US 2021/0198347 A1 · ANTI-COMPLEMENT COMPONENT ANTIBODIES AND METHODS OF USE

Abstract

The invention provides anti-complement component antibodies such as anti-C1s antibodies and anti-C1r antibodies, and methods of using the same. The invention also provides pharmaceutical formulations comprising the antibodies, and methods of treating an individual having a complement-mediated disease or disorder comprising administering the antibody to the individual. The binding specificity and C1q displacement function of the anti-C1s antibodies and anti-C1r antibodies are evaluated. Time dependent complement neutralization function and binding to native and truncated C1s or C1r proteins are also shown for the antibodies.

Claims26

Dependent claims

An isolated antibody that inhibits the interaction between C1q and C1r2s2 complex, wherein the antibody has a displacement function such that the antibody binds to C1qrs complex and promotes dissociation of C1q from C1qrs complex.

An isolated antibody that inhibits the interaction between C1q and C1r2s2 complex,

wherein the antibody specifically binds to an epitope within a CUB1-EGF-CUB2 domain of C1s, and competes for binding to the epitope with an antibody selected from the group consisting of 1)-5) below:
1) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
32, the HVR-H2 sequence of SEQ ID NO:
33, the HVR-H3 sequence of SEQ ID NO:
34, the HVR-L1 sequence of SEQ ID NO:
35, the HVR-L2 sequence of SEQ ID NO:
36, and the HVR-L3 sequence of SEQ ID NO:
37,
2) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
38, the HVR-H2 sequence of SEQ ID NO:
39, the HVR-H3 sequence of SEQ ID NO:
40, the HVR-L1 sequence of SEQ ID NO:
41, the HVR-L2 sequence of SEQ ID NO:
42, and the HVR-L3 sequence of SEQ ID NO:
43,
3) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
44, the HVR-H2 sequence of SEQ ID NO:
45, the HVR-H3 sequence of SEQ ID NO:
46, the HVR-L1 sequence of SEQ ID NO:
47, the HVR-L2 sequence of SEQ ID NO:
48, and the HVR-L3 sequence of SEQ ID NO:
49,
4) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
50, the HVR-H2 sequence of SEQ ID NO:
51, the HVR-H3 sequence of SEQ ID NO:
52, the HVR-L1 sequence of SEQ ID NO:
53, the HVR-L2 sequence of SEQ ID NO:
54, and the HVR-L3 sequence of SEQ ID NO:
55, and
5) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
56, the HVR-H2 sequence of SEQ ID NO:
57, the HVR-H3 sequence of SEQ ID NO:
58, the HVR-L1 sequence of SEQ ID NO:
59, the HVR-L2 sequence of SEQ ID NO:
60, and the HVR-L3 sequence of SEQ ID NO:
61, or
wherein the antibody specifically binds to an epitope within a CUB1-EGF-CUB2 domain of C1r , and competes for binding to the epitope with an antibody selected from the group consisting of 6)-13) below:
6) an antibody comprising the HVR-H1 sequence of SEQ ID NO:119, the HVR-H2 sequence of SEQ ID NO:
127, the HVR-H3 sequence of SEQ ID NO:
135, the HVR-L1 sequence of SEQ ID NO:
143, the HVR-L2 sequence of SEQ ID NO:
151, and the HVR-L3 sequence of SEQ ID NO:
159,
7) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
120, the HVR-H2 sequence of SEQ ID NO:
128, the HVR-H3 sequence of SEQ ID NO:
136, the HVR-L1 sequence of SEQ ID NO:
144, the HVR-L2 sequence of SEQ ID NO:
152, and the HVR-L3 sequence of SEQ ID NO:
160,
8) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
121, the HVR-H2 sequence of SEQ ID NO:
129, the HVR-H3 sequence of SEQ ID NO:
137, the HVR-L1 sequence of SEQ ID NO:
145, the HVR-L2 sequence of SEQ ID NO:
153, and the HVR-L3 sequence of SEQ ID NO:
161,
9) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
122, the HVR-H2 sequence of SEQ ID NO:
130, the HVR-H3 sequence of SEQ ID NO:
138, the HVR-L1 sequence of SEQ ID NO:
146, the HVR-L2 sequence of SEQ ID NO:
154, and the HVR-L3 sequence of SEQ ID NO:
162,
10) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
123, the HVR-H2 sequence of SEQ ID NO:
131, the HVR-H3 sequence of SEQ ID NO:
139, the HVR-L1 sequence of SEQ ID NO:
147, the HVR-L2 sequence of SEQ ID NO:
155, and the HVR-L3 sequence of SEQ ID NO:
163,
11) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
124, the HVR-H2 sequence of SEQ ID NO:
132, the HVR-H3 sequence of SEQ ID NO:
140, the HVR-L1 sequence of SEQ ID NO:
148, the HVR-L2 sequence of SEQ ID NO:
156, and the HVR-L3 sequence of SEQ ID NO:
164,
12) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
125, the HVR-H2 sequence of SEQ ID NO:
133, the HVR-H3 sequence of SEQ ID NO:
141, the HVR-L1 sequence of SEQ ID NO:
149, the HVR-L2 sequence of SEQ ID NO:
157, and the HVR-L3 sequence of SEQ ID NO:
165, and
13) an antibody comprising the HVR-H1 sequence of SEQ ID NO:
126, the HVR-H2 sequence of SEQ ID NO:
134, the HVR-H3 sequence of SEQ ID NO:
142, the HVR-L1 sequence of SEQ ID NO:
150, the HVR-L2 sequence of SEQ ID NO:
158, and the HVR-L3 sequence of SEQ ID NO:
166.

89 more elements

Dependencies are inferred from the claim text.

Anti-complement component antibodies and methods of use

Life of this patent

Anti-complement component antibodies and methods of use

Life of this patent

Abstract

Claims26