US 12,077,575 B2
Humanized tetra-specific octavalent antibody against clostridium difficile toxin A and B
Hanping Feng, Ellicott City, MD (US); Yongrong Zhang, Columbia, MD (US); Zhiyong Yang, West Friendship, MD (US); Hua Yu, Columbia, MD (US); and Yifan Zhang, North Potomac, MD (US)
Assigned to FZATA, INC., Halethorpe, MD (US); and UNIVERSITY OF MARYLAND, BALTIMORE, Baltimore, MD (US)
Appl. No. 17/616,134
Filed by Hanping Feng, Ellicott City, MD (US); Yongrong Zhang, Columbia, MD (US); Zhiyong Yang, West Friendship, MD (US); Hua Yu, Columbia, MD (US); and Yifan Zhang, North Potomac, MD (US)
PCT Filed Jun. 3, 2020, PCT No. PCT/US2020/035925
§ 371(c)(1), (2) Date Dec. 2, 2021,
PCT Pub. No. WO2020/247500, PCT Pub. Date Dec. 10, 2020.
Claims priority of provisional application 62/856,493, filed on Jun. 3, 2019.
Prior Publication US 2022/0235120 A1, Jul. 28, 2022
Int. Cl. C07K 16/12 (2006.01); A61K 39/00 (2006.01); A61P 31/04 (2006.01)
CPC C07K 16/1282 (2013.01) [A61P 31/04 (2018.01); A61K 2039/505 (2013.01); C07K 2317/22 (2013.01); C07K 2317/24 (2013.01)] 19 Claims
 
1. A tetra-specific, octameric binding agent comprising, two sets of linked first and second humanized VHH peptide monomers, and two sets of linked third and fourth humanized VHH peptide monomers,
wherein the binding agent comprises two arms, each arm comprising a heavy chain lacking a variable region and a light chain lacking a variable region, and each chain having an amino terminus,
wherein for each arm of the binding agent, one set of linked first and second humanized VHH peptide monomers is joined to the amino terminus of the light chain, and one set of linked third and fourth humanized VHH peptide monomers is joined to the amino terminus of the heavy chain, and wherein the humanized VHH peptide monomers independently have binding specificity for an epitope of Clostridium difficile toxin A (TcdA) or toxin B (TcdB) and are selected from h5D (SEQ ID NO:1), hE3 (SEQ ID NO:2), hAA6 (SEQ ID NO:3) and hAH3 (SEQ ID NO:4), wherein the first, second, third, and fourth humanized VHH peptide monomers have specificity for one or a combination of epitopes and are selected from h5D (SEQ ID NO: 1), hE3 (SEQ ID NO:2), hAA6 (SEQ ID NO:3) and hAH3 (SEQ ID NO:4).