Similar to this question and this one but different issues. All required fields and tokens are filled in. But db is showing Null for reply_id field, whereas all earlier mailings have an '8' in that field. I can't see if this is settable via the UI and am unsure why this would either now be required, or the default is NULL. This site recently upgraded from 4.4.19 to 4.6.8 with no warnings related to this afaik.
Not sure if this is the answer, or a better identification of the problem.
I see that in Headers, Footers etc Auto-responder ID is '8' but is not set as default.
Not sure if setting it to default, and saving and reopening my mailing resulted in button being clickable or if that was the one I edited in DB.
Will have to look in to whether someone turned that default off or it is was a minor glitch in the upgrading.