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- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20230181725
- Publication Date: June 15, 2023
- Appl. No: 18/058116
- Application Filed: November 22, 2022
- Claim: 1. An infectious, replication-deficient arenavirus viral vector engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, not genetically engineered cells, wherein one arenavirus open reading frame is removed and replaced by a nucleotide sequence selected from the group consisting of: a. a nucleotide sequence encoding a cytomegalovirus glycoprotein gB or an antigenic fragment thereof; b. a nucleotide sequence encoding a cytomegalovirus tegument protein pp65 or an antigenic fragment thereof; c. a nucleotide sequence encoding a cytomegalovirus glycoprotein gH or an antigenic fragment thereof; d. a nucleotide sequence encoding a cytomegalovirus glycoprotein gL or an antigenic fragment thereof, e. a nucleotide sequence encoding a cytomegalovirus UL128 protein or an antigenic fragment thereof, f. a nucleotide sequence encoding a cytomegalovirus UL130 protein or an antigenic fragment thereof, and g. a nucleotide sequence encoding a cytomegalovirus UL131A protein or an antigenic fragment thereof.
- Claim: 2. The viral vector of claim 1 wherein the glycoprotein gB or the antigenic fragment thereof comprises an amino acid sequence that is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 30, SEQ ID NO: 60, or SEQ ID NO: 63, wherein the pp65 antigen is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the pp65 antigen or antigenic fragment of SEQ ID NO: 36, wherein the glycoprotein gH is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the gH antigen or antigenic fragment selected from SEQ ID NO: 39 or SEQ ID NO: 52, wherein the glycoprotein gL is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the gL antigen or antigenic fragment of SEQ ID NO: 41, wherein the UL128 is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the UL128 antigen or antigenic fragment of SEQ ID NO: 43, wherein the UL130 is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the UL130 antigen or antigenic fragment of SEQ ID NO: 46, or wherein the UL131A is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the UL131A antigen or antigenic fragment of SEQ ID NO: 48.
- Claim: 3-8. (canceled)
- Claim: 9. The viral vector of claim 1 comprising at least two, three, four or all five of: a. a nucleotide sequence encoding a cytomegalovirus glycoprotein gH or an antigenic fragment thereof; b. a nucleotide sequence encoding a cytomegalovirus glycoprotein gL or an antigenic fragment thereof, c. a nucleotide sequence encoding a cytomegalovirus UL128 protein or an antigenic fragment thereof, d. a nucleotide sequence encoding a cytomegalovirus UL130 protein or an antigenic fragment thereof, and e. a nucleotide sequence encoding a cytomegalovirus UL131A protein or an antigenic fragment thereof, wherein the two, three, four or five nucleotide sequences selected from a. to e. above are separated by a nucleotide sequence that encodes a self-cleaving peptide or amino acid sequence that leads to release of the upstream amino acid sequence by “ribosome skipping” or a sequence element leading to binding of the ribosome and translation of the downstream sequence such as “internal ribosome entry sites”.
- Claim: 10-12. (canceled)
- Claim: 13. The viral vector of claim 9 wherein expression of the nucleotide sequences produces an antigenic protein complex that elicits higher titers of neutralizing antibodies than expression of the protein complex components individually.
- Claim: 14. The viral vector of claim 9 wherein the self-cleaving peptide (or “ribosome skipping” sequence) is Porcine teschovirus-1 2A, Thoseaasignavirus 2A or Foot-and-mouth disease virus 2A peptide.
- Claim: 15. The viral vector of claim 1 wherein the arenavirus is lymphocytic choriomeningitis virus.
- Claim: 16. The viral vector of claim 1 wherein the open reading frame that encodes the glycoprotein of the arenavirus is deleted or functionally inactivated.
- Claim: 17. The viral vector of claim 1 wherein the genomic information encoding the infectious, replication-deficient arenavirus viral vector is derived from the lymphocytic choriomeningitis virus Clone 13 strain.
- Claim: 18-26. (canceled)
- Claim: 27. An infectious, replication-deficient arenavirus viral vector comprising a nucleotide sequence encoding a cytomegalovirus glycoprotein gB wherein (i) the cytoplasmic domain of the glycoprotein gB has been deleted; or (ii) the cytoplasmic domain and the transmembrane domain of the glycoprotein gB have been deleted.
- Claim: 28. A pharmaceutical or immunogenic composition or vaccine comprising a viral vector of claim 1 and a pharmaceutically acceptable carrier.
- Claim: 29-42. (canceled)
- Claim: 43. An isolated nucleic acid, wherein the nucleic acid encodes an arenavirus genomic segment wherein one open reading frame of the genomic segment is deleted or functionally inactivated and wherein the genomic segment comprises one or more of: a. a nucleotide sequence encoding a cytomegalovirus glycoprotein gB or an antigenic fragment thereof; b. a nucleotide sequence encoding a cytomegalovirus tegument protein pp65 or an antigenic fragment thereof; c. a nucleotide sequence encoding a cytomegalovirus glycoprotein gH or an antigenic fragment thereof; d. a nucleotide sequence encoding a cytomegalovirus glycoprotein gL or an antigenic fragment thereof, e. a nucleotide sequence encoding a cytomegalovirus UL128 protein or an antigenic fragment thereof, f. a nucleotide sequence encoding a cytomegalovirus UL130 protein or an antigenic fragment thereof, and g. a nucleotide sequence encoding a cytomegalovirus UL131A protein or an antigenic fragment thereof.
- Claim: 44-48. (canceled)
- Claim: 49. A method for generating an infectious, replication-deficient arenavirus viral vector comprising: a. transfecting into a host cell the nucleic acid of claim 43; b. maintaining the host cell under conditions suitable for virus formation; and c. harvesting the infectious, replication-deficient arenavirus viral vector; wherein the host cell expresses the open reading frame that is deleted or functionally inactivated of the genomic segment.
- Claim: 50. A recombinant LCMV strain MP.
- Claim: 51-58. (canceled)
- Claim: 59. A recombinant viral vector comprising the nucleotide sequence of SEQ ID NO: 49 or 53.
- Claim: 60. A vaccine composition comprising HCMV gB protein wherein the cytoplasmic domain of HCMV gB is deleted.
- Claim: 61. The vaccine of claim 60 wherein the truncated HCMV gB comprises the N-terminal 772 amino acids of gB strain Merlin (SEQ ID NO: 60) but does not comprise the remaining C-terminal amino acids of gB strain Merlin.
- Claim: 62. The vaccine of claim 60 wherein the truncated HCMV gB consists essentially of the N-terminal 772 amino acids of gB strain Merlin (SEQ ID NO: 60).
- Claim: 63. The vaccine of claim 60 wherein the truncated HCMV gB consists essentially of the N-terminal 772 amino acids of gB strain Merlin (SEQ ID NO: 60) followed by an Arginin residue at position 773.
- Claim: 64. The vaccine of claim 60 wherein the truncated HCMV gB comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, at least 99.5% or 100% identical to the amino acid sequence of SEQ ID NO: 18.
- Claim: 65. (canceled)
- Claim: 66. An infectious, replication-deficient arenavirus viral vector engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, not genetically engineered cells, wherein one arenavirus open reading frame is removed and replaced by a nucleotide sequence encoding a CMV antigen or an antigenic fragment thereof, wherein administration of the arenavirus viral vector to a subject induces a long-lasting immune response against the CMV antigen or an antigenic fragment thereof or wherein the arenavirus viral vector is suitable to protect against a congenital CMV infection.
- Claim: 67-87. (canceled)
- Claim: 88. An immunogenic composition comprising a polypeptide that is at least 80%, 85%, 90%, 95%, 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 3, wherein the polypeptide has a truncation or a deletion in the region of amino acids 772-906 of SEQ ID NO: 3, wherein the percent identity is determined over the length of the polypeptide.
- Claim: 89-90. (canceled)
- Current International Class: 61; 12; 61; 07; 07; 12
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