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
This action is in response to a request for continued examination received June 3rd, 2026.
Status of Claims
Claims 1, 3-4, 8-13, and 16 are pending in the instant application.
Claims 2, 5-7, 14-15, and 17-19 have been canceled.
Claims 9-13 and 16 stand withdrawn.
Information Disclosure Statement
Applicant has submitted no Information Disclosure Statement (IDS) with this application. Applicant is reminded per 37 CFR 1.56, “Each individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability …”
Withdrawn Objections/Rejections
Applicant has traversed the rejection of Claims 1 and 3-4 under 35 U.S.C. 103. In particular, at Page 7 of the remarks filed May 19th, 2026, at the third paragraph, Applicant states, “Furthermore, there is no teaching in Li and McGeer suggesting that the inhibition of UDG by administration of ATA in combination with a pyrimidine analog or folate antimetabolite, such as pemetrexed, overcomes resistance to an antimetabolite chemotherapeutic agent in colorectal cancer cells.” The examiner finds this persuasive, as there is no suggestion or motivation in Li in view of McGeer to combine administration of ATA with at least one of a folate antimetabolite or a pyrimidine analog. This rejection is hereby withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4, and 8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a method of inhibiting UDG in a colorectal cell comprising the administration of ATA and at least one of a folate antimetabolite or a pyrimidine analog.
Breadth of the invention:
The scope of the claimed invention is broad, as it is drawn to the administration of any folate antimetabolite or a pyrimidine analog in combination with ATA. At Paragraph 00106 of the instant specification, antimetabolite agents are broadly defined as “agents, compounds, or small molecules that induce or promote incorporation of a UDG substrate, such as uracil, into DNA of cancer cells of the subject.” Further, the specification provided a non-limiting list of agents that meet this definition.
State of the prior art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
The amount of direction provided and working examples:
Applicant has provided no examples of administration of ATA in combination with a folate antimetabolite or a pyrimidine analog, nor does the instant disclosure provide motivation such that a person having ordinary skill in the art would understand which folate antimetabolites or pyrimidine analogs are appropriate for administration in combination with ATA, nor would it be readily understood the motivation for the administration of a particular combination.
Applicant has provided examples demonstrating the efficacy of administration of ATA in inhibiting UDG. No examples have been provided, however, demonstrating the result of the administration of ATA in combination with at least one of a folate antimetabolite or a pyrimidine analog.
Beginning at Page 44 of the instant application, Applicant discloses examples of the instant invention. Beginning at Page 54, Paragraph 00173 Applicant discloses a high-throughput screening assay employed that resulted in the identification of ATA as an inhibitor of UDG. Characterization of ATA’s activity as a UDG inhibitor is further disclosed in Paragraphs 00175-00183. Beginning at Paragraph 00184, Applicant discloses an example demonstrating ATA’s inhibitory activity against UDG in human DLD1 colon cancer cell extracts.
No examples have been provided in which inhibition of UDG was undertaken by the administration of ATA and a folate antimetabolite or pyrimidine analog. Based on the content of the instant disclosure, the motivation for administering the combination of ATA and a folate antimetabolite or pyrimidine analog would not be readily understood, nor would it be readily understood by a person having ordinary skill in the art which folate antimetabolites or pyrimidine analogs would be suitable for practicing the instant invention. Any examples disclosed of inhibiting UDG are undertaken administering ATA in the absence of a folate antimetabolite or pyrimidine analog.
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F. 2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is nto enabled for the instantly claimed method.
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.
Claims 1, 3-4, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Li et. al. (“First-In-Class Small Molecule Inibitors of the Single-Stand DNA Cytosine Deaminase APOBEC3G”, ACS Chem. Biol., 2012, 7, 506-517; initially cited in non-final rejection mailed October 21st, 2025; hereinafter referred to as Li) in view of McGeer et. al. (US 2015/0290155 A1; cited in final rejection mailed March 19th, 2026; hereinafter referred to as McGeer) in further view of Zhang et. al. (“Effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells”, Cancer Chemother Pharmacol, 72, 767-775, 2013; hereinafter referred to as Zhang).
As noted in the final rejection mailed March 19th, 2026, at Page 508, Second Column, Second Paragraph and at Page 509, Table 1, entry MN1, Li teaches that aurintricarboxylic acid (ATA) is an inhibitor of UDG.
Li does not teach inhibition of UDG in a colorectal cancer cell.
As noted in the final rejection mailed March 19th, 2026, at Page 8, Paragraph 0112, McGeer teaches the effect of ATA on the growth of the human colorectal cancer cell line SW 480 was assessed. At Page 8, Paragraph 0113 McGeer teaches ATA inhibited the growth of human colorectal cancer cells.
As noted above, Li in view of McGeer does not teach or suggest administration of at least one of a folate antimetabolite or a pyrimidine analog in combination with ATA.
Beginning at Page 767, Last Paragraph, Zhang teaches “Preclinical and clinical studies showed that pemetrexed had cytotoxic activity in many kinds of cancers including colorectal cancer.” At Page 770, Second Paragraph of the first column, Zhang teaches “Six human colorectal cancer cells all exhibited a concentration-dependent sensitivity to pemetrexed.” Finally, at Page 773, beginning at the second paragraph of the first column, Zhang states “In present study, the IC50 values of pemetrexed in HT-29, LoVo, SW620, HCT116, SW1116, and WiDr colorectal cancer cells were all much smaller than the human plasma concentration after conventional dose pemetrexed treatment, and they are similar with NSCLC cells, which demonstrated that pemetrexed has a determined cytotoxic effect on the human colorectal cancer cells like non-small cell lung cancer (NSCLC) cells.”
Taken together, Li establishes ATA as an inhibitor of UDG. McGeer demonstrates that administration of ATA to colorectal cancer cells has an inhibitory effect. Therefore, applying KSR exemplary rationale E, a person having ordinary skill in the art would have found it obvious to try inhibiting UDG in a colorectal cancer cell via administration of ATA, as the efficacy of ATA in inhibiting colorectal cancer cell growth was known in the art at the time of filing. Therefore, a person having ordinary skill in the art would have had a reasonable expectation of success in inhibiting UDG in a colorectal cancer cell based on ATA’s ability to interact with and inhibit the growth of colorectal cancer cells.
With respect to the administration of at least one of a folate antimetabolite or pyrimidine analog in combination with ATA, it was known in the art at the time of filing that pemetrexed, a folate antimetabolite, had an inhibitory effect against colorectal cancer cells. Therefore, it was known in the art at the time of filing that both ATA and pemetrexed were effective in inhibiting colorectal cancer cells. Per MPEP 2144.06, I., “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
The prior art is silent regarding “the UDG is maintained in a destabilized, open precatalytic glycosylase conformation that prevents active site closing for functional DNA binding and nuclease flipping needed to excise damaged bases binding in DNA” as recited at Claim 1, “ATA binds free UDG prior to DNA binding” as recited at Claim 3, and “ATA promotes destabilization of UDG” as recited at Claim 4. However, these limitations will naturally flow from the method made obvious by the prior art, since the same compound, ATA, is being administered to the same target, colorectal cancer cells. In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
In other words, even though the prior art is silent regarding the aforementioned limitations, by practicing the method made obvious by the prior art of administering ATA in combination with at least one of a folate antimetabolite or pyrimidine analog, one will also be practicing the aforementioned limitations, even though the prior art was not aware of it.
Apparently, Applicant has discovered a new property or advantage (“the UDG is maintained in a destabilized, open precatalytic glycosylase conformation that prevents active site closing for functional DNA binding and nuclease flipping needed to excise damaged bases binding in DNA”, “ATA binds free UDG prior to binding” and “ATA promotes destabilization of UDG”) of the method made obvious by the prior art.
MPEP 2145, II., states, “The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art, cannot be the basis for patentability when the differences would otherwise be obvious.”
Conclusion
Claims 1, 3-4, and 8 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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/D.J.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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