DETAILED ACTION
A final Office action was mailed on 22 January 2026 (“Office Action”).
Applicant’s after-final request for reconsideration was received on 21 April 2026.
An advisory action was mailed on 24 June 2026.
Applicant’s reply to the advisory action was received on 21 July 2026 (“Reply”).
The Reply was submitted with a Request for Continued Examination (RCE).
Status of the Claims
The listing of claims filed with the Reply and RCE has been entered and examined.
Claims 1–5 and 7–20 are pending. Claim 6 is canceled.
Claims 1, 2, 8, and 10 are amended.
Status of Rejections and Objections
The text of those sections of Title 35, U.S. Code and/or text providing the basis for non-statutory double patenting rejections not included in this action are set forth in the Office Action.
Unless repeated herein, any objection or rejection in the Office Action is withdrawn.
Claim Rejections - 35 U.S.C. § 102
Claims 1–5 and 7–15 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by the compound having Registry Number RN 2131044-41-0, STN/CAPLUS (28 September 2017) (“Compound RN 2131044-41-0”).
Compound RN 2131044-41-0 (shown below) was indexed in the Registry database on the date noted above.
PNG
media_image1.png
371
711
media_image1.png
Greyscale
Compound RN 2131044-41-0 reads on instantly claimed Formula (I): n = 1 (adjacent to A); A = aryl; R2 = ethyne; Y = NR13R14; n = 0 (adjacent to R1); and R1, R3, R4, R5, R13, R14 = H.
The rejected claims do not require any components other than a compound of Formula I. The broadest reasonable interpretation of “pharmaceutical composition” does not require additional components other than a compound.
Claim Rejections - 35 U.S.C. § 103
Claims 1–5 and 7–20 are rejected under 35 U.S.C. § 103 as being unpatentable over Compound RN 2131044-41-0 in view of Santa Maria et al., ACS Chemical Biology (2017), 12(9), 2448–2456 (“Santa Maria”) and US 4,118,561 (“Ledig”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
Compound RN 2131044-41-0 (shown above) was indexed in the Registry database.
Compound RN 2131044-41-0 reads on instantly claimed Formula (I): n = 1 (adjacent to A); A = aryl; R2 = ethyne; Y = NR13R14; n = 0 (adjacent to R1); and R1, R3, R4, R5, R13, R14 = H.
Compound RN 2131044-41-0 was indexed in connection with Santa Maria.
Santa Maria discloses the results of a high throughput screening study comprising 55,000 compounds with respect to ability to effect bacterial targets. (Santa Maria, Abstract).
Santa Maria identifies compounds considered active against certain bacterial strains using data from previous studies (an antibacterial phenotypic screen and a screen for bacterial targets in ALIS-based biophysical biding assays). (Id., pp.2449, 2453 (Methods)).
Ledig discloses compounds according to formula I,
PNG
media_image2.png
112
198
media_image2.png
Greyscale
, and compounds of the formulae II, III, and IV—each of which being structurally related to the instantly claimed compounds.
Ledig discloses screening the compounds at a dose as low as 5 mg/kg. (Id., col. 5 (table); col. 38 (Table IX)).
Ledig discloses formulating and administering the compounds in a composition. (Id., 3:46–63; 4:46–7:17; 27:20–41:12) (col:lines).
Ledig discloses the compounds are present in an amount sufficient to exhibit anticancer properties when administered in vivo. (Id., 4:62–5:17).
Ledig discloses administering the compounds with a sulfa drug to give a synergistic effect. (Id., 3:64–68).
Ascertaining the differences between the prior art and the claims at issue
Compound RN 2131044-41-0 anticipates certain claims as established above, but the reference discloses the compound per se rather than a composition comprising one or more additional components. Santa Maria and Ledig are relied on for the claimed features related to dosage, additional components, and methods of treating a patient having cancerous tissue.
The units for a dose of a compound in Ledig is reported in mg/kg, whereas the instant claims recites units in nM and mM. The weight of the subject in the instant claims is not known. As such, the corresponding dosage may be different.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application provides comparative data for Compound 1 against pemetrexed and methotrexate in the context of cells down-regulating RFC. (Spec., 43:24–44:8) (page:lines).
The question of obviousness
Based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to combine the teachings of Compound RN 2131044-41-0, Santa Maria, and Ledig to arrive at the claimed subject matter because Compound RN 2131044-41-0 discloses an anticipatory compound while Santa Maria and Ledig disclose using related compounds as pharmaceutical agents for the treatment of one or more diseases. Compound RN 2131044-41-0 and the compounds in Santa Maria and Ledig are related in structure and utility. Accordingly, there would have been a reasonable expectation of success at combining their teachings and arriving at the claimed invention.
Regarding claims 10 and 11, the concentration ranges for a compound of Formula (I) recited in the claims are not specifically disclosed in the cited references, however determining the concentration of an active ingredient is considered optimization for one of ordinary skill in the art and therefore generally not sufficient to support patentability. MPEP § 2144.06.
Regarding claims 12–15 and 18: The inhibition of purine or thymine biosynthesis in pancreatic cancer cells in recited claims 12 and 13, exhibition of higher potency relative to pemetrexed or methotrexate for cancer cells down-regulating reduced folate carrier recited in claim 14, inhibition of colorectal tumor growth recited in claim 15, and down-regulation of reduced folate carrier by cancer cells recited in claim 18 are each considered inherent properties of a compound encompassed by the instantly claimed Markush group. Thus, any compound encompassed by the Markush group, including Compound RN 2131044-41-0, would be expected to possess the inherent properties of other members of the Markush group. MPEP § 2117(I) (“A Markush grouping is proper if the members of a group share a single structural similarity and a common use.”).
Regarding claim 16, Ledig discloses a combination of the disclosed compounds and a sulfa drug, which reads on the claimed adjuvant.
Regarding claim 19, the IC50 value of less than 0.1 nM recited in the claim is considered an intended result. Courts have held that expressions of an intended result in a method claim are not given much patentable weight. MPEP § 2111.04(I).
The examples and data in the instant specification have been considered. The examples and data compare Compound 1 to pemetrexed and methotrexate in the context of cells down-regulating RFC. That data is not commensurate in scope with the claimed compositions with the compounds of Formula (I). Further, there is no evidence of criticality with respect to the concentration of the compound of Formula (I) recited in claims 10 and 11.
Response to Arguments
It should be noted that the rejection above has been modified relative to the rejection in the Office Action. Compound RN 2131044-41-0 is relied on for its disclosure of a compound according to the claimed formula (I). Santa Maria and Ledig are relied on for their disclosures of the claimed features related to dosage, additional components, and methods of treating a patient having cancerous tissue. To the extent Applicant’s arguments apply to the revised rejection, they are addressed in turn below.
Applicant’s arguments submitted with the Reply have been fully considered but are not persuasive. Applicant first argues that Compound RN 2131044-41-0 is not disclosed in Santa Maria. (Remarks, p.7). Regardless of whether that statement is true, indexing the compound in a publicly available database is sufficient to qualify as prior art. Applicant next argues the compounds in Santa Maria were developed as antibacterial compounds, and “[m]echanisms of action and associated compound structure for antibacterials have no relevance or correlation to that of cancer cells. . . . If alkynyl moieties were effective for anticancer properties, they would have been included in the disclosure of Ledig.” (Id., pp.7–8). In response to the first point, it is noted that attorney arguments are not evidence. Gemtron Corp. v. Saint-Gobtain Corp., 572 F.3d 1371, 1380 (Fed. Cir. 2009). And the second point is mere speculation. Moreover, certain compounds in the instant claims may have antibacterial and anticancer properties. Indeed, related compounds having the same structural core are disclosed as having antibacterial properties in Applicant’s copending application No. 18/014,032 (discussed in double patenting section below). Thus, the attorney arguments about relevance overlook Applicant’s own disclosures.
Double Patenting
(i) Claims 1–5 and 7–16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1–4, 6–16, and 18–22 of copending App. No. 18/014,032 (reference claims).
18/013,302
18/014,032
PNG
media_image3.png
138
269
media_image3.png
Greyscale
PNG
media_image4.png
155
295
media_image4.png
Greyscale
The instant claims are directed to a pharmaceutical composition comprising a compound of Formula (I) above left, and the reference claims are directed to a compound of Formula (I) above right and pharmaceutical compositions comprising the compound. The respective Formula (I) structures cover identical compounds. In the instant claims, e.g., when A = aryl and R2 = alkynyl, cover the same embodiments covered in the reference claims when R2 = arylene-alkynyl.
The instant claims recite, “wherein the compound of Formula (I) is present in the pharmaceutical composition in an amount sufficient to exhibit anticancer properties.” The reference composition claims recite, “wherein the compound of Formula (I) is present in the pharmaceutical composition in an amount sufficient to exhibit antibacterial properties.” Those clauses are directed to the amount of compound present, and the respective dependent claims recite overlapping ranges for a sufficient amount. Furthermore, the functional language tied to the amount (to exhibit anticancer or antibacterial properties) does not distinguish the structural features of the compounds and compositions. Thus, an infringer of a patent granted based on the instant claims or the reference claims would also be an infringer of a patent granted from the other claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(ii) Claims 1–5 and 7–16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4–8, 10–12, and 26–32 of copending App. No. 17/314,196 (reference claims).
18/013,302
17/314,196
PNG
media_image3.png
138
269
media_image3.png
Greyscale
PNG
media_image5.png
158
293
media_image5.png
Greyscale
The instant claims are directed to a pharmaceutical composition comprising a compound of Formula (I) above left, and the reference claims are directed to a pharmaceutical composition comprising a compound of Formula (I) above right. The respective Formula (I) structures cover identical compounds. For example, the instant claims, when A = aryl and R2 = alkynyl, cover the same embodiments in the reference claims when R2 = aryl substituted by alkynyl.
The instant claims recite, “wherein the compound of Formula (I) is present in the pharmaceutical composition in an amount sufficient to exhibit anticancer properties.” The reference claims recite, “wherein the compound of Formula (I) is present in the pharmaceutical composition at a minimum inhibitory concentration (MIC) of 0.1 mg/ml to 10 mg/ml to inhibit growth of cells of a disease.” Those clauses are directed to the amount of compound present, and the instant dependent claims recite a range that overlaps with the clause in the reference claims. Furthermore, the functional language tied to the amount (to exhibit anticancer properties or inhibit growth of cells of a disease) does not distinguish the structural features of the compounds and compositions. Thus, an infringer of a patent granted based on the instant claims or the reference claims would also be an infringer of a patent granted from the other claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reply to Arguments
Applicant requests that the rejections be held in abeyance until a claim is allowed. (Remarks, p.6). The rejections are maintained.
Conclusion
No claims are allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to submit an Automated Interview Request: http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached on 571-270-7674.
/JASON M. NOLAN/Patent Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
Prosecution Insights