IP Library › Granted Patent US 12,474,348
Granted Patent B2
US 12,474,348 · App. 17/823,356 · Granted Nov 18, 2025

Complexes between CD40 and compounds comprising benzimidazole moieties

Inventors: James Philip O′Connell (Slough, GB); John Robert Porter (Slough, GB); Alastair Lawson (Slough, GB); Boris Kroeplien (Slough, GB); Stephen Edward Rapecki (Slough, GB); Timothy John Norman (Slough, GB); Graham John Warrellow (Slough, GB)
Assignee: UCB BIOPHARMA SRL
G01N33/6845A61K47/6425A61P35/00A61P37/00C07D213/72C07D235/04C07D239/26C07D401/14C07D471/00C07D471/04C07K14/525C07K14/70575C07K16/241G01N33/6854G01N33/6863C07K2317/55C07K2317/92G01N2333/525G01N2500/02
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Quick Facts
Patent No.
US 12,474,348
App. No.
17/823,356
Granted
Nov 18, 2025
Kind
B2
Abstract

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Accordingly, these compounds can be used as modulators of TNF. Anew assay for identifying compounds with this mechanism of action is also disclosed.

Claims (15)

1 . A complex comprising a trimeric protein that is a TNF superfamily member and a compound comprising a benzimidazole moiety that is capable of binding to the trimeric protein that is a TNF superfamily member, whereby the compound-trimer complex binds to a requisite TNF superfamily receptor and modulates the signalling induced by the trimeric protein that is a TNF superfamily member through the receptor,

wherein the TNF superfamily member is TNFα and the requisite receptor is TNF receptor, or wherein the TNF superfamily member is CD40L and the requisite receptor is CD40.

2 . The complex of claim 1 , wherein the compound antagonises the signalling induced by the trimer through the receptor.

3 . The complex of claim 2 , wherein:

a) the compound increases the stability of the trimeric form of the TNF superfamily member compared to the stability of the trimeric form of the TNF superfamily member in the absence of the compound; or

b) the compound increases the stability of the trimeric form of the TNF superfamily member compared to the stability of the trimeric form of the TNF superfamily member in the absence of the compound and the increase in stability results in an increase in the thermal transition midpoint (T m ) of the trimeric form of the TNF superfamily member of at least 1° C., of at least 10° C., or between 10° C. and 20° C.

4 . The complex of claim 1 , wherein:

a) the compound increases the binding affinity of the TNF superfamily member to the requisite receptor compared to the binding affinity of the TNF superfamily member to its receptor in the absence of the compound;

b) the compound increases the binding affinity of the TNF superfamily member to the requisite receptor compared to the binding affinity of the TNF superfamily member to its receptor in the absence of the compound and the compound increases the binding affinity of the TNF superfamily member to the requisite receptor by increasing the on rate (k on-r ) and/or decreasing the off rate (k off-r ) compared to the k on-r and k off-r values for binding of the TNF superfamily member to its receptor in the absence of the compound;

c) the compound increases the binding affinity of the TNF superfamily member to the requisite receptor compared to the binding affinity of the TNF superfamily member to its receptor in the absence of the compound the compound increases the binding affinity of the TNF superfamily member to the requisite receptor by increasing the on rate (k on-r ) compared to the k on-r value for binding of the TNF superfamily member to its receptor in the absence of the compound;

d) the compound decreases the K D-r of the TNF superfamily member to the requisite receptor compared to the K D-r of the TNF superfamily member to its receptor in the absence of the compound, wherein the compound decreases the K D-r of the TNF superfamily member to the requisite receptor by at least 10 times compared to the K D-r of the TNF superfamily member to its receptor in the absence of the compound and the K D-r value of the TNF superfamily member for binding to the requisite receptor in the presence of the compound is less than 10 nM; or

e) the compound decreases the K D-r of the TNF superfamily member to the requisite receptor compared to the K D-r of the TNF superfamily member to its receptor in the absence of the compound, wherein the compound decreases the K D-r of the TNF superfamily member to the requisite receptor by at least 4 times compared to the K D-r of the TNF superfamily member to its receptor in the absence of the compound and the K D-r value of the TNF superfamily member for binding to the requisite receptor in the presence of the compound is less than 600 pM or less than 200 pM.

5 . The complex of claim 1 , wherein:

a) said compound has an IC 50 value of 500 nM or less.

6 . A pharmaceutical composition comprising the complex of claim 1 and a pharmaceutically acceptable carrier.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 26, 2025
From: UCB S.A.
To: UCB PHARMA S.A.
Reel/Frame 072119/0968 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2022
From: O'CONNELL, JAMES PHILIP; PORTER, JOHN ROBERT; LAWSON, ALASTAIR; KROEPLIEN, BORIS; RAPECKI, STEPHEN EDWARD; NORMAN, TIMOTHY JOHN; WARRELLOW, GRAHAM JOHN
To: CELLTECH R&D LIMITED
Reel/Frame 060948/0912 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2022
From: CELLTECH R&D LIMITED
To: UCB S.A.
Reel/Frame 060948/0975 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2022
From: UCB PHARMA S.A.
To: UCB BIOPHARMA SPRL
Reel/Frame 060948/0996 →
CHANGE OF NAME Recorded Aug 31, 2022
From: UCB BIOPHARMA SPRL
To: UCB BIOPHARMA SRL
Reel/Frame 061364/0163 →
Priority Claims (1)
GB 1510758 · Jun 18, 2015 · national
Continuity (3)
Division 16883859 · May 26, 2020
Division 15736520
Related Publication 20230194541A1 · Jun 22, 2023
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