There are only a few inventions that have been licensed ten or more times (have been licensed to >= 10 companies). These are all NIH inventions and include:
* Vaccinia virus vectors - A 1992 patent application with 22 licenses granted, "Recombinant Vaccinia Virus Containing a Chimeric Gene Having Foreign DNA Flanked by Vaccinia Regulatory DNA," invented by Dr. Moss, et al., NIAID. This concerns vaccinia virus vectors for recombinant protein expression by transformed mammalian cells. This technology is widely used for mammalian cell culture production of human and other proteins with glycosylation and structures similar to native proteins. Many companies appear to be using this for production of antigens, immunodiagnostics, vaccines and reagents. Licensees using vaccinia virus expression systems include Chiron Corp. (developing a hepatitis C virus vaccine) and Immuno AG (developing a HIV gp160 vaccine).
* Breast carcinoma monoclonal antibodies - Two related patents (1985 and 1986) with 20 nonexclusive licenses and one exclusive license (for a specific field of use) each, invented by Dr. J. Schlom, et al., NCI. These concern TAG-72 monoclonal antibodies selective for breast carcinoma tissue, useful for assays, diagnostics, immunotoxins and radioimmune conjugates. Most licensees are using these antibodies for screening of potential breast cancer treatments or development of breast cancer immunodiagnostics. Using related second-generation antibodies, NeoRx Corp., along with Boehringer Ingelheim GmbH, is developing TAG-72 antibody-radioisotope (radioimmune) conjugates for cancer diagnosis and tumor detection; Neoprobe Corp., along with Dow Chemical, is developing hand-held devices (RIGS) for visualization of tumors during surgery; and Enzon Corp. is developing radioimmune conjugates for tumor detection and cancer diagnosis.
* HIV - Five related patents (the first issued in 1985) with from 12 to 17 nonexclusive licenses each, invented by Dr. R. Gallo, et al., NCI. These concern the discovery of HIV, its culturing and the production of viral antigens and immunodiagnostics for HIV-infection. HIV patents are now co-assigned to PHS/NIH and the Institut Pasteur (Paris, France) and a dispute over credit for discovery of HIV and division of royalties was resolved this summer. HIV patent licenses are by far the most lucrative of all federal invention licenses. PHS/NIH has collected about $20 million and Institut Pasteur about $14 million since these inventions were first licensed in the mid-1980s. The recent settlement will redistribute royalties so that each party gets a more equal share over the life of the patent. The great majority of blood test kits for screening and diagnosis of HIV-infection are based on the detection of human HIV antibodies reacting with HIV antigens produced using this technology.
* Muscarinic acetylcholine receptors - A patent application (1992) with 16 nonexclusive licenses, invented by Dr. T.I. Bonner, et al., shared by NINDS and NIMH. This concerns cloned muscarinic acetylcholine receptors and cell lines expressing these. These nerve receptor genes, expressed and synthetic proteins, antibodies, oligonucleotide probes and stable cell lines expressing specific subtypes of muscarinic acetylcholine receptors are useful for the screening of potential treatments and the development of diagnostics for muscarinic receptor-associated and parasympatholytic disorders.
* Capillary bioreactors - A 1975 patent (now expired) with 14 nonexclusive licenses, invented by Dr. R.A. Knazek, et al., NCI. This concerns woven fiber capillary bioreactors widely used for eukaryotic, mammalian and other cell culture. Bioreactors based on this technology with capacities ranging from lab desktop to large-scale production models are marketed by a number of companies. Capillary bioreactors are commonly used for hybridoma cell culture for production of monoclonal antibodies.
* Pseudomonas exotoxin (immunotoxins) - A patent and two patent applications,
each from 1990, with from 7 to 9 nonexclusive licenses each and two with 3
exclusive licenses, invented by Dr. I.H. Pastan, et al., NCI. These concern
genetically modified Pseudomonas exotoxin (PE) genes and recombinant expressed
PE proteins designed and well-suited for use in immunotoxins (antibody-PE
conjugates), including both fusion proteins formed by expression of fused
antibody-PE genes and chemical conjugates (often using chemical conjugation
technologies covered by other multiply licensed NCI patents).
Various immunotoxins and receptor targeted conjugates from licensees that have reached the clinical trials stage of development include: Protein Design Labs. developing Recombinant Anti-Tac Immunotoxin (Tac T-cell receptor anti body-PE) for treatment of organ transplant rejection, graft-versus-host disease, and other autoimmune diseases; Oncologix Inc. developing OLX-209, an immunotoxin for treatment of erbB-2 expressing tumors; Merck & Co. developing a transforming growth factor-PE immunotoxin for bladder cancer treatment; Seragen Inc. developing interleukin-2/PE immunotoxin (along with Eli Lilly & Co.) for treatment of cancer, HIV-infection and autoimmune diseases; Seragen developing interleukin-4/PE for cancer treatment; Upjohn Co. developing CD4-PE for treatment of HIV-infection; and NeoRx Corp. developing a tumor antibody-PE immunotoxin for cancer treatment.