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According to Deadline McHale will play a character called Rex who repeatedly tries to hit on his co-worker, played by Mila Kunis.
The film's surreal plot involves a man being forced to redefine his friendship with an anthropomorphic teddy bear that comes alive after his childhood wish comes true.
The Fighter star Mark Wahlberg will play the film's lead role opposite Kunis, McHale, and Giovanni Ribisi.
Director MacFarlane has also co-written the film alongside regular Family Guy collaborators Alec Sulkin and Willesley Wild.
Ted is expected to be released in 2012.
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