. 
The web.config entries were all correct, but until i reset the script mappings i had no luck.

Try adding this under <system.web> in web.config: -

<httpHandlers>

</httpHandlers>