IP Library › Granted Patent US 12,509,497
Granted Patent B2
US 12,509,497 · App. 18/054,596 · Granted Dec 30, 2025

Relaxin-2 fusion protein analogs and methods of using same

Inventors: John Diener (Watertown, MA); Andrew Kruse (Watertown, MA); Franz Gruswitz (Watertown, MA)
Assignee: Tectonic Operating Company, Inc.
C07K14/64A61P43/00C12N15/63C07K2319/30
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Quick Facts
Patent No.
US 12,509,497
App. No.
18/054,596
Granted
Dec 30, 2025
Kind
B2
Abstract

The present disclosure provides relaxin-2 fusion protein analogs with enhanced in vivo half-life and methods for making the same. Also disclosed herein are methods of treating relaxin-2-associated disorders or diseases using the relaxin-2 fusion protein analogs described herein.

Claims (84)

1 . A fusion protein comprising, from N-terminus to C-terminus,

a first peptide;

a linker peptide; and

a second peptide,

wherein:

(a) the first peptide comprises an amino acid sequence that differs at 0, 1, 2, 3, 4, or 5 amino acids when compared to the amino acid sequence of SEQ ID NO: 7, and the second peptide comprises an amino acid sequence that differs at 0, 1, 2, 3, 4, or 5 amino acids when compared to the amino acid sequence of SEQ ID NO: 9; or

the first peptide comprises an amino acid sequence that differs at 0, 1, 2, 3, 4, or 5 amino acids when compared to the amino acid sequence of SEQ ID NO: 9; and the second peptide comprises an amino acid sequence that differs at 0, 1, 2, 3, 4, or 5 amino acids when compared to the amino acid sequence of SEQ ID NO: 7; and

(b) the linker peptide comprises an amino acid sequence with 12-15 amino acids, comprising 2-5 acidic amino acids and 10-13 non-acidic amino acids, wherein:

(i) the linker peptide comprises an amino acid sequence selected from the group consisting of:

R 1 R 1 R 1 R 2 R 1 R 1 R 1 R 2 R 1 R 1 R 1 R 2 R 1 ;

R 1 R 1 R 1 R 2 R 1 R 1 R 1 R 2 R 1 R 1 R 1 R 2 R 1 R 1 R 1 ;

R 1 R 1 R 2 R 1 R 1 R 1 R 2 R 2 R 1 R 1 R 1 R 2 R 1 R 1 ;

R 1 R 1 R 1 R 2 R 2 R 1 R 1 R 1 R 2 R 2 R 1 R 1 R 1 ; and

R 1 R 1 R 2 R 1 R 2 R 1 R 1 R 2 R 1 R 2 R 1 R 1 R 1 ,

wherein R 1 is a non-acidic amino acid and R 2 is an acidic amino acid;

(ii) each of the acidic amino acids in the linker peptide is aspartate; or

(iii) each of the acidic amino acids in the linker peptide is glutamate.

2 . The fusion protein of claim 1 , wherein

the linker peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 14-23.

3 . The fusion protein of claim 1 , wherein one or more of the non-acidic amino acid(s) are glycine, proline, or serine.

4 . The fusion protein of claim 1 , wherein:

the first peptide comprises the amino acid sequence of DSWX 3 EEVIKLCGRELVRAQIAICGX 4 ST (SEQ ID NO: 3), wherein X 3 is methionine, lysine, or glutamine, and wherein X 4 is methionine or lysine;

the first peptide comprises the amino acid sequence of X 5 QX 6 YSALANKCCHVGCTKRSLAX 7 FC (SEQ ID NO: 4), wherein X 5 is arginine or absent, wherein X 6 is leucine or aspartate, and wherein X 7 is arginine, glutamine, or glutamate;

the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5-7;

the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 8-13;

the second peptide comprises the amino acid sequence of DSWX 3 EEVIKLCGRELVRAQIAICGX 4 ST (SEQ ID NO: 3), wherein X 3 is methionine, lysine, or glutamine, and wherein X 4 is methionine or lysine;

the second peptide comprises the amino acid sequence of X 5 QX 6 YSALANKCCHVGCTKRSLAX 7 FC (SEQ ID NO: 4), wherein X 5 is arginine or absent, wherein X 6 is leucine or aspartate, and wherein X 7 is arginine, glutamine, or glutamate;

the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5-7; and/or

the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 8-13.

5 . The fusion protein of claim 1 , wherein:

the first peptide comprises the amino acid sequence of SEQ ID NO: 5 and the second peptide comprises the amino acid sequence of SEQ ID NO: 8;

the first peptide comprises the amino acid sequence of SEQ ID NO: 5 and the second peptide comprises the amino acid sequence of SEQ ID NO: 9;

the first peptide comprises the amino acid sequence of SEQ ID NO: 5 and the second peptide comprises the amino acid sequence of SEQ ID NO: 10;

the first peptide comprises the amino acid sequence of SEQ ID NO: 5 and the second peptide comprises the amino acid sequence of SEQ ID NO: 11;

the first peptide comprises the amino acid sequence of SEQ ID NO: 5 and the second peptide comprises the amino acid sequence of SEQ ID NO: 12;

the first peptide comprises the amino acid sequence of SEQ ID NO: 5 and the second peptide comprises the amino acid sequence of SEQ ID NO: 13;

the first peptide comprises the amino acid sequence of SEQ ID NO: 6 and the second peptide comprises the amino acid sequence of SEQ ID NO: 8;

the first peptide comprises the amino acid sequence of SEQ ID NO: 6 and the second peptide comprises the amino acid sequence of SEQ ID NO: 9;

the first peptide comprises the amino acid sequence of SEQ ID NO: 6 and the second peptide comprises the amino acid sequence of SEQ ID NO: 10;

the first peptide comprises the amino acid sequence of SEQ ID NO: 6 and the second peptide comprises the amino acid sequence of SEQ ID NO: 11;

the first peptide comprises the amino acid sequence of SEQ ID NO: 6 and the second peptide comprises the amino acid sequence of SEQ ID NO: 12;

the first peptide comprises the amino acid sequence of SEQ ID NO: 6 and the second peptide comprises the amino acid sequence of SEQ ID NO: 13;

the first peptide comprises the amino acid sequence of SEQ ID NO: 7 and the second peptide comprises the amino acid sequence of SEQ ID NO: 8;

the first peptide comprises the amino acid sequence of SEQ ID NO: 7 and the second peptide comprises the amino acid sequence of SEQ ID NO: 9;

the first peptide comprises the amino acid sequence of SEQ ID NO: 7 and the second peptide comprises the amino acid sequence of SEQ ID NO: 10;

the first peptide comprises the amino acid sequence of SEQ ID NO: 7 and the second peptide comprises the amino acid sequence of SEQ ID NO: 11;

the first peptide comprises the amino acid sequence of SEQ ID NO: 7 and the second peptide comprises the amino acid sequence of SEQ ID NO: 12;

the first peptide comprises the amino acid sequence of SEQ ID NO: 7 and the second peptide comprises the amino acid sequence of SEQ ID NO: 13;

the second peptide comprises the amino acid sequence of SEQ ID NO: 5 and the first peptide comprises the amino acid sequence of SEQ ID NO: 8;

the second peptide comprises the amino acid sequence of SEQ ID NO: 5 and the first peptide comprises the amino acid sequence of SEQ ID NO: 9;

the second peptide comprises the amino acid sequence of SEQ ID NO: 5 and the first peptide comprises the amino acid sequence of SEQ ID NO: 10;

the second peptide comprises the amino acid sequence of SEQ ID NO: 5 and the first peptide comprises the amino acid sequence of SEQ ID NO: 11;

the second peptide comprises the amino acid sequence of SEQ ID NO: 5 and the first peptide comprises the amino acid sequence of SEQ ID NO: 12;

the second peptide comprises the amino acid sequence of SEQ ID NO: 5 and the first peptide comprises the amino acid sequence of SEQ ID NO: 13;

the second peptide comprises the amino acid sequence of SEQ ID NO: 6 and the first peptide comprises the amino acid sequence of SEQ ID NO: 8;

the second peptide comprises the amino acid sequence of SEQ ID NO: 6 and the first peptide comprises the amino acid sequence of SEQ ID NO: 9;

the second peptide comprises the amino acid sequence of SEQ ID NO: 6 and the first peptide comprises the amino acid sequence of SEQ ID NO: 10;

the second peptide comprises the amino acid sequence of SEQ ID NO: 6 and the first peptide comprises the amino acid sequence of SEQ ID NO: 11;

the second peptide comprises the amino acid sequence of SEQ ID NO: 6 and the first peptide comprises the amino acid sequence of SEQ ID NO: 12;

the second peptide comprises the amino acid sequence of SEQ ID NO: 6 and the first peptide comprises the amino acid sequence of SEQ ID NO: 13;

the second peptide comprises the amino acid sequence of SEQ ID NO: 7 and the first peptide comprises the amino acid sequence of SEQ ID NO: 8;

the second peptide comprises the amino acid sequence of SEQ ID NO: 7 and the first peptide comprises the amino acid sequence of SEQ ID NO: 9;

the second peptide comprises the amino acid sequence of SEQ ID NO: 7 and the first peptide comprises the amino acid sequence of SEQ ID NO: 10;

the second peptide comprises the amino acid sequence of SEQ ID NO: 7 and the first peptide comprises the amino acid sequence of SEQ ID NO: 11;

the second peptide comprises the amino acid sequence of SEQ ID NO: 7 and the first peptide comprises the amino acid sequence of SEQ ID NO: 12; or

the second peptide comprises the amino acid sequence of SEQ ID NO: 7 and the first peptide comprises the amino acid sequence of SEQ ID NO: 13.

6 . The fusion protein of claim 1 , wherein the fusion protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 25-48, optionally wherein the fusion protein further comprises an IgG Fc, optionally wherein:

the IgG Fc comprises the amino acid alanine at EU positions 234 and 235;

the IgG Fc comprises the amino acid alanine at EU position 329;

the IgG Fc comprises the amino acid alanine at EU positions 234, 235, and 329;

the IgG Fc comprises the amino acids alanine, alanine, alanine, leucine, and serine at EU positions 234, 235, 329, 428, and 434, respectively;

the IgG Fc comprises the amino acids lysine, phenylalanine, and tyrosine at EU positions 433, 434, and 436, respectively;

the IgG Fc comprises the amino acids tyrosine, threonine, and glutamate at EU positions 252, 254, and 256, respectively;

the IgG Fc comprises the amino acids leucine and serine at EU positions 428 and 434, respectively;

the IgG Fc comprises an amino acid sequence at least 85% identical to the amino acid sequence of the human IgG1 Fc set forth in SEQ ID NO: 49;

the IgG Fc comprises the amino acid sequence of the human IgG1 Fc set forth in SEQ ID NO: 49;

the IgG Fc comprises an amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 50-52 and 201-203; and/or

the IgG Fc comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 50-52 and 201-203.

7 . The fusion protein of claim 6 , wherein the IgG Fc is linked to the N-terminus of the first peptide or to the C-terminus of the second peptide.

8 . The fusion protein of claim 1 , wherein the first and second peptides do not comprise the amino acid sequence of a peptide selected from the group consisting of SEQ ID NOs:187-190.

9 . A fusion protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 53-118, 204-211, and 214-221.

10 . A pharmaceutical composition comprising an effective amount of the fusion protein of claim 1 .

11 . A kit comprising an effective amount of the fusion protein of claim 1 , and an instruction of use.

12 . The fusion protein of claim 1 , wherein the fusion protein has a pI from 6.0 to 8.2.

Assignments (2)
MERGER AND CHANGE OF NAME Recorded Nov 7, 2024
From: ALPINE MERGER SUBSIDIARY, INC.; TECTONIC THERAPEUTIC, INC.
To: TECTONIC OPERATING COMPANY, INC.
Reel/Frame 069187/0774 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 8, 2024
From: DIENER, JOHN; KRUSE, ANDREW; GRUSWITZ, FRANZ
To: TECTONIC THERAPEUTIC, INC.
Reel/Frame 067352/0622 →
Continuity (2)
Provisional Application 63263917 · Nov 11, 2021
Related Publication 20230340058A1 · Oct 26, 2023
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