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US 8,771,956 B2Granted
Modulation of human mouse double minute 2 homolog activity
AssigneeRyogen LLC
InventorJames Ryan
Life of this patent
Estimating the term…
Abstract
The invention is directed to isolated genomic polynucleotide fragments that encode human carboxypeptidase M and human mouse double minute 2 homolog, vectors and hosts containing these fragments and fragments hybridizing to noncoding regions as well as antisense oligonucleotides to these fragments. The invention is further directed to methods of using these fragments to obtain human carboxypeptidase M and human mouse double minute 2 homolog and to diagnose, treat, prevent and/or ameliorate a pathological disorder.
Claims2
A method for modulating levels of human mouse double minute 2 homolog activity in a subject in need thereof comprising administering to said subject an amount of an isolated genomic nucleic acid molecule, said nucleic acid molecule selected from the group consisting of:
- (a) a nucleic acid molecule consisting of a nucleic acid sequence which has at least 99% identity to the nucleic acid molecule of SEQ ID NO:4 that encodes a polypeptide that has human mouse double minute 2 homolog activity and
- (b) a fragment of the nucleic acid molecule of (a), said fragment comprising at least nucleotides 41738-9502 of SEQ ID NO:4 and which encodes a polypeptide having human mouse double minute 2 homolog activity
- effective to modulate said human mouse double minute 2 homolog levels.
A method for modulating levels of human mouse double minute 2 homolog activity in a subject in need thereof comprising administering to said subject an amount of an isolated nucleic acid molecule 20-51039 contiguous nucleotides in length consisting of a reverse or forward strand of a region of SEQ ID NO:4, wherein said region is selected from the group consisting of a 5′-non coding region between nucleotides 51039-41739 of SEQ ID NO:4;
- a 3′-non-coding region between nucleotides 9503-1 of SEQ ID NO:4;
- a contiguous intron-exon region between nucleotides 41738-9502 of SEQ ID NO:4, wherein a sequence segment between nucleotides 41738-9502 of SEQ ID NO:4 encodes human mouse double minute 2 homolog depicted in SEQ ID NO:2;
- a contiguous exon-intron region between nucleotides 41738-9502 of SEQ ID NO:4, wherein a sequence segment between nucleotides 41738-9502 of SEQ ID NO:4 encodes human mouse double minute 2 homolog depicted in SEQ ID NO:2;
- an intron depicted in nucleotides 36385-40645, 36309-33127, 32994-29616, 29564-25577, 25507-25384, 25287-21169, 21006-14110, 13953-13267, and/or 13188-10665;
- a region comprising a dinucleotide of the following group:
- 41739-41738, 40645-40646, 36309-36310, 36384-36385, 32994-32995, 33126-33127, 29564-29565, 29615-29616, 25507-25508, 25287-25288, 25383-25384, 25576-25577, 21006-21007, 21168-21169, 14109-14110, 13953-13954, 13266-13267, 13188-13189, 10664-10665 and/or 9504-9503;
- a transcription binding site selected from the group consisting of
- BINDING SITES
- huMDM2, location in SEQ ID NO:
- 4
- AP1_C:
- 36-46, 2876-2886;
- AP4_Q5:
- 7944-7980;
- AP4_Q6:
- 7943-59, 8924-8940, 9294-9310;
- ARNT_01:
- 1682-1706, 2193-2217, 9201-9225;
- BRN2_01:
- 1040-1058, 7803-7821;
- CAAT_01:
- 3292-3306;
- CDPCR3HD_01:
- 6522-6540;
- CEBPB_01:
- 1424-1438, 3917-3931, 4178-4192, 4787-4801, 6855-6869;
- CREL_01:
- 5630-5642;
- DELTAEF1_01:
- 83-95, 6328-6340;
- FREAC7_01:
- 2757-2773, 5154-5170, 5823-5839;
- GATA1_04:
- 4846-4858, 7017-7029;
- GATA1_05:
- 8464-8476;
- GATA2_02:
- 6045-6057, 6073-6085, 6142-6154;
- GATA2_03:
- 2489-2501, 3323-3335, 3384-3396, 7393-7405:
- GATA3_02:
- 3264-3276, 6870-6882:
- GATA3_03:
- 40-52, 5729-5741, 6529-6541, 6874-6886, 7041-7053, 7589-7601;
- GATA_C:
- 7
- 349-7361, 8188-8200;
- HFH2_01:
- 1743-1759, 7995-8011;
- HFH3_01:
- 502-518, 1739-1755, 4160-4176, 9402-9418, 9418-9434;
- HFH8_01:
- 8184-8200;
- IK2_01:
- 951-963, 3588-3600;
- MZF1_01:
- 1202-1210, 1447-1455, 4997-4005, 5424-5432;
- NF1_Q6:
- 1480-1500, 8166-8182;
- NFAT_Q6:
- 4190-4208, 6009-6027;
- NKX25_01:
- 741-755, 1648-1662, 1885-1899, 1984-1998, 3609-3623, 4928-4942,
- 5060-5074, 5889-5903, 8850-8864, 9190-9204;
- NKX25_02:
- 2584-2599, 2970-2984, 4644-4658, 5179-5193, 6482-6496;
- NMYC_01:
- 2560-2572;
- RORA1_01:
- 220-238, 2638-2656;
- S8_01:
- 4644-4656, 4842-4854, 4845-4857, 5200-5212, 5371-5383,
- 5735-5747, 6482-6494, 6541-6553, 6544-6556, 6772-6784, 7270-7292, 7273-7285;
- SOX5_01:
- 1355-1371, 1430-1446, 3094-3110, 3155-3171, 4669-4685,
- 4692-4708, 4789-4805;
- SRY_02:
- 4164-4180, 5665-5681;
- TATA_01:
- 1261-1277, 2574-2590, 2723-2739, 2733-2749, 2770-2786,
- 4199-4215, 4206-4222;
- TATA_C:
- 5900-5916, 7456-7472, 7702-7718, 7917-7933;
- and
- XFD2_01:
- 7702-7218, 7917-7933;
- a transcription binding site selected from the group consisting of
- BINDING SITES
- huMDM2, location in SEQ ID NO:
- 4
- AP1_C:
- 12109-12119, 12695-12705, 22600-22610, 24166-24176, 31311-31321,
- 35234-35244, 39184-39194;
- AP1_Q2:
- 11952-11962, 12068-12078, 14798-14808, 21748-21758, 22613-22623,
- 23676-23686, 26562-26572, 30046-30056;
- AP1_Q4:
- 12695-12705, 31311-31321, 35234-35244, 36295-36305, 38784-38794,
- 39188-39198;
- AP4_Q6:
- 31635-31651;
- BRN2_01:
- 13448-13466, 14764-14782, 28094-28112, 40027-40045;
- CAAT_01:
- 11288-11302, 15054-15068;
- CDPCR3HD_01:
- 11286-11304, 13284-13302, 20846-20864, 29344-29362;
- CEBPB_01:
- 29241-29255;
- CREL_01:
- 36091-36103, 38873-38885;
- DELTAEF1_01:
- 18083-18095, 20385-20397, 26955-26967;
- FREAC7_01:
- 11982-11998, 15187-15202, 16523-16539, 16529-16545, 16587-16603,
- 16604-16620, 16676-16642, 16633-16649, 16644-16660, 16650-16666, 16657-16673, 16673-
- 16689, 16762-16778, 21332-21348, 25689-25700, 26529-26545, 27767-27783, 29495-29511;
- GATA1_02:
- 10916-10928, 15775-15789, 18162-18174, 26088-26100, 32518-32530;
- GATA1_03:
- 28012-28024;
- GATA1_04:
- 11153-11165, 11630-11642, 13778-13790, 17439-17451, 19300-19312,
- 21606-21618, 22743-22755, 23747-23759, 25806-25818, 26529-26541, 29424-29436, 30455-
- 30467, 32761-32778, 33352-33364, 33960-33972, 36101-36113, 40007-40019;
- GATA1_05:
- 11590-11602, 26550-26562, 36737-36749;
- GATA1_06:
- 18772-18784, 23054-23066, 35568-35580, 37855-37867;
- GATA2_02:
- 20755-20767, 30830-30842, 34755-34767, 36285-36297, 39143-39155,
- 39641-39653, 40586-40598;
- GATA2_03:
- 13535-13547, 22711-22723, 23161-23173, 25028-25040, 27237-27249,
- 36277-36289;
- GATA3_02:
- 11558-11570, 16470-16482, 17225-17237, 19619-19631, 22156-22168,
- 22443-22455, 24713-24725, 27619-27631, 32716-32728, 34124-34136, 34163-34175, 36832-
- 36844, 38403-38415;
- GATA3_03:
- 10869-10881, 11515-11527, 13845-13857, 17221-17233, 18952-18964,
- 20050-20062, 40171-40183;
- GATA_C:
- 15848-15860, 18899-18911, 23640-23652, 29072-29084, 30881-30893,
- 33198-33210, 37472-37484, 38621-38633;
- GFI1_01:
- 35469-35481, 35492-35504;
- HFH2_01:
- 15939-15955, 24636-24652, 25866-25882, 32171-32187, 35372-35388,
- 39457-35473;
- HFH3_01:
- 13340-13356, 19218-19234, 21328-21344, 21336-21352, 21344-21360,
- 28062-28078, 32125-32141;
- HFH8_01:
- 14133-14149, 22578-22584;
- HNF3B_01:
- 13150-13166, 16505-16521, 25264-25280, 29443-29459, 37654-37670;
- IK2_01:
- 11547-11559, 17144-17156, 18961-18973, 23883-23895, 27617-27629,
- 28908-28920, 29241-29253, 30752-30764, 34768-34780;
- LYF1_01:
- 12319-12331, 19191-19203, 37226-37238, 39430-39442;
- MAX_01:
- 22974-22986, 33339-33351;
- MZF1_01:
- 26105-26113, 35187-35195;
- NF1_Q6:
- 12048-12064, 33334-33354;
- NFAT_Q6:
- 13295-13313, 14157-14175, 14311-14329, 14414-14432, 18269-18287.
- 19326-19344, 20801-20819, 21177-21195, 22537-22555, 23861-23879, 25392-25410, 25879-
- 25897, 27524-27542, 30636-30654, 30718-30736, 31525-31543, 33655-33673, 34726-34744,
- 34917-34535, 34990-35008, 35979-35997, 36479-36493, 36577-36595, 37154-37172, 40224-
- 40242, 40365-40383;
- NKX25_01:
- 12041-12055, 12340-12354, 12471-12485, 12742-12756, 12877-12891,
- 13849-13863, 18995-19009, 21440-21454, 21883-21897, 28426-28440, 30964-30978, 32033-
- 32047, 32265-32279;
- NKX25_02:
- 10998-11012, 12711-12725, 14131-14145, 14726-14740, 16024-16038;
- NMYC_01:
- 18753-18765, 18754-18766, 23076-23088, 30534-30546, 34400-34412;
- RORA1_01:
- 13134-13152, 22966-22984, 24934-24952, 33341-33359, 34760-34778;
- S8_01:
- 11000-11012, 11977-11989, 12048-12060, 12051-12063, 13747-13759,
- 13923-13935, 13926-13938, 14676-14688, 14679-14691, 16026-16038, 16313-16325, 16316-
- 16328, 17515-17527, 20756-20768, 20759-20771, 23154-23166, 23157-23169, 25198-25210,
- 25201-25213, 26651-26663, 27508-27520, 27511-27523, 29450-29462, 29478-28490, 29775-
- 29787, 29778-29790, 29813-29825, 29816-29828, 31329-31341, 31677-31689, 31680-31692,
- 31732-31744, 31735-31747, 36137-36149, 36140-36152, 36812-36824, 36815-36827, 37413-
- 37425, 38679-38691, 39474-39486, 39477-39489;
- SOX5_01:
- 27397-27413, 27572-27588, 28100-28116, 29230-29246, 29439-29455,
- 30690-30706, 31595-31611, 33871-33887, 34113-34129, 34624-34640, 37668-37684, 38582-
- 38598, 39124-39140, 40410-40426;
- SRY_02:
- 20016-20032, 22410-22426, 27329-27345, 29162-29178, 29499-29515,
- 30646-30662, 31503-31519, 35928-35944, 37324-37340;
- TATA_01:
- 32722-32738, 32729-32745, 32807-32823, 33825-33841, 34120-34136,
- 35433-35449, 36593-36609;
- TATA_C:
- 11015-11031, 11817-11833, 13635-13651, 14930-14946;
- TCF11_01:
- 18543-18549, 22574-22580, 31281-31297, 31489-31505, 38754-38770;
- USF_01:
- 23075-23087, 32577-32589;
- VMYB_02:
- 11526-11538, 17384-17396, 18400-18412, 19549-19561, 22188-22200,
- 40486-40508 and
- XFD2_01:
- 16620-16636. 18153-18169, 22102-22118, 23141-23157.
- And a transcription binding site selected from the group consisting of
- BINDING SITES
- huMDM2, 1
- location in SEQ ID NO:
- 4
- AP1_C:
- 44584-44594, 49069-49079:
- AP1_Q2:
- 42174-42184, 45217-45227, 48422-48422, 50447-50457;
- AP1_Q4:
- 42702-42712, 50806-50816;
- AP4_Q6:
- 42117-42133, 42118-42134, 42244-42260, 45432-45448;
- 45433-45449,
- 46609-46625;
- BRN2_01:
- 42310-42328, 44022-44040, 47514-47532, 48900-48918, 48967-48985;
- CAAT_01:
- 44866-44880;
- CDPCR3HD_01:
- 45671-45689, 49219-49237;
- CREL_01:
- 42437-42449, 49797-49809;
- FREAC7_01:
- 47026-47042, 47292-47308, 47658-47674;
- GATA1_02:
- 43482-43494, 48926-48938, 49284-49296;
- GATA1_03:
- 47371-47383;
- GATA1_04:
- 43054-43066, 43162-43162, 43967-43979, 45464-45476, 45916-45928,
- 47763-47775;
- GATA1_05:
- 49319-49331, 49459-49471;
- GATA1_06:
- 47590-47602;
- GATA2_02:
- 42660-42672, 43475-43487;
- GATA2_03:
- 43714-43726, 50948-50960;
- GATA3_02:
- 49155-49167, 49844-49856;
- GATA3_03:
- 42202-42214, 44810-44822, 48438-48450, 49136-49148, 49337-49349,
- 49869-49881;
- GATA_C:
- 44011-44023, 45256-45268, 45823-45835, 47915-47927, 49201-49213,
- 49573-49585;
- GFI1_01:
- 46606-46618, 47063-47075;
- HFH3_01:
- 47030-47046, 47284-47300, 47288-47304;
- IK2_01:
- 45275-45287;
- LYF1_01:
- 44564-44576, 46991-47003, 49567-49579;
- MAX_01:
- 43234-43246, 48726-48738;
- MZF1_01:
- 41772-41780, 42290-42298, 42295-42303, 44507-44515, 45105-45113,
- 45203-45211, 49948-49956, 50774-50782;
- NF1_Q6:
- 50209-50229;
- NFAT_Q6:
- 42061-42079, 44418-44436, 46399-46417, 47974-47992, 49267-49285,
- 49964-49982, 50392-50410;
- NKX25-01:
- 42394-42408, 43507-43521, 46115-46129;
- RORA1_01:
- 45073-45091, 48718-48736;
- S8_01:
- 43552-43564, 45214-45226, 47160-47172, 48419-48431, 49295-49307,
- 50379-50391;
- SOX5_01:
- 43716-43732, 46351-46367, 47156-47172, 47774-47790, 47868-47884,
- 47974-47990, 48915-48931, 50323-50339;
- TATA_01:
- 45588-45604, 47625-47641, 48026-48042, 48659-48675, 49056-49072,
- 49079-49095, 49152-49168;
- TCF11_01:
- 49115-49131;
- VMYB_02:
- 42010-42022, 42279-42291, 44651-44663;
- and
- XFD2_01:
- 42870-42886, 42910-42926.
296 more elements
Dependencies are inferred from the claim text.