Several years before the global scientific community accepted the reality of RNAi in mammalian cells, Benitec was the first to show the universality of RNAi by demonstrating the down-regulation of target gene expression in human and mammalian cells, inventing a reliable means of triggering the RNAi process using DNA constructs. Benitec's core patents and patent rights are based on this early research and are supported by subsequent filings that extend the scope and jurisdiction of its intellectual property.
Benitec's patent estate represents a dominant position in DNA-directed gene silencing, and potentially the dominant position in RNAi applications for humans and mammals. Benitec has over 60 filed patents and has licensed several additional patents that extend the scope of its patent estate and enhance the utility and value of ddRNAi.
Benitec's main patented technology is DNA-directed RNAi, whereby transiently transfected or stably integrated DNA constructs are transcribed to form double-stranded RNA that induces gene silencing. The issued claims cover the design of such DNA constructs, whether they are inverted repeats coding for hairpin RNA or sense and antisense sequences under the control of separate promoters and regardless of the means of delivery.
On June 4 and 5, 2003, Benitec was awarded the first US and UK patents for the application of RNA interference to mammalian cells. Benitec's ddRNAi patent estate currently comprises 10 issued patents, covering 19 jurisdictions.
In addition to its patents, Benitec has significant proprietary know-how in the design, development and production of constructs, tools and high throughput methodologies for the use and practice of RNA interference.
RNAi patents - Among the companies, Alnylam and Benitec have strong patent positions.
On 5 June 2003, Benitec Ltd was granted its core technology patents in the US and the UK. These patents, with priority dating to 1998, describe a method for silencing any gene in any cell using ddRNAi. US Patent 6,573,099 is entitled "Genetic constructs for delaying or repressing the expression of a target gene" and UK Patent 2353282 is entitled "Control of gene expression". Both patents contain world first claims that describe the effect of RNAi in human cells and the DNA constructs which trigger RNAi.
Benitec Ltd, originally founded in Australia in 1997 (listed on Australian Stock Exchange), pioneered ddRNAi and was the first company to demonstrate RNAi in human cells. It holds a dominant international intellectual property position in RNAi...
Benitec's technology has the potential to treat human disease as a form of gene therapy. The types of diseases amenable to treatment with the company's gene silencing technology include; cancers where the shutdown of oncogenes can lead to disease remission; autoimmune disorders where the knockdown of specific immune system genes can reverse the disease process; and chronic degenerative viral infections where programming cells to silence critical viral genes can prevent infection.
Published with permission from Professor Jain's report entitled "RNAi- Technologies, Companies and Markets, Jain PharmaBiotech, Basel, Switzerland, August 2006.
| Patent/Application Number | Invention Title | Inventor(s) | Patent Summary |
| US 6,573,099 | GENETIC CONSTRUCTS FOR DELAYING OR REPRESSING THE EXPRESSION OF A TARGET GENE* | Graham, Michael W Rice, Robert N | The present invention relates generally 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 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. |
PCT/ AU99/00195 (WO99/49029) AU 2005202658 AU 2005211538 AU 2005209648 AU 2007201023 AU 2008249157 BR PI9908967.0 BR PI9917642.4 CA 2487328 CA 2513336 CN 99804255.2 CN 200510083325.1 EP 04015041.9 EP 05013010.3 EP 07008204.5 HG PO101225 HG PO5000631 IN 2000/00169/DE IN 3413/DELNP/2005 IN 3901/DELNP/2005 JP 2000-537990 JP 2005-223953 JP 2007-302237 JP 2009-161847 KR 7010419/00 KR 7005341/2006 MX PA/a/2000/008631 MX PA/a/2005/006838 NZ 547283 PL P-343064 PL P-377017 SG 200205122.5 SG 30312226 SL PV1372-2000ZA 2000/4507 |
CONTROL OF GENE EXPRESSION * | Graham, Michael W Rice, Robert N Waterhouse, Peter Wang, MingBo | The present invention relates generally to 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 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. |
US 10/821,726 US 10/646,070 US 10/759,841 US 10/346,853 US 11/218,999 |
SYNTHETIC GENES AND GENETIC CONSTRUCTS COMPRISING THE SAME* | Waterhouse, Peter Graham, Michael Wang, MingBo Rice, Robert N |
The present invention relates generally to 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. |
PCT/AU2001/000297 UK GB2377221SG P-91678 ZA 2002/7428 BR 0109269-3 JP 2001-569332 |
GENETIC SILENCING | Graham, Michael W Rice, Robert N Reed, Kenneth C Murphy, Kathleen | The present invention relates generally to a method of inducing, promoting or otherwise facilitating a change in the phenotype of an animal cell or group of animal cells including a animal comprising said cells. The modulation of phenotypic expression is conveniently accomplished via genotypic manipulation through such means as reducing translation of transcript to proteinaceous product. The ability to induce, promote or otherwise facilitate the silencing of expressible genetic sequences provides a means for modulating the phenotype in, for example, the medical, veterinary and the animal husbandry industries. The modulation of phenotypic expression may be achieved with a genetic construct comprising a nucleotide sequence substantially identical to an endogenous target sequence of nucleotides in the genome of a mammalian cell, and a nucleotide sequence substantially complementary to said endogenous target nucleotide sequence, wherein the nucleotide sequences are separated by a spacer sequence, and 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. Expressible genetic sequences contemplated by the present invention including not only genes normally resident in a particular animal cell (i.e. indigenous genes) but also genes introduced through recombinant means or through infection by pathogenic agents such as viruses. |
PCT/AU04/00075 US 10/861191CA 2527907 EP 04735856.9 IL 172191 JP 2006/508084 SG 200507474-5 ZA 2005/09813 AU 2004243347 AU 2009202763 NZ 543815 NZ 575242 |
DOUBLE-STRANDED NUCLEIC ACID | Graham, Michael W Rice, Robert N Roelvink, Petrus W Suhy, David A Kolkykhalov, Alexander A Harrison, Bruce T Reed, Kenneth C. | The invention is directed towards constructs for RNAi techniques. The invention provides 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. |
| PCT/US2005/0017447 US 11/072592 AU 2005222084 CA 2558771 CN 0580013979.5 EP 05727680.0 IL 177862 JP 2007-502094 KR 20067020986 NZ 550284 NZ 575361 |
MULTIPLE PROMOTER EXPRESSION CASSETTES FOR SIMULTANEOUS DELIVERY OF RNAI AGENTS | Roelvink, Petrus W Suhy, David A Kolkykhalov, Alexander A | The present invention provides multiple-promoter expression cassettes for simultaneous delivery of RNAi, preferably to mammalian cells in vivo. In one preferred embodiment of the invention the genetic construct comprises 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. Other RNAi species are preferably encoded by SEQ ID NO: 6 and/or 19. |
| PCT/US2005/038139 AU 2005299672 CA 2583826 SG 200702839-2 EP 05812449.6 |
THERAPEUTIC RNAi AGENTS FOR TREATING PSORIASIS | Reed, Kenneth C.; Brashears, Sarah J. | The present invention provides compositions and methods suitable for delivering RNAi agents against genetic targets in skin tissues so as to treat psoriasis. A number of genetic constructs may be used to express the RNAi agents in the cell. |
| PCT/US2006/000091 AU 2006204120 CA 2593509 US 11/794726 IL 184434 JP 2007-550422 SG 200704975-2 EP 06717315.3 |
RNAi AGENTS FOR MAINTENANCE OF STEM CELLS | Evertsz, Elizabeth Brashears, Sarah J |
The present invention provides compositions and methods suitable for delivering RNAi agents against genetic targets in stem cells so as to direct cell growth and differentiation. A number of genetic constructs may be used to express the RNAi agents in the cell. |
| PCT/US2006/004003 US 11/347028 US 11/883645 CN 200680010811.3 HK 08112495.7 EP 06734372.3 CA 2596711 AU 2006210443 IL 185315 NZ 560936 |
RNAi EXPRESSION CONSTRUCTS | Roelvink, Petrus W Suhy David A Kolkykhalov, Alexander A Couto, Linda |
The present invention provides compositions and methods suitable for expressing 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. In one preferred embodiment of the invention the genetic construct comprises an RNAi expression cassette encoding two or more RNAi agents, the RNAi expression cassette comprising a promoter for promoting expression of the two or more RNAi agents, the RNAi agents when expressed each comprising a stem-loop structure, wherein the stem loop structures of the RNAi agents are separated by one or more spacer regions, and wherein at least one of the stem-loop structures is encoded by a sequence according to SEQ ID No: 6 or SEQ ID No: 42. Other RNAi species are preferably encoded by SEQ ID NO: 39. |
US 11/355516 |
RNAi EXPRESSION CONSTRUCTS WITH LIVER-SPECIFIC ENHANCER/PROMOTER |
Roelvink, Petrus W Suhy, David A Kolykhalov, Alexander A Kay, Mark A Giering, Jeffery C |
The present invention provides compositions and methods suitable for RNAi specifically in the liver so as to treat diseases or disorders. The DNA directed RNA interference (ddRNAi) expression construct comprise specific enhancer elements and promoters for liver expression. The RNAi agents encoded by the construct target hepatitis virus genes that are desired to be repressed in a liver cell or whole liver. |
PCT/US2006/016507 |
MULTIPLE RNAi EXPRESSION CASSETTES FOR SIMULTANEOUS DELIVERY OF RNAi AGENTS RELATED TO HETEROZYGOTIC EXPRESSION PATTERNS |
Evertsz, Elisabeth Brashears, Sarah J |
The present invention provides compositions and methods suitable for expressing multiple RNAi agents against an allele or alleles of interest in a heterozygotic allelic pair so as to treat diseases, without affecting the expression of the other allele in the heterozygotic pair. The expression constructs preferably allow for stable expression of the RNAi agents. |
US 11/731198 |
MINIGENE EXPRESSION CASSETTE |
Kay, Mark A Hebert, Michael L Roelvink, Petrus W Suhy, David A |
The present invention provides compositions and methods suitable for RNAi specifically in the liver so as to treat diseases or disorders. 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 adeno-associated viral (AAV) vector, such as a self-complementary AAV vector. |
