The show originally centered on five characters living in Pasadena, California: Leonard Hofstadter and Sheldon Cooper, both physicists at Caltech, who share an apartment; Penny, a waitress and aspiring actress who lives across the hall; and Leonard and Sheldon's similarly geeky and socially awkward friends and co-workers, aerospace engineer Howard Wolowitz and astrophysicist Raj Koothrappali.[4][5] Over time, supporting characters were promoted to starring roles, including neuroscientist Amy Farrah Fowler, microbiologist Bernadette Rostenkowski, physicist Leslie Winkle and comic book store owner Stuart Bloom.
Kaley Cuoco's life after The Big Bang Theory is going to be animated. Cuoco has signed on to voice and executive produce DC Universe's new Harley Quinn series. She'll play the titular character in the new streaming series targeted toward mature audiences. In 2017, she got the rights to The Flight Attendant, a miniseries based on the book of the same name, which she was poised to star in. The Flight Attendant follows Cassandra Bowden, a flight attendant, who wakes up, hungover, in her hotel room with a dead body next to her. She goes about her day and heads back to New York. is she the killer? That's what she wonders. "This is the first time I have a project that I'm kind of nurturing from the beginning, so it's been a really interesting experience," she told PopSugar in March. "It's got a lot of aspects. It's very sexy. It's a really well-written book, which is why I wanted to option it. I'm ready to bring the character to life."

In scenes set at Howard's home, he interacts with his rarely-seen mother (voiced by Carol Ann Susi until her death) by shouting from room to room in the house. She similarly interacts with other characters in this manner.[85] She reflects the Jewish mother stereotype in some ways, such as being overly controlling of Howard's adult life and sometimes trying to make him feel guilty about causing her trouble. She is dependent on Howard, as she requires him to help her with her wig and makeup in the morning. Howard, in turn, is attached to his mother to the point where she still cuts his meat for him, takes him to the dentist, does his laundry and "grounds" him when he returns home after briefly moving out.[86] Until Howard's marriage to Bernadette in the fifth-season finale, Howard's former living situation led Leonard's psychiatrist mother to speculate that he may suffer from some type of pathology,[87] and Sheldon to refer to their relationship as Oedipal.[88] In season 8, Howard's mother dies in her sleep while in Florida, which devastates Howard and Stuart, who briefly lived with Mrs. Wolowitz.

In November 2016, it was reported that CBS was in negotiations to create a spin-off of The Big Bang Theory centered on Sheldon as a young boy. The prequel series, described as "a Malcolm in the Middle-esque single-camera family comedy" would be executive-produced by Lorre and Molaro, with Prady expected to be involved in some capacity, and intended to air in the 2017–18 season alongside The Big Bang Theory.[211][212] The initial idea for the series came from Parsons, who passed it along to The Big Bang Theory producers.[213] In early March 2017, Iain Armitage was cast as the younger Sheldon, as well as Zoe Perry as his mother, Mary Cooper. Perry is the real-life daughter of Laurie Metcalf, who portrays Mary Cooper on The Big Bang Theory.[213]
In March 2017, CBS renewed the series for two additional seasons, bringing its total to twelve, and running through the 2018–19 television season.[3] On August 22, 2018, CBS and Warner Bros. Television officially announced that the twelfth season would be the series' last. This stems from Jim Parsons' decision to leave the series at the end of the season if the show were to have been renewed for a thirteenth season.[1][4][5] The series concluded with an hour-long finale consisting of two back-to-back episodes on May 16, 2019.[6][7] A retrospective, hosted by Johnny Galecki and Kaley Cuoco, aired at 9:30 P.M. ET/PT, the night of the finale, following the season two finale of Young Sheldon.[8]

The episode opens with a short montage of clips from the series' twelve seasons, then segues to Sheldon and Amy, who are up late waiting for a call from the Nobel Committee. Following a prank call from Kripke, they are told they've won the Nobel Prize in Physics for their super-asymmetry work. The attention from the media and the university bothers Sheldon. Amy is saddened by an unflattering picture of her in a news report, so Raj convinces her to get a makeover. She loves her new look but Sheldon demands she change it back. Leonard calls him out for being rude, but Sheldon flees when he sees Penny emerge from the newly repaired elevator. Sheldon and Penny go to the Cheesecake Factory and Penny tells Sheldon that change is the only constant thing in life. On a TV, they see Bernadette and Howard take credit as Sheldon and Amy's best friends. Raj and Leonard defend Amy, with Leonard accidentally breaking Sheldon's DNA molecule model in Apartment 4A. Penny convinces Sheldon to ride in the elevator.

Sheldon needs half a billion dollars to prove his latest concept of string theory, which the University cannot afford to fund. Crowdfunding and selling some of his most valuable comic books to Stuart give him a small start. When Raj mentions gambling in Las Vegas, Sheldon goes there but is caught calculating odds by security before he can make any bets. Meanwhile, Amy takes Penny and Bernadette shopping for her wedding dress. She loves an old-fashioned one that the other girls admit that they find ugly, though Penny assures Amy she can make her own decisions about her wedding. Sheldon, however, comes home and sees Amy in the dress and loves how she looks.
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