Antibody-peptide fusion proteins for treating amyloid disorders

Patent metadata

Field	Value
Publication number	US-12139529-B2
Application number	US-202318298953-A
Country	US
Kind code	B2
Filing date	Apr 11, 2023
Priority date	May 18, 2021
Publication date	Nov 12, 2024
Grant date	Nov 12, 2024

Abstract

Provided herein are antibody-peptide fusion proteins comprising an amyloid-reactive peptide linked to an antibody. Also provided herein are methods of treating amyloid-based diseases by administering an antibody-peptide fusion protein.

First claim

We claim:

1. An antibody-peptide fusion protein, comprising:
an antibody that binds to human amyloid fibrils comprising i) a heavy chain and ii) a light chain with an amyloid-reactive peptide fused to the C-terminus of the light chain via a linker,
wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:91, and the light chain with the amyloid-reactive peptide fused to the C-terminus of the light chain via the linker comprises the amino acid sequence of SEQ ID NO:89.

2. A pharmaceutical composition comprising
the antibody-peptide fusion protein of claim 1 and a pharmaceutical acceptable carrier.

3. A polynucleotide encoding an antibody-peptide fusion protein comprising:
an antibody that binds to human amyloid fibrils comprising i) a heavy chain and ii) a light chain with an amyloid-reactive peptide fused to the C-terminus of the light chain via a linker,
wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:91, and the light chain with the amyloid-reactive peptide fused to the C-terminus of the light chain via the linker comprises the amino acid sequence of SEQ ID NO:89.

4. A vector comprising the polynucleotide of claim 3 .

5. A host cell comprising the vector of claim 4 .

6. An antibody-peptide fusion protein that binds to human amyloid fibrils produced by a method comprising:
a) culturing a host cell comprising a vector encoding the antibody-peptide fusion protein under perfusion cell culture conditions suitable for expression of the antibody-peptide fusion protein, wherein the antibody-peptide fusion protein comprises an antibody that binds to human amyloid fibrils comprising i) a heavy chain and ii) a light chain with an amyloid-reactive peptide fused to the C-terminus of the light chain via a linker, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:91, and the light chain with the amyloid-reactive peptide fused to the C-terminus of the light chain via a linker comprises the amino acid sequence of SEQ ID NO: 89; and
b) recovering the antibody-peptide fusion protein produced by the host cell.

7. The antibody-peptide fusion protein of claim 6 , wherein the method comprises recovering the antibody-peptide fusion protein about every 12-36 hours.

8. The antibody-peptide fusion protein of claim 6 , wherein the host cell is a Chinese hamster ovary (CHO) cell.

9. An antibody-peptide fusion protein that bind to human amyloid fibrils, wherein the fusion protein comprises a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide, wherein the first polypeptide and the second polypeptide each comprise the amino acid sequence set forth in SEQ ID NO:89, and the third polypeptide and the fourth polypeptide each comprise the amino acid sequence set forth in SEQ ID NO:91.

Assignees

• Univ Tennessee Res Found
• Attralus Inc

Inventors

• Wall Jonathan S
• Foster James S
• Guthrie Spencer
• Pons Jaume
• Klein Michael L

Classifications

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · 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

• C07K14/001

  by chemical synthesis · CPC title

• A61K51/1093

  conjugates with carriers being antibodies · CPC title