Best Practices: IP Strategies for Diagnostics


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Discusses the available scope of patent protection for advances in diagnostics as well as the types of claims available in different jurisdictions. Additionally covers "support", i.e. the enabling teaching that is the trade-off for the patent monopoly, in the context of diagnostic patent applications. Finally, considers the enforcement and exploitation of patents directed to diagnostics.
Presenters: Anna Wilkinson and Cynthia Tape, Ogilvy Renault

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Best Practices: IP Strategies for Diagnostics

  1. 1. MaRS Best Practices Series: IP Strategies for Diagnostics Cynthia Tape Anna Wilkinson MaRS, Toronto February 28, 2008
  2. 2. Outline 1. Brief review of patent basics 2. Scope of patent protection for diagnostics 3. Types of claims 4. Support 5. Enforcement and exploitation 2
  3. 3. 1. Brief review of patent basics What is a patent • Patent is a bargain/contract between an inventor and the state:  the inventor discloses his/her know-how so that others can practice the invention;  in return for a time limited monopoly • Restrictions on the type and quality of information that is patentable  categories of patentable subject matter  information must be new, useful, unobvious 3
  4. 4. 1. Brief review of patent basics What is a patent (continued) • Bargain is reflected in the format of a patent:  a description (text and maybe drawings), wherein inventor teaches how to practice the invention  a set of claims, which define the monopoly • Bargain assessed during examination of a patent application:  detailed examination procedure before the patent office  meant to ensure scope of monopoly reflects new subject matter that the inventor actually invented and taught to the public 4
  5. 5. 1. Brief review of patent basics The patent monopoly • Patent monopolies are territorially limited • generally, must apply for a patent and application must be examined in each country in which a monopoly is desired • Patent monopolies are time limited • generally, 20 years from filing application • Patent monopolies are exclusionary • a patent does not give the patentee the right to practice the invention, only the right to sue someone else who practices it without permission 5
  6. 6. 1. Brief review of patent basics The monopoly (continued) • Patent excludes others from making, using or selling your invention without permission • Your patent may not allow you to practice the invention: No guarantee of Freedom to Operate • Filing preserves your place in line: right to enforce only when patent issues, which can take many years 6
  7. 7. 2. Scope of patent protection for diagnostics What can be patented? • An “invention”: defined very broadly, with exceptions carved out either through legislation or by case law:  In the United States: “anything new and useful made by man”  In Canada: any new and useful art, process, machine, manufacture or composition of matter, or any new and useful improvement thereon  In Europe: any inventions, in all fields of technology, provided that they are new, involve an inventive step and are susceptible of industrial application…followed by a list of specific exclusions 7
  8. 8. 2. Scope of patent protection for diagnostics What can be patented? (continued) • Selection patents:  permit a species of a previously patented genus to be patented based on a special advantage • requirements: no prior specific disclosure; unpredictable, unexpected advantage  arise in context of chemical patents; could be relevant to diagnostics  hot issue in Canadian patent law: • long recognized in UK and US law; also here • SCC case being heard in April – whether they should be recognized in Canada 8
  9. 9. 2. Scope of patent protection for diagnostics What can be patented? (continued) • Subject-matter restrictions relevant to diagnostics:  no patents for scientific principles or abstract theorems (Patent Act, section 27(8)) • E=mc2, Newton’s laws not patentable • restriction relevant to diagnostics, but distinction may not be clear: LabCorp v. Metabolite Laboratories, Inc. USSC 2006  be aware of limitations on methods of medical treatment, higher life forms, biotech 9
  10. 10. 2. Scope of patent protection for diagnostics What can be patented? (continued) • LabCorp v. Metabolite Laboratories  Patent for a test for detecting vitamin B deficiencies by measuring amino acid homocysteine in a patient’s blood; method claim: assaying levels of homocysteine and correlating level with vitamin deficiency  LabCorp, licensee of Metabolite, began using a different method for measuring homocysteine; stopped paying royalties  Metabolite sued and was successful at trial: LabCorp enjoined from using any homocysteine test  US Supreme Court dismissed appeal by LabCorp without explanation; dissent would have held that broad method claim was unpatentable for being a basic scientific fact  value in having a variety of different types of claims 10
  11. 11. 2. Scope of patent protection for diagnostics Medical methods • Medical methods are not patentable in Canada and Europe • may be able to claim “method” as a new use e.g. use of drug X for treating Y • diagnostic methods are not patentable in Europe • patentability of diagnostics in Canada may depend on whether invention includes an invasive step and if what you are doing could also have a therapeutic effect • Canadian example: diagnostic method that involved injection of radiolabelled antibodies as tumour markers was permitted on basis that would not have a therapeutic effect 11
  12. 12. 2. Scope of patent protection for diagnostics Medical methods (continued) • Medical and diagnostic methods are patentable in the United States, but medical methods are not enforceable against a doctor  can’t sue a doctor for infringement, but can sue a lab technician 12
  13. 13. 2. Scope of patent protection for diagnostics Higher life forms • Not patentable in Canada per se • Harvard College v. Commissioner of Patents, SCC 2002 • 5:4 split decision: Harvard Mouse not patentable subject matter (not a composition of matter) • But note Schmeiser v. Monsanto, SCC 2004 • 5:4 split decision: claims for genes and cells of genetically modified canola could be enforced against grower of canola plants • Patentable in the U.S. and Europe 13
  14. 14. 2. Scope of patent protection for diagnostics Biotechnological inventions • Patent Offices and Courts have had to wrestle with various issues in determining what biotechnological matter is patentable: • Basic scientific facts are not patentable • Novelty: i.e. if sequence is present in nature, can it be patented as new once isolated and sequenced? • Utility: what is required to show that a gene sequence is useful? 14
  15. 15. 2. Scope of patent protection for diagnostics Biotechnological inventions (continued) • In Europe biological material (including sequence or partial sequence of a gene) which is isolated from its natural environment or produced by means of a technical process even if it previously occurred in nature • In US novelty is also based on isolation from nature • Will also need to demonstrate utility of what you have isolated/sequenced 15
  16. 16. 3. Types of claims Common claim types • Product • Structure • Process by which it is made (product-by-process) • Physical or chemical properties • Machine or apparatus • System • Method or process • New use (of a new or known product) • Kit 16
  17. 17. 3. Types of claims Subject matter • Subject matter of claims dictated by technological developments • In-vitro diagnostic testing (IVD): analyzing blood/urine/other specimens to screen for or monitor diseases or other medical conditions • Molecular diagnostics: determining the function of genes and gene products • Pharmacogenomics: functional genomics + molecular pharmacology • Personalized medicine 17
  18. 18. 3. Types of claims Subject matter (continued) • Diagnostic tests can be: • Predictive • Screening • Prognostic • Monitoring • Pharmacogenomic 18
  19. 19. 3. Types of claims Participants in field • When formulating claims, should consider different participants: • Innovators • Manufacturers • Users: • Commercial labs • Hospital labs • Physician office labs • Patients • Supervised • Over the counter • Payers 19
  20. 20. 3. Types of claims Structure of a claim • Preamble (green) • Transition language (red)  open: “comprising”, “including”  closed: “consisting of” • Body (blue) • Claims are numbered • Independent claim (claim 1) does not make reference to another claim and is broadest in scope; a dependent claim incorporates the limitations of a preceding claim and so is narrower 20
  21. 21. 3. Types of claims Examples of subject matter • Amplification • Fluorescent in situ hybridization • DNA probes • Molecular labels • Biochips • Microfluidics • Signal detection • Biosensors • Medical imaging 21
  22. 22. 3. Types of claims Example: Method (US 5314809) 1. A method for nested amplification of a sequence within a target nucleic acid in a sample, the method comprises: (a) simultaneously mixing said sample in an amplification reaction mixture containing an outer primer pair and an inner primer pair, wherein said outer primer pair is capable of amplifying a target nucleic acid to provide an amplified target sequence, and said inner primer pair is capable of amplifying a subsequence within said target sequence; (b) treating the amplification reaction mixture of step (a) in an amplification reaction at a temperature for annealing and extending said outer primer pair on said target nucleic acid and at a temperature for denaturing the extension products of said outer primer pair to provide an amplified target sequence, wherein said temperature for annealing and extending said outer primer pair is higher than the temperature for annealing and extending said inner primer pair to said target nucleic acid and said temperature does not allow efficient extension of at least one member of said inner primer pair; and (c) treating the mixture of step (b) in an amplification reaction at said temperature for annealing and extending said inner primer pair on said amplified target sequence, and at an temperature for denaturing the extension products of said inner primer pair to provide an amplified subsequence. 22
  23. 23. 3. Types of claims Example: Product (US 6576424) 1. An array comprising a solid substrate and a plurality of positionally distinguishable sequence specific polynucleotides attached to the solid substrate of at least 100 polynucleotides per cm2, at least a plurality of said polynucleotides comprising at least 25 nucleotides. 23
  24. 24. 3. Types of claims Example: Apparatus (US 7238323) 1. A sequencing apparatus comprising: a body having a top portion, a bottom portion and an interior portion; the interior portion comprising at least two intersecting channels, wherein at least one of the two intersecting channels has at least one cross sectional dimension between about 0.1 µm and 500 µm; an electrokinetic fluid direction system for moving a first sequencing reagent through at least one of the two intersecting channels; a source of sequencing primers; an electropipettor for introducing sequencing primers from the source of sequencing primers to the at least two intersecting channels; a mixing zone fluidly connected to the at least two intersecting channels for mixing the first sequencing reagent with a second sequencing reagent; a size separation zone fluidly connected to the mixing zone for separating sequencing products by size, thereby providing the sequence of a target nucleic acid; and a computer having computer-readable code for selecting a sequencing primer. 24
  25. 25. 3. Types of claims Example: System (US 6816742) 1. A sampling system for monitoring the concentration of an analyte present in a subject, said sampling system comprising: a sensing device comprising a collection reservoir comprising an enzyme capable of reacting with the analyte to produce hydrogen peroxide and a sensor element in operative contact with the reservoir, wherein said sensor element reacts electrochemically with the hydrogen peroxide produced in the reservoir to provide a detectable signal, and said sensor element comprises an electrode having a geometric surface area which ranges from about 0.1 to 3 cm2, a background current which ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity which ranges from about 6 to 180 nA/µM of hydrogen peroxide when measured in a buffer solution at 0.6V, and one or more microprocessors in operative communication with the sensing device comprising programming to control operation of the sensing device. 25
  26. 26. 3. Types of claims Example: Use (EP 0241106) 1. The use of detectably labeled immunoglobulin or a fragment thereof, wherein said immunoglobulin or fragment (a) substantially accumulates at an inflammation site when said site is inflamed, (b) has no substantial epitopic specificity for said inflamed site, and (c) comprises one or more of: (i) pooled, human, polyclonal immunoglobulin; (ii) Fc fragment of pooled, human immunoglobulin; (iii) monoclonal antibody; (iv) Fc fragment of monoclonal antibody; in the preparation of an agent for the detection of an inflammation site in vivo. 26
  27. 27. 3. Types of claims Example: Use (US 785 216) 1. Use of an isolated nucleic acid which comprises the coding sequence set forth in SEQ ID NO: 1 from nucleotide position 229 to nucleotide position 10482 and further comprising the mutation associated with a predisposition to breast cancer, wherein T at nucleotide position 6174 is deleted, for diagnosing a predisposition to breast cancer in Ashkenazi-Jewish women in vitro. 27
  28. 28. 3. Types of claims Example: Kit (US 7122324) 1. A diagnostic test kit for assaying for the presence of C- terminal human glycoprotein IIb (hGPIIb) fragments in a body fluid sample, comprising a package containing an antibody composition comprising antibody molecules that: a) immunoreact with a polypeptide having an amino acid residue sequence as shown in SEQ ID NO: 3 from residues 173 to 193, 173 to 181, residues 179 to 189, residues 187 to 200, or residues 194 to 200; b) do not immunoreact with a second polypeptide having the amino acid residue sequence REQNSLDSWGPK, as shown in SEQ ID NO: 3 from residue 113 to residue 124. 28
  29. 29. 4. Support The Examination Procedure: Key Criteria • Subject matter: is it a patentable invention? • Novelty: is it new? • Inventiveness: is it obvious? • Utility: is it useful? • Enablement or sufficiency: do the teachings you have provided entitle you to the scope of the monopoly you are seeking? • Specifics vary among jurisdictions 29
  30. 30. 4. Support Enablement • Description must enable a person skilled in the art to practice the invention without undue experimentation • How much disclosure is necessary to support broad claims? Fact dependent • May involve sequence listing for amino acid or nucleic acid sequences • May involve deposit of biological material 30
  31. 31. 4. Support Enablement: Factors to consider • Breadth of claims • Nature of invention • Predictability of art • State of prior art • Relative skill of those in art • Quantity of experimentation necessary • Presence of working examples 31
  32. 32. 4. Support Utility • What is the use or function? • Credible, specific, substantial (i.e. real world use) • Unpredictable factors associated with chemical reactions and physiological activity may make standard harder to meet than in some other art fields 32
  33. 33. 4. Support Sound prediction • Do not have to test every species in a genus – may be able to rely on the Doctrine of Sound Prediction  Apotex v. Wellcome Foundation, SCC 2002 • AZT – new use for an old compound • issue: Could the data in the patent support claims to the treatment and prevention of HIV? • test for establishing a sound prediction: 1.Factual basis 2.Sound line of reasoning 3.Proper disclosure 33
  34. 34. 4. Support Sound prediction (continued) • Patent can be defeated if challenger can show that the prediction was not sound (i.e., if any element of 3-part test not met):  Eli Lilly v. Apotex, Federal Court 2008: factual basis and sound line of reasoning, but lack of proper disclosure  patent invalid  interesting because SCC gave little guidance on this issue in Apotex v. Wellcome case  note: proper disclosure a hot button issue generally • Patent can also be defeated if, despite soundness of prediction, invention in fact does not work 34
  35. 35. 4. Support Description requirements: diagnostics • Generally molecular diagnostic applications will require working examples • Prophetic examples have been sanctioned by court, but must not be written in past tense • For utility: • With genetic sequences, “research tool” not enough • Gene probe will require disclosure of specific target • Claim to receptor will only be granted with disclosure of disease or condition 35
  36. 36. 5. Enforcement and exploitation Developing a patent portfolio • Patent as a commercial tool: • To develop or insure market position • To find an investment partner • To license • May enable access to other technologies 36
  37. 37. 5. Enforcement and exploitation Decision to obtain patent protection • Importance of invention • Scope of likely patent protection • Potential commercial life of invention • Simple or complex technology • Ability to keep secret • Ability to police patent • Role in larger portfolio/strategy • Financing/licensing • Defensive reasons 37
  38. 38. 5. Enforcement and exploitation When to seek patent protection • Key considerations:  Timing of your own disclosure  State of development of technology: ability to satisfy description requirements • Want sufficient disclosure, but do not want to wait too long and be blocked by somebody else • Filing patent at the time of genetic discovery increases probability that funding can be found to develop actual clinical test 38
  39. 39. 5. Enforcement and exploitation Diagnostics field • Includes large entrenched participants • Stand alone IVD companies • Companies affiliated with pharmaceutical or medical device companies • Large diagnostic laboratories 39
  40. 40. 5. Enforcement and exploitation Business models • Different models:  Build a business  License out  Something in between, e.g. a partnering model • Appropriate model can depend on a number of factors: • Who funded the research? • How much funding is available for ongoing R&D, testing, regulatory processes? • What is the scope of your patent protection? • Are there roadblock patents? Can you obtain licenses or work around them? • What jurisdictions will you be working? e.g. socialized versus private healthcare • What is likelihood/timeline of regulatory approval? 40
  41. 41. 5. Enforcement and exploitation Motivation to partner • Well-established companies looking for new molecular markers; junior partner gets access to other necessities, including funding and regulatory expertise • Likely to involve a cross-licensing arrangement • Technology in field rapidly progressing, requires significant R & D investments to remain competitive • Diagnostic tests require regulatory approval: requires funding and expertise 41
  42. 42. 5. Enforcement and exploitation Freedom to operate • Something to consider from the outset • Other market participants may control roadblock (e.g. a patented process that must be practised in order to use your kit) or complementary technologies (e.g. reagents, devices beneficially used in conjunction with your invention) • Early investigation might stop wasted outlay on research/patents/regulatory approval • FTO opinion a search of current patents (pending applications) and an analysis of the scope (likely scope) of their claims 42
  43. 43. 5. Enforcement and exploitation Freedom to operate (continued) • Steps taken at the outset to ensure proper IP protection is obtained increase the chance of a partnering opportunity in the future • If going to “build a business” rather than licensing out, then will be important to ensure from the outset access to the necessary technologies • Even if plan is only to license out technology, can be a covenant to hold licensee harmless 43
  44. 44. 5. Enforcement and exploitation Licensing • Open license i.e. available to all for payment of a “toll” • Results in more extensive use • May be better for a test with broad applicability • May insulate the patent from challenge • Exclusive license i.e. single vendor • May yield more money at the outset • May be better for a test with more specific applicability • Something in between these two extremes e.g. license to specifically selected class of licensees 44
  45. 45. 5. Enforcement and exploitation Licensing (continued) • Issues to consider:  “patent thickets” and “royalty stacking”: • overlapping rights can lead to complicated scenarios • for a single test, licenses may be necessary from a number of parties  large payers may have significant influence  public and private cost v. return on investment: one size fits all? 45
  46. 46. 5. Enforcement and exploitation Example: Cancer susceptibility genes BRCA1 and BRCA2 • Myriad Genetics – patents for genes, mutation detection • Built business around performing the tests itself:  BRACAnalysis® assesses a woman's risk of developing breast or ovarian cancer based on detection of mutations in the BRCA1 and BRCA2 genes  blood sent to Myriad’s laboratories (or very small group of licensed laboratories), then results sent to doctor who discusses them with the patient 46
  47. 47. 5. Enforcement and exploitation Example: Cancer susceptibility genes BRCA1 and BRCA2 • United States: • Myriad licensed the rights to perform these tests to about a dozen laboratories in exchange for high royalties on each test performed • federal government brokered deal to pay lower royalties when the genes are used by NCI and NIH-sponsored research institutions and investigators 47
  48. 48. 5. Enforcement and exploitation Example: Cancer susceptibility genes BRCA1 and BRCA2 • Canada:  provinces performing genetic testing using BRCA genes but a different method • in 2001, Myriad sent cease and desist letters: • provincial governments infringing Myriad gene patents • stop using any tests to detect the BRCA1 and 2 genes other than BRACAnalysis® • use Myriad testing at higher cost • BC stopped testing for a time; Ontario continued testing (now using a different system) 48
  49. 49. 5. Enforcement and exploitation Example: Cancer susceptibility genes BRCA1 and BRCA2 • Europe:  opposition from research institutes, ministries of health and political parties  October 2007, Board of Appeal of EPO upheld revocation of one Myriad patent (EP 705 902) regarding the BRCA1 gene and its applications (other opposition proceedings ongoing)  patent claimed isolated gene, corresponding protein, therapeutic applications and diagnostic kits (use of probes or primers specific to certain mutations)  revoked on basis of lack of novelty (i.e. sequence had already been isolated and determined) 49
  50. 50. 5. Enforcement and exploitation Example: Cancer susceptibility genes BRCA1 and BRCA2 • Diagnostic patents can raise highly politicized issues related to access and publicly funded research and treatment • But, this time limited monopoly has been put in place to try to provide an appropriate reward for inventor disclosure of useful inventions 50
  51. 51. Thank You! Any Questions? Ogilvy Renault LLP 200 Bay Street, Suite 3800 P.O. Box 84 Royal Bank Plaza, South Tower Toronto, Canada M5J 2Z4 Cynthia Tape T 416.216.4063 Anna Wilkinson T 416.216.3975