US 12,473,363 B2
NK/monocyte engagers
Daniel J. Capon, Hillsborough, CA (US)
Assigned to BIOMOLECULAR HOLDINGS LLC
Filed by Biomolecular Holdings LLC, Burlingame, CA (US)
Filed on Feb. 10, 2025, as Appl. No. 19/050,008.
Application 19/050,008 is a continuation of application No. 18/949,940, filed on Nov. 15, 2024.
Application 18/949,940 is a continuation in part of application No. 18/188,412, filed on Mar. 22, 2023.
Application 18/188,412 is a continuation in part of application No. 18/153,840, filed on Jan. 12, 2023.
Claims priority of provisional application 63/434,866, filed on Dec. 22, 2022.
Claims priority of provisional application 63/322,594, filed on Mar. 22, 2022.
Claims priority of provisional application 63/298,999, filed on Jan. 12, 2022.
Prior Publication US 2025/0179183 A1, Jun. 5, 2025
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 39/395 (2006.01); A61P 35/02 (2006.01); C07K 16/24 (2006.01); C07K 16/40 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/2818 (2013.01) [C07K 16/244 (2013.01); C07K 16/2803 (2013.01); C07K 16/2827 (2013.01); C07K 16/2878 (2013.01); C07K 16/2896 (2013.01); C07K 16/40 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/35 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01)] 13 Claims
 
1. A tetrahedral antibody comprising a first domain, a second domain, a third domain, a fourth, a fifth domain, and a sixth domain which is formed by a first H1 polypeptide chain, a second H1 polypeptide chain, a first H2 polypeptide chain, a second H2 polypeptide chain, a first L1 polypeptide chain, a second L1 polypeptide chain, a first L2 polypeptide chain, and a second L2 polypeptide chain, wherein:
a) the first domain and the second domain are each a Fc domain of an IgG antibody;
b) the third domain and the fourth domain are each a Fab domain of an anti-CD19 antibody;
c) the fifth domain and the sixth domain are each a Fab domain of an anti-CD20 antibody;
d) the first and second H1 polypeptide chains comprise the amino acid sequence set forth in SEQ ID NO: 4775, the first and second H2 polypeptide chains comprise the amino acid sequence set forth in SEQ ID NO: 4730, the first and second L1 polypeptide chains comprise the amino acid sequence set forth in SEQ ID NO: 4819, and the first and second L2 polypeptide chains comprise the amino acid sequence set forth in SEQ ID NO: 4810;
e) the C-terminal portion of the first H1 polypeptide chain and the C-terminal portion of the first H2 polypeptide chain pair with one another to form the first domain;
f) the C-terminal portion of the second H1 polypeptide chain and the C-terminal portion of the second H2 polypeptide chain pair with one another to form the second domain;
g) the N-terminal portion of the first H1 polypeptide chain pairs with the first L1 polypeptide chain to form the third domain;
h) the N-terminal portion of the second H1 polypeptide chain pairs with the second L1 polypeptide chain to form the fourth domain;
i) the N-terminal portion of the first H2 polypeptide chain pairs with the first L2 polypeptide chain to form the fifth domain;
j) the N-terminal portion of the second H2 polypeptide chain pairs with the second L2 polypeptide chain to form the sixth domain; and
k) the first H1 polypeptide chain dimerizes with the second H1 polypeptide chain at an ACE2 collectrin-like domain dimerizing polypeptide which is within each H1 chain between the C-terminal portion that pairs with the H2 polypeptide chain and the N-terminal portion that pairs with the L1 polypeptide chain.