Sciclips's Blog

Cell Based Reporter Assays vs. Animal Studies in Drug Discovery- Potential Limitations, Risks and Liabilities

sciclips — Mon, 16 Jan 2012 03:35:50 +0000

This blog critically analyzes the potential scientific limitations, risks and liabilities of cell based reporter assays, including non-natural protein based reporter assays (e.g. circularly permuted firefly luciferase or GFP reporter assays) and stem cell based assays, in drug discovery and development. Scientific arguments have been put forward to suggest that current format of cell based reporter assays may not be ideal for replacing animal studies. This blog also analyzes the potential negative impact of patents and intellectual property (IP) rights in fostering innovations in cell based assays. Finally, this blog warrants imposing accountability, tighter regulations and demanding higher standards in cell based assays that are used in drug discovery and development.

There is a notion that cell based assays can be an attractive alternative for animal based drug discovery assays, an argument based on the fact that human cell based assays are more relevant to humans rather than the animal model studies. Convenient assay readout format, including GMP method development, and low cost are the other factors that favor cell based assays over animal based studies. However, cell based assays, including 3-D cell culture assays, do not replicate the complex nature of cellular organization, cell-to-cell communication, coordinated cell signaling pathways, tumor microenvironment etc., like in animal model studies. Even then, cell based assays (especially primary cell based assays) provide valuable information that are very critical for drug discovery and development. On the contrary, several reporter based or genetically modified (GM) cell based assays that are marketed for drug discovery may not only a scientifically non-viable alternative for animal studies but also come with several limitations and potential liabilities, possibly in animal studies.

Cell based reporter assays may not be considered as an alternative to animal model studies?

Cell based reporter assays that are marketed for drug discovery assays are often projected as an alternative to animal based studies, without well-proven scientific basis to support these claims. The assay principle and the methods appear to be scientifically appealing if it is not subjected to in-depth or comprehensive scientific analysis, which is often ignored or not considered as a factor that may have long-term consequences in any drug discovery/development studies. There are several key issues with cell based reporter assays, some of which we have already addressed in earlier blogs. Genetically modified cells used in cell based assays can be different from parental cells, primarily due to genetic and physiological alterations resulted from long-term cell culture conditions and forced expression of reporter gene/proteins, often with human or non-human protein fusion partners. Long term cultures can induce mutations and forced expression of reporter genes/proteins can alter the cell signaling pathways, which may result in false positive/negative results. The genetic and epigenetic impact of random integration of reporter genes, can vary based on the integration site or copy number of integrated reporter genes or heterogeneity (both genetic and epigenetic) of such cells, are often not thoroughly studied or understood in cell based reporter assays. Random integration of reporter genes, both in coding and non-coding regions, can alter or silence certain genes or affect genetic regulatory mechanism, and the resulting cell lines may not be uniform for such genetic or epigenetic changes. In addition, differential expression of microRNA (miRNA) or variations in metabolite pathways, which play significant role in cellular regulation and signaling process, are not well studied in genetically modified cell lines with reporter genes. The above-mentioned genetic and non-genetic factors, some of which have been discovered in recent years, can be major challenges in developing cell based reporter assays. However, if cell based reporter assays are used in drug discovery studies without understanding these critical factors successful drug discovery/development process can be scientifically challenging, cost-prohibitive and time-consuming.

It can be even worse if cell based reporter assays are based on non-natural reporter proteins such as circularly permuted firefly luciferase or GFP based reporter protein. Circular permutation is considered to be an elusive molecular evolution process that involves gene duplication or exon shuffling and circularly permuted proteins may not be naturally present in mammalian cells. Very few naturally occurring circularly permuted proteins have been reported in bacteria and in plants (e.g. chloroplast associated bacterial homolog protein). Based on these scientific evidences, the reliability of circularly permuted firefly luciferase based reporter assays needs to be carefully analyzed since in vivo expression of circularly permuted proteins in cells may lead to significant changes in genetic regulatory mechanism (e.g. translational machinery), cellular metabolism, cellular physiology and cell signaling pathways. The question is, can we rely on non-natural reporter protein based cell based assays in drug discovery or development? Though the drugs that are initially selected using such cell based reporter assays do not reach up to human clinical trials, testing such experimental drugs in animals may pose liabilities. The obvious reason is, these drugs are screened and selected using non-natural reporter protein expressing cells, which may be abnormal cells. Since the natural genetic machinery of normal cells may not tolerate such non-natural proteins, forced expression of these proteins in normal cells may result in genetic or epigenetic abnormalities, which may lead to anomalous cell signaling or metabolic pathways. Extensive scientific validation of these cells or cell lines is required, prior to any animal testing, to address the biological relevance of the assay and biological or genetic or toxicity equivalence to normal cells. We do not disregard the fact that there are several reports on the use for circularly permuted proteins for improving enzyme stability or protease resistance etc. But, these proteins were artificially synthesized, expressed and purified using recombinant methods for functional or structural studies. On the contrary, in drug discovery/development applications cell based circularly permuted reporter proteins are being used for analyzing and predicting critical drug-induced outcomes using in vivo studies.

The truth is that current cell based reporter assays did not adapt or evolve in parallel with recent scientific discoveries, which may have significant impact on cell-based assay outcomes. Integrated multidisciplinary considerations are needed to develop efficient cell based assays. There are several technologies currently available for analyzing the genetic, proteomic, epigenetic, miRNA or metabolite changes in genetically modified reporter cell lines. At least, some of these analyses need to be done before we use cell based reporter assays in drug discovery/development studies. In contrast, emerging technologies like non-invasive imaging of metabolic changes in tissues or whole animals using Raman spectroscopy look very promising in drug discovery research. Innovations in similar non-invasive tissue or animal/human based technologies, which do not involve genetic modification of cells or tissues, may open up new avenues in developing alternative technologies to cell based reporter assays.

The utility of stem cell based drug discovery assays can be misleading?

Stem cells are often projected as an alternative cell based system for drug toxicity, cardiotoxicitiy etc. We have addressed the limitations of stem cell based assays in drug discovery in our earlier blogs. Here we would like to address whether currently used or proposed stem cell based assays can be an alternative to animal model studies. Our answer would be no. Like any genetically modified cells, stem cells are also prone to genetic, epigenetic and physiological changes. Without understanding the physiological and genetic/epigenetic consequences of stem cell based assays, including stem cell based reporter assays, any testing of drugs selected using such assays may have adverse consequences in animal studies. However, stem cells can be a potential alternative to animal studies, provided that stem cell based drug discovery assays are developed with sound scientific principles where critical and fundamental questions are addressed and solved; with careful consideration of long-term impact. It should also be noted that normal cell based assays may not be an ideal tool for predicting adverse drug reactions (ADR), which may require animal studies. However, stem cell based assays coupled with cell/tissue-specific differentiation may offer unique tools for predicting ADR, which can be characterized though genetic, epigenetic, proteomic or metabolomic analysis. In order to achieve these goals, the scientific knowledge generated from basic discoveries needs to be tested and validated scientifically for developing technically competent and commercially viable drug discovery tools that can be used for developing safer and cost-effective drugs. Any efforts in developing “commercially fast-track” stem cell based assays based on speculative or nascent assumptions, projected from indirect experimental results, will be scientifically misleading and commercially unsuccessful in the long-term.

Intellectual property (IP) rights can be a road block to innovations in cell based assays that can replace animal studies?

The patent scenario in cell based assays can be a real road block to further innovations in this area. The major limitations are the availability of cell based assays to the customers because of the intellectual property (IP) rights, a significant factor that affects the development of improved or superior products. Exceptions are cross licensing, which itself is a very complicated process heavily associated with brand name, profitability and market share. Customers are often left with limited choices of using certain assays, which are patented with scientifically questionable broader claims and applications. Often, “Claims” and “Experiments results/observations” in patents can be scientifically unrelated. With respect to product end-user license, the use of reagents is also restricted to specific cell based assay products, even though similar superior reagents may be available in the market. The IP rights may also lead to extended licensing agreement that can generate royalty from drugs discovered though certain cell based assays, including stem cell based assays. The question is, if a drug fails due to adverse drug reactions (ADR) in patients, whether the manufactures of cell based reporter assays are also responsible for the liabilities similar to the drug manufacturer? Irrespective of these IP related issues, cell based assays that are marketed without considering the scientific merits and potential long-term risks and liabilities in animal or human studies may have to be cautiously used in drug discovery/development. Also, the use of certain cell based reporter assays, like the non-natural reporter proteins, in publically funded drug discovery projects needs to be reevaluated because the scientific validity of these assays are not clearly demonstrated. Such accountability may lead to the generation of patents with scientifically valid claims that are established through strong scientific and experimental design and analysis. This approach may ultimately help in developing innovative cell based drug discovery/development assay products or similar technologies that can replace, at least part, extensive animal studies.

What are the solutions?

The primary goal of this blog is not to find or suggest a solution, rather to address the issues that are not often discussed; and to create scientific awareness and facilitate scientific consensus to develop innovative cell based assay tools. We believe imposing accountability, tighter regulations and demanding higher standards in cell based assays may lead to the discovery of innovative cell based tools that can ultimately replace animal model studies, at least in part.

Sciclips Consultancy Services

sciclips — Sun, 15 Jan 2012 06:37:17 +0000

Fostering innovation through scientific intelligence

Sciclips consultancy service team is comprised of highly qualified and experienced scientists who have several years of research experience in academic and industrial laboratories. We offer following custom services at competitive price:

Scientific and technical areas covered: Drug discovery, Stem cells, Genomics, Proteomics, Biomarkers, Clinical diagnostics, Companion diagnostics, Molecular diagnostics, Personalized medicine (theranostics), Plant and agricultural biotechnology

1. Patent search: Custom intellectual property (IP) analysis; Comprehensive patent database search and evaluation
2. Custom data analysis and data mining: From patents, research articles, meeting abstracts and web based information. Custom meta analysis.
3. Competitive intelligence analysis: Comprehensive analysis of competitive technologies and products; Technology trend prediction; Identification of technology licensing opportunities; Acquisition target identification; Identification of collaborative technology development opportunities.
4. Technology development: Identification of potential development opportunities in drug discovery assay development, cell based assay development, recombinant protein expression (in vitro and in vivo) and mass spectrometry/proteomics reagents and tools; Product development strategy.
5. Diagnostics and Theranostics technology development: Diagnostic assay development; Diagnostic target identification (molecular or protein or miRNA or metabolomic biomarkers); Prognostic and drug efficacy biomarkers; Theranostics tools, biomarkers and therapeutic drug targets; Identification of emerging technologies and methods.
6. Custom database development
7. Customized bioinformatics tools: Offered through our partnering companies.
8. Proteomics and Drug discovery services (laboratory based): Offered through our partnering companies.

For custom order please contact us at: contact@sciclips.com

Key examples of our capabilities:

1. Therapeutic drug targets/Biomarkers: http://www.sciclips.com/sciclips/drug-targets-all.do
2. Diagnostic and Prognostic Biomarkers: http://www.sciclips.com/sciclips/diagnostic-biomarker-prognostic-biomarker-db.do
3. Technology blogs: http://www.sciclips.com/sciclips/blogMain.do

Cancer Theranostics – Potential Applications of Cancer Biomarker Database

sciclips — Mon, 09 Jan 2012 01:11:34 +0000

Availability of a comprehensive cancer biomarker database may opens up scientific and technical opportunities in developing innovative oncologic theranostics (Rx/Dx), a diagnostic therapy process that leads to the development of successful personalized medicine strategies in cancer treatment.

With the growing trend towards the advancement of personalized medicine concept, there is a need to develop strategies and tools that can be used for individualized diagnosis and treatment. Theranostics based tools, a combination of diagnostics and therapeutics approach, offer promising agents that can be used for the improved diagnosis and treatment of various diseases. In oncologic theranostics, developing innovative personalized cancer treatment rely on the identification of novel cancer biomarkers and diagnostic assays to identify patient’s response to a particular drug, for optimizing personalized drug treatment regimen (drug dose, drug treatment schedule etc) and for monitoring the efficacy of treatment (disease stage, tumor progression, tumor recurrence etc). A best example for this will be the approval of Genentech’s Herceptin® with DakoCytomation’s HercepTest® for breast cancer theranostics. Future development of cancer theranostic tools depends on the discovery and validation of existing or novel cancer biomarkers. A database that contains comprehensive information on discovery phase or clinically validated biomarkers, along with therapeutic drug target information, can be a powerful tool in developing novel theranostic assays as well as for the discovery of new drug targets based on theranostics (Fig.1). A combination of therapeutic drug target and biomarker pathway analysis, in particular companion diagnostics pathways, can pave the path towards developing innovative strategies in cancer theranostics.

Fig. 1: Theranostics and cancer biomarker database in personalized medicine

Biomarkers that have potential applications in cancer theranostics can be broadly classified into:

1. Imaging biomarkers: Drug molecules labeled with imaging tags (e.g. NRI, MRI etc.) and antigen-directed imaging drugs (e.g. radiolabeled antibody drugs) are the very good examples. In this case, a single molecule can be used as a diagnostic and therapeutic agent, EGFR, VEGF and TAG-72 are very good examples where antibodies against these drug targets tagged with imaging markers can be used in theranostics. Imaging biomarkers can also be very useful in targeted surgical treatment of cancer. Labeled antibody based detection of phosphorylated or dephosphorylated will be an attractive theranostics tool in phosphorylation-dependent targeted cancer therapy and diagnosis. Epigenetic biomarkers are another attractive target for developing cancer theranostics. Applications of additional tools such as nanoparticles and gold particles have been demonstrated in theranostics.

2. Diagnostic/prognostic protein biomarkers: Immunohisotchemistry and immunoassays (e.g. ELISA) can be used in theranostic applications. Identification of diagnostic biomarkers that can be used as therapeutic drug targets will have significant impact in theranostics. Development of protein biomarker-directed antibodies (labeled) or small molecules or aptamers can be a potential theranostics tool.

3. Molecular diagnostic markers (genes/SNPs/miRNA/epigenetic): PCR, qPCR, DNA sequencing (including next generation sequencing), and microarray based technologies can be used as theranostics tools. Single step diagnostic therapy, like labeled antibody drug based theraostics, may be a challenging task with molecular diagnostic biomarkers, possible exceptions are siRNA or miRNA based cancer therapies.

4. Cell based biomarkers: Cancer stem cells, circulating tumor cells (CTCs) and tumor-infiltrating immune cells (CD68-positive macrophages/T-cells etc.) can be used in cancer theranostics. The diagnostic and therapeutic significance of these cell based biomarkers have been demonstrated in several published studies.

5. Drug efficacy/response/predictive biomarkers: Biomarkers include proteins, gene, miRNA, SNPs, metabolites etc., which can be successfully used for the development of companion diagnostic assays. These biomarkers can also become a therapeutic drug target for further discovery of theranostics based therapeutic drug targets.

6. Combination therapy response biomarkers: Combination therapy approaches have been demonstrated as an efficient treatment method for various cancers. However, the availability of companion therapy response biomarkers are limited (some of these biomarkers are included in our cancer biomarker database). Wide adoption of combination therapy as a method for cancer treatment may warrants a need for the discovery and validation of new biomarkers associated with combination therapy.

Identification of new biomarkers and availability of large number biomarkers may result in the development of theranostics for most of the cancer types. A cancer biomarker database that contains comprehensive and cumulative information on experimental and clinically validated biomarkers, especially companion diagnostic biomarkers and therapeutically relevant biomarkers, may opens up scientific and technical opportunities in developing innovative oncologic theranostics (Rx/Dx) tools.

Sciclips cancer biomarker database contains more than 8700 cancer biomarkers, which are classified into 1) diagnostic biomarkers 2) disease predictive/risk assessment biomarkers 3) drug efficacy/response biomarkers 4) prognostic biomarkers and 5) cancer companion diagnostics biomarker pathway. The biological and molecular functions, biological process associated, chromosomal location, SNPs and protein-protein interaction networks of each biomarker are listed in this database. This comprehensive information will be useful for the validation of existing biomarkers and for the identification and validation of new biomarkers for cancer theranostics. Please follow the link to see the details of cancer biomarker database: http://www.sciclips.com/sciclips/diagnostic-prognostic-cancer-biomarker-main.do

Cancer Biomarker Database

sciclips — Tue, 06 Dec 2011 01:13:42 +0000

A comprehensive oncology biomarker database with cancer companion diagnostic biomarker pathway maps (theranostic biomarkers)

With the growing trend of personalized healthcare concept and advancement in biomarker research, there is a need for a comprehensive cancer biomarker database that can help in finding new diagnostic, prognostic and companion diagnostic biomarkers. Future success in developing innovative personalized cancer drugs lies in adopting new differential diagnostic procedures along with companion biomarker assays to identify the most appropriate cancer patient, tumor type and disease state.

Sciclips has launched a comprehensive diagnostic and prognostic cancer biomarker database with cancer companion diagnostics biomarker pathway maps. This database contains more than 8500 discovery phase or preclinical or clinical cancer biomarkers that were identified or validated using patient derived samples. This database covers a wide variety of biomarkers such as blood cancer biomarkers (peripheral blood, plasma, serum etc), tumor biomarkers, urinary cancer biomarkers, fecal cancer biomarkers, saliva cancer biomarkers, breath cancer biomarkers etc.

Our cancer biomarker database contains biomarkers for more than 100 types of cancer. For each cancer type, the biomarkers are classified into 1) diagnostic biomarkers: for the diagnostics application, 2) disease predictive/risk assessment biomarkers: for predicting the risk or genetic susceptibility in developing cancer, 3) drug efficacy/response biomarkers: biomarkers for studying the efficacy of anti-cancer drug treatments, including predictive biomarkers and 4) prognostic biomarkers: for determining the clinical outcome in cancer patients. The types of cancer biomarkers include protein biomarkers, miRNA biomarkers, SNP biomarkers, Gene expression biomarkers, epigenetic biomarkers and metabolomic biomarkers. Patient/sample details, experimental results/observations, biological and molecular functional analysis, biological process analysis, protein-protein interaction networks of each biomarker are listed in this database.This database will be a useful tool for the discovery of new cancer biomarkers as well as clinical validation of biomarkers.

The cancer companion diagnostics biomarker pathway database is an innovative database of protein-protein interactions networks of cancer drug efficacy/response/predictive biomarkers. A model pathway from the database is shown in Fig.1. This pathway maps can be useful in identifying new anti-cancer drug predictive and response biomarkers, including theranostic biomarkers, for the discovery of new drug targets with improved efficacy or targeted therapy to overcome side effects, patient stratification, developing personalized strategies for monitoring cancer progression, treatment, diagnosis and prognosis.

Please follow this link to view the database (preview is available): Details: http://www.sciclips.com/sciclips/diagnostic-prognostic-cancer-biomarker-main.do

Fig.1: Companion diagnostics pathway analysis of biomarkers associated with doxorubicin cardiotoxicity in childhood acute lymphoblastic leukemia (ALL)- please see the database for more details.

Recent Biomarker and Companion Diagnostics Patents

sciclips — Wed, 19 Oct 2011 17:07:56 +0000

Highlights of recent US patents (issued) and US/WO(PCT) patent applications:

1. AIMP1 protein as a novel biomarker for the diagnosis of rheumatoid arthritis or osteoarthritis
2. Cerebrospinal fluid (CSF) biomarkers for the diagnosis of cancer, rheumatoid arthritis, asthma, diabetes, and obesity
3. Biomarkers for diagnosing auto-immune chronic urticaria
4. MicroRNA (miRNA) biomarkers for determining the risk level of a neuroblastoma patient
5. Biomarkers for predicting post-lung transplantation complications
6. Biomarkers for the prognosis of the progression of septic syndrome in a patient
7. Biomarkers for determining a patient’s susceptibility of contracting a nosocomial infection
8. Novel biomarkers for the diagnosis of diabetes
9. Biomarker associated with increased risk in developing a cardiovascular disease, or an autoimmune disease or inflammatory diseases
10. Autoantigen biomarkers for the diagnosis of type 1 diabetes
11. ATF2 and SH3GL2 as autoantigen biomarkers of systemic lupus erythematosus (SLE)
12. Biomarkers for predicting the clinical response to antidepressants
13. HLA complexes for predicting drug induced adverse reactions
14. Biomarkers for predicting the response of a patient with ankylosing spondylitis to anti-TNFalpha therapy
15. Gene expression markers for the diagnosis and prognosis of preeclampsia
16. Point-of-care (POC) devices for stress response profiling in saliva
17. CXCL3 as a biomarker of colon cancer
18. Serum biomarkers of differentiating chronic obstruction pulmonary disease (COPD) and lung cancer patients
19. Sirtuin assay

Details: http://www.sciclips.com/sciclips/biomarker-news.do

Related blogs:

Highlights of Recent Biomarker and Molecular Diagnostics Patents

sciclips — Tue, 11 Oct 2011 14:36:49 +0000

Highlights of recent US patents (issued) and US/WO(PCT) patent applications:

1. Agouti-related protein as a biomarker for schizophrenia
2. MMP-3 as a biomarker for major depressive disorder
3. ABCG2 and CD44 as colon cancer stem cell markers
4. Serum amyloid A (SAA) as a biomarker for the diagnosis of myocardial infarction
5. Molecular method for the detection of Candida albicans
6. Eotaxin-3 as a biomarker for eosinophilic esophagitis
7. Biomarkers of oxidative stress
8. SNP markers for determining the prognosis of a clinical response to antidepressants
9. Cell based assay for the diagnosing interstitial cystitis
10. IL-17 as a biomarker for predicting the efficacy of IFN-beta therapy in multiple sclerosis patients
11. Hypoxia-inducible protein 2 (HIG2) as a diagnostic biomarker for clear cell renal cell carcinoma
12. mGluR4 imaging markers for the diagnosis of CNS disorders
13. Benzothiazoles as diagnostic imaging biomarkers of Alzheimer’s disease
14. EMT and tumor stem cell markers as surrogate markers to stratify breast cancer patients for personalized therapies
15. Soluble endoglin as a biomarker for diagnosing pre-eclampsia and eclampsia
16. Serum biomarker for the early on-set detection of a renal tubular cell injury
17. Diagnosing Alzheimer’s disease using a giant magnetoresistance sensor
18. Non-invasive prenatal diagnosis of Down’s syndrome and Turner’s syndrome using maternal plasma
19. Peripheral blood immune cell based method for diagnosing allergic asthma in patients
20. Biomarkers in the patient’s Bruch’s membrane for the diagnosis of age-related macular degeneration
21. A panel of multiple serum biomarkers for the diagnosis of major depressive disorder
22. Apolipoprotein CIII as a diagnostic biomarker of type I diabetes
23. Beta arrestin 2 as a biomarker for the diagnosis of insulin resistance
24. A cell based method for diagnosing asthma
25. Prenatal diagnosis of a fetal chromosomal aneuploidy
26. Personalized medicine approach for FOLFOX treatment in cancer patients
Details: http://www.sciclips.com/sciclips/biomarker-news.do

Related blogs:

Recent US Patent Applications in Drug Discovery

sciclips — Wed, 05 Oct 2011 17:07:52 +0000

Highlights of recent US patent applications in drug discovery published on September 29, 2011:

1. Nicotinic acetylcholine receptor as a drug target for the treatment of peripheral nerve sensory loss
2. New kinase inhibitors for enhancing memory and learning and for treating Alzheimer’s disease
3. Combination therapy for treating psoriasis
4. Combination of glucocorticoid receptor (GR) ligand and a V-ATPase inhibitor for treating autoimmune and inflammatory diseases
5. Soluble CD47 binding for treating autoimmune and inflammatory disorders
6. DEPDC1- ZNF224 protein interaction as a therapeutic drug target for treating bladder cancer
7. Splice-splice switching oligomers for TNF superfamily receptors for the treatment of various diseases
8. Bicyclic peptidomimetic inhibitors of aspartyl-proteases for the treatment of infectious diseases
9. Triazolopyrimidinones as fatty acid binding protein (FABP) inhibitors
10. Spiro azepane-ox-azolidinones as voltage gated Kv1.3 potassium channel blockers
11. Combination therapy for treating infantile spasms or refractory adult seizureshttp://sciclips.wordpress.com/?p=500&preview=true
12. Combination therapy for the treatment of fungal infections
13. Compounds having the capability to release carbon monoxide (CO) in vivo for treating rheumatoid arthritis
14. Compounds that inhibit MMP-9, VEGFR2 and inflammation-mediated cytokines for treating dry eye syndrome and inflammatory eye disease
15. Beta-N-acetylglucosaminidase as a drug target for treating lysosomal storage disorders
16. Vanoxerine for treating cardiac arrhythmia
17. Combination therapy for treating schizophrenia
18. Huperzine A derivatives for treating migraine
19. siRNA targeting ZEB1 and BLIMP-1 for treating asthma
20. siRNA targeting transthyretin for treating leptomeningeal amyloidosis or familial amyloid polyneuropathy
21. siRNA targeting ZFAT gene for the treatment of leukemia
22. Alpha-1-antitrypsin for the treatment of tissue necrosis
23. Artificial microRNA based acyl-CoA:Cholesterol Acyltransferase 1 (ACAT1) inhibitors for treating Alzheimer’s disease
24. Chromenone derivatives as transient receptor potential vanilloid 3 (TRPV3) antagonists
25. Oral composition containing daidzein and cyanidin for treating acne
26. Treating muscle wasting in patients with non-small cell lung cancer (NSCLC)
27. Combination therapy for treating polycythemia vera
28. Vitamin U for healing wounds and improving skin wrinkles
29. Monocholine succinate salts for the treatment of depression, anxiety, schizophrenia, sleep disorder, and epilepsy
30. S1P receptor modulators for treating multiple sclerosis
31. Transglutaminase II inhibitors, as a tocolytic agent, for treating preterm labour
32. Nanoparticle based photodynamic therapy for the treatment of cancer
33. Systemic drug delivery through nails
34. Proliferation inhibitor of Helicobacter pylori
35. Contraceptive peptide from spider venom

Details: http://www.sciclips.com/sciclips/drug-discovery-news.do

Related blogs:

Recent US Patent Applications in Biomarkers and Molecular Diagnostics

sciclips — Tue, 04 Oct 2011 04:39:39 +0000

Highlights of US patent applications published on September 29, 2011:

1. Biomarker for predicting increased risk of coronary heart disease (CHD) in patients with type 2 diabetes.
2. Diagnostic biomarker for brain disease caused by brain injury .
3. Gene expression biomarkers for the diagnosis and prognosis of prostate cancer patients.
4. Total FVII protein as a biomarker of pre-eclampsia.
5. Biomarkers of IgA nephropathy or TGBM nephropathy.
6. Serum biomarker panel for the diagnosis of Alzheimer’s disease.
7. PSA glycans as biomarkers for the diagnosis of prostate cancer.
8. Exosomal biomarkers for the diagnosis of prostate cancer and colon cancer.
9. Biomarkers for the diagnosis of exposure to electromagnetic radiation.
10. Phage microarrays for the diagnosis of prostate cancer.
11. LTBP2 as a biomarker of renal dysfunction.
12. LTBP2 as predictive marker for mortality in patients with acute dyspnea.
13. NMR based diagnosis of asthma, COPD and other respiratory diseases using metabolomic biomarkers.
14. Predicting chemotherapy outcome for individualized cancer treatment.
15. MicroRNA biomarkers for the diagnosis of motor neuron diseases.
16. Protein polymorphism biomarkers in human hair for paternity testing and forensic analysis.
Details: http://www.sciclips.com/sciclips/biomarker-news.do

Related blogs:

Recent Stem Cell Patents and Patent Applications

sciclips — Thu, 29 Sep 2011 18:50:59 +0000

From recent US patents (issued), US and WO (PCT) patent applications.

1. Method for the isolation of circulating breast cancer/tumor cells and cancer stem cells
2. GLP-1 secreting stem cells for treating acute myocardial infarction
3. Functional CD4 T cells from hematopoietic stem cells
4. Autologous mesenchymal stem cell-derived neural precursors for treating multiple sclerosis
5. Stem cells from neural crest
6. Methods for differentiating stem cells into dopaminergic cells
7. Single lentiviral vector system for induced pluripotent stem (IPS) cells
8. Method for differentiation of dental stem cells
9. In vivo stem cell mobilization for improving vision
10. In vivo stem cell mobilization for increasing cognitive function
11. Oligonucleotide mediated inhibition of cancer stem cells
12. Stem cells for producing animal food products having increased muscle mass
13. Ficus plant extracts promotes hair growth by increasing the viability of epidermal stem cells
14. Acute liver failure (ALF) treatment using stem cell mobilizing agents
15. Human stem-like cells (hSLCs) and metabolomics to discover biomarkers of developmental toxicity of pharmaceutical compounds
16. HATHFUN-tagged transcription factor vectors for generating iPS cells or for inducing stem cell differentiation
17. Non-invasive biosensors to measure kinetic profile of cardiomyocyte stem cells or neural stem cells
18. KIT binding antibodies for inducing stem cell differentiation
19. Generating iPS cells from differentiated cells by the transient expression of reprogramming genes
20. BMP-4 derived peptides for increasing osteogenesis or chondrogenesis in stem cells
21. Long-term stability of epidermal stem cells for the screening of pharmaceutical and cosmetic agents
22. CXCR4 antagonists to purge an ex vivo hematopoietic stem cell culture of cancer cells
23. 3D scaffolds for growing stem cells
24. Neuregulin for inducing cardiomyogenesis in embryonic stem cells
25. Synchronous neural differentiation of embryonic stem cells
26. Cells exhibiting neuronal progenitor cell characteristics from bone marrow adherent stem cells
27. Direct differentiation of hESCs and iPS cells into chondrogenic cells
Details: http://www.sciclips.com/sciclips/drug-discovery-news.do

Related blogs:

1. Cancer Theranostics – Potential Applications of Cancer Biomarker Database
2. Are stem cells ready as a next generation drug discovery tool?
3. Cell based reporter assays: misleading approach in drug discovery?

Related tools:

1. Drug discovery protocols
2. Bioprotocols
3. Drug discovery reagents
4. Drug discovery news
5. Comprehensive cancer biomarker database with companion diagnostics pathway

Recent US Patent Applications in Biomarkers and Molecular Diagnostics

sciclips — Mon, 26 Sep 2011 19:55:42 +0000

Highlights of US patent applications published on Sept. 22, 2011

1. Biomarkers for prognosing responsiveness to anti-TNF alpha therapy in patients with inflammatory bowel disease
2. Urinary biomarker for the diagnosis of polycystic kidney disease
3. Syngap1 as a biomarker for the diagnosis of mental retardation
4. Molecular diagnostic method for the detection of Turner Syndrome
5. Phosphorylated Beclin-1 as a biomarker for the diagnosis Alzheimer’s disease, Huntington’s disease and Parkinson’s disease
6. Azurophilic granule proteases as markers in cardiological diseases
7. SNP biomarkers for determining increased susceptibility to thyroid cancer
8. Biomarker for accurate diagnosis of cystic fibrosis (CF)
9. Biomarker for determining an increased risk for side effects of selective serotonin reuptake inhibitor (SSRI) treatment
10. Predictive biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis
11. ELISPOT assay for early detection of antigen exposure
12. Biomarkers for predicting the recurrence, progression, and metastatic potential of a prostate cancer

Details: http://www.sciclips.com/sciclips/biomarker-news.do