Back to results
US 11,628,218 B2Granted
Engineered chimeric fusion protein compositions and methods of use thereof
AssigneeMyeloid Therapeutics, Inc.
InventorsDaniel Getts, Yuxiao Wang, Bruce McCreedy, Jr.
Life of this patent
Estimating the term…
Abstract
Compositions and methods for making and using engineered cells, such as, engineered myeloid cells that express a chimeric fusion protein that has a binding domain capable to binding surface molecules on target cells such as diseased cells.
Claims22
A method of treating a TROP2-expressing cancer in a subject in need thereof, comprising:
- administering to the subject a therapeutically effective amount of 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 of the subject 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.
10 more elements
A method of treating a TROP2-expressing cancer in a subject in need thereof, comprising:
- administering to the subject a therapeutically effective amount of 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 of the subject that express endogenous FcR-gamma receptors;
- wherein the extracellular domain further comprises an extracellular domain from CD16a, CD64, CD68 or CD89;
- wherein the extracellular domain from CD16a, CD64, CD68 or CD89 comprises an amino acid sequence of IHQDYTTQN (SEQ ID NO:
- 82).
5 more elements
A method of treating a TROP2-expressing cancer in a subject in need thereof, comprising:
- administering to the subject a therapeutically effective amount of 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 of the subject that express endogenous FcR-gamma receptors;
- wherein the transmembrane domain is a transmembrane domain from CD16a, CD64, CD68 or CD89;
- and
- wherein the transmembrane domain from CD16a, CD64, CD68 or CD89 comprises an amino acid sequence of LIRMAVAGLVLVALLAILV (SEQ ID NO:
- 83).
6 more elements
A method of treating a TROP2-expressing cancer in a subject in need thereof, comprising:
- administering to the subject a therapeutically effective amount of 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 of the subject that express endogenous FcR-gamma receptors;
- wherein the transmembrane domain is a transmembrane domain from CD16a, CD64, CD68 or CD89;
- and
- wherein the intracellular domain comprises an amino acid sequence of ENWHSHTALNKEASADVAEPSWSQQMCQPGLTFARTPSVCK (SEQ ID NO:
- 84).
6 more elements
A method of treating a TROP2-expressing cancer in a subject in need thereof, comprising:
- administering to the subject a therapeutically effective amount of 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 of the subject that express endogenous FcR-gamma receptors;
- and
- wherein the signal peptide sequence is a GMCSF signal peptide sequence.
4 more elements
A method of treating a TROP2-expressing cancer in a subject in need thereof, comprising:
- administering to the subject a therapeutically effective amount of 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), wherein the CFP comprises:
- (i) an extracellular domain comprising:
- (I) an anti-TROP2 binding domain comprising:
- an scFv having a heavy chain variable domain and a light chain variable domains on a single polypeptide chain linked via a linker, wherein the scFv comprises a sequence selected from the group consisting of SEQ ID NO:
- 34 and 35;
- and
- (II) a hinge domain comprising an amino acid sequence of IHQDYTTQN (SEQ ID NO:
- 82);
- (ii) a transmembrane domain having an amino acid sequence of LIRMAVAGLVLVALLAILV (SEQ ID NO:
- 83);
- and
- (iii) an intracellular domain comprising an amino acid sequence of ENWHSHTALNKEASADVAEPSWSQQMCQPGLTFARTPSVCK (SEQ ID NO:
- 84).
10 more elements
Dependencies are inferred from the claim text.