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Biss (34) has represented New Zealand on the track and in cross-country and mountain running and ran a best marathon time of 2hr 39min in Melbourne this year.
It is a strong female field but Biss is the only runner capable of breaking the race record of 5hr 23min 34sec, which Zelah Morrall ran in 2003.
Biss will be challenged by the winners from the past three years: Vanessa Haverd (Canberra) in 2009, Shireen Crumpton (Dunedin) in 2010 and Victoria Beck (Dunedin) last year.
Haverd, who has finished runner-up in the past two years, has a best time of 5hr 52min.
However, she lacks the speed over the final 20km to match the other runners.
Beck (30) and Crumpton (40) have prepared for the race in different ways.
Beck, who won last year's race in 5hr 51min, has a best marathon time of 2hr 45min.
She has run for more than five hours on three occasions during her preparation for the Kepler.
"I have done more long running this year and it has made me stronger," Beck said. "I have competed in long-distance duathlons and am used to being on my feet for that time."
Beck made her mark as an international athlete in the duathlon before switching to long-distance running. She was eighth in the Hong Kong marathon last year.
Crumpton injured her left knee near Rocky Point last year and was flown back to Te Anau.
She has adopted a different approach to Beck and has trained in the same way she did when representing New Zealand in the marathon. Crumpton has refused to join Beck and others on their five-hour training runs.
"You don't need it," Crumpton said. "You just need sheer mental determination."
Crumpton is prepared to run between two and three hours on training runs but pulls the plug on any more than that.
"It makes you slow if you run too long," she said. "It takes too long to recover and you can't do quality training for a few days."
Crumpton underwent an Achilles tendon operation on her left foot after last year's Kepler Challenge and spent the first few months of the year in recovery mode.
Her best race since the operation has been her third place at the New Zealand championships in Auckland, when she ran 2hr 52min.
Other contenders in the women's race are Elina Ussher (Nelson), Johanna Ottosson (Rotorua), who won the Rotorua marathon this year and has a best time of 2hr 45min, and Whitney Dagg (Dunedin), who broke the women's record for the Routeburn race this year.
Vajin Armstrong (Christchurch) will be attempting to win his third successive Kepler Challenge in the men's event.
Armstrong (32) will be challenged by fellow Christchurch runner Marty Lukes (41), who won the event three years in a row (2007 to 2009) and has been runner-up in the past two years.
He has a best Kepler time of 4hr 49min.
Other contenders are Australians Tony Fattorini and Andrew Tuckey, Jason Schlarb (United States) and Nick Hirschfeld (Hanmer).
A capacity field of 450 will start in the 60km Kepler Challenge and 150 in the 27km Luxmore Grunt.
- Venue: Te Anau.
- Distance: 60km.
- First held: 1988.
- Men, Phil Costley, 4hr 37min 41sec (2005).
- Women, Zelah Morrall, 5hr 23min 34sec (2003).
Luxmore Grunt (27km):
- Men, Phil Costley, 1hr 52min 30sec (2008).
- Women, Shireen Crumpton, 2hr 4min 18sec (1998).