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 .
DETAILED ACTION
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/24/2025 has been entered.
Status of 17/423,289
Claims 1-3, 6, 9, and 47-48 are currently pending.
Priority
The instant application 17/423,289, filed 7/15/2021, claims priority as follows:
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The effective filing date of a claimed invention is determined on a claim-by-claim basis.
See MPEP § 2152.01. The priority document US Provisional Application number 62/793,725 fails to provide support under 35 U.S.C. 112 for compounds listed in the table in claim 9. However, the priority document PCT/US2020/014195 does provide support for these compounds and claim 9 is therefore entitled to the effective filing date of 1/17/2020.
The priority document 62/793,725 contains support for the limitations of claims
1-3, 6, and 47-48. Therefore, claims 1-3, 6, and 47-48 are entitled to an effective filing date of 1/17/2019.
Information Disclosure Statement
All references from the Information Disclosure Statements received 7/15/2021, 11/10/2021, 3/31/2022, and 10/11/2023 have been considered unless marked through with a strikethrough.
Response to Arguments/Amendments
The amendment filed 9/24/2025 has been entered. Applicant has amended claims 1-2 and 9.
In the Final Rejection dated 5/28/2025, the abstract was objected to for insufficient length. The abstract submitted with the response filed 9/24/2025 overcomes the rejection. Thus, the objection is withdrawn.
Claim 9 was rejected under 35 U.S.C. 112(b) in the Final dated 5/28/2025. Upon the amendments of claim 9 to omit “therapeutically effective amount”, the rejection has been overcome for claim 9 and thus, withdrawn.
Claims 1 and 3 were rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Abivax (US 2017/0226095 A1) in the Final Rejection of 5/28/2025. In response, Applicant amended claim 1 to recite that the ring of R1 and R2 is a cycloalkyl ring to overcome the rejection. However, claim 1 still recites, “or R1 and R2 together can form a ring;” in line 11 of the claim, which still includes the compound of Abivax in the instant claim. However, the addition of, “R1 and R2 together can form a cycloalkyl ring” in the next line of the claim introduces a 112(b) rejection due the recitation of both broad and narrow limitations in the same claim. See below. Therefore, the rejection is maintained.
In the Final Rejection dated 5/28/2025, claims 2, 9, and 47 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fujii (Fujii, S. et. al. Bioorg. Med. Chem. Lett. 2010, 20, 5139-5142). In response, Applicant amended the claims to recite where the compound is not
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, which is also known as instant compound 37. However, this does not overcome the rejection as instant compound 37 contains an alkyl at the instant R4 position, whereas the compound of Fuji, also known as instant compound 39, has a hydrogen at the R4 position. Thus, the rejection is maintained.
Claim 6 was rejected under 35 U.S.C. 103 in the Final dated 5/28/2025. In response, Applicant amended claim 1 as stated above, which did not overcome the 102 rejection. Therefore, the 103 rejection is not overcome and maintained.
In the Final Rejection dated 5/28/2025, claim 48 was rejected under 35 U.S.C. 103. The amendments submitted do not overcome the rejection and thus, the rejection is maintained.
In addition to the maintained rejections, new rejections necessitated by amendment are included in this Office Action.
Election/Restrictions
Applicant’s election of Group I, claims 1-3, 6, 9, and 10 without traverse in the reply filed on 7/19/2024 is acknowledged. Applicant’s election of the species compound:
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is also acknowledged.
Examination will begin with the elected species. In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
In the Non-Final dated 11/27/2024, the elected species was searched and no prior art was identified. Therefore, the scope of the search was expanded to compounds of Formula (I):
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Where one X2 is CH, X4 is C, R4 is H, X1 is NR8, and R5 is H. Upon the amendments to claims 1-3 and 9, and the cancellation of claim 10, submitted 3/27/2025, the 35 U.S.C. 102 and 103 rejections set forth in the 11/27/2024 Non-Final were overcome. The Examiner then moved onto alternative species recited in the instant claims. Subsequent examination is based on compounds of Formula I where R1 and R2 together form a ring and X1 is NR8 , for claim 1 and its dependents, and Formula (IV):
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where R1 and R2 together form a ring, R8 is alkyl, and R5 is H, for claims 2 and 9 and their dependents. The rejections under 35 U.S.C. 102 and 103 of the Final Rejection dated 5/28/2025 were not overcome, and thus the expanded species is the subject of this Office Action. Claims 1-3, 6, 9, and 47-48 read on the expanded species. No claims are withdrawn.
MAINTAINED OBJECTIONS AND REJECTIONS
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 3 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Abivax (US 2017/0226095 A1). This rejection applies to the expanded species of Formula (I) where R1 and R2 together form a ring and X1 is NR8.
The reference Abivax discloses compounds to treat cancer, AIDS, and/or premature aging (abstract), and specifically teaches compound 59 (page 68, para [1985]):
Methyl 6-(quinoline-2-ylamino)nicotinate
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Which anticipates a compound of instant Formula (I):
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When both X2’s are N, R1 and R2 together form a ring, R3 is H, X4 is C, R4 is H, X1 is NR8, R8 is H, X3 is CH, and R5 is alkyl. Regarding claim 3, Abivax discloses the pharmaceutical composition of compound 59 in a 10% DMSO/90% PBS solution for biological assays (page 35, para [0659]).
Claims 2, 9, and 47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fujii (Fujii, S. et. al. Bioorg. Med. Chem. Lett. 2010, 20, 5139-5142). This rejection applies to the expanded species of Formula (IV) where R1 and R2 together form a ring, R8 is alkyl, and R5 is H.
The reference Fujii discloses RXR agonists, and specifically discloses compound 11 (page 5140, Scheme 1):
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Which anticipates instant formula (IV):
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When R1 and R2 together form a ring, R3 is H, R4 is H, R8 is alkyl, and R5 is H. With respect to claim 47, compound 11 of Fujii is disclosed in DMSO, generating a pharmaceutical composition (Supporting Information, page 6, first paragraph). Additionally, compound 11 of Fujii anticipates compound 39 of instant claim 9. In addition to the pharmaceutical composition disclosed above, compound 11 is also found to have activity against RXRα (page 5140, Figure 2), demonstrating a therapeutically effective amount. Thus, Fujii anticipates instant claims 2, 9, and 47.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Abivax (US 2017/0226095 A1) as applied to claims 1 and 3 above, and further in view of Ohta (Ohta, K. Chem. Pharm. Bull. 2000, 48(10), 1504-1513.) This rejection applies to the expanded species of Formula (I) where R1 and R2 together form a ring and X1 is NR8.
Determining the scope and contents of the prior art
The reference Abivax teaches as disclosed above and at least those teachings are incorporated herein.
The reference Ohta teaches compounds as RAR and RXR receptors, and specifically teaches the compounds in a pharmaceutical composition with Am80, a known chemotherapeutic agent (page 1504, para 2 and page 1507, table 2).
Ascertaining the differences between the prior art and the claims at issue
The reference Abivax fails to teach compound 59 in a pharmaceutical composition with an anti-PD-L1 antibody or chemotherapeutic agent.
Ohta fails to teach the pharmaceutical composition of the chemotherapeutic agent, Am80, with compound 59.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of compounds and compositions for immune modulation and treatment of cancer. An artisan possess the technical knowledge necessary to make adjustments to the compounds and compositions to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to use of said compounds and compositions for immune modulation and treatment of cancer and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR prong (A), it would have been prima facie obvious to combine the pharmaceutical composition comprising compound 59, DMSO, and PBS of Abivax with the additional compound Am80 of Ohta because Ohta teaches combinations of compounds for the same purpose. A skilled artisan would have been motivated before the effective filing date of the claimed invention to test combination of compounds taught for the same purpose as in Abivax and Ohta, and would be motivated to improve the overall activity of the pharmaceutical compositions.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Fujii (Fujii, S. et. al. Bioorg. Med. Chem. Lett. 2010, 20, 5139-5142) as applied to claims 2, 9, and 47 above, and further in view of Ohta (Ohta, K. Chem. Pharm. Bull. 2000, 48(10), 1504-1513). This rejection applies to the expanded species of Formula (IV) where R1 and R2 together form a ring, R8 is alkyl, and R5 is H.
Determining the scope and contents of the prior art
The reference Fujii teaches as disclosed above and at least those teachings are incorporated herein.
The reference Ohta teaches compounds as RAR and RXR receptors, and specifically teaches the compounds in a pharmaceutical composition with Am80, a known chemotherapeutic agent (page 1504, para 2 and page 1507, table 2).
Ascertaining the differences between the prior art and the claims at issue
The reference Fujii fails to teach compound 11 in a pharmaceutical composition with an anti-PD-L1 antibody or chemotherapeutic agent.
Ohta fails to teach the pharmaceutical composition of the chemotherapeutic agent, Am80, with compound 11.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of compounds and compositions for immune modulation and treatment of cancer. An artisan possess the technical knowledge necessary to make adjustments to the compounds and compositions to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to use of said compounds and compositions for immune modulation and treatment of cancer and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR prong (A), it would have been prima facie obvious to combine the pharmaceutical composition comprising compound 11 and DMSO of Fujii with the additional compound Am80 of Ohta because Ohta teaches combinations of compounds for the same purpose. A skilled artisan would have been motivated before the effective filing date of the claimed invention to test combination of compounds taught for the same purpose as in Fujii and Ohta, and would be motivated to improve the overall activity of the pharmaceutical compositions.
NEW REJECTIONS AND OBJECTIONS NECESSITATED BY AMENDMENT
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 6, and 47-48 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 1 and 2 recite the broad limitation “R1 and R2 together can form a ring”, but the claims also recite “R1 and R2 together can form a cycloalkyl ring” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Dependent claims 3, 6, and 47-48 do not resolve this issue by claiming compounds with a ring or cycloalkyl ring formed by R1 and R2 and are therefore also rejected. Appropriate correction is required.
Claim 1 is rejected for the limitation of “the compound is not
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, as it could not be a compound of the instant formula (I), because X2 can only be N or CR9, where R8 and R9, together with the atoms to which they are each attached, form a heterocyclyl group. Stated differently, the compound excluded can’t be a compound of instant formula (I) because R9 can’t be H, thus generating a lack of antecedent basis. Appropriate correction is required.
Claim 2 recites the variable, X3. However, no formulae of independent claim 2 include the variable X3 and thus, the limitation is deemed indefinite. Dependent claims 47 and 48 do not resolve this limitation by including a formula with the variable X3 and are therefore also rejected. Appropriate correction is required.
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 1-3, 6, 9, and 47-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 13-14, 19-21, and 24-31 of copending Application No. 19/125,967 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘967 Application recite methods of treatment with compounds of formula (I):
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With overlapping limitations of instant formula (I), and under which the elected and expanded species falls. The compounds and utility disclosed in the instant specification provides further support for a nonstatutory double patenting rejection. See MPEP § 804(I)(B)(1) and Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-3, 6, 9, and 47-48 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621