Patents Assigned to Connaught Laboratories Limited
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Patent number: 5968776Abstract: Multimeric hybrid genes encoding the corresponding chimeric protein comprise a gene sequence coding for an antigenic region of a protein from a first pathogen linked to a gene sequence coding for an antigenic region of a protein from a second pathogen. The pathogens particularly are parainfluenza virus (PIV) and respiratory syncytial virus (RSV). A single recombinant immunogen is capable of protecting infants and similar susceptible individuals against diseases caused by both PIV and RSV.Type: GrantFiled: June 6, 1995Date of Patent: October 19, 1999Assignee: Connaught Laboratories LimitedInventors: Michel H. Klein, Run-Pan Du, Mary E. Ewasyshyn
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Patent number: 5965385Abstract: The three-dimensional structure of crystalline pertussis holotoxin (PT) has been determined by X-ray crystallography. Crystal structures have also been determined for complexes of pertussis toxin with molecules relevant to the biological activity of PT. These three-dimensional structures were analyzed to identify functional amino acids appropriate for modification to alter the biological properties of PT. Similar procedures may be used to predict amino acids which contribute to the toxicity of the holotoxin, to produce immunoprotective, genetically-detoxified analogs of pertussis toxin.Type: GrantFiled: June 6, 1995Date of Patent: October 12, 1999Assignees: Connaught Laboratories Limited, University of AlbertaInventors: Randy J. Read, Penelope E. Stein, Stephen A. Cockle, Raymond P. Oomen, Sheena Loosmore, Michel H. Klein, Glen D. Armstrong, Bart Hazes
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Patent number: 5955342Abstract: The present invention is concerned with the ability to differentiate between infection by HIV and immunization with an immunogenic preparation. Accordingly, the present invention provides a non-infectious, non-replicating, HIV retrovirus-like particle containing a heterologous antigenic marker, comprising an assembly of (a) an env gene product; (b) a pol gene product; (c) a gag gene product; and, (d) at least one non-retroviral, non-mammalian antigenic marker. The antigenic marker may have between 5 and 100 amino acid residues. In one embodiment, the amino acid sequence contains a tobacco mosaic virus (TMV) epitope obtained from the coat protein. In another embodiment, the marker is inserted into the gag gene product at an antigenically-active insertion site.Type: GrantFiled: August 15, 1994Date of Patent: September 21, 1999Assignee: Connaught Laboratories LimitedInventors: Benjamin Rovinski, Shi-Xian Cao, Fei-Long Yao, Roy Persson, Michel H. Klein
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Patent number: 5951986Abstract: Novel synthetic peptides are provided which are candidate vaccines against HIV-1 and which are useful in diagnostic application. The peptides comprise an amino acid sequence of a T-cell epitope of the gag protein of HIV-1, specifically p24E linked directly to an amino acid sequence of a B-cell epitope of the V3 loop protein of an HIV-1 isolate and containing the sequence GPGR, and/or the gp41 containing the sequence ELKDWA. Multimeric forms of the tandem synthetic peptides are provided.Type: GrantFiled: June 6, 1995Date of Patent: September 14, 1999Assignee: Connaught Laboratories LimitedInventors: Charles D. Y. Sia, Pele Chong, Michel H. Klein
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Patent number: 5942401Abstract: The presence of cytotoxic T-cells to the Rev and/or Tat protein in samples from a subject infected with immunodeficiency virus, particularly HIV in humans, is an indication of a stable disease condition and a favourable prognosis of lack of progression to disease. Immunogenic compositions containing at least one cytotoxic T-cell epitope of the Rev and/or Tat protein of an immunodeficiency virus, particularly HIV, or a vector encoding the T-cell epitope, may be used to prevent infection by disease caused by the immunodeficiency virus, by stimulating, in the host, a specific cytotoxic T-cell response specific for the respective Rev and/or Tat proteins.Type: GrantFiled: December 22, 1997Date of Patent: August 24, 1999Assignee: Connaught Laboratories LimitedInventors: Carel A. van Baalen, Albertus D. M. E. Osterhaus
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Patent number: 5942418Abstract: An expression system for expressing gene products from recombinant Bordetella strains and specific nucleic acid molecules useful in transforming Bordetella strains for such expression are described. A nucleic acid molecule may comprise a Bordetella promoter operatively coupled to a heterologous gene encoding a non-Bordetella gene product with the heterologous gene transcriptionally regulated by the Bordetella promoter. The nucleic acid molecule may further comprise a further nucleic acid molecule encoding a leader sequence for secretion of the non-Bordetella gene product. Another nucleic acid molecule may comprise a Bordetella promoter coupled to a nucleic acid sequence encoding a non-Bordetella leader sequence for secretion of a gene product, which may be a Bordetella gene product or a non-Bordetella gene product.Type: GrantFiled: December 1, 1997Date of Patent: August 24, 1999Assignee: Connaught Laboratories LimitedInventors: Sheena M. Loosmore, Reza K. Yacoob, Gavin R. Zealey, Michel H. Klein
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Patent number: 5939297Abstract: An isolated and purified analog of Haemophilus influenzae Hin47 protein has a decreased protease activity which is less than about 10% of that of natural Hin47 protein and preferably substantially the same immunogenic properties as natural Hin47 protein. An isolated an purified nucleic acid molecule encoding the Hin47 analog may be provided in a recombinant plasmid which may be introduced into a cell which is grown to produce the Hin47 analog. Immunogenic compositions comprising the Hin47 analog and the encoding nucleic acid may be formulated as vaccines for in vivo administration to a host, including a human, to confer protection against diseases caused by a bacterial pathogen, including Haemophilus species, such as Haemophilus influenzae, that produces Hin47 protein or a protein capable of inducing antibodies in the host specifically reactive with Hin47 protein. The Hin47 analog and the encoding nucleic acid also may be employed in diagnostic applications.Type: GrantFiled: August 26, 1994Date of Patent: August 17, 1999Assignee: Connaught Laboratories LimitedInventors: Sheena M. Loosmore, Yan-Ping Yang, Pele Chong, Raymond P. Oomen, Michel H. Klein
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Patent number: 5935573Abstract: An isolated and purified analog of Haemophilus influenzae Hin47 protein has a decreased protease activity which is less than about 10% of that of natural Hin47 protein and preferably substantially the same immunogenic properties as natural Hin47 protein. An isolated an purified nucleic acid molecule encoding the Hin47 analog may be provided in a recombinant plasmid which may be introduced into a cell which is grown to produce the Hin47 analog. Immunogenic compositions comprising the Hin47 analog and the encoding nucleic acid may be formulated as vaccines for in vivo administration to a host, including a human, to confer protection against diseases caused by a bacterial pathogen, including Haemophilus species, such as Haemophilus influenzae, that produces Hin47 protein or a protein capable of inducing antibodies in the host specifically reactive with Hin47 protein. The Hin47 analog and the encoding nucleic acid also may be employed in diagnostic applications.Type: GrantFiled: June 7, 1995Date of Patent: August 10, 1999Assignee: Connaught Laboratories LimitedInventors: Sheena M. Loosmore, Yan-Ping Yang, Pele Chong, Raymond P. Oomen, Michel H. Klein
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Patent number: 5932714Abstract: An expression system for expressing gene products from recombinant Bordetella strains and specific nucleic acid molecules useful in transforming Bordetella strains for such expression are described. A nucleic acid molecule may comprise a Bordetella promoter operatively coupled to a heterologous gene encoding a non-Bordetella gene product with the heterologous gene transcriptionally regulated by the Bordetella promoter. The nucleic acid molecule may further comprise a further nucleic acid molecule encoding a leader sequence for secretion of the non-Bordetella gene product. Another nucleic acid molecule may comprise a Bordetella promoter coupled to a nucleic acid sequence encoding a non-Bordetella leader sequence for secretion of a gene product, which may be a Bordetella gene product or a non-Bordetella gene product.Type: GrantFiled: June 7, 1995Date of Patent: August 3, 1999Assignee: Connaught Laboratories LimitedInventors: Sheena M. Loosmore, Reza Khayyam Yacoob, Gavin Ross Zealey, Michel Henri Klein
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Patent number: 5922562Abstract: Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbp1 or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.Type: GrantFiled: November 8, 1994Date of Patent: July 13, 1999Assignee: Connaught Laboratories LimitedInventors: Sheena Loosmore, Robin Harkness, Anthony Schryvers, Pele Chong, Scott Gray-Owen, Yan-Ping Yang, Andrew Murdin, Michel Klein
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Patent number: 5922841Abstract: Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbp1 or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.Type: GrantFiled: June 7, 1995Date of Patent: July 13, 1999Assignee: Connaught Laboratories LimitedInventors: Sheena Loosmore, Robin Harkness, Anthony Schryvers, Pele Chong, Scott Gray-Owen, Yan-Ping Yang, Andrew Murdin, Michel Klein
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Patent number: 5922323Abstract: Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbp1 or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.Type: GrantFiled: June 7, 1995Date of Patent: July 13, 1999Assignee: Connaught Laboratories LimitedInventors: Sheena Loosmore, Robin Harkness, Anthony Schryvers, Pele Chong, Scott Gray-Owen, Yan-Ping Yang, Andrew Murdin, Michel Klein
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Patent number: 5916562Abstract: The nucleotide sequence of the P2 gene and the derived amino acid sequence of the P2 protein of Haemophilus influenzae type b are disclosed and the methods used to determine the same. Also disclosed are the methods used to clone and express the P2 gene as well as the purification protocol for the gene and protein. Also disclosed is the synthesis of peptides corresponding to the N-terminal and C-terminal ends of the P2 protein. Also disclosed is the use of the P2 protein as a protective agent for the disease caused by Haemophilus influenzae type b and the use of the protein as a carrier for conjugation with an oligosaccharide derived from Haemophilus to generate a potentially efficacious vaccine against the disease. Also disclosed is the use of P2 peptide-conjugates as immunising agents.Type: GrantFiled: September 20, 1993Date of Patent: June 29, 1999Assignees: Connaught Laboratories Limited, Washington UniversityInventors: Robert S. Munson, Jr., Robert Tolan, Pele Chong, Raafat Fahim, Patrick McVerry, Michel Klein
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Patent number: 5889176Abstract: Non-infectious, retrovirus-like particles comprise an assembly of an env gene product, a pol gene product and a gag gene product contain an antigenic marker which is non-retroviral or non-HIV retroviral. In one embodiment, the marker comprises an amino acid sequence containing an epitope inserted into the gag gene product at an antigenically-active insertion site. In another embodiment, the marker comprises an antigenic anchor sequence operatively connected to the env gene product replacing endogenous anchoring function. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis. The presence of the antigenic marker enables recognition that antiserum containing anti-retroviral antibodies has been generated by exposure to the non-infectious retrovirus-like particles by testing for antibodies specific to the antigenic marker.Type: GrantFiled: December 6, 1996Date of Patent: March 30, 1999Assignee: Connaught Laboratories LimitedInventors: Benjamin Rovinski, Shi-Xian Cao, Fei-Long Yao, Roy Persson, Michel H. Klein
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Patent number: 5879925Abstract: Non-infectious, retrovirus-like particles comprise an assembly of an env gene product, a pol gene product and a gag gene product contain an antigenic marker which is non-retroviral or non-HIV retroviral. In one embodiment, the marker comprises an amino acid sequence containing an epitope inserted into the gag gene product at an antigenically-active insertion site. In another embodiment, the marker comprises an antigenic anchor sequence operatively connected to the env gene product replacing endogenous anchoring function. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis. The presence of the antigenic marker enables recognition that antiserum containing anti-retroviral antibodies has been generated by exposure to the non-infectious retrovirus-like particles by testing for antibodies specific to the antigenic marker.Type: GrantFiled: December 6, 1996Date of Patent: March 9, 1999Assignee: Connaught Laboratories LimitedInventors: Benjamin Rovinski, Shi-Xian Cao, Fei-Long Yao, Roy Persson, Michel H. Klein
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Patent number: 5880104Abstract: Vectors containing a nucleotide sequence coding for an F protein of respiratory syncytial virus (RSV) and a promoter for such sequence, preferably a cytomegalovirus promoter, are described. Such vectors also may contain a further nucleotide sequence located adjacent to the RSV F protein encoding sequence to enhance the immunoprotective ability of the RSV F protein when expressed in vivo. Such vectors may be used to immunize a host, including a human host, by administration thereto. Such vectors also may be used to produce antibodies for detection of RSV infection in a sample.Type: GrantFiled: May 1, 1997Date of Patent: March 9, 1999Assignee: Connaught Laboratories LimitedInventors: Xiaomao Li, Mary E. Ewashysyn, Michel H. Klein
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Patent number: 5877018Abstract: Synthetic inducible eukaryotic promoters for the regulation of transcription of a gene achieve improved levels of protein expression and lower basal levels of gene expression. Such promoters contain at least two different classes of inducible elements, usually by modification of a native promoter containing one of the inducible elements by inserting the other of the inducible elements. In embodiments, additional metal responsive elements IR:Es) and/or glucocorticoid responsive elements (GREs) are provided to native promoters, particularly the hMT-IIA and MMTV-LTR promoters. One or more constitutive elements may be functionally disabled to provide the lower basal levels of gene expression.Type: GrantFiled: April 16, 1996Date of Patent: March 2, 1999Assignee: Connaught Laboratories LimitedInventors: Jorge Filmus, Michel Klein
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Patent number: 5876731Abstract: Novel synthetic peptides are provided which are candidate vaccines against HIV-1 and which are useful in diagnostic application. The peptides comprise an amino acid sequence of a T-cell epitope of the gag protein of HIV-1, specifically p24E linked directly to an amino acid sequence of a B-cell epitope of the V3 loop protein of an HIV-1 isolate and containing the sequence GPGR, and/or the gp41 containing the sequence ELKDWA. Multimeric forms of the tandem synthetic peptides are provided.Type: GrantFiled: June 5, 1995Date of Patent: March 2, 1999Assignee: Connaught Laboratories LimitedInventors: Charles D. Y. Sia, Pele Chong, Michel H. Klein
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Patent number: 5869302Abstract: An isolated and purified analog of Haemophilus influenzae Hin47 protein has a decreased protease activity which is less than about 10% of that of natural Hin47 protein and preferably substantially the same immunogenic properties as natural Hin47 protein. An isolated an purified nucleic acid molecule encoding the Hin47 analog may be provided in a recombinant plasmid which may be introduced into a cell which is grown to produce the Hin47 analog. Immunogenic compositions comprising the Hin47 analog and the encoding nucleic acid may be formulated as vaccines for in vivo administration to a host, including a human, to confer protection against diseases caused by a bacterial pathogen, including Haemophilus species, such as Haemophilus influenzae, that produces Hin47 protein or a protein capable of inducing antibodies in the host specifically reactive with Hin47 protein. The Hin47 analog and the encoding nucleic acid also may be employed in diagnostic applications.Type: GrantFiled: June 7, 1995Date of Patent: February 9, 1999Assignee: Connaught Laboratories LimitedInventors: Sheena M. Loosmore, Yan-Ping Yang, Pele Chong, Raymond P. Oomen, Michel H. Klein
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Patent number: 5866320Abstract: Non-infectious, retrovirus-like particles comprise an assembly of an env gene product, a pol gene product and a gag gene product contain an antigenic marker which is non-retroviral or non-HIV retroviral. In one embodiment, the marker comprises an amino acid sequence containing an epitope inserted into the gag gene product at an antigenically-active insertion site. In another embodiment, the marker comprises an antigenic anchor sequence operatively connected to the env gene product replacing endogenous anchoring function. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis. The presence of the antigenic marker enables recognition that antiserum containing anti-retroviral antibodies has been generated by exposure to the non-infectious retrovirus-like particles by testing for antibodies specific to the antigenic marker.Type: GrantFiled: June 6, 1995Date of Patent: February 2, 1999Assignee: Connaught Laboratories LimitedInventors: Benjamin Rovinski, Shi-Xian Cao, Fei-Long Yao, Roy Persson, Michel H. Klein