Relaxin immunoglobulin fusion proteins and methods of use

Patent metadata

Field	Value
Publication number	US-12275771-B2
Application number	US-202117458136-A
Country	US
Kind code	B2
Filing date	Aug 26, 2021
Priority date	Dec 9, 2015
Publication date	Apr 15, 2025
Grant date	Apr 15, 2025

Abstract

Disclosed herein are relaxin immunoglobulin fusion proteins useful for the treatment or prevention of a disease or condition in a subject.

First claim

What is claimed is:

1. An antibody comprising a light chain comprising light chain complementarity determining regions CDRL1, CDRL2, and CDRL3, and a heavy chain comprising heavy chain complementarity determining regions CDRH1, CDRH2, and CDRH3, wherein:
the CDRL1 comprises the amino acid sequence of SEQ ID NO: 89 (KCQLSVGYMH),
the CDRL2 comprises the amino acid sequence of SEQ ID NO: 90 (DTSKLAS),
the CDRL3 comprises the amino acid sequence of SEQ ID NO: 96 (FQGNGYPFT),
the CDRH1 comprises the amino acid sequence of SEQ ID NO: 72 (TFSGFSLSTSGMSVG),
the CDRH2 comprises the amino acid sequence of SEQ ID NO: 73 (DIWWDDKKDYNPSLKS),
and the CDRH3 comprises the amino acid sequence of SEQ ID NO: 79 (SMITFGGFDV).

2. The antibody of claim 1 , wherein the light chain comprises a sequence at least 90% identical to SEQ ID NO: 12.

3. The antibody of claim 1 , wherein the heavy chain comprises a sequence at least 90% identical to SEQ ID NO: 16.

4. The antibody of claim 1 , wherein—the light chain comprises a sequence at least 90% identical to SEQ ID NO: 12, and the heavy chain comprises a sequence at least 90% identical to SEQ ID NO: 16.

5. The antibody of claim 1 , wherein the light chain comprises SEQ ID NO: 12, and the heavy chain comprises SEQ ID NO: 16.

6. A composition comprising a relaxin polypeptide connected to the antibody of claim 1 .

7. The composition of claim 6 , wherein the relaxin polypeptide is connected to the amino-terminus of the antibody.

8. The composition of claim 6 , wherein the relaxin polypeptide comprises a B chain and an A chain.

9. The composition of claim 8 , wherein the B chain comprises SEQ ID NO: 46.

10. The composition of claim 8 , wherein the A chain comprises SEQ ID NO: 45.

11. The composition of claim 8 , wherein the B chain comprises SEQ ID NO: 46, and the A chain comprises SEQ ID NO: 45.

12. The composition of claim 6 , wherein the relaxin polypeptide comprises a sequence at least 90% identical to-SEQ ID NO: 49.

13. The composition of claim 6 , wherein the heavy chain sequence comprises SEQ ID NO: 22.

14. A composition comprising a first polypeptide comprising a relaxin polypeptide connected to the amino-terminus of a heavy chain antibody variable domain, and a second polypeptide comprising a light chain antibody variable domain, wherein;
i) the heavy chain variable domain is at least 90% identical to SEQ ID NO: 16 and comprises heavy chain complementarity determining regions CDRH1, CDRH2, and CDRH3, wherein the CDRH1 comprises the amino acid sequence of SEQ ID NO: 72 (TFSGFSLSTSGMSVG), the CDRH2 comprises the amino acid sequence of SEQ ID NO: 73 (DIWWDDKKDYNPSLKS), and the CDRH3 comprises an amino acid sequence selected from SEQ ID NO: 79 (SMITFGGFDV), SEQ ID NO: 80 (SMITNAYFDV), and SEQ ID NO: 81 (SMITNGYFDV); and
ii) the light chain antibody variable domain is at least 90% identical to SEQ ID NO: 12 and comprises light chain complementarity determining regions CDRL1, CDRL2, and CDRL3, wherein the CDRL1 comprises the amino acid sequence of SEQ ID NO: 89 (KCQLSVGYMH), wherein the CDRL2 comprises the amino acid sequence of SEQ ID NO: 90 (DTSKLAS) and wherein the CDRL3 comprises an amino acid sequence selected from SEQ ID NO: 91 (FOGSGYPFT), SEQ ID NO: 95 (FOYSGYPFT), and SEQ ID NO: 96 (FOGNGYPFT); and
wherein the heavy chain antibody variable domain and the light chain antibody variable domain form an immunoglobulin domain that binds to RSV F protein; wherein the relaxin polypeptide comprises a B chain comprising SEQ ID NO: 46, and an A chain comprising SEQ ID NO: 45.

15. The composition of claim 14 , wherein the relaxin polypeptide comprises a sequence at least 90% identical to SEQ ID NO: 49.

16. The composition of claim 14 , wherein the first polypeptide comprises SEQ ID NO: 22 and the second polypeptide comprises SEQ ID NO: 12.

17. The composition of claim 14 , wherein the heavy chain variable domain is at least 95% identical to SEQ ID NO: 16, and the light chain antibody variable domain is at least 95% identical to SEQ ID NO: 12.

18. The composition of claim 14 , wherein the first polypeptide comprises SEQ ID NO: 22 and the second polypeptide comprises SEQ ID NO: 10.

19. The composition of claim 14 , wherein the first polypeptide comprises SEQ ID NO: 22 and the second polypeptide comprises SEQ ID NO: 11.

20. The composition of claim 14 , wherein the first polypeptide comprises SEQ ID NO: 20 and the second polypeptide comprises SEQ ID NO: 10.

21. The composition of claim 14 , wherein the first polypeptide comprises SEQ ID NO: 20 and the second polypeptide comprises SEQ ID NO: 11.

22. The composition of claim 14 , wherein the first polypeptide comprises SEQ ID NO: 20 and the second polypeptide comprises SEQ ID NO: 12.

Assignees

• Scripps Research Inst

Inventors

• Wang Feng
• Liu Yan
• Wang Ying
• Fu Guangsen
• Schultz Peter G

Classifications

• C07K16/11

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K2319/30

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