MULTIFUNCTIONAL NATURAL KILLER (NK) CELL ENGAGERS BINDING TO NKp46 AND CD123
AssigneeSanofi
InventorsMarielle CHIRON, Angela Virone-Oddos, Laurent Gauthier
Life of this patent
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Abstract
The present disclosure relates to multifunctional binding proteins comprising a first and a second antigen binding domains (ABDs) and all or part of an immunoglobulin Fc region or variant thereof, wherein the first ABD binds specifically to human CD123 and the second ABD binds specifically to human NKp46 and wherein all or part of the immunoglobulin Fc region or variant thereof to a human Fc-γ receptor. The disclosure also relates to methods for making said binding proteins, compositions thereof, and their uses, including the treatment or prevention of proliferative disorders, including Acute Myeloid Leukemia (AML) and myelodysplastic syndromes (MDS).
Claims22
1-19. (canceled)
An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a binding protein comprising a first and a second antigen binding domain (ABD) and all or part of an immunoglobulin Fc region or variant thereof, wherein each of said ABD comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein each VH and VL comprises three complementary determining regions (CDR-1 to CDR-3);
- and wherein:
- (i) the first ABD binds specifically to human CD123 and comprises:
- a VH1 comprising a CDR-H1, H2 and H3 corresponding to the amino acid sequences of SEQ ID NO:
- 1 to 3 respectively or corresponding to the amino acid sequences of SEQ ID NO:
- 4 to 6 respectively, and
- a VL1 comprising a CDR-L1, L2 and L3 corresponding to the amino acid sequences of SEQ ID NO:
- 7 to 9 respectively or corresponding to the amino acid sequences of SEQ ID NO:
- 10 to 12 respectively;
- (ii) the second ABD binds specifically to human NKp46 and comprises:
- a VH2 comprising a CDR-H1, 2 and 3 corresponding to:
- the amino acid sequences of SEQ ID NO:
- 13 to 15 respectively;
- the amino acid sequences of SEQ ID NO:
- 16 to 18 respectively;
- the amino acid sequences of SEQ ID NO:
- 19 to 21 respectively;
- the amino acid sequences of SEQ ID NO:
- 22 to 24 respectively;
- or
- the amino acid sequences of SEQ ID NO:
- 16, 25 and 26 respectively;
- and
- a VL2 comprising a CDR-L1, 2 and 3 corresponding to:
- the amino acid sequences of SEQ ID NO:
- 27 to 29 respectively;
- the amino acid sequences of SEQ ID NO:
- 30 to 32 respectively;
- the amino acid sequences of SEQ ID NO:
- 33 to 35 respectively;
- the amino acid sequences of SEQ ID NO:
- 36 to 38 respectively;
- or
- the amino acid sequences SEQ ID NO:
- 39, 31 and 40 respectively;
- and wherein all or part of the immunoglobulin Fc region or variant thereof binds to a human Fc-γ receptor.
A method of treating or preventing a blood cancer, the method comprising administering to a subject in need of said treatment or prevention a binding protein comprising a first and a second antigen binding domain (ABD) and all or part of an immunoglobulin Fc region or variant thereof, wherein the first ABD binds specifically to human CD123, the second ABD binds specifically to human NKp46, and wherein all or part of the immunoglobulin Fc region or variant thereof binds to a human Fc-γ receptor.
A method of treating or preventing a myelodysplastic syndrome (MDS) or a lymphoproliferative disorder, the method comprising administering to a subject in need of said treatment or prevention a binding protein comprising a first and a second antigen binding domain (ABD) and all or part of an immunoglobulin Fc region or variant thereof, wherein the first ABD binds specifically to human CD123, the second ABD binds specifically to human NKp46, and wherein all or part of the immunoglobulin Fc region or variant thereof binds to a human Fc-γ receptor.
A method of treating or preventing an Acute Myeloid Leukemia (AML), the method comprising administering to a subject in need of said treatment or prevention a binding protein comprising a first and a second antigen binding domain (ABD) and all or part of an immunoglobulin Fc region or variant thereof, wherein the first ABD binds specifically to human CD123, the second ABD binds specifically to human NKp46, and wherein all or part of the immunoglobulin Fc region or variant thereof binds to a human Fc-γ receptor.
(canceled)
A method of treating or preventing a CD64-positive Acute Myeloid Leukemia (AML), the method comprising administering to a subject in need of said treatment or prevention a binding protein comprising a first and a second antigen binding domain (ABD) and all or part of an immunoglobulin Fc region or variant thereof, wherein the first ABD binds specifically to human CD123, the second ABD binds specifically to human NKp46, and wherein all or part of the immunoglobulin Fc region or variant thereof binds to a human Fc-γ receptor.
Dependencies are inferred from the claim text.