Advanced Bioinformatics, DTU Genes and Patents

1. Advanced Bioinformatics, DTUGenes and Patents Jens Viktor Nørgaard, NsGene A/S

2. 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

3. 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

4. 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

5. 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

6. 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

7. Patents? What is a patent?????

8. What is a Patent? • Which rights arise from a granted patent?

9. 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

10. 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

11. Patentability Requirements

12. Patentability Requirements • Novelty • Inventive step • Clarity • Conciseness • Enablement • Sufficiency of disclosure • Utility • Industrial applicability • Exceptions to patentability

13. Novelty

14. 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

15. State of the Art (known) a cup a cup a cup a cup a cup Patent Application a cup with a handle (novel) a 15 cm tall cup (novel) a cup adapted to hold coffee (non-novel) a red cup (novel) a container for liquid (not novel) The Concept of Novelty

16. State of the art cells secrete a protein with activity X the protein with acivity X can be purified from organism Y using method Z protein with sequence ... peptide with sequence: ypskpdnpgedapaedmaryysalrhyinlitrqry (NPY) conservative substitutions can be made in NPY Patent application an isolated protein with sequence ... having activity X an isolated protein with sequence ... having activity X glycosylated protein with sequence ... peptide with sequence: ypskpdnpgeeapaedmaryysalrhyinlitrqry peptide with sequence: ypskpdnpgeeapaedmaryysalrhyinlitrqry The Concept of Novelty

17. State of the art gene X was cloned using primers A and B genes 1 to N can be used for treating diseases 1 to N gene x promotes cell division Patent application gene X having sequence ........... gene 5 for treatment of obesity...... use of gene x as a growth factor The Concept of Novelty

18. Inventive StepNon-obviousness

19. 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

20. 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?

21. State of the art (known) a cup a cup a cup a cup a cup Patent application a cup with a handle (inventive?) a 15 cm tall cup (inventive?) a cup adapted to hold coffee (non-novel) a red cup (inventive?) a container for liquid (not novel) The Concept of Inventive Step

22. State of the art cells secrete a protein with activity X the protein with acivity X can be purified from organism Y using method Z protein with sequence ... peptide with sequence: ypskpdnpgedapaedmaryysalrhyinlitrqry (NPY) conservative substitutions can be made in NPY Patent application an isolated protein with sequence ... having activity X an isolated protein with sequence ... having activity X glycosylated protein with sequence ... peptide with sequence: ypskpdnpgeeapaedmaryysalrhyinlitrqry peptide with sequence: ypskpdnpgeeapaedmaryysalrhyinlitrqry The Concept of Inventive Step

23. State of the art gene X was cloned using primers A and B genes 1 to N can be used for treating diseases 1 to N gene x promotes cell division an EST annotated as having homology to an enzyme with activity Y Patent application gene X having sequence ........... gene 5 for treatment of obesity...... use of gene x as a growth factor isolated and purified protein having sequence X and enzyme activity Y The Concept of Inventive Step

24. Clarity, Sufficiency, Enablement, Utility

25. 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)

26. Clarity, Conciseness • The claims must be clear and concise • Results in many definitions: • Sequence homology • Alignment • Hybridisation • High stringency • Receptor binding

27. 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

28. 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

29. Patent Claims

30. 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

31. 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.

32. 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.

33. Claim Types, Product • Nucleic acid • Polypeptide • Antibody • Expression vector • Screening assay (kit) • Array • Pharmaceutical composition • Cells • Data carrier

34. 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

35. Timelines The Typical Life of an International Application

36. PCT Patent Application Process PUBLICATION OF PCT APPLICATION PRELIMINARY EXAMINATION FILING NATIONAL OR REGIONAL APPLICATIONS PRIORITY PATENT APPLICATION FILING AN UPDATED PCT APLICATION THE INVENTION NOVELTY SEARCH 0 12 16 18 28 30 MONTHS

37. Patenting Process THE INVENTION PRIORITY PATENT APPLICATION • 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)

38. 0 12 16 18 28 30 Patenting Process FILING AN UPDATED PCT APPLICATION • 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)

39. 0 12 16 18 28 30 Patenting Process NOVELTY SEARCH • Novelty search (database search) • Identification and classification of publications (patent applications and scientific papers) • Possibility to evaluate the fate of the patent application

40. 0 12 16 18 28 30 Patenting Process PUBLICATION • Publication of the application 18 months from first filing

41. 0 12 16 18 28 30 Patenting Process PRELIMINARY EXAMINATION • 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

42. 0 12 16 18 28 30 Patenting Process NATIONAL, REGIONAL APPLICATIONS • Entry into national phase (US, JP, CA, AU etc) or regional phase (Europe, Eurasia, Africa). • Selection of countries • Geographic strategy • Language - translations • Costs

43. 0 12 16 18 28 30 Patenting Process NATIONAL PHASE • 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

44. Patents and Applications as Information Source How to Read a Patent Application

45. 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

46. 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

47. 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)

48. PCT Countries

49. PCT-applications • Filed, searched, published, examined • Timeline: priority year, published after 18 months, PCT phase ends after 2½ years • Example: WO0212514.pdf

50. 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)