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Real Time Coverage @BIOConvention #BIO2019: Keynote Address Jamie Dimon CEO @jpmorgan June 5 Philadelphia

Reporter: Stephen J. Williams, PhD @StephenJWillia2

 

  • Dr Janet Woodcock from FDA was given the BIO Heritage award for leading the FDA from safety focus of 90s to the Voice of the Patient. She became a champion for advocacy groups
  • Governor Phil Murphy, Governor of New Jersey, received the Governor of the Year Award.  New Jersey known as medicine chest of the world, have first 3D printed drug on market and number two in biotech and number one on drug approvals.  We must do more to foster stem education.  It will take private and public capital investment.  New Jersey matches federal dollars and had doubled the angel investor tax credit.
  • Dr. Kakkis CEO of Ultragenix wins the Genzyme Henri Termeer Award for visionary work.  Dr. Termeer recently passed.  Dr. Kakkis is awarded for work with patients of rare diseases and help formulating legislation to help patients with rare disease have access to investigational drugs quickly.
  • Dr. Jeremy Levin from OVID named new chair of BIO

Interview with Jamie Dimon, CEO of JPMorgan

  • Mr Dimon had recently survived throat cancer and now has a renewed dedication to improving people’s lives.  With Amazon had embarked on a nonprofit experimental model to streamline healthcare for their employees.  He said the hardest part of going through cancer was telling his parents and children.
  • On the bailout he said it was a lie all banks needed TARP but could not just give to some and not all.  He says the financial system in US is very solid so next downturn will not come from financial sector and never is from geopolitical but trade issues could be a catalyst. Policy usually always does the opposite of what is intended.  He announced no intention of running for President of US.
  • We need to keep a growth agenda which includes education and infrastructure, without these competitive business tax relief does no account for much.  We need a better conversation of how government handles finances
  • Immigration, education very important.  Higher education needs to reduce costs and incentivize the people they bring in to stay here.
  • on healthcare:  JPM had reduced the deductables to zero for workers making $60,000 or less

Please follow LIVE on TWITTER using the following @ handles and # hashtags:

@Handles

@pharma_BI

@AVIVA1950

@BIOConvention

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#BIO2019 (official meeting hashtag)

Other Article on this Open Access Journal on Global Partnerships, Global Investing and JPMorgan Include:

 

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UPDATED – Gene Editing Consortium of Biotech Companies: CRISPR Therapeutics $CRSP, Intellia Therapeutics $NTLA, Caribou Biosciences, ERS Genomics, UC, Berkeley (Doudna’s IP) and University of Vienna (Charpentier’s IP), is appealing the decision ruled that there was no interference between the two sides, to the U.S. Court of Appeals for the Federal Circuit, targeting patents from The Broad Institute.

 

Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED on 8/1/2019

Unpatentable claims

In its newest brief, UC identified a list of motions it would like permission to file with the PTAB. Among these motions, UC has asked the PTAB to judge all the Broad’s claims involved in the interference unpatentable.

First, UC alleges that the Broad’s patents fall under the provisions of AIA’s “first to file” system. All of the Broad’s involved cases issued from applications with a filing date on or after March 16, 2013 when the AIA took effect, but claim priority benefit to one or more applications filed before that date, the motion said. However, the Broad’s involved cases and/or the applications involved in the cases “contains or contained at one time at least one claim that was not supported by Broad’s applications filed before March 16, 2013,” the university added. “Thus, Broad’s involved cases, the application from which each of Broad’s involved patents issued, and/or a parent application to which each of Broad’s involved cases claims benefit, contains or contained at one time at least one claim to subject matter having an effective filing date on or after March 16, 2013 — thereby subjecting each of Broad’s involved cases to AIA prior art provisions.”

In its filing, UC noted that this motion should be enough for the PTAB to decide the unpatentability of the Broad’s claims. However, the filing adds, if this argument isn’t enough, there are other provisions that would render the Broad’s claims unpatentable.

Misidentified inventors

In the next motion, UC claims that “Broad deliberately misidentified the inventors on its involved patents and application, as demonstrated by the fact that its own prosecuting attorney’s sworn declaration contradicts the inventive entities named during prosecution of the involved applications.”

The Broad’s patents name either Zhang as the sole inventor or Zhang in combination with Le Cong, Fei Ran, Randall Platt, Patrick Hsu, and/or Sanjana. However, UC claims, Broad attorney Thomas Kowalski identified “a substantially different set of inventors” in a declaration provided to the European Patent Office.” Specifically, Kowalski’s declaration attests that several individuals who weren’t listed on the official patents “had contributed in a not insubstantial manner” to various CRISPR inventions, including Cong, Ran, Shuailiang Lin, Platt, Ophir Shalem, Matthias Heidenreich, and Lukasz Swiech.

“As one example, Broad’s attorney determined that Dr. Cong contributed to the invention of ‘the CRISPR-Cas9 system adapted in for [sic] uses in eukaryotic cells,’ a critical feature of every involved claim in the Interference. But Dr. Cong is not named on 8 of the 14 patents/application involved,” UC’s motion notes. “If all inventors are not named, then a patent or application is unpatentable unless it is corrected.”

“Inequitable… untrue… materially false”

UC’s next motion, alleging the Broad engaged in “inequitable conduct” is the most explosive, however.

The university said that the Broad’s claims are unpatentable because it made “at least one affirmative material misstatement” in each of its applications. Specifically, UC alleges that Zhang made statements he knew to be “untrue” at the time he made them, and that Sanjana had made a “materially false declaration.”

Zhang alleged in his declaration that he had a complete conception and reduction to practice of the technology he’d claimed he’d invented, USC said. But the university alleges that the evidence shows Zhang’s experiments failed to include tracrRNA, which is a required component of a functional CRISPR-Cas9 cleavage complex.

“The evidence shows that Dr. Zhang did not include tracrRNA in his experiments to form a CRISPR-Cas9 complex at that time and therefore could not have had a complete conception, much less a reduction to practice, of a functional CRISPR-Cas9 system for cleaving DNA,” UC wrote.

The university also claimed that Zhang didn’t include tracrRNA in his CRISPR-Cas9 complex until after he’d read a 2012 Science paper co-authored by Doudna, Charpentier, and Martin Jinek, which showed that tracrRNA is essential for cleavage of target DNA.

“Dr. Zhang was aware of the Jinek paper, and cited it in his own publications before he signed his declaration and before his counsel submitted it to the [USPTO],” UC said.

UC also accused Zhang of omitting unfavorable data and context from a summary panel the Broad showed the patent office. The full data would have showed the experimental failure of not including tracrRNA, as well as Zhang’s “failure to understand the criticality of tracrRNA at the time he conducted the experiments,” UC said.

“The Broad’s affirmative mischaracterization of data… is part of a larger pattern of deception,” the university added. In filing a claim for one of the involved patents, the Broad submitted a declaration from Sanjana, stating that the researchers had achieved successful cleavage of target DNA in eukaryotic cells by a CRISPR-Cas9 system comprising a single-guide RNA. As evidence, the team included a copy of an experimental gel. But UC said that gel was misrepresented, and clearly shows that Zhang and Sanjana’s experiment was “a failure.”

By presenting the gel as proof of a successful experiment, UC added, “Sanjana materially misstated facts in an attempt to prove an even earlier date of invention. Those acts evidence Broad’s pattern of deceptive behavior in its dealings with the patent office.”

In its supporting documents, UC submitted a February 2015 email from Shuailiang Lin, a researcher who had worked in Zhang’s lab from 2011 to 2012 and who was listed as an inventor on the Broad’s provisional applications.

“The 15-page declaration of [Feng Zhang] and Le Cong’s luciferase data is mis- and overstated to change the examiner’s decision, which seems to be a joke. After seeing your in virto [sic, in vitro] paper, Feng Zhang and Le Cong quickly jumped to the project without letting me know. My lab notebooks, emails and other files like dropbox or gel pictures recorded every step of the lab’s failure process. I am willing to give more details and records if you are interested or whoever is interested to clear the truth. We did not work it out before seeing your paper, it’s really a pity,” the e-mail said, according to UC’s filing.

The bottom line, UC concluded, is that the Broad’s patents should be canceled.

SOURCE

https://www.genomeweb.com/business-news/crispr-patent-fight-turns-ugly-uc-accuses-broad-researchers-lying-about-claims#.XUNJBJNKggo

https://www.statnews.com/2019/07/31/latest-crispr-patent-fight-mudslinging/

https://acts.uspto.gov/ifiling/PublicView.jsp?identifier=106115&identifier2=null&tabSel=4&action=filecontent&replyTo=PublicView.jsp

 

UPDATED on 3/2/2019

U.S. patent office indicates it will issue third CRISPR patent to UC

Patent involved in interference proceedings will add to university’s gene-editing portfolio

The U.S. Patent and Trademark Office has issued a notice of allowance for a University of California patent application covering systems and methods for using single molecule guide RNAs that, when combined with the Cas9 protein, create more efficient and effective ways for scientists to target and edit genes. U.S. patent application number 13/842,859, which had notably been examined in advance of a prior interference proceeding involving the Broad Institute, specifically focuses on methods and systems for modifying a target DNA molecule in any setting, both in vitro and within live cells, using one or multiple single guide RNAs, across every cell type. The associated patent is expected to issue in the next 6-9 weeks.

This CRISPR-Cas9 DNA-targeting technology, invented by Jennifer Doudna and Martin Jinek of the University of California, Berkeley, along with Emmanuelle Charpentier at Umea University and Krzystof Chylinski at the University of Vienna, is a fundamental molecular tool for editing genes. Together, this patent application and prior U.S. Patent Numbers 10,000,772 and 10,113,167, cover CRISPR-Cas9 methods and compositions useful as gene-editing scissors in any setting, including in vitro, as well as within live plant, animal and human cells.

“We are pleased the patent application is now allowed and that the issued patent will encompass the use of CRISPR-Cas9 technology in any cellular or non-cellular environment. We expect to see continued momentum in the expansion of UC’s CRISPR patent portfolio in the coming months,” said Eldora L. Ellison, Ph.D., lead patent strategist on CRISPR matters for the University of California and a director at Sterne, Kessler, Goldstein & Fox. “The steadfast protection of the CRISPR intellectual property pioneered by the Doudna-Charpentier team is wholly focused on the improvement of human welfare.”

SOURCE

https://news.berkeley.edu/2019/02/08/u-s-patent-office-indicates-it-will-issue-third-crispr-patent-to-uc/

UPDATED on 11/22/2017

John Leonard to helm Intellia

SOURCE

https://endpts.com/synergy-ceo-passes-torch-to-cco-troy-hamilton-president-steven-kafka-resigns-from-foundation-abbvie-vet-john-leonard-to-helm-intellia/?utm_medium=email&utm_campaign=376%20Friday%20122217%20Year-end%20biotech%20bash%20FDA%20approves%20record%2046th%20drug%20Roche%20triggers%2017B%20buyout%20JJ%20pays%20350M%20for%20BCMA%20pact&utm_content=376%20Friday%20122217%20Year-end%20biotech%20bash%20FDA%20approves%20record%2046th%20drug%20Roche%20triggers%2017B%20buyout%20JJ%20pays%20350M%20for%20BCMA%20pact+CID_1bdfc3dd8fa117ef7d943125e8d312d8&utm_source=ENDPOINTS%20emails&utm_term=Synergy%20CEO%20passes%20torch%20to%20CCO%20Troy%20Hamilton%20President%20Steven%20Kafka%20resigns%20from%20Foundation%20AbbVie%20vet%20John%20Leonard%20to%20helm%20Intellia

See Background:

UPDATED – Status “Interference — Initial memorandum” – CRISPR/Cas9 – The Biotech Patent Fight of the Century

 

|
Source: Intellia Therapeutics, Inc.
  • Appeal to the U.S. Court of Appeals for the Federal Circuit seeks review and reversal of the Patent Trial and Appeals Board’s (PTAB) decision to terminate CRISPR/Cas9 interference
  • In parallel, the companies and their licensors plan to pursue additional patents in the U.S. and worldwide covering the CRISPR/Cas9 technology and its use in cellular and non-cellular settings, including eukaryotic cells

BASEL, Switzerland;

CAMBRIDGE, Massachusetts;

BERKELEY, California;

DUBLIN, Ireland,

April 13, 2017

(GLOBE NEWSWIRE) — CRISPR Therapeutics (NASDAQ:CRSP), Intellia Therapeutics (NASDAQ:NTLA), Caribou Biosciences and ERS Genomics announced today that The Regents of the University of California, the University of Vienna, and Dr. Emmanuelle Charpentier (collectively “UC”), co-owners of foundational intellectual property relating to CRISPR/Cas9 genome engineering, have appealed to the U.S. Court of Appeals for the Federal Circuit (the “Federal Circuit”) the decision by the Patent Trial and Appeal Board (“PTAB”) to terminate the interference between certain CRISPR/Cas9 patent claims owned by UC and patents and patent applications owned by the Broad Institute, Harvard University and the Massachusetts Institute of Technology (collectively, “Broad”).

In the appeal, UC is seeking review and reversal of the PTAB’s February 15, 2017 decision, which terminated the interference without determining which inventors actually invented the use of the CRISPR/Cas9 genome editing technology in eukaryotic cells. In its decision, the PTAB concluded that, although the claims overlap, the respective scope of UC and Broad’s claim sets as presented did not define the same patentable invention and, accordingly, terminated the interference without deciding which party first invented the use of the CRISPR/Cas9 technology in eukaryotic cells. UC is asking the Federal Circuit to review and reverse the PTAB’s decision.

In parallel with the appeal, UC is pursuing applications in the U.S. and other jurisdictions worldwide to obtain patents claiming the CRISPR/Cas9 technology and its use in non-cellular and cellular settings, including eukaryotic cells. Corresponding patents have already been granted in the United Kingdom, and the European Patent Office is also granting a patent to UC, which will issue on May 10, 2017. UC’s earliest patent application describing the CRISPR/Cas9 genome editing technology and its use was filed on May 25, 2012, while the Broad’s earliest patent application was filed more than six months later, on December 12, 2012.

The law firm of Munger, Tolles & Olson LLP will be handling the appeal, with Don Verrilli, former Solicitor General of the United States, as lead counsel.

SOURCE

https://globenewswire.com/news-release/2017/04/13/960152/0/en/CRISPR-Therapeutics-Intellia-Therapeutics-Caribou-Biosciences-and-ERS-Genomics-Announce-Appeal-of-CRISPR-Cas9-U-S-Patent-Board-Decision.html

 

Editas’ rivals appeal a recent setback on patent fight, mapping a global war for CRISPR supremacy

They say they are “pursuing applications in the U.S. and other jurisdictions worldwide to obtain patents claiming the CRISPR/Cas9 technology and its use in non-cellular and cellular settings, including eukaryotic cells. Corresponding patents have already been granted in the United Kingdom, and the European Patent Office is also granting a patent to UC, which will issue on May 10, 2017. UC’s earliest patent application describing the CRISPR/Cas9 genome editing technology and its use was filed on May 25, 2012, while the Broad’s earliest patent application was filed more than six months later, on December 12, 2012.”

The group said today it is also waging a global patent battle for CRISPR/Cas9 supremacy over Editas and its scientific founder, Feng Zhang, who patented the rival technology at The Broad.

SOURCE

https://endpts.com/editas-rivals-appeal-a-recent-setback-on-patent-fight-mapping-a-global-war-for-crispr-supremacy/?utm_medium=email&utm_campaign=201%20Thursday%2041317%20Biogen%20Roche%20forge%2011B%20in%20deals%20for%20Bristol%20drugs%20Busy%20week%20for%20the%20biotech%20jobs%20scene&utm_content=201%20Thursday%2041317%20Biogen%20Roche%20forge%2011B%20in%20deals%20for%20Bristol%20drugs%20Busy%20week%20for%20the%20biotech%20jobs%20scene+CID_1d65272f5e757d7ae0245395295e6e12&utm_source=ENDPOINTS%20emails&utm_term=Editas%20rivals%20appeal%20a%20recent%20setback%20on%20patent%20fight%20mapping%20a%20global%20war%20for%20CRISPR%20supremacy

 

REFERENCES

Other press releases by Intellia Therapeutics, Inc.

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Milestones in Physiology & Discoveries in Medicine and Genomics: Request for Book Review Writing on Amazon.com


physiology-cover-seriese-vol-3individualsaddlebrown-page2

Milestones in Physiology

Discoveries in Medicine, Genomics and Therapeutics

Patient-centric Perspective 

http://www.amazon.com/dp/B019VH97LU 

2015

 

 

Author, Curator and Editor

Larry H Bernstein, MD, FCAP

Chief Scientific Officer

Leaders in Pharmaceutical Business Intelligence

Larry.bernstein@gmail.com

Preface

Introduction 

Chapter 1: Evolution of the Foundation for Diagnostics and Pharmaceuticals Industries

1.1  Outline of Medical Discoveries between 1880 and 1980

1.2 The History of Infectious Diseases and Epidemiology in the late 19th and 20th Century

1.3 The Classification of Microbiota

1.4 Selected Contributions to Chemistry from 1880 to 1980

1.5 The Evolution of Clinical Chemistry in the 20th Century

1.6 Milestones in the Evolution of Diagnostics in the US HealthCare System: 1920s to Pre-Genomics

 

Chapter 2. The search for the evolution of function of proteins, enzymes and metal catalysts in life processes

2.1 The life and work of Allan Wilson
2.2  The  evolution of myoglobin and hemoglobin
2.3  More complexity in proteins evolution
2.4  Life on earth is traced to oxygen binding
2.5  The colors of life function
2.6  The colors of respiration and electron transport
2.7  Highlights of a green evolution

 

Chapter 3. Evolution of New Relationships in Neuroendocrine States
3.1 Pituitary endocrine axis
3.2 Thyroid function
3.3 Sex hormones
3.4 Adrenal Cortex
3.5 Pancreatic Islets
3.6 Parathyroids
3.7 Gastointestinal hormones
3.8 Endocrine action on midbrain
3.9 Neural activity regulating endocrine response

3.10 Genomic Promise for Neurodegenerative Diseases, Dementias, Autism Spectrum, Schizophrenia, and Serious Depression

 

Chapter 4.  Problems of the Circulation, Altitude, and Immunity

4.1 Innervation of Heart and Heart Rate
4.2 Action of hormones on the circulation
4.3 Allogeneic Transfusion Reactions
4.4 Graft-versus Host reaction
4.5 Unique problems of perinatal period
4.6. High altitude sickness
4.7 Deep water adaptation
4.8 Heart-Lung-and Kidney
4.9 Acute Lung Injury

4.10 Reconstruction of Life Processes requires both Genomics and Metabolomics to explain Phenotypes and Phylogenetics

 

Chapter 5. Problems of Diets and Lifestyle Changes

5.1 Anorexia nervosa
5.2 Voluntary and Involuntary S-insufficiency
5.3 Diarrheas – bacterial and nonbacterial
5.4 Gluten-free diets
5.5 Diet and cholesterol
5.6 Diet and Type 2 diabetes mellitus
5.7 Diet and exercise
5.8 Anxiety and quality of Life
5.9 Nutritional Supplements

 

Chapter 6. Advances in Genomics, Therapeutics and Pharmacogenomics

6.1 Natural Products Chemistry

6.2 The Challenge of Antimicrobial Resistance

6.3 Viruses, Vaccines and immunotherapy

6.4 Genomics and Metabolomics Advances in Cancer

6.5 Proteomics – Protein Interaction

6.6 Pharmacogenomics

6.7 Biomarker Guided Therapy

6.8 The Emergence of a Pharmaceutical Industry in the 20th Century: Diagnostics Industry and Drug Development in the Genomics Era: Mid 80s to Present

6.09 The Union of Biomarkers and Drug Development

6.10 Proteomics and Biomarker Discovery

6.11 Epigenomics and Companion Diagnostics

 

Chapter  7

Integration of Physiology, Genomics and Pharmacotherapy

7.1 Richard Lifton, MD, PhD of Yale University and Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension

7.2 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

7.3 Diagnostics and Biomarkers: Novel Genomics Industry Trends vs Present Market Conditions and Historical Scientific Leaders Memoirs

7.4 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

7.5 Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

7.6 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

7.7 Neuroprotective Therapies: Pharmacogenomics vs Psychotropic drugs and Cholinesterase Inhibitors

7.8 Metabolite Identification Combining Genetic and Metabolic Information: Genetic association links unknown metabolites to functionally related genes

7.9 Preserved vs Reduced Ejection Fraction: Available and Needed Therapies

7.10 Biosimilars: Intellectual Property Creation and Protection by Pioneer and by

7.11 Demonstrate Biosimilarity: New FDA Biosimilar Guidelines

 

Chapter 7.  Biopharma Today

8.1 A Great University engaged in Drug Discovery: University of Pittsburgh

8.2 Introduction – The Evolution of Cancer Therapy and Cancer Research: How We Got Here?

8.3 Predicting Tumor Response, Progression, and Time to Recurrence

8.4 Targeting Untargetable Proto-Oncogenes

8.5 Innovation: Drug Discovery, Medical Devices and Digital Health

8.6 Cardiotoxicity and Cardiomyopathy Related to Drugs Adverse Effects

8.7 Nanotechnology and Ocular Drug Delivery: Part I

8.8 Transdermal drug delivery (TDD) system and nanotechnology: Part II

8.9 The Delicate Connection: IDO (Indolamine 2, 3 dehydrogenase) and Cancer Immunology

8.10 Natural Drug Target Discovery and Translational Medicine in Human Microbiome

8.11 From Genomics of Microorganisms to Translational Medicine

8.12 Confined Indolamine 2, 3 dioxygenase (IDO) Controls the Homeostasis of Immune Responses for Good and Bad

 

Chapter 9. BioPharma – Future Trends

9.1 Artificial Intelligence Versus the Scientist: Who Will Win?

9.2 The Vibrant Philly Biotech Scene: Focus on KannaLife Sciences and the Discipline and Potential of Pharmacognosy

9.3 The Vibrant Philly Biotech Scene: Focus on Computer-Aided Drug Design and Gfree Bio, LLC

9.4 Heroes in Medical Research: The Postdoctoral Fellow

9.5 NIH Considers Guidelines for CAR-T therapy: Report from Recombinant DNA Advisory Committee

9.6 1st Pitch Life Science- Philadelphia- What VCs Really Think of your Pitch

9.7 Multiple Lung Cancer Genomic Projects Suggest New Targets, Research Directions for Non-Small Cell Lung Cancer

9.8 Heroes in Medical Research: Green Fluorescent Protein and the Rough Road in Science

9.9 Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

9.10 The SCID Pig II: Researchers Develop Another SCID Pig, And Another Great Model For Cancer Research

Epilogue

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Licensing Agreements for CRISPR/Cas9 Genome Editing Technology Patent

Curator: Aviva Lev-Ari, PhD, RN

AstraZeneca’s CRISPR research collaborations are with the following institutions:

The Wellcome Trust Sanger Institute, Cambridge, UK

Under the terms of the collaboration with the Wellcome Trust Sanger Institute, research will focus on deleting specific genes relevant to cancer, cardiovascular, metabolic, respiratory, autoimmune & inflammatory diseases and regenerative medicine to understand their precise role in these conditions. AstraZeneca will provide cell lines that can be targeted using the Sanger Institute’s collection of genome-wide CRISPR guide-RNA libraries to generate populations of cells in which defined genes are switched off. Genes will subsequently be identified by next-generation sequencing and cell populations tested to validate the effects of a given gene on a wide range of physical and biological traits.

“The Sanger Institute’s guide-RNA library enables researchers to target genes with incredible specificity,” said Dr. Kosuke Yusa, Member of Faculty at the Sanger Institute. “CRISPR has transformed the way we study the behaviour of cells and now the application of this powerful technology to the search for effective drugs has the potential to benefit patients.”

The Innovative Genomics Initiative, California

The Innovative Genomics Initiative (IGI) is a joint venture between the University of California, Berkeley and University of California, San Francisco. The research collaboration will focus on either inhibiting (CRISPRi) or activating (CRISPRa) genes to understand their role in disease pathology. The IGI and AstraZeneca will work closely together to identify and validate gene targets relevant to cancer, cardiovascular, metabolic, respiratory, autoimmune and inflammatory diseases and regenerative medicine to understand their precise role in these conditions.

“We are excited to pair the IGI’s premier expertise in CRISPR gene editing and regulation with AstraZeneca’s deep experience in therapeutics,” said Jacob Corn, Scientific Director of the Innovative Genomics Initiative. “I’m confident that, working side-by-side with scientists at AstraZeneca, our collaboration will positively impact drug discovery and development to hasten treatments to patients.”

Thermo Fisher Scientific, Waltham, Massachusetts

Under the terms of the collaboration with Thermo Fisher Scientific, a world-leading reagent and instrument provider, AstraZeneca will receive RNA-guide libraries that target individual known human genes and gene families. AstraZeneca can screen these guides against cell lines to identify new disease targets.

“Through this research collaboration with AstraZeneca, Thermo Fisher is helping to accelerate access to cutting edge genome-editing applications for next generation drug discovery. Enabling more relevant disease models will improve target identification and translation to therapeutics,” said Dr. Jon Chesnut, Director of Synthetic Biology R&D at Thermo Fisher Scientific.

Broad Institute/Whitehead Institute, Cambridge, Massachusetts

The collaboration with the Broad Institute and Whitehead Institute will evaluate a genome-wide CRISPR library against a panel of cancer cell lines with a view to identifying new targets for cancer drug discovery.

In addition to the new collaborations, AstraZeneca’s in-house programme is currently adapting CRISPR technology to streamline and accelerate the production of cell lines and translational models that mimic complex genomic and disease-relevant scenarios.

“Application of the CRISPR technology for precise genome editing in recombinant cell lines and in relevant disease models should enable us to identify novel targets, build better test systems for drug discovery and enhance the translatability of our efficacy and safety models,” said Dr. Lorenz Mayr, Vice President, Reagents & Assay Development, AstraZeneca.

The short video above explaining how CRISPR technology works is available in English, Mandarin and Spanish, and a still image illustrating the technology is available.

Download broadcast video and high-resolution image

About The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute is one of the world’s leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.http://www.sanger.ac.uk/

About Innovative Genomics Initiative

The Innovative Genomics Initiative (IGI) was established in early 2014 at the Li Ka Shing Center for Genomic Engineering at the University of California, Berkeley, and is a joint UC Berkeley/UC San Francisco initiative catalyzing and guiding the global effort in both the academic and commercial research communities to unleash the transformative potential of CRISPR/Cas9 technology for positive human impact.

About the Broad Institute of Harvard and MIT

The Eli and Edythe L. Broad Institute of Harvard and MIT was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.

Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to http://www.broadinstitute.org.

About Whitehead Institute

Whitehead Institute is a world-renowned non-profit research institution dedicated to improving human health through basic biomedical research. Wholly independent in its governance, finances, and research programs, Whitehead shares a close affiliation with Massachusetts Institute of Technology through its faculty, who hold joint MIT appointments. http://wi.mit.edu

About Thermo Fisher Scientific

Thermo Fisher Scientific Inc. is the world leader in serving science, with revenues of $17 billion and 50,000 employees in 50 countries. Our mission is to enable our customers to make the world healthier, cleaner and safer. We help our customers accelerate life sciences research, solve complex analytical challenges, improve patient diagnostics and increase laboratory productivity. Through our four premier brands – Thermo Scientific, Life Technologies, Fisher Scientific and Unity Lab Services – we offer an unmatched combination of innovative technologies, purchasing convenience and comprehensive support. For more information, please visit www.thermofisher.com.

SOURCE

https://www.astrazeneca.com/media-centre/press-releases/2015/astrazeneca-crispr-technology-genome-editing-29012015.html

Novartis

  • Caribou BioSciences – Jennifer Daudna
  • Intellia

Novartis bought in to Intellia–as well as Caribou, which out-licensed some pioneering CRISPR tech created by Jennifer Doudna at UC Berkeley–with a clear interest in tapping the science for its ambitious CAR-T work reengineering T cells into cancer weapons. John Leonard was wooed in from the Big Pharma world, after a stint in charge of R&D at AbbVie ($ABBV). And gene editing–deleting, repairing and inserting genetic information to correct an ailment–has what is widely viewed as a potent future in devising a new generation of potential cures.

“CRISPR/Cas9 technology has potential to transform medicine by addressing previously untreatable genetic targets and serving as the basis for new and better therapies,” said Leonard in a statement. “This novel technology could potentially eliminate many severely disabling and life-threatening diseases for patients.”

But after the Big Vision, detailed insights into the company’s plans can be hard to glean. Asked about the apparent likelihood of an IPO in the offing, CEO Nessan Bermingham declined comment.

SOURCE

SOURCE

http://www.fiercebiotech.com/story/crispr-player-intellia-looks-ipo-ready-after-70m-round/2015-09-01?utm_medium=nl&utm_source=internal

Bayer LifeScience Center (BLSC)

  • ERS Genomics – Emmanuelle Charpentier
  • CRISPR Therapeutics – Emmanuelle Charpentier and

Bayer Inks CRISPR Patent Licensing Agreement

NEW YORK (GenomeWeb) – Bayer and ERS Genomics announced today that they have signed a patent license agreement, giving the Bayer LifeScience Center (BLSC) access to ERS’s foundational CRISPR/Cas9 genome editing technology.

Financial and other details of the agreement were not disclosed.

ERS Genomics was formed to commercialize patents held by CRISPR pioneer Emmanuelle Charpentier, now director of the Max Planck Institute for Infection Biology. She is a co-inventor on a foundational CRISPR/Cas9 patent application currently at the center of a patent interference trial being conducted by the US Patent and Trademark Office. A team led by the Broad Institute currently holds the key patent for CRISPR/Cas9 technology.

The BLSC has also recently created a joint venture with CRISPR Therapeutics, a firm Charpentier co-founded, to develop new CRISPR-based therapies.

SOURCE

https://www.genomeweb.com/business-news/bayer-inks-crispr-patent-licensing-agreement

Vertex Therapeutics

  • CRISPR Therapeutics – Emmanuelle Charpentier

IDT

  • Caribou BioSciences – Jennifer Daudna

DuPont

  • Caribou BioSciences – Jennifer Daudna

Evotec

  • Broad Institute

Regeneron

  • ERS Genomics – Emmanuelle Charpentier
  • Intellia – Jennifer Daudna

Licensing deal with Regeneron to accelerate CRISPR biotech Intellia (Jennifer Doudna’s Start Up) for an IPO

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/04/12/licensing-deal-with-regeneron-to-accelerate-crispr-biotech-intellia-jennifer-doudnas-start-up-for-an-ipo/

Albany Molecular Research (AMRI)

  • Broad Institute

https://www.genomeweb.com/gene-silencinggene-editing/broad-institute-licenses-crisprcas9-amri?utm_source=SilverpopMailing&utm_medium=email&utm_campaign=Daily%20News:%20Broad%20Institute%20Licenses%20CRISPR/Cas9%20to%20AMRI%20-%2008/24/2016%2011:15:00%20AM

MERCK

  • Moderna Therapeutics

Cases in Biotech Entrepreneurship: Selective Start Ups in 2016

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/03/06/cases-in-biotech-entrepreneurship-selective-start-ups-in-2016/

Moderna Therapeutics Deal with Merck: Are Personalized Vaccines here?

Curator & Reporter: Stephen J. Williams, Ph.D.

https://pharmaceuticalintelligence.com/2016/08/11/moderna-therapeutics-deal-with-merck-are-personalized-vaccines-here/

at #JPM16 – Moderna Therapeutics turns away an extra $200 million: with AstraZeneca (collaboration) & with Merck ($100 million investment)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/13/at-jpm16-moderna-therapeutics-turns-away-an-extra-200-million-with-astrazeneca-collaboration-with-merck-100-million-investment/

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Thriving Three Groups on LinkedIn

Groups Launcher and Group Manager: Aviva Lev-Ari, PhD, RN

 

Cardiovascular Biotech & Pharma UK & US Networking Group

954 members

https://www.linkedin.com/groups/4357927

 

 

Leaders in Pharmaceutical Business Intelligence

350 members

https://www.linkedin.com/groups/4346921

 

 

Innovation in Israel

205 members

https://www.linkedin.com/groups/2987122

 

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PATENT EXPIRY DATES

Reporter: Stephen J Williams, PhD

The global generic pharmaceuticals market is likely to witness strong growth in the next few years owing to the patent expiration of key blockbuster drugs and the judicious cost containment efforts…

Source: PATENT EXPIRY DATES

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TSUNAMI in HealthCare under the New Name Verily.com

Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED on 6/8/2016

The Tricorder project was announced only 3 months after Google entered the life sciences field, according to the report, and came from the same incubator which rolled out the company’s self-driving car and recently cancelled Google Glass.

Verily CEO Andrew Conrad said the scientific basis for the device was proven upon unveiling in 2014, but experts have presented conflicting views on the reality of such a device, STAT Newsreports.

“What (Verily is) really good at is physical measurements — things like temperature, pulse rate, activity level. They are not particularly good at … the chemical and the biological stuff,” Walt toldSTAT news.

Four former Verily employees said the Tricorder “has been seen internally more as a way to generate buzz than as a viable project,” according to the report.

SOURCE

http://www.massdevice.com/googles-star-trek-tricorder-bid-flops/?spMailingID=9031578&spUserID=MTI2MTQxNTczMjM5S0&spJobID=940786327&spReportId=OTQwNzg2MzI3S0

 

UPDATED on 4/16/2016

SOURCE

http://recode.net/2016/04/13/verily-alphabet-profitable/

Verily, Alphabet’s medical business, is profitable, Sergey Brin tells Googlers

20160413-verily-google-life-sciences

Verily | YouTube

SCIENCE

Publicly, Alphabet has said very little about its assortment of companies not named Google.

But internally, Alphabet is a little more forthcoming.

As we reported earlier, Nest CEO Tony Fadell appeared before Google’s all-hands meeting two weeks ago to address recent criticism of his company. During that meeting, Google co-founder and Alphabet exec Sergey Brin also defended another company under the holding conglomerate: Verily, the medical tech unit previously called Google Life Sciences.

Lumped together, Alphabet’s moonshots aren’t making money yet — but Verily is, Brin said.

Verily was the target of a scathing article — in Stat, a medical publication from the Boston Globe — scrutinizing its CEO, Andy Conrad. Several former employees told Stat that Verily suffered a talent exodus due to “derisive and impulsive” leadership by Conrad.

Here’s what Brin said in response at Google’s TGIF meeting:

I have seen a smattering of articles. And, you know, it’s actually sad to see sometimes where it appeared that … former employees or soon-to-be former employees talked to the press. But, anyhow, I can tell you what’s going on with these companies, fortunately. So in Verily’s case, despite a handful of examples, their attrition rate is below Google’s and Alphabet’s as a whole. And also, there are articles that have generally said we are blowing a lot of money and so forth. It’s true that, you know, as whole our Other Bets are not yet profitable, but some of them are, including Verily on a cash basis and increasingly so. So we’re pretty excited about these efforts.

Verily makes money through

  • partnerships with pharmaceutical companies — such as Novartis, which is licensing and planning to sell Verily’s smart contact lens — and
  • medical institutions.

It is one of three units contributing to the Other Bets total revenue ($448 million) in 2015, along with

  • Google Fiber and
  • Nest.

As we reported earlier, Nest likely brought in around $340 million of that and Fiber pulled close to $100 million, meaning that Verily’s sales were somewhere around $10 million. During the year, all the moonshot units combined reported operating losses of $3.6 billion.

Note Brin’s stipulation that Verily’s profit comes on a “cash basis.” That probably means that it’s not making profit on the normal basis, meaning when you take into account total sales minus total costs. But “cash positive” suggests they’re booking sales faster than they’re spending money, which is a positive sign. Companies normally report financials accounting for all costs. And that’s how Alphabet will next week, when it shares first-quarter results for Google and the Other Bets — although we almost certainly won’t see figures on Verily’s profitability.

We reached out to Alphabet and Verily reps for more clarity, but didn’t get any.

SOURCE

http://recode.net/2016/04/13/verily-alphabet-profitable/

 

Original Curation dated 12/14/2015

  1. Part 1: Verily in Action
  2. Part II: Innovations at a Different Scale: GDE Enterprises – A Case in Point of Healthcare in Focus – Work-in-Progress

12/31/2015 – All time

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Part 1: Verily in Action

They write @ https://verily.com/

When Google[x] embarked on a project in 2012 to put computing inside a contact lens — an immensely challenging technical problem with an important application to health — we could not have imagined where it would lead us. As a life sciences team within Google[x], we were able to combine the best of our technology heritage with expertise from across many fields. Now, as an independent company, Verily is focused on using technology to better understand health, as well as prevent, detect, and manage disease.

Andy Conrad, Ph.D.

Chief Executive OfficerFormerly the chief scientific officer of LabCorp, Andy is a cell biologist with a doctorate from UCLA. He has always been passionate about early detection and prevention of disease: Andy co-founded the National Genetics Institute, which developed the first cost-effective test to screen for HIV in blood supply.

Brian Otis, Ph.D.

Chief Technical OfficerBrian’s team focuses on end-to-end innovation ranging from integrated circuits to biocompatible materials to sensors. He joined Google[x] as founder of the smart contact lens project and now leads our efforts across all hardware and device projects, including wearables, implanted devices, and technology like Liftware.

Jessica Mega, M.D., MPH

Chief Medical OfficerJessica leads the clinical strategy and research team at Verily. She is a board-certified cardiologist who trained and practiced at Massachusetts General Hospital and Brigham and Women’s Hospital. As a faculty member at Harvard Medical School and a senior investigator with the TIMI Study Group, Jessica directed large, international trials evaluating novel cardiovascular therapies.

Linus Upson

Head of EngineeringA long-time Google software engineer, Linus has been a team lead in developing products that now help billions of people worldwide find the information they need on the Internet, including Chrome and Chrome OS. He now oversees our engineering teams.

Tom Stanis

Head of SoftwareTom spent nine years working on core Google products before joining Google[x] in 2014 to work on the Baseline Study. He now leads all our Software projects, including the development of machine learning algorithms for applications ranging from robotic-assisted surgery to diabetes management.

Vikram (Vik) Bajaj, Ph.D.

Chief Scientific OfficerVik’s broad research interests in industry and as a former academic principal investigator have included structural and systems biology, molecular imaging, nanoscience, and bioinformatics. Vik now leads the Science team in research directions related to our mission.

What are the Dimensions of the Tsumani in Healthcare?

  • prevention,
  • detection,
  • management of disease

 

Hardware

  • contact lens with an embedded glucose sensor for measuring the glucose in human tears.

Software

  • multiple sclerosis, for example, combines wearable sensors with traditional clinical tests
  • signals that could lead to new knowledge about the disease and why it progresses differently among individuals.

Clinical

  • Constituencies industry, hospitals, government, academic centers, medical societies, and patient advocacy groups
  • The Baseline Study is one of these dedicated efforts, a multi-year initiative that aims to identify the traits of a healthy human by closely observing the transition to disease.

Science

  • Understand processes that lead to conditions like cancer, heart disease, and diabetes
  • computational systems biology platforms and life sciences tools
  • bio-molecular nanotechnology for precision diagnostics and therapeutic delivery
  • advanced imaging methods for applications ranging from early diagnosis to surgical robotics.

 

FOLLOW the LEADER of Parish in the Tsunami

 

Google[x] searches for ways to boost cancer immunotherapy | Science/AAAS | News

http://news.sciencemag.org/math/2015/01/googlex-searches-ways-boost-cancer-immunotherapy

 

Google Life Sciences and American Heart Association commit $50M to study heart disease | VentureBeat

http://venturebeat.com/2015/11/08/google-life-sciences-and-american-heart-association-commit-50m-to-study-heart-disease/

 

Google Life Sciences Division Is Now Called… Verily?

http://gizmodo.com/google-life-sciences-division-is-now-called-verily-1746729894

 

WIRED: Google’s Verily Is Spinning Off ‘Verb,’ a Secretive Robot-Surgery Startup

Alphabet’s Verily, née Google Life Sciences, has announced its first spinoff, a brand new robot-assisted surgery company.

http://www.wired.com/2015/12/googles-verily-is-spinning-off-verb-a-secretive-robot-surgery-startup/

 

Google Life Sciences Rebrands as Verily under Alphabet – Fortune

Vik Bajaj, CSO

http://fortune.com/2015/12/08/google-alphabet-verily/

Verily, I Swear, Google Life Sciences debuts a New Name

By CHARLES PILLER  DECEMBER 7, 2015

http://www.statnews.com/2015/12/07/verily-google-life-sciences-name/

 

Why biomedical superstars are signing on with Google Tech firm’s ambitious goals and abundant resources attract life scientists.

Erika Check Hayden 21 October 2015

http://www.nature.com/news/why-biomedical-superstars-are-signing-on-with-google-1.18600

 

GOOGLE LIFE SCIENCES MAKES DIABETES ITS FIRST BIG TARGET

http://www.wired.com/2015/08/google-life-sciences-makes-diabetes-first-big-target/

 

GOOGLE WON THE INTERNET. NOW IT WANTS TO CURE DISEASES

http://www.wired.com/2015/08/google-won-internet-now-wants-cure-diseases/

 

Google Reveals Health-Tracking Wristband

Caroline Chen and Brian Womack

June 23, 2015 — 9:30 AM EDT

http://www.bloomberg.com/news/articles/2015-06-23/google-developing-health-tracking-wristband-for-health-research

 

Google Moves to the Operating Room in Robotics Deal With J&J

ALISTAIR BARR and JOSEPH WALKER

http://blogs.wsj.com/digits/2015/03/27/google-moves-to-the-operating-room-in-robotics-deal-with-jj/

 

Google, Biogen Seek Reasons for Advance of Multiple Sclerosis

Caroline Chen

January 27, 2015 — 9:00 AM EST

http://www.bloomberg.com/news/articles/2015-01-27/google-biogen-seek-reasons-for-advance-of-multiple-sclerosis

 

Google’s Newest Search: Cancer Cells

Google X Team Hopes to Develop Nanoparticles to Provide Early Detection of Cancer, Other Diseases

ALISTAIR BARR and RON WINSLOW

Updated Oct. 29, 2014 11:17 a.m. ET

http://www.wsj.com/articles/google-designing-nanoparticles-to-patrol-human-body-for-disease-1414515602

 

A Spoon That Shakes To Counteract Hand Tremors

Updated May 14, 201411:43 AM ET

INA JAFFE

http://www.npr.org/sections/health-shots/2014/05/13/310399325/a-spoon-that-shakes-to-counteract-hand-tremors

 

Google’s New Moonshot Project: the Human Body

Baseline Study to Try to Create Picture From the Project’s Findings

ALISTAIR BARR

Updated July 27, 2014 7:24 p.m. ET

http://www.wsj.com/articles/google-to-collect-data-to-define-healthy-human-1406246214

 

Novartis Joins With Google to Develop Contact Lens That Monitors Blood Sugar

MARK SCOTT JULY 15, 2014

http://www.nytimes.com/2014/07/16/business/international/novartis-joins-with-google-to-develop-contact-lens-to-monitor-blood-sugar.html

 

Google[x] searches for ways to boost cancer immunotherapy

Jon Cohen

15 January 2015 6:25 am

http://news.sciencemag.org/math/2015/01/googlex-searches-ways-boost-cancer-immunotherapy

 

SOURCE

https://verily.com/

Part II: Innovations at a Different Scale: GDE Enterprises

A Case in Point of Healthcare in Focus –

Work-in-Progress

 

 

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Pharmacy International Conference

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

 

3rd Nirma Institute of Pharmacy International Conference
NIPiCON – 2016
January 21 – 23, 2016 ………….http://www.nipicon.org/.

Anthony Melvin Crasto   https://www.facebook.com/groups/worlddrugtracker/permalink/1170816792946389/

The pharmaceutical sciences is a dynamic and interdisciplinary field that combines a broad range of scientific disciplines that are critical to the discovery and development of new drugs and therapies. Over the years, pharmaceutical scientists have been instrumental in discovering and developing innovative drugs that save people’s lives and improve the quality of life.

NIPiCON was initiated in a year 2013 to offer a common platform for academicians, researchers, industrialists, clinical practitioners and young budding pharmacists to share their ideas and research work and finally emerge with new concepts, innovations and novel strategies for various challenges in the pharmaceutical field.

The 3 International Conference, NIPiCON 2016 aims to provide a knowledge sharing experience in the area of “Global Challenges in Drug Discovery, Development and Regulatory Affairs”.

Pharmaceutical innovation is a complex creative process that harnesses the application of knowledge and creativity for discovering, developing and bringing to clinical use, new medicinal products that extend or improve the lives of patients.A successful pharmaceutical R&D process is one that minimizes the time and cost needed to bring a compound from the scientific ‘idea’, through discovery and clinical development, to final regulatory approval and delivery to the patient. This conference will provide an open forum for the academicians, researchers, clinicians and professionals of pharmaceutical industry to enrich their knowledge in the area of drug discovery, development and its regulatory requirements.

The conference features plenary sessions which will be delivered by eminent national and international speakers from different disciplines of pharmaceutical field. In addition, there will be invited lectures and sessions delivered by distinguished and young researchers in their respective fields during parallel technical sessions. The conference willalso provide the opportunity to scientists and research scholars from various organizations to put forth their innovative ideas and research findings by means of deliberations, discussions and poster presentations.

 

NIPiCON was initiated in a year 2013 to offer a common platform for academicians, researchers, industrialists, clinical practitioners and young budding pharmacists to share their ideas and research work and finally emerge with new concepts, innovations and novel strategies for various challenges in the pharmaceutical field.

The 3 International Conference, NIPiCON 2016 aims to provide a knowledge sharing experience in the area of “Global Challenges in Drug Discovery, Development and Regulatory Affairs”.

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targeting of GSK-3α and GSK-3β

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

 

4′-((5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-yl-thio)-methyl)-4-fluorobiphenyl-2-carboxamide

by DR ANTHONY MELVIN CRASTO Ph.D

str1

 

Cas 1820758-44-8

C24 H18 F N3 O4 S

4′-((5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-yl-thio)-methyl)-4-fluorobiphenyl-2-carboxamide

https://pharmaceuticalintelligence.wordpress.com/wp-admin/post-new.php

 

Glycogen synthase kinase-3 (GSK-3) is a constitutively active, ubiquitous serine/threonine kinase that takes part in a number of physiological processes ranging from glycogen metabolism to apoptosis. GSK-3 is a key mediator of various signaling pathways, such as the Wnt and the insulin/AKT signaling pathways.

Therefore, dysregulation of GSK-3 has been linked to various human diseases, such as cancer, diabetes, and neurodegenerative diseases.Two related isoforms of GSK-3 exist in mammals, GSK-3α and -β, which share a sequence identity within their catalytic domains of 98%.

Beyond the catalytic domains they show significant differences. Although these isoforms are structurally related, they are not functionally equivalent, and one cannot compensate for loss of the other.

The debate on the respective contributions of the isoforms GSK-3α and GSK-3β on the pathogenesis of different diseases is ongoing.

Various studies indicate that the therapies of certain diseases benefit from specific targeting of GSK-3α and GSK-3β. GSK-3α was recently identified as a differentiation target in acute myeloid leukemia (AML). AML is a hematopoietic malignancy defined by uncontrolled proliferation and disrupted myeloid differentiation. AML is the second most common form of leukemia in adults.

The current treatment of AML with conventional chemotherapy is very aggressive yet ineffective for the majority of patients with the disease.Thus, alternative targeted treatment approaches for AML are highly desirable. GSK-3α recently emerged as a potential target in this disease.

Abstract Image

http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jmcmar/0/jmcmar.ahead-of-print/acs.jmedchem.5b01200/20151105/images/medium/jm-2015-01200x_0015.gif

 

The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML), may require α-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3α selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3α/β with the highest GSK-3α selectivity reported to date. Compound 27was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3α targeting in AML cell lines was achieved with compound 27, resulting in a strong differentiation phenotype and colony formation impairment, confirming the potential of GSK-3α inhibition in AML therapy.

Evaluation of Improved Glycogen Synthase Kinase-3α Inhibitors in Models of Acute Myeloid Leukemia

Clemens Schöpf Institute of Organic Chemistry and Biochemistry, Technische Universität Darmstadt, 64287 Darmstadt, Germany
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, United States
J. Med. Chem., Article ASAP
Publication Date (Web): October 23, 2015   Copyright © 2015 American Chemical Society

http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01200

http://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.5b01200/suppl_file/jm5b01200_si_001.pdf

compound 27 as a colorless solid. HPLC: 96%, tR = 6.93 min.

1H NMR (DMSO-d6, 500 MHz, 300 K): δ (ppm) = 4.32 (td, J = 5.2 Hz, J = 3.7 Hz, 4H), 4.60 (s, 2H), 7.05 (d, J = 8.4 Hz, 1H), 7.25 (dd, J = 9.1 Hz, J = 2.7 Hz, 1H), 7.31 (td, J = 8.6 Hz, J = 2.8 Hz, 1H), 7.38 (m, 3H), 7.41 (d, J = 2.0 Hz, 1H), 7.45 (dd, J = 8.4 Hz, J = 2.1 Hz, 1H), 7.49 (d, J = 8.2 Hz, 2H), 7.73 (s, 1H).

13C NMR (DMSO, 125 MHz, 300 K): δ (ppm) = 35.6, 64.1, 64.4, 114.3 (d, JC–F = 21 Hz), 115.0, 115.9 (d, JC–F = 21 Hz), 115.9, 118.1, 120.0, 128.6 (2C), 128.8 (2C), 132.0 (d, JC–F = 8 Hz), 134.8, 135.5, 138.9, 139.0 (d, JC–F = 7 Hz), 143.8, 146.7, 160.9 (d, JC–F = 247 Hz), 162.7, 164.9, 169.5.

EI-MS: m/z = 463 (100, [M+]), 464 (26, [M+ + H]), 465 (7, [M+ + 2H].

 

 

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