DETAILED ACTION
A non-final Office action was mailed 22 September 2025 (“Office Action”).
Applicant’s reply to the Office Action was received 19 February 2026 (“Reply”).
Status of the Claims
The listing of claims filed with the Reply has been examined.
Claims 1, 2, 4, 14–16, 18, 29, 33, 39, 42, 46–49, 53, 55, 56, and 94–101 are pending.
Claims 3, 5–13, 17, 19–28, 30–32, 34–38, 40, 41, 43–45, 50–52, 54, 57–93 are canceled.
Claims 1, 2, 4, 14–16, 18, and 33 are amended. Claims 94–101 are new.
Claims 39, 42, 46–49, 53, 55, and 56 are withdrawn.
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Unless repeated herein, any objection or rejection in the Office Action is withdrawn.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 Objections
Claim 101 is objected to for using improper capitalization. Trademarks may not be improperly used in claims. (MPEP § 2173.05(u)). In this case, the capitalizations appear to be a typographical error rather than a reference to a trademark because terms like topotecan and doxorubicin, for example, are common names for the compounds in branded drugs. The capitalization of a common name is not necessary or proper.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
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.
Claims 16, 99, and 101 are rejected under 35 U.S.C. § 112(b) 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 16 recites, “advanced stage of cancer,” which is a relative term that renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 99 depends from claim 16 and is rejected because it incorporates the indefinite claim language without resolving its ambiguity.
Claim 101 recites, “wherein at least of the following applies:” along with nine options (a)–(i). The claim is ambiguous because it is unclear whether one, two, three, etc. of the nine options is required (e.g., “wherein at least one of the following applies”).
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 102
Claims 1, 2, 14–16, 29, 33, 94–96, and 99 are rejected under 35 U.S.C. §§ 102(a)(1) and/or 102(a)(2) as being anticipated by US 2006/0099712 (“Gilman”) [IDS].
Regarding claims 1, 15, and 16, Gilman discloses a method of administering to a mammal a cyanine dye compound with anticancer properties to treat carcinomas or melanomas. (Gilman, ¶¶63; 73; 74; 81; 84; 125–134). Carcinomas include colon, breast, pancreatic, bladder, lung, squamous, and adrenal cortex. (Id., ¶¶85; 125–134).
Regarding claim 1, Gilman discloses cyanine dye compounds including, for example, D-122, which reads on instant Formula I when X = O; Y = S; n = 2; R2 & R3 = C1–5 hydrocarbyl:
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. (Id., ¶73).
Gilman explains cyanine dyes have a positive charge that is delocalized between nitrogen atoms positioned at terminal ends of a methine chain. (Id., ¶5). One of ordinary skill in the art would appreciate the positive charge in D-122 is delocalized between the nitrogen atoms as the electrons in the conjugated double bonds are delocalized between resonance structures, resulting in a corresponding structure that reads on instant Formula I when X = S and Y = O.
Regarding claims 2 and 96, compound D-122 is an iodide salt.
Regarding claim 14, Gilman discloses compound D-165 (below left, m = 1) and a related compound (Table III, line 2, m = 2) corresponding to the compound in instant claim 14.
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(Id., ¶¶73; 139).
Regarding claim 29, Gilman discloses the treatment of cancer in people. (Id., ¶4). Gilman discloses a screening of cyanine dyes against human cell lines. (Id., ¶¶16 (Table 1); 25; 36; 93). A human subject is also implied in additional disclosures. (Id., ¶¶2; 82).
Regarding claims 94 and 95, Gilman discloses administering a pharmaceutical composition comprising a cyanine dye compound. The administration can be intravenous (IV). (Id., ¶¶81–87).
Regarding claim 16, Gilman does not exclude any particular patient population in the context of treating carcinomas of the colon, breast, pancreatic, bladder, lung, squamous, and adrenal cortex; thus, advanced-stage patients fall within the scope of Gilman’s disclosure.
Regarding claim 99, Gilman does not distinguish between neuroendocrine or non- neuroendocrine cancers, and therefore does not exclude any particular pancreatic cancers. A pancreatic neuroendocrine tumor falls within the scope of Gilman’s disclosure.
Claim 33 requires the subject to have a certain desired concentration of the compound in the plasma or pancreas “after administration.” The desired concentrations relate to an intended result. Courts have held expressions of an intended result in a method claim are not given much patentable weight. (MPEP § 2111.04). In this case, compound D-122 falls within the scope of instantly claimed Formula I. For a Markush group to be proper, the members of the Markush group are expected to possess one or more similar properties. Accordingly, one of ordinary skill in the art would expect compound D-122, which falls within the claimed Markush group, to share properties with the other Markush members and be capable of the claimed intended result.
Claim Rejections - 35 U.S.C. § 103
(i) Claims 4, 97, and 98 are rejected under 35 U.S.C. § 103 as being unpatentable over Gilman in view of Lee et al., Small (2018), 14, 1702564, 7 pages (“Lee”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
The disclosures of Gilman are discussed above and are hereby incorporated by reference.
Lee discloses a drug delivery system comprising nanomaterials. Lee explains that mutation of cancer cells are a main problem in anticancer therapy because a mutation can make single small molecule therapy ineffective. (Id., p.1). Lee discloses a strategy of combination therapy, which may induce synergistic anticancer effect. (Id., pp.1–2). Lee discloses a system designed for combination therapy (“dual-cargo”), in which the drugs are released through different sized pores. (Lee, pp.1–2). The system comprises silica nanoparticles and has been used to deliver cyanine dye 5 fluorescently labeled DNA in a human cervical cancer cell line. (Id.).
Claim 98 further defines the targeting agent in claim 97 but does not actually require a targeting agent to be selected from the options in claim 97. Claim 98 does not recite, for example: “The method of claim 97, wherein the encapsulating agent comprises a targeting agent, and wherein the targeting agent comprises . . .” Such a clause requiring the targeting agent will not be implicitly read into the claim. As a dependent claim, claim 98 incorporates all limitations from claims 1, 4, and 97; and, if claim 98 were written into independent form the combination of Gilman and Lee would be sufficient to reject the claim.
Ascertaining the differences between the prior art and the claims at issue
Gilman does not disclose the use of an encapsulating agent. Lee is relied on for that claim feature.
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 examples and data in the instant application has been considered but do not show any unexpected results with respect to an encapsulating agent.
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 Gilman and Lee to arrive at a method of treating one or more types of cancer by administering a cyanine dye compound from Gilman in an encapsulating agent in Lee. One of ordinary skill in the art would have been motivated to combine the teachings of the cited references because Lee teaches an encapsulating agent can be used to deliver a cyanine dye along with another agent to a cancer cell in order to thwart a potential mutation that can make the cyanine dye ineffective; and there would have been a reasonable expectation of success because Lee demonstrates the encapsulating agent using a cyanine dye compound.
(ii) Claims 18, 100, and 101 are rejected under 35 U.S.C. § 103 as being unpatentable over Gilman in view of Zhan et al., ACS Appl. Mater. Interfaces (2019), 11, 15354–365 (“Zhan”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
The disclosures of Gilman are discussed above and are hereby incorporated by reference.
Zhan states, “5-Fluorouracil (5-FU) is a pyrimidine analogue and a traditional anticancer drug widely used to treat various cancers, especially colorectal and breast cancers.” (Zhan, p.15354).
Zhan states, “In recent years, several approaches have been developed to address these issues [e.g., short half-life, drug resistance, lack of targeting, side effects], including combining other chemotherapies (such as, leucovorin and irinotecan) and loaded with drug vehicles (nano-biomaterials).” (Id.).
Zhan states, “Cyanine 5 (Cy5) is a fluorescent probe, which can be attached to nucleotide sequences and be commonly used to track the intracellular location of biomaterials because of its stable fluorescence intensity.” (Id., p.15355).
Zhan states, “In this study, we constructed and characterized DNA-based nanomedicine modified with 5-FU and AS1411 (AS1411-T-5-FU), determined its tumor cell-killing effects, and then attached with Cy5 to analyze the cellular uptake using flow cytometry and immunofluorescence staining. The results revealed that AS1411-T-5-FU possessed structural stability, biocompatibility, potent toxicity, and preferential killing ability toward cancer cells, converging the multiple benefits of 5-FU, AS1411, and DNA tetrahedron. Moreover, AS1411-T-5-FU also showed enhanced therapeutic efficacy against breast cancer cells (MCF7 cell line) mediated by improved nuclear absorbability than 5-FU. More importantly, the DNA-based nanomedicine did not have side effects on breast normal cells (MCF10A cell line), implying the amelioration of 5-FU.” (Id.).
Ascertaining the differences between the prior art and the claims at issue
Gilman does not disclose a combination therapy for treating cancer. Zhan is relied on for that claim feature.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill is resolved in a rejection above.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Example 2 is directed to MIA-PaCa2 pancreatic cancer cells. Example 2 states “a variety of compounds having the Formula I structure (JAC-B1, JAC-B1.5, JAC-B2, JAC-B2.5, JAC-B3, JAC-R1, JAC-R2, JAC-R3 also known as dithiazanine iodide)” were used. Table 2 shows a summary of the combined efficacy of a compound of Formula I and an additional therapeutic agent, but the Table only summarizes results for JAC-B2 and only in the context of pancreatic cancer. The data disclosed in the Table does not refer to compounds other than JAC-B2 or to subjects other than MIA-PaCa2 pancreatic cancer cells.
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 Gilman and Zhan to arrive at a method of treating a cancer (e.g., breast cancer) with a cyanine dye compound of instant Formula I (e.g., Gilman D-122) and at least one other chemotherapeutic agent (e.g., 5-FU). Gilman discloses a method of treating cancer with, e.g., compound D-122, and Zhan discloses that combination therapy is useful to treat cancers, e.g., breast cancer, to address issues like drug resistance and lack of cancer cell targeting. Although Cy5 was used as an imaging agent as opposed to an anticancer agent, Zhan teaches 5-FU can be safely combined with a cyanine dye. Therefore, one of ordinary skill in the art would have been motivated to combine the teachings of the cited references to address issues with single small molecule therapy and to arrive at the claimed method with a reasonable expectation of success.
The evidence in the instant application has been considered but is not commensurate in scope with the claims and/or not sufficient to overcome a prima facie case of obviousness.
Conclusion
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 C.F.R. § 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 C.F.R. § 1.17(a)) pursuant to 37 C.F.R. § 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Communication
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/J.M.N./Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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