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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 August 07, 2026 has been entered.
Claim Status
Claims 1-19, 22 and 25-26 are canceled.
Thus, claims 20-21 and 23-24 as amended are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the final office action on May 08, 2026:
The rejection of claims 20-21 and 23-24 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendments to these claims and remarks filed August 07, 2026.
Response to Arguments
In view of Applicant’s argument of unexpected results, particularly the improved EC50 inhibition data of the recited compounds of instant claim 20 to IDO1 based on a HeLa-cell based inhibition assay as argued by Applicant on pg. 8, last paragraph; the Examiner as made a new 112(a)-scope of enablement rejection against claims 23-24 which is discussed below.
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 23-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating cervical cancer, does not reasonably provide enablement for treating cancer . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As a result, substantiation of utility and its scope is required when utility is speculative, sufficiently unusual or not provided, and enablement must be commensurate with the scope of the claim language. As MPEP § 2164.08 states, “The Federal Circuit has repeatedly held that "the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’." In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)”.
As stated in MPEP § 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”.
The applicant’s attention is drawn to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), where the court set forth eight factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. They are: (1) The nature of the invention; (2) The state of the prior art; (3) The level of skill in the art; (4) The
predictability or lack thereof in the art; (5) The breadth of the claims; (6) The amount of direction or guidance present; (7) The presence or absence of working examples; and (8) The quantity of experimentation needed.
It is noted that all of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
The nature of the invention: The invention is directed at a method for treating cancer per se recited in claims 23-24 by administering the compounds recited in claim 20.
Accordingly, to be enabled for the full scope of treatment, one skilled in the art must reasonably be able to ascertain which agents are effective, obtain said agents, and successfully use said agents for treating cancer per se.
The Examiner notes the compounds recited in claim 20 are disclosed as inhibitors of the enzyme IDO1 supported by EC50 inhibition data of these compounds in Table 1 as screened in a HeLa-cell based IDO1 inhibition assay which measures kynurenine (Kyn) generated from L-tryptophan (L-Trp) oxidation by cellular IDO1 in HeLa cells, see specification, pg. 69, paragraph [0259]-[0269].
The state of the prior art: The state of the art does not recognize indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors, e.g. the amide-substituted imidazo compounds recited in claim 20, as useful in treating cancer per se. Attention is drawn to Hornyak et al. (Published 30 January 2018, Frontiers in Immunology: Cancer Immunity and Immunotherapy, Vol. 9, Article 151, pp. 1-8, PTO-892), Hornyak discloses a review of the role of IDO in cancer development, diagnostics and therapy, see title.
Hornyak discloses the discovery of IDO-1-mediated immunosuppressive functions where the pro-cancer activity of the enzyme has been recognized. Hornyak discloses in cervical cancer IDO1 show a significantly higher mRNA transcription and protein expression level than in normal cervix, also in comparison to other cancers. See pg. 4, left column, paragraph 2.
Hornyak discloses IDO1 overexpression increases the relative concentration of kynurenine (Kyn) compared to tyrptophan (TRP), and concludes the Kyn/Trp ratio can be used as a prognostic clinco-pathological marker to monitor cancer invasiveness and progression, by exemplifying increased systemic Kyn/TRP ratio and elevated IDO1 activity having been associated with poor prognosis and low survival of patients diagnosed with cervical cancer, see pg. 4, right column, IDO1 in Cancer Diagnositics and Therapy, paragraph 1.
Although further attention is drawn to Fujiwara et al. (Published 30 August 2022, Cancer Treatment Reviews, Vol. 110, Article 102461, pp. 1-11, PTO-892), where Fujiwara discloses several IDO pathway inhibitors/modulators have been evaluated in clinical trials (summarized in Supplementary Table 1) where many of these trials showed disappointing results either with the use of IDO inhibitor monotherapy or when combined with other agents in a randomized setting, see pg. 4, left column, first full paragraph.nh
Fujiwara also openly questions whether IDO1 inhibitors block the activity of IDO1 and change tryptophan and kynurenine levels in cancer cells, adding an IDO1 blockade might be insufficient to suppress the production of tryptophan derivatives that are ligands to the aryl hydrocarbon receptor (AhR), where activation of the AhR suppresses anti-tumor immunity and induces tumor progression, and thus Fujiwara considers if tryptophan metabolites need to be fully reduced to exert the efficacy of IDO pathway inhibitors, see pg. 4, right column, last paragraph.
Moreover, particular attention is drawn to Huang et al. (Published 05 April 2019, CN-109574988-A, IDS filed 03/17/2022 known as CHENGDU HIGHBRED PHARMACEUTICAL CO LTD., et al., English Machine Translation used and provided in PTO-892 mailed 10/08/2024), where Huang discloses amide-substituted imidazo compounds in general formula (VIII)(g), including encompassing the compounds recited in claim 20 as IDO1 inhibitors, see CN-109574988-A, pg. 8, claim #18, compound (g).
Although Huang teaches these compounds as having inhibitory activity to oxidoreducing enzyme indoleamine 2,3-dioxygenase (IDO) and can be used for treating associated disease for example cancer, see CN-109574988-A, English Machine Translation, pg. 1, abstract; Huang only tests these compounds for IDO1 inhibition in one inhibition cell based assay using HeLa cells, see CN-109574988-A, paragraph [0613], and English Machine Translation, pg. 43, biological assay, paragraph 1.
Furthermore, although Applicant provides IDO1 inhibition as the potential mechanism of action for treating cancer cells as demonstrated by their HeLa-cell based IDO1 inhibition assay discussed in greater detail below, Croce (Published 31 January 2008, New England Journal of Medicine, Vol. 358, pp. 502-511, PTO-892) discloses tumors occur via a multistep process of sequential mutations in often several oncogenes, tumor-suppressor genes, or microRNA genes, see pg. 502, first paragraph, lines 1-7.
Croce further discloses that tumors possess cytogenetically different clones that arise from an initial transformed cell through additional genetic alterations, and that "this heterogeneity contributes to differences in clinical behavior and responses to treatment of tumors of the same diagnostic type", see pg. 502, second paragraph, lines 1-4.
Croce concludes by disclosing these heterogenous populations can differ in sensitivity to chemotherapy, radiotherapy, and other treatments making clinical management difficult, pg. 502, second paragraph, lines 6-8.
Thus, in viewing the state of the art as discussed above in its totality, the actual use of amide-substituted imidazo compounds in treating cancer per se, even if you consider the treatment mechanism of said compounds is mediated through inhibition of the IDO1 enzyme, said treatment in a subject in need thereof is currently unclear.
The relative skill in the art: The relative skill of those in the art is high.
The predictability or lack thereof in the art: As discussed above, the use of amide-substituted imidazo compounds in treating cancer per se is unknown. As a result, at the time of the invention the field of therapies to treat cancer per se by administering amide-substituted imidazo compounds were limited. Therefore, at the time of the invention the field of therapeutic use to treat cancer per se by administering amide-substituted imidazo compounds was relatively underdeveloped and unpredictable.
The breadth of the claims: The breadth of the claims is seen to encompass a method for treating any cancer by administering a compound of claim 20, or a pharmaceutically acceptable salt thereof.
The amount of direction or guidance present: The specification suggests a method for treating hyperproliferative disorders, such as cancer, by inhibiting indoleamine 2,3-dioxygenase (IDO), comprising administering to a subject a compound selected from and including compounds of Formula (I), see paragraph [0078]. The Examiner notes the compounds recited in instant claim 20 are encompassed by Formula (I) as disclosed in the specification.
However, Applicant’s suggestion of using said compounds recited in claim 20 for treating cancer per se via inhibition of IDO as the mechanism of action is based on Applicant’s speculation and is not supported by any existing experimental results in the art regarding the administration of amide-substituted imidazo compounds to treat any cancer in view of the state of the art above.
The presence or absence of working examples: Applicants’ specification provides Example F, a biological assay, see paragraph [0259], where cellular activity data, e.g. EC50s, of the instantly claimed compounds of claim 20 screened against HeLa cell-based IDO1 were tested, see paragraph [0269] and table 1; wherein all compounds recited in instant claim 20 exhibited inhibition of IDO1 in HeLa-cells with demonstrated EC50 values ranging less than 40.2 nM in Table 1, see paragraph [0269].
However, this experimental example is not an actual example of treating any cancer in a subject. Rather, it’s based on the extrapolation of the role IDO1 may have on cancer as a genus in view of the state of the art above and Applicants’ hypothesis regarding the mechanism of IDO1 activity level and the potential therapeutic effect it may have on any cancer.
Note the lack of working examples is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art such as the use of amide-substituted imidazo compounds in the treatment of any cancer in a subject.
The quantity of experimentation needed: In order to translate the suggestions in Applicants’ disclosure into an actual therapeutic model with the full range of all possible treatment methods beyond those known in the art, one skilled in the art would have to undertake a novel and extensive research program to show that any compound according to instant claim 20 could successfully treat any cancer in a subject. Therefore, because this research would have to be exhaustive, and because it would involve such a wide and unpredictable scope of cancers, it would constitute an undue and unpredictable search and experimental burden.
Genentech, 108 F.3d at 1366, 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 an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art and the lack of guidance or working examples, Applicants fail to provide sufficient information to practice the claimed invention.
Allowable Subject Matter
Claims 20-21 are allowed.
The following is a statement of reasons for the indication of allowable subject matter: Huang.
Applicant argues in their remarks filed August 07, 2026, the recited compounds of instant claim 20 achieve an unexpected potency of IDO1 inhibition in a HeLa-cell based inhibition assay as compared to compound 88 exemplified by Huang (see pg. 8, last paragraph), the results of said assay are demonstrated in Table 1 (see specification, pg. 70, paragraph [0269], Table 1).
Applicant argues compound 88 of Huang was directly compared to the recited compounds of instant claim 20 in said assay above where compound 88 of Huang is disclosed as Example Number 1 (Ex. No. 1) which demonstrated an EC50 value in said assay of 64.1 nM; whereas the compounds recited in instant claim 20 all demonstrated EC50 values of 40.2 nM or less, specifically the compounds of instant claim 20 correspond to said examples in Table 1 of the specification respectively where the EC50 value for each is provided within the parenthetical Ex. No. 4 (26.9 nM), 5 (38.8 nM), 6 (40.2 nM), 9 (12.6 nM), 10 (27.1 nM), 10b (17.1 nM), 14 (14.4 nM), 20 (6.9 nM), 21 (8.9 nM), 22 (3.12 nM), 22b (0.96 nM), and 24 (24.9 nM).
The Examiner notes when comparing the EC50 value of compound 88 of Huang (i.e. Ex No. 1) against the recited compounds of instant claim 20 said instantly claim compounds have an EC50 value that is between 37-99% lower than Ex. No. 1 which the Examiner reiterates is the exemplified compound 88 of Huang.
Additionally, as evidenced within the final rejection mailed March 25, 2026, on pg. 7, compound 88 of Huang comprises a methyl-substituted amido on the benzimidzole ring, whereas all instantly recited compounds of instant claim 20 comprise either a C3-C6 cycloalkyl-substituted amido or a phenyl-substituted amido on the benzimidzole ring.
Moreover, although Huang exemplifies within their HeLa-cell based IDO1 inhibition assay that substituting an unsubstituted amido on the benzimidzole ring, exemplified as compound 87 of Huang, for a methyl-substituted amido, exemplified as compound 88 of Huang, lowers the IC50 of compound 88 by 27% as discussed in the advisory action mailed July 10, 2026; Huang does not exemplify a structure comprising either a C3-C6 cycloalkyl-substituted amido or a phenyl-substituted amido on the benzimidzole ring; nor does Huang test such an exemplified compound within their IDO1 inhibition assay as discussed above.
Accordingly, in view of these considerations, the teachings of Huang as a whole, and in view of the EC50 values in Table 1 of the specification as discussed above, it would not have been obvious based on the teachings of Huang in their totality to expect substituting the methyl-substituted amido, exemplified as compound 88 of Huang to further lower the EC50 value by at least 37% and as much as 78% when the methyl group is substituted with either a C3-C6 cycloalkyl or phenyl as demonstrated in Ex. Nos. 4, 5, 6 and 14 where applicable; nor would it have been obvious to expect the additional limitations required within the recited compounds of instant claim 20 as a whole to have maintained said lowered EC50 value in said assay, as the Examiner reiterates for convenience all instantly recited compounds in claim 20 have a lower EC50 value between 37-99% when compared to Ex. No. 1 (i.e. compound 88 of Huang) as discussed above.
Therefore, in view of the foregoing reasons above, the teachings of Huang do not anticipate nor make obvious the compounds recited in instant claim 20 and are thus free of the prior art.
Claim 21 relies on the compounds recited in claim 20.
Conclusion
Claims 20-21 are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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