VIB Licensing and R&D opportunities

Sven Verheyen — Tue, 08 May 2012 12:29:50 GMT

Click here to leave your contact information and receive further information on the WIWAM

WIWAM is a robot developed by SMO and VIB for the high-throughput and reproducible phenotyping of Arabidopsis plants. The robot allows to automatically measure a variety of plant growth parameters at regular time intervals. There is a standard version of the WIWAM, but the robot can also be tailored to your specific needs.
WIWAM replaces a lot of manual handling, saving time and costs. Because the growth conditions are standardized and larger sets of plants can be screened, the robot also allows obtaining statistically more significant results. In addition, the image analysis provides information which are overlooked by the naked eye.

WIWAM is composed of a robotic arm, one or more stations for weighing, watering and imaging. Plants are grown individually in pots. At preset time intervals the robotic arm brings the pots to any of the stations. Each pot is transferred to the weighing station and the watering is based on the determined weight. This allows for accurate soil humidity levels throughout the whole experiment.

The phenotypic analysis is conducted through automatic image analysis. At regular time intervals, each plant is transferred to the imaging station to take a picture. All images are stored and can be used for image analysis. The sequential images allow constructing reliable growth curves over time.

WIWAM is chaperoned by image analysis software which can for instance be used to extract
information such as the compactness, perimeter and stockiness of each plant.

Tailor-made WIWAM
A standard WIWAM handling 230 plants is routinely used, but the set-up can be tailored to meet your specific needs.

Applications
WIWAM can for instance be used to study
tolerance and growth performance of mutants
under drought stress, salinity or heavy metals. It can also be used to study the effect of chemicals or to analyze the growth of plants under various light conditions, nutrient levels or soil types.

Click here to leave your contact information and receive further information on the WIWAM

Stijn Dhondt

+32 (0)9 331 39 53

stdho@psb.ugent.be

(+32) 9 244 66 11

VIB\baley — Mon, 11 Oct 2010 16:11:47 GMT

Summary

Decreased activity of an oxygen sensor in hypoxic conditions prompts endothelial vessel cells to readjust their shape and phenotype to restore oxygen supply and reduces metastasis events.

A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD (prolyl hydroxylase) proteins serve as oxygen sensors and may regulate oxygen delivery. VIB scientists under the supervision of Peter Carmeliet and Massimiliano Mazzone studied the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2+/_ mice. Haplodeficiency of PHD2 normalized vessel cells resulted in improved tumor perfusion and oxygenation and inhibited tumor cell invasion, intravasation, and metastasis.

Application

Inhibition of PHD2
- may offer alternative therapeutic opportunities for anticancer therapy
- is complementary to existing treatments such as chemotherapy

IP position

“PHD2 inhibition for blood vessel normalization, and uses thereof”
Patent application PCT/EP2010/050645
Priority Date: 20th January 2009

Licensing.Manager@vib.be

VIB Licensing Manager

VIB\jebie — Wed, 29 Sep 2010 12:54:24 GMT

The synergistic effect of combination therapy with a single dose of α-galactosylceramide followed b and sub-therapeutic levels of TNF can be exploited to safely combat cancer without the typical side effects of TNF treatment.

Summary of the Invention

Tumor necrosis factor (TNF) is cytotoxic to tumor cells but treatment with TNF is not possible due to its systemic side effects such as hypotension, fever and headache. α-Galactosylceramides have previously been shown to exhibit anti-tumor and immune-stimulating activity in pre-clinical animal models, but failed to display sufficient anti-tumor activity in clinical studies.

VIB researchers have found that α-galactosylceramide specifically activates natural killer cells and induces a selective increase of the anti-tumor effect of TNF. Low levels of TNF used are display synergy with α-galactosylceramide treatment and result in surprising tumor regression of various tumor cancer models. Furthermore, no significant cytotoxic effects on normal cells were observed in animals subjected to the combination treatment.

+32 9 244 66 11

licensingmanager@vib.be

VIB Licensing Manager

VIB\jebie — Wed, 29 Sep 2010 12:43:23 GMT

Plasmin agonists can be used to enhance HSC mobilization to treat leukopenia and neutropenia more effectively, whether resulting from chemotherapy or not.
Plasmin antagonists can be used to inhibit HSC mobilization to assist in treating malignant disorders such as leukemia, lymphoma and myeloma.

Summary of the Invention

Transplantation of hematopoietic stem cells (HSC) is common practice in the treatment of various hematological diseases, such as leucopenia or leukemia. The therapeutic success of mobilization of sufficient numbers of HSC’s to the peripheral blood with G-CSF prior to donation is limited due to refractoriness to G-CSF.
Well-known and broadly available plasmin agonists, such as microplasmin, tPA and uPA, enhance the recruitment of HSCs:

In vivo administration of microplasmin or tenecteplase in combination with G-CSF was up to 3x as efficient as administration of G-CSF alone
Peripheral blood collected from AMI patients before and after thrombolytic treatment with tPA, showed that the number of HSCs was 4-fold increased after that treatment

Conversely, plasmin antagonists can be used to inhibit recruitment of HSCs in leukemia, as was indirectly evidenced in vivo in mice deficient in plasminogen/plasmin.

+32 9 244 66 11

licensingmanager@vib.be

VIB Licensing Manager

VIB\jebie — Wed, 29 Sep 2010 10:36:56 GMT

Sip1 is a bio-marker for breast cancer stem cells, which are the cells responsible for tumor extension and metastasis. Sip1 can also be used therapeutically to inactivate breast cancer stem cells and as such treat breast cancer morbidity and mortality.

Summary of the Invention

IP1 (Smad-interaction protein 1), a multi-zinc finger transcriptional repressor, has been demonstrated to downregulate E-cadherin expression. This loss of E-cadherin results in reduced aggregation and acquisition of invasive properties and plays an important role in epithelial-to-mesenchymal transition (EMT) in cancers.

VIB scientists found that knocking down SIP1 expression in breast cancer cells resulted in

reduced mesenchymal morphology,
very reduced ability to migrate and
much stronger adhesion.

Furthermore, when injected in mammary fat pads of mice, tumor cells with knocked down SIP1 expression resulted halting tumor growth compared to the fast growing tumors of mice injected with control breast cancer stem cells. When injected in the tail vein of mice, cancer cells with knocked down SIP1 expression could home to and colonise the lungs in only 20 % of the mice, compared to 70 % with mice injected with control cancer cells. In xenographed human tumors and in human breast cancers the expression of SIP1 is limited to cancer stem cells, indicating its selectiveness.

Application

Biomarker for breast cancer stem cells which can be used for tumor classification
Therapeutic target in breast cancer stem cells, which are at the basis of morbidity and mortality in breast cancer, amenable to antibody, peptide or RNAi inhibition

+32 9 244 66 11

licensingmanager@vib.be

VIB Licensing Manager

VIB\jebie — Wed, 29 Sep 2010 10:12:53 GMT

MALT1 is a novel drug target in multiple disease areas:

auto-immune disease (MS, Arthritis, lupus)
allergic disease (asthma)
lymphoma
immunosuppression for organ transplantation

Summary of the invention

MALT1 is a paracaspase protease fine-tuning the regulation of the NFκB gene induction. MALT1 mediates cleavage of the NFκB inhibitor A20, which is a (de)ubiquitination protein.
VIB scientists have identified a peptide inhibitor of MALT1 that inhibits NFκB-induced pro-inflammatory gene-expression.

Application

MALT-Paracaspase can be used as a screening method to identify novel MALT1 inhibitors

+32 9 244 66 11

licensingmanager@vib.be

VIB Licensing Managers

VIB\jebie — Wed, 29 Sep 2010 09:55:48 GMT

The duplication of MYB, a gene encoding for a transcription factor, can be used in the molecular phenotyping of T-cell acute lymphoblastic leukemia (T-ALL) patients. The knock-down of MYB expression or the biochemical inhibition of MYB leads to T-ALL cell line differentiation and can be exploited therapeutically.

Summary of the invention

T-ALL is an aggressive T-cell malignancy that is most common in children and adolescents. VIB scientists identified a duplication of the MYB oncogene in a subset of T-ALL patients. This duplication is associated with a 3-fold increase in MYB expression. MYB overexpression is known to impair hematopoetic differentiation.

Moreover inhibition of MYB in combination with the inhibition of NOTCH1 signaling through a γ-secretase inhibitor results in a strong synergistic effect on proliferation and viability of malignant cells.

Application

MYB duplication can be used for patient stratification in T-ALL in the context of therapy or selection of clinical trial subjects
Inhibitory compounds against MYB promise to allow therapeutic intervention in T-ALL
A synergistic effect between MYB inhibition and NOTCH1 inhibition can be therapeutically exploited through lower dosing regimes

+32 9 244 66 11

licensingmanager@vib.be

Molecular-diagnosis-of-T-ALL-leukemia-predicts-therapeutic-success

VIB\jebie — Wed, 29 Sep 2010 09:32:47 GMT

Molecular diagnosis using FISH or a PCR-based assay detecting the NUP214-ABL1 fusion can be used to predict the success of the tyrosine kinase inhibitor pathway

Summary of the Invention

T-cell acute lymphoblastic leukemia (T-ALL) accounts for ~15% of newly diagnosed cases of childhood acute lymphoblastic leukemia. Children with T-ALL generally have a poorer prognosis than those with B-ALL. In T-ALL, transcription factors are known to deregulated by chromosomal rearrangements, but mutations in tyrosine kinases have only rarely identified.

VIB researchers have identified extrachromosomal or episomal amplification of ABL1 in T-ALL, which is not normally detectable using conventional cytogenetics. This episomal amplification results of a fusion between NUP214 and ABL1. NUP214-ABL1 results in the expression of a constitutively phosphorylated tyrosine kinase, which is sensitive to the tyrosine kinase inhibitor imatinib.

Therefore, NUP214-ABL1 expression defines a new subgroup that can benefit from imatinib treatment.

Application

Molecular diagnosis of the NUP214-ABL1 expression can be used for patient stratification for therapeutic purposes or selection of clinical trial subjects

VIB Licensing Manager

+32 9 244 66 11

licensingmanager@vib.be

VIB Licensing Manager

VIB\jebie — Wed, 29 Sep 2010 08:15:30 GMT

The presence of PRGN mutations or decreased PRGN mRNA or protein levels can be used as a diagnostic method for dementia or disease risk for dementia.
In addition, increasing the levels of PRGN in patients at risk for dementia promises to be therapeutic.

Summary of the invention

A study identified dozens of mutations in the progranulin gene (PRGN) which are linked to dementia in patients suffering from either frontotemporal dementia (FTD) or Alzheimer´s disease.

Progranulin is a growth factor involved in multiple physiological and pathological processes, including tumorigenesis, and likely mediates neuronal survival. Null-mutations in PRGN, including insertions, deletions, and substitutions, in the coding and non-coding regions of PRGN reduce Progranulin levels through different mechanisms including the formation of premature stop-codons, splicing errors, frameshifts and misfolding.

PRGN haploinsufficiency was shown to lead to neurodegeneration and ubiquitin-immunoreactive neuronal inclusions, characteristic of FTDU-17.

Applications

Increasing the level of PRGN can be used therapeutically through

gene therapy,
administration of PRGN polypeptide or
medication with an agent, such as a peroxisome proliferator-activated receptor (PRAR) agonist in combination with non-steroid anti-inflammatory drug.

+32 9 244 66 11

licensingmanager@vib.be

VIB Licensing Manager

VIB\jebie — Wed, 29 Sep 2010 07:31:04 GMT

Detection of the described mutation in the promoter region of APP can be used in to diagnose familial Alzheimer's disease. In addition, it provides a novel method for the construction of transgenic cell lines or model organisms with increased APP production which can model Alzheimer´s disease.

Summary of the invention

Alzheimer´s disease (AD) can be caused by mutations in the amyloid precursor protein (APP) or the presenilins which frequently increase the production of amyloid-β₄₂ peptide, thereby fostering its deposition in plaques.

Overproduction of APP due to a duplication of the APP-gene or due to mutations in the regulatory sequences in the APP promoter was shown to lead to AD via increased production of Aβ.

Several point mutations in the proximal promoter region of the APP were identified only in AD patients (-118C>A, -369C>G, -479C>T, -534G>A). These mutations result in increased expression of APP due to differential affinity of nuclear factors for these mutated sites.

+32 9 244 66 11

licensingmanager@vib.be

VIB Licensing and R&D opportunities

(+32) 9 244 66 11

Summary​

Application

IP position

VIB Licensing Manager

VIB Licensing Manager

VIB Licensing Manager

VIB Licensing Manager

VIB Licensing Managers

Molecular-diagnosis-of-T-ALL-leukemia-predicts-therapeutic-success

VIB Licensing Manager

VIB Licensing Manager

Summary