Novel Eosinophil Cationic Proteins used in the Treatement of Asthematic and Allergic Disorders
| Title: | Novel Eosinophil Cationic Proteins used in the Treatement of Asthematic and Allergic Disorders |
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| Document Number: | 20060183114 |
| Publication Date: | August 17, 2006 |
| Appl. No: | 10/275658 |
| Application Filed: | May 08, 2001 |
| Abstract: | The present invention relates to novel eosinophil cationic proteins characterised by the presence of a single nucleotide polymorphism. The presence of such polymorphism has been correlated to an advantageous phenotype being a reduced disposition to allergic and asthmatic disorders. |
| Inventors: | Hogbom, Erik (Uppsala, SE); Bystrom, Jonas (Uppsala, SE); Jonsson, Ulla-Britt (Uppsala, SE); Venge, Per (Uppsala, SE) |
| Claim: | 1. Use of a protein selected from; (a) an ECP, (b) a mutant of said ECP, and (c) a fragment of (a) or (b), said protein lacking an arginine 97 of wild-type ECP or its equivalent, in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. |
| Claim: | 2. Use of a DNA molecule encoding a protein selected from; (a) an ECP, (b) a mutant of said ECP, and (c) a fragment of (a) or (b), said protein lacking an arginine 97 of wild-type ECP or its equivalent, or of a protein encoded thereby, in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. |
| Claim: | 3. Use according to claim 1 or 2 wherein arginine 97, or its equivalent, is replaced by threonine or a bioisostere thereof. |
| Claim: | 4. Use of an Eosinophil cationic protein (ECP), or a fragment thereof, comprising a modification at amino acid residue 97 or its equivalent such that residue 97 or its equivalent is any amino acid other than arginine; in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. |
| Claim: | 5. Use of a protein having the amino acid sequence as shown in SEQ I.D. No. 1, or a fragment thereof, wherein residue 97 is any amino acid other than arginine; in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. |
| Claim: | 6. Use according to claims 4 or 5 wherein residue 97 or its equivalent is threonine or a bioisostere thereof. |
| Claim: | 7. Use according to any of claims 1-6, wherein the protein includes the sequence C T Y corresponding to amino acid residues 96-98 of wild-type ECP, or a biostere thereof. |
| Claim: | 8. Use according to claim 7, wherein the biostere is of formula C X1 Y, wherein X1 is any amino acid residue other than arginine. |
| Claim: | 9. Use of a protein having SEQ ID No. 4 in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. |
| Claim: | 10. A protein selected from; (a) an ECP, (b) a mutant of said ECP, and (c) a fragment of (a) or (b), wherein arginine 97 of wild-type ECP, or its equivalent, is replaced by any amino acid other than valine, glycine or lysine. |
| Claim: | 11. A protein according to claim 10 wherein arginine 97, or its equivalent, is replaced by threonine or a bioisostere thereof |
| Claim: | 12. An Eosinophil cationic protein (ECP), or fragment thereof, comprising a modification at amino acid residue 97 or its equivalent such that residue 97 or its equivalent is any amino acid other than arginine, valine, glycine or lysine. |
| Claim: | 13. A protein having the amino acid sequence as shown in SEQ I.D. No. 1, or a fragment thereof, wherein residue 97 is any amino acid other than arginine. |
| Claim: | 14. A polypeptide according to claims 12 or 13 wherein residue 97 or its equivalent is threonine or a bioisostere thereof |
| Claim: | 15. A protein according to any of claims 10-14, including the sequence C T Y corresponding to amino acid residues 96-98 of wild-type ECP, or a biostere thereof. |
| Claim: | 16. A protein according to claim 15, wherein the biostere is of formula C X1 Y, wherein X1 is any amino acid residue other than arginine, valine, glycine or lysine. |
| Claim: | 17. A protein having SEQ ID No. 4. |
| Claim: | 18. An isolated DNA molecule encoding a protein of any preceding claim. |
| Claim: | 19. An isolated DNA molecule comprising an ECP-encoding polynucleotide in which guanosine at position 926 or its equivalent is substituted by cytosine. |
| Claim: | 20. A DNA molecule according to claim 19, having the nucleotide sequence shown as SEQ ID No. 3, or a fragment thereof comprising residue 926. |
| Claim: | 21. A DNA molecule according to claim 18, having SEQ ID No. 3. |
| Claim: | 22. Use of a DNA molecule of any of claims 18-21, or of a polypeptide encoded thereby, in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. |
| Claim: | 23. Use of an isolated DNA molecule comprising an ECP-encoding polynucleotide or a fragment thereof in a method of determining in a biological sample the nucleotide residue at position 926 or its equivalent. |
| Claim: | 24. Use of a pair of oligonucleotide primers which comprise nucleotide sequences flanking position 926, or its equivalent, of an ECP-encoding polynucleotide in a method of determining in a biological sample the nucleotide residue at position 926 or its equivalent. |
| Claim: | 25. A method of diagnosis of a predisposition to an allergic or asthmatic disorder or an increased likelihood of having such a disorder comprising determining in a biological sample, the presence or absence of a protein as defined in any of claims 10-17 or a nucleotide sequence as defined in any of claims 18-21. |
| Claim: | 26. A method according to claim 25, using an antibody capable of recognising a said protein. |
| Claim: | 27. A method according to claim 25, comprising detecting the presence of a G to C polymorphism at position 926 on an ECP encoding polynucleotide. |
| Claim: | 28. The method according to claim 27, wherein the polymorphism is detected using PCR primers which amplify a DNA segment comprising a nucleotide at position 926 on an ECP encoding polynucleotide. |
| Claim: | 29. The method according to claim 28, wherein the PCR primers are SEQ ID NO: 5 and SEQ ID NO: 6. |
| Claim: | 30. A pair of PCR primers which amplify a DNA segment of an ECP encoding polynucleotide, wherein the amplified DNA segment is up to 500 base pairs in length and nucleotide position 926 of the ECP encoding polynucleotide is substantially towards the middle of the DNA segment. |
| Claim: | 31. A PCR primer, which is selected from the group consisting of SEQ ID Nos: 5 and 6. |
| Claim: | 32. A method of detecting the presence or absence of WT-ECP-DNA or an ECP encoding nucleotide sequence, comprising making a Pst I digest of a sample believed to contain said WT-ECP-DNA or nucleotide sequence and detecting the fragments produced. |
| Claim: | 33. An assay for detecting a compound capable of mimicing a protein as defined in any of claims 10-17 or a nucleotide sequence as defined in any of claims 18-21. |
| Claim: | 34. An assay for detecting a compound capable of antagonising wild-type ECP expression and/or activity. |
| Claim: | 35. An assay of claim 33 or 34 comprising detecting cytotoxic properties with respect to the killing of bacteria and/or cancer cells. |
| Claim: | 36. An assay of claim 33 or 34 comprising measuring RNase activity. |
| Claim: | 37. An assay of claim 33 or 34 comprising measuring the capacity of the compound to affect fibroblasts in their production of proteoglycans. |
| Claim: | 38. A compound identified by means of the assay of any of claims 33-37. |
| Claim: | 39. Host cells capable of expressing a protein defined in any of claims 10-17. |
| Claim: | 40. Host cells according to claim 25, comprising a nucleotide sequence defined in any of claims 18-21. |
| Claim: | 41. A diagnostic kit comprising the pair of PCR primers according to claim 30. |
| Claim: | 42. A diagnostic kit comprising an antibody as defined in claim 26. |
| Claim: | 43. A kit comprising a diagnostic kit according to claim 41 or 42, and a therapeutic agent. |
| Claim: | 44. A kit according to claim 43, wherein the therapeutic agent is for the treatment of an allergy or asthmatic disorder. |
| Claim: | 45. A kit according to claim 43 or 44, wherein the therapeutic agent is a compound as defined in claim 38. |
| Current U.S. Class: | 435006/000 |
| Current International Class: | 12; 01; 01; 01; 01; 01; 07; 07 |
| Accession Number: | edspap.20060183114 |
| Database: | USPTO Patent Applications |
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| Items | – Name: Title Label: Title Group: Ti Data: Novel Eosinophil Cationic Proteins used in the Treatement of Asthematic and Allergic Disorders – Name: DocumentID Label: Document Number Group: Patent Data: 20060183114 – Name: DateEntry Label: Publication Date Group: Patent Data: August 17, 2006 – Name: DocumentID Label: Appl. No Group: Patent Data: 10/275658 – Name: DateFiled Label: Application Filed Group: Patent Data: May 08, 2001 – Name: Abstract Label: Abstract Group: Ab Data: The present invention relates to novel eosinophil cationic proteins characterised by the presence of a single nucleotide polymorphism. The presence of such polymorphism has been correlated to an advantageous phenotype being a reduced disposition to allergic and asthmatic disorders. – Name: Author Label: Inventors Group: Patent Data: <searchLink fieldCode="ZA" term="%22Hogbom%2C+Erik%22">Hogbom, Erik</searchLink> (Uppsala, SE); <searchLink fieldCode="ZA" term="%22Bystrom%2C+Jonas%22">Bystrom, Jonas</searchLink> (Uppsala, SE); <searchLink fieldCode="ZA" term="%22Jonsson%2C+Ulla-Britt%22">Jonsson, Ulla-Britt</searchLink> (Uppsala, SE); <searchLink fieldCode="ZA" term="%22Venge%2C+Per%22">Venge, Per</searchLink> (Uppsala, SE) – Name: Comment Label: Claim Group: Patent Data: 1. Use of a protein selected from; (a) an ECP, (b) a mutant of said ECP, and (c) a fragment of (a) or (b), said protein lacking an arginine 97 of wild-type ECP or its equivalent, in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. – Name: Comment Label: Claim Group: Patent Data: 2. Use of a DNA molecule encoding a protein selected from; (a) an ECP, (b) a mutant of said ECP, and (c) a fragment of (a) or (b), said protein lacking an arginine 97 of wild-type ECP or its equivalent, or of a protein encoded thereby, in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. – Name: Comment Label: Claim Group: Patent Data: 3. Use according to claim 1 or 2 wherein arginine 97, or its equivalent, is replaced by threonine or a bioisostere thereof. – Name: Comment Label: Claim Group: Patent Data: 4. Use of an Eosinophil cationic protein (ECP), or a fragment thereof, comprising a modification at amino acid residue 97 or its equivalent such that residue 97 or its equivalent is any amino acid other than arginine; in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. – Name: Comment Label: Claim Group: Patent Data: 5. Use of a protein having the amino acid sequence as shown in SEQ I.D. No. 1, or a fragment thereof, wherein residue 97 is any amino acid other than arginine; in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. – Name: Comment Label: Claim Group: Patent Data: 6. Use according to claims 4 or 5 wherein residue 97 or its equivalent is threonine or a bioisostere thereof. – Name: Comment Label: Claim Group: Patent Data: 7. Use according to any of claims 1-6, wherein the protein includes the sequence C T Y corresponding to amino acid residues 96-98 of wild-type ECP, or a biostere thereof. – Name: Comment Label: Claim Group: Patent Data: 8. Use according to claim 7, wherein the biostere is of formula C X1 Y, wherein X1 is any amino acid residue other than arginine. – Name: Comment Label: Claim Group: Patent Data: 9. Use of a protein having SEQ ID No. 4 in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. – Name: Comment Label: Claim Group: Patent Data: 10. A protein selected from; (a) an ECP, (b) a mutant of said ECP, and (c) a fragment of (a) or (b), wherein arginine 97 of wild-type ECP, or its equivalent, is replaced by any amino acid other than valine, glycine or lysine. – Name: Comment Label: Claim Group: Patent Data: 11. A protein according to claim 10 wherein arginine 97, or its equivalent, is replaced by threonine or a bioisostere thereof – Name: Comment Label: Claim Group: Patent Data: 12. An Eosinophil cationic protein (ECP), or fragment thereof, comprising a modification at amino acid residue 97 or its equivalent such that residue 97 or its equivalent is any amino acid other than arginine, valine, glycine or lysine. – Name: Comment Label: Claim Group: Patent Data: 13. A protein having the amino acid sequence as shown in SEQ I.D. No. 1, or a fragment thereof, wherein residue 97 is any amino acid other than arginine. – Name: Comment Label: Claim Group: Patent Data: 14. A polypeptide according to claims 12 or 13 wherein residue 97 or its equivalent is threonine or a bioisostere thereof – Name: Comment Label: Claim Group: Patent Data: 15. A protein according to any of claims 10-14, including the sequence C T Y corresponding to amino acid residues 96-98 of wild-type ECP, or a biostere thereof. – Name: Comment Label: Claim Group: Patent Data: 16. A protein according to claim 15, wherein the biostere is of formula C X1 Y, wherein X1 is any amino acid residue other than arginine, valine, glycine or lysine. – Name: Comment Label: Claim Group: Patent Data: 17. A protein having SEQ ID No. 4. – Name: Comment Label: Claim Group: Patent Data: 18. An isolated DNA molecule encoding a protein of any preceding claim. – Name: Comment Label: Claim Group: Patent Data: 19. An isolated DNA molecule comprising an ECP-encoding polynucleotide in which guanosine at position 926 or its equivalent is substituted by cytosine. – Name: Comment Label: Claim Group: Patent Data: 20. A DNA molecule according to claim 19, having the nucleotide sequence shown as SEQ ID No. 3, or a fragment thereof comprising residue 926. – Name: Comment Label: Claim Group: Patent Data: 21. A DNA molecule according to claim 18, having SEQ ID No. 3. – Name: Comment Label: Claim Group: Patent Data: 22. Use of a DNA molecule of any of claims 18-21, or of a polypeptide encoded thereby, in the preparation of a medicament for the prevention and/or treatment of allergic or asthmatic disorders. – Name: Comment Label: Claim Group: Patent Data: 23. Use of an isolated DNA molecule comprising an ECP-encoding polynucleotide or a fragment thereof in a method of determining in a biological sample the nucleotide residue at position 926 or its equivalent. – Name: Comment Label: Claim Group: Patent Data: 24. Use of a pair of oligonucleotide primers which comprise nucleotide sequences flanking position 926, or its equivalent, of an ECP-encoding polynucleotide in a method of determining in a biological sample the nucleotide residue at position 926 or its equivalent. – Name: Comment Label: Claim Group: Patent Data: 25. A method of diagnosis of a predisposition to an allergic or asthmatic disorder or an increased likelihood of having such a disorder comprising determining in a biological sample, the presence or absence of a protein as defined in any of claims 10-17 or a nucleotide sequence as defined in any of claims 18-21. – Name: Comment Label: Claim Group: Patent Data: 26. A method according to claim 25, using an antibody capable of recognising a said protein. – Name: Comment Label: Claim Group: Patent Data: 27. A method according to claim 25, comprising detecting the presence of a G to C polymorphism at position 926 on an ECP encoding polynucleotide. – Name: Comment Label: Claim Group: Patent Data: 28. The method according to claim 27, wherein the polymorphism is detected using PCR primers which amplify a DNA segment comprising a nucleotide at position 926 on an ECP encoding polynucleotide. – Name: Comment Label: Claim Group: Patent Data: 29. The method according to claim 28, wherein the PCR primers are SEQ ID NO: 5 and SEQ ID NO: 6. – Name: Comment Label: Claim Group: Patent Data: 30. A pair of PCR primers which amplify a DNA segment of an ECP encoding polynucleotide, wherein the amplified DNA segment is up to 500 base pairs in length and nucleotide position 926 of the ECP encoding polynucleotide is substantially towards the middle of the DNA segment. – Name: Comment Label: Claim Group: Patent Data: 31. A PCR primer, which is selected from the group consisting of SEQ ID Nos: 5 and 6. – Name: Comment Label: Claim Group: Patent Data: 32. A method of detecting the presence or absence of WT-ECP-DNA or an ECP encoding nucleotide sequence, comprising making a Pst I digest of a sample believed to contain said WT-ECP-DNA or nucleotide sequence and detecting the fragments produced. – Name: Comment Label: Claim Group: Patent Data: 33. An assay for detecting a compound capable of mimicing a protein as defined in any of claims 10-17 or a nucleotide sequence as defined in any of claims 18-21. – Name: Comment Label: Claim Group: Patent Data: 34. An assay for detecting a compound capable of antagonising wild-type ECP expression and/or activity. – Name: Comment Label: Claim Group: Patent Data: 35. An assay of claim 33 or 34 comprising detecting cytotoxic properties with respect to the killing of bacteria and/or cancer cells. – Name: Comment Label: Claim Group: Patent Data: 36. An assay of claim 33 or 34 comprising measuring RNase activity. – Name: Comment Label: Claim Group: Patent Data: 37. An assay of claim 33 or 34 comprising measuring the capacity of the compound to affect fibroblasts in their production of proteoglycans. – Name: Comment Label: Claim Group: Patent Data: 38. A compound identified by means of the assay of any of claims 33-37. – Name: Comment Label: Claim Group: Patent Data: 39. Host cells capable of expressing a protein defined in any of claims 10-17. – Name: Comment Label: Claim Group: Patent Data: 40. Host cells according to claim 25, comprising a nucleotide sequence defined in any of claims 18-21. – Name: Comment Label: Claim Group: Patent Data: 41. A diagnostic kit comprising the pair of PCR primers according to claim 30. – Name: Comment Label: Claim Group: Patent Data: 42. A diagnostic kit comprising an antibody as defined in claim 26. – Name: Comment Label: Claim Group: Patent Data: 43. A kit comprising a diagnostic kit according to claim 41 or 42, and a therapeutic agent. – Name: Comment Label: Claim Group: Patent Data: 44. A kit according to claim 43, wherein the therapeutic agent is for the treatment of an allergy or asthmatic disorder. – Name: Comment Label: Claim Group: Patent Data: 45. A kit according to claim 43 or 44, wherein the therapeutic agent is a compound as defined in claim 38. – Name: CodeClass Label: Current U.S. Class Group: Patent Data: 435006/000 – Name: CodeClass Label: Current International Class Group: Patent Data: 12; 01; 01; 01; 01; 01; 07; 07 – Name: AN Label: Accession Number Group: ID Data: edspap.20060183114 |
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| RecordInfo | BibRecord: BibEntity: Languages: – Text: English Titles: – TitleFull: Novel Eosinophil Cationic Proteins used in the Treatement of Asthematic and Allergic Disorders Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Hogbom, Erik – PersonEntity: Name: NameFull: Bystrom, Jonas – PersonEntity: Name: NameFull: Jonsson, Ulla-Britt – PersonEntity: Name: NameFull: Venge, Per IsPartOfRelationships: – BibEntity: Dates: – D: 17 M: 08 Text: August 17, 2006 Type: published Y: 2006 |
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