MMS Merged Markush Service The Questel

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MMSMerged Markush ServiceThe QuestelOrbit
Alternative for Chemical Information
227th ACS National Meeting Anaheim, CA 28 March
2004

• Elliott Linder, QuestelOrbit
• Joe Terlizzi, QuestelOrbit

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Scenario

• Hypothetical Pharm X has developed a compound
  with the structure below, which they are finding
  to be a useful contraceptive in animal tests.
  Should they try to patent or commercialize this
  compound and/or its use?

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Scenario

• What does Pharm X need to know?
• Has the compound been documented or patented,
  i.e., is the compound really new?
• Is its intended use new?
• If the compound and/or its use have been
  patented, what is the status of the patent or
  patents?

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Search

• Pharm X searchers will want to check the standard
  chemical structure databases on key vendor
  systems
• CAS Registry for exact structure
• MARPAT for open substitution on benzene rings or
  amino group
• Beilstein

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Search

• With patentability and potential infringement at
  stake, Pharm X also decides to extend their
  structure search to MMS, the Merged Markush
  Service from QuestelOrbit.
• But what is MMS?

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MMS Coverage and Structure

• Four segments
• Front File (FRONTF) from Derwent week 9816
• WPIM 1987-1998
• MPHARM 1987-1999
• Backfile (BACKF) 1978-1987 (FR back to 1961)
• The user can choose which segment(s) to search

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MMS Coverage and Structure

• Updating MMS
• Front File (Derwent) updated weekly
• Back File now goes back to 1978
• No additional updates of MPHARM from year 2000

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Link to bibliographic files
CN Compound Number
Markush query
CN 1
CN 2
CN 4
CN link
CN 3
CN link
MMS structure file
AN 1 CN 3------------ PN---------------
AN 1 CN 1-------------- PN-----------------
Patent retrieval
PHARM biblio file
WPIL biblio file
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Link to bibliographic files
FRONTF
CN YYWW-CCCSS
WPIL
WPIM
CN YYMMXXXX-NN
MPHARM
2 CN formats
PHARM
BACKF
BIBLIOGRAPHIC FILES
MMS STRUCTURE FILE
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MMS Search

• Structure Searching Steps
• Open Imagination or STN Express.
• Draw query using Query Text (QT) or import
  structure from Derwents Markush Topfrag.
• Verify and exit query input.
• REtrieve candidates. Candidates contain fragments
  of the queried structure.
• Run an Atom-by-Atom search on RE candidates.
• Cross to QuestelOrbit bibliographic system.

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Verifying MMS Structure using Imagination
Steps 2 3
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MMS Search
Step 4
RE search is conducted first. There are over
35,000 candidates containing structural
fragments of the original query.
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MMS Search
Step 5
When AA search is conducted, one answer is found.
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Search
Step 6

• Compound number is transferred to the PHARM
  database. PHARM record is as follows
• AN - 83115153
• CN - 83115153-01-K 83115153-01-T
  83115153-01-U
• PN - US4415585 - 19831115 US4415585
• AP - US35716082 19820311 1982US-0357160
• PA - UNIVERSITY OF ILLINOIS FOUNDATION
  /Urbana/IL (US)
• IN - JOYCE CATHY L (US)
• - ZANEVELD LOURENS J (US)
• IC1 - A61K-031/53
• IC2 - A61K-031/415
• ET - Contraceptive method.

Indicates known structure further investigation
required
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Search
Pharm record contd

• EAB - Use of pyrazolone derivatives of formula
  (I) wherein A is H, halo, trihalomethyl, lower
  C1-8 alkyl, -X-OH, -X-CO-R, -X-CO-OR, -X-SO-D,
• -X-S-D or -NR1R2 X is a lower (C1-C8) alkylene
  group R, R1, and R2 are hydrogen, or the same or
  different lower alkyl groups, and B, C, and D,
  which can be the same or different, are phenyl,
  hydroxyphenyl or lower alkylphenyl, further
  provided that B and C together can form a chain
  of formula (II), as contraceptive agents.
• - The contraceptive method comprises maintaining
  in the genital tract of a female mammal a
  pyrazolone derivative in a concentration
  effective to inhibit the fertilization of ova. In
  addition to effectively, inhibiting the enzymes
  or other sperm components necessary for
  conception, the compounds used in the method of
  the invention are advantageous in having low
  toxic, caustic or irritating properties, so that
  the contraceptive compositions are suitable for
  long-term use without adverse side-effects.

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Analysis

• The compound number 83115153-01, reveals that the
  answer is a Markush structure indexed by INPI in
  1983.
• The BACKF, produced by INPI, dates back to 1978
  for US patents. This structure will not be found
  in Marpat since it only goes back to 1988.
• The generic structure cannot be searched in
  Registry. MMS contains both specific and generic
  structures.

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Analysis

• The PHARM record reveals that the retrieved
  patent contains many possible structures, and
  contains a variation of our structure, with a
  methyl group substituted on the fused benzene
  ring.
• The patent assignee is the University of Illinois
  Foundation, and the patent was published in 1983.
  The compound was also used as a contraceptive.
• Therefore, an infringement is possible.

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Analysis

• Some things we will need to check are
• Are there any family members, meaning has the
  patent been applied for and/or granted in any
  other countries?
• What is the status of these patents, i.e., are
  they still valid or have they expired or lapsed?
• Are there cited references that reveal any
  additional prior art about this compound?
• Are there patents citing this patent that give us
  more information about this compound?

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Analysis

• These points are easy to check using the PlusPat
  database on QuestelOrbit.
• Using the MEM and MEM commands, the Standardized
  Patent Number XPN is extracted and searched in
  PlusPat. (Standardization of the all
  publication, application, and priority numbers on
  QuestelOrbit simplifies cross-file searching.)
• The FAM command is executed on the publication
  number, and the FAMSTAT command is used to
  display the family members and their LEGAL
  STATUS.

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Analysis
1/1 PlusPat - (C) QUESTEL-ORBIT- image CPIM PN -
US4415585 A 19831115 US4415585 . . 1/1 LGST -
(C) EPO PN - US4415585 A 19831115 US4415585 AP
- US35716082 19820311 1982US-0357160 ACT -
19820607 US/AS02-A ASSIGNMENT OF ASSIGNOR'S
INTEREST OWNER UNIVERSITY OF ILLINOIS
FOUNDATION, A CORP. OF ILL. EFFECTIVE DATE
19820310 - 19820607 US/AS02-A ASSIGNMENT OF
ASSIGNOR'S INTEREST OWNER JOYCE, CATHY L.
EFFECTIVE DATE 19820310 - 19820607
US/AS02-A ASSIGNMENT OF ASSIGNOR'S
INTEREST OWNER ZANEVELD, LOURENS J. D.
EFFECTIVE DATE 19820310 - 19920128 US/FP-A
- EXPIRED DUE TO FAILURE TO PAY MAINTENANCE
FEE EFFECTIVE DATE 19911117 UP - 2003-22  
FAMSTAT format. (PlusPat record edited for
brevity.)
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Analysis

• The PlusPat record reveals that there are no
  other family members, and the LGST record that
  the patent expired in 1991 due to a failure to
  pay the maintenance fee.
• A citation analysis can be conducted on
  QuestelOrbit using the FAM command and FAMCITE
  display, that contains
• All patent families citing the source patent
  family
• All patents families cited in the source patent
  family
• The citation analysis can be helpful in finding
  additional prior art.

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Conclusions

• In this hypothetical scenario, Pharm X has a
  potential opportunity due to the expiration of
  the patent retrieved.
• In general, no single resource is sufficiently
  comprehensive on its own.
• As many resources as possible should be searched
  for prior art and infringement.