Humanized complement 5a receptor 1 antibodies and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12264203-B2
Application number	US-202418731146-A
Country	US
Kind code	B2
Filing date	May 31, 2024
Priority date	Jan 13, 2021
Publication date	Apr 1, 2025
Grant date	Apr 1, 2025

Abstract

The present disclosure provides, among other things, two different formats of humanized antibodies against human complement component 5a receptor I. The disclosure also provides a method of treating a subject having dysfunctions of C5a/C5aR1 axis pathway, including but not limited to ANCA-associated vasculitis, comprising administering to the subject in need thereof an effective amount of antibody or a nucleic encoding an antibodies binding to C5aR1 described herein, and wherein administering results in a decrease in symptoms associated with C5a/C5aR1 associated dysfunction in the subject.

First claim

The invention claimed is:

1. An antibody or antigen binding fragment thereof that binds complement component 5a receptor 1 (C5aR1), comprising a heavy chain variable (VH) region, wherein the VH comprises three heavy chain complementarity determining regions (HCDRs), wherein the HCDR1, HCDR2, and HCDR3 sequences comprising amino acid sequences of SEQ ID Nos: 6, 7, and 8, respectively and a light chain variable (VL) region, wherein the VL comprises three light chain complementarity determining regions (LCDRs), wherein the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID Nos: 9, 10, and 11, respectively.

2. The antibody or antigen binding fragment thereof of claim 1 , wherein the VH comprises an amino acid sequence at least 95% identical to SEQ ID NO: 14.

3. The antibody or antigen binding fragment thereof of claim 2 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 14.

4. The antibody or antigen binding fragment thereof of claim 1 , wherein the VL comprises an amino acid sequence at least 95% identical to SEQ ID NO: 25.

5. The antibody or antigen binding fragment thereof of claim 4 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 25.

6. An antibody or antigen binding fragment thereof, that binds complement component 5a receptor 1 (C5aR1) comprising:
a heavy chain variable region (VH) of SEQ ID NO: 14; and
a light chain variable region (VL) of SEQ ID NO: 25.

7. The antibody or antibody or antigen binding fragment thereof according to claim 1 , wherein the antibody or antigen binding fragment thereof, further comprises a Fc region.

8. The antibody or antibody or antigen binding fragment thereof according to claim 7 , wherein the Fc domain is independently selected from IgG1, IgG2, IgG3, and IgG4.

9. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment is humanized.

10. The antibody or the antigen binding fragment thereof of claim 1 , wherein the VH or the VL has been modified to enhance the stability of the molecule.

11. A nucleic acid encoding the antibody or antigen binding fragment of claim 1 .

12. A cell comprising the nucleic acid of claim 11 .

13. A composition comprising the antibody or antigen binding fragment of claim 1 .

Assignees

• Visterra Inc

Inventors

• Viswanathan Karthik
• Booth Brian
• Ramakrishnan Boopathy
• Wollacott Andrew
• Babcock Gregory
• Shriver Zachary
• Olinski Lauren

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/77

  Internalization into the cell · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title