Patent Use in the Pharmaceutical Industry

1
Patent Use in the Pharmaceutical Industry

• By Fiona Murray, Kyle Jensen, Ilya Vaynshteyn

2
The Hatch Waxman Act (1984) simplified the
approval process for generic drugs

• Started the generic drug industry
• Provided for ANDAs (cheaper, faster)
• Generic Drugs can be manufactured even while
  originals are still under patent
• FDA Orange Book
• Purpose To make generic pharmaceutical firms
  aware of patents protecting brand-name drugs
• All patents that claim a new drug, or some method
  of using this drug are listed in the Orange Book
• ALL new patent-protected drugs since Hatch-Waxman
  are listed in the Orange Book

3
Our analysis focused on linking data from the
FDA Orange Book with data from European Patent
Office

• Orange Book Focus on patent-protected, RLD NDAs
• Reference Listed Drugs (RLDs) Designated by FDA
  to be imitated by generics
• To prevent biochemical differences between
  brand-name drug and generic versions
• The core drug
• Patent-protected NDAs NDAs that list patents
  (appear in PATENT.TXT see Appendix)
• Data processing automated via Python and GNU text
  processing
• Open Patent Services (OPS)
• Online European Patent Office database containing
  patent info
• Data from European Patent Office, US Patent
  Office, Japanese Patent Office
• Patent family data, legal data, and bibliographic
  data
• For example Classification Symbols
  (International or European), Abstract, Inventor
  Name
• Python code accesses OPS via SOAPpy (Python SOAP
  implementation)
• Given patent number, can retrieve assignee
  name(s)

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The number of RLD NDAs approved per year is
slowly increasing

• Since 1982, approximately 20 of all NDAs are RLD
  NDAs
• The number of RLD NDAs approved is less variable
  than the number of total NDAs approved

5
Most drugs (RLD NDAs) are protected by very few
patents

• Average RLD NDA lists 2.69 patents

6
There appears to be little evidence of platform
technologies

• Average patent is listed in 1.40 RLD NDAs

There are 22 patents that cover 5 or more drugs
each. Half of these patents concern two areas 5
are related to treatment of the HIV or AIDS virus
and 6 cover methods of production of
microcapsules.
7
The companies with the most drugs (RLD NDAs)
tend to be big pharma firms
Subsidiaries and mergers ARE NOT considered
8
Subsidiary companies and mergers play an
important role in the pharmaceutical industry
Subsidiaries and mergers ARE considered
9
In-licensing plays a significant role for more
than 50 of drugs
Firms with the most drugs (RLD NDAs) where the
drug maker owns all the patents protecting the
drug
10
Out-licensing varies significantly by firm
Firms by most patents owned on RLD NDAs in the
Orange Book
11
Certain families of drugs tend to be covered by
patent-thickets
Oval patent Line shared NDA
12
Close-up view of a sample patent-thicket
Oval patent Line shared NDA
Method for inhibiting bone resorption
Oral liquid alendronate formulations
13 of the 16 patents in this thicket belong to
Merck and Co, Inc. The three patents that do not
belong to Merck are highlighted. There are a
total of 4 NDAs shared between the patents in
this thicket. Three of these are different NDAs
for Mercks drug Fosamax, and the other is an NDA
for Procter and Gambles drug Actonel. Both of
these drugs are used to treat osteoporosis.
13
Research Institutions are active in filing
joint-patent Applications
Research institutions are HIGHLIGHTED
46 out of 1382 (3.3) patents on RLD NDAs in the
Orange Book have multiple applicants. A sample of
1744 random patents was found to have a slightly
higher percentage (4.4) of patents with joint
applicants. The difference in ratios was
statistically significant at a 90 confidence
level, but not at a 95 confidence level.
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The relationship between patenting, drugs (RLD
NDAs) and RD is very complex
Shading RD expense, not including subsidiaries
(lighter more spent) Size proportional to
number of RLD NDAs (also in parenthesis) Distance
to diagonal dependency of licensing
There seems to be a general correlation between
greater RD spending, more RLD NDAs and more
parents covering those NDAs. However, this
pattern does not apply to Sanofi-Aventis and
Roche (high RD expense, few NDAs) and Bristol
Myers Squibb (many NDAs, few self-owned patents).
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Conclusions / Summary

• There are only 2491 drugs (RLD NDAs) listed in
  the FDA Orange Book
• 717 are patent protected
• Fewer than 1382 patents cover all drugs (RLD
  NDAs) approved since 1984
• Firms try to be self sufficient
• For close to 60 of their RLD NDAs, own all the
  patents listed in the NDA
• One-fourth of patents in the Orange Book are
  out-licensed
• But collaboration still necessary
• Acquisition of subsidiaries plays major role
• Joint-patent applications show small, but
  important effect of non-profits
• Licensing, joint-ventures needed also
• Own RD and subsidiaries not enough to provide
  firms with the patents they need to protect all
  of their drugs (RLD NDAs)

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Conclusions / Summary

• Effects of the Hatch-Waxman Act
• Generic vs. brand-name drug competition
• Benefits
• Forces collaboration and more research by big
  pharma firms
• Stimulates innovation Pharmaceutical companies
  need to keep developing new drugs, because older
  drugs replaced by cheaper generics

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Thank You

• Questions/Answers

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Appendix Data File Structure
Format Column 1 NDA Number Column 2 Patent
Number Column 3 Patent Applicant Name Column
4 Country of Patent Applicant Column 5 NDA
Applicant Name Sample Data 004782 5210081
AMERICAN HOME PROD (US) WYETH PHARMACEUTICALS
INC 010971 5210081 AMERICAN HOME
PROD (US) WYETH AYERST LABORATORIES 011522 638402
0 SHIRE LAB INC (US) SHIRE DEVELOPMENT
INC 013217 6407128 ELAN PHARM INC (US) JONES
PHARMA INC 013718 5872147 BIO TECHNOLOGY GENERAL
CORP (US) SAVIENT PHARMACEUTICALS
INC 013718 6090799 BTG PHARMA CORP (US)
SAVIENT PHARMACEUTICALS INC 013718 6576659 BIO
TECHNOLOGY GENERAL CORP (US) SAVIENT
PHARMACEUTICALS INC 013718 6670351 BIO
TECHNOLOGY GENERAL CORP (US) SAVIENT
PHARMACEUTICALS INC 013718 6828313 BIO
TECHNOLOGY GENERAL CORP (US) SAVIENT
PHARMACEUTICALS INC 017922 5482931 FERRING
AB (SE) AVENTIS PHARMACEUTICAL PRODUCTS INC
NDA No. Pat. No. Patent Applicant
Country NDA Applicant
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Appendix Orange Book Data Details

• Data available online (http//www.fda.gov/cder/ora
  nge/obreadme.htm)
• PRODUCTS.TXT Information about FDA approved
  Drugs
• PATENT.TXT List of patents and the NDAs they
  site
• NDA Number is a common field
• All fields delimited by tilde ()
• Sample Sizes
• 13,500 NDAs total in PRODUCTS.TXT
• 2,491 RLD NDAs
• 737 Patent-Protected RLD NDAs (5.5)
• Our data file incorporates 717 (97.3) of them
  because OPS query failed for some patents. This
  means the NDAs listing only those patents were
  not included in the data file because the entry
  was not complete (patent assignee was missing)