Apo-2 ligand/trail variants and uses thereof
OwnerRobert Kelley, Sarah Hymowitzinventors
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Abstract
The disclosure provides Apo-2 ligand variant polypeptides. Methods of making and chemically modifying Apo-2 ligand variant polypeptides are also provided. In addition, formulations of Apo-2 ligand variant polypeptides are provided. In addition, therapeutic methods for using Apo-2 ligand variant polypeptides are provided.
Claims38
An isolated Apo-2 ligand variant polypeptide comprising an amino acid sequence which differs from the native sequence Apo-2 ligand polypeptide sequence of FIG. 1 (SEQ ID NO:1) and has one or more of the following amino acid substitutions at the residue position(s) in FIG. 1 (SEQ ID NO:1):
- S96C;
- S101C;
- S111C;
- R170C;
- K179C.
An isolated Apo-2 ligand variant polypeptide comprising one or more amino acid mutations in the amino acid sequence of native Apo-2 ligand polypeptide sequence of FIG. 1 (SEQ ID NO:1), said mutations comprising one or more amino acid substitutions recited in Table II.
An isolated Apo-2 ligand variant polypeptide comprising an amino acid sequence which differs from the native sequence Apo-2 ligand polypeptide sequence of FIG. 1 (SEQ ID NO:1) and has a set of amino acid substitutions at the residue position(s) in FIG. 1 (SEQ ID NO:1) selected from the group consisting of:
- Y189A:R191K:Q193K,
- Y189A:R191K:Q193K:H264A,
- Y189Q:R191K:Q193R:H264R:1266L:D267Q,
- Y189A:R191K:Q193K:H264D:1266L:D267Q:D269E, and
- Y189A:R191K:Q193R:H264S:1266L:D269E.
An isolated Apo-2 ligand variant polypeptide comprising one or more amino acid mutations in the amino acid sequence of native Apo-2 ligand polypeptide sequence of FIG. 1 (SEQ ID NO:1), said mutations comprising one or more amino acid substitutions recited in Table III.
An isolated Apo-2 ligand variant polypeptide comprising one or more amino acid mutations in the amino acid sequence of native Apo-2 ligand polypeptide sequence of FIG. 1 (SEQ ID NO:1), said mutations comprising one or more amino acid substitutions recited in Table VII.
An isolated Apo-2 ligand variant polypeptide comprising an amino acid sequence which differs from the native sequence Apo-2 ligand polypeptide sequence of FIG. 1 (SEQ ID NO:1) and has a set of amino acid substitutions at the residue position(s) in FIG. 1 (SEQ ID NO:1) selected from the group consisting of:
- Y189Q:R191K:Q193R;
- H264R;
- 1266L;
- D267Q;
- Y189Q:R191K:Q193R;
- and
- Y189Q:R191K:Q193R:1266L.
Dependencies are inferred from the claim text.