Molecular diagnostics company Xenomics (New York) is studying whether its patented findings could lead to earlier detection in prenatal screening of such genetic diseases as Down syndrome, as well as the possibility of detecting DNA in tumors and HIV and tuberculosis (TB).

The company is being built upon its transrenal DNA (Tr-DNA)-focused intellectual property.

Xenomics CEO Randy White, PhD, discussed the company’s technology and future prospects in an online Q&A session sponsored by the American Association for Clinical Chemistry (AACC; Washington) last week.

“Our scientists in 1996 [discovered] that yes, in fact, DNA from inside the body cross through the kidneys and ends up in urine, and they patented that,” White told Diagnostics & Imaging Week. “They patented it with claims that are so broad – they said the use of transrenal DNA, which is DNA outside the urinary tract system, from inside the body, [can be used] for diagnostic purposes.”

White said those patents were not issued until 2001 and 2002, and explained that the lag time was due to a question that has been asked of the company more than once.

“The Patent and Trademark Office said that same thing that almost anyone else did,” White said, including a person in the Q&A session. “They said, ‘Wait a minute, surely somebody discovered this before 1996.’”

An “exhaustive search” was conducted, and then the patents were finally awarded. He described the power of the patent by saying that “if you use urine to interrogate DNA for fetal genetic defects, then the only way that they would have gotten into the urine was transrenally ... and that belongs to us.”

An article on the findings was published in the AACC’s journal, Clinical Chemistry, in 2000.

White told a questioner in the AACC session that “Tr-DNA appears to have the histone shell intact; this may be one of the reasons Tr-DNA is relatively stable in urine.”

About a month ago, the company also published a patent on Down syndrome after having identified markers for the condition. Xenomics patented “not only the process of discovery, but the markers themselves,” he said.

White noted in his AACC presentation that there are several advantages to DNA analysis in urine. Among the advantages he cited was that it is safe, simple and easy to collect; that urine is a concentrating medium; that the kidneys act as a pre-filtration step; urine is not infectious, while blood samples are, making it more safe for healthcare workers to collect; and that Tr-DNA originates inside the body, vs., for example, a hair follicle or skin.

Xenomics’ first focus is on prenatal testing for Down syndrome, and it is currently in clinical trials for that condition. But the same patents apply with liver cancer. White said, “If you’re going to develop a test in urine to measure k-ras, the only way it could have gotten there was to have crossed the kidneys, and therefore it belongs to us. That’s the power of the patent.”

White told D&IW that the studies are three-pronged and loosely based on six-month components for Down syndrome. The first six months will be dedicated to perfecting the technology, he said.

“What I mean by that is we have a number of markers that are discovered for Down syndrome,” he said. “We have to decide which one is the most sensitive and specific. And then we have to develop the exact primers that we want to use with those markers.”

The second prong of the study involves taking urine samples from women when they come in to their doctor’s office to get an amniocentesis, which usually occurs at 16 to 18 weeks of pregnancy. The test is run, and if it shows that the mother is carrying a Down syndrome baby, then Xenomics will use that urine sample to run its “now-perfected method on it. Just to validate it,” White said.

Finally, he said the company would “push the envelope” and move that testing into the first trimester.

The company is planning to study 400 women, whereby the company will be taking urine samples over the whole course of the women’s pregnancy from the earliest possible time following conception –- two to four days into the pregnancy – until two to four days after delivery.

“What we’re trying to do is on a large cross-spectrum of women, plot the appearance of DNA, fetal in origin, and then the ultimate disappearance of fetal DNA, post delivery,” White said.

And while White said “it’s theory at this point until proven,” the company believes that the fetal DNA will continue to grow in quantity in the mother’s urine, throughout the pregnancy.

“The other thing that this study will tell us is what is the earliest week in pregnancy at which there is always sufficient DNA to perform our test,” he said.

Following the 18 months of study, depending on the number of specimens gotten and how fast, the company would be read to file an FDA submission, White said.

Xenomics is initially looking at Down syndrome, also known as trisomy-21, the company may also look at trisomy-13 and trisomy-18. In trisomy-13, the child is “actually born alive but only lives about three or five days.” In trisomy-18, the child is “terribly affected,” he said, but may live up to five years of age.

Ultimately, the company hopes to use its technology on screening for tumors and infectious diseases, including HIV and TB.

Simultaneously with the Down syndrome studies, Xenomics has entered a joint venture with the National Institute for Infectious Diseases (informally the Spallanzi Institute) in Rome to conduct studies on its technology for HIV and TB. Xenomics contributed intellectual property and Tr-DNA expertise, and the institute is providing space, personnel and money to conduct the studies.

“Xenomics has a 100% worldwide marketing right to anything that gets developed out of the joint venture,” and the institute is due royalties on any commercialized products.

White, former CEO of Nanogen, also said he has just raised $9 million for the company, which has a burn rate of about $3 million a year. The company now has four employees, and White said Xenomics has about 5,000 square feet of lab space in New Jersey.