Alnylam Releases New Data for Three Preclinical Programs
Alnylam Pharmaceuticals this week announced new preclinical results for its hypercholesterolemia, Huntington's disease, and neuropathic pain programs.
The company said the data were presented at this year’s Keystone Symposium in Keystone, Colo.
The company’s lead compound in its hypercholesterolemia program is ALN-PSC01, which targets PCSK9, a gene involved in the metabolism of low-density lipoprotein cholesterol. According to Alnylam, the new findings show that systemic administration of the drug in mice was “associated with dose-dependent and rapid silencing of the PCSK9 messenger RNA to more than 70 percent of control levels, with peak silencing effects observed as soon as 48 hours after dosing.”
Additionally, a single intravenous injection of the drug led to a greater than 50-perecnt knockdown of PCSK9 over a two-week period. A complete return to normal PCSK9 levels occurred 23 days after dosing.
Alnylam also noted that ALN-PCS01 led to as much as a 30-percent reduction in total cholesterol levels at well-tolerated doses. The company expects to file an investigational new drug application to test ALN-PCS01 in humans sometime this year.
The latest research in Alnylam’s Huntington’s disease program showed that an siRNA targeting the huntingtin gene inhibited the progression of Huntington's disease in a mouse model, the company said.
Preclinical data showed “both a reduction of neuronal pathology and an improvement in abnormal behavior in the disease model with administration of a cholesterol-conjugated siRNA,” Alnylam said. “Pathological protein aggregates in the neuropil were decreased by about 70 percent … [while] two types of abnormal behavior — clasping and footslips — were ameliorated by approximately 50 percent and 70 percent, respectively.”
Lastly, siRNA treatment cut levels of huntingtin mRNA by about 70 percent in the mice.
Alnylam said that these data support further development of an RNAi-based treatment for Huntington’s disease, but did not offer a timeline.
In Alnylam’s neuropathic pain program, new preclinical data demonstrated that an intrathecal injection of an siRNA targeting neuropeptide Y prevented the development of neuropathic pain in a rat model, the company said, adding that a more effective siRNA is slated for in vivo testing.
Alnylam did not offer a timeline for its neuropathic pain program.
Nucleonics Says Patent Office Rejects Benitec IP for Second Time
Nucleonics said this week that the US Patent and Trademark Office has for the second time rejected all remaining claims in a key US patent held by Benitec.
The patent at issue — US patent No. 6,573,099 — covers the knocking down of gene expression using DNA that transcribes double-stranded RNA, one strand of which has a sequence complementary to that of the target gene. It had been one of the earliest issued RNAi-related patents and the centerpiece of Benitec’s intellectual property portfolio.
According to Nucleonics, Benitec can appeal the USPTO decision.
In 2004, Benitec sued three companies for infringing the patent: Nucleonics, Ambion, and GenScript (see RNAi News, 4/2/2005). While Ambion and GenScript took licenses to the patent to settle the issue, Nucleonics filed its own lawsuits and asked the USPTO to reexamine the patent for validity. The patent office eventually rejected claims in the ‘099 patent (see RNAi News, 9/9/2005).
Benitec appealed the USPTO ruling, but has since handed off control of its IP estate to its partner, Australia’s Commonwealth Scientific and Industrial Research Organization, amid a corporate reorganization (see RNAi News, 9/14/2006).
“Nucleonics has always maintained that its freedom to operate is assured through Nucleonics' own intellectual property estate and that Benitec's litigation position was ungrounded,” Bob Towarnicki, president and CEO, of Nucleonics, said in a statement.
“The re-examination process, while still ongoing, is progressing in a direction supporting Nucleonics' contention that its [expressed RNAi] technology platform is free and clear of Benitec's alleged intellectual property,” he added. “We are pleased to see the USPTO issue a second rejection of all Benitec patent claims and look forward to final USPTO rulings as the re-examination process completes."
Officials from Benitec were not available for comment by press time.
Genomics Consortium to Use Invitrogen siRNA Libraries in Screening Work
Invitrogen said this week that it has formed a collaboration with Baylor College of Medicine and the University of Texas at Houston, which are part of the John S. Dunn Gulf Coast Consortium for Chemical Genomics, under which consortium researchers will use the company’s Stealth siRNA libraries and other tools in screening experiments.
"This partnership allows us to work with many key decision makers in the academic marketplace," Lewis Vann, business development manager for Invitrogen's consortium program, said in a statement.
Initial experiments will incorporate Invitrogen's human kinase, human nuclear receptor, and mouse nuclear receptor siRNA collections, the company said. The quantitative effects of the siRNA molecules on gene and protein expression will then be assessed using Invitrogen's SYBR GreenER real-time qPCR technology, as well as image-based tools from its Molecular Probes portfolio.
"Access to Invitrogen's siRNA library and hardware/software resources for screens that reach down to the individual investigator laboratory is very efficient," Michael Mancini, an associate professor in Baylor’s department of molecular and cellular biology and co-director of the GCC-CG, added.
Vanderbilt, University of Michigan Join Sigma’s RNAi Partnership Program
Research centers at Vanderbilt University and the University of Michigan have joined Sigma-Aldrich’s RNAi Partnership Program, part of the RNAi Consortium, the company said last week.
Terms of the membership call for the Vanderbilt-Ingram Cancer and the Comprehensive Cancer Center at the University of Michigan to receive Sigma-Aldrich genomics products, including the TRC shRNA libraries for human and mouse genes, the company said.
Shawn Levy, scientific director of microarray shared resource at the VICC, said the group’s researchers are working on targeted gene-knockdown projects, and said access to the shRNA library will “greatly accelerate their ability to prioritize genes identified from various proteomic and genomic screens."
University of Michigan professor Mikhail Nikiforov said having access to the library is “extremely important for assessing specificity and efficacy of new and existing pharmaceutical agents designed for inhibition of genes and proteins.”
Sigma-Aldrich established the RNAi Partnership Program last year to advance functional genomics research by giving academic researchers access to the company’s new technologies and select IP (see RNAi News, 4/27/2006). Other partnering organizations include Washington University, Princeton University, Rutgers University.