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WO 2010/106788 Al
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1. lt PGAM4 WO 2010 106788 10 PCT JP2010 001850 023 0024 0025 mS HCA MR MA MH BOANSOUR BR EAEE HR PGAM4 PG AM 4 DNA mRNA PGAM4 PGAM4 5 PGAM4
2. PGAM4 yamichev Lyamichey WO 2010 106788 17 PCT JP2010 001850 0044 V et al Nat biotechnol 17 292 1999 2 3 5 2 L AD 3 a
3. PGAM 4 PGAM4 PGA M 4 S ICSI Testicu lar sperm extraction Intracytoplas mic sperm injection
4. 2 FOB 2 2 AO 3 0061 3 Position eer Number of SNP Pyalne Nucleotide Amino acid Infertile Proven fertile 75 Trp25 G G 95 5 238 98 8 T 25Cys C C a 4 5 3 1 2 0 05 123 Gly41 C C 380 99 7 249 99 6 0750 T T 1 0 3 1 0 4 138 Arg46 A A 380 99 7 249 100 0764 C C 1 0 3 0 0 539 Arg 180 G G 382 99 7 251 100 0 418 Arg180His A A 1 0 3 0 0 062 PGAM4
5. PGAM4 PGAM4 DNA PCR PGAM4 DNA ABI PRISM 3 0 Genetic Analyzer Appl ied Biosystem SInc DNA
6. PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 75 lt 539
7. P GAM4 PG AM 4 PGAM4 PGAM4 PGAM4 CT PGAM4 PGAM4 7 5 39 539
8. PGAM4 539 18 0 WO 2010 106788 9 PCT JP2010 001850 0 0 0021 022 PGAM4 7 5 53 lt
9. P GA M4 0 O 0 PGAM4 DNA 0 00 INSO 0 7 0 lt 0 5 0 0O 3 0 WO 2010 106788 13 PCT JP2010 001850 0 0 0081 082
10. PGAM4 WO 2010 106788 8 PCT JP2010 001850 0015 ool 6 0017 0018 0019 PGAM4 P GAM4 POGAM4 PGAM4 4 l
11. PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 JI SA nzyme lin
12. Fr eund I SA 2 1I gG PGAM4 PGAM4 PGAM 4
13. PGAM4 PGAM4 7 5 3 8 539 ORRORE PGAM4 PGAM4 HR Jn 171 WO 2010 106788 PCT JP2010 001850 1 INTERNATIONAL SEARCH REPORT International application No PCT JP2010 001850 A CLASSIFICATION OF SUBJECT MATTER C12N1 5 09 2006 01 C07K1 6 4 0 2006 01 i CI2N9 90 2006 01 i 2006 01 i C22027 68 2006 01 i GOIN33 53 2006 01 i C1201 533 According to International Patent Classification IPC or to both national classification and IPC B FIELDS SEARCHED Minimum documentation searched classification system followed by classification symbols C12N15 09 CO7K16 40 C12N9 90 C12O
14. 0 5 lt S8 2 0 PGAM4 WO 2010 106788 16 PCT JP2010 001850 0041 0042 0043 PGAM4 6 7 PG A M 4 GenBank
15. 1 096 a 2 3 3 a 3 b Z 3 4 5 5 a 5 b 5 c WO 2010 106788 28 PCT JP2010 001850 1 2 3 4 5 6 PGAM4 PGAM4 7 5 13 8
16. OIigo N ational Bioscience Inc RUG N TYX Y Appl ied Biosystems I nC 392 KICK A G C A G C
17. 3 3 D 5 a 3 a NCHS 3 D 3a 5 2 3 3 2 ra 2 3 cleavase 4 3 3
18. 1 5 2004 19 228 PCT ISA 210 2 2009 7 PC JP2010 001850 I 1 1 c 1 eT a b Ju Jiu jJ LE LS jj jj SOR l s 3 PCT ISA 210 1 1 2009 7
19. 000 00 0008 0004 lt
20. PCR PG A M 4 0 O0 PGAM4 PCR RF P RF JP P G AM 4
21. PGAM4 WO 2010 106788 14 PCT JP2010 001850 0033 0084 0035 0086 PGAM4 PGAM4 PGAM4 PGAM4
22. N 383 r 396 3 9 lt 5 X 0 Am J 3 3 2 39 Guideline for sperm donation ertil Steril 2004 82 Suppl 1 S8 S12 N 25 DNA 066 DNA
23. RJ IT MB 03 3581 1101 AR 3488 2009 7 Betran E et al Evo1luti on of the phosphoglyce yate rautase PC JP2010 001850 C processed gene in human and chimpanzee Tevea1i ng the origin of a new primate gene Mol Biol Evol 2002 Vol 19 p 654 663 single nucl ootide polymorphism SNP EHT p P 2007 152 1153H SNP p p 2008 8 2 83H 2004 Vol 20 2 9 3 4
24. PGAM4 7 5 139 539 yr rO 2 PGAM4 WO 2010 106788 7 PCT JP2010 001850 001 0 0011 0012 0013 001 4 3 PGAM4 ERO 1
25. 5 5 5 b fi PGAM4 PGAM4 2 3 5 2 PGAM 4 3 PGAM4 3 3 a PGAM4 5 PGAM4
26. 0 O0 R 6 MINES 1 3 8 7 Pat 5 6 ke R 8 Pac 5 2 9 PGAM 4 ye 8 0 PGAM4 PGAM4
27. WO 2010 106788 27 PCT JP2010 001850 0068 0069 PGAM4 SCOT t 42299 735 PRM2 4276691 TP 2 007 089409 CC ntrin 2 08 237114 TSSK 2 008 067649 Meise tz 2 09 065882 SNP 1 096 5 1 096
28. 5 2 3 PGAM4 2 4 3 c PGAM4 LAF K3 a05 2 3 WO 2010 106788 19 PCT JP2010 001850 0047 0048 3 c PGA M 4 2 3 c PGAM4
29. PGAM4 0 7 5 539 PGAM4 PGAM4 P GAM4 PGAM4 PGAM4 PGAM4 PGAM4
30. PGAM4 Chow M et al Proc Natl Acad Sc i USA 82 910 914 Francis M J et al J Gen Virol 66 2347 23 54 1985 NOK KIH N m N MBS WO 2010 106788 21 PCT JP2010 001850 0051
31. PGAM4 2 PGAM4 2 PGA M 4 75 WO 2010 106788 20 PCT JP2010 001850 0049 0 0 539 PGAM4
32. 3D 3 C 5 5 3 3D 5 a 5BD 5C 5 a 3 3 c 5BD 5 a 5 WO 2010 106788 18 PCT JP2010 001850 0045 0046 5 5 C 5 b 5 3 3 c 3 4 5 5
33. 1 Matzuk Nature Cell Biology 2002 4 Supp D S41 S 49 2 Mori 4 Y Molecular reproduction and development 9 9 6 44 4 2 2 3 Buehr CCournal of reproduction and fertility 98 6 3 6 9 7 3 4 Vemuganti 5 Developmental biology 2007 3 09 r8 3 5 Miki 8 Proceedings of the Nationa Academy of Sciences of the United States of America 2 004 0 4 7 65 0 65 06
34. PCR WO 2010 106788 15 PCT JP2010 001850 087 008 0039 0 0 PGAM4 DNA DNA 5kb lt 3 kK D lt 2kb lt 5kb
35. PGAM4 PGAM4 PGAM4 GenBank N C 000023 9 PGAM4 PGAM4 7 65Dp 2 PGAM4 PGAM4 X Xq 3
36. PGAM4 PGAM4 KT SHOR PGA M 4 PGAM4 PGAM4
37. 74 81 1 1 Tokyo JP TSUJIMURA Akira JP JP T 5650871 1 1 Osaka JP MIYA GAWA Yccushi JP JP T 5650871 1 1 os aka JP TANAKA Hiromitsu JP JP T 8593298 2 8 25 7 Nagasaki JP SUZUKI Shirou et al 1006620 9 2 Tokyo JP AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN C CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW Mx MY MZ NA NG NI NO NZ M PE PG PH PL PT RO RS RU SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW 7J 54 Title FERTILITY TEST METHOD FERTILITY TEST KIT POLYNUCLEOTIDE POLYPEPTIDE AND ANTIBODY RUN KR R
38. 7 5 3 0 0 0 0O0 75 3 0 0 00 3 PGAM4 0 PGAM4 7 5 mRNA cDNA
39. cDNA ADNA PGAM4 3 g 4 0 0 0 OO 3 8 4 0 0 0O0O 4 PGAM4 0 PGAM4 3 8
40. 1 VF In Vitro Fertilization WO 2010 106788 2 PCT JP2010 001850 0005 hexokinase 2
41. 8 0 25 VE 7 5 PGAM4 PGAM4 3 8 PGAM4
42. M 0 o E bA PGAM PGAM BH PGAM2 M r PGAM4 PGAM3 PGAM B 2 WO 2010 106788 3 PCT JP2010 001850 00 M PGAM 3 4 P GAM4 PGAM4 PGAM
43. ISA SIP 100 8915 T 4 3 PCT IrsA 210 2 BIOSIS STN A phosphoglycerate is localized within the human Menkes PCT JP2010 001850 C07K16 40 2006 01 i C12N9 90 2006 01 i C12Q1 533 2006 01 i C12Q1 68 G01N33 53 CAplus STN MEDLINE STN REGISTRY STN rautase brain isoforra disease JP 7 258299 A 1995 10 09 IX IY 1
44. DNA PGAM4 539 5 0 5 0 0 0O0O 539 0 0 0O0O WO 2010 106788 12 PCT JP2010 001850 0 8 029 5 PGAM4 0 PGAM4 5 3 9 mRNA
45. WO 2010 106788 24 PCT JP2010 001850 067 068 069 Sambrnnk J et al Isnlatio of D NA from Mammalian Cells New York Cold Sp ing Harbor Press 1989 op 9 16 9 21 MR BRT SDNAKUGenomiPhi G DNA P GAM4 INA R 2 PCR fe 5 PGAM4 98 H 5 PGAM4 850 1 Sequence F GAG TGGTTAGGGAATAAGGGTGGG AGTGTGACATG TGCAGGTGGGAGG 2 Primers Denaturing Annealing E
46. 3 5 lt 3 PGAM4 PGAM4 7 5 3 8 539 lt 75 53 9
47. 2kb 5kb Okb 0 7kb 2 0Dp lt 3 0Dp lt 4 Obp 5 0Dp PGAM4 2 0Dp PGAM4
48. 3R WO 2010 106788 26 PCT JP2010 001850 0063 0064 0065 0066 0067 36 4 6 249 PGAM4 7 5 3 6 7 mene 2 5 2 4 3 PGAM4 539 3 8 3
49. 2 PGAM4 7 5 53 9 3 a b a 3 0 5 0 0 0 O b a 4 c d WO 2010 106788 6 PCT JP2010 001850 c 772 5 0 0 O0 O O d c 5 MBS PGAM4 7 5 539
50. 53 9 PGAM4 7 5 539 a b a 772 3 0 0 0 0O0O b a c d c 772 0 0 0 0O0O d c
51. gt phosphoglucose isomerase QERRE MR 3 SR aldolase 4 glycerald ehyde 3 phosphate dehydrogenase F 5 phosphoglycerate kinase hh 6 phosphoglycerate mutase 7 eno lase 0 8 5 g lyceraldehyde 3 pho sphate _ dehydrogenase AZ Phosphoglycerate mutase fa mi ly member PGAM Pgam 1 Pgam 2 2 M PGAM 3 3 M 4 6 SM 9 o
52. 7 5 539 R 1 3 8 kK WO 2010 106788 7 8 9 10 11 12 13 29 PCT JP2010 001850 6 5 2 PGAM 4 8 PGAM4
53. PGAM4 BTM BARSTAD TETEE LU BIE DNA DNA mRNA RNA RNA cDNA PGAM4 Taqman
54. WO 2010 106788 22 PCT JP2010 001850 062 063 PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 PGAM4 PGA M 4
55. 2 005 4 2 5 A Human Genome Organisation 2 008 2 2 CURL http www genenames org data hgnc_data php hgne_id 21 731 13 McCarrey Nature 9g87 326 6 2 5 0 5 05 14 Dahl 4 Genomics 9 9 0 8 2 2 2 5 2 3 2 WO 2010 106788 5 PCT JP2010 001850 0008 00
56. 6 McCarrey 6 Developmental genetics 996 9 4 3 2 3 32 WO 2010 106788 4 PCT JP2010 001850 0007 7 Broceno 4 European ournal of biochemistry 9 9 5 227 3 6 2 9 6 35 6 Orce 4 kaa Ccournal of andrology 2 004 25 5 824 8 2 9 9 indele 4 Developmental biology 98 7 2 4 2 5 62 5 6 6 10 Zhang 8 Gene 200 2 6 4 2 2 7 3 2 7 9 11 Sakoda 4 The ournal of biological chemistry 98 8 2 63 32 6 899 6 9 05 12 Symbol Report PGAM4 onl ne
57. IntC1 C12N1S709 C07K16 40 C12N9 90 C12Q17533 ISTPlus J MEDPlus JST 7580 Dreamll WPI c Dierick H A et al PGAM1 pseudogene gene ATP7A Gene 1997 Vol 198 p 37 41 A A C IA lt 30 0
58. or after the international filing date document which may throw doubts on priority claim s or which is cited to establish the publication date of another citation or other special reason as specified document referring to an oral disclosure use exhibition or other means document published prior to the international filing date but later than the priority date claimed Date of the actual completion of the international search 30 March 2010 30 03 10 Name and mailing address of the ISA Japanese Patent Office Facsimile No Form PCT ISA 210 second sheet July 2009 LO See patent family annex later document published after the international filing date or priority date and not in conflict with the application but cited to understand the principle or theory underlying the invention document of particular relevance the claimed invention cannot be considered novel or cannot be considered to involve an inventive step when the document is taken alone document of particular relevance the claimed invention cannot be considered to involve an inventive step when the document is combined with one or more other such documents such combination being obvious to a person skilled in the art document member of the same patent family Date of mailing of the international search report 13 Apri 1 2010 13 04 10 Authorized officer Telephone No INTERNATIONAL SEARCH REPORT DOCUMENTS CONSIDERED TO BE C Continuatio
59. 1 533 C1201 68 GO1N33 53 Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched 1922 1996 1996 2010 1971 2010 1994 2010 Jitsuyo Shinan Koho Jitsuyo Shinan Toroku Koho Kokai Jitsuyo Shinan Koho Toroku Jitsuyo Shinan Koho Elecatonic data base consulted during the international search name of data base and where practicable search terms used JSTPlus JMEDPlus JST7580 JDreamll MEDLINE STN REGISTRY STN C DOCUMENTS CONSIDERED TO BE RELEVANT Dierick H A et al brain isoform PGAM1 within the human Menkes Gene 1997 Vol 198 Pb 37 41 JP 7 258299 A 09 October 1995 Family none Oriental Yeast 09 10 1995 Betran E et al Evolution phosphoglycerate and chimpanzee primate gene m revealing t MoI Biol Evol WPI Citation of document with indication where appropriate of the relevant passages A phosphoglycerate pseudogene disease BIOSIS STN CAplus STN Relevant to claim No mutase 7 1 6 8 13 is localized gene ATP7A Coy LE of the utase processed gene he origin of a new in human 2002 Vol 19 p 654 663 X A A A Further documents are listed in the continuation of Box C Special categories of cited documents document defining the general state of the art which is not considered to be of particular relevance earlier application or patent but published on
60. OH 57 Abstract Provided are a fertility test diagnosis method whereby the possibility of fertility can be estimated on the basis of the ability of sperm to fuse to an egg and a cause of infertility can be identified a polynucleotide which is used in this method and a fertility test kit A fertility test diagnosis method which comprises a detection step for detecting the presence or absence of deletion or mutation of human PGAM4 gene in a biological sample that is collected from a human subject a polynucleotide com prising the base sequence of human wild type PGAM4 gene or the base sequence of the translation region of said gene which comprises a sequence of 10 100 consecutive bases including a single nucleotide polymorphism mutation site that correlates highly with fertility and a fertility test kit which comprises a reagent for detecting the presence or absence of deletion or mutation of hu man PGAM4 gene 57 WO 2010 106788 A1 ilRRRRRRDRRCRE ATA INUN MN MN M TUINN 84 1 CF CG CI CM GA GN GQ GW ML MR NE SN ARIPO BW GH GM KE LS MW MZ TD TG NA SD SL SZ TZ UG ZM ZW kanem AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FL FR GB 21 3 GR HR H
61. SMMD Simultaneous Multiple Mutat ion Detect ion System PCR RFLP pol ymerase chain react ion restriction fragment rength polymorphism MA SA ZS Taqman PGAM4 WO 2010 106788 11 PCT JP2010 001850 0 6 027 PGAM4 PGAM 4 NCB1I NCBI Hum an Genome Resources http www ncb i nim nih gov genome guide human mRNA cDNA DNA PGAM4
62. U IE IS IT LT LU LV MC MK MT NL __ NO PL PT Ro SE SL SK SM TR OAPI BF BJ 5 28 PGAM4 PGAM 4 LAF 10 10 0 P GA M4 WO 2010 106788 1 PCT JP2010 001850
63. keU Immunosorbent As say WO 2010 106788 23 PCT JP2010 001850 1ISA PGAM4 PGAM4 PGAM4 064 lt 1 005 PGAM4 PGAM 4
64. n DOCUMENTS CONSIDERED TO BE RELEVANT Citation of document with indication where appropriate of the relevant passages Hiromitsu TANAKA et al Seiso Seishoku Saibo Tokuiteki Tdensh1 no ee nucleotide polymorphism SNP Kaiseki Proceedings of the Japan Society of Andrology the Annual Meeting 2007 pages 152 to 153 C C Continuation DOCUMENTS CONSIDERED TO BE RELEVANT Category Yasushi MIYAGAWA et al Dansei Funinsho ni Okeru Seiso Seishoku sabo Tokuiteki SNP Kaiseki to sono Rinsho Oyo Proceedings the Japan Society of Andrology the Annual Meeting 2008 pages 82 to 83 Kanja Idenshi of MIYAGAWA et al Dansei Keisei Idenshi Proc edit of the Society of Animal Models for Human 2004 vol 20 pages 29 to 34 Yasushi Funinsho to Seishi Japanese Diseases 1 TANAKA Funinsho no Gen in Oyo Kosei Rodo Hito Genome Saisei Iryo 15 Nendo Sokatsu Kenkyu 19 TO 22 Dansei to Rinsho Hojokin Jigyo Heisei 2004 pages Hiromitsu Idenshi no Dotei Kagaku Kenkyuhi To Kenkyu Hokokusho Form PCT ISA 2 10 continuation of second sheet July 2009 International application No PCT JP2010 001850 Relevant to claim No IPC IntC1 C12N13709 2006 01 i C12Q1 68 2006 01 i GOIN33 53 2006 01 i B IPC
65. o201 1067 Asli H SM TITIAN 12 19 43 2010 9 A 23 23 09 2010 Ca A L ee 10 WO 2010 106788 Al 1 21 22 25 26 30 71 72 75 54 C12N 15 09 2006 01 C07K 16 40 2006 01 CI2N 2006 01 C12Q 1 533 2006 01 C12Q 1 68 2006 01 GOIN 33 53 2006 01 PCT JP2010 001850 2010 3 is 15 03 2010 2009 065 110 2009 3 7 17 03 2009 jp lt A TOPPAN PRINTING CO LTD JP JP 1108360 1 5 1 Tokyo JP OSAKA UNIVERSITY JP JP 75650871 1 1 Osaka JP Kyushu Bunka Gakuen School Foundation JP JP 73593298 4 3 Nagasaki JP IRIE Shinii JP JP T 1108560
66. t 1 FPGAM4 PGAM4 X PGAM 4 X PGAM4 75 25 PGAM4 3 6 3 8 4 6
67. xtension cyc le Prodyct temp and time temp and time temp and time number Size Pi F MSE 98 C 10sec 68 C 30sec 72 60seo 40cycle 948bp PCR AMPure ASencourt Biosciencec PCH BigDve Tarminator V3 1 Cycle Sequenci ng Kit Clea WO 2010 106788 25 PCT JP2010 001850 nS Q Agencourt Bioscience ABI PRISM 3730 Genetic Analyze r 0060 R 3 4 2
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