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US 2014/0274874 A1Published application
Variants of tissue inhibitor of metalloproteinase type three (timp-3), compositions and methods
AssigneeAmgen Inc.
InventorsRandal R. KETCHEM, Jason Charles O'NEILL, Jeonghoon SUN
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Abstract
There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them.
Claims18
An isolated TIMP-3 mutein having a mature region that is at least 95% identical in amino acid sequence to the mature region of TIMP-3 set forth in SEQ ID NO:2, having at least one mutation, the mutation being selected from the group consisting of:
- (a) K45E, K49S;
- (SEQ ID NO:
- 5);
- (b) K45E, K49E;
- (SEQ ID NO:
- 6);
- (c) K45E, T63E;
- (SEQ ID NO:
- 7);
- (d) K45E, Q80E;
- (SEQ ID NO:
- 8);
- (e) K45E, T63E, H78E;
- (SEQ ID NO:
- 10);
- (f) T63E, H78E, Q80E;
- (SEQ ID NO:
- 11);
- (g) K45E, T63E, H78E, Q80E;
- (SEQ ID NO:
- 12);
- (h) T63E, T74E, H78E;
- (SEQ ID NO:
- 13);
- (i) T63E, T74E, H78D;
- (SEQ ID NO:
- 14);
- (j) L51T, T74E, H78D;
- (SEQ ID NO:
- 53);
- (k) T74E, H78E, Q80E;
- (SEQ ID NO:
- 16);
- (l) T74E, H78D, Q80E;
- (SEQ ID NO:
- 17);
- (m) K45N, V47T;
- (SEQ ID NO:
- 26);
- (n) K65N, M67T;
- (SEQ ID NO:
- 37);
- (o) K45N, V47T, T63E, T74E, H78E;
- (SEQ ID NO:
- 18);
- (p) K49N, L51T, T63E, T74E, H78E;
- (SEQ ID NO:
- 19);
- (q) K45E, K49N, L51T, T63E;
- (SEQ ID NO:
- 20);
- (r) K49N, L51T, T74E, H78E;
- (SEQ ID NO:
- 21);
- (s) K49N, L51T;
- (SEQ ID NO:
- 27);
- (t) K50N, V52T;
- (SEQ ID NO:
- 30);
- (u) L51N, K53T;
- (SEQ ID NO:
- 54);
- (v) F57N;
- (SEQ ID NO:
- 33);
- (w) P56N, G58T;
- (SEQ ID NO:
- 31);
- (x) T63N, K65T;
- (SEQ ID NO:
- 36);
- (y) P56N, G58T, T63N, K65T;
- (SEQ ID NO:
- 32);
- (z) K75N, P77T;
- (SEQ ID NO:
- 38);
- (a′) H78N, Q80T;
- (SEQ ID NO:
- 39);
- (b′) K94N, E96T;
- (SEQ ID NO:
- 40);
- (c′) E96N, N98T;
- (SEQ ID NO:
- 41);
- (d′) V97N, K99T;
- (SEQ ID NO:
- 42);
- (e′) D110N, K112T;
- (SEQ ID NO:
- 43);
- (f′) Q126N;
- (SEQ ID NO:
- 44);
- (g′) R138N, H140T;
- (SEQ ID NO:
- 46);
- (h′) R138T;
- (SEQ ID NO:
- 45);
- (i′) T158N, K160T;
- (SEQ ID NO:
- 47);
- (j′) T166N, M168T;
- (SEQ ID NO:
- 48);
- (k′) G173T;
- (SEQ ID NO:
- 49);
- (l′) H181N, A183T;
- (SEQ ID NO:
- 50);
- (m′) R186N, K188T;
- (SEQ ID NO:
- 51);
- (n′) P201N, K203T;
- (SEQ ID NO:
- 52);
- (n′) A208Y;
- (SEQ ID NO:
- 55);
- (o′) A208V;
- (SEQ ID NO:
- 56);
- (p′) K45S, F57N;
- (SEQ ID NO:
- 23);
- (q′) K49S, F57N;
- (SEQ ID NO:
- 28);
- (r′) K68S, F57N;
- (SEQ ID NO:
- 34);
- (s′) K133S, F57N;
- (SEQ ID NO:
- 35);
- (t′) K45S, K133S, F57N;
- (SEQ ID NO:
- 24);
- and
- (u′) K49S, K68S, F57N (SEQ ID NO:
- 29).
141 more elements
An isolated TIMP-3 mutein selected from the group consisting of:
- (a) A TIMP-3 polypeptide comprising the mutation F57N, and
- (b) A TIMP-3 polypeptide comprising the mutation F57N and a mutation selected from the group consisting of:
- a K45S mutation;
- a K49S mutation;
- a K68S mutation;
- a K133S mutation;
- a K45S mutation and a K133S mutation;
- and a K49S mutation and a K68S mutation.
5 more elements
An isolated TIMP-3 mutein selected from the group consisting of:
- (a) a TIMP-3 polypeptide comprising the mutations P56N, G58T;
- (b) a TIMP-3 polypeptide comprising the mutations T63N, K65T;
- and
- (c) a TIMP-3 polypeptide comprising the mutations P56N, G58T, T63N, K65T.
1 more element
Dependencies are inferred from the claim text.