Monoclonal antibodies against JC virus

Patent metadata

Field	Value
Publication number	US-12410238-B2
Application number	US-202017620496-A
Country	US
Kind code	B2
Filing date	Jun 19, 2020
Priority date	Jun 19, 2019
Publication date	Sep 9, 2025
Grant date	Sep 9, 2025

Abstract

Provided herein are monoclonal antibodies and antigen-binding fragments thereof that bind to the John Cunningham virus. Also provided are pharmaceutical compositions comprising the monoclonal antibodies and antigen-binding fragments thereof, as well as methods of using such monoclonal antibodies and antigen-binding fragments thereof, including methods for the treatment and/or prevention of JCV infections and/or progressive multifocal leukoencephalopathy.

First claim

The invention claimed is:

1. An antibody or antigen-binding fragment thereof which binds to the John Cunningham virus (JCV), the antibody or antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region;
wherein each of the heavy chain and the light chain variable regions comprises a CDR1, CDR2, and CDR3; and wherein:
(a) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:5, CDR2H comprises SEQ ID NO:12, CDR3H comprises SEQ ID NO:23, CDR1L comprises SEQ ID NO:36, CDR2L comprises the sequence KVS, and CDR3L comprises SEQ ID NO:45;
(b) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:1, CDR2H comprises SEQ ID NO:12, CDR3H comprises SEQ ID NO:23, CDR1L comprises SEQ ID NO:36, CDR2L comprises the sequence KVS, and CDR3L comprises SEQ ID NO:45;
(c) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:3, CDR2H comprises SEQ ID NO:12, CDR3H comprises SEQ ID NO:25, CDR1L comprises SEQ ID NO:36, CDR2L comprises the sequence KVS, and CDR3L comprises SEQ ID NO:45;
(d) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:3, CDR2H comprises SEQ ID NO:12, CDR3H comprises SEQ ID NO:26, CDR1L comprises SEQ ID NO:36, CDR2L comprises the sequence KVS, and CDR3L comprises SEQ ID NO:45;

(e) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:3, CDR2H comprises SEQ ID NO:14, CDR3H comprises SEQ ID NO:28, CDR1L comprises SEQ ID NO:37, CDR2L comprises the sequence KVS, and CDR3L comprises SEQ ID NO:45;
(f) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:4, CDR2H comprises SEQ ID NO:15, CDR3H comprises SEQ ID NO:28, CDR1L comprises SEQ ID NO:36, CDR2L comprises the sequence KVS, and CDR3L comprises SEQ ID NO:45;
(g) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:6, CDR2H comprises SEQ ID NO:16, CDR3H comprises SEQ ID NO:29, CDR1L comprises SEQ ID NO:39, CDR2L comprises the sequence WAS, CDR3L comprises SEQ ID NO: 48;
(h) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:6, CDR2H comprises SEQ ID NO:16, CDR3H comprises SEQ ID NO:30, CDR1L comprises SEQ ID NO:39, CDR2L comprises the sequence WAS, CDR3L comprises SEQ ID NO: 49;
(i) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:8, CDR2H comprises SEQ ID NO:18, CDR3H comprises SEQ ID NO:32, CDR1L comprises SEQ ID NO:41, CDR2L comprises the sequence AAS, and CDR3L comprises SEQ ID NO:51;
(j) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:8, CDR2H comprises SEQ ID NO:19, CDR3H comprises SEQ ID NO:32, CDR1L comprises SEQ ID NO:41, CDR2L comprises the sequence AVS, and CDR3L comprises SEQ ID NO:52;
(k) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:11, CDR2H comprises SEQ ID NO:22, CDR3H comprises SEQ ID NO:35, CDR1L comprises SEQ ID NO:44, CDR2L comprises the sequence GTS, and CDR3L comprises SEQ ID NO:55;
(l) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:9, CDR2H comprises SEQ ID NO:20, CDR3H comprises SEQ ID NO:33, CDR1L comprises SEQ ID NO:42, CDR2L comprises the sequence WAS, and CDR3L comprises SEQ ID NO:53; or
(m) CDR1H of the antibody or antigen-binding fragment thereof comprises SEQ ID NO:10, CDR2H comprises SEQ ID NO:21, CDR3H comprises SEQ ID NO:34, CDR1L comprises SEQ ID NO:43, CDR2L comprises the sequence GAS, and CDR3L comprises SEQ ID NO:54.

2. The antibody or antigen-binding fragment thereof according to claim 1 , wherein:
(a) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 101, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:102;
(b) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 69, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:70;
(c) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 73, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:74;
(d) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 75, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:76;
(e) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 81, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:82;
(f) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 79, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEO ID NO: 80;
(g) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 83, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:84;
(h) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 85, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:86;
(i) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 87, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:88;
(j) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 91, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:92;
(k) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 103, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:104;
(1) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 97, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:98;
(m) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 93, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:94; or
(n) the heavy chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO: 95, and wherein the light chain variable region comprises a sequence that is at least 90% identical to SEQ ID NO:96.

3. The antibody or antigen-binding fragment thereof according to claim 2 , wherein:
(a) the heavy chain variable region comprises SEQ ID NO:101 and the light chain variable region comprises SEQ ID NO:102;
(b) the heavy chain variable region comprises SEQ ID NO:69 and the light chain variable region comprises SEQ ID NO:70;
(c) the heavy chain variable region comprises SEQ ID NO:73 and the light chain variable region comprises SEQ ID NO:74;
(d) the heavy chain variable region comprises SEQ ID NO:75 and the light chain variable region comprises SEQ ID NO:76;
(e) the heavy chain variable region comprises SEQ ID NO:81 and the light chain variable region comprises SEQ ID NO:82;
(f) the heavy chain variable region comprises SEQ ID NO:79 and the light chain variable region comprises SEQ ID NO:80;
(g) the heavy chain variable region comprises SEQ ID NO:83 and the light chain variable region comprises SEQ ID NO:84;
(h) the heavy chain variable region comprises SEQ ID NO:85 and the light chain variable region comprises SEQ ID NO:86;
(i) the heavy chain variable region comprises SEQ ID NO:87 and the light chain variable region comprises SEQ ID NO:88;
(j) the heavy chain variabl

Assignees

• Icahn School Med Mount Sinai

Inventors

• Moran Thomas
• Kraus Thomas
• Duty J Andrew
• Tortorella Domenico

Classifications

• C07K16/084 Primary

  Papillomaviridae (F); Polyomaviridae (F), e.g. SV40, BK virus or JC virus · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title