Police charged Clark after reviewing some 300 pieces of evidence, including DNA samples taken from Clark a day before he was arrested. His bond was set at $3 million, and he did not enter a plea.
Officials reportedly found DNA from Le and Clark in the ceiling and in the recess where Le's body was found.
The evidence is so overwhelming that police believe they don't necessarily have to uncover Clark's motive for the killing to convince jurors of his guilt, according to a law enforcement official who spoke to The Associated Press on condition of anonymity because the investigation is ongoing.
That likely leaves Clark's attorneys with going after how that evidence was gathered - rather than what it showed - and have prosecutors defend their decision not to seal the lab building until Le's body was found.
"You attempt to attack the investigative process as well as the conclusions," said William Dow III, a prominent New Haven-based defense lawyer, who does not represent anyone in this case. Clark's court-appointed attorneys did not return calls seeking comment Saturday. Clark's bond was set at $3 million, and he did not enter a plea.
Yale students were allowed into the basement of the research building for at least three days after Le disappeared. The Hartford Courant reported that Clark was in the lab cleaning while police were conducting interviews shortly after the grad student disappeared, and tried to hide lab cleaning equipment that they later discovered contained blood spatters.
At the time, police said they were not sure whether the Le case was a homicide or a missing persons case. The building wasn't sealed until Le's body was found and the case declared a homicide.
Prosecutors won't be able to deny that the area where the body was found was different from the scene when the murder took place, attorneys said.
"DNA can be transferred in many, many ways, and when people work together, DNA can be transferred in ways that are very legitimate," said Michael Georgetti, a Hartford defense attorney.
But the attorneys also said the prosecutor's case appears very strong.
If they have Clark's DNA in the crawl space where the body was found, Le's DNA on his clothing, scratches that an expert can say were defensive wounds, and more, it will be much harder to base a defense on problems with collecting that evidence.
"If a jury is looking for something to grab on to, then this could be something for them to grab on to," said Hugh Keefe, another top Connecticut defense attorney. "But stepping back, and going just on what I have read in the newspapers, this is a tough case from a defense standpoint."
Police said Friday they didn't expect more arrests in the case, but they're continuing to gather evidence. On Friday, they towed a Ford Taurus from the parking lot of the Super 8 hotel in Cromwell, Conn., where Clark was arrested the previous day.
Police wouldn't confirm who owns the car, but said the seizure was part of the Yale murder investigation. Clark's father, Raymond John Clark Jr., was registered at the hotel through Saturday and had been staying there at times, according to a person familiar with the family who spoke on the condition of anonymity because of the nature of the charges.
Clark was a technician in the lab where Le conducted research. The law enforcement official who spoke to the AP said co-workers called Clark a "control freak" who was territorial about the mice whose cages he cleaned. Authorities are investigating whether that attitude might have set off a clash between Clark and Le.
Le's work involved experiments on mice that were part of research into enzymes that could have implications for treatment of cancer, diabetes and muscular dystrophy.
Her family has returned to Le's hometown of Placerville, Calif., to prepare for Le's funeral, said family spokesman Dennis Smith, a New Haven pastor.
Her death has been hard for the family, and the widespread media attention has been uncomfortable for them because of their private nature, Smith said.
But the family is grateful for support that he said has included e-mail messages from across the country.
"They love Annie of course, and they appreciate all the expressions of sympathy, the candlelight vigil and all that," Smith said.
Associated Press reporter Susan Haigh in New Haven contributed to this report.