Atrial natriuretic peptide engrafted antibodies

Patent metadata

Field	Value
Publication number	US-12331094-B2
Application number	US-201917046509-A
Country	US
Kind code	B2
Filing date	Apr 10, 2019
Priority date	Apr 12, 2018
Publication date	Jun 17, 2025
Grant date	Jun 17, 2025

Abstract

The present invention relates to an antibody or a fragment thereof comprising at least one heterologous amino acid sequence incorporated within at least one CDR region of said antibody or fragment thereof, wherein said at least one heterologous amino acid sequence comprises an N-terminal linker sequence (Nils), an Atrial Natriuretic Peptide (ANP) and a C-terminal linker sequence (Ctls). Optionally, at least a portion of said at least one CDR region is replaced by said at least one heterologous amino acid sequence incorporated therein. The present invention further relates to such antibody or fragment thereof for use in a method for treatment, a composition comprising such antibody or fragment thereof, a nucleic acid or a mixture of nucleic acids encoding such antibody or fragment thereof, a host cell comprising such nucleic acid or such mixture of nucleic acids and to a process for producing such antibody or fragment thereof.

First claim

The invention claimed is:

1. An antibody or a fragment thereof comprising at least one heterologous amino acid sequence incorporated within at least one CDR region of said antibody or fragment thereof, and wherein said at least one heterologous amino acid sequence comprises an N-terminal linker sequence (Ntls), an Atrial Natriuretic Peptide (ANP) and a C-terminal linker sequence (Ctls), and wherein:
the Ntls comprises at least 12 and up to 30 amino acid residues and the Ctls comprises at least 9 and up to 30 amino acid residues, and wherein:
i) in case of an incorporation of said heterologous amino acid sequence within CDRH1, the Ntls is present between amino acid residue HC res25 according to Kabat and the first amino acid residue of said ANP, and the Ctls is present between the last amino acid residue of said ANP and amino acid residue HC res35a according to Kabat; and/or
ii) in case of an incorporation of said heterologous amino acid sequence within CDRH2, the Ntls is present between amino acid residue HC res51 according to Kabat and the first amino acid residue of said ANP, and the Ctls is present between the last amino acid residue of said ANP and amino acid residue HC res57 according to Kabat; and/or
iii) in case of an incorporation of said heterologous amino acid sequence within CDRH3, the Ntls is present between amino acid residue HC res92 according to Kabat and the first amino acid residue of said ANP, and the Ctls is present between the last amino acid residue of said ANP and amino acid residue HC res106 according to Kabat; and/or
iv) in case of an incorporation of said heterologous amino acid sequence within CDRL1, the Ntls is present between amino acid residue LC res26 according to Kabat and the first amino acid residue of said ANP, and the Ctls is present between the last amino acid residue of said ANP and amino acid residue LC res 32 according to Kabat; and/or
v) in case of an incorporation of said heterologous amino acid sequence within CDRL2, the Ntls is present between amino acid residue LC res49 according to Kabat and the first amino acid residue of said ANP, and the Ctls is present between the last amino acid residue of said ANP and amino acid residue LC res57 according to Kabat; and/or
vi) in case of an incorporation of said heterologous amino acid sequence within CDRL3, the Ntls is present between amino acid residue LC res88 according to Kabat and the first amino acid residue of said ANP, and the Ctls is present between the last amino acid residue of said ANP and amino acid residue LC res98 according to Kabat; and

wherein:
i) said Ntls and said Ctls each comprise a GS linker sequence; or
ii) said Ntls and said Ctls each comprise a PN linker sequence; or
iii) said Ntls comprises the sequence of any one of SEQ ID NOs 1, 2 or 4 and said Ctls comprises the sequence of any one of SEQ ID NOs 1, 3 or 5; or
iv) said Ntls and said Ctls each comprise the sequence of SEQ ID NO 6; or
v) said Ntls comprises the sequence of SEQ ID NO 7 and said Ctls comprises the sequence of SEQ ID NO 8; or
vi) said Ntls comprises the sequence of SEQ ID NO 9 and said Ctls comprises the sequence of SEQ ID NO 10; or
vii) said Ntls comprises the sequence of SEQ ID NO 11 and said Ctls comprises the sequence of SEQ ID NO 12; or
viii) said Ntls comprises the sequence of SEQ ID NO 13 and said Ctls comprises the sequence of SEQ ID NO 14; or
ix) said Ntls and said Ctls each comprise the sequence of SEQ ID NO 15; or
x) said Ntls comprises the sequence of SEQ ID NO 9 and said Ctls comprises the sequence of SEQ ID NO 20; or
xi) said Ntls comprises the sequence of SEQ ID NO 21 and said Ctls comprises the sequence of SEQ ID NO 22, and

wherein said antibody or a fragment thereof is a human or humanized antibody or fragment thereof; and
wherein said antibody or fragment thereof is of the class IgG.

2. The antibody or fragment thereof according to claim 1 , wherein said ANP is selected from the group consisting of human ANP having the sequence of SEQ ID NO: 23 and a peptide having at least 95% sequence identity therewith.

3. The antibody or fragment thereof according to claim 1 , wherein said Ntls further comprises an anchoring element A1 at its C terminal end and/or said Ctls further comprises an anchoring element A2 at its N terminal end, and
wherein, when A1 and/or A2 are present, at least 60% of the amino acid residues of A1 and/or A2 are selected from glycine and serine residues.

4. The antibody or fragment thereof according to claim 1 , wherein;
i) the Ntls comprises the amino acid sequence of SEQ ID NO: 95 and the Ctls comprises the amino acid sequence of SEQ ID NO: 96; or
ii) the Ntls comprises the amino acid sequence of SEQ ID NO: 97 and the Ctls comprises the amino acid sequence of SEQ ID NO: 98; or
iii) the Ntls comprises the amino acid sequence of SEQ ID NO: 99 and the Ctls comprises the amino acid sequence of SEQ ID NO: 100; or
iv) the Ntls comprises the amino acid sequence of SEQ ID NO: 101 and the Ctls comprises the amino acid sequence of SEQ ID NO: 102; or
v) the Ntls comprises the amino acid sequence of SEQ ID NO: 103 and the Ctls comprises the amino acid sequence of SEQ ID NO: 102; or
vi) the Ntls comprises the amino acid sequence of SEQ ID NO: 105 and the Ctls comprises the amino acid sequence of SEQ ID NO: 106; or
vii) the Ntls comprises the amino acid sequence of SEQ ID NO: 119 and the Ctls comprises the amino acid sequence of SEQ ID NO: 120; or
viii) the Ntls comprises the amino acid sequence of SEQ ID NO: 121 and the Ctls comprises the amino acid sequence of SEQ ID NO: 122; or
ix) the Ntls comprises the amino acid sequence of SEQ ID NO: 123 and the Ctls comprises the amino acid sequence of SEQ ID NO: 124; or
x) the Ntls comprises the amino acid sequence of SEQ ID NO: 125 and the Ctls comprises the amino acid sequence of SEQ ID NO: 126; or
xi) the Ntls comprises the amino acid sequence of SEQ ID NO: 127 and the Ctls comprises the amino acid sequence of SEQ ID NO: 116; or
xii) the Ntls comprises the amino acid sequence of SEQ ID NO: 128 and the Ctls comprises the amino acid sequence of SEQ ID NO: 129; or
xiii) the Ntls comprises the amino acid sequence of SEQ ID NO: 130 and the Ctls comprises the amino acid sequence of SEQ ID NO: 126; or
xiv) the Ntls comprises the amino acid sequence of SEQ ID NO: 131 and the Ctls comprises the amino acid sequence of SEQ ID NO: 132; or
xv) the Ntls comprises the amino acid sequence of SEQ ID NO: 133 and the Ctls comprises the amino acid sequence of SEQ ID NO: 134; or
xvi) the Ntls comprises the amino acid sequence of SEQ ID NO: 137 and the Ctls comprises the amino acid sequence of SEQ ID NO: 116; or
xvii) the Ntls comprises the amino acid sequence of SEQ ID NO: 138 and the Ctls comprises the amino acid sequence of SEQ ID NO: 116; or
xviii) the Ntls comprises the amino acid sequence of SEQ ID NO: 139 and the Ctls comprises the amino acid sequence of SEQ ID NO: 140; or
xix) the Ntls comprises the amino acid sequence of SEQ ID NO: 145 and the Ctls comprises the amino acid sequence of SEQ ID NO: 146; or
xx) the Ntls comprises the amino acid sequence of SEQ ID NO: 147 and the Ctls comprises the amino acid sequence of SEQ ID NO: 146; or
xxi) the Ntls comprises the amino acid sequence of SEQ ID NO: 145 and the Ctls comprises the amino acid sequence of SEQ ID NO: 148; or
xxii) the Ntls comprises the amino acid sequence of SEQ ID NO: 145 and the Ctls comprises the amino acid sequence of SEQ ID NO: 149; or
xxiii) the Ntls comprises the amino acid sequence of SEQ ID NO: 147 and the Ctls comprises the amino acid sequence of SEQ ID NO: 149; or
xxiv) the Ntls comprises the amino acid sequence of SEQ ID NO: 150 and the Ctls comprises the amino acid sequence of SEQ ID NO: 149; or
xxv) the Ntls comprises the amino acid sequence of SEQ ID NO: 150 and the Ctls compris

Assignees

• Bayer Ag

Inventors

• Mayer-Bartschmid Anke
• Brockschnieder Damian
• Geertz Marcel
• Greven Simone
• Hofmeister Lucas Hudson
• Jörissen Hannah
• Mahlert Christoph
• Marquardt Tobias
• Mathar Ilka
• Mondritzki Thomas
• Noack Claudia
• Tebbe Jan
• Walsh Stuart
• Weber Ernst
• Wilmen Andreas
• Wunder Frank

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K2319/31

  fusions, other than Fc, for prolonged plasma life, e.g. albumin · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K2318/10

  Immunoglobulin or domain(s) thereof as scaffolds for inserted non-Ig peptide sequences, e.g. for vaccination purposes · CPC title

• C07K2318/00

  Antibody mimetics or scaffolds · CPC title