Bridging the Licensing Gap Between Academia and Industry

The difficulty that academia experiences in licensing technology to industry often lies in the lack of appreciation for what industry requires to justify in-licensing. Considerations such as stage of development, technology niche, value, competitive position, and risk factors will be discussed, and licensing and partnership scenarios presented. Dr. Thuning-Roberson received her Bachelor of Arts degree in Biology from St. Mary-of- the-Woods College, Indiana, in 1967, Medical Technology certification at St. Vincent Charity Hospital, Cleveland, Ohio, in 1968, and Ph.D. degree in Biological Sciences from Nova University, Florida, in 1982. Dr. Thuning-Roberson first published with Dr. William Whalen in the field of physiology with special emphasis on autoregulation of the microvascular system at St. Vincent’s. She joined Goodwin Institute for Cancer Research in 1974 where her research efforts focused on immunology and pharmacology with emphasis on autoimmune diseases and drug synergism in cancer. She was appointed Director of the Institute in 1989, managing a team of 36 people, directing the physical expansion and construction of its operations, and procuring over $8 million in contracts with government and industry. In this position, she was instrumental in the establishment of a GMP manufacturing facility including development of its initial documentation system and filing of three Drug Master Files with the FDA. In 1992, Dr. Thuning-Roberson was responsible for conceiving the business strategy for and co-founding of Goodwin Biotechnology Incorporated, a for profit spin-off from the Institute. As President of GBI, she directed the design and construction of GBI’s GMP Manufacturing Core, thus providing a full integration of services, and managed operations. The company was successful in procuring over 35 industrial contracts for development and manufacture of product for clinical trials. Dr. Thuning-Roberson joined Sunol Molecular in 2000 as Vice President of Product Development and Compliance and manages pre-clinical and clinical development. She is also Chairman of BioFlorida, the state affiliate for BIO, the biotechnology industry organization

Safety and Pharmacokinetics of Chimeric Anti-Shiga Toxin 1 and Anti-Shiga Toxin 2 Monoclonal Antibodies in Healthy Volunteers▿

Shiga toxin (Stx)-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic-uremic syndrome (HUS). The rates of STEC infection and complications, including death, are highest among young children and elderly individuals. There are no causal therapies. Because Stx is the primary pathological agent leading to organ injury in patients with STEC disease, therapeutic antibodies are being developed to neutralize systemically absorbed toxin during the early phase of the infection. Two phase I, single-dose, open-label, nonrandomized studies were conducted to evaluate the safety and pharmacokinetics of the chimeric monoclonal antibodies (antitoxins) against Stx 1 and 2 (cαStx1 and cαStx2, respectively). In the first study, 16 volunteers received 1 or 3 mg/kg of body weight of cαStx1 or cαStx2 as a single, short (1-h) intravenous infusion (n = 4 per group). In a second study, 10 volunteers received a 1-h infusion of cαStx1 and cαStx2 combined at 1 or 3 mg/kg (n = 5 per group). Treatment-emergent adverse events were mild, resolved spontaneously, and were generally unrelated to the antibody infusion. No serious adverse events were observed. Human antichimeric antibodies were detected in a single blood sample collected on day 57. Antibody clearance was slightly greater for cαStx1 (0.38 ± 0.16 ml/h/kg [mean ± standard deviation]) than for cαStx2 (0.20 ± 0.07 ml/h/kg) (P = 0.0013, t test). The low clearance is consistent with the long elimination half-lives of cαStx1 (190.4 ± 140.2 h) and cαStx2 (260.6 ± 112.4 h; P = 0.151). The small volume of distribution (0.08 ± 0.05 liter/kg, combined data) indicates that the antibodies are retained within the circulation. The conclusion is that cαStx1 and cαStx2, given as individual or combined short intravenous infusions, are well tolerated. These results form the basis for future safety and efficacy trials with patients with STEC infections to ameliorate or prevent HUS and other complications

Phase 1 Safety and Pharmacokinetic Study of Chimeric Murine-Human Monoclonal Antibody cαStx2 Administered Intravenously to Healthy Adult Volunteers

Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated cαStx2, that has neutralizing activity in a mouse model was produced and tested in healthy adult volunteers. In this phase I dose escalation study, cαStx2 was generally well tolerated. Pharmacokinetic studies indicated that clearance was stable over the dose range of 1.0 to 10 mg/kg of body weight (0.249 ± 0.023 ml/kg/h) but was higher for the 0.1-mg/kg dose (0.540 ± 0.078 ml/kg/h), suggesting saturable elimination. A similar nonlinear trend was observed for the volume of distribution, where average values ranged from 0.064 ± 0.015 liter/kg for the 1.0- to 10-mg/kg doses and 0.043 ± 0.005 for the 0.01-mg/kg dose. The relatively small volume of distribution suggests that the antibody is limited to the vascular (plasma) compartment. The mean half-life was 165 ± 66 h, with lowest values observed for the 0.1-mg/kg dose (56.2 ± 9.7 h) and the highest values reported for the 10.0-mg/kg dose (206.4 ± 12.4 h). Future studies are needed to confirm the safety of this cαStx2, and innovative clinical trials will be required to measure its efficacy in preventing or treating HUS