FREISING, GERMANY & REHOVOT, ISRAEL, October 21, 2014 –
Yeda Research and Development Company Ltd., the technology transfer arm of the Weizmann Institute of Science, Israel, and XL-protein GmbH, Germany, a privately owned biopharmaceutical company, have signed a business collaboration agreement to commercialize a PASylated interferon superagonist – PAS-YNSα8 – which has been jointly developed by scientists at the Weizmann Institute and XL-protein. Under this agreement, YEDA acquires the worldwide exclusive rights for marketing and out-licensing of this compound.
One of the potential uses of PAS-YNSα8 is for treating inflammatory diseases, in particular of the central nervous system. An example is multiple sclerosis (MS), a devastating chronic, progressive immune disease of the central nervous system that can eventually lead to paralysis. Among the drugs today used to treat MS are those based on interferon-beta (IFN-beta).
Weizmann Institute scientists developed a novel, highly active interferon variant, YNSα8. This modified IFN was engineered to bind much more tightly to the interferon receptors. The result is a very potent molecule, which shows a gene activation profile and biological activities that surpass any naturally existing interferon.
Together with scientists at XL-protein, the activity of PAS-YNSα8 was boosted by extending its half-life in the body using PASylation® technology. PASylation® involves the genetic fusion of the therapeutic protein or peptide with a non-structured, expanded polypeptide made of the small amino acids Pro, Ala and Ser (PAS).
In a study that appeared in the Journal of Biological Chemistry (2014, Vol. 289, No. 42, pp. 29014-29029) and was led by Dr. Daniel Harari and Prof. Gideon Schreiber at the Weizmann Institute, it was found that the in vivo half-life of PAS-YNSα8 was increased 10-fold in comparison to standard interferon. Most importantly, the PASylation® did not interfere with the biological activity of this potent IFN; this has been a common technical problem for other methods of extending drug circulation. In a head-to-head comparison with conventional IFN-beta, this long-living superagonist conferred highly improved protection from disease progression in a mouse model of human multiple sclerosis, despite being injected four times less often than IFN-beta and at one-sixteenth of the dosage.
“We are excited by the pronounced therapeutic effect of our PASylated IFN superagonist, which was not accompanied by any observable immunogenic side effects in mice,” said Prof. Schreiber. “Our studies suggest that this potential drug could be safe and might provide clinical benefit surpassing that of IFN-beta, all this with a significantly reduced number of injections and lower dosage. We hope it will soon be possible to check the effectiveness of our molecule in clinical trials in humans.”
“The biological potency and bioavailability of this novel IFN-based molecule is remarkable. Improved receptor binding, achieved by advanced protein engineering, in synergy with the half-life extension provided by our PASylation® technology, will result in more effective and less frequent dosing for the benefit of patients,” said Prof. Arne Skerra, CSO of XL-protein and co-author of the study. “We are pleased to forge this business alliance with a renowned partner such as YEDA to commercialize this potent biological drug candidate,” added Claus Schalper, CEO of XL-protein.
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XL-protein Signs Licensing Agreement with MSD Animal Health to Develop Biopharmaceuticals using its PASylation® Technology
/in News /by web28627236FREISING, GERMANY, February 12, 2015 – XL-protein GmbH, Germany, a privately owned biopharmaceutical company, announced today that they have entered into a license agreement with MSD Animal Health (known as Merck Animal Health in the USA and Canada) to develop PASylated biopharmaceuticals for use in animal health. This license agreement follows a research collaboration between the two companies which began in 2012 and included a feasibility study in target animals.
Under the terms of the agreement, MSD Animal Health acquires worldwide exclusive rights for certain biopharmaceutical drug candidates. In support of the commercialization effort, XL-protein will further optimize the drug candidates against undisclosed MSD Animal Health targets using its proprietary PASylation® platform for plasma half-life extension. This technology has been previously used for human health medications. MSD Animal Health will be responsible for clinical development and commercialization of biopharmaceuticals generated under the collaboration.
“We are delighted to be working with such a renowned partner as MSD Animal Health, who is a leader in the field of veterinary medicine”, said Claus Schalper, CEO&CFO of XL-protein. Prof. Dr. Arne Skerra, CSO of XL-protein, added: “This agreement with MSD Animal Health reflects the significant advantages we have seen for our PASylation® platform over competing technologies for creating biologic drug candidates with extended half-life and enhanced action, especially with regard to tolerance and biodegradability in treated subjects.”
“We strongly believe in the product development synergies between human and animal health and look forward to the opportunities this collaboration will offer to meet the unique challenges in the animal health market,” says Holger Lehmann, Head of Drug Discovery at MSD Animal Health.
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XL-protein and YEDA sign business collaboration agreement to commercialize PASylated interferon superagonist
/in News /by web28627236FREISING, GERMANY & REHOVOT, ISRAEL, October 21, 2014 –
Yeda Research and Development Company Ltd., the technology transfer arm of the Weizmann Institute of Science, Israel, and XL-protein GmbH, Germany, a privately owned biopharmaceutical company, have signed a business collaboration agreement to commercialize a PASylated interferon superagonist – PAS-YNSα8 – which has been jointly developed by scientists at the Weizmann Institute and XL-protein. Under this agreement, YEDA acquires the worldwide exclusive rights for marketing and out-licensing of this compound.
One of the potential uses of PAS-YNSα8 is for treating inflammatory diseases, in particular of the central nervous system. An example is multiple sclerosis (MS), a devastating chronic, progressive immune disease of the central nervous system that can eventually lead to paralysis. Among the drugs today used to treat MS are those based on interferon-beta (IFN-beta).
Weizmann Institute scientists developed a novel, highly active interferon variant, YNSα8. This modified IFN was engineered to bind much more tightly to the interferon receptors. The result is a very potent molecule, which shows a gene activation profile and biological activities that surpass any naturally existing interferon.
Together with scientists at XL-protein, the activity of PAS-YNSα8 was boosted by extending its half-life in the body using PASylation® technology. PASylation® involves the genetic fusion of the therapeutic protein or peptide with a non-structured, expanded polypeptide made of the small amino acids Pro, Ala and Ser (PAS).
In a study that appeared in the Journal of Biological Chemistry (2014, Vol. 289, No. 42, pp. 29014-29029) and was led by Dr. Daniel Harari and Prof. Gideon Schreiber at the Weizmann Institute, it was found that the in vivo half-life of PAS-YNSα8 was increased 10-fold in comparison to standard interferon. Most importantly, the PASylation® did not interfere with the biological activity of this potent IFN; this has been a common technical problem for other methods of extending drug circulation. In a head-to-head comparison with conventional IFN-beta, this long-living superagonist conferred highly improved protection from disease progression in a mouse model of human multiple sclerosis, despite being injected four times less often than IFN-beta and at one-sixteenth of the dosage.
“We are excited by the pronounced therapeutic effect of our PASylated IFN superagonist, which was not accompanied by any observable immunogenic side effects in mice,” said Prof. Schreiber. “Our studies suggest that this potential drug could be safe and might provide clinical benefit surpassing that of IFN-beta, all this with a significantly reduced number of injections and lower dosage. We hope it will soon be possible to check the effectiveness of our molecule in clinical trials in humans.”
“The biological potency and bioavailability of this novel IFN-based molecule is remarkable. Improved receptor binding, achieved by advanced protein engineering, in synergy with the half-life extension provided by our PASylation® technology, will result in more effective and less frequent dosing for the benefit of patients,” said Prof. Arne Skerra, CSO of XL-protein and co-author of the study. “We are pleased to forge this business alliance with a renowned partner such as YEDA to commercialize this potent biological drug candidate,” added Claus Schalper, CEO of XL-protein.
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XL-protein announces publication of key scientific data on its PASylation® technology
/in News /by web28627236FREISING, GERMANY, August 30, 2013 – XL-protein GmbH announced today that key scientific data have been published in the journal Protein Engineering, Design & Selection (2013, Vol. 26, No. 8, pp. 489–501, 2013). The Open Access Publication “PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins” is also available for download at XL-protein’s web site (http://www.xl-protein.com/publications.html).
A major limitation of biopharmaceutical proteins is their fast clearance from circulation via kidney filtration which strongly hampers efficacy in human therapy. XL-protein has developed conformationally disordered polypeptide chains with expanded hydrodynamic volume comprising the small residues Pro, Ala and/or Ser (PAS). PAS sequences are hydrophilic, uncharged, genetically encodable amino acid polymers with biophysical properties very similar to poly-ethylene glycol (PEG), whose conjugation to drugs is a well known method for plasma half-life extension.
In contrast, beside chemical coupling PAS polypeptides offer fusion to a therapeutic protein on the genetic level, permitting production of fully active proteins in E. coli and other widely used host organisms (including cell culture secretion) without any in vitro modification steps. Importantly, PAS polypeptides are biodegradable, thus avoiding organ accumulation, while showing stability in serum and lacking toxicity or immunogenicity in animals. The publication describes that PASylation® furnishes typical biologics, such as interferon, growth hormone or antibody Fab fragments, with considerably prolonged circulation in vivo.
This work is complemented by another publication “High-yield production of PASylated human growth hormone (hGH) using secretory E. coli technology” that has appeared in the journal BioProcess International (2013, Vol. 11, No. 4, pp. 30–38) and is also available for download at XL-protein’s web site.
“PASylation® offers unique advantages, that is, surprisingly similar biophysical behavior compared with PEGylation, strong and tunable PK extending effects and conservation of high target-binding activity,” stated Uli Binder, CTO of XL-protein GmbH.
Arne Skerra, CEO of XL-protein GmbH, said: “PASylation® enables the preparation of biologically and/or pharmaceutically functional proteins with prolonged and enhanced in vivo activity, which constitutes a bottleneck in current biological drug development and opens exciting commercial opportunities.”
XL-protein’s proprietary PASylation® technology can be applied both to existing biologics, yielding biobetters, or to innovative therapeutic proteins or peptides, leading to tunable prolonged plasma half-life by a factor 10-100 as demonstrated in numerous animal studies up to now.
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XL-protein and GENERIUM sign broad therapeutic license and collaboration agreement to develop PASylated therapeutics for the Russian Federation
/in News /by web28627236Freising, Germany & Moscow, Russia, June 25, 2013
XL-protein and GENERIUM announce the closing of a license and a collaboration agreement. Under these agreements, XL-protein will license a PASylated blood clotting factor and apply its proprietary PASylation® technology for plasma-half life extension to a cytokine, respectively, for use in the Russian Federation and Commonwealth of Independent States (CIS).
GENERIUM acquires exclusive marketing rights for the Russian Federation and CIS and will assume responsibility for further development and marketing of said compounds within this territory. XL-protein retains development and marketing rights for Rest of World.
Under the terms of the license agreement, XL-protein receives a seven digit US$ upfront payment upon signing of the agreement. In addition, XL-protein will receive payments for the achievement of preclinical, clinical, regulatory, and commercial milestones as well as significant royalties on sales.
“This strategic cooperation with a renowned pharmaceutical company of GENERIUM’s caliber demonstrates the high potential of our PASylation® technology to develop biologics with superior activities”, noted Prof. Dr. Arne Skerra, CEO of XL-protein.
“Setting up multiple international collaborations is a key element of Generium’s strategy. The Company provides unique opportunities for international collaborative R&D projects which are often associated with technology and know-how transfer and are actively supported by the Russian Ministry of Industry and Trade”, noted PhD Sergey Ruchko, CEO of IBC Generium.
XL-protein’s proprietary PASylation® technology is a biological alternative to PEGylation, conferring an expanded hydrodynamic volume onto the biopharma-ceutical which leads to retarded kidney filtration based on a molecular size effect. A tunable prolonged plasma half-life by a factor 10-100 has been demonstrated for various compounds in preclinical animal studies. Thus, PASylation® offers a cost-effective and patient-friendly solution to a general problem in biopharmaceutical drug development.
First data from this collaboration will be presented at the 38th Congress of the Federation of European Biochemical Societies (FEBS) in St. Petersburg, Russia, July 6-11, 2013.
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XL-protein and Wacker Biotech produce a PASylated antibody fragment (Fab) with prolonged plasma half-life at more than four grams per liter culture in an E. coli expression system
/in News /by web28627236High Yield with ESETEC® and PASylation®: Wacker Biotech and XL-protein Produce More than Four Grams per Liter of Fab Antibody Fragment with Prolonged Plasma Half-Life
Munich, Jena and Freising, April 18, 2013 – In the course of their
collaboration, Wacker Biotech and XL-protein have produced record yields of a PASylated Fab antibody using WACKER’s E. coli based ESETEC® secretion technology. WACKER developed an efficient bacterial cell line and was able to produce the Fab antibody in concentrations of more than four grams per liter of culture broth. This Fab antibody is being tested as a novel therapeutic agent for treating autoimmune diseases. These results open up new opportunities for developing monovalent antibody drugs that can be produced at lower cost, with fewer side-effects and with a tunable plasma half-life. As part of their recent collaboration agreement, WACKER and XL-protein are offering pharmaceutical customers access to the combination of the PASylation® platform and the ESETEC® technology. WACKER also has the necessary expertise for GMP-compliant production of biologics.
In a feasibility study, Wacker Biotech and XL-protein tested the use of WACKER’s patented ESETEC® technology to produce PASylated Fab antibody fragments for the development of new drugs to treat autoimmune
diseases. The study not only confirmed that the biopharmaceutical can be produced in high yield (4.3 g/l) by the patented ESETEC® technology. It also demonstrated that correctly folded, fully functional antibody fragments are efficiently secreted into the culture broth – this greatly simplifies downstream purification. Detailed biochemical characterization revealed monodispersity of the product and excellent antigen-binding activity.
For many years, antibody products have been a promising growth area for the pharmaceutical industry. Antibodies are highly specific in their ability to intervene with disease mechanisms, and they usually circulate in the body for several weeks. However, in certain indications, some of their features can be detrimental: stimulation of the immune system via the antibody effector region; bivalent binding or crosslinking of the antigen; or the antibodies’ long biological half-life. XL-protein therefore decided to develop a monovalent antigen-binding antibody fragment (Fab) that does not bind immunoreceptors and promises fewer sideeffects. Furthermore, PASylation® prolongs its plasma half-life and thus allows for optimal tuning of drug activity. Fab fragments are derived from human antibodies and can be manufactured as separate recombinant proteins. One of their advantages over full-length antibodies is an improved ability to penetrate the diseased tissue. Since Fabs are not glycosylated, they can be produced cost-effectively in microbial organisms such as E. coli. Nonetheless, Fab antibody fragments are much more difficult to produce than other therapeutic proteins, as they are composed of two different protein subunits and contain several disulfide bridges. So far, conventional production methods have yielded less than 2 grams per liter of culture.
“We are delighted – the results open up new avenues for the development of antibody products,” says Dr. Thomas Maier, managing director of Wacker Biotech. “ESETEC® produces Fab antibody fragments in record yields that until now had only been possible for whole antibodies using mammalian cell cultures. Yet, development and production times with ESETEC® are much faster than with mammalian cells. This saves our customers costs and shortens the time to market.” ESETEC® is a proprietary WACKER technology with a track record of cost-effective production of proteins and antibody fragments. It is based on an E. coli K12 strain which has the ability to secrete correctly folded recombinant proteins into the culture broth during fermentation. Secretion facilitates purification of the target protein, since there is no longer any need for complicated process steps such as homogenization and refolding. This makes the entire manufacturing process significantly more efficient and cost-effective. A number of biologics that have been manufactured with ESETEC® are already being evaluated in preclinical and clinical studies. Plus, a successful preliminary study with XL-protein has shown that the WACKER technology is highly efficient at producing PASylated human growth hormone.
According to Prof. Arne Skerra, managing director of XL-protein GmbH, “The fact that our PASylation® technology allows efficient and inexpensive production of antibody fragments with extended plasma half-life abolishes a major disadvantage of these highly effective and low-side-effect biologics, compared to conventional antibodies. Especially in conjunction with ESETEC®, it is now possible to rapidly manufacture improved antibody products with tailored properties in high yield.”
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Wacker Biotech and XL-protein Sign Long-Term Cooperation Agreement to Produce PASylated Biopharmaceuticals
/in News /by web28627236Munich / Freising / Jena, October 30, 2012
Wacker Biotech GmbH and XL-protein GmbH are to collaborate more intensely on the production of PASylated therapeutic proteins. Today, the two companies announced the signature of an agreement to this effect. Through this collaboration, WACKER and its customers will gain access to XL-protein’s PASylation® platform. The PASylation® technology enables the development of biopharmaceuticals with extended plasma half-lives, which require less frequent injection and thus are more patient friendly. In a recent feasibility study, PASylated human growth hormone was successfully produced in high yields using WACKER’s E. coli-based ESETEC® technology.
In a feasibility study, Wacker Biotech and XL-protein tested WACKER’s patented ESETEC® technology for the production of large-sized PASylated therapeutic proteins. The study showed that ESETEC® produced a PASylated human growth hormone – correctly folded and fully functional – in high yields (3 to 4 g/l). Moreover, WACKER successfully used its secretion technology to develop an E. coli cell line for manufacturing the PASylated hormone. The production process is easy to implement on an industrial scale.
“Following the successful feasibility study, we are very much looking forward to intensifying our collaboration with XL-protein,” said Dr. Thomas Maier, managing director of Wacker Biotech GmbH. “More and more pharmaceutical companies are looking for efficient ways of prolonging the therapeutic effect of biologics. With this cooperation agreement with XL-protein,” he continued, “we can now offer our customers feasibility studies for the production of PASylated variants of their therapeutic lead candidates. Thanks to our innovative ESETEC® technology, we can supply research quantities of PASylated active ingredients for pre-clinical studies within a couple of weeks.”
“After our positive experience with WACKER’s innovative secretion technology in producing PASylated therapeutic proteins,” said Prof. Arne Skerra, XL-protein’s co-founder and CEO, “we want to continue our collaboration in this field on a long-term basis. By partnering with Wacker Biotech, we can offer access to our innovative technology to a much wider circle of customers,” he emphasized. “As an experienced GMP manufacturer, WACKER can ensure that PASylated proteins are produced quickly and professionally.”
ESETEC®, WACKER’s patented E. coli-based secretion system, is a well-established technology for producing proteins and antibody fragments cost-efficiently. It is based on a patented strain of E.coli, K12, which is capable of secreting recombinant proteins in their native conformation directly into the culture broth during fermentation. This facilitates the subsequent purification of the target protein, since complicated process steps such as homogenization and refolding are unnecessary. This makes the entire manufacturing process significantly more efficient and cost-effective. A number of biologics manufactured with ESETEC® are already being evaluated in preclinical and clinical trials.
XL-protein and Wacker demonstrate high-yield production of PASylated biopharmaceuticals using ESETEC®
/in News /by web28627236Munich / Jena, June 11, 2012 – Wacker Biotech and XL-protein have successfully completed a feasibility study on the production of PASylated therapeutic proteins using WACKER’s ESETEC® E. coli secretion technology. In the study, WACKER technology was used to investigate the production of a PASylated human growth hormone as model protein. WACKER developed a cell line which, utilizing the ESETEC® technology, generated high yields of the PASylated protein. The PASylation® technology enables the development of biopharmaceuticals with extended plasma half-life, thus leading to a new generation of drugs with improved tolerability and requiring less frequent administration due to their longer lasting activity.
The aim of the study was to assess whether clinically established therapeutic proteins that have been improved by PASylation® can be produced in high yields by using state-of-the-art, cost-effective manufacturing processes. The study used WACKER’s proprietary E. coli-based secretion technology to produce a PASylated human growth hormone.
The feasibility study demonstrated that the desired PASylated protein, carrying a 600 amino-acid sequence consisting of proline, alanine and serine, can be successfully produced with ESETEC®. In addition, it also led to an efficient cell line which, during fermentation, secretes the correctly folded, fully functional protein into the culture medium in high yield (3-4 g/l). This is remarkable, as the availability of sufficient quantities of amino acid building blocks from the bacterial primary metabolism for the biosynthesis of large PASylated proteins represented a potential challenge. Moreover, detailed analytical studies showed that the PASylated human growth hormone was produced with high homogeneity in monomeric, non-aggregated form, retaining a remarkably high affinity for its receptor.
Compared to PEGylation, the current standard technology for extending the plasma half-life of biopharmaceuticals, PASylation® has the major advantage of avoiding an expensive and poorly selective chemical modification step during production. Moreover, unlike the chemical polymer PEG, the PAS amino acid sequences are biodegradable and therefore do not accumulate in cells or organs.
ESETEC®, WACKER’s patented E. coli-based secretion system, is a well-established technology for producing proteins and antibody fragments cost-efficiently. It is based on a patented strain of E. coli K12, which is capable of secreting recombinant proteins in their native conformation into the culture broth during fermentation. Secretion into the medium facilitates the purification of the target protein considerably, since complicated process steps such as homogenization and refolding are no longer necessary, making the entire manufacturing process significantly more efficient and cost-effective. A number of biopharmaceuticals (biologics) manufactured with ESETEC® are already being evaluated in preclinical and clinical trials.
According to Dr. Thomas Maier, managing director of Wacker Biotech GmbH, he and his team “are delighted by the early results of our collaboration with XL-protein. PASylation® is an extremely interesting technology for selectively improving the properties of biopharmaceuticals. With our innovative ESETEC® secretion technology, such products can now be manufactured cost-effectively on an industrial scale.”
Prof. Dr. Arne Skerra, CEO of XL-protein GmbH, concurs. “We are extremely satisfied with the results of the feasibility study. This allows us to bypass the expensive in-vitro modification steps as they are required in other processes currently available. The successful combination of our PASylation® technology with WACKER’s ESETEC® secretion technology has a high potential for synergies with respect to the efficient and rapid production of novel therapeutic proteins using an established host organism like E. coli with its well-known advantages.”
XL-protein announces in vitro and in vivo data for its PASylated hGH
/in News /by web28627236FREISING, GERMANY, September 23, 2011 – XL-protein GmbH, a German biotech company specialised in the development of biopharmaceuticals with extended plasma half-life, announced today preclinical in vitro and in vivo data for its xl020 PAS-hGH program. The xl020 data demonstrate XL-protein’s ability to furnish an approved biological drug with improved in vivo stability and plasma half-life using its proprietary PASylation® technology, leading to enhanced efficacy in an established animal model.
The results of XL-protein’s xl020 studies will be presented at the R&D of Novel Protein Therapeutics and Post-Translational Modifications Conferences on Tuesday and Wednesday 27/28 September 2011 in Berlin, Germany, in a presentation entitled “PASylation: a biological alternative to PEG for extending the plasma half-life of biopharmaceuticals”.
“This program is extremely exciting because it provides an in vivo proof of concept that a PASylated biological does not only show prolonged pharmacokinetics but also increased potency, even if applied at longer time intervals compared with the unmodified protein,” stated Uli Binder, co-founder and CTO of XL-protein GmbH.
XL-protein researchers documented that xl020 has much longer plasma-half life than the unmodified recombinant growth hormone while retaining high receptor binding activity, which translated into increased in vivo efficacy. In a preclinical mouse model of growth hormone deficieny, xl020 administration showed continuous strong weight gain over at least 10 days.
Arne Skerra, co-founder and CEO of XL-protein GmbH, said: “Our PASylated hGH program highlights XL-protein’s strategy of developing superior therapeutics based on approved biopharmaceuticals. xl020 is a promising development candidate that addresses a multi-billion dollar market world-wide.”
hGH is a natural peptide hormone that regulates body growth and metabolism. Growth hormone deficiency (GHD) can occur in both pediatric and adult patients (GHDA). Furthermore, hGH is currently approved for several other indications, for example AIDS wasting and cachexia or short stature caused by Turner’s Syndrome or Prader-Willi syndrome. xl020 should allow less frequent and lower dosing, promising better tolerability and patient compliance, also benefiting from the inherent biodegradability of PAS polypeptides.
XL-protein’s proprietary PASylation® technology can be applied both to existing biologics, yielding ‘biobetters’, or to innovative therapeutic proteins or peptides, leading to tunable prolonged plasma half-life by a factor 10-100 as demonstrated in numerous animal studies. Thus, PASylation® offers a superior solution to a general problem in biological drug development.
European patent granted for XL-protein’s PASylation® technology
/in News /by web28627236FREISING, GERMANY, MARCH 17th, 2011 – XL-protein GmbH, a German biotech company that specialises in the development of biopharmaceuticals with extended plasma half-life, today announced that the European Patent Office granted a core patent (EP2173890) for XL-protein’s PASylation® technology.
Beside the granted PASylation® EP patent, several other corresponding national patent applications are currently processed worldwide. The European patent covers the use of random coil polypeptide sequences comprising the natural amino acids Proline, Serine, and Alanine (PAS) to enhance the stability of biologically active proteins if attached as part of a fusion protein.
The N- or C-terminal PAS tag can be directly produced together with the therapeutic protein in microbial hosts, e.g. E. coli, or in cell culture, thus avoiding costly in vitro coupling steps that are required for other presently available approaches such as PEGylation. Furthermore, the biodegradability of the PAS polypeptide should prevent organ accumulation during chronic treatment.
PASylation® can be applied both to existing biologics, yielding ‘biobetters’, or to innovative therapeutic proteins or peptides, leading to a prolonged plasma half-life by a factor 10-100 as demonstrated in numerous animal studies. Thus, PASylation® offers a superior solution to a general problem in biological drug development, eventually allowing less frequent and lower dosing together with better tolerability for patients.
Dr. Arne Skerra, founder and CEO of XL-protein GmbH, said: “This patent is an important milestone for our company and its collaboration partners. It reinforces our competitive market position and will strengthen corporate development”.
This revolutionary principle for increasing drug stability was originally developed at the Technische Universität München (TUM). In 2009, XL-protein entered into a license agreement with TUM via Bayerische Patentallianz GmbH, the central patent and marketing agency for 28 Bavarian universities and universities of applied sciences, and acquired the exclusive worldwide rights for the PASylation® technology, which also includes the right to grant sublicenses.
Mr. Peer Biskup, CEO of the Bayerische Patentallianz GmbH, commented: “The Bayerische Patentallianz is very pleased with the timely decision of the EPO to grant the first PASylation® patent and with the positive development of XL-protein’s business, which involves both in house drug development activities and partnering with pharma and biotech companies.”
Phylogica collaborates with XL-protein on inflammation Program
/in News /by web28627236XL-protein Collaborates with Phylogica on Inflammation Program
PERTH, AUSTRALIA, January 13, 2011 – Phylogica Ltd (ASX: PYC), a leading Australian-based drug discovery company, announced today an alliance with XL-protein GmbH, a German-based biotech company that specialises in extending the circulation half-life of biopharmaceuticals. Through this alliance, Phylogica gains access to a unique modification technology that strengthens the Company’s Phylomer drug discovery platform.
XL-protein’s PASylation technology was originally developed by a leading academic group at the prestigious Technical University of Munich (TUM). The technology utilises a genetic technique to fuse a polymer of natural amino acids onto the relevant peptide or protein-based therapeutic, which slows the body’s clearance of the drug and prolongs the therapeutic effect.
Phylogica and XL-protein will initially collaborate on a pilot study to validate the technology in combination with one of Phylogica’s Phylomer peptides targeting CD40 ligand from its in-house anti-inflammatory programme. Under the terms of the agreement, Phylogica has an option to obtain an exclusive license to the PASylation technology for peptide-based products in relation to CD40 ligand and has rights of negotiation for a license to the technology for Phylomers that bind other targets.
It is anticipated that the plasma half-life of PASylated Phylomers will be significantly extended, making them more suitable for less frequent administration and at lower dose. Long acting Phylomers would be ideal for treating chronic indications, such as rheumatoid arthritis, coronary artery disease and inflammatory bowel disease, in which CD40 ligand has been implicated as a potential target.
Phylogica’s Chief Executive Officer, Dr Paul Watt, commented: “Phylogica is excited to enter into this collaboration with XL-protein. This deal provides us with access to the next generation of polypeptide fusions for optimising the half-life of our Phylomers. The technology combination of XL-protein and Phylogica could also significantly facilitate the ease of manufacturing and lower the cost of goods.”
Dr Arne Skerra, founder and CEO of XL-protein GmbH, said: “XL-protein is delighted to apply its PASylation technology to Phylomers, which will serve to validate the benefit of this revolutionary half-life extension technology to a highly promising class of therapeutic peptide drugs.”