Anti-N3PGLU amyloid beta peptide antibodies and uses thereof
The present invention provides anti-N3pGlu Aβ antibodies or antigen-binding fragment thereof. In addition, the present invention provides the use of the anti-N3pGlu Aβ antibodies or antigen-binding fragment thereof for the treatment of Alzheimers disease.
1. A human engineered anti-N3pGlu Aβ monoclonal antibody or antigen-binding fragment thereof, comprising a light chain variable region (LCVR) and a heavy chain variable region (IICVR), wherein said LCVR comprises LCDR1, LCDR2, and LCDR3 polypeptides and HCVR comprises HCDR1, HCDR2, and HCDR3 polypeptides which are selected from the group consisting of:
a)
(SEQ ID NO: 3)
LCDR1 is KSSQSLLYSRGKTYLN,
(SEQ ID NO: 4)
LCDR2 is AVSKLDS,
(SEQ ID NO: 5)
LCDR3 is VQGTHYPFT,
(SEQ ID NO: 6)
HCDR1 is GYDFTRYYIN,
(SEQ ID NO: 8)
HCDR2 is WINPGSGNTKYNEKFKG,
and
(SEQ ID NO: 9)
HCDR3 is EGITVY;
b)
(SEQ ID NO: 3)
LCDR1 is KSSQSLLYSRGKTYLN,
(SEQ ID NO: 4)
LCDR2 is AVSKLDS,
(SEQ ID NO: 5)
LCDR3 is VQGTHYPFT,
(SEQ ID NO: 7)
HCDR1 is GYTFTRYYIN,
(SEQ ID NO: 8)
HCDR2 is WINPGSGNTKYNEKFKG,
and
(SEQ ID NO: 10)
HCDR3 is EGTTVY;
c)
(SEQ ID NO: 3)
LCDR1 is KSSQSLLYSRGKTYLN,
(SEQ ID NO: 4)
LCDR2 is AVSKLDS,
(SEQ ID NO: 5)
LCDR3 is VQGTHYPFT,
(SEQ ID NO: 40)
HCDR1 is GYTFTDYYIN,
(SEQ ID NO: 8)
HCDR2 is WINPGSGNTKYNEKFKG,
and
(SEQ ID NO: 41)
HCDR3 is EGETVY;
d)
(SEQ ID NO: 3)
LCDR1 is KSSQSLLYSRGKTYLN,
(SEQ ID NO: 35)
LCDR2 is AVSKLGS,
(SEQ ID NO: 5)
LCDR3 is VQGTHYPFT,
(SEQ ID NO: 7)
CDR1 is GYTFTRYYIN,
(SEQ ID NO: 8)
HCDR2 is WINPGSGNTKYNEKFKG,
and
(SEQ ID NO: 10)
HCDR3 is EGTTVY;
and
e)
(SEQ ID NO: 45)
LCDR1 is KSTRSLLYSRSKTYLN,
(SEQ ID NO: 4)
LCDR2 is AVSKLDS,
(SEQ ID NO: 5)
LCDR3 is VQGTHYPFT,
(SEQ ID NO: 40)
HCDR1 is GYTFTDYYIN,
(SEQ ID NO: 8)
HCDR2 is WINPGSGNTKYNEKFKG,
and
(SEQ ID NO: 46)
HCDR3 is EGVTVY.
2. The human engineered anti-N3pGlu Aβ monoclonal antibody or antigen binding fragment thereof of claim 1 comprising a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein said LCVR and HCVR are polypeptides selected from the group consisting of:
a) LCVR of SEQ ID NO: 11 and HCVR of SEQ ID NO: 12;
b) LCVR of SEQ ID NO: 11 and HCVR of SEQ ID NO: 13;
c) LCVR of SEQ ID NO: 11 and HCVR of SEQ ID NO: 42;
d) LCVR of SEQ ID NO: 36 and HCVR of SEQ ID NO: 13; and
e) LCVR of SEQ ID NO: 47 and HCVR of SEQ ID NO: 48.
3. The human engineered anti-N3pGlu Aβ monoclonal antibody or antigen binding fragment thereof of claim 2 comprising a light chain (LC) and a heavy chain (HC), wherein the LC and HC polypeptides are selected from the group consisting of:
a. LC of SEQ ID NO: 14 and HC of SEQ ID NO: 15;
h. LC of SEQ ID NO: 14 and HC of SEQ ID NO: 16;
c. LC of SEQ ID NO: 14 and HC of SEQ ID NO: 44;
d. LC of SEQ ID NO: 38 and HC of SEQ ID NO: 16; and
e. LC of SEQ ID NO: 49 and HC of SEQ ID NO: 50.
4. The human engineered anti-N3pGlu Aβ monoclonal antibody or antigen binding fragment thereof of claim 3 comprising two light chains and two heavy chains wherein each light chain and each heavy chain are polypeptides selected from the group consisting of:
a. LC of SEQ ID NO: 14 and HC of SEQ ID NO: 15;
b. LC of SEQ ID NO: 14 and HC of SEQ ID NO: 16;
c. LC of SEQ ID NO: 14 and HC of SEQ ID NO: 44;
d. LC of SEQ ID NO: 38 and HC of SEQ ID NO: 16; and
e. LC of SEQ ID NO: 49 and HC of SEQ ID NO: 50.
5. A pharmaceutical composition comprising the human engineered antibody or antigen-binding fragment of claim 4 , and a pharmaceutically acceptable carrier, diluent, or excipient.
6. A method of treating a condition selected from a group consisting of clinical or pre-clinical Alzheimer's disease, prodromal Alzheimers disease, Down's syndrome, and clinical or pre-clinical amyloid angiopathy (CAA), comprising administering to a human in need thereof the human engineered antibody of claim 4 .
7. A method of treating Alzheimer's disease, comprising administering to a human in need thereof the human engineered antibody of claim 4 .
8. A method of treating a condition selected from a group consisting of clinical or pre-clinical Alzheimer's disease, prodromal Alzheimers disease, Down's syndrome, and clinical or pre-clinical amyloid angiopathy (CAA), comprising administering to a human in need thereof the pharmaceutical composition of claim 5 .
9. A method of treating Alzheimer's disease, comprising administering to a human in need thereof the pharmaceutical composition of claim 5 .