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US 2026/0226142 A1Published application
Therapeutic vhh antibodies against alpha-hemolysin from staphylococcus aureus
AssigneeMax-Planck-Gesellschaft zur Forderung der Wissenschaften e.V.
InventorsDirk GÖRLICH, Metin AKSU
Life of this patent
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Abstract
The present invention pertains in the fields of antibody technology, medicine, pharmacology, infection biology, and medical diagnostics. More specifically, the present disclosure provides VHH antibodies that prevent membrane-binding and/or oligomerization of and hemolysis by S. aureus alpha-hemolysin (HLA).
Claims17
A VHH antibody recognizing an S. aureus hemolysin (HLA), which competes
- (i) with the VHH antibody Ma7A07 having a VHH sequence as shown in SEQ. ID NO:
- 3 for the binding to HLA;
- or
- (ii) with the VHH antibody Ma7B01 having a VHH sequence as shown in SEQ. ID NO:
- 19 and/or the VHH antibody Ma7F02 having a VHH sequence as shown in SEQ. ID NO:
- 31 for the binding to HLA;
- or
- (iii) with the VHH antibody Ma8A05 having a VHH sequence as shown in SEQ. ID NO:
- 55 for the binding to HLA or
- (iv) with the VHH antibody Ma8D07 having a VHH sequence as shown in SEQ. ID NO:
- 63 for the binding to HLA.
8 more elements
A VHH antibody recognizing an S. aureus hemolysin (HLA) which interacts with amino acid residues on HLA according to FIG. 7 (SEQ ID NO:
- 107) selected from
- (a):
- (i) amino acid residues at positions 54-61, particularly Y54, K56, E57, M60, and/or H61,
- (ii) amino acids residues at positions 86-96, particularly T86, A88, Y91, R92, V93, Y94, and/or E96,
- (iii) amino acid residues at positions 233-239, particularly A233, D234, D238, P239, and
- (iv) amino acid residues at positions 279-302, particularly R279, W300 and D302,
- (b):
- (i) amino acid residues at positions 38-44, particularly T38, D39, I40, G41, S42, N43 and/or T44,
- (ii) amino acids residues at positions 141-143, particularly T141 and/or T143, and
- (iii) amino acid residues at positions 162-169, particularly I162, G163, N165, V166, S167, I168 and/or G169,
- (c):
- (i) amino acid residues at positions 210-219, particularly R210, D211, S212, W213, P215 and/or N219, and
- (ii) amino acids residues at positions 285-297, particularly H285, T287, S289, K292, T294, N295 and/or K297,
- (d):
- (i) amino acid residues at positions 204-208, particularly N204, W205, G206 and/or Y208, and
- (ii) amino acids residues at positions 213-227, particularly W213, N214, V216, Q220, M223, K224, T225, R226 and/or N227 or
- (e):
- (i) amino acid residues at positions 55-59, particularly D55, K56, E57, N58 and/or G59,
- (ii) amino acids residues at positions 88-97, particularly A88, G89, Q90, R92, V93, Y94, S95, E96 and/or E97, and
- (iii) amino acid residues at positions 240-302, particularly K240, R277, R279, W300 and/or D302.
17 more elements
A VHH antibody recognizing an S. aureus hemolysin (HLA) having a VHH sequence
- (a) comprising amino acid residues that interact with HLA based on the numbering of FIG. 6A:
- A, V, or D at position 55;
- Y at position 59;
- I at position 60;
- D at position 62;
- K at position 65;
- T at position 69;
- W at position 103;
- R at position 104;
- W at position 105;
- V at position 106;
- P at position 107 and
- S at position 108;
- (b) comprising amino acid residues that interact with HLA based on the numbering of FIG. 6B:
- Y or H at position 32;
- F at position 47;
- N, T or S at position 52;
- W or Y at position 59;
- Y at position 60;
- P at position 61;
- D at position 62;
- S or N at position 104;
- Y at position 105;
- W at position 106;
- W at position 109;
- H at position 111 and
- E at position 112;
- (c) comprising amino acid residues that interact with HLA based on the numbering of FIG. 6C:
- Y at position 29;
- K at position 30;
- L at position 31;
- N at position 32;
- A at position 33;
- L at position 47;
- T at position 50;
- S at position 52;
- S at position 53;
- G at position 54;
- F at position 58;
- N at position 98;
- P at position 99;
- T at position 100;
- Y at position 101;
- N at position 102 and
- H at position 103;
- (d) comprising amino acid residues that interact with HLA based on the numbering of FIG. 6D:
- A at position 53;
- S at position 57;
- D at position 58,
- I at position 60;
- T at position 61;
- Y at position 62;
- Y at position 63;
- S at position 64;
- D at position 65;
- A at position 103;
- F at position 104;
- D at position 105;
- and
- F at position 106;
- or
- (e) comprising amino acid residues that interact with HLA based on the numbering of FIG. 6E:
- N at position 30;
- S at position 31;
- Y at position 32;
- Q at position 44;
- R at position 45;
- S at position 54;
- D at position 100;
- H at position 102;
- Y at position 104;
- A at position 105;
- F at position 106;
- G at position 107;
- and
- D at position 109.
73 more elements
A VHH antibody recognizing an S. aureus hemolysin (HLA an S. aureus HLA polypeptide, comprising
- (1):
- (a) a CDR3 sequence as shown in SEQ. ID NO:
- 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102 or 106;
- (b) a CDR3 sequence, which has an identity of at least 80%, at least 90% or at least 95% to a CDR3 sequence of (a);
- (2):
- (a) a combination of CDR1, CDR2 and CDR3 sequences as shown in SEQ. ID NO:
- 4-6, 8-10, 12-14, 16-18, 20-22, 24-26, 28-30, 32-34, 36-38, 40-42, 44-46, 48-50, 52-54, 56-58, 60-62, 64-66, 68-70, 72-74, 76-78, 80-82, 84-86, 88-90, 92-94, 96-98, 100-102 or 104-106;
- (b) a combination of CDR1, CDR2 and CDR3 sequences which has an identity of at least 80%, at least 90% or at least 95% to a combination of CDR1, CDR2 and CDR3 sequences of (a), or
- (3):
- (a) a VHH sequence as shown in SEQ. ID NO:
- 3, 7, 11, 15, 19, 23, 27, 31, 35 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, 79, 83, 87, 91, 95, 99 or 103;
- (b) a sequence, which has an identity of at least 80%, at least 90%, at least 95% or at least 99% to a VHH sequence of (a).
9 more elements
Dependencies are inferred from the claim text.