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The Colts (6-4) had their four-game winning streak stopped. The Patriots (7-3) won their fourth straight game and extended their lead in the AFC East to three games.
Even so, Brady doesn't want the Patriots to start patting themselves on the back.
"I don't think we're anywhere (near) where we need to be at this point," he said.
Julian Edelman scored on a 68-yard punt return three plays before Talib's interception put the Patriots ahead to stay, 21-14.
"I don't think guys panicked" after that one-two punch, Luck said. "Playing hard is not enough, as evidenced tonight."
Brady completed 24 of 35 passes for 331 yards and no interceptions. Luck was 27 for 50 for two touchdowns and 334 yards and set an NFL record as the first rookie with five 300-yard games.
The Colts were competitive for one half. The Patriots led 24-17 heading into the third quarter.
Then the Patriots scored on passes of 2 yards to Edelman and 24 yards to Gronkowski and Dennard's interception return.
Luck followed with a 43-yard scoring pass to T.Y. Hilton, the second of the game to the fellow rookie, but the Patriots responded with touchdown runs of 3 yards by Stevan Ridley and 4 yards by Shane Vereen.
The game began with touchdowns on the first three series: a 1-yard run by Delone Carter of the Colts, a 4-yard pass from Brady to Gronkowski, and a 14-yard pass from Luck to Hilton.
"A lot of plays motivated the defense," said Talib, playing his first game since being obtained from the Tampa Bay Buccaneers. "About that third or fourth (Colts) series, we kind of got into it. It was kind of quiet out there early (then) we started talking."
The Patriots obtained him before last Sunday's 37-31 win over Buffalo. But he sat that one out to complete a four-game suspension for violating the NFL policy on performance-enhancing substances.
NOTES: The Colts outgained the Patriots 448 yards to 446. ... The 59 points equals the Patriots record set in a 59-0 win over the Tennessee Titans on Oct. 18, 2009. ... The Patriots are 18-0 in the second half of the season starting in 2010. ... Welker stretched his streak to 104 games with at least one reception. ... Reggie Wayne tied Cris Carter's NFL mark with 58 consecutive games with at least three catches.
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