Case 1:15-cv-00474-RGA Document 68-1 Filed 05/10/17 Page 10 of 302 PageID #: 970
`Case 1:15-cv—00474-RGA Document 68-1 Filed 05/10/17 Page 10 of 302 PagelD #: 970
`
`EXHIBIT 2
`   ¤
`
`Par Pharm., Inc.
`Exhibit 1 1 21
`
`Case IPR201 6-01 479
`
`Par Pharm., Inc. v. Novartis AG
`
`Ex. 1121 -0001
`
`Ex. 1121-0001
`
`

`

`Case 1:15-cv-00474-RGA Document 68-1 Filed 05/10/17 Page 11 of 302 PageID #: 971
`Case 1:15-cv—00474-RGA Document 68-1 Filed 05/10/17 Page 11 of 302 PagelD #: 971
`
`PROPOSED JOINT PRETRIAL ORDER EXHIBIT 2:
`
` 


` 
`
`
` n
`NOVARTIS’S STATEMENT OF DISPUTED FACTS
`¥
`

f

  

 

`
`*
`
`Ex. 1121 -0002
`
`Ex. 1121-0002
`
`

`

`Case 1:15-cv-00474-RGA Document 68-1 Filed 05/10/17 Page 12 of 302 PageID #: 972
`
`s`# `#%
`
`Z& G¢I]¢ZIY G^.G¢R]_ZCeC8RCIR.D¦IœZCCcIC_GXI
`DI8ZDID&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
`
`R& _36eO'),6+,&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
`
`X& _36eQQW'),6+,&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&Q
`
`ZZ& Z._]GDc8_ZG.&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&O
`
`}
`R& R-*+*,/1
`
`:I061/(*472=R+@Z,2R991/06@Z+@*5),*/+2&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&W
`
`X& Y62,VY)1@e2R.DR^*(*+>&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&U
`
`ZZZ& _HIeO'R_I._ZC¢RTZD&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&U
`
`R& _36'612/+G-G1@*+)1KC[*((Z+_36R1,&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&U
`
`X& _36R2261,6@8()*42G-_36eO'),6+,R16./,GF0*/72&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&P
`
`& G0610*6B&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&P
`
`Q& X)5[>1/7+@G+]88&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&M
`
`O& R'GCRY/7(@./,H)06X66+q/,*0),6@_/C6(65,
`I061/(*472^/1D606(/946+,R2R_361)9K^/1R@0)+56@
`]88&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&d
`
`W& 8()*42VOG-_36eO'),6+,R16./,GF0*/72G061_36
`eMMQ'),6+,Z+¢*6BG-H*@)(>/QLLLEH7,53*+2/+QLLL
`R+@_36eNMO'),6+,&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&W
`
`U& _3616Z2GFj65,*06I0*@6+56_3),_36eO'),6+,Y/7(@
`./,H)06X66+GF0*/72&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&d
`
`Z¢& _HIeQQW'R_I._ZC¢RTZD&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&QM
`
`R& _36'612/+G-G1@*+)1KC[*((Z+_36R1,&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&QM
`
`X& _36R2261,6@8()*4G-_36eQQW'),6+,Z2./,GF0*/72&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&Qd
`
`& G0610*6B&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&Qd
`
`Q& X)5[>1/7+@G+R@0)+56@'.I_2&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&Qd
`
`O& R'GCRY/7(@./,H)06X66+q/,*0),6@_/C6(65,
`I061/(*472^/1_36D606(/946+,G-R.6B_361)9K^/1
`
`**
`
`Ex. 1121-0003
`
`

`

`Case 1:15-cv-00474-RGA Document 68-1 Filed 05/10/17 Page 13 of 302 PageID #: 973
`Case 1:15-cv—00474-RGA Document 68-1 Filed 05/10/17 Page 13 of 302 PagelD #: 973
`
`Advanced PNETs After Failure Of Cytotoxic
`¨©ª«¬­®©¯°±²³¨´µ®¶·«§¸¹¶®º´»¼µ½µ½¾§­
`Chemotherapy .......................................................................................... ..32
`»¿®À½µ¿®¶«Á¼ÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÃÄ
`4.
`Claim 1 Of The ’224 Patent Is Not Obvious Over The ’541
`Å »¸«§Àƺ´²¿®ÇÄÄů«µ®¬µÈ³°½µºÉª§½¹³ºª®¶²¿®ÇÊÅÆ
`Publication Or Boulay 2004 With Tabemero 2005, In View
`¯¹É¸§­«µ§½¬º¶Ë½¹¸«¼ÄÌÌÅͧµ¿²«É®¶¬®¶½ÄÌÌÊÎȬϧ®Ð
`Of Duran 2005 And/Or Dancey 2005 ...................................................... ..37
`º´Ñ¹¶«¬ÄÌÌʨ¬©Òº¶Ñ«¬­®¼ÄÌÌÊÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÃÓ
`5.
`Claim 1 Of The ’224 Patent Is Not Obvious Over Von
`Ê »¸«§Àƺ´²¿®ÇÄÄů«µ®¬µÈ³°½µºÉª§½¹³ºª®¶Ï½¬
`Wichert 2000 In View Of Dutcher-I 2004, The ’772 Patent,
`ͧ­¿®¶µÄÌÌÌȬϧ®Ðº´Ñ¹µ­¿®¶ÔÈÄÌÌÅβ¿®ÇÓÓį«µ®¬µÎ
`Tabemero 2005, Duran 2005 And/Or Dancey 2005 ................................ ..45
`²«É®¶¬®¶½ÄÌÌÊÎѹ¶«¬ÄÌÌʨ¬©Òº¶Ñ«¬­®¼ÄÌÌÊÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÅÊ
`6.
`Claim 1 Of The ’224 Patent Is Not Obvious Over Duran
`Õ »¸«§Àƺ´²¿®ÇÄÄů«µ®¬µÈ³°½µºÉª§½¹³ºª®¶Ñ¹¶«¬
`2005 In Combination With Dancey 2005, In View Of
`ÄÌÌÊȬ»½Àɧ¬«µ§½¬Í§µ¿Ñ«¬­®¼ÄÌÌÊÎȬϧ®Ðº´
`Tabemero 2005 ........................................................................................ ..50
`²«É®¶¬®¶½ÄÌÌÊÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÊÌ
`7.
`A POSA Would Not Have Reasonably Expected
`Ó ¨¯ºÖ¨Í½¹¸©°½µ×«ª®Ø®«³½¬«É¸¼±¾Á®­µ®©
`Everolimus As A Monotherapy To Treat Advanced PNETs
`±ª®¶½¸§À¹³¨³¨Ù½¬½µ¿®¶«Á¼²½²¶®«µ¨©ª«¬­®©¯°±²³
`After Failure Of Cytotoxic Chemotherapy Based On The
`¨´µ®¶·«§¸¹¶®º´»¼µ½µ½¾§­»¿®À½µ¿®¶«Á¼Ë«³®©º¬²¿®
`Biology Of PNETs ................................................................................... ..50
`˧½¸½Ú¼º´¯°±²³ÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÊÌ
`
`8.
`There Is Objective Evidence That The ’224 Patent Would
`Û ²¿®¶®È³ºÉÜ®­µ§ª®±ª§©®¬­®²¿«µ²¿®ÇÄÄů«µ®¬µÍ½¹¸©
`Not Have Been Obvious .......................................................................... ..52
`°½µ×«ª®Ë®®¬ºÉª§½¹³ÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÂÊÄ
`
`iii
`§§§
`
`Ex. 1121 -0004
`
`Ex. 1121-0004
`
`

`

`Case 1:15-cv-00474-RGA Document 68-1 Filed 05/10/17 Page 40 of 302 PageID #: 1000
`Case 1:15-cv-00474-RGA Document 68-1 Filed 05/10/17 Page 40 of 302 PagelD #: 1000
`
`144.
`It would have been unexpected as of February 2001 that the same claimed
`ÆÅÅ ȵн¹¸©¿«ª®É®®¬¹¬®¾Á®­µ®©«³½´·®É¶¹«¶¼ÄÌÌƵ¿«µµ¿®³«À®­¸«§À®©
`
`methods of treatment would be safe and effective to treat both malignant and benign tumors of
`À®µ¿½©³½´µ¶®«µÀ®¬µÐ½¹¸©É®³«´®«¬©®´´®­µ§ª®µ½µ¶®«µÉ½µ¿À«¸§Ú¬«¬µ«¬©É®¬§Ú¬µ¹À½¶³½´
`
`the kidney.
`µ¿®§©¬®¼Â
`
`145. No other drug as of 2001 was, or is today, approved for the treatment of
`ÆÅÊ °½½µ¿®¶©¶¹Ú«³½´ÄÌÌÆЫ³Î½¶§³µ½©«¼Î«ÁÁ¶½ª®©´½¶µ¿®µ¶®«µÀ®¬µ½´
`
`malignant and benign tumors.
`À«¸§Ú¬«¬µ«¬©É®¬§Ú¬µ¹À½¶³Â
`
`IV.
`THE ’224 PATENT IS VALID
`ÝàÞ çáé ûæçáåçÝèàæÝë
`
`A.
`The Person Of Ordinary Skill In The Art
`æÞ ç÷øûø
` þßß
`þü
` è!Ýþç÷øæ
`ý
`146.
`The priority date for claim 1 of the ’224 Patent is November 21, 2005. West-
`ÆÅÕ ²¿®Á¶§½¶§µ¼©«µ®´½¶­¸«§Àƽ´µ¿®ÇÄÄů«µ®¬µ§³°½ª®ÀÉ®¶ÄÆÎÄÌÌÊÂÍ®³µÔ
`
`Ward has not contested this date and uses November 21, 2005 as the priority date in its analysis.
`Í«¶©¿«³¬½µ­½¬µ®³µ®©µ¿§³©«µ®«¬©¹³®³°½ª®ÀÉ®¶ÄÆÎÄÌÌÊ«³µ¿®Á¶§½¶§µ¼©«µ®§¬§µ³«¬«¸¼³§³Â
`
`147.
`The POSA with respect to the ’224 Patent as of November 21, 2005 would have
`ÆÅÓ ²¿®¯ºÖ¨Ð§µ¿¶®³Á®­µµ½µ¿®ÇÄÄů«µ®¬µ«³½´°½ª®ÀÉ®¶ÄÆÎÄÌÌÊн¹¸©¿«ª®
`
`had (1) a Ph.D. in biology, biochemistry, pharmaceutical sciences, molecular biology, cancer
`¿«©ðÆ󫯿Âѧ¬É§½¸½Ú¼Îɧ½­¿®À§³µ¶¼ÎÁ¿«¶À«­®¹µ§­«¸³­§®¬­®³ÎÀ½¸®­¹¸«¶É§½¸½Ú¼Î­«¬­®¶
`
`biology, or other biological sciences; and/or (2) a medical degree and experience conducting
`ɧ½¸½Ú¼Î½¶½µ¿®¶É§½¸½Ú§­«¸³­§®¬­®³«¬©Ò½¶ðÄó«À®©§­«¸©®Ú¶®®«¬©®¾Á®¶§®¬­®­½¬©¹­µ§¬Ú
`
`preclinical, clinical, and/or laboratory research relating to cancer of the neuroendocrine system,
`Á¶®­¸§¬§­«¸Î­¸§¬§­«¸Î«¬©Ò½¶¸«É½¶«µ½¶¼¶®³®«¶­¿¶®¸«µ§¬Úµ½­«¬­®¶½´µ¿®¬®¹¶½®¬©½­¶§¬®³¼³µ®ÀÎ
`
`including PNETs. To the extent necessary, the POSA would also have collaborated with persons
`§¬­¸¹©§¬Ú¯°±²³Â²½µ¿®®¾µ®¬µ¬®­®³³«¶¼Îµ¿®¯ºÖ¨Ð½¹¸©«¸³½¿«ª®­½¸¸«É½¶«µ®©Ð§µ¿Á®¶³½¬³
`
`having ordinary skill in areas pertinent to the above subject matter, including, for example,
`¿«ª§¬Ú½¶©§¬«¶¼³§¸¸§¬«¶®«³Á®¶µ§¬®¬µµ½µ¿®«É½ª®³¹ÉÜ®­µÀ«µµ®¶Î§¬­¸¹©§¬Ú佶®¾«ÀÁ¸®Î
`
`pharmacologists, formulators, and biochemists.
`Á¿«¶À«­½¸½Ú§³µ³Î´½¶À¹¸«µ½¶³Î«¬©É§½­¿®À§³µ³Â
`
`148.
`Contrary to West-Ward’s assertion, a POSA would not specifically have had
`ÆÅÛ »½¬µ¶«¶¼µ½Í®³µÔÍ«¶©Ç³«³³®¶µ§½¬Î«¯ºÖ¨Ð½¹¸©¬½µ³Á®­§´§­«¸¸¼¿«ª®¿«©
`
`experience conducting preclinical, clinical and/or laboratory research relating to rapamycin and its
`®¾Á®¶§®¬­®­½¬©¹­µ§¬ÚÁ¶®­¸§¬§­«¸Î­¸§¬§­«¸«¬©Ò½¶¸«É½¶«µ½¶¼¶®³®«¶­¿¶®¸«µ§¬Úµ½¶«Á«À¼­§¬«¬©§µ³
`
`analogs, or intracellular signaling pathways, because that assumes that a POSA would have been
`«¬«¸½Ú³Î½¶§¬µ¶«­®¸¸¹¸«¶³§Ú¬«¸§¬ÚÁ«µ¿Ð«¼³ÎÉ®­«¹³®µ¿«µ«³³¹À®³µ¿«µ«¯ºÖ¨Ð½¹¸©¿«ª®É®®¬
`
`interested in rapamycin or its analogs and/or a therapy that targeted intracellular signaling
`§¬µ®¶®³µ®©§¬¶«Á«À¼­§¬½¶§µ³«¬«¸½Ú³«¬©Ò½¶«µ¿®¶«Á¼µ¿«µµ«¶Ú®µ®©§¬µ¶«­®¸¸¹¸«¶³§Ú¬«¸§¬Ú
`
`pathways.
`Á«µ¿Ð«¼³Â
`
`149.
`As of November 2005, many compounds were being studied for the development
`ÆÅö ¨³½´°½ª®ÀÉ®¶ÄÌÌÊÎÀ«¬¼­½ÀÁ½¹¬©³Ð®¶®É®§¬Ú³µ¹©§®©´½¶µ¿®©®ª®¸½ÁÀ®¬µ
`
`of a new treatment for advanced PNETs, including after failure of cytotoxic chemotherapy.
`½´«¬®Ðµ¶®«µÀ®¬µ´½¶«©ª«¬­®©¯°±²³Î§¬­¸¹©§¬Ú«´µ®¶´«§¸¹¶®½´­¼µ½µ½¾§­­¿®À½µ¿®¶«Á¼Â
`
`27
`ÄÓ
`
`Ex. 1121 -0005
`
`Ex. 1121-0005
`
`

`

`Case 1:15-cv-00474-RGA Document 68-1 Filed 05/10/17 Page 41 of 302 PageID #: 1001
`Case 1:15-cv-00474-RGA Document 68-1 Filed 05/10/17 Page 41 of 302 PagelD #: 1001
`
`While a POSA would have been aware of rapamycin and its analogs and intracellular signaling
`Í¿§¸®«¯ºÖ¨Ð½¹¸©¿«ª®É®®¬«Ð«¶®½´¶«Á«À¼­§¬«¬©§µ³«¬«¸½Ú³«¬©§¬µ¶«­®¸¸¹¸«¶³§Ú¬«¸§¬Ú
`
`pathways, a POSA’s experience would not be specific to rapamycin or its analogs and/or
`Á«µ¿Ð«¼³Î«¯ºÖ¨Ç³®¾Á®¶§®¬­®Ð½¹¸©¬½µÉ®³Á®­§´§­µ½¶«Á«À¼­§¬½¶§µ³«¬«¸½Ú³«¬©Ò½¶
`
`compounds that target intracellular signaling pathways. West-Ward’s contention to the contrary
`­½ÀÁ½¹¬©³µ¿«µµ«¶Ú®µ§¬µ¶«­®¸¸¹¸«¶³§Ú¬«¸§¬ÚÁ«µ¿Ð«¼³ÂÍ®³µÔÍ«¶©Ç³­½¬µ®¬µ§½¬µ½µ¿®­½¬µ¶«¶¼
`
`is based on hindsight knowledge of the invention.
`§³É«³®©½¬¿§¬©³§Ú¿µ¬½Ð¸®©Ú®½´µ¿®§¬ª®¬µ§½¬Â
`
`B.
`The Asserted Claim Of The ’224 Patent Is Not Obvious
`ïÞ ç÷øæø
`ýøêüßç÷øé ûüýøþýÝå ýß"  
`1.
`Overview
`ùÞ ß ø
` ø#
`150. Claim 1 of the ’224 Patent would not have been obvious to a POSA in light of the
`ÆÊÌ »¸«§Àƽ´µ¿®ÇÄÄů«µ®¬µÐ½¹¸©¬½µ¿«ª®É®®¬½Éª§½¹³µ½«¯ºÖ¨§¬¸§Ú¿µ½´µ¿®
`
`prior art as a whole as of November 21, 2005.
`Á¶§½¶«¶µ«³«Ð¿½¸®«³½´°½ª®ÀÉ®¶ÄÆÎÄÌÌÊÂ
`
`151. As of November 21, 2005, a POSA would not have been motivated to select
`ÆÊÆ ¨³½´°½ª®ÀÉ®¶ÄÆÎÄÌÌÊΫ¯ºÖ¨Ð½¹¸©¬½µ¿«ª®É®®¬À½µ§ª«µ®©µ½³®¸®­µ
`
`everolimus for the development of a new treatment for advanced PNETs after failure of
`®ª®¶½¸§À¹³´½¶µ¿®©®ª®¸½ÁÀ®¬µ½´«¬®Ðµ¶®«µÀ®¬µ´½¶«©ª«¬­®©¯°±²³«´µ®¶´«§¸¹¶®½´
`
`cytotoxic chemotherapy.
`­¼µ½µ½¾§­­¿®À½µ¿®¶«Á¼Â
`
`152. As of November 21, 2005, a POSA would not have reasonably expected that
`ÆÊÄ ¨³½´°½ª®ÀÉ®¶ÄÆÎÄÌÌÊΫ¯ºÖ¨Ð½¹¸©¬½µ¿«ª®¶®«³½¬«É¸¼®¾Á®­µ®©µ¿«µ
`
`everolimus monotherapy would be safe and effective for the treatment of advanced PNETs after
`®ª®¶½¸§À¹³À½¬½µ¿®¶«Á¼Ð½¹¸©É®³«´®«¬©®´´®­µ§ª®´½¶µ¿®µ¶®«µÀ®¬µ½´«©ª«¬­®©¯°±²³«´µ®¶
`
`failure of cytotoxic chemotherapy.
`´«§¸¹¶®½´­¼µ½µ½¾§­­¿®À½µ¿®¶«Á¼Â
`
`153.
`There is compelling objective evidence further supporting the nonobviousness of
`ÆÊಿ®¶®§³­½ÀÁ®¸¸§¬Ú½ÉÜ®­µ§ª®®ª§©®¬­®´¹¶µ¿®¶³¹ÁÁ½¶µ§¬Úµ¿®¬½¬½Éª§½¹³¬®³³½´
`
`the claimed method of administering everolimus as a monotherapy for the treatment of advanced
`µ¿®­¸«§À®©À®µ¿½©½´«©À§¬§³µ®¶§¬Ú®ª®¶½¸§À¹³«³«À½¬½µ¿®¶«Á¼´½¶µ¿®µ¶®«µÀ®¬µ½´«©ª«¬­®©
`
`PNETs after failure of cytotoxic chemotherapy, in the form of a long-felt unmet medical need,
`¯°±²³«´µ®¶´«§¸¹¶®½´­¼µ½µ½¾§­­¿®À½µ¿®¶«Á¼Î§¬µ¿®´½¶À½´«¸½¬ÚÔ´®¸µ¹¬À®µÀ®©§­«¸¬®®©Î
`
`failure of others and unexpected results.
`´«§¸¹¶®½´½µ¿®¶³«¬©¹¬®¾Á®­µ®©¶®³¹¸µ³Â
`
`2.
`Background On Advanced PNETs
` Þ ïü!
` þßþæ üþøûåáç
`154.
`Pancreatic neuroendocrine tumors (PNETs) are a type of neuroendocrine tumor
`ÆÊÅ ¯«¬­¶®«µ§­¬®¹¶½®¬©½­¶§¬®µ¹À½¶³ð¯°±²³ó«¶®«µ¼Á®½´¬®¹¶½®¬©½­¶§¬®µ¹À½¶
`
`(NET) that arise in the endocrine cells (or islet cells) of the pancreas. PNETs are distinct from
`𰱲󵿫µ«¶§³®§¬µ¿®®¬©½­¶§¬®­®¸¸³ð½¶§³¸®µ­®¸¸³ó½´µ¿®Á«¬­¶®«³Â¯°±²³«¶®©§³µ§¬­µ´¶½À
`
`other neuroendocrine tumors called carcinoid tumors, which arise in organs other than the
`½µ¿®¶¬®¹¶½®¬©½­¶§¬®µ¹À½¶³­«¸¸®©­«¶­§¬½§©µ¹À½¶³Îп§­¿«¶§³®§¬½¶Ú«¬³½µ¿®¶µ¿«¬µ¿®
`
`pancreas, and other less common neuroendocrine tumors also arising outside of the pancreas.
`Á«¬­¶®«³Î«¬©½µ¿®¶¸®³³­½ÀÀ½¬¬®¹¶½®¬©½­¶§¬®µ¹À½¶³«¸³½«¶§³§¬Ú½¹µ³§©®½´µ¿®Á«¬­¶®«³Â
`
`28
`ÄÛ
`
`Ex. 1121 -0006
`
`Ex. 1121-0006
`
`