BLy antagonists and uses thereof
AssigneeGenentech, Inc.
InventorsAndrew Chan, Nathaniel Gordon, Robert Kelley, Michael Koehler, Melissa Starovasnik
Life of this patent
Estimating the term…
Abstract
The present invention relates to polypeptides that block BLyS signaling, nucleic acid molecules encoding the polypeptides, and compositions comprising the polypeptides. The present invention also relates to methods for treating an immune-related disease or cancer using the polypeptides and compositions of the invention. The present invention also relates to methods for identifying inhibitors of BLyS signaling.
Claims91
A polypeptide comprising the sequence of Formula I:
- X1-CN-X3-D-X5-L-X7-X8-X9-X10-X11-X12-CT-X14-X15-X16-X17 (Formula I) (SEQ ID NO:1)
- wherein X1, X3, X5, X7, X8, X9, X10, X11, X12, X14, X15 and X17 are any amino acid except cysteine;
- and
- wherein X16 is an amino acid selected from the group consisting of L, F, I and V;
- wherein the polypeptide does not comprise a cysteine within seven amino acid residues N-terminal to CN (cysteine N terminal) and C-terminal to CT (cysteine C terminal) of Formula I;
- wherein CN and CT are joined by disulfide bonding;
- wherein the conformation of X5LX7X8 forms a type I beta turn structure with the center of the turn between L and X7;
- and
- wherein X8 has a positive value for the dihedral angle phi.
A polypeptide comprising the sequence of Formula II:
- X1-CN-X3-D-X5-L-V-X8-X9-W-X11-X12-CT-X14-X15-L-X17 (Formula II) (SEQ ID NO:18)
- wherein X1, X3, X5, X8, X9, X10, X11, X12, X14, X15 and X17 are any amino acid except cysteine;
- wherein the polypeptide does not comprise a cysteine within seven amino acid residues N-terminal to CN (cysteine N terminal) and C-terminal to CT (cysteine C terminal) of Formula II;
- and
- wherein CN and CT are joined by disulfide bonding.
A polypeptide comprising an amino acid sequence of Formula III:
- E-CN-F-D-X5-L-V-X8-X9-W-V-X12-CT-X14-X15-X16-X17 (Formula III) (SEQ ID NO:26)
- wherein X5, X8, X9, X12, X14, X15 and X17 are any amino acid except cysteine;
- wherein X16 is an amino acid selected from the group consisting of L, F, I and V;
- wherein the polypeptide does not comprise a cysteine within seven amino acid residues N-terminal to CN (cysteine N terminal) and C-terminal to CT (cysteine C terminal) of Formula III;
- and
- wherein CN and CT are joined by disulfide bonding.
A polypeptide comprising a polypeptide sequence selected from the group consisting of:
- SEQ ID NO:13 through SEQ ID NO:17 and SEQ ID NO:
- 62 through SEQ ID NO:137.
(canceled)
A polypeptide comprising at least two peptides selected from the group consisting of:
- SEQ ID NO:13 through SEQ ID NO:17 and SEQ ID NO:
- 62 through SEQ ID NO:137.
Dependencies are inferred from the claim text.