Plavix Patent Issue

8/9/2019 Plavix Patent Issue

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Plavix Patent Issue


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Group No 4

MembersGaurav Rawal(17)

Sayli Vaidya(55)

Sagar More(40)

Laxmikant Shimpi(45)

Vaibhav Patil(34)

Neha More(61)


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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


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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.


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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


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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


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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


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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


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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


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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


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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.)


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November 1997: Plavix approved for sale in US by

FDA.

The 265 patent is exclusively licensed to Bristol-

Myers Squibb Sanofi Pharmaceuticals Holding

Partnership.


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Launch of Generic Clopidogrel by

Apotex


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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.


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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.


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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


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Sanofis Action


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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


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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??


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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.


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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.


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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.


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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).


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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.


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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.


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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.


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Conclusion

Obviousness to try doesn't mean that experiment and

its results are obvious


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Documents

Plavix Patent Issue