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`Exhibit B
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`Exhibit B
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
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`UNITED THERAPEUTICS
`CORPORATION,
`
`
`Plaintiff and Counterclaim-
`Defendant,
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`
`v.
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`SANDOZ INC.,
`
`
`Defendant and Counterclaim-
`Plaintiff.
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`DECLARATION OF CLAYTON H. HEATHCOCK, Ph.D.
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`)
`)
`)
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`))
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`))
`
`
`) Civil Action No.
`)
` 3:14-cv-5499 (PGD)(LHG)
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`)
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`)
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`I, Clayton H. Heathcock, hereby declare as follows:
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`1.
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`I have been retained by Sandoz Inc. as an expert in the above captioned
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`matter. I submit this declaration in support of Sandoz’s Opening Claim
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`Construction Brief.
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`2.
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`I have a Ph.D. in Chemistry from the University of Colorado, which I
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`obtained in 1963. I held various professorial ranks in the Department of Chemistry
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`at the University of California at Berkeley from 1964 through 2004. I was Dean of
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`the College of Chemistry from 1999 through 2005 and Chief Scientist of QB3
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`Berkeley, a branch of the California Institute for Quantitative Bioscience from
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`2005 to 2008. I am currently Emeritus Professor.
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`1
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`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 3 of 52 PageID: 336
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`3.
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`For the more than 50 years, I conducted research in organic chemistry. In
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`particular, my work focused on the chemical synthesis of complex, polycyclic
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`natural products.
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`4.
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`I have published over 280 research papers and book chapters. I have
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`served as Chair of the Division of Organic Chemistry of the American Chemical
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`Society, Chair of the National Institutes of Health Medicinal Chemistry Study
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`Section, Chair of the Gordon Research Conference on Stereochemistry, Chair of
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`the Chemistry Division of the American Association for the Advancement of
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`Science, and Editor-in-Chief of the Journal of Organic Chemistry and of the
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`annual publication Organic Syntheses. I have received numerous awards and
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`honors for my work in the field of chemistry. Noteworthy examples include the
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`Ernest Guenther Award (ACS) (1986); ACS Award for Creative Work in Organic
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`Synthesis (1990); A.C. Cope Scholar (1990); Prelog Medal, ETH (1991);
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`American Academy of Art and Sciences (1991); National Academy of Sciences
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`(1995); Centenary Medal, Royal Society of Chemistry (1996); H.C. Brown Award
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`(ACS) (2002); Paul Gassman Award for Distinguished Service (ACS) (2004).
`
`Additional information regarding my background, experience, and credentials is
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`set forth in my curriculum vitae, which is attached as Exhibit 1 to this declaration.
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`2
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`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 4 of 52 PageID: 337
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`I.
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`THE ’393 PATENT
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`5.
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`U.S. Patent No. 8,497,393 (“the ’393 patent”) is entitled “Process to
`
`prepare treprostinil, the active ingredient in Remodulin®.”1 I understand that the
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`’393 patent issued on July 30, 2013 and claims priority to a provisional application
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`filed on December 17, 2007.
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`6.
`
`The ’393 patent has a total of 22 claims. I understand that UTC has
`
`asserted six claims in the present litigation: claims 1, 2, 4, 8, 9 and 16.
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`7.
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`Claim 1 recites as follows:
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`1 A copy of the ’393 patent is attached as Exhibit 2 to my Declaration.
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`3
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`8.
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`Claim 1 is drawn to a product comprising a compound of a genus that
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`includes the treprostinil compound, or a pharmaceutically acceptable salt thereof.
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`9.
`
`Claim 9 is identical to claim 1 except that it is drawn to a product
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`comprising the specific treprostinil compound, a species of the genus of claim 1,
`
`made by the same process.
`
`10. Each of the independent claims 1 and 9 includes limitations that the
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`claimed compound is made by a process comprising three specified steps: (a)
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`alkylating a benzindene triol to form a benzindene nitrile intermediate; (b)
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`hydrolyzing the benzindene nitrile with a base to form treprostinil acid; and (c)
`
`contacting the treprostinil acid with a base to form treprostinil salt.
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`4
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`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 6 of 52 PageID: 339
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`11. Claims 2, 4, and 8 each depend from claim 1. Claim 2 adds the limitation
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`that the purity of treprostinil in the final product be at least 99.5%. Claim 4 adds
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`the limitation that the base in step (b) must be KOH or NaOH. Claim 8 adds the
`
`limitation that the product of step (a) is not purified.
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`12. Claim 16 depends from claim 9 and adds the limitation that the process
`
`does not include purifying the product of step (a).
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`13. The specification of the ’393 patent teaches a method of preparing a
`
`genus of compounds that includes treprostinil and its salts.
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`14. This method involves starting with an intermediate called a “benzindene
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`triol” and performing an alkylation step to convert the “benzindene triol” to a
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`nitrile intermediate (step (a)). The next step involves hydrolyzing the nitrile
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`intermediate to produce treprostinil acid (step (b)). Next, treprostinil acid is
`
`converted into treprostinil diethanolamine salt (step (c)). Finally, treprostinil
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`diethanolamine salt may be converted back into treprostinil acid (optional step (d)).
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`15. Embodiments of steps (a) through (d) are described in the examples of
`
`the ’393 patent.
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`16. The first five examples illustrate the conversion of a particular
`
`benzindene triol intermediate into treprostinil acid by way of treprostinil
`
`diethanolamine salt. (Ex. 2, Col. 9:25-17:26).
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`5
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`17. Example 6 provides a “working example of the Process according to the
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`present invention.” It combines all the required steps and many others into a
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`commercial-scale embodiment of the process described in the ’393 patent
`
`specification.
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`18. The process disclosed in Examples 1-5 is set forth below with graphics
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`taken from the patent:
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`
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`6
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`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 8 of 52 PageID: 341
`Case 3:l4—cv—05499—PGS—LHG Document 41-3 Filed 07/07/15 Page 8 of 52 Page|D: 341
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`
`Emunplc 3
`
`Conversion ofTrcprost1'JJJ'J to Tmpmstiuil
`Diethannlanline Salt (1:1)
`
`
`
`,i'
`H— N1.
`
`
`[I] EJDH, Etflfin:
`[TI]: H::'pfs.r.: Slunjr
`
`‘K,
`OH
`
`
`
`OH
`
`Exsm1p1c 4
`
`.‘.::I:r: Filu n'~' of Ta:
`
`:-.'-sI[I:i| !'JEc1|'.;nn[nIni:u~ !‘~.~nEr r1:1fi
`
`Nu:u.c
`
`Bal:5I1\'-::u.
`
`.='|.::u:rJ1'.‘.
`
`Ratio
`
`1':r:_:m'Jsti1Li|
`D:v:lEIrLI;o|an1:I;~: Salt
`I-In:_:«L'-_n:
`’J':r:;mstiui|
`DIEeI_FmI'_-:.|amEI:~e S.:[t
`%[L"_::-Ir-.n::
`
`1
`
`—
`2
`
`—
`
`31-53 g
`
`315 L
`3071 g
`
`sum L
`
`1
`
`E:
`1
`
`E2
`
`
`
`7
`
`
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`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 9 of 52 PageID: 342
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`(Ex. 2, Col. 9:25-14:65).
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`
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`19. The ’393 specification describes the benefits of the disclosed process as
`
`follows:
`
`The quality of treprostinil produced according to this invention
`is excellent. The purification of benzindene nitrile by column
`chromatography is eliminated. The impurities carried over from
`intermediate steps (i.e. alkylation of triol and hydrolysis of
`benzindene nitrile) are removed during the carbon treatment
`and the salt formation step. Additional advantages of this
`process are: (a) crude treprostinil salts can be stored as raw
`material at ambient temperature and can be converted to
`treprostinil by simple acidification with diluted hydrochloric
`
`8
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`
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`acid, and (b) the treprostinil salts can be synthesized from the
`solution of treprostinil without isolation. This process provides
`better quality of final product as well as saves significant
`amount of solvents and manpower in purification of
`intermediates.
`
`(Ex. 2, Col. 17:27-40).
`
`20.
`
`It is my understanding that the claims at issue in this case are “product by
`
`process” claims, which I am informed means that they cover the recited product
`
`made by a process that includes the recited process steps.
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`II. LEGAL STANDARDS
`21.
`
`I understand that claim construction is the process by which the Court
`
`determines the meaning and scope of the terms in a claim.
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`22.
`
`I understand that, in general, claims are construed to have their plain and
`
`ordinary meaning as understood by a person of ordinary skill in the art as of the
`
`filing date of the patent. It is also my understanding that claim terms should be
`
`construed in a manner that is consistent with the language of the claims and the
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`disclosure in the specification.
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`23. For the purposes of my analysis, I assumed that the filing date of the ’393
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`patent was December 17, 2007.
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`24.
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`I understand that the prosecution history of a patent is the record of the
`
`communications between the Applicant and the Patent Office that led to the
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`issuance of the patent. It is also my understanding that claim terms should
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`9
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`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 11 of 52 PageID: 344
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`generally be construed in a manner that is consistent with the statements made to
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`the Patent Office during prosecution.
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`25.
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`It is my understanding that inventors may define terms in the
`
`specification in a way that is not consistent with the plain and ordinary meaning of
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`the term; in other words, is entitled to be his own lexicographer. It is my
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`understanding that in such cases, the claim term should be construed to have the
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`definition set forth in the specification.
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`26.
`
`In my analysis, I relied upon the standards as set forth above in addition
`
`to my 50 years of experience in the field of organic chemistry.
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`27.
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`I have reviewed the claims, specification, and prosecution history of the
`
`’393 patent. I have also reviewed the parties’ Joint Claim Construction and
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`Prehearing Statement.
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`III. LEVEL OF ORDINARY SKILL
`28. A person of ordinary skill in the art would have a Ph.D. in organic or
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`medicinal chemistry and at least a few years of experience in medicinal chemistry,
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`including in the development of potential drug candidates. A person of ordinary
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`skill in the art would also include a person who has a Bachelor’s or Master’s
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`degree in organic chemistry or medicinal chemistry if such a person had more
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`years of experience in medicinal chemistry and the development of potential drug
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`candidates.
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`10
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`IV. DISCUSSION
`29. As I explained above, the ’393 patent teaches a method of preparing a
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`genus of compounds including treprostinil and its salts. The claims of the ’393
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`patent are drawn to products that contain, for example, treprostinil and its salts
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`made through a process that includes three steps (a)-(c) followed by an optional
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`fourth step. In this section, I will explain the chemistry underlying each of these
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`steps in greater detail.
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`A.
`Step (a): The Alkylation Step
`30. Step (a) is the alkylation step. Example 1 of the ’393 patent describes an
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`alkylation reaction, as shown below:
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`11
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`31. As is shown above, in Example 1, alkylation, or an alkylation reaction or
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`alkylation step, refers to the addition of an “alkyl” group. An alkyl group is
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`hydrocarbon consisting of the general formula CnH2n +1, and is derived from an
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`alkane group by removal of a hydrogen.
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`32.
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`In organic chemistry, the simplest compounds are those that are made up
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`of carbon and hydrogen, called hydrocarbons, in which the carbon atoms are joined
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`12
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`by single bonds. Such compounds are known as alkanes. Removal of a hydrogen
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`from one of the carbon atoms of an alkane creates an “alkyl” group, which can
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`bind to other groups. In other words, an alkyl group is one or more carbon atoms
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`that are connected by single bonds.
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`
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`33. A “nitrile” is a substituent in which a carbon is bonded to a single
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`nitrogen through a triple bond. It is often depicted in chemistry as “CN,” as is used
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`in the ’393 patent claims and in the specification (see above, Example 1).
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`34. An alkyl group can be “simple,” such as the C4H9 example illustrated in
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`¶32 above, or it can obtain additional substituents. Examples of “simple” and
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`“substituted” alkyl groups are methyl and cyanomethyl, illustrated below:
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`13
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`35. As discussed below, the alkylation reaction claimed in the ’393 patent is
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`limited to a sub-class of alkylation reactions, in which the alkylating agent is a
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`cyanoalkyl group.
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`B.
`Step (b): The Hydrolysis Step
`36. Step (b) is the hydrolysis step, in which the benzindene nitrile
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`intermediate formed in step (a) reacts with water in the presence of a strong base to
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`produce treprostinil acid. Hydrolysis reactions are those in which water “lyses” –
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`i.e. cuts – the bonds in a molecule. Hence the term hydro (water) –lysis (cuts).
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`37. When a strong base, such as potassium hydroxide (KOH), is added to an
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`aqueous solution containing the benzindene nitrile, potassium hydroxide
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`dissociates (or splits) into a positively charged potassium cation (K+) and a
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`negatively charged hydroxide ion (OH–).
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`38. Hydroxide ions are known to cause hydrolysis reactions of nitrile groups.
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`This means that hydroxide ions (OH–) cause water to react with nitrile groups (CN)
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`to form the corresponding carboxylic acid (COOH).
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`39.
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`In the case of the ’393 patent, the benzindene nitrile reacts with water
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`under the influence of a base such as NaOH or KOH to form treprostinil acid as
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`shown in Example 2 of the ’393 specification:
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`14
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`C.
`Step (c): The Salt Formation Step
`40. Step (c) in the ’393 patent process is a salt formation step.
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`41.
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`In general, a salt is an ionic species consisting of a positively charged
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`moiety called a “cation” with a negatively charged moiety called an “anion.”
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`42. For example, the chemical formula for table salt, or sodium chloride, is
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`NaCl. The cation in table salt is the sodium ion, or Na+. The anion is the chloride
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`ion, or Cl–. In the solid form, the Na+ and Cl– ions exist in a lattice wherein each
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`Na+ is surrounded by six Cl– ions and vice versa:
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`15
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`When dissolved in water, the sodium ions and the chloride ions separate from the
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`crystal lattice and exist in solution as Na+ cations and Cl– anions.
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`43. The most common method of forming a salt is through the reaction of an
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`acid with a base, which is called an “acid-base reaction.” In step (c) of the ’393
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`patent process, a salt is formed by reacting an acid with a base.
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`44.
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`In chemistry, there are different types of bases. The salt formation step
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`that is described in the ’393 patent involves use of a particular type of base.
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`45. Acid-base reactions typically take place in a solvent such as water, or as
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`chemists would say, “in solution.” The particulars of acid-base reactions are more
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`readily understood in the context of how water behaves on a chemical level.
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`46. Water can exist as the whole molecule H2O or in dissociated form as a
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`balance of H+ and OH– ions. The H+ ions are hydrogen ions, which is simply a
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`proton.2 The OH– ions are called hydroxide ions.
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`2 Although it is convenient to depict the species resulting from dissociation of water
`as a proton and a hydroxide ion, bare protons do not exist in solution; rather, the
`proton is bonded to a neutral water molecule to give a species called a hydronium
`ion, H3O+:
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`16
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`47.
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`In any given sample of water, the bonds between hydroxide ions and
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`hydrogen ions are constantly breaking and reforming. This means that at any
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`given point in time, a sample of water contains H2O molecules as well as
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`dissociated hydrogen ions and hydroxide ions. In pure water one-ten millionth
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`(10–7) of the water molecules are dissociated at any given time, as shown in the
`
`following equation:
`
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`When a sample of water has an equal number of H+ and OH– ions it is said to be
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`“neutral”. If there are more H+ than OH– ions it is said to be “acidic” and if there
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`are more OH– than H+ ions it is said to be “basic.”
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`48. A base is a chemical compound that alters the balance of hydrogen ions
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`and hydroxide ions in water or aqueous solution so that there are fewer hydrogen
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`ions than hydroxide ions. A base can accomplish this in two related but slightly
`
`different ways:
`
`a. Bases like NaOH and KOH dissolve and dissociate to contribute
`additional OH– ions to the solution.
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`17
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`b. Bases like NH3 react with some of the H+ ions, leaving an excess of
`OH– ions.
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`49. The base used in the hydrolysis step of Example 2, as described above, is
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`potassium hydroxide (KOH). As shown in the preceding paragraph potassium
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`hydroxide dissociates to form K+ and OH– ions. The greater concentration of OH–
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`causes the hydrolysis reaction that converts the CN group to COOH.3
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`50.
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`In contrast, the base used in the salt formation step of the ’393 patent
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`“accepts” hydrogen ions, giving a salt in which the cation is an ammonium ion, as
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`illustrated in ¶48b.
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`51. Example 3 provides an embodiment of this step. In example 3, the base
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`used is diethanolamine, and the salt formed is treprostinil diethanolamine salt. In
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`Example 3, the acid (treprostinil acid)—forms an anion by giving up – “donating”
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`– its hydrogen atom. The carboxylic acid anion produced in this reaction is a
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`“carboxylate” ion and for convenience it will be referred to in this report as
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`“(treprostinil)– ”.
`
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`3 Strictly speaking, the hydrolysis reaction converts the CN group to CO2
`–, giving
`treprostinil carboxylate. Treprostinil acid is produced in the workup of the
`hydrolysis reaction described in Example 2, when the aqueous solution obtained by
`the reaction of the benzindene nitrile with KOH and water is acidified by the
`addition of 3M HCl (col. 11:12-16). This is a second chemical reaction that is
`considered to be a part of “step (b).”
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`18
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`52. The base used in Example 3 is diethanolamine, which is a hydrogen ion
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`acceptor. When combined with treprostinil, diethanolamine “accepts” a hydrogen
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`ion from treprostinil acid and thereby forms a cation which is called the
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`
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`diethanolammonium ion.
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`53.
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`(Treprostinil)– is also called the “conjugate base” of treprostinil acid, and
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`the diethanolammomium ion is the “conjugate acid” of diethanolamine.
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`D. Chemical reactions versus physical manipulation
`54. Steps (a) through (c) described above are chemical reactions. The
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`examples also describe physical separation and purification steps that follow the
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`chemical reactions and produce the final product.
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`19
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`55. Chemical steps are those in which chemical bonds are broken or
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`exchanged and new molecules form. Physical steps, by contrast, rely on the
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`physical properties of compounds to separate them from each other.
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`56. Purification can be accomplished using a variety of different methods.
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`Some of them are chemical; others are physical. Examples of physical purification
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`methods are filtration, drying and recrystallization.
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`57. Filtration is a method of separating a solid material from admixed liquids
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`by passing the mixture through a porous membrane, such as “filter paper.” The
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`liquid passes through the membrane while the admixed solids are retained.
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`58. Drying is a means of separating the desired product from water or other
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`solvent through simple heating, sometimes under reduced pressure (vacuum). In
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`this process, heating causes water and/or other volatile materials to evaporate,
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`leaving the desired product.
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`59. Recrystallization is a process in which an impure or semipure crystalline
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`material is taken into solution and allowed to slowly crystallize while the
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`temperature is reduced or the solvent is allowed to gradually evaporate. This
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`process generally results in increased purity of the recrystallized material.
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`20
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`V.
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`PRIOR ART
`60.
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`It is my understanding that the general facts surrounding the early
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`development and commercialization of treprostinil have been addressed in prior
`
`litigation.
`
`61.
`
`It is further my understanding that UTC hired Dr. Robert Moriarty to
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`develop a new commercial manufacturing process for treprostinil. That process
`
`was disclosed in U.S. Patent No. 6,765,117 (the “’117 patent”), as well as other
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`publications, including Moriarty et al., “The Intramolecular Assymetric Pauson-
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`Khand Cyclization as a Novel and General Stereoselective Route to Benzindene
`
`Prostacyclins: Synthesis of UT-15 (Treprostinil),” 69 J. Org. Chem. 1890-1902
`
`(2004) (“Moriarty 2004”).
`
`62. Like the ’393 process, the process described in the ’117 patent and
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`Moriarty 2004 includes the steps of alkylating a benzindene triol to form a
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`benzindene nitrile and hydrolyzing the benzindene nitrile with a base to form
`
`treprostinil acid. Moriarty 2004 discloses an example in which the treprostinil
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`obtained through the described method was 99.7% pure.
`
`63. Other references in the prior art also describe processes for making
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`treprostinil and treprostinil salts. For example, the article “Synthetic Approaches
`
`To The 2002 New Drugs” by Jin Li and Kevin K.-C. Liu (Mini-Reviews in
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`21
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`Medicinal Chemistry, Vol. 4 at pp. 207-233 (2004) (“Li”)) describes the synthesis
`
`of twenty-two drugs brought to market in 2002, including treprostinil.
`
`64. The Li article discloses a process of making treprostinil that involves
`
`alkylating the benzindene triol (compound 226) to obtain a nitrile intermediate
`
`(compound 227), hydrolyzing the nitrile with a base to form treprostinil acid
`
`(compound 228), and then contacting the treprostinil acid with a base (NaOH) to
`
`form treprostinil sodium salt (compound 26), as shown below:
`
`(Li at p. 229).
`
`VI. DISPUTED TERMS
`65.
`
`I have reviewed the parties’ proposed constructions for each disputed
`
`
`
`term and discuss each in turn.
`
`22
`
`
`
`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 24 of 52 PageID: 357
`
`
`A. Term 1 (claims 1 and 9): “product”
`
`“product”
`
`Sandoz’s Construction
`“A chemical composition.”
`
`UTC’s Construction
`Plain and ordinary meaning.
`To the extent the Court determines that
`this term requires construction, UTC
`proposes the following:
`“a substance resulting from a chemical
`reaction”
`
`
`
`66. Both claims 1 and 9 are directed to “a product comprising a
`
`compound….” I have been informed by counsel that in the context of patent law,
`
`the term “comprising” when used in a patent claim means “including but not
`
`limited to.”
`
`67. This is in agreement with the way the inventors defined the term
`
`“comprising” in the specification:
`
`The expression “comprising” means “including but not limited to.”
`Thus, other non-mentioned substances, additives, carriers, or steps
`may be present.
`
`(Ex. 2, Col. 4:23-24).
`
`68. Therefore, the term “product” as it is used in claims 1 and 9 of the ’393
`
`patent is not restricted to the depicted compound but can include other compounds.
`
`In my opinion, a person of ordinary skill in the art would understand that the term
`
`“product” as it is used in claims 1 and 9 of the ’393 patent refers to a chemical
`
`composition.
`
`23
`
`
`
`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 25 of 52 PageID: 358
`
`
`69.
`
`In particular, a person of ordinary skill in the art would understand that
`
`UTC’s proposed construction is not consistent with the plain and ordinary meaning
`
`of “product” as read in the context of the claim language as defined by the
`
`teachings in the specification.
`
`70. UTC’s construction requires that the claimed product is the substance
`
`resulting from a chemical reaction.
`
`71. Under UTC’s proposed construction, it is unclear whether the claimed
`
`“product” would include substances resulting from non-chemical reactions, such as
`
`physical separation, purification, or drying steps, or additional steps for
`
`formulating a finished drug product. As a result, UTC’s proposed construction is
`
`not consistent with what I understand to be the open-ended language of the process
`
`term in the claims (“a process comprising”), which does not limit the process to
`
`chemical reactions. Nor is it consistent with the teachings in the specification of
`
`the ’393 patent, which disclose processes for making treprostinil that include
`
`additional steps following the final chemical reaction.
`
`72. Example 6, which describes a “Working Example of the Process
`
`According to the Present Invention” (Ex. 2, Col. 15:2-5), includes numerous
`
`separate process steps that culminate in the production of treprostinil. (Id., Col.
`
`15:1-17:25). However, the final chemical reaction described in this process is the
`
`conversion of treprostinil diethanolamine salt into treprostinil acid by reaction with
`
`24
`
`
`
`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 26 of 52 PageID: 359
`
`
`HCl (step 35). All of the subsequent steps are process steps designed to purify the
`
`final product, and these include extraction, a water wash, a brine wash, filtration,
`
`evaporation, crude drying, crystallization, an additional filtration step, washing,
`
`and drying in a vacuum oven.
`
`73.
`
`It is only after all of these process steps are complete that the purity of
`
`the “product” is calculated.
`
`74. Example 5 also describes several steps that take place following the final
`
`chemical reaction, and these include physical separation steps, washing, brining,
`
`drying, filtration, concentration under vacuum, recrystallization of the crude
`
`treprostinil, further filtration, washing, drying and drying in a vacuum oven. (Ex.
`
`2, Col. 14:1-54).
`
`75. Similarly, in Example 3, treprostinil diethanolamine salt—after it has
`
`formed chemically—undergoes non-chemical steps: filtration, washing, air-drying,
`
`and vacuum-drying. (Id., Col. 12:46-52).
`
`76. Thus, the ’393 patent makes clear that the “product” is not limited to a
`
`substance that results from a chemical reaction. The “product” can result from
`
`chemical reactions along with any other type of process step, whether it is
`
`filtration, washing, evaporation, or recrystallization.
`
`25
`
`
`
`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 27 of 52 PageID: 360
`
`
`B.
`
`Term 2 (claim 1) and term 12 (claim 9): “a product comprising a
`compound of formula I or a pharmaceutically acceptable salt
`thereof” and “a product comprising a compound of formula IV or
`a pharmaceutically acceptable salt thereof.”
`
`Term 2 (claim 1)
` “a product comprising a compound of formula I:
`
`
` or a pharmaceutically acceptable salt thereof”
`UTC’s Construction
`Sandoz’s Construction
`“A chemical composition that includes,
`Plain and ordinary meaning.
`but is not limited to, a compound of
`To the extent the Court determines that
`formula I, or a pharmaceutically
`this term requires construction, UTC
`acceptable salt thereof, and that may
`proposes the following:
`also include other non-mentioned
`“a substance resulting from a chemical
`substances (including impurities),
`reaction constituted primarily of formula
`additives, or carriers, without limitation
`I
`as to the types or relative amounts
`thereof”
`
`
`
`or a pharmaceutically acceptable salt
`thereof”
`
`Term 12 (claim 9)
` “a product comprising a compound of formula IV
`
`
` or a pharmaceutically acceptable salt thereof”
`
`26
`
`
`
`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 28 of 52 PageID: 361
`
`
`Plain and ordinary meaning.
`To the extent the Court determines that
`this term requires construction, UTC
`proposes the following:
`“a substance resulting from a chemical
`reaction constituted primarily of formula
`IV
`
`“A chemical composition that includes,
`but is not limited to, a compound of
`formula IV, or a pharmaceutically
`acceptable salt thereof, and that may
`also include other non-mentioned
`substances (including impurities),
`additives, or carriers, without limitation
`as to the types or relative amounts
`thereof”
`
`
`or a pharmaceutically acceptable salt
`thereof”
`
`
`77. As I explained above, I have been informed by counsel that the term
`
`“comprising” means “including but not limited to” in the context of patent claims,
`
`and it is further my understanding that the ’393 patent specification defines
`
`“comprising” to mean “including but not limited to.”
`
`78. As a result, the person of ordinary skill in the art would understand that
`
`terms 2 and 12, as depicted above, refer to a chemical composition that includes
`
`the recited chemical compound but that may also include other substances, without
`
`limitation as to the types or relative amounts thereof. Such other substances could
`
`include impurities, additives or carriers, as is stated in the ’393 patent specification.
`
`(Ex. 2, Col. 4:23-24).
`
`27
`
`
`
`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 29 of 52 PageID: 362
`
`
`79. Thus, in my opinion, Sandoz’s proposed construction is consistent with
`
`the understanding of a person of ordinary skill in the art based on the context of the
`
`’393 patent.
`
`80. UTC’s construction is not consistent with the language of the claims as
`
`understood by the person of ordinary skill in the art. As I explained above, the
`
`term “product” should not be limited to the product of a chemical reaction. Also,
`
`as I have been informed by counsel that in the context of patent law, the term
`
`“comprising” means “including but not limited to,” and in view of the definition
`
`provided in the specification, the claimed product does not need to consist
`
`“primarily” of the depicted compound.
`
`C. Terms 3 and 13: “a process comprising”
`
`Term 3 (claim 1)
`“a process comprising”
`UTC’s Construction
`Sandoz’s Construction
`Plain and ordinary meaning.
`“A process that includes, but is not
`limited to, the recited process steps, and
`
`may include, without limitation, any
`other non-recited steps.”
`Term 13 (claim 9)
`“the process comprising”
`“The process that includes, but is not
`limited to, the recited process steps, and
`may include, without limitation, any
`other non-recited steps.”
`
`Plain and ordinary meaning.
`
`
`
`
`28
`
`
`
`Case 3:14-cv-05499-PGS-LHG Document 41-3 Filed 07/07/15 Page 30 of 52 PageID: 363
`
`
`81. As explained above, the person of ordinary skill in the art would
`
`understand that the term “comprising” means “including but not limited to”. Also,
`
`as explained above, the ’393 patent specification defines “comprising” as
`
`“including but not limited to” and explains that “other non-mentioned…steps may
`
`be present.” (Ex. 2, Col. 4:23-24). Thus, a person of ordinary skill in the art
`
`would understand that the term “a process comprising” refers to a process that
`
`includes the three steps recited in the claim but may also include other, non-
`
`mentioned steps. Such steps could include purification steps or formulation steps.
`
`82. Because the specification places no limits on what other, non-recited
`
`steps may be present, “a process comprising” is best understood as “a process that
`
`includes, but is not limited to, the recited process steps, and may include, without
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