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 .
Election/Restrictions
Applicant’s election without traverse of Group I claims 1-12 in the reply filed on 01/27/2026 is acknowledged.
Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups II and III, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/27/2026.
Priority
The instant application claims domestic priority to PRO 63/260,255 filed 08/13/2021. The instant application is a 371 of PCT/CN2022/112047 filed 08/12/2022.
Information Disclosure Statement
The information disclosure statements (IDS) dated 07/23/2025 and 02/08/2024 both comply with provisions of 37 CFR 1.97, 1.98 and MPEP §609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Specification
The disclosure is objected to because of the following informalities: blurry image, the structural diagram on page 1 is blurry the term believed to be fluoride may or may not have a charge present in the structure.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
A) Claims 1-3, 5, and 7-12 are rejected under 35 U.S.C. 103 as being unpatentable over Raptis (US Patent Application Publication 20220047628A1).
Raptis recites a silver complex;
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with PTA and a halogen (fluoride is a halogen) (Raptis at claim 1). Raptis recites the use of fluoride (Raptis at claim 7). Raptis recites a structure (5)
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Raptis teaches Ag(I) pyrazolido complexes, according to the subject invention, can be provided separately or in combination as medicaments that are antibacterial, antiviral, antifungal, or any combination thereof. The medicaments can be formulated according to known methods for preparing pharmaceutically useful compositions. Such pharmaceutical compositions can be adapted for various forms of administration, such as, but not limited to, oral, parenteral, intravenous, nasal, topical, pulmonary, and transdermal. The Ag(I) pyrazolido complexes, according to the subject invention, can be provided as solutions, amorphous compounds, injectables, pills, inhalants, or in any other form for administration. The compositions comprising Ag(I) pyrazolido complexes of the subject invention can include pharmaceutically acceptable carriers or diluents. Formulations are described in a number of sources, which are well known and readily available to those skilled in the art. For example, Remington's Pharmaceutical Science (Martin E W [1995] Easton Pa., Mack Publishing Company, 19th ed.) describes formulations that can be used in connection with embodiments of the invention (Raptis at [0132]). It should be noted that Remington’s Pharmaceutical Science teaches the use of ethanol, water, oil, and emulsions. Raptis teaches that formulations suitable for administration include, e.g., aqueous sterile injection solutions, which may contain antioxidants, buffers, bacteriostats, and solutes, which render the formulation isotonic with the blood of the intended recipient; and aqueous and nonaqueous sterile suspensions, which may include suspending agents and thickening agents (Raptis at [0133]). Raptis teaches that formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze dried (lyophilized) condition requiring only the condition of the sterile liquid carrier, for example, water for injections, prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powder, granules, or tablets of the Ag(I) pyrazolido complex comprising compositions. It should be understood that in addition to the ingredients particularly mentioned above, the formulations of the subject invention can include other agents conventional in the art having regard to the type of formulation in question (Raptis at [0134]). Raptis further teaches pharmaceutically acceptable carriers used in Ag(I) pyrazolido complex formulations according to the subject invention include, but are not limited to, inert diluents and vehicles such as: one or more excipients, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and aerosol sprays. Tablets, troches, pills, capsules, and the like may, but do not necessarily, contain binders, such as gum tragacanth, acacia, corn starch or gelatin; excipients, such as dicalcium phosphate; disintegrating agents, such as corn starch, potato starch, or alginic acid; lubricants, such as magnesium stearate; sweetening agents, such as sucrose, fructose, lactose or aspartame; flavoring agents, such as peppermint, oil of wintergreen, or cherry flavoring; liquid carriers, such as a vegetable oil or a polyethylene glycol; and/or solid carriers; such as finely divided solids such as talc, clay, microcrystalline cellulose, silica, or alumina. Any material used in preparing the dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed. The dosage form may be a sustained-release preparation. Other dosage forms can include surfactants or other adjuvants. Liquid compositions for topical use can be applied from absorbent pads or be impregnated on bandages and other dressings. Thickeners, such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified celluloses or modified mineral materials, can be employed with liquid carriers (Raptis at [0135]).
Raptis differs from the instant claims in this rejection insofar as it does not teach the combination of the instantly recited components with sufficient specificity for anticipation. Raptis teaches the components of the instant recited composition and uses each component of their established function in the art but does not explicitly combine the components together into a single embodiment or a preferred composition. However, given the disclosure of each component individually, it would have been prima facie obvious to a person having ordinary skill in the art at a time prior to the filing of the present patent application and following the teachings of Raptis to have selected and combined known components for their established functions with predictable results. MPEP §2143 and §2144.06(I).
Regarding instant claim 1-3, Raptis recites a structure (5) with the two silver PTA complexes.
Instant Application
Raptis et al
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Raptis recites a silver complex; with PTA and a halogen (fluoride is a halogen) (Raptis at claim 1). Raptis recites the use of fluoride (Raptis at claim 7).
Regarding instant claim 5, Raptis recites a structure (5) with the two silver PTA complexes.
Instant Application
Raptis et al
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Raptis recites a silver complex; with PTA and a halogen (fluoride is a halogen) (Raptis at claim 1). Raptis recites the use of fluoride (Raptis at claim 7). Raptis teaches that formulations suitable for administration include, e.g., aqueous sterile injection solutions (Raptis at [0133]).
Regarding instant claim 7, Raptis teaches that the composition may be stored in a freeze dried (lyophilized) condition requiring only the condition of the sterile liquid carrier, for example, water for injections (Raptis at [0134]).
Regarding instant claim 8, Raptis teaches that formulations suitable for administration include, e.g., aqueous sterile injection solutions, which may contain antioxidants, buffers, bacteriostats, and solutes, which render the formulation isotonic with the blood of the intended recipient; and aqueous and nonaqueous sterile suspensions, which may include suspending agents and thickening agents (Raptis at [0133]).
Regarding instant claim 9, Raptis teaches that formulations suitable for administration include, e.g., aqueous sterile injection solutions, which may contain antioxidants, buffers, bacteriostats, and solutes, which render the formulation isotonic with the blood of the intended recipient; and aqueous and nonaqueous sterile suspensions, which may include suspending agents and thickening agents (Raptis at [0133]).
Regarding instant claim 10, Raptis teaches the use of liquid carriers, such as a vegetable oil or a polyethylene glycol (Raptis at [0135]). Polyethylene glycol is miscible with water. Raptis further teaches that formulations are described in a number of sources, which are well known and readily available to those skilled in the art. For example, Remington's Pharmaceutical Science (Martin E W [1995] Easton Pa., Mack Publishing Company, 19th ed.) describes formulations that can be used in connection with embodiments of the invention (Raptis at [0132]). It should be noted that Remington’s Pharmaceutical Science teaches the use of ethanol, water, oil, and emulsions. One of ordinary skill in the art would therefore be able to select a solvent that is water miscible.
Regarding instant claim 11, Raptis teaches that formulations are described in a number of sources, which are well known and readily available to those skilled in the art. For example, Remington's Pharmaceutical Science (Martin E W [1995] Easton Pa., Mack Publishing Company, 19th ed.) describes formulations that can be used in connection with embodiments of the invention (Raptis at [0132]). It should be noted that Remington’s Pharmaceutical Science teaches the use of ethanol, water, oil, and emulsions. One of ordinary skill in the art would therefore be able to select the use of ethanol with water as taught by Remington’s Pharmaceutical Science.
Regarding instant claim 12, Raptis teaches the use of flavoring agents, such as peppermint, oil of wintergreen, or cherry flavoring; liquid carriers, such as a vegetable oil or a polyethylene glycol (Raptis at [0135]). Raptis further teaches the use of suspensions (Raptis at [0135]). Therefore, Raptis teaches aqueous sterile injection solutions (Raptis at [0133]), oils and suspensions. Raptis further teaches that formulations are described in a number of sources, which are well known and readily available to those skilled in the art. For example, Remington's Pharmaceutical Science (Martin E W [1995] Easton Pa., Mack Publishing Company, 19th ed.) describes formulations that can be used in connection with embodiments of the invention (Raptis at [0132]). It should be noted that Remington’s Pharmaceutical Science teaches the use of ethanol, water, oil, and emulsions. Therefore, one of ordinary skill in the art would be able to make the oil and water into an emulsion.
B) Claims 4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Raptis (US Patent Application Publication 20220047628A1) as applied to claims 1-3, 5, 7-12 above, and further in view of Endrizzi et al (Cu(i) and Ag(i) complex formation with the hydrophilic phosphine 1,3,5-triaza-7-phosphadamantane in different ionic media. How to estimate the effect of a complexing medium. Endrizzi et al. Dalton Trans., 2017,46, 1455-1466).
The teachings of Raptis are discussed above.
The teachings of Raptis differ from the instant claims insofar as they do not specifically teach the use of [Ag(1,3,5-triaza-7- phosphaadamantane)2]F alone. The teachings of Endrizzi cure this deficit.
Endrizzi teaches that the complexes of Cu(I) and Ag(I) with 1,3,5-triaza-7-phosphadamantane (PTA) are currently studied for their potential clinical use as anticancer agents, given the cytotoxicity they exhibited in vitro towards a panel of several human tumor cell lines. These metallodrugs are prepared in the form of [M(PTA)4]+ (M = Cu+, Ag+) compounds and dissolved in physiological solution for their administration. However, the nature of the species involved in the cytotoxic activity of the compounds is often unknown. In the present work, the thermodynamics of formation of the complexes of Cu(I) and Ag(I) with PTA in aqueous solution is investigated by means of potentiometric, spectrophotometric and microcalorimetric methods. The results show that both metal(I) ions form up to four successive complexes with PTA. The formation of Ag(I) complexes is studied at 298.15 K in 0.1 M NaNO3 whereas the formation of the Cu(I) one is studied in 1 M NaCl, where Cu(I) is stabilized by the formation of three successive chloro-complexes. Therefore, for this latter system, conditional stability constants and thermodynamic data are obtained. To estimate the affinity of Cu(I) for PTA in the absence of chloride, Density Functional Theory (DFT) calculations have been done to obtain the stoichiometry and the relative stability of the possible Cu/PTA/Cl species. Results indicate that one chloride ion is involved in the formation of the first two complexes of Cu(I) ([CuCl(PTA)] and [CuCl(PTA)2]) whereas it is absent in the successive ones ([Cu(PTA)3]+ and [Cu(PTA)4]+). The combination of DFT results and thermodynamic experimental data has been used to estimate the stability constants of the four [Cu(PTA)n]+ (n = 1–4) complexes in an ideal non-complexing medium. The calculated stability constants are higher than the corresponding conditional values and show that PTA prefers Cu(I) to the Ag(I) ion. The speciation for the two systems shows that the [M(PTA)4]+ (M = Cu+, Ag+) complexes present in the metallodrugs are dissociated into lower stoichiometry species when diluted to the micromolar concentration range, typical of the in vitro biological testing. Accordingly, [Cu(PTA)2]+, [Cu(PTA)3]+ and [Ag(PTA)2]+ are predicted to be the species actually involved in the cytotoxic activity of these compounds (Endrizzi at abstract).
The teachings of Endrizzi differ from the instant claim insofar as they do not specifically teach the use of fluoride. The teachings of Raptis cure this deficit.
One of ordinary skill in the art would be motivated to combine the [Ag(PTA)2]+ with the composition of Raptis for the benefit of cytotoxic activity as taught by Endrizzi.
One of ordinary skill in the art would have been motivated to combine the [Ag(PTA)2]+ with the composition of Raptis for the benefit of it dissociating into the smaller sections due to the micromolar concentrations used to in biological study as taught by Endrizzi.
One of ordinary skill in the art would be motivated to add fluoride as the anion in the composition of Endrizzi as Raptis teaches it a halogen along with other halogens like chloride. See MPEP 2144.06(I). See MPEP2144.07.
Conclusion
No claims are presently allowable.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA MICHELLE PETRITSCH whose telephone number is (571)272-6812. The examiner can normally be reached M-F 08:30-17:00 EST ALT Fridays.
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/AMANDA MICHELLE PETRITSCH/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612