Alnylam, Inex Announce USPTO’s Allowance of Delivery Tech Patent Claims
Alnylam Pharmaceuticals and Inex Pharmaceuticals said this week that the US Patent and Trademark Office has issued a notice of allowance for claims in an Inex patent application covering nucleic acid-lipid compositions, including cationic liposomes, a family of specialized lipid molecules.
These lipid molecules are being used by the companies to deliver siRNA-based drugs.
The patent application, No. 09/431,594, is part of a patent family Inex exclusively licensed from the University of British Columbia. Inex later granted Alnylam an exclusive license to the IP for RNAi drug applications.
The patented technology is currently the subject of a legal dispute between Inex and its former subsidiary, Protiva Biotherapeutics (see RNAi News, 9/14/2006).
Benitec’s 2H 2006 Losses Drop Amid Cost Cutting Effort
Benitec last week reported its financial results for the six-month period ended Dec. 31, 2006, posting a sharply lower net loss despite a drop off in revenues as the Australian firm curbed its expenses as part of a corporate reorganization.
For the six-month period, Benitec’s net loss was Aus$873,816 ($680,222), or Aus$0.05 per share, versus a net loss of Aus$3.9 million, or $2.50 per share, a year earlier.
Benitec’s revenues dropped to Aus$277,811 from Aus$3.6 million in the six months ended Dec. 31, 2005.
Research and development spending, meanwhile, plummeted to Aus$108,727 from Aus$1.7 million, reflecting Benitec’s shuttering of its US operations and cut virtually its entire staff last year in order to reorganize itself as a much smaller, Australian-based biotech (see RNAi News, 6/29/2006).
Benitec ended 2005 with about Aus$1 million in cash and equivalents.
In a letter to shareholders, Benitec Director Peter Francis noted that the company expects to incur additional costs associated with the shutdown of its US facilities.
CytRx Details Employment Agreement with Subsidiary CEO in SEC Filing
CytRx last week reported that Tod Woolf, the newly appointed president and CEO of the company’s pure-play RNAi drugs spinout RXi Pharmaceuticals, has signed an employment agreement that would keep him at the helm of the new firm until the end of next year.
In a filing with the US Securities and Exchange Commission, CytRx also noted that Woolf would receive an annual salary of $250,000.
Rosetta Announces Close of IPO’s Over-Allotment Option
Rosetta Genomics said this week that it has closed on the sale of 562,500 shares of its common stock pursuant to the exercise of an over-allotment option granted to the underwriters of its recently completed initial public offering (see RNAi News, 3/1/2007).
With the closing of this purchase, a total of 4.3 million of Rosetta’s common shares were sold in the IPO, resulting in gross proceeds of $30.2 million. Rosetta said the net proceeds of the offering are $26.2 million.
Isis’ Q4 Losses Rise on Lower Revenues, Higher Expenses
Isis Pharmaceuticals this week released its financial results for the fourth quarter, posting higher losses on lower revenues.
For the fourth quarter, Isis’ net loss was $14.1 million, or $0.18 per share, versus a year-ago loss of $7.9 million, or $0.11 per share.
Revenues in the quarter dropped to $11.9 million from $14.6 million, primarily due to a decrease in revenues associated with Isis’ antisense collaboration with Eli Lilly.
Expenses, meanwhile, edged up to $28.7 million from $23.2 million, in part reflecting a rise in research and development costs to $24.4 million from $21 million in the fourth quarter of 2005.
As of Dec. 31, 2006, Isis had cash, cash equivalents, and short-term investments totaling $193.3 million.
Pharma Impressed With Cell-Based RNAi Screens, But Acknowledges Limits
Pharmaceutical firms think cell-based RNAi screens are valuable drug-discovery tools, but are finding that the approach still has a number of limitations, according to speakers at Cambridge Healthtech Institute’s Molecular Medicine Tri-Conference, held in San Francisco last week.
Several speakers at the conference noted a number of advantages of cell-based RNAi screens over small-molecule screening for target identification, Cell-Based Assay News, a sister publication of RNAi News, reported last week. The reasons include the fact that most cell types are amenable to RNAi, it’s relatively easy to knock down any gene of interest, and the resulting data is extremely informative.
The approach still has some limitations, however, most notably RNAi’s well-known tendency to produce off-target effects. In addition, several speakers discussed challenges related to the cells themselves, according to Cell-Based Assay News.
For example, John Reidhaar-Olson, research leader in the department of research informatics for genetics and genomics at F. Hoffman-La Roche, noted that cell-based RNAi assays are particularly prone to edge effects because the cells in the outer wells of the plates grow at a different rate than the cells in the inner wells. As a result, his group usually ignores the outer wells in most studies, he said.
Steven Haney, group leader in oncology genomics in the department of biological technologies at Wyeth Research, said that his lab has had problems with the “penetrance” of some RNAi screens, in which the level of GFP in the cells is heterogeneous, making it difficult to interpret.
After further study, Haney said his team found that the expression levels of several proteins varied significantly within cells grown in culture, meaning that the problem is not heterogeneity of the siRNA knockdown, but heterogeneity of protein expression.
The issue is an “artifact of the cell culture itself,” Haney said, perhaps due to the fact that cells proliferate faster in culture than they would under normal biological conditions. While low penetrance can ultimately “reduce the impact of the data” from an assay, Haney said that his group has found they can improve their analysis of the data by looking at single cells rather than entire wells.
Michael Byrne, director of biochemistry at Altana Pharma, discussed another challenge related to cell lines. In this case, Altana was using the LAD 2 cell line in an RNAi screen to identify kinases related to mast cell degranulation. The problem, he said, is that LAD 2 is “a difficult cell line to work with” and “notoriously difficult to transfect.”
While the Altana team was able to account for these challenges in its assay, siRNA transfection caused a very strong interferon stress response in the cells – an unexpected side effect, Byrne said.
While the researchers first feared that this effect might be a “showstopper,” Byrne said that after further study, they found that the effects of degranulation could be “uncoupled” from the stress response, permitting them to proceed with the assay. Ultimately, he said, they were able to identify 10 novel kinase targets “that we wouldn’t have found any other way.”