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 .
DETAILED ACTION
Pursuant to the amendment dated 10/09/2025, claims 2, 6, 22, and 24-26 are cancelled and claims 1, 3, 21, and 23 are amended. Claims 1, 3-5, 7-21, and 23 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National State Application of PCT/US2021/012655, filed on 01/08/2021. The instant application claims benefit to provisional application 62/959,510 filed on 01/10/2020.
Information Disclosure Statement
The information disclosure statements (IDS) dated 10/09/2025 and 10/14/2025 comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609, except where noted. A copy of the non-patent literature document titled “The EBV 20 lytic switch protein, Z, preferentially binds to and activates the methylated viral genome” listed in the IDS dated 10/09/2025 was not provided. Accordingly, the IDS documents have been placed in the application file and the information therein has been considered as to the merits.
Withdrawn Objections
Applicant’s amendment, filed on 10/09/2025, with respect to the objection of the specification has been fully considered and is persuasive. Applicant has amended the specification to replace BLZF1 with BZLF1. The rejection is hereby withdrawn.
Withdrawn Rejections
Applicant’s amendment, filed on 10/09/2025, with respect to the rejection of claim 23 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, regards as the invention, has been fully considered and is persuasive. Applicant has amended claim 23 to replace BLZF1 with BZLF1. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 10/09/2025, with respect to the rejection of claim 1, 3-5 and 9-14 under 35 U.S.C. 102(a)(2) as being anticipated by Macbeth (US 2015/0359810 A1, published 12/17/2015, see IDS dated 07/08/2022) as evidenced by Frost (Current Opinion in Virology, published 09/15/2018, see PTO-892 dated 04/15/2025) and as evidenced by Gulati et al (Recent Patents on Drug Delivery & Formulation, published 03/08/2011, see PTO-892 dated 04/15/2025) has been fully considered and is persuasive. Macbeth does not exemplify the use of AZA on a mammal and applicant has amended claims 1 and 3 to add the limitation of wherein the mammal has at least 10% or more tumor cells in latency I relative to latency II/III. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 10/09/2025, with respect to the rejection of claims 1 and 8 under 35 U.S.C. 103 as being unpatentable over Macbeth (US 2015/0359810 A1, published 12/17/2015, see IDS dated 07/08/2022) as evidenced by Frost (Current Opinion in Virology, published 09/15/2018, see PTO-892 dated 04/15/2025) has been fully considered and is persuasive. Applicant has amended claim 1 to add the limitation of wherein the mammal has at least 10% or more tumor cells in latency I relative to latency II/III. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 10/09/2025, with respect to the rejection of claims 7, 15, and 16 under 35 U.S.C. 103 as being unpatentable over Macbeth (US 2015/0359810 A1, published 12/17/2015, see IDS dated 07/08/2022) as evidenced by Frost (Current Opinion in Virology, published 09/15/2018, see PTO-892 dated 04/15/2025) as applied to claim 1 above, and further in view of Bollard et al. (Journal of Clinical Oncology, published 03/10/2014, see PTO-892 dated 04/15/2025) been fully considered and is persuasive. . Applicant has amended claim 1 to add the limitation of wherein the mammal has at least 10% or more tumor cells in latency I relative to latency II/III. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 10/09/2025, with respect to the rejection of claims 15-20 under 35 U.S.C. 103 as being unpatentable over Macbeth (US 2015/0359810 A1, published 12/17/2015, see IDS dated 07/08/2022) as evidenced by Frost (Current Opinion in Virology, published 09/15/2018, see PTO-892 dated 04/15/2025) as applied to claim 1 above, and further in view of Dugan et al. (Frontiers in Oncology, published 03/15/2019, see PTO-892 dated 04/15/2025) been fully considered and is persuasive. Applicant has amended claim 1 to add the limitation of wherein the mammal has at least 10% or more tumor cells in latency I relative to latency II/III. The rejection is hereby withdrawn.
Rejections Necessitated by Amendment
The following are new ground(s) necessitated by Applicants' amendment, filed on 10/09/2025, wherein instant independent claims 1, 3, and 21 were amended to alter the breadth and scope of the claim, and wherein the remaining pending claims 4-5, 7-20, and 23 depend from said independent claims.
New or Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
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 and 3-5, and 7-20 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.
Regarding claims 1 and 3, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of applying prior art, the claim will be interpreted as “latency I relative to latency II/III”. Claims 4-5 and 7-20 are rejected for being based on a rejected claim base.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 21 and 23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more than the judicial exception.
The claim is evaluated below using the “Subject Matter Eligibility Test for Products and Processes” flow chart as shown in MPEP § 2106 III.
Step 1: Is the claim to a process, machine, manufacture or composition of matter?
Yes. The claims are drawn to a method (process) which is one of the four statutory categories.
Step 2A, Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes. The claims are directed towards a method of contacting EBV latency I tumor cells with one or more agents and determining whether the one or more agents convert the EBV latency I tumor cells to EBV latency II/III tumor cells by increasing expression of an EBV latency II/III marker.
In the broadest reasonable interpretation of the claim, the steps of determining whether the one or more agents increases expression of an EBV latency II/II marker thereby identifying the agent as an agent that converts the EBV latency I tumor cells to EBV latency II/III tumor cells comprise mental steps, which are abstract ideas.
Step 2A, Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
No. There are no additional steps recited in the claim that integrate the judicial exceptions into a practical application. The claimed method ends with the determination of whether the one or more agents convert the EBV latency I tumor cells to EBV latency II/III tumor cells. The claim does not further limit the determination with additional steps beyond the mental step.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
No. The judicial exceptions are recited without additional limitations amounting to significantly more than the judicial exceptions.
While the claims require contacting the EBV latency I tumor cells with an agent that increases expression of an EBV latency II/III marker, which could require that tests be performed, these are considered to be insignificant extra-solution activity that do not amount to more than the recited judicial exceptions. See MPEP 2106.05(g).
As the active steps of the claim are considered to be well-understood, routine, and conventional in the field or significant extra-solution activity, these steps do not amount to significantly more than the recited judicial exceptions.
As the instant claims recite judicial exceptions that are not integrated into a practical application and recite no elements that amount to significantly more than the judicial exceptions, the claims were found to not be drawn to eligible subject matter under 35 USC 101. Claim 23 is rejected for being dependent from a rejected claim base.
Response to Arguments
Applicant’s arguments filed on 10/09/2025 have been fully considered in so far as they apply to the rejections of the office action dated 04/15/2025, but were not persuasive.
Regarding the rejection of instant claims 21 rejected under 35 U.S.C. 101, applicant argues that the amended claim 21 is not directed to an abstract idea and that the claim as a whole integrates the idea into a practical laboratory application that amounts to significantly more. Applicant argues that amended claim 21 is directed to statutory subject matter because the claim is not focused on a mere mental process, but rather is directed to a concrete, laboratory implemented assay that physically alters EBV-infected tumor cells ex vivo. The claim therefore “improves the functioning of a laboratory technique itself.” The argument is not persuasive. Claim 21 is directed to the mental steps of “identifying” a latency-converting agent by contacting the tumor cells with a test agent and the mental step of determining of the test agent increases expression of an EBV latency II/III marker thereby identifying an agent that converts the EBV latency I tumor cells to EBV latency II/III tumor cells. The limitations “identifying” and “determining” are considered mental steps.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 21 and 23 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Macbeth (US 2015/0359810 A1, published 12/17/2015, see IDS dated 07/08/2022) as evidenced by Frost (Current Opinion in Virology, published 09/15/2018, see PTO-892 dated 04/15/2025).
Macbeth is drawn to methods for treating subjects having an EBV-associated cancer, including Burkitt’s lymphoma, wherein the method comprises administering to the subject 5-azacytidine (AZA) alone or in combination with one or more anti-cancer agents (abstract). Macbeth teaches the method of invention may be used for treating EBV-associated cancers (paragraph 011). Macbeth discloses an in vitro method using the RAEL and Ramos Burkitt’s lymphoma cell lines (paragraph 0430) to determine if AZA is capable of reactivating viral latency genes, such as LMP1, and disclosed that AZA did increase the expression of LMP1 and Zta (Figure 16 and paragraph 435). Further, Macbeth teaches that AZA induced expression of EBV proteins, including EBNAl, EBNA2, Zta, and LMP1 in the RAEL, but not in the EBV-negative (EBV-) Ramos, cell line. Collectively, these results indicated that AZA caused demethylation of EBV promoters and induced expression of several EBV genes/proteins, suggesting that AZA may be used in the clinic to enhance the immunogenicity of tumors in human malignancies associated with EBV infection (paragraph 0425). Macbeth does not directly disclose that the method converts EBC latency I tumors in a mammal to EBV latency II/II tumors or to sensitize EBV+ tumors in a mammal to T-cell mediated killing.
Machbeth does not expressing teach that demethylating agents convert EBV latency I tumors to EBV latency II/III tumors.
As evidenced by Frost , demethylating agents upregulate latency III transcripts in latency I B-Cells reactivating the genes (ex. LMP1 or EBNA2) implying the conversion of EBV latency I tumors to EBV latency II/III tumors (column 1, page 17).
Therefore, the conversion of EBV latency I tumors to EBV latency II/II tumors would necessarily have occurred with the method of application of AZA in Macbeth as it was disclosed that the AZA resulted in an increase of LMP1 expression as shown in Fig 11.
Accordingly, the instant claim is anticipated by the prior art.
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.
Claims 1, 3-5 and 8-15 are rejected under 35 U.S.C. 103 as being unpatentable over Macbeth (US 2015/0359810 A1, published 12/17/2015, see IDS dated 07/08/2022), Price et al. (PLOS Pathogens, published 03/19/2015, see PTO-892), and Frost (Current Opinion in Virology, published 09/15/2018, see PTO-892 dated 04/15/2025) and as evidenced by Gulati et al (Recent Patents on Drug Delivery & Formulation, published 03/08/2011, see PTO-892 dated 04/15/2025).
Macbeth is drawn to methods for treating subjects having an EBV-associated cancer, including Burkitt’s lymphoma, wherein the method comprises administering to the subject 5-azacytidine (AZA) alone or in combination with one or more anti-cancer agents (abstract). Macbeth teaches the method of invention may be used for treating EBV-associated cancers (paragraph 011). Macbeth teaches that reactivation of viral genes from latency by DNA demethylating agents could serve as a therapeutic strategy for EBV-associated tumors (paragraph 0004). Macbeth teaches that the results indicated that AZA caused demethylation of EBV promoters and induced expression of several EBV genes/proteins, suggesting that AZA may be used in the clinic to enhance the immunogenicity of tumors in human malignancies associated with EBV infection (paragraph 0425). Macbeth teaches that the AZA may alter the natural course of myelodysplastic syndromes by diminishing the transformation to acute myelogenous leukemia through its cytotoxic activity and its inhibition of DNA methyltransferase meeting the limitation of instant claim 11 (paragraph 0009). The pharmaceutical composition containing AZA may be formulated for oral, parenteral, and topical administration (paragraph 0104). Parenteral administration is administration by injection as evidenced by Gulati (column 1, page 133). Macbeth discloses an in vitro method using the RAEL and Ramos Burkitt’s lymphoma cell lines (paragraph 0430) to determine if AZA is capable of reactivating viral latency genes, such as LMP1, and disclosed that AZA did increase the expression of LMP1 and Zta (Figure 16 and paragraph 435). Further, Macbeth teaches that AZA induced expression of EBV proteins, including EBNA1, EBNA2, Zta, and LMP1 in the RAEL, but not in the EBV-negative (EBV-) Ramos, cell line. Collectively, these results indicated that AZA caused demethylation of EBV promoters and induced expression of several EBV genes/proteins, suggesting that AZA may be used in the clinic to enhance the immunogenicity of tumors in human malignancies associated with EBV infection (paragraph 0425).
Regarding instant claim 4, Macbeth teaches that a pharmaceutical composition containing AZA may be administered to humans (paragraph 0106).
Regarding instant claim 8, Macbeth teaches that EBV has been known to be associated with a variety of cancers including Burkitt’s lymphoma, nasopharyngeal carcinoma, and gastric carcinoma (paragraph 0003).
Regarding instant claim 9, Macbeth disclosed that AZA strongly induced expression of LMP1 (Figure 11 and paragraph 0434).
Regarding instant claim 15, Macbeth teaches co-administering AZA with one or more therapeutic agents such as immunosuppressants (paragraphs 0198-0199).
Macbeth does not directly teach that the method converts EBC latency I tumors in a mammal to EBV latency II/II tumors or to sensitize EBV+ tumors in a mammal to T-cell mediated killing. Macbeth does not directly teach that the mammal has at least 10% more tumor cells in latency I relative to latency II/III.
Price is drawn to the study of EBV latency establishment and the consequences for B cell tumorigenesis (title). Price teaches that in vivo, the major pool of EBV latently-infected B cells are resting, peripheral blood class-switched memory cells. No viral proteins are expressed in these cells (Latency 0) except during cell division, when EBNA1 is expressed from Qp (Latency I). These cells are poorly recognized by the T cell immune response (page 4). Price further teaches that in Burkitt’s lymphoma, 85% of the cells are Latency I (Fig. 2, page 5).
Frost is drawn to a review of advances in the understanding of epigenetic contribution to EBV latency states, lytic reactivation, EBV super enhancers, silencing of tumor suppressors BCL2L11 and PRDM1, and in EBNA3-mediated suppression of LMP1/2A-driven plasmablast differentiation (column 2, page 15). Frost teaches that demethylating agents upregulate latency III transcripts in latency I B-Cells reactivating the genes (ex. LMP1 or EBNA2) implying the conversion of EBV latency I tumors to EBV latency II/III tumors.
It would have been prima facie obvious to combine the teachings of Macbeth, Price, and Frost before the effective filing date of the claimed invention by administering AZA to a mammal with EBV tumors as taught by Macbeth wherein the mammal has a majority EBV latency I cells as taught by Price and the administration of the AZA results in the conversion of EBV latency I to EBV latency II/III tumors as taught by Frost. It would have been prima facie obvious for one of ordinary skill in the art to administer AZA to a mammal with EBV tumors such as Burkitt Lymphoma that are the majority of EBV latency I to convert the tumors to EBV latency II/III latency because Macbeth teaches the administration of AZA to humans and that AZA increases the expression of LMP1, Price teaches that the majority of Burkitt Lymphoma cells are in latency I, and Frost teaches that demethylating agents may convert EBV latency I tumors to EBV latency II/III tumors. One of ordinary skill in the art would have a reasonable expectation of success because Macbeth shows that AZA induced expression of EBV proteins, including EBNA1, EBNA2, Zta, and LMP1 in the RAEL, but not in the EBV-negative (EBV-) Ramos, cell line.
Claim 7 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Macbeth (US 2015/0359810 A1, published 12/17/2015, see IDS dated 07/08/2022), Price et al. (PLOS Pathogens, published 03/19/2015, see PTO-892), and Frost (Current Opinion in Virology, published 09/15/2018, see PTO-892 dated 04/15/2025) as applied to claims 1 and 15 above and further in view of Bollard et al. (Journal of Clinical Oncology, published 03/10/2014, see PTO-892 dated 04/15/2025).
Claim 1 is rejected as discussed above.
Claim 15 is rejected as discussed above.
The combined teachings of Macbeth, Price, and Frost are discussed above.
The combined teachings of Macbeth Price, and Frost differ from that of the instantly claimed invention in that they did not teach the limitation wherein the mammal has Hodgkin lymphoma. The combined teachings of Macbeth Price, and Frost do not teach the administration of an immunotherapeutic wherein the immunotherapeutic comprises EBV-specific cytotoxic T-cells.
Bollard is drawn to a study of the sustained complete responses in patients with lymphoma that received autologous cytotoxic T lymphocytes (CTL) targeting EBV latent membrane proteins. Bollard teaches that tumor cells from approximately 40% of patients with Hodgkin or non-Hodgkin lymphoma expressed the type II latency EBV antigens latent membrane protein 1 (LMP1) and LMP2, which represented targets for immunotherapy. Bollard further teaches that AZA upregulates TAAS by hematologic malignancies and epigenetic modifiers to increase tumor associated antigen (TAA) expression by tumor cells, such as AZA, could be incorporated into LMP-CTL therapy (page 908, column 2).
It would have been prima facie obvious to combine the combined teachings of Macbeth, Price, and Frost with the teachings of Bollard before the effective filing date of the claimed invention by modifying the method of Macbeth by co-administering AZA and LMP CTL to patients including those with Hodgkin lymphoma to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the method to include co-administration of AZA and LMP CTL to patients including those with Hodgkin lymphoma because Macbeth teaches co-administering AZA with additional therapeutics and Bollard directly suggests combining AZA and LMP CTL. One of ordinary skill in the art would have a reasonable expectation of success because Bollard teaches the importance of eliciting a T-cell response to TAAs and AZA was demonstrated to upregulate TAAs.
Claims 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Macbeth (US 2015/0359810 A1, published 12/17/2015, see IDS dated 07/08/2022), Price et al. (PLOS Pathogens, published 03/19/2015, see PTO-892), and Frost (Current Opinion in Virology, published 09/15/2018, see PTO-892 dated 04/15/2025) as applied to claims 1 and 15 above, and further in view of Dugan et al. (Frontiers in Oncology, published March 15, 2019).
Claim 1 is rejected as discussed above.
Claim 15 is rejected as discussed above.
The combined teachings of Macbeth, Price, and Frost are discussed above.
Macbeth further teaches that AZA may be administered in combination with another anti-cancer agent (paragraph 0014) and that they may be administered in the same route (paragraph 0015).
The combined teachings of Macbeth, Price, and Frost differ from that of the instantly claimed invention in that they did not teach the method of claim 1 further comprising administering an immunotherapeutic such as EBV-specific cytotoxic T-cells or a checkpoint inhibitor.
Dugan is drawn to opportunities to target the life cycle of EBV in EBV-associated lymphoproliferative disorders. Dugan teaches the importance of the viral gene programs expressed during specific viral phases and discusses the established and emerging treatment approaches for EBV-associated lymphoproliferative disorders (LPDs) based on EBV gene expression programs (abstract). Dugan teaches that EBV promoter demethylation in lymphomas by AZA inhibits DNA methyltransferase. Dugan discusses T-cell immunotherapy and discusses the use of EBV-specific cytotoxic T-lymphocytes (CTLs). EBV was permitted to proliferate due to the depletion of CTLs. Adoptive T-cell immunotherapy involved infusing EBV-specific CTLs generated in vitro with the aim of reconstituting the EBV immunity and influence targeted destruction of EBV infected tumor cells (column 2, page 5). Dugan further suggests that combining checkpoint inhibitors with lytic induction could be a promising strategy for treating EBV mediated malignancy (page 6, column 2).
It would have been obvious to combine the combined teachings of Macbeth, Price, and Frost with the teachings of Dugan before the effective filing date of the claimed invention by modifying the method from the teachings of Macbeth to administer an immunotherapeutic, such as EBV-specific toxic T-cells or a checkpoint inhibitor, in addition to the AZA to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the method to co-administer either EBV-specific cytotoxic T-cells or a checkpoint inhibitor with the AZA that is orally, parentally, or topically administered because Macbeth taught that AZA could be co-administered with an additional anti-cancer agent and Dugan suggests combining a checkpoint inhibitor with lytic induction. One of ordinary skill in the art would have a reasonable expectation of success because Macbeth teaches that AZA can cause lytic induction and Dugan suggests the combination of lytic induction with a checkpoint inhibitor.
Response to Arguments
Applicant’s arguments filed on 10/09/2025 have been fully considered in so far as they apply to the rejections of the office action dated 04/15/2025, but were not persuasive.
Regarding the rejection of instant claims 21 and 23, applicant argues that Macbeth does not explicitly teach converting a latency I tumor to latency II/III tumor nor teach the determination step of claim 21. Further, applicant argues that Macbeth does not teach any screen assay in which unknown compounds are evaluated for latency conversion. Applicant argues that a 102 rejection must rest on a single reference and that importing critical subject matter from Frost and Gulati into Macbeth is legally impermissible. The argument is not persuasive. Macbeth exemplifies an in vitro assay where AZA is contacted with Rael and Ramos Burkitt’s lymphoma cells to determine if AZA was capable reactivating viral latency genes, such as LMP1. Regarding the screen assay, Macbeth exemplifies the use of AZA which can reasonably be considered a test agent and the test of adding AZA to cells to determine the capable of reactivating viral latency genes such as LMP1 to be a screen to determine AZA’s ability to increase the expression marker LMP1. Regarding the secondary references used in evidence of, Frost and Gulati, it is legally permissible to utilize secondary references that disclose that a characteristic is inherent. Frost was used to show that a demethylating agent would have necessarily caused EBV latency I tumors to convert EBV latency II/III tumors. The limitation “converts” and “increases” are mere results of the active step in which the cells were contacted with the agent. Therefore, because reactivating viral latency genes, such as LMP1, necessarily means converting from EBV latency I to EBV latency II/III, and because Macbeth directly made the determination that AZA was capable of increasing the LMP1, the claims are anticipated by Macbeth.
Applicant argues that Macbeth is silent on T-cell response. The argument is not persuasive. Instant claim 1 is written in the alternative form of converting EBV latency II/II tumors or to sensitize EBV+ tumors in a mammal to T-cell mediated killing. As Macbeth addresses the latency conversion, Macbeth meets the limitation of instant claim 1 and “to sensitize EBV+ tumors in a mammal to T-cell mediated killing” does not need to be addressed.
Applicant argues that the unexpected results showing that decitabine induces EBV latency-III antigens (EBNA2, LMP1) in vivo in latency I BL xenografts (Fig. 3), does not significantly up-regulate lytic BZLF1 (Fig. 9); and renders the tumors highly susceptible to EBY-specific CTL killing (Fig. 7). The argument is unpersuasive. Decitabine is the alternative to azacytidine in instant claim 10. Macbeth showed that AZA can induce LMP1 in vitro and teaches administration to a mammal. Therefore, it would have been reasonable to try the administration of AZA to a mammal to induce LMP1 in vivo. Further, Macbeth teaches that decitabine could be administered to determine whether gene promoter methylation levels may influence overall survival in patients with EBV-associated cancer (paragraph 0303). Further, the argument of unexpected results must be commensurate in scope with claim limitation which included both decitabine and AZA (see MPEP 716).
Regarding the rejection of instant claims 7 and 15-16, applicant argues that Bollard does not remedy the deficiencies of Macbeth and Frost as Bollard does not exemplify the use of AZA. The argument is not persuasive. Bollard teaches that AZA upregulates TAAs by hematologic malignancies and that AZA could be incorporated into LMP-CTL therapy for Hodgkin’s lymphoma.
Regarding the rejection of instant claims 15-20, applicant argues that Dugan does not propose co-administration of a hypomethylating agent with an immunotherapeutic. The argument is not persuasive. Dugan is not relied upon for the co-administration of an immunotherapeutic as Macbeth teaches the co-administration of AZA with one or more cancer agents (abstract) or therapeutic agents (paragraph 0320).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693