NZ770391B2 - Compositions and methods for diagnosis and treatment of cancer - Google Patents
Compositions and methods for diagnosis and treatment of cancer Download PDFInfo
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- NZ770391B2 NZ770391B2 NZ770391A NZ77039119A NZ770391B2 NZ 770391 B2 NZ770391 B2 NZ 770391B2 NZ 770391 A NZ770391 A NZ 770391A NZ 77039119 A NZ77039119 A NZ 77039119A NZ 770391 B2 NZ770391 B2 NZ 770391B2
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- New Zealand
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- edb
- xaa
- cys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/415—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
- C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/81—Protease inhibitors
- G01N2333/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
- G01N2333/811—Serine protease (E.C. 3.4.21) inhibitors
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- G01N33/574—
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- G01N33/57484—
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6887—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids from muscle, cartilage or connective tissue
Abstract
The present invention relates to the diagnosis and treatment of diseases expressing Fibronectin Extra Domain B (EDB) such as diseases characterized by tissue remodeling and/or angiogenesis, in particular cancerous diseases, such as head and neck, brain, colorectal, lung, prostate and breast cancer. More particularly, the invention concerns peptides targeting Fibronectin Extra Domain B.
Claims (18)
1. A ectin Extra Domain B (EDB) binding peptide which ses the amino acid sequence: (Xaa)n1 Cys (Xaa)n2 Arg Ile/Val Arg Leu (Xaa)n3 Cys (Xaa)n4 Cys (Xaa)n5 Cys (Xaa)n6 Cys Arg (Xaa)n7’ Cys (Xaa)n8 wherein the Cys residues form a cystine knot structure, each Xaa is independently any amino acid, and n1, n2, n3, n4, n5, n6, n7’, and n8 are the respective numbers of amino acids, wherein n1 is 1 or 2, n2 is 4, 5, 6 or 7, n3 is 0 or 1, n4 is 4, 5 or 6, n5 is 2, 3 or 4, n6 is 1 or 2, n7’ is 3, 4, or 5, and n8 is 1 or 2, and each amino acid Xaa and the number of amino acids n1, n2, n3, n4, n5, n6, n7’ and n8 are selected such that a e knot structure can form between the Cys residues.
2. The EDB g peptide of claim 1, wherein n2 is 5 or 6, n3 is 0 or 1, n4 is 5, n5 is 3, n6 is 1, and n7’ is 4.
3. The EDB binding peptide of claim 1, which comprises the amino acid sequence: (Xaa)n1 Cys (Xaa)n2 Arg Ile/Val Arg Leu (Xaa)n3 Cys Arg Arg Asp Ser Asp Cys (Xaa)n5 Cys Ile Cys Arg Gly Asn Gly Tyr Cys (Xaa)n8, or (Xaa)n1 Cys (Xaa)n2 Arg Ile/Val Arg Leu (Xaa)n3 Cys Arg Arg Asp Ser Asp Cys (Xaa)n5 Cys Ile Cys Arg Gly Asn Gly Tyr Cys Gly.
4. The EDB binding peptide of claim 1, which comprises an amino acid sequence ed from: (i) SerValCysLysAsnValSerIleMetArgIleArgLeuCysArgArgAspSerAspCys ProGlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 8), (ii) SerValCysAlaHisTyrAsnThrIleArgValArgLeuCysArgArgAspSerAspCys ProGlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 9), (iii) ProMetCysThrGlnArgLysAsnArgIleArgLeuCysArgArgAspSerAspCysThr GlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 11), (iv) SerValCysLysGlnAlaAsnPheValArgIleArgLeuCysArgArgAspSerAspCys ProGlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 12), (v) AlaMetCysThrGlnArgLysAsnArgIleArgLeuCysArgArgAspSerAspCysThr GlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 13), (vi) ProAlaCysThrGlnArgLysAsnArgIleArgLeuCysArgArgAspSerAspCysThr GlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 14), (vii) ProMetCysAlaGlnArgLysAsnArgIleArgLeuCysArgArgAspSerAspCysThr GlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 15), (viii) ProMetCysThrAlaArgLysAsnArgIleArgLeuCysArgArgAspSerAspCysThr CysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 16), (ix) ProMetCysThrGlnAlaLysAsnArgIleArgLeuCysArgArgAspSerAspCysThr CysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 17), (x) ProMetCysThrGlnArgAlaAsnArgIleArgLeuCysArgArgAspSerAspCysThr GlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 18), (xi) ProMetCysThrGlnArgLysAlaArgIleArgLeuCysArgArgAspSerAspCysThr GlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 19), (xii) ProMetCysThrGlnArgLysAsnArgIleArgLeuCysAlaArgAspSerAspCysThr GlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 24), and (xiii) ProMetCysThrGlnArgLysAsnArgIleArgLeuCysArgAlaAspSerAspCysThr GlyAlaCysIleCysArgGlyAsnGlyTyrCysGly (SEQ ID NO: 25).
5. The EDB g peptide of any one of claims 1 to 4, which forms or is part of a scaffold, and/or which is ized by a covalent modification.
6. The EDB binding peptide of claim 5, which is stabilized by a covalent modification, wherein said covalent modification is cyclization via one or more disulfide bridges.
7. The EDB g peptide of any one of claims 1 to 6, which forms and/or is part of an inhibitor cystine knot structure.
8. A Fibronectin Extra Domain B (EDB) binding agent comprising the EDB binding peptide of any one of claims 1 to 7.
9. The EDB binding agent of claim 8, wherein the EDB binding peptide is covalently and/or non-covalently associated with at least one further moiety selected from a carrier protein, a label, a er, and a tag.
10. An EDB binding agent, which comprises at least two subunits which are covalently and/or non-covalently associated, each of said subunits comprising the EDB binding peptide of any one of claims 1 to 7, wherein the EDB binding es are identical or different.
11. The EDB binding agent of claim 8, covalently and/or non-covalently associated with at least one detectable label or reporter and/or at least one therapeutic effector moiety.
12. A recombinant nucleic acid which encodes an EDB binding peptide of any one of claims 1 to 7.
13. A host cell comprising the recombinant nucleic acid of claim 12, wherein the host cell is not a cell within a human body.
14. A test kit or an assay device comprising the EDB g peptide of any one of claims 1 to 7.
15. A method for assaying for the ce and/or amount of Fibronectin Extra Domain B (EDB) in a sample comprising using the EDB binding peptide of any one of claims 1 to 7, comprising: (i) contacting a sample with the EDB binding peptide or an EDB binding agent comprising the EDB binding peptide, and (ii) detecting the formation of and/or ining the quantity of a complex n the EDB g peptide or the EDB binding agent and EDB.
16. A method for diagnosis, detection or monitoring of cancer in a patient, comprising ng for the presence and/or amount of Fibronectin Extra Domain B (EDB) in said patient using the EDB binding peptide of any one of claims 1 to 7 or the EDB binding agent of any one of claims 8 to 11, comprising assaying a biological sample isolated from said patient according to the method of claim 15.
17. A pharmaceutical composition comprising the EDB binding peptide of any one of claims 1 to 7.
18. Use of the EDB binding peptide of any one of claims 1 to 7 in the cture of a medicament for treating a patient which has cancer or is at risk of developing cancer. reduced reduced non—reduced "U , , C: , reduced F1\-6789 S9 FN—67B89 0
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2018/065205 WO2019233605A1 (en) | 2018-06-08 | 2018-06-08 | Compositions and methods for diagnosis and treatment of cancer |
| PCT/EP2019/064872 WO2019234190A1 (en) | 2018-06-08 | 2019-06-06 | Compositions and methods for diagnosis and treatment of cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ770391A NZ770391A (en) | 2024-09-27 |
| NZ770391B2 true NZ770391B2 (en) | 2025-01-07 |
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