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Advanced Bioinformatics, DTU
Genes and Patents
Jens Viktor Nørgaard,
NsGene A/S
Who am I
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Msc in forestry, KVL (RAU, Royal Agricultural University)
Phd in genetics & biochemistry, KVL
10 years of academic research, University of Copenhagen
Patent consultant since 1998
European Patent Attorney 2003
Director of IPR (Intellectual Property Rights), NsGene A/S
[email protected]
www.nsgene.com
What is a patent attorney?
• Represents clients/employer before patent authorities
• No authorisation requirements in Denmark
• Authorisation required in a number of countries: United
Kingdom, Germany, France, United States, Japan, EPO
(European Patent Office)
• Qualifications (European patent attorney):
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Scientific degree; Msc, Phd or equivalent
Linguistic skills, writing & speaking
Business attitude
Patent training > 3 years
Pass a qualifying exam
What does a patent attorney do
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Writing patent applications
Preparing legal documents
Monitoring dead-lines
Searching for and analysing technical information
Providing legal opinions on patent issues
Preparing and filing responses to patent authorities
Training of scientists/clients/students/trainees
Strategic advice/planning to Universities and Corporations
License negotiations and agreements
Links
• Training of Danish patent attorneys (Certified Danish Patent
Attorney): http://www.difi.dk/
• How to become a European Patent Attorney:
http://www.european-patentoffice.org/epo/pubs/pat_attorney/pdf/patbro_e.pdf
Agenda
• What is a patent
• Patentability basics
– Novelty, inventive step & other criteria
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Claims
Break
Timelines
Patents as information source
Ethics and patent law
Searching for patent information
Searching for patented genes
Patents?
What is a patent?????
What is a Patent?
• Which rights arise from a granted patent?
Patents I
• A patent application - ”paid-for publication”, source of
information
• A granted patent – a legal document defining an injunction
right & a right to claim damages
• A patent does not give the patentee any right to exploit the
invention
Patents II
• Agreement between inventor and society
– Inventor gets a time-limited monopoly
– Society gets a description of the invention
• Patenting forces publication
– Stimulates exchange of information
– Stimulates research and development
• Alternative to patents
– Secrecy
Patentability Requirements
Patentability Requirements
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Novelty
Inventive step
Clarity
Conciseness
Enablement
Sufficiency of disclosure
Utility
Industrial applicability
Exceptions to patentability
Novelty
Novelty
• Novelty = not available to the public on the date of filing
• Available = made available to the public without any
confidentiality barriers
• A compound (including proteins and genes) is not known
merely because it is found in nature
• Compounds can be made available by
– decribing the structure of the compound (structural formula or
sequence)
– describing a method of producing/synthesising
– describing a method of isolating/purifying the compound
The Concept of Novelty
State of the Art (known)
1. a cup
Patent Application
1. a cup with a handle (novel)
2. a cup
2. a 15 cm tall cup (novel)
3. a cup
3. a cup adapted to hold coffee
(non-novel)
4. a cup
4. a red cup (novel)
5. a cup
5. a container for liquid (not novel)
The Concept of Novelty
State of the art
1. cells secrete a protein with
activity X
2. the protein with acivity X can be
purified from organism Y using
method Z
3. protein with sequence ...
4. peptide with sequence:
ypskpdnpgedapaedmaryysalrhyin
litrqry (NPY)
5. conservative substitutions can
be made in NPY
Patent application
1. an isolated protein with
sequence ... having activity X
2. an isolated protein with
sequence ... having activity X
3. glycosylated protein with
sequence ...
4. peptide with sequence:
ypskpdnpgeeapaedmaryysalrhyin
litrqry
5. peptide with sequence:
ypskpdnpgeeapaedmaryysalrhyin
litrqry
The Concept of Novelty
State of the art
1. gene X was cloned using primers
A and B
2. genes 1 to N can be used for
treating diseases 1 to N
3. gene x promotes cell division
Patent application
1. gene X having sequence
...........
2. gene 5 for treatment of
obesity......
3. use of gene x as a growth factor
Inventive Step
Non-obviousness
Inventive Step/Non-obviousness
• Inventive step/”non-obviousness”
– Difference between prior art and invention must be of a certain
”size”
– No patents for trivial inventions
– Patents promote technical progress, not stand-still
– Non-obvious for the person skilled in the art
– Person skilled in the art
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Fictitious person
Not a Nobel prize winner
Average skills
Knows everything (all languages) but is conservative, does not go against
established prejudice, does not try to enter unpredictable areaas nor take
uncalculable risks
Inventive Step/Non-obviousness
• Complex arguments
• Room for creativeness
• Large differences between major patent autorities: EP, JP,
US:
• New sequence (new compound, new structure)
– US – any new stucture is non-obvious
– JP – a significant and unexpected effect must be associated with the
new structure, or undue difficulty in obtaining new sequence
– EP – was the sequence difficult to make? any unexpected technical
effects associated with the new sequence? was it obvious to try and
see?
The Concept of Inventive Step
State of the art (known)
1. a cup
Patent application
1. a cup with a handle (inventive?)
2. a cup
2. a 15 cm tall cup (inventive?)
3. a cup
3. a cup adapted to hold coffee
(non-novel)
4. a cup
4. a red cup (inventive?)
5. a cup
5. a container for liquid (not novel)
The Concept of Inventive Step
State of the art
1. cells secrete a protein with
activity X
2. the protein with acivity X can be
purified from organism Y using
method Z
3. protein with sequence ...
4. peptide with sequence:
ypskpdnpgedapaedmaryysalrhyin
litrqry (NPY)
5. conservative substitutions can
be made in NPY
Patent application
1. an isolated protein with
sequence ... having activity X
2. an isolated protein with
sequence ... having activity X
3. glycosylated protein with
sequence ...
4. peptide with sequence:
ypskpdnpgeeapaedmaryysalrhyin
litrqry
5. peptide with sequence:
ypskpdnpgeeapaedmaryysalrhyin
litrqry
The Concept of Inventive Step
State of the art
1. gene X was cloned using primers
A and B
2. genes 1 to N can be used for
treating diseases 1 to N
3. gene x promotes cell division
4. an EST annotated as having
homology to an enzyme with
activity Y
Patent application
1. gene X having sequence
...........
2. gene 5 for treatment of
obesity......
3. use of gene x as a growth factor
4. isolated and purified protein
having sequence X and enzyme
activity Y
Clarity, Sufficiency, Enablement, Utility
Clarity, Sufficiency, Enablement
• ”Quality requirements”
– No short cuts by trying to keep part of the invention secret
– No short cuts by filing too early – before invention is complete
– Legal certainty (possible for 3rd party to determine scope of claims)
Clarity, Conciseness
• The claims must be clear and concise
• Results in many definitions:
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Sequence homology
Alignment
Hybridisation
High stringency
Receptor binding
Sufficiency, Written Description
• Description must be sufficient
• Sufficiency – when the skilled person can carry out the
invention – don’t try to leave anything out
• Also a question of credibility
• Written description – you must show that you were in
possession of the invention upon filing – do not file before
you completed the invention
Utility
• Industrial applicability/”utility”
– USA – credible, substantial and specific utility (a use for the
invention) – high hurdle, used by the Patent Office to refuse trivial
or premature applications
– EPO – the industrial applicability of a sequence must be given in the
application (Biotekdirektivet) – low hurdle
Patent Claims
Patent Claims
• The claim defines the invention
• The claim must satisfy the patentability requirements
• The description may only be used to interpret the features
of the claims
Rights arising from Patent I
• Productpatent – forbid others to:
– make, use, offer for sale, sell, import
• Claims
– 1. An isolated polypeptide comprising the amino acid sequence of
SEQ ID No. 2, or a biologically active sequence variant having at
least 70% sequence identity to SEQ ID No. 2.
– 2. A pharmaceutical composition comprising protein X.
– 3. An expression vector comprising a sequence coding for protein X.
Rights arising from Patent II
• Method patent – forbid others to
– Use the method
– Method of manufacture also protects the products
• Claims:
– 1. Use of protein X for the preparation of a pharmaceutical
composition.
– 2. Use of protein X for the preparation of a medicament for the
treatment of disease Y.
– 3. A method for identifying a compound with activity X, comprising
testing the compound in screening assay Y.
– 4. A method of producing protein X, comprising culturing a host cell
transfected with vector Y and recovering protein X from the culture
medium.
Claim Types, Product
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Nucleic acid
Polypeptide
Antibody
Expression vector
Screening assay (kit)
Array
Pharmaceutical composition
Cells
Data carrier
Claim Types, Methods
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Method of treatment (of disorder)
Medical use (any therapeutic use)
Second medical use (disease specific therapeutic use)
Method of preparing compound/protein
Method of identifying modulator of activity
Method of isolating compound/protein/gene
Timelines
The Typical Life of an International Application
PCT Patent Application Process
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12
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MONTHS
Patenting Process
• First filing– timing
• Early filing –
– Easier to get novelty
– Enablement, sufficiency, utility?
• Later filing –
– More time to prove function (of a gene or protein)
– Longer patent term (evergreening of Pharmaceutical products)
Patenting Process
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• Filing of updated PCT-application
• Filed within 12 months of the first filing
• Claims priority from the earlier filing => prior art is
anything published before the priority date
• One single application in one language can give patents in
130+ countries (1 October, 2006, 133 countries)
Patenting Process
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• Novelty search (database search)
• Identification and classification of publications (patent
applications and scientific papers)
• Possibility to evaluate the fate of the patent application
Patenting Process
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• Publication of the application 18 months from first filing
Patenting Process
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• Preliminary examination –
– A possibility to evaluate the patentability
– Dialog with examiner at EPO or PRV (Swedish PTO); written
procedure, but possibilty for interview.
• International preliminary report on patentability
– Report on the patentability
– Preliminary, so not binding on national authorities
Patenting Process
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• Entry into national phase (US, JP, CA, AU etc) or regional
phase (Europe, Eurasia, Africa).
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Selection of countries
Geographic strategy
Language - translations
Costs
Patenting Process
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The application is adjusted to national law
Patent grant/refusal
Possibility for opposition from third parties
Can be maintained up to 20 years from PCT filing date
Patents and Applications
as Information Source
How to Read a Patent Application
Patent Applications Layout I
• Frontpage
– Bibliographic information
• Background of the invention
– Corresponds to introduction
• Summary of the invention
– Copy of the indpendent claims, perhaps arguments
• Brief description of the drawings
– Figure legends
• Detailed description
– Definitions, description of alternatives, variations, uses
– Supports sub-claims, fall-back positions, enablement, how to make
and use the invention
Layout II
• Examples
– Materials & methods, results, rarely any discussion
• Claims
– Main claims and independent claims
• Drawings
– Always at the end of the application
• Sequence listing
– Amino acid and nucleotide sequences
– Made according to special formal requirements
International (PCT) Applications
• APPLICATIONS!! NOT PATENTS
• Filed locally (e.g. Denmark)
• Treated and published centrally (WIPO, EPO, USPTO, PRV,
JPO).
• Covers 133 countries (holes in South America and the Arab
world)
PCT Countries
PCT-applications
• Filed, searched, published, examined
• Timeline: priority year, published after 18 months, PCT
phase ends after 2½ years
• Example: WO0212514.pdf
US-applications/Patents
• US-applications published at 18 months
– Long numbers, US20020098547 A1 (Tornoe et al)
• US-patents, published at issue
– Granted patents
– Short numbers, fx US 6,555,674 (Tornoe et al)
US-patent
US-application
EP-patents
• Applications published at 18 months
• Most are published as PCT applications (WO number)
• Published as B1 publication at grant
Granted European patent
Ethics and Patent Law
Ethics and Patent Law
• Why ethics?
• Controversial issues:
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Patents on life (Harvard Onco-mouse)
Plant patents
Human genes
Stem cells
Human embryos (cryopreserved embryos)
Breast cancer diagnostics (brca genes)
Computer programs
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Patents on weapons
Patents on nuclear power plants/weapons
Patents on chain-saws
Industrial fishing equipment
For & Against Patents on Genes
• Not novel – but novel in isolated (=available) form
• Not invented by the inventor – but isolated by the inventor
• Isolation is no invention – but the isolated gene can solve a technical
problem and has utility
• Immoral to patent life – why? – living creatures (animals, plants,
microorganisms) have been regarded as goods for centuries
• Patenting genes is contrary to development – mere allegation, do not
confuse patent applications with valid patents
Ethics
• Allegation: claims are way too broad
– Cover all uses (product claims)
– Gene claims should be restricted to use (Biotechnology directive as
implented in France and Germany)
– Stops research
• My answer: gene claims should have same scope as all other claims
– Traditional compound claims cover all uses
– Why should gene patent stop development and research while patents in
other fields enhance research?
– Again: do not confuse patent applications with valid granted claims
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Backlog of human gene patent applications results in uncertainty
Sequence non-obviousness in the US
USPTO grants invalid patents
Very limited research exemption in the US
Human Gene Patent Applications
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The result of high-througput sequencing
Genes predicted with software
No biological data
Limited expression data (rarely quantitative)
Long list of genes (several 1000)
Laundry list of possible functions
Laundry list of possible uses
– Diagnostics
– Therapeutics
– Screening
Finding Patent Information
for Free
Finding Patent Information – for Free
• espacenet
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Link: http://ep.espacenet.com
Simple search functions
Abstract from the application
OCR text available for English, French and German language applications
Publication as pdf-file, page by page
• USPTO
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Link: http://www.uspto.gov/patft/index.html
Simple and advanced search tools
Patent number search
Free text search
OCR text available
Publication available in Tiff format, page by page
Finding Patent Information – for Free
• Patentscope (WIPO)
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Link: http://www.wipo.int/pctdb/en/
Advanced, simple, or structured search functions
Abstract from the application
OCR text available for English, French and German language
applications
– Publication as pdf-file
– Other documents (priority documents etc) as pdf-file
Downloading Patent Documents for Free
• pdf’s of US patents: www.freepatentsonline.com
• pdf’s of European patents and applications (since 2004):
https://publications.european-patentoffice.org/PublicationServer/search.jsp
• pdf’s of PCT applications from Patentscope (WIPO):
http://www.wipo.int/pctdb/en/
• pdf’s of PCT applications file inspection at EPO:
http://www.epoline.org/portal/public/!ut/p/kcxml/04_Sj9
SPykssy0xPLMnMz0vM0Y_QjzKLN4i3dAHJgFjGpvqRqCKOcAFvf
VP_NxU_QD9gtzQiHJHRUUA43OWZA!!/delta/base64xml/L3dJ
dyEvUUd3QndNQSEvNElVRS82XzBfOUc!
Finding Patent Information
• Blast searches in patent database at NCBI:
http://www.ncbi.nlm.nih.gov/BLAST/
• Example:
• Find US patents covering persephin:
http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=protei
n&val=2935710
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Copy sequence
Paste into NCBI Blast (pat) http://www.ncbi.nlm.nih.gov/BLAST/
Searching.....
Copy patent number
Go to http://www.uspto.gov/patft/index.html
Go to Patent Number Search
Paste number - search
Limitations of NCBI Blast
• Accession policy appears inconsistent / random
• Only a small fraction of patented sequences are found at
NCBI
• Alternatives:
– Search for gene names
– Commercial sequence databases (Chemical Abstracts Registry, PCTgen (WIPO), DGene (Derwent))
Good Hunting!