Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Reexamination Certificate
1995-06-07
2001-06-19
Caputa, Anthony C. (Department: 1642)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
C530S388100
Reexamination Certificate
active
06248513
ABSTRACT:
The invention relates to human anticytomegalovirus monoclonal antibodies (HCMV) and to a process for the in vitro diagnosis of infections induced by human cytomegaloviruses. It relates more particularly to antibodies of this type which are capable of simultaneously detecting human cytomegaloviruses (CMV), human cells infected by CMV and a polypeptide, particularly a protein induced by HCMV and having protein-kinase activity.
The invention relates also to the aforesaid polypeptide having the aforesaid protein-kinase activity.
It is known that CMV is the cause of numerous clinical infections, ranging between benign infectious manifestations, and congenital manifestations, for example, particularly severe malformations. CMV has also been recognised as a cause of morbidity and mortality in persons who have undergone organ transplants, for example, of the kidney. The detection of CMV is a problem which poses itself therefore particularly acutely. In addition, the recognition and isolation of vaccinating polypeptides or proteins, or which can be rendered vaccinating with respect to CMV would open up serious possibilities of prevention of said complications against which at the present time, few means of treatment are available.
Various authors have already brought their attention to bear on diagnosis techniques, which could be based on the use of monoclonal antibodies with respect to the human cytomegalovirus. The monoclonal antibodies obtained hitherto, did not yet contribute the expected solution for performing a diagnosis, which is both easy and reliable, of infection with cytomegamoviruses.
In fact, it is known that CMV (a member of the family of viruses of herpes) induces in the infected cells a considerable number of polypeptides, at various stages of the infectious process, and at various levels of the infected cells. L. N. PEREIRA and Coll. (“Infection and Immunity”), June 1982, p. 924-932, report, that they have produced a large number of hybridomas secretors of monoclonal antibodies, capable, of recognising in previously unfixed cells, polypeptides, or glycoproteins induced by the CMV in cultures of these cells. The differences observed by PEREIRA and Coll. at the level of the relative behaviour of different antibodies with respect to the virus itself, infected cells and proteins, glycoproteins, or polypeptides, isolatable from extracts of these cells, has led them to formulate the hypothesis, that the conformation of the viral glycoproteins recognised by certain of these antibodies at the membranal surface of the cells infected by the CMV's, could be different from the conformation of the envelope of the virion. The utilization of certain of the antibodies isolated to perform diagnosis operations of the above-indicated type, has been evoked by these authors. It follows however from the foregoing and from the experimental results provided, that the monoclonal antibodies judged the most interesting, were also capable of precipitating several polypeptides at the same time. The use of these antibodies to recognise antigenic determinants, or specific epitopes, could not therefore be contemplated by reason of the non-discriminating character of the recognition.
L. C. GOLDSTEIN and Coll. (“Infections and Immunity”, October 1982, p. 273-281) also described a certain number of monoclonal antibodies which can recognise certain polypeptides localised in the nuclei, or in cytoplasmic inclusions of cells infected by CMV. These monoclonal antibodies have been selected by their capacity to react with cells infected by CMV, and previously fixed with absolute methanol and dried in air. It does not however follow from the article that these monoclonal antibodies were adapted to recognise still intact infected cells.
Lastly, C. AMEDEI and Coll. (Ann. Virol. (Institut Pasteur), describe a battery, of 24 monoclonal antibodies directed against human cytomegalovirus. The larger number of monoclonal antibodies obtained, arises apparently, from the techniques which have been used to detect them. In particular, detection has employed immunofluorescent techniques of detection of antibodies retained on previously infected cells, which had been fixed with acetone and dried in air. The same monoclonal antibodies are revealed to be practically devoid of activity with respect to cells obtained from identical cell lines, previously infected by the same virus, when these infected cells had been fixed beforehand with methanol. Perhaps there should be sought in this observation, the cause of the low number of hybridomas secreting monoclonal antibodies selective against cells infected with HCMV, which had been isolated by L. C GOLDSTEIN and Coll.
Among these monoclonal antibodies, some have been found to show neutralising properties with respect to several strains of virus. These monoclonal antibodies have moreover been the subject of a French Patent Application No. 83 05384, filed Mar. 31, 1983. These particular monoclonal antibodies have been adopted for the carrying out of in vitro diagnosis tests-of an infection with HCMV. However, the Patent Application and indeed, moreover, the above-mentioned article, have not recognised among the various hybridomas described, that which is established in the following to secrete monoclonal antibodies, particularly effective for diagnosis operations, and suitable to permit the isolation of a polypeptide inducible by HCMV's and endowed with biological properties permitting a particularly refined diagnosis operation.
REFERENCES:
Michelson, European Symposium on New Horizons in Microbiology, A. Sanna and G. Morace eds., Elsevier Science Publishers B.V., 149-156, 1984.*
Michelson et al., Virology, 134:259-268, 1984.*
Amadei et al., Ann. Virol. (Inst. Pasteur) 134, No. 2, 165-180, 1983.*
Mar et al., J. Gen. Virol., 57:149-156, 1981.*
Stinski et al., J. Virol., vol. 26, No. 3:686-701, Jun 1978.*
Britt, W.J. et al., J. Virol., 59:185-188, Jul. 1986.*
Pereira, L. et al., Infection and Immunity, vol. 36, No. 3:924-932, Jun. 1982.*
Li et al., “Production and Characterization of Monoclonal Antibodies against Cytomegalovirus Virions”, p. 293, # S 52, Abstracts of the Annual Meeting of the American Society for Microbiology, Mar. 1983.*
Murayama et al. J. Gen. Virol. 67:1475-1478, 1986.*
Schmitz, H. et al., “Human Immune Response to Proteins of Cytomegalovirus”,Intervirology13:154-161 (1980).
Iêda Siqueira-Linhares, Maria et al., “Polypeptides and Major Antigens of Four New Isolates of Cytomegalovirus”,Medical Microbiology Immunology169:197-208 (1981).
Murayama et al., “Fc Receptors(s) Induced by Human Immunoglobulin G Subclasses”, J. Gen. Virol., 67:1475-1478 (1986).
Lucas et al., “Rapid Diagnosis of Cytomegalovirus by Indirect Immunofluorescence Assay with Monoclonal Antibody F6b in a Commercially Available Kit”, Journal of Clinical Microbiology, 27(2):367-369 (Feb. 1989).
Amadei et al, Ann. Virol., vol. 134, No. 2, pp. 165-180, 1983.*
Goldstein et al, Infection and Immunity, vol. 38, No. 1, p273-281, 1982.*
Pereira et al, Infection and Immunity, vol. 36, p. 924-932, 1982.*
Michelson, Elsevier Science Publishers B.V., New Horizons in Microbiology, A. Sanna and G. Morace Editors, 1984.*
Amadei et al,Ann. Virol., vol. 134, No. 2, pp. 165-180 (1983).
Kim et al,Journal of Clinical Microbiology, vol. 18, No. 2, pp. 331-343 (1983).
Mar et al,Chemical Abstracts, vol. 96, No. 9, p. 237, 64720Z (1982).
Pereira et al,Infection and Immunity, vol. 36, pp. 924-932 (Jun. 1982).
Infection and Immunity, Oct. 1982, p. 273-281, vol. 38 Goldstein et al.*
Virology, vol. 134, p. 259-268 (1984), Michelson et al.
Amadei Claire
Barzu Octavian
Boue Andre
Horaud Florian
Michelson Susan
Brumback Brenda G.
Burns Doane Swecker & Mathis L.L.P.
Caputa Anthony C.
Institut Pasteur
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