January 5, 2021
San Diego, CA
Allele Biotechnology and Pharmaceuticals, Inc., Pfizer, Inc., BioNTech SE, and BioNTech US, Inc. announce today that they have resolved in a mutually satisfactory manner the patent infringement lawsuit brought by Allele concerning mNeonGreen before the United States District Court for the Southern District of California.
May 24, 2021
San Diego, CA
Allele Biotechnology & Pharmaceuticals in San Diego, California, today announced the signing of a MOU with Cellatoz Therapeutics, a South Korean corporation, to form a business relationship on areas of mutual interest in the field of cell therapy.
iPSC-based cell therapy utilizes pluripotent stem cells that are generated by reprogramming patients’ cells obtained from a small skin punch or a tiny amount of blood. This Nobel prize winning technology not only allows ethical use of stem cells but also facilitates personalized medicine and holds great promise in developing effective therapies for numerous incurable human diseases. Recently, stem cell therapy has become a highly valued area in biomedicine and has gained great traction among investment community, with even preclinical stage programs starting to attract transactions in hundreds of millions to billions of dollars.
Allele Biotech has been involved in developing innovative solutions and products in the fields of stem cells and immunotherapy for over a decade. Allele’s core capabilities include its proprietary and patented technologies utilizing mRNA for generating footprint-free iPSCs, and their derivatives, in its state-of-the-art commercialization-ready GMP facility. The FDA registered, California Tissue Bank accredited, GMP facility supports Allele’s cell therapy programs and CDMO business, besides being the first to offer clinical-grade iPSC banking for the public as a commercial service.
Cellatoz Therapeutics is a biotech company with strong expertise in translational research and process development. Equipped with its proprietary cells and commercialization-ready GMP facility in Korea, Cellatoz is specializing in the development of advanced innovative cell therapies in regenerative medicine and immunology fields . The company’s IP protected Muscular Skeletal Stem Cells (MSSC), which can differentiate into muscular skeletal system, are targeting regenerating cartilages and treating complex fractures. The company is also developing treatments for peripheral neuropathies including Charco-Marie-Tooth disease utilizing Neuronal Regeneration Promoting Cells (NRPC), which are Schwann-like cells differentiated from tonsillar mesenchymal stem cells.
Based on the new MOU the parties will utilize Allele’s iPSC lines and product development capabilities, and Cellatoz’s other cell types, in co-developing cell therapy products for various indications including musculoskeletal diseases and neuropathies. The companies will also join hands in exploring personalized iPSC-banking business in South Korea and possibly other Asian territories.
“Allele Biotech has been a leader in iPSC technology, and we are very excited about this opportunity to work closely with them”, said Dr. Jaeseung Lim, CEO of Cellatoz Therapeutics. “Cellatoz’s MSSC-based CLZ-1001 and the NRPC-based CLZ-2002 are fast heading for clinical trials. We expect that this new collaboration would facilitate these cell therapy products to reach more patients and would enable the development of iPSC-based next generation products”, Dr. Lim commented further.
“We are pleased to work with Cellatoz. This agreement will lead us to co-develop more innovative products and widen our portfolio of iPSC-based therapeutic pipeline. Personalized clinical-iPSC banking is one of Allele’s unique capabilities, enabled by our robust and consistent mRNA reprogramming technology. We see this collaboration as a great step forward in expanding our iPSC- banking and future personalized medicine business globally.” said Dr. Jiwu Wang, Allele’s founder and CEO.
An article by Dusko Ilic and Mirjana Liovic published in the journal Regenerative Medicine covering the developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions in July 2020.
“Allele Biotechnology (CA, USA; www.allelebiotech.com) has announced a publication of a step-by-step protocol for manufacturers of iPSC and other types of stem cells with streamlined cleanroom practices for growing clinical grade cell products [5,6]. The paper also provides sources of cGMP-grade culture media, key reagents, equipment as well as the critical steps taken during splitting, stocking, and thawing of frozen iPSC stocks. This is the continuation of a series of protocol publications in the same journal, where Allele has provided procedures for mRNA reprogramming and generating iPSCs using cGMP materials. The mRNA reprogramming technology developed by Allele has proven to be highly efficient, consistent and reproducible. It allows generation of iPSCs that better recapitulate the molecular signatures of human embryonic stem cells and with faster kinetics than other methods. Differentiation potential of iPSC lines generated using published protocols by Allele have been tested toward more than a dozen different cell types successfully by several teams in the industry with minimal line-to-line variations. The company stated that this fully tested protocol for iPSC culture has been optimized for efficient iPSC proliferation and stemness. It allows scalable manufacturing operations that are fully compliant with cGMP standards; it can be adopted by any cGMP facility, providing a valuable platform to generate iPSCs for clinical applications. Moreover, this platform is designed to allow an easy transition to closed cell culture systems toward automation, which facilitates scalability and controllability and reduces operator-introduced variability, a direction of development Allele is actively engaged in.”
To read the full article visit: https://www.futuremedicine.com/doi/10.2217/rme-2020-0122
October 11, 2020 8:00 PM Pacific Daylight Time
SAN DIEGO, CA, USA
CoV-2 S1-Pseudotyped Virus Carrying a Nuclear mNeonGreen Reporter Assayed with Allele Biotech's iPSC-Derived Lung Epithelial Cells
Using pseudotyped viruses to infect target cells is an important assay in developing neutralizing antibodies as well as in testing immunity post vaccination against coronavirus. Allele Biotech demonstrated how human induced pluripotent stem cell (iPSC)-derived lung epithelial cells, the same type of cells that the COVID-19 virus naturally infects in people, can provide an ideal target in such assays.
Virtually all published data of in vitro viral infection use artificially cultured cells: originally derived from monkey or human fetal tissues isolated many years ago that underwent a “transgenic” process to insert the SARS-CoV-2 receptor gene ACE2, which these cells do not naturally express. The Allele team was not impressed by the efficiency of these current assays using cells supplied from the most widely used sources including government-managed repositories.
Utilizing their strength in generating highly potent iPSCs, which are created from tiny adult skin punch biopsies and can be made into any human cell type, scientists at Allele Biotech have used previously developed protocols to generate multiple subtypes of adult human lung tissues; this week, they were tested for SARS-CoV-2 infection. Using mNeonGreen S1-pseudotyped viruses, Allele’s iPSC-derived primary-like lung cells showed a several-fold higher infection rate in less than a day post-infection, as quantified by fluorescence (see figure), when compared to other commonly used cells.
Additionally, these cells closely mimic in vivo viral targets, therefore, should express not only the receptor ACE2, but also co-receptors not expressed in artificially cultured cells. As Allele has built a facility to grow iPSCs as an unlimited supply, this new assay can be scaled to support many ongoing COVID-19 programs. Lung cells derived from iPSCs made from different person’s biopsies can even provide personalized testing, and opportunities to understand the effects of different patients’ genetic background in lung responses to the viral infection. Together, these cells will be extremely useful in assessing neutralizing antibodies and other anti-virus drugs.
Next, Allele researchers have already begun testing the neutralizing effects of their anti-S1 protein (the landing pad for SARS infection) nanoantibodies they recently developed from llamas and look for the best cocktail combinations and the most effective delivery route in stopping the COVID-19 pandemic.
October 2, 2020 5:00 AM Pacific Daylight Time
SAN DIEGO, CA, USA
Allele Biotechnology and Pharmaceuticals, Inc. has been using mRNA as its core technology for creating cGMP-grade induced pluripotent stem cell (iPSC) lines for regenerative medicine and oncology for over a decade. At the onset of the COVID-19 pandemic, Allele had to pause ongoing therapeutic programs developing iPSC derived pancreatic beta cells, neuroprogenitor cells, lung epithelium cells, and CAR-T/CAR-NK cells. The management and scientific teams at Allele, along with academic collaborators, saw a great potential in utilizing Allele’s cGMP capability and iPSC platform to help with the fight against the devastating situations in California, Washington, New York, and many parts of the US, and diverted resources accordingly.
Mimicking the early stages of human development, iPSCs can divide quickly and expand without any limit, making them ideal “production factories” for biomaterials. Allele quickly figured out an innovative way of inducing these active cells to produce significant quantities of extracellular vesicles or exosomes, which can contain both RNAs AND proteins. Working diligently even under lockdown, Allele obtained preliminary data last week showing that mRNAs encoding the SARS-CoV-2 antigen proteins could be packaged in iPSCs and delivered in extracellular vesicles, potentially together with the viral proteins these mRNAs encode—a dual mRNA and protein vaccine naturally packaged in cells. Multiple vaccine mRNAs, as opposed to mostly single mRNA in the ongoing trials, plus the multiple proteins they encode, could provide a more powerful and robust vaccine platform.
The production scale and stability faced by some mRNA vaccines could be solved if Allele’s method of mRNA packaging is used. For instance, some mRNA vaccine candidates need to be stored at -80oC to remain stable, causing difficulties in shipping and storage. In comparison, the SARS-CoV-2 S1 mRNA packaged in Allele’s iPSC-derived vesicles appeared intact for months even when stored in a 4oC refrigerator.
Allele is putting its strength into this novel vaccine program, while at the same time moving forward with a cell phone based rapid COVID-19 antigen diagnostic product using various llama nanoantibodies and proprietary superbright fluorescent proteins. Additionally, as recently published in a front-page article by the San Diego Business Journal, some of Allele’s nanoantibodies are being tested as blocking antibodies for a nasally delivered COVID-19 prophylactic and treatment, or “passive vaccines”.
September 16, 2020 12:00 PM Pacific Daylight Time
SAN DIEGO, CA, USA
Allele Biotechnology has isolated several classes of single-domain nanoantibodies (nAb) against SARS-CoV-2, the virus responsible for the COVID-19 global pandemic. These novel antibodies will be developed for both therapeutic uses and low-cost rapid diagnostic test kits.
As COVID-19 came to the forefront of the news in early 2020, Allele quickly mobilized its nanoantibody group to work on SARS-CoV-2. To date only one other group has generated llama antibodies using proteins from SARS-CoV-2 as immunogens, previous publications demonstrating the effect of llama antibodies on COVID-19 used nanoantibodies against the SARS-CoV-1 virus from 2003 or non-immunized libraries. Targeting the virus responsible for COVID-19 very specifically, antibodies developed by Allele this way will create more precisely targeted therapeutics and diagnostics.
The bioinformatics group at Allele has analyzed over 6,000 COVID-19 genomes in the early months of the pandemic to isolate target regions conserved among SARS-CoV-2 but divergent from other known coronaviruses such as those that cause flu. Armed with this knowledge Allele is developing multivalent biologics that will bind multiple regions to effectively block the virus from entering cells, while still taking advantage of their small size for better tissue penetration. Candidate therapies developed by Allele can serve to reduce the overall viral load and replication of someone infected with COVID-19 and may also serve as a prophylactic treatment to prevent individuals from contracting the virus in the first place. Due to their high stability and ease of production and formulation, nAb candidates are being evaluated for dosing via inhalation, which will allow for convenient administration without a needle!
In addition to therapeutics, Allele is developing low-cost rapid diagnostics with its COVID-19 targeting nAbs. The test currently under development utilizes specific nanoantibody detection of viral antigens combined with Allele’s patented, ultra-bright fluorescent proteins to generate a highly sensitive fluorescence-based readout. Test strips will be imaged and analyzed via a cloud-based cell phone app utilizing machine learning that will provide fast, accurate results anytime, and anywhere.
September 15, 2020 12:00 PM Pacific Daylight Time
SAN DIEGO, CA, USA, EINPresswire.com
Allele Biotech has been selected as a semifinalist for the XPRIZE Rapid COVID Testing competition. Amid the pandemic, to open schools, businesses, and help people live a more normal life, tests are needed which are easily available and can rapidly, accurately, and cost-effectively detect the virus. The FDA has currently authorized 197 nucleic acid tests and 4 antigen tests to be used to detect SARS-CoV-2 in humans. Very few of these tests provide a rapid result and most require a visit to a professional test site.
The Allele test is based on a completely novel design -- a user can simply scan the assay strip using cell phone camera and analyze through app run in the internet cloud. A test should cost less than $10 and take less than 10 min to run, the goal is to give people freedom to do a self-test anytime, anywhere. Allele will apply to the FDA for at work, school, and home use so anybody can use the test at their own convenience.
This product comes together neatly from combining the three core technology platforms developed over decades at Allele Biotech; namely, nanoantibodies created in llamas using SARS-CoV-2 viral antigens, Allele’s own super bright fluorescent proteins, and machine learning developed as part of Allele’s induced pluripotent stem cell (iPSC) pipeline. The Allele COVID Antigen Test is a completely novel antigen diagnostic that does not rely on the current sandwich test format.
In an overall effort to fight the pandemic, Allele has been using the same core technologies to develop a COVID-19 vaccine and antibody cocktail to prevent and treat infection and will continue to update the public regarding their progress.
September 4, 2020 12:00 PM Pacific Daylight Time
SAN DIEGO
Allele Biotechnology has produced lung epithelial cells from induced pluripotent stem cells (iPSCs) for testing drugs developed to inactivate the SARS-CoV-2 virus. Currently, most testing of new COVID-19 drugs, including Allele’s own anti-CoV2 nanoantibodies that block RBD and other viral surface antigens, is performed using monkey cells such as Vero or human kidney cells artificially expressing targets for viral attachment. These cell lines may not have proper post attachment mechanisms that mimic the viral infection circle. iPSC-derived human lung epithelial cells, on the other hand, possess the same properties as a potential patient’s lung surface cells. They can be made with a high degree of quality control for consistency and into an unlimited supply enabling large scale drug discovery. Different human genetic backgrounds can be represented since iPSCs can be derived from any person, or even made completely personalized within just weeks.
Even in post-pandemic times, human lung epithelial cells derived from cGMP iPSCs, such as those produced by Allele’s cGMP business unit, will likely see high demand for treating post-infection symptoms such as partial loss of lung function and lung tissue fibrosis. iPSC-derived lung cell therapy can be further enhanced with other helper cells such as mesenchymal stem cells (MSCs), which can also be derived from iPSCs in unlimited quantities.
Allele has quickly moved to focus on these indications since the start of the pandemic, applying the experience and expertise gained from building the first operational commercial cGMP iPSC facility over the past decade to the development of clinical cell-based therapies.
Prior to the pandemic, Allele’s approach to the fast-growing cell and gene therapy industry has been to develop industry-enabling technologies such as its patented mRNA iPSC generation method, along with the facilities and protocols required to expedite their clinical use. This has led to Allele being widely recognized as a leading source of clinical iPS cell lines, provided through licensing from companies like Astellas Pharma. Before COVID-19, Allele’s cGMP capability had also gained significant traction and generated numerous inquiries as many cell therapy programs require guidance in process development, clinical trial manufacturing, analytical services, and regulatory support.
Moving forward, Allele will put its main strength on creating more patient-ready programs, such as pancreatic beta cells for diabetes, oligodendrocyte precursors for spinal cord damage, and now lung epithelial cells and MSCs for helping people afflicted with COVID-19.
August 31, 2020 08:00 AM Pacific Daylight Time
SAN DIEGO
This week, Allele Biotechnology & Pharmaceuticals Inc. is initiating the clinical study of a COVID-19 serological test aimed at point of care (POC) use. The study is designed to include 100 volunteers recruited through a clinical testing lab in Texas. At the conclusion of the study, in approximately 2-3 weeks, Allele will apply for POC Emergency Use Authorization from the US FDA and expand into other countries and territories. Currently, most FDA-approved COVID-19 tests are for high complexity test centers (CLIA labs); the “POC” designation will enable broader use, helping more people.
The current test under the clinical investigation still uses a conventional IgG test format. Allele is planning further studies for home use with the same single-step product, with the ultimate goal of supplying COVID-19 tests for anybody, anywhere at an affordable cost.
Additionally, Allele is developing a powerful new generation of COVID-19 testing based on its 10+ years of experience with nanoantibodies (also called nanobodiesTM) derived from llamas. This robust technology will enable cheaper, quicker and most importantly, quantitative tests through machine learning. The integration of telemedicine and machine learning will allow for highly accurate testing that will adapt to the dynamic nature of Covid19.
On July 31st, the FDA approved the first semiquantitative test to estimate a patient’s Antibody population from past SARS-CoV-2 Infections. Quantitative tests using llama nanoantibodies for both IgG detection and live virus detection test will assess the likelihood a person has an active SARS-CoV-2 infection or distinguish if COVID-19 like symptoms are caused by COVID-19 or other viruses such as the common cold or flu. The development team at Allele is working diligently to bring these new tests to the market in the in anticipation of cold and flu season. Allele’s leadership is also applying for government funding and developing partnerships within the industry.
July 14, 2020 06:00 AM Eastern Daylight Time
SAN DIEGO--(BUSINESS WIRE)
In their latest paper published in the online prepublication by the peer-reviewed journal Current Protocols, scientists and cGMP operation managers at Allele Biotechnology present a series of step-by-step protocols for manufacturers of iPSC (induced pluripotent stem cells) and other types of stem cells with streamlined cleanroom practices for growing clinical grade cell products. Additionally, in the open access version of the paper, Rivera et al. provide sources of cGMP-grade culture media, key reagents, equipment as well as the critical steps taken during splitting, stocking, and thawing of frozen iPSC stocks.
This is the continuation of a series of protocol publications in the same journal, where Allele has provided procedures for mRNA reprogramming and generating iPSCs using cGMP materials. Five years after establishing Allele’s own iPSC-dedicated cGMP facility and with three years of actual production, the knowledge obtained has been distilled into the most recent publication describing the key elements critical to successful pluripotent stem cell manufacturing for cell and gene therapies.
The mRNA reprogramming technology developed by Allele has proven to be highly efficient, consistent, and reproducible. It allows generation of iPSCs that better recapitulate the molecular signatures of human embryonic stem cells and with faster kinetics than other methods. Differentiation potential of iPSC lines generated using published protocols by Allele have been tested towards more than a dozen different cell types successfully by several teams in the industry with minimal line-to-line variations.
Dr. Jiwu Wang and his coauthors state that “this fully tested protocol for iPSC culture has been optimized for efficient iPSC proliferation and stemness. It allows scalable manufacturing operations that are fully compliant with cGMP standards; it can be adopted by any cGMP facility, providing a valuable platform to generate iPSCs for clinical applications. Moreover, this platform is designed to allow an easy transition to closed cell culture systems towards automation, which facilitates scalability and controllability and reduces operator-introduced variability, a direction of development Allele is actively engaged in.”
The paper can be obtained by visiting the Current Protocols website (click here to view a PDF copy) or by searching for the publication’s reference: Rivera, T., Zhao, Y., Ni, Y., & Wang, J. (2020). Human-induced pluripotent stem cell culture methods under cGMP conditions. Current Protocols in Stem Cell Biology, 54, e117.
January 13, 2020 10:56 AM Eastern Standard Time
SAN DIEGO--(BUSINESS WIRE)--
Allele Biotechnology and Pharmaceuticals, Inc. (President and CEO: Jiwu Wang, Ph.D., “Allele”), a San Diego-based private company, and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”), through its Massachusetts-based subsidiary Astellas Institute for Regenerative Medicine (AIRM), entered into a licensing agreement to expand Astellas’ access to Allele’s induced pluripotent stem cell (iPSC) technologies for various cell therapy programs.
Astellas, one of the largest pharmaceutical companies in Japan and already a leader in the development of cell-based therapeutics, has further dedicated to development of the field through its commitment to state-of-the-art iPS cell generation, modification, and manufacturing. iPSC lines can differentiate into all somatic tissue types, enabling a wide variety of therapeutic applications. The field of iPSC-derived cells has seen dramatic growth in clinical trials recently--the majority of the ~12 clinical trials around the world were initiated within the last 18 months and many more are upcoming.
Allele has been developing its core strength in reprogramming somatic cells into iPSCs with granted patents and the first commercial cGMP system it developed over the past 10 years. Allele also engages in more than a dozen different human tissue derivation activities through its own R&D efforts for internal programs and partnerships. To realize the unparalleled potential of iPSC, Allele’s researchers and cGMP team are committed to setting up and validating cell assays for product quality control, genome analysis pipelines, closed-system automation for reprogramming, and machine learning in iPSC-related fields.
Under the terms of the new license agreement, Astellas will pay Allele upfront and milestones, product-based royalties, and potentially manufacture fees.
SAN DIEGO, CA - EIN NEWS
November 27, 2019 -- Allele’s latest patent extends coverage of the generation of feeder-free induced pluripotent stem cells using synthetic messenger RNA (mRNA).
The United States Patent and Trademark Office has awarded invention number 10,435,711 to Allele Biotechnology and Pharmaceutical, Inc. This patent describes additional methods and conditions of generating induced pluripotent stem cells (iPSC) based on Allele’s core technologies in a highly controlled and reproducible process. It is the third in the patent family of novel approaches to generating iPSCs for the company.
This patent marks the fastest to issue in Allele’s growing portfolio, having been granted in less than a year after filing, joining the first two Allele iPSC patents granted in late 2018. Other patents in the portfolio address the composition of mRNA used to reprogram cells to become stem cells and processes of doing so in an efficient and clinically relevant manner. All of these patents have also being granted or in the process of being granted around the world.
This newly issued patent arrives with excellent timing as Allele realizes its goal of overcoming bottlenecks in the regenerative medicine and cell therapy fields. The industry, now moving to reproducibly provide pancreatic beta cells for diabetes, neural progenitor cells for dementia, or unlimited supply of CAR-NK or CAR-T for treating cancers, etc., is growing rapidly and needs appropriate source of upstream pluripotent stem cells such as cGMP iPSCs that are amenable to regulatory review. Dr. Jiwu Wang, Allele’s Founder and CEO, is the patent’s inventor and is “pleased to be a source of iPSC lines for all clinical applications.”
SAN DIEGO--
June 12th, 2019 -- Allele Biotechnology and Pharmaceuticals, Inc. and Alpine BioTherapeutics Corporation entered into a research agreement for developing iPSC-derived cell therapy for treating retinal diseases. Both companies are based in San Diego, California.
iPSCs (induced pluripotent stem cells) have the potential to differentiate into all human tissue types and play an increasingly important role in regenerative medicine. Approximately a dozen clinical trials using iPSCs are currently underway around the globe.
Allele Biotechnology has been developing technologies to produce GMP grade human iPSCs and high-quality tissue-specific cells derived from them for 10 years. Allele’s core capabilities in this area include its proprietary and patented technologies utilizing mRNA for generation and differentiation of footprint-free iPSCs in its state-of-the-art commercialization-ready cGMP facility.
Alpine BioTherapeutics has developed a patented stem cell differentiation technique to robustly generate human retinal stem cells from pluripotent stem cells. Alpine’s cell therapy products will be used to treat blindness caused by Retinitis Pigmentosa, Stargardt disease, and dry AMD. The company claims their technique as by far the most efficient process known in the manufactured retinal cell category and is expected to yield the highest quality retinal cell for use in patients. This potentially translate into much lower variability and cost while also minimizing regulatory risk.
"This collaboration with Allele Biotechnology provides us a clear path forward for clinical use of our technology. There are only a handful of clinical grade iPSC lines available in the world and we are fortunate that we will now have access to one of the best. Moreover, the support of Allele’s cell scientists and cGMP experts will be of great advantage to enable us to move to IND and into clinical trials quickly”, said Dr. Jack J. Zhao, CEO of Alpine BioTherapeutics.
The agreement will provide Alpine BioTherapeutics priority access to Allele’s cGMP facility and will involve licensing one or more of Allele’s cGMP-grade human iPSC lines to generate cell therapy products for vision loss.
Dr. Jiwu Wang, Founder and CEO of Allele Biotechnology, said “We are excited that our technology synergizes with Alpine’s to make novel products with the potential to make a difference to millions of lives affected with debilitating eye disorders”
SAN DIEGO--(BUSINESS WIRE)--
April 23rd, 2019 -- Allele Biotechnology and Pharmaceuticals Inc., a San Diego based biotechnology company focused on the development and clinical translation of cutting-edge technologies, has partnered with Addgene, a global nonprofit organization helping scientists share plasmids, to further facilitate academic use of mNeonGreen. Addgene will leverage its field-leading distribution platform to increase the availability of mNeonGreen constructs to researchers around the world.
First reported in the journal Nature Methods in 2013 (Shaner et al.), mNeonGreen is the brightest monomeric fluorescent protein available on the market. Upon its release, Allele’s CEO Dr. Jiwu Wang stated, “mNeonGreen surpasses eGFP in every way, it’s brighter, more photostable, enables superresolution imaging, and is compatible with imaging equipment used for eGFP. It will replace eGFP as the fluorescent protein of standard.”
Since its release, mNeonGreen has been available exclusively at Allele Biotechnology, under a novel licensing model created by Allele specifically for academic users (Nature Methods: Technology Feature). According to Allele’s Marketing Director, Abbas Hussain, “Our licensing model was developed to simplify access to mNeonGreen constructs and create a close-knit community to share reagents and ideas of using the protein at far below market costs. We wanted to be a part of the conversation so we could develop new tools and closely assist our users. The model has been a huge success and we appreciate the enthusiastic support from the community.”
Over the years a number of new tools have emerged harnessing mNeonGreen, including species-specific and split versions of the protein and outstanding voltage and calcium. Allele has also developed a camelid derived VHH nanoantibody against mNeonGreen to enable various assays such as co-immunoprecipitation and secondary labeling. Many users further sub-cloned mNeonGreen into various plasmids or viral vectors, as different fusions, or under different promoters. These developments have spurred the discussions between Addgene and Allele to expand the mNeonGreen distribution to the academic community and allow mNeonGreen to truly establish itself as a fluorescent protein of standard.
Allele Biotechnology owns newly issued patents and pending applications on the mNeonGreen protein and antibodies against it, and is still the exclusive source for commercial licensing and opportunities related to mNeonGreen. Allele has funded external research and is continuously committed to developing novel tools that put to use the benefits of this brilliant fluorescent protein. Our current licensees could receive extra benefits from Allele such as nanoantibodies against mNeonGreen and continued technical support by Allele’s expert team.
SAN DIEGO--(BUSINESS WIRE)--
April 15th, 2019 -- San Diego-based Allele Biotechnology and Pharmaceuticals, Inc., officially announced a joint research and development agreement with South Korea’s SCM Lifescience Co., Ltd., for the development of diabetes therapies using pancreatic beta cells derived from induced pluripotent stem cells (iPSCs).
iPSCs can be derived from adult human tissue cells yet share the developmental potentials of embryonic stem cells. Currently Japan has 6 ongoing clinical trials utilizing this technology, but the rest of the world is now joining the movement with 4 clinical trials initiated outside of Japan in the past year.
Since 2009, Allele Biotechnology has been developing clinically compatible technologies to produce high quality iPSCs and tissue-specific cells from iPSCs. The pancreatic beta-cell program is powered by Allele’s core capabilities, including proprietary methods utilizing mRNA for generation and differentiation of iPSCs, and a state-of-art, commercialization-ready cGMP facility in San Diego, California.
Dr. Jiwu Wang, Founder and CEO of Allele Biotechnology, said, “We are excited to have a partnership with SCM Lifescience, which has years of experience in cell therapy clinical trials. This collaborative project will help us quickly generate first-in-human results in the fast-moving field of iPSC-based therapies.”
The purpose of the collaboration is to confirm the therapeutic applicability of Allele’s iPSC-derived pancreatic beta cells for diabetes and related indications. The initial efforts will be focused on developing an autologous product for certain forms of Type 3c Diabetes (T3cDM), that are inherently non-autoimmune in nature. Allele Biotechnology also envisages alternative, off-the-shelf allogeneic therapeutic products for other types of diabetes, taking advantage of its growing bank of cGMP-grade footprint-free iPSCs, and gene editing technologies.
SCM Lifescience currently has a number of allogeneic mesenchymal stem cell therapies in its pipeline, indications include chronic graft versus host disease, acute pancreatitis, severe atopic dermatitis, and liver cirrhosis. The new collaboration will expand its capabilities by exploring the iPSC-based market.
"We are pleased to collaborate with Allele Biotechnology for the development of diabetes treatment which will be a valuable addition to our current pipeline. Knowing Allele’s cGMP manufacturing experience, we are expecting a great synergy with our recent acquisition of CoImmune with its production site in North Carolina,” stated Dr. BG Rhee, CEO of SCM Lifescience.
iPSCs have been created using mRNA technologies, with cGMP control from donor screening, consenting, to skin punch, and throughout cell bank production.
SAN DIEGO, CA, USA, December 4, 2018 — After 3 years of cleanroom construction and 2 years of quality system establishment, Allele Biotech has produced its initial batch of 6 iPSC (induced pluripotent stem cells) lines that are ready for prime time.
Prior to Allele’s cGMP iPSC generation there were only ~3 GMP iPSC lines available for therapy development from other sources around the world, forcing several pluripotency inspired companies to resort to embryonic stem cells (ESCs) as their starting material. ESC lines have a number of limitations due to questions of whether they were created with consent that meets today’s standards, and whether there have been gaps in custody throughout their history of existence. As the stem cell-based therapy field ramps up towards its exponential phase, there are obvious reasons to produce additional functional cGMP iPS cell lines with diverse genetic backgrounds and differentiation potentials.
Allele’s iPSCs were created using its patented mRNA technologies, with full cGMP monitoring and documentation starting from donor consent, screening and tissue biopsy. In its San Diego facility that received California tissue bank license earlier this year, Allele’s highly trained and dedicated stem cell manufacturing team first produced dozens of banked fibroblast stocks that are fully cGMP-compliant. Now they are churning out iPSC lines at unprecedented pace. Even though it takes just 1-2 weeks to reprogram fibroblasts into iPSCs using the mRNA method, production of cGMP-compliant iPSCs takes 3-4 months due to the stringent testing and quality control assays Allele painstakingly developed and qualified.
In addition to iPSC generation and differentiation, Allele’s proprietary mRNA platform can be used to engineer human iPSCs in a one-time genetic modification event to generate a clonal iPSC line that can be developed into a master cell bank.
Allele has received notification that patents have been allowed in EU and Japan one month after receiving 2 US patents on generating mRNA-iPSCs. mRNA produced iPSCs are more stable and easier to differentiate as Allele has previously reported, and their manufacturing process is continually being improved and upgraded. Focusing on industrial use of iPSCs, Allele has established a suspension iPSC culture system that can generate billions of iPS cells in a closed system before induction to differentiation.
SAN DIEGO--(BUSINESS WIRE)--
October 31st, 2018 — Allele Biotechnology & Pharmaceuticals Inc. has received issuance notices from the U.S. Patent and Trademark Office for its first batch of patents covering the derivation of induced pluripotent stem cells (iPSCs). Allele’s proprietary technology uses only messenger RNA (mRNA) to reprogram human or other primate cells, avoiding many operational complications that other methods often encounter.
The patents were purposefully structured for the production of iPSCs using methods fully compliant with current good manufacturing practice (cGMP) regulations suitable even for phase III clinical trials and commercial production. Accordingly, the Allele team developed technologies to enable a feeder-free and genome integration-free reprogramming procedure with unparalleled efficiency and success rates.
“Companies in the iPSC industry, an industry still in its infancy, are able to access only 1 or 2 GMP-compatible lines and are often nervous about whether their highly valued differentiation protocols will work with these lines,” commented Dr. Jiwu Wang, CEO of Allele Biotech and a key inventor of these patents. “What we have put in motion starting this month is to continuously create fully cGMP-compliant iPSC lines. We intend to communicate with the FDA early and often to set high quality standards, which will enhance chances of success in the iPSC therapy field as a whole.”
Allele’s differentiation protocols also use mRNAs to direct cell fate. Because the costs of cGMP production are directly influenced by the time cells spend in culture, Allele’s efficient protocols will show a strong technical and economic advantage. Many academic labs and their spinoff companies have developed protocols to differentiate embryonic stem cells (ESCs) or iPSCs into a chosen lineage. Those protocols typically work well with just one ESC or iPSC line, whereas Allele’s protocols consistently work across all lines tested, ultimately enabling autologous cell therapies, which are widely considered to be the true power of the iPSC technology since its discovery by Dr. Shinya Yamanaka.
Operations are underway at Allele’s cGMP facility to produce dozens of iPSC lines. According to both industry and academic collaborators, lines produced using Allele’s methods are easier to maintain and use when compared to alternative pluripotent stem cells. In addition to internal projects, these iPSC lines and cell fate manipulation methods will be available via partnerships and licensing, providing companies with the most advanced iPSC technologies to further their therapeutic programs.