Patenting Small Molecule Therapeutics

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Patenting Small Molecule Therapeutics

  1. 1. Patenting Small Molecule Therapeutics: From Target to Clinic JUNE 7, 2012 © 2008 Venable LLP1
  2. 2. OUR GOAL To provide a resource for inventors to recognize patentable inventions and provide technical details for strong applications to patent small molecule therapeutics. © 2012 Venable LLP2
  3. 3. Agenda  Why Patent Small Molecule Therapeutics?  Patent Basics – Patentability – Types of Applications – Timelines  Target to Clinic – the Invention Story – Target – Assay – Screen – Compounds – Formulations  Patent Pitfalls © 2012 Venable LLP3
  4. 4. Why Patent Small Molecule Therapeutics? Target discovery/validation Assay development High-throughput screen Lead Selection Lead optimization/candidate selection Preclinical Testing Clinical Trials Clinic 0 1 2 3 4 5 6 7 10-15 Years • 1 in 5000-10000 compounds • $800 million to $1 billion © 2012 Venable LLP4
  5. 5. The Law 1. Patent-eligible subject matter 2. Written Description and Best Mode 3. Enablement 4. Novelty 5. Non-Obviousness © 2012 Venable LLP5
  6. 6. The Patent Application  Detailed sections  Claims  Description  Optional, but detailed sections  Drawings/Figures  Description of Drawings  Minimal sections  Abstract  Background © 2012 Venable LLP6
  7. 7. What’s your invention? Some Patent Eligible Inventions  Chemical Compounds – Organic compounds (small molecules) – Peptides, Proteins, Oligonucleotides, Nucleic Acids  Chemical Compositions – Pharmaceutical Formulations  Methods – Synthetic Methods – Assay Methods – Therapeutic Methods  Genetically Modified Organisms © 2012 Venable LLP7
  8. 8. 8 Invention Disclosure 0 Provisional Appl. International App. 1 Year The Patent Timeline U.S. and Foreign 2.5 National Apps. Years U.S. and Foreign 4-6 Patents Issue Years © 2012 Venable LLP
  9. 9. Patenting Small-Molecule Therapeutics Target Assay Screen Compounds Formulations © 2012 Venable LLP9
  10. 10. Target  Discover a correlation between DNA sequences/genes or proteins/enzymes and a particular disease state.  Important and valuable scientifically  Difficult to Patent  “natural” DNA and proteins  “natural” phenomena  Research tools, not as much commercial value © 2012 Venable LLP10
  11. 11. Patenting Small-Molecule Therapeutics Target Assay Screen Compounds Formulations © 2012 Venable LLP11
  12. 12. Assay  Develop and validate system to measure change in target level or activity  Assay method may be patent eligible (disputed) – Methods of measuring change in target  Components, too – Compounds - enzyme substrates; chimeric proteins, PCR probes, monoclonal antibodies, cDNA – Chemical Compositions - growth or expression media; assay kits (combinations of ingredients) – Organisms - cell lines, transgenic/knockout animals  Research tools, but some commercial value © 2012 Venable LLP12
  13. 13. Invention Disclosure – Assay 1. Use active verbs (mixing, incubating, centrifuging) 2. Begin with the minimum essential steps 3. Include the minimum essential ingredients 4. List additional steps, and identify preferred or optimized conditions and ingredients 5. Consider if there is a diagnostic application 6. List Alternatives such as: – reagents/media – cells/expression systems – detection systems/equipment – reporter proteins/genes13 – times/temperatures/ranges © 2012 Venable LLP
  14. 14. Patenting Small-Molecule Therapeutics Target Assay Screen Compounds Formulations © 2012 Venable LLP14
  15. 15. Screen for Therapeutic Compounds  Discover compounds that modulate the target.  Commercially valuable inventions:  Pharmaceutical compositions  Therapeutic Methods  Methods of screening compounds may be patent eligible  Method of identifying compounds that modulate target  Typically combined with assay description in one application  Can find new uses for known compounds © 2012 Venable LLP15
  16. 16. Therapeutic Methods New uses for old compounds and new compounds too! Example: Method of treating Y comprising administering to a subject in need of treatment an effective amount of a compound of formula X. Can be commercially valuable, especially with previously approved drugs. © 2012 Venable LLP16
  17. 17. Example – Same compound, two uses Patent #1 (1993) Patent #2 (2002) © 2012 Venable LLP17
  18. 18. Pharmaceutical Compositions Pharmaceutical Compositions – Alternative invention if a compound is known/commercially available but has no previously-known biological activity – Combine with therapeutic methods; include with new compounds – Combinations of active ingredients Example: A pharmaceutical composition comprising a compound of formula X and a pharmaceutically acceptable excipient © 2012 Venable LLP18
  19. 19. Patenting Small-Molecule Therapeutics Target Assay Screen Compounds Formulations © 2012 Venable LLP19
  20. 20. Compounds New compounds with therapeutic activity  Commercially valuable, broadest scope of protection, strongest claims.  Protects compounds, regardless of how used; not tied to particular therapeutic use.  Include therapeutic methods and pharmaceutical composition inventions too Example: A compound of formula X. © 2012 Venable LLP20
  21. 21. Example © 2012 Venable LLP21
  22. 22. Invention Disclosure – Compounds Written • A structural class of compounds Description • Structures of all compounds synthesized • General methods for synthesizing the compounds in the class Enablement • Synthesis and analytical details for all compounds made • Biological activity results, including inactives (supports non-obviousness) Patentability • Details of biological activity assay for at least one compound © 2012 Venable LLP22
  23. 23. Structure Description GOAL – Describe a generic structure encompassing compounds with biological activity (measured and predicted), but where no known compounds fall within the generic structure Step 0: Library/on-line research to identify structurally- related compounds – Give all references to OIP/Outside Counsel © 2012 Venable LLP23
  24. 24. Step 1: Core Structure Identify common structures: 1. Aromatic/Heteroaromatic structures 2. Non-aromatic ring structures 3. Saturated/Unsaturated chains Identify variables: 1. Atom Substitutions 2. Connectors 3. Substituents © 2012 Venable LLP24
  25. 25. Step 2: Identify the Variables Atom substitutions: CN; OS; CSi, NO; etc. 1-atom Connections: -C-; -N(R)-; -O-; -S-; -Si-; -C(O)-; -S(O)-; etc. 2-atom Connections: -C-C-; -C=C-; -C-O-; -O-C-; -C(O)N(R)-; -N(R)C(O)-; -OC(O)-; -C(O)O-; -N-O-; -N-N-; -N=N-; etc. © 2012 Venable LLP25
  26. 26. Step 3: Substituents Substituents  Hydrogen, Halogen, Nitro, Nitrile  Alkyl, alkenyl, alkynyl, linear, branched, cyclic, Haloalkyl  Aryl, heteroaryl, substituted aryl and heteroaryl  Hydroxy, Alkoxy, aryloxy, heteroaryloxy  Hydroxyalkyl, alkoxyalkyl, aryloxylalkyl, heteroaryloxyalkyl  Amino, alkylamino, arylamino, heteroarylamino  Aminoalkyl, alkylaminoalkyl, arylaminoalkyl, heteroarylaminoalkyl  Thiol, Alkylthio, arylthio, heteroarylthio, sulfone, sulfoxide  Thioalkyl, alkylthioalkyl, arylthioalkyl, heteroarylthioalkyl  Carbaldehyde, Acyl, O-acyl, N-Acyl, S-Acyl,  C(O)OR, C(O)NHR, C(O)NR2, C(O)-S(alkyl)  Silane, alkylsilane, Arylsilane,  Phosponate, phosphinate, phosphate  Many, many more! © 2011 Venable LLP26
  27. 27. Step 4: Create the Description For each variable, create three lists. 1. All options 2. More favorable options selected from list 1 3. Best options selected from list 2. © 2012 Venable LLP27
  28. 28. Include Multiple Inventions Therapeutic Methods  Uses of old and new compounds to treat disease  Include with all new compound inventions Pharmaceutical Compositions  Mixtures of active compounds and pharmaceutical excipients  Include with all new compound inventions © 2012 Venable LLP28
  29. 29. Invention Disclosure – Therapeutic Methods Written Description Enablement • All diseases/ • Screening assay disorders associated details with target. • Screening assay • Correlation between results of all active compound activity compounds and disease/disorder • Biological activity • Structures of all assay details active compounds • Biological activity • Source for all active assay results for all compounds active compounds • Commercial source; Synthetic Methods © 2012 Venable LLP29
  30. 30. Invention Disclosure – Therapeutic Methods Extras:  Structures of known, but untested, structurally related compounds expected to have similar activity, with sources  Structures and assay results for structurally related compounds confirmed as inactive. If available, include:  Comparative data with known compounds used to treat same diseases or disorders © 2012 Venable LLP30
  31. 31. Describing Diseases/Disorders Be Comprehensive  International Classification of Diseases  http://www.who.int/classifications/icd/en/ Target-based approach  Combine with your library research on the target protein  Consider other targets with similar function  Enzymes with the same function in different pathogens  Proteins that use similar substrates/co-factors, if compounds mimic substrate/co-factor © 2012 Venable LLP31
  32. 32. Invention Disclosure - Compositions Definitely include:  Everything from Therapeutic Methods Also Include:  Types of formulations and compatible excipients – Liquid Formulations • Solutions/Suspensions – Solid formulations - Additives – Salts – Solubility Enhancers  Any known or expected incompatible additives © 2012 Venable LLP32
  33. 33. Patenting Small-Molecule Therapeutics Target Assay Screen Compounds Formulations © 2012 Venable LLP33
  34. 34. Clinical Formulations For known compounds with known activity  Combination of compound with an excipient or delivery system to improve drug properties  May be commercially valuable if new formulation has improved properties.  Usually pursued by pharmaceutical industry to extend patent life, after compounds and therapeutic methods have been patented. Example: A pharmaceutical formulation comprising a compound of formula X and additional ingredient Y. © 2012 Venable LLP34
  35. 35. Example – U.S. 5,686,104 (Nov. 11, 1997) © 2012 Venable LLP35
  36. 36. Invention Disclosure - Formulation Written Description • Generic Compound Structures, with sources. • Specific Compound Structures, with sources. • Additives that produce enhanced properties, with sources. • Include substitutions/equivalents. • Minimum and maximum amounts for all additives • Optional additives, if any. • Minimum and maximum amounts for all optional additives. Enablement • Specific details of all formulations produced and tested. • Details of tests used to measure formulation properties • Results of tests showing improved properties Non-Obviousness • Comparison with formulations lacking additives and using other additives • Reasons why improved properties are important © 2012 Venable LLP36
  37. 37. Patenting Small-Molecule Therapeutics Compounds Formulations Pre-clinical trials Clinical Trials Clinic © 2012 Venable LLP37
  38. 38. Preclinic  Clinical Trials  Clinic  Fewer patentable inventions  Preclinical testing may inspire new patentable formulations or dosage forms  Dosage/efficacy optimization not generally sufficient for patentability © 2012 Venable LLP38
  39. 39. Timing - Avoid the Patent Pitfalls Experiment Publication Invention Disclosure/ Provisional Application © 2012 Venable LLP39
  40. 40. Patent Pitfall #1 – The Unfinished Experiment  A research proposal as part of an invention disclosure may not be patentable and may foreclose a later patent. Why? – Enablement – if the provisional application is not enabled, any non-provisional application may not benefit – Provisional application becomes public after a non-provisional application publishes. The proposal may be accidentally disclosed.  Remedy: include detailed prophetic examples of viable experiments that can be completed within one year © 2012 Venable LLP40
  41. 41. Patent Pitfall #2 – The Accidental Disclosure  Disclosing the invention before the patent application is filed may result in rejection. Why? – Novelty is destroyed by publication  Common types of accidental disclosures – Poster and presentation abstracts – Conference presentations – Dissertations/Theses – Web publications!  Remedy – File at least a Provisional Application before any disclosure, but avoid Patent Pitfall #3 © 2012 Venable LLP41
  42. 42. Patent Pitfall #3 – The Last-minute Provisional Application T=0 0<T<1Yr: T=1Yr: Provisional Disclosure Non-Provisional  Filing a “quickie” provisional application may limit the scope of the patent. Why? – Written Description & Novelty – claims must have written description in the provisional application. If not, any claims broader than the provisional application may be rejected based on the early publication  Remedy: file a provisional application with full description; Promptly file follow-on provisional applications with more data © 2012 Venable LLP42
  43. 43. Thank you!  Michael E. Nelson MENelson@Venable.com 202-344-4766 www.Venable.com © 2011 Venable LLP43
  44. 44. contact information YOUR VENABLE TEAM Henry J. Daley, Ph.D. Michael A. Gollin HJDaley@Venable.com MAGollin@Venable.com t 202.344.4362 t 202.344.4072 Stefan J. Kirchanski, Ph.D. Lars H. Genieser, Ph.D. SJKirchanski@Venable.com LHGenieser@Venable.com t 310.229.9928 t 202.344.8234 Devesh Srivastava, Ph.D. Nancy J. Axelrod, Ph.D. DSrivastava@Venable.com NJAxelrod@Venable.com t 202.344.4447 t 202.344.8334 Michael E. Nelson, Ph.D. And the rest of the Venable MENelson@Venable.com prosecution group… t 202.344-4766 www.Venable.com © 2012 Venable LLP44

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