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 .
Status
Claims 1-30 are pending. Claims 5 and 21-30 are withdrawn. Therefore, Claims 1-4 and 6-20 are examined on the merits.
Election/Restrictions
Applicant’s election without traverse of Group I (a method of treating a subject having cancer) and ARID1A mutated Ovarian Clear Cell Carcinoma (OCCC) as the cancer, MKC-8866 (ORIN1001) as the XRE1 inhibitor, and checkpoint inhibitor therapy as the second cancer therapy in the reply filed on 2/16/2026 is acknowledged.
Claims 5 and 21-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (Claim 5) and invention (Claims 21-30), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/16/2026.
Prosecution on the merits will be restricted to the claimed species if no generic claim is finally held to be allowable.
Priority
This application is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/US2021/019856, filed February 26, 2021, which claims benefit of priority to U.S. Provisional Application Serial No. 62/983,240, filed February 28, 2020.
Claim Objections
Claims 1, 3, 13, 19, and 20 are objected to because of the following informalities:
Claim 1, line 3
The term “inhibitor of IRE-l/XBP-1” at the end of Claim 1 should be clarified as to whether it refers to inhibition of IRE-1, XBP-1 or both. This would enhance readability and understanding or the claim language and is a matter of clarity instead of indefiniteness.
Claim 3 and Claim 19 have the same problem that needs to be corrected.
Claim 3, lines 1-2:
The term “treating said subject with a second cancer therapy” should be changed to “administering a second cancer therapy to said subject”.
Claim 13, line 1:
The term “claim 8” should be changed to “claim 9”. It is clear that Applicant intended for Claim 13 to depend from Claim 9, not from Claim 8.
Claim 19, line 3:
The term “and/or” should be “or”.
Claim 20, line 2:
The term “and” should be “an”.
The term “inibitor" should be changed to “inhibitor”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 3, 14, 15, 17 and 19 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.
Regarding Claim 3, the phrase "such as" at line 2 renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is not clear whether the therapies following the phrase are intended to be limiting or exemplary.
Claims 14, 15, 17, and 19 have the same problem that needs to be corrected.
Regarding Claim 3, the phrase "(e.g., checkpoint inhibitor)" at line 3 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). It is not clear whether the immunotherapy is required to be a checkpoint inhibitor or whether the checkpoint inhibitor is only recited as an example of immunotherapy.
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.
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.
A. Claims 1-4, 6-15, and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Katagiri et al. (Modern Pathology (2012); 25: 282–288; doi:10.1038/modpathol.2011.161) in view of Song et al. (Nature (2018 October); 562(7727): 423–428; doi:10.1038/s41586-018-0597-x) and Tang et al. (J. Clin. Invest. 2014;124(6):2585-2598. https://doi.org/10.1172/JCI73448).
Claimed invention
A method of treating a subject having an ovarian clear cell cancer (OCCC) that exhibits a mutation in ARIDIA comprising administering an inhibitor of IRE-1/XBP-1 to said subject.
Prior art
Katagiri teaches ARID1A mutation is frequently observed in ovarian clear cell carcinoma (OCCC). See p. 283, 1st column; see also p. 284, 1st column. ARID1A was identified as a tumor suppressor gene that is mutated in ~50% of OCCCs and ARID1A mutation was discovered to be significantly correlated with the loss of ARID1A protein expression. See p. 285, ‘Discussion’. Katagiri further teaches that loss of ARID1A expression is related to shorter progression-free survival, advanced disease, and chemoresistance in ovarian clear cell carcinoma. See title and abstract; see also p. 284; Table 2; Figure 2. Loss of ARID1A expression may have the potential to be used to identify OCCC patients who are more susceptible to early recurrence. See p. 286, 1st column.
While Katagiri teaches mutation correlates to loss of ARID1A expression which is related to shorter progression-free survival, advanced disease, and chemoresistance in ovarian clear cell carcinoma, Katagiri does not expressly teach administration of an IRE-1/XBP-1 pathway inhibitor such as MKC-8866 for treatment.
However, the IRE-1α/XBP-1 pathway is active in ovarian cancer and contributes to tumor progression and disruption of this pathway results in reduced tumor burden and improved survival. For example, Song presents experimental evidence indicating that ovarian cancer exploits the IRE1α/XBP1 arm of the Unfolded Protein Response (UPR) to cripple T cell metabolism and anti-tumor capacity. See p. 7. Song reports that ovarian cancer induces endoplasmic reticulum (ER) stress and activation of the IRE1α/XBP1 arm of the UPR in T cells to control their mitochondrial respiration and anti-tumor function. See Song abstract; see also Extended Data Figure 7 and accompanying text at pp. 27-28. Song further teaches IRE1a/XBP1 endows malignant cells with tumorigenic capacity. See Song, p. 2, bottom. Song suggests controlling ER stress or targeting IRE1α/XBP1 signaling as strategies to help restore T cell anti-tumor capacity in cancer hosts. See Song abstract. Ovarian cancer-bearing mice lacking XBP1 selectively in T cells demonstrated superior anti-tumor immunity, delayed malignant progression and increased overall survival. See Song, abstract. Small molecule 4μ8C was used to inhibit or block the activity of IRE1α. See Song, pp. 3, 4, 17.
Tang teaches pharmacologic inhibition of the IRE-1α/XBP-1 pathway using small-molecule B-I09, results in suppression of cancer cell survival and tumor progression. Tang states that targeting XBP-1 as a treatment strategy (see Tang, abstract). Thus, Tang demonstrates that the XBP-1 pathway can be targeted pharmaceutically and its inhibition produces anticancer effects.
A person of ordinary skill in the art (POSA) would have found it obvious to treat a subject with ARID1A mutated OCCC by administering an IRE-1/XBP-1 inhibitor because Katagiri identified mutated ARID1A correlates to loss of ARID1A expression in OCCC patients leading to shorter progression-free survival, advanced disease, chemoresistance, and clinical outcomes, while Song teaches IRE-1α/XBP-1 pathway promotes ovarian cancer progression and that its inhibition produces therapeutic benefit in ovarian cancer, and Tang further teaches that pharmacological inhibition of the IRE-1α/XBP-1 pathway with B-I09 provides anticancer effects. Recognizing the patients with ARID1A-mutated OCCC as being a vulnerable population with an aggressive form of cancer, the POSA would have sought to treat the OCCC patient by inhibiting the IRE-1α/XBP-1 pathway in order to suppress its activity. The POSA would have reasonably believed that such inhibition or suppression would have been beneficial because the pathway was known to be activated and oncogenic in OCCC patients and suppressing it was known to produce antitumor effects.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Claim 2 limits claim 1, wherein the inhibitor is an IRE-1 selective inhibitor, an XBP-1 selective inhibitor, or an inhibitor of both IRE-1 and XBP-1. Tang teaches inhibition of the IRE-1/XBP-1 pathway using inhibitors of IRE1 RNase activity including B-I09. See Tang, p. 2585, 2588.
Claim 3 limits claim 1, further comprising administering to said subject with a second cancer therapy, such as chemotherapy, radiotherapy, immunotherapy (e.g., checkpoint inhibitor), hormonal therapy, toxin therapy or surgery, either sequential or at the same time as said IRE-1/XBP-1 inhibitor. Katagiri teaches that patients with loss of ARID1A may be followed more frequently to detect recurrences early enough to benefit from either secondary cytoreductive surgery or second line chemotherapy.
Claim 4 limits claim 3, wherein the immunotherapy is a checkpoint inhibitor therapy. However, Claim 4 only limits Claim 3 in a meaningful when the immunotherapy option of Claim 3 is selected. Claim 3 recites multiple alternative therapies including, inter alia, chemotherapy, radiotherapy, hormonal therapy and surgery, to which the limitation of Claim 4 does not apply. Therefore, Claim 4 does not narrow the full scope of Claim 3, but only conditionally limits only one optional embodiment, and thus fails to provide a patentably distinct limitation.
Claim 6 limits claim 1, wherein the cancer exhibits a mutation in ARID IA. Claim 7 limits claim 1, wherein the cancer is an ovarian clear cell carcinoma cell or a high grade serous ovarian carcinoma cancer cell. As outlined above, the prior art suggests treatment of ARID1A mutated OCCC.
Claims 8-14 and 17 incorporation of diagnostic steps
Claim 8 limits claim 1, further comprising determining, prior to treating, that said subject carries an ARID1A-mutated cancer cell. Katagiri teaches determining ARID1A status in cancer samples, as evidenced by identification of loss of ARID1A expression in OCCC. See Katagiri, p. 284, 1st column. Katagiri teaches that such determination is clinically relevant to disease characterization. The POSA would further seek to determine the cancer type prior to treatment in order to characterize the cancer early in the therapeutic process.
Claim 9 limits claim 8, wherein determining comprises (a) obtaining a sample from said subject that contains protein and/or nucleic acids and (b) determining mutation status of an ARIDlA protein or nucleic acid encoding ARID1A in said sample. Claim 13 limits claim 9 (see objection above), wherein said sample is a tissue sample. Claim 14 limits claim 13, wherein said tissue sample is a cancer tissue sample. Katagiri teaches obtaining and analyzing tumor samples for ARID1A status. See Katagiri, p. 283.
Claim 10 limits claim 9, wherein determining comprises a nucleic acid-based assay or a protein-based assay. Katagiri teaches determining ARID1A expression using protein-based assay. See Katagiri, p. 283, 2nd column.
Claim 11 limits claim 9, wherein said sample is a fluid sample. Claim 12 limits claim 11, wherein said fluid sample is blood, serum plasma, sputum, saliva, urine or nipple aspirate. Song teaches T cells samples (i.e., blood samples) can be analyzed to determine expression of proteins. See p. 17.
Claim 15 limits claim 1, wherein said subject is a human subject. Song expressly teaches treatment of women. See Song, p. 3.
Claim 17 limits claim 1, wherein said subject has previously been diagnosed with cancer. The Katagiri patients with OCCC were previously diagnosed with cancer.
Claim 18 limits claim 1, wherein said cancer is recurrent, primary, metastatic or multi-drug resistant. Katagiri further teaches treatment of OCCC patients using primary chemotherapy and subsequent treatment upon disease recurrence, thereby explicitly supporting treatment of recurrent and primary cancer. See Katagiri, p. 286.
Claim 19 limits claim 1, wherein said IRE-1/XBP-1 inhibitor is administered more than once. Tang teaches administration of B-I09 on multiple days. See Tang, p. Fig. 7 and accompanying text at pp. 2592 and 2593.
B. Claims 16 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Katagiri et al. (Modern Pathology (2012); 25: 282–288; doi:10.1038/modpathol.2011.161) in view of Song et al. (Nature (2018 October); 562(7727): 423–428; doi:10.1038/s41586-018-0597-x) and Tang et al. (J Clin Invest. 2014;124(6):2585-2598. https://doi.org/10.1172/JCI73448), as applied to Claims 1-4 and 6-15, 17-19 above and Knutson et al. (US 20140128393 A1).
Claimed invention
Claim 16 limits claim 1, wherein said subject is a nonhuman primate.
Claim 20 limits claim 1, wherein said method comprises administering both and IRE-1 inhibitor and an EZH2 inhibitor, either sequentially or at the same time.
Prior art
Katagiri, Song and Tang suggest the treatment of AIRD1A-mutated OCCC with an IRE-1/XBP-1 as described above. The combination however does not expressly teach administering both and IRE-1 inhibitor and an EZH2 inhibitor or treatment of nonhuman primate.
However, Knutson teaches methods of treating cancer by administering an EZH2 inhibitor. See Knutson, abstract. The cancer is associated with the SWI/SNF complex (i.e., SWI/SNF mediated cancer). More particularly, the invention provides methods and compositions which treat, alleviate, prevent, diminish or otherwise ameliorate the symptoms of cancer associated with the SWI/SNF complex. See 0002. Ovarian cancer is a cancer known to involve SWI/SNF. See Knutson claim 1; see also Katagiri, p. 283, 1st column. Humans and nonhuman primates are treated. See Knutson, 0100.
A person of ordinary skill in the art (POSA) would have found it obvious to combine the IRE-1/XBP-1 pathway inhibition taught by Katagiri, Song and Tang with EZH2 inhibition as taught by Knutson, because both approaches target molecular pathways implicated in cancers associated with SWI/SNF dysfunction, including ARID1A-deficient ovarian cancer, The POSA would have reasonably expected that combining such therapies would provide therapeutic effect against ovarian cancer given that both inhibitors were known to be useful against SWI/SFI cancer.
The POSA would have further found it obvious to treat a nonhuman primate because Knutson teaches that SWI/SWF disorders including ovarian cancer can be treated in nonhuman primates.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622