WO99/43706
`
`PCT/DK99/00082
`
`•3
`
`79
`4Lys23
`34Lys23-(Glut-AUt)-GLP-1 (7-36)amide; Arg25
`Arg28•34Lys23-(Glut-ALit)-GLP-1 (7-36); Arg26
`-
`•
`4Lys23-(Glut-Alit)-GLP-1 (7-38); Gly8Asp19Arg26
`34Lys23-(Glut(cid:173)
`•
`34Lys23-(Glut-
`34Lys23-(Glut-Alit)-GLP-1 (7-36); Gly8Asp19Arg26
`•
`·
`34Lys23-(Glut-Alit)-GLP-1 (7-36)amide;
`Gly8Asp 17 Arg26
`•
`
`(Glut-Alit)-GLP-1 (7-37); Arg26
`
`•3
`
`Alit)-GLP-1 (7-36); Gty8Asp 17 Arg26
`
`Alit)-GLP-1 (7-36)amide;
`
`34Lys23-(Glut-Alit)-GLP-1 (7-38);
`5 Gly8 Asp 19Arg26
`34Lys23-(Glut-Alit)-GLP-1 (7-37); Gly8Asp19Arg26
`·
`·
`
`34Lys23-(Glut-Alit)-GLP-1 (7-38);
`Gly8Asp 17 Arg26
`•
`34Lys27-(Glut-Alit)-GLP-1 (7-36)amide; Arg26
`34Lys27
`34Lys27-(Glut-Alit)-GLP-1 (7-36); Arg26
`Arg26
`·
`-
`•
`·
`34Lys27-(Glut(cid:173)
`34Lys27-(Glut-Alit)-GLP-1 (7-38); Gly8Asp19Arg26
`(Glut-Alit)-GLP-1 (7-37); Arg26
`·
`•
`34Lys27 -(Glut-
`Alit)-GLP-1 (7-36); Gly8Asp 17 Arg26
`34Lys27-(Glut-Alit)-GLP-1 (7-36); Gly8Asp 19Arg26
`•
`•
`
`1 o Alit)-GLP-1 (7-36)amide;
`
`Gly8Asp 17 Arg26
`34Lys27-(Glut-Alit)-GLP-1 (7-36)amide;
`•
`
`Gly8Asp 19Arg26
`34Lys27-(Glut-Alit)-GLP-1 (7-37); Gly8Asp19Arg26
`34Lys27-(Glut-ALit)-GLP-1 (7-38);
`·
`·
`34Lys27-(Glut-Alit)-GLP-1 (7-38);
`Gly8Asp 17Arg26
`•
`34Lys 18-(Glut-Alit)-GLP-1 (7-36)amide; Arg26
`34Lys 18-(Glut-Alit)-GLP-1 (7-36); Arg26
`·
`·
`
`34Lys 18
`·
`
`-
`
`Arg26
`
`4Lys 18-(Glut-
`
`•3
`
`34Lys 18-(Glut-Alit)-GLP-1 (7-38); Val8Asp19Arg26
`(Glut-Alit)-GLP-1 (7-37); Arg26
`•
`
`15
`
`Alit)-GLP-1 (7-36); Val8Asp17 Arg26
`34Lys 18-(Glut-Alit)-GLP-1 (7-36); Val8Asp19Arg26
`·
`
`34Lys 18-(Glut(cid:173)
`·
`
`4Lys 18-(Glut-Alit)-GLP-1 (7-36)amide;
`
`•3
`
`Val8Asp17 Arg26
`
`Alit)-GLP-1 (7-36)amide;
`
`Val8Asp 19Arg26
`34Lys 18-(Glut-Alit)-GLP-1 (7-37); Val8Asp19Arg26
`34Lys 18-(Glut-Alit)-GLP-1 (7-38);
`•
`•
`
`Val8Asp 17 Arg26
`34Lys 18-(Glut-Alit)-GLP-1 (7-38);
`•
`
`34Lys23
`34Lys23-(Glut-ALit)-GLP-1 (7-36)amide; Arg26
`Arg26
`34Lys23-(Glut-Alit)-GLP-1 (7-36); Arg26
`-
`•
`•
`•
`34Lys23-(Glut-Alit)-GLP-1 (7-38); Val8Asp19Arg26
`34Lys23-(Glut(cid:173)
`(Glut-ALit)-GLP-1 (7-37); Arg26
`•
`·
`
`20
`
`Alit)-GLP-1 (7-36); Val8Asp17 Arg26
`34Lys23-(Glut-Alit)-GLP-1 (7-36); Val8Asp 19Arg26
`34Lys23-(Glut(cid:173)
`•
`•
`
`Alit)-GLP-1 (7-36)amide;
`
`Val8Asp 17 Arg26
`34Lys23-(Glut-Alit)-GLP-1 (7-36)amide;
`•
`
`Val8Asp19Arg26
`34Lys23-(Glut-Alit)-GLP-1(7-37); Val8Asp 19Arg26
`34Lys23-(Glut-Alit)-GLP-1(7-38);
`·
`·
`
`Val8Asp 17 Arg26
`34Lys23-(Glut-Alit)-GLP-1 (7-38);
`•
`
`25
`
`Arg26
`34Lys27 -(Glut-Alit)-GLP-1 (7-36); Arg26
`•
`
`34Lys27
`34Lys27-(Glut-ALit)-GLP-1 (7-36)amide; Arg26
`-
`•
`•
`
`(Glut-Alit)-GLP-1 (7-37); Arg26
`34Lys27-(Glut-Alit)-GLP-1 (7-38); Val8Asp 19Arg26
`34Lys27-(Glut(cid:173)
`•
`·
`
`ALit)-GLP-1 (7-36); Val8Asp17 Arg26
`34Lys27-(Glut-Alit)-GLP-1 (7-36); Val8Asp19Arg26
`•
`
`34Lys27-(Glut(cid:173)
`•
`
`4Lys27-(Glut-Alit)-GLP-1 (7-36)amide;
`
`Val8Asp17 Arg26
`
`•3
`
`Alit)-GLP-1 (7-36)amide;
`
`Val8Asp19Arg26
`Val8Asp17Arg26
`
`4Lys27-(Glut-Alit)-GLP-1(7-38);
`
`•3
`
`30
`
`34Lys27 -(Glut-Alit)-GLP-1 (7-37); Val8Asp 19Arg26
`·
`
`34Lys27-(Glut-Alit)-GLP-1 (7-38);
`·
`
`4Lys 18
`-
`
`34Lys 18-(Glut-Alit)-GLP-1 (7-36)amide; Arg26
`·
`
`•3
`
`34Lys 18-(Glut-Alit)-GLP-1 (7-36); Arg26
`·
`
`Arg26
`
`34Lys18-(Glut-Alit)-GLP-1 (7-38); Ser8Asp 19Arg26
`34Lys 18-(Glut(cid:173)
`(Glut-Alit)-GLP-1 (7-37); Arg26
`•
`·
`
`34Lys18-(Glut(cid:173)
`4Lys 18-(Glut-ALit)-GLP-1 (7-36); Ser8Asp19Arg26
`•
`
`Alit)-GLP-1 (7-36); Ser8Asp17 Arg26
`
`•3
`
`4Lys 18-(Glut-Alit)-GLP-1 (7-36)amide;
`
`Ser8 Asp17 Arg26
`
`•3
`
`ALit)-GLP-1 (7-36)amide;
`
`FRESENIUS EXHIBIT 1033
`Page 81 of 270
`
`

`

`WO 99/43706
`
`PCT/DK99/00082
`
`Ser8Asp 19Arg26·34Lys 18-(Glut-Alit)-GLP-1 (7-37); Ser8Asp 19Arg26•34Lys 18-(Glut-ALit)-GLP-1 (7-38);
`
`•
`
`•
`
`-
`
`•
`
`10
`
`15
`
`20
`
`25
`
`·
`
`80
`
`Ser8Asp 17 Arg26·34Lys 18-(Glut-Alit)-GLP-1 (7-38);
`34Lys23 -( Glut-ALit)-GLP-1 (7 -36)amide; Arg26·34Lys23
`Arg26·34Lys23 -( Glut-ALit)-GLP-1 (7 -36); Arg26
`(Glut-Alit)-GLP-1 (7-37); Arg26·34Lys23-(Glut-Alit)-GLP-1 (7-38); Ser8Asp 19Arg26·34Lys23-(Glut-
`5 ALit)-GLP-1 (7-36); Ser8Asp17 Arg26·34Lys23-(Glut-ALit)-GLP-1 (7-36); Ser8Asp19Arg26·34Lys23-(Glut(cid:173)
`Ser8 Asp17 Arg26·34Lys23-(Glut-Alit)-GLP-1 (7-36)amide;
`Alit)-GLP-1 (7-36)amide;
`Ser8Asp19Arg26·34Lys23-(Glut-ALit)-GLP-1(7-37); Ser8Asp19Arg26·34Lys23-(Glut-Alit)-GLP-1(7-38);
`Ser8Asp17 Arg26·34Lys23-(Glut-ALit)-GLP-1 (7-38);
`34Lys27 -
`34Lys27 -(Glut-ALit)-GLP-1 (7-36)amide; Arg26
`Arg26·34Lys27-(Glut-Alit)-GLP-1 (7-36); Arg26
`(Glut-Alit)-GLP-1 (7-37); Arg26·34Lys27-(Glut-ALit)-GLP-1 (7-38); Ser8Asp19Arg26·34Lys27-(Glut(cid:173)
`Alit)-G LP-1 (7 -36); Ser8 Asp 17 Arg26·34Lys27 -( Glut-Alit)-GLP-1 (7 -36); Ser8 Asp 19 Arg26·34Lys27 -( Glut(cid:173)
`Ser8Asp17 Arg26·34Lys27-(Glut-Alit)-GLP-1 (7-36)amide;
`ALit)-G LP-1 (7-36)amide;
`Ser8Asp19Arg26·34Lys27-(Glut-Alit)-GLP-1(7-37); Ser8Asp19Arg26·34Lys27-(Glut-ALit)-GLP-1(7-38);
`Ser8Asp 17 Arg26·34Lys27-(Glut-Alit)-GLP-1 (7-38);
`Arg26·34Lys 18-(Glut-Alit)-GLP-1 (7-36); Arg26·34Lys 18-(Glut-Alit)-GLP-1 (7-36)amide; Arg26·34Lys 18-
`•34Lys 18-(Glut-ALit)-GLP-1 (7-38); Thr8Asp19Arg26·34Lys18-(Glut(cid:173)
`(Glut-Alit)-GLP-1 (7-37); Arg26
`Alit)-GLP-1 (7-36); Thr8Asp17 Arg26·34Lys 18-(Glut-Alit)-GLP-1 (7-36); Thr8Asp19Arg26·34Lys 18-(Glut(cid:173)
`Thr8Asp17 Arg26·34Lys 18-(Glut-Alit)-GLP-1 (7-36)amide;
`Alit)-GLP-1 (7-36)amide;
`
`Thr8Asp 19Arg26·34Lys 18-(Glut-Alit)-GLP-1 (7-37); Thr8Asp 19Arg26•34Lys 18-(Glut-Alit)-GLP-1 (7-38);
`Thr8Asp17 Arg26·34Lys 18-(Glut-ALit)-GLP-1 (7-38);
`Arg26·34Lys23-(Glut-Alit)-GLP-1 (7-36); Arg26·34Lys23-(Glut-Alit)-GLP-1 (7-36)amide; Arg26·34Lys23-
`34Lys23-(Glut-Alit)-GLP-1 (7-38); Thr8Asp 19Arg26
`4Lys23-(Glut(cid:173)
`(Glut-Alit)-GLP-1 (7-37); Arg26
`•
`Alit)-GLP-1 (7-36); Thr8Asp17 Arg26·34Lys23-(Glut-Alit)-GLP-1 (7-36); Thr8Asp19Arg26·34Lys23-(Glut(cid:173)
`Thr8Asp 17 Arg26·34Lys23-(Glut-Alit)-GLP-1 (7-36)amide;
`Alit)-GLP-1 (7-36)amide;
`Thr8Asp19Arg26
`34Lys23-(Glut-Alit)-GLP-1 (7-37); Thr8Asp19Arg26·34Lys23-(Glut-Alit)-GLP-1 (7-38);
`34Lys23-(Glut-ALit)-GLP-1(7-38);
`Thr8Asp17Arg26
`·
`Arg26·34Lys27-(Glut-ALit)-GLP-1 (7-36); Arg26·34Lys27-(Glut-Alit)-GLP-1 (7-36)amide; Arg26·34Lys27-
`34Lys27 -(Glut-Alit)-GLP-1 (7-38); Thr8Asp19Arg26·34Lys27-(Glut(cid:173)
`(Glut-Alit)-GLP-1 (7-37); Arg26
`•
`34Lys27 -(Glut-Alit)-GLP-1 (7-36); Thr8Asp 19Arg26·34Lys27-(Glut-
`Alit)-GLP-1 (7-36); Thr8Asp17 Arg26
`Thr8Asp17 Arg26·34Lys27 -(Glut-Alit)-GLP-1 (7-36)amide;
`30 Alit)-GLP-1 (7-36)amide;
`Thr8Asp19Arg26·34Lys27-(Glut-Alit)-GLP-1 (7-37); Thr8Asp 19Arg26
`34Lys27-(Glut-Alit)-GLP-1 (7-38);
`Thr8Asp17 Arg26·34Lys27-(Glut-Alit)-GLP-1 (7-38);
`Arg25Lys34-(Aspa-ADod)-GLP-1 (7-36); Arg34Lys26-(Aspa-ADod)-GLP-1 (7-36);
`(Aspa-ADod)-GLP-1 (7-36); Arg26Lys34-{Aspa-ADod)-GLP-1 (7-36)amide; Arg34
`
`•3
`
`Arg2s.34Lys36-
`
`Lys26-(Aspa-
`
`·
`
`•
`
`FRESENIUS EXHIBIT 1033
`Page 82 of 270
`
`

`

`WO99/43706
`
`PCT/DK99/00082
`
`81
`
`ADod)-GLP-1 (7-36)amide; Arg26
`
`34Lys36-(Aspa-ADod)-GLP-1 (7-36)amide; Arg26 Lys34-(Aspa(cid:173)
`•
`34Lys36-(Aspa-ADod)-GLP-
`ADod)-GLP-1 (7-37); Arg34Lys26-(Aspa-ADod)-GLP-1 (7-37); Arg26
`•
`
`1 (7-37); Arg26Lys34 -(Aspa-ADod)-GLP-1 (7-38); Arg34Lys26 -(Aspa-ADod)-GLP-1 (7-38)
`Arg34Lys26
`-
`
`Arg28
`34Lys38-(Aspa-ADod)-GLP-1 (7-38); Arg26Lys34-(Aspa-ADod)-GLP-1 (7-39);
`•
`
`5
`
`(Aspa-ADod)-GLP-1 (7-39); Arg26
`34Lys39-(Aspa-ADod)-GLP-1 (7-39);
`•
`
`Gly8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-36);
`
`Glya Arg34Lys26-(Aspa-ADod)-GLP-1 (7-36);
`
`4Lys36-(Aspa-ADod)-GLP-1 (7-36); Gly8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-36)amide;
`
`Gly8Arg26
`
`•3
`
`Gly8Arg34Lys26-(Aspa-ADod)-GLP-1 (7-36)amide;
`
`GlyaArg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-
`·
`
`36)amide; Gly8 Arg26Lys34-(Aspa-ADod)-GLP-1 (7-37); Gly8Arg34Lys26-(Aspa-ADod)-GLP-1 (7-
`
`1 o
`
`37); Gly8Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-37); Gly8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-38);
`•
`
`GlyaArg34Lys26 -(Aspa-ADod)-GLP-1 (7-38)
`
`34Lys38-(Aspa-ADod)-GLP-1 (7-38);
`Gly8Arg26
`•
`
`Gly8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-39);
`
`Gly8Arg34Lys26-(Aspa-ADod)-GLP-1 (7-39);
`
`GlyaArg26
`
`•3
`
`4Lys39-(Aspa-ADod)-GLP-1(7-39);
`
`Vais Arg26Lys34-(Aspa-ADod)-GLP-1 (7-36);
`
`ValaArg34Lys26-(Aspa-ADod)-GLP-1 (7-36);
`
`15
`
`Vala Arg26
`34Lys36 -(Aspa-ADod)-GLP-1 (7-36); Vala Arg26Lys34-(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`
`ValaArg34Lys26-(Aspa-ADod)-GLP-1 (7-36)amide;
`
`Val8 Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-
`•
`
`36)amide; ValaArg26Lys34-(Aspa-ADod)-GLP-1 (7-37); ValaArg34Lys26-(Aspa-ADod)-GLP-1 (7-37);
`
`Val8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-38);
`Vais Arg26·34Lys38-(Aspa-ADod)-GLP-1 (7-38);
`
`ValaArg34Lys26-(Aspa-ADod)-GLP-1 (7-39);
`
`Ser8 Arg34Lys26-(Aspa-ADod)-GLP-1 (7-36);
`
`4Lys36-(Aspa-ADod)-GLP-1 (7-37);
`
`•3
`
`ValaArg26
`
`ValaArg34Lys26-(Aspa-ADod)-GLP-1 (7-38)
`
`ValaArg26Lys34-(Aspa-ADod)-GLP-1 (7-39);
`4Lys39 -(Aspa-ADod)-GLP-1 (7-39);
`Ser8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-36);
`
`Vais Arg26
`
`•3
`
`20
`
`34Lys36-(Aspa-ADod)-GLP-1 (7-36); Ser8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-36)amide;
`Ser8Arg26
`•
`
`Ser8Arg34Lys26-(Aspa-ADod)-GLP-1 (7-36)amide;
`
`Ser8Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-
`•
`
`25
`
`36)amide; Ser8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-37); Ser8Arg34Lys26-(Aspa-ADod)-GLP-1 (7-
`
`37); Ser8Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-37); Ser8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-38);
`•
`Ser8 Arg34Lys26-(Aspa-ADod)-GLP-1 (7-38)
`Ser8Arg26
`34Lys38-(Aspa-ADod)-GLP-1(7-38);
`·
`
`Ser8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-39);
`
`Ser8Arg34Lys26-(Aspa-ADod)-GLP-1 (7-39);
`
`34Lys39 -(Aspa-ADod)-GLP-1 (7-39);
`Ser8 Arg26
`•
`
`30
`
`Thr8 Arg26Lys34-(Aspa-ADod)-GLP-1 (7-36);
`
`Thr8 Arg34Lys26 -(Aspa-ADod)-GLP-1 (7-36);
`
`Thr8Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-36);
`Thr8Arg28Lys34-(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`Thr8 Arg34Lys26 -(Aspa-ADod)-GLP-1 (7-36)amide;
`
`Thr8 Arg26
`
`4Lys36-(Aspa-ADod)-GLP-1 (7-
`
`•3
`
`36)amide; Tor8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-37); Thr8Arg34Lys26-(Aspa-ADod)-GLP-1 (7-
`
`4Lys36-(Aspa-ADod)-GLP-1 (7-37); Thr8Arg26Lys34-(Aspa-ADod)-GLP-1 (7-38);
`
`•3
`
`37); Tor8Arg26
`
`FRESENIUS EXHIBIT 1033
`Page 83 of 270
`
`

`

`WO99/43706
`
`PCT/DK99/00082
`
`Thr8 Arg34Lys26-{Aspa-ADod}-GLP-1 (7-38)
`
`Thr8 Arg26
`34Lys38-(Aspa-ADod)-GLP-1 (7-38);
`•
`
`82
`
`Thr8 Arg34Lys26 -(Aspa-ADod)-GLP-1 (7-39);
`
`
`
`Gly8Glu35 Arg26•34Lys36-(Aspa-ADod)-GLP-1 (7-36)amide;
`
`Thr8 Arg26Lys34-(Aspa-ADod}-GLP-1 (7-39);
`Thr8Arg26•34Lys39-(Aspa-ADod)-GLP-1 (7-39); Gly6Glu35Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-36);
`•
`34Lys37 -(Aspa-ADod)-
`GlysGlu36 Arg26
`•
`34Lys39-(Aspa(cid:173)
`34Lys38-(Aspa-ADod)-GLP-1 (7-38); Gly8Glu38Arg26
`5 GLP-1 (7-37); GlysGlu37 Arg26
`·
`·
`4Lys36-(Aspa-ADod)-GLP-1 (7-36); Gly8Glu35Arg26
`4Lys36
`-
`Gly8Glu36 Arg26
`4Lys37 -(Aspa-ADod)-GLP-1 (7-37);
`
`•3
`
`•3
`
`•3
`
`AOod)-GLP-1 (7-39}; GlysGlu35Arg26
`
`(Aspa-ADod}-GLP-1 (7-36)amide;
`
`
`
`GlysGlu37 Arg26•34Lys38-(Aspa-ADod)-GLP-1 (7-38}; Gly8Glu38 Arg26
`34Lys39-(Aspa-ADod)-GLP-1 (7-
`•
`
`39);
`1 o Gly8 Asp35 Arg26
`4Lys36-(Aspa-ADod)-GLP-1 (7-
`34Lys36-(Aspa-ADod)-GLP-1 (7-36); Gly8 Asp35 Arg26
`•
`34Lys37-(Aspa-ADod)-GLP-1 (7-37); Gly8Asp37 Arg26
`4Lys38-{Aspa(cid:173)
`36)amide; Gly8Asp36Arg26
`·
`34Lys36
`34Lys39-(Aspa-ADod)-GLP-1 (7-39); Gly8Asp35Arg26
`ADod)-GLP-1 (7-38); Gly8Asp38Arg26
`•
`•
`-
`34Lys36 -(Aspa-ADod)-GLP-1 (7-36)amide;
`Gly8 Asp35 Arg26
`•
`
`•3
`
`•3
`
`(Aspa-ADod)-GLP-1 (7-36);
`
`4Lys37-(Aspa-ADod)-GLP-1 (7-37); Gly8Asp37 Arg26
`34Lys38-(Aspa-ADod)-GLP-1 (7-
`•
`
`•3
`
`Gly6Asp36Arg26
`
`15
`
`38); Gly8 Asp38 Arg26
`34Lys39 -(Aspa-ADod)-GLP-1 (7-39);
`•
`
`4Lys36-(Aspa-ADod)-GLP-1 (7-
`
`•3
`
`4Lys36-(Aspa-ADod)-GLP-1 (7-36); Val8Glu35Arg26
`
`Val8Glu35Arg26
`
`•3
`
`Val8Glu37 Arg26
`34Lys38-{Aspa(cid:173)
`4Lys37-(Aspa-ADod)-GLP-1 (7-37};
`•
`34Lys36
`4Lys39-(Aspa-ADod)-GL~:-1 (7-39); Val8Glu35Arg26
`-
`•
`ValsGlu35 Arg26
`4Lys36-(Aspa-ADod}-GLP-1 (7-36)amide;
`
`Val8Glu36Arg26
`
`•3
`
`36)amide;
`
`ADod)-GLP-1 (7-38); Val8Glu38Arg26
`
`•3
`
`•3
`
`(Aspa-ADod)-GLP-1 (7-36};
`
`4Lys37-(Aspa-ADod)-GLP-1 (7-37); Val8Glu37 Arg26
`
`•3
`
`4Lys38-(Aspa-ADod)-GLP-1 (7-
`
`Val8Glu36Arg26
`
`•3
`
`20
`
`38); Val8Glu38Arg26
`34Lys39-(Aspa-ADod)-GLP-1 (7-39);
`•
`
`Val8 Asp35Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-36); Vais Asp35Arg26
`34Lys36-(Aspa-ADod}-GLP-1 (7 -
`•
`·
`ValsAsp37 Arg26
`34Lys38-(Aspa(cid:173)
`•
`34Lys39-(Aspa-ADod)-GLP-1 (7-39); Val8Asp35Arg26
`34Lys36
`ADod)-GLP-1 (7-38); Val8Asp38Arg26
`•
`-
`•
`
`Val8Asp36Arg26
`34Lys37 -(Aspa-ADod}-GLP-1 (7-37);
`•
`
`36)amide;
`
`25
`
`(Aspa-ADod)-GLP-1 (7-36);
`
`Val8Asp35Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`
`•3
`
`4Lys38-(Aspa-ADod)-GLP-1 (7-
`
`34Lys37 -(Aspa-ADod}-GLP-1 (7-37); Vais Asp37 Arg26
`•
`
`Val8 Asp36 Arg26
`
`38); ValsAsp38Arg26
`34Lys39-{Aspa-ADod)-GLP-1(7-39);
`·
`
`Ser8Glu35 Arg26
`34Lys36 -(Aspa-ADod)-GLP-1 (7-36); Ser8Glu35 Arg26
`34Lys36 -(Aspa-ADod}-GLP-1 (7-
`•
`·
`Ser8Glu37 Arg26
`34Lys38-(Aspa-
`•
`34Lys39-(Aspa-ADod)-GLP-1 (7-39); Ser8Glu35Arg26
`34Lys36
`ADod)-GLP-1 (7-38}; Ser8Glu36Arg26
`•
`-
`•
`
`Ser8Glu36Arg26
`34Lys37-(Aspa-ADod)-GLP-1 (7-37);
`•
`
`36)amide;
`
`30
`
`(Aspa-ADod)-GLP-1 (7-36);
`
`Ser8Glu35Arg28
`34Lys36-(Aspa-ADod)-GLP-1 (7-36}amide;
`•
`
`•3
`
`4Lys38-(Aspa-ADod)-GLP-1 (7-
`
`4Lys37 -(Aspa-ADod)-GLP-1 (7-37}; Ser8Glu37 Arg26
`
`•3
`
`Ser8Glu36 Arg26
`
`38}; Ser8Glu38Arg26
`34Lys39-{Aspa-ADod)-GLP-1 (7-39);
`·
`
`FRESENIUS EXHIBIT 1033
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`

`

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`
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`
`83
`
`34Lys36-(Aspa-ADod)-GLP-
`Ser8 Asp35 Arg26
`Ser8 Asp35 Arg26·34Lys36 -(Aspa-ADod)-GLP-1 (7-36};
`•
`34Lys37 -(Aspa-ADod)-GLP-1 (7-37); Ser8 Asp37 Arg26
`34Lys38-(Aspa(cid:173)
`1 (7-36)amide; Ser8 Asp36 Arg26
`•
`·
`4Lys36
`34Lys39 -(Aspa-ADod)-GLP-1 (7-39); Ser8 Asp35 Arg26
`ADod)-GLP-1 (7-38); Ser8 Asp38 Arg26
`•
`-
`
`•3
`
`4Lys36-(Aspa-ADod)-GLP-1 (7-36)amide;
`
`•3
`
`Ser8 Asp35 Arg26
`
`(Aspa-ADod)-GLP-1 (7-36);
`
`5
`
`Ser8 Asp36Arg26·34Lys37 -(Aspa-ADod)-GLP-1 (7-37);
`
`Ser8Asp37 Arg26
`
`34Lys38-(Aspa-ADod)-GLP-
`·
`
`1 (7-38); Ser8Asp38Arg26
`34Lys39-(Aspa-ADod}-GLP-1 (7-39);
`•
`Thr8Glu35Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-36); Thr8Glu35Arg28
`34Lys36-{Aspa-ADod)-GLP-1 (7-
`•
`•
`34Lys38-(Aspa(cid:173)
`Thr8Glu37 Arg26
`Thr8Glu36Arg26
`34Lys37 -(Aspa-ADod)-GLP-1 (7-37);
`•
`•
`34Lys39 -(Aspa-ADod)-GLP-1 (7-39); Thr8Glu35 Arg26
`4Lys36
`ADod)-GLP-1 (7-38); Thr8Glu38 Arg26
`-
`•
`Thr8Glu35Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`
`•3
`
`36)amide;
`
`1 o
`
`(Aspa-ADod)-GLP-1 (7-36);
`
`4Lys37-(Aspa-ADod)-GLP-1 (7-37); Thr8Glu37 Arg26
`34Lys38-(Aspa-ADod)-GLP-1 (7-
`·
`
`•3
`
`Thr8Glu36Arg26
`
`38); Thr8Glu38Arg26
`34Lys39-(Aspa-ADod)-GLP-1 (7-39);
`·
`
`Thr8Asp35Arg26
`
`34Lys36-(Aspa-ADod)-GLP-1(7-36); Thr8Asp35Arg26
`34Lys36-(Aspa-ADod)-GLP-1(7-
`•
`·
`Thr8Asp37 Arg26
`4Lys38-(Aspa-
`34Lys37-(Aspa-ADod)-GLP-1 (7-37);
`Thr8Asp36Arg26
`36)amide;
`•
`15 ADod)-GLP-1 (7-38); Thr8Asp38Arg26
`34Lys39-(Aspa-ADod)-GLP-1 (7-39}; Thr8Asp35Arg26
`34Lys36
`·
`•
`-
`
`•3
`
`(Aspa-ADod)-GLP-1 (7-36);
`
`Thr8Asp35Arg26
`34Lys36-(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`
`4Lys38-(Aspa-ADod)-GLP-1 (7-
`
`Thr8 Asp36 Arg26
`34Lys37 -(Aspa-AOod)-GLP-1 (7-37); Thr8 Asp37 Arg26
`•
`
`•3
`
`38); Thr8 Asp38 Arg26
`34Lys39 -(Aspa-ADod)-GLP-1 (7-39);
`·
`4Lys 18-(Aspa-ADod)-GLP-1 (7-36)amide;
`Arg26
`34Lys 18 -(Aspa-ADod)-G LP-1 (7 -36);
`Arg26
`·
`34Lys 18-(Aspa-ADod)-GLP-1 (7-38);
`Arg26
`34Lys 18-(Aspa-ADod)-GLP-1 (7-37);
`20 Arg26
`•
`•
`34Lys18-(Aspa-ADod)-GLP-1(7-
`Gly8Asp19Arg26
`34Lys18-(Aspa-ADod)-GLP-1(7-36); Gly8Asp17Arg26
`•
`·
`34Lys 18-(Aspa-ADod)-GLP-1 (7-36)amide; Gly8 Asp 17 Arg26
`34Lys 18-(Aspa(cid:173)
`36); Gly8 Asp 19 Arg26
`·
`•
`ADod)-GLP-1 (7-36)amide;
`Gly8Asp19Arg26
`34Lys 18-(Aspa-ADod)-GLP-1 (7-37);
`·
`
`•3
`
`Gly8Asp 19Arg26
`34Lys 18-(Aspa-ADod)-GLP-1 (7-38); Gly8Asp17 Arg26
`34Lys 18-(Aspa-ADod)-GLP-1 (7-
`·
`•
`
`25
`
`38);
`
`Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-36);
`•
`Arg28
`34Lys23-(Aspa-ADod)-GLP-1 (7-37);
`•
`
`Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-36)amide;
`·
`Arg28
`34Lys23-(Aspa-ADod)-GLP-1 (7-38);
`•
`
`Gly8Asp 19Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-36); Gly8Asp 17 Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-
`•
`•
`
`34Lys23-{Aspa-ADod)-GLP-1(7-36)amide; Gly8Asp 17Arg26
`34Lys23-(Aspa-
`36); Gly8Asp19Arg26
`•
`·
`
`Gly8Asp19Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-37);
`30 ADod)-GLP-1 (7-36)amide;
`•
`Gly8 Asp 19Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-38); Gly8Asp 17 Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-
`•
`•
`
`38);
`
`34Lys27-(Aspa-ADod)-GLP-1 (7-36);
`Arg26
`•
`
`Arg26
`34Lys27-(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`
`Arg26
`34Lys27 -(Aspa-ADod)-GLP-1 (7-37);
`•
`
`Arg26
`
`34Lys27 -(Aspa-ADod)-GLP-1 (7-38);
`•
`
`FRESENIUS EXHIBIT 1033
`Page 85 of 270
`
`

`

`WO 99/43706
`
`PCT/DK99/00082
`
`84
`4Lys27-(Aspa-ADod)-GLP-1 (7-
`Gly8Asp 19Arg26•34Lys27-(Aspa-ADod)-GLP-1 (7-36); Gly8Asp17 Arg26
`34Lys27 -(Aspa-ADod)-GLP-1 (7-36)amide; Gly8 Asp 17 Arg26·34Lys27 -(Aspa(cid:173)
`36); Gly8 Asp 19 Arg26
`·
`34Lys27-(Aspa-ADod)-GLP-1(7-37);
`Gly8Asp19Arg26
`•
`4Lys27 -(Aspa-ADod)-GLP-1 (7-
`4Lys27 -(Aspa-ADod)-GLP-1 (7-38); Gly8 Asp 17 Arg26
`
`ADod)-GLP-1 (7-36)amide;
`
`•3
`
`Gly8Asp 19 Arg26
`
`•3
`
`•3
`
`5
`
`38);
`
`Arg26
`
`34Lys 18-(Aspa-ADod)-GLP-1 (7-36);
`·
`
`
`
`Arg26•34Lys 18-(Aspa-ADod)-GLP-1 (7-36)amide;
`
`34Lys 18-{Aspa-ADod)-GLP-1 (7-37);
`Arg26
`•
`Val8Asp 19Arg26·34Lys 18-(Aspa-ADod)-GLP-1 (7-36); Val8Asp17 Arg26
`
`34Lys 18 -(Aspa-ADod)-GLP-1 (7-38);
`Arg26
`•
`
`34Lys 18-(Aspa-ADod}-GLP-1 (7-
`·
`Vais Asp 17 Arg26
`4Lys 1s-(Aspa-
`
`•3
`
`Val8 Asp 19 Arg26
`34Lys 18-(Aspa-ADod}-GLP-1 (7-36)amide;
`36};
`·
`1 o ADod)-GLP-1 (7-36)amide;
`34Lys 18 -(Aspa-ADod}-GLP-1 (7-38); Val8 Asp 17 Arg26
`Val8 Asp 19 Arg26
`•
`
`Val8Asp 19Arg26
`
`34Lys 18-{Aspa-ADod)-GLP-1 (7-37);
`·
`
`4Lys 18 -(Aspa-ADod)-GLP-1 (7-
`
`•3
`
`38);
`
`34Lys23-(Aspa-ADod)-GLP-1 (7-36);
`Arg26
`·
`
`Arg26
`
`34Lys23-(Aspa-ADod}-GLP-1 (7-36)amide;
`·
`
`34Lys23-(Aspa-ADod)-GLP-1 (7-37);
`Arg26
`•
`34Lys23-(Aspa-ADod)-GLP-1(7-36); Val8Asp17Arg26
`34Lys23-(Aspa-ADod)-GLP-1(7-
`Val8Asp19Arg26
`•
`•
`4Lys23-{Aspa(cid:173)
`
`•3
`
`Val8Asp17Arg26
`
`36);
`
`Val8Asp19Arg26
`34Lys23-(Aspa-ADod)-GLP-1(7-36)amide;
`·
`
`Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-38);
`•
`
`15
`
`4Lys23 -(Aspa-ADod)-GLP-1 (7-37);
`
`•3
`
`Val8 Asp 19 Arg26
`
`ADod)-GLP-1 (7-36)amide;
`
`Val8Asp19Arg26
`
`34Lys23-{Aspa-ADod)-GLP-1 (7-
`34Lys23-(Aspa-ADod)-GLP-1 (7-38); VaI8Asp17 Arg26
`·
`·
`
`34Lys27-(Aspa-ADod)-GLP-1 (7-36}amide;
`Arg26
`•
`
`4Lys27 -(Aspa-ADod}-GLP-1 (7-36);
`
`•3
`
`38);
`Arg26
`
`20
`
`34Lys27-(Aspa-ADod}-GLP-1 (7-37);
`Arg26
`•
`
`Arg26
`34Lys27-(Aspa-ADod)-GLP-1 (7-38);
`•
`
`Val8 Asp 19 Arg26
`34Lys27 -(Aspa-ADod)-GLP-1 (7 -
`34Lys27 -(Aspa-ADod)-GLP-1 (7-36}; Vais Asp 17 Arg26
`·
`·
`Val8Asp17Arg26
`34Lys27-(Aspa(cid:173)
`·
`
`Val8Asp19Arg26
`34Lys27-(Aspa-ADod)-GLP-1(7-36)amide;
`•
`
`36);
`
`ADod)-GLP-1 (7-36)amide;
`
`34Lys27-(Aspa-ADod)-GLP-1 (7-37);
`·
`34Lys27 -(Aspa-ADod)-GLP-1 (7-
`Val8 Asp 19 Arg26
`34Lys27 -(Aspa-ADod)-GLP-1 (7-38}; Val8 Asp 17 Arg26
`•
`·
`
`Val8Asp 19Arg26
`
`25
`
`38);
`
`Arg26
`
`34Lys 18 -(Aspa-ADod)-G LP-1 (7 -36};
`·
`
`34Lys 18-(Aspa-ADod)-GLP-1 (7-36)amide;
`Arg26
`•
`
`34Lys 18-(Aspa-ADod)-GLP-1 (7-38);
`Arg26
`•
`
`4Lys 18-(Aspa-ADod)-GLP-1 (7-37);
`
`Arg26
`
`•3
`
`4Lys 18-(Aspa-ADod)-GLP-
`
`Ser8 Asp 17 Arg26
`
`•3
`
`Ser8 Asp 19 Arg26
`34Lys 18 -(Aspa-ADod)-GLP-1 (7-36};
`•
`
`30
`
`34Lys 18-(Aspa-ADod)-GLP-1 (7-36)amide; Ser8Asp 17 Arg26
`34Lys 18-(Aspa(cid:173)
`1 (7-36); Ser8Asp19Arg28
`·
`•
`
`4Lys18-(Aspa-ADod)-GLP-1(7-37);
`
`Ser8Asp19Arg26
`
`•3
`
`ADod}-GLP-1 (7-36)amide;
`
`Ser8Asp 19Arg26
`34Lys 18-(Aspa-ADod)-GLP-1 (7-38);
`•
`
`Ser8Asp 17 Arg26
`34Lys 18-(Aspa-ADod)-GLP-
`·
`
`1 (7-38);
`
`FRESENIUS EXHIBIT 1033
`Page 86 of 270
`
`

`

`WO99/43706
`
`PCT/DK99/00082
`
`Arg26•34Lys23-(Aspa-ADod)-GLP-1 (7-36);
`
`Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-36)amide;
`·
`
`Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-37);
`•
`
`Arg26
`
`34Lys23-(Aspa-ADod)-GLP-1 (7-38);
`·
`
`85
`
`•3
`
`Ser8Asp19Arg26
`
`•3
`
`1 (7-36); Ser8Asp 19Arg26
`
`Ser8Asp17Arg26
`4Lys23-(Aspa-ADod)-GLP-
`4Lys23-(Aspa-ADod)-GLP-1(7-36);
`34Lys23-(Aspa-ADod)-GLP-1 (7-36)amide; Ser8Asp17 Arg26
`34Lys23-(Aspa-
`·
`·
`34Lys23-(Aspa-ADod)-GLP-1 (7-37);
`·
`
`5
`
`ADod)-GLP-1 (7-36)amide;
`
`Ser8Asp 19Arg26
`
`Ser8Asp19Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-38);
`·
`
`Ser8Asp 17 Arg26
`34Lys23-(Aspa-ADod)-GLP-
`•
`
`1 (7-38);
`
`Arg26
`
`34Lys27 -(Aspa-ADod)-GLP-1 (7-36);
`·
`
`Arg26
`34Lys27-(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`
`Arg26
`34Lys27 -(Aspa-ADod)-GLP-1 (7-38);
`•
`
`•3
`
`4Lys27 -(Aspa-ADod)-GLP-1 (7-37);
`Arg26
`1 o Ser8 Asp 19Arg26
`34Lys27 -(Aspa-ADod)-GLP-1 (7-36)amide; Ser8 Asp 17 Arg26
`34Lys27 -(Aspa(cid:173)
`1 (7-36); Ser8 Asp 19 Arg26
`•
`•
`
`34Lys27 -(Aspa-ADod)-GLP-1 (7-36);
`·
`
`Ser8Asp 17 Arg26
`34Lys27 -(Aspa-ADod)-GLP-
`·
`
`ADod)-GLP-1 (7-36)amide;
`
`Ser8Asp 19Arg26
`34Lys27-(Aspa-ADod)-GLP-1 (7-37);
`•
`
`Ser8 Asp 19 Arg26
`34L ys 27 -(Aspa-ADod)-G LP-1 (7-38);
`·
`
`Ser8Asp 17 Arg26
`
`34Lys27-(Aspa-ADod)-GLP-
`·
`
`1(7-38);
`
`15
`
`34Lys 18-(Aspa-ADod)-GLP-1 (7-36);
`Arg26
`·
`
`34Lys 18-(Aspa-ADod)-GLP-1 (7-36)amide;
`Arg26
`·
`
`34Lys18-(Aspa-ADod)-GLP-1 (7-37);
`Arg26
`·
`
`Arg26
`
`34Lys 18-(Aspa-ADod)-GLP-1 (7-38);
`·
`
`4Lys 18-(Aspa-ADod)-GLP-1 (7-
`34Lys 18-(Aspa(cid:173)
`Thr8 Asp 17 Arg26
`•
`
`Thr8 Asp 19 Arg26
`34Lys 18-(Aspa-ADod)-GLP-1 (7-36); Thr8 Asp 17 Arg26
`·
`
`•3
`
`4Lys 18-(Aspa-ADod)-GLP-1 (7-36)amide;
`
`•3
`
`Thr8 Asp 19 Arg26
`
`36);
`
`4Lys 18-(Aspa-ADod)-GLP-1 (7-37);
`
`Thr8 Asp 19 Arg26
`
`•3
`
`ADod)-GLP-1 (7-36)amide;
`Thr8Asp19Arg26
`34Lys18-(Aspa-ADod)-GLP-1 (7-38); Thr8Asp17 Arg26
`34Lys 18-(Aspa-ADod)-GLP-1 (7-
`•
`·
`
`20
`
`38);
`
`Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-36);
`•
`
`Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`
`Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-37);
`·
`
`Arg26
`34L ys23 -(Aspa-ADod)-GLP-1 (7-38);
`·
`
`Thr8Asp19Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-36); Thr8Asp17 Arg26
`•
`
`34Lys23-(Aspa-ADod)-GLP-1 (7-
`•
`
`25
`
`36);
`
`Thr8 Asp 19 Arg26
`34Lys23-(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`
`Thr8 Asp 17 Arg26
`
`34Lys23-(Aspa(cid:173)
`·
`
`ADod)-GLP-1 (7-36)amide;
`
`Thr8Asp 19 Arg26
`
`34Lys23-(Aspa-ADod)-GLP-1 (7-37);
`·
`
`34Lys23-(Aspa-ADod)-GLP-1 (7-
`·
`
`4Lys23-(Aspa-ADod)-GLP-1 (7-38); Thr8Asp17 Arg26
`
`Thr8Asp 19Arg26
`
`•3
`
`38);
`
`Arg26
`
`34Lys27-(Aspa-ADod)-GLP-1 (7-36);
`·
`
`Arg26
`
`34Lys27-(Aspa-ADod)-GLP-1 (7-36)amide;
`·
`
`4Lys27-(Aspa-ADod)-GLP-1 (7-38);
`
`Arg26
`
`•3
`
`4Lys27 -(Aspa-ADod)-GLP-1 (7-37);
`
`Arg26
`
`•3
`
`30
`
`Thr8 Asp 19 Arg26
`34Lys27 -(Aspa-ADod)-GLP-1 (7-36); Thr8 Asp 17 Arg26
`34Lys27 -(Aspa-ADod)-GLP-1 (7-
`·
`•
`
`36);
`
`Thr8 Asp 19 Arg26
`
`34Lys27 -(Aspa-ADod)-GLP-1 (7-36)amide;
`•
`
`Thr8 Asp 17 Arg26
`
`34Lys27 -(Aspa(cid:173)
`·
`
`ADod)-GLP-1 (7-36)amide;
`
`34Lys27 -(Aspa-ADod)-GLP-1 (7-37);
`Tor8 Asp 19 Arg26
`·
`
`FRESENIUS EXHIBIT 1033
`Page 87 of 270
`
`

`

`WO99/43706
`
`PCT /DK99/00082
`
`86
`
`34Lys27-(Aspa-ADod)-GLP-1 (7-
`4Lys27-(Aspa-ADod)-GLP-1 (7-38); Thr8Asp17 Arg26
`•
`
`Thr8Asp 19Arg26
`
`•3
`
`•3
`
`•3
`
`5
`
`38);
`4Lys36-(Aspa(cid:173)
`Arg26Lys34-(Aspa-A Tet)-GLP-1 (7-36); Arg34Lys26-(Aspa-A Tet)-GLP-1 (7-36); Arg26
`A Tet)-GLP-1 (7-36); Arg26Lys34-(Aspa-ATet)-GLP-1 (7-36)amide; Arg34 Lys26-(Aspa-ATet)-GLP-
`4Lys36-(Aspa-ATet)-GLP-1 (7-36)amide; Arg26 Lys34-(Aspa-ATet)-GLP-1 (7-
`1 (7-36)amide; Arg26
`37); Arg34Lys26-(Aspa-ATet)-GLP-1 (7-37); Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-37); Arg26Lys34
`-
`•
`(Aspa-A Tet)-GLP-1 (7-38); Arg34Lys26 -(Aspa-A Tet)-GLP-1 (7-38)
`34Lys38 -(Aspa-ATet)(cid:173)
`; Arg26
`•
`Arg26Lys34-(Aspa-ATet)-GLP-1 (7-39); Arg34Lys26-(Aspa-ATet)-GLP-1 (7-39);
`GLP-1 (7-38);
`Arg26
`34Lys39 -(Aspa-A Tet)-GLP-1 (7-39);
`•
`10 Git Arg26Lys34-(Aspa-A Tet)-GLP-1 (7-36);
`34Lys36-(Aspa-A T et)-GLP-1 (7-36);
`Git Arg26
`Gly8 Arg26Lys34-(Aspa-A Tet)-GLP-1 (7-36)amide;
`•
`Gly8Arg34Lys26-(Aspa-ATet)-GLP-1(7-36)amide;
`Git Arg26
`34Lys36-(Aspa-A Tet)-GLP-1 (7-
`•
`36)amide; Gly8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-37); Gly8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-37);
`34Lys36-(Aspa-ATet)-GLP-1 (7-37);
`Gly8Arg26
`•
`15 Gly8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-38)
`Gly8Arg26Lys34-(Aspa-A Tet)-GLP-1 (7-39);
`34Lys39-(Aspa-ATet)-GLP-1(7-39);
`Gly8Arg26
`•
`Val8Arg26Lys34-{Aspa-ATet)-GLP-1 (7-36);
`VaI8Arg34Lys26-(Aspa-ATet)-GLP-1(7-36);
`Val8Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-36);
`Val8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-36)amide;
`•
`Val8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-36)amide;
`Val8Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-
`·
`36)amide; Val8Arg26Lys34-(Aspa-A Tet)-GLP-1 (7-37); Val8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-37);
`34Lys36-(Aspa-A Tet)-GLP-1 (7-37);
`Val8 Arg26
`Val8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-38);
`•
`Val8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-38)
`Val8 Arg26
`34Lys38 -(As pa-AT et )-GLP-1 (7 -38);
`•
`Val8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-39);
`25 Val8Arg26
`34Lys39-(Aspa-ATet)-GLP-1 (7-39);
`•
`Ser8 Arg26Lys34-(Aspa-A Tet)-GLP-1 (7-36);
`Ser8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-36);
`Ser8Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-36);
`Ser8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-36)amide;
`•
`Ser8 Arg34lys26 -(Aspa-A Tet)-GLP-1 (7-36)amide;
`36)amide; Ser8 Arg26Lys34 -(Aspa-A Tet)-GLP-1 (7-37); Ser8 Arg34Lys26-(Aspa-A Tet)-GLP-1 (7-37);
`Ser8Arg26
`34Lys36-(Aspa-ATet}-GLP-1 (7-37);
`•
`Ser8Arg34Lys26-{Aspa-ATet)-GLP-1 (7-38)
`Ser8 Arg26Lys34 -(As pa-AT et )-G LP-1 (7 -39);
`Ser8Arg26
`34Lys39-(Aspa-ATet)-GLP-1 (7-39);
`•
`
`Gly8 Arg34Lys26-(Aspa-A Tet)-GLP-1 (7-36);
`
`Gly8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-38);
`
`4Lys38-(Aspa-A Tet)-GLP-1 (7 -38);
`Gly8 Arg26
`Gly8Arg34Lys26-(Aspa-ATet)-GLP-1(7-39);
`
`•3
`
`Val8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-39);
`
`Ser8 Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-
`•
`
`Ser8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-38);
`
`Ser8 Arg26
`34Lys'J8-(Aspa-A Tet)-GLP-1 (7-38);
`•
`Ser8 Arg34Lys26 -(Aspa-A T et)-GLP-1 (7-39);
`
`20
`
`30
`
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`
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`

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`
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`
`Thr8Arg26Lys34-(Aspa-ATet)-GLP-1(7~36);
`
`Thr8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-36);
`
`Thr8Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-36);
`•
`
`Thr8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-36)amide;
`
`34Lys36-(Aspa-ATet)-GLP-1 (7-
`Thr8Arg26
`Thr8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-36)amide;
`•
`36)amide; Thr8Arg26Lys34-(Aspa-ATet)-GLP-1(7-37); Thr8Arg34Lys26-(Aspa-ATet)-GLP-1(7-37);
`Thr8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-38);
`
`Thr8 Arg26
`34L ys36 -(Asp a-AT et )-GLP-1 (7-37);
`•
`
`5
`
`Thr8Arg34Lys26-(Aspa-ATet)-GLP-1 (7-38)
`
`Thr8Arg26
`34Lys38-(Aspa-ATet)-GLP-1 (7-38);
`•
`
`Thr8Arg26Lys34-(Aspa-ATet)-GLP-1 (7-39);
`
`Thr8 Arg34Lys26-(Aspa-A Tet)-GLP-1 (7-39);
`
`Thr8 Arg26
`
`34Lys39-(Aspa-A Tet)-GLP-1 (7-39);
`·
`
`Gly8Glu35 Arg26
`
`34Lys36-(Aspa-A Tet)-GLP-1 (7-36); Gly8Glu35 Arg26
`•
`
`34Lys36 -(Aspa-A Tet)-GLP-1 (7-
`•
`
`1 o
`
`34Lys37-(Aspa-A Tet)-GLP-1 (7-37); Gly8Glu37 Arg26
`36)amide; Gly8Glu36Arg26
`·
`
`34Lys38-(Aspa-ATet)(cid:173)
`•
`34Lys36-(Aspa(cid:173)
`GLP-1 (7-38); Gly8Glu38 Arg26
`34Lys39 -(Aspa-A Tet)-GLP-1 (7-39); Gly8Glu35 Arg26
`•
`•
`
`A Tet)-GLP-1 (7-36);
`
`Gly8Glu35Arg26
`34Lys36-{Aspa-ATet)-GLP-1 (7-36)amide;
`•
`
`4Lys38-(Aspa-ATet)-GLP-1 (7-
`
`•3
`
`Gly8Glu36Arg26
`34Lys37-(Aspa-A Tet)-GLP-1 (7-37); Gly8Glu37 Arg26
`•
`38); Gly8Glu38Arg26
`34Lys39-(Aspa-ATet)-GLP-1 (7-39);
`•
`
`4Lys36-(Aspa-ATet)-GLP-1 (7-
`15 Gly8Asp35Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-36); Gly8Asp35Arg26
`•
`36)amide; Gly8 Asp36 Arg28
`34Lys37 -(Aspa-A Tet)-GLP-1 (7 -37); Gly8Asp37 Arg26
`34Lys38-(Aspa-A Tet)(cid:173)
`·
`·
`
`•3
`
`GLP-1 (7-38); Gly8Asp38Arg26
`34Lys39-(Aspa-ATet)-GLP-1 (7-39); Gly8Asp35Arg26
`34Lys36-(Aspa(cid:173)
`•
`•
`
`4Lys36-(Aspa-ATet)-GLP-1 (7-36)amide;
`
`Gly8Asp35Arg26
`
`•3
`
`A Tet)-GLP-1 (7-36);
`
`34Lys37 -(Aspa-A T et)-GLP-1 (7-37); Gly8 Asp37 Arg26
`34Lys38-(Aspa-A Tet)-GLP-1 (7-
`Gly8 Asp36 Arg26
`•
`•
`
`20
`
`34Lys39-(Aspa-ATet)-GLP-1 (7-39);
`38); Gly8Asp38Arg26
`•
`Val8Glu35Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-36);
`Val8Glu35Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-
`•
`•
`
`4Lys38-(Aspa-ATet)(cid:173)
`
`4Lys37-(Aspa-ATet)-GLP-1 (7-37); Val8Glu37 Arg26
`
`•3
`
`•3
`
`36)amide; Val8Glu36Arg26
`
`34Lys36-(Aspa(cid:173)
`GLP-1 (7-38); Val8Glu38Arg26
`34Lys39-(Aspa-ATet)-GLP-1 (7-39); Val8Glu35Arg26
`•
`•
`
`4Lys36-(Aspa-A T et)-GLP-1 (7-36)amide;
`
`Val8Glu35 Arg26
`
`•3
`
`A Tet)-GLP-1 (7-36);
`Val8Glu36Arg26
`34Lys37 -(Aspa-ATet)-GLP-1 (7-37);
`•
`38); Val8Glu38Arg26
`34Lys39-(Aspa-ATet)-GLP-1(7-39);
`·
`
`25
`
`4Lys38-(Aspa-ATet)-GLP-1 (7-
`
`•3
`
`Val8Glu37 Arg26
`
`4Lys36-(Aspa-ATet)-GLP-1 (7-
`
`•3
`
`Val8Asp35Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-36); Val8Asp35Arg26
`•
`
`4Lys38 -(Aspa-A Tet)(cid:173)
`
`36)amide; Vais Asp36 Arg26
`34Lys37 -(Aspa-A Tet)-GLP-1 (7-37); Vais Asp37 Arg26
`•
`
`•3
`
`4L ys36-(Aspa-
`
`GLP-1 (7-38); Vais Asp38 Arg26
`34Lys39 -(Aspa-A T et)-G LP-1 (7-39); Vais Asp35 Arg26
`•
`
`•3
`
`4Lys36-(Aspa-ATet)-GLP-1 (7-36)amide;
`
`Val8Asp35Arg26
`
`•3
`
`30 ATet)-GLP-1(7-36);
`
`Vais Asp36Arg26
`34Lys37 -(Aspa-A Tet)-GLP-1 (7-37); Val8Asp37 Arg26
`34Lys38-(Aspa-A Tet)-GLP-1 (7-
`•
`•
`38); Val8Asp38 Arg26
`Ser8Glu35 Arg26
`4Lys36-(Aspa-A Tet)-GLP-1 (7-36); Ser8Glu35 Arg26
`34Lys36-(Aspa-A Tet)-GLP-1 (7-
`•
`
`4Lys39-(Aspa-ATet)-GLP-1 (7-39);
`
`•3
`
`•3
`
`34Lys38-(Aspa-ATet)-
`34Lys37-{Aspa-ATet)-GLP-1 (7-37); Ser8Glu37 Arg26
`36)amide; Ser8Glu36Arg26
`•
`•
`
`FRESENIUS EXHIBIT 1033
`Page 89 of 270
`
`

`

`WO99/43706
`
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`
`88
`
`34Lys39-(Aspa-ATet)-GLP-1 (7-39); Ser8Glu35Arg26
`34Lys36-(Aspa(cid:173)
`GLP-1 (7-38); Ser8Glu38Arg26
`•
`•
`A Tet)-GLP-1 (7-36);
`Ser8Glu35Arg26
`34Lys36-(Aspa-A Tet)-GLP-1 (7-36)amide;
`•
`
`34Lys37-(Aspa-ATet)-GLP-1 (7-37); Ser8Glu37 Arg26
`Ser8Glu36Arg26
`34Lys38-(Aspa-ATet)-GLP-1 (7-
`•
`•
`
`38); Ser8Glu38Arg26
`34Lys39-(Aspa-ATet)-GLP-1 (7-39);
`•
`Ser8Asp35Arg26
`4Lys36-(Aspa-ATet)-GLP-1 (7-36); Ser8Asp35Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-
`•
`34Lys38-(Aspa-ATet)(cid:173)
`36)amide; Ser8Asp36Arg26
`34Lys37 -(Aspa-ATet)-GLP-1 (7-37); Ser8Asp37 Arg26
`•
`•
`4L ys39 -(Aspa-A T et )-G LP-1 (7 -39); Ser8 Asp35 Arg26
`34Lys36 -(Aspa(cid:173)
`•
`Ser8Asp35Arg26
`
`•3
`
`5
`
`GLP-1 (7 -38); Ser8 Asp38 Arg26
`
`•3
`
`A T et)-GLP-1 (7-36);
`
`4Lys36-(Aspa-A Tet)-GLP-1 (7-36)amide;
`
`•3
`
`Ser8 Asp36Arg26
`4Lys37 -(Aspa-A Tet)-GLP-1 (7-37); Ser8 Asp37 Arg26
`34Lys38-(Aspa-ATet)-GLP-1 (7-
`•
`38); Ser8Asp38Arg26
`34Lys39-(Aspa-ATet)-GLP-1(7-39);
`•
`
`•3
`
`10
`
`4L ys36-(Aspa-A T et)-GLP-1 (7-36);
`Thr8Glu35 Arg26
`Thr8Glu35 Arg26
`34Lys36-(Aspa-A T et)-GLP-1 (7-
`•
`36)amide; Thr8Glu36Arg26
`34Lys37 -(Aspa-ATet)-GLP-1 (7-37); Thr8Glu37 Arg26
`34Lys38-(Aspa-ATet)(cid:173)
`•
`•
`GLP-1 (7-38); Thr8Glu38Arg26
`34Lys39-(Aspa-ATet)-GLP-1 (7-39); Thr8Glu35Arg26
`•
`
`34Lys36-(Aspa(cid:173)
`·
`
`•3
`
`•3
`
`•3
`
`4Lys38-(Aspa-ATet)-GLP-1 (7-
`
`15
`
`4Lys36 -(Aspa-A Tet)-GLP-1 (7-36)amide;
`Thr8Glu35Arg26
`A Tet)-GLP-1 (7-36);
`Thr8Glu36Arg26
`34Lys37-(Aspa-ATet)-GLP-1 (7-37); Thr8Glu37 Arg26
`•
`38); Thr8Glu38Arg26
`34Lys39-(Aspa-A Tet)-GLP-1 (7-39);
`•
`Thr8Asp35Arg26
`4Lys36-(Aspa-ATet)-GLP-1 (7-36); Thr8Asp35Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-
`•
`36)amide; Thr8Asp36Arg26
`34Lys37-(Aspa-ATet)-GLP-1(7-37); Thr8Asp37Arg26
`·
`GLP-1 (7-38); Thr8 Asp38 Arg26
`34Lys39 -(Aspa-ATet)-GLP-1 (7-39); Thr8 Asp35 Arg26
`34Lys36 -(Aspa-
`•
`•
`
`4Lys38-(Aspa-ATet)(cid:173)
`
`•3
`
`•3
`
`20 ATet)-GLP-1 (7-36);
`
`Thr8Asp35Arg26
`34Lys36-(Aspa-ATet)-GLP-1 (7-36)amide;
`•
`
`Thr8Asp36Arg26
`34Lys37-(Aspa-ATet)-GLP-1 (7-37); Thr8Asp37 Arg26
`34Lys38-(Aspa-ATet)-GLP-1 (7-
`•
`•
`38); Thr8Asp38Arg26
`34Lys39-(Aspa-ATet)-GLP-1(7-39);
`•
`Arg26
`34Lys 18-(Aspa-ATet)-GLP-1 (7-36);
`•
`Arg26
`34Lys 18 -(Aspa-A Tet)-GLP-1 (7-37);
`•
`25 Gly8Asp19Arg26
`34Lys 18-(Aspa-ATet)-GLP-1 (7-36); Gly8Asp17 Arg26
`34Lys 18-(Aspa-ATet)-GLP-1 (7-
`•
`•
`36); Gly8Asp 19Arg26
`34Lys 18-(Aspa-ATet)-GLP-1 (7-36)amide; Gly8Asp 17 Arg26
`34Lys 18-(Aspa-ATet)(cid:173)
`·
`•
`GLP-1 (7-36)amide; Gly8Asp19Arg26
`34Lys18-(Aspa-ATet)-GLP-1(7-37); Gly8Asp19Arg26
`•
`
`34Lys 18-(Aspa-ATet)-GLP-1 (7-36)amide;
`Arg26
`•
`
`4Lys 18 -(As pa-AT et)-GLP-1 (7-38);
`
`Arg26
`
`•3
`
`•3
`
`4Lys18
`-
`
`•3
`
`4Lys 18-(Aspa-A Tet)-GLP-1 (7-38);
`
`Arg26
`34Lys23-(Aspa-ATet)-GLP-1 (7-36)amide;
`•
`
`•3
`
`•3
`
`(Aspa-A Tet)-GLP-1 (7-38); Gly8 Asp 17 Arg26
`Arg26·34Lys23-(Aspa-ATet)-GLP-1 (7-36);
`4Lys23 -(Aspa-A T et)-GLP-1 (7 -37);
`30 Arg26
`4Lys23-(Aspa-A Tet)-GLP-1 (7-38);
`Arg26
`Gly8Asp19Arg26
`34Lys23-(Aspa-ATet)-GLP-1 (7-36); Gly8Asp 17 Arg26
`34Lys23-(Aspa-ATet)-GLP-1 (7-
`•
`•
`36); Gly8Asp 19Arg26
`34Lys23-(Aspa-ATet)-GLP-1 (7-36)amide; Gly8Asp 17 Arg26
`·
`GLP-1 (7-36)amide; Gly8Asp19Arg26
`34Lys23-(Aspa-ATet)-GLP-1 (7-37); Gly8Asp19Arg26
`34Lys23
`•
`•
`-
`
`34Lys23-(Aspa-ATet)(cid:173)
`·
`
`(Aspa-ATet)-GLP-1 (7-38); Gly8Asp17Arg26
`34Lys23-(Aspa-ATet)-GLP-1 (7-38);
`•
`
`FRESENIUS EXHIBIT 1033
`Page 90 of 270
`
`

`

`WO 99/43706
`
`PCT/DK99/00082
`
`89
`
`Arg26
`34Lys27 -(Aspa-A Tet)-GLP-1 (7-36)amide;
`•
`
`34Lys27-(Aspa-ATet)-GLP-1 (7-38);
`Arg26
`•
`
`•3
`
`•3
`
`Arg26
`
`4Lys27 -(Aspa-A Tet)-GLP-1 (7-36);
`34Lys27 -(Aspa-A Tet)-GLP-1 (7-37);
`Arg26
`•
`Gly8 Asp 19 Arg26
`4Lys27 -(Aspa-A Tet)-GLP-1 (7-36); Gly8 Asp 17 Arg26
`34Lys27 -(Aspa-A Tet)-GLP-1 (7 -
`•
`
`36); Gly8 Asp 19 Arg26
`34Lys27 -(Aspa-A Tet)-GLP-1 (7-36)amide; Gly8 Asp 17 Arg26
`34Lys27 -(Aspa-ATet)-
`•
`·
`34Lys27
`·
`
`5 GLP-1 (7-36)amide; Gly8Asp19Arg26
`34Lys27-(Aspa-ATet)-GLP-1(7-37); Gly8Asp19Arg26
`·
`
`-
`
`4Lys27-(Aspa-ATet)-GLP-1 (7-38);
`
`(Aspa-ATet)-GLP-1 (7-38); Gly8Asp 17 Arg26
`
`•3
`
`4Lys 18-(Aspa-ATet)-GLP-1 (7-36)amide;
`
`•3
`
`Arg26
`
`Arg26
`34Lys 18-(Aspa-ATet)-GLP-1 (7-36);
`•
`
`34Lys 18-(Aspa-ATet)-GLP-1 (7-37);
`Arg26
`·
`
`34Lys 18-(Aspa-ATet)-GLP-1 (7-38);
`Arg26
`·
`
`Val8Asp 19Arg26
`34Lys 18-(Aspa-ATet)-GLP-1 (7-36); Val8Asp17 Arg26
`34Lys 18-(Aspa-ATet)-GLP-1 (7-
`•
`·
`36); Val8Asp19Arg26
`34Lys 18-(Aspa-ATet)(cid:173)
`34Lys 18-(Aspa-ATet)-GLP-1 (7-36)amide; Val8Asp17 Arg26
`·
`•
`
`10
`
`GLP-1 (7-36)amide; Val8Asp19Arg26
`34Lys18-(Aspa-ATet)-GLP-1 (7-37); Val8Asp19Arg26
`34Lys18
`•
`-
`·
`
`(Aspa-ATet)-GLP-1 (7-38); Val8Asp17Arg26
`
`34Lys 18-(Aspa-ATet)-GLP-1 (7-38);
`·
`
`4Lys23-(Aspa-A Tet)-GLP-1 (7-36)amide;
`
`Arg26
`
`•3
`
`Arg26
`
`34Lys23-(Aspa-ATet)-GLP-1 (7-36);
`·
`
`4Lys23-(Aspa-A Tet)-GLP-1 (7-37);
`Arg26
`Arg26
`34Lys23-(Aspa-ATet)-GLP-1 (7-38);
`•
`Val8Asp19Arg26
`34Lys23-(Aspa-ATet)-GLP-1 (7-36); Val8Asp17 Arg26
`34Lys23-(Aspa-ATet)-GLP-1 (7-
`•
`•
`
`•3
`
`15
`
`36); Val8Asp 19Arg26
`34Lys23-(Aspa-A Tet)-GLP-1 (7-36)amide; Val8Asp17 Arg26
`34Ly