Molecular Staging

Molecular Staging Inc. Receives SBIR Grant From The National Cancer Institute

admin — Thu, 27 Aug 2009 08:57:19 +0000

NEW HAVEN, October 8, 2001 /– Molecular Staging Inc. (MSI) announced today that it received a Small Business Innovative Research (SBIR) grant to develop a method of detecting rare Human Papillomavirus (HPV) transformed cells using Rolling Circle Amplification Technology (RCATTM).

MSI received the SBIR grant in order to develop a method using RCAT to analyze individual cells within a cervical sample for the presence of HPV DNA. HPV analysis of individual cells could distinguish between transient benign infections and cells that are progressing to cancer. The goal is to help clarify ambiguous cytology results and better identify women who are at risk of developing cervical cancer.

Testing for the presence of HPV DNA in cervical samples is considered useful as an additional diagnostic tool when Pap smear screening of cervical samples produces ambiguous cytology results known as ASCUS.

HPV is the most common sexually transmitted virus and is believed to be a leading cause of cervical cancer. Potential outcomes of MSI’s work in this area include a reduction in the need for unnecessary biopsies as well as the earlier detection of cervical cancer.

The utility and benefits of RCAT in molecular tissue pathology are described more fully in American Journal of Pathology 2001 159(1): 63-69; Rolling Circle Amplification – A New Approach to Increase Sensitivity for Immunohistochemistry and Flow Cytometry.

MSI is a life science company developing a portfolio of technologies for detection and measurement of proteins and nucleic acids across a broad range of applications, including proteomics, genomics, pharmacogenomics and diagnostics. One of MSI’s core technologies is Rolling Circle Amplification Technology (RCATTM), an amplification process that has significant advantages in terms of sensitivity, multiplexing, dynamic range and scalability. MSI has exclusively licensed RCATTM from Yale University. Additional information about MSI can be found at www.molecularstaging.com.

Molecular Staging Inc. Awarded Two Additional Patents For Rolling Circle Amplification Technology

admin — Thu, 27 Aug 2009 08:56:22 +0000

NEW
HAVEN, September 27, 2001/– Molecular Staging Inc.
(MSI) announced today that it has been awarded two
additional patents for Rolling Circle Amplification
Technology (RCAT^TM).

This further expands the
intellectual property estate surrounding MSI’s Rolling
Circle Amplification Technology to a total of 11 issued
patents, including eight U.S. patents and three
international patents.

Rolling Circle
Amplification Technology detects and measures proteins as
well as nucleic acids with unprecedented sensitivity and
expanded multiplexing capabilities.

Patent number 6,287,824
for “Molecular cloning using rolling circle
amplification” was issued September 11, 2001. This application of Rolling Circle Amplification Technology
enables scientists to clone DNA without using biological
host organisms such as bacteria, viruses or yeast cells.
The outcome is cloned DNA with far greater coverage
than is possible with methods which need to use a
biological host. Patent
number 6,291,187 for “Polyprimed amplification of
nucleic acid sequences,” which was issued September 18,
2001, relates to further enhancements of the significant
sensitivity advantages enabled by Rolling Circle
Amplification Technology.

In other patent news,
the company was also awarded patent number 6,287,825,
“Methods for reducing the complexity of DNA
sequences,” on September 11, 2001.
This patent adds to the Company’s existing patent
portfolio on Allele Frequency Distortion (AFD), another of
MSI’s proprietary technologies.

MSI is a life science
company developing a portfolio of technologies for
detection and measurement of proteins and nucleic acids
across a broad range of applications, including proteomics,
genomics, pharmacogenomics and diagnostics.
One of MSI’s core technologies is Rolling Circle
Amplification Technology (RCAT^TM),
a proprietary amplification process that has significant
advantages in terms of sensitivity, multiplexing, dynamic
range and scalability.
Additional information about MSI can be found at www.molecularstaging.com

CONTACT:

Molecular
Staging, Inc.

Jennifer Joiner, 203/772-5000

Molecular Staging Inc granted a US Patent covering

admin — Thu, 27 Aug 2009 08:55:13 +0000

NEW HAVEN,
September 11, 2001 / –
Molecular Staging Inc. (MSI) announced today that it had been granted
a US Patent (6,280,949) covering Multiple Displacement Amplification
technology (MDA^TM) and it’s use in life science research
and diagnostic products. This is the second patent granted for Multiple Displacement
Amplification, invented by Dr. Paul Lizardi and colleagues at Yale
University and exclusively licensed by MSI.

Using MDA
technology, MSI has developed the first simple, fast and effective
whole genome amplification kit called MDA AmpliPhi^TM.

This one step
method facilitates genetic testing by increasing the amount of genomic
DNA in samples about one million fold.

Genetic
testing focuses on the analysis of genetic information for disease
pre-disposition, earlier detection of disease, identity testing such
as forensics and paternity testing and more effective drug discovery
and development.

Currently,
clinical genetic analyses require large blood and tissue samples in
order to access sufficient genomic DNA.
In some cases there is insufficient DNA to perform the desired
number of tests.

The MDA
AmpliPhi kit will facilitate genetic testing by enabling:

use of smaller routine blood or tissue samples (such as a
finger prick).

-
analysis on single cells from precious samples such as tissue
biopsies and cerebrospinal fluid.

-
an increase in the practice of archiving DNA for subsequent
testing or retesting.

“We are pleased to have secured a second patent on this important
technology” said Torben Christensen, President and CEO of MSI.

“Our MDA AmpliPhi kit effectively ensures that DNA samples
can now be considered as renewable resources, enabling researchers to
return to them again and again for new tests or confirmatory
diagnosis.”

MSI is a life science company developing a
portfolio of technologies for detection and measurement of proteins
and nucleic acids across a broad range of applications, including
proteomics, genomics, pharmacogenomics and diagnostics.
One of MSI’s core technologies is Rolling Circle
Amplification Technology (RCAT^TM), a proprietary
amplification process that has significant advantages in terms of
sensitivity, multiplexing, dynamic range and scalability.
Additional information about MSI can be found at www.molecularstaging.com.

CONTACT:

Molecular
Staging Inc.

Jennifer Joiner, (203)772-5000

Molecular Staging Inc. Awarded Six U.S. Patents and Three International Patents

admin — Thu, 27 Aug 2009 08:53:42 +0000

Patents Issued in US, Europe, and Australia further expands Molecular Staging Inc.’s Rolling Circle Amplification Technology Patent Portfolio

NEW HAVEN, September 5, 2001 / — Molecular Staging Inc. (MSI) announced today that it has received 6 US patents covering Rolling Circle Amplification Technology (RCATTM) and its use in life science research and diagnostic products. The United States Patent and Trademark Office (USPTO) awarded MSI patent numbers 06210884, 06183960, and 05854033 for “Rolling Circle Replication Reporter System”, and patent number 06143495 for “Unimolecular Segment Amplification & Sequencing” by RCAT.

These patents cover inventions by Dr. Paul Lizardi and colleagues at Yale University, which have been exclusively licensed by MSI. The USPTO also awarded MSI patent number 06235502 for “Methods for selectively isolating DNA using Rolling Circle Amplification” and patent number 06150112 for “Methods for identifying DNA sequences for use in comparison of DNA samples by their lack of polymorphism” by RCAT. One European patent, number 00862656, has been awarded to MSI, as have two Australian patents, numbered 704750 and 714486, covering RCAT.

“Patents provide important protection for our development and marketing partners as we expand the availability of life science research and diagnostic products incorporating RCAT globally,” said Torben Christensen, President and Chief Executive Officer of Molecular Staging Inc. “The intellectual property estate surrounding our Rolling Circle Amplification Technology is firmly established in the United States with six issued patents, and now extends internationally with three issued patents. Amersham Pharmacia Biotech, MSI’s life science research product partner is currently marketing two products, TempliPhiTM and SNiPerTM worldwide and we expect to expand to all major life science research and diagnostic markets in the future.”

In other patent news, the company was awarded patent number 06124120 by the USPTO for “Multiple Displacement Amplification” (MDA), the amplification technology underpinning AmpliPhiTM, the company’s novel method for whole genome amplification. MSI has licensed MDA to Amersham Pharmacia Biotech for life science research product development, and MSI is investigating the method as a potential future diagnostic product.

MSI is a life science company developing a portfolio of technologies for detection and measurement of proteins and nucleic acids across a broad range of applications, including proteomics, genomics, pharmacogenomics and diagnostics. One of MSI’s core technologies is Rolling Circle Amplification Technology (RCATTM), a proprietary amplification process that has significant advantages in terms of sensitivity, multiplexing, dynamic range and scalability. Additional information about MSI can be found at www.molecularstaging.com

Contact:

Jennifer Joiner
Tel: (203)772-5000
Fax: (203)776-5276
JenniferJ@MolecularStaging.com

Revolutionary Amplification Technology for Drug Discovery Goes Molecular

admin — Thu, 27 Aug 2009 08:52:02 +0000

A highly sensitive and practical alternative amplification method is being developed for use in drug discovery and genetic analysis. Through an agreement between Molecular Staging Inc. and Amersham Pharmacia Biotech, Amersham Pharmacia Biotech has gained exclusive rights to commercialise reagents for all research uses of the new and revolutionary amplification procedure.

This highly innovative technology, called Rolling Circle Amplification, can be used to detect and amplify, routinely and simply, single target molecules such as individual DNA and RNA molecules and indirectly to measure single protein molecules. The two businesses will work together to develop Rolling Circle Amplification for a wide range of applications designed to improve methods of drug discovery and genetic analysis. Molecular Staging will retain its rights to develop Rolling Circle Amplification for clinical diagnostic applications.

Rolling Circle Amplification, which was discovered in 1995 by Dr. Paul Lizardi in the laboratory of Professor David Ward at Yale University School of Medicine, enables target amplification to take place at a constant temperature. This eliminates the need for thermal cycling used in existing methods such as Polymerase Chain Reaction (PCR®). Apart from the remarkable sensitivity for DNA, RNA and protein detection, Rolling Circle Amplification has several other advantages over rival technologies, including increases in amplification efficiency, ability to pinpoint the location of molecules that have been amplified, and ease as well as accuracy of quantitation.

Several aspects of Rolling Circle Amplification make this technology especially valuable in the area of genomics and pharmacogenomics. For example, since the amplified product can remain attached to its template, Rolling Circle Amplification has considerable promise for applications where probe localisation is essential, such as microarrays or in situ hybridisation. In addition, because Rolling Circle Amplification can amplify very long DNA fragments, the technology can also be used in genetic mapping, for cloning in vitro and for preparation of DNA samples for sequencing.

“This exciting and highly innovative new technology will offer scientists a whole new level of detection capability when it comes to discovering and analysing potential new drugs,” said Mike Evans, Amersham Pharmacia Biotech’s vice-president of drug discovery. “Over the next few years, we intend to look at how Rolling Circle Amplification could provide our popular Microarray Technology Access Program with a significant improvement in sensitivity. Other applications could include the development of direct genomic sequencing and tangible improvements to immunoassay methods used in cell biology.”

According to Torben Christensen, Chief Executive Officer of Molecular Staging Inc.: “Molecular Staging is very fortunate to have gained access to Rolling Circle Amplification and other novel technologies developed by Yale scientists. We intend to use these procedures to develop a new generation of ultra-sensitive diagnostic tests. Rolling Circle Amplification provides us with the opportunity to simultaneously target both genes and their products, a significant advance in efforts to characterise the normal and abnormal behaviour of cells. An important aspect of our strategy to effectively exploit this technology is to make it broadly available to academic and industrial scientists alike. We are delighted that Amersham Pharmacia Biotech, a premier life sciences company, has recognised the enormous potential of Rolling Circle Amplification and has chosen to work with us to commercialise research reagents based on this technology.”

Amersham Pharmacia Biotech is a major international biotechniques company; it provides innovative and leading-edge technology solutions to the problems faced by researchers and engineers aiming to discover and produce new drugs and therapies, faster and more cost-effectively than ever before. The market leader in virtually all of its markets, the company’s novel systems are used to sequence DNA, uncover the function of genes and proteins, separate biomolecules, screen potential drugs and manufacture biopharmaceuticals.

Molecular Staging Inc. is a development-stage company focused on the development of novel diagnostic tests for the detection, staging and prognosis of disease. The following technologies have been licensed by the company: Rolling Circle Amplification, a procedure for detection, identification and quantitation of genes and the proteins they encode; MFISH (multiplexed fluorescent in situ analysis), a technique for facilitating chromosomal analysis; and AFD (allele frequency distortion), a method of identifying genes associated with disease and response of patients to therapy. Molecular Staging has facilities in Guilford, Connecticut and Allendale, New Jersey.

Genomics

admin — Thu, 27 Aug 2009 08:50:23 +0000

The company will also implement next-generation high-throughput technologies for drug target discovery and pharmacogenomics applications. RCAT™ adds significant value in the genomics area. It can be used to localize DNA sequences to particular sites on chromosomes, to amplify and isolate DNA sequences without cloning in vivo, and to identify single base-pair genetic differences between individuals. MSI is developing biochips based on RCAT that perform ultra-high throughput Single-Nucleotide Polymorphism (SNP) analysis (both genotyping and haplotyping) for identification of disease genes and drug response genes. Designs for RCAT SNP Chips include arraying thousands of distinct patient samples or tens of thousands of SNPs on a single biochip. RCAT is the only amplification method that can perform direct molecular haplotype analysis. MSI will also utilize its Allele Frequency Distortion technology to rapidly identify genes linked to disease.

RCAT™—Research Reagents

admin — Thu, 27 Aug 2009 08:49:26 +0000

MSI is developing an exciting new generation of research products based on RCAT. In collaboration with Amersham Pharmacia Biotech, we will be developing new methods and reagents for a wide range of research applications in the molecular biology laboratory. Application kits will provide everything needed by academic researchers and industrial scientists for RCAT including reagents, enzymes, control DNA templates, and instruction manuals that guide the researcher to success.

RCAT™—Biochips

admin — Thu, 27 Aug 2009 08:39:34 +0000

RCAT™ is the ideal amplification method for biochips. No other practical amplification method can recognize, amplify and detect target molecules directly on a solid surface. Currently, gene arrays place spots or “elements” in a high-density matrix on slides. Each spot contributes a single piece of genetic information to the analysis. RCAT, from a single element in such an array, can obtain information on multiple analytes simultaneously, exponentially increasing the level of information available. Since RCAT can amplify and detect signal from a solid-phase target simultaneously, it provides the only means for a homogeneous biochip assay.

Gene-Based Diagnostics

admin — Thu, 27 Aug 2009 08:38:34 +0000

Gene-Based Diagnostics Through RCAT™—Fast and Accurate
Gene-based diagnostic tests are the fastest growing segment of the in vitro diagnostic market. They use the tools of molecular biology to identify nucleotide substitutions, deletions, or insertions in genes of medical interest. These tests provide several advantages over immunodiagnostic tests. For example, an immunodiagnostic HIV test, the current industry standard, detects the presence of HIV antibodies in blood. A person’s immune system can take several weeks to produce antibodies after an infection so there can be a long window of time between infection and detection. Gene-based diagnostic tests can measure the RNA of the HIV virus directly, greatly reducing the time it takes to diagnose the disease.

Genetic materials can be measured directly by RCAT. The technology is ultra-sensitive and has the capability of detecting the presence of rare genetic mutations within otherwise normal tissues and cell populations. RCAT promises to greatly improve the performance of gene-based diagnostic testing and to facilitate the detection of a wide variety of infectious agents, cancerous cells, and genetic variances.

A robust DNA diagnostics method requires accurate single-base discrimination, low background, and, ultimately, complete automation. For some applications, amplification and/or quantitation of the target nucleic acid sequence is also required. Technology based on the polymerase chain reaction (PCR) uses repeated thermal denaturation of double-stranded DNA and extension by a thermostable DNA polymerase of two primers to achieve a maximum DNA amplification of one billion-fold in about an hour. This method requires rapid changes in sample temperature, for which specialized thermal cycling instruments are required. RCAT offers a simple and rapid alternative for gene-based diagnostics, which can yield an amplification of signal from a target nucleic acid of a trillion-fold in about an hour without the need for thermal cycling.

Flexible Testing Formats
RCAT is a highly flexible platform that can be performed in solution, in situ, and in microarrays and can be used for single-base discrimination as well as target quantitation. Furthermore, as RCAT is a continuous, isothermal process, specialized thermal-cycling equipment is not needed. Finally, in contrast to target amplification methods such as PCR, which make an enormous amount of target nucleic acid sequences where once there was little, RCAT is essentially a signal amplification system so contamination of new reactions with previously amplified target sequences is not a concern. Therefore, the need to carry out the different parts of the amplification process in separate areas of the laboratory, a significant barrier for using PCR in a clinical setting, is eliminated.

RCAT™—Immunodiagnostics

admin — Thu, 27 Aug 2009 08:36:56 +0000

Proteins and small molecules are commonly measured indirectly in diagnostics, through the use of antibodies (“immunodiagnostics”). Immunodiagnostic testing is the current “gold standard” for many diagnostic determinations. The application of RCAT™ in immunodiagnostics offers a significant opportunity for increasing the sensitivity of these tests.

More Sensitive Than Conventional Immunoassays
Protein detection by conventional immunoassay is relatively insensitive. Some recent approaches to molecular diagnostics use mRNA measurement as a surrogate for direct protein measurement, but changes in the concentration of an mRNA and its encoded protein are at times not proportional. In immuno-RCAT™, a unique DNA sequence tag is associated with a particular antibody using a covalent linkage. Antibodies bound to antigen are then measured by RCAT-based amplification of the associated DNA tag.

Each antibody-bound DNA tag is amplified and the resulting long DNA product remains bound to the antibody-antigen complex during the entire reaction. The amplified product can then be collapsed to a point source, permitting ultrasensitive localized detection capability (the technology has been demonstrated to detect single antibody-antigen complexes). Immuno-RCAT is readily adaptable to high-throughput surface array formats and simultaneous multi-analyte detection systems.