Antibody which binds to abetape3
AssigneeBioArctic AB
InventorsPaulina APPELKVIST, Emma BOSTRÖM, Christer MÖLLER, Adeline RACHALSKI, Jessica SIGVARDSON, Linda SÖDERBERG, Karin TEGERSTEDT, James MCCLORY
Life of this patent
Estimating the term…
Abstract
Disclosed is an antibody or antigen-binding fragment thereof, which binds to AβpE3, i.e. to an N-terminally truncated and pyroglutamate-modified form of amyloid beta (Aβ), and therapeutic and diagnostic uses thereof.
Claims14
An antibody, which has affinity for AβpE3, and in which the six complementarity determining regions of the heavy and light chain variable domain consist of the following amino acid sequences:
- VH-CDR1:
- (SEQ ID NO:
- 1)
- GX1TX2N
- wherein
- X1 is selected from Y and F;
- and
- X2 is selected from L and M;
- VH-CDR2:
- (SEQ ID NO:
- 2)
- LINPYNGX3TTYNX4KFX5G
- wherein
- X3 is selected from I and V
- X4 is selected from P and Q;
- and
- X5 is selected from M and K;
- VH-CDR3:
- (SEQ ID NO:
- 3)
- EGNWEGVY
- VL-CDR1:
- (SEQ ID NO:
- 4)
- X6SSQSLLDSNGKTYLH
- wherein
- X6 is selected from K and R;
- VL-CDR2:
- (SEQ ID NO:
- 5)
- LVSX-LDS
- wherein
- X7 is selected from I and K;
- VL-CDR3:
- (SEQ ID NO:
- 6)
- VQGTHFPFT,
- or an antigen-binding fragment thereof.
An antibody or antigen-binding fragment thereof according to any preceding claim, which comprises a heavy chain variable domain and a light chain variable domain, wherein said heavy chain variable domain comprises an amino acid sequence selected from
- i) the group consisting of SEQ ID NO:15-22;
- and
- ii) an amino acid sequence having at least 80% identity to any one of SEQ ID NO:15-22, provided that the three VH-CDR regions consist of SEQ ID NO:7, SEQ ID NO:8 and SEQ ID NO:3.
An antibody or antigen-binding fragment thereof according to any preceding claim, in which the amino acid sequence of VL-CDR1 is
- (SEQ ID NO:
- 10)
- RSSQSLLDSNGKTYLH.
An antibody or antigen-binding fragment thereof according to any preceding claim, wherein the heavy chain variable domain and the light chain variable domain are represented by the following VH/VL combinations:
- a) a heavy chain variable domain comprising SEQ ID NO:15 and a light chain variable domain comprising SEQ ID NO:23;
- b) a heavy chain variable domain comprising SEQ ID NO:16 and a light chain variable domain comprising SEQ ID NO:23;
- c) a heavy chain variable domain comprising SEQ ID NO:17 and a light chain variable domain comprising SEQ ID NO:23;
- d) a heavy chain variable domain comprising SEQ ID NO:18 and a light chain variable domain comprising SEQ ID NO:23;
- e) a heavy chain variable domain comprising SEQ ID NO:19 and a light chain variable domain comprising SEQ ID NO:23;
- f) a heavy chain variable domain comprising SEQ ID NO:20 and a light chain variable domain comprising SEQ ID NO:23;
- g) a heavy chain variable domain comprising SEQ ID NO:21 and a light chain variable domain comprising SEQ ID NO:24;
- h) a heavy chain variable domain comprising SEQ ID NO:22 and a light chain variable domain comprising SEQ ID NO:23.
An antibody or antigen-binding fragment thereof according to any preceding claim, wherein said AβpE3 is in a form selected from the group consisting of monomers, protofibrils, fibrils and plaques.
An antibody or antigen-binding fragment thereof according to any preceding claim, which has a binding affinity for protofibrils comprising AβpE3 that corresponds to a KD value of no more than 1 nM, such as between 1 and 200 μM, such as between 10 and 100 μM, as determined by surface plasmon resonance.
An antibody or antigen-binding fragment thereof according to any preceding claim, which has a binding affinity for AβpE3 monomers that corresponds to a KD value of no more than 100 nM, such as between 0.1 and 50 nM, such as between 0.5 and 10 nM, as determined by surface plasmon resonance.
Pharmaceutical composition, comprising an antibody or antigen-binding fragment thereof according to any preceding claim and a pharmaceutically acceptable carrier or excipient.
Dependencies are inferred from the claim text.