Blog

In previous installments of Nanomedicine, we have discussed the usage of nanoparticles in cancer and other diseases as both diagnostics and therapeutic agents. See, for example, magnetic nanoparticles for theranostics (Part VIII and Part X), quantum dots for bioimaging (Part VII), nanoparticles as cancer biomarkers (Part VI) and for cancer therapy (Part V), and nanoparticles as drug delivery carriers (Part IV).  These applications of nanotechnology not only have attracted increased attention from pharmaceutical companies and academic researchers, but have led to the development of innovative candidatesin clinic trials and even successful products selling in global markets. Beyond this thriving therapeutic field, another huge market for utilizing nanotechnology that might not be as widely recognized, but which already has had a great impact, is the market for cosmeceuticals.

Sequencing whole human genomes presents many technical challenges. Whole human genomes have a large number of long repetitive sequence segments of more than 1,000 bp, which cannot be distinguished by short-read instruments. Since it has been reported that each individual human genome has 2.7 to 4.1 million variants, then, for the 3.2 Gigabyte whole human genome, there is at least one variant per every 1,000 bases. These long repetitive sequence segments could include structure alteration and gene mutations relating to diseases, but might not be efficiently and accurately characterized by short-read NGS technologies.  To address these challenges, long-read sequencing technologies have been developed and have already provided some astounding applications. For example, in 2014, scientists successfully applied nanopore sequencing technology developed by Oxford Nanopore Technologies (ONT) to monitor the transmission history and disease evolution of the Ebola virus, essentially in real time, during its outbreak. In this installment, we will discuss two of the main long-read sequencing technologies: (i) the synthetic approach and (ii) the single-molecule sequencing approach, and will review the relevant patents.

In 2001, the first entire human genome was successfully sequenced under the support of the Human Genome Project. This endeavor took 15 years and cost nearly 3 billion dollars. Since then, high-throughput sequencing technology, also known as Next Generation Sequencing (NGS), was developed to reduce the time and cost of human genome sequencing. In 2005, the first NGS sequencer was released to the market by 454 Life Sciences.  This sequencer reduced the cost of human genome sequencing by 50,000-fold.

Magnetic nanoparticles are superior imaging contrast agents for Magnetic Resonance Imaging (MRI) due to the intrinsic magnetic properties of nanoparticles. As of 2012, the FDA has approved several MNPs as MRI contrast agents or therapeutic agents: ferumoxides (also known as Feridex in the USA) as an MRI contrast agent for imaging liver lesions; ferucarbotran (also known as Resovist) as MRI contrast agent for imaging liver lesions; ferumoxsil (also known as GastroMARK or Lumirem) as an orally administered MRI contrast agent; and ferumoxytol (also known as Feraheme) as an intravenously administered nanoparticle to treat iron deficiency in adults with chronic kidney disease.

Recently, Draper announced a three-year agreement with Pfizer. This collaboration focuses on developing effective disease models for testing potential drug candidates based on microphysiological systems, also known as “organs-on-a-chip”.

The organs-on-a-chip technology is a three-dimensional microfluidic based multi-cell co-culture system that models the physiological, mechanical, and molecular environment of the human body and mimics the physiological functions of human organs. This technology offers unique in vitro disease models for new drug screening and toxicology testing. This technology has attracted attentions not only from academic institutes but also from the pharmaceutical industry. One of the main reasons for this interest is the potential cost and time savings for drug research and the development process. As required by the FDA drug approval process, new drug chemical entities are tested in animals before going into human Phase I testing for the drug approval process. The preclinical animal testing process is tedious and extremely expensive. Additionally, animal models are not always predictive for characterizing drug safety in humans. About 40% of drug compounds fail in Phase I clinical trials (Clinical Development Success Rates 2006-2015, BIO Industry Analysis, June 2016). To address these challenges, organs-on-a-chip has been proposed as a novel method to develop human disease models and replace preclinical animal testing.

Dilworth IP is delighted to officially announce the launch of our new Chinese language website on March 16, 2017. Visitors can find the Firm’s website in Mandarin at: /zh-hans/
This new site will be a convenient way for our Chinese friends and clients to learn about the firm: our history, our philosophy, and our team. Michael Dilworth, the firm’s founder and managing partner, stated, “this new site is an exciting step in the firm’s continued work to strengthen ties with our colleagues and friends in China. Dilworth IP is committed to building lasting relationships and providing quality patent and trademark representation to our clients and the launch of this new site is an important sign of our commitment to that.”
We hope you find this new website informative and helpful. Please feel free to contact us for any questions, suggestions, feedback, or comments at info@dilworthip.com.

Magnetic nanoparticles, also known as superparamagnetic nanoparticles are small inorganic crystals about 5-20 nm in diameter. Two main classes of MNPs currently used for clinical imaging are ferromagnetic iron oxide nanoparticles and ultrasmall superparameganetic iron oxide nanoparticles (USPION). MNPs are usually multilayer materials, which give them their various properties and functionalities for diagnosis and disease treatment. The structure of iron oxide nanoparticles has three main components: an iron oxide core as a Magnetic Resonance Imaging (MRI) contrast agent, a biocompatible coating outside the core, and an outer therapeutic coating with specific ligands for biomarker targeting. See (US 8,945,628 by Dr. Ralph Weissleder at Massachusetts General Hospital and US 7,462,446 by Dr. Miqin Zhang at the University of Washington). This unique structure enables MNP accumulation in the sites of interest via biomarker targeting. It further allows the diagnosis of diseases, the evaluation of treatment efficacy, and the localized delivery of drugs and disease therapies. The integration of both diagnostic and therapeutic modalities into one single agent is called a theranostic agent. We will discuss the diagnostic and therapeutic properties of MNPs in cancer.

On December 2016, another CAR-T patent fight temporarily came to the end by the issuing of the final written decision from the Patent Trial and Appeal Board (PTAB) (IPR2015-01719). This Inter Partes Review (IPR) was initiated by Kite Pharma Inc. (“Kite”) to challenge a patent held by Memorial Sloan Kettering Cancer Center (MSKCC), relating to chimeric antigen receptors (CAR) T-cells for cancer immunotherapy (US 7,446,190). The IPR petition was filed on August 2015 and granted by the US PTAB on February 2016. After review, the PTAB determined that Kite did not show by a preponderance of the evidence that all the claims in the ‘190 patent are unpatentable.

According to the Allied Market Research report, the global market for quantum dots will grow from about $300 million to over $5 billion dollars in the period from 2013-2020 period. So, what exactly is a quantum dot and how are they useful?

In 1988, the term “quantum dot” (or “QD” for short) was introduced by Dr. Mark Reed at Yale University to describe nanocrystalline semiconducting fluorophores. Fluorophores are chemical materials that re-emit light when excited by a light pulse. QDs are usually core-shell systems with a semiconductor core enclosed within a shell of another semiconductor material. They usually have confined diameters in the range of 2-20 nanometers (a nanometer is 1 x 10-9 meters) in all three spatial dimensions, resulting in size quantization effects. This size quantization means the band gap (the electron and hole excitation energy levels) of the QD can be “tuned” to provide different light emission frequencies by changing the composition of the QDs and varying their diameters. For example, the larger the QD, the redder, i.e.the lower the energy, emission. Researchers have utilized QDs as efficient materials for advanced photoelectric devices and solar cells. Dr. Arthur Nozik is one of the great leaders in this field (US 4,634,641). During his tenure at the National Renewable Energy Laboratory (NREL), he led a research group to discover variant semiconductor QDs for novel optical and energy systems (US 8,685,781 and US 9,324,562 ). Additionally the surfaces of QDs can be conjugated to various molecules to vary their physical properties, for example, to increase water solubility, reduce cytotoxicity, and resist reactive oxygen formation. The QDs can also be conjugated with specific molecules to target tumor biomarkers. These unique physical properties and the surface chemical modification of QDs have attracted increasing attention to applications in bio-imaging (reviewed in Part VI), bio-analytical assays and diagnostics, as well as the development of new therapeutic agents.

A critical step to effectively fighting cancer is detecting it at a very early stage. Currently the clinical diagnosis of cancer mainly relies on imaging techniques such as X-ray, mammography, ultrasound, endoscopy, computed tomography (CT), magnetic resonance imaging (MRI) and histopathology [e.g., examination of a tissue biopsy under a microscope]). However, these techniques often cannot distinguish differences between healthy and diseased cells/tissues at the early stage of cancer, when the malignancy of tissues are not sufficiently visible, but the alternation of far more subtle protein and molecular markers due to the cancer have already presented. Although notable successful techniques have been developed in the molecular analysis such as enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and fluorescence in situ hybridization (FISH), these techniques are labor intensive, involving complex operational procedures, and requiring high stability of reagents. Therefore, the market is calling to develop new techniques and tools to enhance the biomarker detection at the very early stages of cancer.