IL218091A - Polypeptide or polypeptide construct comprising at least one single domain antibody directed against von willebrand factor, a composition comprising it, a nucleic acid encoding it and uses thereof in the preparation of a medicament for prevention and/or alleviation of conditions of platelet-mediated aggregation - Google Patents
Polypeptide or polypeptide construct comprising at least one single domain antibody directed against von willebrand factor, a composition comprising it, a nucleic acid encoding it and uses thereof in the preparation of a medicament for prevention and/or alleviation of conditions of platelet-mediated aggregationInfo
- Publication number
- IL218091A IL218091A IL218091A IL21809112A IL218091A IL 218091 A IL218091 A IL 218091A IL 218091 A IL218091 A IL 218091A IL 21809112 A IL21809112 A IL 21809112A IL 218091 A IL218091 A IL 218091A
- Authority
- IL
- Israel
- Prior art keywords
- polypeptide
- single domain
- domain antibody
- alleviation
- platelet
- Prior art date
Links
Landscapes
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
- 172 - 218091/2 A polypeptide or polypeptide construct comprising at least one single domain antibody directed against von Willebrand Factor (vWF), wherein the at least one single domain antibody corresponds to a sequence represented by any of SEQ ID NO:s 5, 3 or 7, or to: i. an homologous sequence of any of SEQ ID NO:s 5, 3 or 7 with a sequence identity of more than 70% with the parent sequence; or ii. a functional portion of any of SEQ ID NO:s 5, 3 or 7 that maintains the interaction with vWF with affinity of 1 x 10"6 M or better; or iii. a functional portion of any of SEQ ID NO:s 5, 3 or 7 that comprises a partial deletion of the complete amino acid sequence and still maintains the binding site(s) and protein domain(s) necessary for the binding of and interaction with vWF; and, at least one single domain antibody directed against serum albumin (SA), wherein the at least one single domain antibody corresponds to a sequence represented by any of SEQ ID NO:s 16 to 19, or to: i. an homologous sequence of any of SEQ ID NO:s 16 to 19 with a sequence identity of more than 70% with the parent sequence.
The polypeptide or polypeptide construct according to claim 1 , in which at least one single domain antibody is a VHH domain.
The polypeptide or polypeptide construct according to claims 1 to 2, in which at least one single domain antibody is a VHH domain comprising an amino acid at position 45 according to the Kabat numbering that is selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, tyrosine, tryptophan, methionine, serine, threonine, asparagine, and glutamine.
The polypeptide or polypeptide construct according to claims 1 to 3, in which at least one single domain antibody is a VHH domain comprising an amino acid at position 103 according to the Kabat numbering selected from the group consisting of arginine, serine or an uncharged residue, optionally glycine.
The polypeptide or polypeptide construct according to claims 1 to 4, in which at least one single domain antibody is a VHH domain that is obtained by immunising a camel and obtaining hybridoma's therefrom, or by cloning a library of single domain antibodies and subsequently selecting the VHH using phage display. - 173 - 218091/2 . The polypeptide or polypeptide construct according to claims 1 to 5, in which at least one single domain antibody is humanized.
. The polypeptide or polypeptide construct according to claims 1 to 6, in which at least one single domain antibody is a humanized VHH domain.
. The polypeptide or polypeptide construct according to claims 1 to 7, in which at least one single domain antibody is humanized by replacing one or more of the Camelidae amino acids by their human counterparts as found in a human consensus sequence.
. The polypeptide or polypeptide construct according to claims 1 to 8, in which at least one single domain antibody is humanized by replacing any of the following residues either alone or in combination: FR1 positions 1 , 5, 28 and 30, the hallmark amino acids at FR2 positions 37, 44, 45 and 47, FR3 positions 74, 75, 76, 83, 84, 93 and 94 and FR4 positions 103, 104, 108 and 111 , wherein the numbering of the positions is according to the Kabat numbering.
. The polypeptide or polypeptide construct according to claims 1 to 9, in which the C- terminal end of the first single domain antibody is linked to the N-terminal end of the next single domain antibody. 11. The composition comprising a polypeptide or polypeptide construct according to claims 1 to 10 and a pharmaceutically acceptable vehicle. 12. The composition comprising a polypeptide or polypeptide construct according to claims 1 to 10 adapted to the chosen route of administration, wherein the route of administration is orally or parenterally, intra-nasally by inhalation, intravenous, intramuscular, topical or subcutaneous routes; and a pharmaceutically acceptable vehicle. 13. The nucleic acid encoding a polypeptide or polypeptide construct according to claims 1 to 10. 14. The use of a polypeptide or polypeptide construct according to claims 1 to 10 for the preparation of a medicament for the prevention, treatment and/or alleviation of conditions of platelet-mediated aggregation wherein said conditions are any of the formation of a non-occlusive thrombus, the formation of an occlusive thrombus, arterial thrombus formation, acute coronary occlusion, restenosis, restenosis after PCTA or stenting, thrombus formation in stenosed arteries, hyperplasia after angioplasty, atherectomy or arterial stenting, occlusive syndrome in a vascular system or lack of patency of diseased arteries.
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03447005 | 2003-01-10 | ||
| EPPCT/EP03/06581 | 2003-06-23 | ||
| EPPCT/EP03/07313 | 2003-07-08 | ||
| PCT/BE2003/000189 WO2005044858A1 (en) | 2003-11-07 | 2003-11-07 | Camelidae single domain antibodies vhh directed against epidermal growth factor receptor and uses therefor |
| PCT/BE2003/000193 WO2004041865A2 (en) | 2002-11-08 | 2003-11-07 | Stabilized single domain antibodies |
| PCT/BE2003/000190 WO2004041867A2 (en) | 2002-11-08 | 2003-11-07 | Camelidae antibodies against imminoglobulin e and use thereof for the treatment of allergic disorders |
| PCT/BE2003/000194 WO2004041863A2 (en) | 2002-11-08 | 2003-11-07 | Single domain antibodies directed against interferon- gamma and uses therefor |
| PCT/BE2003/000192 WO2004041862A2 (en) | 2002-11-08 | 2003-11-07 | Single domain antibodies directed against tumour necrosis factor-alpha and uses therefor |
| BEPCT/BE03/00206 | 2003-12-01 | ||
| BEPCT/BE03/00191 | 2003-12-02 | ||
| PCT/BE2004/000002 WO2004062551A2 (en) | 2003-01-10 | 2004-01-09 | RECOMBINANT VHH SINGLE DOMAIN ANTIBODY FROM CAMELIDAE AGAINST VON WILLEBRAND FACTOR (vWF) OR AGAINST COLLAGEN |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL218091A0 IL218091A0 (en) | 2012-03-29 |
| IL218091A true IL218091A (en) | 2014-11-30 |
Family
ID=42358025
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL169068A IL169068A (en) | 2003-01-10 | 2005-06-08 | Polypeptide or polypeptide construct comprising at least one single domain antibody directed against von willebrand factor, a composition comprising it, a nucleic acid encoding it and its uses in the preparation of a medicament for prevention and/or alleviation of conditions of platelet mediated aggregation |
| IL218091A IL218091A (en) | 2003-01-10 | 2012-02-14 | Polypeptide or polypeptide construct comprising at least one single domain antibody directed against von willebrand factor, a composition comprising it, a nucleic acid encoding it and uses thereof in the preparation of a medicament for prevention and/or alleviation of conditions of platelet-mediated aggregation |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL169068A IL169068A (en) | 2003-01-10 | 2005-06-08 | Polypeptide or polypeptide construct comprising at least one single domain antibody directed against von willebrand factor, a composition comprising it, a nucleic acid encoding it and its uses in the preparation of a medicament for prevention and/or alleviation of conditions of platelet mediated aggregation |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP5491308B2 (en) |
| IL (2) | IL169068A (en) |
| NZ (1) | NZ576284A (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2197210T3 (en) * | 1994-11-30 | 2004-01-01 | Ajinomoto Co., Inc. | ANTITHROMBOTIC AGENT AND MONOCLONAL ANTIBODIES AGAINST THE VON WILLEBRAND FACTOR. |
| CA2344606A1 (en) * | 1998-10-23 | 2000-05-04 | Huabing Yuan | Conformation-specific anti-von willebrand factor antibodies |
| CA2441903C (en) * | 2000-05-26 | 2012-07-31 | National Research Council Of Canada | Single-domain brain-targeting antibody fragments derived from llama antibodies |
| JP2005289809A (en) * | 2001-10-24 | 2005-10-20 | Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) | Mutant heavy-chain antibody |
-
2004
- 2004-01-09 NZ NZ576284A patent/NZ576284A/en not_active IP Right Cessation
-
2005
- 2005-06-08 IL IL169068A patent/IL169068A/en active IP Right Grant
-
2010
- 2010-07-22 JP JP2010164586A patent/JP5491308B2/en not_active Expired - Lifetime
-
2012
- 2012-02-14 IL IL218091A patent/IL218091A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| JP2011004747A (en) | 2011-01-13 |
| NZ576284A (en) | 2010-07-30 |
| IL169068A (en) | 2012-05-31 |
| IL218091A0 (en) | 2012-03-29 |
| JP5491308B2 (en) | 2014-05-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed |