Claims for Patent: 6,803,197

Summary for Patent: 6,803,197

Title:	Method for determining susceptibility to bone damage by screening polymorphisms in the vitamin D receptor gene
Abstract:	The present invention relates to a prognostic method and means for determining susceptibility to bone damage in a subject, by screening for polymorphisms in the Vitamin D receptor or collagen I.alpha.1 genes. In particular, the method for determining susceptibility to bone damage comprises analyzing the genetic material of a subject to determine which of the B/b, A/a or T/t alleles of the restriction enzyme sites BsmI, ApaI and TaqI respectively are present. The method may further comprise determining which allele is present at die SpI restriction site of the collagen I.alpha.1 gene. Specific combinations of the above alleles represent a haplotype which is associated with susceptibility to bone damage.
Inventor(s):	Uitterlinden; Andreas Gerardus (Poortugaal, NL), Van Leeuwen; Johannes Petrus Thomas Maria (Amstelveen, NL), Pols; Huibert Adriaan Pieter (Papendrecht, NL)
Assignee:	Erasmus Universiteit Rotterdam (Rotterdam, NL)
Application Number:	09/786,991
Patent Claims:	1. A method of determining susceptibility to bone fracture in a subject said method comprising analyzing genetic material of a subject to determine the presence of the baT haplotype of the vitamin D receptor gene, wherein the presence of the baT haplotype is indicative of an increased susceptibility to bone fracture. 2. A method of determining susceptibility to bone fracture according to claim 1 said method further comprising determining the presence of a G to T polymorphism at the Sp1 site of the collagen I.alpha.1 gene, wherein detection of said polymorphism is indicative of an increased susceptibility to bone fracture. 3. A method of determining susceptibility to bone fracture according to claim 1 said method further comprising determining the copy number of the b, a or T alleles of the vitamin D receptor gene and/or the s allele of the collagen I.alpha.1 gene. 4. A method according to claim 3 comprising comparing the allele(s) present in the genetic material of the subject with genotypes of the vitamin D receptor or collagen I.alpha.1 genes having known degrees of risk of bone fracture. 5. A method according to claim 2, further comprising determining calcium levels in a subject. 6. A method according to claim 5 wherein daily calcium intake is measured. 7. A method according to claim 1, wherein said method is performed in vitro. 8. A method according to claim 7, wherein said method is performed on blood, or tissue samples of a subject. 9. A method of treating a subject to reduce the risk of bone fracture comprising analysing genetic material of a subject to determine the presence of the baT haplotype of the vitamin D receptor gene, wherein the presence of the baT haplotype is indicative of an increased susceptibility bone fracture, and treating the subject to reduce the risk of bone fracture if the subject has the baT haplotype. 10. A method according to claim 9, wherein suitable treatments include modifications to lifestyle, regular exercise, changes in diet or pharmaceutical preparations. 11. A method according to claim 1, wherein the subject is a mammal. 12. A method according to claim 11, wherein the subject is a human. 13. A method according to claim 11 or 12, wherein the subject is a female. 14. A method of formulating a treatment regimen to decrease the risk of bone fracture, said method comprising analysing genetic material of a subject to determine the presence of the baT haplotype of the vitamin D receptor gene, wherein said haplotype is associated with risk of bone fracture, and formulating a treatment regimen to decrease the risk of bone fracture based on said haplotype. 15. A method according to claim 14, further comprising determining the presence of a G to T polymorphism at the Sp1 site of the collagen I.alpha.1 gene. 16. A method according to claims 14 or 15 further comprising administering the appropriate treatment. 17. A method of determining susceptibility to bone fracture in a subject comprising determining whether the baT haplotype of the vitamin D receptor gene is present in a subject, wherein said determining step utilizes a kit and, wherein said kit comprises (i) one or more nucleic acid primer molecules for amplification of a portion of the vitamin D receptor gene, and (ii) means for determining whether the baT haplotype of said gene is present, and wherein presence of the baT haplotype in the subject is indicative of susceptibility to bone fracture. 18. The method according to claim 17 further comprising the step of determining whether the s allele of a collagen I.alpha.1 gene is present in the subject, said kit further comprising (i) one or more nucleic acid primer molecules for amplification of a portion of the collagen I.alpha.1 gene and (ii) means for determining whether the s allele of the collagen I.alpha.1 gene is present. 19. A method according to claim 1, wherein the haplotype is determined by amplification of a portion of the vitamin D receptor gene between exon 7 and the 3' UTR, followed by restriction enzyme digestion; or any other technique suitable for determining the genotype of a subject. 20. A method according to claim 2, wherein the haplotype is determined by amplification of a portion of the vitamin D receptor gene between exon 7 and the 3' UTR, or amplification of the first intron of the collagen I.alpha.1 gene, followed by restriction enzyme digestion; or any other technique suitable for determining the genotype of a subject.

Details for Patent 6,803,197

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2018-09-10
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2018-09-10
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2018-09-10
Emergent Biosolutions Canada Inc.	BAT	botulism antitoxin heptavalent (a, b, c, d, e, f, g) - (equine)	Solution	125462	03/22/2013		2018-09-10