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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1, 2, 4-16, and 19-22) in the reply filed on 05/08/2026 is acknowledged. Clams 1-16, 19-22 and 27 are pending; claims 3 and 27 are withdrawn from prosecution for being drawn to non-elected subject matter. Claims 1, 2, 4-16, and 19-22 are examined.
Information Disclosure Statement
The information disclosure statements (IDS)s submitted on 07/07/2023, 01/05/2024, 07/18/2024, and 05/08/2024 were considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to because they are barely readable (especially Figures 1, 2 and 4). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-16, 19 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Steinmetz et al. (WO2018208828) in view of Yeung et al. (U.S. Pub. No. 20180318356) and Patel et al. (Radiation therapy combined with cowpea mosaic virus nanoparticle in situ vaccination initiates immune-mediated tumor regression, ACS Omega, 3, 3702−3707, 2018).
The claims are drawn to a method for inhibiting, delaying, slowing down, or preventing relapse of cancer in a subject in need thereof, comprising administering to the subject: (a) an adjuvant which comprises a cowpea mosaic virus (CPMV) particle; and (b) one or more cancer antigen(s) or a cancer cell comprising the one or more cancer antigen(s). The cell comprising the one or more antigen(s) is irradiated. Also claimed is a method of treating cancer by administration of the composition mentioned above. The cell is treated by one or more of: an irradiation, one or more of freeze and thaw cycles, a heat-shock, or a hypochlorous acid (HOCl) oxidization. The irradiation is with 10-100 Gray. The subject is further treated with one or more of: an ablative therapy, a chemotherapy, a radiation therapy, an immune checkpoint blockade therapy, or another anti-cancer therapy.
Steinmetz et al. teaches a method of treating cancer that includes administering in situ to the cancer a therapeutically effective amount of a plant virus or virus-like particle to the subject. The method can further include administering a therapeutically effective amount of an anticancer agent to the subject ([0001]). The plant virus or virus-like particle is a cowpea mosaic virus-like particle that is an empty RNA free cowpea mosaic virus-like particle (eCPMV) ([0011]).
Virus like particles (VLP)s possess inherent immunogenic properties that can stimulate immune responses against infectious agents that do not carry any antigen included in the VLP. They have robust induction of both innate and adaptive immunity and that the VLPs utilized were not antigenically related to the infectious agents, yet appeared to exert their therapeutic effect via the inherent immunomodulatory nature of the particles ([0006]). The immunomodulatory effect of eCPMV inhalation on the lung microenvironment was determined next, both in terms of immune cell composition and changes in cytokine and chemokine levels ([00135], Fig. 2A).
The virus-like particle may be loaded with or conjugated to a cargo molecule, including an anticancer agent. The method can further include the step of ablating the cancer. The method can further include the step of administering a therapeutically effective amount of a radiotherapy (RT) to the subject The cancer treated can be selected from the group consisting of melanoma, breast cancer, ovarian cancer, colon cancer and melanoma ([0013]-[0015]). The reference also indicates a tumor growth delay of ID8-Defb29/ Vegf-A orthotopic ovarian serous carcinoma cells (nota bene, the same tumor cells used in the instant Application) tumors in C57BL/6 female mice were treated with radiotherapy (RT), in situ vaccine (CPMV), both RT+ CPMV, or PBS (placebo group); treatment was begun when tumors reached a volume of 100-150 mm3 RT (10 Gray) was given in a single session on day 0, whereas the CPMV treatment was repeated 5 times in weekly intervals starting on day 1 (Fig. 23A).
The method can further include the step of ablating the cancer. Ablating the cancer can be accomplished using a method selected from the group consisting of cryoablation, thermal ablation, radiotherapy, chemotherapy, radiofrequency ablation, electroporation, alcohol ablation, high intensity focused ultrasound, photodynamic therapy, administration of monoclonal antibodies, immunotherapy, and administration of immunotoxins ([0091]). The cancer cells may be autologous or allogeneic whole tumor cells ([0095]).
The reference dose not expressly teach adding one or more cancer antigen(s) or a cancer cell comprising the one or more cancer antigen(s), even though it acknowledges that tumor vaccines generally may comprise tumor cell lysates, whole tumor associated antigens (produced by means of genetic engineering or by chemical synthesis) or peptides derived from protein antigens.
Yeung et al. teaches methods for treating an individual having solid or lymphatic tumor comprising local administration to the site of the tumor an infectious agent an immunomodulator (including a combination of immunomodulators). The methods may further comprise local administration to the site of the tumor inactivated tumor cells. Also provided are compositions and kits for the cancer therapy methods (abstract). The effective amounts, timing, and sequences of the therapeutic components are each independently adjustable based on the specific condition of the tumor. For example, administration of a combination of an infectious agent, immunomodulators and optionally inactivated tumor cells can give rise to the right amount of immune-related molecules from the individual's own bodily reactions, and/or from the optionally administered live tumor cells, leading to a release of tolerance breaking antigens (TBAs), which contribute to the immune signal confirmations (such as the 1, 2, 3 signals of CD4 and CD8 T cells) and generation of the effector cells ([0010]). The inactivated tumor cells may be obtained from a variety of sources, including, but not limited to, autologous source, allogenic source, a tumor cell line and combinations thereof. Typically, the inactivated tumor cells are of the same type, or express one or more of the same tumor antigens and the solid or lymphatic tumor being treated. In some embodiments, the inactivated tumor cells consist of a single population of tumor cells. In some embodiments, the inactivated tumor cells comprise a plurality (such as 2, 3, 4, 5, 6, or more) of population of tumor cells ([0258]).
The solid or lymphatic tumor to be treated is selected from the group consisting of head and neck squamous cell cancer, breast cancer, colorectal cancer, pancreatic adenocarcinoma, ovarian cancer, non-small cell lung cancer, prostate cancer, and melanoma. The methods are applicable to solid or lymphatic tumors of all stages, including stages, I, II, III, and IV, according to the American Joint Committee on Cancer (AJCC) staging groups. In some embodiments, the solid or lymphatic tumor is an/a: early stage cancer, non-metastatic cancer, primary cancer, advanced cancer, locally advanced cancer, metastatic cancer, cancer in remission, cancer in an adjuvant setting, or cancer in a neoadjuvant setting. In some embodiments, the solid or lymphatic tumor is localized resectable, localized unresectable, or unresectable. In some embodiments, the solid or lymphatic tumor is localized resectable or borderline resectable. In some embodiments, the cancer has been refractory to prior therapy ([0160]).
Patel et al. is even more specific about using CPMV and antigens to delay and induce regression of tumor cells. The reference disclosed an immunotherapeutic approach utilizing combination radiation therapy (RT) with immunostimulatory cowpea mosaic virus (CPMV) in a preclinical syngeneic mouse model of ovarian carcinoma. ID8-Defb29/Vegf tumors were generated in C57BL/6 mice. Compared to placebo-treated control tumors or those treated with a single agent RT or CPMV, the combination treatment resulted in a significantly improved tumor growth delay (p < 0.05). Additionally, immunohistochemical profiling of tumor samples after treatment with CPMV demonstrated an increase in tumor infiltrating lymphocytes (TILs). These results suggest that utilizing CPMV particles in combination with RT can turn an immunologically “cold” tumor (with low number of TILs) into an immunologically “hot” tumor. This combination treatment approach of RT and CPMV demonstrated the ability to control tumor growth in a preclinical ID8 ovarian cancer model (abstract). RT can improve the efficacy of immunotherapeutic agents, including inducing immunogenic cell death, enhancing release of neoantigens. Tumor cells exposed to radiation have been shown to have a greater diversity of antigens presented on their surface MHC-I molecules (p. 3705, col 1). The potent efficacy of RT + CPMV in a mouse model of serous ovarian cancer was demonstrated. Data indicate that the combination of RT + CPMV enhances efficacy over RT alone, and that this may be attributed to expansion of T cells within the tumors. In situ vaccination with plant-derived viral nanotechnologies has advantages over mammalian vectors or systemically administered checkpoint blockade: plant virus based nanotechnologies are not infectious toward mammals; the localized treatment is safer than systemic administration of immunotherapeutic reagents; and there is no requirement to identify antigens in the tumor or relate those antigens to the patient’s human leukocyte antigen. The combination of the viral in situ vaccine with RT may be a particularly powerful
strategy because RT debulks tumors, providing a burst of tumor antigens in the context of immunogenic cell death, therefore, synergizing with the CPMV in situ immune stimulation that further augments antitumor immunity (p. 3705, col.2).
It would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have combined the CPMV of Steinmetz et al. with the cancer antigens of Yeung et al and Patel et al. and inhibit or delay the cancer cell growth and treat cancer with a reasonable expectation of success. This is because Steinmetz et al. underscored the superior properties of CPMV as vaccine adjuvant and immune modulator and Yeung et al. underscored the role of cancer cell antigens in regressing the growth of tumor cells. The motivation to do so is set forth by Patel et a. which successfully induced ovarian cell tumor regression using CPMV and tumor cell antigen created by radiation.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Steinmetz et al. in view of Patel et al. (both cited supra) and in further view of Hodge et al. (The tipping point for combination therapy: cancer vaccines with radiation, chemotherapy, or targeted small molecule inhibitors. Sem. Oncol. 39, 323-339, 2012).
The claim adds the limitation that the method of independent claim 1 is performed when the cancer is clinically undetectable.
The teachings of Steinmetz et al. and Patel et al. were presented supra and they were silent about using the methods in conditions that the cancer was clinically undetectable.
Hodge et al. examines the preclinical and clinical interactions between vaccine-mediated tumor-specific immune responses and local radiation, systemic chemotherapy, or select small molecule inhibitors, as well as the potential synergy between these modalities. The reference underscores that local control of the primary tumor is necessary and can usually prevent metastasis, but radiation alone generally fails to control pre-existing systemic disease, which may be present as undetectable micrometastases. Immunomodulators (cancer vaccines) in concert with the radiation-induced cell death wherein dying tumor cells release tumor-associated antigens (TAAs) that can potentially be exploited to stimulate robust tumor-specific immune responses (Abstract, Figure 1).
it would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to combine the teachings of Steinmetz et al. and Patel et al. and treat or inhibit clinically undetectable cancer growth with a reasonable expectation of success. This is because Hodge et al. indicated the superior results of combining cancer vaccines and tumor antigens resulted from radiation of the tumor cells.
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, 2 and 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11, 998,594. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the Patent are drawn to a method of treating or decreasing the risk of developing a HER2-expressing cancer in a subject, by comprising administering to a subject in need thereof an effective amount of an anti-cancer particle composition comprising an icosahedral-shaped plant virus or virus-like particle linked to a HER2 antigen, wherein the HER2 antigen comprises a B-cell and a T-cell epitope from the extracellular domain of HER2 epitope homologous to the species of subject being treated. The HER2-expressing cancer may be Ovarian cancer. Thus, the claims or the Patent are drawn to the same subject matter as the instant claims 1, 2 and 9 and anticipate them.
Claims 1, 2 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6 and 10 of U.S. Patent No. 11,260,121 in view of Patel et al. (cited above).
The claims are drawn to a method for inhibiting, delaying, slowing down, or preventing relapse of cancer in a subject in need thereof, comprising administering to the subject: (a) an adjuvant which comprises a cowpea mosaic virus (CPMV) particle; and (b) one or more cancer antigen(s) or a cancer cell comprising the one or more cancer antigen(s). Further the method comprises treating the subject with one or more of: an ablative therapy, a chemotherapy, a radiation therapy, an immune checkpoint blockade therapy, or another anti-cancer therapy.
The claims of the U.S. Patent are drawn to a method of treating cancer in a subject in need thereof, the method comprising administering directly to the cancer a therapeutically effective amount of an in situ vaccine, the in situ vaccine comprising at least one of cowpea mosaic virus or cowpea mosaic virus-like particles, wherein the cowpea mosaic virus and cowpea mosaic virus-like particles are not used as a vehicle for drug or antigen delivery. The cancer may be ovarian cancer and the method
further comprising the step of ablating the cancer by treating the subject with a therapeutically effective amount of radiotherapy, chemotherapy or immunotherapy.
The patent does not teach using tumor antigens. However this step is made obvious by the teachings of Patel et al., which indicated the use of tumor antigens generated by exposing tumor cells to radiation.
Claims 1-2, 9 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,433,123 in view of Patel et al. (cited above).
The claims are drawn to a method for inhibiting, delaying, slowing down, or preventing relapse of cancer in a subject in need thereof, comprising administering to the subject: (a) an adjuvant which comprises a cowpea mosaic virus (CPMV) particle; and (b) one or more cancer antigen(s) or a cancer cell comprising the one or more cancer antigen(s). Further the method comprises treating the subject with one or more of: an ablative therapy, a chemotherapy, a radiation therapy, an immune checkpoint blockade therapy, or another anti-cancer therapy. The tumor antigens are from ovarian cancer cells.
The claims of the Patent are drawn to a method of treating cancer in a subject in need thereof, the method comprising: administering in situ to cancer cells of the subject a nanoparticle construct, the nanoparticle construct comprising: a plurality of cowpea mosaic virus or virus-like particles and a plurality of G4 dendrimers having a different surface charge than the cowpea mosaic virus or virus-like particles electrostatically coupled to the cowpea mosaic virus or virus-like particles, the nanoparticle construct upon in situ delivery to the subject providing a sustained release of the cowpea mosaic virus or virus-like particles and/or nanoparticles to the cancer cells, wherein the cancer is selected from the group consisting of melanoma, breast cancer, colon cancer, lung cancer, and ovarian cancer.
The patent does not teach using tumor antigens. However this step is made obvious by the teachings of Patel et al., which indicated the use of tumor antigens generated by exposing tumor cells to radiation.
Claims 1-2, 4, 13 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 16-17 of U.S. Patent No. 11,617,787 in view of Patel et al. (cited above).
The claims are drawn to a method for inhibiting, delaying, slowing down, or preventing relapse of cancer in a subject in need thereof, comprising administering to the subject: (a) an adjuvant which comprises a cowpea mosaic virus (CPMV) particle; and (b) one or more cancer antigen(s) or a cancer cell comprising the one or more cancer antigen(s). Further the method comprises treating the subject with one or more of: an ablative therapy, a chemotherapy, a radiation therapy, an immune checkpoint blockade therapy, or another anti-cancer therapy. The cell comprising the one or more antigen(s) is irradiated.
The claims of the Patent are drawn to a method of treating cancer in a subject in need thereof, the method comprising administering directly to the cancer a therapeutically effective amount of an in situ vaccine, the in situ vaccine comprising at least one of cowpea mosaic virus or cowpea mosaic virus-like particles, wherein the cowpea mosaic virus and cowpea mosaic virus-like particles are not used as a vehicle for drug or antigen delivery, and wherein the subject is a non-human animal. The cancer may be ovarian cancer and the method further comprises the step of ablating the cancer by treating the subject with a therapeutically effective amount of radiotherapy, chemotherapy, high intensity focused ultrasound or immunotherapy.
While the patent does not teach using tumor antigens. However this step is made obvious by the teachings of Patel et al., which indicated the use of tumor antigens generated by exposing tumor cells to radiation.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Steinmetz et al. (WO2013181557) teaches A filamentous plant virus carrier comprising a filamentous plant virus particle that has been modified to carry an imaging agent or cytotoxic compound is described. The filamentous plant virus carrier can be used in a method of targeting cancer cells and tissue by administering it to a subject. Cancer tissue targeted by the filamentous plant virus carrier can be imaged using an imaging agent, or treated using a cytotoxic compound (abstract). One of the viruses may be Cowpea mosaic virus ([0006]).
Bindi Patel, (Plant viral nanoparticle-based vaccine targeting NY-ESO-1+ triple negative breast cancer, Master of Science Thesis, Case Western Reserve University, May 2018) used a highly immunostimulatory and biocompatible viral nanoparticle (VNP) carrier derived from cowpea mosaic virus (CPMV) to stimulate an effective and sustained cytotoxic T cell (CTL) response targeting NY-ES0-1 and test its efficacy in in vitro and ex vivo models.
Zhang et al. (Abscopal effects with hypofractionated schedules extending into the effector phase of the tumor-specific T-cell response, Int. J. Radiat. Onc., 101, 63-73, 2018) teaches combination therapy with hRT schedules extending into the period during which treatment-induced T cells infiltrate the irradiated tumor can provoke local and systemic antitumor effects similar to those with therapy using shorter schedules, if the regional lymph nodes supply sufficient tumor-specific T cells.
Conclusion
No claims are allowed.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
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