Interference No. 105,188 Short v. Punnonnen response to the unaltered antigen comprises: a) creating a library of DNA encoding a natural B7-2 antigen and DNA altered to encode a B7-2 variant having reduced activity or enhanced inactivity; b) inducing homologous recombination between the 5 natural DNA and the altered DNA comprising a DNA library; and c) screening all new DNA resulting from homologous recombination of natural DNA and altered DNA comprising the DNA library for expression of B7-2 variants which reduce the animal’s immune response to a vaccine as compared to its natural immune response. 10 See the following excerpts from the Freeman PCT (Exh. 2040, p. 22, l. 17, to p. 23, l. 17; emphasis added): A transgene is a DNA which is integrated into the genome of a cell from which a transgenic animal develops. In one embodiment, murine B7-2 cDNA or an appropriate sequence 15 thereof can be used to generate transgenic animals that contain cells which express B7-2 protein. Methods for generating transgenic animals, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Patent Nos. 4,736,866 and 4,870,009. 20 Typically, particular cells would be targeted for B7-2 transgene incorporation with tissue specific enhancers, which could result in T cell costimulation and enhanced T cell proliferation and autoimmunity. Transgenic animals that include a copy of a B7-2 transgene introduced into the 25 germ line of the animal at an embryonic stage can be used to examine the effect of increased B7 expression. Such animals can be used to examine the effect of increased B7 expression. Such animals can be used as tester animals for reagents thought to confer protection from, for example, 30 autoimmune disease. In accordance with this facet of the invention, an animal is treated with the reagent and a reduced incidence of the disease, compared to untreated animals bearing the transgene, would indicate a potential therapeutic intervention for the disease. -13-Page: Previous 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 NextLast modified: November 3, 2007