Office Action 2: Notice of Allowance (2025-02-26)

CLAIMS:
In the Claims

This listing of claims will replace all prior versions, and listings, of claims in the application.

1\. (Original) 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\. (Original) The pharmaceutical composition of claim 1, wherein the genetic modification comprises a disruption of M153 gene.
3\. (Original) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated for systemic administration.
4\. (Original) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated for local administration.
5\. (Original) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated for parenteral administration.
6\. (Original) 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\. (Original) 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\. (Original) 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\. (Original) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises the MYXV at a dose effective to increase expression of at least two
 the MIYXV to the subject.

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

11\. (Original) The pharmaceutical composition of claim 1, wherein the MYXV is effective to reduce viability of a cancer cell.

12\. (Original) The pharmaceutical composition of claim 8, wherein the cancer cell comprises a solid tumor cell.

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

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

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

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

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

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

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


20\. (Original) The pharmaceutical composition of claim 1, wherein the transgene encodes the cytokine and the MIYXV further comprises a second transgene that encodes the cell matrix protein.

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

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.


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%.