US 12,331,094 B2
Atrial natriuretic peptide engrafted antibodies
Anke Mayer-Bartschmid, Wülfrath (DE); Damian Brockschnieder, Haan (DE); Marcel Geertz, Remscheid (DE); Simone Greven, Dormagen (DE); Lucas Hudson Hofmeister, Wuppertal (DE); Hannah Jörissen, Heiligenhaus (DE); Christoph Mahlert, Wuppertal (DE); Tobias Marquardt, Wuppertal (DE); Ilka Mathar, Düsseldorf (DE); Thomas Mondritzki, Essen (DE); Claudia Noack, Berlin (DE); Jan Tebbe, Cologne (DE); Stuart Walsh, Hamburg (DE); Ernst Weber, Langenfeld (DE); Andreas Wilmen, Cologne (DE); and Frank Wunder, Wuppertal (DE)
Assigned to Bayer Aktiengesellschaft, Leverkusen (DE)
Appl. No. 17/046,509
Filed by Bayer Aktiengesellschaft, Leverkusen (DE)
PCT Filed Apr. 10, 2019, PCT No. PCT/EP2019/059093
§ 371(c)(1), (2) Date Oct. 9, 2020,
PCT Pub. No. WO2019/197470, PCT Pub. Date Oct. 17, 2019.
Claims priority of application No. 18167102 (EP), filed on Apr. 12, 2018.
Prior Publication US 2021/0139555 A1, May 13, 2021
Int. Cl. A61K 38/00 (2006.01); A61K 38/22 (2006.01); C07K 14/58 (2006.01); C07K 16/00 (2006.01)
CPC C07K 14/58 (2013.01) [A61K 38/00 (2013.01); C07K 16/00 (2013.01); A61K 38/2242 (2013.01); C07K 2317/10 (2013.01); C07K 2317/565 (2013.01); C07K 2318/00 (2013.01); C07K 2318/10 (2013.01); C07K 2319/31 (2013.01)] 18 Claims
 
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.