Coalition for Affordable Drugs II LLC
`v. NPS Pharmaceuticals, Inc.
`
`IPR2015-00990 & IPR2015-01093
`Patent No. 7,056,886
`
`Counsel for Petitioner
`Merchant & Gould
`June 23, 2016
`
`CFAD Exhibit 1091
`CFAD v. NPS
`IPR2015-00990
`IPR2015-01093
`
`

`
`Merchant & Gould
`
`.-\111n1cl1cc1u;1| Pmpcrly 1.21\-V lilrm
`
`my United States Patent
`lsaacs
`
`Exhibit 1003
`’886 patent
`
`[54] GL1’-2 l*"()R_‘|-'IUI.A'I'IU NS
`
`[75]
`
`[nw:'.n1L*rr:
`
`Indu .1. Iuaaus. .-‘u1dJ;m:1'. MA {[15}
`
`Exhibit 1003
`
`’886 patent
`
`um Patent No.:
`[45] Date of Patent:
`
`US 7,056,886 B2
`Jun. 6, 2006
`
`. A
`._.1
`5.511.122‘) A
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`11.3. I‘.-'(1'1".N'I' DE]-C'T.J.‘vI1EN'['S
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`Buhl or al.. Nnmrally Gccinrrlilg Pmducts of Pm-glL1cago11
`11 I
`1151] in lhc 1’nrc:inL' and [Iu1nu11 E":.a1n11 ]111c51ir1c_ 1. Biol.
`(‘In-nu. 263. 81121 81124 119881.‘
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`.-‘k1L§_g.14.:r['L'.-:11 I51I.:1 1-’II.: pn:g1LIL;ugu1I [1. D\'us:1v;;miI.14.:
`'.L1..
`[.Lu1.d U1.
`and cnrrcspnnding amino acid !~‘n:q11c'n1nn::e of the c1'1N:1.,
`.1.
`13101
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`(74) .-11!tmw_L'.
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`1-'o1e}' & Lardner LLP
`AIi5i'I'I~UL("l'
`
`1571
`
`'1‘11ci|1ucnI1m1is rdiru-c1u(i to l'ormu1:nIj-.ms. of {;'L£‘—2 peptides
`and wiulugs l11¢.:rvI.11‘ L:.1a11i|:Ii1iI1g supcrmr siubilily iiullmh-'i11g.
`:4lnr*ag1:
`.:1nriu"ur cxpuxttrc tn EJ1.L"\.-'a|.L‘Il'.1.
`temperatures. The
`GT.P—2 o::uIn]sm:1'1im'::-; r.5nnmr'1.t::: 2| GT1"-2 ]1upI1':1+.-nr:an :|11:a1ng
`tl1ur<:m°. 2: plmsplmtc buffer, I.-11isti-:1i11c. and um1mitn|.
`
`2
`
`4.935.244 .-\
`
`“
`
`l-1991 Ma]-Linuel a1.
`
`............. .. 424.39
`
`75 Claims, I’: Drawing SIM-Hts
`
`

`
`Exhibit 1003
`’886 patent
`
`Col. 1, ll. 5-55
`
`3
`
`

`
`Merchant & Gould
`
`.-\111nIcllccIu;1| l’ropcrI)' L21\-V l’ll‘l11
`
`Oran e Book: Approved Drug Products with Thera eutic Equivalence Evaluations
`Searc results from the "DB_Rx ' table for query on "1 3441."
`
`Exhibit 1039
`Orange Book, Gattex
`
`Active Ingredient:
`Dosage Form;Route:
`
`Proprietary Name:
`
`Applicant:
`strw
`Application Number:
`
`"'"“"”“”‘“'""“"‘
`
`Approval Date:
`
`Reference Listed Drug
`RXIOTCIDISCN:
`TE Code:
`
`TEDUGLUTIDE RECDMBINANT
`PDW'DER;SUBCUTANEDUS
`
`GAT|'E){ I(]T
`
`NP5 PHARI-IS INC
`swam
`N2 03441
`
`"'31
`
`Dec 21, 2012
`
`Yes
`RX
`
`Patent and Exclusivitv Info for this product: View
`
`Exhibit 1039
`
`Orange Book, Gattex
`
`Patent Data
`
`“'9' "°
`NEDS4-41
`
`NEDS4-41
`
`NEDS4-41
`
`N2[l3-'-M1
`
`Exclusivitv Data
`
`Appl No
`
`Drug Stlnstalce
`claim
`
`Dmg Product
`claim
`
`‘I’
`
`‘I’
`
`‘I’
`
`Exclusivitv Code
`
`Exclusivitv Exuiraliun
`
`Dec 21, 2019
`
`Dec 21, 201?
`
`4
`
`

`
`Exhibit 1029
`Drucker ’379
`
`Col. 4, ll. 26-67
`Col. 5, ll. 1-55
`
`5
`
`

`
`Exhibit 1003
`’886 patent
`
`Col. 4, ll. 18-50
`
`6
`
`

`
`Exhibit 1043
`Carpenter Deposition Transcript
`
`p. 111, l. 22-p. 112, l. 16
`
`7
`
`

`
`Merchant & Gould
`
`.-\n ln1cil<.'L‘ELI;1|
`
`|’mpcrl\
`
`l;1\\'l'I|’m
`
`W. Structures of GLPs and Family of G1ueagon-
`Related Peptides
`
`Exhibit 1018
`Kieffer & Habener
`
`Exhibit 101 8
`
`p. 879
`
`Kieffer & Habener
`
`p. 879
`
`GL1"-'—1{?—3?] and —['.5'—3Er}amide, GIP, e:~:endin—3
`and -41, secretin, peptide histidine—methiorIine amide {PHM},
`-he1ospectin—1 and -2, helodermin, pituitary adenyl
`cyclase—activating polypeptides
`[PACi'3LP}—3B, and -23’,
`P.#LCA.P—t'elated peptide {PEP}, C.H—re1easing factor [GEE],
`and vasoactive intestinal polypeptide [VIP] {Fig. 3}. These
`peptide hormones are produced in the gut, pancreas, and the
`central and peripheral nervous systems and exhibit a wide
`variety of biological actions in whidt several act as neuro-
`transmitters. hlotat:-ly, even peptide hormones that are co-
`encoded within the same precursor, such as the peptide
`hormones derived from the cleavages of preproglucagon,
`differ significandy in the physiological processes that they
`regulate. For example, the major function of glucagnn is to
`maintain blood glucose levelsduring fasting, whereas {3LP—1
`functions primarily during feeding to stimulate insulin re-
`lease and to lower blood glucose levels. On the other hand,
`GLP—2 appears to regulate the growth of intestinal epithelial
`cells.
`
`8
`
`

`
`Merchant {St Gould
`
`An lmccllccluzll Property Law Firm
`
`Exhibit 1018
`Kieffer & Habener
`
`Exhibit 101 8
`
`p. 879
`
`Kieffer & Habener
`
`p. 879
`
`flLLl|2i|I.|!.-'nlIIP<I-------
`|3l.P-‘Ii?’-3Ti""'““'
`flI..F"-1li'-3IiIHI‘|i-
`gp............. ..
`ExEHD!".3_ .... ..
`EIEI~lE|'|H-II----
`
`Members of the Super Family of Giucagnri-Related Peptides
`5
`
`EDDDDHHHZU-'Ii'||'|'|M.'I'3I7|El
`
`]rriirrrrr:I-TlI11-—fifl:_:_:-
`
`llIfl|'.l!|ll3lll3lll1'lu[|‘fl3l-RI‘-I:'h'-H1I'.'§'l:'l=
`
`l'l"l"g|"|="E.'fl‘ 3i|FflIlIF:-IIIHHRIIJP-'.i|l|‘|":
`
`HIE-RH
`
`-{l'_'I-I.--I-III-I-I.
`
`HIFUUMI-I*U_
`
`=II'|'3PH"lI'|'|'|'||'I|'|'||'I-
`
`1:
`'F~EH:lnI3EEhlf3EFIl3.l.IlA.HLHH2
`I L‘-It-Ii
`
`FIG. 3. Aminuacidsequenue-sefttiememhers effliesuperfamilynfglucagmi-rela1.ed peptides. Sequeiiuesiuclude human glucagun, human GLPs,
`human GIP, exendiusffleiadermaharfidmlil, huJnansecretiJLhumanpe|;rtide]1istidiJ1emet]:iunine{PI-Ilulii, heluspectinsffleiedernm Iiarriciiimi,
`heludermin ffleiiicirriria , humaii PACAP, human PACAP-related peptide {PEP}, h1.u1:IaJi GRF, and human ‘VIP. Residues identical
`tn these efglumgun in the same position are shmieii Smndurd singfie letter abbreuiciiiens are used fur amino acids {IU'P.FiC—IU'B Cumilzlissiun
`an Eiuchelnical Neu1eni:]atu1'e]I: 1'1, Ma; C, C35; D, Asp; E, Glu; F, Phe; G, G11; H, His; I, De; K, Lye; L, Lei]; M, Met; P, Pro; 421, G111; R, iirg; 5,
`Ser, T, Tim V, 1:731; W, Trp; and "1', ‘T31.
`
`9
`
`

`
`Merchant & Gould
`
`.-\111n1cllc:c1LI;1l
`
`l’mpL‘r1)' Law lilrm
`
`Exhibit 1022
`Munroe et al.
`
`EXhflflt1O22
`
`p. 1573
`
`Munroe et al.
`
`p.1573
`
`lrt 'l-'1-'l-‘I5
`
`aetivit:,r§
`Ftetiue
`
`Partially aetive
`Inaetive
`Ftetive
`fitetive
`Inaetive
`Inaetive
`
`Partially aetive
`Inaetive
`Ftetive
`Ftetive
`Inaetive
`Inaetive
`Inaetive
`
`3 3:9 ill?
`gr-
`
`[I
`
`T 2
`
`ID
`
`5 E 5 E 4 6
`
`ha
`
`ID
`
`D-
`
`I I I I 1 1 1 I I I I A A A
`
`22
`2
`
`Table 2.
`
`In titre and in tire flfllltflljf profiles nf selected peptide—
`
`K,-, n1":-‘P’
`
`Peptide
`
`Higl1—a[finit}r
`
`L.~:Jw—alinit'_I,'
`
`E1355, nlhll
`
`I1Dfi:[I.[I]
`_
`NA
`ND
`I15fi:[I.3
`
`reLP.2u-33;r|
`N—r*Le—rGLF—E{]—33}
`[Arg-1]rG LF—2{— 1.33;.
`[Arg—3=1-|r~GLP—2{]—34-}
`[Tyr—3-=l]ht'3LF—2
`reLP.2.[233;.
`rC'.]_P—2{3—33;u
`reLP.2u-29;.
`[Thr-Tinsertiun|
`[eI;.r.2]eLr-.2.;1.22;
`
`hG-LP‘-EH l-33)‘
`
`t']LP-1[?-Sfijamide
`err
`
`2591 4::
`14:21
`2
`m
`E In!
`
`§§§E§§E§E'l'l'l'l'l'
`
`l‘l'l'l'l'l'l'l'l'l'l'l'
`
`1th--.1-.1
`
`I—lE\.D'-.|'|§E5£I
`
`"ms in = 1;.
`
`1.001 -12
`20.3 1 -11
`9411
`1 41
`3.1 1 0.3
`1.4 1 :11
`210
`122
`1-12 1 -12
`3.501 -14
`um 12::
`2.0 1 -12
`
`1.3 I I121]
`
`NA
`
`NA
`NA
`
`NFL, not aetit-e—ne deteetah-le binding; ND. net determined.
`‘H = 2, except where indicated.
`fr! = 3-.
`iflelatitre tn Ill] nM rG-LP-2[l-33). n = 3.
`§Relati'I.re tn vehicle-treated e-nntrul animals. at = 4 or greater. In n‘-L-r:-I aetivity is based on ehangts in small lxmrel wet weight after 14-day treatment
`as deseribed in Medioztt and Materials.
`
`‘rGLF-2111-33] is native rat GLF-2 peptide; hGLF-21.1-33] is native human GLF-2 peptide.
`
`10
`
`

`
`Exhibit 1027
`Kornfelt
`
`Col. 2, ll. 20-57
`
`11
`
`

`
`Exhibit 1027
`Kornfelt
`
`Col. 3, ll. 9-29
`
`12
`
`

`
`Exhibit 1029
`Drucker ’379
`
`Col. 9, ll. 25-56
`
`Exhibit 1029
`Drucker ’379
`
`Col. 10, ll. 25-33
`
`13
`
`

`
`Exhibit 1028
`Drucker ’600
`
`IPR2015-00990
`
`p. 21, ll. 15-30
`
`14
`
`

`
`Exhibit 1030
`Osterberg
`
`pp. 301, 304, 305
`
`Exhibit 1030
`Osterberg
`
`p. 307
`
`***
`
`***
`
`15
`
`

`
`Merchant & Gould
`
`.'\11]l11L‘HCL'lLl21| l’mpcr1)' L21\-V Firm
`
`Exhibit 1024
`Cleland et al.
`
`Exhibit 1024
`
`Cleland er al.
`
`p. 6
`
`p' 6
`
`sun-an ----a--------------a E-state
`
`-Illnillnnlll-I-I-'5.
`
`F:llu.r:2I. Eirn;I]iJ':-ad.|n'v.'||:-us:-diagrlan‘finr En1.1:I1u.1II.i.n:In d-u1I':L:I]:-u'|:nI! [.'ifl=Tfl'bI|: II and
`lust Eu: |isI.IiIn'.| Ilil|:I.|::i-Ln:I}I.
`
`16
`
`

`
`Exhibit 1043
`Carpenter Deposition Transcript
`
`p. 121, ll. 17-24
`
`17
`
`

`
`***
`
`***
`***
`
`***
`
`***
`
`***
`
`***
`
`***
`
`Exhibit 1050, Carpenter 1997, pp. 969-974
`
`18
`
`

`
`***
`
`***
`
`***
`
`***
`
`***
`
`Exhibit 1050, Carpenter 1997, pp. 969-974
`
`19
`
`

`
`***
`
`***
`
`***
`
`***
`
`Exhibit 1049, Carpenter 1996, pp. 201, 202, 220, 221, 225, 251
`
`20
`
`

`
`Merchant & Gould
`
`.-\n lnLcll<:L‘1LI;1|
`
`|’mpL'r1} I
`
`;1\\’ l’Irm
`
`SECONDARY
`CONSIDERATIONS
`
`SECONDARY
`
`CONSIDERATIONS
`
`21
`
`

`
`Merchant & Gould
`
`.-\n1n1cllcc1
`
`Lull l’mpcr1}' Lam’
`
`Firm
`
`EXAMPLES
`
`EXAMPLES
`
`22
`
`

`
`Exhibit 1003
`’886 patent
`
`Example 2
`
`23
`
`

`
`Exhibit 1003
`’886 patent
`
`Example 3
`
`24
`
`

`
`Exhibit 1003
`’886 patent
`
`Example 4
`
`25
`
`

`
`Merchant €31 Gould
`
`.-\11 lnLs:ll<:L‘1LI;1| Pmpcrl} la1\\’l*'Irm
`
`COMMERCIAL SUCCESS
`
`COMMERCIAL SUCCESS
`
`26
`
`

`
`The Board’s Analysis Of Commercial
`Success In The Institution Decision
`
`Institution Decision, IPR2015-00990, Paper 28, p.21
`
`27
`
`

`
`The Board’s Analysis Of Commercial Success
`In The Institution Decision
`
`Institution Decision, IPR2015-01093, Paper 26, p.18
`
`28
`
`

`
`Dr. Rausser Estimates That Less Than 20%
`Of Eligible Patients Take Gattex
`
`Exhibit 2041, Rausser Declaration, ¶ 49
`
`Exhibit 2041, Rausser Declaration, ¶ 28
`
`29
`
`

`
`Claim 1 Of Drucker ’379
`
`Exhibit 1029
`Drucker ’379
`
`Col. 21, l. 44 –
`Col. 22, l. 64
`
`30
`
`

`
`The Role Of Drucker ’379 Patent
`
`Exhibit 1077
`Rausser Deposition
`Transcript
`
`p. 160, ll. 12-17
`
`31
`
`

`
`The Orange Book Patents For Gattex
`
`32
`
`

`
`Dr. Rausser’s View Of The Gattex Patents
`
`Exhibit 1077
`Rausser Deposition
`Transcript
`
`p. 206, ll. 15-23
`
`33
`
`

`
`Dr. Rausser’s View Of The Gattex Patents
`
`Exhibit 2041
`Rausser Declaration
`¶ 71
`
`34
`
`

`
`Marketing The Efficacy of Gattex
`
`Exhibit 2075, Gattex Physician ATU Final Report, p. 59
`
`35
`
`

`
`Gattex Website
`
`Exhibit 1060, Gattex Website
`
`36
`
`

`
`NPS Statements on Marketing Of Gattex
`
`Exhibit 2019, Transcript of Statements of NPS CEO during Q1 2014 Earnings Call, p. 3
`
`Exhibit 2013, Transcript of Statements of NPS Chief Commercial Officer during
`Q2 2013 Earnings Call, p. 8
`
`37
`
`

`
`Physician Statements About Gattex Marketing
`
`Exhibit 2075
`Gattex Physicial
`ATU Final
`Report, p. 60
`
`38
`
`

`
`Shire Statements On Marketing Of Gattex
`
`Exhibit 1056, Shire Presentation, Jan. 11, 2015, p. 10
`
`Exhibit 1063, Shire Presentation, Feb. 11, 2016, p. 7
`
`39
`
`

`
`NPS And Shire Offer Patient
`Support Programs For Gattex
`
`Exhibit 1064, NPS Press Release, p. 3
`
`Exhibit 1074, Gattex Website, p. 2
`
`40
`
`

`
`The Cost of Gattex
`
`Exhibit 1068, Fox Business Press Release, p. 2
`
`41
`
`

`
`The NPS Stock Price
`
`Exhibits 1053, 1083, 1084 (Historical Stock Prices for NBI Pharmaceutical
`Index, NPS Pharmaceuticals, and XBI Pharmaceutical Index)
`
`42
`
`

`
`The Cost Of Orphan Drugs
`
`Exhibit 1081, Managed Care article on cost of Orphan Drugs, p. 3
`
`43
`
`

`
`Shire’s Valuation Of NPS
`
`Exhibit 1056, Shire Presentation, p. 3
`
`Exhibit 1055, Shire Press Release, p. 1
`
`44
`
`

`
`Merchant & Gould
`
`.-\n1n1s:ll<:c1LI;1|
`
`l’mpcr1}'
`
`l.;1\\' I"Irm
`
`LONG-FELT NEED
`
`LONG-FELT NEED
`
`45
`
`

`
`The Board’s Analysis Of Long-Felt
`Need In The Institution Decision
`
`Institution Decision, IPR2015-00990, Paper 28, p. 20
`
`46
`
`

`
`The Board’s Analysis Of Long-Felt
`Need In The Institution Decision
`
`Institution Decision, IPR2015-01093, Paper 26, pp. 16-17
`
`47
`
`

`
`Dr. Rausser focuses on the “novel
`mechanism of action” of teduglutide as
`the “most associated attribute” with Gattex
`
`Exhibit 2041
`Rausser
`Declaration ¶ 47
`
`48
`
`

`
`The Role Of Drucker ’379 Patent
`
`Exhibit 1077
`Rausser Deposition Transcript
`
`p. 160, ll. 12-17
`
`49
`
`

`
`Dr. Rausser Did Not Talk To A Physician
`About Gattex
`
`Exhibit 1077
`Rausser Deposition
`Transcript
`p. 137, ll. 2-9
`
`50
`
`

`
`The Use Of Gattex
`
`Exhibit 1077
`Rausser Deposition
`Transcript
`p. 82, ll. 11-20
`
`51
`
`

`
`Ivan Hofmann
`• Managing Director at Gleason IP, and leader of
`the Intellectual Property Practice
`• Experience in valuation of intellectual property
`and analysis of objective indicia of non-
`obviousness
`• Certified Public Accountant
`• Member of Licensing Executives Society
`• Double Major in Economics and Accounting
`
`Exhibit 1071, Hofmann CV
`
`52