new dna sequence encoding modified retrovirus gag polypeptide; gag protein with gp120 or gp41...

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This section provides information on worldwide patents relevant to vaccine design and production. The Patent Report gives the following information: title of patent, patentee, patent number, publication date and summary of the patent. A number of patents in this report are reproduced from 'Biotechnology Abstracts' with permission of Derwent Publications Ltd. Rochdale House, 128 Theobalds Road, London WC1X 8RP, UK. Subregion of retrovirus env protein; application in diagnosis, prophylaxis and therapy of retrovirus, especially HIV virus-l, infections, and in vaccine development Wolf HJ Eur. 448 095; 25 September 1991 A subregion (A) of the retrovirus env protein is claimed, which is biologically equivalent to the V3 region of the HIV virus-1 env protein, and is recognized by at least 70% of randomly selected sera of individuals infected with the retrovirus from which it is derived. The following are also claimed : (1) a DNA sequence (I) encoding (A); (2) a recombinant vector containing (I); (3) a recombinant virus containing (I); and (4) a host transformed with the recombinant vector or virus. The V3 region consists of amino acids 294-332 of the major env protein gpl20 of HIV virus-1 isolate BH10. The conserved oligopeptide contains 3-10 amino acids, and preferably comprises GPGR. At least two Cys residues are present in subregion (A). (A) may be produced by culturing the transformed host, and may be used for the diagnosis, prophylaxis or therapy of retrovirus, especially HIV virus-l, infections, and may be used in vaccine production. 025-92 DNA of fish hemorrhagic-septicemia virus, nucleoprotein-N production by Saccharomyces cerevisiae transformed with vector plasmid pSHV-N2, plasmid pYSHVN containing DNA sequence; application in recombinant vaccine, etc. INRA World 9113 987; 19 September 1991 The following are claimed: (a) a DNA sequence derived from the genomic RNA of hemorrhagic-septicemia virus (HSV) and consisting of a nucleoprotein-N gene; (b) peptides encoded by the DNA of (a) or its fragments ; (c) cloning and/or expression vectors containing the DNA of (a) or its derivatives or fragments; and (d) host cells, preferably Saccharomyces cerevisiae, transformed with the vectors of (c). The DNA of (a), designated SHV-N2, was isolated from cDNA generated from the RNA of HSV-infected Epithelioma papulosum cyprini cells, and cloned in plasmid pUC13 to give plasmid pSHV-N2. DNA amplified from pSHV-N2 was used to construct expression vector plasmid pYSHVN (derived from plasmid pEGT101 ) for transformation of yeast cells. A 1235 bp fragment of SHV-N2 (nucleotides 101-1336), designated SHV-N1, was isolated in a similar fashion and cloned in plasmid pBS-SK. The peptides can be used to prepare vaccines against HSV infections in salmonid fish, and as diagnostic agents for anti-HSV antibodies. The HSV DNA can be used for recombinant nucleoprotein-N production, transgenic animal construction and as DNA probes and DNA primers. 026 92 Potent Report New synthetic peptide corresponding to an epitope of HIV virus-I or HIV virus-2 envelope protein prepared by recombinant DNA techniques, and useful as a vaccine against HIV, for therapy of HIV infection or for diagnosis Proteus Mol. Des. World 9113 909 ; 19 September 1991 A synthetic peptide is claimed which has at least one antigenic property of the envelope protein of at least one strain of HIV virus, and optionally also contains at least one T-lymphocyte epitope. Also claimed are DNA molecules encoding such peptides, and an antibody or its antigen-binding fragment which specifically binds to such peptides. The peptides can be used for the therapeutic or prophylactic treatment of HIV infections (e.g. as vaccines) and/or for stimulating the mammalian immune system and/or blocking the cellular receptors for the HIV virus. The antibodies are used for passive immunization of HIV patients. The peptides and antibodies can also be used for detecting HIV or HIV antibodies. Preferred peptides have the sequence: X- DQSLKGIWGCSGKLAC-Y ; X-DQQLLGIWGCSGKLAC- Y; or X-ETR3R4KNSWGCAFRQVC-Y, where R3 is Ser when R4 is Ile, or R3 is Ala when R4 is Arg or Gln. The peptides are prepared by chemical synthesis or by recombinant DNA techniques. 027-92 Modified recombinant poxvirus with DNA core from non-pox source; gene expression in cell culture and transformed host; potential application recombinant vaccine construction Health Res. World 9112 318; 22 August 1991 The following are claimed : i. a modified recombinant poxvirus having an internal core containing DNA from a non-pox source in a non-essential region of the poxvirus genome, where the recombinant poxvirus is modified by dissociating the internal core from outer membranes of the poxvirus ; ii. a method for expressing a gene product in a cell cultured in vitro which involves introducing into the cell a modified recombinant poxvirus of (i.) ; and iii. a method for expressing a gene product in a host which involves inoculating the host with a modified recombinant poxvirus of (i.). The modified recombinant poxviruses express gene products without productive replication of the poxviruses. The modified recombinant poxviruses can be used in vaccines for inducing an immunological response in bird and other vertebrates to an antigen. The vaccines have the advantages of a live virus vaccine with few or none of the disadvantages of a live virus vaccine or a killed virus vaccine. The virus is self-limiting, reducing the possibility of spreading to non-vaccinated hosts. 028-92 New DNA sequence encoding modified retrovirus gag polypeptide; gag protein with gpl20 or glM1 epitope; gene cloning in e.g. Drosophila sp. Schneider insect cell culture using a baculovirus vector; vaccinia virus vector for recombinant vaccine construction Wolf HJ Eur 449 116; 2 October 1991 The following are new : a DNA sequence encoding a modified retrovirus gag protein, containing a non-gag antigenic determinant (derived from HTLV-I virus, HTLV-II virus, HIV virus-l, HIV virus-2 or SIV virus), which may be all or part of the CD4-binding domain of gpl20, variable region-3 of gpl20, or the fusogenic region of gp41 ; a recombinant vector Vaccine, Vol. 10, Issue 4, 1992 293

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Page 1: New DNA sequence encoding modified retrovirus gag polypeptide; gag protein with gp120 or gp41 epitope; gene cloning in e.g. Drosophila sp. Schneider insect cell culture using a baculovirus

This section provides information on worldwide patents relevant to vaccine design and production. The Patent Report gives the following information: title of patent, patentee, patent number, publication date and summary of the patent. A number of patents in this report are reproduced from 'Biotechnology Abstracts' with permission of Derwent Publications Ltd. Rochdale House, 128 Theobalds Road, London WC1X 8RP, UK.

Subregion of retrovirus env protein; application in diagnosis, prophylaxis and therapy of retrovirus, especially HIV virus-l, infections, and in vaccine development Wolf HJ Eur. 448 095; 25 September 1991

A subregion (A) of the retrovirus env protein is claimed, which is biologically equivalent to the V3 region of the HIV virus-1 env protein, and is recognized by at least 70% of randomly selected sera of individuals infected with the retrovirus from which it is derived. The following are also claimed : (1) a DNA sequence (I) encoding (A); (2) a recombinant vector containing (I); (3) a recombinant virus containing (I); and (4) a host transformed with the recombinant vector or virus. The V3 region consists of amino acids 294-332 of the major env protein gpl20 of HIV virus-1 isolate BH10. The conserved oligopeptide contains 3-10 amino acids, and preferably comprises GPGR. At least two Cys residues are present in subregion (A). (A) may be produced by culturing the transformed host, and may be used for the diagnosis, prophylaxis or therapy of retrovirus, especially HIV virus-l, infections, and may be used in vaccine production. 025-92

DNA of fish hemorrhagic-septicemia virus, nucleoprotein-N production by Saccharomyces cerevisiae transformed with vector plasmid pSHV-N2, plasmid pYSHVN containing DNA sequence; application in recombinant vaccine, etc. INRA World 9113 987; 19 September 1991

The following are claimed: (a) a DNA sequence derived from the genomic RNA of hemorrhagic-septicemia virus (HSV) and consisting of a nucleoprotein-N gene; (b) peptides encoded by the DNA of (a) or its fragments ; (c) cloning and/or expression vectors containing the DNA of (a) or its derivatives or fragments; and (d) host cells, preferably Saccharomyces cerevisiae, transformed with the vectors of (c). The DNA of (a), designated SHV-N2, was isolated from cDNA generated from the RNA of HSV-infected Epithelioma papulosum cyprini cells, and cloned in plasmid pUC13 to give plasmid pSHV-N2. DNA amplified from pSHV-N2 was used to construct expression vector plasmid pYSHVN (derived from plasmid pEGT101 ) for transformation of yeast cells. A 1235 bp fragment of SHV-N2 (nucleotides 101-1336), designated SHV-N1, was isolated in a similar fashion and cloned in plasmid pBS-SK. The peptides can be used to prepare vaccines against HSV infections in salmonid fish, and as diagnostic agents for anti-HSV antibodies. The HSV DNA can be used for recombinant nucleoprotein-N production, transgenic animal construction and as DNA probes and DNA primers.

026 92

Potent Report New synthetic peptide corresponding to an epitope of HIV virus-I or HIV virus-2 envelope protein prepared by recombinant DNA techniques, and useful as a vaccine against HIV, for therapy of HIV infection or for diagnosis Proteus Mol. Des. World 9113 909 ; 19 September 1991

A synthetic peptide is claimed which has at least one antigenic property of the envelope protein of at least one strain of HIV virus, and optionally also contains at least one T-lymphocyte epitope. Also claimed are DNA molecules encoding such peptides, and an antibody or its antigen-binding fragment which specifically binds to such peptides. The peptides can be used for the therapeutic or prophylactic treatment of HIV infections (e.g. as vaccines) and/or for stimulating the mammalian immune system and/or blocking the cellular receptors for the HIV virus. The antibodies are used for passive immunization of HIV patients. The peptides and antibodies can also be used for detecting HIV or HIV antibodies. Preferred peptides have the sequence: X- DQSLKGIWGCSGKLAC-Y ; X-DQQLLGIWGCSGKLAC- Y; or X-ETR3R4KNSWGCAFRQVC-Y, where R3 is Ser when R4 is Ile, or R3 is Ala when R4 is Arg or Gln. The peptides are prepared by chemical synthesis or by recombinant DNA techniques. 027-92

Modified recombinant poxvirus with DNA core from non-pox source; gene expression in cell culture and transformed host; potential application recombinant vaccine construction Health Res. World 9112 318; 22 August 1991

The following are claimed : i. a modified recombinant poxvirus having an internal core containing DNA from a non-pox source in a non-essential region of the poxvirus genome, where the recombinant poxvirus is modified by dissociating the internal core from outer membranes of the poxvirus ; ii. a method for expressing a gene product in a cell cultured in vitro which involves introducing into the cell a modified recombinant poxvirus of (i.) ; and iii. a method for expressing a gene product in a host which involves inoculating the host with a modified recombinant poxvirus of (i.). The modified recombinant poxviruses express gene products without productive replication of the poxviruses. The modified recombinant poxviruses can be used in vaccines for inducing an immunological response in bird and other vertebrates to an antigen. The vaccines have the advantages of a live virus vaccine with few or none of the disadvantages of a live virus vaccine or a killed virus vaccine. The virus is self-limiting, reducing the possibility of spreading to non-vaccinated hosts. 028-92

New DNA sequence encoding modified retrovirus gag polypeptide; gag protein with gpl20 or glM1 epitope; gene cloning in e.g. Drosophila sp. Schneider insect cell culture using a baculovirus vector; vaccinia virus vector for recombinant vaccine construction Wolf HJ Eur 449 116; 2 October 1991

The following are new : a DNA sequence encoding a modified retrovirus gag protein, containing a non-gag antigenic determinant (derived from HTLV-I virus, HTLV-II virus, HIV virus-l, HIV virus-2 or SIV virus), which may be all or part of the CD4-binding domain of gpl20, variable region-3 of gpl20, or the fusogenic region of gp41 ; a recombinant vector

Vaccine, Vol. 10, Issue 4, 1992 293

Page 2: New DNA sequence encoding modified retrovirus gag polypeptide; gag protein with gp120 or gp41 epitope; gene cloning in e.g. Drosophila sp. Schneider insect cell culture using a baculovirus

or virus (e.g. vaccinia virus) containing the DNA; a host (e.g. a Drosophila Schneider insect cell culture containing a baculovirus vector) transformed with the vector or virus; a modified retrovirus gag protein encoded by the DNA; and an aggregate particle of the protein. The foreign DNA is inserted into the gag gene so that the encoded protein elicits an immune response (e.g. amino acid position 15-57, 99-154, 211-241 or 436-471 ), or is fused to the C- or N-terminus of the gag protein. The modified retrovirus gag proteins have improved immuno- genicity, and may be used in recombinant vaccines for immunization of mammals against retrovirus infection, e.g. AIDS. 029-92

Pathogenesis factors from dermatophytes, and vaccines containing them; e.g. Trichophyton sp., Microsporium sp., Epidermophyton floecorum keratinase application dermato- phytosis vaccine, and antibody application in passive immunization Bayer DE 4007 927 ; 19 September 1991

Pathogenesis factors (I) from dermatophytes, and antibodies against (I), are new. (I) preferably exhibit keratinase activity and have a mol. wt of more than 10000. (I) can be prepared by parasitic cultivation of dermatophytes in the presence of keratin, and then isolating (I) from the culture supernatant. (I) have antigenic properties and can be used as vaccines for prophylactic immunization against fungal disease of the skin caused by dermatophytes, e.g. Trichophyton and Microsporium. (I )-Specific antibodies can be used for passive immunization. In an example, dermatophyte (e.g. Trichophyton sp., Microsporium sp., Epidermophyton floccorum) conidia were cultivated at 28-32°C with agitation in mineral medium (0.5 g/1 MgSO4. 7H20 , 0.1 g/1 KH2PO4, 0.01 g/1 FeSO4.7H20 and 0.05 g/1 ZnSO4.7H20) containing 3-10 g/1 keratin-containing material (e.g. guinea-pig, cat, dog or human hair, skin or nail material) as the only organic substance. After 6-7 days, the culture filtrate was lyophilized and dialysed. The role of the dermatophyte extract in dermatophytosis was demonstrated.

030-92

Attenuated mutant strains of A eromonas; A eromonas salmonicida non-reverting mutant construction; protein sequence; potential application in salmon, trout vaccine production against furunculosis Trinity College, Dublin World 9113 978; 19 September 1991

The following are claimed : i. an attenuated strain of Aeromonas bearing a non-reverting mutation in the aroA gene; ii.

Aeromonas salmonicida DU5847 deposited as NCIMB 40261 or a strain similar to it in the region of DNA encoding a mutant gene (aroA) of the aromatic biosynthetic pathway, the strain also being attenuated; iii. A. salmonicida DU5847 with its kanamycin-resistant marker excised; and iv. A. salmonicida DU5860 deposited as NCIMB 40391 or a strain similar to it in the region of DNA encoding a mutant gene of the aromatic biosynthetic pathway, the strain also being attenuated. More specifically, the aroA gene of A. salmonicida was cloned and sequenced. The aroA gene was then inactivated and mutant sequences were introduced into A. salmonicida. The attenuated mutant strains can be used in vaccines for fish, especially salmon and trout, for the prevention of furunculosis. The mutants are avirulent, survive for up to 2 weeks in infected fish and stimualte strong protective immunity. The attenuated bacterium retains surface antigen present on the virulent organism and is thus a good immunogen. 031-92

Plasmodium falciparum sporozoite antigen DNA sequence and protein sequence; gene cloning and expression in Eseherichia coli; potential application to recombinant vaccine preparation Roche Eur 447 956 ; 25 September 1991

The following are claimed: (A) polypeptides (I) which correspond to at least one specific epitope within a Plasmodium falciparum sporozoite antigen having a specified N-terminal protein sequence; (B) fusion proteins (II) comprising (I) linked to an affinity peptide; (C) polypeptides including a (NXY)n, (YNX)n or (XYN)n sequence, where N = Ash, X = a charged amino acid (e.g. Gly or Lys), Y = a hydrophobic amino acid (e.g. Val or Met), and n = 3-120; (D) DNA coding for ( I ) - ( I I I ) , replicable microbial vectors containing such DNA, and microorganisms transformed with such vectors; and (E) antibodies against ( I ) - ( I I I ) . A gene (NXY) coding for the P. falciparum sporozite antigen was isolated from a P. falciparum gene bank. Insertion of a 1400 bp AseI fragment of NXY into plasmid pDS56/RBSII,6xHis yielded a vector, plasmid pDS-NXY. Escherichia coli SG13009 (plasmid pUHA1) transformed with pDS-NXY produced a 69 kDa fusion protein comprising the NXY fragment linked N-terminally to an affinity peptide containing six His units, and C-terminally to a vector-derived sequence. ( I ) - ( I I I ) are useful in the production of vaccines against malaria. 032-92

294 Vaccine, Vol. 10, Issue 4, 1992