Healthcare analytics, AI solutions for biological big data, providing an AI platform for the biotech, life sciences, medical and pharmaceutical industries, as well as for related technological approaches, i.e., curation and text analysis with machine learning and other activities related to AI applications to these industries.
How Immunotherapy may sometimes make Cancer worse?
Reporter: Aviva Lev-Ari, PhD, RN
A potential explanation is
Advances in Brief Cancer Cell Motility-inhibitory Protein in the Dunning Adenocarcinoma Model1 (2013)
by James L. Mohler , Elaine N. Broskie , Dipak J. Ranparia , Et Al , Contact The Aacr Publications , L. Mohler , Elaine N. Broskie , Dipak J. Ranparia , Yousuf Sharief , William B. Coleman , Cary J. Smith
Some cancer cells may just be more differentiated and therefore easier to kill with immunotherapy. Simultaneously since they are more differentiated they may be the sort of cells that hold more rogue cancer cells in check. http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.326.7968
How Immunotherapy may sometimes make Cancer worse?
Warning signs
Kurzrock began asking around, collecting anecdotes about people — and even about laboratory mice — whose tumours had advanced rapidly after treatment with an immunotherapy. Even after collecting examples from several sources, she felt nervous about releasing her results. “We thought, ‘Who’s going to publish this? They’re not going to believe us,’” she says.
Meanwhile, researchers at the Gustave Roussy Institute in Villejuif, France, had stumbled on the same problem. Charles Ferté, an oncologist at the institute, recalls attending a meeting in which several physicians reported bizarre responses to PD-1 treatment. “Some friends and colleagues were saying, ‘I treated lung patients with that drug and the tumour completely exploded in two weeks’,” says Ferté.
Ferté and his colleagues decided to launch a systematic study of tumour growth in their patients. Last November, they published their results: of 131 people who received anti-PD-1 therapies, 9% developed what the investigators called “hyperprogressive” disease, with accelerated tumour growth1. The phenomenon appeared to be more common in people over the age of 65.
On 28 March, Kurzrock and her colleagues published their data from 155 people treated with PD-1 inhibitors and other immunotherapies2. Six of the people had extra copies of MDM2 or MDM4 and 10 had mutations in a gene called EGFR, which is associated with cancer. The team did not see any correlation between age and rapidly worsening disease, but they did notice that tumours grew faster in four of those with the extra MDM2 or MDM4 genes, and in two of the people with EGFR mutations.
Various cells of the human physiological system have the capability to release extracellular vesicles (EVs) involved in intercellular transport of proteins and nucleic acids. Exosomes are a subtype of extracellular vesicles having their origin through endocytic pathway. While being involved in intercellular transport of macromolecules, exosomes, due to their presence in several body fluids, can also be utilized as a system to commute RNA molecules and proteins in the body. Recent advances in gene therapy have provided a new outlook in disease therapeutics by modulation of gene expression using oligonucleotide based approach and exosomes have been reported a potential carrier for nucleic acid based therapeutic moieties. In recent years, small interfering RNA (siRNA) has emerged as promising therapeutic alternative for diseases with gene-based pathophysiology, however poor bioavailability limits its therapeutic potential. For effective delivery and enhancement of bioavailability of siRNA, several carriers including dendrimers, liposomes, siRNA conjugates, and siRNA aptamer chimeras, to name a few, have been explored. Exosomes can be considered a promising carrier for effective delivery of siRNA due to their existence in body’s endogenous system and high tolerance. The present review focuses on delivering knowledge about exosomes, siRNA, and capability of exosomes to act as natural carriers for siRNA delivery.
Keywords: Extracellular vesicles, endogenous, exosomes, oligonucleotide, small interfering RNA.
The top five in the business saw their collective spending jump by more than $5 billion, from 2015 to 2016, based on the annual numbers filed largely — though not entirely — with the SEC and gathered by Endpoints News. Two of those companies,
Roche and the new number 2, a hard charging
Merck, accounted for the lion’s share of the increase. (To be sure, some onetime non-R&D spending, such as Merck’s patent settlement with Bristol-Myers on Keytruda, figured in. But so did bread and butter spending.)
Gilead also saw a significant increase in research costs, with
Eli Lilly — now off course following two bad setbacks for solanezumab and baricitinib — and the ever aggressive
Celgene joining the action as they pressed the accelerator on new drug programs.
The Rutgers Global Health Institute, part of Rutgers Biomedical and Health Sciences, Rutgers University, New Brunswick, New Jersey – A New Venture Designed to Improve Health and Wellness Globally
Author: 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
Article ID #233: The Rutgers Global Health Institute, part of Rutgers Biomedical and Health Sciences, Rutgers University, New Brunswick, New Jersey – A New Venture Designed to Improve Health and Wellness Globally. Published on 4/17/17
WordCloud Image Produced by Adam Tubman
The newly formed Rutgers Global Health Institute, part of Rutgers Biomedical and Health Sciences (RBHS) of Rutgers University, New Brunswick, New Jersey (http://rbhs.rutgers.edu/), represents a new way of thinking by providing positive health outcomes to potential patients around the world affected by disease and/or by a negative environmental impact. The goal of the Institute is three-fold:
to improve the health and wellness of individuals and populations around the world,
to create a healthier world through innovation, engineering, and technology, and
to educate involved citizens and effective leaders in global health.
Richard G. Marlink, M.D., a former Harvard University professor recognized internationally for research and leadership in the fight against AIDS, was recently appointed as the inaugural Henry Rutgers Professor of Global Health and Director of the Rutgers Global Health Institute.
The Rutgers Global Health Institute was formed last year after research by the University into the most significant health issues affecting under-served and under-developed populations. While conducting research for its five-year strategic plan, the RBHS looked for bold and ambitious ways that they could take advantage of the changing health care environment and band together to tackle the world’s leading health and environmental causes, contributing to the betterment of society. One of the results was the formation of the Rutgers Global Health Institute, supporting cross-functionally Rutgers faculty, scientists, and clinicians who represent the best in their respective fields of health innovation, research and patient care related to global health.
More broadly, the RBHS, created in 2013, is one of the nation’s leading – and largest — academic health centers that provides health care education, research and clinical service and care. It is an umbrella organization that encompasses eight schools – Ernest Mario School of Pharmacy, Graduate School of Biomedical Sciences, New Jersey Medical School, Robert Wood Johnson Medical School, Rutgers School of Dental Medicine, School of Health Professions, School of Nursing and School of Public Health.
In addition, the RBHS encompasses six centers and institutes that provide cancer treatment and research, neuroscience, advanced biotechnology and medicine, environmental and occupational health and health care policy and aging research. Those centers and institutes are the Brain Health Institute, Center for Advanced Biotechnology and Medicine, Environmental and Occupational Health Sciences Institute, Institute for Health, Health Care Policy and Aging Research, Rutgers Cancer Institute of New Jersey, and Rutgers Institute for Translational Medicine and Research. And lastly, the RBHS includes the University Behavioral Health Care.
Image SOURCE: Photograph courtesy of the Rutgers Global Health Institute, Rutgers Biomedical and Health Sciences, Rutgers University, New Brunswick, New Jersey.
Below is my interview with the Inaugural Henry Rutgers Professor of Global Health and Director of the Rutgers Global Health Institute Richard G. Marlink, M.D., which occurred in April, 2017.
You were recently appointed as the inaugural Henry Rutgers Professor of Global Health and Director of the new Rutgers Global Health Institute at Rutgers Biomedical and Health Sciences (RBHS). What are the goals of the new Institute?
Dr. Marlink: The overarching goal of the Rutgers Global Health Institute is to improve the health and wellness of individuals and populations in need both here and around the world, to create a healthier world through innovation, engineering, and technology, and to educate involved citizens and effective leaders in global health. We will do that by building on the aspiration of our originating organization — RBHS, which is to be recognized as one of the best academic health centers in the U.S., known for its education, research, clinical care, and commitment to improving access to health care and reducing health care disparities.
As the newly formed Rutgers Global Health Institute, we are embarking on an ambitious agenda to take advantage of the changing health care environment. Working across schools and disciplines at Rutgers University, we plan to have a significant impact within at least four signature programs identified by RBHS, which are cancer, environmental and occupational health, infection and inflammation, and public health. We also will include all other parts of Rutgers, as desired, beyond RBHS.
My background as a global health researcher, physician, and leader of grassroots health care delivery will help develop programs to undertake global health initiatives that assist populations locally and around the world. I believe that involved citizens, including students, can greatly impact major societal issues.
A key role in the strategic growth of Rutgers Biomedical and Health Sciences – an umbrella organization for eight schools, four centers and institutes and a behavioral health network — is to broaden the Rutgers University’s presence in the public health community globally to improve health and wellness. How will the new Rutgers Global Health Institute be part of this growth?
Dr. Marlink: Our RBHS Chancellor Brian Strom [M.D., M.P.H.] believes that we are positioned to become one of the finest research universities in the country, working cross-functionally with our three campuses in Newark, Camden and New Brunswick. In developing the strategic plan, Dr. Strom notes that we become much stronger and more capable and productive by leveraging our strengths to collaborate and working together across disciplines to best serve the needs of our community locally and globally.
Specifically, we are formulating plans to focus on these areas: old and new infectious disease epidemics; the expanding burden of noncommunicable diseases in poor populations; the social and environmental threats to health, poverty and humanitarian crises; and inadequate local and developing country health systems. We will support the development of global health research programs university-wide, the recruitment of faculty with interests in global health, and the creation of a web-based global health resource center for faculty and students with interests in these areas.
We are still a very young part of RBHS, and of Rutgers overall, so our plans are a work in progress. As tangible examples of our commitment to improving health and wellness globally, we plan to enhance global public health by establishing links between global public health and environmental and occupational health faculty in studies related to air pollution, climate change, and pesticide health.
Another example the Institute has in the works is expanding links with the School of Engineering. In fact, we are creating a senior-level joint faculty position with the School of Engineering and Rutgers-New Brunswick. Still other plans involve forging collaborative relationships between the Rutgers Cancer Program, under the auspices of Rutgers Cancer Institute of New Jersey, which is New Jersey’s only National Cancer Institute (NCI)-designated comprehensive cancer center, and other organizations and partners around the world, especially in poor and less-developed countries.
How is the Rutgers Global Health Institute strategically prepared for changing the health care paradigm?
Dr. Marlink: We intend to be an international global health leader in the health sciences, in public health, and in other related, but non-biomedical professions. This means that we will incorporate our learnings from laboratory sciences and the clinical, behavioral, and public health sciences, as well as from engineering, business, economics, law, and social sciences. This broad approach is critical in this health care environment as accountability for patient care is shifting to large groups of providers. Health care will be more value-driven and our health care teams must work collaboratively to be innovative. Our focus on health care is now also population-based, rather than only individual-based, and we are moving from large regional centers toward community centers, even in small and remote areas of the world. We are encouraged by rapid changes in technology that will provide new opportunities for shared knowledge, patient care and research.
Additionally, we are exploring ways to identify and recruit key faculty who will increase our breadth and depth of key disease areas as well as provide guidance on how to pursue science grants from the National Institute of Health (NIH)-funded program project grants and specialized research programs.
Currently, Rutgers University receives NIH funding for research in public health, population health, health promotion, wellness, health behavior, preventive medicine, and global health.
As a researcher, scholar and leader of grassroots health care delivery, how have your past positions prepared you for this new challenge? Your last position was the Bruce A. Beal, Robert L. Beal, and Alexander S. Beal Professor of the Practice of Public Health at Harvard University’s T.H. Chan School of Public Health and Executive Director of the Harvard AIDS Initiative.
Dr. Marlink: I have been a global health practitioner, researcher, and executive leader for almost three decades. I am trained in medical oncology and HIV medicine and have conducted clinical, epidemiological and implementation research in Africa since 1985. I was first introduced to global health when finishing my Hematology/Oncology fellowship at what is now the Beth Israel Deaconess Medical Center in the mid-1980’s in Boston.
During my Hematology/Oncology fellowship and after the co-organizing the first, hospital-based AIDS care clinic in the New England region, I was trying to learn the ropes in virology and molecular biology in the laboratory group of Max Essex at Harvard University. During that time in the mid-1980s, our laboratory group along with Senegalese and French collaborators discovered the first evidence for the existence of a new human retrovirus, HIV-2, a distinct second type of human AIDS virus, with its apparent origins in West Africa.
As a clinician, I was able to assist in Senegal, helping set up clinical care and create a research cohort in Dakar for hundreds of women sex workers infected with this new human retrovirus and care for them and their families. I discovered that a little can go a long way in poor settings, such as in Senegal. I became hooked on helping create solutions to help people in poor settings in Africa and elsewhere. Long-term partnerships and friendships have subsequently been made in many developing countries. Throughout my career, I have built successful partnerships with many governments, companies, and non-profit organizations, and those relationships have been the foundation to build successful public health partnerships in poor regions of the world.
In the 1990s, I helped create the Botswana-Harvard Partnership for HIV Research and Education (BHP). Through this partnership, the Government of Botswana and BHP have worked together to combat the AIDS epidemic in Botswana. Under my direction, and in partnership with the Botswana Ministry of Health, BHP launched the KITSO AIDS Training Program in 1999. Kitso is the Setswana word for ‘knowledge.”
KITSO is the national training program for physicians, nurses, and pharmacists, which has trained more than 14,000 health professionals in HIV/AIDS care and antiretroviral treatment. KITSO training modules address issues, such as antiretroviral therapy, HIV/AIDS-related disease management, gender-specific HIV issues, task-sharing, supportive and palliative care, and various psychosocial and counseling themes.
In addition, I was the Botswana County Director for Harvard Chan School’s 3-country President’s Emergency Plan AIDS Relief (PEPFAR) grant, The Botswana PEPFAR effort includes a Clinical and Laboratory Master Training Program and the creation of the Botswana Ministry of Health’s Monitoring and Evaluation Unit. Concurrently, I was the Principal Investigator of Project HEART in five African countries with the Elizabeth Glaser Pediatric AIDS Foundation.
Also in Botswana, in 2000, I was a co-founder of a distinct partnership involving a large commitment to the Government of Botswana from the Bill and Melinda Gates and Merck Foundations. This commitment continues as an independent non-governmental organization (NGO) to provide support for various AIDS prevention and care efforts in Botswana and the region.
All these global health experiences, it seems, have led me to my new role at the Rutgers Global Health Institute.
What is your advice for ways that the business community or university students can positively impact major societal issues?
Dr. Marlink: My advice is to be optimistic and follow that desire to want to make a difference. Margaret Mead, the American cultural anthropologist, said years ago, “Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.” I believe that to be our guiding principle as we embark on this new initiative.
I also believe that students should become specialized in specific areas prior to going fully into “global health,” as they develop in their careers, since they will then add more value later. For example, students should be grounded in the theory of global health in their undergraduate studies and then develop a specialization, such as becoming a statistician, economist, or medical doctor, to make a longer and greater impact in improving global health. As for the business community, we are looking for committed individuals who are specialized in specific areas to bring their knowledge to our organization, as partners in the fight against disease, improving the environment, or helping with humanitarian issues. We are committed to improving health and wellness, increasing access to the best health care, and reducing health disparities.
What is it about your current role that you enjoy the most?
Dr. Marlink: I enjoy building research, learning, and clinical programs, as I have in the HIV arena since the early 1980s. At that time, there were limited resources and funding, but a willingness among universities, non-governmental organizations, hospitals and the pharmaceutical industry to make a difference. Today in my new role, I’d like all of us to have an impact on health and wellness for those in need – to build programs from the ground up while partnering with organizations with the same goal in mind. I know it can be done.
Over my career, when I have a patient here or in a developed country who has been diagnosed with cancer, but is cured or in remission, that puts a huge smile on my face and in my heart. It also impacts you for the rest of your life. Or when I see an infant born without HIV because of the local country programs that are put in place, that also makes me feel so fulfilled, so happy.
I have worked with many talented individuals who have become great friends and partners over my career who have helped create a positive life for under-served populations around the world. We need to remember that progress happens with one person at a time or one program at a time. That’s how you truly improve health around the world.
Image SOURCE: Photograph of Inaugural Henry Rutgers Professor of Global Health and Director of the Rutgers Global Health Institute at Rutgers Biomedical and Health Sciences, courtesy of Rutgers University, New Brunswick, New Jersey.
Richard G. Marlink, M.D. Inaugural Henry Rutgers Professor of Global Health
Director of the Rutgers Global Health Institute
Rutgers Biomedical and Health Sciences
Richard G. Marlink, M.D., a Harvard University professor recognized internationally for research and leadership in the fight against AIDS, was recently appointed as the inaugural Henry Rutgers Professor of Global Health and Director of a new Rutgers Global Health Institute at Rutgers Biomedical and Health Sciences (RBHS). His role is to develop the strategic growth of RBHS by broadening the Rutgers University’s presence in the public health community to improve health and wellness.
Previously, Dr. Marlink was the Bruce A. Beal, Robert L. Beal, and Alexander S. Beal Professor of the Practice of Public Health at Harvard’s T.H. Chan School of Public Health and Executive Director of the Harvard AIDS Initiative.
At the start of the AIDS epidemic, Dr. Marlink was instrumental in setting up the first, hospital-based HIV/AIDS clinic in Boston, Massachusetts, and studied the impact of the HIV virus in west and central Africa. After helping to start the Botswana-Harvard Partnership in 1996, he founded the Kitso AIDS Training Program, which would become Botswana’s national AIDS training program. Kitso means knowledge in the local Setswana language.
Dr. Marlink was the principal investigator for the Tshepo Study, the first large-scale antiretroviral treatment study in Botswana, in addition to conducting other clinical and epidemiological studies in the region. Also in Botswana, he was the country director for Harvard’s contribution to the joint Botswana and United States governments’ HIV/AIDS and TB training, monitoring and evaluation PEPFAR effort.
In the mid-1980s in Senegal, Dr. Marlink was part of the team of Senegalese, French and American researchers who discovered and then studied the second type of human AIDS virus, HIV-2. Since then, he has been involved in multiple HIV/AIDS care, treatment and prevention programs in many African countries, including in Botswana, Côte d’Ivoire (Ivory Coast), Democratic Republic of the Congo, Kenya, Lesotho, Malawi, Mozambique, Rwanda, Senegal, South Africa, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe. He has also organized initiatives to enhance HIV/AIDS care in Brazil, Puerto Rico and Thailand.
Dr. Marlink has served as the scientific director, the vice president for implementation and the senior adviser for medical and scientific affairs at the Elizabeth Glaser Pediatric AIDS Foundation, where he was principal investigator of Project HEART, a five-country CDC/PEPFAR effort in Africa. That project began in 2004 and by 2011 had placed more than 1 million people living with HIV into care clinics. More than 565,000 of these people were placed on life-saving antiretroviral treatment.
Since 2000, Dr. Marlink has been the founding member of the board of directors of the African Comprehensive HIV/AIDS Partnerships, a public-partnership among the government of Botswana and the Bill and Melinda Gates and Merck Foundations to provide ongoing support for numerous HIV/AIDS prevention, care and treatment efforts in that country.
He has authored or co-authored more than 130 scientific articles; written a textbook, Global AIDS Crisis: A Reference Handbook; and co-edited the book, AIDS in Africa, 2nd Edition. Additionally, he served as chief editor for two special supplements to the journal AIDS and as executive editor of the seminal 320-author, three-volume textbook, From the Ground Up: A Guide to Building Comprehensive HIV/AIDS Care Programs in Resource Limited Settings.
A trained fellow in hematology/oncology at the Beth Israel Deaconess Medical Center at Harvard Medical School, Dr. Marlink received his medical degree from the University of New Mexico and his bachelor’s degree from Brown University.
Editor’s note:
We would like to thank Marilyn DiGiaccobe, head of Partnerships and Strategic Initiatives, at the Rutgers Global Health Institute, for the help and support she provided during this interview.
Where Infection meets with Cancer: Kaposi’s sarcoma (KS) is the most common cancer in HIV-1-infected persons and is caused by one of only 7 human cancer viruses, i.e., human herpesvirus 8 (HHV-8)
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, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair
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 decisionruled 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.
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.”
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.
Editas’ rivals appeal a recent setback on patent fight, mapping a global war for CRISPR supremacy
by john carroll
April 13, 2017 08:37 AM EDT
Updated: 09:07 AM
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.
World’s Top Ten Cancer Drugs by 2020 (million USD)
Reporter: Aviva Lev-Ari, PhD, RN
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Opdivo Setback May Yield Lessons for Pharma – Advancing Immunotherapies With PD-L1 Testing
Sep 12, 2016 | Turna Ray
The anti-PD-1/PD-L1 drug market is estimated to be worth around $30 billion by 2020. The negative Phase III results for Opdivo in first-line NSCLC shocked market analysts, and pharmaceutical companies developing drugs in this space “are taking stock of the situation” and surely assessing whether they have the right test methods in place in their drug studies, said Peter Keeling, CEO of consulting firm Diaceutics.
Most drugmakers developing anti-PD-1/PD-L1 drugs are evaluating whether their therapies work especially well in patients whose tumor cells express PD-L1, a protein that cancer cells use to hide from an immune system attack. But studies have demonstrated that PD-L1 expression status doesn’t neatly bucket responders and non-responders in the same way that testing for EGFR mutations or ALK rearrangements can, making it difficult for pharmaceutical companies to integrate PD-L1 testing for patient stratification in clinical trials.
In the absence of a universal diagnostic, Cancer Genetics is one lab that does offer all the FDA-approved companion and complementary PD-L1 tests, but also spends a lot of time educating doctors and pathologists on the differences between these tests and which to order for a particular immunotherapy. “There’s a big need for our pharma cousins to really push more knowledge about the associated diagnostics and tests and how to use them,” Sharma said. “That’s the only way they’re going to get uptake in the community setting.”
Despite the muddled messages around PD-L1 testing, healthcare providers and researchers nonetheless seem interested in PD-L1 testing as part of the tumor profiling workup for patients. Diaceutics’ surveys show a sharp uptick in the number of labs offering PD-L1 testing over the past year-and-a-half and 52 labs in the US offer at least one PD-L1 test. The company also reviewed biomarkers being studied in 95 Phase II/III NSCLC, and found that approximately half are incorporating patients’ PD-L1 status either alone or in combination with other markers, such as EGFR and ALK mutations.
At Cancer Genetics over the past year, there has also been a notable ramp up in orders for PD-L1 testing for lung cancer patients, but also for melanoma and head and neck cancer patients. “One our biggest volume increased tests this year has been PD-L1 testing,” Sharma said. “We think there is a lot of opportunity for significant additional growth.”
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