Office Action 1: Non-Final Rejection (2024-10-01)
Rejection types: Double Patenting

CLAIMS:
CLAIMS

WHAT IS CLAIMED IS:

1\. A pharmaceutical composition comprising:
i) a myxoma virus (MYXV) comprising a genetic modification at its M153 locus and a transgene encoding a cytokine or a cell matrix protein; and
ii) a pharmaceutically acceptable excipient.

2\. The pharmaceutical composition of claim 1, wherein the genetic modification comprises a disruption of M153 gene.

3\. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated for systemic administration.

4\. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated for local administration.

5\. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated for parenteral administration.

6\. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises the MYXV at a dose of less than 1x109 focus forming units (FFU).

7\. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises the MYXV at a dose of at least 1x107 focus forming units (FFU).

8\. The pharmaceutical composition of claim 1, wherein upon administration of the MYXV to a subject, the transgene is effective to increase expression of at least two cytokines in a cancer cell of the subject at least about 30% compared to before the administering.

9\. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises the MYXV at a dose effective to increase expression of at least two cytokines in a cancer cell of a subject at least about 30% upon administration of the MYXV to the subject.

10\. The pharmaceutical composition of claim 8, wherein the at least two cytokines comprise IFN-7, IL-2, IL-6, IL-10, IL-12, or TNF-a.

11\. The pharmaceutical composition of claim 1, wherein the MYXV is effective to reduce viability of a cancer cell.
12\. The pharmaceutical composition of claim 8, wherein the cancer cell comprises a solid tumor cell.

13\. The pharmaceutical composition of claim 8, wherein the cancer cell comprises an osteosarcoma, triple negative breast cancer, or melanoma cell.

14\. The pharmaceutical composition of claim 1, wherein the transgene encodes the cytokine.

15\. The pharmaceutical composition of claim 8, wherein the at least two cytokines comprise TNF-a and IL-12.

16\. The pharmaceutical composition of claim 1, wherein the transgene encodes human TNFa.

17\. The pharmaceutical composition of claim 1, wherein the transgene encodes human IL-12.

18\. The pharmaceutical composition of claim 1, wherein the transgene encodes the cell matrix protein.

19\. The pharmaceutical composition of claim 1, wherein the transgene encodes human decorin.

20\. The pharmaceutical composition of claim 1, wherein the transgene encodes the cytokine and the MYXV further comprises a second transgene that encodes the cell matrix protein. -65- -66-

OFFICE ACTION:
DETAILED ACTION
Notice of Pre-AIA  or AIA  Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA  as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8, 16-23, 26, 27 of U.S. Patent No. 11,117,934. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘934 claims recite MYXV’s having an attenuated or disrupted M153 gene and a transgene encoding a cytokine or cell matrix protein (claims 1-4).  The MYXV’s are administered in methods of treating cancer and are thus pharmaceuticals and formulated for administration (claims 18-21). The administration is at a dose sufficient to increase expression of at least two cytokines (claim 26) and is effective to reduce tumor or cancer viability or volume (claims 22, 27).  The cytokines may be TNF-alpha or IL-12 (claims 6, 8).  Tumors are considered solid and the cancer may be osteosarcoma (claim 23).  The cell matrix protein may be decorin (claim 16) and include both a cytokine and a cell matrix protein (claims 16, 17).
Conclusion
No claim is allowed.

APPLICANT REBUTTAL: REMARKS
Claims 1-20 are currently pending and under consideration.
Double Patenting (U.S. Patent No. 11,117,934)
The Examiner has rejected claims 1-20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8, 16-23, 26, and 27 of U.S. Patent No. 11,117,934. The Examiner asserts that the claims in the patent are directed to MYXV having an attenuated or disrupted M153 gene and transgene encoding a cytokine or cell matrix protein (claims 1-4) and administered in methods of treating cancer and are thus pharmaceuticals and formulated for administration (claims 18-21).
Applicants understand that a timely filed Terminal Disclaimer in compliance with 37 C.F.R. § 1.321(c) may be used to overcome such a non-statutory type of double patenting rejection. Accordingly, Applicants are filing the appropriate Terminal Disclaimer herewith. Therefore, Applicants respectfully submit that the double patenting rejection has been overcome.
Summary
Early consideration and allowance of the claims in the present application is requested at the earliest possible time.
Respectfully submitted, Douglas Grant McFadden, et al.

NEXT OFFICE ACTION: EXAMINER'S COMMENT
Terminal Disclaimer
The terminal disclaimer filed on 1/2/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US 11,117,934 has been reviewed and is accepted.  The terminal disclaimer has been recorded.
Reasons for Allowance
The relevant prior art does not teach or suggest the combination of modifications to myxoma virus as found in claim 1, or the use of M153-attenuated myxoma virus in the treatment of cancer. The M153 gene is not taught by the prior art to have any positive or negative effect on the anti-cancer properties of myxoma virus.
Conclusion

CITED REFERENCE SUMMARIES: Ref US11117934: Claims:
A myxoma virus (MYXV) having enhanced anti-cancer activity, wherein the MYXV is genetically engineered to attenuate an activity or expression level of its M153 protein, and to express a non-viral molecule, wherein the non-viral molecule is a cytokine or a cell matrix protein.
The MYXV of claim 1 , wherein the activity or the expression level of the M153 protein is attenuated at least 80%.
The MYXV of claim 1 , wherein the MYXV is engineered to introduce a mutation in a nucleic acid encoding the M153 protein, wherein the mutation comprises an insertion, deletion, or substitution mutation.
The MYXV of claim 1 , wherein at least a portion of a nucleic acid encoding the M153 protein in MYXV genome is knocked out.
The MYXV of claim 1 , wherein the MYXV comprises an inhibitory molecule targeting M153 transcript that thereby attenuates the M153 protein expression, wherein the inhibitory molecule comprises dsRNA, siRNA, antisense RNA, or miRNA.
The MYXV of claim 1 , wherein the non-viral molecule is tumor necrosis factor alpha (TNFÎ±), interleukin-12 subunit alpha (IL-12Î±), interleukin-12 subunit beta (IL-12Î²), or decorin.
The MYXV of claim 1 , wherein the non-viral molecule is a human protein.
The MYXV of claim 1 , wherein the MYXV expresses at least two non-viral molecules selected from a group consisting of TNFÎ±, IL-12Î±, IL-12Î², and decorin.
A composition comprising a plurality of cells treated ex vivo by a MYXV, wherein the MYXV is genetically engineered to attenuate an activity or expression level of its M153 protein, and to express a non-viral molecule, wherein the non-viral molecule is a cytokine or a cell matrix protein.
The composition of claim 9 , wherein the plurality of cells comprises peripheral blood mononuclear cells (PBMCs), bone marrow (BM) cells, or a combination thereof.
A recombinant nucleic acid comprising at least a portion of MYXV genome, wherein the portion of the MYXV genome is modified to i) reduce expression of M153 gene, and ii) comprise a nucleic acid encoding a non-viral molecule, wherein the non-viral molecule is a cytokine or a cell matrix protein.
The recombinant nucleic acid of claim 11 , wherein the portion of the MYXV genome is modified to knock out at least a portion of the M153 gene in the portion of the MYXV genome.
The recombinant nucleic acid of claim 11 , wherein the non-viral molecule is human TNFÎ± (hTNFÎ±), human IL-12Î±, human IL-12Î², or human decorin.
The recombinant nucleic acid of claim 11 , wherein the nucleic acid encoding the non-viral molecule comprises a vMyx-hTNFÎ± cassette, and the nucleic acid encoding the non-viral molecule replaces or is adjacent to an M135R gene of the MYXV genome.
The recombinant nucleic acid of claim 11 , wherein the nucleic acid encoding the non-viral molecule comprises a vMyx-hTNFÎ± cassette, and the nucleic acid encoding the non-viral molecule is inserted between an M135R gene and an M136R gene of the MYXV genome.
The recombinant nucleic acid of claim 11 , wherein the nucleic acid encoding the non-viral molecule comprises an hDecorin-hIL-12 cassette, and the nucleic acid encoding the non-viral molecule replaces at least a portion of the M153 gene of the MYXV genome.
The recombinant nucleic acid of claim 11 , wherein the nucleic acid encoding the non-viral molecule comprises a vMyx-hTNFÎ±-hDecorin-hIL-12-M153KO (vMyx-Triple) cassette.
A method of inhibiting or alleviating a cancer in a subject in need thereof, comprising administering to the subject a MYXV or a plurality of cells treated with the MYXV, wherein the MYXV is genetically engineered to attenuate an activity or expression level of its M153 protein.
The method of claim 18 , wherein the MYXV is further genetically engineered to express a non-viral molecule.
The method of claim 19 , wherein the non-viral molecule is tumor necrosis factor alpha (TNFÎ±), interleukin-12 subunit alpha (IL-12Î±), interleukin-12 subunit beta (IL-12Î²), or decorin.
The method of claim 18 , wherein the MYXV or the plurality of cells is administered by systemic administration.
The method of claim 18 , wherein the administration reduces tumor cell viability, or activates immunogenic cell death in the cancer.
The method of claim 18 , wherein the cancer is a solid tumor, an osteosarcoma, triple negative breast cancer, or melanoma.
The method of claim 18 , wherein the cancer has metastasized to a lung, a brain, a liver, or a lymph node in the subject.
The method of claim 18 , further comprising administering to the subject an immune checkpoint modulator.
The method of claim 18 , wherein the administration is performed in a dose and a schedule effective to increase expression of at least two cytokines in PBMC or cancer cells of the subject, wherein the at least two cytokines comprise IFN-Î³, IL-2, IL-6, IL-10, IL-12, or TNF-Î±.
The method of claim 18 , wherein the administration is performed in a dose and a schedule effective to reduce volume of the cancer at least 10%.
Ref US20120141427: Claims:
An attenuated Myxoma virus in which the genes M151R, M152R, M153R, M154L, M156R, and M001R are inactivated.
The attenuated Myxoma virus for use as an oncolytic medicament as claimed in claim 1 , characterized in that one or more of the genes M008.1R, M008R, M007R, M006R, M005R, M004.1R, M004R, M003.2R, M003.1R, and M002R, of said Myxoma virus are additionally inactivated.
The attenuated Myxoma virus for use as an oncolytic medicament as claimed in claim 2 , characterized in that it additionally contains a mutation in the M011L gene resulting in the expression of a mutant M11L protein, free of the 51 N-terminal amino acids of the native M11L protein.
The attenuated Myxoma virus for use as an oncolytic medicament as claimed in claim 3 , characterized in that said Myxoma virus is the SG33 virus (CNCM 1-1594).
A method of killing a cancer cell comprising contacting the cell with the attenuated Myxoma virus of claim 1 .
The method of claim 5 wherein the cancer cell is present in a human subject.
The method of claim 5 wherein the cancer cell is selected from the group consisting of colorectal, pancreatic and ovarian cancer cells.
The method of claim 5 wherein the cancer cell is present in a glial tumor.
The method of claim 6 wherein the glial tumor is a glioblastoma.
Ref US20130209406: Claims:
A chimeric viral genomic segment or a chimeric viral genome, wherein the chimeric viral genomic segment or chimeric viral genome is derived from an RNA virus and wherein the chimeric viral genomic segment or chimeric viral genome comprises a heterologous RNA, wherein the heterologous RNA is transcribed in a cell to give rise to an effector RNA that interferes with the expression of a target gene in the cell, and wherein the effector RNA is miRNA, a mirtron, an shRNA, an siRNA, a piRNA, or an svRNA.
The chimeric virus gene segment or chimeric viral genome of claim 1 , wherein the chimeric virus gene segment comprises: (a) packaging signals found in the 3′ non-coding region of an orthomyxovirus gene segment; (b) a first nucleotide sequence that forms part of an open reading frame of an orthomyxovirus virus gene; (c) a splice donor site; (d) a heterologous RNA sequence; (e) a splice acceptor site; and (f) a second nucleotide sequence that forms part of the open reading frame of the orthomyxovirus virus gene; and (g) packaging signals found in the 5′ non-coding region of an orthomyxovirus virus gene segment.
The chimeric virus gene segment or chimeric viral genome of claim 1 , wherein the chimeric virus gene segment comprises: (a) packaging signals found in the 3′ non-coding region of an orthomyxovirus virus gene segment; (b) a first nucleotide sequence that forms part of an open reading frame of a first orthomyxovirus virus gene and a second influenza virus gene; (c) a splice donor site; (d) a second nucleotide sequence that forms part of the open reading frame of the first orthomyxovirus virus gene; (e) a heterologous RNA sequence; (e) a splice acceptor site; (f) a third nucleotide sequence that forms part of the open reading frame of the second orthomyxovirus virus gene; and (g) packaging signals found in the 5′ non-coding region of an orthomyxovirus virus gene segment.
The chimeric virus gene segment or chimeric viral genome of claim 3 , wherein: (a) the first orthomyxovirus virus gene is the influenza virus NS1 gene and the second orthomyxovirus virus gene is the influenza virus NS2 gene; or (b) the first orthomyxovirus virus gene is the influenza virus M1 gene and the second orthomyxovirus virus gene is the influenza virus M2 gene.
The chimeric viral genomic segment or chimeric viral genome of claim 1 , wherein the RNA virus is a segmented, single-stranded, negative sense RNA virus or a segmented double stranded RNA virus.
The chimeric viral genomic segment or chimeric viral genome of claim 1 , wherein the RNA virus is a non-segmented, single stranded, negative sense RNA virus or a non-segmented, single stranded, positive sense RNA virus.
A recombinant RNA virus comprising the chimeric viral genomic segment or the chimeric viral genomic segment of claim 1 .
A nucleic acid encoding the chimeric viral genomic segment or the chimeric viral genomic segment of claim 1 .
The nucleic acid of claim 11 , wherein the nucleic acid is DNA.
A method of making a recombinant RNA virus, wherein the method comprises introducing the nucleic acid of claim 12 into a cell that expresses all other components for generation of the recombinant RNA virus; and purifying the recombinant RNA virus from the supernatant of the cell.
A substrate comprising the chimeric viral genomic segment or chimeric viral genome of claim 1 .
A pharmaceutical composition or immunogenic composition comprising the recombinant RNA virus of claim 10 .
A method of treating and/or preventing a disease in a subject, the method comprising administering the recombinant RNA virus of claim 10 to the subject, wherein the effector RNA interferes with expression of a gene that is overexpressed or ectopically expressed in the disease.
The chimeric viral genomic segment or chimeric viral genome of claim 1 , wherein the RNA virus is an orthomyxovirus, a bunyavirus, or an arenavirus.
The chimeric viral genomic segment or chimeric viral genome of claim 20 , wherein the orthomyxovirus is influenza A virus, influenza B virus, influenza C virus, thogoto virus, or infectious salmon anemia virus; wherein the bunyavirus is bunyamwera virus, Hantaan virus, Dugbe virus, Rift Valley fever virus, or tomato spotted wilt virus; or wherein the arenavirus is Lassa virus, Junin virus, Machupo virus, or lymphocytic choriomeningitis virus.
The chimeric viral genomic segment or chimeric viral genome of claim 1 , wherein the RNA virus is a rhabdovirus, a paramyxovirus, a filovirus, a hepatitis delta virus, a bornavirus, a picornavirus, a togavirus, a flavivirus, a coronavirus, a reovirus, a rotavirus, an orbivirus, or a Colorado tick fever virus.
The chimeric viral genomic segment or chimeric viral genome of claim 22 , wherein the rhabdovirus is vesicular stomatitis virus (VSV), rabies, or a rabies-related virus; wherein the paramyxovirus is Newcastle Disease Virus (NDV), measles virus, mumps virus, Sendai virus, respiratory syncytial virus (RSV) or metapneumovirus; wherein the filovirus is Ebola virus or Marburg virus; or wherein the togavirus is Sindbis virus.
A kit comprising, in one or more containers, a chimeric viral genomic segment or chimeric viral genome, wherein the chimeric viral genomic segment or chimeric viral genome is derived from an RNA virus and wherein the chimeric viral genomic segment or chimeric viral genome comprises a heterologous RNA, wherein the heterolgous RNA is transcribed in a cell to give rise to an effector RNA that interferes with the expression of a target gene in the cell, and wherein the effector RNA is miRNA, a mirtron, an shRNA, an siRNA, a piRNA, or an svRNA.
A kit comprising, in one or more containers, a recombinant RNA virus, wherein said recombinant RNA virus comprises a chimeric viral genomic segment or chimeric viral genome, wherein the chimeric viral genomic segment or chimeric viral genome is derived from an RNA virus and wherein the chimeric viral genomic segment or chimeric viral genome comprises a heterologous RNA, wherein the heterolgous RNA is transcribed in a cell to give rise to an effector RNA that interferes with the expression of a target gene in the cell, and wherein the effector RNA is miRNA, a mirtron, an shRNA, an siRNA, a piRNA, or an svRNA.
A substrate comprising the recombinant RNA virus of claim 10 .
Ref US20140328804: Claims:
A method of treating or preventing graft versus host disease (GVHD) in a subject receiving a graft comprising hematopoietic cells, the method comprising: contacting the graft ex vivo with an amount of a Myxoma Virus effective to inhibit proliferation of T lymphocytes in the graft and to treat or prevent GVHD in the subject following infusion of the graft into the subject; and after the contacting, transplanting the virus-treated graft into the subject.
contacting the graft ex vivo with an amount of a Myxoma Virus effective to inhibit proliferation of T lymphocytes in the graft and to treat or prevent GVHD in the subject following infusion of the graft into the subject; and
after the contacting, transplanting the virus-treated graft into the subject.
The method of claim 1 , wherein the transplanting comprises a technique from the group consisting of an allogeneic hematopoietic cell transplant, a donor cell infusion, and a supportive blood product transfusion.
The method of claim 1 , wherein the graft comprises an allogeneic graft
The method of claim 1 , wherein the graft comprises bone marrow or human peripheral blood cells.
The method of claim 1 , wherein the T lymphocytes comprise CD3 + T lymphocytes.
A method for inhibiting the proliferation of T lymphocytes in a biological sample comprising contacting the biological sample with an amount of Myxoma Virus effective to inhibit the proliferation of T lymphocytes in the biological sample.
The method of claim 6 , wherein the biological sample comprises at least one member from the group consisting of a bone marrow sample and a blood sample.
The method of claim 6 , wherein the T lymphocytes comprise CD3 + T lymphocytes.
The method of claim 1 , further comprising administering at least one of chemotherapy, biotherapy, immunosuppression or radiotherapy to the host subject before transplanting the virus-treated graft into the subject.
administering at least one of chemotherapy, biotherapy, immunosuppression or radiotherapy to the host subject before transplanting the virus-treated graft into the subject.
The method of claim 9 , wherein the graft comprises an allogeneic graft
The method of claim 9 , wherein the graft comprises at least one member from the group consisting of bone marrow and human peripheral blood cells.
The method of claim 9 , wherein the cancer is a hematologic malignancy.
A graft comprising hematopoietic cells, said graft treated with an amount of a Myxoma Virus, ex vivo, effective to inhibit proliferation of T lymphocytes in the graft.
The graft of claim 17 , wherein said graft comprises bone marrow.
The graft of claim 17 , wherein said graft comprises human peripheral blood cells.
The graft of claim 17 , wherein said graft comprises a reduced amount of T lymphocytes.
Ref US20160130317: Claims:
- 73 . (canceled)
A composition, vector construct or virus comprising: a lentiviral vector, wherein the lentiviral vector comprises: a central polypurine tract (cPPT) sequence, optionally SEQ ID NO: 2 and/or a woodchuck hepatitis virus post-transcriptional regulatory element (WPRE), optionally SEQ ID NO: 3; a 5′-Long terminal repeat (LTR); HIV signal sequence; HIV Psi signal 5′-splice site (SD); delta-GAG element; Rev Responsive Element (RRE); 3′-splice site (SA); a promoter optionally selected from a CMV promoter and/or an Elongation factor (EF) 1-alpha promoter; and a 3′-Self inactivating LTR (SIN-LTR); and an IL-12 expression cassette, wherein the IL-12 expression cassette comprises a polynucleotide operably linked to the promoter, wherein the polynucleotide is optionally i) a polynucleotide encoding a p35 polypeptide and a p40 polypeptide; or ii) a polynucleotide encoding an IL-12 fusion polypeptide comprising fused p35 and p40 subunits wherein the IL-12 fusion polypeptide activates an IL-12 receptor.
a lentiviral vector, wherein the lentiviral vector comprises: a central polypurine tract (cPPT) sequence, optionally SEQ ID NO: 2 and/or a woodchuck hepatitis virus post-transcriptional regulatory element (WPRE), optionally SEQ ID NO: 3; a 5′-Long terminal repeat (LTR); HIV signal sequence; HIV Psi signal 5′-splice site (SD); delta-GAG element; Rev Responsive Element (RRE); 3′-splice site (SA); a promoter optionally selected from a CMV promoter and/or an Elongation factor (EF) 1-alpha promoter; and a 3′-Self inactivating LTR (SIN-LTR); and an IL-12 expression cassette,
wherein the IL-12 expression cassette comprises a polynucleotide operably linked to the promoter, wherein the polynucleotide is optionally i) a polynucleotide encoding a p35 polypeptide and a p40 polypeptide; or ii) a polynucleotide encoding an IL-12 fusion polypeptide comprising fused p35 and p40 subunits wherein the IL-12 fusion polypeptide activates an IL-12 receptor.
The composition, vector construct or virus of claim 74 , wherein the IL-12 expression cassette comprises a polynucleotide encoding an IL-12 fusion polypeptide.
The composition, vector construct or virus of claim 74 , wherein the IL-12 fusion polypeptide comprises a p40 subunit fused to a p35 subunit.
The composition, vector construct or virus of claim 74 , wherein the IL-12 fusion polypeptide comprises a p35 subunit fused to a p40 subunit.
The composition, vector construct or virus of claim 76 , wherein the polynucleotide encodes an IL-12 fusion polypeptide, the p40 subunit has an amino acid sequence that has at least 90% sequence identity to the polypeptide specified by SEQ ID NO: 22; and the p35 subunit has an amino acid sequence that has at least 90% sequence identity to the polypeptide specified by SEQ ID NO: 24.
The composition, vector construct or virus of claim 77 , wherein the polynucleotide encodes an IL-12 fusion polypeptide, the p40 subunit has an amino acid sequence that has at least 90% sequence identity to the polypeptide specified by SEQ ID NO: 22; and the p35 subunit has an amino acid sequence that has at least 90% sequence identity to the polypeptide specified by SEQ ID NO: 24.
The composition, vector construct or virus of claim 74 , wherein the IL-12 fusion polypeptide has at least 90% sequence identity to an amino acid sequence encoded by SEQ ID NO: 20.
The composition, vector construct or virus of claim 74 , wherein the lentiviral vector further comprises a sequence corresponding to position 100 to position 3513 of SEQ ID NO: 18.
The composition, vector construct or virus of claim 74 , wherein the cPPT sequence is the sequence of SEQ ID NO: 2 and/or the WPRE is the sequence in SEQ ID NO: 3
The composition, vector construct or virus of claim 74 , further comprising a detection cassette, optionally wherein the detection cassette comprises a CD19, truncated CD19, CD20, human CD24, murine HSA, human CD25 (huCD25), a truncated form of low affinity nerve growth factor receptor (LNGFR), truncated CD34, eGFP, eYFP, or any other fluorescent protein or erythropoietin receptor (EpoR) polynucleotide.
The composition, vector construct or virus of claim 74 , further comprising an immune modulatory cassette, optionally wherein the immune modulatory cassette comprises a polynucleotide that encodes a polypeptide that modulates an immune cell, optionally a dendritic cell or a T cell, optionally a CD4+ T cell, optionally CD40L, IL-7, or IL-15.
The composition of claim 84 , wherein the immune modulatory cassette compris
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