Alnylam Pharmaceuticals Inc. in-licensed intellectual property that could prove helpful in one of its drug discovery collaborations.

The Cambridge, Mass.-based company gained exclusive access from Hybridon Inc. to patents that protect targets to vascular endothelial growth factor (VEGF) for ocular indications with RNA interference molecules. In exchange for out-licensing its intellectual property related to the therapeutic use of oligonucleotides (including antisense and RNAi compounds), which inhibit the production of VEGF, Hybridon received an undisclosed up-front payment and is eligible for future milestone payments and royalties.

Acquiring the rights makes sense on a couple of levels for Alnylam, given its focus on RNAi drug development, perhaps most notably as it relates to its partnership with Merck & Co. Inc. First reported earlier this summer, that relationship is directed at the development of an RNAi therapeutic for age-related macular degeneration and other ocular diseases.

"[The in-licensing transaction] is part of an overall attractive IP position that we've built that helps us form partnerships with pharma companies," Vincent Miles, Alnylam's senior vice president of business development, told BioWorld Today. He said the intellectual property on small interfering RNA and chemical modifications, specific intellectual property relating to VEGF from Hybridon and other siRNA applications give Alnylam a "strong IP position we felt we needed, and obviously Merck was happy to see for our AMD program."

He noted that for some time, Alnylam has employed an overall strategy of gaining intellectual property that features three components. The first relates to rights that cover fundamental aspects of siRNA and their use as drugs. The next element relates to chemical modification. Both intellectual property categories apply to all programs in development at the company. Lastly, Alnylam seeks to acquire rights to target-specific patents, as it did in the transaction with Hybridon.

"In this particular case, Hybridon has been active in antisense for many years," Miles said. "On the basis of work they had done with antisense oligonucleotides targeted toward VEGF, they were able to get broad, issued claims covering therapeutic uses of VEGF-specific oligonucleotides for diseases that we are interested in, in particular, ocular diseases like age-related macular degeneration and diabetic retinopathy."

Alnylam's ocular disease collaboration with Whitehouse Station, N.J.-based Merck follows a broader agreement between the companies, reached almost a year ago, to find therapies for a variety of indications. That deal marked the first major biotech-pharmaceutical collaboration focused on RNAi therapeutics. (See BioWorld Today, Sept. 10, 2003.)

In their more targeted arrangement, the partners expect to enter the clinic with an AMD therapy by the end of next year. On a slightly broader scope, the collaboration relates to ocular diseases with micro-vascular components caused by abnormal growth or leakage of blood vessels. Diabetic retinopathy also fits into that category, though Miles declined to specify whether the partners also would tackle that indication. (See BioWorld Today, July 1, 2004.)

Outside the Merck collaboration, Alnylam is working with the Mayo Clinic in Rochester, Minn., to develop an RNAi product for Parkinson's disease. Still in early preclinical research, the partners are working to silence the alpha-synuclein gene; its overexpression is implicated in the cause of the disease, the death of dopamine-producing neurons.

For Hybridon, which also is based in Cambridge, the out-licensing deal allowed it to move its series of patents and patent applications into hands that will put them to near-term use.

"We have a very substantial patent portfolio, and in keeping with our strategy to promote that portfolio as much as possible, we clearly can't develop everything ourselves," Robert Anderson, Hybridon's chief financial officer and vice president of operations, told BioWorld Today. "This is a great opportunity to work with a company that we have a lot of respect for and will take this technology forward. We wouldn't be able to do that for quite some time."

The company is developing therapeutics through two technology platforms, including the use of antisense technology that uses synthetic DNA to block the production of disease-causing proteins at the cellular level. Internally, it has completed Phase I evaluations of a second-generation antisense oligonucleotide called GEM231, which is targeted to protein kinase A, in combination with irinotecan. Partnered antisense programs include oncology work with Aegera Therapeutics Inc., of Montreal, and research in human papillomavirus with Micrologix Biotech Inc., of Vancouver, British Columbia.

Its other technology platform stems from the use of synthetic immunomodulatory oligonucleotide (IMO) motifs that act to modulate responses of the immune system. Hybridon is putting together Phase II plans in solid-tumor cancer patients with HYB2055 (IMOxine), a second-generation IMO, with the aim of soon launching the studies. The same product is the subject of a partnership with The Immune Response Corp., of Carlsbad, Calif., in which it is called Amplivax and used as an adjuvant for HIV.

"And we're delighted to work with Alnylam," Anderson said, "as we apply the technology as broadly as we can."

On Wednesday, Alnylam's stock (NASDAQ:ALNY) lost 10 cents to close at $5.25. Hybridon's shares (AMEX:HBY) fell 1 cent to close at 45 cents.

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