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 .
Priority
The application 18/594305 filed on 03/04/2024 claims priority from the Provisional application 63/505109 filed on 05/31/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/04/2024 was filed after the mailing date of the PROVISIONAL 63/505109 on 05/31/2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claims 1 and 6-18 are rejected under 35 U.S.C 102(a) as being anticipated by Greten et al. (EP3915585A1; hereafter Greten; PTO-892).
As to claim 1, Greten teaches “An agonist of ferroptosis for use in aiding a treatment with an immune checkpoint inhibitor in a subject, by enhancing susceptibility of cells or tissue involved with a proliferative disorder to the treatment with the immune checkpoint inhibitor” [claim 8]. “In some preferred embodiments of the present invention, the agonist of ferroptosis is Withaferin A, which is a plant derived steroidal lactone ((4β,5β,6β,22β)-4,27-Dihydroxy-5,6:22,26-diepoxyergosta-2,24-diene-1,26-dione)” [0022]. “A proliferative disorder in context of the invention in all aspects and embodiments is preferably a cancer or tumour disease. As used herein, "cancer" can include the term "solid tumour" [0039].
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As to claims 6 and 7, Greten teaches “In certain embodiments, the cancer can be, for example, esophageal cancer, gastroesophageal junction cancer, gastroesophageal adenocarcinoma, gastric cancer, chondrosarcoma, colorectal adenocarcinoma, breast cancer, ovarian cancer, head and neck cancer, melanoma, gastric adenocarcinoma, lung cancer, pancreatic cancer, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, brain tumour, multiple myeloma, leukemia, lymphoma, prostate cancer, cholangiocarcinoma, endometrial cancer, small bowel adenocarcinoma, uterine sarcoma, or adrenocorticoid carcinoma. In certain embodiments, the cancer can be, for example, esophageal cancer, gastroesophageal junction cancer, gastroesophageal adenocarcinoma, colorectal adenocarcinoma, breast cancer, ovarian cancer, head and neck cancer, melanoma, gastric adenocarcinoma, lung cancer, pancreatic cancer, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, brain tumour, multiple myeloma, leukemia, lymphoma, prostate cancer, cholangiocarcinoma, endometrial cancer, small bowel adenocarcinoma, uterine sarcoma, or adrenocorticoid carcinoma. In certain embodiments, the cancer can be, for example, breast cancer. In certain embodiments, the cancer can be, for example, colorectal adenocarcinoma. In certain embodiments, the cancer can be, for example, small bowel adenocarcinoma. In certain embodiments, the cancer can be, for example, hepatocellular carcinoma. In certain embodiments, the cancer can be, for example, head and neck cancer. In certain embodiments, the cancer can be, for example, renal cell carcinoma. In certain embodiments, the cancer can be, for example, ovarian cancer. In certain embodiments, the cancer can be, for example, prostate cancer. In certain embodiments, the cancer can be, for example, lung cancer. In certain embodiments, the cancer can be, for example, uterine sarcoma. In certain embodiments, the cancer can be, for example, esophageal cancer. In certain embodiments, the cancer can be, for example, endometrial cancer. In certain embodiments, the cancer can be, for example, cholangiocarcinoma. In certain embodiments, each of the cancers can be, for example, unresectable, advanced, refractory, recurrent, or metastatic. A preferred cancer is a solid cancer, in particular hepatocellular carcinoma or colorectal cancer” [0049].
As to claims 8-15, Greten teaches “The agonist of ferroptosis for use of claim 3, wherein the immune checkpoint inhibitor is selected from an immunotherapy comprising (administration of) an antibody binding to an immune checkpoint molecule, a non-antibody peptide or a small molecule, targeting and inhibiting CTLA-4, PD-1 or PD-L1” [claim 4]. The term "checkpoint inhibitor" or "immune checkpoint inhibitor", as used herein, refers to an agent used in cancer immunotherapy. A checkpoint inhibitor blocks an inhibitory immune checkpoint and thus restores immune system function, for example, an inhibitor of the immune checkpoint molecule CTLA-4, such as ipilimumab, or an inhibitor of PD-1, such as nivolumab or pembrolizumab, or an inhibitor of PD-L1, such as atezolizumab, avelumab, and durvalumab” [0028].
As to claim 16 and 17, Greten teaches “In addition, the treatment may comprise at least one or more cancer therapies including chemotherapy, a radiation therapy, or immune therapy after preconditioning the tumour or tumour environment with agonists of ferroptosis, optionally together with MSDC inhibitors. The treatment regimen and schedule may vary depending on the type(s) of preconditioning and cancer therapies” [0037]. The treatment of the invention may further comprise the administration of at least one additional anti-proliferative therapeutic such as a chemotherapeutic agent” [0038].
As to claim 18, Greten teaches “To be used in therapy, the compounds and compositions of the invention may be formulated into a pharmaceutical composition appropriate to facilitate administration to animals or humans. The term "pharmaceutical composition" means a mixture of substances including a therapeutically active substance (such as an agonist or antagonist of the invention) for pharmaceutical use” [0056].
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 2-5 are rejected under 35 U.S.C. 103 as being unpatentable over Greten et al. (EP3915585A1; hereafter Greten; PTO-892) in view of Xie et al. (2022; hereafter Xie; PTO-892).
Greten teaches all features of claims 1 and 6-18, as laid out above.
As to claim 2-5, Greten teaches “The agonist of ferroptosis for use of any one of the preceding claims, wherein the proliferative disorder is a solid tumour, preferably hepatocellular carcinoma (HCC)” [claim 12]. “A proliferative disorder is a tumour disease, preferably a tumour disease characterized by a reduced susceptibility to a therapy with an immune checkpoint inhibitor” [0049]. “The invention provides such combinatorial approaches to treat proliferative disorders, preferably solid cancers which are characterized by a resistance to immune checkpoint inhibition, which often is observed in Hepatocellular Carcinoma (HCC)” [0001]. HCC is a heterogeneous disease known to be resistant to conventional radio- and chemo-therapies [0002]. “The agonist of ferroptosis for use of claim 1 or 2, wherein (ii) sensitizing cells involved with the proliferative disorder to a cell-mediated immune response involves the administration of an immune checkpoint inhibitor to the subject” [claim 3]. “An agonist of ferroptosis for use in aiding a treatment with an immune checkpoint inhibitor in a subject, by enhancing susceptibility of cells or tissue involved with a proliferative disorder to the treatment with the immune checkpoint inhibitor” [claim 8]. “The agonist of ferroptosis for use of any one of the preceding claims, wherein the proliferative disorder is a solid tumour, preferably hepatocellular carcinoma (HCC)” [claim 12].
Greten does not appear to explicitly teach: “The method wherein the cancer is resistant or has developed resistance to treatment with the immune checkpoint blocker alone, as in claim 2; or that the cancer is resistant or has developed resistance to treatment with the immune checkpoint blocker in combination with another therapeutic agent other than withaferin A (claim 3). Further, Greten does not appear to explicitly teach that the cancers may be susceptible to developing resistance with a checkpoint blocker alone (Claim 4) or with another therapeutic agent other than withaferin A (Claim 5).
Xie teaches “Tumor cells with inherently low tumor mutational burden (TMB) are more likely to be deficient in neoantigens and are more susceptible to ICI resistance”. Xie also teaches that tumor intrinsic mechanisms are closely associated with tumor cell alterations that affect neoantigen expression, antigen presentation, and expression of immune co-inhibitory signals, resulting in defective antigen recognition and decreased T-cell recruitment and activity in tumors. Xie teaches key mechanisms of immune checkpoint inhibitor resistance in hepatocellular carcinoma (HCC), such as inadequate, absence or alterations in the presentation or processing of tumor neoantigens and alterations in oncogenic pathways.
Xie also teaches nivolumab (ICI) monotherapy did not significantly enhance overall survival (OS) in the first-line setting for advanced HCC patients compared with sorafenib (not an ICI) in a clinical phase 3 trial study. Similarly, second-line pembrolizumab (ICI) treatment also did not significantly improve OS and progression-free survival (PFS) compared with sorafenib in a phase 3 trial.
Thus, one of ordinary skill in the art at the time of filing would consider it prima facie obvious to combine a therapeutically effective amount of withaferin A and immune checkpoint inhibitor because it would have been reasonable to expect that some tumors (like HCC) would not benefit from an immune checkpoint blocker alone as it was well known that many tumors can be resistant and/or be susceptible to developing resistance to immune checkpoint therapy alone as set forth by the teachings of both Xie and Greten. Also, the method to use a combination of immune checkpoint inhibitor with another therapeutic agent other than withaferin A would be obvious and very desirable because one of ordinary skill in the art would use it as a strategy to increase the possibility of therapeutic combinations to successfully overcome cancer resistance and/or susceptibility to developing resistance to well-known therapeutic agents, such as immune checkpoint blockers, radio- and chemotherapy as taught by Xie and Greten.
Also, KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02), discloses a rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PRICILA HAUK TEODORO whose telephone number is (571) 272-2784. The examiner can normally be reached M-F 6:30AM-2:00PM.
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/PRICILA NMN HAUK TEODORO/ Examiner, Art Unit 1645
/GARY B NICKOL/ Primary Examiner, Art Unit 1643