(WO202036655) Methods of using genetic markers associated with endometriosis 机翻标题: 暂无翻译,请尝试点击翻译按钮。

源语言标题
(WO202036655) Methods of using genetic markers associated with endometriosis
公开号/公开日
WO2020/036655WO2020/036655WO2020/036655 / 2020-06-042020-04-022020-02-20
申请号/申请日
WOUS2019/029218 / 2019-04-25
发明人
ALBERTSEN HANSCHETTIER RAKESH NWARD KENNETH;
申请人
JENU BIOSCIENCES;
主分类号
IPC分类号
A61K-031/56 A61K-031/566 A61K-039/395 A61P-015/00 C07H-021/04 C12N-015/09
摘要
(WO2020/036655) Disclosed herein are methods of using genetic markers associated with endometriosis, for example via a computer-implemented program to predict risk of developing endometriosis, and methods of preventing or treating endometriosis or a symptom thereof. For example, the present disclosure provides a method of testing for endometriosis and treating a subject having at least one genetic mutation in at least one gene of UGT2B28, USP17L2 (alias DUB3), and METTL11B such that the subject is prevented from developing endometriosis or such that endometriosis in the subject is prevented from progressing. The treatment may be a surgical intervention, a hormone treatment, a pharmaceutical treating, or a combination thereof.
机翻摘要
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地址
代理人
(WO202036655) ARONIN, Caren P. ([US])
代理机构
;
优先权号
2018US-62662469
主权利要求
(WO2020/036655) CLAIMS  WHAT IS CLAIMED: 1. A method comprising assaying a genetic sample of a subject, the method comprising detecting in the sample a genetic mutation in UGT2B28, USP17L2, or METTL1 IB; and applying at least one endometriosis therapeutic to the subject. 2. The method of claim 1, wherein the assaying comprises sequencing, array comparative genomic hybridization (CGH), polymerase chain reaction (PCR), or the use of a DNA microarray. 3. The method of claim 1 or 2, wherein the at least one genetic mutation comprises a hemizygous deletion mutation or a rare missense mutation. 4. The method of any one of claims 1-3, wherein the at least one genetic mutation comprises at least one of a hemizygous deletion mutation in UGT2B28 or USP17L2 and a rare missense mutation in METTL11B. 5. The method of any one of claims 1-4, wherein the subject manifests a pelvic pain, infertility, or dysmenorrhea. 6. The method of any one of claims 1-5, wherein the endometriosis therapeutic comprises a   hormonal treatment, canceling a contemplated hormonal treatment, a surgical procedure, or canceling a contemplated surgical procedure. 7. The method of claim 6, wherein the hormonal treatment comprises at least one of an estrogen containing composition, a progesterone containing composition, a progestin containing composition, a gonadotropin releasing-hormone (GnRH) agonist, a GnRH antagonist, or any combination thereof. 8. A method comprising applying a endometriosis therapeutic to a subject having a genetic mutation in UGT2B28, USP17L2, or METTLl IB in DNA of the subject. 9. The method of claim 8, wherein the genetic mutation comprises a hemizygous deletion mutation or a rare missense mutation. 10. The method of claim 8 or 9, wherein the genetic mutation comprises at least one of a hemizygous deletion mutation UGT2B28 or USP17L2 and a rare missense mutation in METTLl IB. 11. The method of any one of claims 8-10, wherein the subject manifests a pelvic pain, infertility, or dysmenorrhea. 12. The method of any one of claims 8-11, wherein the endometriosis therapeutic comprises a   hormonal treatment, canceling a contemplated hormonal treatment, surgical procedure, or canceling a contemplated surgical procedure. 13. The method of claim 12, wherein the hormonal treatment comprises an estrogen containing   composition, a progesterone containing composition, a progestin containing composition, a gonadotropin releasing-hormone (GnRH) agonist, orany combination thereof. 14. The method of any one of claims 1-13, wherein the genetic sample is obtained from a blood sample. 15. The method of any one of claims 1-14, further comprising providing a treatment for the subject, wherein the treatment comprises a recommendation for the treatment. 16. The method of any one of claims 1-15, wherein the detecting comprises comparing a data set obtained from the genetic sample to a control data set of a control sample. 17. The method of claim 16, wherein the data set comprises sequencing data. 18. The method of claim 16, wherein at least a portion of data from the data set is removed. 19. The method of claim 16, wherein at least a portion of data from the control data set is removed. 20. The method of claim 18 or claim 19, wherein an accuracy of the detecting is improved after a removal of the portion of data. 21. The method of claim 18 or claim 19, wherein a false positive rate of the detecting is reduced after a removal of the portion of data. 22. The method of claim 19, wherein the portion of data removed from the control data set is data of a sample that is familial to the genetic material. 23. The method of any one of claims 16-2, wherein the control sample is selected based on one or more parameters of associated with the genetic material. 24. The method of claim 23, wherein the one or more parameters comprise an ethnicity, an age, a gender, a geographical location, a diet, a medical history, a familial history, a sample preparation, or any combination thereof. 25. A method comprising:   (a) hybridizing a nucleic acid probe to a nucleic acid sample from a human subject suspected of having or developing endometriosis; and   (b) detecting a genetic variant in a panel comprising two or more genetic variants defining a minor allele listed in Tables 1 and 2. 26. The method of claim 25, wherein the nucleic acid sample comprises mRNA, cDNA, genomic DNA, or PCR amplified products produced therefrom, or any combination thereof. 27. The method of claim 25, wherein the nucleic acid sample comprises PCR amplified nucleic acids produced from cDNA or mRNA. 28. The method of claim 25, wherein the nucleic acid sample comprises PCR amplified nucleic acids produced from genomic DNA. 29. The method of any one of claims 25-28, wherein the nucleic acid probe is a sequencing primer. 30. The method of any one of claims 25-28, wherein the nucleic acid probe is an allele specific probe. 31. The method of any one of claims 25-30, wherein the detecting comprises sequencing,   hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, or any combination thereof. 32. The method of any one of claims 25-31, wherein the detecting yields a data set. 33. The method of claim 32, further comprising inputting the data set into a programmed computer having a trained algorithm. 34. The method of any one of claims 25-33, further comprising outputting an electronic report that comprises a result. 35. The method of claim 31, wherein the detecting comprises the sequencing and wherein the   sequencing comprises next-gen sequencing. 36. The method of claim 31, wherein the detecting comprises the sequencing and wherein the   sequencing comprises nanopore sequencing. 37. The method of claim 36, wherein the nanopore sequencing is performed with a biological   nanopore, a solid state nanopore, a hybrid nanopore, or any combination thereof. 38. The method of claim 25, wherein the detecting comprises labeling the one or more SNPs. 39. The method of claim 38, wherein the labeling comprises associating a fluorescent label with the one or more SNPs. 40. The method of claim 38 or 39, wherein the labeling comprises covalently labeling the one or more SNPs. 41. The method of any one of claims 25-40, wherein the nucleic acid sample is at least partially isolated from a blood sample. 42. The method of any one of claims 25-41, wherein the nucleic acid sample is at least partially isolated from a cell -free sample. 43. The method of any one of claims 25-42, wherein the nucleic acid sample is comprised in a cell- free DNA. 44. The method of any one of claims 25-43, wherein the panel comprises at least: 5, 10, 15, or 20 genetic variants defining minor alleles listed in Tables 1 and 2. 45. The method of any one of claims 25-44, wherein the genetic variant comprises a synonymous mutation, a non-synonymous mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof. 46. The method of any one of claims 25-45, wherein the genetic variant comprises a protein   damaging mutation. 47. The method of any one of claims 25-46, wherein the panel comprises one or more protein   damaging or loss of function variants in one or more genes selected from the group consisting of UGT2B28, USP17L2, METTL11B , and any combinations thereof. 48. The method of claim 47, further comprising sequencing the one or more genes to identify the one or more protein damaging or loss of function variants. 49. The method of claim 47, wherein the one or more protein damaging or loss of function variants is identified based on a predictive computer algorithm. 50. The method of claim 47, wherein the one or more protein damaging or loss of function variants is identified based on reference to a database. 51. The method of claim 46, wherein the one or more protein damaging or loss of function variants comprises a stop-gain mutation, a splice-site mutation, a frameshift mutation, a missense mutation, or any combination thereof. 52. The method of any one of claims 25-51, wherein the panel is capable of identifying a human subject as having or being at risk of developing endometriosis with a specificity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. 53. The method of any one of claims 25-52, wherein the panel is capable of identifying a human subject as having or being at risk of developing endometriosis with a sensitivity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. 54. The method of any one of claims 25-53, wherein the panel is capable of identifying a human subject as having or being at risk of developing endometriosis with an accuracy of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. 55. The method of any one of claims 25-54, further comprising administering a therapeutic to the human subject. 56. The method of claim 55, wherein the therapeutic comprises a regenerative therapy, a medical device, a pharmaceutical composition, a medical procedure, or any combination thereof. 57. The method of claim 55, wherein the therapeutic comprises a non-steroidal anti-inflammatory, a hormone treatment, a dietary supplement, a cannabis-derived therapeutic or any combination thereof. 58. The method of claim 55, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises an at least partially hemp-derived therapeutic, an at least partially cannabis-derived therapeutic, a cannabidiol (CBD) oil derived therapeutic, or any combination thereof. 59. The method of claim 55, wherein the therapeutic comprises the medical procedure, and wherein the medical procedure comprises a laparoscopy, a laser ablation procedure, a hysterectomy or any combination thereof. 60. The method of claim 55, wherein the therapeutic comprises the regenerative therapy, and wherein the regenerative therapy comprises a stem cell, a cord blood cell, a Wharton’s jelly, an umbilical cord tissue, a tissue, or any combination thereof. 61. The method of claim 55, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises cannabis, cannabidiol oil, hemp, or any combination thereof. 62. The method of claim 55, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition is formulated in a unit dose. 63. The method of claim 54, wherein the therapeutic comprises hormonal therapy, an advanced   reproductive therapy, a pain managing medication, or any combination thereof. 64. The method of claim 54, wherein the therapeutic comprises a hormonal contraceptive,   gonadotropin-releasing hormone (GnRH) agonist, gonadotropin-releasing hormone (GnRH) antagonist, progestin, danazol, or any combination thereof. 65. The method of any one of claims 25-64, further comprising administering an imaging procedure to a subject. 66. The method of claim 64, wherein the imaging procedure comprises an ultrasound, an x-ray, a magnetic resonance imaging (MRI), a computed tomography (CT) scan, or any combination thereof. 67. The method of any one of claims 25-66, wherein the human subject is asymptomatic for   endometriosis. 68. The method of any one of claims 25-67, wherein the human subject is a teenager. 69. A method comprising detecting one or more genetic variants defining a minor allele listed in Tables 1 and 2 in genetic material from a human subject suspected of having or developing endometriosis. 70. The method of claim 69, wherein the genetic material comprises mRNA, cDNA, genomic DNA, or PCR amplified products produced therefrom, or any combination thereof. 71. The method of claim 69 or 70, wherein the detecting comprises DNA sequencing, hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, of any combination thereof. 72. The method of claim 69 or 70, wherein the detecting comprises hybridizing a nucleic acid probe to the genetic material. 73. The method of any one of claims 69-72, wherein the detecting comprises testing for the presence or absence of at least: 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 genetic variants defining a minor allele listed in Table 1 and Table 2. 74. The method of any one of claims 69-73, further comprising administering a therapeutic to the human subject. 75. A method comprising:   (a) sequencing all or a portion of one or more genes or gene expression products selected from the group consisting of UGT2B28, USP17L2 , METTL1 IB and any combinations thereof to identify one or more protein damaging or loss of function variants in a human subject suspected of having or developing endometriosis; and   (b) identifying the human subject as having or being at risk of developing endometriosis when the one or more protein damaging or loss of function variant is identified. 76. The method of claim 75, wherein the one or more protein damaging or loss of function variants comprises a deletion of all or a portion of the one or more genes. 77. The method of claim 75, wherein the one or more protein damaging or loss of function variants is identified based on a predictive computer algorithm, reference to a database, or a combination thereof. 78. The method of claim 75, wherein the one or more protein damaging or loss of function variants comprises a stop-gain mutation, a splice-site mutation, a frameshift mutation, a missense mutation, or any combination thereof. 79. The method of any one of claims 75-78, further comprising administering a hormonal therapy to the human subject. 80. The method of claim 79, wherein the hormonal therapy comprises administration of hormonal contraceptives, gonadotropin-releasing hormone (GnRH) agonists, gonadotropin-releasing hormone (GnRH) antagonists, progestin, danazol, or any combination thereof. 81. The method of any one of claims 75-80, further comprising administering to the human subject an assisted reproductive therapy. 82. The method of claim 81, wherein the assisted reproductive therapy comprises in vitro fertilization, intrauterine insemination, ovulation induction, gamete intrafallopian transfer, or any combination thereof. 83. The method of any one of claims 75-82, further comprising administering to the human subject a pain medication. 84. The method of claim 83, wherein the pain medication comprises a nonsteroidal anti-inflammatory drug (NS AID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof. 85. The method of any one of claims 75-84, further comprising detecting the at least one genetic   variant in a genetic material from the human subject. 86. The method of claim 85, wherein the detecting comprises DNA sequencing, hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, or any combination thereof. 87. The method of claim 85, wherein the detecting comprises hybridizing a nucleic acid probe to the genetic material. 88. The method of claim 87, wherein the nucleic acid probe is a sequencing primer or an allele- specific probe. 89. The method of any one of claims 75-88, wherein the human subject has at least one genetic   variant that comprises a synonymous mutation, a non-synonymous mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof. 90. A kit comprising: one or more probes for detecting one or more single nucleotide   polymporphisms (SNPs) of Table 1, Table 2, or a combination thereof in a sample. 91. The kit of claim 90, further comprising a control sample. 92. The kit of claim 90, wherein the control sample comprises one or more of SNPs of Table 1, Table 2, or a combination thereof. 93. The kit of any one of claims 90-92, wherein a probe of the one or more probes comprises a   sequence having at least 80% sequence complementarity to a sequence adjacent thereto a SNP of the one or more SNPs of Table 1 , Table 2, or a combination thereof. 94. The kit of any one of claims 90-93, wherein the one or more probes comprise a hybridization probe or amplification primer. 95. The kit of any one of claims 90-94, wherein the one or more probes is configured to detect a   variant allele in the sample. 96. The kit of any one of claims 90-95, wherein the one or more probes is configured to hybridize to a portion of a nucleic acid of the sample when a variant allele is present in the nucleic acid. 97. The kit of any one of claims 90-96, wherein the one or more probes is configured to associate with a solid support. 98. The kit of any one of claims 90-97, wherein the kit further comprises instructions for use and wherein the instructions for use comprise high stringent hybridization conditions. 99. The kit of any one of claims 90-98, wherein the one or more probes is configured to hybridize to a target region of a nucleic acid of the sample, wherein the target region comprises one or more SNPs. 100. A system comprising: (a) a computer processor configured to receive sequencing data obtained from assaying a sample, wherein the computer processor is configured to identify a presence or an absence of one or more SNPs comprising one or more SNPs of Table 1, Table 2, or a combination thereof in the sample, and (b) a graphical user interface configured to display a report comprising the identification of the presence or the absence of the one or more SNPs in the sample. 101. The system of claim 100, wherein the computer processor comprises a trained algorithm. 102. The system of claim 100 or 101, wherein the computer processor communicates a result. 103. The system of claim 102, wherein the result comprises an identification of the presence or the absence of one or more SNPs in the sample.
法律状态
PENDING
专利类型码
A9A3A2
国别省市代码
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