Bill Cosby's defence lawyers have called his accuser a "pathological liar".

Cosby, 80, the once-beloved comedian and TV dad, is on trial on three counts of aggravated indecent assault of Andrea Constand, 45, at his home outside Philadelphia in January 2004.

Ms Constand, a former administrator of the Temple University women's basketball team, is one of a number of women who claim Cosby drugged and violated them.

The comedian's lawyers attacked the credibility of the women who testified against him at his sexual assault trial, singling out accuser Ms Constand during closing arguments on Tuesday.

Defence lawyer Thomas Mesereau said Ms Constand made inconsistent statements.

Mr Mesereau told the jury that she continued to call Cosby after the alleged assault. He said Cosby "must be acquitted on all counts."

"He made some mistakes for sure, but he is no criminal," Mr Mesereau told the jury at Montgomery County Courthouse in Norristown, Pennsylvania.

"This is a very serious moment for an 80-year-old man who had a very successful career and is looking at absolute ruin."

Cosby built his television career on having a wholesome image and made family-friendly jokes as a comedian.

Prosecutors say he used this good-guy image to gain unsuspecting women's trust before knocking them out with powerful drugs and violating them.

"He is nothing like the image that he played on TV," prosecutor Kristen Feden told jurors in her closing argument.

"In fact, he utilised that image and cloaked it around himself so that he could gain the trust, gain the confidences of these aspiring, unsuspecting women."

Image:Bill Cosby arrives with his wife Camille for his sexual assault trial

Mr Mesereau's fellow defence lawyer Kathleen Bliss assailed the five other witnesses who made accusations against Cosby, saying it was unfair that they were "digging up stuff from three decades ago."

She said the five accusers were fabricating stories in the hopes of personal gain.

"What is this case about? Money, press conferences, TV shows, salacious coverage, ratings. Sex sells," Ms Bliss said.

In all, around 50 women have accused Cosby of sexual assault going back decades, though only Ms Constand's case was recent enough for criminal prosecution.

Cosby was tried last year – just as the #MeToo movement saw sexual assault and harassment allegations against rich and powerful men gained momentum – but the jury was unable to reach a verdict.

Cosby declined to testify on his own behalf at both his trials. He has denied wrongdoing, saying any sexual contact he had was consensual.

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His wife of more than 50 years, Camille, only attended court for closing arguments during both trials.

If convicted of all three counts, Cosby would likely face up to 10 years in prison under state sentencing guidelines, although Pennsylvania law allows for a maximum penalty of three consecutive 10-year terms.

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