US 12,473,375 B2
Methods for controlling blood pharmacokinetics of antibodies
Tomoyuki Igawa, Shizuoka (JP); Hiroyuki Tsunoda, Shizuoka (JP); and Tatsuhiko Tachibana, Shizuoka (JP)
Assigned to Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed by Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed on Jun. 28, 2021, as Appl. No. 17/359,867.
Application 17/359,867 is a continuation of application No. 12/295,039, granted, now 11,046,784, previously published as PCT/JP2007/057036, filed on Mar. 30, 2007.
Claims priority of application No. 2006-097796 (JP), filed on Mar. 31, 2006.
Prior Publication US 2021/0324109 A1, Oct. 21, 2021
Int. Cl. A61K 39/395 (2006.01); C07K 16/40 (2006.01)
CPC C07K 16/40 (2013.01) [C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/56 (2013.01)] 28 Claims
 
1. A method for producing a nucleic acid, the method comprising:
(a) identifying a nucleotide sequence encoding a first heavy chain of a first humanized IgG antibody, the first heavy chain comprising a first heavy chain variable region (VH) and an FcRn-binding domain; and
(b) producing a nucleic acid encoding a second heavy chain comprising a second VH and an FcRn-binding domain,
wherein the second heavy chain is identical to the first heavy chain except that two or more positions in the second VH corresponding to positions in the first VH that are exposed on the surface of the first humanized IgG antibody when the first humanized IgG antibody is present in blood are occupied by amino acid residues that differ in charge from the amino acid residues at the corresponding positions in the first VH,
wherein at least one of the two or more positions is Kabat numbering position H97 or H105, and
wherein a second humanized IgG antibody comprising two copies of the second heavy chain:
binds to the same antigen as the first humanized IgG antibody,
has a pI shift compared to the pI of the first humanized IgG antibody, and
has altered pharmacokinetics in blood compared to the first humanized IgG antibody.