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 instant application is a 371 National Stage Entry of PCT/CN2022/081439 filed on March 17, 2022 which claims priority to foreign application No. CN202210227577.0 filed on March 8, 2022.
No English Translation
Examiner notes that no certified translation of the Foreign Application CN202210227577.0 (filed March 8, 2022) has been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file.
Status of Claims
Acknowledgement is made of original (11-12, 19-20), amended (13-18), and cancelled (1-10) claims filed on September 6, 2024. Claims 11-20 are pending in instant application.
Information Disclosure Statement
The information disclosure statements filed on September 6, 2024; May 14, 2025; October 10, 2025 have been considered.
Specification
The title of the invention not in accordance with MPEP since the word “novel” is recited, “NOVEL USE…”. Furthermore, the title of the invention is not descriptive (i.e. “USE”). A new title is required that is clearly indicative of the invention to which the claims are directed.
Per MPEP § 606, The words listed below are not considered as part of the title of an invention, these words should not be included at the beginning of the title of the invention and will be deleted when the Office enters the title into the Office’s computer records, and when any patent issues. The term "new" will not be deleted when it is a part of a proper name, such as "New York". Similarly, the term "design" will not be deleted when it is a part of a term, such as "Design-aiding apparatus...". A, An, The, Improved, Improvement(s) in/for/of, New, Novel, Related to, Design, Design for/of (a), Ornamental design, Ornamental.
Furthermore, the title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed (e.g. shared compound structure and specific utility). The following title is suggested: “QUINOLINE COMPOUNDS FOR TREATING M2 TAM DOMINANT CANCER”
Claim Objections
Claims 11, 13-16 are objected to because of the following informalities:
The claims appear to be missing the final conjunction at the end of the variable lists.
Claim 11 should read “wherein Y is selected… cyano; and each of R2 and R3…”.
Claim 13 should read “; or n is 3 when Y…”
Claim 14 should read “wherein R1 is selected…cyano; and each of R2 and R3…”.
Claim 15 should read “wherein R1 is selected…methyl; and each of R2 and R3…”.
Claim 16 should read “wherein A is selected…hydrogen; and each of R2 and R3…”.
Appropriate correction is required.
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.
Claim(s) 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020118753 A1 to Liu et. al.1 in view of van Dongen et. al.2
Regarding a compound of Formula I and claims 11-17, Liu teaches the same instantly claimed compounds 1-40 (see Liu at pp. 10-12).
Exemplary Formula Ia Species Comparison
Liu Compound 1
Instant Compound 1
PNG
media_image1.png
136
214
media_image1.png
Greyscale
PNG
media_image2.png
96
144
media_image2.png
Greyscale
Exemplary Formula Ib Species Comparison
Liu Compound 28
Instant Compound 28
PNG
media_image3.png
174
276
media_image3.png
Greyscale
PNG
media_image4.png
98
168
media_image4.png
Greyscale
Regarding a method of treating cancer and claims 11, 18, Liu teaches administering the compounds to a patient (see Liu Trans at p. 45 ¶2). Liu teaches the compounds are for treating solid tumors (including benign or particularly malignant types), particularly sarcomas,
gastrointestinal stromal tumors (GIST), colorectal cancer, acute myeloblastic leukemia (AML), chronic myelogenous leukemia (CML), tumor formation, thyroid cancer, systemic mast cell disease, eosinophilic syndrome, fibrosis, erythema, Lupus, graft-versus-host disease,
neurofibroma, pulmonary hypertension, Alzheimer's disease, seminoma, dysgerminoma,
mast cell tumor, lung cancer, bronchial carcinoma, testicular intraepithelial neoplasia,
melanoma, breast cancer, neuroblastoma, papillary/follicular thyroid carcinoma, malignant
lymphoma, non-Hodgkin's lymphoma, type 2 multiple endocrine neoplasia,
pheochromocytoma, thyroid cancer, parathyroid hyperplasia/adenoma, colon cancer,
colorectal adenoma, ovarian cancer, prostate cancer, glioblastoma, brain tumor, malignant
glioma, pancreatic cancer, malignant pleural mesothelioma, angioblastoma, hemangioma,
kidney cancer, liver cancer, adrenal cancer, bladder cancer, stomach cancer, rectal cancer,
vaginal cancer, cervical cancer, endometrial cancer, multiple myeloma, neck and head
tumors, and other proliferative or proliferative diseases or similar diseases, or combinations
thereof (see Liu Trans at pp. 48-49 ¶[0089]).
The prior art differs from the instant claims as follows: while Liu teaches instant compounds for treating cancer or tumors, Liu does not specify that M2 macrophages are dominant in the tumor microenvironment or a therapeutically effective amount.
However,
Recall Liu teaches the compounds for treating gastrointestinal stromal tumors.
Regarding claims 11 and 18, van Dongen teaches the macrophage population in gastrointestinal stromal tumors showed a dominance of anti-inflammatory cells, as the M2 type scavenger receptor CD163 was abundantly present (see van Dongen at Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
It would have been obvious to an artisan to administer a therapeutically effective amount of the compounds taught by Liu in order to treat a desired condition taught by Liu, such as gastrointestinal stromal tumors. Furthermore, by practicing a method taught by the prior art, (administering a compound of Formula I to treat a gastrointestinal stromal tumor, as taught by Liu) an artisan would be practicing the instant method of treating a tumor in which M2 macrophages are dominant in the tumor microenvironment because the prior art teaches gastrointestinal stromal tumors have a dominance of M2 macrophages (as taught by van Dongen).
Furthermore, it is well-within the ordinary skill in art to administer a known compound according to known methods.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 11-17, 19 are rejected under 35 U.S.C. 103 as being unpatentable over Liu in view of Shen et. al.3
Regarding a compound of Formula I and claims 11-17, Liu teaches the same instantly claimed compounds 1-40 (see Liu at pp. 10-12).
Exemplary Formula Ia Species Comparison
Liu Compound 1
Instant Compound 1
PNG
media_image1.png
136
214
media_image1.png
Greyscale
PNG
media_image2.png
96
144
media_image2.png
Greyscale
Exemplary Formula Ib Species Comparison
Liu Compound 28
Instant Compound 28
PNG
media_image3.png
174
276
media_image3.png
Greyscale
PNG
media_image4.png
98
168
media_image4.png
Greyscale
Regarding a method of treating cancer and claims 11, 18, Liu teaches administering the compounds to a patient (see Liu Trans at p. 45 ¶2). Liu teaches the compounds are for treating solid tumors (including benign or particularly malignant types), particularly sarcomas,
gastrointestinal stromal tumors (GIST), colorectal cancer, acute myeloblastic leukemia (AML), chronic myelogenous leukemia (CML), tumor formation, thyroid cancer, systemic mast cell disease, eosinophilic syndrome, fibrosis, erythema, Lupus, graft-versus-host disease,
neurofibroma, pulmonary hypertension, Alzheimer's disease, seminoma, dysgerminoma,
mast cell tumor, lung cancer, bronchial carcinoma, testicular intraepithelial neoplasia,
melanoma, breast cancer, neuroblastoma, papillary/follicular thyroid carcinoma, malignant
lymphoma, non-Hodgkin's lymphoma, type 2 multiple endocrine neoplasia,
pheochromocytoma, thyroid cancer, parathyroid hyperplasia/adenoma, colon cancer,
colorectal adenoma, ovarian cancer, prostate cancer, glioblastoma, brain tumor, malignant
glioma, pancreatic cancer, malignant pleural mesothelioma, angioblastoma, hemangioma,
kidney cancer, liver cancer, adrenal cancer, bladder cancer, stomach cancer, rectal cancer,
vaginal cancer, cervical cancer, endometrial cancer, multiple myeloma, neck and head
tumors, and other proliferative or proliferative diseases or similar diseases, or combinations
thereof (see Liu Trans at pp. 48-49 ¶[0089]).
The prior art differs from the instant claims as follows: while Liu teaches instant compounds for treating cancer or tumors, Liu does not specify that M2 macrophages are dominant in the tumor microenvironment or a therapeutically effective amount.
However,
Recall Liu teaches the compounds for treating non-Hodgkin's lymphoma.
Regarding claims 11 and 19, Shen teaches diffuse large B cell lymphoma (DLBCL) is the most frequent Non-Hodgkin’s lymphoma (NHL), accounting for 30–40% of newly diagnosed lymphomas (see Shen at p. 1 ¶). Shen teaches a high percentage of M2 TAMs predicts poor outcomes in DLBCL patients (see Shen at Abstract and p. 7 ¶1).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
It would have been obvious to an artisan to administer a therapeutically effective amount of the compounds taught by Liu in order to treat a desired condition taught by Liu, such as NHL. Furthermore, by practicing a method taught by the prior art, (administering a compound of Formula I to treat NHL, as taught by Liu) an artisan would be practicing the instant method of treating a tumor in which M2 macrophages are dominant in the tumor microenvironment because the prior art teaches common NHL tumors have a dominance of M2 macrophages (as taught by Shen).
Furthermore, it is well-within the ordinary skill in art to administer a known compound according to known methods.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 11-17, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Liu in view of Xu et. al.4
Regarding a compound of Formula I and claims 11-17, Liu teaches the same instantly claimed compounds 1-40 (see Liu at pp. 10-12).
Exemplary Formula Ia Species Comparison
Liu Compound 1
Instant Compound 1
PNG
media_image1.png
136
214
media_image1.png
Greyscale
PNG
media_image2.png
96
144
media_image2.png
Greyscale
Exemplary Formula Ib Species Comparison
Liu Compound 28
Instant Compound 28
PNG
media_image3.png
174
276
media_image3.png
Greyscale
PNG
media_image4.png
98
168
media_image4.png
Greyscale
Regarding a method of treating cancer and claims 11, 18, Liu teaches administering the compounds to a patient (see Liu Trans at p. 45 ¶2). Liu teaches the compounds are for treating solid tumors (including benign or particularly malignant types), particularly sarcomas,
gastrointestinal stromal tumors (GIST), colorectal cancer, acute myeloblastic leukemia (AML), chronic myelogenous leukemia (CML), tumor formation, thyroid cancer, systemic mast cell disease, eosinophilic syndrome, fibrosis, erythema, Lupus, graft-versus-host disease,
neurofibroma, pulmonary hypertension, Alzheimer's disease, seminoma, dysgerminoma,
mast cell tumor, lung cancer, bronchial carcinoma, testicular intraepithelial neoplasia,
melanoma, breast cancer, neuroblastoma, papillary/follicular thyroid carcinoma, malignant
lymphoma, non-Hodgkin's lymphoma, type 2 multiple endocrine neoplasia,
pheochromocytoma, thyroid cancer, parathyroid hyperplasia/adenoma, colon cancer,
colorectal adenoma, ovarian cancer, prostate cancer, glioblastoma, brain tumor, malignant
glioma, pancreatic cancer, malignant pleural mesothelioma, angioblastoma, hemangioma,
kidney cancer, liver cancer, adrenal cancer, bladder cancer, stomach cancer, rectal cancer,
vaginal cancer, cervical cancer, endometrial cancer, multiple myeloma, neck and head
tumors, and other proliferative or proliferative diseases or similar diseases, or combinations
thereof (see Liu Trans at pp. 48-49 ¶[0089]).
The prior art differs from the instant claims as follows: while Liu teaches instant compounds for treating cancer or tumors, Liu does not specify that M2 macrophages are dominant in the tumor microenvironment or a therapeutically effective amount.
However,
Recall Liu teaches the compounds for treating acute myeloblastic leukemia (AML).
Regarding claims 11 and 20, Xu teaches patients with AML exhibited increased frequencies of M2 macrophages (see Xu at Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
It would have been obvious to an artisan to administer a therapeutically effective amount of the compounds taught by Liu in order to treat a desired condition taught by Liu, such as AML. Furthermore, by practicing a method taught by the prior art, (administering a compound of Formula I to treat AML, as taught by Liu) an artisan would be practicing the instant method of treating a tumor in which M2 macrophages are dominant in the tumor microenvironment because the prior art teaches AML tumors have a dominance of M2 macrophages (as taught by Xu).
Furthermore, it is well-within the ordinary skill in art to administer a known compound according to known methods.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
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.
Claims 11-15, 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,404,244 B25 in view of van Dongen (claims 11-15, 17-18), or in view of Shen (claims 11-15, 17, 19), or in view of Xu (claims 11-15, 17, 20).
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Regarding a compound of Formula I and claims 11-15, 17, US’244 claims some of the same compounds as those instantly claimed, in particular species of Formula Ia (see US’244 claims 1-4) and composition comprising them (US’244 claim 5).
Exemplary Formula Ia Species Comparison
US’244 Compound 1
Instant Compound 1
PNG
media_image5.png
150
244
media_image5.png
Greyscale
PNG
media_image2.png
96
144
media_image2.png
Greyscale
Regarding a method of treating cancer and claims 11, 18, US’244 claims a method of inhibiting KIT tyrosine kinase comprising administering a compound of Formula I to a subject (US’244 claim 6) such as for treating gastrointestinal stromal tumor (US’244 claims 7-8), or non-Hodgkin’s lymphoma (NHL), or acute myeloblastic leukemia (AML) (US’244 claim 7).
The patented claims differ from the instant claims as follows: While US’244 claims compounds for treating cancer or tumors, US’244 does not specify that M2 macrophages are dominant in the tumor microenvironment or a therapeutically effective amount.
However,
Regarding claims 11 and 18 and gastrointestinal stromal tumor, van Dongen teaches the macrophage population in gastrointestinal stromal tumors showed a dominance of anti-inflammatory cells, as the M2 type scavenger receptor CD163 was abundantly present (see van Dongen at Abstract).
Regarding claims 11 and 19 and NHL, Shen teaches diffuse large B cell lymphoma (DLBCL) is the most frequent Non-Hodgkin’s lymphoma (NHL), accounting for 30–40% of newly diagnosed lymphomas (see Shen at p. 1 ¶). Shen teaches a high percentage of M2 TAMs predicts poor outcomes in DLBCL patients (see Shen at Abstract and p. 7 ¶1).
Regarding claims 11 and 20 and AML, Xu teaches patients with AML exhibited increased frequencies of M2 macrophages (see Xu at Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
It would have been obvious to an artisan to administer a therapeutically effective amount of the compounds claimed by US’244 in order to treat a desired condition claimed by US’244, such as gastrointestinal stromal tumors, NHL, or AML. Furthermore, by practicing a method previously claimed, (administering a compound of Formula I to treat a gastrointestinal stromal tumor, as claimed by US’244) an artisan would be practicing the instant method of treating a tumor in which M2 macrophages are dominant in the tumor microenvironment because the prior art teaches gastrointestinal stromal tumors have a dominance of M2 macrophages (as taught by van Dongen or Shen or Xu).
Furthermore, it is well-within the ordinary skill in art to administer a known compound according to known methods.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Conclusion
Claims 11-20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Published June 18, 2020. Hereinafter Liu. Machine Translation of WO 2020118753 A1, Translated by Patent Translate Espacenet.org on 7/27/26, x pages, hereinafter Liu Trans.
2 Van Dongen et. al. "Anti-inflammatory M2 type macrophages characterize metastasized and tyrosine kinase inhibitor-treated gastrointestinal stromal tumors" Tumor Immunology 2010, 127, 4, 899-909. DOI: 10.1002/ijc.25113. Hereinafter van Dongen.
3 Shen et. al. "M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma" Scientific Reports 2016, 6, 30347, 1-10. DOI: 10.1038/srep30347. Hereinafter Shen.
4 Xu et. al. "The M2 macrophage marker CD206: a novel prognostic indicator for acute myeloid leukemia" OncoImmunology 2020, 8, 1683347, 1-15. Published November 3, 2019. DOI: 10.1080/2162402X.2019.1683347
5 Patented September 2, 2025. Hereinafter US’244.
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