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US5527690A Expired / Lapsed US ⏱️ 0.0 years remaining

Methods and compositions relating to sterol regulatory element binding proteins

Assignee: The University of Texas System
•
Filing: 1993-10-01
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Granted: 1996-06-18
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Expires: 2013-10-01
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Abstract

Abstract A sterol regulatory element (SRE) binding protein (SREBP) which activates transcription from SREs, such as SRE-1 of the low density lipoprotein (LDL) receptor gene, is disclosed, as are DNA segments encoding SREBPs such as an SREBP-1 or SREBP-2. Also described are methods for using SREBP to promote SRE-mediated transcription and LDL receptor production in the presence of sterols, and screening assay for the identification of further agents with such properties. The SREBP and other agents may be used to reduce plasma cholesterol levels and to treat various medical problems associated with hypercholesterolemia.

Inventors

  • 👤 Joseph L. Goldstein
  • 👤 Michael S. Brown
  • 👤 Michael R. Briggs
  • 👤 Xiaodong Wang

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-09 18:37
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/52; C07K14/525; C07K14/46; C07K14/47; C07K14/4701; C07K14/4702; C07K14/575; C07K14/61; C12; C12N; C12N15/00; C12N15/09; C12N15/63; C12N15/67; C12N15/79; C12N15/85; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/6456; C12N9/6459; C12Y; C12Y304/00; C12Y304/21; C12Y304/21069; C12N2830/00; C12N2830/001; C12N2830/002; C12N2830/008; C12N2830/15; C12N2830/80; C12N2830/85

Claims Analysis

Total Claims: 48
Claim 1
Independent Claim 24 words
A nucleic acid segment comprising an isolated gene encoding an SREBP, said SREBP containing a bHLH-Zip region which binds to an SRE-1 DNA segment.
Claim 2
Dependent Claim 24 words
A nucleic acid segment comprising an isolated gene encoding an SREBP, said SREBP containing a bHLH-Zip region which binds to an SRE-1 DNA segment.
Claim 3
Dependent Claim 30 words
The nucleic acid segment of claim 1, wherein said isolated gene encodes a polypeptide having an in vivo molecular weight of approximately 59 to 68 KD when measured by SDS-PAGE.
Claim 4
Dependent Claim 31 words
The nucleic acid segment of claim 1, wherein the encoded SREBP stimulates transcription of a gene under the control of such an SRE-1 element in the absence or presence of sterols.
Claim 5
Dependent Claim 17 words
The nucleic acid segment of claim 1, wherein the isolated gene encodes an SREBP-1 or SREBP-2 protein.
Claim 6
Dependent Claim 13 words
The nucleic acid segment of claim 1, further defined as a DNA segment.
Claim 7
Dependent Claim 12 words
A recombinant host cell comprising the nucleic acid segment of claim 1.
Claim 8
Dependent Claim 15 words
The nucleic acid segment of claim 4, wherein the isolated gene encodes an SREBP-1 protein.
Claim 9
Dependent Claim 15 words
The nucleic acid segment of claim 4, wherein the isolated gene encodes an SREBP-2 protein.
Claim 10
Dependent Claim 25 words
The nucleic acid segment of claim 7, wherein the isolated gene encodes an SREBP-1a protein consisting of the amino acid sequence of SEQ ID NO:38.
Claim 11
Dependent Claim 20 words
The nucleic acid segment of claim 9, further defined as comprising the SREBP-1a-coding nucleic acid sequence of SEQ ID NO:37.
Claim 12
Dependent Claim 25 words
The nucleic acid segment of claim 8, wherein the isolated gene encodes an SREBP-2 protein consisting of the amino acid sequence of SEQ ID NO:54.
Claim 13
Dependent Claim 20 words
The nucleic acid segment of claim 11, further defined as comprising the SREBP-2-coding nucleic acid sequence of SEQ ID NO:53.
Claim 14
Dependent Claim 19 words
The nucleic acid segment of claim 5, wherein the isolated gene is positioned under the control of a promoter.
Claim 15
Dependent Claim 18 words
The nucleic acid segment of claim 13, further defined as a recombinant vector which comprises the isolated gene.
Claim 16
Dependent Claim 15 words
The nucleic acid segment of claim 14, wherein the vector is a recombinant expression vector.
Claim 17
Dependent Claim 15 words
The recombinant host cell of claim 6, wherein the host cell is a procaryotic cell.
Claim 18
Dependent Claim 15 words
The recombinant host cell of claim 6, wherein the host cell is a eucaryotic cell.
Claim 19
Dependent Claim 27 words
A nucleic acid segment which comprises at least a 10 nucleotide long contiguous stretch of the nucleic acid sequence of SEQ ID NO:37 or SEQ ID NO:53.
Claim 20
Dependent Claim 27 words
A nucleic acid segment which comprises at least a 10 nucleotide long contiguous stretch of the nucleic acid sequence of SEQ ID NO:37 or SEQ ID NO:53.
Claim 21
Dependent Claim 32 words
The nucleic acid segment of claim 18, further defined as comprising at least a 15 nucleotide long contiguous stretch of the nucleic acid sequence of SEQ ID NO:37 or SEQ ID NO:53.
Claim 22
Dependent Claim 32 words
The nucleic acid segment of claim 19, further defined as comprising at least a 20 nucleotide long contiguous stretch of the nucleic acid sequence of SEQ ID NO:37 or SEQ ID NO:53.
Claim 23
Dependent Claim 21 words
The nucleic acid segment of claim 19, further defined as a nucleic acid fragment of up to 10,000 basepairs in length.
Claim 24
Dependent Claim 32 words
The nucleic acid segment of claim 20, further defined as comprising at least a 30 nucleotide long contiguous stretch of the nucleic acid sequence of SEQ ID NO:37 or SEQ ID NO:53.
Claim 25
Dependent Claim 32 words
The nucleic acid segment of claim 22, further defined as comprising at least a 50 nucleotide long contiguous stretch of the nucleic acid sequence of SEQ ID NO:37 or SEQ ID NO:53.
Claim 26
Dependent Claim 32 words
The nucleic acid segment of claim 23, further defined as comprising at least a 100 nucleotide long contiguous stretch of the nucleic acid sequence of SEQ ID NO:37 or SEQ ID NO:53.
Claim 27
Dependent Claim 32 words
The nucleic acid segment of claim 24, further defined as comprising at least a 1000 nucleotide long contiguous stretch of the nucleic acid sequence of SEQ ID NO:37 or SEQ ID NO:53.
Claim 28
Dependent Claim 23 words
The nucleic acid segment of claim 25, further defined as having the nucleic acid sequence of SEQ ID NO:37 or SEQ ID NO:53.
Claim 29
Dependent Claim 21 words
The nucleic acid segment of claim 21, further defined as a nucleic acid fragment of up to 1,000 basepairs in length.
Claim 30
Dependent Claim 21 words
The nucleic acid segment of claim 27, further defined as a nucleic acid fragment of up to 500 basepairs in length.
Claim 31
Dependent Claim 21 words
The nucleic acid segment of claim 28, further defined as a nucleic acid fragment of up to 50 basepairs in length.
Claim 32
Independent Claim 59 words
A method for promoting SRE-1 mediated transcription with SREBP comprising the steps of: (a) positioning a gene construct that includes a coding region under the transcriptional control of an SRE-1 sequence and suppressing the expression of said gene construct with a sterol; (b) preparing a recombinant SREBP protein, and promoting the expression of said gene construct with said protein.
Claim 33
Independent Claim 59 words
A method for promoting SRE-1 mediated transcription with SREBP comprising the steps of: (a) positioning a gene construct that includes a coding region under the transcriptional control of an SRE-1 sequence and suppressing the expression of said gene construct with a sterol; (b) preparing a recombinant SREBP protein, and promoting the expression of said gene construct with said protein.
Claim 34
Dependent Claim 47 words
A DNA segment free of an associated protein coding gene, said segment comprising an SRE-1 sequence as defined by SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18 or SEQ ID NO:19.
Claim 35
Dependent Claim 47 words
A DNA segment free of an associated protein coding gene, said segment comprising an SRE-1 sequence as defined by SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18 or SEQ ID NO:19.
Claim 36
Dependent Claim 13 words
The DNA segment of claim 31, further defined as comprising SEQ ID NO:2.
Claim 37
Dependent Claim 13 words
The DNA segment of claim 31, further defined as comprising SEQ ID NO:3.
Claim 38
Dependent Claim 13 words
The DNA segment of claim 31, further defined as comprising SEQ ID NO:4.
Claim 39
Dependent Claim 13 words
The DNA segment of claim 31, further defined as comprising SEQ ID NO:10.
Claim 40
Dependent Claim 13 words
The DNA segment of claim 31, further defined as comprising SEQ ID NO:15.
Claim 41
Dependent Claim 13 words
The DNA segment of claim 31, further defined as comprising SEQ ID NO:16.
Claim 42
Dependent Claim 13 words
The DNA segment of claim 31, further defined as comprising SEQ ID NO:17.
Claim 43
Dependent Claim 13 words
The DNA segment of claim 31, further defined as comprising SEQ ID NO:18.
Claim 44
Dependent Claim 13 words
The DNA segment of claim 31, further defined as comprising SEQ ID NO:19.
Claim 45
Dependent Claim 17 words
The DNA segment of claim 31, further defined as comprising from 10 to 100 nucleotides in length.
Claim 46
Dependent Claim 50 words
A DNA segment free of an associated protein coding gene, said segment comprising a non-active SRE-1 mutant consisting of the sequences of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:14.
Claim 47
Dependent Claim 50 words
A DNA segment free of an associated protein coding gene, said segment comprising a non-active SRE-1 mutant consisting of the sequences of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:14.
Claim 48
Dependent Claim 18 words
The DNA segment of claim 42, further defined as a DNA from 10 to 100 nucleotides in length.

References Cited (Backward Citations)

US5215910A Cited
US4935363A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1999-06-18 1999-12-18 2000-06-18 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2003-06-18 2003-12-18 2004-06-18 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2007-06-18 2007-12-18 2008-06-18 $7700.00 Window Closed / Lapsed

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