DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`:>1—N ‘
`
`R4,
`
`form a 5 to 7 membered ring containing a total of 2 to 4 heteroatoms selected
`
`from N, O, S, S0, or S02;
`
`or optionally R1 and R3 together with
`
`I~I*“‘*“'N
`
`‘x
`
`,.-n
`
`R4
`
`form a 4 to 8 membered cycloheteroalkyl ring wherein the cycloheteroalkyl ring
`
`has an optional aryl ring fused thereto or an optional 3 to 7 membered cycloalkyl
`
`ring fused thereto;
`
`with the proviso that where X is l and y is 0, X is H, n is 0, and one of R1 and R2 is H and
`
`the other is alkyl, then R3 is other than pyridyl or substituted pyridyl;
`
`including all stereoisomers thereof;
`
`Q[and] a pharrnaceutically acceptable salt thereof[, or a prodrug ester thereof], and all
`
`stereoisomers thereof.
`
`Amend claim 12 as follows:
`
`12.
`
`A pharmaceutical combination comprising a [DP4 inhibitor] compound as defined
`
`in claim 1 and an antidiabetic agent other than a DP4 inhibitor for treating diabetes and related
`
`diseases, an anti-obesity agent and/or a lipid-modulating agent.
`
`sun-Amneal-IPR2o1§?c§’ri’1]d‘4°-fI5°’;?. 1006. Part 2, p. 277 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:26)(cid:26)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0536
`0536
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`Amend claim 13 as follows:
`
`PATENT
`
`13.
`
`The pharmaceutical combination as defined in claim 12 comprising said [DP4
`
`inhibitor] compound as defined in claim 1 and [an] tliantidiabetic agent other than a DP4
`
`inhibitor.
`
`Amend claim 16 as follows:
`
`16.
`
`The combination as defined in claim 13 wherein the compound as defined in
`
`claim 1 is present in a weight ratio to the antidiabetic agent within the range from about 0.01 to
`
`about 100:1.
`
`Amend claim 17 as follows:
`
`17.
`
`The combination as defined in claim 12 wherein the anti-obesity agent is a beta 3
`
`adrenergic agonist, a lipase inhibitor, [a serotonin (and dopamine) reuptake inhibitor,] a thyroid
`
`receptor beta compound, an anorectic agent, and/or a fatty acid oxidation upregulator.
`
`Amend claim 21 as follows:
`
`21.
`
`The combination as defined in claim 19 wherein the compound as defined in
`
`claim 1 [DP4 inhibitor] is present in a weight ratio to the lipid-modulating agent within the range
`
`from about 0.01 to about 100:1.
`
`Amend claim 22 as follows:
`
`22.
`
`A pharmaceutical combination comprising a [DP4 inhibitor] compound as defined
`
`in claim 1 and an agent for treating infertility, an agent for treating polycystic ovary syndrome,
`
`an agent for treating a growth disorder and/or frailty, an anti-arthritis agent, an agent for
`
`preventing Qinhibiting allograft rejection in transplantation, an agent for treating autoimmune
`
`disease, an anti-AIDS agent, an agent for treating inflammatory bowel disease/syndrome, an
`
`agent for treating anorexia nervosa, an anti-osteoporosis agent and/or an anti-obesity agent.
`
`Amend added claim 29 to read as follows:
`
`29.
`
`The composition of claim 27 or 28 further comprising an antidiabetic agent other
`
`than a DP4 inhibitor.
`
`Sun-Amneal-|PR201g5’@l’1](?4°-flibf. 1006. Part 2, p. 273 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:26)(cid:27)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0537
`0537
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`Amend added claim 30 to read as follows:
`
`PATENT
`
`30.
`
`The composition of claim 29 wherein the antidiabetic agent is metforrnin.
`
`Amend added claim 31 to read as follows:
`
`31.
`
`The composition of claim 29 wherein the antidiabetic agent is a SGLT2 inhibitor.
`
`Cancel added claims 36 and 37.
`
`Amend added claim 38 to read as follows:
`
`38.
`
`The method of any one of claims 32, 33, 34, or 35, wherein the pharmaceutical
`
`composition further comprises an antidiabetic agent other than a DP4 inhibitor.
`
`Amend added claim 39 to read as follows:
`
`39.
`
`The method of claim 38 wherein the antidiabetic agent is metforrnin.
`
`Amend added claim 40 to read as follows:\
`
`40.
`
`The method of claim 38 wherein the antidiabetic agent is a SGLT2 inhibitor.
`
`Add new claims 41 to 45 to read as follows:
`
`41.
`
`A method for treating type II diabetes in a mammal comprising administering to
`
`the mammal a pharmaceutical composition comprising a compound that is
`
`jm.
`
`sun-Amneal-IPR2o1§?c§’ri’1?c94°-fI5°’;?. 1006. Part 2, p. 279 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:26)(cid:28)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0538
`0538
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
`
`42.
`
`The method of claim 41, wherein the pharmaceutically acceptable salt is the
`
`hydrochloride salt.
`
`43.
`
`The method of any one of claims 41 or 42, wherein the pharmaceutical
`
`composition further comprises an antidiabetic agent other than a DP4 inhibitor.
`
`44.
`
`The method of claim 43, wherein the antidiabetic agent is metformin.
`
`45.
`
`The method of claim 43, wherein the antidiabetic agent is a SGLT2 inhibitor.
`
`Sun-Amneal-|PR201g5’@l’1?(l4°-f|E3)§. 1006. Part 2, p. 230 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:19)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0539
`0539
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`Complete Listing of Claims As Amended (including status identifiers):
`
`1.
`
`(Amended)
`
`A compound having the structure
`
`
`
`wherein X is 0 or 1 and y is 0 or 1, provided that
`
`X=l when y=0 and
`
`X=0 when y=l; and wherein
`
`n is 0 or 1;
`
`X is H or CN;
`
`R1, R2, R3 and R4 are the same or different and are independently selected from hydrogen,
`
`alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, bicycloalkyl, tricycloalkyl,
`
`alkylcycloalkyl, hydroxyalkyl, hydroxyalkylcycloalkyl, hydroxycycloalkyl,
`
`hydroxybicycloalkyl, hydroxytricycloalkyl, bicycloalkylalkyl, alkylthioalkyl,
`
`arylalkylthioalkyl, cycloalkenyl, aryl, aralkyl, heteroaryl, heteroarylalkyl,
`
`cycloheteroalkyl or cycloheteroalkylalkyl; all optionally substituted through
`
`available carbon atoms with l, 2, 3, 4 or 5 groups selected from hydrogen, halo,
`
`alkyl, polyhaloalkyl, alkoxy, haloalkoxy, polyhaloalkoxy, alkoxycarbonyl,
`
`alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, polycycloalkyl, heteroarylamino,
`
`arylamino, cycloheteroalkyl, cycloheteroalkylalkyl, hydroxy, hydroxyalkyl, nitro,
`
`sun-Amneal-IPR2o1§?c§’ri’1?t¥4°-fI5°5?. 1006. Part 2, p. 231 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:20)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0540
`0540
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`cyano, arnino, substituted arnino, alkylarnino, dialkylarnino, thiol, alkylthio,
`
`alkylcarbonyl, acyl, alkoxycarbonyl, arninocarbonyl, alkynylarninocarbonyl,
`
`alkylarninocarbonyl, alkenylarninocarbonyl, alkylcarbonyloxy,
`
`alkylcarbonylarnino, arylcarbonylarnino, alkylsulfonylarnino,
`
`alkylarninocarbonylarnino, alkoxycarbonylarnino, alkylsulfonyl, arninosulfinyl,
`
`arninosulfonyl, alkylsulfinyl, sulfonarnido or sulfonyl;
`
`and R1 and R3 may optionally be taken together to form (CR5R6)m where rn is 2 to 6, and
`
`R5 and R6 are the same or different and are independently selected from hydroxy,
`
`alkoxy, H, alkyl, alkenyl, alkynyl, cycloalkyl, halo, arnino, substituted arnino,
`
`cycloalkylalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,
`
`cycloheteroalkyl, cycloheteroalkylalkyl, alkylcarbonylarnino, arylcarbonylarnino,
`
`alkoxycarbonylarnino, aryloxycarbonylarnino, alkoxycarbonyl, aryloxycarbonyl,
`
`or alkylarninocarbonylarnino, or R1 and R4 may optionally be taken together to
`
`form (CR7R8)p wherein p is 2 to 6, and R7 and R8 are the same or different and are
`
`independently selected from hydroxy, alkoxy, cyano, H, alkyl, alkenyl, alkynyl,
`
`cycloalkyl, cycloalkylalkyl, cycloalkenyl, halo, arnino, substituted arnino, aryl,
`
`arylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl,
`
`alkylcarbonylarnino, arylcarbonylarnino, alkoxycarbonylarnino,
`
`aryloxycarbonylarnino, alkoxycarbonyl, aryloxycarbonyl, or
`
`alkylarninocarbonylarnino, or optionally R1 and R3 together with
`
`H~-—-—--1~~:
`
`‘
`
`1&4
`
`form a 5 to 7 rnernbered ring containing a total of 2 to 4 heteroatoms selected
`
`from N, O, S, S0, or S02;
`
`or optionally R1 and R3 together with
`
`sun-Amneal-IPR2o1§?c§’ri’1?t3"*4°-fI5°’;?. 1006. Part 2, p. 232 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:21)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0541
`0541
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`H_""""'N
`
`R 4
`
`form a 4 to 8 membered cycloheteroalkyl ring wherein the cycloheteroalkyl ring
`
`has an optional aryl ring fused thereto or an optional 3 to 7 membered cycloalkyl
`
`ring fused thereto;
`
`with the proviso that where X is l and y is 0, X is H, n is 0, and one of R1 and R2 is H and
`
`the other is alkyl, then R3 is other than pyridyl or substituted pyridyl;
`
`including all stereoisomers thereof;
`
`Q[and] a pharrnaceutically acceptable salt thereof[, or a prodrug ester thereof], and all
`
`stereoisomers thereof.
`
`2.
`
`(Original)
`
`The compound as defined in claim 1 having the structure:
`
`?3
`
`R2 R1
`
`/ N
`
`H
`
`1'].
`
`N
`
`R4
`
`o
`
`X
`
`_
`
`3.
`
`(Original)
`
`The compound as defined in claim 1 having the structure:
`
`3
`
`|R
`/ N
`
`R2 R1
`
`N
`
`H
`
`1'].
`
`R4
`
`o
`
`x
`
`_
`
`4.
`
`(Original)
`
`The compound as defined in claim 1 having the structure:
`
`sun-Amneal-IPR2o1§?é’ri’1?6‘49fI5°’;?. 1006. Part 2, p. 233 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:22)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0542
`0542
`
`

`
`DOCKET NO.: BMS—2856
`
`Application N0.: 13/308,658
`Office Action Dated: May 8, 2012
`
`R3
`
`R1
`
`PATENT
`
`N
`
`N
`
`/H W
`
`R4
`
`0
`
`NC
`
`5.
`
`Ori inal
`g
`
`The com ound as defined in claim 1 havin the structure:
`P
`g
`
`T3
`H/N
`
`R1
`
`1'1
`
`R4
`
`N
`
`o
`
`NC
`
`H
`\\\x\
`
`5
`E
`
`6.
`
`(Original)
`
`The compound as defined in claim 1 wherein:
`
`R3 is H, R1 is H, alkyl, cycloalkyl, bicycloalkyl, tricycloalkyl, alkylcycloalkyl,
`
`hydroxyalkyl, hydroxyalkylcycloalkyl, hydroxycycloalkyl hydroxybicycloalkyl,
`
`or hydroxytricycloalkyl,
`
`R2 is H or alkyl, n is 0,
`
`X is CN.
`
`7.
`
`(Original)
`
`The compound as defined in claim 1 wherein the cyclopropyl fused
`
`to the pyrrolidine has the configuration:
`
`Sun-Amneal-|PR201g5’@i’1?é4°-f|E3)§. 1006. Part 2, p. 234 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:23)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0543
`0543
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`8.
`
`(Original)
`
`A compound having the structure:
`
`N
`
`CN
`
`HO
`
`F
`
`NH2 0
`
`I
`
`H2N
`
`N
`
`o
`
`HO
`
`CN
`
`I
`
`PATENT
`
`N
`
`0
`
`NC
`
`H2N
`
`I
`
`H2N
`
`N: 5
`
`ONC
`
`I
`
`F
`
`H2N
`
`N: 5
`
`ONC
`
`I
`
`HM
`
`2
`
`Ni B
`
`CNI
`
`o
`
`HO
`
`H2N
`
`N; 5
`
`ONC
`
`or
`
`HO
`
`mm
`
`N
`
`0
`
`CN
`
`or a pharrnaceutically acceptable salt thereof.
`
`9.
`
`(Original)
`
`The compound as defined in claim 8 wherein the pharrnaceutically
`
`acceptable salt is the hydrochloride salt or the trifluoroacetic acid salt.
`
`10.
`
`(Original)
`
`A compound which is
`
`
`
`(lS,2 (ZS) ,3S,5S)
`
`Sun-Amneal-|PR201g5’@l’1?(§4°-f|E3)§. 1006. Part 2, p. 235 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:24)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0544
`0544
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`wherein R1
`
`is
`
`alkyl,
`
`cycloalkyl, bicycloalkyl,
`
`tricycloalkyl,
`
`alkylcycloalkyl,
`
`hydroxyalkyl, hydroxycycloalkyl, hydroxyalkylcycloalkyl, hydroxybicycloalkyl, or
`
`hydroxytricycloalkyl,
`
`OI‘
`
`
`
`(lR, 2S, 3 (ZS) , 5S)
`
`wherein R1
`
`is
`
`alkyl,
`
`cycloalkyl, bicycloalkyl,
`
`tricycloalkyl,
`
`alkylcycloalkyl,
`
`hydroxyalkyl, hydroxycycloalkyl, hydroxyalkylcycloalkyl, hydroxybicycloalkyl, or
`
`hydroxytricycloalkyl.
`
`11.
`
`(Original)
`
`A pharmaceutical composition comprising a compound as defined
`
`in claim 1 and a pharrnaceutically acceptable carrier therefor.
`
`12.
`
`(Amended)
`
`A pharmaceutical combination comprising a [DP4 inhibitor]
`
`compound as defined in claim 1 and an antidiabetic agent other than a DP4 inhibitor for treating
`
`diabetes and related diseases, an anti-obesity agent and/or a lipid-modulating agent.
`
`13.
`
`(Twice Amended)
`
`The pharmaceutical combination as defined in claim 12
`
`comprising said [DP4 inhibitor] compound as defined in claim 1 and [an] ‘tl1_eantidiabetic agent
`
`other than a DP4 inhibitor.
`
`14.
`
`(Original)
`
`The combination as defined in claim 13 wherein the antidiabetic
`
`agent is 1, 2, 3 or more of a biguanide, a sulfonyl urea, a glucosidase inhibitor, a PPAR agonist, a
`
`PPAR/ dual agonist, an SGLT2 inhibitor, an aP2 inhibitor, a glycogen phosphorylase inhibitor,
`
`an AGE inhibitor, an insulin sensitizer, a glucagon-like peptide-1 (GLP-1) or mimetic thereof,
`
`insulin and/or a meglitinide.
`
`Sun-Amneal-|PR201g5’@l’1?(74°-f|E3)§. 1006. Part 2, p. 286 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:25)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0545
`0545
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`15.
`
`(Original)
`
`The combination as defined in Claim 14 wherein the antidiabetic
`
`agent is 1, 2, 3 or more of metforrnin, glyburide, glimepiride, glipyride, glipizide,
`
`chlorpropamide, gliclazide, acarbose, miglitol, pioglitazone, troglitazone, rosiglitazone, insulin,
`
`Gl-262570, isaglitazone, JTT-501, NN-2344, L895645, YM-440, R-119702, AJ9677,
`
`repaglinide, nateglinide, KAD1129, AR-HO39242, GW-409544, KRP297, AC2993, Exendin-4,
`
`LY307161, NN2211, and/or LY315902.
`
`16.
`
`(Amended)
`
`The combination as defined in claim 13 wherein the compound Q
`
`defined in claim 1 is present in a weight ratio to the antidiabetic agent within the range fiom
`
`about 0.01 to about 100:1.
`
`17.
`
`(Amended)
`
`The combination as defined in claim 12 wherein the anti-obesity
`
`agent is a beta 3 adrenergic agonist, a lipase inhibitor, [a serotonin (and dopamine) reuptake
`
`inhibitor,] a thyroid receptor beta compound, an anorectic agent, and/or a fatty acid oxidation
`
`upregulator.
`
`18.
`
`(Original)
`
`The combination as defined in claim 17 wherein the anti-obesity
`
`agent is orlistat, ATL-962, AJ9677, L750355, CP331648, sibutramine, topiramate, axokine,
`
`dexamphetamine, phenterrnine, phenylpropanolamine, famoxin, and/or mazindol.
`
`19.
`
`(Original)
`
`The combination as defined in claim 12 wherein the lipid
`
`modulating agent is an MTP inhibitor, an HMG COA reductase inhibitor, a squalene synthetase
`
`inhibitor, a fibric acid derivative, an upregulator of LDL receptor activity, a lipoxygenase
`
`inhibitor, an ACAT inhibitor, a cholesteryl ester transfer protein inhibitor, or an ATP citrate
`
`lyase inhibitor.
`
`20.
`
`(Original)
`
`The combination as defined in claim 19 wherein the lipid
`
`modulating agent is pravastatin, lovastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin,
`
`nisvastatin, visastatin, fenofibrate, gemfibrozil, clofibrate, implitapide, CP-529,414, avasimibe,
`
`TS-962, MD-700, and/or LY295427.
`
`Sun-Amneal-|PR201g5’@l’1?6§4°-f|E3)§. 1006. Part 2, p. 237 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:26)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0546
`0546
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`21.
`
`(Amended)
`
`The combination as defined in claim 19 wherein the compound as
`
`defined in claim 1 [DP4 inhibitor] is present in a weight ratio to the lipid-modulating agent
`
`within the range from about 0.01 to about 100:1.
`
`22.
`
`(Amended)
`
`A pharmaceutical combination comprising a [DP4 inhibitor]
`
`compound as defined in claim 1 and an agent for treating infertility, an agent for treating
`
`polycystic ovary syndrome, an agent for treating a growth disorder and/or frailty, an anti-arthritis
`
`agent, an agent for preventing Qinhibiting allograft rejection in transplantation, an agent for
`
`treating autoimmune disease, an anti-AIDS agent, an agent for treating inflammatory bowel
`
`disease/syndrome, an agent for treating anorexia nervosa, an anti-osteoporosis agent and/or an
`
`anti-obesity agent.
`
`23.
`
`(Canceled)
`
`24.
`
`(Canceled)
`
`25.
`
`New A com ound that is
`
`
`
`' or a harrnaceuticall acce table salt thereof.
`
`26.
`
`New The com ound as defined in claim 25 wherein the harrnaceuticall
`
`acce table salt is the h drochloride salt.
`
`27.
`
`New A harrnaceutical com osition com risin the com ound of claim 25 and
`
`a pharmaceutically acceptable carrier therefor.
`
`sun-Amneal-IPR2o1§?c§’ri’1?c?4°-fI5°5?. 1006. Part 2, p. 233 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:27)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0547
`0547
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`28.
`
`New A harrnaceutical com osition com risin the com ound of claim 26 and
`
`a pharmaceutically acceptable carrier therefor.
`
`29.
`
`New/Amended
`
`The com osition of claim 27 or 28 further com risin an
`
`antidiabetic agent other than a DP4 inhibitor.
`
`30.
`
`New/Amended
`
`The com osition of claim 29 wherein the antidiabetic a ent
`
`is metforrnin.
`
`3 l.
`
`New/Amended
`
`The com osition of claim 29 wherein the antidiabetic
`
`agent is a SGLT2 inhibitor.
`
`32.
`
`New Amethod for treatin diabetes insulin resistance h
`
`er 1 cemia
`
`hgperinsulinemia, impaired glucose homeostasis, or impaired glucose tolerance in a mammal
`
`comprising administering to the mammal a pharmaceutical composition comprising a compound
`
`that is
`
`
`
`or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
`
`33.
`
`New The method of claim 32 wherein the harrnaceuticall acce table salt is
`
`the hydrochloride salt.
`
`34.
`
`New The method of claim 32 for treatin diabetes.
`
`sun-Amneal-IPR2o1§?c§’ri’13c94°-fI5°5?. 1006. Part 2, p. 239 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:27)(cid:28)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0548
`0548
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`35.
`
`New The method of claim 33 for treatin diabetes.
`
`36.
`
`(Canceled)
`
`37.
`
`(Canceled)
`
`38.
`
`New/Amended
`
`The method of an one of claims 32 33 34 or 35 wherein
`
`the pharmaceutical composition further comprises an antidiabetic agent other than a DP4
`
`inhibitor.
`
`39.
`
`New/Amended
`
`The method of claim 38 wherein the antidiabetic a ent is
`
`metformin.
`
`40.
`
`New/Amended
`
`The method of claim 38 wherein the antidiabetic a ent is a
`
`SGLT2 inhibitor.
`
`41.
`
`New A method for treatin t
`
`e II diabetes in a mammal com risin
`
`administerin to the mammal a harrnaceutical com osition com risin a com ound that is
`
`
`
`ora harrnaceuticall acce table salt thereof anda harrnaceuticall acce table carrier therefor.
`
`42.
`
`New The method of claim 41 wherein the harrnaceuticall acce table salt is
`
`the hydrochloride salt.
`
`43.
`
`New The method of an one of claims 41 or 42 wherein the harrnaceutical
`
`composition further comprises an antidiabetic agent other than a DP4 inhibitor.
`
`sun-Amneal-IPR2o1§?é’ri’13d49fI5°’;?. 1006. Part 2, p. 290 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:28)(cid:19)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0549
`0549
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`44.
`
`New The method of claim 43 wherein the antidiabetic a ent is rnetforrnin.
`
`45.
`
`New The method of claim 43 wherein the antidiabetic a ent is a SGLT2
`
`inhibitor.
`
`Sun-Amneal-|PR201g5’@i’13(¥4°-f|E3)§. 1006. Part 2, p. 291 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:28)(cid:20)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0550
`0550
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`REMARKS
`
`PATENT
`
`Claims 1, 12, 13, 16, 17, 21, 22, 29, 30, 31, 38, 39, and 40 are amended herein. Claims
`
`36 and 37 are canceled and new claims 41 to 45 are added herein. Support for each of the new
`
`claims and/or amendments is implicit in the prior versions of the claims, or is set forth in the
`
`chart that was submitted with the preliminary amendment filed December 1, 2011. No new
`
`matter is added.
`
`After entry of the present amendments, claims 1-22, 25-35, and 38-45 will remain
`
`pending.
`
`Summary of the Interview
`
`The undersigned thanks Examiners Polansky and Anderson for the courtesy of the
`
`telephonic interview conducted on May 22, 2012. The pending claims were discussed, as well as
`
`the objections and alleged rejections set forth in the May 8, 2012 Office Action. In particular,
`
`the undersigned thanks the Examiners for clarifying the objections to the Applicants’ reissue
`
`declaration, the incorporation of corrections provided in the Certificates of Correction for the
`
`original patent, and the procedures to be followed to remedy any perceived errors.
`
`Reissue Oath/Declaration
`
`The Office alleges that the reissue declaration is defective because it fails to identify at
`
`least one specific error which is relied upon to support the reissue application. Without
`
`conceding the propriety of this assertion and in the interest of advancing prosecution of the
`
`application, a supplemental declaration is filed herewith, which states that the specific error
`
`relied upon is that, while the patent included claims encompassing the compound below, the
`
`patentee failed to include claims that are specifically directed to the compound:
`
`
`
`sun-Amneal-IPR2o1§?c§’ri’13¢3"*4°-fI5°’;?. 1006. Part 2, p. 292 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:28)(cid:21)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0551
`0551
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`or a pharmaceutical salt thereof, as set forth in added claims 25 to 35 and 38 to 45.
`
`The supplemental declaration also sets forth the mailing addresses and residences of the
`
`inventors. Patent Owner asserts that the supplemental reissue declaration complies with 37
`
`C.F.R. 1.175.
`
`Certificates of Correction
`
`The Office has noted that changes to the specification and claims made via the
`
`Certificates of Correction for the original patent should be incorporated into the reissue patent.
`
`Said changes have been effected by the Patent Owner according to the procedure described in the
`
`Office Action. See MPEP 1453.VI.(C).
`
`Claim Objections
`
`The Office objects to added claim 38 for reciting, "The method of any one of claims 32,
`
`33, 34, 25, 26, or 37..." Added claim 38 has been amended to recite "The method of any one of
`
`claims 32, 33, 34, or 35 ..." Withdrawal of the objection is requested.
`
`The Office obj ects to claim 38 for reciting "an agent for preventing inhibiting allograft
`
`rejection in transplantation..." As discussed in the telephonic interview, claim 22, not claim 38,
`
`recites the identified language. Claim 22 has accordingly been amended to recite, "an agent for
`
`preventing Q inhibiting allograft rejection in transplantation." Withdrawal of the obj ection is
`
`requested.
`
`Rejections under 35 U.S.C. § 112, Second Paragraph
`
`Claims 1-7, 11-22, 29-31, and 38-40 stand rejected under 35 U.S.C. § 112, second
`
`paragraph, as allegedly indefinite. In light of the present claim amendments, withdrawal of the
`
`rejections is requested.
`
`Claim 1 has been amended to more clearly identify pharrnaceutically acceptable salts as
`
`an alternative, z'.e.,
`
`"0_l‘ a pharrnaceutically acceptable salt thereof." The rejection of claim 1
`
`therefore is considered moot.
`
`Sun-Amneal-|PR201g5’@i’13(ll4°-flibf. 1006. Part 2, p. 293 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:28)(cid:22)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0552
`0552
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`Claim 12 has been amended to recite "a [DP4 inhibitor] compound as defined in claim 1."
`
`Claim 13 has been similarly amended. The rejection of claims 12 and 13 is considered moot.
`
`Claim 22 has been amended to recite "A pharmaceutical combination comprising a [DP4
`
`inhibitor] compound as defined in claim 1." The rejection of claim 22 is considered moot.
`
`Patent Owner notes that claim 21 has been amended to recite, "The combination as defined in
`
`claim 19 wherein the compound as defined in claim 1 [DP4 inhibitor] is present in a weight ratio
`
`to the lipid-modulating agent within the range from about 0.01 to about 100:1." Claim 16 has
`
`been amended similarly to claim 21.
`
`Claim 17 has been amended to delete the limitation, "a serotonin (and dopamine)
`
`reuptake inhibitor." The rejection of claim 17 is considered moot.
`
`Claim 29 has been amended to recite, "The composition of claim 27 or 28 further
`
`comprising Q antidiabetic agent other than a DP4 inhibitor." The rejection of claim 29 is
`
`considered moot. Dependent claims 30 and 31 have been amended to recite, "wherein the
`
`antidiabetic agent is .
`
`.
`
`."
`
`Claim 38 has been amended to recite, "The method of any one of claims 32, 33, 34, or
`
`35." The rejection is considered moot.
`
`. Claim 38 has also been amended to recite, “wherein the
`
`pharmaceutical composition further comprises an antidiabetic agent other than a DP4 inhibitor.”
`
`Dependent claims 39 and 40 have been amended to recite “wherein the antidiabetic agent is...”
`
`Dependent claim 40 has also been amended to recite “The method of claim 38. . .”
`
`Rejections under 35 U.S.C. § 112, First Paragraph
`
`Claims 1-7 and 11-22 stand rejected under 35 U.S.C. §112, first paragraph, as allegedly
`
`not complying with the written description requirement for reciting the "prodrug esters" of the
`
`compounds of claim 1. While not conceding the propriety of the rejection, the term "prodrug
`
`ester thereof" has been deleted from claim 1 to advance prosecution. Withdrawal of the rejection
`
`is requested.
`
`Sun-Amneal-|PR201g?@l’fi4°-f|E3)§. 1006. Part 2, p. 294 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(cid:36)(cid:80)(cid:81)(cid:72)(cid:68)(cid:79)(cid:16)(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:20)(cid:19)(cid:23)(cid:16)(cid:3)(cid:40)(cid:91)(cid:17)(cid:3)(cid:20)(cid:19)(cid:19)(cid:25)(cid:17)(cid:3)(cid:51)(cid:68)(cid:85)(cid:87)(cid:3)(cid:21)(cid:15)(cid:3)(cid:83)(cid:17)(cid:3)(cid:21)(cid:28)(cid:23)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:26)(cid:22)
`
`0553
`0553
`
`

`
`DOCKET NO.: BMS—2856
`
`Application No.: 13/308,658
`Office Action Dated: May 8, 2012
`
`PATENT
`
`CONCLUSION
`
`Patent Owner believes that the foregoing addresses all issues raised in the Office Action
`
`dated May 8, 2012, and that the application is now in condition for allowance. If any further
`
`issues remain, the Examiner is invited to contact Patent Owner’s undersigned representative at
`
`the contact number listed below.
`
`/S. Maurice Valla/
`S. Maurice Valla
`
`Registration No. 43,966
`
`Date: August 8, 2012
`
`Woodcock Washbum LLP
`
`Cira Centre
`
`2929 Arch Street, 12th Floor
`Philadelphia, PA 19104-2891
`Telephone: (215) 568-3100
`Facsimile: (215) 568-3439
`
`Sun-Amneal-|PR201g5’@i’13(§4°-f|E3)§. 1006. Part 2, p. 295 of 373
`(cid:54)(cid:88)(cid:81)(cid:16)(c