Follow us on Twitter
twitter icon@FreshPatents

Browse patents:

Ip-10 based immunological monitoring / Hvidovre Hospital

Title: Ip-10 based immunological monitoring.
Abstract: The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of IP-10. The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other suitable biological samples. The methods of the present invention are useful in therapeutic and diagnostic protocols for human, livestock and veterinary and wild life applications, thus the invention further relates to a method for diagnosing an infection in a mammal. ...

Browse recent Hvidovre Hospital patents

USPTO Applicaton #: #20120015386
Inventors: Morten Ruhwald, Pernille Ravn, Jesper Eugen-olsen

The Patent Description & Claims data below is from USPTO Patent Application 20120015386, Ip-10 based immunological monitoring.


- Top of Page

This application is a divisional of and claims the benefit of priority to U.S. patent application Ser. No. 12/438,515, filed Oct. 14, 2009, which is a National Phase application of and claims the benefit of priority to International Application No. PCT/DK2007/000399, filed on Sep. 5, 2007, designating the United States of America and published in the English language, which is an International Application of and claims the benefit of priority to Danish Patent Application No. PA200601145, filed Sep. 5, 2006, and Danish Patent Application No. PA200700262, filed Feb. 20, 2007. The disclosures of the above-referenced applications are hereby expressly incorporated by reference in their entireties.


The present invention relates generally to an immunological assay and, more particularly, an assay for measuring cell-mediated immune reactivity (CMI). Even more particularly, the present invention provides an assay and a kit for measuring a cell-mediated response to an antigen using whole blood or other suitable biological samples. The assay is useful in therapeutic and diagnostic protocols for human, livestock and veterinary and wild life applications.

Measurement of cell-mediated immune responses is important for immune diagnosis of many infectious and autoimmune diseases, as a marker for immunocompetence, and for detection of T-cell responses to endogenous and exogenous antigens (i.e. infections and vaccines).

The present invention provides a method for measuring CMI in a mammal by incubating a sample from the mammal which comprises T-cells or other cells of the immune system with an antigen. Production of IP-10 is then detected. The presence or level of immune effecter is then indicative of the level of cell mediated responsiveness of the subject.


- Top of Page


The discovery of mycobacterium tuberculosis (MTB)-specific immunodominant antigens has led to a significant new avenue for the diagnosis of tuberculosis (TB). Early work had shown the potential to replace the Tuberculin Skin Test (TST) by a test that assayed the in vitro production of interferon gamma (IFN-γ) by T cells in response to defined MTB antigens. Around the same time, a major advance was the discovery of the highly immunogenic antigens, early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) and TB7.7 that improved specificity significantly. These antigens are encoded within the region of difference 1 (RD1) of the pathogen and are consequently absent from all Bacille Calmette Guerin (BCG) vaccine strains and most non-tuberculous mycobacteria (exceptions include Mycobacterium kansasii, Mycobacterium marinum Mycobacterium szulgai). IFN-γ responses to overlapping peptides of the RD1 encoded antigens ESAT-6, CFP-10, TB7.7 form the basis for the detection of MTB infection in two licensed and commercially available tests.

QuantiFERON-TB Gold (Cellestis Limited, Carnegie, Victoria, Australia), a whole blood enzyme-linked immunoassay (ELISA) has European CE mark approval and recently received American Food and Drug Administration (FDA) approval for the detection of both latent TB infection and disease.

T-SPOT.TB (Oxford Immunotec, Oxford, UK), an enzyme-linked immunospot assay (ELISPOT) that uses peripheral blood mononuclear cells has European CE mark approval and was approved for use in Canada in 2005. T-SPOT.TB only uses ESAT-6 and CFP10.

However, the limitations of the currently available tests are: 1) The sensitivity may be impaired in immunosuppressed individuals (such as HIV positive or patients receiving immunosupressing medication), 2) In some situations a relatively large volume of blood is necessary (3 ml per QuantiFERON test and 8 ml for the T-SPOT.TB), which may limit its use in infants and severely ill and anaemic children, 3) The tests do not discriminate between active, latent and recent infection 4) The tests have not been demonstrated to be able to predict who will progress from recent or latent TB to active TB.

Most of the test limitations are due to measurement of the effect parameter IFN-γ at very low levels, close to the limit of even the most sensitive method (in the QuantiFERON test down to 0.35 IU/ml (17.5 pg/ml) and in the T-SPOT.TB 5 spots/field). Decreasing cut-off to enhance sensitivity will eventually result in impaired specificity of the tests. A recent publication based on the QuantiFERON test has shown that that repeated testing of people with test results in the lower range of IFN-γ varies around the cut-off level which underlines the potential risk of false positive and false negative results of the QuantiFERON (QFT) test (Pai, M. et al).

To overcome the evident fragility of the tests, sensitivity could be improved by using additional M. tuberculosis specific antigens and this has been done in the third generation of the QuantiFERON tests (QFT), the QuantiFERON In tube test (QFT-IT) which now comprises an additional antigen named TB7.7(p4) and potentially sensitivity is improved, but it still depends on measurements at very low IFN-γ levels.

This approach has been tried by others, i.e. recently is was shown that the Monokine Induced by IFN-γ (MIG/CXCL9) was specifically expressed in vitro after stimulation with M. tuberculosis specific antigens (ESAT-6/CFP10) and PPD. The sensitivity of CXCL9, however was very low and lower than that of IFN-γ. Another smaller study based on intracellular cytokine cytometry in CD4+ T cells following ESAT-6 stimulation, tested if expression of IFN-γ, IL-2, IL-4, IL-10 or the activation marker CD40L could distinguish TB from non-TB disease. None of these markers were found to be comparable or superior to IFN-γ (Abramo C, et al) (Hughes, A. et al).

Yet no sensitive and specific markers to replace IFN-γ for diagnosis of TB infection have been identified in the presently published literature. Various have disclosed IP-10 in connection to infections, but not as a marker in the diagnosis of infection with a prior antigen stimulation.


The diagnosis of genital chlamydial infections evolved rapidly from the 1990s. Nucleic acid amplification tests (NAAT), such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), and the DNA strand displacement assay (SDA) now are the mainstays. The most commonly used and widely studied chlamydia NAATs in the US and many other industrialized countries are Aptima (Gen-Probe), Probe-Tec (Becton-Dickinson), and Amplicor (Roche). The Aptima Combo II assay tests simltaneously for C. trachomatis and Neisseria gonorrhoeae, the cause of gonorrhea. NAAT for chlamydia may be performed on swab specimens collected from the cervix (women) or urethra (men)

At present, the NAATs have regulatory approval only for testing urogenital specimens. The NAATs have largely replaced culture, the historic gold standard for chlamydia diagnosis, and the non-amplified probe tests, such as Pace II (Gen-Probe). The latter test is relatively insensitive, successfully detecting only 60-80% of infections in asymptomatic women, and occasionally giving falsely positive results. Culture remains useful in selected circumstances and is currently the only assay approved for testing non-genital specimens.

Chlamydia diagnosis is thus based on complicated and resource demanding technology such as PCR, not readily available in the developing world. A fast and easy technology would improve diagnostic measures for this important disease,

CA 2,478,138 discloses that elevated blood levels of the chemokine CXCL10 polypeptide are associated with respiratory illnesses (e.g. SARS, influenza and community-acquired pneumonia) and are useful in diagnosis of patients. Methods are provided for diagnosis and treatment of patients suffering from respiratory illnesses.

WO 05/091969 discloses markers for TSE (Transmissible Spongiform Encephalopaties) that are present prior to formation of detectable pathological prion protein are useful to detect this infection prior to clinical signs. IP-10 is just one of several markers disclose and this application does not disclose any antigen stimulation.

US2004-038201 discloses distinct gene expression programs activated in response to different pathogens in macrophages. IP-10 is again just one in many markers mentioned and this application does not disclose any antigen stimulation.

Annalisa Azzurri et al. discloses IFN-γ-inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium Tuberculosis infection. The article shows that IP-10 plasma level is spontaneously increased in patients with TB, again this reference does not disclose any antigen stimulation.

WO 03/063759 discloses a method of identifying a heat shock protein (Hsp) derived peptide useful for diagnosis or therapy. The effect of the compounds of this invention was tested on pheripheral blood monocytes by measuring the IP-10 level in response to subsequent stimulation with LPS. Direct stimulation with the test compounds without subsequent stimulation with LPS, did not give rise to an increase in the IP-10 level.

← Previous       Next →
Advertise on - Rates & Info

You can also Monitor Keywords and Search for tracking patents relating to this Ip-10 based immunological monitoring patent application.


Browse recent Hvidovre Hospital patents

Keyword Monitor How KEYWORD MONITOR works... a FREE service from FreshPatents
1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored.
3. Each week you receive an email with patent applications related to your keywords.  
Start now! - Receive info on patent apps like Ip-10 based immunological monitoring or other areas of interest.

Previous Patent Application:
Interleukin-1 alpha antibodies and methods of use
Next Patent Application:
Methods and kits for the differential diagnosis of alzheimer's disease versus frontotemporal dementia and for the diagnosis of frontotemporal dementia, comprising fas-l and ck 18 as biomarkers
Industry Class:
Chemistry: molecular biology and microbiology
Thank you for viewing the Ip-10 based immunological monitoring patent info.
- - -

Results in 0.21558 seconds

Other interesting categories:
Tyco , Unilever , 3m


Data source: patent applications published in the public domain by the United States Patent and Trademark Office (USPTO). Information published here is for research/educational purposes only. FreshPatents is not affiliated with the USPTO, assignee companies, inventors, law firms or other assignees. Patent applications, documents and images may contain trademarks of the respective companies/authors. FreshPatents is not responsible for the accuracy, validity or otherwise contents of these public document patent application filings. When possible a complete PDF is provided, however, in some cases the presented document/images is an abstract or sampling of the full patent application for display purposes. Terms/Support
Browse patents:

stats Patent Info
Application #
US 20120015386 A1
Publish Date
Document #
File Date
Other USPTO Classes
International Class

Follow us on Twitter
twitter icon@FreshPatents

Hvidovre Hospital

Browse recent Hvidovre Hospital patents

Chemistry: Molecular Biology And Microbiology   Measuring Or Testing Process Involving Enzymes Or Micro-organisms; Composition Or Test Strip Therefore; Processes Of Forming Such Composition Or Test Strip   Involving Antigen-antibody Binding, Specific Binding Protein Assay Or Specific Ligand-receptor Binding Assay   Assay In Which An Enzyme Present Is A Label   Heterogeneous Or Solid Phase Assay System (e.g., Elisa, Etc.)  

Browse patents:
20120119|20120015386|ip-10 based immunological monitoring|The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of IP-10. The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other suitable biological samples. |Hvidovre-Hospital