Advanced Bioinformatics, DTU

Genes and Patents

Jens Viktor Nørgaard,NsGene A/S

Who am I

• 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• jvn@nsgene.dk• 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):– 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

• 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-patent-office.org/epo/pubs/pat_attorney/pdf/patbro_e.pdf

Agenda

• What is a patent• Patentability basics

– Novelty, inventive step & other criteria

• 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

• 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

2. a cup

3. a cup

4. a cup

5. a cup

Patent Application1. a cup with a handle (novel)

2. a 15 cm tall cup (novel)

3. a cup adapted to hold coffee (non-novel)

4. a red cup (novel)

5. a container for liquid (not novel)

The Concept of Novelty

State of the art1. cells secrete a protein with

activity X2. the protein with acivity X can

be purified from organism Y using method Z

3. protein with sequence ...

4. peptide with sequence: ypskpdnpgedapaedmaryysalrhyinlitrqry (NPY)

5. conservative substitutions can be made in NPY

Patent application1. an isolated protein with

sequence ... having activity X2. an isolated protein with

sequence ... having activity X

3. glycosylated protein with sequence ...

4. peptide with sequence: ypskpdnpgeeapaedmaryysalrhyinlitrqry

5. peptide with sequence: ypskpdnpgeeapaedmaryysalrhyinlitrqry

The Concept of Novelty

State of the art1. gene X was cloned using

primers A and B2. genes 1 to N can be used for

treating diseases 1 to N3. gene x promotes cell division

Patent application1. gene X having

sequence ...........2. gene 5 for treatment of

obesity......3. use of gene x as a growth

factor

Inventive StepNon-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

– 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

2. a cup

3. a cup

4. a cup

5. a cup

Patent application1. a cup with a handle

(inventive?)

2. a 15 cm tall cup (inventive?)

3. a cup adapted to hold coffee (non-novel)

4. a red cup (inventive?)

5. a container for liquid (not novel)

The Concept of Inventive Step

State of the art1. cells secrete a protein with

activity X2. the protein with acivity X can

be purified from organism Y using method Z

3. protein with sequence ...

4. peptide with sequence: ypskpdnpgedapaedmaryysalrhyinlitrqry (NPY)

5. conservative substitutions can be made in NPY

Patent application1. an isolated protein with

sequence ... having activity X2. an isolated protein with

sequence ... having activity X

3. glycosylated protein with sequence ...

4. peptide with sequence: ypskpdnpgeeapaedmaryysalrhyinlitrqry

5. peptide with sequence: ypskpdnpgeeapaedmaryysalrhyinlitrqry

The Concept of Inventive Step

State of the art1. gene X was cloned using

primers A and B2. genes 1 to N can be used for

treating diseases 1 to N3. gene x promotes cell division4. an EST annotated as having

homology to an enzyme with activity Y

Patent application1. gene X having

sequence ...........2. gene 5 for treatment of

obesity......3. use of gene x as a growth

factor4. 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:

– 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

• Nucleic acid• Polypeptide• Antibody• Expression vector• Screening assay (kit)• Array• Pharmaceutical composition• Cells• Data carrier

Claim Types, Methods

• 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

THE INVENTIO

N

PRIORIT

Y PATENT

APPLICATIO

N

FILIN

G AN U

PDATED PCT

APLICATIO

N

NOVELTY S

EARCH

PUBLICATIO

N OF P

CT

APPLICATIO

N

PRELIM

INARY

EXAMIN

ATION

FILIN

G NATIO

NAL OR

REGIONAL

APPLICATIO

NS

MONTHS0 12 16 18 28 30

Patenting Process

PRIORIT

Y PATENT

APPLICATIO

N

• 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)

THE INVENTIO

N

Patenting ProcessFIL

ING A

N

UPDATED PCT

APPLICATIO

N

0 12 16 18 28 30

• 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

NOVELTY

SEARCH

0 12 16 18 28 30

• 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

PUBLICATIO

N

0 12 16 18 28 30

• Publication of the application 18 months from first filing

Patenting Process

PRELIM

INARY

EXAMIN

ATION

0 12 16 18 28 30

• 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 ProcessNATIO

NAL,

REGIONAL

APPLICATIO

NS

0 12 16 18 28 30

• Entry into national phase (US, JP, CA, AU etc) or regional phase (Europe, Eurasia, Africa).– Selection of countries– Geographic strategy– Language - translations– Costs

Patenting ProcessNATIO

NAL

PHASE

0 12 16 18 28 30

• 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:

– Patents on life (Harvard Onco-mouse)– Plant patents– Human genes– Stem cells– Human embryos (cryopreserved embryos)– Breast cancer diagnostics (brca genes)– Computer programs

• ”Non-controversial” issues:– 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

• Part of the problem:– 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

• 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 Informationfor Free

Finding Patent Information – for Free

• espacenet– 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– 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)– 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-patent-office.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_Sj9SPykssy0xPLMnMz0vM0Y_QjzKLN4i3dAHJgFjGpvqRqCKOcAFvfV-P_NxU_QD9gtzQiHJHRUUA43OWZA!!/delta/base64xml/L3dJdyEvUUd3QndNQSEvNElVRS82XzBfOUc!

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=protein&val=2935710– 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, PCT-gen (WIPO), DGene (Derwent))

Good Hunting!