US2013136736A1PendingUtilityA1
Single Domain VHH Antibodies Against Von Willebrand Factor
Est. expiryMay 20, 2025(expired)· nominal 20-yr term from priority
Inventors:Karen Silence
A61P 41/00A61P 9/10A61P 7/00A61P 9/14A61P 43/00A61P 7/02A61K 38/36C07K 2317/76C07K 2317/22C07K 14/47C07K 2317/24C07K 16/36C07K 2317/569C07K 2317/92A61K 2039/505B82Y 5/00Y02A50/30
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Claims
Abstract
The present invention relates to improved Nanobodies™ against von Willebrand Factor (vWF), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.
Claims
exact text as granted — not AI-modified1 . Nanobody against Von Willebrand Factor (vWF), said Nanobody consisting of 4 framework regions (FR1 to FR4 respectively) and 3 complementarity determining regions (CDR1 to CDR3 respectively), in which:
i) CDR1 comprises an amino acid sequence selected from the group consisting of:
[SEQ ID NO: 15]
NYGMG
[SEQ ID NO: 16]
SYTLG
[SEQ ID NO: 17]
NYNMG
[SEQ ID NO: 18]
SSAMA
[SEQ ID NO: 19]
YYNTG
[SEQ ID NO: 20]
IGAMG
[SEQ ID NO: 21]
IGTMG
[SEQ ID NO: 22]
YNPMG
and amino acid sequences that have 2 or only 1 “amino acid difference(s)” with SEQ ID NOS: 15-22,
and in which:
ii) CDR2 comprises an amino acid sequence selected from the group consisting of:
[SEQ ID NO: 23]
SISWSGTYTAYSDNVKG
[SEQ ID NO: 24]
GISWSGVSTDYAEFAKG
[SEQ ID NO: 25]
TSISWSGSYTAYADNVKG
[SEQ ID NO: 26]
SISWSGMSTYYTDSVKG
[SEQ ID NO: 27]
TITSGGRTSYADSVKG
[SEQ ID NO: 28]
AISWSGGLTYYADSVKG
[SEQ ID NO: 29]
TITSGGSTNYADPVKG
[SEQ ID NO: 30]
TITSGGSTNYADSVKG
[SEQ ID NO: 31]
AISRTGGSTYYARSVEG
[SEQ ID NO: 32]
AISRTGGSTYYPDSVEG
and amino acid sequences that have at least 80%, sequence identity with SEQ ID NOS: 23-32, and in which:
iii) CDR3 comprises an amino acid sequence selected from the group consisting of:
[SEQ ID NO: 33]
QSRYRSNYYDHDDKYAY
[SEQ ID NO: 34]
LGRYRSNWRNIGQYDY
[SEQ ID NO: 35]
QSRYSSNYYDHDDKYAY
[SEQ ID NO: 36]
SNRYRTHTTQAMYNY
[SEQ ID NO: 37]
VVDGKRAP
[SEQ ID NO: 38]
NRRQKTVQMGERAYDY
[SEQ ID NO: 39]
NLKQGSYGYRFNDY
[SEQ ID NO: 40]
NLKQGDYGYRFNDY
[SEQ ID NO: 41]
AGVRAEDGRVRTLPSEYNF
[SEQ ID NO: 42]
AGVRAEDGRVRTLPSEYTF
[SEQ ID NO: 43]
AGVRAEDGRVRSLPSEYTF
and amino acid sequences that have at least 80%, sequence identity with SEQ ID NOS: 33-43.
2 . The Nanobody of claim 1 , wherein
a) CDR1 comprises
the amino acid sequence YNPMG [SEQ ID NO: 22]; or
an amino acid sequences that has 2 or only 1 amino acid difference(s) with the amino acid sequence YNPMG [SEQ ID NO: 22];
and b) CDR2 comprises
the amino acid sequence AISRTGGSTYYPDSVEG [SEQ ID NO: 32]; or
an amino acid sequence that has at least 80% sequence identity with the amino acid sequence AISRTGGSTYYPDSVEG [SEQ ID NO: 32];
and c) CDR3 comprises
the amino acid sequence AGVRAEDGRVRTLPSEYTF [SEQ ID NO: 42]; or
an amino acid sequence that has at least 80% sequence identity with the amino acid sequence AGVRAEDGRVRTLPSEYTF [SEQ ID NO: 42].
3 . Nanobody according to claim 2 , in which CDR1 comprises the amino acid sequence YNPMG [SEQ ID NO: 22]; CDR2 comprises the amino acid sequence AISRTGGSTYYPDSVEG [SEQ ID NO: 32] and CDR3 comprises the amino acid sequence AGVRAEDGRVRTLPSEYTF [SEQ ID NO: 42].
4 . Nanobody according to claim 1 , wherein any amino acid substitution is a conservative amino acid substitution.
5 . Nanobody according to claim 1 , wherein the Nanobody is a KERE-class Nanobody.
6 . Humanized variant of the Nanobody of claim 1 .
7 . Nanobody which has at least 80% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO's 60-73 and SEQ ID NO's 86-97.
8 . The Nanobody of claim 7 , wherein the Nanobody has at least 80% sequence identity with the Nanobody 12A2H1 (SEQ ID NO: 90).
9 . Humanized variant of the Nanobody of claim 7 .
10 . Nanobody 12A2H1 (SEQ ID NO: 90).
11 . A polypeptide which comprises the Nanobody of claim 1 .
12 . A polypeptide which comprises the Nanobody of claim 7 .
13 . A polypeptide which comprises at least two Nanobodies of claim 1 .
14 . A polypeptide which comprises at least two Nanobodies of claim 7 .
15 . The polypeptide according to claim 13 , wherein the at least two Nanobodies are linked to each other via a linker.
16 . The polypeptide according to claim 14 , wherein the at least two Nanobodies are linked to each other via a linker.
17 . A polypeptide which has at least 80% sequence identity an amino acid sequence selected from the group consisting of SEQ ID NOS: 74-82 and SEQ ID NOS 98-106.
18 . The polypeptide of claim 17 , wherein the polypeptide has at least 80% sequence identity with SEQ ID NO: 98.
19 . Pharmaceutical composition comprising the Nanobody of claim 1 and a pharmaceutically acceptable carrier.
20 . Pharmaceutical composition comprising the Nanobody of claim 7 and a pharmaceutically acceptable carrier.
21 . Pharmaceutical composition comprising the polypeptide of claim 11 and a pharmaceutically acceptable carrier.
22 . Pharmaceutical composition comprising the polypeptide of claim 12 and a pharmaceutically acceptable carrier.
23 . A method of treating a disease or disorder related to platelet-mediated aggregation, the method comprising:
administering the pharmaceutical composition of claim 19 to treat the disease or disorder related to platelet-mediated aggregation.
24 . A method of treating a disease or disorder related to platelet-mediated aggregation, the method comprising:
administering the pharmaceutical composition of claim 20 to treat the disease or disorder related to platelet-mediated aggregation.
25 . A method of treating a disease or disorder related to platelet-mediated aggregation, the method comprising:
administering the pharmaceutical composition of claim 21 to treat the disease or disorder related to platelet-mediated aggregation.
26 . A method of treating a disease or disorder related to platelet-mediated aggregation, the method comprising:
administering the pharmaceutical composition of claim 22 to treat the disease or disorder related to platelet-mediated aggregation.Cited by (0)
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