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 .
Status of the Claims
Claims 1-9, 11-24 are pending in this application. Claim 10 has been cancelled by Applicant.
Claim Objections
Claim 23 is objected to because of the following informalities:
Claim 23 ends with “or R5 is.” Either remove this incomplete line from the claim or include intended additional limitation for R5.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 1-8, 12-16, and 23-24 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Ali et al. (WO 2014/101120 A1 – Pub Date: July 3rd, 2014) (“Ali”).
Regarding claims 1-8, 12-15, and 23-24, Ali discloses the compounds 1-3 below (pages 66 and 92-93) which anticipate the instant claims when instant R1-2, 4 are H; R3 is -O-C1 alkyl (-OMe); Y is C1-2 alkyl (
PNG
media_image1.png
37
61
media_image1.png
Greyscale
or
PNG
media_image2.png
37
83
media_image2.png
Greyscale
); and R5 is Cl (halogen), -OH, or -SO2Me (-SO2R6 wherein R6 is methyl).
PNG
media_image3.png
147
282
media_image3.png
Greyscale
(1)
PNG
media_image4.png
156
302
media_image4.png
Greyscale
(2)
PNG
media_image5.png
161
231
media_image5.png
Greyscale
(3)
Further regarding claim 15, Ali’s compound 2 is the same as the instantly claimed compound below:
PNG
media_image6.png
96
180
media_image6.png
Greyscale
Regarding claim 16, Ali discloses compound 2 in DMF (a pharmaceutically acceptable carrier) (page 39, [0130]).
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.
Claims 1-9, 11-13, 15-16, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ali et al. (WO 2014/101120 A1) (“Ali”); as applied to claims 1-8, 12-16, and 23-24; in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) ("Morita").
The teachings of Ali are disclosed in the 102-section above and incorporated herein.
Further regarding claims 1-8, 13, 15-16, and 23-24, Ali discloses their compounds of Formula GII below as A2A inhibitors [0014]. Ali’s compounds render the instant claims obvious when: RGaa, Gba, Gca are H, C1-6 alkyl, alkoxy, F, Cl, etc.; GGf (corresponding to instant Y) can be -CH2-, ethyl, or -C(O)CH2; and RGe (corresponding to instant R5) can be polycyclic aryl/ heteroaryl.
PNG
media_image7.png
247
372
media_image7.png
Greyscale
Ali specifically discloses the compounds 7 and 13 below (page 41-42), which read on the instant compounds when instant R5 is
PNG
media_image8.png
67
281
media_image8.png
Greyscale
substituted with alkyl or C3 cycloalkyl.
PNG
media_image9.png
163
397
media_image9.png
Greyscale
(Ex. 13)
PNG
media_image10.png
166
393
media_image10.png
Greyscale
(Ex. 7)
While Ali doesn’t specifically teach their compounds wherein the group corresponding to instant R5 is
PNG
media_image8.png
67
281
media_image8.png
Greyscale
(since they have a nitrogen as part of the 6-member ring of their bicyclic groups); the teachings of Morita are relied upon to leverage these differences.
Morita teaches that bioisosteres introduce structural changes that can be beneficial to in the context of lead and drug compound optimization by improving potency, selectivity, and altering physical properties (page 3, bottom). Morita discloses -NH-, -CH2-, -O-, and -S- as classical divalent bioisosteres, and thus as an obvious modification in the context of drug and lead compound optimization (page 4, top).
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Ali’s disclosed formula GII and compounds 1-3 above, in view of Morita; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of A2A inhibitor compounds disclosed by Ali, in view of Morita’s teaching that -NH- and -CH-2- are obvious bioisosteric modifications in the context of lead and drug optimization. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, by replacing the -N- in Ali’s heterocycles corresponding to instant R5 with a -C- to arrive at the claimed invention.
Further regarding instant claim 15, the compounds below, for example, are particularly obvious in light of the disclosures above:
PNG
media_image11.png
115
232
media_image11.png
Greyscale
PNG
media_image12.png
101
285
media_image12.png
Greyscale
PNG
media_image13.png
91
253
media_image13.png
Greyscale
Applicant is advised that compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Furthermore, a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950).
Regarding claim 9, wherein Y is a branched alkyl group, Applicant is advised that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Note In re Wood 199 USPQ 137; In re Lohr 187 USPQ 548 and In re Bowers 149 USPQ 573. Note also In re Fauque 121 USPQ 425 in which differences were 2H’s vs 2 methyl groups. Also see MPEP 2144.09. Thus, Ali’s compounds, wherein the group corresponding to instant Y is a straight ethylene chain, read on the instant compounds when one of the H is replaced by a Me to produce a branched alkyl chain.
Regarding claims 11-12, Morita teaches that -CH2-, -O- and -S- are divalent bioisosteres. Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Ali’s disclosed formula GII and compounds 1-3 above, in view of Morita. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of A2A inhibitor compounds disclosed by Ali, in view of Morita’s teaching that -O-, -S-, and -CH-2- are obvious bioisosteric modifications in the context of lead and drug optimization. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Thus, the following groups corresponding to instant Y are obvious modifications of Ali’s disclosure:
PNG
media_image14.png
38
91
media_image14.png
Greyscale
PNG
media_image15.png
50
171
media_image15.png
Greyscale
.
Regarding claim 16, Ali discloses pharmaceutical compositions comprising their compounds and acceptable excipients (reading on carrier) ([0085] and [0102]).
Claims 17-22 are rejected under 35 U.S.C. 103 as being unpatentable over Ali et al. (WO 2014/101120 A1) (“Ali”); in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) ("Morita"); as applied to claims 1-9, 11-13, 15-16, and 23-24; further in view of Sek et al. (Int. J. Mol. Sci. 2018, 19, 3837, 23 pages) (“Sek”).
The teachings of Ali and Morita are disclosed above and incorporated herein.
Ali teaches their compounds are A2A- receptor agonists (abstract).
While Ali in view of Morita does not teach: (i) treatment of cancers, like head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma (claims 17-18); (ii) or administration with another agent, like a PD-1 antagonist, such as pembrolizumab (claims 19-22); the teachings of Sek are relied upon for these disclosures.
Sek teaches that therapeutic agents have been developed to target downstream adenosine receptors (A1R, A2AR, A2BR, A3R) to enhance anti-tumor immune responses (abstract) and that the A2AR is overexpressed in some cancers, such as head and neck squamous cell carcinoma (HNSCC), and in several breast and melanoma cell lines (page 5, last para.). Sek specifically teaches that inhibition of A2AR in combination with anti-PD-1, has been shown to elicit enhanced anti-tumor T cell responses (page 9, para. 1, 13-20). Sek also teaches pembrolizumab as a PD-1 inhibitor being administered in combination with an A2A inhibitor for treating solid cancers (table 1, page 10, 3rd from last row).
Therefore, regarding claims 17-22, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Ali’s A2A receptor inhibitors alone or in combination with a known PD-1 inhibitor, such as pembrolizumab, in view of Sek. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Ali in view of Morita disclose their compounds and pharmaceutical compositions thereof as A2AR inhibitors. Further because Sek teaches A2AR is overexpressed in some cancers, such as head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma; that targeting adenosine receptors enhances anti-tumor immune responses; and that inhibition of A2AR in combination with anti-PD-1, such as pembrolizumab, has been shown to elicit enhanced anti-tumor T cell responses.
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 1-9, 11-13, 15-16, and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,011,615 B2 (US ‘615); in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) ("Morita").
Regarding instant claims 1-9, 11-13, 15-16, and 23-24, US ‘615 claims the compounds of Formula GI below, reading on the instant compounds when RGa1 is -OH, -CN, halogen, C1-8 alkyl, or O(C1-4 alkyl); RG5 and RG6 are independently -H, or C1-10 alky optionally substituted with one or more F atoms, (reading on instant Y being a straight or branched alkyl and R5 being a substituted cycloheteroalkyl). US ‘615 specifically claims wherein their group corresponding to instant R5 is
PNG
media_image16.png
127
117
media_image16.png
Greyscale
(US ‘615’s claims 1-12).
PNG
media_image17.png
172
226
media_image17.png
Greyscale
wherein RG3 is
PNG
media_image18.png
226
387
media_image18.png
Greyscale
While US ‘615 doesn’t specifically teach their compounds wherein the group corresponding to instant R5 is
PNG
media_image8.png
67
281
media_image8.png
Greyscale
(since they have a nitrogen as part of the 6-member ring of their bicyclic groups); the teachings of Morita are relied upon to leverage these differences.
Morita teaches that bioisosteres introduce structural changes that can be beneficial to in the context of lead and drug compound optimization by improving potency, selectivity, and altering physical properties (page 3, bottom). Morita discloses -NH-, -CH2-, -O-, and -S- as classical divalent bioisosteres, and thus as an obvious modification in the context of drug and lead compound optimization (page 4, top).
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by US ‘615’s disclosed formula in view of Morita. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of A2A inhibitor compounds disclosed by US ‘615 (abstract), in view of Morita’s teaching that -NH- and -CH-2- are obvious bioisosteric modifications in the context of lead and drug optimization. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, by replacing the -N- in US ‘615’s heterocycles corresponding to instant R5 with -C- to arrive at the claimed invention.
Further regarding instant claim 15, the compounds below, for example, are particularly obvious in light of the disclosures above:
PNG
media_image12.png
101
285
media_image12.png
Greyscale
PNG
media_image13.png
91
253
media_image13.png
Greyscale
Applicant is reminded that compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
Furthermore, Applicant is reminded that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results.
Regarding claim 9, wherein Y is a branched alkyl group, Applicant is reminded that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Thus, US ‘615’s compounds, wherein the group corresponding to instant Y is a straight ethylene chain, read on the instant compounds when one of the H is replaced by a Me to produce a branched alkyl chain.
Regarding claims 11-12, Morita teaches that -CH2-, -O- and -S- are divalent bioisosteres. Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by US ‘615’s disclosed formula above, in view of Morita. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of A2A inhibitor compounds disclosed by US ‘615, in view of Morita’s teaching that -O-, -S-, and -CH-2- are obvious bioisosteric modifications in the context of lead and drug optimization. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Thus, the following groups corresponding to instant Y are obvious modifications of US ‘615’s disclosure:
PNG
media_image14.png
38
91
media_image14.png
Greyscale
PNG
media_image15.png
50
171
media_image15.png
Greyscale
.
Regarding claim 16, US ‘615 claims a pharmaceutical composition comprising their compounds and a carrier (US ‘615’s claim 13).
Claims 17-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,011,615 B2 (US ‘615); in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) ("Morita"); as applied to claims 1-9, 11-13, 15-16, and 23-24; further in view of Sek et al. (Int. J. Mol. Sci. 2018, 19, 3837, 23 pages) (“Sek”).
The teachings of US ‘615 and Morita are disclosed above and incorporated herein.
US ‘615 discloses their compounds are A2A- receptor agonists (abstract).
While US ‘615 in view of Morita does not teach: (i) treatment of cancers, like head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma (claims 17-18); (ii) or administration with another agent, like a PD-1 antagonist, such as pembrolizumab (claims 19-22); the teachings of Sek are relied upon for these disclosures.
Sek teaches that therapeutic agents have been developed to target downstream adenosine receptors (A1R, A2AR, A2BR, A3R) to enhance anti-tumor immune responses (abstract) and that the A2AR is overexpressed in some cancers, such as head and neck squamous cell carcinoma (HNSCC), and in several breast and melanoma cell lines (page 5, last para.). Sek specifically teaches that inhibition of A2AR in combination with anti-PD-1, has been shown to elicit enhanced anti-tumor T cell responses (page 9, para. 1, 13-20). Sek also teaches pembrolizumab as a PD-1 inhibitor being administered in combination with an A2A inhibitor for treating solid cancers (table 1, page 10, 3rd from last row).
Therefore, regarding instant claims 17-22, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer US ‘615’s A2A receptor inhibitors alone or in combination with a known PD-1 inhibitor, such as pembrolizumab, in view of Sek. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘615 in view of Morita disclose their compounds and pharmaceutical compositions thereof as A2AR inhibitors. Further because Sek teaches A2AR is overexpressed in some cancers, such as head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma; that targeting adenosine receptors enhances anti-tumor immune responses; and that inhibition of A2AR in combination with anti-PD-1, such as pembrolizumab, has been shown to elicit enhanced anti-tumor T cell responses.
Claims 1-9, 11-13, 15-16, and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9,708,347 B2 (US ‘347); in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) ("Morita").
Regarding instant claims 1-9, 11-13, 15-16, and 23-24, US ‘347 claims the compounds below, which read on the instant compounds when each RGda is, independently, an H, Me, or Et (reading on straight or branched alkyl for instant Y) and RGe (not shown in the image and presumed to be a typo) is
PNG
media_image19.png
123
202
media_image19.png
Greyscale
, etc. (corresponding to instant R5) (US ‘347’s claims 1-2 and 13).
PNG
media_image20.png
215
380
media_image20.png
Greyscale
PNG
media_image21.png
156
342
media_image21.png
Greyscale
While US ‘347 doesn’t specifically teach their compounds wherein the group corresponding to instant R5 is
PNG
media_image8.png
67
281
media_image8.png
Greyscale
(since they have a nitrogen as part of the 6-member ring of their bicyclic groups); the teachings of Morita are relied upon to leverage these differences.
Morita teaches that bioisosteres introduce structural changes that can be beneficial to in the context of lead and drug compound optimization by improving potency, selectivity, and altering physical properties (page 3, bottom). Morita discloses -NH-, -CH2-, -O-, and -S- as classical divalent bioisosteres, and thus as an obvious modification in the context of drug and lead compound optimization (page 4, top).
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by US ‘347’s disclosed formula in view of Morita. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of A2A inhibitor compounds disclosed by US ‘347 (abstract), in view of Morita’s teaching that -NH- and -CH-2- are obvious bioisosteric modifications in the context of lead and drug optimization. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, by replacing the -N- in US ‘347’s heterocycles corresponding to instant R5 with -C- to arrive at the claimed invention.
Applicant is reminded that compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. Therefore, while US ‘347 claims a 5-5 bicyclic ring system, the addition of an additional methylene to make the instant 5-6 ring system is obvious in the absence of unexpected results.
Further regarding instant claim 15, the compounds below, for example, are particularly obvious in light of the disclosures above:
PNG
media_image12.png
101
285
media_image12.png
Greyscale
PNG
media_image13.png
91
253
media_image13.png
Greyscale
Applicant is reminded that H vs. Me is considered an obvious modification in the absence of superior, unexpected results.
Regarding claim 9, wherein Y is a branched alkyl group, Applicant is reminded that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Thus, US ‘347’s compounds, wherein the group corresponding to instant Y is a straight ethylene chain, read on the instant compounds when one of the H is replaced by a Me to produce a branched alkyl chain.
Regarding claims 11-12, Morita teaches that -CH2-, -O- and -S- are divalent bioisosteres. Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by US ‘347’s disclosed formula above, in view of Morita. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of A2A inhibitor compounds disclosed by US ‘347, in view of Morita’s teaching that -O-, -S-, and -CH-2- are obvious bioisosteric modifications in the context of lead and drug optimization. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Thus, the following groups corresponding to instant Y are obvious modifications of US ‘347’s disclosure:
PNG
media_image14.png
38
91
media_image14.png
Greyscale
PNG
media_image15.png
50
171
media_image15.png
Greyscale
.
Regarding claim 16, US ‘347 claims a pharmaceutical composition comprising their compounds and a carrier (US ‘347’s claim 15).
Claims 17-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9,708,347 B2 (US ‘347); in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) ("Morita"); as applied to 1-9, 11-13, 15-16, and 23-24; further in view of Sek et al. (Int. J. Mol. Sci. 2018, 19, 3837, 23 pages) (“Sek”).
The teachings of US ‘347 and Morita are disclosed above and incorporated herein.
US ‘347 discloses their compounds are A2A- receptor agonists (abstract).
While US ‘347 in view of Morita does not teach: (i) treatment of cancers, like head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma (claims 17-18); (ii) or administration with another agent, like a PD-1 antagonist, such as pembrolizumab (claims 19-22); the teachings of Sek are relied upon for these disclosures.
Sek teaches that therapeutic agents have been developed to target downstream adenosine receptors (A1R, A2AR, A2BR, A3R) to enhance anti-tumor immune responses (abstract) and that the A2AR is overexpressed in some cancers, such as head and neck squamous cell carcinoma (HNSCC), and in several breast and melanoma cell lines (page 5, last para.). Sek specifically teaches that inhibition of A2AR in combination with anti-PD-1, has been shown to elicit enhanced anti-tumor T cell responses (page 9, para. 1, 13-20). Sek also teaches pembrolizumab as a PD-1 inhibitor being administered in combination with an A2A inhibitor for treating solid cancers (table 1, page 10, 3rd from last row).
Therefore, regarding instant claims 17-22, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer US ‘347’s A2A receptor inhibitors alone or in combination with a known PD-1 inhibitor, such as pembrolizumab, in view of Sek. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘347 in view of Morita disclose their compounds and pharmaceutical compositions thereof as A2AR inhibitors. Further because Sek teaches A2AR is overexpressed in some cancers, such as head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma; that targeting adenosine receptors enhances anti-tumor immune responses; and that inhibition of A2AR in combination with anti-PD-1, such as pembrolizumab, has been shown to elicit enhanced anti-tumor T cell responses.
Claims 1-9, 11-13, 15-16, and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,498,923 B2 (US ‘923).
Regarding instant claims 1-9, 11-13, 15-16, and 23-24, US ‘923 claims the compounds of Formula I below, wherein Z’ can be CH2-phenyl, optionally substituted with halogen, alkyl, etc., anticipating the instant compounds when Y is C1 alkyl and R5 is aryl, optionally substituted (US ‘923’ claims 1-2).
PNG
media_image22.png
142
222
media_image22.png
Greyscale
PNG
media_image23.png
145
291
media_image23.png
Greyscale
PNG
media_image24.png
155
315
media_image24.png
Greyscale
Regarding instant claim 16, US ‘923 claims a pharmaceutical composition comprising their compounds and an acceptable excipient (US ‘923’s claim 3).
Claims 17-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,498,923 B2 (US ‘923); as applied to claims 1-9, 11-13, 15-16, and 23-24; in view of Sek et al. (Int. J. Mol. Sci. 2018, 19, 3837, 23 pages) (“Sek”).
The teachings of US ‘923 are disclosed above and incorporated herein.
US ‘923 claims a method of inhibiting adenosine signaling in a patient comprising administration of their compounds – reading on instant claims (US ‘923 claim 4).
While US ‘923 does not teach: (i) treatment of cancers, like head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma (claims 17-18); (ii) or administration with another agent, like a PD-1 antagonist, such as pembrolizumab (claims 19-22); the teachings of Sek are relied upon for these disclosures.
Sek teaches that therapeutic agents have been developed to target downstream adenosine receptors (A1R, A2AR, A2BR, A3R) to enhance anti-tumor immune responses (abstract) and that the A2AR is overexpressed in some cancers, such as head and neck squamous cell carcinoma (HNSCC), and in several breast and melanoma cell lines (page 5, last para.). Sek specifically teaches that inhibition of A2AR in combination with anti-PD-1, has been shown to elicit enhanced anti-tumor T cell responses (page 9, para. 1, 13-20). Sek also teaches pembrolizumab as a PD-1 inhibitor being administered in combination with an A2A inhibitor for treating solid cancers (table 1, page 10, 3rd from last row).
Therefore, regarding instant claims 17-22, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer US ‘923’s A2A receptor inhibitors alone or in combination with a known PD-1 inhibitor, such as pembrolizumab, in view of Sek. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘923 discloses their compounds and pharmaceutical compositions thereof as A2AR inhibitors. Further because Sek teaches A2AR is overexpressed in some cancers, such as head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma; that targeting adenosine receptors enhances anti-tumor immune responses; and that inhibition of A2AR in combination with anti-PD-1, such as pembrolizumab, has been shown to elicit enhanced anti-tumor T cell responses.
Claims 1-9, 11-13, 15-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 and 22-29 of copending Application No. 18/015,387 (Copending ‘387); in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) ("Morita").
Regarding instant claims 1-9, 11-13, 15-24, Copending ‘387 claims the compounds of Formula I below and pharmaceutical compositions thereof, which read on the instant compounds when Y is a C1-5 alkyl, wherein one or more -CH2 – has been replaced by -NH--, and R5 can be
PNG
media_image25.png
80
117
media_image25.png
Greyscale
.
PNG
media_image26.png
197
300
media_image26.png
Greyscale
Regarding instant claims 17-22, Copending ‘387 claims a method of treating cancer (Copending ‘387 claims 23-24) comprising administration of their compounds of Formula I. Copending ‘387 also speaks to coadministration of an additional therapeutic agent that is a PD-1 antagonist, such as pembrolizumab (Copending ‘387 claims 25-28).
Applicant is reminded, similar properties may normally be presumed when compounds are very close in structure. (“When chemical compounds have very close’ structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious.
While Copending ‘387 does not teach their Y group being an alkyl chain, wherein a -CH2- group is not substituted with -NH-, or optionally substituted for -O- or -S-, the teachings of Morita are relied upon to leverage these differences.
Morita teaches that bioisosteres introduce structural changes that can be beneficial to in the context of lead and drug compound optimization by improving potency, selectivity, and altering physical properties (page 3, bottom). Morita discloses -NH-, -CH2-, -O-, and -S- as classical divalent bioisosteres, and thus as an obvious modification in the context of drug and lead compound optimization (page 4, top).
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Copending ‘387’s disclosed formula in view of Morita. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of A2A inhibitor compounds disclosed by Copending ‘387 in methods of treating cancers (Copending ‘387’s claims 23-28), in view of Morita’s teaching that -NH- and -CH-2- are obvious bioisosteric modifications in the context of lead and drug optimization. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, by replacing the -N- in Copending ‘387’s Y group for a -CH2- to arrive at the instant invention.
Further regarding instant claim 15, the compound below, for example, is particularly obvious in light of the disclosures above:
PNG
media_image27.png
108
290
media_image27.png
Greyscale
Applicant is reminded that compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
Regarding claim 9, wherein Y is a branched alkyl group, Applicant is reminded that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Thus, Copending ‘387’s compounds, wherein the group corresponding to instant Y is a straight ethylene chain, read on the instant compounds when one of the H is replaced by a Me to produce a branched alkyl chain.
Regarding claims 11-12, Morita teaches that -CH2-, -O- and -S- are divalent bioisosteres of -NH-. Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Copending ‘387’s disclosed formula above, in view of Morita. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of A2A inhibitor compounds disclosed by Copending ‘387, in view of Morita’s teaching that -O-, -S-, and -CH-2- are obvious bioisosteric modifications in the context of lead and drug optimization. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Thus, the following groups corresponding to instant Y are obvious modifications of Copending ‘387’s disclosure:
PNG
media_image14.png
38
91
media_image14.png
Greyscale
PNG
media_image15.png
50
171
media_image15.png
Greyscale
.
Regarding claim 16, Copending ‘387 claims a pharmaceutical composition comprising their compounds and a carrier (Copending ‘387’s claim 22).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Claims
Claim amendments are acknowledged and have been entered. No new matter has been introduced.
Specification
Applicant’s comment is acknowledged. No amendments have been made to the specification. No new matter has been introduced.
Claim Objections
Applicant’s arguments are acknowledged, however, upon further consideration however, previously objected claims 11 and 13-14 are no longer considered allowable and stand rejected in this non-final office action.
Previous objection is withdrawn. However, a new ground of objection is raised herein over informalities in new claim 23.
Double Patenting
Applicant’s arguments, see pages 18-22, filed 12/02/2025, with respect to obviousness-type double patenting (ODP) rejections have been fully considered and are persuasive for ODP rejections over U.S. Patent No. 9,676,780 B2 (US ‘780); 11,312,719 B2 (US ‘719); and 12,263,171 B2 (US ‘171); and Copending App. No. 18/836,154 (Copending ‘154). The ODP rejections of the claims over U.S. Patent No. 9,676,780 B2 (US ‘780); 11,312,719 B2 (US ‘719); and 12,263,171 B2 (US ‘171); and Copending App. No. 18/836,154 (Copending ‘154) have been withdrawn.
However, claims stand rejected under ODP over US Patent No. 10,011,615 B2 (US ‘615); 9,708,347 B2 (US ‘347); US 11,498,923 B2 (US ‘923); and Copending App. No. 18/015,387 (Copending ‘387).
This action is non-final.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627