Leadership In Controlled Gene Expression


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Newsletter 12/2015

Review Of Business Year 2015

The year 2015 was another successful business year for TET Systems. By the end of November, 35 new contracts were signed. In addition to agreements with new licensees, these agreements comprise extensions of contract terms, expansions of territories, and expansion of patent rights (i.e. access to the Tet-On 3G technology) with existing licensees. Based on 2014 surveys, one hundred percent of the 10 world’s biggest pharmaceutical companies (www.forbes.com) and 80% of the top 25 pharmaceutical and biotechnology companies (www.pmlive.com) have a license to the Tet technology.

TET Systems’ IP portfolio

In 2015, one US and one Canadian patent were granted. With these two additionally issued patents the latest version of the Tet transactivator (Tet-On 3G) and the tightest Tet-responsive promoter (PTRE3G) is protected by issued patents in all relevant territories. This brings the total number of issued patents protecting the Tet technology to 30.

Tet technology

There are always new molecular biology technologies emerging that move basic and applied life sciences forward (e.g. RNAi; iPSC). Over the years, the Tet technology has proven to be an invaluable tool to improve those novel technologies and, in some instances, to make them more user friendly. The Tet-Advanced system for example, was successfully employed by the Jaenisch group to facilitate generation of induced pluripotent stems cells (iPSCs) a few years ago and this improved technology is still used by many academic groups.

Genome editing, in particular using the CRISPR-Cas technology, has become the most recent ground-breaking technology. This new method allows to effectively manipulate any cell type to study gene function in vivo. Initial studies were hampered by off-target effects mediated by continuous Cas9 expression. However, selective On/Off control using the Tet system allowed turning on genome editing at different time points in cellular systems and in specific tissues in in vivo models. Combining CRISPR-Cas and the Tet technology in mice was recently also shown to significantly speed up the process of generating transgenic mice in comparison to conventional knockout approaches. Please see our website (www.tetsystems.com) for publications describing these technologies.

Updated information on TET Systems’ website

On our home page we regularly make available comprehensive updates of the relevant Tet literature and transgenic animal databases. TET Systems provides this service to the scientific community as up to date overview of the Tet systems’ technical applications.

Although being an established technology for more than a decade, the Tet technology is still widely employed. In 2014, 1.469 peer reviewed articles were published in scientific journals, more than 200 articles more than in the previous year. This brings the total number of publications on application of our technology to 12.880. The graph below indicates the number of publications per year and supports the continuously increasing use of our proprietary Tet technology.

Number of peer-reviewed articles employing the Tet technology per year

The graph above shows the number of publications using the Tet technology since 1992. Specific numbers of published articles per year are indicated above each bar. The insert highlights the first three years after invention and demonstrates the rapid spread of the technology.

On our website one can find a database of transgenic mouse lines expressing either Tet transactivators in various tissues or different genes of interest under Tet promoter control. At present, this compilation lists almost 200 Tet-transregulator lines and more than 430 Tet-responsive mouse lines which are available to the scientific community.

To our Readers

We are continuously trying to improve our services and information to all users of the Tet technology. We appreciate your comments and feed-back regarding this Newsletter and all other proposals regarding our homepage. Please send your comments/proposals info@tet-systems.com

Holiday Notice

Our offices will be closed starting on Dec. 24th until Jan. 8th, 2016. We wish you all an enjoyable Holiday Season and a great start into a successful New Year 2016.

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Newsletter 01/2015

TET Systems’ 10th Anniversary

While founded in December 2003, TET Systems started operations in January 2004. To commemorate this date, TET Systems celebrated its 10th anniversary with the inventors of the technology, its directors and friends, members of the Bujard group and colleagues from the Center for Molecular Biology, Heidelberg (ZMBH).

TET Systems’ business still growing

TET Systems is marketing licenses to its proprietary Tet Technology. Even after more than two decades the number of applications of the Tet Technology is still expanding which is reflected by 36 signed agreements in 2014 including new licenses, amendments and settlement agreements. TET Systems’ customer base comprises early stage biotechnology and multinational pharmaceutical companies which use the Tet Technology in various internal R&D projects to identify and validate their drug development candidates. In addition, TET Systems has signed a number of new licenses with companies that offer specific services to the scientific community based on the Tet Technology. Moreover, the number of academic institutions which offer Tet reagents and animals models is also a growing business.

TET Systems is actively protecting its intellectual property rights, and, to date, has filed 10 complaints in US courts and has successfully enforced its rights including a recent complaint filed in 2014 against a US-based company.

Prof. Bujard receives Robert Koch Gold Medal

The importance of the Tet Technology has also been recognized by the ‘Robert Koch Stiftung’, a charitable foundation supporting basic scientific research in the field of infectious disease. Every year, the foundation grants several prestigious scientific awards, among these the ‘Robert Koch Gold Medal’ in recognition of outstanding scientific lifetime achievements. In November 2014, Prof. H. Bujard, one of the inventors of the Tet Technology and one of TET Systems’ founders, was awarded the Robert Koch Gold medal for his research on malaria infections and in the field of eukaryotic gene regulation.

TET Systems’ Patent Portfolio

In 2014, two new patents were granted covering Tet components in Europe and Canada. Moreover patent protection was obtained in Japan for the Tet-On 3G promoter further broadening the Tet Technology IP portfolio which now covers 40 patents and patent applications. 

Use of Tet Technology is still expanding

The utility of the Tet Technology continues to grow as documented by the increasing number of scientific publications covering such diverse fields as disease models, drug screening and numerous studies on gene function. The Tet Technology has become the gold standard for reversible gene expression systems in eukaryotic cells and animals and is widely used as documented by a total number of 11.240 publications describing applications in various fields of research. The figure below documents the increasing number of publications per year in peer-reviewed journals which in 2013 reached a new ‘all time high’ of 1.264 papers.

 

Transgenic Animal database updated

TET Systems monitors publications on new Tet transgenic animals and posts lists of transgenic rodents on its website. These lists are available for download and at present comprise more than 170 lines expressing Tet trans-regulators and 400 lines of mice expressing various genes under Tet promoter control. Information regarding availability of transgenic mouse lines from repositories like ‘The Jackson Labs’, ‘EMMA’ or ‘Riken’ is also provided. Future updates will also include other Tet transgenic species like dogs or pigs.

 

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Newsletter 04/2012

Tet Technology Anniversary

Twenty years ago, M. Gossen and H. Bujard published the original article on the Tet gene expression system. The successful adaptation of a bacterial transcriptional control system to eukaryotic cells was the first step of an ongoing success story as the Tet Technology has become the most applied technology to tightly and reversibly control gene expression in eukaryotic cells and animals. TET Systems is commemorating this historic achievement with a number of marketing activities, including a series of webinars on the Tet Technology and a brochure.

The utility of the Tet Technology continues to grow as documented by the increasing number of scientific publications covering such diverse fields as disease models, drug screening and numerous studies on gene function. Its success is based on validation in thousands of academic laboratories which have adapted the Tet Technology to all existing eukaryotic cellular and animal model systems. Due to its fully reversible nature, even in in vivo models, the Tet Technology has been instrumental in gaining insights into complex biological processes such as disease development (Bishop et al., 2002) and learning (Kandel et al., 1996), in some cases even disproving current hypothesis (i.e. metastasis model, Varmus et al., 2008). The Tet Technology has also been instrumental in advancing and standardizing new emerging technologies including interfering RNA and inducible pluripotent stem cells.

TET Systems, the inventors and their collaborators are dedicated to the continuous improvement of the technology which, in 2010, lead to the launch of the first Tet products based on the latest technology generation (Tet-On® 3G) by Clontech, our long-time marketing partner.

 

TET Systems’ business year 2011

TET Systems markets licenses to its IP portfolio protecting the Tet Technology. The still expanding application of the Tet gene switch in academic and corporate research and the launch of new product lines form the basis of TET Systems’ growing business success. 2011 was the second best year with respect to signing new and to expanding existing license agreements and its best year regarding corporate revenues. The number of corporate licensees ranging from multinational pharmaceutical to early stage biotech companies is growing every year and exceeded the 200 mark in 2011. In particular academic institutions marketing their Tet-containing inventions or offering research to the pharmaceutical and biotech industry represent a rapidly growing line of business.

 

Updated information on TET Systems’ website

TET Systems’ home page is a source of information for the Tet Technology and regularly provides updates of the relevant Tet literature and transgenic animal data bases. TET Systems provides this service to the scientific community. Compilation of peer reviewed articles making use of the Tet Technology in 2011 revealed a record high of 1.169 publications. The graph below indicates the number of publications per year and clearly demonstrates an increasing use of the technology making it one of the most used molecular biology technologies.

Over the past 12 months, 40 new transgenic mouse lines were published. Overall the transgenic mouse data base comprises 100 transactivator and more than 250 Tet-responsive mouse lines available to the scientific community. In addition, we created a first compilation of Tet-transgenic rats emphasizing the increasing importance of the Tet Technology in other model organisms.

We also added new mechanistic videos for the Tet-Off® and Tet-On® systems in various resolutions (also available for download).

 

New patents granted

In 2011, four new Tet Technology patents were granted. Three new Japanese patents cover Tet promoters and transcriptional regulators. The fourth patent was issued in Europe protecting Tet-On®3G transactivators. The IP portfolio protecting the Tet Technology comprises 40 issued patents and 14 pending applications.

 

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Newsletter 03/2011

2010 Retrospective

2010 was another very successful business year for TET Systems with many new R&D licenses signed. In addition, a commercial license agreement was signed, allowing Sirion Biotech to offer customized cell lines and to produce and manufacture recombinant viral vectors. This further broadens the range of Tet materials and services offered by our partners which now comprises Tet reagents, different formats of viral vectors, cell lines as well as generation and distribution of transgenic laboratory animals. Based on the new IP acquired in 2009, Clontech launched new products (see below) and many existing licensees amended their license agreements to get access to this new product line. Taken together, the combined total of newly signed licenses and license upgrades exceeded previous years.

 

Tet-On® 3G Launch by Clontech

In August 2010 Clontech launched the Tet-On® 3G System consisting of a new Tet-responsive promoter and an improved Tet-On® transactivator. Together, these components confer the all-time lowest background in the non-induced state and a tenfold increase in sensitivity towards the effector substance doxycycline, compared to previous generations of the Tet-On® System.
In 2009, the IP underlying the Tet-On® 3G System was acquired from AMC/STW in Amsterdam, The Netherlands and the University of Heidelberg and was first licensed to Clontech, our long-time partner in the reagent market.

 

New Products

A number of new Tet products will be launched by Clontech in 2011. The “Tet-Express System” was the first new product launched in February 2011. This system requires only a modified version of the Tet-Off® Advanced protein which was optimized for self-transduction by Clontech to induce expression of a gene of interest under Tet control. Thus, using Tet-Express for tight gene regulation circumvents the need to establish double-stable cell lines and will be particularly advantageous for difficult-to-transfect cell lines. The Tet-Express protein, which is available separately and compatible with all of Clontech’s previous TRE promoters, will significantly reduce the time to perform a Tet-inducible experiment. Later this year, Clontech will launch additional products containing the Tet-On® 3G system.

 

New IP

On December 12th, 2010 we received a communication under Rule 71(3) from the European Patent Office regarding TET Systems’ patent application ‘Inducible Expression Systems’ which covers the new TET-On® 3G trans-activator. Based on this communication, we expect the patent to be granted in the first half of 2011.

 

Additional information on TET Systems’ website

TET Systems together with Clontech, through its European affiliate Takara Bio Europe, is planning to set up a series of webinars on specific aspects of the optimal use of the technology as well as selected applications of the Tet Technology. These webinars will be held by renowned scientists in the respective scientific field. The webinars will be available on TET Systems’ website for those who cannot attend to the original presentation. In the near future, a new section on applications of the Tet Technology will be added to TET Systems’ website. In this new section, the role of our technology during the development of “hot” scientific academic research fields and published industrial applications will be highlighted.

 

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Newsletter 08/2010

Launch of the new Tet-On 3G Inducible Gene Expression System

Clontech, TET Systems’ partner for life science reagents for many years, announced the launch of a new generation of the Tet Gene Expression Systems. ‘Tet-On 3G’ consists of an improved transactivator, developed by scientists at the University of Amsterdam, Netherlands and a new Tet-responsive minimal promoter, developed at the University of Heidelberg, Germany. 

Tet-On 3G offers greater control of gene expression compared to Tet-On Advanced with a tenfold increase in sensitivity to the effector (Doxycycline) and significant reduction of non-induced gene expression thus making the new system even more attractive for transient transfection studies and in vivo applications. Generation of Tet-On 3G became possible after TET Systems acquired the rights to both components of the system in 2009. Clontech will launch Tet-On 3G in early August.

 

New license agreement signed

TET Systems and Sirion Biotech GmbH, a privately-held German biotech company recently entered into a commercial license agreement. Under this agreement Sirion will apply the Tet Technology to generate customized, Tet-containing cell lines and to manufacture recombinant viral products. In particular Sirion will provide recombinant adenoviral production services, which so far were unavailable through TET Systems’ network of Authorized Partners. 

 

TET Systems and IP Merchandisers have merged

In January, TET Systems announced the merger with IP Merchandisers, its fully owned daughter company. TET Systems has taken over all operational activities including the marketing and administration of licenses for the Tet Technology.TET Systems is very committed to its licensing program and will continue to provide quality service to its clients and partners.

 

TET Systems’ IP Portfolio

Since the beginning of this year, 4 new patents covering Tet transactivators and chromosomal loci for the stringent control of gene activities were granted in Europe and in the United States to TET Systems. Moreover several world-wide patent applications covering transactivators with further improved properties were acquired from Amsterdam Medical Center (AMC) and Technology Foundation (STW). This further broadens the Tet Technology patent portfolio, which now comprises 36 granted patents and 14 pending patent applications.

 

New Tet bibliography online

The new Tet bibliography was recently updated and now contains more than 7 000 references. Last year more than 750 new, original studies using the Tet Technology were published in peer reviewed scientific journals, making the Tet Technology one of the most widely used molecular biology technologies and by far the most applied gene regulation system. The Tet reference database is updated annually and access is free to all visitors of our website.

 

New online tool to search the Tet reference database

As announced in the last TET Newsletter, a new tool to search the Tet bibliography online is now available. This tool enables interested visitors of our website to find papers relevant to their field of interest without the need to first download the entire Tet reference database. To use the new tool simply sign in and access bonus information like the Tet literature collection or the complete list of Tet-transgenic mice.

 

New list of transgenic mouse lines online

We recently updated the list of transgenic Tet mouse strains. Only new Tet transactivator or Tet-responsive lines are included while mice generated previously and reused again (recycled) are not listed. This continuously growing list allows the evaluation of specific mice in various unrelated projects and will significantly facilitate the generation of new, double transgenic animals. 

For more comprehensive information on recent developments in Tet mouse transgenesis, we would like to direct your attention to a comprehensive review which will be published in August in the series:  ‘Methods in Enzymology’ (Guide to Techniques in Mouse Development 477: 429-453): The Power of Reversibility: Regulating Gene Activities via Tetracycline-Controlled Transcription by K.Schönig, H.Bujard and M.Gossen.

 

New Publication Highlight

A recent publication in Nature by Herrera and colleagues indicated new ways to restore the population of pancreatic cells after extreme damage by converting existing a-cells into insulin producing b-cells. The Tet-On Advanced System was instrumental to show that regenerated b-cells were actually derived from adult a-cells through a trans-differentiation process documenting a previously unrecognized flexibility in the functioning of the pancreas. Herrera’s results suggest new ways for the regeneration of b-cells which may eventually provide new approaches to cure diabetes.

 

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Newsletter December 2009

                       
Assignment Agreement signed with AMC/STW
TET Systems, AMC (Academic Medical Center) and STW Technology Foundation entered into an assignment agreement. Previously, scientists at the AMC had developed a new series of Tet-On transactivators with improved properties. Under the terms of the agreement, eight international patent applications covering these novel transactivators were assigned to TET Systems for commercialization. The acquisition of these patent applications broadens TET Systems` IP portfolio and makes TET Systems the only source for licensing all relevant IP covering the Tet Technology.
 
New license agreements signed

This year TET Systems has signed a record number of new license agreements. New licensees comprise Takara Bio, BioFocus DPI, and most recently, Novo Nordisk to name a select few. This year, TET Systems filed a law suit for Patent Infringement in the US against Pharmasset. As part of the settlement agreement, TET Systems agreed to dismiss further legal action while Pharmasset agreed to take a license for the Tet Technology for precise and efficient control of gene expression in higher eukaryotes.
 
TET Systems Conference Activities 2009
TET Systems successfully attended this year`s Bio International Convention in Atlanta and Bio-Europe in Vienna. TET`s major focus at these conferences was on partnering new technologies and on identifying new potential licensees for the Tet Technology.
This year`s Conference highlight was a sponsored workshop during the "First EMBO Conference" in Amsterdam, the first annual life science conference organized by EMBO. TET Systems together with its partner Clontech, sponsored a scientific symposium titled "The Tet Technology and its Impact on Modern Life Sciences". After an introduction by Prof. H. Bujard, one of the inventors of the Tet Technology, several distinguished scientists (R.Jaenisch, MIT, D.Felsher, Stanford University and L.Alphey, Oxitec) presented data on exciting new applications of the Tet Technology.
In 2010 TET Systems plans to attend Bio International Convention in Chicago in May and BioEurope2010 in Munich.
 
New Publication Highlight

M.S.H. Ko and colleagues recently published a highly interesting paper on early responses of gene regulatory networks. Placing 50 transcription factors encoded in the mouse genome systematically under Tet control in a highly defined chromosomal locus (ROSA-Tet), they generated ES cell lines in which one transcription factor can be induced at a time, enabling analyses of resulting transcription factor network changes. These highly standardized ES cell lines which are freely provided to the academic research community by the authors have already documented that not all transcription factors are equal and will be valuable research tools to gain further insights into gene regulatory networks.

New online tool to search Tet bibliography

Early next year, a new tool to search our Tet bibliography online will become available to visitors of our website. This new tool will enable interested parties to search the entire Tet literature database without a required previous download. Our database meanwhile comprises 6,200 references of peer reviewed scientific articles on applications of the Tet Technology underlining the importance of the Tet Technology as the most widely used inducible gene expression system. The Tet bibliography is the most comprehensive list of Tet references and is updated on a yearly basis as a free service that TET Systems provides to its licensees and the scientific community.
 
Holiday Notice
Our offices will be closed starting on Dec. 24th until Jan. 4th, 2010. We wish you all an enjoyable Holiday Season and a great start into a successful New Year.
 
To our Readers

We are continuously trying to improve our services and information to all users of the Tet Technology. We appreciate your comments and feed-back regarding this Newsletter and all other proposals regarding our homepage. Please send your comments/proposals to info@tet-systems.com.

 

 

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Newsletter July 2009


TET Systems attends the first  "EMBO Meeting" in Amsterdam  

TET Systems will attend the first EMBO Meeting in Amsterdam both as exhibitor and sponsor of a scientific symposium on Monday, August 31: "The Tet Technology and its Impact on Modern Life Sciences" which we organize together with our partner Clontech. A prominent group of speakers (R.Jaenisch, D.Felsher and L.Alphey) will summarize recent advances in the fields of stem cell biology, cancer disease and progression and sterile insect technology. Prof. H. Bujard, one of the inventors of the Tet Technology, will provide an introductory overview. Please join us at this interesting workshop. We also look forward to meeting our customers, partners and all interested parties in Amsterdam.


New marketing agreement signed with Takara Bio


Takara Bio Inc., an innovative biotechnology company based in Japan, listed on the Tokyo Stock Exchange, and TET Systems Holding, a privately-held, German-based biotech company have entered into a marketing agreement in May. Takara Bio Inc. has been engaged in development, manufacturing, and sales of research reagents and equipment to the life science research market in Japan as well as other countries, and has extensive experience in establishing various types of alliances with Japanese companies and public institutions. Takara Bio Inc. will use this experience and its sales and marketing expertise to exclusively market the Tet Technology for TET Systems Holding in Japan.


TET`s web based services

On its home page (www.tet-systems.com), TET Systems offers a range of services for registered users including reviews of recently published scientific articles. We also provide a comprehensive list of transgenic animals and all scientific publications using the Tet Technology.


Publication Highlights

This section provides regular summaries and/or reviews of scientific manuscripts which we consider of particular interest to the users of the Tet Technology. Publications are selected that cover applications of our technology in a "hot" field of research (e.g. RNAi, iPS or sterile insect control) or novel and innovative applications of our Tet Technology. We also highlight scientific publications describing break-through research where the Tet Technology was instrumental for new and groundbreaking insights in an established field.   


List of Tet transgenic mouse lines updated

A first update of the table of Tet transgenic mice is now available online under "SUPPORT". This comprehensive list is based on a recent literature search for new transgenic mouse lines expressing either Tet transactivators (e.g. Tet-On, Tet-Off or Tet-On/Off Advanced) or mice expressing various genes under Tet control. The table also provides referencing of the original publication to facilitate understanding of the genealogy of the Tet transgenic mouse. The availability of these transgenic mouse lines from our partners, certified repositories like "the Jackson Labs","EMMA" or "Riken", are also provided.


New Tet bibliography online

The new, comprehensive list of Tet references (scientific articles using our Tet Technology) is available for download now. This updated list comprises more than 6200 peer reviewed scientific articles underlining the importance of the Tet Technology as the most widely used inducible gene expression system. The Tet bibliography is updated on a yearly basis and covers original work. Review articles are only included when the Tet gene expression systems are the focus of the review.


To our Readers

We are continuously trying to improve our services and information to all users of the Tet Technology. We appreciate your comments and feed-back regarding this Newsletter and all other proposals regarding our homepage. Please send your comments/proposals to info@tet-systems.com.
    

 

 

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