Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 1 of 40
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF NEW YORK
`
`
`Civil Action No. 14-CV-2758 (PAC)
`
`Civil Action No. 14-CV-2760 (PAC)
`
`Civil Action No. 14-CV-2759 (PAC)
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`v.
`
`Amneal Pharmaceuticals, LLC,
`
`
`Defendants.
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`v.
`
`Zydus Pharmaceuticals (USA) Inc., and Cadila
`Healthcare Ltd. (dba Zydus Cadila),
`
`
`Defendants.
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`v.
`
`Orient Pharma Co., Ltd.,
`
`
`Defendants.
`
`
`
`
`1
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 2 of 40
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`
`v.
`
`Sawai USA, Inc., and
`Sawai Pharmaceutical Co., Ltd.,
`
`
`Defendants.
`
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`
`v.
`
`Apotex, Inc. and Apotex Corp.,
`
`
`Defendants.
`
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`
`v.
`
`Lupin Ltd. and Lupin Pharmaceuticals, Inc.,
`
`
`Defendants.
`
`
`
`
`
`Civil Action No. 14-CV-5575 (PAC)
`
`Civil Action No. 14-CV-7934 (PAC)
`
`Civil Action No. 15-CV-3935 (PAC)
`
`
`
`2
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 3 of 40
`
`DEFENDANTS PROPOSED FINDINGS AND CONCLUSIONS OF LAW RE:
`
`INVALIDITY OF THE ’336 PATENT IN LIGHT OF
`THE DOCTRINE OF OBVIOUSNESS-TYPE DOUBLE PATENTING
`
`PRESENTED ON BEHALF OF AMNEAL, ORIENT, SAWAI AND ZYDUS
`
`
`
`
`
`3
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`

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`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 4 of 40
`
`TABLE OF CONTENTS
`
`I. 
`
`PROPOSED FINDINGS OF FACT REGARDING THE INVALIDITY OF THE ’336
`PATENT UNDER THE DOCTRINE OF OBVIOUSNESS-TYPE DOUBLE
`PATENTING ...................................................................................................................... 1 
`
`A. 
`
`Technical Background ............................................................................................ 1 
`
`1. 
`
`2. 
`
`3. 
`
`Stereochemistry of a molecule – generally. ................................................ 1 
`
`Statins .......................................................................................................... 2 
`
`Salts ............................................................................................................. 3 
`
`B. 
`
`The ’336 Patent ....................................................................................................... 5 
`
`1. 
`
`2. 
`
`Background ................................................................................................. 5 
`
`The Definition of a Person of Ordinary Skill in the Art ............................. 7 
`
`C. 
`
`The Obviousness-Type Double Patenting References ............................................ 8 
`
`1. 
`
`2. 
`
`Patent No. 5,872,130 ................................................................................... 8 
`
`Patent No. 5,284,953 (“the ’953 Patent”) ................................................. 10 
`
`II. 
`
`PROPOSED CONCLUSIONS OF LAW REGARDING THE INVALIDITY OF
`CLAIMS 1 AND 2 OF THE ‘336 PATENT UNDER THE DOCTRINE OF
`OBVIOUSNESS-TYPE DOUBLE PATENTING OBVIOUSNESS .............................. 15 
`
`A. 
`
`B. 
`
`Obviousness-Type Double Patenting-Legal Standard .......................................... 16 
`
`Claims 1 and 2 of the ’336 Patent Are Invalid for Obviousness Type Double-
`Patenting In View of Claims 1 and 5 of the ’130 Patent ...................................... 18 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`The ’130 Patent and the ’336 Patent Have the Same Assignee and
`Inventors ................................................................................................... 18 
`
`Plaintiffs Have not Rebutted that Claims 1 and 2 of the ’336 Patent is
`Patentably Indistinct from Claims 1 and 5 of the ’130 Patent .................. 18 
`
`The ’130 Patent Is Available as an Obviousness-Type Double Patenting
`Reference .................................................................................................. 21 
`
`a) 
`
`The Safe Harbour Provision of 35 U.S.C. §121 is Inapplicable ... 21 
`
`The ’130 Patent Is Available as an Obviousness Type Double Patenting
`Reference .................................................................................................. 22 
`
`
`
`i
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`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 5 of 40
`
`C. 
`
`Claims 1 and 2 of the ’336 Patent Are Invalid for Obviousness Type Double
`Patenting In View of Claim 1 of the ’953 Patent .................................................. 23 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`The ’336 Patent and the ’953 Patent Have the Same Assignee ................ 23 
`
`The One-Way Test Applies ...................................................................... 23 
`
`The ’336 Patent Is Patentably Indistinct from the ’953 Patent Under the
`One-Way Test ........................................................................................... 25 
`
`Claims 1 and 2 of the ’336 Patent Is Patentably Indistinct from the Claim 1
`of the ’953 Patent Under the Two-Way Test ............................................ 29 
`
`a) 
`
`b) 
`
`It Would Have Been Obvious to Isolate the Single Steroisomer
`from the Mixture of Steroisomers ................................................. 30 
`
`It Would Have Been Obvious to Go from the Calcium Salt to the
`Phenethylamine Salt...................................................................... 34 
`
`ii
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`
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`

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`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 6 of 40
`
`I.
`
`PROPOSED FINDINGS OF FACT REGARDING THE INVALIDITY OF THE
`’336 PATENT UNDER THE DOCTRINE OF OBVIOUSNESS-TYPE DOUBLE
`PATENTING
`
`A.
`
`Technical Background
`
`1.
`
`Stereochemistry of a molecule – generally.
`
`Two or more chemical structures may have the same molecular formula and the same
`
`atom-connectivity, yet they can be distinct chemical compounds if they are arranged differently
`
`in three-dimensional space. Such spatial differences arise when a carbon atom is connected to
`
`four different groups. The carbon that has the four different groups attached is called a chiral
`
`center. These different spatial arrangements of the compounds are called stereoisomers. Two
`
`stereoisomers that are non-superimposable mirror image structures are called enantiomers, or
`
`“optical isomers.” The hands depicted below provide a simple illustration of non-
`
`superimposable mirror image structures:
`
`
`
`
`
`(Anticipated testimony of Anthony Palmieri III, Ph.D.)
`
`Molecules containing multiple chiral centers give rise to stereoisomers that are not mirror
`
`images of one another. Such molecules are called diastereomers. Molecules containing two
`
`chiral centers give rise to four stereoisomers, two pairs of which are optical isomers. Chemists
`
`characterize each enantiomer in a given pair of enantiomers based on the spatial arrangement, or
`
`configuration, of the atoms around the stereogenic atom using the symbols “(S)” and “(R).” The
`
`illustration below shows the difference between diastereomers and enantiomers:
`
`
`
`1
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 7 of 40
`
`
`
` (Anticipated testimony of Anthony Palmieri III, Ph.D.)
`
`2.
`
`Statins
`
`Statins are compounds that lower cholesterol. Statins bind to the enzyme involved in the
`
`cholesterol biosynthesis, called HMG-CoA reductase. By binding to HMG-CoA reductase,
`
`statins stop the production of mevalonic acid, which is needed for cholesterol production. The
`
`structural formula of mevalonic acid is as follows:
`
`A common feature of statins is a mevalonic acid side chain, bonded to a statin core as
`
`
`
`illustrated below:
`
`OH
`
`OH
`
`O
`
`Statin Core
`
`OH
`
`
`
`Like other statins, the pitavastatin molecule contains the mevalonic side chain.
`
`
`
`2
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 8 of 40
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`In pitavastatin calcium, the mevalonic side chain is ionically bound to calcium and
`
`therefore forms a calcium salt. (Anticipated testimony of Anthony Palmieri III, Ph.D.)
`
`
`
`3.
`
`Salts
`
`A salt consists of a positively charged cation and a negatively charged anion. Statins, the
`
`type of compound at issue in this litigation, can form salts, as illustrated below with a calcium
`
`salt:
`
`
`
`(Anticipated testimony of Anthony Palmieri III, Ph.D.)
`
`Frequently, compounds used as active pharmaceutical ingredients are present in their salt
`
`form, because salts generally have better handling and stability and higher melting points
`
`compared to free acids or bases. Pharmaceutical formulators select a specific salt through
`
`routine evaluations that ordinarily involve salt stability, hygroscopicity, and flowability of the
`
`resulting bulk drug. (Anticipated testimony of Anthony Palmieri III, Ph.D.; DTX-1245, Berge et
`
`al., “Pharmaceutical Salts,” J. of Pharmaceutical Sciences, (1977), 1-19. (“Berge”) at p.1.)
`
`
`
`3
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 9 of 40
`
`The compounds of claim 1 of the ’336 patent (DTX-0032, Col. 32:22-40) are negatively
`
`charged (anionic), and thus only positively charged cations are capable of forming salts with
`
`them. Sodium, potassium, and calcium are the most frequently used, cation salts for
`
`pharmaceutical ingredients. The relative frequency of use for sodium, potassium, and calcium
`
`are 61.97%, 10.82%, and 10.49%, respectively. The frequency of use of the cation-salts of drugs
`
`approved by FDA has not substantially changed over the four decades since the publicaction of
`
`Berge. (Anticipated testimony of Anthony Palmieri III, Ph.D.; DTX-1245, Berge at p.1.)
`
`The prior art statin patents, including U.S. Patent Nos. 4,647,576 (DTX-1257), 4,739,073
`
`(DTX 1258), 4,681,893 (DTX-1255), U.S. Patent No. 4,613,610 (DTX-1259) and U.S. Patent
`
`No. 4,761,419 (DTX-1247) generally disclosed pharmaceutically acceptable metal and amine
`
`cations. Calcium salts in particular were disclosed as a pharmaceutically acceptable salt option
`
`for compounds meant to inhibit the biosynthesis of cholesterol. U.S. Patent No. 4,537,859
`
`(DTX-1256, “the ’859 patent”) discloses compounds that “have the ability to inhibit the
`
`biosynthesis of cholesterol and are therefore of value in the therapy and/or prophylaxis of
`
`hyperlipaemia and arteriosclerosis” (abstract). The ’859 patent further discloses that calcium
`
`salts were among the three “most preferred” metal salts in this invention. DTX-1256 at col.
`
`11:67-col. 12:5. U.S. Patent No. 4,647,576 (DTX-1257) discloses that calcium salts are among
`
`the pharmaceutically acceptable metal cations useful for compounds of the inventions with
`
`hypolipidemic and hypocholesterolemic properties. Finally, U.S. Patent No. 4,761,419 (DTX-
`
`0408) discloses salts for all of the examples of synthesized open chain compounds. The ’419
`
`patent states “‘pharmaceutically acceptable metal cation’ contemplates positively charged metal
`
`ions derived from sodium, potassium, calcium, magnesium, aluminum, iron, zinc and the like.”
`
`DTX-0408 at col. 9:65-68.
`
`
`
`4
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`

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`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 10 of 40
`
`B.
`
`The ’336 Patent
`
`1.
`
`Background
`
`U.S. Patent No. 5,856,336 (“the ’336 patent”), entitled “Quinoline Type
`
`Mevalonolactones,” is assigned to Nissan Chemical Industries, Ltd. (“Nissan”). The ’336 patent
`
`issued on January 5, 1999. It expires on December 25, 2020. The ’336 patent’s expiration date
`
`of December 25, 2020 is due to an award of 1,823 days of Patent Term Extension1 by the
`
`USPTO. In the absence of the Patent Term Extension, the ’336 Patent would have expired on
`
`December 29, 2015 (due to the filing of a terminal disclaimer). (DTX-1238, ’336 patent.)
`
`[A]
`
`
`
`
`
`The two claims of the ‘336 patent read as follows:
`
`1.
`
`A compound of the formula,
`
`
`
`
`
`
`
`
`
`
`
`
`
`Z=-CH(OH)-CH2-CH(OH)-CH2-COO·1/2Ca.
`
`2.
`A method for reducing hyperlipidemia, hyperlipoproteinemia or
`atherosclerosis, which comprises administering an effective amount of the
`compound of formula A as defined in claim 1.
`
`
`1 Patent term extension is codified at 35 U.S.C. §156 and enables the owners of certain patents to
`restore to the terms of those patents some of the time lost while awaiting premarket government
`approval from a regulatory agency.
`
`
`
`5
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 11 of 40
`
`Compounds claimed in claim 1 can also be represented by the following structural
`
`formula:
`
`(DTX-1238, ’336 patent.)
`
`The structural formula depicted above has two chiral centers. The two chiral centers are
`
`indicated by asterisks below:
`
`
`
`F
`
`N
`
`OH
`
`OH
`
`O
`
`*
`
`*
`
`O . 1/2 Ca
`
`
`
`The parties agree that because there are two chiral centers, claim 1 of the ’336 patent
`
`includes four stereoisomers of pitavastatin in a calcium salt form as well as all mixtures of these
`
`isomers. D.I. 97 at p. 2. These four stereoisomers are depicted as below:
`
`
`
`6
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 12 of 40
`
`OH
`
`OH
`
`O
`
`*
`
`*
`
`O . 1/2 Ca
`
`OH
`
`OH
`
`O
`
`*
`
`*
`
`O . 1/2 Ca
`
`F
`
`N
`
`F
`
`N
`
`F
`
`N
`
`F
`
`N
`
`OH
`
`OH
`
`O
`
`*
`
`*
`
`O . 1/2 Ca
`
`OH
`
`OH
`
`O
`
`*
`
`*
`
`O . 1/2 Ca
`
`
`
`(Anticipated testimony of Anthony Palmieri III, Ph.D.; DTX-0647, D.I. 97, Opinion and Order
`
`Regarding Claim Construction at 2-3.)
`
`According to stereochemistry convention, a visual representation of a chemical bond
`
`facing towards the observer is indicated by the
`
` symbol. (See, e.g., DTX-1248, Ager D.,
`
`HANDBOOK OF CHIRAL CHEMICALS (1999) at p. 35 (depicting stereochemical formulas for
`
`simvastatin and pravastatin).) A visual representation of a chemical bond facing away from the
`
`observer is indicated by the
`
` symbol. The active pharmaceutical ingredient known as
`
`pitavastatin calcium is the structural formula depicted in the top left. (Anticipated testimony of
`
`Anthony Palmieri III, Ph.D.; DTX-1248 at p. 35.)
`
`2.
`
`The Definition of a Person of Ordinary Skill in the Art
`
`With respect to the ’336 patent, a person of ordinary skill in the art would include
`
`someone with a Ph.D. in a relevant field (such as pharmaceutical chemistry, pharmaceutical
`
`formulation, or medicinal chemistry), a Pharm.D., or an M.D. preferably with some postdoctoral,
`
`
`
`7
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 13 of 40
`
`clinical, or industrial experience in those fields. Such a person would have understood the prior
`
`art references and would have the ability to draw inferences from them. (Anticipated testimony
`
`of Anthony Palmieri III, Ph.D.)
`
`C.
`
`The Obviousness-Type Double Patenting References
`
`1.
`
`Patent No. 5,872,130
`
`The ’130 Patent was filed on December 19, 1990 and issued on February 16, 1999 and is
`
`entitled “Quinoline Type Mevalonoactones.” The ’130 Patent and the ’336 Patent have common
`
`inventors, Yoshihiro Fujikawa, Mikio Suzuki, Hiroshi Iwasaki, Mitsuaki Sakashita, and Masaki
`
`Kitahara, and a common assignee, Nissan Chemical Industries, Ltd. The ’130 patent expired on
`
`February 16, 2016. The core structures of the compounds in claim 1 of the ’130 patent and claim
`
`1 of the ’336 patent are the same. (Compare DTX-1238, ’336 patent, with DTX-1242, ’130
`
`patent). Both of these patents also claim a method of reducing hyperlipidemia,
`
`hyperlipoproteinemia or atherosclerosis. Id. A side-by side comparison of claims 1 and 2 of the
`
`’336 patent with claim 1 and 5 of the ’130 patent is shown below:
`
`The ’336 Patent
`
`
`1. A compound of the formula,
`
`
`The ’130 Patent
`
`A compound of the formula:
`
`
`
`
`1.
`
`
`
`
`
`
`
`8
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 14 of 40
`
`
`
`2. A method for reducing
`hyperlipidemia, hyperlipoproteinemia or
`atherosclerosis, which comprises
`administering an effective amount of the
`compound of formula A as defined in
`claim 1.
`
`5. A method for reducing
`hyperlipidemia, hyperlipoproteinemia or
`atherosclerosis, which comprises
`administering an effective amount of the
`compound of formula A as defined in claim
`1.
`
`(Anticipated testimony of Anthony Palmieri III, Ph.D.; DTX-1242, ’130 patent.)
`
`The “∆” group in the claim of the ’336 patent is the same as alternatively designated “c-
`
`Pr” (cyclopropyl) in the claim of the ’130 patent. (Compare DTX-1238, ’336 patent, with DTX-
`
`1242, ’130 patent.) Indeed, the only difference between claim 1 of the ’130 patent and claim 1
`
`of the ’336 patent is that the ’336 patent claims the calcium salt while claim 1 of the ’130 patent
`
`claims the free acid, sodium salt, C1-C3 esters, and lactone forms. But it was well known in the
`
`art that sodium and calcium salts are mutually interchangeable, and indeed both sodium and
`
`calcium are among the most frequently used pharmaceutically acceptable salts. (Anticipated
`
`testimony of Anthony Palmieri III, Ph.D.)
`
`In fact, the testing in the specification of the ’336 patent is conducted with sodium salts
`
`and ethyl esters, despite the fact that the ’336 patent claims only the calcium salts. This testing
`
`indicates the inventors’ belief that the data obtained with the sodium salts and ethyl esters were
`
`
`
`9
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 15 of 40
`
`applicable to (and could support a claim to) calcium salts. (Anticipated testimony of Anthony
`
`Palmieri III, Ph.D.; DTX-1238, ’336 patent at col. 12-15 (reflected in Tests A-C, and toxicology
`
`testing in Test D).)
`
`Indeed preparing the pitavastatin compound as a calcium salt as opposed to a sodium salt
`
`would have been a matter of routine experimentation for a person of skill, and the person of skill
`
`would have had a reasonable expectation of success in creating the calcium salt as opposed to the
`
`sodium salt. Thus, the calcium salts of the compounds claimed in claim 1 of the ’336 patent are
`
`patentably indistinct from the sodium salts of the compounds in claim 1 of the ’130 patent.
`
`Plaintiffs do not dispute this fact. (Anticipated testimony of Anthony Palmieri III, Ph.D.)
`
`Similarly, the method of claim 2 of the ’336 patent is virtually identical to dependent
`
`claim 5 of the ’130 patent. (Compare DTX-1238, ’336 patent at col. 32 ll. 37-41, with DTX-
`
`1242, ’130 patent, col. 40 ll. 26-31.) Both claims are directed to “reducing hyperlipidemia,
`
`hyperlipoproteinemia or atherosclerosis.” The specification of the ’336 patent explains the
`
`pharmaceutical uses for the claimed compounds as “anti-hyperlipidemic, hypolipoproteinemic
`
`and anti-atherosclerotic agents.” (DTX-1238, ’336 patent, col. 1 ll. 9-10.) The specification of
`
`the ’130 patent similarly explains the pharmaceutical uses for the claimed compounds as “anti-
`
`hyperlipidemic, hypolipoproteinemic and anti-atherosclerotic agents.” (DTX-1242, ’130 patent,
`
`col. 1 ll. 8-9.) Thus, a person of ordinary skill in the art would also find the dependent claim 2 of
`
`the ’336 patently indistinguishable over dependent claim 5 of the ’130 patent. Plaintiffs also do
`
`not dispute this fact. (Anticipated testimony of Anthony Palmieri III, Ph.D.)
`
`2.
`
`Patent No. 5,284,953 (“the ’953 Patent”)
`
`The ’953 Patent was filed on June 23, 1992 and issued on February 8, 1994 and is
`
`entitled “Diastereomer Salt of Optically Active Quinolinemevalonic acid.” The ‘953 Patent is
`
`
`
`10
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 16 of 40
`
`assigned to Nissan Chemical Industries, Ltd., the same assignee as the ’336 Patent. The ’953
`
`patent expired on June 23, 2012. (DTX-1240, ’953 patent.)
`
`During prosecution of the ’953 patent, the USPTO was not made aware of co-pending
`
`claims 1 and 2 of the ’336 patent application and as such did not address the issue of double
`
`patenting. The USPTO allowed the sole claim of the ’953 patent to issue, after the applicants
`
`distinguished the prior art of record by arguing that the prior art was “concerned with structurally
`
`completely different and nonrelated compounds” from pitavastatin. (DTX-1262, ’953 patent
`
`prosecution history at Request for Reconsideration.)
`
`Claim 1 of the ’953 patent reads as follows:
`
`
`
`The compound of claim 1 of the ’953 patent is the phenethylamine salt of one of the four
`
`pitavastatin stereoisomers recited in claim 1 of the ’336 patent. That is, claim 1 of the ’953
`
`patent sets forth the phenethylamine salt of one species found within the genus of claim 1 of the
`
`’336 patent. In particular, it is the phenethylamine salt of the isomer that is the active
`
`pharmaceutical ingredient, pitavastatin. (Anticipated testimony of Anthony Palmieri III, Ph.D.;
`
`DTX-1238, ’336 patent; DTX-1240, ’953 patent.)
`
`
`
`11
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 17 of 40
`
`There are thus only two differences between claim 1 of the ’953 patent and claim 1 of the
`
`’336 patent. First, claim 1 of the ’953 patent claims the phenethylamine salt while claim 1 of the
`
`’336 patent claims the calcium salt. Second, claim 1 of the ’953 patent is directed to a single
`
`stereoisomer whereas the claim 1 of the ’336 patent is directed to all four possible stereoisomers
`
`and mixtures thereof. These differences do not make claim 1 of the ’336 patent patentably
`
`distinct over claim 1 of the ’953 patent. (Anticipated testimony of Anthony Palmieri III, Ph.D.)
`
`First, calcium salts of pitavastatin are obvious variants of the phenethylamine salt. The
`
`portion of the ’953 specification describing the utility of a phenethylamine salt indicates that it is
`
`merely an “important intermediate” compound which is unsuitable for a tablet or other
`
`pharmaceutical formulation. (DTX-1240, ’953 patent, col. 1 ll. 5-10.) A person of ordinary skill
`
`in the art would recognize that phenethylamine is a classic chiral resolving agent, frequently used
`
`for chiral separation of the diastereomeric mixtures of acids. The presence of the chiral amine
`
`indicates to one of ordinary skill that the claimed compound was initially part of a stereoisomeric
`
`mixture that was then separated out using phenethylamine. Thus, once resolved, a person of
`
`ordinary skill in the art would recognize that there was a need to substitute phenethylamine with
`
`one of the known pharmaceutically acceptable salts, such as those listed in DTX 1245, Berge.
`
`At the time of the alleged invention of the ’336 patent, it was common knowledge that sodium,
`
`potassium and calcium were the most widely used cation salts. DTX 1245, Berge. This remains
`
`true today as well. Organic amines could form basic salts, but they have been used less
`
`frequently.
`
`In addition, Example 3 of the ’953 patent teaches the process for making a calcium salt of
`
`pitavastatin, as follows:
`
`
`
`12
`
`

`

`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 18 of 40
`
`
`
`(DTX-1240, ’953 patent, col. 12 ll. 36-53.)
`
`The example discloses that a pitavastatin calcium salt was obtained as 9.0 g of white
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`precipitate. The fact that the phenethylamine salt in Example 3 of the ’953 patent was used to
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`synthesize a pitavastatin calcium salt would further encourage a person of ordinary skill in the art
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`to make a calcium salt. (Anticipated testimony of Anthony Palmieri III, Ph.D.) Indeed, calcium
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`salts had already been disclosed as a metal cation option with statin compounds meant to inhibit
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`the biosynthesis of cholesterol. DTX-1256, ’859 patent at col. 11:67-col. 12:5; DTX0-622, the
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`’576 patent at col. 17:50-53. A person of ordinary skill in the art would have considered a
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`calcium salt among the first “go to” salts for basic salt formation.
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`Second, the single stereoisomer of pitavastatin in claim 1 of the ’953 patent is one of the
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`four stereoisomers of encompassed within claim 1 of the ’336 patent. Reviewing claim 1 of the
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`’953 patent, a person of ordinary skill in the art would have known that pitavastatin has two
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`chiral centers, meaning that there are a total of four stereoisomers. Although only one
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`stereoisomer of the phenethylamine salt is claimed in claim 1 of the ’953 patent phenethylamine
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`is a chiral organic amine it would have been understood by one of skill that this salt was used for
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`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 19 of 40
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`chiral separation of the racemic mixture consisting of all four stereoisomers. In other words, the
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`presence of the chiral amine indicates that the claimed compound was initially part of an
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`isomeric mixture that was then separated out using phenethylamine. Thus, there is nothing
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`patentably distinct about the ’336 patent claiming all four stereoisomers and mixtures thereof,
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`over the single stereoisomer claimed by claim 1 of the ’953 patent. (Anticipated testimony of
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`Anthony Palmieri III, Ph.D.)
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`Moreover, salt formation does not depend on whether a single isomer or a mixture of
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`isomers is used. A person of ordinary skill in the art would also have understood that the
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`procedure disclosed in the ’953 patent would apply with equal measure to the pitavastatin
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`isomeric mixture and that following the procedure of the ’953 patent with the pitavastatin
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`isomeric mixture would produce calcium salts of the isomers in the pitavastatin isomeric mixture
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`claimed in claim 1 of the ’336 patent. Therefore, the calcium salts of the pitavastatin
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`diastereomeric mixture of the ’336 patent is merely an obvious modification of the chiral
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`pitavastatin phenylethylamine salt disclosed by claim 1 of the ’953 patent. (Anticipated
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`testimony of Anthony Palmieri III, Ph.D.).
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`A person of ordinary skill in the art equipped with the disclosure of the ’953 patent would
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`have had a reasonable expectation of success in making calcium salts of the pitavastatin
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`diastereomeric mixture because he or she could simply repeat Example 3 of the ’953 patent with
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`the pitavastatin racemic mixture as a starting material. Thus, a person of ordinary skill in the art
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`would find calcium salts of the compounds claimed in claim 1 of the ’336 patentably indistinct
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`over the phenethylamine salt of pitavastatin claimed in the ’953 patent. (Anticipated testimony
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`of Anthony Palmieri III, Ph.D.)
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`
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`14
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`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 20 of 40
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`Claim 2 of the ’336 patent is a method claim dependent on claim 1. This claim is
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`directed to a method of treatment of several cholesterol-related conditions, such as
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`“hyperlipidemia, hyperlipoproteinemia or atherosclerosis” using calcium salts of pitavastatin.
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`The ’953 patent does not contain any method claims, but the portion of the specification
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`disclosing the utility of the phenethylamine salt of pitavastatin states that the intermediate is to
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`be used for making compounds useful for “hyperlipidemia, atherosclerosis etc.” For this reason,
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`as well as for all those reasons set forth above regarding the compounds of ’336 patent claim 1,
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`the person of ordinary skill in the art would have found claim 2 of the ’336 patent to be
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`patentably indistinct over claim 1 of the ’953 patent. (Anticipated testimony of Anthony
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`Palmieri III, Ph.D.; DTX-1238, ’336 patent; DTX-1240, ’953 patent at col 1 ll. 5-10.)
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`Further, a person of ordinary skill in the art would have modified the racemate and
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`mixtures of enantiomers of the ’336 Patent claim 1 to yield the single steroisomer of pitavastatin
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`of claim 1 of the ’953 Patent. As of 1987 was common knowledge in the pharmaceutical industry
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`and in academia that individual enantiomers frequently possessed higher potency than their
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`racemic mixture, and others in the art were making single enantiomers for statins. See e.g.,
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`DTX-514, DTX-1290. Indeed, a person of ordinary skill in the art would have been very
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`interested in developing single enantiomer drugs as opposed to racemic mixtures based on what
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`was already known in the art about statins specifically. The diastereomer compound of claim 1 of
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`the ‘993 Patent is readily obtained by resolving the compounds of claim 1 of the ‘336 Patent with
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`α-methylbenzylamine. Therefore, a person of ordinary skill in the art would have tried to use α-
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`methylbenzylamine to resolve the pitavastatin diastereomeric mixture and would have had a
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`reasonable expectation of success that the mixture could eventually be resolved.
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`PROPOSED CONCLUSIONS OF LAW REGARDING THE INVALIDITY OF
`CLAIMS 1 AND 2 OF THE ‘336 PATENT UNDER THE DOCTRINE OF
`
`15
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`II.
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`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 21 of 40
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`OBVIOUSNESS-TYPE DOUBLE PATENTING OBVIOUSNESS
`
`A.
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`Obviousness-Type Double Patenting-Legal Standard
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`Obviousness-type double patenting is a judicially created doctrine that “prohibit[s] a
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`party from obtaining an extension of the right to exclude through claims in a later patent that are
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`not patentably distinct from claims in a commonly owned earlier patent.” Eli Lilly & Co. v. Barr
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`Labs., Inc., 251 F.3d 955, 967 (Fed. Cir. 2001); see also In re Basell Poliolefine Italia S.P.A.,
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`547 F.3d 1371, 1375 (Fed. Cir. 2008); Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d 955, 967
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`(Fed. Cir. 2001). “[T]he primary ill avoided by enforcement of the double patenting doctrine is
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`restriction on the public’s freedom to use the invention claimed in a patent and all obvious
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`modifications of it after that patent expired.” Gilead Scis., Inc. v. Natco Pharma Ltd., 753 F.3d
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`1208, 1215 (Fed. Cir. 2014) (emphasis in original). In other words, if a company owns patent A
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`(expires first) and patent B (expires second), and the later to expire patent B is patentably
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`indistinct from the earlier to expire patent A, the doctrine of obviousness-type double patenting
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`holds that patent B should expire on the same date that patent A expires. Id.
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`There are two reasons why obviousness-type double patenting exists. The first is “to
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`prevent unjustified timewise extension of the right to exclude granted by a patent no matter how
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`the extension is brought about.” In re Van Ornum, 686 F.2d 937, 943-44 (CCPA 1982). The
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`second is “to prevent multiple infringement suits by different assignees asserting essentially the
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`same patented invention.” In re Hubbell, 709 F.3d 1140, 1145 (Fed. Cir. 2013) (citing In re
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`Fallaux, 564 F.3d 1313, 1319 (Fed. Cir. 2009)) (recognizing that “harassment by multiple
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`assignees” provides “a second justification for obviousness-type double patenting”).
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`In order for the doctrine of obviousness-type double patenting to apply, the two patents in
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`question (the patent at issue and a reference patent) must have at least one common inventor,
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`common applicant, and/or be either commonly owned/assigned or non-commonly
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`
`
`16
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`Case 1:14-cv-02758-PAC Document 106 Filed 12/16/16 Page 22 of 40
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`assigned/owned but subject to a joint research agreement. In re Hubbell, 709 F.3d 1140, 1144
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`(Fed. Cir. 2013), citing Manual of Patent Examining Procedure §804(I)(A).
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`Once a reference patent having an earlier expiration date is found, the obviousness-type
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`double patenting analysis involves two steps. “First, ‘a court construes the claim[s] in the earlier
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`patent and the claim[s] in the later patent and determines the differences.’ ” Pfizer, Inc. v. Teva
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`Pharm., 518 F.3d 1353, 1363 (Fed. Cir. 2008) (quoting Eli Lilly, 251 F.3d at 968). “Second, it
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`determines whether those differences render the claims patentably distinct.” Id. “A later patent
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`claim is not patentably distinct from an earlier patent claim if the later claim is obvious over, or
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`anticipated by, the earlier claim.” Eli Lilly, 251 F.3d at 968. Double patenting is a question of
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`law. Pfizer, Inc., 518 F.3d at 1363.
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`When determining whether the claims are patentably distinct, it is permissible in some
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`circumstances to consult the specification of the reference patent. For example, a reference
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`patent specification’s “disclosure of an intended use for [a] previously claimed … composition”
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`may be used “to reject a later claim directed to that use of the same compound.” Eli Lilly & Co.
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`v. Teva Parenteral Medicines, Inc., 689 F.3d 1368, 1379 (Fed. Cir. 2012); see also Geneva
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`Pharmaceuticals, Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373, 1385-86 (Fed. Cir. 2003) (“Our
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`predecessor court recognized that a claim to a method of using a composition is not patentably
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`dist