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 .
Information Disclosure Statement
Three information disclosure statement (IDS) submitted: One on February 15th, 2023; one on May 8th, 2023; and one on October 11th, 2023. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
The listing of references in the specification (starting on page 150) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Election/Restrictions
Applicant's election with traverse of Group I (drawn to claims 1-19 and 25), drawn to a method of treating a proliferative disorder in a patient using the compounds of Formula I, in the reply filed on September 11th, 2025, is acknowledged. The traversal is on the ground(s) that all three groups are linked by a special technical feature due to having similar structures.
This is not found persuasive because Formulae I, II, and III have different structures and would be expected to have different properties in a method of treating a proliferative disease.
Applicant disagrees with assertion that Formula I and II are disclosed by the cited prior art (Zhao et al.; New J. Chem., 2015, 39, 6016-6024 – cited in the IDS). However, applicant fails to specifically point out the discrepancies between the prior art compound the instant compounds.
The requirement is still deemed proper and is therefore made FINAL.
Upon election of Group I, Applicant was further required to elect a single compound of Formula I with all variables defined. Applicant elected the compound below, wherein R1 is N; L1 is
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; ring A
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; and ring B is unsubstituted
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(b1 = 0) reading on instant claims 1-12, 14-19, and 25.
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The elected compound is known in the art (Rice et al. (Angew. Chem. Int. Ed., 2018, 57, 13071-13075 – cited in IDS)), although not in the context of cancer treatment. The search was expanded to encompass the compounds of Formula I when R1 is N or phenyl, ring B is unsubstituted, and ring A is a monocyclic or bicyclic heterocycle.
Claims 1-12, 14-19, and 25 are under examination herein. Claims 13 and 20-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 11th, 2025.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The Description of the Drawings should be its own section in the specification, not part of the Examples. See 37 CRF 1.74. Both a Brief Description of the drawings and a detailed description of the drawings are required when drawings are present.
Drawings
The drawings are objected to because, in Figure 15a, one of the charts fails to show what the black box represents in the legend. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Status of the Claims
Claims 1-25 are pending in this application. Claims 1-12, 14-19, and 25 are under examination herein. Claims 13 and 20-24 are withdrawn from consideration.
Claim Objections
Claims 4-12, 14-15, 17-19, and 25 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claims and should refer to other claims in the alternative only. See MPEP § 608.01(n). See claim interpretations.
Claim 8 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 7. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Appropriate correction is required.
Claim Interpretation
For the purposes of expediting prosecution, instant claims 3-12, 14-15, 18-19, and 25, have considered on the merits by interpreting them as being dependent from claim 1 only. Claim 17 has been interpreted as being dependent from claim 16 only.
Claim 15 mentions “spherical monoanions, dianionic tetrahedrial, or trianionic tetrahedral.” The specification defines these anions as halides, sulphate, and phosphate, respectively [0297].
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 1-12, 14-19, and 25 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 written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the present case, while Applicant discloses exemplary compounds of Formula I that meet all the claim limitations [0226], the written description lacks enough detail to make use of the invention in the context of a method of treating cancer by administering any of the instant compounds of Formula I and a metal source.
Applicant discloses the synthesis of the elected compound of Formula I (hereafter L) and a related compound L1 [0349] and [0352]. No synthetic methods are disclosed for the preparation of embodiments where the group corresponding to instant R1 is anything other than nitrogen.
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Applicant discloses methods for the synthesis of mononuclear complexes [LZn](ClO4)2 and [LMn](ClO4)2 [0355] and trinuclear complexes [L2Zn3(SO4)](ClO4)4; [L2Mn3(SO4)](ClO4)4; [L2Cu3(O3POPh)](ClO4)4; and [L2Zn3(PO4)](ClO4)3 [0356].
Applicant discloses that the compounds of Formula II and III are active against a range of human cancer cell lines and inhibit a number of kinases; and that therapeutic uses involve administration of Formula I with a source of metal [0310]. Applicant discloses chemo-selectivity studies in vitro for some [L2M3]6+ complexes, wherein M is Zn, Cu, or Mn ([0369]-[0389]), in which metal complexes are pre-formed in DMSO prior to dilution for assays. Applicant shows in ovo (used interchangeably with in vivo) anticancer activity of [L2M3]6+, wherein M is Zn or Cu ([0391]-[0410]), in metal complexes were pre-formed in DMSO prior to further dilution before administration.
The written description provides no information on the specific anticancer activity of Formula I (without a metal complexed to it). In vitro and in ovo (in vivo) studies show premixing of the ligand and metal source to form complexes of Formula II or III prior to administration. The specification does not disclose the efficacy of treatment when the ligand and metal source are administered without pre-mixing. At least claim 1 calls for administering…a compound of formula I “in combination with a source of M…” Claim 1 does not require a complex between formula I and M. Thus, if Formula I were to be administered as a solid, with a source of M in the same or separate solid compositions, would this be effective for the treatment of cancers? Would the complexes of Formula II and III form in vivo without premixing in DMSO?
Since the formation of metal complexes is only demonstrated with ligand L; do all heterocycles (corresponding to rings A and B in Formula I) complex to metals (M) in the same fashion, so as to afford complexes of Formula II and III? Particularly, it is not explored whether heterocycles bearing an oxygen (as specified in the claims, wherein Xa/ b can be N or O), rather than nitrogen, will complex in the same fashion as ligand L. Furthermore, complexation of ligands wherein the group corresponding to R1 is anything other than nitrogen is not explored. Will ligands wherein R1 is anything other than nitrogen form metal complexes of Formulae II or III capable of treating cancer? The examples of the disclosure are not representative of the full scope of the claims.
In addition, while the claims speak to metals like Fe, Co, and Ni, the specification only explores complexes of L with Cu, Zn, and Mn, and shows that these metal complexes possess different properties (for example, in [0373], Applicant states that, unlike the Zn and Cu complexes, the Mn complex only showed modest selectivity of cancer cells over normal cells). Therefore, the examples shown are not representative of the full scope of the claims.
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 1-12, 14-19, and 25 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 regards as the invention.
Claim 1 recites the limitations “(in which case ring A is bonded directly to ring B)” and “(e.g. (1-3C)alkyl)”. The inclusion of such parentheses and the use of the exemplary “e.g.” raises the question as to whether this limitation is required. Examiner suggests removing the parentheses and content therein. See MPEP § 2173.05(d).
Regarding claim 17, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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, 3, 5-6, 11-12, 14-15, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao Jin’an et al. (hereafter Zhao) (New J. Chem., 2015, 39, 6016-6024 – previously cited and cited in IDS).
Regarding claim 1 and 25, Zhao discloses their compound tpbb below (scheme 1, page 6017, col. 1), which can form Zn complexes line 1 (Fig. 1, page 6017, col. 2). Zhao’s compound reads on the instant compounds of Formula I when instant R1 is aryl (phenyl); L1 is –(W)n-(X)m-(Y)o-(Z)p-, wherein W is C1-3 alkyl, n = 1, and m, o, and p are 0; A-Xa is a bicyclic heteroaryl, wherein Xa is N; L2 is absent; and B-Xb is a monocyclic heteroaryl, wherein Xb is N (pyridine). Zhao further teaches their compounds and metal complexes were regarded as potential candidates for fighting cancer (page 6020, col. 2, para. 2, lines 1-4).
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Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Zn-complex 1 for the treatment of a proliferative disorder, such as cancer. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Zhao’s disclosure of a compound tpbb and Zn-complex 1; further in view of Zhao’s disclosure that their Zn-complex shows potential as a candidate for fighting cancer.
Regarding claim 3, Zhao discloses their tpbb compound wherein the group corresponding to instant ring B is pyridine (6-membered heteroaryl with N immediately adjacent to the carbon bonded to L2).
Regarding claim 5, Zhao discloses their tpbb compound wherein the group corresponding to instant ring B is pyridine.
Regarding claim 6, Zhao discloses their compound tpbb above, wherein the group corresponding to instant W is C1-3 alkyl and n = 1, and m, o, and p are 0.
Regarding claim 10, Zhao discloses their compound tpbb above, wherein the group corresponding to instant L2 is absent.
Regarding claims 11-12, Zhao discloses their compound tpbb above, wherein the group corresponding to instant R1 is phenyl.
Regarding claim 14, Zhao discloses their complex 1 above complexing to Zinc ions.
Regarding claim 15, Zhao discloses their complex 1 above wherein the anions are chlorides (spherical monoanionic).
Relevant Art of Record
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Tyagi (Dalton Trans., 2015, 44, 15591 – cited in IDS) discloses the compound Bz-NI below (page 15592, scheme 1), which can form copper complexes like 2. Tyagi discloses the potential of these biomimetic compounds as cytotoxic anticancer agents (abstract, last line).
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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.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627