Wales wing George North inspired Northampton to a Heineken Cup Pool 1 win at Ospreys.
to remain top, but Saints can finish top of the group with a heavy win over Castres on Friday if Ospreys beat the Irish province in Dublin at the same time.
Saints led 12-3 when ex-Scarlet North struck from 70 metres out in Swansea.
Rhys Webb struck back but George Pisi and Glenn Dickson went over to seal the visitors' win.
That left the home side with only one win from the opening five rounds and with nothing other than pride to play for when they travel to Leinster, on 17 points, in round six.
On the same night Northampton, who have 13 points, host Castres, who also cannot now progress in this season's tournament.
The home side went into the encounter this season.
And Jim Mallinder's side were quick to further exploit Ospreys' frailties in that department.
Northampton's dominance up front was the platform to build a 12-3 lead by the break, fly-half Myler kicking four first-half penalties to Biggar's solitary effort.
Myler's first shot came after the home side's front-row buckled at the opening scrum after two minutes.
The once-capped England fly-half added a second penalty before Biggar struck back after he put pressure on the visitors' defence with a well-executed chip-and-chase attack.
But two more Myler shots at goal underlined their opening period superiority that also prompted loose-head prop Ryan Bevington's sin-binning.
Myler added his last penalty before the break after Justin Tipuric's late challenge on him.
Rare attacking momentum from the hosts as the opening period drew to a close ended in Tipuric sending wing Jeff Hassler over, but the score was ruled out as the Wales flanker's pass was deemed forward.
And soon after the restart former Ospreys half-back Kahn Fotuali'i sent Wales wing North on a 70-metre run to the line after another home attack faltered.
Another North burst, this time after coming into midfield, emphasised the danger he posed.
But the game's momentum began to change when home coach Steve Tandy sent Adam Jones on at tight-head in place of fellow Wales prop Aaron Jarvis.
As the home side's pack began to get on top, Saints lock Christian Day was sin-binned for illegally halting an Ospreys surge near the visitors' line.
And from that platform scrum-half Webb eventually went over and Biggar converted.
That left the home side a converted score from levelling, but Saints resisted any temptation to sit on their lead with a telling response.
It ended with centre Pisi going over, albeit past a high tackle that led to Aisea Natoga's sin-binning.
Back came the home side for skipper Alun Wyn Jones to drive over, Biggar converting.
But a mix-up at the back of defensive ruck gave North the chance to help create replacement Dickson's try, which he also converted.
VIEWS FROM THE DRESSING ROOM
Ospreys boss Steve Tandy: "There's a lot of good within our game, but... there are points where we take our foot off the gas a little bit.
"Like when we go 22-17, our exits are poor, there's poor ball presentation and we switch off. They get a foot through and we cough up a cheap try.
"We created some decent opportunities and looked have decent when we had the ball at times.
"But… in these games if you switch off for a second it's curtains."
Northampton boss Jim Mallinder: "We are playing quite well at the moment, but tinged with a little bit of disappointment that we didn't go on and get the fourth try and a bonus point.
"The quality of the Heineken Cup is there are six tough pool games, and you have got to be accurate in all six.
"If you look at Leinster, to win at Castres, Ospreys and Franklin's Gardens, they've deserved to do well in the group. We need that consistency."
Ospreys: Richard Fussell; Jeff Hassler, Tom Isaacs, Jonathan Spratt, Aisea Natoga; Dan Biggar, Rhys Webb; Ryan Bevington, Richard Hibbard, Aaron Jarvis, Alun-Wyn Jones (capt), Ian Evans, Sam Lewis, Joe Bearman, Justin Tipuric.
Replacements: Ben John for Isaacs (67), Scott Baldwin for Hibbard (55), Adam Jones for Jarvis (46), James King for Evans (64), Duncan Jones for Lewis (31-41), Morgan Allen for Lewis (51),
Not Used: Habberfield, Davies.
Sin-bin: Bevington (30), Natoga (71).
Northampton Saints: Tom Collins; Jamie Elliott, George Pisi, Luther Burrell, George North; Steve Myler, Kahn Fotuali'i; Alex Waller, Dylan Hartley (capt), Salesi Ma'afu, Courtney Lawes, Christian Day, Calum Clark, Samu Manoa, Tom Wood.
Replacements: Fa'atoina Autagavaia for Collins (41), Glenn Dickson for Myler (73), Ethan Waller for A Waller (64), Mikey Haywood for Hartley (73), Tom Mercey for Ma'afu (51), Phil Dowson for Clark (60), Sam Dickinson for Wood (73).
Not used: L. Dickson.
Sin-bin: C Day (59).
Ref: Pascal Gauzere (France).