US 2018/0002415 A1 · ANTI-C5 ANTIBODIES AND METHODS OF USE

Abstract

An objective of the invention is to provide anti-C5 antibodies and methods of using the same. The invention provides anti-C5 antibodies and methods of using the same. In some embodiments, an isolated anti-C5 antibody of the present invention binds to an epitope within the β chain of C5 with a higher affinity at neutral pH than at acidic pH. The invention also provides isolated nucleic acids encoding an anti-C5 antibody of the present invention. The invention also provides host cells comprising a nucleic acid of the present invention. The invention also provides a method of producing an antibody comprising culturing a host cell of the present invention so that the antibody is produced. The invention further provides a method of producing an anti-C5 antibody comprising immunizing an animal against a polypeptide which comprises the MG1-MG2 domain of the β chain of C5. Anti-C5 antibodies of the present invention may be for use as a medicament. Anti-C5 antibodies of the present invention may be for use in treating a complement-mediated disease or condition which involves excessive or uncontrolled activation of C5. Anti-C5 antibodies of the present invention may be for use in enhancing the clearance of C5 from plasma.

Claims73

Dependent claims

-28. (canceled)

A method of neutralizing C5 in a biological sample comprising contacting a biological sample containing C5 with an antibody that binds C5 under conditions permissive for binding of the antibody to C5, and inhibiting the activation of C5;

and wherein the antibody comprises:
(a) a HVR-H1 comprising the amino acid sequence SSYYX1X2, wherein X1 is M or V, X2 is C or A (SEQ ID NO:
126);
(b) a HVR-H2 comprising the amino acid sequence X1IX2TGSGAX3YX4AX5WX6KG, wherein X1 is C;
A or G, X2 is Y or F, X3 is T, D or E, X4 is Y, K or Q, X5 is S, D or E, X6 is A or V (SEQ ID NO:
127);
and
(c) a HVR-H3 comprising the amino acid sequence DX1GYX2X3PTHAMX4X5, wherein X1 is G or A, X2 is V, Q or D, X3 is T or Y, X4 is Y or H, X5 is L or Y (SEQ ID NO:
128);
(d) a HVR-L1 comprising the amino acid sequence X1ASQX2IX3SX4LA, wherein X1 is Q or R, X2 is N, Q or G, X3 is G or 5, X4 is D, K or S (SEQ ID NO:
129);
(e) a HVR-L2 comprising the amino acid sequence GASX1X2X3S, wherein X1 is K, E or T, X2 is L or T, X3 is A, H, E or Q (SEQ ID NO:
130);
and
(f) a HVR-L3 comprising the amino acid sequence QX1TX2VGSSYGNX3, wherein X1 is S, C, N or T, X2 is F or K, X3 is A, T or H (SEQ ID NO:
131).

13 more elements

A method of reducing the concentration of C5 in a biological sample comprising contacting a biological sample containing C5 with an antibody that binds C5 under conditions permissive for binding of the antibody to the C5, and removing the complex formed between the antibody and the C5;

and wherein the antibody comprises:
(a) a HVR-H1 comprising the amino acid sequence SSYYX1X2, wherein X1 is M or V, X2 is C or A (SEQ ID NO:
126);
(b) a HVR-H2 comprising the amino acid sequence X1IX2TGSGAX3YX4AX5WX6KG, wherein X1 is C, A or G, X2 is Y or F, X3 is T, D or E, X4 is Y, K or Q, X5 is S, D or E, X6 is A or V (SEQ ID NO:
127);
and
(c) a HVR-H3 comprising the amino acid sequence DX1GYX2X3PTHAMX4X5, wherein X1 is G or A, X2 is V, Q or D, X3 is T or Y, X4 is Y or H, X5 is L or Y (SEQ ID NO:
128);
(d) a HVR-L1 comprising the amino acid sequence X1ASQX2IX3SX4LA, wherein X1 is Q or R, X2 is N, Q or G, X3 is G or 5, X4 is D, K or S (SEQ ID NO:
129);
(e) a HVR-L2 comprising the amino acid sequence GASX1X2X3S, wherein X1 is K, E or T, X2 is L or T, X3 is A, H, E or Q (SEQ ID NO:
130);
and
(f) a HVR-L3 comprising the amino acid sequence QX1TX2VGSSYGNX3, wherein X1 is S, C, N or T, X2 is F or K, X3 is A, T or H (SEQ ID NO:
131).

12 more elements

A method of treating an individual having a complement-mediated disease or condition which involves excessive or uncontrolled activation of C5, the method comprising administering to the individual an effective amount of an antibody that binds C5;

and wherein the antibody comprises:
(a) a HVR-H1 comprising the amino acid sequence SSYYX1X2, wherein X1 is M or V, X2 is C or A (SEQ ID NO:
126);
(b) a HVR-H2 comprising the amino acid sequence X1IX2TGSGAX3YX4AX5WX6KG, wherein X1 is C, A or G, X2 is Y or F, X3 is T, D or E, X4 is Y, K or Q, X5 is S, D or E, X6 is A or V (SEQ ID NO:
127);
and
(c) a HVR-H3 comprising the amino acid sequence DX1GYX2X3PTHAMX4X5, wherein X1 is G or A, X2 is V, Q or D, X3 is T or Y, X4 is Y or H, X5 is L or Y (SEQ ID NO:
128);
(d) a HVR-L1 comprising the amino acid sequence X1ASQX2IX3SX4LA, wherein X1 is Q or R, X2 is N, Q or G, X3 is G or S, X4 is D, K or S (SEQ ID NO:
129);
(e) a HVR-L2 comprising the amino acid sequence GASX1X2X3S, wherein X1 is K, E or T, X2 is L or T, X3 is A, H, E or Q (SEQ ID NO:
130);
and
(f) a HVR-L3 comprising the amino acid sequence QX1TX2VGSSYGNX3, wherein X1 is S, C, N or T, X2 is F or K, X3 is A, T or H (SEQ ID NO:
131).

12 more elements

A method of enhancing the clearance of C5 from plasma in an individual comprising administering to the individual an effective amount of an antibody that binds C5 to enhance the clearance of C5 from plasma;

and wherein the antibody comprises:
(a) a HVR-H1 comprising the amino acid sequence SSYYX1X2, wherein X1 is M or V, X2 is C or A (SEQ ID NO:
126);
(b) a HVR-H2 comprising the amino acid sequence X1IX2TGSGAX3YX4AX5WX6KG, wherein X1 is C, A or G, X2 is Y or F, X3 is T, D or E, X4 is Y, K or Q, X5 is S, D or E, X6 is A or V (SEQ ID NO:
127);
and
(c) a HVR-H3 comprising the amino acid sequence DX1GYX2X3PTHAMX4X5, wherein X1 is G or A, X2 is V, Q or D, X3 is T or Y, X4 is Y or H, X5 is L or Y (SEQ ID NO:
128);
(d) a HVR-L1 comprising the amino acid sequence X1ASQX2IX3SX4LA, wherein X1 is Q or R, X2 is N, Q or G, X3 is G or S, X4 is D, K or S (SEQ ID NO:
129);
(e) a HVR-L2 comprising the amino acid sequence GASX1X2X3S, wherein X1 is K, E or T, X2 is L or T, X3 is A, H, E or Q (SEQ ID NO:
130);
and
(f) a HVR-L3 comprising the amino acid sequence QX1TX2VGSSYGNX3, wherein X1 is S, C, N or T, X2 is F or K, X3 is A, T or H (SEQ ID NO:
131).

12 more elements

Dependencies are inferred from the claim text.

Anti-c5 antibodies and methods of use

Life of this patent

Anti-c5 antibodies and methods of use

Life of this patent

Abstract

Claims73