Technology

TECHNOLOGY

OTraces’ IP focuses on in vitro diagnostic (IVD) predictive power enhancement, mainly using computational methods commonly used in other fields but adapted to the requirements of disease detection with extraordinary success thus far. Two illustrations are noise suppression techniques and spatial proximity correlations that orchestrate the action and interactions of biomarkers to achieve optimal results. No other competitive technologies are known to be pursuing this approach.

The principal omnibus patent filing, dated January 22, 2016 provides comprehensive patent protection for OTraces, Inc. for all known computational methods for achieving predictive power of 95%-plus and that apply to all types and classes of biomarkers and biomolecules, and specifically covers the following:

TECHNICAL ADVANCES INCORPORATED IN THE OTRACES PLATFORM

  • Incrementally improving correlation method predictive power, (several),
  • Using non protein based independent variables in a meta-variable approach,
  • Methods for extracting data using novel and non-traditional methods, and
  • Methods for “personalized” diagnosis based upon personalized “baseline” measurements.

Company management believes that the current IP portfolio of submissions constitutes “blocking patents”, some of which may be combined in the patent prosecution process but all concepts have been validated and will be included in the patents prosecuted through to issuance. The company’s IP strategy is to continue to patent methods it discovers that will improve predictive power of the correlation methods used in the OTraces method.

PERFORMANCE TRACK RECORD

The OTraces method represents a cancer detection platform for a number of solid tumor cancers, as all solid tumors investigated with the OTraces method demonstrate high predictive power. The table below shows results for the five cancers investigated to date. The data from the Gertsen Clinical Laboratory in Moscow represents the third party clinical trial for market clearance in the Russian Federation.

Company management believes that the current IP portfolio of submissions constitutes “blocking patents”, some of which may be combined in the patent prosecution process but all concepts have been validated and will be included in the patents prosecuted through to issuance. The company’s IP strategy is to continue to patent methods it discovers that will improve predictive power of the correlation methods used in the OTraces method.


PROTEOMIC COMPLEXITY

A principal roadblock to diagnostic performance are various sources of disease “noise”– corruption from extraneous sources that conventional testing methods cannot resolve. In today’s chemistry-based assays, protein (or other biomolecule) concentration levels can be altered by scores of medical conditions in the population (or drugs routinely consumed by this population) that affect the up or down regulation of the biomarkers of choice. Furthermore, biological systems can exhibit complex non-linear behaviors that are very difficult to model in a correlation method.

The following table illustrates some of the non-cancer sources of “noise” as it pertains to human Interleukin-6, a widely used diagnostic protein that is part of the OTraces breast cancer screening panel.

Non-Cancer Medical Conditions/Administered Drugs
Up-regulated by Interleukin 6

Alcoholism Cardiomyopathy Rheumatoid Arthritis
Asthma COPD Schizophrenia
Autoimmune Disease Major Depressive Disorder Viral infections
Bacterial infections Pulmonary Hypertension Vaccines

Figure 1 from the OTraces’ breast cancer trial at the Gertsen Institute shows two important biomarkers used in the test, IL 6 and VEGF, sampled in women who have been diagnosed either with breast cancer (red) or who have been previously diagnosed as cancer-free (blue). This plot is typical of hundreds of others where non-cancer and cancer are poorly discriminated, and contaminated from unknowable information confounds the correlation of these concentrations to the disease transition.

Figure 2 shows the same biomarkers employed in the Gertsen validation trials using OTraces’ math-based methods, including patented noise-suppression and computational techniques. This is not a full reflection of OTraces’ diagnostic capacity as only two of the five biomarkers (and thus only a fraction of the five-dimensional grid) were utilized.

EARLY DETECTION

Figure 3 traces biomarker levels in the Gertsen Institute validation trials for breast cancer, tracking them from healthy (-1 on the horizontal axis) through Stage 3, showing two noteworthy developments: (i) how quickly immune response takes place well before tumor formation; and (ii) how dramatically biomarkers surge during transition from healthy to Stage 0 tumors and most reach their highest levels at this stage —- further evidence of the accuracy enhancement potential of the OTraces technology.

Figure 3, Action of Biomarkers by breast cancer stage

PROSTATE CANCER

Solving the High Level of Unnecessary Biopsies

OTraces has just completed a third party blind validation of its prostate cancer test at Johns Hopkins Medical Center, James Buchanan Brady Urological Institute. Figure 4 below shows the resulting receiver operator curve (ROC) for the test. The green curve shows the current Prostate Specific Antigen (PSA) test used for screening men for prostate cancer. The green “X” indicates the current medical indication.  At a PSA level of 4 nano-gram/milliliter or higher in a man’s serum, a biopsy is indicated. This level achieves a false negative rate of 10%, 90% sensitivity, but gives up a 75% false positive rate (25% specificity). This means that the test misses 10 out 100 men with prostate cancer and 75% of those who measure positive for the PSA test get biopsies, though they do not have cancer.

In contrast OTraces test will only miss 5% of men with cancer. The false positive rate the test is only 11%, a far better outcome for men.

By increasing the ROC curve cut point the false negative rate can be as low as 1% with the false positive rate increasing slightly to 17%. That is 99 out of 100 cancers are detected.  Also samples from 40 men with high PSA levels but without prostate cancer were tested.  One sample had a PSA level of 124 nano-grams/milliliter, 30 times the level for cut off, indicating a biopsy is needed.  All of these men properly tested as negative for prostate cancer using OTraces’ test. This indicates that the current very high rate of false positives with the PSA test is resolved. These men generally have a condition known as Benign Prostate Hyperplasia (BPH). This condition interferes with the PSA test. OTraces’ test is not effected.