US2017369530A1PendingUtilityA1

Macrocyclic inhibitors of the pd-1/pd-l1 and cd80(b7-1)/pd-l1 protein/protein interactions

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Assignee: BRISTOL MYERS SQUIBB COPriority: Mar 15, 2013Filed: Aug 9, 2017Published: Dec 28, 2017
Est. expiryMar 15, 2033(~6.6 yrs left)· nominal 20-yr term from priority
Inventors:Michael M. MillerClaudio MapelliMartin Patrick AllenMichael S. BowsherKenneth M. BoyEric P. GillisDavid R. LangleyEric MullMaude A. PoirierNishith SanghviLi-Qiang SunDaniel J. TenneyKap-Sun YeungJuliang ZhuPatrick ReidPaul Michael Scola
A61P 37/02A61P 43/00A61P 31/18A61P 31/12A61P 35/04A61P 37/04A61P 31/22A61P 35/00A61P 31/04A61P 31/14A61P 31/16A61P 31/20A61P 1/16G01N 33/575C07K 7/08G01N 2800/26A61K 38/00G01N 2500/02A61K 39/39C07K 7/56G01N 2333/70532A61K 45/06A61K 38/10G01N 33/574Y02A50/30
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Claims

Abstract

The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of enhancing, stimulating, and/or increasing the immune response in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of at least one macrocyclic peptide that has a net charge between −2 and +3 under physiological conditions, wherein the net charge is calculated by adding the charges of each amino acid side chain; wherein the charge of each side chain is assigned as positive if the group can accept a proton and negative if it can donate a proton. 
     
     
         2 . A method of inhibiting growth, proliferation, or metastasis of cancer cells in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of at least one macrocyclic peptide that has a net charge between −2 and +3 under physiological conditions, wherein the net charge is calculated by adding the charges of each amino acid side chain; wherein the charge of each side chain is assigned as positive if the group can accept a proton and negative if it can donate a proton. 
     
     
         3 . A method of treating an infectious disease in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of at least one macrocyclic peptide that has a net charge between −2 and + under physiological conditions 3, wherein the net charge is calculated by adding the charges of each amino acid side chain; wherein the charge of each side chain is assigned as positive if the group can accept a proton and negative if it can donate a proton. 
     
     
         4 . A method of treating septic shock in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of at least one macrocyclic peptide that has a net charge between −2 and +3 under physiological conditions, wherein the net charge is calculated by adding the charges of each amino acid side chain; wherein the charge of each side chain is assigned as positive if the group can accept a proton and negative if it can donate a proton.

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