US 12,264,196 B2
Fc-receptor binding modified asymmetric antibodies and methods of use
Joerg Thomas Regula, Munich (DE); Wolfgang Schaefer, Mannheim (DE); and Tilman Schlothauer, Penzberg (DE)
Assigned to Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed by Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed on Oct. 2, 2019, as Appl. No. 16/590,938.
Application 16/590,938 is a continuation of application No. 14/927,022, filed on Oct. 29, 2015, abandoned.
Application 14/927,022 is a continuation of application No. PCT/EP2014/058416, filed on Apr. 25, 2014.
Claims priority of application No. 13165725 (EP), filed on Apr. 29, 2013; and application No. 14151314 (EP), filed on Jan. 15, 2014.
Prior Publication US 2020/0095310 A1, Mar. 26, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/00 (2006.01); C07K 16/22 (2006.01); C07K 16/28 (2006.01); C07K 16/46 (2006.01); C12P 21/08 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/22 (2013.01) [C07K 16/00 (2013.01); C07K 16/2863 (2013.01); C07K 16/468 (2013.01); A61K 2039/505 (2013.01); A61K 2039/54 (2013.01); C07K 2317/31 (2013.01); C07K 2317/33 (2013.01); C07K 2317/35 (2013.01); C07K 2317/41 (2013.01); C07K 2317/52 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/71 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)] 14 Claims
 
1. An IgG1 Fc-region, comprising a first Fc-region polypeptide and a second Fc-region polypeptide, wherein:
the first and the second Fc-region polypeptide are human IgG1 Fc-region polypeptide of SEQ ID NO: 60 and have the following mutations (numbering according to Kabat EU index numbering system):
1253A in the first variant Fc-region polypeptide, and H310A and H435A in the second variant Fc-region polypeptide, or
I253A and H310A in the first variant Fc-region polypeptide, and H435A in the second variant Fc-region polypeptide, or
1253A and H435A in the first variant Fc-region polypeptide, and H310A in the second variant Fc-region polypeptide; and
wherein:
the IgG1 Fc-region has an affinity to a human Fc-receptor that is decreased in comparison to that of an IgG1 Fc-region that does not have said mutations,
wherein
i) the first IgG1 Fc-region polypeptide is a human IgG1 Fc-region polypeptide with the mutations L234A, L235A and the second IgG1 Fc-region polypeptide is a human IgG1 Fc-region polypeptide with the mutations L234A, L235A, or
iii) the first IgG1 Fc-region polypeptide is a human IgG1 Fc-region polypeptide with the mutations L234A, 1235A, P329G and the second IgG1 Fc-region polypeptide is a human IgG1 Fc-region polypeptide with the mutations L234A, L235A, P329G, or
iv) the first IgG1 Fc-region polypeptide is a human IgG1 Fc-region polypeptide with the mutations L234A, L235A, S354C, T366W and the second IgG1 Fc-region polypeptide is a human IgG1 Fc-region polypeptide with the mutations L234A, L235A, Y349C, T366S, L368A, Y407V, or
v) the first IgG1 Fc-region polypentide is a human IgG1 Fc-region polypeptide with the mutations L234A, L235A, P329G, S354C, T366W and the second IgG1 Fc-region polypeptide is a human IgG1 Fc-region polypeptide with the mutations L234A, L235A, P329G, Y349C, T366S, L368A, Y407V, or
or
vi) the first IgG1 Fc-region polypeptide is a human IgG1 Fc-region polypeptide with the mutation K392D and the second IgG1 Fc-region polypeptide is a human IgG1 Fc-region polypeptide with the mutations D399K, D356K, and/or E357K, and
wherein the IgG1 Fc-region has a reduced binding to Staphylococcus protein A than an IgG1 Fc-region comprising the first IgG1 Fc-region polypeptide of a) and the second IgG1 Fc-region polypeptide of a).