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US5288641A Expired / Lapsed US ⏱️ 0.0 years remaining

Herpes Simplex virus as a vector

Assignee: Arch Development Corp
•
Filing: 1992-07-30
•
Granted: 1994-02-22
•
Expires: 2012-07-30
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Abstract

Abstract A foreign gene is inserted into a viral genome under the control of promoter-regulatory regions of the genome, thus providing a vector for the expression of the foreign gene. DNA constructs, plasmid vectors containing the constructs useful for expression of the foreign gene, recombinant viruses produced with the vector, and associated methods are disclosed.

Inventors

  • 👤 Bernard Roizman

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-07 08:56
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/63; C12N15/79; C12N15/85; C12N15/86; C12N2710/00; C12N2710/00011; C12N2710/16011; C12N2710/16611; C12N2710/16622; C12N2710/16641; C12N2710/16643; C12N2710/16651; C12N2710/16652

Claims Analysis

Total Claims: 65
Claim 1
Independent Claim 29 words
A recombinant viral genome of a Herpes simplex virus (HSV) containing an expressable non-HSV nucleotide sequence encoding a desired protein permanently integrated at a non-lethal site of said genome.
Claim 2
Dependent Claim 29 words
A recombinant viral genome of a Herpes simplex virus (HSV) containing an expressable non-HSV nucleotide sequence encoding a desired protein permanently integrated at a non-lethal site of said genome.
Claim 3
Dependent Claim 14 words
The recombinant viral genome of claim 1 wherein said Herpes simplex virus is HSV-1.
Claim 4
Dependent Claim 26 words
The recombinant viral genome of claim 1 wherein said non-lethal site and said sequence are selected by the use of a selectable marker in said genome.
Claim 5
Dependent Claim 19 words
The recombinant viral genome of claim 2 wherein said marker is the thymidine kinase (TK) gene of said genome.
Claim 6
Dependent Claim 32 words
The recombinant viral genome of claim 3 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV alpha gene promoter.
Claim 7
Dependent Claim 22 words
The recombinant viral genome of claim 5 wherein said promoter-regulatory region comprises an alpha gene promoter of an infected cell protein gene.
Claim 8
Dependent Claim 24 words
The recombinant viral genome of claim 6 wherein said promoter-regulatory region comprises an alpha gene promoter of an infected cell protein number 4 gene.
Claim 9
Dependent Claim 32 words
The recombinant viral genome of claim 3 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV beta gene promoter.
Claim 10
Dependent Claim 23 words
The recombinant viral genome of claim 8 wherein said beta gene promoter is a promoter of the thymidine kinase gene of said genome.
Claim 11
Dependent Claim 21 words
The recombinant viral genome of claim 1 wherein said sequence comprises a structural coding sequence of hepatitis B surface antigen (HBsAg).
Claim 12
Dependent Claim 14 words
The recombinant viral genome of claim 1 wherein said Herpes simplex virus is HSV-2.
Claim 13
Dependent Claim 29 words
A plasmid vector containing an expressable non-HSV nucleotide sequence encoding a desired protein permanently integrated at a non-lethal site of a viral genome of a Herpes simplex virus (HSV).
Claim 14
Dependent Claim 29 words
A plasmid vector containing an expressable non-HSV nucleotide sequence encoding a desired protein permanently integrated at a non-lethal site of a viral genome of a Herpes simplex virus (HSV).
Claim 15
Dependent Claim 14 words
The plasmid vector of claim 12 comprising plasmid pRB 3223 (ATCC Accession No. 39716).
Claim 16
Dependent Claim 14 words
The plasmid vector of claim 12 comprising plasmid pRB 3225 (ATCC Accession No. 39715).
Claim 17
Dependent Claim 13 words
The plasmid vector of claim 12 wherein said Herpes simplex virus is HSV-1.
Claim 18
Dependent Claim 25 words
The plasmid vector of claim 12 wherein said non-lethal site and said sequence are selected by the use of a selectable marker in said genome.
Claim 19
Dependent Claim 18 words
The plasmid vector of claim 16 wherein said marker is the thymidine kinase (TK) gene of said genome.
Claim 20
Dependent Claim 31 words
The plasmid vector of claim 16 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV alpha gene promoter.
Claim 21
Dependent Claim 20 words
The plasmid vector of claim 18 wherein said promoter-regulatory region comprises an alpha gene promoter of an infected cell protein.
Claim 22
Dependent Claim 23 words
The plasmid vector of claim 19 wherein said promoter-regulatory region comprises an alpha gene promoter of an infected cell protein number 4 gene.
Claim 23
Dependent Claim 31 words
The plasmid vector of claim 16 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV beta gene promoter.
Claim 24
Dependent Claim 22 words
The plasmid vector of claim 21 wherein said beta gene promoter is a promoter of the thymidine kinase gene of said genome.
Claim 25
Dependent Claim 20 words
The plasmid vector of claim 12 wherein said sequence comprises a structural coding sequence for hepatitis B surface antigen (HBsAg).
Claim 26
Dependent Claim 13 words
The plasmid vector of claim 12 wherein said Herpes simplex virus is HSV-2.
Claim 27
Dependent Claim 35 words
A recombinant virus comprising a product of cotransfection of the plasmid vector of claim 12 with intact Herpes simplex virus DNA in a suitable host and screening of resulting progeny for progeny containing said sequence.
Claim 28
Dependent Claim 14 words
The recombinant virus of claim 25 comprising recombinant virus R3223 (ATCC Accession No. VR2086).
Claim 29
Dependent Claim 14 words
The recombinant virus of claim 25 comprising recombinant virus R3225 (ATCC Accession No. VR2087).
Claim 30
Dependent Claim 40 words
The recombinant virus of claim 25 wherein said non-lethal site and said sequence are selected by the use of a selectable marker in said genome, and said progeny are screened by selection for the presence or absence of said marker.
Claim 31
Dependent Claim 81 words
A method of obtaining a desired protein, comprising the steps of: (a) preparing a plasmid vector according to claim 12 wherein said expressible non-HSV nucleotide sequence codes for the expression of said protein; (b) cotransfecting said plasmid vector with intact Herpes simplex virus DNA to produce viral progeny; (c) screening and isolating progeny containing said sequence to obtain a recombinant virus; and, (d) infecting a suitable host with said recombinant virus and culturing said infected cells whereby said protein is produced.
Claim 32
Dependent Claim 15 words
The method of claim 29 including the further steps of harvesting and purifying said protein.
Claim 33
Dependent Claim 15 words
The method of claim 29 wherein said Herpes Simplex virus of said vector is HSV-1.
Claim 34
Dependent Claim 42 words
The method of claim 29 wherein said non-lethal site and said sequence are selected by the use of a selectable marker in said genome, and said screening step (c) is carried out by selecting for the presence or absence of said marker.
Claim 35
Dependent Claim 17 words
The method of claim 32 wherein said marker is the thymidine kinase (TK) gene of said genome.
Claim 36
Dependent Claim 30 words
The method of claim 32 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV alpha gene promoter.
Claim 37
Dependent Claim 20 words
The method of claim 34 wherein said promoter-regulatory region comprises an alpha gene promoter of an infected cell protein gene.
Claim 38
Dependent Claim 22 words
The method of claim 35 wherein said promoter-regulatory region comprises an alpha gene promoter of an infected cell protein number 4 gene.
Claim 39
Dependent Claim 30 words
The method of claim 32 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV beta gene promoter.
Claim 40
Dependent Claim 21 words
The method of claim 37 wherein said beta gene promoter is a promoter of the thymidine kinase gene of said genome.
Claim 41
Dependent Claim 19 words
The method of claim 29 wherein said sequence comprises a structural coding sequence for hepatitis B surface antigen (HBsAg).
Claim 42
Dependent Claim 15 words
The method of claim 29 wherein said Herpes Simplex virus of said vector is HSV-2.
Claim 43
Independent Claim 51 words
A method of preparing a recombinant viral genome of a Herpes Simplex virus (HSV), said method comprising the steps of: (a) isolating a viral genome of said Herpes Simplex virus; and, (b) permanently integrating into said genome at a non-lethal site thereof an expressable non-HSV nucleotide sequence encoding a desired protein.
Claim 44
Independent Claim 51 words
A method of preparing a recombinant viral genome of a Herpes Simplex virus (HSV), said method comprising the steps of: (a) isolating a viral genome of said Herpes Simplex virus; and, (b) permanently integrating into said genome at a non-lethal site thereof an expressable non-HSV nucleotide sequence encoding a desired protein.
Claim 45
Dependent Claim 12 words
The method of claim 41 wherein said Herpes Simplex virus is HSV-1.
Claim 46
Dependent Claim 24 words
The method of claim 41 wherein said non-lethal site and said sequence are selected by the use of a selectable marker in said genome.
Claim 47
Dependent Claim 17 words
The method of claim 43 wherein said marker is the thymidine kinase (TK) gene of said genome.
Claim 48
Dependent Claim 30 words
The method of claim 43 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV alpha gene promoter.
Claim 49
Dependent Claim 19 words
The method of claim 45 wherein said promoter-regulatory region comprises an alpha gene promoter of an infected cell protein.
Claim 50
Dependent Claim 21 words
The method of claim 46 wherein said promoter-regulatory region comprises an alpha promoter of an infected cell protein number 4 gene.
Claim 51
Dependent Claim 30 words
The method of claim 41 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV beta gene promoter.
Claim 52
Dependent Claim 21 words
The method of claim 48 wherein said beta gene promoter is a promoter of the thymidine kinase gene of said genome.
Claim 53
Dependent Claim 19 words
The method of claim 41 wherein said sequence comprises a structural coding sequence for hepatitis B surface antigen (HBsAg).
Claim 54
Dependent Claim 12 words
The method of claim 41 wherein said Herpes Simplex virus is HSV-2.
Claim 55
Dependent Claim 46 words
A method of obtaining a recombinant virus, comprising the steps of : (a) cotransfecting the plasmid vector of claim 12 with intact Herpes Simplex virus DNA in a suitable host; and, (b) screening the resulting progeny for a recombinant virus containing said expressible non-HSV nucleotide sequence.
Claim 56
Dependent Claim 12 words
The method of claim 52 wherein said Herpes Simplex virus is HSV-1.
Claim 57
Dependent Claim 42 words
The method of claim 52 wherein said non-lethal site and said sequence are selected by the use of a selectable marker in said genome, and said screening step (b) is carried out by selecting for the presence or absence of said marker.
Claim 58
Dependent Claim 17 words
The method of claim 54 wheren said marker is the thymidine kinase (TK) gene of said genome.
Claim 59
Dependent Claim 30 words
The method of claim 54 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV alpha gene promoter.
Claim 60
Dependent Claim 19 words
The method of claim 56 wherein said promoter-regulatory region comprises an alpha gene promoter of an infected cell protein.
Claim 61
Dependent Claim 22 words
The method of claim 57 wherein said promoter-regulatory region comprises an alpha gene promoter of an infected cell protein number 4 gene.
Claim 62
Dependent Claim 30 words
The method of claim 54 wherein said sequence is flanked at its respective ends with a suitable transcription termination signal and a promoter-regulatory region comprising an HSV beta gene promoter.
Claim 63
Dependent Claim 21 words
The method of claim 59 wherein said beta gene promoter is a promoter of the thymidine kinase gene of said genome.
Claim 64
Dependent Claim 19 words
The method of claim 52 wherein said sequence comprises a structural coding sequence for hepatitis B surface antigen (HBsAg).
Claim 65
Dependent Claim 15 words
The method of claim 52 wherein said Herpes Simplex virus of said vector is HSV-2.

References Cited (Backward Citations)

EP0074808A2 Cited
US4769331A Cited
EP0083286A2 Cited
US4603112A Cited
WO1983002393A1 Cited
WO1984002077A1 Cited

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