DETAILED ACTION
The present application is a national stage entry of PCT/US22/15951, filed 10 February 2022, which claims priority to US Provisional Application No. 63/148,426, filed 11 February 2021.
The preliminary amendment filed 10 February 2026 is acknowledged. Claims 1, 2, 6, 7, 9, 15, 26, 28, 36, 50, 59, 60, 65, 67 and 69-78 are pending in the current application.
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 “Breast cancer carrying a BRCA mutation” as a first species of cancer; DMXAA as a second species of STING agonist; olaparib as a third species of PARP inhibitor; Osimertinib as a fourth species of TK inhibitor; and gemcitabine as a fifth species of DNA synthesis inhibitor in the reply filed on 10 February 2026 is acknowledged.
To advance prosecution of the present application, the species of STING agonist has been expanded to include ADU-S100.
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 59, 60, 65 and 67 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more.
The claim(s) recite(s) “detecting an M2 enrichment score for a tumor from the subject, and selecting the subject if the score is higher than 0.27”. This judicial exception is not integrated into a practical application. And the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claim 59 recite(s) “detecting an M2 enrichment score for a tumor from the subject”. The step of “detecting” can be practiced in the mind. The claim additionally sets forth “selecting the subject if the score is higher than 0.27”. The step “selecting” can also be practiced in the human mind by comparing scores. These steps encompass a data analysis process which can be practiced in the mind. Additionally, the claims are drawn to an abstract idea because obtaining an M2 enrichment score appears to include data analysis and mathematical calculations.
These judicial exceptions are not integrated into a practical application because the steps of data gathering steps do not apply or integrate the judicial exceptions in any way. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claim 60 further defines the cancer being selected, from which the enrichment score is detected, thus, is a field of use limitation which does not amount to significantly more.
Claim 65 further defines the subject and/or cancer being selected, from which the enrichment score is detected, is a field of use limitation which does not amount to significantly more.
Claim 67 is rejected under 35 U.S.C. 101 because it is not a proper process claim. The claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
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 15, 67 and 78 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.
Present claim 67 recites “comprising administering to the subject, optionally wherein the administration is about 10 mg/kg body weight of a STING agonist conjointly with about 50 mg/kg body weight of a PARP inhibitor” does not require administering anything. Thus, present claim 67 does not recite an active step. Thus, it is unclear how this use is actually practiced. See MPEP 2173.05(q).
Because of the high level of uncertainty as to what the claim refers to and what is required of the invention as claimed, claim 67 is not further examined on the merits herein.
Claims 15 and 78 are directed towards limitations (i), (ii), (iii), (iv), (v), (vi), however, there is no “and”, “or”, or “and/or” between limitations (v) and (vi). Thus, it is not clear if the claim requires all six limitations, or only one. For purposes of examination, and consistent with other claims including for example claim 14, the claim is interpreted to only include one of the six limitations.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 2, 6, 7, 9, 15, 26, 28, 36, 50 and 69-72 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pantelidou et al. 2021 (bioRxiv, preprint posted 27 January 2021, cited in IDS submitted 12 December 2023; hereinafter referred to as Pantelidou 2021).
Pantelidou 2021 teach the use of a PARP inhibitor in combination with STING agonism in BRCA-associated breast cancer (abstract). Combined PARP inhibition and STING agonism induced a greater degree of STING pathway activation and proinflammatory cytokine production compared to monotherapies in BRCA1-deficient human and mouse triple-negative breast cancer cell lines (abstract). The combination markedly improved anti-tumor efficacy in vivo compared to monotherapy treatment, with evidence of complete tumor clearance and prolongation of survival (abstract).
Pantelidou 2021. teach testing ADU-S100 as a STING agonist in a K14-Cre;Brca1f/f TNBC (triple negative breast cancer) mouse model (p.6, first para). Olaparib (species of PARP inhibitor) was administered by intraperitoneal injection at a dose of 50 mg/kg daily. ADU-S100 (STING agonist) was administered in a single 40 µl injection of 50 µg (1.25 µg/µL) intratumorally weekly (p.6, first para). Combination therapy significantly increased total T-cell counts compared to monotherapies, with both CD8+ and CD4+ T cell subsets significantly augmented (p.9-10, bridging para).
ADU-S100 is a modified nucleotide STING agonist. The STING agonist and PARP inhibitor are administered concurrently.
The features of Pantelidou 2021 anticipates claims 1, 2(ii), 6(i), 7(ii), 9(i)-inherently, (iv)-inherently and (vii), 15(i)(ii)(iii), 26, 28(i)-inherently,(iii),(iv)-inherently,(v)-inherently,(viii), 36(i)(ii)(v)(vii)(viii), 50(optional limitation), 69, 70(i)(ii)(iii)(iv)(v)(viii), 71(i)-inherently, (ii)(v)(vi)(vii)(viii), and 72(i).
Thus, the disclosure of Pantelidou 2021 anticipates claims 1, 2, 6, 7, 9, 15, 26, 28, 36, 50 and 69-72 of the present application.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 6, 7, 9, 15, 26, 28, 36, 50 and 69-78 are rejected under 35 U.S.C. 103 as being unpatentable over Pantelidou 2021 (cited above) in view of Pantelidou 2019 (Cancer discovery, 2019, vol. 9, no. 6, pp. 722-737, cited in PTO-892; hereinafter referred to as Pantelidou 2019).
Pantelidou 2021 teaches as discussed above.
Pantelidou 2021 does not expressly disclose DMXAA (STING agonist). Pantelidou 2021 does not expressly disclose administering the STING agonist by systemic delivery (present claim 73).
Pantelidou 2019 demonstrates cross-talk between PARP inhibition and STING/TBK1/IRF3 pathway activation in cancer cells that governs CD8+ T-cell recruitment and antitumor efficacy (abstract). Pantelidou 2019 specifically demonstrated this relationship in triple-negative breast cancer (TNBC), specifically K14-Cre-Brca1f/f;Trp53f/f immunocompetent genetically engineered mouse model (GEMM) of TNBC (p.723-724, bridging para). Pantelidou 2019 teaches olaparib-treated K14 cells demonstrated a dose-dependent increase in the expression of phospho-TBK1Ser172, phosphor-IRF3Ser396, and phosphor-H2AXSer139 expression, comparable to that of the STING agonist DMXAA (p.726, left column, last para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer DMXAA conjointly with an effective amount of olaparib to a subject having breast cancer carrying a BRCA mutation.
According to MPEP 2144.06: “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).
Combining known therapies into a single therapy is a commonly applied method for identifying improved therapeutic outcomes with minimal adverse effect for the patient because each monotherapy is already known to be effective. Here, olaparib was observed to have a positive antitumor immune response on BRCA deficient triple negative breast cancer cells by activating the STING pathway in these tumor cells, and DMXAA is a STING agonist which also observed to have a positive antitumor immune response on BRCA deficient triple negative breast cancer cells. Thus, the skilled artisan would have been motivated to combine the two drugs for the treatment of breast cancer carrying a BRCA mutation.
Additionally, the ordinary artisan would have been motivated to substitute the ADU-S100 with DMXAA because they are both recognized as STING agonists, and both were studied in TNBCs carrying the same BRCA mutation. The ordinary artisan would have had a reasonable expectation of success in treating TNBCs carrying a BRCA mutation with conjoint administration of DMXAA and olaparib, because Pantelidou et al. found combined PARP inhibition and STING agonism induced a greater degree of STING pathway activation and proinflammatory cytokine production compared to monotherapies in BRCA1-deficient human and mouse triple-negative breast cancer cell lines. The combination markedly improved anti-tumor efficacy in vivo compared to monotherapy treatment, with evidence of complete tumor clearance and prolongation of survival.
It would have been obvious to administer the STING agonist systemically, because olaparib was administered systemically and found to activate the STING pathway. Thus, it would have been obvious to also administer the STING agonist systemically with a reasonable expectation of success.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 1, 2, 6, 7, 9, 15, 26, 28, 36, 50 and 69-78 are rejected under 35 U.S.C. 103 as being unpatentable over Pantelidou 2019 (Cancer discovery, 2019, vol. 9, no. 6, pp. 722-737, cited in PTO-892; hereinafter referred to as Pantelidou 2019).
Pantelidou 2019 teach as discussed above.
Pantelidou 2019 does not expressly disclose conjointly administering DMXAA and olaparib.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer DMXAA conjointly with an effective amount of olaparib to a subject having breast cancer carrying a BRCA mutation.
According to MPEP 2144.06: “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).
Combining known therapies into a single therapy is a commonly applied method for identifying improved therapeutic outcomes with minimal adverse effect for the patient because each monotherapy is already known to be effective. Here, olaparib was observed to have a positive antitumor immune response on BRCA deficient triple negative breast cancer cells by activating the STING pathway in these tumor cells, and DMXAA is a STING agonist which also observed to have a positive antitumor immune response on BRCA deficient triple negative breast cancer cells. Thus, the skilled artisan would have been motivated to combine the two drugs for the treatment of breast cancer carrying a BRCA mutation, with a reasonable expectation of success.
It would have been obvious to administer the STING agonist systemically, because olaparib was administered systemically and found to activate the STING pathway. Thus, it would have been obvious to also administer the STING agonist systemically with a reasonable expectation of success.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699