Signalling System

Patent metadata

Field	Value
Publication number	US-2019330299-A1
Application number	US-201716076760-A
Country	US
Kind code	A1
Filing date	Feb 10, 2017
Priority date	Feb 12, 2016
Publication date	Oct 31, 2019
Grant date	—

Abstract

The present invention provides a chimeric antigen receptor (CAR) system comprising; (i) a receptor component comprising a antigen binding domain and a first binding domain; and (ii) a signalling component comprising a signalling domain and a second binding domain which binds the single domain binder of the first binding domain of the receptor component wherein either the first or second binding domains comprise a single domain binder, and wherein, binding of the first and second binding domains is disrupted by the presence of an agent, such that in the absence of the agent, the receptor component and the signalling component heterodimerize and binding of the antigen binding domain to antigen results in signalling through the signalling domain; whereas in the presence of the agent, the receptor component and the signalling component do not heterodimerize and binding of the antigen binding domain to antigen does not result in signalling through the signalling domain.

First claim

1 - 27 . (canceled)

28 . A chimeric antigen receptor (CAR) system comprising;
(i) a receptor component comprising an antigen binding domain, a transmembrane domain and first binding domain which comprises a single domain binder which binds an agent, and (ii) an intracellular signalling component comprising a signalling domain and a second binding domain which binds the single domain binder of the first binding domain of the receptor component; wherein binding of the first and second binding domains is disrupted by the presence of an agent, such that in the absence of the agent, the receptor component and the signalling component heterodimerize and binding of the antigen binding domain to antigen results in signalling through the signalling domain; whereas in the presence of the agent, the receptor component and the signalling component do not heterodimerize and binding of the antigen binding domain to antigen does not result in signalling through the signalling domain.

29 . A chimeric antigen receptor (CAR) system comprising;
(i) an intracellular signalling component comprising a signalling domain and a first binding domain comprises a single domain binder, and (ii) a receptor component comprising an antigen binding domain, a transmembrane domain and second binding domain which binds the single domain binder of the intracellular signalling component; wherein binding of the first and second binding domains is disrupted by the presence of an agent, such that in the absence of the agent, the receptor component and the signalling component heterodimerize and binding of the antigen binding domain to antigen results in signalling through the signalling domain; whereas in the presence of the agent, the receptor component and the signalling component do not heterodimerize and binding of the antigen binding domain to antigen does not result in signalling through the signalling domain.

30 . A nucleic acid sequence encoding a CAR signalling system according to claim 28 , wherein the receptor component and signalling component are co-expressed with a self-cleaving peptide which is cleaved between the receptor component and the signalling component after translation of the components.

31 . A nucleic acid sequence encoding a CAR signalling system according to claim 29 , wherein the receptor component and signalling component are co-expressed with a self-cleaving peptide which is cleaved between the receptor component and the signalling component after translation of the components.

32 . A vector comprising a nucleic acid sequence according to claim 30 .

33 . A vector comprising a nucleic acid sequence according to claim 31 .

34 . A cell which expresses
(i) a receptor component comprising an antigen binding domain, a transmembrane domain and first binding domain which comprises a single domain binder which binds an agent, and (ii) an intracellular signalling component comprising a signalling domain and a second binding domain which binds the single domain binder of the first binding domain of the receptor component; wherein binding of the first and second binding domains is disrupted by the presence of an agent, such that in the absence of the agent, the receptor component and the signalling component heterodimerize and binding of the antigen binding domain to antigen results in signalling through the signalling domain; whereas in the presence of the agent, the receptor component and the signalling component do not heterodimerize and binding of the antigen binding domain to antigen does not result in signalling through the signalling domain.

35 . A cell which expresses
(i) an intracellular signalling component comprising a signalling domain and a first binding domain comprises a single domain binder, and (ii) a receptor component comprising an antigen binding domain, a transmembrane domain and second binding domain which binds the single domain binder of the intracellular signalling component; wherein binding of the first and second binding domains is disrupted by the presence of an agent, such that in the absence of the agent, the receptor component and the signalling component heterodimerize and binding of the antigen binding domain to antigen results in signalling through the signalling domain; whereas in the presence of the agent, the receptor component and the signalling component do not heterodimerize and binding of the antigen binding domain to antigen does not result in signalling through the signalling domain.

36 . A pharmaceutical composition comprising a plurality of cells according to claim 34 .

37 . A pharmaceutical composition comprising a plurality of cells according to claim 35 .

38 . A method for treating and/or preventing a disease in a subject, which comprises the step of administering a pharmaceutical composition according to claim 36 to the subject.

39 . A method for treating and/or preventing a disease in a subject, which comprises the step of administering a pharmaceutical composition according to claim 37 to the subject.

40 . A method for making a cell according to claim 34 , which comprises the step of introducing into the cell a nucleic acid sequence according to claim 30 or a vector according to claim 32 .

41 . A method for making a cell according to claim 35 , which comprises the step of introducing into the cell a nucleic acid sequence according to claim 31 or a vector according to claim 33 .

42 . A method for inhibiting a CAR signalling system according to claim 28 in a subject,
wherein the subject comprises a cell according to claim 34 and the method comprises the step of administering the agent to the subject.

43 . A method for inhibiting a CAR signalling system according to claim 29 in a subject,
wherein the subject comprises a cell according to claim 35 and the method comprises the step of administering the agent to the subject.

Assignees

• Autolus Ltd

Inventors

• Pulé Martin
• Cordoba Shaun
• Thomas Simon
• Onuoha Shimobi
• Stavrou Maria

Classifications

• C07K2319/33

  fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies · CPC title

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• C07K14/7051 Primary

  T-cell receptor (TcR)-CD3 complex · CPC title

• C07K14/70521

  CD28, CD152 · CPC title

• C07K2319/03

  containing a transmembrane segment · CPC title