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The Team Rocket leader, Giovanni, has found Mewtwo in a remote area of the Johto region. As Giovanni tries to re-capture Mewtwo, Ash and his friends are kidnapped by Domino, a new Team Rocket member, while trying to rescue Pikachu from Jessie and James.

Dr. Fuji, a research scientist of Team Rocket, briefly describes in a prologue how his researchers uncovered a fossil of the remnants of Mew, one of the rarest Pokémon in existence, believed to be extinct (although this is not the case).

A Pokémon Collector, Lawrence III, wishes to capture the three legendary birds and follow the legend's tale. This is all part of his plan to capture the Beast of the Sea, Lugia.

Professor Spencer Hale, once one of Professor Oak's top students and a good friend of the Ketchum family, is obsessed with discovering the secret behind the mysterious glyph-like Pokémon called Unown. One day while investigating some ruins, he disappears after encountering the enigmatic creatures, leaving his only daughter, Molly, alone and lonely back at his mansion.

When a great demon fox attacked Hidden Leaf Village, a powerful man known as the 4th Hokage had sealed the demon inside a newborn named Naruto, who then grew up detested by his fellow Leaf villagers. As a child, Naruto is isolated from the Konoha community, who regards him as if he was the Nine-Tails.

Naruto: Shippuuden is the continuation of the original animated TV series Naruto.The story revolves around an older and slightly more matured Uzumaki Naruto and his quest to save his friend Uchiha Sasuke from the grips of the snake-like Shinobi, Orochimaru.