DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-15, 18, 28 and 32-34 are pending.
Election/Restrictions
Applicant’s election without traverse of Group 1 in the reply filed on December 5, 2025 is acknowledged. Applicant’s election without traverse of the species, Erlotinib and Isoniazid in the reply filed on December 5, 2025 is acknowledged. Claims 33 and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 5 and 9-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species.
Claims 1-4, 6-9 13-15, 18, 28 and 32 are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/7/2022, 4/29/2024 and 7/12/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement have been considered by the examiner.
However, based on submitted references, it appears as if there are information disclosure statements filed on 12/7/2022 that were not in readable format. Please resubmit the information disclosure statements to be considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in paragraph 434. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
In addition there is no title for Fig. 5O in the specification.
Drawings
The drawings are objected to because the panels of Figure 11 are completely black. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-4, 6-9 13-15, 18, 28 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Taylor et al (Current Cancer Drug Discovery 12:197-209, 2012) in view of Pi et al (WO 2015/009879, published January 22, 2015, IDS) in further view of Kankia et al (Oxidative Medicine and Medicine and Cellular Longevity, ID 1864578, pages 1-19, 2017, IDS), Zhang et al (Bioscience Hypotheses, 2:261-263, 2009, IDS) and Ma et al (Med Oncol 32:1-6, 2015).
The claims are drawn to a method for treating glioma comprising administering an agent that modulates epidermal growth factor receptor (EGFR) signaling, and an agent that modulates Nrf2 signaling wherein the agent that modulates EGFR signaling is erlotinib and the Nrf2 inhibitor is isoniazid.
Taylor discloses the treatment of malignant glioma with EGFR-targeted therapies including erlotinib. (page 201; Table 1). Taylor discloses that EGFR-targeted agents hold great potential, however, successful treatment of malignant gliomas continues to be a major therapeutic challenge due to both inherent and acquired resistance (page 202-203).
Taylor does not discloses the treatment of malignant glioma with an agent that modulates Nrf2 signaling.
Pi discloses the treatment of cancer comprising the administration of an agent that modulates Nrf2 signaling (page 3, lines 29-31) Pi discloses that constitutive activation of Nrf2 has been observed in many human solid nonlymphoid tumors, including gliomas cancer (page 2, lines 4-8). Pi discloses that inhibitors of Nrf2-
Nrf2 inhibitors may result in enhancing the effectiveness of other agents (e.g., therapeutic agents) or treatment modalities (e.g. radiation treatment for cancer) that would otherwise be less effective or ineffective for treating cancer characterized by constitutive activation of Nrf2 (page 3, line 32 to page 7). Pi discloses that Nrf2 inhibitors include isoniazid (page 4, lines 14-27). Pi disclose that two therapeutic agents may be administered simultaneously or sequentially (page 6, line 29 to page 7, line 5; page 15, lines 5-19).
One of ordinary skill in the art would have been motivated to apply Pi’s method of treating glioma with an agent that modulates Nrf2 signaling with Taylor discloses the treatment of malignant glioma with EGFR-targeted therapies including erlotinib because both Pi and Taylor disclose the treatment of glioma with agent that modulates Nrf2 signaling and erlotinib, respectively. it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
In addition, the court has held that it is obvious to combine two compositions, in order to form a third composition, when each of the two compositions is taught by the prior art to be useful for the same purpose. (In re Kerkhoven, 626, F.2s 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine Taylor disclosure of the treatment of malignant glioma with EGFR-targeted therapies including erlotinib with Pi’s method of treating glioma with an agent that modulates Nrf2 signaling because the prior art teaches that both an Nrf2 inhibitor and erlotinib are useful for the treatment of malignant glioma.
Furthermore, Pi discloses that Nrf2 inhibitors may enhance the effectiveness of other therapeutic agents for treating cancer that would otherwise be less effective or ineffective for treating cancer characterized by constitutive activation of Nrf2. Kankia discloses that erlotinib have been in clinical use over the last decade but the efficacy of these drugs is potentially reduced due to frequent emergence of resistance (page 15). Kankia discloses that studies have implicated NRF2 in promoting resistance to chemotherapeutic agents (page 2, 1st column). Kankia suggests that manipulating Nrf2 may enhance the effectiveness of RTK inhibition (Id). Kankia discloses that there was a significant increased cytotoxicity of erlotinib in ovarian cancer cells following the pharmacological inhibition of NRF2 (Figure 9).
Zhang discloses that EGFR-Nrf2 pathway plays a role in cancer cells’ chemoresistance (Abstract). Zhang discloses that Nrf2 is upregulated in resistant cancer cells and is thought to be responsible for acquired chemoresistance (page 262, 2nd column). Further, Zhang disclose that RNAi-mediated silencing of Nrf2 gene expression in non-small cell lung cancer can inhibit tumor growth and increase efficacy of chemotherapy (Id).
Ma discloses that overexpression of Nrf2 in the glioma treated with the combination of TMZ and irradiation was shown to play an important role in the acquisition of drug resistance (page 4, 2nd column). Ma demonstrated that TMZ is sufficient to induce the expression of Nrf2, and this event renders the insensitivity of glioma to TMZ (page 5, 2nd column). Ma discloses that that p38 MAPK signaling mediates the promoting effect of TMA on Nrf2 abundance in glioma cells (Id).
Thus, Kankia, Zhang and Ma all disclose that expression of Nrf2 correlated with chemoresistance. As stated in KSR International Co. v. Teleflex., 82 USPQ2d 1385 (US 2007)
"When a person of ordinary skill is faced with "a finite number of identified,
predictable solutions" to a problem and pursues "the known options within his or her technical grasp," the resulting discovery "is likely the product not of innovation but of ordinary skill and common sense." KSR, 127 S. Ct. at 1742. So too, "[glranting patent protection to advances that would occur in the ordinary course without real innovation retards progress."
Given the disclosure that overexpresson of Nrf2 in cancer including glioma correlates with chemoresistance, given that EGFR-targeted therapies including erlotinib are used in the treatment of malignant glioma and given that resistance frequently occurs during treatment of glioma with EGFR-targeted therapies, it would have been obvious to administer both an agent that modulates EGFR signaling and an agent that modulates Nrf2 signaling for the treatment of malignant glioma.
One of ordinary skill in the art would have had a reasonable expectation of success given the role of overexpresson of Nrf2 in chemoresistance and the treatment of glioma with EGFR-targeted therapies. Furthermore, the art discloses that both EGFR-targeted therapies and agent that modulates Nrf2 signaling may be used for the treatment of glioma.
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.
Claim 1-4, 6-9 13-15, 18, 28 and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22, 23, 25 and 45-50 of copending Application No. 17/609757. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of are drawn to a pharmaceutical composition comprising an agent that inhibits EGFR signaling, and isoniazid while the specification disclosers that the pharmaceutical composition may be used to treat glioma (paragraph 6).,
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Summary
No claims allowed.
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/MARK HALVORSON/ Primary Examiner, Art Unit 1646