Weitere ähnliche Inhalte Ähnlich wie Patenting Small Molecule Therapeutics (20) Kürzlich hochgeladen (20) Patenting Small Molecule Therapeutics2. 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 LLP
2
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 LLP
3
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 LLP
4
5. The Law
1. Patent-eligible subject matter
2. Written Description and Best Mode
3. Enablement
4. Novelty
5. Non-Obviousness
© 2012 Venable LLP
5
6. The Patent Application
Detailed sections
Claims
Description
Optional, but detailed sections
Drawings/Figures
Description of Drawings
Minimal sections
Abstract
Background
© 2012 Venable LLP
6
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 LLP
7
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
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 LLP
10
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 LLP
12
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/genes
13
– times/temperatures/ranges © 2012 Venable LLP
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 LLP
15
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 LLP
16
17. Example – Same compound, two uses
Patent #1 (1993)
Patent #2 (2002)
© 2012 Venable LLP
17
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 LLP
18
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 LLP
20
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 LLP
22
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 LLP
23
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 LLP
24
25. Step 2: Identify the Variables
Atom substitutions: CN; OS; CSi, NO; 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 LLP
25
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 LLP
26
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 LLP
27
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 LLP
28
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 LLP
29
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 LLP
30
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 LLP
31
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 LLP
32
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 LLP
34
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 LLP
36
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 LLP
38
39. Timing - Avoid the Patent Pitfalls
Experiment Publication
Invention
Disclosure/
Provisional
Application
© 2012 Venable LLP
39
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 LLP
40
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 LLP
41
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 LLP
42
43. Thank you!
Michael E. Nelson
MENelson@Venable.com
202-344-4766
www.Venable.com
© 2011 Venable LLP
43
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 LLP
44