Patent Estate

Issued Patent Estate

A. GRANTED/ALLOWED PATENTS

1. GRAHAM (Benitec Biopharma has an exclusive, irrevocable worldwide licence from CSIRO for human therapeutics)

Title, Description, Inventors Country Number Main Claims
GENETIC CONSTRUCTS FOR DELAYING OR REPRESSING THE EXPRESSION OF A TARGET GENE

Synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the invention provides novel synthetic genes and genetic constructs which are capable of repressing, delaying or otherwise reducing the expression of an endogenous gene or a target gene in an organism when introduced thereto.

Graham, Rice, Waterhouse

US 6,573,099 Re-issued 16/2/2011
4. An isolated double-stranded DNA construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in an animal cell which is transfected with said double-stranded DNA construct, wherein said double-stranded DNA construct comprises at least two identical copies of a structural gene sequence and each identical copy of said structural gene sequence is separately placed under the control of a promoter which is operable in said cell, and wherein said structural gene sequence comprises a nucleotide sequence which is substantially identical to a region of said target gene, wherein at least one identical copy of said structural gene sequence is placed operably in the same orientation under the control of an individual promoter sequence, and wherein at least one other identical copy of said structural gene sequence is placed operably in the antisense orientation under the control of another individual promoter sequence.
5. An isolated double-stranded DNA construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in an animal cell which is transfected with said double-stranded DNA, wherein said double-stranded DNA construct comprises at least two identical copies of a structural gene sequence, wherein said structural gene sequence comprises a nucleotide sequence which is substantially identical to a region of said target gene, and wherein said at least two identical copies of said structural gene sequence are placed operably under the control of a single promoter sequence which is operable in said cell, wherein at least one copy of said structural gene sequence is placed operably in the sense orientation under the control of said promoter sequence, wherein at least one other copy of said structural gene sequence is placed operably in the antisense orientation under the control of said promoter sequence, and wherein said at least one copy of said structural gene sequence that is placed in the sense orientation relative to said promoter and said at least one copy of said structural gene sequence that is placed in the antisense orientation relative to said promoter are spaced from each other by a nucleic acid stuffer fragment.
SYNTHETIC GENES AND GENETIC CONSTRUCTS COMPRISING THE SAME

A method of modifying gene expression and to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the present invention utilises recombinant DNA technology to post-transcriptionally modify or modulate the expression of a target gene in a cell, tissue, organ or whole organism, thereby producing novel phenotypes. Novel synthetic genes and genetic constructs which are capable or repressing delaying or otherwise reducing the expression of an endogenous gene or a target gene in an organism when introduced thereto are also provided.

Waterhouse, Graham, Wang, Rice

US 8067383
Granted
29 Nov 2011
A double-stranded DNA construct comprising:
a first structural gene sequence comprising about 20-30 consecutive nts identical in sequence to a region of target gene encoding a viral DNA polymerase, a viral RNA polymerase, or a viral coat protein in a mammalian cell;
a second structural gene sequence comprising about 20-30 consecutive nucleotides identical in sequence to, and in an inverted orientation relative to, the about 20-30 consecutive nucleotides of the first structural gene sequence, such that a repeating sequence which is only about 20-30 consecutive nucleotides in length identical to the region of the target gene is present in the DNA construct;
a stuffer fragment which consists of nucleotides and which separates and links the first and second structural gene sequences;
a promoter operable in the mammalian cell; and
a transcription termination sequence active in the mammalian cell,
wherein the repeating sequence of about 20-30 consecutive nucleotides is present within the first structural gene sequence and the second structural gene sequence,
wherein the first structural gene sequence, the stuffer fragment and the second structural gene sequence are all operably connected to the promoter and the transcription termination sequence
    7754697
Granted
July 2010
1. A double-stranded synthetic DNA gene, comprising
multiple copies of a structural gene region, wherein the structural gene region comprises a nucleotide sequence which consists of greater than 20 consecutive nucleotides and which is identical to a nucleotide sequence of a target gene in a eukaryotic cell,
wherein one of the copies is placed in the sense orientation and another of the copies is placed in the antisense orientation operably under the control of a single promoter sequence which is operable in the cell,
wherein the copy of the structural gene region placed in the sense orientation and the copy of the structural gene region placed in the antisense orientation are arranged so as to form an interrupted palindrome sequence which is operably under the control of the single promoter sequence, and
wherein the structural gene region placed in the sense orientation and the structural gene region placed in the antisense orientation are separated by a sequence of nucleotides that is 50-100 nucleotides in length or 100-500 nucleotides in length.
    8048670
Issued
Nov 2011
1. A double-stranded DNA construct comprising:
a first structural gene sequence comprising about 20 consecutive nucleotides identical in sequence to a region of a target gene encoding a viral DNA polymerase, a viral RNA polymerase or a viral coat protein in a mammalian cell;
a second structural gene sequence comprising about 20 consecutive nucleotides identical in sequence to, and in an inverted orientation relative to, the about 20 consecutive nucleotides of the first structural gene sequence, such that a repeating sequence which is only about 20 consecutive nucleotides in length identical to the region of the target gene is present in the DNA construct;
a stuffer fragment which consists of nucleotides other than the nucleotides of the repeating sequence, and which separates and links the first and second structural gene sequences;
a promoter operable in the mammalian cell; and
a transcription termination sequence active in the mammalian cell,
wherein the repeating sequence within the DNA construct is only about 20 nucleotides in length, and
wherein the first structural gene sequence, the stuffer fragment and the second structural gene sequence are all operably connected to the promoter and the transcription termination sequence.
12. A mammalian cell having a DNA comprising…
21. An isolated mammalian cell, tissue or organ, having a DNA comprising…
    8053419
Granted 2011
1. A double-stranded DNA construct comprising:
a first structural gene sequence whose nucleotide sequence is identical to the nucleotide sequence of a region of a target gene in an animal cell;
a second structural gene sequence identical in sequence to, and in an inverted orientation relative to, the first structural gene sequence such that a repeating sequence which is identical to the region of the target gene is present in the DNA construct;
a stuffer fragment which consists of nucleotides other than the nucleotides of the repeating sequence, and which separates and links the first and second structural gene sequences;
a promoter operable in the animal cell; and
a transcription termination sequence active in the animal cell;
wherein the first structural gene sequence, the stuffer fragment and the second structural gene sequence are all operably connected to the promoter and the transcription termination sequence.
16. An animal cell having…
31. A process for delaying…
CONTROL OF GENE EXPRESSION WO99/49029

A method of modifying gene expression and to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the invention utilises recombinant DNA technology post-transcriptionally modify or modulate the expression of a target gene in a cell, tissue, organ or whole organism, thereby producing novel phenotypes. Novel synthetic genes and genetic constructs which are capable or repressing delaying or otherwise reducing the expression of an endogenous gene or a target gene in an organism when introduced thereto are also provided.

Graham, Rice, Waterhouse, Wang

AU 2005211538 A method of repressing, delaying or reducing the expression of a target gene in an animal cell, tissue or organ, by introducing one or more dispersed or foreign nucleic acid molecules comprising tandem copies of a nucleotide sequence which is substantially identical to the nucleotide sequence of the target gene or region thereof or complementary thereto and wherein said tandem copies are presented as an inverted repeat of the nucleotide sequence; wherein the nucleic acid molecules are operably connected to a promoter sequence operable in said cell, tissue or organ; for a time and under conditions sufficient for translation of the mRNA product of said target gene to be modified, subject to the proviso that the transcription of said mRNA product is not exclusively repressed or reduced.
4. herein one or more of the repeats of the tandem copies is separated from another unit by a nucleic acid-containing stuffer fragment.
    2005209648 18. A synthetic gene which is capable of repressing, delaying or otherwise reducing the expression of a target gene in a eukaryotic cell, comprising a foreign or dispersed nucleic acid molecule which comprises multiple copies of a nucleotide sequence (a) which is substantially identical to the target gene or a region thereof, wherein said nucleotide sequence is (a) greater than 20 nucleotides in length, and wherein the multiple copies are presented as an inverted repeat of the nucleotide sequence and are operably under the control of a single promoter sequence which is operable in the cell.
19. A synthetic gene which is capable of repressing, delaying or otherwise reducing the expression of a target gene in eukaryotic cell, comprising a foreign or dispersed nucleic acid molecule which comprises multiple copies of a nucleotide sequence (a) which is substantially identical to the target gene or a region thereof, wherein said nucleotide sequence (a) is greater than 20 nucleotides in length, and wherein one of the multiple copies is operably connected in the sense orientation to a first promoter sequence which is operable in the cell and one other of the copies is operably connected in the antisense orientation to a second promoter sequence which is operable in the cell.
    2008249157 A synthetic gene which is capable of repressing, delaying or otherwise reducing the expression of a target gene in an animal cell,
wherein said synthetic gene comprises a foreign nucleic acid molecule comprising multiple copies of a nucleotide sequence of greater than 20 nucleotides which is substantially identical to a nucleotide sequence of said gene,
wherein the multiple copies are presented as an interrupted palindrome sequence,
and the foreign nucleic acid is operably under the control of a single promoter sequence.
  CA 2323726 1. An isolated genetic construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a vertebrate animal cell containing said genetic construct, wherein said genetic construct comprises at least two copies of a structural gene sequence, wherein said structural gene sequence comprises a nucleotide sequence which is substantially identical to at least a region of said target gene, and wherein said at least two copies of said structural gene sequence are placed operably under the control of a single promoter sequence which is operable in said cell, wherein at least one copy of said structural gene sequence is placed operably in the sense orientation under the control of said promoter sequence and wherein at least one other copy of said structural gene sequence is placed operably in the antisense orientation under the control of said promoter sequence.
2. An isolated genetic construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a vertebrate animal cell containing said genetic construct, wherein said genetic construct comprises at least two copies of a structural gene sequence wherein each copy of said structural gene sequence is separately placed under the control of a promoter which is operable in said cell, and wherein said structural gene sequence comprises a nucleotide sequence which is substantially identical to at least a region of said target gene, wherein at least one copy of said structural gene sequence is placed operably in the sense orientation under the control of an individual promoter sequence and at least one other copy of said structural gene sequence is placed operably in the antisense orientation under the control of one other individual promoter sequence.
10. An isolated genetic construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a vertebrate animal cell, tissue or organ which contains said genetic construct, wherein said genetic construct comprises at least two copies of a nucleotide sequence which is substantially identical to at least a region of said target gene, and wherein at least one of said copies is in the sense orientation and wherein at least one other of said copies is in the antisense orientation.
11. An isolated nucleic acid molecule which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a vertebrate animal cell, comprising at least two copies of a nucleotide sequence which is substantially identical to at least a region of a target gene, wherein at least one of said copies is in the sense orientation and wherein at least one other of said copies is in the antisense orientation, wherein post-transcriptional expression of the target gene is repressed, delayed or otherwise reduced when the nucleic acid molecule is expressed.
18. An isolated nucleic acid molecule which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a vertebrate animal cell, wherein said nucleic acid molecule comprises:
one or more copies of a nucleic acid sequence which is substantially identical to at least a region of said target gene,
wherein said one or more copies of said nucleotide sequence are placed between opposing first and second promoter sequences,
wherein said one or more copies of said nucleotide sequence are placed operably in the sense orientation under control of said first promoter sequence and operably in the antisense orientation under the control of said second promoter sequence, and
wherein transcription of said one or more copies of said nucleotide sequence produces two single stranded RNA transcripts which hybridize to form double stranded RNA.
  CZ 295108 A synthetic gene containing a dispersed or foreign deoxyribonucleic molecule, said gene comprising at least two copies of a structural gene sequence where at least 80 percent of the first copy of the structural gene sequence is identical with a nucleotide sequence being complementary to a target gene section, and wherein the synthetic gene is capable of producing a post-transcription repression, delay or another reduction of said target gene expression if expressed in a host cell of a mammal by sequentially-specific degradation of RNA transcription of the target gene by an endogenous host cell system. The present invention also relates to a gene construct containing such a synthetic gene.; The synthetic genes and gene constructs according to the present invention are capable to suppress, delay or in another way to reduce expression of an endogenous gene or a target gene in an organism in which they are introduced.
  EP 1555317
Issued Jan 2012
A synthetic gene which is capable of repressing, delaying or otherwise reducing the expression of a target gene
In an animal cell
Wherein said gene comprises …multiple copies of a nucleotide sequence
Of greater than 20 nucleotides
Which is substantially identical to a nucleotide sequence of a target gene
Wherein the multiple copies are presented as an interrupted palindrome sequence
Operably under the control of a single promoter
  EP 1624060 A synthetic gene which is capable of repressing, delaying or otherwise reducing the expression of a target gene
In a eukaryotic cell
Wherein said gene comprises …multiple copies of a nucleotide sequence
Of 100 nucleotides
Which is substantially identical to a nucleotide sequence of a target gene
Wherein the multiple copies are presented as an interrupted palindrome sequence
Operably under the control of a single promoter
  HK 1035742 A genetic construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a vertebrate animal cell, tissue or organ which is transfected with said genetic construct, wherein said genetic construct comprises one or more dispersed or foreign nucleic acid molecules which include multiple copies of a nucleotide sequence which is substantially identical to the target gene, or a region of said target gene, and wherein at least one of said copies is in the sense orientation and wherein at least one other of said copies is in the antisense orientation.
20. A genetic construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a vertebrate animal cell, tissue or organ which is transfected with said genetic construct, wherein said genetic construct comprises multiple copies of a nucleotide sequence which is substantially identical to said target gene, or a region of said target gene, and wherein said multiple copies are placed operably under the control of a single promoter sequence which is operable in said cell, tissue or organ, wherein at least one of said copies is placed operably in the sense orientation under the control of said promoter sequence, wherein at least one other of said copies is placed operably in the antisense orientation under the control of said promoter sequence, and wherein the at least one copy that is placed in the sense orientation relative to said promoter and the at least one other copy that is placed in the antisense orientation
  IN 3901/DELNP
/2005
1. A synthetic gene which is capable of repressing, delaying or otherwise reducing the expression of a target gene in a eukaryotic cell,
wherein said genetic gene comprises a foreign nucleic acid molecule comprising an inverted repeat of a sense and an antisense nucleotide sequence each of which are greater than 20 nucleotides and which are substantially identical to a nucleotide sequence of said target gene,
wherein the inverted repeat is presented as an interrupted palindrome sequence,
and the foreign nucleic acid is operably under the control or a single promoter sequence.
    2000/00169/DEL An ex vivo method of repressing, delaying or reducing the expression of a target gene in an animal cell, tissue or organ, by introducing one or more dispersed or foreign nucleic acid molecules comprising tandem copies of a nucleotide sequence which is substantially identical to the nucleotide sequence of the target gene or region thereof or complementary thereto and wherein said tandem copies are presented as an inverted repeat of the nucleotide sequence; wherein the nucleic acid molecules are operably connected to a promoter sequence operable in said cell, tissue or organ; for a time and under conditions sufficient for translation of the mRNA product of said target gene to be modified, subject to the proviso that the transcription of said mRNA product is not exclusively repressed or reduced.
4. herein one or more of the repeats of the tandem copies is separated from another unit by a nucleic acid-containing stuffer fragment.
  JP 2000-537990 A genetic construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a plant cell which is transfected with said genetic construct, wherein said genetic construct comprises multiple copies of a nucleotide sequence of greater than 20 nucleotides which is identical to the coding region of said target gene or a region thereof, at least one copy being in the sense orientation and at least one other copy being in the antisense orientation and wherein said multiple copies are placed operably under the control of a single promoter sequence which is operable in said plant cell.
    2007-302237 1. An isolated genetic construct, wherein said genetic construct comprises multiple copies of a nucleotide sequence of greater than 20 nucleotides which is at least 95% identical to a target gene in a eukaryotic cell or a region thereof, at least one copy being in the sense orientation and at least one other copy being in the antisense orientation and wherein said multiple copies are placed operably under the control of a single promoter sequence which is operable in the eukaryotic cell.
2. An isolated genetic construct, wherein said genetic construct comprises multiple copies of a nucleotide sequence of greater than 20 nucleotides which is at least 95% identical to a target gene in a eukaryotic cell or a region thereof, wherein one of the multiple copies is operably connected in the sense orientation to a first promoter sequence and one other of the copies is operably connected in the antisense orientation to a second promoter sequence, wherein said first and second promoter sequences are operable in the eukaryotic cell.
  KR 10-2010-7006892 An isolated genetic construct, wherein said genetic construct comprises multiple copies of a nucleotide sequence of greater than 20 nucleotides which is at least 95% identical to a target gene in a eukaryotic cell or a region thereof, at least one copy being in the sense orientation and at least one other copy being in the antisense orientation and wherein said multiple copies are placed operably under the control of a single promoter sequence which is operable in the eukaryotic cell.
2. An isolated genetic construct, wherein said genetic construct comprises multiple copies of a nucleotide sequence of greater than 20 nucleotides which is at least 95% identical to a target gene in a eukaryotic cell or a region thereof, wherein one of the multiple copies is operably connected in the sense orientation to a first promoter sequence and one other of the copies is operably connected in the antisense orientation to a second promoter sequence, wherein said first and second promoter sequences are operable in the eukaryotic cell.
  NZ 506648 1. A method of repressing, delaying or otherwise reducing the expression of a target gene in a cell, tissue or organ, said method comprising introducing to said cell, tissue or organ one or more dispersed nucleic acid molecules or foreign nucleic acid molecules comprising multiple copies of a nucleotide sequence which is substantially identical to the nucleotide sequence of said target gene or a region thereof or complementary thereto for a time and under conditions sufficient for translation of the mRNA product of said target gene to be modified, subject to the proviso that the transcription of said mRNA product is not exclusively repressed or reduced. 2. The method according to claim 1 wherein the dispersed nucleic acid molecules or foreign nucleic acid molecules comprise inverted repeats of the target gene sequence or a region thereof or complementary thereto. 3. The method according to claim 1 wherein the dispersed nucleic acid molecules or foreign nucleic acid molecules comprise direct repeats of the target gene sequence or a region thereof or complementary thereto. 4. The method according to claim 1 wherein the dispersed nucleic acid molecules or foreign nucleic acid molecules comprise both direct and inverted repeats of the target gene sequence or a region thereof or complementary thereto.
    547283 Disclosed is an isolated nucleic acid molecule comprising a first ribonucleotide (RNA) sequence which is greater than 20~100 nucleotides in length and which is at least 80% identical to the nucleotide sequence of a target gene or a region thereof, and a second RNA sequence which is at least 80% identical to the complement of said nucleotide sequence of the target gene or the region thereof, wherein said nucleic acid molecule is capable of reducing expression of the target gene in a eukaryotic cell when the nucleic acid molecule is introduced into said eukaryotic cell. Also disclosed is a synthetic gene, comprising multiple structural gene regions, wherein each structural gene region comprises an identical nucleotide sequence which consists of greater than 20 consecutive nucleotides which is identical to a nucleotide sequence of a target gene in a eukaryotic cell, wherein one of the structural gene regions is placed in the sense orientation and another of the structural gene regions is placed in the antisense orientation operably under the control of a single promoter sequence which is operable in the cell, and wherein the structural gene region placed in the sense orientation and the structural gene region placed in the antisense orientation are arranged as an interrupted palindrome sequence which is operably under the control of the single promoter sequence.
  SG 75542 1. A method of repressing, delaying or otherwise reducing the expression of a target gene in a cell, tissue or organ, said method comprising introducing to said cell, tissue or organ one or more dispersed nucleic acid molecules or foreign nucleic acid molecules comprising multiple copies of a nucleotide sequence which is substantially identical to the nucleotide sequence of said target gene or a region thereof or complementary thereto for a time and under conditions sufficient for translation of the mRNA product of said target gene to be modified, subject to the proviso that the transcription of said mRNA product is not exclusively repressed or reduced. 2. The method according to claim 1 wherein the dispersed nucleic acid molecules or foreign nucleic acid molecules comprise inverted repeats of the target gene sequence or a region thereof or complementary thereto. 3. The method according to claim 1 wherein the dispersed nucleic acid molecules or foreign nucleic acid molecules comprise direct repeats of the target gene sequence or a region thereof or complementary thereto. 4. The method according to claim 1 wherein the dispersed nucleic acid molecules or foreign nucleic acid molecules comprise both direct and inverted repeats of the target gene sequence or a region thereof or complementary thereto.
    115493 A synthetic genetic construct which is capable of repressing, delaying or otherwise reducing the expression of a target gene in a eukaryotic cell, tissue or organ, wherein the construct comprises multiple copies of a nucleotide sequence of greater than 20 nucleotides which is substantially identical to or complementary to the target gene or a region of the target gene, wherein the multiple copies are placed operably under the control of a single promoter sequence which is operable in the eukaryotic cell, tissue or organ and wherein at least two of the copies are placed operably in the sense orientation under the control of the promoter sequence
2. … wherein at least one of the copies is placed operably in the sense orientation under the control of a promoter
3. …according to claim 2, wherein further at least one other of the copies is placed operably in the antisense orientation under the control of a promoter.
7. …wherein the at least one copy that is placed in the sense orientation…and the at least one other copy that is placed in the antisense orientation.., are spaced from each other by a stuffer fragment comprising a sequence of nucleotides.
The target gene can be endogenous, or a viral gene.
    141233 1. A synthetic gene which is capable of repressing, delaying or otherwise reducing the expression of a target gene in an animal cell
Wherein said gene comprises a nucleic acid molecule comprising multiple copies of a nucleotide sequence of > 20 nts which is substantially identical to a nucleotide sequence of said target gene
Wherein the multiple copies are presented as an interrupted palindrome sequence, and the nucleic acid is operably under the control of a single promoter sequence
2. wherein the target gene is endogenous to the genome of the cell
3. wherein the target gene is non-endogenous to the genome of the cell
7. An isolated animal cell comprising a synthetic gene according to the claims
  SK 287538 There is disclosed a synthetic gene containing a dispersed or foreign deoxyribonucleic molecule, said gene comprising at least two copies of a structural gene sequence where at least 80 percent of the first copy of the structural gene sequence is identical with a nucleotide sequence of the target gene section and at least 80 percent of the second copy of the structural gene sequence is identical with a nucleotide sequence being complementary to a target gene section and wherein the synthetic gene is capable of post-transcription repressing, delaying or otherwise reducing the expression of said target gene if it is exprimed in a host cell of a mammal by sequentially-specific degradation of RNA transcription of the target gene by an endogenous host cell system.; These synthetic genes and gene constructs are capable of repressing, delaying or otherwise reducing the expression of an endogenous gene or a target gene in an organism in which they are introduced. The present invention also relates to a gene construct containing such a synthetic gene and a preparation comprising said synthetic gene.
  UK GB2353282
Request for Revocation received December 2010

A genetic construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a vertebrate animal cell, tissue or organ which is transfected with said genetic construct, wherein said genetic construct comprises one or more dispersed or foreign nucleic acid molecules which include multiple copies of a nucleotide sequence which is substantially identical to the target gene, or a region of said target gene, and wherein at least one of said copies is in the sense orientation and wherein at least one other of said copies is in the antisense orientation.
20.  A genetic construct which is capable of delaying, repressing or otherwise reducing the expression of a target gene in a vertebrate animal cell, tissue or organ which is transfected with said genetic construct, wherein said genetic construct comprises multiple copies of a nucleotide sequence which is substantially identical to said target gene, or a region of said target gene, and wherein said multiple copies are placed operably under the control of a single promoter sequence which is operable in said cell, tissue or organ, wherein at least one of said copies is placed operably in the sense orientation under the control of said promoter sequence, wherein at least one other of said copies is placed operably in the antisense orientation under the control of said promoter sequence, and wherein the at least one copy that is placed in the sense orientation relative to said promoter and the at least one other copy that is placed in the antisense orientation

  US 8168774
Granted May 1, 2012
(11/218,999)

1. A double-stranded DNA construct comprising two copies of a structural gene region whose nucleotide sequence is identical to the nucleotide sequence of a region of a target gene in an animal cell,
wherein one of the two copies is in the sense orientation and the other of the two copies is in the antisense orientation operably under the control of a single promoter sequence which is operable in the cell, and wherein
the copy of the structural gene region in the sense orientation and the copy of the structural gene region in the antisense orientation are arranged as an interrupted palindrome sequence such that the copy of the structural gene region in the sense orientation and the copy of the structural gene region in the antisense orientation are separated and linked by nucleotides other than the nucleotides of the copy of the structural gene region in the sense orientation and the copy of the structural gene region in the antisense orientation.
26. An animal cell having a DNA comprising …
51. A method of modulating the expression of a target gene in an animal cell…

  ZA 2000/04507  

2. WATERHOUSE PATENTS (Benitec Biopharma has an exclusive worldwide license from CSIRO for human therapeutics)

Title, Description, Inventors Country Number Main Claims
METHODS AND MEANS FOR OBTAINING MODIFIED PHENOTYPES

Methods for reducing the phenotypic expression of a nucleic acid of interest in eukaryote cells by providing aberrant RNA molecules, preferably unpolyadenylated RNA molecules comprising at least one target specific nucleotide sequence homologous to the nucleic acid of interest, preferably a sense strand, into the nucleus of plant cells.

Waterhouse, Wang, Graham, (Smith)

 
AU 760041 A method for reducing the phenotypic expression of a nucleic acid of interest, which is normally capable of being expressed in a eucaryotic cell, comprising the step of introducing a chimeric DNA comprising the following operably linked parts: a) a promoter, operative in said eucaryotic cell; b) DNA region, which when transcribed, yields an RNA molecule comprising an RNA region capable of forming an artificial stem-loop structure, wherein one of the annealing RNA sequences of the stem-loop structure comprises a sequence, essentially similar to at least part of the nucleotide sequence of said nucleic acid of interest, and wherein the second of said annealing RNA sequences comprises a sequence essentially similar to at least part of the complement of at least part of said nucleotide sequence of said nucleic acid of interest; and optionally c) a DNA region involved in transcription termination and polyadenylation. 2. A method for reducing the phenotypic expression of a nucleic acid of interest, which is normally capable of being expressed in a eucaryotic cell, comprising the step of introducing a chimeric DNA comprising the following operably linked parts: a) a promoter, operative in said eucaryotic cell; b) a DNA region, which when transcribed, yields an RNA molecule with a nucleotide sequence comprising i. a sense nucleotide sequence of at least 10 consecutive nucleotides having between 75 and 100% sequence identity with at least part of the nucleotide sequence of said nucleic acid of interest; and ii. an antisense nucleotide sequence including at least 10 consecutive nucleotides, having between about 75% to about 100% sequence identity with the complement of said at least 10 consecutive nucleotides of said sense nucleotide sequence; wherein the RNA is capable of forming an artificial hairpin RNA structure with a double stranded RNA stem by base-pairing between the regions with sense and antisense nucleotide sequence such that at least said 10 consecutive nucleotides of the sense sequence basepair with said 10 consecutive nucleotides of the antisense sequence; and optionally c) a DNA region involved in transcription termination and polyadenylation. 3. The method of claim 2, wherein said RNA molecule further comprises a spacer nucleotide sequence located between said sense and said antisense nucleotide sequence.

 

CN ZL99805925.0 (CN1202246-C)

15.  A eukaryotic cell, comprising a nucleic acid of interest, which is normally capable of being phenotypically expressed, further comprising a chimeric DNA molecule comprising the following operably linked parts:
a)  a promoter, operative in said eukaryotic cell;
b)  a DNA region, which when transcribed, yields an RNA molecule with at least one RNA region with a nucleotide sequence comprising
i.  a sense nucleotide sequence of at least 20 consecutive nucleotides of the nucleotide sequence of the nucleic acid of interest; and
ii.  an antisense nucleotide sequence including at least 20 consecutive nucleotides, having 100% sequence identity with the complement of said at least 20 consecutive nucleotides of said sense nucleotide sequence;
  wherein the RNA is capable of forming an artificial hairpin RNA structure with a double stranded RNA stem by base-pairing between the regions with sense and antisense nucleotide sequence; and
c)  a DNA region involved in transcription termination and polyadenylation
wherein the phenotypic expression of said nucleic acid of interest is reduced.
16.  A eukaryotic cell, comprising a nucleic acid of interest, which is normally capable of being phenotypically expressed, further comprising a chimeric RNA molecule comprising at least one RNA region with a nucleotide sequence comprising
i.  a sense nucleotide sequence of at least 20 consecutive nucleotides of the nucleotide sequence of the nucleic acid of interest; and
ii.  an antisense nucleotide sequence including at least 20 consecutive nucleotides, having 100% sequence identity with the complement of said at least 20 consecutive nucleotides of said sense nucleotide sequence;
wherein said RNA is capable of forming an artificial hairpin RNA with a double stranded RNA region by base-pairing between the regions with sense and antisense nucleotide sequence such that at least said 20 consecutive nucleotides of the sense sequence basepair with said 20 consecutive nucleotides of the antisense sequence.

  EP

EP1068311
Accepted
27 April 2011

Currently under opposition at the EPO

A chimeric RNA molecule comprising at least one RNA region with a nucleotide sequence comprising
i.  a sense nucleotide sequence of at least 10 consecutive nucleotides having between 75 and 100% sequence identity with at least part of a coding region of a nucleic acid of interest; said nucleic acid of interest being a gene incorporated in the genome of a eukaryotic cell and
ii.  an antisense nucleotide sequence including at least 10 consecutive nucleotides, having between 75% to 100% sequence identity with the complement of said at least 10 consecutive nucleotides of said sense nucleotide sequence;

wherein the RNA is capable of forming an artificial hairpin RNA structure with a double stranded RNA stem by base-pairing between the regions with sense and antisense nucleotide sequence such that at least said 10 consecutive nucleotides of the sense sequence base pair with said 10 consecutive nucleotides of the antisense sequence.
  NZ 507093 A method for reducing the phenotypic expression of a nucleic acid of interest, which is normally capable of being expressed in a eucaryotic cell, comprising the step of introducing a chimeric DNA comprising the following operably linked parts: a) a promoter, operative in said eucaryotic cell; b) DNA region, which when transcribed, yields an RNA molecule comprising an RNA region capable of forming an artificial stem-loop structure, wherein one of the annealing RNA sequences of the stem-loop structure comprises a sequence, essentially similar to at least part of the nucleotide sequence of said nucleic acid of interest, and wherein the second of said annealing RNA sequences comprises a sequence essentially similar to at least part of the complement of at least part of said nucleotide sequence of said nucleic acid of interest; and optionally c) a DNA region involved in transcription termination and polyadenylation. 2. A method for reducing the phenotypic expression of a nucleic acid of interest, which is normally capable of being expressed in a eucaryotic cell, comprising the step of introducing a chimeric DNA comprising the following operably linked parts: a) a promoter, operative in said eucaryotic cell; b) a DNA region, which when transcribed, yields an RNA molecule with a nucleotide sequence comprising i. a sense nucleotide sequence of at least 10 consecutive nucleotides having between 75 and 100% sequence identity with at least part of the nucleotide sequence of said nucleic acid of interest; and ii. an antisense nucleotide sequence including at least 10 consecutive nucleotides, having between about 75% to about 100% sequence identity with the complement of said at least 10 consecutive nucleotides of said sense nucleotide sequence; wherein the RNA is capable of forming an artificial hairpin RNA structure with a double stranded RNA stem by base-pairing between the regions with sense and antisense nucleotide sequence such that at least said 10 consecutive nucleotides of the sense sequence basepair with said 10 consecutive nucleotides of the antisense sequence; and optionally c) a DNA region involved in transcription termination and polyadenylation. 3. The method of claim 2, wherein said RNA molecule further comprises a spacer nucleotide sequence located between said sense and said antisense nucleotide sequence.

3. BENITEC BIOPHARMA-OWNED PATENTS

Title, Description, Inventors Country Number Main Claims
MULTIPLE PROMOTER EXPRESSION CASSETTES FOR SIMULTANEOUS
DELIVERY OF RNAi AGENTS

(105)

(Licensed to Tacere Therapeutics for HCV)
A genetic construct comprising a multi-promoter expression cassette comprising at

NZ 550284
Granted
13/8/2009
A genetic construct comprising a multi-promoter expression cassette comprising at least three promoter/RNAi/terminator components wherein each promoter/RNAi/terminator component comprises a promoter element, a terminator element and a sequence coding an RNAi species operably linked to the promoter element and the terminator element, at least one of the RNAi species being coded by a sequence of SEQ ID No: 22.
least three promoter/RNAi/terminator components wherein each promoter/RNAi/terminator component comprises a promoter element, a terminator element and an RNAi species operably linked to the promoter element and the terminator element, and wherein each of the RNAi species is different from one another.

 

AU 200522084 Granted
5/8/2010

A genetic construct comprising a multi-promoter expression cassette comprising at least three promoter/RNAi/terminator components wherein each promoter/RNAi/terminator component comprises a promoter element, a terminator element and a sequence encoding an RNAi species operably linked to the promoter element and the terminator element, and wherein at least one of the RNAi species is encoded by SEQ ID NO: 22.

105 diagram

Roelvink, Suhy, Kolykhalov,
EP

1725660
Granted
11 July 2011

A genetic construct comprising a multi-promoter expression cassette comprising at least three promoter/RNAi/terminator components wherein each promoter/RNAi/terminator component comprises a promoter element, a terminator element and a sequence encoding an RNAi species operably linked to the promoter element and the terminator element, wherein the RNAi species target a transcribed nucleic acid sequence and at least one of the RNAi species is encoded by SEQ ID NO: 22.

  JP 2007-502094 A genetic construct comprising a multi-promoter expression cassette comprising at least three promoter/RNAi/terminator components wherein each promoter/RNAi/terminator component comprises a promoter element, a terminator element and a sequence encoding an RNAi species operably linked to the promoter element and the terminator element, wherein at least one of the RNAi species is encoded by SEQ ID NO: 22.
  US

7727970
Granted
June 1, 2010

1.  A method of inhibiting the level of one or more Hepatitis C virus nucleic acid targets that are expressed in a cell comprising contacting the cell with a genetic construct comprising a multi-promoter expression cassette, the multi-promoter expression construct comprising at least three promoter/RNAi/terminator components wherein each promoter/RNAi/terminator component comprises a promoter element, a terminator element and an RNAi sequence, the RNAi sequence operably linked to the promoter element and terminator element, and wherein the RNAi sequences are SEQ ID NO: 6, 19 and 22.
2.  A method of treating an animal cell, tissue or organ, to inhibit the level of one or more Hepatitis C virus nucleic acid targets expressed in a cell, said method comprising introducing to said animal cell, tissue or organ a genetic construct comprising a multi-promoter expression cassette, the multi-promoter expression construct comprising at least three promoter/RNAi/terminator components wherein each promoter/RNAi/terminator component comprises a promoter element, a terminator element and an RNAi sequence operably linked to the promoter element and the terminator element, wherein the RNAi species are SEQ ID NO: 6, 19 and 22.
(NB: Product claims being pursued in 12/723466)

GENETIC SILENCING (106)

A method of inducing, promoting or otherwise facilitating a change in the phenotype of an animal cell or group of animal cells including an animal. The modulation of phenotypic expression is accomplished via genotypic manipulation by inducing, promoting or otherwise facilitating the silencing of expressible genetic sequences thus reducing translation of transcript to protein. Expressible genetic sequences contemplated by the invention include not only genes normally resident in a particular cell (i.e. indigenous genes) but also genes introduced through recombinant means or through infection by pathogenic agents such as viruses.

Graham, Rice, Murphy, Reed

UK GB2377221

1.  A genetic construct comprising a sequence of nucleotides substantially identical to a target endogenous sequence of nucleotides in the genome of a vertebrate animal cell and a nucleotide sequence complementary to said target endogenous nucleotide sequence wherein the nucleotide sequences identical and complementary to said target endogenous nucleotide sequence are separated by a spacer sequence wherein upon introduction of said genetic construct to said animal cell, an RNA transcript resulting from transcription of a gene comprising said endogenous target sequence of nucleotides exhibits an altered capacity for translation into a proteinaceous product.
3.  A genetic construct comprising:
(i)  a nucleotide sequence substantially identical to a target endogenous sequence of nucleotides in the genome of a vertebrate animal cell;
(ii)  a single nucleotide sequence substantially complementary to said target endogenous nucleotide sequence defined in (i);
(iii)  an intron nucleotide sequence separating said nucleotide sequence of (i) and (ii);
wherein upon introduction of said construct to said animal cell, an RNA transcript resulting from transcription of a gene comprising said endogenous target sequence of nucleotides exhibits an altered capacity for translation.
4.  A genetic construct comprising:
(i)  a nucleotide sequence substantially identical to a target endogenous sequence of nucleotides in the genome of a vertebrate animal cell;
(ii)  a nucleotide sequence substantially complementary to said target endogenous nucleotide sequence defined in (i);
(iii)  an intron nucleotide sequence separating said nucleotide sequence of (i) and (ii);

wherein upon introduction of said construct to said animal cell, an RNA transcript resulting from transcription of a gene comprising said endogenous target sequence of nucleotides exhibits an altered capacity for translation into a proteinaceous product and wherein there is substantially no reduction in the level of transcription of said gene comprising the endogenous target sequence and/or total level of RNA transcribed from said gene comprising said endogenous target sequence of nucleotides is not substantially reduced.

 

SG 91678

1.  A genetic construct comprising a sequence of nucleotides substantially identical to a target endogenous sequence of nucleotides in the genome or a vertebrate animal cell and a nucleotide sequence complementary to said target endogenous nucleotide sequence wherein the nucleotide sequences identical and complementary to said target endogenous nucleotide sequences are separated by a spacer sequence wherein upon introduction of said genetic construct to said animal cell, an RNA transcript resulting from transcription of a gene comprising said endogenous target sequence of nucleotides exhibits an altered capacity for translation into a proteinaceous product.
12.  A genetic construct comprising:-
(i)  a nucleotide sequence substantially identical to a target endogenous sequence of nucleotides in the genome of a vertebrate animal cell;
(ii)  a single nucleotide sequence substantially complementary to said target endogenous nucleotide sequence defined in (i);
(iii)  an intron nucleotide sequence separating said nucleotide sequence of (i) and (ii);

wherein upon introduction of said construct to said animal cell, an RNA transcript resulting from transcription of a gene comprising said endogenous target sequence of nucleotides exhibits an altered capacity for transcription.
  ZA 2002/07428

1.  A genetic construct comprising a sequence of nucleotides substantially identical to a target endogenous sequence of nucleotides in the genome or a vertebrate animal cell and a nucleotide sequence complementary to said target endogenous nucleotide sequence wherein the nucleotide sequences identical and complementary to said target endogenous nucleotide sequences are separated by a spacer sequence wherein upon introduction of said genetic construct to said animal cell, an RNA transcript resulting from transcription of a gene comprising said endogenous target sequence of nucleotides exhibits an altered capacity for translation into a proteinaceous product.
12.  A genetic construct comprising:-
(i)  a nucleotide sequence substantially identical to a target endogenous sequence of nucleotides in the genome of a vertebrate animal cell;
(ii)  a single nucleotide sequence substantially complementary to said target endogenous nucleotide sequence defined in (i);
(iii)  an intron nucleotide sequence separating said nucleotide sequence of (i) and (ii);
wherein upon introduction of said construct to said animal cell, an RNA transcript resulting from transcription of a gene comprising said endogenous target sequence of nucleotides exhibits an altered capacity for transcription.

DOUBLE-STRANDED NUCLEIC ACID (107)

(LONG HAIR PIN)
A ribonucleic acid (RNA) for use as interfering RNA in gene silencing techniques to silence a target gene comprising in a 5’ to 3’ direction at least four sequences being a first and second effector sequence 17 to 21 nucleotides in length; a sequence substantially complementary to the second effector sequence; and a sequence substantially complementary to the first effector sequence; wherein the complementary sequences are capable of forming double stranded regions with their respective effector sequences and wherein at least one of the four sequences is substantially identical to the predicted transcript of a region of the target gene; and the RNA further comprising a spacing sequence of one or more nucleotides,  the spacing sequence being located between and spacing the first effector sequence and the second effector sequence, or between the sequence substantially complementary to the second effector sequence and the sequence substantially complementary to the first effector sequence.

Graham, Rice, Roelvink, Suhy, Kolkykhalov, Harrison, Reed.
AU 2004243347

1.  A ribonucleic acid (RNA) for use as interfering RNA in gene silencing techniques to silence one or more target genes comprising in a 5' to 3' direction at least four sequences being:
a first effector sequence;
a second effector sequence;
a sequence substantially complementary to the second effector sequence; and
a sequence substantially complementary to the first effector sequence
wherein the first and second effector sequences are each 17 to 30 nucleotides in length, and
wherein the complementary sequences are capable of forming double stranded regions with their respective effector sequences, and wherein at least one of the four sequences is substantially identical to the predicted transcript of a region of the target gene,
the RNA further comprising a spacing sequence of 1 to 20 nucleotides, the spacing sequence being located between and spacing the first effector sequence and the second effector sequence, or between the sequence substantially complementary to the second effector sequence and the sequence substantially complementary to the first effector sequence.
12.  A double stranded nucleic acid construct including a sequence encoding a ribonucleic acid (RNA) suitable for use as interfering RNA in gene silencing techniques to silence one or more target genes, the construct comprising in a 5' to 3' direction at least four sequences being:
a first effector-encoding sequence;
a second effector-encoding sequence;
a sequence encoding RNA that is capable of forming double stranded regions with RNA encoded by the second effector-encoding sequence; and
a sequence encoding RNA that is capable of forming double stranded regions with RNA encoded by the first effector- encoding sequence,
wherein the first and second effector-encoding sequences are each 17 to 30 nucleotides in length, and wherein at least one of these sequences is substantially identical to a region of the target gene,

the nucleic acid construct further comprising a spacing sequence of one or more nucleotides, the spacing sequence being located between and spacing the first effector sequence and the second effector sequence, or between the sequence substantially complementary to the second effector sequence and the sequence substantially complementary to the first effector sequence.
  NZ 543815

1.  A ribonucleic acid (RNA) for use as interfering RNA in gene silencing techniques to silence a target gene comprising in a 5’ to 3’ direction at least a first effector sequence, a second effector sequence, a sequence substantially complementary to the second effector sequence and a sequence substantially complementary to the first effector sequence, wherein the complementary sequences are capable of forming double stranded regions with their respective effector sequences and wherein at least one of these sequences is substantially identical to the predicted transcript of a region of the target gene, the RNA further comprising a spacing sequence of one or more nucleotides wherein any two of the sequences are spaced by the spacing sequence.
18.  A nucleic acid construct including a sequence encoding a ribonucleic acid (RNA) suitable for use as interfering RNA in gene silencing techniques to silence a target gene, the construct comprising in a 5¢ to 3¢ direction at least a first effector-encoding sequence, a second effector-encoding sequence, a sequence substantially complementary to the second effector-encoding sequence and a sequence substantially complementary to the first effector-encoding sequence, wherein the transcripts of the complementary sequences are capable of forming double stranded regions with the transcripts of their respective effector-encoding sequences and wherein at least one of these sequences is substantially identical to a region of the target gene.

  ZA 2005/09813

.  A ribonucleic acid (RNA) for use as interfering RNA in gene silencing techniques to silence a target gene comprising in a 5’ to 3’ direction at least four sequences being:
a first effector sequence;
a second effector sequence;
a sequence substantially complementary to the second effector sequence; and
a sequence substantially complementary to the first effector sequence;
wherein the first and second effector sequences are each 10 to 200 nucleotides in length; and
wherein the complementary sequence are capable of forming double stranded regions with their respective effector sequences and wherein at least one of the four sequences is substantially identical to the predicted transcript of a region of the target gene
the RNA further comprising a spacing sequence of one or more nucleotides wherein any two of the effector sequences and the sequences substantially complementary to the effector sequences are spaced by the spacing sequence.
17.  A double stranded nucleic acid construct including a sequence encoding a ribonucleic acid (RNA) suitable for use as interfering RNA in gene silencing techniques to silence a target gene, the construct comprising in a 5’ to 3’ direction at least four sequences being:
a first effector sequence;
a second effector sequence;
a sequence encoding RNA that is capable of forming double stranded regions with RNA encoded by the second effector-encoding sequence; and
a sequence encoding RNA that is capable of forming double stranded regions with RNA encoded by the first effector-encoding sequence;
wherein the first and second effector-encoding sequences are each 10 to 200 nucleotides in length, and
wherein at least one of the four sequences is substantially identical to a region of the target gene,

the nucleic acid construct further comprising a spacing sequence of one or more nucleotides wherein any two of the effector encoding sequences are spaced by the spacing sequence.
  SG 200507474-5

1.  A ribonucleic acid (RNA) for use as interfering RNA in gene silencing techniques to silence a target gene comprising in a 5’ to 3’ direction at least four sequences being:
a first effector sequence;
a second effector sequence;
a sequence substantially complementary to the second effector sequence; and
a sequence substantially complementary to the first effector sequence;
wherein the first and second effector sequences are each 10 to 200 nucleotides in length; and
wherein the complementary sequence are capable of forming double stranded regions with their respective effector sequences and wherein at least one of the four sequences is substantially identical to the predicted transcript of a region of the target gene
the RNA further comprising a spacing sequence of one or more nucleotides wherein any two of the effector sequences and the sequences substantially complementary to the effector sequences are spaced by the spacing sequence.
17.  A double stranded nucleic acid construct including a sequence encoding a ribonucleic acid (RNA) suitable for use as interfering RNA in gene silencing techniques to silence a target gene, the construct comprising in a 5’ to 3’ direction at least four sequences being:
a first effector sequence;
a second effector sequence;
a sequence encoding RNA that is capable of forming double stranded regions with RNA encoded by the second effector-encoding sequence; and
a sequence encoding RNA that is capable of forming double stranded regions with RNA encoded by the first effector-encoding sequence;
wherein the first and second effector-encoding sequences are each 10 to 200 nucleotides in length, and
wherein at least one of the four sequences is substantially identical to a region of the target gene,

the nucleic acid construct further comprising a spacing sequence of one or more nucleotides wherein any two of the effector encoding sequences are spaced by the spacing sequence.
RNAi EXPRESSION CONSTRUCTS (single promoter) (114)

Compositions and methods suitable for expressing 1-x RNAi agents against a gene or genes in cells, tissues or organs of

US 7,803,611 Granted 28/9/2010 1.  A 1-x RNAi expression cassette encoding x stem-loop structures, wherein x is two or more, and the stem-loop structures are separated from one another by one or more spacer regions, wherein the stem-loop structures are RNAi agents and at least one of the RNAi agents is encoded by SEQ ID NO:42.
interest in vitro and in vivo so as to treat diseases or disorders.
patentfig1 Roelvink, Suhy, Kolykhalov, Couto
US 8,076,471 Granted
Dec 2011

21.  A genetic construct capable of modifying expression of one or more genes, the genetic construct comprising a 1-x RNAi expression cassette encoding x stem-loop structures, wherein x is two or more, and the stem-loop structures are separated from one another by one or more spacer regions, wherein the stem-loop structures are RNAi agents and at least one stem-loop structure is encoded by SEQ ID NO: 39.
30.  A 1-x RNAi expression cassette encoding x stem-loop structures, wherein x is two or more, and the stem-loop structures are separated from one another by one or more spacer regions, wherein the stem-loop structures are RNAi agents and at least one stem-loop structure is encoded by SEQ ID NO: 39.

  AU 2006210443

1.  A 1-x RNAi expression cassette for targeting multiple regions of a HCV genome comprising:
a promoter;
x RNAi agent coding sequences, wherein x is at least two; and
sequences coding for spacer regions;
wherein transcription of the RNAi agent coding sequences produces RNAi agents which form stem-loop structures, the stem loop structures being spaced  from one another by the spacer regions.
8.  A genetic construct comprising a 1-x RNAi expression cassette for targeting multiple regions of a HCV genome comprising:
a promoter;
RNAi agent coding sequences wherein x is two or more; and
sequences coding for spacer regions;
wherein transcription of the RNAi agent coding sequences produces RNAi agents which form stem-loop structures, the stem loop structures being spaced from one another by the spacer regions.

  NZ 560936
Granted
12/8/2010

1.  A 1-x RNAi expression cassette for targeting multiple regions of a HCV genome comprising:
a promoter;
x RNAi agent coding sequences, wherein x is at least two; and
sequences coding for spacer regions;
wherein transcription of the RNAi agent coding sequences produces RNAi agents which form stem-loop structures, the stem loop structures being spaced  from one another by the spacer regions.
8.  A genetic construct comprising a 1-x RNAi expression cassette for targeting multiple regions of a HCV genome comprising:
a promoter;
RNAi agent coding sequences wherein x is two or more; and
sequences coding for spacer regions;
wherein transcription of the RNAi agent coding sequences produces RNAi agents which form stem-loop structures the stem loop structures being spaced from one another by the spacer regions.

  CN

200680010811.3
April 2012:
Ready for allowance.

Removal of the use of “about” in the claims that define the loops and spacers to be “about 5 to 9 nucleotides” and “about 6 nucleotides” respectively. Deletion of that term should therefore hopefully see this application proceed to allowance.
RNAi EXPRESSION CONSTRUCTS WITH LIVER-SPECIFIC ENHANCER/ PROMOTER

An expression construct comprising: one or more enhancer elements selected from the group consisting of ApoE enhancer elements and SynEnh enhancer elements; one or more liver-specific promoters; and one or more RNAi constructs that provide one or more RNAi agents.

Roelvink, Suhy, Kolykhalov, Kay, Giering
US

8008468
Granted

30 August 2011

 1.  A DNA directed RNA interference (ddRNAi) expression construct comprising:
one or more enhancer elements selected from the group consisting of ApoE enhancer elements and SynEnh enhancer elements;
one or more liver-specific promoters; and
one or more RNAi constructs that provide three or more RNAi agents;

wherein the RNAi agents target hepatitis virus genes that are desired to be repressed in a liver cell or whole liver, and wherein at least one of the three or more RNAi agents is coded by SEQ ID NO: 42.
MINIGENE EXPRESSION CASSETTE

(STANFORD)

Methods and compositions for expressing a gene or nucleotide sequence of interest. The compositions include an expression cassette that includes a synthetic enhancer, a transthyretin promoter, and a nucleotide sequence operably under the control of the synthetic enhancer and the transthyretin promoter. The expression cassette may be used in an AAV vector, such as a self-complementary AAV vector.

Kay, Hebert, Roelvink, Suhy
US

8129510
Granted
6th March 2012

An expression cassette, comprising:
a synthetic enhancer;
a transthyretin promoter; and
a nucleotide sequence operably under the control of the synthetic enhancer and the transthyretin promoter,
wherein the synthetic enhancer and the transthyretin promoter comprise a sequence having at least 95% sequence identity over the entire length of SEQ ID NO:3.

B. PENDING APPLICATIONS

1. GRAHAM

Title, Description, Inventors Country Number Status
SYNTHETIC GENES AND GENETIC CONSTRUCTS COMPRISING THE SAME

A method of modifying gene expression and to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the present invention utilises recombinant DNA technology to post-transcriptionally modify or modulate the expression of a target gene in a cell, tissue, organ or whole organism, thereby producing novel phenotypes. Novel synthetic genes and genetic constructs which are capable or repressing delaying or otherwise reducing the expression of an endogenous gene or a target gene in an organism when introduced thereto are also provided.

Waterhouse, Graham, Wang, Rice

US

90/007,247

Earliest Date Priority
19 Jun 1998

Pending
CONTROL OF GENE EXPRESSION WO99/49029

A method of modifying gene expression and to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the invention utilises recombinant DNA technology post-transcriptionally modify or modulate the expression of a target gene in a cell, tissue, organ or whole organism, thereby producing novel phenotypes. Novel synthetic genes and genetic constructs which are capable or repressing delaying or otherwise reducing the expression of an endogenous gene or a target gene in an organism when introduced thereto are also provided.

Graham, Wang, Waterhouse, Rice

BR PI9908967.0 Under examination
BR PI9917642.4 Awaiting examination
CN 200510083325.1 Pending
CN 200910206175.7 Pending
EP 07008204.5 Pending
EP 10183258.2 Divisional
HG PO5000631 Pending
HG PO101225 Pending
JP 2009-161847 Pending
MX PA/a/2005/
006838
Pending
PL P-377017 Pending

2. WATERHOUSE

Title, Description, Inventors Country Number Status
METHODS AND MEANS FOR OBTAINING MODIFIED PHENOTYPES

Methods for reducing the phenotypic expression of a nucleic acid of interest in eukaryote cells by providing aberrant RNA molecules, preferably unpolyadenylated RNA molecules comprising at least one target specific nucleotide sequence homologous to the nucleic acid of interest, preferably a sense strand, into the nucleus of plant cells.

Waterhouse, Wang, Graham, (Smith)

AU 2007201023 Divisional
CA 2325344 Under examination
JP 2000-543598 Under examination
US 09/287632 Under examination
US 11/364183 Continuation pending
US 11/841737 US20080104732. Divisional, under examination.
     
     

3. BENITEC

Title, Description, Inventors Country Number Status
MULTIPLE PROMOTER EXPRESSION CASSETTES FOR SIMULTANEOUS DELIVERY OF RNAi AGENTS

(105)

(Not available for HCV)

 genetic construct comprising a multi-promoter expression cassette comprising at least three promoter/RNAi/terminator components wherein each promoter/RNAi/terminator component comprises a promoter element, a terminator element and an RNAi species operably linked to the promoter element and the terminator element, and wherein each of the RNAi species is different from one another.

105 diagram

Roelvink, Suhy, Kolykhalov,

EP 11161216 Filed France, UK, Ireland, Switzerland, Luxembourg, Denmark, Spain, Italy, Sweden, Germany, Monaco, Netherlands
CA 2558771 Response to OA filed Dec 2011
CN 200580013979.5 Exam in progress
IL 177862 Exam in progress
KR 2006-7020986 Exam in progress
KR 10-2012-7000533 Filed 6 January 2012
US 12/723466 Filed 22 March 2010, To Constructs
     
     
     
     
GENETIC SILENCING (106)

A method of inducing, promoting or otherwise facilitating a change in the phenotype of an animal cell or group of animal cells including an animal. The modulation of phenotypic expression is accomplished via genotypic manipulation by inducing, promoting or otherwise facilitating the silencing of expressible genetic sequences thus reducing translation of transcript to protein. Expressible genetic sequences contemplated by the invention include not only genes normally resident in a particular cell (i.e. indigenous genes) but also genes introduced through recombinant means or through infection by pathogenic agents such as viruses.

Graham, Rice, Murphy, Reed

 

JP 2011-179375 Pending
BR PI0109269-3 Pending
DOUBLE-STRANDED NUCLEIC ACID (107)
(LONG HAIR PIN)

A ribonucleic acid (RNA) for use as interfering RNA in gene silencing techniques to silence a target gene comprising in a 5’ to 3’ direction at least four sequences being a first and second effector sequence 17 to 21 nucleotides in length; a sequence substantially complementary to the second effector sequence; and a sequence substantially complementary to the first effector sequence; wherein the complementary sequences are capable of forming double stranded regions with their respective effector sequences and wherein at least one of the four sequences is substantially identical to the predicted transcript of a region of the target gene; and the RNA further comprising a spacing sequence of one or more nucleotides,  the spacing sequence being located between and spacing the first effector sequence and the second effector sequence, or between the sequence substantially complementary to the second effector sequence and the sequence substantially complementary to the first effector sequence.

Graham, Rice, Roelvink, Suhy,, Kolkykhalov, Harrison, Reed.

EP 04735856.9 Exam in Progress
CA 2527907 Exam in Progress
JP 2006-508084 Exam in Progress
IL 172191 Exam in Progress
US 12/914893
Continuation of
10/861191
Filed 28/10/2010
RNAi EXPRESSION CONSTRUCTS (single promoter) (114)

Compositions and methods suitable for expressing 1-x RNAi agents against a gene or genes in cells, tissues or organs of interest in vitro and in vivo so as to treat diseases or disorders.

Roelvink, Suhy, Kolykhalov, Couto

HK 08112495.7 Application filed
EP 09015950.0
(Divisional of 06734372.3)
Exam in progress
CA 2596711 Exam requested Feb 3, 2011

 





 

 
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