CTNF 18/041,059 CTNF 77145 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Response to Amendments and Arguments 2. Claims 2 and 4-11 are pending. Claims 1 and 3 have been cancelled. Claims 2, 4-7 and 11 have been amended. Claims 2 and 4-11 are examined on the merits. Withdrawn Objections Claim Objections 3. Claim 1 is no longer objected to because it has been cancelled, see Amendment to the Claims submitted March 2, 2026. Withdrawn Grounds of Rejection Claim Rejections - 35 USC § 102 4. The rejection of claim(s) 4-8 and 11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Harvey et al., WO 2007/109571 A2 (published 27 September 2007/ IDS reference #1 Foreign Patent Documents submitted October 11, 2024) is withdrawn because the prior art does not teach a receptor tyrosine kinase (RTK) inhibitor that targets a VEGF receptor (VEGFR) and a fibroblast growth factor receptor (FGFR). Claims 1 and 3 have been cancelled. 5. The rejection of claim(s) 2 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by DePinho et al., US 2010/0255004 A1 (published October 7, 2010/ IDS reference #121 submitted September 5, 2023) because the prior art does not teach a receptor tyrosine kinase (RTK) inhibitor that targets a VEGF receptor (VEGFR) and a fibroblast growth factor receptor (FGFR). Claims 1 and 3 have been cancelled. Claim Rejections - 35 USC § 103 6. The rejection of claim(s) 2 and 4-11 is/ under 35 U.S.C. 103 as being unpatentable over Harvey et al., WO 2007/109571 A2 (published 27 September 2007/ IDS reference #1 Foreign Patent Documents submitted October 11, 2024), and further in view of Deng et al., (Liver Cancer 9: 338-357, published online February 25, 2020) is withdrawn because the prior art does not teach a receptor tyrosine kinase (RTK) inhibitor that targets a VEGF receptor (VEGFR) and a fibroblast growth factor receptor (FGFR). Claims 1 and 3 have been cancelled. 7. The rejection of claim(s) 2 under 35 U.S.C. 103 as being unpatentable over Harvey et al., WO 2007/109571 A2 (published 27 September 2007/ IDS reference #1 Foreign Patent Documents submitted October 11, 2024), and further in view of Deng et al., (Liver Cancer 9: 338-357, published online February 25, 2020) is withdrawn because the prior art does not teach a receptor tyrosine kinase (RTK) inhibitor that targets a VEGF receptor (VEGFR) and a fibroblast growth factor receptor (FGFR). Claims 1 and 3 have been cancelled. Double Patenting 8. The provisional nonstatutory double patenting rejection over claim 2 as being unpatentable over claims 1, 3, 5-9 and 11 of copending Application No. 18/041,058 (effectively filed August 12, 2020) in view of Deng et al., (Liver Cancer 9: 338-357, published online February 25, 2020) because the prior art does not teach a receptor tyrosine kinase (RTK) inhibitor that targets a VEGF receptor (VEGFR) and a fibroblast growth factor receptor (FGFR). Claims 1 and 3 have been cancelled. 12-256 AIA New Grounds of Rejection Claim Rejections - 35 USC § 103 07-20-aia AIA 9. 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. 07-21-aia AIA 10. Claim (s) 2 and 4-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Harvey et al., WO 2007/109571 A2 (published 27 September 2007/ IDS reference #1 Foreign Patent Documents submitted October 11, 2024), and further in view of Taylor et al. (Journal of Clinical Oncology 36: Abstract 6016, June 1, 2018) and Deng et al., (Liver Cancer 9: 338-357, published online February 25, 2020). Harvey teaches “…genetic markers described herein are genotyped to detect the presence or absence of a variant allele, e.g., an activating mutation. Preferably, one or more biochemical or serological markers are measured in combination with one or more genetic markers.”, see page 9, section 0025. Genetic markers to be assayed for mutations include phosphatase and tensin homolog deleted on chromosome 10 (PTEN), as well as tyrosine kinase signaling components including Akt and PI3K, see page 9, section 0025. These genetic markers are one or more genes involved in the phosphoinositide 3-kinase (PI3K) signaling pathway and can be assayed using routine methods, see pages 34-45 . These genetics markers are assayed in human biological samples including whole blood, red blood cells, white blood cells, saliva, urine, lymph, tumor tissue, biopsy of a tumor and cellular extracts thereof, see page 12, section 0034; page 23, sections 0073 and 0074; and page 34, section 0113. The assessment of the aforementioned genetic markers or biomarkers allows those skilled in the art to create a genotypic profile distinctive and characterize cancers, see section 0026 spanning pages 9 and 10. These cancers “…includes all known cancers and neoplastic conditions, … grades including pre- and post-metastatic cancers. Examples of different types of cancer include, … head and neck cancers...”, see page 7, section 0022. The taught metastatic head and neck cancers include the metastatic head and neck squamous cell carcinoma (R/M HNSCC). Treatment of these cancer includes administering tyrosine kinase inhibitors, immunotherapy and combinations thereof, see page 12, section 0035. “Additionally, the tyrosine kinase inhibitors described herein can be co-administered with conventional immunotherapeutic agents including, but not limited to, immunostimulants (e.g., Bacillus Calmette-Guerin (BCG), levamisole, interleukin-2, alpha-interferon, etc.), monoclonal antibodies (e.g., anti-CD20, anti-HER2, anti-CD52, anti-HLA-DR, and anti-VEGF monoclonal antibodies), immunotoxins (e.g., anti-CD33 monoclonal antibody- calicheamicin conjugate, anti-CD22 monoclonal antibody- pseudomonas exotoxin conjugate, etc.),”, see pages 65-67, sections 0203, 0204, 0206 and 0207. The ”…tyrosine kinase inhibitor (TKI) is administered at the same time, just prior to, or just after the administration of a second drug (e.g., another tyrosine kinase inhibitor, a drug useful for reducing the side-effects associated with tyrosine kinase inhibitor therapy, a chemotherapeutic agent, a radiotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, etc.).”, see page 66, section 0204; and page 67, section 0207. Harvey does not teach the taught method, wherein the TKI is administered with a cancer immunotherapeutic that is an immune checkpoint inhibitor, a PD-1 inhibitor. Nor, does Harvey teach the TKI or receptor tyrosine kinase (RTK) is lenvatinib and the head and neck cancer is explicitly R/M HNSCC. However, Taylor teaches a combinatorial treatment, “…lenvatinib plus pembrolizumab in squamous cell carcinoma of the head and neck”, see title; and entire document. “Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor receptor 1 − 3, fibroblast growth factor receptor 1 − 4, platelet-derived growth factor receptor α, RET, and KIT. Pembrolizumab (PEM) is an anti-PD-1 antibody approved for the second-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) based on durable responses and an objective response rate (ORR) …, see Background. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Harvey, Taylor and Deng to treat R/M HNSCC with the combination of a TKI and an anti-PD-1 antibody because all documents teach the benefit of combinatorial treatment of cancer, Harvey, section VIII. Spanning pages 65-67; entire Jones document; and entire Deng article. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by the successful teachings in Taylor, “LEN + PEM demonstrated promising clinical activity and manageable toxicities, supporting further evaluation of the LEN + PEM combination in [patients] with SCCHN”, see entire document. Moreover, Deng teaches “[t]yrosine kinase inhibitors are well-known anti-angiogenic agents and offer potential for combination with anti-PD-1 antibodies”, last complete sentence on page 338; italicized subtitles on pages 344, 348 and 351; and entire document . 07-21-aia AIA 11. Claim (s) 2 and 4-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over DePinho et al., US 2010/0255004 A1 (published October 7, 2010/ IDS reference #121 submitted September 5, 2023) , and further in view of Taylor et al. (Journal of Clinical Oncology 36: Abstract 6016, June 1, 2018) and Deng et al., (Liver Cancer 9: 338-357, published online February 25, 2020). DePinho teaches “…methods of detecting the presence of one or more mutations in an RTK gene.”, see page 13, section 0130 and Genetic Mutations segment spanning pages 13 and 14. PTEN, AKT and additional genes involved in the PIK3K signaling pathway were assessed and evaluated, see page 1, section 0005; page 3, section 0034; page 17, section 0179; and Example 5 beginning on page 30 and the entire document . DePinho further teaches administering therapeutic treatments for subjects with cancer, wherein biological samples were derived. The biological sample may comprise cancer cells, “…tissue biopsies, urine, sputum, blood, cells, tissue scrapings…or other cellular materials.”, see page 7, section 0070. The cancer is treated with receptor tyrosine kinase (RTK) inhibitors, see page 4, section 0037 and 0038; and page 19, section 0191. The subject with cancer is human and afflicted with head and neck cancer, see page 2, section 0019. The taught metastatic head and neck cancers include the metastatic head and neck squamous cell carcinoma (R/M HNSCC). "Cancer" refers to all neoplastic cell growth and proliferation, to all cancerous cells and tissues, and to all metastases.”, see page 5, section 0058. DePinho also teaches RTK inhibitors, see page 1, section 0005; and page 25, sections 0241 and 0248. “The inhibitors also can be administered in conjunction with nondrug treatments, such as surgery, radiation therapy, chemotherapy, immunotherapy and diet/exercise regimens. The other therapy may be administered before, concurrent with, or after treatment with the inhibitors. There may also be a delay of several hours, days and in some instances weeks between the administration of the different treatments, such that the inhibitors may be administered before or after the other treatment. In certain embodiments, the selected group of RTK inhibitors is administered in combination with (i.e., before, during or after) other anti-cancer therapy, and in particular other anti-cancer therapy that does not comprise the administration of RTK pathway inhibitors to the subject.”, page 19, sections 0190 and 0191. DePinho does not teach the taught method, wherein the RTK inhibitor or TKI targets vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs) is administered in combination with immune checkpoint inhibitor, a PD-1 inhibitor. Nor, does DePinho teach the TKI or receptor tyrosine kinase (RTK) is lenvatinib and the head and neck cancer is explicitly R/M HNSCC. However, Taylor teaches a combinatorial treatment, “…lenvatinib plus pembrolizumab in squamous cell carcinoma of the head and neck”, see title; and entire document. “Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor receptor 1 − 3, fibroblast growth factor receptor 1 − 4, platelet-derived growth factor receptor α, RET, and KIT. Pembrolizumab (PEM) is an anti-PD-1 antibody approved for the second-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) based on durable responses and an objective response rate (ORR) …, see Background. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Harvey, Taylor and Deng to treat cancer with the combination of a TKI and an anti-PD-1 antibody because both documents teach the benefit of combinatorial treatment of cancer, see the entireties of DePinho, Jones and Deng documents. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by the successful teachings in Taylor, “LEN + PEM demonstrated promising clinical activity and manageable toxicities, supporting further evaluation of the LEN + PEM combination in [patients] with SCCHN”, see entire document. Moreover, Deng teaches “[t]yrosine kinase inhibitors are well-known anti-angiogenic agents and offer potential for combination with anti-PD-1 antibodies”, last complete sentence on page 338; italicized subtitles on pages 344, 348 and 351; and entire document . Double Patenting 08-33 AIA 12. 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. 08-37 AIA 13. Claim 2 and 4-11 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-11 of copending Application No. 18/041,058 (effectively filed August 12, 2020) in view of Taylor et al. (Journal of Clinical Oncology 36: Abstract 6016, June 1, 2018) and Deng et al., (Liver Cancer 9: 338-357, published online February 25, 2020). Both sets of claims read on treating cancer comprising determining the presence of a mutation in one or more genes involved in the phosphoinositide 3-kinase (PI3K) signaling pathway in a subject’s sample and administered a receptor tyrosine kinase (RTK) inhibitor with cancer immunotherapeutic, immune checkpoint inhibitor, PD-1 inhibitor. And while RTK inhibitor, axitinib targets vascular endothelial growth factor receptors (VEGFRs), it does not target fibroblast growth factor receptors (FGFRs). However, Taylor teaches a combinatorial treatment, “…lenvatinib plus pembrolizumab in squamous cell carcinoma of the head and neck”, see title; and entire document. “Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor receptor 1 − 3, fibroblast growth factor receptor 1 − 4, platelet-derived growth factor receptor α, RET, and KIT. Pembrolizumab (PEM) is an anti-PD-1 antibody approved for the second-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) based on durable responses and an objective response rate (ORR) …, see Background. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Taylor and Deng with the instant claims to treat R/M HNSCC with a combination of a dual TKI and an anti-PD-1 antibody because all the prior art documents teach the benefit of combinatorial treatment of cancer, see the entireties of both Taylor and Deng. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by the successful teachings in Taylor, “LEN + PEM demonstrated promising clinical activity and manageable toxicities, supporting further evaluation of the LEN + PEM combination in [patients] with SCCHN”, see Conclusions; and entire document. Moreover, Deng teaches “[t]yrosine kinase inhibitors are well-known anti-angiogenic agents and offer potential for combination with anti-PD-1 antibodies”, last complete sentence on page 338; italicized subtitles on pages 344, 348 and 351; and entire document . This is a provisional nonstatutory double patenting rejection. Conclusion 14. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule , however she can normally be reached on 8AM-8PM. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. ALANA HARRIS DENT Primary Examiner Art Unit 1643 20 May 2026 /Alana Harris Dent/ Primary Examiner, Art Unit 1643 Application/Control Number: 18/041,059 Page 2 Art Unit: 1643 Application/Control Number: 18/041,059 Page 3 Art Unit: 1643 Application/Control Number: 18/041,059 Page 4 Art Unit: 1643 Application/Control Number: 18/041,059 Page 5 Art Unit: 1643 Application/Control Number: 18/041,059 Page 6 Art Unit: 1643 Application/Control Number: 18/041,059 Page 7 Art Unit: 1643 Application/Control Number: 18/041,059 Page 8 Art Unit: 1643 Application/Control Number: 18/041,059 Page 9 Art Unit: 1643 Application/Control Number: 18/041,059 Page 10 Art Unit: 1643 Application/Control Number: 18/041,059 Page 11 Art Unit: 1643 Application/Control Number: 18/041,059 Page 12 Art Unit: 1643 Application/Control Number: 18/041,059 Page 13 Art Unit: 1643 Application/Control Number: 18/041,059 Page 14 Art Unit: 1643 Application/Control Number: 18/041,059 Page 15 Art Unit: 1643 Application/Control Number: 18/041,059 Page 16 Art Unit: 1643 Application/Control Number: 18/041,059 Page 17 Art Unit: 1643
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