44 AUGUST 2006 www.sp2.uk.com Biopharmaceuticals Ensuring access to antibody technologies Do recent acquisitions in the monoclonal antibodies sector restrict access to intellectual property and technologies for the development of new biologics? Eskil Söderlind, business development director of BioInvent International AB, considers the issue. F ollowing AstraZeneca’s recent offer for the shares of Cambridge Antibody Technology and last year’s acquisition of Abgenix by Amgen, it’s not unreasonable to ask whether such acquisitions will lead to reduced access to intellectual property (IP) for the development of new monoclonal antibody therapeutics. According to Dr Eskil Söderlind, business development director of BioInvent International AB, such moves may limit access to IP in the future, but for the moment companies are still using monoclonal antibody technology under well- established licensing agreements. These technologies have developed considerably since the potential of monoclonal antibodies as therapeutics was first recognised. Söderlind explains how the technology has evolved over the years: “The concept of using monoclonal antibodies as therapeutics was very new in the 1980s,” he says. “Initially the investigations were based on mouse antibodies, which were seen as potential ‘Magic Bullets’ that could solve difficult therapeutic problems and unmet medical needs, but soon the drawbacks due to their non-human nature became apparent, as the antibodies produced immune responses in patients. The obvious strategy was to make them more human-like, and by the mid-1980s chimeric amitbodies, which were half-human, half-mouse, were under development. This was the first major use of recombinant technologies in the antibody development field, and further refinement of these technologies produced humanised antibodies that were more than 95 per cent human. This was achieved by using those parts of the antibodies that were responsible for their binding activities against antigens - researchers combined mouse CDR loops with a human antibody scaffold to make the antibodies even more human than chimeric antibodies. “By the early 1990s fully human monoclonal antibodies were being produced,” he continues. “There are two main approaches to achieving this. The first is the use of a ‘human’ mouse, that is, a genetically-modified mouse that is capable of producing human antibodies. The second is the use of antibody libraries, that is, of large collections of antibodies. The method using antibody libraries is to ‘fish out’ an existing antibody from the collection using a target that binds to the antibody. There are three approaches that can be used to generate the libraries: first, systems can be developed based on how the immune system operates and triggers antibody binding; second, antibodies with potentially the best binding characteristics can be rationally designed in the laboratory; and third, what we at BioInvent believe is the most efficient method, the combination of specific human CDR loops in a single human antibody framework. “As described above, the first research on monoclonal antibodies were BioInvent: freely operating with the latest technologies for identification, development and production of human monoclonal antibody therapeutics. “Alliances allow Big Pharma to gain access to human antibody technology” “Acquisitions reflect the growing importance of human antibody therapeutics”
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44 AUGUST 2006 www.sp2.uk.com
Biopharmaceuticals
Ensuring access to antibody technologiesDo recent acquisitions in the monoclonal antibodies sector restrict access to intellectual property
and technologies for the development of new biologics? Eskil Söderlind, business development
director of BioInvent International AB, considers the issue.
Following AstraZeneca’s recent offer for the shares ofCambridge AntibodyTechnology and
last year’sacquisition ofAbgenix byAmgen, it’snotunreasonableto askwhether suchacquisitions willlead to reducedaccess to intellectualproperty (IP) for the development of new monoclonal antibodytherapeutics.
According to Dr Eskil Söderlind, business developmentdirector of BioInvent International AB, such moves may limitaccess to IP in the future, but for the moment companies arestill using monoclonal antibody technology under well-established licensing agreements.
These technologies have developed considerably since thepotential of monoclonal antibodies as therapeutics was firstrecognised. Söderlind explains how the technology has evolvedover the years:
“The concept of using monoclonal antibodies as therapeuticswas very new in the 1980s,” he says. “Initially the
investigations were based on mouse antibodies, which wereseen as potential ‘Magic Bullets’ that could solve difficulttherapeutic problems and unmet medical needs, but soon thedrawbacks due to their non-human nature became apparent, asthe antibodies produced immune responses in patients. Theobvious strategy was to make them more human-like, and bythe mid-1980s chimeric amitbodies, which were half-human,half-mouse, were under development. This was the first majoruse of recombinant technologies in the antibody developmentfield, and further refinement of these technologies producedhumanised antibodies that were more than 95 per cent human.This was achieved by using those parts of the antibodies thatwere responsible for their binding activities against antigens -researchers combined mouse CDR loops with a human antibody
scaffold to make theantibodies even more
human thanchimericantibodies.
“By theearly 1990s
fully humanmonoclonal
antibodies werebeing produced,” he
continues. “There are two mainapproaches to achieving this. The first is the use of a ‘human’
mouse, that is, a genetically-modifiedmouse that is capable of producinghuman antibodies. The second is theuse of antibody libraries, that is, oflarge collections of antibodies. Themethod using antibody libraries is to‘fish out’ an existing antibody from thecollection using a target that binds tothe antibody. There are threeapproaches that can be used togenerate the libraries: first, systems canbe developed based on how theimmune system operates and triggersantibody binding; second, antibodieswith potentially the best bindingcharacteristics can be rationallydesigned in the laboratory; and third,what we at BioInvent believe is themost efficient method, the combinationof specific human CDR loops in asingle human antibody framework.
“As described above, the firstresearch on monoclonal antibodies were
BioInvent: freely operating with the latest technologies for identification, development and productionof human monoclonal antibody therapeutics.
“Alliancesallow Big Pharma to
gain access to humanantibody technology”
“Acquisitionsreflect the growing
importance of humanantibody therapeutics”
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46 AUGUST 2006 www.sp2.uk.com
Biopharmaceuticals
investigations into ways of making them more human, one ofthe early pioneers being US company Protein DesignLaboratories, Inc,” says Söderlind. “The ‘human mouse’approach was extensively studied in the late 1980s and early1990s, companies such as Medarex, Inc and Abgenix, Inc inthe USA and Kirin in Japan being prominent in the field. Sincethen the antibody library approach has yielded very promisingresults, with companies like Cambridge Antibody Technology(CAT) in the UK; Dyax, Inc in the USA; MorphoSys AG inGermany; and BioInvent International AB in Sweden havinggreat success in developing pipelines of antibodies with realtherapeutic potential.”
Strategic partnershipswith Big PharmaSöderlind says that initiallycompanies such as the onesmentioned above operatedas technology providersalong the lines of servicecompanies, but later thebusiness models adopted weremore those of being strategicpartners in strong, long-term allianceswith the major pharmaceutical companies forantibody development:
“These alliances allow Big Pharma to gain access to humanantibody technology and IP, and this is an area of growinginterest as more and more antibodies are registered astherapeutics,” he says. “However, several of the antibodycompanies themselves are increasing their value by developingtheir own therapeutic products, the most notable examplesbeing BioInvent, MorphoSys and CAT.”
So how have the recent mergers and acquisitions affectedaccess to IP and changed business models? “The mostsignificant deals of late are the acquisition of Abgenix by Amgenlate last year, and AstraZeneca’s acquistion of its strategicpartner CAT,” says Söderlind. “These acquisitions reflect thegrowing importance of human antibody therapeutics, as thereare a large number of products in companies’ pipelines. Thereare many interesting projects that are attractive topharmaceutical companies wishing to expand their biologicsportfolios. Both Amgen and AstraZeneca completed theiracquisitions in order to have in-house competence to progress
their activities in biologics morequickly.
“BioInvent already has full freedomto operate with the latest technologiesin the identification, development andproduction of human monoclonalantibody therapeutics through severallicences including its access to CAT’stechnologies under the companies’licence agreement completed last year.However, a potential problem in thesector is that when companies areacquired it may be the case thattechnology becomes no longeravailable for outlicensing. We willhave to wait and see how this worksout in practice in the future,” he says.
New technologies constantlyemergeSöderlind believes that new
technologies will continue to emerge in the monoclonal antibodysector:
“Our experience and observations are that there are alwaysnew technologies being developed that drive the sector forward,”he says. “In fact, the acquisitions mentioned should stimulateother companies to come up with new technologies and developnew IP in order to circumvent the potential lack of access totechnologies that have been acquired by and locked up in BigPharma.
“There are many human monoclonal antibodies indevelopment pipelines and there will be many more in the
marketplace in the next few years. These will come from theBig Pharma companies that have acquired new
technologies and also from the antibodycompanies themselves. We may see
more acquisitions of antibodycompanies by large multinationalpharmaceutical companies in thefuture, but of course each deal isdependent on technological and
financial fit for success.“The antibodies market is large and
growing, and in fact will grow very rapidlyover the next five years. The latest
technologies make it possible to find antibodiesagainst any disease target, and the challenge for the sector nowis to find novel, antibody-druggable targets so that the potentialin human monoclonal antibody therapeutics can be fully utilisedand new antibody drugs can be developed and unmet medicalneeds met,” concludes Söderlind. sp2
FURTHER INFORMATIONEskil Söderlind, PhDBusiness Development DirectorBioInvent International ABSE-223 70 LundSwedenTel: +46 46 286 85 77Fax: +46 46 211 08 06
