Products and Technologies

Caldera Health is now clinically testing and refining RNA biomarkers that are highly specific for defining and staging prostate cancers.

 

Caldera’s solution is being developed in two stages:

Product 1: Non-invasive diagnostic test
Product 2: Non-invasive prognostic test

 

Caldera Diagnostic Test

Caldera has developed a clinical laboratory test that measures the expression of a range of RNA biomarkers (Caldera’s patented gene signature) to accurately and reliably diagnose prostate cancer. Caldera’s recent clinical study (clinical study 2B) has proven that Caldera’s patented gene signature enables the accurate diagnosis of prostate cancer with 97% sensitivity and 97% specificity on prostate biopsy tissue by standard quantitative PCR.

The company is now in the process of transitioning the prostate tissue based diagnostic test to the non-invasive urine based test. To achieve this goal Caldera is currently developing a prostate cell capture device that will enable the specific capture of prostate cells from urine. RNA will then be isolated from these captured cells and used for analysis with the patented gene signature. Caldera expects this novel test will enable them to provide the same
level of accuracy as shown using the biopsy tissue, with a less invasive test than the PSA.

Importantly, Caldera believes that urine sampling of prostate cells will provide insight into prostate cancer, and be superior to the current biopsy procedure. This is because prostate tumours occur almost exclusively on the ducts that feed into the urethra. Therefore, the cancer cells feed into the urine stream. If there is more than one tumour, both will be evident in prostate cells captured from urine, thereby reducing the risk of a biopsy only picking up one cancer, when there are actually multiple cancers. When compared to PSA as a screening test, Caldera’s solution would provide a significant improvement for the defined population.

Caldera Prognostic Test

Caldera’s RNA based technology could be used to not only identify prostate cancer, but also to accurately differentiate between indolent and aggressive cancers. This breakthrough would enable Caldera to provide the world’s most accurate urine based prognostic assessment for prostate cancer. The Gleason score given upon histological examination of a prostate biopsy sample is the current gold standard for the diagnosis and prognosis of prostate cancer. Currently men with biopsy Gleason scores of 6, low PSA score and low digital rectal examination score, are deemed low risk. Such low risk men can go on active surveillance programs and receive no immediate treatment. However, there is considerable uncertainty associated with such a prognosis as discussed previously (section 3.1.3 above) particularly with d under-sampling of the prostate by the biopsy procedure. Thus, distinguishing between indolent and aggressive forms of cancers is still a major unmet need in prostate cancer.

As mentioned before, urine provides a better opportunity to sample the prostate, and that is even more the case for a prognostic test. In more than 90% of the cases, the larger tumour focus in the prostate is also the highest grade. The cells from a higher grade tumour are also not as tightly organised in cell layers as is the case with healthy tissue. Therefore, by sampling urine, the likelihood of sampling the highest grade tumour is much higher as it will be shedding more cells into the urine. These cells can then be captured with Caldera’s microfluidic device.

By combining Caldera’s expertise of developing gene signatures with Caldera’s non-invasive prostate cell capture device, Caldera believes it will be able to develop a prognostic gene signature to differentiate between indolent and aggressive tumours. The availability of both accurate diagnostic and prognostic tests for prostate cancer would make screening for prostate cancer a viable reality. It would enable very accurate diagnosis of the disease followed by stratification of those with the disease into indolent and aggressive cancers. This solution would reduce the main costs to the health system of diagnostic false positives and overtreatment.

 

 

Intellectual Property

Caldera uses Speckman Law Group in Seattle, United States, as its patent attorneys for filings to protect its technology in the United States and worldwide. Patent applications have been filed with the aim of offering wide protection and a significant field of use. The patents filed are listed under Intellectual property and those with claims awarded are indicated.

International filings under the Patent Cooperation Treaty (PCT) will be pursued within the normal timelines, for all major territories.

Caldera recognises that the biomarker combinations that form the basis of the diagnostic and prognostic assays, and the analytical processes being developed for diagnosic and prognosic use of gene signatures, represent Caldera’s most commercially valuable information. However, while we believe gene-based signatures are the most valuable diagnostic targets we have also been mindful that the examination of sequences will also indicate which proteins are encoded and secreted from cells. We have used this protein information to select sets of secreted proteins which might also form signatures of prostate cancer as these proteins are produced directly either by prostate cancer cells or by the immune system responding to the presence of cancer. These signatures do not identify the stage of the cancer but can be used to follow whether the cancer is still present after treatment of a patient irrespective of the therapeutic approach such as radiation or chemotherapy.

Based on this approach we developed tests based on the enzyme linked immune assay or ELISA platform, to detect these blood biomarkers. The ProscanZ™ test was designed as a multi-protein assay to improve the PSA test, and the Auditor™ test was designed to monitor blood of patients undergoing chemotherapy to follow the effectiveness of treatment. Patents have been filed and claims awarded and these blood tests are ready for further clinical validation.

Our patent estate thus comprises both gene-based signatures and protein-based signatures.

 

Atty docket no. & country Title Status
1002AU
Australia
Methods for determining personalised treatment compositions for prostate cancer and breast cancer PENDING
1009NP
USA
Methods and materials for the diagnosis of prostate cancer PENDING
Published Jan. 2, 2014 as US-2014-0005058-A1
1009AU
Australia
Targeted RNA-SEQ methods and materials for the diagnosis of prostate cancer PENDING
1009CA
Canada
Targeted RNA-SEQ methods and materials for the diagnosis of prostate cancer PENDING
1009CN
China
Targeted RNA-SEQ methods and materials for the diagnosis of prostate cancer PENDING
Published July 15, 2015 as CN 104781415A
1009EP
Europe
Targeted RNA-SEQ methods and materials for the diagnosis of prostate cancer PENDING
Claims accepted May 30, 2016 (grant expected late 2016, early 2017)
1009JP
Japan
Targeted RNA-SEQ methods and materials for the diagnosis of prostate cancer PENDING
1009 US6
USA
Gene expression profiling for the diagnosis of prostate cancer PENDING
Published November 24, 2016 as US-20160340745-A1
1010 US3
USA
Gene expression profiling for the diagnosis of prostate cancer PENDING
1010PCT Gene expression profiling for the diagnosis of prostate cancer PENDING
Application published September 11 2015 as WO 2015/133911 A1
1002NP
USA
Methods for determining personalised treatment compositions for prostate cancer and breast cancer ISSUED
Expires July 3, 2033
1003 US2
USA
Methods and materials for the diagnosis of prostate cancers
(Proscanz)
ISSUED
Expires Nov. 8, 2031
1003 US3
USA
Methods and materials for the diagnosis of prostate cancers
(Proscanz)
ISSUED
Expires Nov. 8, 2031
1003 US4
USA
Methods and materials for the diagnosis of prostate cancers
(Proscanz)
ISSUED
Expires Nov. 8, 2031
1005 US2
USA
Methods and materials for determining the ef cacy of prostate cancer therapies
(Auditor)
ISSUED
Expires Nov. 8, 2031
1009SG
Singapore
Targeted RNA-SEQ methods and materials for the diagnosis of prostate cancer ISSUED
Expires June 28, 2033
1009NZ
New Zealand
Targeted RNA-SEQ methods and materials for the diagnosis of prostate cancer ISSUED
Expires July, 2033