IP Library › Granted Patent US 12,331,357
Granted Patent B2
US 12,331,357 · App. 17/141,885 · Granted Jun 17, 2025

Methods for assessing risk of developing a viral disease using a genetic test

Inventors: Eli Hatchwell (Winchester, GB); Peggy S. Eis (Fitchburg, WI); Edward B. Smith, III (New York, NY); Yassine Taoufik (Paris, FR)
Assignees: PML Screening, LLC; The Université Paris-Saclay; The Assistance Publique—Hòpitaux de Paris (APHP); The Institut National de la Santé et de la Recherche Medicale (INSERM)
C12Q1/6883C07K16/2839G01N33/56983A61K2039/505A61K2039/54A61K2039/545C12Q2600/106C12Q2600/118C12Q2600/156G01N2333/025G01N2800/065G01N2800/285G01N2800/52
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,331,357
App. No.
17/141,885
Granted
Jun 17, 2025
Kind
B2
Abstract

This document provides methods and materials related to treating a disease. For example, this document provides methods for treating a subject's disease based on identifying the risk of progressive multifocal leukoencephalopathy PML using a genetic test.

Claims (70)

1. A method of treating a condition in a subject in need of an immunosuppressive medication comprising: administering to the subject a therapeutically effective amount of an immunosuppressive medication that has a potential to induce progressive multifocal leukoencephalopathy (PML) due to an infection of the brain by John Cunningham virus (JCV), wherein the subject has been tested for a presence of one or more genetic variations with a genetic assay and has been identified as not having the one or more genetic variations,

wherein:

(i) the one or more genetic variations is an insertion, a deletion, or a base substitution in a gene selected from the group consisting of a PRKDC gene, a ZAP70 gene, a RAG1 gene, an IRAK4 gene, a PLCG2 gene, a TLR3 gene, a CHD7 gene, a GATA2 gene, a STIM1 gene, an IFIH1 gene, a TBK1 gene, a CARD11 gene, an ATR gene, a RIPK3 gene, or a LYST gene; or

(ii) the one or more genetic variations comprise chr9: 286491 G>A, chr9: 286593 C>A, chr9: 304628 G>A, chr9: 312134 G>A, chr9: 328047 T>A, chr9: 334277 G>A, chr9: 368128 C>T, chr9: 446401 A>G, chr4: 103522068 A>G, chr4: 103522150 G>A, or chr4: 103528328 C>T, wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19; and

wherein:

(A) the subject has been tested with a JCV antibody test, a CD62L test or a CSF IgM oligoclonal bands test, or (B) the condition is Crohn's disease, multiple sclerosis, or a relapsing form of multiple sclerosis.

2. The method of claim 1 , wherein the one or more genetic variations comprise chr9: 286491 G>A, chr9: 286593 C>A, chr9: 304628 G>A, chr9: 312134 G>A, chr9: 328047 T>A, chr9: 334277 G>A, chr9: 368128 C>T, chr9: 446401 A>G, chr4: 103522068 A>G, chr4: 103522150 G>A, chr4: 103528328 C>T, or any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

3. The method of claim 1 , wherein the method comprises testing the subject for the presence of the one or more genetic variations with the genetic assay prior to the administering.

4. The method of claim 3 , wherein the genetic assay comprises microarray analysis, PCR, sequencing, nucleic acid hybridization, or any combination thereof.

5. The method of claim 3 , wherein the genetic assay comprises whole exome sequencing or whole genome sequencing.

6. The method of claim 3 , wherein the genetic assay comprises analyzing nucleic acid information of the subject obtained by whole exome sequencing or whole genome sequencing.

7. The method of claim 1 , wherein the subject has been tested with a JCV antibody test.

8. The method of claim 1 , wherein the one or more genetic variations is a single nucleotide polymorphism (SNP) or a single nucleotide variation (SNV).

9. The method of claim 1 , wherein the one or more genetic variations is a deletion.

10. The method of claim 1 , wherein the one or more genetic variations comprises (i) a genetic variation in the PRKDC gene selected from the group consisting of chr8: 48690299 A>G, chr8: 48773526 T>C, chr8: 48798507 T>C, and chr8: 48826575 C>G; (ii) a genetic variation in the ZAP70 gene selected from the group consisting of chr2: 98351032 C>G, chr2: 98351066 C>T, and chr2: 98351081 C>T; (iii) a genetic variation in the RAG1 gene selected from the group consisting of chr11: 36595321 C>T, chr11: 36596528 G>C, chr11: 36596863 C>T, and chr11: 36597513 G>A; or (iv) any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

11. The method of claim 1 , wherein the one or more genetic variations comprises (i) a genetic variation in the IRAK4 gene selected from the group consisting of chr12: 44166753 A>G and chr12: 44167821 A>T; (ii) a genetic variation in the PLCG2 gene selected from the group consisting of chr16: 81902826 C>T, chr16: 81904539 C>T, chr16: 81939089 T>C, chr16: 81942175 A>G, and chr16: 81946278 A>G; (iii) a genetic variation in the TLR3 gene selected from the group consisting of chr4: 187003729 C>G, chr4: 187004074 C>T, and chr4: 187005854 A>C; or (iv) any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

12. The method of claim 1 , wherein the one or more genetic variations comprises (i) a genetic variation in the CHD7 gene selected from the group consisting of chr8: 61654298 T>A, chr8: 61732632 A>G, chr8: 61757805 C>T, chr8: 61769428 A>G, chr8: 61777914 C>G, and chr8: 61777922 C>G; (ii) a genetic variation in the GATA2 gene selected from the group consisting of chr3: 128204761 C>T and chr3: 128205808 C>T; (iii) a genetic variation in the STIM1 gene selected from the group consisting of chr11: 4104626 C>A and chr11: 4112582 C>T; or (iv) any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

13. The method of claim 1 , wherein the one or more genetic variations comprise two or more genetic variations.

14. The method of claim 13 , wherein the one or more genetic variations comprise at least 5 genetic variations.

15. The method of claim 3 , wherein prior to testing the subject for the presence of the one or more genetic variations with the genetic assay the method further comprises obtaining biological samples from subjects with PML and (a) confirming each biological sample is not a duplicate of any other biological sample based on nucleic acid information of the biological samples or (b) determining a sex genotype for each biological sample based on nucleic acid information of the biological samples, and confirming the sex genotype of each biological sample is the same as a sex phenotype of the subject with PML from which the biological sample was obtained.

16. The method of claim 1 , wherein the condition is Crohn's disease.

17. The method of claim 1 , wherein the condition is multiple sclerosis.

18. The method of claim 1 , wherein the condition is a relapsing form of multiple sclerosis.

19. The method of claim 1 , wherein the one or more genetic variations comprises (i) a genetic variation in the IFIH1 gene selected from the group consisting of chr2: 163124051 C>T, chr2: 163134203 G>T, chr2: 163136505 C>G, and chr2: 163139085 A>T; (ii) a genetic variation in the TBK1 gene selected from the group consisting of chr12: 64878241 G>A and chr12: 64879775 C>T; (iii) a genetic variation in the CARD11 gene selected from the group consisting of chr7: 2959240 C>T, chr7: 2962933 C>T, and chr7: 2983958 T>C; or (iv) any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

20. The method of claim 1 , wherein the one or more genetic variations comprises (i) a genetic variation in the ATR gene selected from the group consisting of chr3: 142272098 A>G, chr3: 142274880 G>C, chr3: 142281353 C>G, and chr3: 142286928 C>T; (ii) a genetic variation in the RIPK3 gene selected from the group consisting of chr14: 24805463 G>T and chr14: 24806303 G>A; (iii) a genetic variation in the LYST gene selected from the group consisting of chr1: 235840495 G>T, chr1: 235897907 C>T, and chr1: 235909815 A>T, or any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

21. The method of claim 10 , wherein the one or more genetic variations comprises a genetic variation in the PRKDC gene selected from the group consisting of chr8: 48690299 A>G, chr8: 48773526 T>C, chr8: 48798507 T>C, chr8: 48826575 C>G, and any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

22. A method of determining whether to administer an immunosuppressive medication to a subject with a condition in need of an immunosuppressive medication comprising:

(a) testing for the presence of one or more genetic variations in a sample obtained from the subject, wherein testing comprises testing for the presence of the one or more genetic variations with a genetic assay; and

(b) excluding the subject from an immunosuppressive medication that has a potential to induce progressive multifocal leukoencephalopathy (PML) due to an infection of the brain by John Cunningham virus (JCV) based on the presence of the one or more genetic variations in the subject;

(i) wherein the one or more genetic variations is an insertion, a deletion, or a base substitution in a gene selected from the group consisting of a PRKDC gene, a ZAP70 gene, a RAG1 gene, an IRAK4 gene, a PLCG2 gene, a TLR3 gene, a CHD7 gene, a GATA2 gene, a STIM1 gene, an IFIH1 gene, a TBK1 gene, a CARD11 gene, an ATR gene, a RIPK3 gene, or a LYST gene; or

(ii) wherein the one or more genetic variations comprise chr9: 286491 G>A, chr9: 286593 C>A, chr9: 304628 G>A, chr9: 312134 G>A, chr9: 328047 T>A, chr9: 334277 G>A, chr9: 368128 C>T, chr9: 446401 A>G, chr4: 103522068 A>G, chr4: 103522150 G>A, or chr4: 103528328 C>T, wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19; and

wherein:

(A) the subject has been tested with a JCV antibody test, a CD62L test or a CSF IgM oligoclonal bands test, or

(B) the condition is Crohn's disease, multiple sclerosis, or a relapsing form of multiple sclerosis.

23. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the PRKDC gene selected from the group consisting of chr8: 48690299 A>G, chr8: 48773526 T>C, chr8: 48798507 T>C, and chr8: 48826575 C>G, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

24. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the ZAP70 gene selected from the group consisting of chr2: 98351032 C>G, chr2: 98351066 C>T, and chr2: 98351081 C>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

25. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the RAG1 gene selected from the group consisting of chr11: 36595321 C>T, chr11: 36596528 G>C, chr11: 36596863 C>T, and chr11: 36597513 G>A, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

26. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the IRAK4 gene selected from the group consisting of chr12: 44166753 A>G and chr12: 44167821 A>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

27. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the PLCG2 gene selected from the group consisting of chr16: 81902826 C>T, chr16: 81904539 C>T, chr16: 81939089 T>C, chr16: 81942175 A>G, and chr16: 81946278 A>G, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

28. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the TLR3 gene selected from the group consisting of chr4: 187003729 C>G, chr4: 187004074 C>T, and chr4: 187005854 A>C, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

29. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the CHD7 gene selected from the group consisting of chr8: 61654298 T>A, chr8: 61732632 A>G, chr8: 61757805 C>T, chr8: 61769428 A>G, chr8: 61777914 C>G, and chr8: 61777922 C>G, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

30. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the GATA2 gene selected from the group consisting of chr3: 128204761 C>T and chr3: 128205808 C>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

31. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the STIM1 gene selected from the group consisting of chr11: 4104626 C>A and chr11: 4112582 C>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

32. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the IFIH1 gene selected from the group consisting of chr2: 163124051 C>T, chr2: 163134203 G>T, chr2: 163136505 C>G, and chr2: 163139085 A>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

33. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the TBK1 gene selected from the group consisting of chr12: 64878241 G>A and chr12: 64879775 C>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

34. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the CARD11 gene selected from the group consisting of chr7: 2959240 C>T, chr7: 2962933 C>T, and chr7: 2983958 T>C, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

35. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the ATR gene selected from the group consisting of chr3: 142272098 A>G, chr3: 142274880 G>C, chr3: 142281353 C>G, and chr3: 142286928 C≥T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

36. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the RIPK3 gene selected from the group consisting of chr14: 24805463 G>T and chr14: 24806303 G>A, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

37. The method of claim 1 , wherein the one or more genetic variations comprises a genetic variation in the LYST gene selected from the group consisting of chr1: 235840495 G>T, chr1: 235897907 C>T, and chr1: 235909815 A>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

38. The method of claim 22 , wherein the one or more genetic variations comprises (i) a genetic variation in the PRKDC gene selected from the group consisting of chr8: 48690299 A>G, chr8: 48773526 T>C, chr8: 48798507 T>C, and chr8: 48826575 C>G; (ii) a genetic variation in the ZAP70 gene selected from the group consisting of chr2: 98351032 C>G, chr2: 98351066 C>T, and chr2: 98351081 C>T; (iii) a genetic variation in the RAG1 gene selected from the group consisting of chr11: 36595321 C>T, chr11: 36596528 G>C, chr11: 36596863 C>T, and chr11: 36597513 G>A; or (iv) any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

39. The method of claim 22 , wherein the one or more genetic variations comprises (i) a genetic variation in the IRAK4 gene selected from the group consisting of chr12: 44166753 A>G and chr12: 44167821 A>T; (ii) a genetic variation in the PLCG2 gene selected from the group consisting of chr16: 81902826 C>T, chr16: 81904539 C>T, chr16: 81939089 T>C, chr16: 81942175 A>G, and chr16: 81946278 A>G; (iii) a genetic variation in the TLR3 gene selected from the group consisting of chr4: 187003729 C>G, chr4: 187004074 C>T, and chr4: 187005854 A>C; or (iv) any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

40. The method of claim 22 , wherein the one or more genetic variations comprises (i) a genetic variation in the CHD7 gene selected from the group consisting of chr8: 61654298 T>A, chr8: 61732632 A>G, chr8: 61757805 C>T, chr8: 61769428 A>G, chr8: 61777914 C>G, and chr8: 61777922 C>G; (ii) a genetic variation in the GATA2 gene selected from the group consisting of chr3: 128204761 C>T and chr3: 128205808 C>T; (iii) a genetic variation in the STIM1 gene selected from the group consisting of chr11: 4104626 C>A and chr11: 4112582 C>T; or (iv) any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

41. The method of claim 22 , wherein the one or more genetic variations comprises (i) a genetic variation in the IFIH1 gene selected from the group consisting of chr2: 163124051 C>T, chr2: 163134203 G>T, chr2: 163136505 C>G, and chr2: 163139085 A>T; (ii) a genetic variation in the TBK1 gene selected from the group consisting of chr12: 64878241 G>A and chr12: 64879775 C>T; (iii) a genetic variation in the CARD11 gene selected from the group consisting of chr7: 2959240 C>T, chr7: 2962933 C>T, and chr7: 2983958 T>C; or (iv) any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

42. The method of claim 22 , wherein the one or more genetic variations comprises (i) a genetic variation in the ATR gene selected from the group consisting of chr3: 142272098 A>G, chr3: 142274880 G>C, chr3: 142281353 C>G, and chr3: 142286928 C>T; (ii) a genetic variation in the RIPK3 gene selected from the group consisting of chr14: 24805463 G>T and chr14: 24806303 G>A; (iii) a genetic variation in the LYST gene selected from the group consisting of chr1: 235840495 G>T, chr1: 235897907 C>T, and chr1: 235909815 A>T, or any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

43. The method of claim 38 , wherein the one or more genetic variations comprises a genetic variation in the PRKDC gene selected from the group consisting of chr8: 48690299 A>G, chr8: 48773526 T>C, chr8: 48798507 T>C, chr8: 48826575 C>G, and any combination thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

44. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the PRKDC gene selected from the group consisting of chr8: 48690299 A>G, chr8: 48773526 T>C, chr8: 48798507 T>C, and chr8: 48826575 C>G, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

45. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the ZAP70 gene selected from the group consisting of chr2: 98351032 C>G, chr2: 98351066 C>T, and chr2: 98351081 C>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

46. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the RAG1 gene selected from the group consisting of chr11: 36595321 C>T, chr11: 36596528 G>C, chr11: 36596863 C>T, and chr11: 36597513 G>A, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

47. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the IRAK4 gene selected from the group consisting of chr12: 44166753 A>G and chr12: 44167821 A>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

48. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the PLCG2 gene selected from the group consisting of chr16: 81902826 C>T, chr16: 81904539 C>T, chr16: 81939089 T>C, chr16: 81942175 A>G, and chr16: 81946278 A>G, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

49. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the TLR3 gene selected from the group consisting of chr4: 187003729 C>G, chr4: 187004074 C>T, and chr4: 187005854 A>C, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

50. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the CHD7 gene selected from the group consisting of chr8: 61654298 T>A, chr8: 61732632 A>G, chr8: 61757805 C>T, chr8: 61769428 A>G, chr8: 61777914 C>G, and chr8: 61777922 C>G, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

51. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the GATA2 gene selected from the group consisting of chr3: 128204761 C>T and chr3: 128205808 C>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

52. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the STIM1 gene selected from the group consisting of chr11: 4104626 C>A and chr11: 4112582 C>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

53. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the IFIH1 gene selected from the group consisting of chr2: 163124051 C>T, chr2: 163134203 G>T, chr2: 163136505 C>G, and chr2: 163139085 A>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

54. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the TBK1 gene selected from the group consisting of chr12: 64878241 G>A and chr12: 64879775 C>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

55. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the CARD11 gene selected from the group consisting of chr7: 2959240 C>T, chr7: 2962933 C>T, and chr7: 2983958 T>C, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

56. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the ATR gene selected from the group consisting of chr3: 142272098 A>G, chr3: 142274880 G>C, chr3: 142281353 C>G, and chr3: 142286928 C>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

57. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the RIPK3 gene selected from the group consisting of chr14: 24805463 G>T and chr14: 24806303 G>A, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

58. The method of claim 22 , wherein the one or more genetic variations comprises a genetic variation in the LYST gene selected from the group consisting of chr1: 235840495 G>T, chr1: 235897907 C>T, and chr1: 235909815 A>T, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2023
From: HATCHWELL, ELI; EIS, PEGGY S.; SMITH, EDWARD B., III
To: POPULATION BIO, INC.
Reel/Frame 063642/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2023
From: POPULATION BIO, INC.
To: PML SCREENING, LLC
Reel/Frame 063642/0015 →
MERGER AND CHANGE OF NAME Recorded May 15, 2023
From: UNIVERSITE PARIS-SUD; UNIVERSITE PARIS-SACLAY; UNIVERSITE PARIS-SACLAY
To: UNIVERSITE PARIS-SACLAY
Reel/Frame 063642/0025 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2023
From: TAOUFIK, YASSINE
To: THE UNIVERSITE PARIS-SUD; THE ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP); THE INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
Reel/Frame 063642/0988 →
Continuity (5)
Division 16245849 · Jan 11, 2019
Continuation 15639591 · Jun 30, 2017
Provisional Application 62524324 · Jun 23, 2017
Provisional Application 62454676 · Feb 3, 2017
Related Publication 20210371928A1 · Dec 2, 2021
References Cited (400)
US 696589A · Pleck · 1902 [cited by applicant]
US 3625214A · Higuchi · 1971 [cited by applicant]
US 4683195A · Mullis et al. · 1987 [cited by applicant]
US 4789734A · Pierschbacher · 1988 [cited by applicant]
US 4897268A · Tice et al. · 1990 [cited by applicant]
US 4906474A · Langer et al. · 1990 [cited by applicant]
US 4925673A · Steiner et al. · 1990 [cited by applicant]
US 4992445A · Lawter et al. · 1991 [cited by applicant]
US 5001139A · Lawter et al. · 1991 [cited by applicant]
US 5023252A · Hseih · 1991 [cited by applicant]
US 5075109A · Tice et al. · 1991 [cited by applicant]
US 5143854A · Pirrung et al. · 1992 [cited by applicant]
US 5190029A · Byron et al. · 1993 [cited by applicant]
US 5223409A · Ladner et al. · 1993 [cited by applicant]
US 5272071A · Chappel · 1993 [cited by applicant]
US 5288514A · Ellman · 1994 [cited by applicant]
US 5376359A · Johnson · 1994 [cited by applicant]
US 5384261A · Winkler et al. · 1995 [cited by applicant]
US 5424186A · Fodor et al. · 1995 [cited by applicant]
US 5445934A · Fodor et al. · 1995 [cited by applicant]
US 5451683A · Barrett et al. · 1995 [cited by applicant]
US 5510270A · Fodor et al. · 1996 [cited by applicant]
US 5527681A · Holmes · 1996 [cited by applicant]
US 5665549A · Pinkel et al. · 1997 [cited by applicant]
US 5700637A · Southern · 1997 [cited by applicant]
US 5744305A · Fodor et al. · 1998 [cited by applicant]
US 5776434A · Purewal et al. · 1998 [cited by applicant]
US 5811128A · Tice et al. · 1998 [cited by applicant]
US 5814344A · Tice et al. · 1998 [cited by applicant]
US 5820883A · Tice et al. · 1998 [cited by applicant]
US 5837832A · Chee et al. · 1998 [cited by applicant]
US 5853763A · Tice et al. · 1998 [cited by applicant]
US 5858659A · Sapolsky et al. · 1999 [cited by applicant]
US 5928647A · Rock · 1999 [cited by applicant]
US 5942252A · Tice et al. · 1999 [cited by applicant]
US 5945334A · Besemer et al. · 1999 [cited by applicant]
US 6040138A · Lockhart et al. · 2000 [cited by applicant]
US 6054270A · Southern · 2000 [cited by applicant]
US 6146834A · Schaad et al. · 2000 [cited by applicant]
US 6207392B1 · Weiss et al. · 2001 [cited by applicant]
US 6210878B1 · Pinkel et al. · 2001 [cited by applicant]
US 6251607B1 · Tsen et al. · 2001 [cited by applicant]
US 6300063B1 · Lipshutz et al. · 2001 [cited by applicant]
US 6423499B1 · Song et al. · 2002 [cited by applicant]
US 6429027B1 · Chee et al. · 2002 [cited by applicant]
US 6733977B2 · Besemer et al. · 2004 [cited by applicant]
US 6858394B1 · Chee et al. · 2005 [cited by applicant]
US 6858412B2 · Willis et al. · 2005 [cited by applicant]
US 6892141B1 · Nakae et al. · 2005 [cited by applicant]
US 6916621B2 · Shah · 2005 [cited by applicant]
US 6951761B2 · Star et al. · 2005 [cited by applicant]
US 6969589B2 · Patil et al. · 2005 [cited by applicant]
US 6977148B2 · Dean et al. · 2005 [cited by applicant]
US 7011949B2 · Amorese et al. · 2006 [cited by applicant]
US 7014997B2 · Knoll et al. · 2006 [cited by applicant]
US 7030231B1 · Craik et al. · 2006 [cited by applicant]
US 7034144B2 · Van Dongen et al. · 2006 [cited by applicant]
US 7238484B2 · Pinkel et al. · 2007 [cited by applicant]
US 7364858B2 · Barany et al. · 2008 [cited by applicant]
US 7424368B2 · Huang et al. · 2008 [cited by applicant]
US 7702468B2 · Chinitz et al. · 2010 [cited by applicant]
US 7910353B2 · Shaffer et al. · 2011 [cited by applicant]
US 7957913B2 · Chinitz et al. · 2011 [cited by applicant]
US 7985913B2 · Machell · 2011 [cited by applicant]
US 7998744B2 · Stevenson et al. · 2011 [cited by applicant]
US 8367417B2 · Stevenson et al. · 2013 [cited by applicant]
US 8655599B2 · Chinitz et al. · 2014 [cited by applicant]
US 8862410B2 · Hatchwell et al. · 2014 [cited by applicant]
US 10059997B2 · Hatchwell et al. · 2018 [cited by applicant]
US 10240205B2 · Hatchwell et al. · 2019 [cited by applicant]
US 10240502B2 · De Smet et al. · 2019 [cited by applicant]
US 10544463B2 · Hatchwell et al. · 2020 [cited by applicant]
US 10563264B2 · Hatchwell et al. · 2020 [cited by applicant]
US 10941448B1 · Hatchwell et al. · 2021 [cited by applicant]
US 10961585B2 · Hatchwell et al. · 2021 [cited by applicant]
US 20020012921A1 · Stanton · 2002 [cited by applicant]
US 20020012930A1 · Rothberg et al. · 2002 [cited by applicant]
US 20020112930A1 · Arita et al. · 2002 [cited by applicant]
US 20030023070A1 · Ni et al. · 2003 [cited by applicant]
US 20030049663A1 · Wigler et al. · 2003 [cited by applicant]
US 20030068629A1 · Rothberg et al. · 2003 [cited by applicant]
US 20030082606A1 · Lebo et al. · 2003 [cited by applicant]
US 20030100102A1 · Rothberg et al. · 2003 [cited by applicant]
US 20030148344A1 · Rothberg et al. · 2003 [cited by applicant]
US 20030207295A1 · Gunderson et al. · 2003 [cited by applicant]
US 20030215821A1 · Gunderson et al. · 2003 [cited by applicant]
US 20040018491A1 · Gunderson et al. · 2004 [cited by applicant]
US 20040137473A1 · Wigler et al. · 2004 [cited by applicant]
US 20040157243A1 · Huang et al. · 2004 [cited by applicant]
US 20040197774A1 · Wigler et al. · 2004 [cited by applicant]
US 20040248161A1 · Rothberg et al. · 2004 [cited by applicant]
US 20050032095A1 · Wigler et al. · 2005 [cited by applicant]
US 20050037393A1 · Gunderson et al. · 2005 [cited by applicant]
US 20050037414A1 · Lee et al. · 2005 [cited by applicant]
US 20050079510A1 · Berka et al. · 2005 [cited by applicant]
US 20050100893A1 · Gunderson et al. · 2005 [cited by applicant]
US 20050100932A1 · Lapidus et al. · 2005 [cited by applicant]
US 20050112595A1 · Zhao et al. · 2005 [cited by applicant]
US 20050124022A1 · Srinivasan et al. · 2005 [cited by applicant]
US 20050196799A1 · Wigler et al. · 2005 [cited by applicant]
US 20050233339A1 · Barrett et al. · 2005 [cited by applicant]
US 20050266444A1 · Wigler et al. · 2005 [cited by applicant]
US 20050282196A1 · Costa · 2005 [cited by applicant]
US 20060012784A1 · Ulmer · 2006 [cited by applicant]
US 20060012793A1 · Harris · 2006 [cited by applicant]
US 20060024678A1 · Buzby · 2006 [cited by applicant]
US 20060024711A1 · Lapidus et al. · 2006 [cited by applicant]
US 20060063168A1 · Albertson et al. · 2006 [cited by applicant]
US 20060078909A1 · Srinivasan et al. · 2006 [cited by applicant]
US 20060134674A1 · Huang et al. · 2006 [cited by applicant]
US 20070141577A1 · Moore · 2007 [cited by applicant]
US 20070207141A1 · Lieberburg · 2007 [cited by applicant]
US 20070207481A1 · Wigler et al. · 2007 [cited by applicant]
US 20070259351A1 · Chinitz et al. · 2007 [cited by applicant]
US 20080131887A1 · Stephan et al. · 2008 [cited by applicant]
US 20080305967A1 · Ward et al. · 2008 [cited by applicant]
US 20090026082A1 · Rothberg et al. · 2009 [cited by applicant]
US 20090098547A1 · Ghosh · 2009 [cited by applicant]
US 20090127589A1 · Rothberg et al. · 2009 [cited by applicant]
US 20090170712A1 · Beatty et al. · 2009 [cited by applicant]
US 20090304653A1 · Messier · 2009 [cited by applicant]
US 20100003685A1 · Aasly et al. · 2010 [cited by applicant]
US 20100028931A1 · Eggan et al. · 2010 [cited by applicant]
US 20100035252A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100120046A1 · Brennan et al. · 2010 [cited by applicant]
US 20100137143A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100167286A1 · Reijo et al. · 2010 [cited by applicant]
US 20100188073A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100197507A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100227768A1 · Wigler et al. · 2010 [cited by applicant]
US 20100248236A1 · Chinitz et al. · 2010 [cited by applicant]
US 20110021366A1 · Chinitz et al. · 2011 [cited by applicant]
US 20110111014A1 · Langston · 2011 [cited by applicant]
US 20110130337A1 · Eriksson et al. · 2011 [cited by applicant]
US 20110264376A1 · Chinitz et al. · 2011 [cited by applicant]
US 20110311512A1 · Hakonarson et al. · 2011 [cited by applicant]
US 20120059594A1 · Hatchwell et al. · 2012 [cited by applicant]
US 20120100995A1 · Scherer et al. · 2012 [cited by applicant]
US 20130247249A1 · Singh et al. · 2013 [cited by applicant]
US 20130305410A1 · Bent et al. · 2013 [cited by applicant]
US 20130316911A1 · Scherer · 2013 [cited by applicant]
US 20140088882A1 · Chinitz et al. · 2014 [cited by applicant]
US 20140155271A1 · Hatchwell et al. · 2014 [cited by applicant]
US 20140161721A1 · Hatchwell et al. · 2014 [cited by applicant]
US 20140162894A1 · Hatchwell et al. · 2014 [cited by applicant]
US 20140162933A1 · Hatchwell et al. · 2014 [cited by applicant]
US 20140208449A1 · Malek · 2014 [cited by applicant]
US 20150051086A1 · Hatchwell et al. · 2015 [cited by applicant]
US 20150132295A1 · Hatchwell et al. · 2015 [cited by applicant]
US 20160019336A1 · Chinitz et al. · 2016 [cited by applicant]
US 20170016919A1 · Plavina et al. · 2017 [cited by applicant]
US 20170253930A1 · Hatchwell et al. · 2017 [cited by applicant]
US 20180073076A1 · Hatchwell et al. · 2018 [cited by applicant]
US 20180223360A1 · Hatchwell et al. · 2018 [cited by applicant]
US 20190071726A1 · Hatchwell et al. · 2019 [cited by applicant]
US 20210381052A1 · Hatchwell et al. · 2021 [cited by applicant]
US 20230265519A1 · Hatchwell et al. · 2023 [cited by applicant]
US 20230265520A1 · Hatchwell et al. · 2023 [cited by applicant]
CN 1733937A · 2006 [cited by applicant]
CN 101148684A · 2008 [cited by applicant]
CN 101403008A · 2009 [cited by applicant]
CN 103436606A · 2013 [cited by applicant]
EP 0373203A1 · 1990 [cited by applicant]
EP 0373203B1 · 1994 [cited by applicant]
EP 0619321A1 · 1994 [cited by applicant]
KR 20090080105A · 2009 [cited by applicant]
KR 20110114664A · 2011 [cited by applicant]
WO WO9002809A1 · 1990 [cited by applicant]
WO WO9106667A1 · 1991 [cited by applicant]
WO WO9117271A1 · 1991 [cited by applicant]
WO WO9201047A1 · 1992 [cited by applicant]
WO WO9209690A2 · 1992 [cited by applicant]
WO WO9210092A1 · 1992 [cited by applicant]
WO WO9215679A1 · 1992 [cited by applicant]
WO WO9218619A1 · 1992 [cited by applicant]
WO WO9220791A1 · 1992 [cited by applicant]
WO WO9209690A3 · 1992 [cited by applicant]
WO WO9301288A1 · 1993 [cited by applicant]
WO WO9322684A1 · 1993 [cited by applicant]
WO WO9511995A1 · 1995 [cited by applicant]
WO WO9820019A1 · 1998 [cited by applicant]
WO WO02099129A2 · 2002 [cited by applicant]
WO WO03048318A2 · 2003 [cited by applicant]
WO WO2004018633A2 · 2004 [cited by applicant]
WO WO2004044225A2 · 2004 [cited by applicant]
WO WO2004075010A2 · 2004 [cited by applicant]
WO WO2005042763A2 · 2005 [cited by applicant]
WO WO2005068664A2 · 2005 [cited by applicant]
WO WO2005108997A1 · 2005 [cited by applicant]
WO WO2004044225A3 · 2006 [cited by applicant]
WO WO2006050475A2 · 2006 [cited by applicant]
WO WO2006091254A1 · 2006 [cited by applicant]
WO WO2006116873A1 · 2006 [cited by applicant]
WO WO2007070640A2 · 2007 [cited by applicant]
WO WO2007070640A3 · 2007 [cited by applicant]
WO WO2007129000A2 · 2007 [cited by applicant]
WO WO2007131135A2 · 2007 [cited by applicant]
WO WO2008016374A2 · 2008 [cited by applicant]
WO WO2007129000A3 · 2008 [cited by applicant]
WO WO2007131135A3 · 2008 [cited by applicant]
WO WO2009038684A1 · 2009 [cited by applicant]
WO WO2009043178A1 · 2009 [cited by applicant]
WO WO2009073764A1 · 2009 [cited by applicant]
WO WO2010036353A2 · 2010 [cited by applicant]
WO WO2010056897A1 · 2010 [cited by applicant]
WO WO2010124101A2 · 2010 [cited by applicant]
WO WO2011012672A1 · 2011 [cited by applicant]
WO WO2011035012A2 · 2011 [cited by applicant]
WO WO2011112961A1 · 2011 [cited by applicant]
WO WO2012023519A1 · 2012 [cited by applicant]
WO WO2012027491A1 · 2012 [cited by applicant]
WO WO2012047234A1 · 2012 [cited by applicant]
WO WO2013067451A2 · 2013 [cited by applicant]
WO WO2013071119A2 · 2013 [cited by applicant]
WO WO2014043519A1 · 2014 [cited by applicant]
WO WO2015131078A1 · 2015 [cited by applicant]
WO WO2018158632A2 · 2018 [cited by applicant]
WO WO2020033700A1 · 2020 [cited by applicant]
Ross et al. Pharmacogenomics and its implications for autoimmune disease. Journal of Autoimmunity (2007) 28: 122-128. [cited by examiner]
Belot et al. PRKDCmutations associated with immunodeficiency, granuloma and aire-dependent autoimmunity. Pediatric Rheumatology 2014, 12(Suppl 1):p. 42. [cited by examiner]
Mooney S.D. Progress towards the integration of pharmacogenomics in practice. Hum Genet. May 2015; 134(5):459-65. [cited by examiner]
Del Poeta et al. The Addition of Rituximab to Fludarabine Improves Clinical Outcome in Untreated Patients with ZAP-70-Negative Chronic Lymphocytic Leukemia. Cancer 2005;104: 2743-52. [cited by examiner]
Corcoran et al. ZAP-70 methylation status is associated with ZAP-70 expression status in chronic lymphocytic leukemia. Haematologica 2005; 90:1078-1088. [cited by examiner]
Pastore et al. Integration of gene mutations in risk prognostication for patients receiving fi rst-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation… [cited by examiner]
Abravaya, et al. Detection of point mutations with a modified ligase chain reaction (Gap-LCR). Nucleic Acids Research. 1995;23(4):675-682. [cited by applicant]
Agami, R. RNAi and related mechanisms and their potential use for therapy. Curr Opin Chem Biol. Dec. 2002;6(6):829-34. [cited by applicant]
Agarwal et al., Novelty in the target landscape of the pharmaceutical. Nat. Rev. Drug Discovery 12(8):575-6 (2013). [cited by applicant]
Aitman, et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature. Feb. 16, 2006;439(7078): 851-5. [cited by applicant]
Albertson, et al. Profiling breast cancer by array CGH. Breast Cancer Res Treat. Apr. 2003;78(3):289-98. [cited by applicant]
Alexander Zimprich, et al., A mutation in, encoding a subunit of the retromer complex, causes late-onset parkinson disease, American journal of human genetics, American society of human genetics. Jun. 2011; 89(1):168-17… [cited by applicant]
Altschul, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. Sep. 1, 1997;25(17):3389-402. [cited by applicant]
Amarzguioui, et al. Approaches for chemically synthesized siRNA and vector-mediated RNAi. FEBS Lett. Oct. 31, 2005;579(26):5974-81. Epub Sep. 20, 2005. [cited by applicant]
Ansel, Howard C, et al. Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia, PA: Lippincott-Williams & Wilkins, 1999. Print. [cited by applicant]
Antoniol, et al., Immunological markers for PML prediction in MS patients treated with natalizumab. Frontiers in Immunology. Jan. 2015; 5(668): pp. 1-9. [cited by applicant]
Arakawa, et al. Advances in characterization of neuroprotective peptide, humanin. Curr Med Chem. 2011;18(36):5554-63. [cited by applicant]
Ausubel (Ed.), Current Protocols in Molecular Biology (2007 John Wiley & Sons, NY). [cited by applicant]
Ausubel, et al. Current Protocols in Molecular Biology. John Wiley & Sons, New York, 1999. [cited by applicant]
Bailey, et al. Analysis of Segmental Duplications and Genome Assembly in the Mouse. Genome Res. 2004; 14:789-801. [cited by applicant]
Bakkaloglu, et al. Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am J Hum Genet. Jan. 2008;82(1):165-73. [cited by applicant]
Bangham et al. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol. 1965;13:238-252. [cited by applicant]
Bedell, et al. In vivo genome editing using a high-efficiency TALEN. Nature. 491.7422 (2012): 114-118. [cited by applicant]
Benjamini, Y and Hochberg Y, “Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing”, Journal of the Royal Statistical Society. Series B (Methodological, vol. 57, No. 1, (1995), 289… [cited by applicant]
Bennett, C. Efficiency of antisense oligonucleotide drug discovery. Antisense Nucleic Acid Drug Dev. Jun. 2002;12(3):215-24. [cited by applicant]
Berkel, et al. Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. Nat Genet. Jun. 2010;42(6):489-91. Epub May 16, 2010. [cited by applicant]
Bernard, et al. Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumours. Embo J. 1983;2(12):2375-83. [cited by applicant]
Bernstein, et al. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. Jan. 18, 2001;409(6818):363-6. [cited by applicant]
Betancur, et al. The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders. Trends Neurosci. Jul. 2009;32(7):402-12. doi: 10.1016/j.tins.2009.04.003. Epub Jun. 21, 2009. [cited by applicant]
Bier, et al. DNA microarrays. Adv Biochem Eng Biotechnol. 2008;109:433-53. [cited by applicant]
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. Mar. 2001;69(3):89-95. [cited by applicant]
Bochukova, et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature. Feb. 4, 2010;463(7281):666-70. Epub Dec. 6, 2009. [cited by applicant]
Bodmer, et al. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet. Jun. 2008;40(6):695-701. [cited by applicant]
Bodzioch, et al. Evidence for potential functionality of nuclearly-encoded humanin isoforms. Genomics. Oct. 2009;94(4):247-56. Epub May 27, 2009. [cited by applicant]
Bosher, et al. RNA interference: genetic wand and genetic watchdog. Nat Cell Biol. Feb. 2000;2(2):E31-6. [cited by applicant]
Bowen, et al., HIV-associated opportunistic CNS infections: pathophysiology, diagnosis and treatment.Nat Rev Neurol. Oct. 27, 2016;12(11):662-674. doi: 10.1038/nrneurol.2016.149. [cited by applicant]
Bremer, et al. Copy number variation characteristics in subpopulations of patients with autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet. Mar. 2011;156(2):115-24. doi: 10.1002/ajmg.b.31142. Epub Dec. 8, … [cited by applicant]
Brummelkamp, et al. A system for stable expression of short interfering RNAs in mammalian cells. Science. Apr. 19, 2002;296(5567):550-3. Epub Mar. 21, 2002. [cited by applicant]
Bult, et al. The Mouse genome Database (MGD): mouse biology and model systems. Nucleic Acids Research. 2008; 36 Database Issue: D724-D728. doi:10.1093/nar/gkm961. [cited by applicant]
Bych, et al., The iron-sulphur protein Ind1 is required for effective complex I assembly. The EMBO Journal (2008) 27, 1736-174. [cited by applicant]
Calabrese, et al., Sorting out the risks in progressive multifocal leukoencephalopathy. Nat Rev Rheumatol. Feb. 2015;11(2):119-23. doi: 10.1038/nrrheum.2014.167. Epub Oct. 14, 2014. [cited by applicant]
Calabrese, et al., Sorting out the risks in progressive multifocal leukoencephalopathy. Nat. Rev. Rheumatol. advance online publication Oct. 14, 2014; pp. 1-5. [cited by applicant]
Calvo, et al. High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Nat Genet. Oct. 2010;42(10):851-8. Epub Sep. 5, 2010. [cited by applicant]
Carles Vilario-Guell, et al., Mutations in Parkinson disease, American journal of human genetics, american society of human genetics. Jun. 2011; 89(1):162-167. [cited by applicant]
Chahin, et al., A risk classification for immunosuppressive treatment-associated progressive multifocal leukoencephalopathy. J. Neurovirol. (2015) 21:623-631 DOI 10.1007/s13365-014-0303-1. [cited by applicant]
Chan, et al., Identification of key residues essential for the structural fold and receptor selectivity within the A-chain of human gene-2 (H2) relaxin. The Journal of Biological Chemistry vol. 287, No. 49, pp. 41152-41… [cited by applicant]
Chavanpatil et al. Novel sustained release, swellable and bioadhesive gastroretentive drug delivery system for olfoxacin. International Journal of Pharmaceutics. 2006;316(1-2):86-92. [cited by applicant]
Chen, et al., Correlation between SMN2 copies and the phenotype of spinal muscular atrophy. Chin J Neurol, Nov. 30, 2005; 38(11):673-676. [cited by applicant]
Chen, et al., Identification of small molecule agonists of human relaxin family receptor 1 (RXFP1) by utilizing a homogenous cell-based cAMP assay. [cited by applicant]
Chen, et al. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet. Feb. 2007;8(2):93-103. [cited by applicant]
Chen, H. Clinical development of antisense oligonucleotides as anti-cancer therapeutics. Methods Mol Med. 2003;75:621-36. [cited by applicant]
Chi, et al. Genomewide view of gene silencing by small interfering RNAs. Proc Natl Acad Sci U S A. May 27, 2003;100(11):6343-6. Epub May 2, 2003. [cited by applicant]
Ching, et al., Integrated analysis of copy number and loss of heterozygosity in primary breast carcinomas using high-density SNP array. International journal of oncology, 2011; 39:621-633. [cited by applicant]
Chinn, et al., Severe combined immunodeficiency disorders. Immunol Allergy Clin N Am 35 (2015) 671-694. [cited by applicant]
CNV: 14q23.3 summary output from https://gene.sfari.org/database/cnv/14q23.3 Nov. 30, 2017, pp. 1-3. (year: 2017). [cited by applicant]
Cohen, Jonathan C. “Emerging LDL therapies: Using human genetics to discover new therapeutic targets for plasma lipids.” Journal of clinical lipidology vol. 7,3 Suppl (2013): S1-5. doi:10.1016/j.jacl.2013.03.005. [cited by applicant]
Colin et al.,Drug-induced progressive multifocal leukoencephalopathy: a case/noncase study in the French pharmacovigilance database. Fundam Clin Pharmacol. Oct. 13, 2016: pp. 1-8. [cited by applicant]
Conrad, et al. Origins and functional impact of copy number variation in the human genome. Nature. Apr. 1, 2010;464(7289):704-12. Epub Oct. 7, 2009. [cited by applicant]
Copy Number Variants summary for 12q23.3-q24.13 from gene.sfari.org/database/cnv/, two pages printed on Dec. 2, 2017. (Year:2017). [cited by applicant]
Corti, et al. What Genetics tells us about the causes and mechanisms of parkinson's disease. Physiological reviews.Oct. 2011; 91(4): 1161-1218. [cited by applicant]
Coskun, et al., A Mitochondrial Etiology of Alzheimer and Parkinson Disease. Biochim Biophys Acta. May 2012 ; 1820(5): 553-564. doi:10.1016/j.bbagen.2011.08.008. [cited by applicant]
Crespi, et al. Association testing of copy number variants in schizophrenia and autism spectrum disorders. J Neurodev Disord. May 30, 2012;4(1):15. doi: 10.1186/1866-1955-4-15. [cited by applicant]
Cronin, et al. Analysis of genome-wide copy number variation in Irish and Dutch ALS populations. Hum Mol Genet. Nov. 1, 2008;17(21):3392-8. Epub Aug. 7, 2008. [cited by applicant]
D'Amico, et al., Treatment-related progressive multifocal leukoencephalopathy in multiple sclerosis: A comprehensive review of current evidence and future needs. Drug Saf. 2016;39:1163-1174. [cited by applicant]
Daruwala, et al. A versatile statistical analysis algorithm to detect genome copy number variation. Proc Natl Acad Sci U S A. Nov. 16, 2004;101(46):16292-7. Epub Nov. 8, 2004. [cited by applicant]
Day-Williams, et al., Whole Genome Sequencing Reveals a Chromosome 9p Deletion Causing DOCK8 Deficiency in an Adult Diagnosed with Hyper IgE Syndrome Who Developed Progressive Multifocal Leukoencephalopathy. J Clin Immu… [cited by applicant]
De Krom, et al. A common variant in DRD3 receptor is associated with autism spectrum disorder. Biol Psychiatry. Apr. 1, 2009;65(7):625-30. doi: 10.1016/j.biopsych.2008.09.035. Epub Dec. 5, 2008. [cited by applicant]
Desmet, et al., Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Research, 2009, vol. 37, No. 9 e67. [cited by applicant]
Dias, et al. Antisense oligonucleotides: basic concepts and mechanisms. Mol Cancer Ther. Mar. 2002;1(5):347-55. [cited by applicant]
Dibbens, et al. Familial and sporadic 15q13.3 microdeletions in Idiopathic Generalized Epilepsy: Precedent for Disorders with Complex Inheritance. Hum Mol Genet. Jul. 10, 2009. [Epub ahead of print]. [cited by applicant]
Dijkhuizen, et al. FISH and array-CGH analysis of a complex chromosome 3 aberration suggests that loss of CNTN4 and CRBN contributes to mental retardation in 3pter deletions. Am J Med Genet A. Nov. 15, 2006;140(22):2482… [cited by applicant]
Durandy, et al., Primary antibody deficiencies.Nature Reviews: Immunology. Jul. 2013; 13: pp. 519-533. [cited by applicant]
Durandy, et al., Supplementary Information Table 1. Nature Reviews: Immunology. Jul. 2013; 1 page. [cited by applicant]
Durandy, et al., Supplementary Information Table 2. Nature Reviews: Immunology. Jul. 2013; 1 page. [cited by applicant]
Elbashir, et al. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. Jan. 15, 2001;15(2):188-200. [cited by applicant]
ENCODE project consortium, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. Sep. 6, 2012;489(7414):57-74. doi: 10.1038/nature11247. [cited by applicant]
Estivill, et al. Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies. PLoS Genet. Oct. 2007;3(10):1787-99. [cited by applicant]
European search report and opinion dated Feb. 11, 2015 for EP Application No. 12839712.2. [cited by applicant]
European search report and opinion dated Feb. 27, 2015 for EP Application No. 11814903.8. [cited by applicant]
European search report and opinion dated Jun. 9, 2015 for EP Application No. 12846660.4. [cited by applicant]
European search report dated Apr. 11, 2016 for EP Application No. 13840476.9. [cited by applicant]
European Search Report dated Jun. 9, 2015 for European Patent Application No. 14192587.5. [cited by applicant]
European Search Report dated Sep. 2, 2016 for European Application No. 13836501.0. [cited by applicant]
European search report dated Oct. 14, 2015 for EP Application No. 13746934.2. [cited by applicant]
ExAC Browser (BETA) | Exome aggregation consortium. Available at http://exac.broadinstitute.org/. Accessed on Jun. 8, 2017. [cited by applicant]
Fan, et al. Illumina universal bead arrays. Methods Enzymol. 2006;410:57-73. [cited by applicant]
Fassbender, A., et al., “Biomarkers of endometriosis”, Fertility and Sterility, 99(4), (Mar. 15, 2013), 1135-1145. [cited by applicant]
Fassone, et al., Complex I deficiency: clinical features, biochemistry and molecular genetics. J Med Genet 2012;49:578-590. doi:10.1136/jmedgenet-2012-101159. [cited by applicant]
Fernandez, et al. Disruption of contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome. Addendum. Am J Hum Genet. Jun. 2008;82(6):1385. [cited by applicant]
Fernandez, et al. Disruption of contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome. Am J Hum Genet. Jun. 2004;74(6):1286-93. [cited by applicant]
Fernandez, et al. Gene Discovery in Developmental Neuropsychiatric Disorders: Clues from Chromosomal Rearrangements. Yale Journal of Biology and Medicine, vol. 78 (2005), pp. 95-130. on p. 103. Abstract. [cited by applicant]
Fire et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391 (1998): 806-811. [cited by applicant]
Flannick, et al., Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nat Genet. Author manuscript; available in PMC Jun. 10, 2014. [cited by applicant]
Freeman, et al. Copy number variation: new insights in genome diversity. Genome Res. Aug. 2006;16(8):949-61. Epub Jun. 29, 2006. [cited by applicant]
Freshney, R. I., Culture of Animal Cells: A Manual of Basic Technique. Wiley-Liss; 5th edition (2005). [cited by applicant]
Gagne, et al. Natalizumab-related PML 2 weeks after negative anti-jcv antibody assay. Neurology. 2016; 86:484-486. [cited by applicant]
Gagneux, et al. Genetic differences between humans and great apes. Mol Phylogenet Evol. Jan. 2001;18(1):2-13. [cited by applicant]
Galfre et al. Antibodies to major histocompatibility antigens produced by hybrid cell lines. Nature 266:550-552 (1977). [cited by applicant]
Gatto, et al. Genetic controls balancing excitatory and inhibitory synaptogenesis in neurodevelopmental disorder models. Frontiers in Synaptic Neuroscience. Jun. 2010; 2(4):1-19. [cited by applicant]
Gelb, et al., Diagnostic Criteria for Parkinson Disease. Arch Neurol. 1999;56(1):33-39. doi:10.1001/archneur.56.1.33. [cited by applicant]
Gelmann, et al. Identification of reciprocal translocation sites within the c-myc oncogene and immunoglobulin mu locus in a Burkitt lymphoma. Nature. Dec. 22, 1983-Jan. 4, 1984;306(5945):799-803. [cited by applicant]
GeneCards output for ATXN2 gene, from www.genecards.ord, pritned on May 20, 2015, pp. 1-13. [cited by applicant]
GeneCards output for DIAPH2 gene, from www.genecards.ord, printed on Jun. 11, 2015, pp. 1-11. [cited by applicant]
Gheuens, et al., Role of human leukocyte antigen class I alleles in progressive multifocal leukoencephalopathy. Journal of NeuroVirology, 2010; 1-7. [cited by applicant]
Gilling, et al. Breakpoint cloning and haplotype analysis indicate a single origin of the common Inv(10)(p11.2q21.2) mutation among northern Europeans. Am. J. Hum. Genet. 2006; 78(5):878-83. [cited by applicant]
Glessner, et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. May 28, 2009;459(7246):569-73. Epub Apr. 28, 2009. [cited by applicant]
Gokcumen, et al., Copy number variants (CNVs) in primate species using array-based comparative genomic hybridization. Methods 2009;49:18-25. [cited by applicant]
Goldstein. Common genetic variation and human traits. N Engl J Med. Apr. 23, 2009;360(17):1696-8. Epub Apr. 15, 2009. [cited by applicant]
GPHN Gene—GeneCards output. pp. 1-14. Printed on Jul. 2, 2015 from www.genecards.org. [cited by applicant]
Gregoriadis. Chapter 14: Liposomes. Drug Carriers in Biology and Medicine (57 pgs) (Academic Press, 1979). [cited by applicant]
Gribble, et al. The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes. J. Med. Genet. 2005; 42:8-16. [cited by applicant]
Griffiths, et al. Human anti-self antibodies with high specificity from phage display libraries. Embo J. Feb. 1993;12(2):725-34. [cited by applicant]
Griswold, et al. A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis. Autism Res. Jun. 2011;4(3):221-7. doi: 10.1002/aur.186. Epub Feb. 28, 2011. [cited by applicant]
Grskovic, et al. Induced pluripotent stem cells—opportunities for disease modelling and drug discovery. Nat Rev Drug Discov. Nov. 11, 2011;10(12):915-29. doi: 10.1038/nrd3577. [cited by applicant]
Guatelli et al. Isothermal, in vitro amplification of nucleic acids by a multienzyme reaction modeled after retroviral replication. PNAS USA 87(5):1874-1878 (1990). [cited by applicant]
Guilmatre, et al. Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation. Arch Gen Psychiatry. Sep. 2009;66(9):947-56. doi: 10.100… [cited by applicant]
Harada, et al. Subtelomere specific microarray based comparative genomic hybridisation: a rapid detection system for cryptic rearrangements in idiopathic mental retardation. J. Med. Genet. 2004; 41:130-136. [cited by applicant]
Hastings PJ, Ira G, Lupski Jr, (2009) “A Microhomology-Mediated Break-Induced Replication Model for the Origin of Human Copy Number Variation” PLOS Genetics 5(1): e1000327. https://doi.org/10.1371/journal.pgen. 1000327. [cited by applicant]
Hatchwell, E. Is there a (host) genetic predisposition to progressive multifocal leukoencephalopathy? Frontiers in Immunology. May 2015; 6(216): pp. 1-5. [cited by applicant]
Hatchwell, et al. High rate of submicroscopic human genomic polymorphism detected by array CGH. Proceedings of XIX International Genetics Congress. Melbourne, Australia. Abstracts and Posters. 2003; 1.E.0092. pp. 168 an… [cited by applicant]
Hattersley, et al. What makes a good genetic association study? Lancet. Oct. 8, 2005;366(9493):1315-23. [cited by applicant]
Hay et al. Bacteriophage cloning and [cited by applicant]
He, et al. Analysis of de novo copy number variations in a family affected with autism spectrum disorders using high-resolution array-based comparative genomic hybridization. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. Jun. 20… [cited by applicant]
Hegele, et al. “SNP Judgments and Freedom of Association”, Arterioscler. Thromb. Vase. Biol. 22 (2002): 1058-1061. [cited by applicant]
Helbig, et al. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet. Feb. 2009;41(2):160-2. Epub Jan. 11, 2009. [cited by applicant]
Henchcliffe, et al., Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat. Clin. Pract. Neurology, 2005;4(11):600-609. [cited by applicant]
Hicks et al., “Novel patterns of genome rearrangement and their association with survival in breast cancer,” Genome Res 16:1465-1479, 2006. [cited by applicant]
Hirschhorn, et al. A comprehensive review of genetic association studies. Genet Med. Mar.-Apr. 2002;4(2):45-61. [cited by applicant]
Hoffman, et al. Pharmacokinetic and pharmacodynamic aspects of gastroretentive dosage forms. Int J Pharm. Jun. 11, 2004;277(1-2):141-53. [cited by applicant]
Hoheisel, J. Microarray technology: beyond transcript profiling and genotype analysis. Nat Rev Genet. Mar. 2006;7(3):200-10. [cited by applicant]
Huang, et al. Whole genome DNA copy number changes identified by high density oligonucleotide arrays. Hum Genomics. May 2004;1(4):287-99. [cited by applicant]
Hudson, et al., Two-stage association study and meta-analysis of mitochondrial DNA variants in Parkinson disease. American Academy of Neurology. 2013;80: 2042-2048. [cited by applicant]
Human Genome CGH Microarrays—Details & Specifications, six printed pages from www.agilent.com, printed on May 20, 2015. [cited by applicant]
Hunt et al., Silent (Synonymous) SNPs: Should We Care About Them?, Methods in Molecular Biology. 2009; 578: 23-39. [cited by applicant]
Hunter, C. Genetics: a touch of elegance with RNAi. Curr Biol. Jun. 17, 1999;9(12):R440-2. [cited by applicant]
Huse, et al. Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda. Science. Dec. 8, 1989;246(4935):1275-81. [cited by applicant]
Hutvagner, et al. A microRNA in a multiple-turnover RNAi enzyme complex. Science. Sep. 20, 2002;297(5589):2056-60. Epub Aug. 1, 2002. [cited by applicant]
Iafrate, et al. Detection of large-scale variation in the human genome. Nat Genet. Sep. 2004;36(9):949-51. Epub Aug. 1, 2004. [cited by applicant]
International Preliminary Report on Patentability dated Mar. 16, 2017 for International Application No. PCT/US2015/000093. [cited by applicant]
International search report and written opinion dated Jan. 15, 2014 for PCT/US2013/062346. [cited by applicant]
International search report and written opinion dated Jan. 20, 2014 for PCT/US2013/059739. [cited by applicant]
International search report and written opinion dated Apr. 9, 2012 for PCT/US2011/001363. [cited by applicant]
International search report and written opinion dated Apr. 22, 2013 for PCT/US2012/063451. [cited by applicant]
International search report and written opinion dated Jun. 21, 2013 for PCT/IB2012/002498. [cited by applicant]
International search report and written opinion dated Jul. 3, 2013 for PCT/IB2012/002498. [cited by applicant]
International Search Report dated Sep. 11, 2008 for PCT Application No. US2007/68183. [cited by applicant]
“Introducing Genome-Wide SNP Array 6.0 Pure performance & Genetic Power.” May 21, 2008. Available at http://www.genehk.com/news/doc/Genomics_genome-wide Human SNP Array 6.0.pdf. Accessed on Dec. 22, 2016. [cited by applicant]
Itsara, et al. Population analysis of large copy number variants and hotspots of human genetic disease. Am J Hum Genet. Feb. 2009;84(2):148-61. Epub Jan. 22, 2009. [cited by applicant]
Jelcic, et al., Broadly neutralizing human monoclonal JC polyomavirus VP1-specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy. Science Translational Medicine Sep. 23, 2015: vol. … [cited by applicant]
Jonsson, et al., A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature. Aug. 2, 2012;488(7409):96-9. doi: 10.1038/nature11283. [cited by applicant]
Jorde, et al. Population genomics: a bridge from evolutionary history to genetic medicine. Hum. Mol. Genet. 2001; 10(20):2199-2207. [cited by applicant]
Juppner. Functional properties of the PTH/PTHrP receptor. Bone. Aug. 1995; 17(2):Supplement 39S-42S. [cited by applicant]
Kalamatas, et al. Evaluation of serum JCV-Test and Index values in Natalizumab-treated individuals. American Neurological Association. 2015; S63:S507. [cited by applicant]
Kallioniemi, et al. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. Oct. 30, 1992;258(5083):818-21. [cited by applicant]
Kaminsky, et al., An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genetics in medicine, 2011; 13(9): 777-784. [cited by applicant]
Karlin, et al. Applications and statistics for multiple high-scoring segments in molecular sequences. Proc Natl Acad Sci U S A. Jun. 15, 1993;90(12):5873-7. [cited by applicant]
Ketting, et al. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. Oct. 15, 2001;15(20):2654-9. [cited by applicant]
Kevelam, et al., NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern. Neurology. Apr. 23, 2013; 80(17): 1577-1583. [cited by applicant]
Kim, et al. Strategies for silencing human disease using RNA interference. Nat Rev Genet. Mar. 2007;8(3):173-84. [cited by applicant]
Kim, et al., Synthetic dsRNA dicer substrates enhance RNAi potency and efficacy. Nature biotechnology. 2005; 23(2): 222-226. [cited by applicant]
Kimchi-Sarfaty, et al. A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science. Jan. 26, 2007;315(5811):525-8. Epub Dec. 21, 2006. [cited by applicant]
Klausner, et al. Novel gastroretentive dosage forms: evaluation of gastroretentivity and its effect on levodopa absorption in humans. Pharm Res. Sep. 2003;20(9):1466-73. [cited by applicant]
Klein, et al. Comparative genomic hybridization, loss of heterozygosity, and DNA sequence analysis of single cells. Proc Natl Acad Sci U S A. Apr. 13, 1999;96(8):4494-9. [cited by applicant]
Knight, et al. A cytogenetic abnormality and rare coding variants identify ABCA13 as a candidate gene in schizophrenia, bipolar disorder, and depression. Am J Hum Genet. Dec. 2009;85(6):833-46. doi: 10.1016/j.ajhg.2009.… [cited by applicant]
Kohler, et al. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. Aug. 7, 1975;256(5517):495-7. [cited by applicant]
Kozbor, et al. The production of monoclonal antibodies from human lymphocytes. Immunol. Today. 1983; 4(3): 72-79. [cited by applicant]
Kraus, et al. Detection and isolation of novel protein-tyrosine kinase genes employing reduced stringency hybridization. Methods Enzymol. 1991;200:546-56. [cited by applicant]
Kumar, et al. A de novo 1p34.2 microdeletion identifies the synaptic vesicle gene RIMS3 as a novel candidate for autism. J Med Genet. Jun. 21, 2009. [Epub ahead of print]. [cited by applicant]
Kumar, et al. Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet. Feb. 15, 2008;17(4):628-38. Epub Dec. 21, 2007. [cited by applicant]
Kumar Kishore, et al., Genetics of parkinson disease and other movement disorders, Current opinion in neurology, Aug. 2012; 25(4): 466-474. [cited by applicant]
Kurreck, J. Antisense technologies. Improvement through novel chemical modifications. Eur J Biochem. Apr. 2003;270(8):1628-44. [cited by applicant]
Kutyavin, et al. A novel endonuclease IV post-PCR genotyping system. Nucleic Acids Res. 2006;34(19):e128. Epub Sep. 29, 2006. [cited by applicant]
Kwoh et al. Transcription-based amplification system and detection of amplified human immunodeficiency virus type 1 with a bead-based sandwich hybridization format. PNAS USA 86(4):1173-1177 (1989). [cited by applicant]
Lakowicz, J. (1983) Principles of fluorescence spectroscopy. Plenum Press, New York. [cited by applicant]
Landegren, et al. A ligase-mediated gene detection technique. Science. Aug. 26, 1988;241(4869):1077-80. [cited by applicant]
Langston et al. Multisystem Lewy body disease and the other parkinsonian disorders. Nature Genetics 47(12):1378-1385 (2015). [cited by applicant]
Latchman, et al. Viral vectors for gene therapy in Parkinson's disease. Rev Neurosci. 2001;12(1):69-78. [cited by applicant]
Lavery, et al. Antisense and RNAi: powerful tools in drug target discovery and validation. Curr Opin Drug Discov Devel. Jul. 2003;6(4):561-9. [cited by applicant]
Lerner. How to make a hybridoma. Yale J Biol Med. 54(5):387-402 (1981). [cited by applicant]
Liu, Qing-Rong, et al. “Addiction molecular genetics: 639,401 SNP whole genome association identifies many “cell adhesion” genes.”American Journal of Medical Genetics Part B: Neuropsychiatric Genetics val. 141 (2006): p… [cited by applicant]
Lizardi, et al. Exponential amplification of recombinant-RNA hybridization probes. Nature Biotechnology 6.10 (1988): 1197-1202. [cited by applicant]
Lucentini, J. Gene Association Studies Typically Wrong. The Scientist, 18(24):20 (2004). [cited by applicant]