Claims for Patent: 5,538,853

Summary for Patent: 5,538,853

Title:	Bone resorption assay based on a peptide liberated during collagen degradation
Abstract:	An antibody raised to type I collagen carboxyterminal cross-linked telopeptide isolated from decalcified human or animal bone, may be used in an assay to determine the concentration of liberated carboxyterminal telopeptide region of the type I collagen molecule in a sample. When the sample is a body fluid such as serum or urine the degradation product measured is resistant to further degradation, since it contains a multivalent intermolecular cross-link, and can thus be found in the body fluid. The assay may be used to assess the degradation of type I collagen, the major organic constituent of bone matrix.
Inventor(s):	Risteli; Juha P. (Oulu, FI), Risteli; Leila T. (Oulu, FI)
Assignee:	Orion Corporation, Orion Diagnostica (Koivumankkaankuja, FI)
Application Number:	08/274,105
Patent Claims:	1. A method for testing for the presence or level of a type I collagen degradation product in a sample other than urine, comprising combining with the sample an antibody which specifically binds to a peptide derived from type I collagen carboxyterminal telopeptide selected from the group consisting of ##STR2## wherein the antibody binds an immunological determinant comprising amino acids other than the cross-links in the peptide, and detecting the binding of the antibody to the type I collagen degradation product. 2. A method for assaying a type I collagen degradation product, which comprises contacting in any order (i) a sample other than urine which is known or suspected to contain such product; (ii) an antibody which specifically binds to a peptide derived from type I collagen carboxyterminal telopeptide selected from the group consisting of ##STR3## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, and (iii) a label; under conditions such that the label becomes bound in an antibody-containing complex in an amount which depends on the amount of type I collagen degradation product in said sample, and then assaying the bound and/or unbound label to determine the presence or level of the type I collagen degradation product in said sample. 3. A method according to claim 2, wherein labelled type I collagen carboxyterminal telopeptide and the sample are both contacted with said antibody, the antigen-antibody complexes so formed are separated from uncomplexed starting materials, and the complexed or the uncomplexed label is assayed. 4. A method according to claim 3 wherein the antigen-antibody complex is contacted with a second antibody which specifically binds to the first antibody, and the antigen-antibody-antibody complex so formed is separated from the uncomplexed starting materials. 5. A method according to any one of claims 2 to 4 wherein the label is a radioactive, enzymatic, or fluorescent label. 6. A method according to any one of claims 2 or 3 wherein the antibody is immobilized to a solid support, and the antigen-antibody complex formed is separated from a medium in which the contact takes place by separating said solid support from said medium. 7. A method according to claim 4 wherein the second antibody is immobilized to a solid support, and the antigen-antibody-antibody complex so formed is separated from a medium in which the contact takes place by separating said solid support from said medium. 8. A method according to any one of claims 2-4 wherein the antibody when specifically binds to a peptide derived from type I collagen carboxyterminal telopeptide is raised against type I collagen carboxyterminal cross-linked telopeptide. 9. A method according to claim 8 in which the telopeptide used to raise the antibody was obtained from bone from a human or animal vertebrate. 10. A method according to any one of claims 1 to 4 in which the antibody when specifically binds to a peptide derived from type I collagen carboxyterminal telopeptide is a monoclonal antibody. 11. A kit suitable for use in carrying out an assay method according to claim 2 comprising an antibody which specifically binds to a peptide derived from type I collagen carboxyterminal telopeptide selected from group consisting of ##STR4## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, and a label. 12. A kit suitable for use in carrying out an assay method according to claim 3 comprising an antibody which specifically binds to a peptide derived from type I collagen carboxyterminal telopeptide selected from the group consisting of ##STR5## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, and labelled type I collagen carboxyterminal telopeptide. 13. A kit suitable for use in carrying out an assay method according to claim 4 comprising a first antibody which specifically binds to a peptide derived from type I collagen carboxyterminal telopeptide selected from the group consisting of ##STR6## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, labelled type I collagen carboxyterminal telopeptide, and a second antibody which specifically binds to the first antibody. 14. A kit suitable for use in carrying out an assay method according to claim 6 comprising an antibody which specifically binds to a peptide derived from type I collagen carboxyterminal telopeptide selected from the group consisting of ##STR7## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, a label, and a solid support to which is immobilized the antibody. 15. A kit suitable for use in carrying out an assay method according to claim 7 comprising a first antibody which specifically binds to a peptide derived from type I collagen carboxyterminal telopeptide selected from the group consisting of ##STR8## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, a second antibody which specifically binds to the first antibody, a label, and a solid support to which is immobilized the first or second antibody. 16. An antibody raised against type I collagen carboxyterminal cross-linked telopeptide which specifically binds to a peptide selected from the group consisting of ##STR9## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide. 17. An antibody according to claim 16 in which the telopeptide is obtained from bone from a human or non-human vertebrate. 18. An antibody according to any one of claim 16 or 17 wherein the antibody is a monoclonal antibody. 19. A method for testing for the presence or level of a type I collagen degradation product in a sample other than urine, comprising combining with the sample an antibody which specifically bind to ##STR10## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, and detecting the binding of the antibody to the type I collagen degradation product. 20. A method for assaying a type I collagen degradation product, which comprises contacting in any order (i) a sample other than urine which is known or suspected to contain such product; (ii) an antibody which specifically binds to ##STR11## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, and (iii) a label, under conditions such that the label becomes bound in an antibody-containing complex in an amount which depends on the amount of collagen degradation product in said sample, and then assaying the bound and/or unbound label to determine the presence or level of the type I collagen degradation product in said sample. 21. A kit suitable for use in carrying out an assay method according to claim 20 comprising an antibody which specifically binds to ##STR12## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, and a label. 22. An antibody raised against type I collagen carboxyterminal cross-linked telopeptide which specifically binds to ##STR13## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide. 23. A method for testing for the presence or level of a type I collagen degradation product in a sample other than urine, comprising combining with the sample an antibody which specifically binds to ##STR14## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, and detecting the binding of the antibody to the type I collagen degradation product. 24. A method for assaying a type I collagen degradation product, which comprises contacting in any order (i) a sample other than urine which is known or suspected to contain such product; (ii) an antibody which specifically binds to ##STR15## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, and (iii) a label, under conditions such that the label becomes bound in an antibody-containing complex in an amount which depends on the amount of collagen degradation product in said sample, and then assaying the bound and/or unbound label to determine the presence or level of the type I collagen degradation product in said sample. 25. A kit suitable for use in carrying out an assay method according to claim 24 comprising an antibody which specifically binds to ##STR16## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide, and a label. 26. An antibody raised against type I collagen carboxyterminal cross-linked telopeptide which specifically binds to ##STR17## wherein the antibody binds to an immunological determinant comprising amino acids other than the cross-links in the peptide. 27. A method according to claims 1, 2, 19, 20, 23 or 24 wherein the peptide is obtained by subjecting denatured bone collagen to digestion with a proteolytic enzyme selected from the group consisting of bacterial collagenase and trypsin. 28. A kit according to claims 12, 13, 15, 21 or 25 wherein the peptide is obtained by subjecting denatured bone collagen to digestion with a proteolytic enzyme selected from the group consisting of bacterial collagenase and trypsin. 29. An antibody according to claim 16 or claim 26 wherein the peptide is obtained by subjecting denatured bone collagen to digestion with a proteolytic enzyme selected from the group consisting of bacterial collagenase and trypsin.

Details for Patent 5,538,853

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2013-07-23