• Aastrom Biosciences Inc., of Ann Arbor, Mich., and the Institut de Terapia Regenerativa Tissular have begun patient enrollment in a trial with the Institut de Cirugia Maxilofacial e Implantologia in Barcelona, Spain, testing Aastrom's Tissue Repair Cells (TRCs) in maxillary sinus lift bone graft procedures for dental implants. The study will target areas in the upper jaw where bone has thinned due to premature tooth loss and surgery is required to replace the teeth. It will examine TRCs' ability to regenerate and thicken the maxillary sinus bone and is the fourth clinical trial testing the technology to generate local bone tissue.

• Arena Pharmaceuticals Inc., of San Diego, said that Merck & Co. Inc., of Whitehouse Station, N.J., extended and increased research funding under their existing cardiovascular collaboration until October 2007, and expanded the scope of the collaboration to include a wider range of potential therapies for cardiovascular diseases. Merck also purchased $7.5 million of Arena common stock at $8 per share, representing a 70 percent premium to the prior day's closing price. Under the amended collaboration, Merck will fund $5.7 million a year for collaboration research at Arena. The amendment also limits the circumstances by which Merck can terminate the research funding and improves Arena's royalty terms.

• Biolog Inc., of Hayward, Calif., received a Small Business Technology Transfer grant from the National Institutes of Health to work with Washington University in St. Louis to develop its Phenotype MicroArray technology to test microbial cells, particularly bacteria, yeast and filamentous fungi. The system will be applied to Helicobacter pylori and Campylobacter jejuni. Biolog said near-term applications include using PMs to determine the effect of genetic changes on cells and the results of drugs on cells.

• Cleveland Clinic, of Cleveland, said its researchers believe a gene they discovered last year, confirmed as a cause of heart disease in humans, is more prevalent in Americans than first thought, with as many as 1 to 2 percent of all heart attack and coronary artery disease patients in the U.S. carrying mutations of the MEF2A gene. Findings are published online in the Oct. 20, 2004, issue of Human Molecular Genetics.

• Clinical MicroArrays Inc., of Natick, Mass., closed a $7.5 million Series A round led by Oxford Bioscience Partners. Rock Maple Ventures, Fletcher Spaght Venture Partners and individual investors led by the company's chairman, Jean Montagu, also participated. Oxford's Michael Lytton and Rock Maple's Jason Henrichs joined Clinical MicroArrays' board, which also added Caroline Popper, previously with MDS Proteomics. The company develops multiplexed protein biomarker immunoassay systems.

• CytoGenix Inc., of Houston, entered an agreement with the Section of Pediatric Infectious Diseases of Baylor College for mice and cell studies using its antimicrobial agent against a strain of Staphylococcus aureus. The company's products are based on its DNA-expression technology.

• Genaissance Pharmaceuticals Inc., of New Haven, Conn., and Pyxis Genomics Inc. signed a multiyear deal in which Genaissance will provide its high-throughput genotyping services to Pyxis for the commercialization of the company's Profile-1 system. Comprised of a panel of SNPs and a search engine and database created by IBM Life Sciences, the system tracks animals and meat products through production and distribution. The companies collaborated on validating the assays and expect commercial samples later in the quarter. Pyxis will pay Genaissance a fee per test. Separately, Genaissance decreased its revenue guidance for 2004 from $25 million to between $20 million and $21 million, including the acquisition of Lark Technologies Inc. in April. On a pro-forma basis the updated revenue guidance, previously $27 million, now is $22 million to $23 million. The adjustments resulted from changes in the timing of specific contracts and receipt of related samples, the company said. It will share third-quarter results on Nov. 9. Genaissance's stock (NASDAQ:GNSC) lost 35 cents Wednesday, or 12.6 percent, to close at $2.43.

• Genencor International Inc., of Palo Alto, Calif., and colleagues from the Department of Energy's National Renewable Energy Laboratory (NREL) said completion of collaborative work on converting biomass to ethanol reduces the costs of enzymes to enable a process using cellulosic biomass, such as agricultural waste, to make ethanol. Genencor said it achieved about 30-fold improvement over the NREL's cost model per gallon of ethanol.

• Icoria Inc., of Research Triangle Park, N.C., raised $5 million in gross proceeds through the sale of a three-year secured convertible term note in a private placement with Laurus Master Fund Ltd. The note is payable in cash or can be converted into Icoria common stock at a fixed conversion price of 53 cents per share beginning May 2005. The initial interest rate is 2.5 percent, subject to fluctuations in Icoria's share price. The company also issued warrants for about 1.65 million shares of common stock at a weighted average price of 79 cents. Equal amounts of the warrants expire two and five years following issuance.

• Insmed Inc., of Richmond, Va., granted exclusive marketing rights to SomatoKine to Tzamal Pharma, of Petah Tikva, Israel, for certain Middle Eastern territories including Israel. Insmed also granted Tzamal exclusive rights to expand Insmed's named-patient program for the IGF-I replacement therapy in those Middle Eastern territories. Financial terms were not disclosed.

• Integrated BioPharma Inc., of Hillside, N.J., said its wholly owned biotech subsidiary, INB Biotechnologies Inc., entered an agreement with Fraunhofer USA Inc., of Newark, Del., to develop a flu vaccine using transient expression vectors based on plant viruses. Financial terms were not disclosed, but INB Biotechnologies said it would use the same technology for the flu vaccine that is being developed for an oral anthrax vaccine as part of a Cooperative Research and Development Agreement with the U.S. Navy.

• Isolagen Inc., of Houston, said it plans to establish a cGMP facility in the Northeast as the primary manufacturing facility and headquarters in the U.S. for the global commercialization of the Isolagen Process. The effort will be to minimize local production facilities, while improving the processing and delivery for the technology being tested in a Phase III SPA program. The company, which has decided to close its Australian facility though it will retain a lab in Houston, expects to file a biologics license application in the second half of 2005. The autologous cellular system technology extracts patients' collagen-producing cells and reintroduces replicated versions in the affected area via injection.

• Lilly ICOS LLC, the joint venture between Eli Lilly and Co., of Indianapolis, and ICOS Corp., of Bothell, Wash., released third-quarter financial results featuring $154.1 million in worldwide sales of Cialis (tadalafil), its erectile dysfunction drug, compared to $50.2 million in last year's third quarter. The company projects 2004 Cialis sales to range from $500 million to $600 million.

• NPS Pharmaceuticals Inc., of Salt Lake City, reported data at the American College of Rheumatology meeting in San Antonio showing that its anabolic agent can reduce the risk of a first vertebral fracture in postmenopausal osteoporotic women. The findings are additional results from the company's pivotal Phase III TOP study of Preos (parathyroid hormone), which also reduced the incidence of new vertebral fractures in patients who already had fractured.

• OctoPlus Technologies BV, of Leiden, the Netherlands, entered a collaboration to develop and market a new injectable drug delivery platform with InnoCore Technologies BV, of Groningen, the Netherlands. The platform is based on SynBiosys, a biodegradable polymeric system that enables development of controlled-release formulations of peptides and small molecules, and complements OctoPlus' existing PolyActive and OctoDEX drug delivery platforms. Financial terms were not disclosed.

• Royal Adelaide Hospital in Adelaide, Australia, reported data at the American College of Rheumatology meeting in San Antonio showing that bosentan (Tracleer, from Actelion Ltd.) improves patient quality of life in the treatment of pulmonary arterial hypertension related to connective tissue diseases. In a study called VITAL, patients with pulmonary arterial hypertension and scleroderma treated with bosentan significantly improved at three months compared to baseline measures, particularly in terms of physical function (p<0.0001), social function (p=0.002), vitality (p=0.02), emotional role (p=0.03) and physical role (p<0.0001). The results were maintained or improved out to six months.

• Transkaryotic Therapies Inc., of Cambridge, Mass., said the House of Lords ruled in TKT's favor in a patent-infringement suit involving Sanofi-Aventis Group, of Paris, and Amgen Inc., of Thousand Oaks, Calif. Earlier the house upheld a unanimous appeals court decision that Dynepo-related activities, TKT's gene-activated erythropoietin product for anemia, did not infringe on Amgen's European patent. The court invalidated the patent, stating that after creating a process for making EPO and its analogues, Amgen mistakenly tried to patent the protein that, even when isolated, was not new, TKT said. TKT said it remains on track to make Dynepo (epoietin delta) available to the European Union market in late 2005 or early 2006. (See BioWorld Today, Oct. 19, 2004.)

• Washington University School of Medicine in St. Louis and the University of Pennsylvania in Philadelphia said their researchers published findings in this month's issue of Nature Medicine detailing their discovery of an immune system cell that can remember a parasite's attack and help the body mount a more effective defense against subsequent invasions by the same parasite. In their studies, in mice that had cleared the Leishmania parasite, the CD4+ central memory T cell still reacted to the parasite in the test tube. Mice that never had Leishmania and were given injections of those T cells fought off the parasite more effectively than mice that didn't get the T cells.

• Zonagen Inc., of The Woodlands, Texas, filed a registration statement with the SEC for a public offering of 4 million shares of common stock. Zonagen has granted the underwriter an option to purchase up to 600,000 additional shares to cover overallotments. Punk, Ziegel and Co. is the managing underwriter.