US 11,142,584 B2 · CD20-binding proteins comprising Shiga toxin A subunit effector regions for inducing cellular internalization and methods using same

Abstract

The present invention provides CD20-binding proteins that bind to and rapidly internalize in a CD20-mediated fashion from a cell surface location to the interior of the cell. CD20-binding proteins of the invention comprise a CD20 binding region and a Shiga toxin effector region. Certain of the disclosed CD20-binding proteins kill cells that express CD20 on their surface. Further, the presently disclosed CD20-binding proteins can comprise additional exogenous materials, such as, e.g., antigens, and are capable of targeted delivery of these additional exogenous materials into the interior of CD20 expressing cells. These CD20-binding proteins have uses in methods such as, e.g., methods involving the efficient cellular internalization of CD20, targeted killing of CD20 expressing cells, delivering exogenous materials inside CD20 expressing cells, detecting CD20 expressing cells, and treating a variety of conditions involving CD20 expressing cells including cancers, tumors, growth abnormalities, and immune disorders.

Claims18

Dependent claims

A CD20-binding protein comprising:

a) a CD20 binding region capable of specifically binding an extracellular part of CD20, wherein the CD20 binding region comprises the polypeptide represented by amino acids 2 to 245 of any one of SEQ ID NOs:
46-63, 90-98, 103-105, 108-110, and 112, and
b) a Shiga toxin A Subunit effector region polypeptide comprising an amino acid sequence that is at least 95% identical to an amino acid sequence selected from:
i) amino acids 75 to 251 of SEQ ID NO:
1 or SEQ ID NO:
2;
ii) amino acids 1 to 251 of SEQ ID NO:
1 or SEQ ID NO:
2;
and
iii) amino acids 1 to 261 of SEQ ID NO:
1 or SEQ ID NO:
2;
wherein the CD20 binding region is linked via one or more peptide linker(s) to the Shiga toxin A Subunit effector region polypeptide;
wherein, when the CD20-binding protein is administered to CD20 positive cells at a concentration equivalent to 50% cell-surface CD20 occupancy, the CD20-binding protein internalizes into one or more of the CD20 positive cells within five hours at 37 degrees Celsius.

12 more elements

Dependencies are inferred from the claim text.

CD20-binding proteins comprising Shiga toxin A subunit effector regions for inducing cellular internalization and methods using same

Life of this patent

CD20-binding proteins comprising Shiga toxin A subunit effector regions for inducing cellular internalization and methods using same

Life of this patent

Abstract

Claims18