Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1994-09-30
2003-02-04
Saunders, David (Department: 1644)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S012200, C530S350000, C530S395000
Reexamination Certificate
active
06514936
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to novel truncated forms of intercellular adhesion molecule (ICAM), designated “tICAMs”, which effectively bind to human rhinovirus (HRV) and to lymphocyte-function associated antigen-1 (LFA-1). The present invention also pertains to DNA sequences coding for various tICAMs and to methods for preventing or amelio-rating infection and inflammation using said tICAMs.
Human rhinoviruses, the major causative agent of the common cold, belong to the picornavirus family. The three-dimensional structure of several rhinovirus serotypes have now been determined to atomic resolution by Rossmann, M. G., E. Arnold, J. W. Erickson, E. W. Frankenberger, P. J. Griffith, H. Hecht, J. E. Johnson, G. Kamer, M. Luo, A. G. Mosser, R. R. Rueckert, B. Sherry, and G. Vriend, Nature (1985) 317:145-153; Kim, S., T. J. Smith, M. M. Chapman, M. G. Rossmann, D. C. Pevear, F. J. Dutko, P. J. Felock, G. D. Diana, and M. A. McKinlay, J. Mol. Biol. (1990) 210:91-111. The virion is composed of a protein capsid of 60 protomeric units, consisting of the four protein subunits VP1-4, surrounding an RNA genome. Each of the 60 protomeric units possesses a recessed “canyon” that is believed to contain the site that binds to the receptor on the target cell surface [reviewed in Rossmann, M. G., J. Biol. Chem. (1989) 264:14587-14590]. The dimensions of the canyon are such that it is too small to admit the combining site of an antibody but is apparently large enough to admit the virus-binding site of the receptor.
In order to infect host cells, viruses must bind to and then enter cells to initiate an infection. Since 1959, evidence has accumulated in the literature indicating that the presence of specific binding sites (receptors) on host cells could be a major determinant of tissue tropism of certain viruses. [Holland, J. J., and L. C. McLaren, “The mammalian cell-virus relationship. II. Absorption, reception, and eclipse of poliovirus by HeLa cells,” J. Exp. Med. 109:487-504 (1959); Holland, J. J., “Receptor affinities as major determinants of enterovirus tissue tropisms in humans,” Virology 15:312-326 (1961)]. Among picornaviruses such as poliovirus, Coxsackie virus, and rhinoviruses, specific binding to host cells has been demonstrated. By competition experiments, it has been demonstrated that some of these receptors are distinct from one another in that the saturation of the receptor of one virus had no effect on the binding of a second virus. [Lonberg-Holm, K., R. L. Crowell, and L. Philipson. “Unrelated animal viruses share receptors,” Nature 259:679-681 (1976)].
Rhinoviruses can be classified according to the host cell receptor to which they bind. Tomassini, J. E. and R. J. Colonno, “Isolation of a receptor protein involved in attachment of human rhinoviruses,” J. Virol. 58:290 (1986) reported the isolation of a receptor protein involved in the cell attachment of HRV. Approximately 90% of the more than 115 serotypes of rhinoviruses, as well as several types of Coxsackie A virus, bind to a single common receptor termed the “major” human rhinovirus receptor (HRR) [Abraham, G., and R. J. Colonno, “Many rhinovirus serotypes share the same cellular receptor,” J. Virol. 51:340-345 (1984)]; the remaining 10% bind to one or more other cell receptors.
The major human rhinovirus receptor has been transfected, identified, purified, and reconstituted as described in co-pending U.S. patent applications Ser. No. 07/262,428 and 07/262,570, both filed Oct. 25, 1988. Greve, J. M., G. Davis, A. M. Meyer, C. P. Forte, S. C. Yost, C. W. Marlor, M. E. Kamarck, and A. McClelland, “The major human rhinovirus receptor is ICAM-1,” Cell 56:839 (1989), identified the major HRR as a glycoprotein with an apparent molecular mass of 95 kD and having an amino acid sequence essentially identical to that deduced from the nucleotide sequence of a previously described cell surface protein named intercellular adhesion molecule (ICAM-1). ICAM-1 had first been identified based on its role in adhesion of leukocytes to endothelial cells [Rothlein, R., et al., J. Immunol. 137:1270-1274 (1986); see also Simmons, D., M. W. Makgoba, and B. Seed, Nature (1988) 331:624; Staunton, D. E., S. D. Marlin, C. Stratowa, M. L. Dustin, and T. A. Springer, “Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families,” Cell (1988) 52:925-933]. Induction of ICAM-1 expression by cytokines during the inflammatory response may regulate leukocyte localization to inflammatory sites. Subsequently, Staunton, D. E., et al., Cell 56:849 (1989) confirmed that ICAM-1 is the major cell surface receptor for HRV. See also Staunton, D. E., M. L. Dustin, H. P. Erickson, and T. A. Springer, “The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus,” Cell (1990) 61:243-254. The precise extent of the virus-binding site on ICAM-1 remains to be determined, although results from mouse-human chimeras and site-directed mutagenesis indicate that the two N-terminal domains play a major role in virus binding [Staunton, et al., Cell (1990) 61:243-254], and a model has been developed for the interaction of the N-terminal domain of ICAM-1 with HRV14 [Giranda, V. L., M. S. Chapman, and M. G. Rossmann, Proteins (1990) 7:227-233].
European Patent Application 0 289 949 describes membrane-associated ICAM-1, which mediates attachment of many cell types, including endothelial cells, to leukocytes expressing lymphocyte function associated molecule-1 (LFA-1; CD18/CD11a, a member of the beta-2 integrin family). This patent application provides a discussion of the prior research in the field of intercellular adhesion molecules.
Heterotypic binding of LFA-1 to ICAM-1 mediates cellular adhesion of diverse cell types and is important in a broad range of immune interactions [Marlin, et al., Cell (1987) 51:813-819]. ICAM-1 also binds to MAC-1 (CD18/CD11b), another beta-2 integrin, but not to p150/95 (CD18/CD11c) [Staunton, D. E., S. D. Marlin, C. Stratowa, M. L. Dustin, and T. A. Springer, Cell (1988) 52:925-933]. MAC-1 and p150/95 differ from LFA-1 by their alpha subunit. Although minimal peptide recognition sites have been identified for many other integrins, the recognition site for LFA-1 on ICAM-1 remains obscure. Staunton, et al., Cell (1990) 61:243-254 have reported that a transmembrane form of the first two domains of ICAM-1 retains some LFA-1-binding activity and that a number of mutations in the first two domains of the full-length molecule cause reductions in LFA-1-binding activity.
The primary structure of ICAM-1 is homologous to two other cellular adhesion molecules: neural cell adhesion molecule (NCAM) and myelin-associated glycoprotein (MAG). This suggests that ICAM-1 is a member of the immunoglobulin supergene family [Simmons, et al., Nature (1988) 331:624-627; Staunton et al., Cell (1988) 52:925-933]. The cDNA sequences are described in the above-referenced papers by Simmons et al. and Staunton et al., from which the amino acid sequence of ICAM-1 has been deduced.
ICAM-1 is an integral membrane protein 505 amino acids long and has: i) five immunoglobulin-like extra-cellular domains at the amino-terminal (extracellular) end (designated domain 1 [amino acid residues 1-88], domain 2 [89-185], domain 3 [186-284], domain 4 [285-385], and domain 5 [386-453] [Staunton, et al., Cell (1988) 52:925-933]); ii) a hydrophobic transmembrane domain (454-477); and iii) a short cytoplasmic domain at the carboxy-terminal end (478-505). Electron microscopy has indicated that ICAM-1 is a highly elongated molecule [Staunton, et al., Cell (1990) 61:243-2541].
Several approaches to decreasing infectivity of viruses in general, and of HRV in particular, have been pursued including: i) developing antibody to the cell surface receptor for use in blocking viral binding to the cell; ii) using
Davis Gary
Greve Jeffrey M.
McClelland Alan
Bayer Corporation
Saunders David
Tong Mary Beth
LandOfFree
Antiviral methods using human rhinovirus receptor (ICAM-1) does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Antiviral methods using human rhinovirus receptor (ICAM-1), we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antiviral methods using human rhinovirus receptor (ICAM-1) will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3128699