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Archive for the ‘Advanced Drug Manufacturing Technology’ Category


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

RNA plays various roles in determining how the information in our genes drives cell behavior. One of its roles is to carry information encoded by our genes from the cell nucleus to the rest of the cell where it can be acted on by other cell components. Rresearchers have now defined how RNA also participates in transmitting information outside cells, known as extracellular RNA or exRNA. This new role of RNA in cell-to-cell communication has led to new discoveries of potential disease biomarkers and therapeutic targets. Cells using RNA to talk to each other is a significant shift in the general thought process about RNA biology.

 

Researchers explored basic exRNA biology, including how exRNA molecules and their transport packages (or carriers) were made, how they were expelled by producer cells and taken up by target cells, and what the exRNA molecules did when they got to their destination. They encountered surprising complexity both in the types of carriers that transport exRNA molecules between cells and in the different types of exRNA molecules associated with the carriers. The researchers had to be exceptionally creative in developing molecular and data-centric tools to begin making sense of the complexity, and found that the type of carrier affected how exRNA messages were sent and received.

 

As couriers of information between cells, exRNA molecules and their carriers give researchers an opportunity to intercept exRNA messages to see if they are associated with disease. If scientists could change or engineer designer exRNA messages, it may be a new way to treat disease. The researchers identified potential exRNA biomarkers for nearly 30 diseases including cardiovascular disease, diseases of the brain and central nervous system, pregnancy complications, glaucoma, diabetes, autoimmune diseases and multiple types of cancer.

 

As for example some researchers found that exRNA in urine showed promise as a biomarker of muscular dystrophy where current studies rely on markers obtained through painful muscle biopsies. Some other researchers laid the groundwork for exRNA as therapeutics with preliminary studies demonstrating how researchers might load exRNA molecules into suitable carriers and target carriers to intended recipient cells, and determining whether engineered carriers could have adverse side effects. Scientists engineered carriers with designer RNA messages to target lab-grown breast cancer cells displaying a certain protein on their surface. In an animal model of breast cancer with the cell surface protein, the researchers showed a reduction in tumor growth after engineered carriers deposited their RNA cargo.

 

Other than the above research work the scientists also created a catalog of exRNA molecules found in human biofluids like plasma, saliva and urine. They analyzed over 50,000 samples from over 2000 donors, generating exRNA profiles for 13 biofluids. This included over 1000 exRNA profiles from healthy volunteers. The researchers found that exRNA profiles varied greatly among healthy individuals depending on characteristics like age and environmental factors like exercise. This means that exRNA profiles can give important and detailed information about health and disease, but careful comparisons need to be made with exRNA data generated from people with similar characteristics.

 

Next the researchers will develop tools to efficiently and reproducibly isolate, identify and analyze different carrier types and their exRNA cargos and allow analysis of one carrier and its cargo at a time. These tools will be shared with the research community to fill gaps in knowledge generated till now and to continue to move this field forward.

 

References:

 

https://www.nih.gov/news-events/news-releases/scientists-explore-new-roles-rna

 

https://www.cell.com/consortium/exRNA

 

https://www.sciencedaily.com/releases/2016/06/160606120230.htm

 

https://www.pasteur.fr/en/multiple-roles-rnas

 

https://www.nature.com/scitable/topicpage/rna-functions-352

 

https://www.umassmed.edu/rti/biology/role-of-rna-in-biology/

 

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UPDATED on 3/17/2019

https://www.medpagetoday.com/cardiology/prevention/78202?xid=nl_mpt_SRCardiology_2019-02-25&eun=g99985d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=CardioUpdate_022519&utm_term=NL_Spec_Cardiology_Update_Active

Transgender hormone therapy appears to increase cardiovascular risk. (Circulation)

A mobile app with a step-by-step guide to prepping vasoactive drugs for CPR of children in the emergency room substantially cut medication errors, drug preparation time, and delivery time compared with using infusion-rate tables in a study using manikins. (The Lancet Child & Adolescent Health)

 

Artificial ovary instead of conventional hormone replacement

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

During menopause a woman’s ovaries stop working—leading to hot flashes, sleep problems, weight gain, and worse, bone deterioration. Now scientists are exploring whether transplanting lab-made ovaries might stop those symptoms. In one of the first efforts to explore the potential of such a technique, researchers say they used tissue engineering to construct artificial rat ovaries able to supply female hormones like estrogen and progesterone. A research carried out at Wake Forest Baptist Medical Center, suggests a potential alternative to the synthetic hormones millions of women take after reaching middle age. A paper describing the findings was published in Nature Communications.

 

Women going through menopause, as well as those who have undergone cancer treatment or had their ovaries removed for medical purposes, lose the ability to produce important hormones, including estrogen and progesterone. Lower levels of these hormones can affect a number of different body functions. To counteract unpleasant symptoms, many women turn to combinations of hormone replacement medications—synthetic estrogen and progestin. Pharmacologic hormone replacement therapy (pHRT) with estrogen alone or estrogen and progestogens is known to effectively ameliorate the unpleasant symptoms. But hormone replacement carries an increased risk of heart disease and breast cancer, so it’s not recommended for long-term use. In these circumstances artificial ovaries could be safer and more effective.

 

Regenerative medicine approaches that use cell-based hormone replacement therapy (cHRT) offer a potential solution to temporal control of hormone delivery and the ability to restore the HPO (Hypothalamo-Pituitary-Ovarian) axis in a way not possible with pHRT. Scientists have previously described an approach to achieve microencapsulation of ovarian cells that results in bioengineered constructs that replicate key structure-function relationships of ovarian follicles as an approach to cHRT. In the present study the scientists have adapted an isogeneic cell-based construct to provide a proof-of-concept for the potential benefits of cHRT.

 

Tissue or cell encapsulation may offer effective strategies to fabricate ovarian constructs for the purpose of fertility and/or hormone replacement. Approaches using segmental ovarian tissue or whole-follicle implantation (typically with a focus on cryopreservation of the tissue for reproductive purposes) have resulted in detectable hormone levels in the blood after transplantation. Previous studies have also shown that autotransplantation of frozen-thawed ovarian tissue can lead to hormone secretion for over 5 years in humans.

 

Although these approaches can be used to achieve the dual purpose of fertility and hormone replacement in premenopausal women undergoing premature ovarian failure, they would have limited application in postmenopausal women who only need hormone replacement to manage menopausal symptoms and in whom fertility is not desirable. In full development, the technology described in this research is focused on hormone replacement, would meet the needs of the latter group of women that is the postmenopausal women.

 

The cell-based system of hormone replacement described in this report offers an attractive alternative to traditional pharmacological approaches and is consistent with current guidelines in the U.S. and Europe recommending the lowest possible doses of hormone for replacement therapy. In the present research sustained stable hormone release over the course of 90 days of study was demonstrated. The study also demonstrated the effective end-organ outcomes in body fat composition, uterine health, and bone health. However, additional studies will be required to determine the sustainability of the hormone secretion of the constructs by measuring hormone levels from implanted constructs for periods longer than 3 months in the rat model.

 

This study highlights the potential utility of cHRT for the treatment and study of conditions associated with functional loss of the ovaries. Although longer-term studies would be of future interest, the 90-day duration of this rodent model study is consistent with others investigating osteoporosis in an ovariectomy model. However, this study provides a proof-of-concept for cHRT, it suffers the limitation that it is only an isogeneic-based construct implantation. Scientists think that further studies in either allogeneic or xenogeneic settings would be required with the construct design described in this report in the path towards clinical translation given that patients who would receive this type of treatment are unlikely to have sufficient autologous ovarian cells for transplantation.

 

Researchers from Copenhagen, Denmark, were recently able to isolate viable, early stage follicles in ovarian tissue. They have successfully stripped ovarian tissue from its cancerous cells and used the remaining scaffold to support the growth and survival of human follicles. This “artificial ovary” may help y to help women who have become infertile due to cancer and chemotherapy. But, the research is presently at a very preliminary stage and much research is still required to ensure that cancer cells are not reintroduced during the grafting process.

 

References:

 

https://www.technologyreview.com/the-download/609677/will-artificial-ovaries-mean-no-more-menopause/

 

https://www.nature.com/articles/s41467-017-01851-3

 

https://www.ncbi.nlm.nih.gov/pubmed/23274068

 

https://www.ncbi.nlm.nih.gov/pubmed/26210678

 

https://www.ncbi.nlm.nih.gov/pubmed/21954279

 

http://www.frontlinegenomics.com/news/24423/artificial-ovaries-hope-to-help-infertile-women-conceive-following-chemotherapy/

 

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Reporter: Irina Robu, PhD

Using the century-old cutting method, it would take a researcher five hours to cut 100 cells, and by the time they were done, the cells they cut first would be well on their way to healing.

In an effort to comprehend how a single cell heal, mechanical engineer Sing Tand developed a microscopic guillotine that proficiently cuts cells into two.

Tang, who is an assistant professor of mechanical engineering at Stanford University knew that finding a way to competently slice the cell in two could lead to engineering self-healing materials and machines. In order, to efficiently slice a cell in two he developed a tool that could cut 150 cells in just over 2 minutes, and the cuts were much more standardized and synchronized in the stage of their repair process. They attained this rate by creating a scaled-up version of their tool with eight identical parallel channels that run simultaneously. Being able to efficiently study cell healing could eventually help scientists study and treat a variety of human diseases such as cancer and neurodegenerative diseases. Prior to Tang’s cellular guillotine, scientists used to slice cells by hand under a microscope using a glass needle which is a method that can lead to errors.

Tang’s method can be the Holy Grail of engineering self-healing materials and machines.

SOURCE

http://news.stanford.edu/2017/06/26/stanford-scientists-create-cellular-guillotine-studying-single-cell-wound-repair/

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Ultra-Pure Melatonin Product Helps Maintain Sleep for Up to 7 Hours

Curator: Gail S. Thornton, M.A.

Co-Editor: The VOICES of Patients, Hospital CEOs, HealthCare Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures

 

The role of melatonin is important in regulating natural sleep and wake cycles. Typically, melatonin levels decline with age, significantly decreasing after age 40. An estimated 50 to 70 million Americans are affected by sleep difficulties – a process regulated by melatonin — and long-term sleep deprivation has been associated with negative health consequences, including an increased risk of diabetes, hypertension, heart attack, stroke, obesity, and depression.

Clinical data from a new pharmacokinetic study suggests that REMfresh®, the first and only continuous release and absorption melatonin (CRA-melatonin), helps maintain sleep for up to 7 hours. REMfresh® contains 99 percent ultra-pure melatonin and is sourced in Western Europe, a factor that is significant and important to many sleep specialists.

Three research abstracts on the REMfresh® data were published in an online supplement in the journal, Sleep, and were presented recently at the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS).

REMfresh Photo

Image SOURCE: Photograph courtesy of Physician’s Seal®

How REMfresh® Works

REMfresh® (CRA-melatonin) mimics the body’s own 7-hour Mesa Wave™, a natural pattern of melatonin blood levels during a normal night’s sleep cycle.

The study demonstrated the continuous release and absorption of 99 percent ultra-pure melatonin in REMfresh® (CRA-melatonin) was designed to induce sleep onset and provide continuous, lasting restorative sleep over 7 hours.

The scientifically advanced, patented formulation, called Ion Powered Pump (IPP™) technology, replicates the way in which the body naturally releases and absorbs melatonin, unlike conventional melatonin sleep products.

Since REMfresh® (CRA-melatonin) is not a drug, there is no drug hangover.

REMfresh MesaCurveNew-1

Image SOURCE: Diagram courtesy of Physician’s Seal®

 

Data Based on Scientifically Advanced Delivery Technology

According to the primary study author, David C. Brodner, M.D., “These study results represent an unparalleled breakthrough in drug-free, sleep maintenance that physicians and patients have been waiting for in a sleep product.” Dr. Brodner is a sleep specialist who is double board-certified in Otolaryngology – Head and Neck Surgery and Sleep Medicine and is the founder and principle physician at the Center for Sinus, Allergy, and Sleep Wellness in Palm Beach County, Florida.

Dr. Brodner said, “Melatonin products have been used primarily as a chronobiotic to address sleep disorders, such as jet lag and shift work. The patented delivery system in REMfresh mimics the body’s own natural sleep pattern, so individuals may experience consistent, restorative sleep and have an improved quality of life with this drug-free product.”

Study Findings With REMAKT

The study findings are based on REMAKT™ (REM Absorption Kinetics Trial), a U.S.-based randomized, crossover pharmacokinetic (PK) evaluation study in healthy, non-smoking adults that compared REMfresh® (CRA-melatonin) with a market-leading, immediate-release melatonin (IR-melatonin).

The study found that melatonin levels with REMfresh® exceeded the targeted sleep maintenance threshold for a median of 6.7 hours, compared with 3.7 hours with the leading IR-melatonin. Conversely, the levels of the market-leading IR-melatonin formulation dramatically increased 23 times greater than the targeted levels of exogenous melatonin for sleep maintenance and had a rapid decline in serum levels that did not allow melatonin levels to be maintained beyond 4 hours.

Additional analysis presented showed that REMfresh® (CRA-melatonin) builds upon the body of evidence from prolonged-release melatonin (PR-M), which demonstrated in well-conducted, placebo-controlled studies, statistically significant improvement in sleep quality, morning alertness, sleep latency and quality of life in patients aged 55 years and older compared with placebo.

REMfresh® (CRA-melatonin) was designed to overcome the challenges of absorption in the intestines, thereby extending the continual and gradual release pattern of melatonin through the night (known as the Mesa Wave™, a flat-topped hill with steep sides). There was a faster time to Cmax, which is anticipated to result in improved sleep onset, while the extended median plateau time to 6.7 hours and rapid fall-off in plasma levels at the end of the Mesa Wave™ may help to improve sleep maintenance and morning alertness.

REFERENCE/SOURCE

Physician’s Seal® and REMfresh® (www.remfresh.com)

REMfresh® press release, June 5, 2017 (http://www.prnewswire.com/news-releases/scientifically-advanced-delivery-technology-in-sleep-management-debuts-at-sleep-2017-with-clinical-data-showing-remfresh-the-first-and-only-continuous-release-and-absorption-melatonin-helps-maintain-sleep-for-up-to-7-hours-300468218.html)

Dr. David C. Brodner, Center for Sinus, Allergy, and Sleep Wellness  (http://www.brodnermd.com/sleep-hygiene.html)

Other related articles published in this Open Access Online Scientific Journal include the following:

2017

Sleep Research Society announces 2017 award recipients including Thomas S. Kilduff, PhD, Director, Center for Neuroscience at SRI International in Menlo Park, California

https://pharmaceuticalintelligence.com/2017/04/28/sleep-research-society-announces-2017-award-recipients-including-thomas-s-kilduff-phd-director-center-for-neuroscience-at-sri-international-in-menlo-park-california/

2016

Sleep Science

Genetic link to sleep and mood disorders

https://pharmaceuticalintelligence.com/2016/02/27/genetic-link-to-sleep-and-mood-disorders/

2015

Sleep quality, amyloid and cognitive decline

https://pharmaceuticalintelligence.com/2015/10/31/sleep-quality-amyloid-and-cognitive-decline/

2013

Day and Night Variation in Melatonin Level affects Plasma Membrane Redox System in Red Blood Cells

https://pharmaceuticalintelligence.com/2013/02/23/httpwww-ncbi-nlm-nih-govpubmed22561555/

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Topical Solution for Combination Oncology Drug Therapy: Patch that delivers Drug, Gene, and Light-based Therapy to Tumor

Reporter: Aviva Lev-Ari, PhD, RN

 

Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment

Affiliations

  1. Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts 02139, USA
    • João Conde,
    • Nuria Oliva,
    • Mariana Atilano,
    • Hyun Seok Song &
    • Natalie Artzi
  2. School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, UK
    • João Conde
  3. Grup dEnginyeria de Materials, Institut Químic de Sarrià-Universitat Ramon Llull, Barcelona 08017, Spain
    • Mariana Atilano
  4. Division of Bioconvergence Analysis, Korea Basic Science Institute, Yuseong, Daejeon 169-148, Republic of Korea
    • Hyun Seok Song
  5. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
    • Natalie Artzi
  6. Department of Medicine, Biomedical Engineering Division, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    • Natalie Artzi

Contributions

J.C. and N.A. conceived the project and designed the experiments. J.C., N.O., H.S.S. and M.A. performed the experiments, collected and analysed the data. J.C. and N.A. co-wrote the manuscript. All authors discussed the results and reviewed the manuscript.

Nature Materials
15,
353–363
(2016)
doi:10.1038/nmat4497
Received
22 April 2015
Accepted
26 October 2015
Published online
07 December 2015

The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs—a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor)—provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional in vitro and in vivo, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.

SOURCE

http://www.nature.com/nmat/journal/v15/n3/abs/nmat4497.html#author-information

 

 

Patch that delivers drug, gene, and light-based therapy to tumor sites shows promising results

In mice, device destroyed colorectal tumors and prevented remission after surgery.

Helen Knight | MIT News Office
July 25, 2016

Approximately one in 20 people will develop colorectal cancer in their lifetime, making it the third-most prevalent form of the disease in the U.S. In Europe, it is the second-most common form of cancer.

The most widely used first line of treatment is surgery, but this can result in incomplete removal of the tumor. Cancer cells can be left behind, potentially leading to recurrence and increased risk of metastasis. Indeed, while many patients remain cancer-free for months or even years after surgery, tumors are known to recur in up to 50 percent of cases.

Conventional therapies used to prevent tumors recurring after surgery do not sufficiently differentiate between healthy and cancerous cells, leading to serious side effects.

In a paper published today in the journal Nature Materials, researchers at MIT describe an adhesive patch that can stick to the tumor site, either before or after surgery, to deliver a triple-combination of drug, gene, and photo (light-based) therapy.

Releasing this triple combination therapy locally, at the tumor site, may increase the efficacy of the treatment, according to Natalie Artzi, a principal research scientist at MIT’s Institute for Medical Engineering and Science (IMES) and an assistant professor of medicine at Brigham and Women’s Hospital, who led the research.

The general approach to cancer treatment today is the use of systemic, or whole-body, therapies such as chemotherapy drugs. But the lack of specificity of anticancer drugs means they produce undesired side effects when systemically administered.

What’s more, only a small portion of the drug reaches the tumor site itself, meaning the primary tumor is not treated as effectively as it should be.

Indeed, recent research in mice has found that only 0.7 percent of nanoparticles administered systemically actually found their way to the target tumor.

“This means that we are treating both the source of the cancer — the tumor — and the metastases resulting from that source, in a suboptimal manner,” Artzi says. “That is what prompted us to think a little bit differently, to look at how we can leverage advancements in materials science, and in particular nanotechnology, to treat the primary tumor in a local and sustained manner.”

The researchers have developed a triple-therapy hydrogel patch, which can be used to treat tumors locally. This is particularly effective as it can treat not only the tumor itself but any cells left at the site after surgery, preventing the cancer from recurring or metastasizing in the future.

Firstly, the patch contains gold nanorods, which heat up when near-infrared radiation is applied to the local area. This is used to thermally ablate, or destroy, the tumor.

These nanorods are also equipped with a chemotherapy drug, which is released when they are heated, to target the tumor and its surrounding cells.

Finally, gold nanospheres that do not heat up in response to the near-infrared radiation are used to deliver RNA, or gene therapy to the site, in order to silence an important oncogene in colorectal cancer. Oncogenes are genes that can cause healthy cells to transform into tumor cells.

The researchers envision that a clinician could remove the tumor, and then apply the patch to the inner surface of the colon, to ensure that no cells that are likely to cause cancer recurrence remain at the site. As the patch degrades, it will gradually release the various therapies.

The patch can also serve as a neoadjuvant, a therapy designed to shrink tumors prior to their resection, Artzi says.

When the researchers tested the treatment in mice, they found that in 40 percent of cases where the patch was not applied after tumor removal, the cancer returned.

But when the patch was applied after surgery, the treatment resulted in complete remission.

Indeed, even when the tumor was not removed, the triple-combination therapy alone was enough to destroy it.

The technology is an extraordinary and unprecedented synergy of three concurrent modalities of treatment, according to Mauro Ferrari, president and CEO of the Houston Methodist Research Institute, who was not involved in the research.

“What is particularly intriguing is that by delivering the treatment locally, multimodal therapy may be better than systemic therapy, at least in certain clinical situations,” Ferrari says.

Unlike existing colorectal cancer surgery, this treatment can also be applied in a minimally invasive manner. In the next phase of their work, the researchers hope to move to experiments in larger models, in order to use colonoscopy equipment not only for cancer diagnosis but also to inject the patch to the site of a tumor, when detected.

“This administration modality would enable, at least in early-stage cancer patients, the avoidance of open field surgery and colon resection,” Artzi says. “Local application of the triple therapy could thus improve patients’ quality of life and therapeutic outcome.”

Artzi is joined on the paper by João Conde, Nuria Oliva, and Yi Zhang, of IMES. Conde is also at Queen Mary University in London.

SOURCE

http://news.mit.edu/2016/patch-delivers-drug-gene-light-based-therapy-tumor-0725

Other related articles published in thie Open Access Online Scientific Journal include the following:

The Development of siRNA-Based Therapies for Cancer

Author: Ziv Raviv, PhD

https://pharmaceuticalintelligence.com/2013/05/09/the-development-of-sirna-based-therapies-for-cancer/

 

Targeted Liposome Based Delivery System to Present HLA Class I Antigens to Tumor Cells: Two papers

Reporter: Stephen J. Williams, Ph.D.

https://pharmaceuticalintelligence.com/2016/07/20/targeted-liposome-based-delivery-system-to-present-hla-class-i-antigens-to-tumor-cells-two-papers/

 

Blast Crisis in Myeloid Leukemia and the Activation of a microRNA-editing Enzyme called ADAR1

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/06/10/blast-crisis-in-myeloid-leukemia-and-the-activation-of-a-microrna-editing-enzyme-called-adar1/

 

First challenge to make use of the new NCI Cloud Pilots – Somatic Mutation Challenge – RNA: Best algorithms for detecting all of the abnormal RNA molecules in a cancer cell

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/17/first-challenge-to-make-use-of-the-new-nci-cloud-pilots-somatic-mutation-challenge-rna-best-algorithms-for-detecting-all-of-the-abnormal-rna-molecules-in-a-cancer-cell/

 

miRNA Therapeutic Promise

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/05/01/mirna-therapeutic-promise/

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CHI’s  Advancing Bispecifics to the Clinic and Immunotherapy and Bispecifics for Oncology Targets, 3 – 4 November 2016, Lisbon, Portugal

Reporter: Aviva Lev-Ari, PhD, RN

 

Registration

https://chidb.com/reg/pge/reg.asp

 

Eighth Annual

Engineering Bispecifics

New Approaches and Platform Refinements

3 – 4 November 2016   |  Lisbon, Portugal

PEGSummitEurope.com

Register

Register Today for

Savings up to €400!

Engineering for T Cell Engagement at Engineering Bispecifics at PEGS Europe

Cambridge Healthtech’s 8th Annual Engineering Bispecifics conference showcases the latest developments in engineering bispecifics for T-cell engagement with presentations from Rinat Pfizer, Covagen, Immunocore and Glenmark. These focus on selection and validation of target antigens, platform development, tailored architecture for novel modes of action, preclinical and clinical manufacturing, IgG isotype and affinity, efficacy and specificity.

Additional presentations on this topic can be heard at the PEGS Europe tracks on Advancing Bispecifics to the Clinic and Immunotherapy (Chugai, Numab, Pfizer, Xencor and Macrogenics and Roche Innovation Centre. German Cancer Research Center).

Session Preview

High Affinity T Cell Receptor-Based Bi-Functional Biologics for Redirected Tumour Killing

Joseph Dukes, Ph.D., Head, Pre-Clinical Biology, Cell Biology, Immunocore

ImmTACs are bi-specific reagents that target tumours via a soluble monocloncal TCR with exceptionally high sensitivity and specificity and redirect host polyclonal T cells via an anti-CD3 antibody fragment. The selection and validation of appropriate target antigens and the testing of ImmTACs for specificity is critical. Using appropriate tumour and primary human cell lines, the in vitro pre-clinical package can be predictive of in vivo clinical observations.

Pfizer’s T-Cell Engaging Full Length Bispecific Antibody Platform: From Bench to NHS

Javier Chaparro-Riggers, Ph.D., Senior Director, Protein Engineering, Rinat Pfizer, Inc.

The recent clinical success of blinatumomab (antiCD19/CD3) spurred the development of a variety of T cell engaging bispecific antibody architectures. Pfizer developed a T cell engaging antibody platform, which allows the formation of full length human IgG1 and IgG2 antibodies in vitro or in vivo. The effect of IgG isotype and affinities of the T cell- and tumor antigen-targeting arm were explored and optimized.

Engineering of CD3 Bispecific FynomAbs

Julian Bertschinger, Ph.D., VP, Janssen R&D, Managing Director, Covagen

ImmTACs are bi-specific reagents that target tumours via a soluble monocloncal TCR with exceptionally high sensitivity and specificity and redirect host polyclonal T cells via an anti-CD3 antibody fragment. The selection and validation of appropriate target antigens and the testing of ImmTACs for specificity is critical. Using appropriate tumour and primary human cell lines, the in vitro pre-clinical package can be predictive of in vivo clinical observations.

Engineering and Manufacturing of Bispecific Antibodies for T-Cell Redirection

Stanislas Blein, Ph.D., Senior Director, Antibody Engineering, Glenmark Pharmaceuticals

Over the past two decades various functional bispecific antibody formats have been designed with only few molecules reaching clinical trials due to an inherent lack of manufacturability. Herein we describe a versatile bispecific antibody format that fits industrial-scale manufacturing processes and enables the rapid design and making of T-cell redirecting molecules. Engineering, pre-clinical and phase-one manufacturing data will be presented.

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Final Agenda  |  Sponsorship & Exhibits |  Present a Poster  |  View Brochure

Short Courses*

DON’T MISS the short course on Engineering of Bispecific Antibodies

To be led by:
Nicolas Fischer, Ph.D., Head, Research, Novimmune SA
Michaela Silacci, Ph.D., Director, Discovery Research, Covagen AG, part of J&J

* separate registration required for short courses

Breakout Discussions

DON’T MISS the in depth Breakout Discussion on Strategy for Engineering and Design of Bispecific TCR-Based Products

To be moderated by:
Julian Bertschinger, Ph.D., VP, Janssen R&D, Managing Director, Covagen

Agenda-At-A-Glance

NEW MODES OF ACTION / T CELL ENGAGEMENT

KEYNOTE PRESENTATION: Protein Engineering for New Modes of Action

Andreas Plückthun, Ph.D., Director and Professor, Biochemistry, University of Zurich

Pfizer’s T Cell Engaging Full Length Bispecific Antibody Platform: From Bench to NHS

Javier Chaparro-Riggers, Ph.D., Senior Director, Protein Engineering, Rinat Pfizer, Inc.

Presentation to be Announced

Sponsored by Schrödinger

ENGINEERING BISPECIFICS FOR T CELL ENGAGEMENT

Engineering of CD3 Bispecific FynomAbs

Julian Bertschinger, Ph.D., Vice President, Janssen R&D, Managing Director, Covagen


High Affinity T Cell Receptor-Based Bifunctional Biologics for Redirected Tumour Killing

Joseph Dukes, Ph.D., Head, Pre-Clinical Biology, Cell Biology, Immunocore

FOCUS ON BISPECIFIC ENGINEERING FOR TARGETING

Epitopes Matter: Strategies to Generate and Analyse Binders to Different Epitopes

Jonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich

Engineered Fab Domains Promote Efficient Production of Bispecific Antibodies in a Single Cell

Christoph Spiess, Ph.D., Senior Scientist, Antibody Engineering, Genentech, Inc.


A Novel Highly Versatile Multi-Specific Antibody Format

David Urech, Ph.D., CSO and Co-CEO, Numab AG

PLATFORM DEVELOPMENT AND REFINEMENT

CrossMAb Version 2: A Versatile Toolbox for Bispecific Antibody Engineering
Joerg Thomas Regula, Ph.D., Head, Functional Characterisation, Large Molecule Research, Roche Pharmaceutical Research and Early Development

Efficient Generation of Bispecific Mouse Antibodies for Preclinical Investigations

Aran F. Labrijn, Ph.D., Principal Scientist, Antibody Sciences, Genmab BV

Platform Refinements for Bispecifics for Oncology Targets

John de Kruif, Ph.D., CTO, Merus

Sponsored Presentation (Opportunities Available)

NOVEL APPROACHES

Using Alphabodies to Generate Bispecifics with Optimal in vitro and in vivo Characteristics

Yvonne McGrath, Ph.D., CSO, Complix NV

Hapten-Bispecific Antibodies for Drug Discovery and Delivery Applications

Ulrich Brinkmann, Ph.D., Expert Scientist, Roche Innovation Center

Cellular FRET Assay for the Determination of Simultaneous Binding of Bispecific Antibodies

Stefan Seeber, Ph.D., Principal Scientist, Cell Line and Molecule Development, Roche Innovation Center Munich/Large Molecule Research

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From: Bispecific Antibodies <katiev@pegsummiteurope.com>

Date: Tuesday, July 12, 2016 at 9:22 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Latest T-Cell Engagement Research from Pfizer, Covagen, Immunocore & Glenmark

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Hercules Capital Secures up to $30 Million for Aprecia’s proprietary ZipDose(®) technology platform, that utilizes three dimensional printing (3DP) to formulate fast melt pharmaceutical products

Reporter: Aviva Lev-Ari, PhD, RN

Aprecia Pharmaceuticals Secures up to $30 Million from Hercules Capital

LANGHORNE, Pa., July 5, 2016 /PRNewswire/ — Aprecia Pharmaceuticals Company (Aprecia), a commercial stage pharmaceutical company developing, manufacturing and marketing fast melt formulations of high dose pharmaceuticals, today announced that it has entered into an up to $30 million debt financing agreement with Hercules Capital, Inc.. Aprecia manufactures its products using its proprietary ZipDose(®) technology platform, that utilizes three dimensional printing (3DP) to formulate fast melt pharmaceutical products, which incorporates significantly higher amounts of active pharmaceutical ingredient than any other fast melt technology on the market.

Aprecia has received initial funding of $20 million under the debt financing agreement. The proceeds will be used to purchase additional manufacturing equipment, fund the development and approval of Aprecia’s pipeline product candidates and continue to advance its ZipDose technology platform. Under the terms of the agreement, Aprecia has the option to draw up to an additional $10 million tranche upon achievement of a certain performance milestone. Armentum Partners acted as financial advisor and Morgan, Lewis & Bockius LLP acted as legal advisor to Aprecia for this transaction.

About Aprecia

Aprecia is a commercial stage pharmaceutical company developing, manufacturing and marketing fast melt formulations of high dose pharmaceuticals, initially focused on epilepsy and other central nervous system disorders. Aprecia manufactures its products using its proprietary ZipDose technology platform, which utilizes 3DP, to formulate fast melt pharmaceutical products. We launched our first commercial product, SPRITAM(®), in the United States in March 2016. SPRITAM is the only fast melt formulation of levetiracetam and the first pharmaceutical product formulated using 3DP that is approved by the U.S. Food and Drug Administration. Aprecia is privately owned, with affiliates of Prasco, LLC and the Arington family holding a controlling interest. The company’s largest institutional investors are Deerfield Management Company and Great American Insurance Company. For more information visit http://www.aprecia.com.

About Hercules Capital

Hercules Capital, Inc. (NYSE: HTGC) (“Hercules”) is the leading and largest specialty finance company focused on providing senior secured venture growth loans to high-growth, innovative venture capital-backed companies in a broadly diversified variety of technology, life sciences and sustainable and renewable technology industries. Since inception (December 2003), Hercules has committed more than $6.0 billion to over 350 companies and is the lender of choice for entrepreneurs and venture capital firms seeking growth capital financing. Companies interested in learning more about financing opportunities should contact info@htgc.com, or call 650.289.3060.

Forward Looking Statements

Statements in this press release that are not historical facts are forward-looking statements and are subject to risks, assumptions and uncertainties that could cause actual future events or results to differ materially from such statements.

SOURCE Aprecia Pharmaceuticals Company

Aprecia Pharmaceuticals Company

CONTACT: Jennifer.Zieverink@Aprecia.com, 513.864.4114

Web Site: http://www.aprecia.com

SOURCE

From: “Dr. Katie Katie Siafaca” <info@newmedinc.com>

Reply-To: “Dr. Katie Katie Siafaca” <info@newmedinc.com>

Date: Tuesday, July 5, 2016 at 11:40 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: fw: Aprecia Pharmaceuticals Secures up to $30 Million from Hercules Capital

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