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The Denver Broncos set a franchise record for points in a game by beating Philadelphia 52-20 behind red-hot quarterback Peyton Manning's four touchdown strikes.
Manning added to his record-setting touchdown total, racking up 16 through the first four games of the season to set a NFL mark.
"We felt really motivated to score points against these guys," said Manning, who also registered his league-record 24th career game on Sunday with at least four passing strikes.
"We were motivated to be on top of our game offensively, to score points, touchdowns not field goals, and I thought we did that today."
Manning was 28-of-34 for 327 yards and no interceptions. He tied Milt Plum's mark for most touchdown passes to start a season without an interception, set in 1960 with the Browns.
Wes Welker and Demaryius Thomas both caught two scores, and Knowshon Moreno ran for 78 yards and a touchdown on 12 carries for the Broncos, who improved to 4-0.
Denver have won 15 consecutive regular-season contests dating back to last season to set a club record.
Quarterback Michael Vick threw for 248 yards on 14-of-27 passing for the Eagles, who fell to 1-3. Philadelphia lost their third-straight game since opening the season with a victory over the Washington Redskins.
Vick didn't last the game as he was replaced in the fourth quarter by Nick Foles who unlike Vick was able to pass for a touchdown when he hit Jeff Maehl from six yards out.
Denver blew the game open in the second half with 31 consecutive points thanks to Manning's heroics.
He engineered three straight scoring drives, with each one ending in a touchdown pass to give Denver a commanding lead.
Manning completed all five passes on a 65-yard, seven-play series that culminated with a four-yard touchdown pass to Welker to make it 42-13.
In Kansas City, the Chiefs continued their surprising early-season success with a 31-7 rout of the New York Giants thanks to a stingy defense and a productive special teams unit.
Alex Smith shook off a pair of interceptions to throw three touchdown passes for the Chiefs, who are off to their best start to a season since 2003.
"On all three sides of the ball, we're doing a good job of taking care of the ball, scoring points, taking the ball away, scoring on special teams," said Chiefs wide receiver Dwayne Bowe.
Smith threw for 288 yards on 24-of-41 passing, while Jamaal Charles rushed for 127 yards and caught one of Smith's touchdown passes at Arrowhead Stadium as Kansas City improved to 4-0.
Dexter McCluster added a thrilling 89-yard punt return for a touchdown, while a swarming defense limited the last place Giants to just 298 total yards.
"Right now we're 4-0 and the target is on our back, and we have to keep pushing," said Bowe.
New York is now 0-4 for the first time since the 1987 season.
Steven Hauschka booted a 45-yard field goal with 3:19 left in overtime to rally the unbeaten Seattle Seahawks to a 23-20 win over the Texans in Houston.
Seattle scored the final 20 points and are undefeated after four games for the first time in franchise history.
In the late game Sunday, New England held on to beat Atlanta 30-23.
In earlier contests the results were Buffalo 23 Baltimore 20; Arizona 13 Tampa Bay 10; Indianapolis 37 Jacksonville 3; Cleveland 17 Cincinnati 6; Detroit 40 Chicago 32; Minnesota 34 Pittsburgh 27; Tennessee 38 NY Jets 13; Washington 24 Oakland 14; and San Diego 30 Dallas 21.