plavix patent issue
TRANSCRIPT
-
8/9/2019 Plavix Patent Issue
1/29
Plavix Patent Issue
-
8/9/2019 Plavix Patent Issue
2/29
Group No 4
MembersGaurav Rawal(17)
Sayli Vaidya(55)
Sagar More(40)
Laxmikant Shimpi(45)
Vaibhav Patil(34)
Neha More(61)
-
8/9/2019 Plavix Patent Issue
3/29
-
8/9/2019 Plavix Patent Issue
4/29
Anti-platelet medication approved by theU.S. Food and Drug Administration toreduce the risk:
Heart attack
Stroke
Vascular death in patients withestablished peripheral arterial disease
When taken daily can help reduce risk ofhaving a future heart attack or stroke
Used by 48 million Americans
-
8/9/2019 Plavix Patent Issue
5/29
Thrombin
ADPADP
TXATXA22
ADP P2Y12
ADPADP
(fibrinogen(fibrinogenreceptor)receptor)
GP IIb/IIIaGP IIb/IIIaActivation
COX-1
clopidogrel bisulfate
aspirin
cAMP
MECHANISM OF ACTION
SCH 530348E 5555
adapted from SchaferAI. Am J Med. 1996;101:199-209.
-
8/9/2019 Plavix Patent Issue
6/29
Plavix is marketed worldwide in nearly 110countries
Sales of US$6.6 billion in 2009 Global sales of $5.9 billion
Second best selling drug in the world
Marketed through a partnership with Bristol-Myers and Sanofi-Aventis
-
8/9/2019 Plavix Patent Issue
7/29
Headquartered in Paris Worlds third largest Pharmaceutical (#1 in
Europe
Sales = 27 billion euros R&D = 4 billion euros
Bristol-Myers Squibb
Bristol-Myers Squibb 2005 revenue was $19.2b.Plavix sales represent about 30% of totalrevenues
U.S. sales of $3.8b in 2005, up 15% from 2004
-
8/9/2019 Plavix Patent Issue
8/29
Largest Canadian-owned pharmaceuticalcompany
Main business is making and selling generic
pharmaceuticals 2005 sales of $740 million (Canadian)
Received FDA approval for generic Plavix in early2006
-
8/9/2019 Plavix Patent Issue
9/29
The issue
APOTEX INC. and
APOTEX CORP.,
Defendants
SANOFI-SYNTHELABO;SANOFI-SYNTHELABO, INC. and
BRISTOL-MYERSSQUIBB SANOFI
PHARMACEUTICALS
HOLDING PARTNERSHIP
Plaintiffs
UNITED STATES
DISTRICTCOURT
SOUTHERNDISTRICTOFNEW YORK
SIDNEY H. STEIN, U.S. District Judge
Vs
-
8/9/2019 Plavix Patent Issue
10/29
History of Plavix Case
The 596 patent
U.S. Patent No. 4,529,596The 265 patent
U.S. Patent No. 4,847,265
Issued in 1985 Expired in 2003 Issued in1989 Expires in2011
Sanofi
-
8/9/2019 Plavix Patent Issue
11/29
The 596 patent
The 596 patent covers a genus of chemical
compounds called thienopyridines, within which
clopidogrel bisulfate falls
The 596 patent discloses only the free base ofclopidogrel, and does not expressly describe the
dextrorotatory and levorotatory enantiomers or
any salt
-
8/9/2019 Plavix Patent Issue
12/29
The 265 patent
July 11, 1989: Sanofi obtained a patent claiming
clopidogrel bisulphate.
Sanofi employees Alain Badorc and Daniel Frhel as
inventors.
Claims: clopidogrel bisulfate by itschemical name in Claim 3:
Hydrogen sulfate of the dextro-rotatory isomer of methyl
alpha-5(4,5,6,7-tetrahydro(3,2-c)thieno pyridyl)(2-
chlorophenyl)-acetate substantially separated from the levo-
rotatory isomer.
Source: (265 patent at col. 12, ll. 37-41.)
-
8/9/2019 Plavix Patent Issue
13/29
November 1997: Plavix approved for sale in US by
FDA.
The 265 patent is exclusively licensed to Bristol-
Myers Squibb Sanofi Pharmaceuticals Holding
Partnership.
-
8/9/2019 Plavix Patent Issue
14/29
Launch of Generic Clopidogrel by
Apotex
-
8/9/2019 Plavix Patent Issue
15/29
ANDA Application
Nov 2001:
Filed ANDA with the FDA
Sought approval from the FDA to manufacture and
sell clopidogrel bisulfate tabletsbefore the expiration of the 265 patent.
-
8/9/2019 Plavix Patent Issue
16/29
Apotex was the first to file an ANDA for clopidogrel
bisulfate
Thus, secured the right to 180days of market
exclusivityprovided by the Hatch-Waxman Act
August 8, 2006: Apotex initiated an at-risk launch of
its generic clopidogrel bisulphate product.
-
8/9/2019 Plavix Patent Issue
17/29
Abbreviated New Drug Applications (ANDAs) to seek
FDA approval of the generic
Paragraph IV
allows 180 day exclusivity to companies that are the"first-to-file"an ANDA against holders of patents for
branded counterparts.
Hatch-Waxman Act
-
8/9/2019 Plavix Patent Issue
18/29
Sanofis Action
-
8/9/2019 Plavix Patent Issue
19/29
SANOFI-AVENTIS
March 21, 2002:
Filed litigation against Apotex and asserted that Apotexs filing
of the ANDA constituted infringement of the 265 patent,
specifically Claim 3.
Claim 3 of the '265 patent : Hydrogen sulphate of
dextro-clopidogrel seperated from levo-clopidogrel.
Infringement of 265 patent
-
8/9/2019 Plavix Patent Issue
20/29
A person infringes a patent by making, using, offeringto sell, selling, or importing into the country any
patented invention, without authority, during the
term of the patent.
What is Infringement??
-
8/9/2019 Plavix Patent Issue
21/29
Preliminary Injunction
Sanofi moved for a preliminary injunction prohibitingApotex from distributing its generic product.
It is a court order prior to a final determination of the
merits of a legal case whereby a party is required to
do, or to refrain from doing, certain acts.
-
8/9/2019 Plavix Patent Issue
22/29
Apotex Defends
1) Apotex alleges that the 265 patent is anticipated
pursuant to 35 U.S.C. 102(b) by an earlier patent
held by Sanofi that covered a genus of chemical
compounds called thienopyridines, within which
clopidogrel bisulfate falls.
-
8/9/2019 Plavix Patent Issue
23/29
Apotexs Defends.
2) Apotex contends pursuant to 35 U.S.C. 103 that the
subject matter claimed in the 265 patent would
have been obvious to a person of ordinary skillin the
art at the time the invention was made.
3) Apotex contends that the patent is invalid under the
judicial doctrine ofobviousness-type double
patenting.
-
8/9/2019 Plavix Patent Issue
24/29
Other Claims Made by Apotex
Finally, Apotex also asserts that the 265 patent isunenforceable on the basis of Sanofis alleged
inequitable conduct before the U.S. Patent and
Trademark Office (PTO).
-
8/9/2019 Plavix Patent Issue
25/29
Result
After trial on the merits, this Court finds that
Apotex have failed to prove by clear andconvincing evidence that the 265 Patent is invalid
or unenforceable on any of the grounds asserted.
Accordingly, Sanofi are entitled to permanentinjunctive reliefand, as shall be determined bythe Court in a future proceeding, damages.
-
8/9/2019 Plavix Patent Issue
26/29
District Court Judgement District court however, believed that "it is not enough for Apotex to
have shown that the [elements] found in Claim 3 of the 265 patentwould have been obvious to try.
District court reasoned that "evidence of the fact that anyproperty
of clopidogrel bisulfate is unexpected as compared to PCR4099 or
anything else in the prior art rebuts the presumption thatclopidogrel bisulfate is obvious in view of its racemate
Two enantiomers as compared with each other and the racemate
could not have been "predict[ed] with a reasonable expectation of
success.
-
8/9/2019 Plavix Patent Issue
27/29
Federal Circuit Decision It agreed with the district court that clopidogrel bisulfate was
nonobvious regardless of whether the compound was "obvious totry
The Federal Circuit also thought that rendering clopidogrel as thebisulfate salt was not obvious because the scientific literature listedmany acids "as candidates for forming salts with basic drug
compounds," and the parties experts agreed that it was"unpredictable" whether any "particular acid-base combination"would yield a pharmaceutically suitable salt
The Federal Circuit denied Apotexs petition for rehearing.
-
8/9/2019 Plavix Patent Issue
28/29
Conclusion
Obviousness to try doesn't mean that experiment and
its results are obvious
-
8/9/2019 Plavix Patent Issue
29/29