Drug – bio-affecting and body treating compositions – Nonspecific immunoeffector – per se ; or nonspecific... – Synthetic or structurally-modified peptidoglycan or...
Reexamination Certificate
1998-02-23
2001-07-10
Nolan, Patrick J. (Department: 1644)
Drug, bio-affecting and body treating compositions
Nonspecific immunoeffector, per se ; or nonspecific...
Synthetic or structurally-modified peptidoglycan or...
C530S395000, C536S001110
Reexamination Certificate
active
06258364
ABSTRACT:
FIELD OF THE INVENTION
This invention pertains to the characterization and development of the tissue specific, sperm surface glycoprotein SAGA-1, as well as methods of use of the same. This potential immunogen, recognized and bound by the S19 antibody, was first disclosed in Parent Application U.S. application Ser. No. 671,622 filed Jun. 28, 1996. Herein, the epitope recognized by the S19 antibody is demonstrated to be a carbohydrate epitope, the immunogen a component of the matrix which constitutes the coat or surface of human spermatozoa, and the glycoprotein shown to be produced by the epididymis. These features demonstrate the utility of the SAGA-1 glycoprotein, and/or the carbohydrate epitope thereof, as contraceptive immunogens, effective in the preparation of a contraceptive vaccine. Similarly, the utility of the S19 monoclonal antibody as an effective spermicide or “spermistatic” (sperm-binding agent and penetration inhibitor) are reinforced, demonstrating the utility of an antibody which binds this unique epitope as a topical contraceptive. Similarly, the titer of antibodies to SAGA-1 can be used as an indicator of the potential fertility of individuals being treated with the contraceptive vaccine. Further, the S19 monoclonal antibody can be used as the active agent in an immunodiagnostic kit and assay to detect the presence of sperm in a biological sample, such as ejaculate or post coital vaginal lavage.
BACKGROUND OF RELATED WORK
Previously described contraceptive vaccine candidates represent recombinant protein or synthetic peptide immunogens. However, the S19 carbohydrate epitope and other SAGA-1-specific carbohydrate epitopes are components of the sperm glycocalyx, the extracellular matrix of carbohydrate that coats the surface of human spermatozoa. Carbohydrate immunogens provide opportunity for improved immunocontraceptive effects over peptide immunogens as carbohydrate epitopes are more accessible to antibody binding. This is due to the generally protruding character of the carbohydrate chain of a glycoprotein into an aqueous environment, as opposed to short chain peptides or conformational epitopes, which may be obscured or lost depending on the binding conditions.
As more fully described in the parent application, the improvement of available contraceptive methods receives substantially continuous attention. Currently available spermicides employ detergents, specifically, varieties of Nonoxynol-9. The use of this detergent spermicide has been implicated in increasing frequency of urogenital, cervical, and vaginal inflamation in women employing the same. As an alternative, the use of antibodies as “spermicides” has been suggested. See generally Alexander, Scientific American, September: 136-141 (1995).
One antibody studied in terms of its sperm-binding potential is the S19 monoclonal antibody. This monoclonal antibody is described, but not enablingly disclosed, in Anderson et al., J. Reprod. Immunol., 10:1031-257 (1987). This antibody strongly agglutinates human sperm, inhibits tight binding between human sperm and the zona pellucida and blocks sperm penetration of cervical mucus. Mahoney et al., J. Reprod. Immunol., 19:269-285.
The monoclonal antibody of S19 is expressed by the hybridoma cell line deposited at the ATTC, in 10801 University Blvd., Manassas, Va. 20110-2209, USA on Jun. 26, 1996, under accession number HB-12144. This deposit was made pursuant to the Budapest Treaty, and all restrictions thereon will be irrevocably removed upon issuance of a patent on the pending parent application, which has been allowed. Notwithstanding the early publication identifying the existence of the antibody, the same was not made available, or otherwise publicly used or sold, until after the filing of the parent application in June of 1996. The experiments described in Mahoney et al., Supra, were conducted under the control of inventor John Herr, and thus, the S19 monoclonal antibody is the subject of the claims of the parent patent to issue.
While work has continued on topical contraceptives, interest continues in developing a contraceptive vaccine, based on the use of sperm antigens. Decreased fertility rates have been obtained through the immunization of test animals with sperm surface antigens such as LDH-C4, O'Hern et al., Biol. Reprod. 52:331-339 (1995), PH-20, Primakoff et al., Nature 335:543-546 (1988), RSA-1, O'Rand et al., J. Reprod. Immunol. 25:89-102 (1993) and fertilin, Ramarao et al., Mol. Reprod. Dev., 43:70-75 (1995). Unfortunately, as observed in the parent case, the highest rate of efficacy observed in vaccines of this type is about 75% inhibition of fertility. While impressive as an experimental development, this is far below the threshold necessary to provide an acceptable and safe contraceptive vaccine at a level comparable to oral contraceptives and other methods commercially available.
SUMMARY OF THE INVENTION
SAGA-1 was identified with a murine monoclonal antibody (mAb), S19, that agglutinates human spermatozoa, inhibits sperm-zona binding, blocks sperm penetration of cervical mucus, and induces the shaking phenomenon. SAGA-1 is also recognized by H6-3C4, a human sperm-agglutinating mAb produced using lymphocytes from an immunologically infertile woman. The human H
6-3
C4 antibody and the function-inhibitory mAb S19 recognize carbohydrate epitopes present on the SAGA-1 glycoprotein. Microsequence analysis demonstrated that SAGA-1 is related to CDw52, a GPI-anchored protein first identified on lymphocytes and involved in signal transduction. Cdw52 is bound by CAMPATH-1M mAb. The S19 and H6-3C4 carbohydrate epitopes are not present on the CDw52 glycoprotein. Therefore, SAGA-1 and CDw52 represent glycoforms, i.e. glycoprotein isoforms that have the same peptide sequence but possess different oligosaccharide side chains. SAGA-1 is important, therefore, due to its involvement in gamete interactions during fertilization, the fact that it is a glycoprotein on the entire sperm surface, and it serves as a target for isoantibodies involved in the female immune response to spermatozoa. For these reasons, SAGA-1 is a superior immunogen as an active agent in an immunocontraceptive vaccine.
REFERENCES:
patent: WO 90/09802 (1990-09-01), None
Matsudaira, Methods in Enzymology, vol. 182, 1992 pp. 602-605.*
K. Kameda, et al., Biology of Reproduction, vol. 46, pp. 349-357, “Comparative Studies of the Antigens Recognized by Sperm-Immobilizing Monoclonal Antibodies”, 1992.
Diekman Alan B.
Herr John C.
Norton Elizabeth J.
Westbrook-Case V. Anne
Breen John P.
Nolan Patrick J.
University of Virginia Patent Foundation
LandOfFree
Purified sperm surface antigen, monoclonal antibody therefor... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Purified sperm surface antigen, monoclonal antibody therefor..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Purified sperm surface antigen, monoclonal antibody therefor... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2525614