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US 11,306,150 B2Granted
Method of identifying a P-selectin glycoprotein ligand-1 (PSGL-1) antagonist
AssigneesBristol-Myers Squibb Company, Five Prime Therapeutics, Inc.
InventorsRobert J. Johnston, Andrew Rankin, Arathi Krishnakumar, Paul O. Sheppard, Arvind Rajpal
Life of this patent
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Abstract
Methods of identifying and using PSGL-1 antagonists are provided. Such methods include, but are not limited to, methods of treating cancer. PSGL-1 antagonists include, but are not limited to, antibodies that bind PSGL-1 and antibodies that bind VISTA, wherein the antibodies inhibit PSGL-1 binding to VISTA, e.g., at acidic pH (e.g., pH 6.0), as well as PSGL-1 and VISTA extracellular domain polypeptides.
Claims17
A method of identifying a PSGL-1 antagonist, comprising:
- a) forming a composition comprising a candidate molecule, a VISTA molecule, and a PSGL-1 molecule, wherein the VISTA molecule comprises VISTA, a VISTA ECD, or a VISTA ECD fusion molecule, and the PSGL-1 molecule comprises PSGL-1, PSGL-1 ECD, or a PSGL-1 ECD fusion molecule;
- and
- b) detecting binding of the VISTA molecule to the PSGL-1 molecule;
- wherein the composition has a pH in the range of pH 5.5 to pH 6.5, and wherein a reduction in the binding of the VISTA molecule to the PSGL-1 molecule in the presence of the candidate molecule as compared to the binding of the VISTA molecule to the PSGL-1 molecule in the absence of the candidate molecule indicates that the candidate molecule is a PSGL-1 antagonist wherein
- the PSGL-1 ECD comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:
- 3, 4, 16, 17, or 18, and the VISTA ECD comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of amino acids 1-202 of SEQ ID NO:
- 10.
4 more elements
Dependencies are inferred from the claim text.