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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 27, 2026 has been entered.
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on July 27, 2026. Claims 1, 3, 8, 10-18, 20, 22, 29-30 and 39-50 are pending and are currently examined.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, 8, 10-18, 20, 22, 29-30 and 39-48 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The base claims 1, 20 and 42 recites a phrase “…to treat or alleviate one or more symptoms of melanoma or mesothelioma in the subject”, where the “alleviate” and “symptoms “that render the claims indefinite.
For “alleviate”, it is unclear how the “alleviate” is determined or what degree of “alleviate” is necessary. Applicant has not defined the degree of “alleviate” (e.g., 5%, 60%, or total elimination). Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
For “symptoms”, it is not clear what type of “symptoms” that is referred to. The instant specification does not define which “symptoms” are related to melanoma or mesothelioma in the subject that need to be treated or alleviated. Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section
(New Rejection-necessitated by amendment) Claims 1, 3, 8, 10-18, 20, 22, 29-30, 39-50 are rejected under 35 U.S.C. 103 as being unpatentable over Bell et al. (US 2020/0385758 A1, published on Dec. 10, 2020, claimed provisional application filed on Jan. 5, 2018, hereinafter, “Bell”) in view of Liu et al. (Nat Commun. 2017 Mar 27; 8:14754, hereinafter, “liu”), Zhu et al. (J Virol Methods. 2007 Sep;144(1-2):17-26, submitted to IDS filed on 11/18/2021, hereinafter, “Zhu”), Ma et al. (Journal of Leukocyte Biology, Volume 99, June 2016, pages 794-706, hereinafter, “Ma”) and Eriksson et al. (J Transl Med. 2016 Sep 29;14(1):282, hereinafter, “Eriksson”).
The amended base claim 1 is directed to a method of treating melanoma or mesothelioma in a subject, the method comprising administering to the subject:
(a) a pharmaceutical composition comprising an oncolytic virus, and
(b) a therapy that depletes of tumor-induced bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN-MDSCs),
wherein the oncolytic virus is a vaccinia TianTan virus,
wherein the vaccinia TianTan virus is modified to delete a selection of genes wherein the selection of genes consists of MIL, M2L, K1L, and K2L,
wherein the therapy that depletes tumor-induced PMN-MDSCs selectively depletes tumor-induced PMN-MDSCs without affecting tumor-induced monocytic MDSCs, and
wherein the method is effective to treat or alleviate one or more symptoms of melanoma or mesothelioma in the subject.
The amended base claim 20 is directed to a pharmaceutical composition comprising an oncolytic viruses and a pharmaceutically acceptable carrier, wherein the oncolytic virus is a modified vaccinia TianTan viruses, wherein the vaccinia TianTan virus is modified to comprise a deletion of gene consisting of MIL, M2L, K1L, and K2L, and wherein the vaccinia TianTan virus is present in the pharmaceutical composition in an amount effective to treat or alleviate one or more symptoms of melanoma or mesothelioma in a subject. Also, a therapy that depletes tumor-induced bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN-MDSCs), the therapy that depletes tumor-induced PMN-MDSCs selectively depletes tumor-induced PMN-MDSCs without affecting tumor-induced monocytic MDSCs.
The amended base claim 42 is directed to a system comprising: a first composition comprising an oncolytic virus and a pharmaceutically acceptable carrier, wherein the oncolytic virus is a vaccinia TianTan virus,
wherein the vaccinia TianTan virus is modified to delete a gene consists of MIL, M2L, K1L, and K2L; and
a second composition comprising a therapeutic agent that specifically induces depletion of tumor-induced bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN-MDSCs), without affecting tumor-induced monocytic MDSCs and a pharmaceutically acceptable carrier;
wherein the vaccinia TianTan virus is present in the first composition and the therapy that selectively depletes tumor-induced PMN-MDSCs is present in the second composition in an amount effective to treat or alleviate one or more symptoms of melanoma or mesothelioma in a subject.
The amended base claim 49 is directed to a method of generating an immune response to a mesothelioma or melanoma tumor antigen in a subject comprising administering to the subject:
(a) a first composition comprising an oncolytic virus and a pharmaceutically acceptable carrier,
wherein the oncolytic virus is a vaccinia TianTan virus,
wherein the vaccinia TianTan virus is modified to delete a gene consisting of MIL, M2L, K1L, and K2L genes, and
wherein the first composition is administered in an effective amount to recruit myeloid-derived suppressor cells of polymorphonuclear type (PMN-MDSCs) to a tumor site; and
(b) a second composition comprising a therapeutic agent that specifically induces depletion of tumor-induced myeloid-derived suppressor cells of polymorphonuclear type (PMN- MDSCs) without affect monocytic MDSCs, and a pharmaceutically acceptable carrier,
Where administration of the first composition and the second composition is effective to activate dendritic cells and stimulate an immune response to the tumor antigen in the subject, and wherein the administering occurs multiple times over a period of two to fourteen days.
Bell et al. discloses using of Copenhagen-derived Vaccinia virus vectors for the treatment of cancer including melanoma. In particular, the disclosure is based in part on the surprisingly enhanced oncolytic activity, spread of infection, and safety results engendered when a vaccinia virus is genetically modified to contain deletions in some or all, of the following genes: C2L, ClL, NIL, N2L, MIL, M2L, KIL, K2L, K3L, K4L, K5L, K6L, K7R, FIL, F2L, F3L…and B9R (see [0006] [0008] and [0021]), and also teaches a method of administering to a subject (e.g., a patient) a pharmaceutical composition containing a recombinant vaccinia virus vector described herein to treat cancer such as melanoma and mesothelioma (See e.g., [0159], [0187]). Bell et al. further teaches that while it is possible for the recombinant vaccinia virus vector of the invention to be administered alone, it may also be administered as a pharmaceutical formulation in combination with excipients, carriers, and optionally, additional therapeutic agents (See [0160]). Among the vaccinia viruses used for cancer treatment, Five Vaccinia wild type strains (Copenhagen, TianTan, Lister, Wyeth, and Western Reserve) are studied in Bell’s invention (See [0165]). In Fig. 36, Bell et al. discloses the Tiantan virus as claimed (See Fig. 36 and below), where "5P3P", “3P” and “5P” are deletions including MIL, M2L, K1L, and K2L (See Table 1 and below; [0146]).
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Accordingly, Bell et al. teaches a method to administer a pharmaceutical composition treating melanoma, where the composition comprises the modified Vaccinia virus including TianTan virus with a deletion selected from the group consisting of M1L, M2L, K1L, and K2L. Although Bell et al. uses the modified Copenhagen strain of vaccinia virus as an example virus to treat cancer in the invention, it would be obvious for one of ordinary skill in the art to treat cancer using the modified Tiantan virus as well. One of ordinary skill in the art would be motivated to do so given that Bell et. al made constructs of Tiantan (and other viruses) with 5p, 3p and 5p3p deletions and demonstrated that the modified TianTan viruses have cytotoxic effects in HeLa cells (See [0117]). There would be a reasonable expectation of success given the findings for the Copenhagen strain and given the teachings and finds regarding the TianTan virus (see Fig. 36 above). Further, given the teachings of Bell et al., one of ordinary skill in the art is motivated to try any of the modified viruses.
Nevertheless, the newly added limitation “to delete a selection of genes wherein the selection of genes consists of MIL, M2L, KIL, and K2L” can also be teach by Zhu’s study.
Zhu et al. teaches a modified MVTT with M1L-K2L genes deletion and a heterologous GFP inserted in place of the M1L-K2L genes. It teaches that the GFP gene in MVTT2-GFP may serve either as a reverse selection marker for vaccine construction or as a reporter in a neutralization assay (See page 24, left column, paragraph 2; Table 1 and below).
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As for the claim 1 (b) at “a therapy that depletes of tumor-induced bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN-MDSCs)”, Liu et al. describes a rational combination of oncolytic vaccinia virus and PD-L1 blockade that works synergistically to enhance therapeutic efficacy. Liu et al. teaches that both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Furthermore, the treatment reduces the virus-induced PD-L1+ DC, MDSC, TAM and Treg, as well as co-inhibitory molecules-double-positive, severely exhausted PD-1+ CD8+ T cells, leading to reduced tumor burden and improved survival. This combinatorial therapy may be applicable to a much wider population of cancer patients (See Abstract). Anti-mouse PD-L1 Ab (clone 10F.9G2) (See page 9, right column, paragraphs 2 & 3), but also teaches a regimen for treating a Rodent tumor (See page 10, left column, paragraph 3; Page 10, Figure 8; Figure 8C below, modified by the examiner). Liu et al. teaches that the dual therapy enhances beneficial repertoire of anti-tumor T cells (See page 4, left column, paragraph 3), and demonstrates that that an oncolytic vaccinia virus markedly upregulates PD-L1 in the TME, and thereby synergizes with a-PD-L1 treatment leading to over 40% cures in aggressive models of peritoneal carcinomatosis. Multiple histologies tested demonstrated similar upregulation of PD-L1 in response to vaccinia virus infection (See page 9, right column, paragraph 1).
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Accordingly, Liu et al. teaches a method of treating a cancer including the melanoma in a subject (Mice), comprising administering to the subject a combination of an oncolytic virus, vaccinia virus, and a therapy (anti-PD-L1 antibody) that induces depletion of tumor- induced bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN- MDSCs, also known as G-MDSCs).
Based on the description above, Bell and Liu teach a method of treating melanoma claimed by the base claim 1 at both (a) and (b); Teach the base claim 20 at a pharmaceutical composition comprising an oncolytic virus and a pharmaceutically acceptable carrier (See [0149]); Teach the base claim 42 at a system comprising a first composition comprising an oncolytic virus and a pharmaceutically acceptable carrier (See [0181]); Teach the base claim 49 by teaching a combination of oncolytic vaccinia virus and PD-L1 for working synergistically to exert cytotoxicity to cancer cells, eliminate immunosuppressive cells (including MDSC, TAM, Treg and exhausted CD8+ T cells), and elicit more potent and sustained systemic anti-tumor immunity, thus achieving better therapeutic efficacy (See page 9, right column, paragraph 1).
As for the new specific limitation “wherein the therapy that depletes tumor-induced PMN-MDSCs selectively depletes tumor-induced PMN-MDSCs without affecting tumor-induced monocytic MDSCs”, Ma teaches that targeted depletion of G-MDSC but not M-MDSC has been achieved using 1A8 in KPC mice, where 1A8 is an anti-Ly6G antibody (See page 794, middle column, paragraph 1).
Eriksson teaches Gemcitabine reduces MDSCs, tregs and TGFβ‑1 while restoring the teff/treg ratio in patients with pancreatic cancer and discloses that patient blood was investigated by flow cytometry and cytokine arrays at different time points during gemcitabine treatment. The granulocytic MDSCs/ PMN-MDSCs were significantly reduced while monocytic MDSCs were not affected. In vitro, monocytes responding to IL-6 by STAT3 phosphorylation were prevented to respond in gemcitabine medium (See Abstract).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine all teachings from Bell, Zhu, Liu, Ma and Eriksson to arrive at the invention as claimed. One of skill in the art would have been motivated to use the combination therapy of the modified Tiantan virus with gene deletions of MIL, M2L, KIL, and K2L of Bell and Zhu and PD-L1 blockade of Liu for working synergistically to enhance therapeutic efficacy as described above, which can eliminate bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN- MDSCs) as claimed in the instant application. Also, one of skill in the art would have been motivated to introduce Eriksson’ Gemcitabine therapy and Ma’s antibody therapy into Bell, Liu and Zhu’s studies to arrive at an invention as claimed based on its selective treatment. There would have been a reasonable expectation of success based on these teachings to develop a method, a pharmaceutical composition or a system to treat melanoma by inducing a depletion of PMN-MDSCs without affecting tumor-induced monocytic MDSCs and generating an immune response to treat melanoma or mesothelioma in a subject.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claims 3 and 22, Bell et al. teaches that the virus is replication competent (See [0175]).
Regarding claim 8, it requires that the method of claim 1, wherein the therapy that induces depletion of tumor-induced PMN-MDSCs is administered multiple times over a period of two to fourteen days. Liu et al. teaches a method of treating a cancer in a subject (Mice), comprising administering to the subject a combination of an oncolytic virus, vaccinia virus, and a therapy (anti-PD-L1 antibody) that induces depletion of tumor- induced bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN- MDSCs, also known as G-MDSCs) (See Figure 8, page 10). In Figure 8 C (See above), Liu teaches administering multiple times over a period of two to fourteen days.
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce Liu’s method of combination of vaccinia virus and PD-L1 blockade into Bell’s study to arrive at an invention as claimed. One of skill in the art would have been motivated to use the combination of the Bell’s virus and PD-L1 blockade to work synergistically to enhance therapeutic efficacy as described above, which can eliminate bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN- MDSCs) as claimed in the instant application. There would have been a reasonable expectation of success based on the teachings of Bell and Liu to develop a method to treat melanoma by inducing a depletion of PMN-MDSCs to treat or alleviate one or more symptoms of melanoma in the subject.
Regarding claims 10-11 and 50, based on the description above, although Bell et al. does not teach a therapy that induces depletion of tumor-induced bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN-MDSCs), Liu et al. teaches that the grouped mice were intraperitoneally injected with anti-PD-L1 Ab (clone 10F.9G2, 200 mg per injection), VV plus anti-PD-L1 Ab, or PBS (100 ml) per mouse, respectively. In some experiments, anti-CD8 Ab at 250 mg per injection (clone 53-6.7; Bio X Cell), anti-CD4 Ab (clone GK1.5, Bio X Cell; 150 mg per injection), or anti-IFN-g Ab (clone XMG1.2, Bio X Cell; 200 mg per injection) were intraperitoneally injected into mic (See page 10, left column, paragraph 4), where anti-PD-L1 antibody is a PMN-MDSC/G-MDSC depleting antibody (See Figure 5-d, page 7 and below). In Figure 5-C, Liu et al. teaches that the PD-L1+G-MDSC is defined as Ly6G+, which is also known as the lymphocyte antigen 6 complex locus G6D (LY6G6D), and further teaches that the antibody targeting Ly6G+ is clone 1A8 (See page 10, right column, paragraph 2).
It would be obvious for one of ordinary skill in the art to apply the PD-L1 Ab into Bell’s invention to enhance the therapeutic efficacy. One of skill in the art would have been motivated to use the combination therapy based on the advantages described above. There would have been a reasonable expectation of success based on the teachings of Bell and Liu.
Regarding claim 12, Bell et al. teaches the pharmaceutical composition may be administered to the subject in one or more doses (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or more) per a specified time interval (e.g., weekly, daily, or hourly).
Regarding claim 13, Bell et al. teaches that the route of administration may vary with the location and nature of the cancer, and may include, e.g., intradermal, transdermal, parenteral, intravenous, intramuscular, intranasal, subcutaneous and etc. (See [0150]).
Regarding claims 14-17, Liu et al. teaches that the PD-L1 is the additional anti-cancer therapy to the subject as claimed in claim 14, and PD-L1 is a check-point inhibitor as claimed in claim 15 and 16. Liu et al. also teaches the inhibitor of PD-L1 is an antibody that bind to PD-L1 as claimed in claim 17 (See page 9, right column, paragraph 1). Although Bell et al. does not teach the additional anti-cancer therapies to the subject, it would be obvious for one of ordinary skill in the art to introduce the PD-L1 therapy into Bell’s invention, and the result for the dual cancer treatments would be predictable.
Further, the courts have said: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose . . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.) See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). (See MPEP §2144.06(I) – Combining Equivalents Known For The Same Purpose). In this case, applicant is combining two known cancer treatments to form a third composition to be used for the very same purpose. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Regarding claim 18, Bell et al. teaches that in some embodiments, the mammalian patient is a human patient (See [0057]).
Regarding claims 29-30 and 39, Liu et al. teaches that the antibody against Ly6G is 1A8 (See page 10, right column, paragraph 2). Therefore, Bell in view of Liu teaches claims 29-30 and 39.
Regarding claims 40 and 41, they require that the oncolytic virus and therapy that induces depletion of tumor-induced PMN-MDSCs are administered before or simultaneously or consecutively. Liu et al. teaches that they tested whether different time points for the reagent administration could impact the therapeutic effect elicited by the combination therapy. They fixed the first treatment time at day 5 post tumor cell injection and applied treatment using different timing schemes: (1) a-PD-L1 Ab followed in 2 days by VV treatment; (2) VV treatment followed in 2 days by a-PD-L1 Ab therapy; and (3) simultaneous administration of both a-PD-L1 Ab and VV. The survival data showed that the simultaneous administration achieved the best therapeutic effect (See page 3, left column, paragraph 2 and right column, paragraph 1).
It would be obvious for one of ordinary skill in the art to apply the administration regimen into Bell’s invention to enhance the therapeutic efficacy. One of skill in the art would have been motivated to use the combination therapy based on the advantages described above. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated and commonly used as evidenced by the prior art teachings.
Regarding claims 43, Bell et al. teaches that administration of the vaccinia virus to a patient having cancer induce oncolysis, kill cells, inhibit growth, inhibit metastases, decrease tumor size and otherwise reverse or reduce the malignant phenotype of tumor cells (See [0150]).
Reducing claims 44-45 and 48, Bell et al. teaches that Nude CD-1 (Crl:CDl-Foxnlnu) mice were seeded with HT-29 human colon cancer xenograft (5e6 cells). Once subcutaneous tumors have established an approximate 5 mmx5 mm size, mice were treated three times (dashed lines) 24h apart with 1x 10^7 PFU of either vaccinia virus intravenously. Mice were measured approximately every other day for tumor size and weight loss (see FIG. 14) (See [0179]), where the tumor size (cubic millimeters (mm³)) has over 50% reduction at day 16 with the administration. Bell et al. also teaches Unit dose of the present invention may conveniently be described in terms of plaque forming units (pfu) for a viral construct. Unit doses may range from 1x 10^6, 1x10^7… to 1x 10^13 pfu and higher (See [0154]).
Regarding claims 46-47, Liu et al. teaches that the PD-1 is injected intratumorally (See e.g. page 2, right column, paragraph 4). Liu et al. also teaches that a-PD-L1 Ab, 200ug (0.2mg ) per 100 ml, was injected every 2 days for a total of four times (See Figure 4, page 5). Although Liu’s dose does not use the same unit mg/kg as claimed, it is a common knowledge in the art that the unit can be covert to mg/kg, and it would be obvious for one of ordinary skill in the art to optimize the unit based on the subject’s body weight and the result would be predictable to reach a dose ranging from 0.01 mg/kg to 200 mg/kg as claimed.
It would be obvious for one of ordinary skill in the art to apply the administration dose into Bell’s invention based on the subject’s body weight to reach a better treatment result for enhancing the therapeutic efficacy. One of skill in the art would have been motivated to use the combination therapy based on the advantages described above. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated and commonly used as evidenced by the prior art teachings.
Responses to Applicant’s Remarks
Applicant’s arguments filed on July 27, 2026 has been received and fully considered.
Regarding the rejection Under 35 U.S.C. § 103, Applicant’s arguments are not found persuasive as follows:
1. Applicant argue that none of the cited references lead one of ordinary skill in the art to selectively target tumor-induced PMN-MDSCs, rather than M-MDSCs or MDSCs generally, by administering a modified vaccinia Tian Tan virus (MVTT) having only deletion of the MlL, M2L, KlL, and K2L genes, in combination with a therapy that selectively depletes PMN-MDSCs (See Remarks, pages 11-12).
Applicant argument is not persuasive.
1). Bell teaches the MVTT virus and teaches the deletion region of 5p, 3p, and 5p3p of MVTT, where the 5p, 3p, and 5p3p include the MlL, M2L, KlL, and K2L genes deletion (See Fig. 36 and Table 1 above). Gene deletion is a routine technique in the art, it would be obvious for one of ordinary skill in the art to select the deletions of the M1L, M2L, K1L, and K2L through routine experimental optimization, and the result would be predictable based on Bell’s teaching. Nevertheless, a new art reference was cited in the current office action to teach the vaccinia TianTan virus with a specific gene deletion of MIL, M2L, KIL, and K2L.
2). As for the selectively target tumor-induced PMN-MDSCs, rather than M-MDSCs or MDSCs, Bell in view of Ma teaches anti-Ly6G antibody targeted depletion of G-MDSC but not M-MDSC has been achieved using 1A8 in KPC mice (See Ma, page 794, middle column, paragraph 1). In addition, a new art reference was cited in the current office action for teaching the selectively targeting as well.
2. Applicant argued that the Bell's Figure 36, Table 1 and [0146] and the Provisional application No. 62/614,349, filed on Jan. 5, 2018 (See Remarks, pages 12-14).
Applicant argument is not persuasive.
1). Although there is no Bell's Figure 36, Table 1 and [0146] disclosed in the Provisional application No. 62/614,349 of Bell, the Provisional application No. 62/614,349 discloses the TianTan virus and the claimed gene deletions. One of skilled in the art will acquire the comparable knowledge as disclosed in the Bell's Figure 36, Table 1 and [0146] based on its teaching. For example, the Provisional application No. 62/614,349 of Bell teaches “Exemplary strains of the vaccinia virus include, but are not limited to, Copenhagen, Western Reserve, Wyeth, Lister, EM63, ACAM2000, LC16m8, CV-1, modified vaccinia Ankara (MVA), Dairen I, GLV-1 h68, IHD-J, L-IVP, LC16m8, LC16mO, Tashkent, Tian Tan, and WAU86/88-1 (See e.g., page 40).
Therefore, the Provisional application No. 62/614,349 of Bell provides information for Tiantan virus as a prior art.
2). Applicant’s Provisional Application No. 62/687,531, filed on June 20, 2018U.S. and of Provisional Application No. 62/660,546, filed on April 20, 2018 do not claim Tiantan virus in their base claims.
3. Applicant argued that one of ordinary skill in the art would not have selected, from Bell's broad disclosure, a Tian Tan Virus modified only by deletion of MlL, M2L, KlL, and K2L, for treating melanoma or mesothelioma, and none of Liu, Najjar and Zhao cure this deficiency (See Remarks, pages 15-18).
Applicant argument is not persuasive.
1). Based on applicant’s amendment, Najjar, and Zhao are removed from the current office action. The arguments on Najjar, and Zhao is moot.
2). A new reference, Zhu, is cited in the current office action. Bell in view of Zhu teaches a Tiantan virus with deletions of only M1L, M2L, K1L, and K2L.
4. Applicant argued the Liu's anti-PD-L1 antibody acts broadly and non-selectively and does not recognize that the PMN-MDSC subset is the specific cell population responsible for restricting the induction of antitumor immunity during oncolytic virotherapy, nor that specifically depleting this subset (without depleting M-MDSCs) is the solution (See Remarks, pages 18-22).
Applicant argument is not persuasive.
First, a new reference Eriksson and a previous reference Ma are cited in the current office action for the amended claims, Liu in view of Ma and Eriksson teaches “a therapeutic agent that specifically induces depletion of tumor-induced myeloid-derived suppressor cells of polymorphonuclear type (PMN-MDSCs) without affect monocytic MDSCs” in the instant claims.
Second, the instant claims do not cite a limitation on if “not recognize” that the PMN-MDSC subset is the specific cell population responsible for restricting the induction of antitumor immunity” or not.
5. Applicant argued that Claims 27-30 and 38, as amended, are not obvious over the combination of Bell, Liu, Zhao, Najjar, Simpson and Ma (See Remarks, page 22).
Applicant argument is not persuasive.
1). Based on applicant’s amendment, Zhao, Najjar and Simpson are removed from the current office action, and Ma is cited in a different application. The arguments here for these references is moot.
2). Claims 27, 28 and 38 are canceled by the applicant. Claims 29-30 are re-addressed in the current office action.
Conclusion
No claims are allowed.
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/RUIXUE WANG/ Examiner, Art Unit 1672
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