Human tissue kallikrein 1 glycosylation isoforms
AssigneeDiaMedica Inc.
InventorsMatthew Charles, Tadeusz Kolodka, Mark Williams
Life of this patent
Estimating the term…
Abstract
Provided are preparations of tissue kallikrein-1 (KLK1) glycoforms having a defined number of oligosaccharide units per KLK1 molecule. Also provided are mixtures of such glycoforms, pharmaceutical compositions containing such glycoforms or mixtures thereof, methods of obtaining the rhKLK1 glycoforms, and therapeutic uses thereof.
Claims16
A composition comprising a first mature human tissue kallikrein-1 (KLK1) polypeptide and a second mature human tissue kallikrein-1 (KLK1) polypeptide:
- wherein the first mature human KLK1 polypeptide has three glycans attached at three different positions per said first mature human KLK1 polypeptide and the second mature human KLK1 polypeptide has two glycans attached at two different positions per said second mature human KLK1 polypeptide;
- wherein the three glycans of the first mature human KLK1 polypeptide are Asn-linked glycans at residues 78, 84, and 141 as defined by SEQ ID NO:1;
- wherein the two glycans of the second mature human KLK1 polypeptide are Asn-linked glycans at residues 78 and 84 but not 141 as defined by SEQ ID NO:1;
- and
- wherein the first mature human KLK1 polypeptide and the second mature human KLK1 polypeptide are present in the composition in a ratio ranging from 45:55 to 55:45.
A composition comprising a first mature human tissue kallikrein-1 (KLK1) polypeptide and a second mature human tissue kallikrein-1 (KLK1) polypeptide:
- wherein the first mature human KLK1 polypeptide has three glycans attached at three different positions per said first mature human KLK1 polypeptide and the second mature human KLK1 polypeptide has two glycans attached at two different positions per said second mature human KLK1 polypeptide, wherein the mature human KLK1 polypeptides comprise residues 25-262 of SEQ ID NO:1 or SEQ ID NO:2;
- wherein the three glycans of the first mature human KLK1 polypeptide are Asn-linked glycans at residues 78, 84, and 141 as defined by SEQ ID NO:1;
- wherein the two glycans of the second mature human KLK1 polypeptide are Asn-linked glycans at residues 78 and 84 but not 141 as defined by SEQ ID NO:1;
- wherein the first mature human KLK1 polypeptide and the second mature human KLK1 polypeptide are present in the composition in a ratio ranging from 45:55 to 55:45;
- and
- wherein the composition is substantially free of other glycosylated isoforms of KLK1, and wherein the composition demonstrates an increased activity to stimulate glucose uptake from the circulation and/or by tissues in comparison to a composition wherein the first mature human KLK1 polypeptide and the second mature human KLK1 polypeptide are present in the composition in a ratio of about 60:40.
Dependencies are inferred from the claim text.