Antibody epitope
AssigneesUcb Biopharma Srl, Sanofi
InventorsAlastair David Griffiths LAWSON, Daniel John LIGHTWOOD, Rebecca Jayne MUNRO, James Philip O'CONNELL, John Robert PORTER
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Abstract
It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.
Claims43
An antibody which binds to an epitope comprising at least the following residues of trimeric TNFα:
- (a) Y115
- (b) Q149;
- and
- (c) N137 or K98, or both,
- wherein Y115 and Q149 are present on the C chain of trimeric TNFα, and N137 and K98 are present on the A chain of trimeric TNFα, and wherein the residue numbering is according to SEQ ID NO:
- 36.
An antibody according to any one of the preceding claims, which binds to an epitope further comprising one or more residues selected from the group consisting of:
- (a) L63;
- (b) L94;
- (c) S95;
- and
- (d) A96;
- wherein L63 is present on the C chain of trimeric TNFα and L94, S95 and A96 are present on the A chain of trimeric TNFα.
An antibody according to any one of the preceding claims, which binds to an epitope further comprising one or more residues selected from the group consisting of:
- (a) 197;
- (b) L93;
- and
- (c) S81,
- wherein I97, L93 and S81 are all present on the A chain of trimeric TNFα.
An antibody according to any one of the preceding claims, which binds to an epitope further comprising one or more residues selected from the group consisting of:
- (a) K65;
- (b) Q67;
- (c) P113;
- (d) D143;
- (e) T77;
- (f) T79;
- (g) I83;
- (h) T89;
- (g) K90;
- (i) V91;
- (j) N92;
- (k) E135;
- (l) I136;
- and
- (m) R138;
- wherein K65, Q67, P113 and D143 are present on the C chain of trimeric TNFα and T77, T79, I83, T89, K90, V91, N92, E135, I136 and R138 are present on the A chain of trimeric TNFα.
An antibody according to any one of the preceding claims, which binds to an epitope further comprising one or more residues selected from the group consisting of:
- (a) Y119;
- (b) Q47;
- and
- (c) S133,
- wherein all of Y119, Q47 and S133 are present on the A chain of trimeric TNFα.
An antibody according to any one of the preceding claims, which has an affinity (KD-ab) of 1 nM or less.
An antibody according to any one of the preceding claims, which is a humanised antibody.
An antibody according to any one of the preceding claims, which is a Fab, modified Fab, Fab′, modified Fab′, F(ab′)2, Fv, single domain antibody or an scFv.
An antibody according to any one of the preceding claims, which binds a complex of trimeric TNFα and any one of compounds (1)-(7):
An antibody which competes for binding to TNFα with an antibody as defined in any one of the preceding claims.
Dependencies are inferred from the claim text.