Administration of kynurenine depleting enzymes for tumor therapy
AssigneeBoard of Regents, The University of Texas System
InventorsGeorge Georgiou, Everett Stone, Nicholas Marshall, John Blazeck, Wei-Cheng Lu
Life of this patent
Estimating the term…
Abstract
Methods and compositions related to the use of a protein with kynureninase activity are described. For example, in certain aspects there may be disclosed a modified kynureninase capable of degrading kynurenine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with kynurenine depletion using the disclosed proteins or nucleic acids.
Claims20
A method of treating a subject having a tumor that produces kynurenine, the method comprising administering to the subject an effective amount of a formulation comprising a modified human kynureninase enzyme in a pharmaceutically acceptable carrier, said modified enzyme having at least one substitution relative to native human kynureninase comprising the amino acid sequence of SEQ ID NO:
- 8, wherein the at least one substitution is at positions:
- (a) A99, F306, and A436;
- (b) A99, G112, F306, L337, I405, and S408;
- (c) G112, F306, L337, and I405;
- (d) A99, T138, F306, and A436;
- (e) A99, G112, F306, V339, I405, and S408;
- (f) A99 and F306;
- (g) F306, L337, V339, I405, and S408;
- (h) G112, F306, V339, and I405;
- (i) G112, F306, V339, and S408;
- (k) F71, A99, G112, T138, F306, L337, V339, I405, S408, and A436;
- (1) A99, G112, F306, L337, V339, I405, and S408;
- (m) A436;
- (n) A99, G112, T138, V339, and I405;
- (p) A99, G112, F306, I405, S408, and A436;
- (q) F71, A99, I131, F249, and L322;
- (r) A99, I131, F249, E259, and F306;
- (s) F71, A99, and E259;
- (t) F71, A99, S167, and E259;
- (u) I131, F249, and S274;
- (v) L59, G112, F306, V339, I405, and S408;
- (w) I110 and F306;
- (x) A99, I131, F249, and E259;
- (y) F71, E259, and L322;
- (z) H41, Q175, and A436;
- (a′) A99, I131, and F249;
- (b′) I131 and F249;
- (c′) T138 and A436;
- (d′) T138;
- (e′) F71, A99, I131, E259, and V303;
- (f) A99, G112, F306, V339, 1405, and S408;
- (g′) F71, A99, I131, E259, and A282;
- (h′) F71, F249, E259, and V303;
- or (i′) I110, wherein the administration treats the tumor in the subject.
Dependencies are inferred from the claim text.