US 11,944,680 B2
Engineered chimeric fusion protein compositions and methods of use thereof
Daniel Getts, Stow, MA (US); Yuxiao Wang, Belmont, MA (US); and Bruce McCreedy, Jr., Raleigh, NC (US)
Assigned to MYELOID THERAPEUTICS, INC., Cambridge, MA (US)
Filed by Myeloid Therapeutics, Inc., Cambridge, MA (US)
Filed on Jan. 18, 2023, as Appl. No. 18/156,319.
Application 18/156,319 is a division of application No. 17/590,504, filed on Feb. 1, 2022, granted, now 11,628,218.
Application 17/590,504 is a continuation of application No. PCT/US2021/058104, filed on Nov. 4, 2021.
Claims priority of provisional application 63/109,445, filed on Nov. 4, 2020.
Claims priority of provisional application 63/251,400, filed on Oct. 1, 2021.
Claims priority of provisional application 63/196,994, filed on Jun. 4, 2021.
Claims priority of provisional application 63/162,205, filed on Mar. 17, 2021.
Prior Publication US 2023/0277659 A1, Sep. 7, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/395 (2006.01); A61K 9/00 (2006.01); A61K 9/127 (2006.01); A61K 9/51 (2006.01); A61K 38/17 (2006.01); A61K 48/00 (2006.01); A61P 35/00 (2006.01)
CPC A61K 39/3955 (2013.01) [A61K 9/0019 (2013.01); A61K 9/127 (2013.01); A61K 9/51 (2013.01); A61K 38/177 (2013.01); A61K 38/1774 (2013.01); A61K 48/005 (2013.01); A61P 35/00 (2018.01); C07K 2317/622 (2013.01); C07K 2319/00 (2013.01)] 20 Claims
 
1. A composition comprising a recombinant polynucleic acid encapsulated by a nanoparticle delivery vehicle, wherein the recombinant polynucleic acid comprises a sequence encoding a chimeric fusion protein (CFP), the CFP comprising:
(a) an extracellular domain comprising an anti-TROP2 binding domain, and
(b) a transmembrane domain operatively linked to the extracellular domain;
wherein the transmembrane domain is a transmembrane domain from a protein that dimerizes with endogenous FcR-gamma receptors expressed in myeloid cells, monocytes or macrophages of the subject;
wherein the CFP is expressed on the surface of myeloid cells that express endogenous FcR-gamma receptors wherein the anti-TROP2 binding domain comprises a Fab fragment or an scFv domain comprising a heavy chain variable domain and a light chain variable domain on a single polypeptide chain linked via a linker;
and wherein the anti-TROP2 binding domain comprises
(a) a heavy chain complementarity determining region 1 (HC CDR1), a HC CDR2 and a HC CDR3 of SEQ ID NO: 34, and a light chain complementarity determining region 1 (LC CDR1), a LC CDR2 and a LC CDR3 of SEQ ID NO: 34; or
(b) a HC CDR1, a HC CDR2 and a HC CDR3 of SEQ ID NO: 35, and a LC CDR1, a LC CDR2 and a LC CDR3 of SEQ ID NO: 35.