Bob Stembridge of Thomson Reuters investigates the unique
approaches companies are taking to protect their research
and development activity in the generic biomolecule space.
B
iosimilars are pharmaceutically active biological
molecules developed for distribution after
patent protection has expired on the original
composition of matter. Also referred to as “follow-on
biologics,” “subsequent entry biologics,” or “generic
biologics,” these drugs are expected to have a major impact
on the pharmaceutical field as patents expire on the first
generation of products on the market. As with generic
small-molecule pharmaceuticals, the active biomolecules
in biosimilars themselves can no longer be patented, but
considering the unique nature of the requirements for
synthesizing, formulating, and delivering biosimilars,
there are still ample opportunities for organizations to
generate patent protection around the unique advantages
they bring to the space.
By analyzing the patent portfolios of a representative
sample of companies seeking to develop follow-on
biologics, it is possible to see how organizations are taking
different approaches to protecting their competitive
Résumé
Bob Stembridge, IP Patent Analyst, Customer Relations Manager,
Thomson Reuters IP Solutions
Bob graduated from the University of Sussex, UK with an Honours degree
in Chemistry. He joined Derwent (one of the founding components of the
IP Solutions business of Thomson Reuters) in 1980 and has held various
roles in editorial, marketing, sales and product development over the years.
Leaving in 1988 for interludes working as Senior Information Analyst
specialising in patent analytics at British Petroleum and European Sales
Liaison with Dialog, he returned to Thomson Reuters in 1996 and most
recently became Customer Relations Manager with responsibility for
liaising with customer user groups for the organisation.
He is a member of the American Chemical Society (ACS), the Chartered
Institute of Library Information Professionals (CILIP) and the Patent
Information User Group (PIUG), and is Secretary of the Confederacy of
European Patent Information User Groups (CEPIUG) and current Chair
of the Patent and Trademark Group (PATMG). He currently serves on the
Chemical Structure Association (CSA) Trust Board of Trustees to which he
was elected in February 2007.
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advantage, even when the object of primary importance
can’t necessarily be patented. While the focus of this
article is on biosimilars, the approach also provides
guidance for other industries where critical infrastructure
can still be protected with patents, even if the primary
technological approach cannot.
Background on biosimilars
Biosimilars, again, are generic follow-on biological
compositions, but unlike their small-molecule counterparts
it is nearly impossible to completely replicate a large,
complicated biomolecule, since the company producing
the follow-on product doesn’t have access to the specific
methods and conditions that the original company
had in synthesizing and characterizing the compound.
These biomolecules are large-peptide, and protein-based
substances as well as monoclonal antibodies. The use of
biomolecules as pharmaceutical actives has accelerated
since their introduction, and it has been estimated that
the selling of generic versions of these drugs will
save between US$11-33 billion in the European Union
alone by 2020, since biosimilar versions are projected to
cost approximately 30% less than their brand-name
counterparts.1
Biosimilars have been available for some time in
countries other than the United States, but with the
passage of the 2010 Biologic Price Competition and
Innovation Act, the potential for these substances to be
administered in the US became a possibility. This has
culminated in the recent approval of Zarxio, the Sandoz
Inc.’s biosimilar to Amgen Inc.’s Neupogen, by the US
Food and Drug Administration2, the first approval of its
kind in the United States. With these advancements in
the regulatory environment, the door is now open for
biosimilars to enter the US market.
The process for generating a biological-based drug
generally comprises the following steps3:
• identifying and culturing living cells to produce the
substance of interest; these can be naturally occurring
or genetically modified bacteria, yeast, animal, or human
cell lines;
THE PATENT LAWYER
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Unique solutions to biosimilar patenting
Unique solutions
to biosimilar
patenting
Unique solutions to biosimilar patenting
Methods
Data for this article was generated using the Thomson Reuters
Derwent World Patents Index® (DWPI) to identify global innovation
activity associated with the selected organizations and their publically
known subsidiaries. For each organization, we analyzed the total
number of unique inventions issued in worldwide published patent
applications (each invention was counted only once after removal of
filings of the same invention in multiple jurisdictions), and granted
patents published between 2000 and 2014.
The following companies were included: Hospira, Momenta Pharma,
Celltrion, Therapeutic Proteins, and Coherus Biosciences. These were
selected to provide a representative cross-section of organizations
with publically disclosed activities in the generation of biosimilars,
based on their overall size and age. As such, the collection contains
both small and large companies, and those that were established before
2000, as well as within the past five years. Many well-established
biosimilar companies, such as Sandoz and Teva, were not included
in this study since their portfolios contain more references to the
production of small-molecule pharmaceuticals than to biomolecules.
Analyzing the portfolios of the representative companies revealed
several categories of biosimilar-related R&D within the sector. Each
unique invention from the representative companies was assigned to
a category, and this designation was used for the subsequent analyses
to determine the technology advantages wielded by each organization.
The categories used in this work include:
• IV Delivery – inventions associated with technology for the
intravenous delivery of pharmaceutically active substances.
• Protein Characterization – inventions associated with technology
for the identification of specific protein molecules and their
composition.
• Protein Preparation – inventions associated with technology for
the synthesis of specific protein molecules using a variety of methods.
• Protein Purification – inventions associated with technology for
the separation and purification of specific protein molecules from
the methods used to synthesize them.
• Polysaccharide Preparation – inventions associated with technology
for the synthesis of specific sugar-based molecules using a variety
of methods.
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• MAb Preparation – inventions associated with technology for the
synthesis of specific monoclonal antibodies using a variety of
methods.
• Fermentation Preparation – inventions associated with technology
for the synthesis of specific biomolecules using specifically
fermentation-based methods.
• Genetic Engineering – incorporating genetic material for the
synthesis of specific biomolecules into host organisms for the
production of these substances.
• Pharmaceutical Formulation – inventions associated with the
combination of pharmaceutical actives with additional components
to produce a specific medicinal composition for administering to
patients.
• Pharmaceutical Composition – in this study, these are defined
as inventions related to non-biomolecule compounds, such as
antibiotics, or small-molecule pharmaceuticals that the organization
is developing.
Hospira
In addition to its current concentration in biosimilars, Hospira has
long specialized in injectable drugs and infusion technologies, as
the company notes on its website.4 Formerly the hospital products
division of Abbott Laboratories until being spun off as a separate
company in 2004, it is one of the largest companies in the biosimilar
industry. In February 2015, Pfizer announced plans to acquire Hospira
for about US$15 billion dollars.5
Figure 1 provides an analysis of the Hospira patent portfolio
from publication year 2000 to 2014 by category, clearly showing the
company’s emphasis on IV delivery systems.
organization has sought patent protection. In the case of TPI, and
for Coherus Biosciences in the section to follow, the column charts
convey a clearer picture of their areas of interest.
Figure 2 - Analysis of 115 worldwide inventions published by
category assigned to Momenta Pharma from 2007 to 2014
Momenta’s portfolio covers several of the steps associated with the
production of biomolecules, especially in the synthesis of several
categories of compounds and their subsequent characterization.
More recently it can be seen that the company has initiated programs
in genetic engineering, as well as in synthesizing monoclonal antibodies.
Combined, these synthesis categories indicate that Momenta has
almost equally divided its portfolio between the preparation and
characterization of biomolecules.
Celltrion
Celltrion is a Korean biopharmaceutical company established in
2002, with approved pharmaceutical products for autoimmune
disease, breast cancer, non-Hodgkin's lymphoma, and influenza. The
company website emphasizes experience in screening initial
candidates, cell-line expression in recombinant DNA, and large-scale
production.7 Celltrion started with biological cancer therapeutics,
and has used its expertise to expand into the broader field of
biosimilars, especially viral antibody therapeutics. This change in
emphasis is evident in Figure 3 and its depiction of a shift in
patenting from pharmaceutical composition to monoclonal antibody
synthesis and genetic engineering.
Figure 1 - Analysis of 272 worldwide inventions published by
category assigned to Hospira from 2000 to 2014
Figure 1 also specifies elements, such as diagnostic devices,
computer systems, and pharmaceutical containers, that attest to
Hospira’s history as a hospital products company, but the timeline
makes plain that shortly after its 2004 spinoff from Abbott, Hospira
began to concentrate more heavily on the formulation and delivery
of injectable drugs. During its time as a division of Abbott, the
organization was developing expertise in IV delivery systems back to
the early 90’s, and because biosimilars are exclusively delivered by
injection, this expertise became the focus of the new company. The
graph also makes plain that publications in the area of IV Delivery
have grown nearly exponentially in the past three years. Clearly, the
formulation and delivery of biosimilar drugs, as opposed to the
actual synthesis of the substances themselves, is an area where Hospira
is seeking a competitive advantage.
Momenta Pharma
On its website, Momenta Pharma underscores the company’s
specialization in the analysis, characterization, and design of complex
pharmaceutical products, with an emphasis on biosimilars and
potentially interchangeable biologics, particularly aimed at oncology
and autoimmune indications.6 This is clearly a different profile from
that of Hospira. Figure 2 details Momenta’s recent areas of focus.
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Figure 4- Analysis of 31 worldwide inventions published by
category assigned to TPI from 2011 to 2014
As the company’s name suggests, TPI is all about proteins, and
while the company’s manifesto refers to a patented manufacturing
platform, it doesn’t make mention of the technologies in which they
have sought protection for the purification and characterization of
protein molecules. It also doesn’t mention that it uses fermentationbased methods for producing proteins, or that it is interested in
monoclonal antibodies. Overall, though, the emphasis is squarely on
working with proteins.
Coherus Biosciences
Of the companies profiled in this article, Coherus Biosciences was
formed most recently and currently has the smallest portfolio of
published patent applications. Its website, however, hints at a much
larger collection of specialties than their existing portfolio would
suggest, mentioning analytics, process science, and clinical and regulatory
capabilities, all overseen by industry veterans who developed the first
generation of biologics.9 Figure 5 indicates that although Coherus is
claiming expertise in a wide variety of areas, it has only filed patents
in two of the areas covered in this study.
Figure 3 - Analysis of 45 worldwide inventions published by
category assigned to Celltrion from 2007 to 2014
While the overall number of inventions published from Celltrion
has declined from their initial high in 2011, the devotion to their
strategy of covering multiple steps in the production of biosimilars
is evident. The company has patent coverage for the creation of
genetically modified cell lines, protein, and antibody synthesis, and
biomolecule characterization, and formulation. The area of highest
interest most recently is the synthesis of monoclonal antibodies for
use in viral antibody therapies.
Therapeutic Proteins
Therapeutic Proteins (TPI) was founded in 2003 but didn’t begin
having patent applications published until 2011. Its website description
is less detailed than those of the other companies collected here,
alluding to “high-quality, life-altering biologics that are affordable
and accessible to patients around the globe.”8
Because the TPI patent portfolio spans 2011 to 2014, a relatively
short period compared to the other organization being studied,
Figure 4 provides a column chart of the categories in which the
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Figure 5- Analysis of 9 worldwide inventions published by category
assigned to Coherus Biosciences from 2013 to 2014
Patents suffer from the fact that with an 18-month publication
cycle, there is a blind spot when it comes to the most recent filings
associated with a company. Coherus was founded in 2010, so enough
time has elapsed that its area of initial focus, probably based on
limited resources, can be determined. While the company suggests
expertise in a variety of the steps for the production of biosimilars,
the area in which it decided to file its first round of patents involves
the means of synthesizing specific biomolecules, especially fusion
proteins associated with monoclonal antibodies.
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Unique solutions to biosimilar patenting
• establishing a large-scale production process for growing the
cells;
• developing a purification system for separating the compound of
interest from the remainder of the cellular materials;
• characterizing the resulting biomolecules to ensure proper identity
and purity; and
• formulating the material into a form that can be administered to
a patient.
Although each of these steps will be unique to a given drug substance
and the company developing it, in many cases the underlying technology
associated with the creation of biosimilars can be generally applied
to more than one specific substance. Protecting these unique approaches
with patents can provide companies with a sustainable competitive
advantage as they grow and mature in the industry.
In this study, the patent portfolios of a representative number of
organizations – some of them well established, others recently started
– were analyzed to identify the pathways these companies are taking
to success in the field of biosimilars. This examination demonstrates
that companies are focusing on different steps associated with the
generation of follow-on biological pharmaceutical agents in order to
differentiate themselves and increase their likelihood of brokering
deals with established pharmaceutical companies, or to generate
products themselves.
Unique solutions to biosimilar patenting
Conclusions
This article has provided detailed categorization and analysis on five
representative companies interested in the development of biosimilar
pharmaceutical substances. While each of these companies has the
same essential goal in mind, they are taking significantly different
approaches to providing unique solutions, and technology to reach
their objective.
Protecting an organization’s competitive advantage, especially with
the judicious use of patent filings is essential for any technology
focused business, but in the case of industries, where the primary
product or functionality is seemingly unpatentable it is still likely
that key infrastructure processes may in fact be protected with
patents. In the case of biosimilars there are a number of steps
involved in producing these essentially similar, but not identical
substances.
1
Biosimilars: A Global Perspective of a New Market Opportunities, Threats
and Critical Strategies 2014,
http://www.bioworld.com/content/biosimilars-global-perspective-newmarket-opportunities-threats-and-critical-strategies-2014
2
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm436648.htm
3
Producing Biomolecular Substances with Fermenters, Bioreactors, and
Biomolecular Synthesizers, Hochfeld, William, CRC Press, 2006.
4
http://www.hospira.com/en/about_hospira/index
5
Pfizer to buy Hospira to boost biosimilar pipeline,
http://www.cnbc.com/id/102376540
6
http://www.momentapharma.com/about/corporate-overview.php
7
http://www.celltrion.com/EN/TECHNOLOGY/
technology01.asp?menu_num=1
8
http://theraproteins.com/about/
9
http://www.coherus.com/about-us/company-story/
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