De Clercq & Partners - Introduction
Opportunities and Challenges of an
appropriate IP strategy for Cell Therapy
Liesbet Paemen, PhD & Andrej Michalík, PhD
European Patent Attorneys
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Overview
Challenges
Opportunities
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De Clercq & Partners - Introduction
Cellular therapeutic
Development
Living cells
Regulatory
Manufacture
Supply
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Need for Competitive Advantage
• Know-how
• Regulatory provisions
• Data exclusivity for ATMPs, market exclusivity for orphan
indications
• Difficulty for “biosimilars”
• Commercial strategies
• Intellectual property rights
• Patents
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De Clercq & Partners - Introduction
Patents
• Right to exclude others from using the
patented invention
• Commercial product may still be subject to
other rights
• File early, often long before commercial
product is envisaged
• Consider filing strategy to optimize
protection
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Patenting requirements
• Novelty
•
Characterizing cell population
• Inventive step
•
Suggestions in literature do not underscore
difficulties for practical implementation
• Invention must be sufficiently disclosed
•
Representative in vitro or animal model?
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De Clercq & Partners - Introduction
Typical timeline
18m
6-9m
12m
0
US
EP
AU
JP
CN
30/31m
First filing
National phase
Extended filing
entry
PCT
Search report
Publication
Extensive
description of the
invention
Update with
additional
data
Consider
patentability of
invention
Consider filings
on improvements
Decide on
countries
where
protection is
key
Examination
Grant
20y
Discuss
patentability with
national offices
Enforce patent
against third
parties
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Pros – Cons
PRO
CON
Exclusivity to commercialise
Disclosure upon publication of
application
Factor for research grants
Cost before benefit
Factor for investors
May delay scientific
publications
Can be licensed out
Tax incentives
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De Clercq & Partners - Introduction
Decision factors
Nature of
the invention
Timing
Goals of
patent
protection
Budget
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Patents for Inventions relating to
Cell Therapy & Tissue Engineering
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De Clercq & Partners - Introduction
Cell Therapy & Tissue Engineering
• Develop biological substitutes that restore, maintain or
improve tissue function / substitutes for whole organs
• Biochemical techniques inducing tissue regeneration in vivo
• Transplantation techniques involving stem cells or more
specialised cells, alone or as part of bioartificial tissue
• Interdisciplinary: life sciences, engineering, biomaterials
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12000
10000
8000
PCT App
EP App
6000
EP Grant
US App
4000
US Grant
2000
0
1995-1999
2000-2004
2005-2009
2010-2014
Applications & patents mentioning regenerative medicine, cell therapy or tissue engineering
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De Clercq & Partners - Introduction
Example IPC groups (1)
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C12N5
Undifferentiated human, animal or plant cells, cell lines;
Tissues; Cultivation or maintenance; Culture media;…
•
/02
Propagation / maintenance of cells; Culture media
•
/07
Animal cells or tissues
•
/0735
Embryonic stem cells; Embryonic germ cells
•
/074
Adult stem cells
•
/0775
Mesenchymal stem cells; Adipose-tissue derived stem cells
•
/10
Cells modified by introduction of foreign genetic material
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Example IPC groups (2)
•
A61K35 /12 Medicinal preparations containing materials from
mammals; Compositions comprising non-specified tissues
or cells; Compositions comprising non-embryonic stem
cells; Genetically modified cells;…
•
/28
Haematopoietic stem cells; Mesenchymal stem cells
•
/32
Osteocytes; Osteoblasts; Tenocytes; Odontoblasts; Chondrocytes
•
/34
Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes
•
/407
Hepatocytes
•
/545
ES cells; Pluripotent stem cells; Induced pluripotent stem cells
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De Clercq & Partners - Introduction
Example IPC groups (3)
•
A61F2
Prostheses, i.e. artificial substitutes or replacements for
parts of the body
•
A61L27
Materials for prostheses or for coating prostheses
•
/14
Macromolecular materials
•
/38
Materials containing animal cells
•
/56
Porous or cellular materials
•
/58
Materials at least partially resorbable by the body
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12000
10000
8000
C12N 5
6000
A61K 35/12
A61L 27/38
4000
2000
0
1995-1999
2000-2004
2005-2009
2010-2014
PCT applications by IPC classification
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De Clercq & Partners - Introduction
10000
8000
C12N 5 (EP)
6000
A61K 35/12 (EP)
A61L 27/38 (EP)
C12N 5 (US)
4000
A61K 35/12 (US)
A61L 27/38 (US)
2000
0
1995-1999
2000-2004
2005-2009
2010-2014
Granted EP and US patents by IPC classification
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Examples of patents
US 5,197,985
US 5,226,914
US 5,486,359
Caplan et al.
Mesenchymal stem cells
US 5,591,625
Gerson et al.
Transduced MSC
US 6,090,622
US 6,562,619
Gearhart et al.
Human embryonic pluripotent germ cells
US 5,843,780
US 6,200,806
Thomson
Primate embryonic stem cells
US 8,058,065
EP 1 970 446
Yamanaka et al.
Induced pluripotent stem cells
US 7,893,315
Chung et al.
Single blastomere biopsy for obtaining human ES cells
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De Clercq & Partners - Introduction
Examples of patents
US 5,399,665
EP 0 619 732
Barrera et al.
Biodegradable polymers for cell transplantation
US 5,763,416
US 5,962,427
Bonadio et al.
Goldstein et al.
Gene activated matrix
US 6,673,339
Atala et al.
Prosthetic kidney
US 6,986,739
Warren et al.
Three-dimensional structures by deposition of viable
cells
US 7,051,654
Boland et al.
Ink-jet printing of viable cells
US 8,470,520
EP 1 928 519
Taylor et al.
Decellularisation and recellularisation of organs and
tissues
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Protect your technology (1)
• Patents can be obtained for many aspects of cell therapy &
tissue engineering technologies
• A diversified patent portfolio allows you to control the
access of others to your technology  exclusivity
• Exclusivity ensures that developing your technology into a
commercial innovation can be a viable business proposition
• Public only benefits from innovations which reach it
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De Clercq & Partners - Introduction
Protect your technology (2)
• Various aspects of your technology can be protected
•
Products (substances, compositions, devices, apparatus,…)
•
Methods, uses
• A few examples:
•
Cell types, cell populations, (pharmaceutical) formulations
comprising cells, methods for isolating / culturing / characterising /
differentiating / enriching / (genetically) modifying / preserving /
reconstituting cells
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Protect your technology (3)
• A few examples:
•
Biocompatible materials, biodegradable materials, functionalised
biomaterials, methods for producing such, scaffolds and structures
comprised of biomaterials
• Bioengineered tissues and organs, methods and apparatus for
producing such
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De Clercq & Partners - Introduction
Availability of patents
• As a general principle, patents are available for any
inventions, including products and processes, in all fields of
technology
• Certain types of subject-matter are not regarded as
patentable inventions
• Certain categories of inventions may be excluded from
patentability for non-technical reasons
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Patenting issues relating to
cellular therapy
• EP
• Therapeutic or surgical treatments of humans or animals
• Inventions contrary to “ordre public” or morality
•
Impact on human embryonic stem cells
• US
• Laws of nature, natural phenomena
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De Clercq & Partners - Introduction
Europe – medical treatments (1)
• EP patents are not granted for:
•
Methods for treatment of the human or animal body by surgery or
therapy
•
Objective: Physicians should not be inhibited by patents in taking
actions they consider suitable to prevent or to cure a disease
• But: Products for use in such methods can be patented
 Protection possible for commercial product
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Example
•
Claim: “A method for implanting a [new and inventive] bioartificial
tissue construct comprising [surgical steps a), b), and c)].”
• Claim: “A [new and inventive] bioartificial tissue construct
characterised by [structural and/or functional features x), y), and
z)].”
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De Clercq & Partners - Introduction
Example
•
Claim: “A method for implanting a [new and inventive] bioartificial
tissue construct comprising [surgical steps a), b), and c)].”
•
Claim: “A [new and inventive] bioartificial tissue construct
characterised by [structural and/or functional features a), b), and
c)].”
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Europe – medical treatments (3)
• EP patents are also available for 1st and 2nd medical uses of
known substances and compositions
•
A previously known substance or composition, not previously used
in any therapy or surgery, can be claimed broadly for use in therapy
or surgery
•
A substance or composition previously used in therapy or surgery,
can be claimed for a novel and inventive specific use in therapy or
surgery
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De Clercq & Partners - Introduction
Example
• Inventors realise that a cell type “C” previously known to
treat disease “X” is useful in disease “Y”
•
Claim: “A cell type C.”
• Claim: “A cell type C for use in therapy.”
•
Claim: “A method for treating disease Y using cell type C.”
•
Claim: “Cell type C for use in treating disease Y.”
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Novel & Inventive cellular products
• Claim to cell type per se
 Need to distinguish cell type from previously
described cell type
•
Potential issue with new markers – difficult to
assess if not used in prior art
• Claim to use in therapy
 Need to provide representative model
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De Clercq & Partners - Introduction
EP 2258833
(Virga Jesse Hospital, BE)
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To summarise
• EP patents are broadly available for new and inventive
products useful in methods of therapy or surgery
• EP patents are available for 1st and 2nd medical uses of
known substances and compositions
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De Clercq & Partners - Introduction
Europe – human ES cells (1)
• EPC rules and EU Biotech Directive exclude
•
Industrial or commercial uses of human embryos
 Impact on patentability of inventions based on hES cells
•
Human body, at the various stages of its formation & development
 This includes omnipotent stem cells
• Law interpreted by EPO Boards of appeal (BoA) and CJEU
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Europe – human ES cells (2)
• EPO BoA case law excludes
•
Products which at the filing date could be prepared exclusively by a
method necessarily involving the destruction of a human embryo (G
2/06)
• Inventions making use of publicly available human ES cell lines
initially derived by a process resulting in the destruction of the
human embryos (T 2221/10 )
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Methods involving direct use of a human embryo, even nondestructive, unless beneficial for the embryo itself (T1836/10)
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De Clercq & Partners - Introduction
Europe – human ES cells (4)
• CJEU case law excludes
•
Inventions requiring the prior destruction of human embryos or
their use as base material, whatever the point in time at which that
takes place (C-34/10)
• CJEU also ruled that
•
Unfertilised human ova whose division and further development
have been stimulated by parthenogenesis do not constitute a
“human embryo”
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Europe – human ES cells (5)
• Evolution of technology
•
Methods developed for providing human ES cell lines nondestructively
•
Possible to refer to these cell lines as starting material
• Practice of EPO examiners
•
Allow human ES cell-related applications filed as of 10 January
2008 i.e. publication of the single blastomere biopsy (SBB) process
was published (Chung et al., 2008, Cell Stem Cell. 2(2): 113-7)
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De Clercq & Partners - Introduction
To summarise
• European patents are available for human ES cell-related
inventions, for patent applications filed after 10 Jan 2008
• European patents were always available for inventions
employing human adult stem cells (e.g., MSC) and induced
pluripotent stem cells
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U.S. – patent eligibility (1)
• Laws of nature and natural phenomena are patent ineligible
•
Basic tools of scientific and technological work, not to be “tied up”
by patents
• Recent developments unfavourable for biotech
•
Supreme Court decisions (Myriad, Prometheus), as interpreted by
the USPTO
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De Clercq & Partners - Introduction
Myriad (1)
• Original Claim under discussion: An isolated DNA coding for
a BRCA1 polypeptide …
• Supreme Court
• A naturally occurring DNA segment is a product of nature and not
patent eligible merely because it has been isolated
•
cDNA (exon-only molecule) is patent eligible because it is not
naturally occurring
Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. __, 133 S. Ct. 2107 (2013)
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Myriad (2)
• Myriad undercuts availability of patents in U.S. for products
that are identical to or not markedly different from products
occurring in nature
•
Substances, biomolecules (nucleic acids, peptides, proteins,
antibodies…), cells, cell populations…
•
Does not affect claims to “method of production” in the same way
•
Also relevant protection in view of regulatory constraints
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De Clercq & Partners - Introduction
Example
• US 8,962,321 (granted Feb 24, 2015)
• US 8,961,956 (granted Feb 24, 2015)
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USPTO Interim Guidance (Dec 2014)
A claim reciting a nature-based product limitation
Markedly different characteristics from naturally occurring counterpart ?
NO
YES
Additional elements that amount to significantly
more than the natural phenomenon?
YES
NO
Patent eligible
Not natural phenomenon
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Patent eligible
Patent ineligible
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De Clercq & Partners - Introduction
USPTO Interim Guidance (Dec 2014)
• “Markedly different characteristics”
•
Case-by-case analysis based on structure, function, other properties
•
Even a small change can result in markedly different characteristics
• Additional elements that are “significantly more”
•
More than well-understood, routine and conventional activities
•
More than a particular technological environment
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To summarise
• Supreme Court decisions and subsequent USPTO practice
expanded the reach of law of nature / natural phenomenon
exclusions, unfavourably for biotech
• Future decisions will provide more guidance
• Look for meaningful “markedly different characteristics” and
“significantly different” additional elements
• Aim to protect invention in other ways (methods)
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De Clercq & Partners - Introduction
A word on experimental data (1)
• Experimental data should be included in a patent
application to support the invention
•
Especially important in relatively unpredictable fields, such as
biotech
• If patenting envisaged - experimental data should consider
the various requirements for patent grant
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A word on experimental data (2)
• Support (EP) / Written description (US)
•
Support generalisations in the claims
• Inventive step (EP) / Non-obviousness (US)
•
Make it plausible that the claimed invention solves the postulated
technical problem
•
Demonstrate advantageous effects of the claimed invention
compared to closest prior art (choose controls properly)
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De Clercq & Partners - Introduction
A word on experimental data (3)
• Enablement
•
At least one way to practice the invention
•
How to practice the invention over the whole scope claimed
• Industrial applicability
•
At least a prospect of a real possibility of exploitation
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Strategy for optimal protection
• Avoid compromising opportunities
•
Publication before considering filing
•
Collaborations without clear agreements
• Consider timing issues
•
When proof of concept is obtained
•
When supporting evidence can be obtained
•
When input on commercial value is obtained
 Develop optimal filing strategy
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De Clercq & Partners - Introduction
Conclusion
• Exclusivity on the market is an
important asset
• Patents are available for inventions
in the field of cellular therapy
• Effective patent protection requires
a strategic approach
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Thank you!
De Clercq & Partners cvba
Edgard Gevaertdreef 10a
B-9830 Sint-Martens-Latem
Belgium
+32 (0)9 280 23 40
+32 (0)9 280 23 45
[email protected]
www.dcp-ip.com
@DeClercqPartner
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