Variants of tissue inhibitor of metalloproteinase type three (timp-3), compositions and methods
AssigneeAmgen Inc.
InventorsJason C. O'NEILL, Randal R. KETCHEM, TaeWeon LEE, Vishnu CHINTALGATTU, Jennitte LeAnn STEVENS
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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.
Claims12
-12. (canceled)
A method of treating a condition in which matrix metalloproteases (MMPs) and/or other proteinases that are inhibited or inhibitable by Tissue Inhibitor of Metalloproteinase Type Three (TIMP-3) play a causative or exacerbating role, comprising administering to an individual afflicted with such a condition an amount of a composition comprising a TIMP-3 mutein sufficient to treat the condition, wherein the TIMP-3 mutein comprises a mature region that is at least 90% identical in amino acid sequence to the mature region of TIMP-3 set forth in SEQ ID NO:2 and:
- (a) two or more pairs of mutations selected from K45N/V47T;
- K50N/V52T;
- P56N/G58T;
- H78N/Q80T;
- K94N/E96T;
- or D110N/K112T;
- (b) one or more pairs of mutations selected from K45N/V47T;
- K50N/V52T;
- P56N/G58T;
- H78N/Q80T;
- K94N/E96T;
- or D110N/K112T;
- and an additional mutation selected from R138T;
- G173T, or both R138T and G173T;
- or
- (c) the mutations of (a) or (b) further comprising the mutation F57N.
The method of 13, wherein the condition is an inflammatory conditions, osteoarthritis, myocardial ischemia, reperfusion injury, or progression to congestive heart failure.
-20. (canceled)
Dependencies are inferred from the claim text.