cassette vector for construction of poliovirus chimeras; dna cassette for recombinant vaccine...

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Potent Report This section provides information on worldwide patients 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 New attenuated vaccine strain of hog cholera virus; pig cholera virus attenuation by passage in PK15 cell culture Nippon-Seibutsu-Chem. Res. Inst. Jpn 2242 673; 27 September 1990 A new attenuated vaccine strain of pig cholera virus is derived from the domestic pig cholera virus LPC-China strain. The virus is spherical, 35-50 nm in size, lacks an envelope and has a regular icosashedral nucleocapsid. The E + virus reinforces the cytopathic effect of Newcastle disease virus (END method), and the E- virus does not inhibit proliferation of WEE virus (WEE interference method). The E+ virus produces a cytopathic effect of WEE virus, which attacks the E- virus after inhibiting proliferation of the E- virus, when tested by a two-step interference method. Neutralizing antibodies may be produced, for use in passive immunization. The vaccine strain is safe when inoculated into a pig, and causes no abnormal symptoms. The virus strain is obtained by passage through a pig kidney cell culture, preferably a PK 15 cell culture. The live vaccine is produced by growth of attenuated hog cholera virus in the pig kidney cell culture, followed by lyophilization. 054-91 Vaccine again shipping fever in cattle; contains purified Pasteurella haemolytica native or recombinant antigen of mol. wt. 105000; monoclonal antibody production for pneumonic pasteurellosis disease diagnosis in cattle Univ. Texas-Syst USA 4957 739; 18 September 1990 A pharmaceutical composition suitable for use as a vaccine comprises a purified Pasteurella haemolytica antigen together with an excipient, diluent or adjuvant. The antigen is purified from a cell-free P. haemolytica culture supernatant, or is pre- pared by genetic engineering including cloning and expressing the antigen gene. The antigen (mol. wt 105000) binds to immune serum obtained from pasteurellosis-infected cattle and has immunological cross-reactivity with a P. haemolytica antigen of mol. wt 105 000, amino-terminal sequence M-G-T- R-L-T-T-L-S-N and carboxy-terminal sequence -L-S-S-L-Q-F- A-R-A-A. The vaccine is useful for immunizing cattle against pneumonic pasteurellosis (shipping fever). The antigen can be used to produce antibodies (monoclonal antibodies and polyclonal antibodies) against P. haemolytica, which can be used for passive immunization and also for detection and diagnosis of P. haemolytica infections 055-91 Proteins and polypeptides of NS1 protein; of western subtype tick-borne encephalitis virus for use in diagnosis and live vaccine; DNA sequence and DNA probe construction Immuno Eur 402 116; 12 December 1990 A peptide or protein (A) comprising at least part of a specified amino acid sequence of an NS-1 protein of western subtype tick-borne encephalitis (TBE) is claimed. Also claimed are: i. the corresponding DNA sequence (B); ii. a probe of (B) nucleic acid hybridizing to (B); iii. a vector containing (B), a host cell containing the vector; iv. a culture of host cells; and v. processes for the production of (A) and (B). (A) may differ from that of a natural NS-1 sequence by mutations and/or transpositions in the normal range of natural variation of western subtype TBE virus. (B) may differ from DNA molecules corresponding to a natural NS-1 DNA sequence by degeneracy of the genetic code and/or mutations and/or transpositions. The nucleic acids may have additional sequences allowing replication and expression of the DNA molecule in a mammalian cell culture and preferably have sequences functioning as a promoter, an enhancer, a polyadenylation signal and/or a splicing signal. The vector is a plasmid, bacterium, virus (especially vaccinia virus) or phage including (B). (A) may be used as a vaccine or diagnostic reagent. 056-91 Cassette vector for construction of poliovirus chimeras; DNA cassette for recombinant vaccine construction; recombinant DNA sequence insertion in capsid protein VP1 antigenic site-I region Med. Res. Counc World 9015 145; 13 December 1990 A new DNA cassette vector for construction of poliovirus chimeras comprises a full-length infectious cDNA from a poliovirus-1 attenuated strain, with Sail and Dral sites flanking poliovirus antigenic site-1 (residues 94-101 of capsid protein VP1) under promoter control. The following are also new: a process for preparation of a poliovirus chimera, by constructing a double-stranded DNA fragment with the gene, and with a 5'-Sall cohesive end and a 3'-blunt end, digesting a cassette vector with Sail and DraI, ligating the fragment into the vector, and obtaining live virus from the modified vector; a pharma- ceutical formulation containing the virus; the cassette vector; and a method for producing a recombinant protein, by cloning in the vector. Plasmid pCAS1 and plasmid pCAS7 are specifically claimed. The chimeric polioviruses may be used as recombinant vaccines in humans or animals, and may be administered orally, nasally or parenterally. The cassette vector allows rapid and extensive modification of antigenic site-1 of the Sabin-1 poliovirus vaccine strain P1/L5c 2ab, to include foreign amino acid sequences. 057-91 Production of attenuated RNA virus strain; attenuation leading to reduced rate of reversion in mammalian host and use as live vaccine e.g. against poliovirus Am. Cyanamid Eur 401 421; 12 December 1990 Three methods are claimed for producing modified highly attenuated RNA virus strains having a reduced rate of reversion in a mammalian host, by: (a) isolating RNA viral sequences from viral particles; (b) preparing RNA viral cDNA from these sequences; (c) mutating the RNA viral cDNA so that the transcriptional and translation efficiency of RNA viral strains produced from the RNA viral cDNA are altered; (d) transfecting cells (e.g. CV-1, Vero, HeLa) with the mutated RNA viral cDNA; (e) culturing the host cells; and (f) extracting RNA viral strains from the cells. The three methods differ in step (c) by: method A, base pairing of the cDNA is increased; method B, base pairing of the cDNA is decreased; and method C, base pairing of the cDNA to itself is increased or decreased, as is base pairing of cDNA to ribosomal RNA from the host. In all three methods, the RNA viral strain is poliovirus. A live vaccine composition is claimed which causes the formation of antibodies to RNA viral antigens in a patient. Administration is by conventional methods. An example describes the site-directed mutagenesis ofpoliovirus cDNA using phage M 13. 058-91 0264-410X/91/070525-02 © 1991 Butterworth-Heinemann Ltd Vaccine, Vol. 9, July 1991 525

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Page 1: Cassette vector for construction of poliovirus chimeras; DNA cassette for recombinant vaccine construction; recombinant DNA sequence insertion in capsid protein VP1 antigenic site-1

Potent Report This section provides information on worldwide patients 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

New attenuated vaccine strain of hog cholera virus; pig cholera virus attenuation by passage in PK15 cell culture Nippon-Seibutsu-Chem. Res. Inst. Jpn 2242 673; 27 September 1990

A new attenuated vaccine strain of pig cholera virus is derived from the domestic pig cholera virus LPC-China strain. The virus is spherical, 35-50 nm in size, lacks an envelope and has a regular icosashedral nucleocapsid. The E + virus reinforces the cytopathic effect of Newcastle disease virus (END method), and the E - virus does not inhibit proliferation of WEE virus (WEE interference method). The E + virus produces a cytopathic effect of WEE virus, which attacks the E - virus after inhibiting proliferation of the E - virus, when tested by a two-step interference method. Neutralizing antibodies may be produced, for use in passive immunization. The vaccine strain is safe when inoculated into a pig, and causes no abnormal symptoms. The virus strain is obtained by passage through a pig kidney cell culture, preferably a PK 15 cell culture. The live vaccine is produced by growth of attenuated hog cholera virus in the pig kidney cell culture, followed by lyophilization. 054-91

Vaccine again shipping fever in cattle; contains purified Pasteurella haemolytica native or recombinant antigen of mol. wt. 105000; monoclonal antibody production for pneumonic pasteurellosis disease diagnosis in cattle Univ. Texas-Syst USA 4957 739; 18 September 1990

A pharmaceutical composition suitable for use as a vaccine comprises a purified Pasteurella haemolytica antigen together with an excipient, diluent or adjuvant. The antigen is purified from a cell-free P. haemolytica culture supernatant, or is pre- pared by genetic engineering including cloning and expressing the antigen gene. The antigen (mol. wt 105000) binds to immune serum obtained from pasteurellosis-infected cattle and has immunological cross-reactivity with a P. haemolytica antigen of mol. wt 105 000, amino-terminal sequence M-G-T- R-L-T-T-L-S-N and carboxy-terminal sequence -L-S-S-L-Q-F- A-R-A-A. The vaccine is useful for immunizing cattle against pneumonic pasteurellosis (shipping fever). The antigen can be used to produce antibodies (monoclonal antibodies and polyclonal antibodies) against P. haemolytica, which can be used for passive immunization and also for detection and diagnosis of P. haemolytica infections 055-91

Proteins and polypeptides of NS1 protein; of western subtype tick-borne encephalitis virus for use in diagnosis and live vaccine; DNA sequence and DNA probe construction Immuno Eur 402 116; 12 December 1990

A peptide or protein (A) comprising at least part of a specified amino acid sequence of an NS-1 protein of western subtype tick-borne encephalitis (TBE) is claimed. Also claimed are: i. the corresponding DNA sequence (B); ii. a probe of (B) nucleic acid hybridizing to (B); iii. a vector containing (B), a host cell containing the vector; iv. a culture of host cells; and v. processes

for the production of (A) and (B). (A) may differ from that of a natural NS-1 sequence by mutations and/or transpositions in the normal range of natural variation of western subtype TBE virus. (B) may differ from DNA molecules corresponding to a natural NS-1 DNA sequence by degeneracy of the genetic code and/or mutations and/or transpositions. The nucleic acids may have additional sequences allowing replication and expression of the DNA molecule in a mammalian cell culture and preferably have sequences functioning as a promoter, an enhancer, a polyadenylation signal and/or a splicing signal. The vector is a plasmid, bacterium, virus (especially vaccinia virus) or phage including (B). (A) may be used as a vaccine or diagnostic reagent. 056-91

Cassette vector for construction of poliovirus chimeras; DNA cassette for recombinant vaccine construction; recombinant DNA sequence insertion in capsid protein VP1 antigenic site-I region Med. Res. Counc World 9015 145; 13 December 1990

A new DNA cassette vector for construction of poliovirus chimeras comprises a full-length infectious cDNA from a poliovirus-1 attenuated strain, with Sail and Dral sites flanking poliovirus antigenic site-1 (residues 94-101 of capsid protein VP1) under promoter control. The following are also new: a process for preparation of a poliovirus chimera, by constructing a double-stranded DNA fragment with the gene, and with a 5'-Sall cohesive end and a 3'-blunt end, digesting a cassette vector with Sail and DraI, ligating the fragment into the vector, and obtaining live virus from the modified vector; a pharma- ceutical formulation containing the virus; the cassette vector; and a method for producing a recombinant protein, by cloning in the vector. Plasmid pCAS1 and plasmid pCAS7 are specifically claimed. The chimeric polioviruses may be used as recombinant vaccines in humans or animals, and may be administered orally, nasally or parenterally. The cassette vector allows rapid and extensive modification of antigenic site-1 of the Sabin-1 poliovirus vaccine strain P1/L5c 2ab, to include foreign amino acid sequences. 057-91

Production of attenuated RNA virus strain; attenuation leading to reduced rate of reversion in mammalian host and use as live vaccine e.g. against poliovirus Am. Cyanamid Eur 401 421; 12 December 1990

Three methods are claimed for producing modified highly attenuated RNA virus strains having a reduced rate of reversion in a mammalian host, by: (a) isolating RNA viral sequences from viral particles; (b) preparing RNA viral cDNA from these sequences; (c) mutating the RNA viral cDNA so that the transcriptional and translation efficiency of RNA viral strains produced from the RNA viral cDNA are altered; (d) transfecting cells (e.g. CV-1, Vero, HeLa) with the mutated RNA viral cDNA; (e) culturing the host cells; and (f) extracting RNA viral strains from the cells. The three methods differ in step (c) by: method A, base pairing of the cDNA is increased; method B, base pairing of the cDNA is decreased; and method C, base pairing of the cDNA to itself is increased or decreased, as is base pairing of cDNA to ribosomal RNA from the host. In all three methods, the RNA viral strain is poliovirus. A live vaccine composition is claimed which causes the formation of antibodies to RNA viral antigens in a patient. Administration is by conventional methods. An example describes the site-directed mutagenesis ofpoliovirus cDNA using phage M 13.

058-91

0264-410X/91/070525-02 © 1991 Butterworth-Heinemann Ltd Vaccine, Vol. 9, July 1991 525