DETAILED ACTION
All rejections and objections not mentioned below are withdrawn.
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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/049,556, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. A claim by claim analysis failed to find support for myeloid-derived suppressor cell (claim 85) and the compounds of claim 80. Thus a priority date of 7/7/2021 was used for claims 80 and 85. The remaining claims received a priority date of 07/08/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/06/2023, 08/27/2025, 02/10/2026 are being considered by the examiner.
Claim Interpretation
Claims 87-88, 90 are interpreted where the wavy line is an attachment point for an additional chemical group.
Claim Rejections - 35 USC § 112 – New Due to Amendments
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5, 11, 15 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 5 improperly broadens the scope of independent claim 1 from which it depends because claim 5 allows R2= -NR2xR2y but claim 1 has deleted this variable and only allows R2=NH2. Claim 11 improperly broadens the scope of claim 1 from which it depends because claim 11 allows several Y variables including Y=-COCH3, -N3, -SH, -NHNH2, -NHCONH2, -SO2NH2 not allowed by claim 1. Claim 15 improperly broadens the scope of claim 1 from which it depends because claim 15 allows Y variables including Y=-SH not allowed by claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102- New and Edited Due to Amendments and New IDS
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.
Claim(s) 1, 3, 5, 7, 8, 11, 73 is/are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by KREPSKI (KREPSKI et al., WO 2005/051317, 2005-06-09, IDS).
The reference KREPSKI teaches the following structures (pages 126-127, 141 and 143) wherein, R2=NH2, X1-3=N, m=0 or m=1 and R3=H, R1=C3 Alkyl, R4=R5=methyl, n=1, Y=-COR2x’ or COCH3( instant claim 11), R2x’=aryl.
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This anticipates claims 1, 3, 5, 7, 8, 73.
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This anticipate claim 11.
Claim(s) 87-88, 90 is/are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by KSHIRSAGAR (KSHIRSAGAR et al., WO 2005018551 A2, 2005-03-03, previously presented).
The reference KSHIRSAGAR teaches the generic formula Va (page 235) with the specific embodiments given in the table on page 236. Since the instant claim is unclear (112b above) the wavy line can be interpreted as a location additional groups can be attached to the molecule. The broadest reasonable interpretation is that additional groups can be attached. Furthermore, claim 89 reads on comprising a radical – any molecule including the one below can comprise a radical since a radical would be considered a portion of the whole molecule and since it only comprises it additional groups can be added to the radical portion. This anticipates claims 87-88, 90.
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The reference KSHIRSAGAR teaches “Pharmaceutical compositions of the invention contain a therapeutically effective amount of a compound of the invention as described above in combination with a pharmaceutically acceptable carrier” (page 115). This anticipates claims 88 and 90.
Claim Rejections - 35 USC § 103 – Modified Due to Amendments
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.
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.
Claim(s) 1, 5, 7, 8, 11, 40, 51, 59, 61, 63, 65, 73, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86 is/are rejected under 35 U.S.C. 103 as being unpatentable over THOMPSON (THOMPSON et al., WO-2017100305-A2, 2017, previously presented) in view of Kurahara (Kurahara et al,. Clinical Significance of Folate Receptor b–expressing Tumor-associated Macrophages in Pancreatic Cancer, Ann Surg Oncol (2012) 19:2264–2271, previously presented) and further in view of Gabrilovich ( Gabrilovich et al., Myeloid-Derived Suppressor Cells, Cancer Immunol Res; 5(1) January 2017, previously presented) as evidenced by CAS SciFinder (imiquimod and S 34240, 2025, previously presented) .
The reference Thompson teaches compounds of formula 1 “In some aspects, said immune-stimulatory compound is a damage-associated molecular pattern molecule or a pathogen associated molecular pattern molecule In some aspects, said immune-stimulatory compound is a toll-like receptor agonist, STING agonist, or RIG-I agonist. In some aspects, said immune-stimulatory compound is a TLR1 agonist, a TLR2 agonist, a TLR3 agonist, a TLR4 agonist, a TLR5 agonist, a TLR6 agonist, a TLR7 agonist, a TLR8 agonist, a TLR9 agonist, or a TLR10 agonist. In some aspects, said immune-stimulatory compound is selected from a group consisting of: S-27609, CL307, UC-IV150, imiquimod, gardiquimod, resiquimod, motolimod, VTS-1463GS-9620, GSK2245035, TMX-101, TMX-201, TMX-202, isatoribine, AZD8848, MEDI9197, 3M-051, 3M-852, 3M-052, 3M-854A, S-34240, KU34B, and CL663” [0011]. The Scifinder references provide evidence that the compounds taught by Thompson have the structure of instant formula 1.
S-34240
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Imiquimod
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Wherein, R3=H, R2=NH2, X3=X2=N, R1=alkyl or H, X1=N, R4= R5=alkyl or H, n=1, Y=H or COCH3(instant claim 11), COR2x, R2x=alkyl. This helps to teach claims 1, 5, 6, 7, 8, 11, 13, 73, and 75.
The reference teaches “The composition described herein relates to different embodiments of a conjugate. In various embodiments, a conjugate comprises a) an immune-stimulatory compound; b) an antibody construct comprising an antigen binding domain and an Fc domain, wherein said antigen binding domain binds to a first antigen and wherein a Kd for binding of said Fc domain to an Fc receptor in the presence of said immune-stimulatory compound is no greater than about 100 times a Kd for binding of said Fc domain to said Fc receptor in the absence of the immune stimulatory compound; and c) a linker, wherein said linker attaches said antibody construct to said immune-stimulatory compound”[004] This helps to teach claims 75 and 51.
The reference teaches “In addition to the development of antibodies against tumor antigens for cancer treatment, antibodies that target immune cells to boost the immune response have also been developed. For example, an anti-CD40 antibody that is a CD40 agonist can be used to activate dendritic cells to enhance the immune response. [0150] Cluster of Differentiation 40 (CD40) is a member of the Tumor Necrosis Factor Receptor (TNF-R) family. CD40 can be a 50 kDa cell surface glycoprotein that can be constitutively expressed in normal cells, such as monocytes, macrophages, B lymphocytes, dendritic cells, endothelial cells, smooth muscle cells, fibroblasts and epithelium, and in tumor cells, including B-cell lymphomas and many types of solid tumors. Expression of CD40 can be increased in antigen presenting cells in response to IL-1βp, IFN-γ, GM-CSF, and LPS induced signaling events” [0149-150]. This helps to teach claim 75, 77, 83, 84, 86.
The reference Thompson teaches “A linker is linked with an antibody, in which the linker is a pegylated linker…”[0407]. This helps to teach claim 76.
The reference Thompson teaches “In some aspects, said antigen binding domain recognizes a single antigen. In some aspects, said antigen binding domain recognizes two or more antigens. In some aspects, said first antigen is a tumor antigen. In some aspects, said first antigen that is at least 80% homologous to CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC, HLD-DR, carcinoembryonic antigen, TAG-72, EpCAM, MUC1, folate-binding protein…”[0008]. This helps to teach claim 78 and 80.
The reference Thompson teaches “Immune-stimulatory molecular motifs, such as Pathogen-Associated Molecular Pattern molecules, (PAMPs) can be recognized by receptors of the innate immune system, such as Toll- like receptors (TLRs), Nod-like receptors, C-type lectins, and RIG-I-like receptors”[0158]. This helps to teach claim 81.
The reference Thompson teaches “By way of example and not limitation, some cleavable and noncleavable linkers that may be included in the antibody construct immune-stimulatory compound conjugates described herein are described below” [0306]. This helps to teach claim 40.
The reference Thompson teaches “The compositions and methods described herein can be considered useful as pharmaceutical compositions for administration to a subject in need thereof. Pharmaceutical compositions can comprise at least the compositions described herein and one or more pharmaceutically acceptable carriers, diluents, excipients, stabilizers, dispersing agents, suspending agents, and/or thickening agents” [0381]. This helps to teach claim 59.
The reference Thompson teaches “In some embodiments, a method for treating a subject in need thereof, comprises administering a therapeutic dose of said conjugate of any one of the preceding embodiments or said pharmaceutical composition of any of the preceding embodiments. In some aspects, said subject has cancer. In some aspects, said composition is administered intravenously, cutaneously, subcutaneously, or injected at a site of affliction” [0021]. This helps to teach claim 61.
The reference Thompson teaches “Non-limiting examples of cancers can include Acute lymphoblastic leukemia (ALL); Acute myeloid leukemia; Adrenocortical carcinoma; Astrocytoma, childhood cerebellar or cerebral; Basal-cell carcinoma; Bladder cancer; Bone tumor, osteosarcoma/malignant fibrous histiocytoma; Brain cancer; Brain tumors, such as, cerebellar astrocytoma, malignant glioma, ependymoma, medulloblastoma, visual pathway and hypothalamic glioma; Brainstem glioma; Breast cancer; Bronchial adenomas/carcinoids; Burkitt's lymphoma; Cerebellar astrocytoma; Cervical cancer; Cholangiocarcinoma; Chondrosarcoma; Chronic lymphocytic leukemia;
Chronic myelogenous leukemia; Chronic myeloproliferative disorders; Colon cancer; Cutaneous T-cell lymphoma; Endometrial cancer; Ependymoma; Esophageal cancer; Eye cancers, such as, intraocular melanoma and retinoblastoma; Gallbladder cancer; Glioma; Hairy cell leukemia; Head and neck cancer; Heart cancer; Hepatocellular (liver) cancer; Hodgkin lymphoma; Hypopharyngeal cancer; Islet cell carcinoma (endocrine pancreas); Kaposi sarcoma; Kidney cancer (renal cell cancer); Laryngeal cancer; Leukaemia, such as, acute lymphoblastic, acute myeloid, chronic lymphocytic, chronic myelogenous and, hairy cell; Lip and oral cavity cancer; Liposarcoma; Lung cancer…”[0403]. This helps to teach claims 82 and 63.
The reference Thompson teaches “Non-limiting examples of cancers can include Acute lymphoblastic leukemia (ALL); Acute myeloid leukemia; Adrenocortical carcinoma; Astrocytoma, childhood cerebellar or cerebral; Basal-cell carcinoma; Bladder cancer; Bone tumor, osteosarcoma/malignant fibrous histiocytoma…”[0403]. This helps to teach claim 65.
The reference Thompson does not teach Folate Receptor b (claim 79), myeloid-derived suppressor cells (claim 85) or the radicals (all claims) or the structure of the instant claims that is not lacking one methyl group (claims 1, 5, 7, 8, 40, 51, 59, 61, 63, 65, 73, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86).
The reference Kurahara teaches “Clinical Significance of Folate Receptor b–expressing
Tumor-associated Macrophages in Pancreatic Cancer” (title) and “ FRb macrophages are a novel subset of tumor-associated macrophages in pancreatic cancer and may play an important role in the tumor microenvironment in association with systemic metastasis through the interaction with tumor cells and vessels. FRb macrophages may be promising a targeting therapy for pancreatic cancer”(Conclusions). This helps to teach claim 79.
The reference Gabrilovich teaches “Myeloid cells developed evolutionarily as a major mechanism to protect the host. They evolved as a critical barrier against infections and are important contributors to tissue remodeling. However, in cancer, myeloid cells are largely converted to serve a new master—tumor cells. This process is epitomized by myeloid-derived suppressor cells (MDSC).
These cells are closely related to neutrophils and monocytes. MDSCs are not present in the steady state of healthy individuals and appear in cancer and in pathologic conditions associated with chronic inflammation or stress. These cells have emerged as an important contributor to tumor progression. Ample evidence supports a key role for MDSCs in immune suppression in cancer, as well as their prominent role in tumor angiogenesis, drug resistance, and promotion of tumor metastases. MDSCs have a fascinating biology and are implicated in limiting the effects of cancer immunotherapy. Therefore, targeting these cells may represent an attractive therapeutic opportunity” (abstract). This helps to teach claim 85.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Thompson to get the compounds of the instant claims. Claim 11 allows for Y=COCH3 and thus S-34240 is still a compound of claim 11. The rest of the claims only differ from the reference compounds by a single H to methyl group. Further, it is generally noted that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results. In re Druey, 319 F.2d 237, 138 U.S.P.Q. 39 (C.C. P.A. 1963). Given that applicant did not provide unexpected or unobvious results of the invention, it is concluded that the normal desire of scientists or artisans to improve upon what is already generally known would provide the motivation to substitute the H group for a Me. 2144.08(II)(A)(4)(c). Since it is a simple substitution of H for methyl one would have a reasonable expectation of success.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Thompson with Kurahara because Thompson teaches folate-binding protein and cancer treatment and Kurahara teaches FRb macrophages may be promising a targeting therapy for pancreatic cancer. Thus one would have a reasonable expectation of success and be motivated to treat cancer by targeting the folate binding receptor beta because it is suggest as a good target for cancer treatment. Furthermore, it would have been obvious to modify Thompson with Gabrilovich because Thompson teaches cancer treatment of myeloid related cancers and Gabrilovich suggests MDSC as a good target. Thus one would have a reasonable expectation of success and be motivated to treat myeloid related cancers via targeting MDSC cells because it is a suggested target. It would have been prima facie obvious to one of ordinary skill in the art that Thompson’s molecule contains a radical, in the conjugate connected to linker, because the molecule need not be a radical as a whole to fit the instant claims but simply contain (comprise) a radical (a portion of the molecule would be considered a radical if not taken as a whole).
Claim(s) 1 and 74 is/are rejected under 35 U.S.C. 103 as being unpatentable over JOHNSON (JOHNSON et al., US2020369685A1, effective filing date 2019-05-20, previously presented) as evidenced by CAS SciFinder (imiquimod, 2025, previously presented).
The reference Johnson teaches the compound of claim 1: Imiquimod [0432] as “In some embodiments, the polymers herein, or a pharmaceutical composition thereof contain at least one instance of M useful in treating cancer. In certain embodiments, M is a therapeutic agent. In certain embodiments, the therapeutic agent is an anti-cancer agent. In some embodiments, the anti-cancer agent is bortezomid. In some embodiments, the anti-cancer agent is selected from the group consisting of …imiquimod…”[0432].
The Scifinder references provide evidence that the compounds taught by Johnson have the structure of instant formula 1.
Imiquimod
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Wherein, R3=H, R2=NH2, X3=X2=N, R1= H, X1=N, R4= R5= H, n=1, Y=H. This helps to teach claims 1, and 74.
The reference Johnson teaches “Described herein are compounds that include an agent through a linker that includes a boronic ester moiety in the backbone of the linker. In certain embodiments, the agent is a pharmaceutical agent (e.g., bortezomib), cosmetic agent, or nutraceutical agent. In certain embodiments, the compounds include a polymerization handle and are thus monomers. Also provided are polymers (e.g., homopolymers, copolymers, charged polymers, hydrophilic polymers, linear polymers, branched polymers, brush polymers, bottlebrush polymers) prepared by polymerizing the monomers (e.g., via ring-opening metathesis polymerization, condensation polymerization, addition polymerization, radical polymerization, cationic polymerization, anioinc polymerization). The polymers may be useful for delivering the agent to a subject, tissue, biological sample, or a cell. Also provided are methods of preparing the polymers, compositions and kits comprising the polymers, and methods of use (e.g., use in delivering the agent, treating a disease, preventing a disease, diagnosing a disease) involving the polymers or compositions”[0010]. This helps to teach claims 1, and 74.
The reference Johnson does not specifically teach a radical of instant claim 1 (claim 74).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Thompson to get the compounds of the instant claims. The rest of the claims only differ from the reference compounds by a single H to methyl group. Further, it is generally noted that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results. In re Druey, 319 F.2d 237, 138 U.S.P.Q. 39 (C.C. P.A. 1963). Given that applicant did not provide unexpected or unobvious results of the invention, it is concluded that the normal desire of scientists or artisans to improve upon what is already generally known would provide the motivation to substitute the H group for a Me. 2144.08(II)(A)(4)(c). Since it is a simple substitution of H for methyl one would have a reasonable expectation of success.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Johnson to prepare a polymer using the suggested radical polymerization technique using Imiquimod as a monomer. In a radical polymerization mechanism one would have a reasonable expectation to achieve a radical of Imiquimod because a radical mechanism generally proceeds through radical intermediates. One would be motivated to do so to produce a polymer for delivering Imiquimod to treat a disease as suggested by Johnson.
Double Patenting – Updated Due to Amendments
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 1, 5, 7, 8, 11, 40, 51, 59, 61, 63, 65, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87-92 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9, 11, 14, 27-30 of copending Application No. 17/625,461, over claims 1-26 of copending Application No. 19/264,776, over claims 1-25, 31, 37-41 of copending Application No. 18/260,273 over claims 1-6, 8-9, 12, 15-19, 21-23, 25, 28, 30-33 of copending Application No. 18/687,785 in view of THOMPSON (THOMPSON et al., WO-2017100305-A2, 2017) in view of Kurahara (Kurahara et al,. Clinical Significance of Folate Receptor b–expressing Tumor-associated Macrophages in Pancreatic Cancer, Ann Surg Oncol (2012) 19:2264–2271) and further in view of Gabrilovich ( Gabrilovich et al., Myeloid-Derived Suppressor Cells, Cancer Immunol Res; 5(1) January 2017) as evidenced by CAS SciFinder (imiquimod and S 34240, 2025) .
The application ‘461 claims:
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695
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The application also teaches:
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A compound claim can be used to reject a method claim if the utility is disclosed in the specification. See Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F. 3d 1381, 1385 (CAFC 2010). See also MPEP § 804(II)(B)(2)(a).
This helps to teach all claims.
Application ‘461 doesn’t teach the cells (claim 81-85), lung cancer (claim 63) or a specific example of a lead compound (all claims).
The application ‘776 claims:
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219
712
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344
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244
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151
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80
717
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This helps to teach all claims.
Application ‘776 doesn’t teach the cells (claim 81-85), lung cancer (claim 63) or a specific example of a lead compound (all claims).
The application ‘273 claims:
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278
697
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800
687
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125
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657
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343
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804
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109
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Application ‘273 doesn’t teach the cells (claim 81-85), lung cancer (claim 63) or a specific example of a lead compound (all claims).
The application ‘785 claims:
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518
714
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103
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202
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72
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Application ‘785 doesn’t teach the cells (claim 81-85) or lung cancer (claim 63) or the folate receptor or targeting moiety is specific (claims 77-80).
The secondary references further teach that all needed changes would be obvious as outlined in the 103 rejection (which is incorporated herein by reference).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified the applications ‘461, ‘776, ‘785 and ‘273 with the reference THOMPSON because all references teach TLR agonist of similar structure conjugated to a linker to a targeting moiety for cancer treatment. Thus one would have reasonable expectation of success and motivation to do so to treat cancer as suggested similarly by both references. Additionally it would have been obvious to modify Thompson and the applications with Kurahara because Thompson teaches folate-binding protein and cancer treatment and Kurahara teaches FRb macrophages may be promising a targeting therapy for pancreatic cancer. Thus one would have a reasonable expectation of success and be motivated to treat cancer by targeting the folate binding receptor beta because it is suggest as a good target for cancer treatment. Furthermore, it would have been obvious to modify Thompson and the applications with Gabrilovich because Thompson teaches cancer treatment of myeloid related cancers and Gabrilovich suggests MDSC as a good target. Thus one would have a reasonable expectation of success and be motivated to treat myeloid related cancers via targeting MDSC cells because it is a suggested target.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
102 Rejections
Applicant's arguments filed 01/30/2026 have been fully considered but they are not persuasive. The applicant argues that the reference Kshirsagar does not disclose a compound having the specific structure constraints of instant claim 87-88, 90. This is not persuasive because the reference Kshirsagar teaches the specific embodiment of instant claim 87-88, 90 shown below (last embodiment). The applicants argue that this is not the same structure as the instant compounds because of the methylene imine moiety is not part of the instant claimed structure and nothing in the reference says it can be omitted. However, the instant claims recite “comprising a radical of a compound represented by” that formula not “consisting of a radical of a compound represented by” that formula and thus additional unspecified structural components are covered by the claim as long as that specific radical is a portion of the molecule. Since the claimed portion of the molecule is included in the reference compound the claims are anticipated.
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103 Rejections
The applicants also argued that the amendments to the structure of the compounds of the instant claims made the instant claims unobvious over the structures of Imiquimod and S-34240. This argument is unpersuasive however because claim 11 allows for Y=COCH3 and thus S-34240 is still a compound of claim 11 and the rest of the claims only differ from the reference compounds by a single H to methyl group. Further, it is generally noted that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results. In re Druey, 319 F.2d 237, 138 U.S.P.Q. 39 (C.C. P.A. 1963). Given that applicant did not provide unexpected or unobvious results of the invention, it is concluded that the normal desire of scientists or artisans to improve upon what is already generally known would provide the motivation to substitute the H group for a Me. 2144.08(II)(A)(4)(c). Since it is a simple substitution of H for methyl one would have a reasonable expectation of success that the already known drug would have similar properties including side effects to the original drug based on a very close structural similarity .
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
The applicant also argues unexpected results. However, the applicant only tests compounds 1-5 while the claims cover a broad scope of compounds with various structures that may or may not share the unexpected results. In fact, the courts have made a distinction between mechanical elements, which function the same in different circumstances, yielding predictable results, and chemical and biological compounds, which often react unpredictably under different circumstances. Nationwide Chem. Corp. v. Wright, 458 F. supp. 828, 839, 192 USPQ 95, 105(M.D. Fla. 1976); Aff’d 584 F.2d 714, 200 USPQ 257 (5th Cir. 1978); In re Fischer, 427 F.2d 833, 839, 166 USPQ 10, 24(CCPA 1970). Thus, the physiological activity of a chemical or biological compound is considered to be an unpredictable art. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100C). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F .2d 731,741,218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.). To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). Since there is a large number of structures not tested it is unlikely the claimed range is commensurate in scope with the unexpected results. It is also clear from figure 2 that even with the compounds of the instant claim tested (compound 3) some performed worse than the benchmark compound and some performed better (compound 1). Having some compounds that perform worse and some that perform better is not unexpected.
Additionally, paragraphs [0458-0459] do not exist with in the application and thus do not support a persuasive argument.
The applicant argues improper aggregation of references from different technical contexts with no specific motivation to combine the references. This argument is unpersuasive because specific motivations where given to combine the specific references for example: Thompson teaches folate-binding protein and cancer treatment and Kurahara teaches FRb macrophages may be promising a targeting therapy for pancreatic cancer. Thus one would combine the two based on knowledge of folate-binding protein and cancer treatment. Thus one would have a reasonable expectation of success and be motivated to treat cancer by targeting the folate binding receptor beta because it is suggest as a good target for cancer treatment. Furthermore, it would have been obvious to modify Thompson with Gabrilovich because Thompson teaches cancer treatment of myeloid related cancers and Gabrilovich suggests MDSC as a good target. Thus one would have a reasonable expectation of success and be motivated to treat myeloid related cancers via targeting MDSC cells because it is a suggested target. It would have been prima facie obvious to one of ordinary skill in the art that Thompson’s molecule contains a radical, in the conjugate connected to linker, because the molecule need not be a radical as a whole to fit the instant claims but simply contain (comprise) a radical (a portion of the molecule would be considered a radical if not taken as a whole). Since all the references relate to cancer treatment by targeting specific biological components mentioned in two out of the three references one would be motived to combine the references.
Double Patenting Rejections
Additionally, the applicant argues that the double patenting rejections should be withdrawn because the instant claims cite limitations that are not found in the references, however, no specific examples of these differences are given. For example the applicant argues generic differences in specific compound structure or technical problems but no specific examples are given. This is unpersuasive because for instance instant claim 89 and co-pending application ‘273 teach the same exact compound. An additionally, example is the compounds of application ‘785 fall within the generic formula of instant claim 1 – since no structural difference were identified the applicants argument is unpersuasive. A claim that recites a compound for use in a method makes the compound obvious. Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Conclusion
Claims 1, 3, 5, 7, 8, 11, 15, 40, 51, 59, 61, 63, 65, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87-92 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/A.A.H./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627