WO 2006/086653
`
`PCT/US2006/004768
`
`181/221
`
`Asn
`Asn
`Asn
`
`Asn
`Asn
`Asn
`Asn
`
`His
`
`His
`His
`His
`His
`Ile
`Ile
`Tie
`Ile
`Tlie
`
`Asn
`‘Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Tle
`Tle
`Ile
`Ile
`‘Ile
`tie
`Ile
`Tle
`Tie
`Tle
`Tlie
`Tle
`tle
`Ile
`Ile
`ile
`Ile
`Ile
`Tle
`Leu
`
`(SEQ ID NO: 6871 )
`“(SEQ ID NO: 6872 )
`(SEQ ID NO: 6873 )
`(SEQ ID NO: 6874 )
`(SEQ ID NO: 6875 )
`(SEQ ID NO: 6876 )
`(SEQ ID NO: 6877: )
`(SEQ'ID NO: 6878 )
`(SEQ ID NO: 6879 )
`(SEQ ID NO: 6880 )
`(SEQ ID NO: 6881 )
`(SEQ ID NO: 6882 )
`(SEQ ID NO: 6883 )
`"(SEQ ID NO: 6884 )
`(SEQ ID NO: 6885 )
`(SEQ ID NO: 6886 )
`(SEQ ID NO: 6887 ) .
`©. (SEQ ID No: 6888 )
`(SEQ ID NO: 6889 )
`(SEQ ID NO: 6890.)
`“+ (SEQID NO: 6891 )
`"(SEQ ID NO: 6892 )
`(SEQ ID NO: 6893 ).
`(SEQ ID NO: 6894 )
`“2+.
`(SEQ ID NO; 6895 )
`- ,
`(SEQID NO; 6896 )
`“+ (SEQ ID NO;6897 )
`
`(SEQ ID NO: 6898 )_
`(SEQ ID NO: 6899 )
`
`(SEQID NO: 6900 )
`(SEQ ID NO: 6901 )
`(SEQ ID NO: 6902 ).
`(SEQ ID NO; 6903 )
`’
`(SEQ ID NO: 6904 )
`- (SEQ ID NO: 6905 )
`"(SEQ ID NO: 6906 )
`(SEQ ID NO: 6907 ) -
`(SEQ ID NO: 6908 )
`- (SEQ ID No: 6909 )
`(SEQ ID NO: 6910 )
`(SEQ ID NO: 6911 )
`(SEQ ID NO: 6912 )
`(SEQ ID NO: 6913 )
`
`|
`
`_
`
`-
`
`
`
`©
`
`-
`
`_
`
`-
`
`cys
`Cys
`Cys
`Cys
`Cys
`CyB
`cys
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`
`@lu Tyr
`Glu Tyr
`
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`
`Glu Tyr
`Gin Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyz
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`| Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`
`cys
`Cys
`Cys
`cys
`cys.
`cys
`cys
`Cys
`
`Cys
`Cys
`cys
`cys
`Cys
`Cys
`cys
`Cys
`cys’
`Cys
`Cys
`cys
`Cys
`‘cys
`cya
`
`cys
`cys
`Cys
`Cys
`
`Leu
`
`Leu
`Leu
`Leu
`Leu
`Leu
`Leu
`Leu
`Leu
`
`Leu
`Leu
`Leu
`Leu
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`ely
`Gly
`Gly
`“Gly
`Gly
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`‘Pre
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Agn.
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Asn,
`Asn
`
`Asn
`Asn
`
`Gly
`
`Gly.
`
`Ala
`Ala
`
`Ala
`
`Cys
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`Gly
`Ala
`‘Gly
`Ala
`
`Cys
`cys
`ays
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`cys.
`Cys.
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly.
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Cys.
`Cys
`oe
`Cys
`Cys
`Cys.
`Cys
`Cys
`cys
`cys
`cys
`cys
`cys —
`cys
`cys
`Cys —
`Cys
`Cys.
`Cys
`Cys
`cys
`cys: -
`Cys.
`cys ,
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys -
`Cys
`
`Thr
`Thr
`
`Thr
`Thr
`
`Gly
`Gly
`Gly
`Gly
`Gly Thr
`Pro
`Ala
`Pro
`‘Ala
`Pro
`Ala
`Pro
`Ala
`Pro
`Ala
`Ala
`Pro
`
`Pro
`Pro
`Pro
`Pro
`
`Pro
`Pro
`
`Thr
`Thr
`The
`‘Thr
`
`‘Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`
`Thr
`val
`val
`Gly
`Gly
`Thr
`Thr
`val
`Val
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Cys
`cys
`cys
`Cya
`Cys
`cys
`cys”
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cya
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Cys
`Cys
`Cys
`Cys
`Cys.
`Cys
`Cys.
`cys
`cys:
`cys
`Cys
`Cys
`
`Thr
`Thr
`Thr
`
`Ala
`Ala
`Ala
`Ala
`Ala.
`Ala
`
`Thr
`Thr
`Thr
`Thr
`Thr
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Gly
`Gly
`Thr
`Thr
`
`Val
`Val
`
`Gly
`Gly
`Thr
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly’
`Ala
`
`Cys
`cys
`cys
`Cys
`
`Cys
`Cys
`
`Cys
`cys
`
`-
`
`(sheet 50 0f 90)...
`
`MYLAN - EXHIBIT 1022 Part 9 of 16
`2788
`
`2788
`
`MYLAN - EXHIBIT 1022 Part 9 of 16
`
`

`

`WO 2006/086653
`
`182/221
`
`PCT/US2006/004768
`
`~
`
`°
`
`(SEQ ID NO: 6914 )
`(SEQ ID NO: 6915 )
`(SEQ ID NO: 6916 )
`(SEQ IDNO: 6917 )
`(SEQ ID NO: 6918 )
`(SEQ ID NO: 6919 )
`(SEQ ID NO: 6920 )
`(SEQID NO:6921 )
`(SEQ ID NO: 6922 )
`(SEQ ID NO: 6923 )
`(SEQ ID NO: 6924 )
`(SEQ ID NO: 6925 )
`(SEQ ID NO: 6926 ).
`(SEQ ID NO: 6927. )
`(SEQ ID NO; 6928 )
`(SEQ ID NO: 6929 )
`(SEQ ID NO: 6930 )
`(SEQ ID NO: 6931 )
`(SEQ ID NO: 6932 )
`(SEQ ID NO: 6933 )
`(SEQ ID NO: 6934 )
`(SEQ ID NO: 6935 )
`(SEQ ID.NO: 6936 )
`(SEQID NO: 6937 )
`(SEQ ID NO: 6938 )
`(SEQ ID NO: 6939 )
`(SEQ ID NO: 6940 )
`(SEQ ID NO: 6941 ).
`(SEQ ID NO: 6942 ).
`(SEQ ID NO: 6943 )
`(SEQ ID NO: 6944 )
`. (SEQ ID NO: 6945 )
`(SEQ ID NO: 6846 )
`(SEQ ID NO: 6947 )
`(SEQ ID NO: 6948 )
`(SEQ ID NO: 6949 )
`(SEQ ID NO: 6950 )
`(SEQ ID No: 6951 )
`(SEQ ID NO: 6952 )
`(SEQ ID NO: 6953 )
`(SEQ ID NO: 6954 ).
`(SEQ ID NO: 6955 )
`(SEQ ID NO: 6956 )
`
`Leu
`Leu
`Leu
`Leu
`Leu
`Leu
`Leu
`
`Leu
`Leu
`Leu
`
`Asn
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Gly
`Gly
`Gly
`Gly.
`Gly
`Gly
`Gly
`Gly
`Gly
`
`Gly
`Pro
`Pro
`
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Glu Tyr Cys
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyx
`
`Glu Tyr
`Glu Tyr
`
`Glu Tyr
`Glu Tyr
`Glu Tyr
`‘Glu
`Tyr
`Glu
`Tyr
`Glu
`Tyr
`Glu
`Tyr
`Glu
`Tyr
`Glu
`tyr
`Glu
`Glu
`Glu
`Glu
`
`Tyr
`‘yr
`Tyr
`Glu Tyr.
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`
`Glu Tyr Cys
`Giu Tyr Cys
`Glu Tyr Cys
`Glu Tyr Cys
`} dlu Tyr
`cys
`Cys
`Glu Tyr
`Cys
`Cys
`cys
`
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Giu Tyr
`Giu Tyr
`
`Cys
`cys
`cya
`
`Met
`Met
`Met
`
`Met
`Met
`Net
`Met
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Lys
`Lys
`Lys
`Lys
`Lys
`Lys
`Lys
`Lys
`Lys.
`Lys
`Lys
`Lys
`Lys
`Lys
`Lys
`Lys
`Lys
`; Lys
`; Lys
`Lys
`Lys
`Lys
`Lys
`ibys
`Met
`Met
`
`Val
`
`val
`Gly
`Gly
`
`Gly cys
`Ala Cys
`
`Gly Cys
`Ala Cys
`
`cys
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`Thr
`Thr
`
`Thr,
`Thr
`Ala
`
`Ala
`Ala
`Ala
`
`Ala
`Ala
`Thr
`
`Thr
`Thr
`Thr
`
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys.
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`cys
`
`Gly Cys
`Ala Cys
`Gly Cys
`Ala ‘Cys
`Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys”
`Gly Cys
`Ala'Cys _
`Gly Cys
`Ala Cys es
`Gly cys’,
`Ala Cys
`Gly Cys.
`‘Ala
`Cys
`Gly
`Cys©
`Ala
`Cys
`
`Thr
`Val
`‘Val
`
`Gly
`Gly
`“Thr
`Thr
`val
`Val
`
`Gly
`Gly
`Thr:
`
`Thre
`val
`val
`
`Gly
`ely
`Thr
`Thr
`Val
`val
`
`Gly
`Gly.
`‘Thr
`Gly
`Ala
`
`Gly
`Al a
`Gly
`‘Ala
`Gly
`Ala
`
`.
`
`cys |)
`Cys
`Cys-
`cys.
`Cys .
`cya:
`Cys.
`cys
`.
`Cys
`Gly:
`Ala
`Cys:
`cye .
`Gly
`Ala Cys
`Gly Cys
`Ala cys a
`Gly Cys -
`Ala Cys.
`Gly Cys -
`Ala Cys °
`Gly Cys
`Ala Cys
`Gly Cys
`
`“Val
`
`val
`Gly
`Gly
`Thr
`Thr
`Val.
`val
`Gly
`Gly
`Thr
`Thr
`val
`
`Cys”
`
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Asn
`Asn
`Asn.
`Asn
`
`Asn
`Asn
`Asn
`Asn
`Agen
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Thr
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`Thr
`Thr
`
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`
`Ala
`Thr
`Thr
`Thr
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`‘Gly
`Gly .
`Gly
`Pro
`Pro
`Pro
`Pro.
`Pro
`Pro
`Pro
`Pro
`Pro
`
`FIG.3
`(sheet 51 of 90)
`
`2789
`
`2789
`
`

`

`WO 2006/086653
`
`PCT/US2006/004768
`
`183/221
`
`Val
`
`Ala Cys
`
`Met
`Met
`
`Asn
`Asn
`
`Met
`Met
`Met
`
`Cys
`Cys
`
`Pro
`Pro
`Pro
`
`Thr
`Thr
`Thr
`Ala
`
`
`
`.
`.
`Cys Glu Tyr Cys
`(SEQ ID NO: 6987 )
`Gly Cys
`Gly
`(SEQ ID NO: 6958 )
`Cys Glu Tyr Cys
`Asn
`Ala Cys
`Gly.
`(SEQ ID NO: 6959 )
`Cys
`‘cys Glu Tyr Cys
`Thr
`Asn
`Gly Cys
`Cys
`(SEQ ID NO: 6960 )
`Gly
`‘Cys Glu Tyr Cys
`Thr
`Asn
`Ala Cys
`Cys
`Ala
`Cys Glu Tyr Cys.
`Gly
`(SEQ ID NO: 6961 )
`Val
`Asn
`Ala
`Cys
`Cys
`Gly
`Gly
`(SEQ ID NO: 6962 )
`Met
`Cys Glu Tyr Cys
`Ala
`Ala
`Val
`Met
`Asn
`Cys
`Cys
`Gly
`(SEQ ID NO: 6963,).
`Cys Glu Tyr Cys
`Asn
`Ala
`Met
`Gly
`Gly
`Cys —
`Gly
`Cys
`(SEQ ID NO: 6964 )
`Cys Glu Tyr Cys
`Ala:
`Asn
`Ala
`Cys
`Cys
`Gly
`Gly
`(SEQ ID NO: 6965 )
`Cys Giu Tyr Cys
`Asn
`Thr
`Gly
`Thr
`Cys
`Cye
`_ (SEQ ID NO: 6966 )
`Cys Glu Tyr Cys
`Thr
`Thr
`Cys
`Cys
`(SEQ ID NO: 6967 )
`Gly
`Cys Glu Tyr Cys
`Val
`Thr
`Cys
`Cys
`(SEQ ID NO: 6968 )
`Gly
`Cys Glu Tyr Cys
`Val
`Thr
`Cys .
`Cys
`(SEQ ID NO: 6969 )
`Cys
`Gly
`_¢ysGlu Tyr
`Thr
`Gly
`Cys
`Cys
`(SEQ ID NO: 6970 )
`Cys
`Cys Glu Tyr
`Thr
`cys
`Cys
`Cys
`(SEQ ID NO: 6971 )
`Cys Glu Tyr
`Gly
`Ala
`Pro
`Cys
`(SEQ ID NO: 6972 )
`Cys
`Cys Glu Tyr
`Pro
`Ala
`Cys
`Cys
`(SEQ ID NO: 6973 ).
`Cys Glu Tyr
`Ala
`Cys
`(SEQ ID NO: 6974 )|
`Cys Glu Tyx
`Cys
`Ala
`Cys
`(SEQ ID NO: 6975 )
`Cys
`Cys Glu Tyr.
`(SEQ ID NO:6976)
`Cys
`Cys Glu Tyr
`CysGlu Tyr
`(SEQ ID NO: 6977 )
`Cys
`|. (SEQ ID NO: 6978 )
`Cys
`Cys Glu Tyr
`_ (SEQ ID NO: 6979 )
`Cys
`Cys Glu Tyr
`(SEQ ID NO: 6980 )
`Cys
`Cys Giu Tyr
`“© (SEQ ID NO: 6981 )
`Cys
`Cys Glu Tyr
`(SEQ ID NO; 6982 )
`Cys
`Cys Glu Tyr
`“(SEQ ID NO: 6983 )
`Cys
`Cys Glu Tyr
`(SEQ ID NO: 6984 )
`Cys
`Cys Glu Tyr
`(SEQ ID NO: 6985 )
`Cys
`Cys Glu Tyr
`(SEQ ID NO: 6986 )
`Cys.
`Cys Glu Tyr
`(SEQ IDNO: 6987 )
`Tyr
`Cys
`Cys Glu
`(SEQ ID NO: 6988 )
`Tyr
`Cys
`Cys Glu
`(SEQ ID NO: 6989 )
`Tyr
`Cys
`Cys Glu
`‘cys Glu
`(SEQ ID NO: 6990 )
`Tyr
`Cys
`Tyr
`(SEQ ID NO: 6991 )
`Cys Glu
`Cys
`“(SEQ ID NO: 6992 )
`Tyr
`Cys Glu
`Cys
`‘cys
`(SEQ ID NO: 6993 )
`Tyr
`Cys Glu
`Tyr
`(SEQ ID NO: 6994 )
`cys
`Cys Glu
`(SEQ ID NO: 6995 )
`Cys
`Tyr.
`Cys Glu
`(SEQ ID NO; 6996 )
`Tyr Cys
`Cys Glu
`(SEQ ID NO: 6997 )
`Cys Glu
`(SEQ ID NO: 6998 )
`Cys Glu
`__ (SEQ ID NO: 6999 )
`Cys Glu
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn.
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Met |
`Met
`Met
`Met
`Met
`Met
`‘Met
`Phe
`Phe
`Phe
`
`Phe
`Phe
`Phe
`Phe
`Phe
`Phe
`Phe
`Phe
`Phe
`Phe
`Phe
`Phe
`
`Phe
`Phe’
`Phe
`Phe
`Phe
`Phe
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Pro
`
`Pro
`Pro
`Pro
`
`Asn.
`Asn
`Asn
`Asn
`
`Asn
`Asn
`Asn
`
`Asn
`Asn
`Asn
`
`Phe
`Phe
`Phe
`Pro
`Pro
`Pro
`Pro
`
`TyxzCys
`Tyr Cys
`Tyr Cys
`
`Pro
`Pro
`
`Pro
`Pro
`Pro
`
`Pro
`Pro
`
`Pro
`‘Pro
`Pro
`
`‘Ala
`Ala
`Thr
`Thr
`Thr
`Thr
`Thr
`
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`
`Thr
`Thr.
`Thr
`
`Ala
`Ala
`Ala
`Ala
`
`Cys
`Cys
`Cys
`Cys
`Cys
`
`?
`
`"
`
`"
`
`:
`
`‘
`
`»
`
`.
`
`°
`
`©
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Gly
`Gly.
`Thr
`Thr
`val
`
`Val
`
`Gly
`Gly
`Thr
`Thr
`
`Val
`Val
`
`Gly
`Ala
`
`Gly
`Ala
`Gly
`Ala
`
`Gly
`‘Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`cys
`Cys
`.
`
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys -
`Cys
`Cys
`
`cys |
`(Cys
`Cys
`Cys
`Cys
`cys .
`Cys’
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Cys ©
`Cys.
`Cys.
`
`Cys
`Cys
`Cys
`Cys
`
`Cys -
`
`Cys
`Cys
`Cys
`
`Gly
`Gly
`Thr
`Thr
`val
`Val
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys.
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`
`FIG. 3
`(sheet 52 of 90)
`
`-
`
`2790
`
`2790
`
`

`

`WO 2006/086653
`
`PCT/US2006/004768
`
`184/221
`
`cys
`
`Cys
`Cys
`Cys
`Cys:
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys .
`cys
`Cys
`
`Gly
`Ala
`Gly
`Ala
`
`Gly
`Ala.
`
`Cys
`Cys)
`Cys).
`Cys
`Gly
`Ala Cys
`.
`Gly.¢cys
`Ala Cys _—
`Gly Cys’
`‘Ala-Cys.’
`Gly Cys
`Ala Cys |
`Gly cys:
`Ala Cys
`
`Gly
`Gly
`Thr
`
`Thr
`Val
`val
`
`Gly
`Gly
`Thr.
`Thr
`Val
`Val
`
`Gly"
`Gly
`Thr
`Thr
`Val
`Val
`
`(SEQ ID NO: 7000 )
`(SEQ ID NO: 7001 )
`(SEQ ID NO: 7002 )
`(SEQ ID NO: 7003 )
`(SEQ ID NO: 7004 )
`(SEQ ID NO: 7005 )
`(SEQ ID NO: 7006 )
`(SEQ ID NO: 7007 )
`(SEQ ID NO: 7008 )
`(SEQ ID NO: 7009 )
`(SEQ ID NO: 7010 )
`(SEQ ID NO: 7011 )
`(SEQ ID NO: 7012 )
`(SEQ ID NO: 7013 )
`(SEQ ID NO: 7014 )
`(SEQ ID NO:7015 )
`(SEQ ID NO: 7016 )
`(SEQ ID NO: 7017 )
`(SEQ ID NO:7018 )
`(SEQ ID NO:7019 )
`(SEQ ID NO: 7020 )
`(SEQ ID NO: 7021 )
`(SEQ ID NO:7022 ).
`(SEQ ID NO: 7023)”
`(SEQ ID NO: 7024 )
`(SEQ ID NO: 7025 )
`(SEQ ID NO: 7026 )
`(SEQ ID NO; 7027 )
`(SEQ ID NO: 7028 )
`(SEQ ID NO: 7029 )
`(SEQ ID NO: 7030 )
`(SEQ ID NO: 7031 )
`(SEQ ID NO: 7032 )
`(SEQ ID NO: 7033 )
`(SEQ ID NO: 7034 )
`(SEQ ID NO: 7035 )
`(SEQ ID NO: 7036 )
`(SEQ ID NO: 7037 )
`. (SEQ IDNO: 7038 )
`(SEQ ID NO: 7039)
`(SEQ ID NO: 7040 ).
`(SEQ ID NO: 7041 )
`- (SEQ ID NO; 7042 )
`
`©
`
`Asn
`Asn
`
`Asn
`Asn
`Asn
`Asn
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asan
`Asn
`Asn
`Asn
`
`Pro
`Pro
`
`‘Pro
`Pro
`
`Pro
`Pro
`
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`
`‘Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Ser
`ser
`
`Glu Tyr
`Glu Tyr
`
`s Glu Tyr Cys
`Glu Tyr Cys
`Glu Tyr Cys
`Glu Tyr Cys
`Glu Tyr Cys.
`Glu Tyr Cys
`Glu Tyr Cys
`Cys
`Glu Tyr
`Cys
`Glu Tyr
`Cys
`Glu Tyr
`Cys
`Glu Tyr
`Glu Tyr
`Cys
`Cys
`Glu Tyr
`Cys
`Cys
`Cys
`Glu Tyr
`Cys
`Glu Tyr
`Glu Tyr
`Cys
`Cys
`Glu Tyr
`Cys
`Glu Tyr
`Glu Tyr
`Cys
`“Glu Tyr
`Cys
`Glu Tyr
`Cys
`Cys
`Glu Tyr
`Glu Tyr
`Cys
`cys"
`Glu Tyr
`Cys
`Glu Tyr
`Glu Tyr Cys
`Cys
`Glu Tyr
`Cys
`Glu Tyr
`Glu’
`Cys
`Tyr
`; Glu Tyr
`cys
`Glu
`Tyx
`Cys
`Glu
`Tyr
`Glu
`Tyr
`Tyr
`tyr
`Tyr
`Tyr
`
`3 Glu
`Glu
`‘Glu
`Glu
`Glu
`Glu
`Glu
`
`Glu
`
`Tyr
`Tyr
`Tyr
`Tyr Cys
`
`‘Ser
`ser
`Ser
`
`Ser,
`Ser
`Ser
`Ser
`Ser
`Ser
`Ser
`Ser
`
`Ser
`Ser
`Ser
`Ser
`Ser
`Ser
`
`Ser
`Ser
`Ser
`Ser
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`FIG. 3 ©
`(sheet 53 of 90)
`
`Pro
`Pro
`Pro
`Pro-
`Pro
`Pro
`Pro
`Pro
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Pro
`Pro
`Pro
`
`Ala
`Ala
`Thr-
`Thr
`Thr
`Thr
`Thr
`
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`
`Thr
`Thr
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`Cys
`
`Cys
`Cys’
`Cys
`Cys
`Cys
`
`Pro
`Pro
`Pro
`Pro
`
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly.
`Gly
`Gly
`Gly
`Gly
`Gly
`
`Thr
`Thr
`Thr
`Thr
`Thr
`Ala
`Ala
`
`Ala
`Ala
`Ala
`
`Thr
`
`RRR
`
`Thr
`
`‘Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`Gly
`Ala
`Gly
`‘Ala
`
`Gly
`Ala
`
`Cys
`cys
`cys
`Cys
`Cys
`Cys
`
`Gly
`Gly.
`Thr
`thr
`Val
`Val
`
`‘Gly
`Gly
`Thr
`Thr
`val
`val
`
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`
`Gly
`Gly
`Thr
`Thr
`Val
`val
`Gly.
`Gly
`Thr
`Thr
`Val
`Val
`
`Gly
`
`Cys
`Cys
`Cys
`cys
`Cys
`
`cys
`Cys
`Cys
`Cys
`
`cys
`‘Cys
`
`|. ve,
`
`Ala Cys’ :'
`GlyCys
`Ala Cys Oe vt oo
`Gly Cys’
`Ala Cys
`Gly Cys
`Ala Cys
`Gly Cys
`Ala cys |
`Gly: Cys °
`Ala cys
`Gly Cys’
`Ala Cys a
`GlyCys —
`
`2791
`
`2791
`
`

`

`WO 2006/086653
`
`PCT/US2006/004768
`
`185/221...
`
`Gly
`Pro
`Pro
`Pro
`
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro-
`Pro
`Pro
`
`“(SEQ ID NO:7043 )
`__ (SEQ ID‘NO: 7044 )
`(SEQ ID NO: 7045 )
`(SEQ ID NO: 7046 )
`(SEQ ID NO: 7047 )
`(SEQ ID NO:7048 )
`(SEQ ID NO: 7049 )
`(SEQ ID NO: 7050 ).
`(SEQ ID NO: 7051 )
`(SEQ ID NO: 7052 )
`(SEQ ID NO: 7053 )
`(SEQ ID NO: 7054 )
`".+ (SEQ ID NO: 7055 )
`“(SEQ ID NO: 7056)
`| °(SEQ ID NO:7087 )
`(SEQ ID NO: 7058 )
`(SEQ ID NO: 7059 )
`. (SEQ ID NO: 7060 )
`(SEQID NO:7061 )
`"(SEQ ID NO: 7062 )
`“(SEQ ID NO: 7083 )
`
`(SEQ ID NO: 7064 )
`.."_. (SEQ ID NO: 7065 ).
`(SEQ ID NO: 7066 )
`"+ (SEQ ID NO: 7087 )
`2" (SEQ ID NO: 7088 )
`i." (SEQ ID NO: 7069 )
`(SEQ ID NO: 7070 )
`(SEQ ID NO: 7071 ).
`~ (SEQID NO: 7072 )
`(SEQ ID NO: 7073 )
`(SEQ ID NO; 7074 ).
`{SEQ ID NO: 7075 )
`(SEQ ID NO: 7076 )
`(SEQ ID NO: 7077 )
`_
`(SEQ ID NO: 7078 )
`"
`~ (SEQID NO: 7079 )
`(SEQ ID NO: 7080 )
`(SEQ IDNO;7081 )
`(SEQ ID NO: 7082 )
`(SEQ ID NO: 7083 )
`(SEQ ID NO: 7084 )
`-
`__ (SEQ ID NO; 7085 )
`
`°
`
`-
`
`.
`
`
`
`
`~
`
`-
`
`ASD
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`ser
`
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`‘Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`
`Trp
`Trp
`
`Trp
`Txp
`Trp
`Trp
`Trp
`Trp
`Trp
`Trp
`
`Trp
`Trp
`Txp
`Trp
`Trp
`Txp
`Trp
`Txp
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`‘Asn
`Asn
`Asn
`Asn
`
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`. Cys Glu Tyr Cys
`Cys Glu Tyx Cys
`cys Glu Tyx Cys
`Cys Glu Tyx Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`‘Cys Glu ‘Tyr, Cys
`Cys Glu Tyr Cye
`Cys Glu Tyr Cys
`_ Cys Glu Tyr Cys
`‘Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys.
`‘Cys Glu Tyr Cys’
`Cys Glu TyrCys
`’ Cys Glu Tyr cys
`Cys Glu Tyr Cys
`cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr Cys
`Cys Glu Tyr cys
`Cys Glu Tyr Cys
` FIG.3.-
`(sheet 54 of 90).
`
`Pro,
`Pro
`Pro
`Pro
`
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Pro
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`
`Asn
`Asa
`Asn
`Asn
`
`Asn.
`Asn
`Asn
`Asn
`
`Ala
`Ala
`
`‘Ala
`Ala
`Thr
`Thr
`
`Thr
`Thr
`Thr
`Ala
`
`Ala
`Ala
`Ala
`
`Ala
`Ala
`
`
`
`Thr
`Ala
`Ala
`
`cys
`
`cys
`
`Ala Cys
`Cys
`Gly
`Ala
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Pro
`Pro
`
`Ala
`Ala
`
`Ala
`Ala
`Thr
`
`Thr.
`Thr
`Thr
`Thr
`
`Cys
`Cys
`cys
`cys
`cys
`cys.
`Cys
`Cys
`Cys
`cys
`Cys
`
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Ala
`Ala
`
`Gly
`Thr
`Thr
`
`Val
`val
`
`Gly
`Gly
`Thr
`Thr
`val
`Val
`
`Gly
`Gly
`Thr
`Thr
`val
`val
`
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`cys
`Cys
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`.
`
`.
`
`.
`
`«
`
`Cys ©
`Cys.
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys.
`Cys
`Cys |
`cys
`Cys
`Cys
`Cys |
`cys
`cys
`Cys
`Cys —
`cys|
`Cys
`cys
`Cys =
`Cys
`Cys ~
`Cys .
`Cys
`Cys
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Ala
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val.
`
`Gly
`Gly
`Thr
`Thr
`val
`Val
`
`Gly
`Gly
`Thr
`Thr
`val
`
`val
`
`cys
`cys
`Cys
`cys
`cys
`cys
`Cys
`Cys
`
`Gly
`Gly
`Thr
`Thr
`val
`Val
`
`Gly
`Gly
`
`cys
`Cys
`Cys
`cys
`Cys
`cys
`cys
`Cys
`cys
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`
`,
`
`2792
`
`2792
`
`

`

`186/221
`
`Asn
`Asn
`
`Asn.
`Asn
`Asn
`Asn
`
`Asn
`Asn
`Asn
`
`Asa
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Aen
`Asn
`
`WO 2006/086653
`
`~
`
`(SEQ ID NO:-7086 )
`(SEQ ID NO; 7087 )
`(SEQ ID NO: 7088 )
`(SEQ ID NO: 7089 ).
`(SEQ ID NO:7090 )
`_(SEQ ID NO: 7091 )
`(SEQ ID NO: 7092 )
`(SEQ ID NO: 7093 )
`(SEQ ID NO: 7094 )
`(SEQ ID NO: 7095 )
`(SEQ ID NO: 7096 )
`(SEQ ID NO: 7097 )
`(SEQ ID NO: 7098 )
`(SEQ ID NO: 7099 )
`(SEQ ID NO: 7100 )
`(SEQ ID NO: 7101 )
`. (SEQ ID NO: 7102 )
`(SEQ ID NO: 7103 }
`(SEQ ID NO: 7104 )
`(SEQ ID NO: 7105 )
`(SEQ ID NO: 7106 )
`(SEQ ID NO:7107)
`(SEQ ID NO: 7108 )-
`(SEQ ID NO:7109 )
`(SEQ ID NO: 7110 )
`(SEQ ID NO: 7111 )
`"(SEQ ID NO:7112 )
`(SEQ ID NO: 7113 )
`(SEQ ID NO:7114 )
`(SEQ ID NO: 7115 )
`(SEQ ID NO:7116 )
`(SEQ ID NO: 7117 )
`(SEQ ID NO: 7118 )
`(SEQ ID NO:7119 )
`(SEQ ID NO:7120 )
`(SEQ ID NO: 7121 )-
`(SEQ ID NO: 7122 )}
`(SEQ ID NO: 7123 )
`(SEQ ID NO: 7124 )
`(SEQ ID NO:7125 )
`(SEQ ID NO: 7126 )
`(SEQ ID NO: 7127 )
`(SEQ.ID NO: 7128 )
`
`*
`-
`
`_
`
`»
`
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`
`Glu Tyr
`Glu Tyr,
`Glu Tyr
`
`Cys
`Cys
`
`cys
`Cys
`Cys
`cys
`Cys
`Cys
`Cys
`cys
`cys
`Cys
`Cys °
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`
`Giu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu. Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Giu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu Tyr
`Glu tyr
`Glu Tyr
`; Glu Tyr
`Glu Tyr
`Glu Tyr
`Cys
`Glu Tyr
`Cys
`Glu Tyr
`cys
`Glu Tyr
`Cys
`Glu Tyr
`Cys
`Glu Tyr
`Cys
`i Glu Tyr
`Cys
`Glu Tyr
`cys
`“Glu Tyr
`Glu Tyr
`Cys
`Cys
`Glu Tyr
`Cys
`.Glu Tyr
`Cys
`Glu Tyr
`Glu Tyr Cys
`
`Tyr
`Tyr
`
`Tyr
`Tyr
`Tyr
`Tyr
`Tyr
`Tyr.
`Tyr
`Tyr
`Tyr
`Val
`Val
`
`Val
`
`Val
`Val
`Val
`val
`val
`val
`Val
`Val.
`Val
`
`val
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Pro
`Pro
`Pro
`Pro
`
`Thr
`Thr
`Thr
`
`Thr
`Thr
`
`Thr
`‘Ala
`
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`
`Thr
`Thr
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Pro
`Pro.
`Pro
`Pro
`Pro
`Pro
`Pro
`
`
`
`_PCT/0S2006/004768
`
`,
`
`|
`
`:
`
`‘Gly Cys
`Ala Cys
`Gly Cys an
`Ala Cys
`Gly Cys :
`Ala Cys
`Gly Cys
`Ala Cys
`Gly Cys
`—
`Ala Cys
`Gly Cys -
`Ala Cys
`~
`Gly Cys -
`Ala Cys -
`‘Gly Cys
`Ala Cys
`Gly Cys’.
`Ala cys
`Gly Cys
`Ala Cys
`Glycys
`Ala.cys |
`GlyCys’, .
`‘AlaCys .
`Gly Cys
`°
`Ala cys". os
`Gly Cys; .
`Ala Cys):
`Gly Cys =
`Ala Cys»
`Gly Cys’
`Ala Cys .
`Gly Cys °)
`Ala Cys —
`Gly Cys
`Ala Cys
`Gly Cys
`AlaCys:
`Gly Cys -
`AlaCys .
`Gly cys
`Ala Cys fe
`Gly Cys’
`
`Cys
`cys
`cys
`Cys
`Cys
`
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`
`Thr
`Thr
`val
`Val
`
`Gly
`Gly
`‘Thr
`Thr
`val
`val
`Gly
`Gly
`Thr
`Thr
`Val
`
`Val
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Gly
`Gly
`Thr
`“Thr
`Val
`
`Val.
`
`Gly
`Gly'
`
`Thr
`val
`Val
`
`Gly
`Gly
`Thr
`Thr
`Val
`
`Val
`Gly
`Gly
`Thr
`
`cys
`Cys
`cys
`cys
`Cys
`cys
`Cys
`cys
`Cys
`Cys
`Cys.
`Cys
`Cys
`Cys
`Cys
`
`Cys
`Cys
`Cys
`Cys
`Cys
`cys
`
`Thr
`Thr
`Thr
`
`Thre
`Ala
`Ala
`Ala
`
`Ala
`
`Ala
`Ala
`Thr
`Thr
`Thr
`
`Thr
`Thr
`Thr
`Ala
`
`Asn.
`Asn
`
`Asn
`Asn
`
`Asn
`Asn
`
`Asn
`Asn
`Asn
`
`Pro,
`Pro
`Pro
`Pro
`Pro
`
`Gly
`
`FIG. 3 ©
`(sheet 55 0f90)
`
`2793
`
`2793
`
`

`

`WO 2006/08665
`1086653
`
`PCT/US2006/004768
`
`187/221
`
`_
`
`.
`
`cys Glu Tyr Cys Val Asn Gly Ala Cys Thr Ala Cys
`(SEQ ID NO: 7129 )
`Cys Glu Tyr. Cys Val Asn Gly Ala Cys Val’ Gly Cys
`: (SEQ ID NO: 7130. )
`Cys Glu Tyr Cys Val Asn Gly Ala Cys Val Ala Cys
`(SEQ ID NO:7131 )
`cys Glu Tyr Cys Val Asn Gly Ala cys Gly Gly Cys
`(SEQ ID NO:7132 )
`cys Glu Tyr Cys Val Asn Gly Ala Cys Gly Ala Cys
`(SEQ ID NO: 7133 )
`cys Glu Tyx Cys Val Asn Gly Thr Cys Thr Gly Cys
`(SEQ ID NO:7134 )
`cys Glu tyr Cys Val Asn Gly Thr Cys Thr Ala Cys
`"(SEQ ID NO: 7135 )
`cys Glu Tyr Cys Val Asn Gly Thr Cys Val Gly Cys
`(SEQ ID NO:7136 )
`'
`Cys Glu Tyr Cys Val Asn Gly Thr Cys Val Ala Cys
`(SEQ ID NO:7137 )
`(SEQ ID NO:7138 ) ¢ys Glu Tyr Cys Val Asn Gly Thr Cys Gly Gly Cys
`(SEQ ID NO:7139 )
`| ¢ys Glu Tyr Cys Val Asn Gly Thr Cys Gly Ala Cys
`(SEQ ID NO: 7140 ) ys Glu Tyr Cys --- Asn Pro Ala Cys Thr Gly Cys
`'* (SEQ ID:NO:,7144 )
`cys GluTyr Cys --- Asn Pro Ala Cys Thr Ala Cys
`(SEQ ID NO: 7142 )
`Cys Glu Tyr Cys --- Asn Pro Ala Cys Val Gly Cys
`(SEQ ID NO: 7143 )
`Cys Glu Tyr Cys --- Asn Pro Ala Cys Val Ala Cys ©
`(SEQ ID NO:7144 )
`cys Glu Tyr Cys --- Asn pro ‘Ala Cys Gly Gly Cys
`(SEQ ID NO: 7145 )
`cys Glu Tyr Cys <-- Asn Pro Ala Cys Gly Ala Cys
`(SEQID NO: 7146 ).
`Cys Glu Tyr Cys. --- Asn Pro Thr Cys Thr Gly Cys
`(SEQIDNO:7147 )
`Cys Glu Tyr Cys -~- Asn Pro Thr Cys Thr Ala Cys
`_ (SEQ ID NO: 7148 )
`cys Glu Tyr Cys --- Asn Pro ‘Thr Cys Val Gly Cys
`(SEQ ID NO:7149 )
`cys Glu Tyr Cys --- Asn Pro Thr Cys Val Ala Cys |
`(SEQIDNO:7150 )
`Cys Glu Tyr Cys --- Asn Pro Thr Cys Gly Gly Cys
`-
`_
`(SEQ ID NO: 7151 ). Cys Glu Tyr Cys --- Asn Pro Thr Cys Gly Ala Cys
`he (SEQ ID NO: 7152 )
`| Cya Glu Tyr Cys --- Asn Gly Ala Cys Thr Gly Cys
`.« (SEQ 1D NO: 7153 )
`cys Glu Tyr Cys ~--- Asn Gly Ala Cys Thr Ala Cys
`Y. « (SEQ IDNO: 7154 ) Cys Glu Tyr Cys --- Asn Gly AlaCys val Gly Cys
`“i.” (SEQ IDNO:7155 ) Cys Glu Tyr Cys --- Asn Gly Ala Cys Val Ala Cys.
`
`"(SEQID NO: 7156 ) cys Glu Tyr Cys --- Asn Gly Ala Cys. Gly Gly Cys
`' (SEQ ID NO: 7157 )
`- cys Glu Tyr Cys --- Asn Gly Ala Cys Gly Ala Cys
`a (SEQ ID NO: 7158 )
`_ Cys Glu Tyr Cys ~-- Asn Gly Thr Cys Thr Gly Cys
`- (SEQIDNO:7159 )
`Cys Glu tyr Cys"--- Asn Gly Thr Cys Thr Ala cys
`“
`‘(SEQ IDNO:7160 ).
`Cys Glu Tyr Cys --- Asn Gly thr Cys Val Gly cys
`+» (SEQ ID NO: 7161 ) cys GluTyr Cys --- Asn Gly Thr Cys Val Ala Cys
`(SEQ ID NO: 7162 )
`(cys Glu Tyr Cys --- Asn Gly Thr Cys Gly Gly Cys a
`'.
`:
`(SEQID NO:7163 )
`Cys Glu Tyr cys --- Asn Gly Thr Cys Gly Ala Cys.
`,
`(SEQ ID NO: 7164 )
`Cys Glu Trp Cys Bla Asn Pro Ala Cys Thr Giy Cys
`(SEQ ID NO:7165 )
`Cys Glu Trp Cys Ala Asn Pro Ala Cys Thr Ala Cys
`(SEQ ID NO: 7166)
`Cys Glu Trp Cys Ala Asn Pro Ala Cys Val Gly Cys ,
`(SEQ ID NO:7167 )
`Cys Glu Trp Cys Ala Asn Pro Ala Cys Val Ala Cys
`(SEQ ID NO:7168 ). cys Glu Trp Cys Ala Asn Pro Ala Cys Gly Gly Cys |
`(SEQ ID NO: 7169 )
`cys Glu Trp Cys Ala Asn Pro Ala Cys Gly Ala Cys
`(SEQIDNO:7170 )
`Cys Glu Trp Cys Ala Asn Pro Thr Cys Thr Gly Cys
`. (SEQID NO:7171 )
`Cys Glu Trp Cys Ala Asn Pro. Thr Cys Thr Ala Cys
`- FIG.3.°
`|
`(sheet 56 0f90)
`
`-
`
` -
`
`2794
`
`2794
`
`

`

`WO 2006/086653
`
`188/221
`
`PCT/US2006/004768
`
`Asn
`
`val
`Val
`
`Gly
`Ala
`
`Cys
`Cys
`
`
`
`Pro
`Thr
`Ala
`(SEQ ID NO:7172 )
`|
`Glu
`Cys
`Trp
`Thr
`pro
`Asn
`Ala
`Glu
`(SEQ ID NO: 7173 )
`Cys
`Trp
`Pro
`Thr
`Asn.
`Ala
`Glu
`"(SEQ ID NO: 7174 )
`Cys
`Gly
`-Gly
`Trp
`Asn
`Pro
`Ala
`Ala
`Thr
`Glu
`Cys
`(SEQ ID NO: 7175)-
`Cys
`Gly
`Trp
`Ala
`Cys |
`Asn
`Thr
`Glu
`Ala
`(SEQ ID NO: 7176 )
`Cys
`Gly
`Gly
`Trp
`Thr
`Ala
`Asn
`Ala
`Glu
`Cys
`Cys
`(SEQ ID NO:7177 )
`Gly
`Trp
`Gly
`val
`cys
`Asn
`Giu
`Ala
`(SEQ ID NO: 7178 ):
`Cys
`Gly
`Trp
`Val
`Ala
`Asn
`Ala
`Cys
`Cys
`(SEQ ID NO:7179)
`Gly.
`Trp
`Apn
`Ala
`Oly
`(SEQ ID NO: 7180 )
`Cra
`Cys —
`Trp
`Gly -
`Asn
`Ala
`Ala Cys
`_
`(SEQ.ID NO: 7181)
`Cys
`Gly
`Trp
`Asn
`Ala
`Gly Cys
`(SEQ ID NO: 7182 )
`Cys
`Gly
`Trp
`Asn
`Ala
`cys
`Ala Cys
`(SEQ ID NO: 7183 ).
`Gly
`Trp
`Asn
`Ala
`Cys
`(SEQ ID NO: 7184 )
`Gly
`Trp
`Asn
`Ala
`(SEQ ID NO: 7185 )
`Cys
`Gly
`Trp
`Asn’
`Ala
`Cys
`(SEQ ID NO: 7186 -)
`Gly
`Trp
`Ala
`Cys
`(SEQ ID NO: 7187 )
`Gly
`Trp
`Pro
`Cys
`(SEQ ID NO:7188 )
`Trp
`Pro
`Cys
`(SEQ ID NO:7189 )
`Trp
`Pro
`(SEQ IDNO:7190 )
`Cys
`Trp
`Pro
`Cys
`(SEQ ID NO: 7191 )
`Trp
`Pro
`" (SEQ ID NO: 7192.)
`cys
`Trp
`Pro
`"(SEQ ID NO: 7193 )
`Cys
`Trp
`1) (SEQ ID NO: 7194 )-
`Cys
`Trp
`(SEQID NO: 7195 )
`Cys
`Trp
`"(SEQ ID NO: 7198: )
`Cys
`Trp
`Cys
`"2. (SEQ ID NO: 7197 )
`Trp
`Cys
`2's: {SEQ ID NO: 7198 )
`Txp
`~ (SEQ ID NO: 7199 )
`Trp
`cys
`(SEQ ID NO: 7200 )
`Cys
`Trp
`“(SEQ ID NO: 7201 )
`Cys
`Trp
`(SEQ ID NO: 7202 )
`cys
`Trp
`Trp
`2+ (GEQ ID NO: 7203 )
`cys
`(SEQ ID NO: 7204 )
`Cys
`Trp
`s+ (SEQ ID NO:7205 )
`Trp
`"
`(SEQ ID NO: 7206 )
`Top
`| (SEQ ID NO: 7207:)
`Trp
`(SEQ ID NO:7208 ).
`(SEQ ID NO: 7209 )
`_ (SEQ ID NO: 7210 ).
`(SEQ ID NO: 7214 )
`(SEQ ID NO: 7212 )
`(SEQ ID NO: 7213-)
`_ (SEQID No: 7214 )
`
`~
`
`_
`
`Glu
`Glu
`Glu
`Glu
`Glu-
`Glu
`Glu
`
`Glu
`3 Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`
`; Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`
`Glu
`
`Glu
`Glu
`Glu
`
`Glu
`Giu
`;Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`
`Arg
`Arg
`Arg
`Arg
`Arg
`Arg
`arg
`arg
`Arg
`Arg
`Arg
`Arg
`Arg
`Arg
`
`Arg
`Arg
`Arg
`Arg
`Arg
`Arg
`Arg
`Arg
`Arg
`
`Arg
`Asn
`
`§9993
`
`Trp
`Trp Cys
`
`Asn
`Asn
`
`Asn.
`Asn
`Asn
`
`Asn.
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Asn
`Asn
`Asn
`
`Asn
`Asn
`
`Asn
`Asn
`Asn
`Asn
`
`“Asn
`Asn
`Asn
`
`Asn
`Asn
`Asn
`Aen
`Asn
`
`Asn
`Asn
`
`Ala
`Ala
`Ala
`Ala
`Ala.
`Thr
`Thr
`
`Thr
`Thr
`Thr
`Thr
`Ala
`Ala
`Ala
`Ala
`
`Ala
`Ala
`“Thr
`Thr:
`Thr
`Thr
`Thr
`
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Gly
`Gly
`Thr
`
`Thr
`Val
`Val
`
`Gly
`Gly
`Thr
`Thr.
`Val
`val
`
`Gly
`Gly
`“Thr
`Thr
`‘Val
`Val
`
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`
`Pro
`Gly
`Gly
`Gly"
`Gly
`Gly
`Gly
`Cys
`Cys
`Gly
`Cys.
`Gly
`Cys
`Gly
`Cys
`Gly
`Cys
`Gly
`cys
`Thr
`ely
`Ala
`Pro
`Cys
`Pro Ala Cys
`Pro Ala Cys
`
`Thr
`Thr
`Thr
`Thr
`Thr
`
`Gly
`Gly.
`Thr
`Thr
`Val
`Val
`
`Gly
`Gly
`Thr
`Thr
`Val
`val
`
`Gly
`Gly
`Thr
`Thr
`val
`
`Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys
`
`|
`
`GlyCys
`Ala Cys
`Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys
`Gly cys
`Ala Cys .
`GlyCys.
`Ala Cys —
`Gly ‘Cys.
`‘
`Ala Cys
`Gly Cys a
`Ala Cys”
`Gly Cys
`Ala Cys
`Gly Cys
`Ala: Cys
`Gly Cys.
`Ala Cys
`Gly Cys
`
`FIG. 3
`(sheet 57 of90).
`
`2795
`
`2795
`
`

`

`
`
`WO 2006/086653
`
`PCT/US2006/004768
`
`189/221
`
`cys
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys.
`Cys
`Cys
`Cys
`cya
`Cys
`Cys
`
`Thr
`Thr
`Thr
`‘Thr
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`‘Thr
`Thr
`
`Pro
`Pro
`Pro
`Pro
`
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`
`Ala
`Ala
`Ala
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`
`Asn
`Asn
`
`Asn
`Asn
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Asp
`Asp
`Asp
`Asp
`Asp
`Asp
`Asp
`Asp
`Asp
`Asp
`Asp
`
`Aen
`Asn
`Asn
`Asn'
`Asn
`Asn
`Asn
`‘Asn
`Asn
`
`(SEQ ID NO: 7215 )
`(SEQ ID NO:7216 )
`(SEQ ID NO: 7217 )
`(SEQ ID NO:7218 )
`(SEQ ID NO: 7219 )
`(SEQ ID NO: 7220 )
`(SEQ ID NO: 7221 )
`(SEQ ID NO: 7222 )
`(SEQ ID NO: 7223 )
`(SEQ ID NO:7224 )
`(SEQ ID NO: 7225 )
`(SEQ ID NO: 7226 )
`(SEQ ID NO: 7227 )
`(SEQ ID NO: 7228 )
`(SEQ ID NO: 7229 )
`(SEQ ID NO: 7230 )
`(SEQ ID NO:7231 )
`(SEQ ID NO:7232 )
`" (SEQ ID NO: 7233 )
`(SEQ ID NO:7234 )
`(SEQ ID NO: 7235 )
`(SEQ ID NO:7236 )
`(SEQ ID NO: 7237 )
`(SEQ ID NO: 7238 )
`. (SEQ ID NO: 7239 )
`(SEQ ID NO: 7240 )
`(SEQ ID NO: 7241 )
`(SEQ ID NO: 7242 )
`(SEQ ID NO: 7243 )
`(SEQ ID NO: 7244 )
`(SEQ ID NO: 7245 )
`(SEQ ID NO: 7246 )
`(SEQ ID NO: 7247 )
`(SEQ ID NO: 7248 )
`(SEQ ID NO: 7249 )
`(SEQ ID NO:7250)
`(SEQ ID NO: 7251 )
`(SEQ ID NO:7252 )
`(SEQ ID NO: 7253 )
`(SEQ ID NO: 7254 )
`(SEQ ID'NO: 7255 )
`(SEQ ID NO: 7256 )
`(SEQ ID NO: 7257 )
`
`-
`
`Glu Trp Cys
`Glu Trp Cys.
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`GluTrp Cys
`Giu Trp Cys
`Glu Trp cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`‘Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`3 Glu
`Trp Cys
`Glu
`Trp Cys
`Glu
`Trp Cys
`Glu
`Trp Cys
`Trp Cys
`Trp Cys
`Trp Cys
`Trp Cys
`Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`Glu Trp Cys
`
`3 Glu
`
`Glu
`Glu
`Glu
`
`Glu
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Pro
`
`Asp
`
`Asn
`
`Asp
`Asp
`Asp
`Asp
`Asp
`Asp
`
`Asp
`Asp
`Asp
`Asp
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Asn
`Asn
`Asn
`Asn
`
`Gly
`Gly
`Gly
`Gly
`Gly.
`Gly
`Gly
`Gly
`
`Gly
`Gly
`
`. FIG.3 ©
`(sheet 58 of 90)
`
`_
`
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`
`Val
`
`Gly.
`Gly
`Thr
`Thr
`
`Val
`Val
`
`Ala Cys
`Gly Cys
`Ala Cys
`Gly Cys
`Ala cys.
`Gly Cys
`Ala Cys
`Gly Cys
`Ala ‘Cys
`‘Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys
`GlyCys
`Ala, Cys’
`Gly Cys | -
`Ala Cys °
`Gly Cys
`Ala Cys
`Gly Cys
`Ala. Cys
`Gly Cys
`Ala Cys
`Gly Cys -
`Ala Cys
`Gly Cys
`Ala Cys
`Gly Cys.
`Ala Cys |
`Gly Cys ,
`Ala Cys
`Gly Cys:
`Ala Cys ~
`Gly Cys .
`ala Cye
`‘Gly Cys
`Ala Cys’.
`Gly Cys:
`Ala Cys:
`Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys.
`
`Gly
`Gly
`Thr
`
`Thr
`Val
`val
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Gly
`Gly
`Thr
`Thr
`val
`val
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Gly
`Gly
`Thr
`Thr
`val
`Val
`
`Gly
`Gly
`Thr
`The
`
`val
`val
`
`"
`,
`
`‘
`
`2796
`
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`cys.
`Cys
`Cys
`cys
`Cys
`cys
`
`Thr
`Thr
`Ala
`
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`Ther.
`
`Thr
`
`2796
`
`

`

`Cys Glu Txp Cys Asp Asn Gly Thr Cys Gly Gly Cys
`(SEQ ID NO: 7258 )
`cys Glu Trp Cys Asp Asn Gly Thr Cys Gly Ala Cys
`_ (SEQ ID NO: 7259)
`cys Glu Trp Cys Gla Asn Pro Ala Cys Thr Gly Cys
`(SEQ ID NO:7260 )
`(SEQ ID NO: 7261): Cys Glu Trp Cys Gln Asn Pro Ala Cys Thr Ala Cys
`(SEQ ID NO:7262 )
`Cys Glu Trp Cys Gin Asn Pro Ala Cya Val Gly Cys
`(SEQ ID NO:7263 )
`cys Glu TrpCys Gln Asn Pro Ala Cys Val Ale cys.
`(SEQ ID NO: 7264 ) . Cys Glu Trp Cys Gln Asn Pro Ala Cys ‘Gly Gly cys
`(SEQ ID NO: 7265 )
`cys Glu Trp Cys Gin Asn Pro. Ala Cys Gly Ala Cys
`(SEQ ID NO: 7266 )
`cys Glu Trp Cys Gln Asn Pro Thr. Cys Thr Gly Cys
`(SEQ'ID NO: 7267.)
`cys Glu Trp Cys Gln Asn Pro Thr Cys Thr Ala Cys
`*
`_
`(SEQID NO:7268 ) Cys Glu TrpCys Gln Asn Pro Thr Cys Val Gly cys
`". (SEQ ID NO:7269 )
`Cys Glu Trp Cys Gln Asn Pro thr Cys Val Ala Cys
`(SEQ ID NO: 7270 ). Cys Glu Trp Cys Gln Aen Pro Thr Cys Gly Gly Cys
`(SEQ ID NO:7271 ). Cys Glu Txp Cys Gln Asn pro Thr Cys Gly Ala Cys
`(SEQ !D NO: 7272 )
`Cys Glu Trp Cys Gin. Asn Gly Ala Cys Thr Gly Cys
`(SEQ ID NO:7273 )
`Cys Glu Trp Cys ‘gin Asn Gly Ala Cys Thr Ala Cys
`(SEQ ID NO:7274 )
`cys Glu Trp Cys Gin Aen GlyAla Cys val Gly Cys
`(SEQ ID NO:7275 )
`. Cys Glu Trp Cys Gln Aen Gly Ala Cys Val Ala Cys.
`—
`(SEQIDNO:7276 )
`Cys Glu Trp Cys Gin Asn Gly Ala Cys Gly Gly Cys
` (GEQIDNO:7277 )
`Cys Glu Trp Cys Gin Asn Gly Ala Cys Gly Ala Cys
`| (SEQ ID NO: 7278")
`Cys Glu Trp Cys.Gln Asn Gly Thr Cys Thr Gly cys
`-
`(SEQ ID NO:7278 ).
`cys Glu Trp Cys,éin Asn Gly Thr Cys Thr Ala Cys
`o> (SEQID NO: 7280 ). Cys Glu Trp Cys Gln Asn Gly Thr Cys Val Gly Cys
`“' + (SEQ ID NO: 7281 ) ‘Cys Glu Trp Cys Gln Asn Gly Thr Cys Val Ala Cys
`©. (SEQID NO: 7282:).
`Cys Glu Trp Cys Gin Asn Gly Thr Cys Gly Gly Cys
`“+, (SEQ ID NO: 7283 )
`cys Glu Trp Cys GlnAsn Gly Thr Cys Gly Ala Cys
`(SEQ ID NO: 7284 ).. Cys Glu Trp Cys Glu Asn Pro Ala Cys Thr Gly Cys .
`
`~ (GEQID NO: 7285)
`Cys Glu Trp cys Glu Asn pro Ala Cys.Thr Ala Cys
`
`(SEQ IDNO:7286 )
`. Cys Glu Trp Cys Glu Asn Pro Ala Cys Val GlyCys
`(SEQ ID NO: 7287). Cys Glu Trp Cys Glu Asn Pro ‘Ala Cys.Val Ala Cys
`(SEQID NO:7288 ). Cys Glu Trp Cys Glu Asn Pro Ala Cys Gly Gly Cys
`(SEQ ID NO: 7289 ), cys Glu Trp Cys Glu Asn Pro Ala Cys Gly Ala Cys:
`|
`. (SEQ ID NO: 7290: )
`' Cys Glu: Trp Cys Glu Asn Pro Thr Cys Thr Gly Cys .
`(SEQ ID NO:7291 ) ' cys Glu Trp Cys Glu Asn Pro Thr Cys Thr Ala Cys
`(SEQ ID NO: 7282 )
`cys Glu Trp Cys Glu Asn Pro Thr Cys Val Gly Cys -
`(SEQ ID NO: 7293 )
`cys Glu Trp Cys Glu ‘Asn Pro Thr Cys Val Ala Cys
`(SEQ ID NO:7294 )
`cys. Glu Trp Cys Glu Aen Pro Thr Cys Gly Gly Cys
`(SEQ ID NO:7295 )
`Cys, Glu Trp cys Glu’ Asn Pro Thr Cys Gly AlaCys
`(SEQ ID NO;7296 )
`cys Glu Trp Cys Glu Asn Gly Ala Cys Thr Gly Cys
`(SEQ ID NO: 7297 )
`cys Glu Trp Cys Glu AsnGly Ala Cys Thr Ala Cys
`(SEQ ID NO: 7298)
`cys Glu Trp Cys Glu Asn Gly Ala cys Val Gly Cys
`(SEQ ID NO:7299 )
`Cys Glu Trp Cys Glu Asn Gly Ala Cys Val Ala Cys:
`_ (SEQ ID NO: 7300 )
`..¢ys Glu Txp Cys Glu Asn Gly Ala Cys Gly Gly cys
` FIG.3.:
`.
`(sheet 59 of 90)
`
`.
`
`_
`
`*
`
`.
`
`WO 2006/086653
`
`190/221.
`
`PCT/U
`
`$2006/004768
`
`—
`
`.
`
`Ss
`
`2797
`
`2797
`
`

`

`WO 2006/086653
`
`191/221
`
`PCT/US2006/004768
`
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`
`Ala
`Thr
`Thr
`Thr
`
`Thr
`Thr
`Thr
`
`Ala
`Ala.
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`Thr
`Thr
`Thr
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thr
`Thr
`Thr
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Pro.
`Pro
`
`Pro
`Pro
`Pro
`Pro
`
`Pro
`Pro
`Pro
`Pro
`Pro
`Pro
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`"
`
`_
`
`»
`
`©
`
`(SEQ ID NO: 7301 )
`(SEQ ID NO: 7302 )
`(SEQ ID NO: 7303 )
`(SEQ ID NO: 7304 )
`(SEQ ID NO: 7305 )
`(SEQ ID NO: 7306 )
`(SEQ ID NO: 7307 )
`(SEQ ID NO;7308 )
`(SEQ ID NO:7309 )
`: (SEQ ID NO:7310 )
`(SEQ ID NO: 7311 )
`(SEQ ID NO: 7312 )
`(SEQ ID NO: 7313 )
`(SEQ ID NO: 7314 )
`(SEQ ID NO: 7315 )
`(SEQ ID NO: 7316 )
`(SEQ ID NO:7317 )
`_ (SEQ ID NO: 7348 )
`(SEQ ID NO: 7319 ):
`(SEQ ID NO: 7320 )
`(SEQ ID NO: 7321 ) -
`(SEQ ID NO: 7322 )
`(SEQ ID NO: 7323 )
`(SEQ ID NO:7324 )
`(SEQ ID NO: 7325 )
`_ (SEQ ID NO: 7326 )
`(SEQ ID NO: 7327 )
`(SEQ ID NO: 7328 )
`(SEQ ID NO: 7329 )
`(SEQ ID NO: 7330 )
`(SEQ ID NO: 7331 )”
`(SEQ ID NO: 7332 )
`(SEQ ID NO: 7333 )
`(SEQ ID NO: 7334 )
`(SEQ ID NO: 7335 )
`(SEQ ID NO: 7336 )
`(SEQ ID NO: 7337 )
`(SEQ ID NO:7338-)
`(SEQ ID NO: 7339 )
`(SEQ ID NO: 7340 )
`(SEQ ID NO: 7344 )
`(SEQ ID NO: 7342 )
`(SEQ ID NO:7343 )
`
`
`
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Giu
`Glu
`Glu
`
`Glu
`Glu
`Giu
`Glu
`
`Glu
`Glu
`3 Glu
`Glu
`Glu
`
`Glu
`Glu
`Glu
`
`Glu
`Glu
`Glu
`Glu.
`Glu
`
`Glu
`
`Trp
`Trp
`Trp
`Trp
`Trp
`Trp
`Trp
`
`Trp
`Trp
`Txp
`Trp
`Trp
`Trp
`Trp
`Trp
`Trp
`Txp
`Txp
`Txp
`Trp
`Trp
`
`_TIp
`Trp
`Trp
`Trp
`Trp
`Trp
`Trp
`Trp
`Trp
`Trp
`Trp
`Txp
`Trp
`Trp
`Trp
`Trp
`
`Trp
`Trp
`Trp
`Trp
`
`‘Clu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`
`Glu |
`Trp
`Glu Trp
`
`cys
`Cys
`Cys
`Cys
`Cys
`cys
`Cys
`cys
`Cys
`Cya
`Cys
`Cys
`Cys
`Cys
`Cys
`cys
`cys
`cys
`cys
`
`cys
`Cys
`Cys
`Cya
`Cys
`Cys
`cys
`Cys
`Cys
`cys
`cys
`
`cys
`cys
`Cys
`Cys
`Cys
`Cys
`cys
`‘ys
`cys
`
`Glu
`
`Glu
`Glu
`Glu
`Glu
`Glu
`Glu
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`‘ely
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Giy
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`His
`
`His
`His
`His
`His
`
`His
`His
`His
`
`His
`His
`His
`
`‘His
`
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`Asn
`
`Asn
`Asn
`
`Asn
`Asn
`Asn
`
`Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`‘Gly
`Gly
`Gly
`Gly
`Gly
`Gly
`Pro
`Pro
`Pro
`Pro
`Pro
`
`‘Pro
`Pro.
`Pro
`Pro
`Pro
`
`Pro
`Pro
`
`Cys
`Cys
`Cys
`Cys
`FIG.3
`(sheet 60 of 90)
`
`-
`
`Gly
`Thr
`Thr
`Val
`Val
`
`Gly
`Gly
`Thr
`Thr
`Val
`
`Val
`Gly
`Gly
`Thr
`Thr
`
`Val.
`Val
`
`Ala Cys
`Gly. cys
`Ala ‘Cys :
`Gly Cys
`Ala Cys —
`Gly cys
`Ala Cys.
`Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys
`Gly Cys
`Ala Cys _
`Gly: Cys
`Ala Cys’
`Gly Cys.”
`Ala Cys:
`|
`Gly Cys...
`Alacys ~
`Gly Cys |.
`Ala Cys.’
`Gly Cye’
`Ala cys
`Gly Cys"
`Cys
`Ala
`cys
`cys
`cys 0°
`pee
`
`Gly
`Gly
`Thr
`Thr
`Val
`Val
`
`Gly
`Gly
`Thr
`Thr
`Val
`val
`Gly
`Gly
`Thr
`
`Gly
`Ala
`Gly
`‘Ala
`
`Val
`
`val
`Gly
`
`Gly:
`Thr
`
`Thr
`
`Val
`Val
`
`Gly
`Gly
`
`Gly
`Cys
`Ala
`Cys
`Cys
`Gly
`Cys
`Ala
`Cys
`Gly
`Ala Cys |
`Gly Cye
`Ala Cys
`Gly Cys.
`Ala Cys .
`Gly Cys.
`Ala Cys -
`Gly Cys:
`Ala. Cys
`
`2798
`
`cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`cys
`Cys
`Cys
`Cys
`cys
`cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`Cys
`
`Thr
`Thr
`Thr
`Ala
`Ala
`Ala
`Ala
`Ala
`Ala
`Thre
`Thr
`Thr
`Thr
`
`Thr
`Thr
`
`2798
`
`

`

`WO 2006/086653
`
`PCT/US2006/004768
`
`192/221
`
`Thr
`Thr’
`val
`val
`Gly
`Gly
`Thr
`Thr
`Val
`val
`Gly
`Gly
`Thr
`Thr
`Val
`val
`
`_
`
`
`
`(SEQ ID NO: 7344 )
`_
`- (SEQ IDNO: 7345 )
`(SEQ ID NO:7346.
`)
`(SEQ ID NO:7347 )
`(SEQ ID NO: 7348 )
`(SEQ ID NO: 7349 )
`(SEQ ID NO: 7350 )
`(SEQ ID NO:7351 )
`(SEQ ID NO: 7352 )
`.(SEQ'ID NO: 7353 )
`(SEQ ID NO: 7354 )
`- (SEQ ID NO: 7355 )
`(SEQ ID N