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 .
Priority
The instant claims benefit to provisional application No. 63/531,954 filed on August 10, 2023.
Status of Claims
Acknowledgement is made of original (1-24) claims filed on August 12, 2024. Claims 1-24 are pending in instant application.
Information Disclosure Statement
The information disclosure statement filed on June 18, 2025 has been considered.
Claim Rejections - 35 USC § 112(b)
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.
Claim 23 is 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 23 recites “A supramolecular complex comprising: sulfonato-C-methylresorcin[4]arene (SRsC1); and a fluoroquinolone compound; or a salt thereof.” It is unclear is “a salt thereof” is referring to SRsC1 or the fluoroquinolone compound or both.
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.
Claim(s) 1-4, 6, 10-11, 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Rafols et. al.1 in view of Kashapov et. al.2
Regarding a complex, Rafols teaches strategies to improve solubility of poor-solubility drugs, such as inclusion in complexes with macromolecules such as cyclodextrines (see Rafols at p. 61 ¶1).
Regarding claims 1-4 a fluoroquinone and claims 10-11 and treating an infection, Rafols teaches ciprofloxacin is a poorly soluble fluoroquinolone antibiotic, active against Gram-positive and Gram-negative bacteria (see Rafols at p. 62 ¶1). Rafols teaches co-crystalizing ciprofloxacin with resorcinol improves dissolution rate at intermediate pHs (see Rafols at p. 68 ¶1). It would be obvious to an artisan to administer a known antibiotic drug to a subject in need for its intended purpose.
Regarding claim 6 and a binding ratio, Rafols teaches co-crystals of two components are stoichiometric systems connected by non-covalent interactions such as van der Waals, π-π interactions, and H-bonding (see Rafols at p. 61 ¶2 - p. 62 ¶1).
The prior art differs from the instant claims as follows: While Rafols teaches ciprofloxacin can complex with macromolecules like cyclodrextrin or co-crystallize with resorcinol to improve solubility and treat infection, Rafols does not specify i) a macrocycle according to Formula I, ii) killing or inhibiting the growth of bacteria, or iii) a stoichiometric ratio.
However,
Regarding claims 17-18 and killing a bacteria or inhibiting growth, an artisan would recognize a known treatment for known bacteria infections would be killing and/or inhibiting the growth of the bacteria responsible as it comes in contact.
Regarding claim 1 and a compound of Formula I, Kashapov teaches macrocycle upper-rim sulfonated calix[4]resorcinol (USR), also known as CAS# 2701589-89-9 (see Kashapov at p.18277 Figure 1). CAS# 2701589-89-9 reads on instant Formula I when R1 is C1-20alkoxy specifically propanol, R2 is H, and X+ is a cation, specifically Na+.
Kashapov USR
CAS# 2701589-89-9
Instant Formula I
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388
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352
388
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Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding claim 1 and a complex, per MPEP § 2144.07, a prima facie case of obviousness exists for the selection of a known material based on its suitability for its intended use. Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). Per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to one skilled in the art to complex ciprofloxacin (as taught by Rafols) with a known resorcinol-macrocycle such as CAS# 2701589-89-9 (as taught by Kashapov) or a derivative with a reasonable expectation of success, because the prior art teaches ciprofloxacin is poorly soluble, its solubility is improved by crystallizing with resorcinol, and complexing with a macrocycle is a known strategy in the art for improving solubility (see Rafols at p. 61 ¶1 and Abstract).
Regarding claim 6 and a 1:1 stoichiometric ratio, Per MPEP § 2144.05(II), generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. It would have been obvious to one skilled in the art to determine a stoichiometric ratio for loading ciprofloxacin into a macrocycle through routine optimization. Rafols teaches multi-component systems have stoichiometric ratios, and it would have been obvious to one skilled in the art to determine the ratio of a resorcinol macrocycle-ciprofloxacin mixture when isolating or characterizing.
Furthermore, it is well-within the ordinary skill in art to improve upon a known drug by combining with another known substance when the art teaches such a strategy improves the drug.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 5, 23, 24 are rejected under 35 U.S.C. 103 as being unpatentable over Rafols in view of Kashapov as applied to claims 1-4, 6, 10-11, 17-18 above and in further view of Hasselbrink et. al.3
Regarding claims 5, 23, 24 and SRsC1, Kashapov’s CAS# 2701589-89-9 only differs from instant SRsC1 by R1. Whereas CAS# 2701589-89-9 has propane, instant SRsC1 has methyl.
However,
Hasselbrink teaches compound 3S, a resorcinol macrocycle (see Hasselbrink at p. 16074 Figure 1) wherein R1 is ethyl, differing by instant SRsC1 by only a change of -CH2-.
Hasselbrink 3S
CAS# 2648020-97-5
Instant SRsC1
CAS# 3075219-21-2
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386
392
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304
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Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because “[c]ompounds which are…homologs…are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties” (see, e.g., MPEP § 2144.09(I)-(II)), and the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. In addition, per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. Here, the prior art teaches highly similar structural resorcinol derivative of the instantly claimed invention. Accordingly, an artisan would readily appreciate that such compounds could be utilized for the same purposes.
Furthermore, it is well-within the ordinary skill in art to make an alkyl group change of ethyl for methyl in a known compound.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Rafols in view of Kashapov as applied to claims 1-4, 6, 10-11, 17-18 above and in further view of Remington et. al.4
The prior art differs from the instant claims as follows: While Rafols and Kashapov teach complexing ciprofloxacin with a resorcinol macrocycle, they do not specify an additional carrier or formulation.
Remington teaches artisans how to formulated compositions for different administration routes (see Remington at pp. xxi "Pharmaceutical Manufacturing"). For example, parenteral drugs administered intravenously offer rapid distribution in the body and faster onset of action (see Remington at p. 843 left col. ¶1), and drugs can be formulated with saline, sugars, amino acids, or electrolytes with the fluids serving as the vehicle (reading on instant carriers) (see Remington at p. 837 right col. and p. 838 left col. ¶3).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
It would have been obvious to formulate a treatment (as taught by Rafols and Kashapov) for a desired administration route such as parenteral including with the addition of a carrier, because the prior art instructs artisans how, in order to administer to a patient (as taught by Remington).
Furthermore, it is well-within the ordinary skill in art to formulate a known treatment for a specified administration route as taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 12-16, 19-22 are rejected under 35 U.S.C. 103 as being unpatentable over Rafols in view of Kashapov as applied to claims 1-4, 6, 10-11, 17-18 above and in further view of Shariati et. al.5
The prior art differs from the instant claims as follows: While Rafols and Kashapov teach complexing ciprofloxacin with a resorcinol macrocycle for treating Gram-negative or Gram-positive bacteria infections (see also claims 14, 20) or killing/inhibiting growth of bacteria, they do not specify i) bacterial infection classes, ii) bacteria species, iii) antibiotic resistance, iv) or disrupting bacteria biofilm.
However,
Regarding claim 12 and a bacterial infection, Shariati teaches ciprofloxacin has been used to treat a range of diseases, including chronic otorrhea, endocarditis, lower respiratory tract, gastrointestinal, skin and soft tissue, and urinary tract infections (see Shariati at p.1 ¶1)
Regarding claims 13, 15-16, 19 and bacteria species and antibiotic resistance, Shariati teaches Salmonella typhi, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa have all shown an increase in ciprofloxacin resistance over time (see Shariati at p.01 ¶1).
Regarding claims 21-22 and disrupting biofilm, Shariati teaches nano-platforms could enhance the efficiency of ciprofloxacin against bacterial cells, interfere with the biofilm community, enhance the penetration and protect the drug from deactivation or efflux (Shariati at p. 16 left col. ¶4).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
It would have been obvious to one skilled in the art to administer a ciprofloxacin with a resorcinol macrocycle (as taught by Rafols and Kashapov) to a subject infected with a ciprofloxacin-resistant species (as taught by Shariati) because the prior art indicates incorporation of ciprofloxacin with larger components such as nano-platforms enhances ciprofloxacin efficiency against bacterial cells, biofilm, and drug penetration.
Furthermore, it is well-within the ordinary skill in art to administer a known treatment for known infections as taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Conclusion
Claims 1-24 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./ Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Rafols "Dissolution ratesof ciprofloxacin and its cocrystal with resorcinol" ADMET 2018, 61-70.
DOI: 10.5599/admet.6.1.497. Hereinafter Rafols.
2 Kashapov et. al. "Supraamphiphilic Systems Based on Metallosurfactant and Calix[4]resorcinol: Self-Assembly and Drug Delivery Potential" Inorganic Chemistry, 2020, 59, 24, 18276-18286.
DOI: 10.1021/acs.inorgchem.0c02833. Hereinafter Kashapov.
3
4 Remington's Pharmaceutical Sciences (21st Ed) New York, NY: Lippincott Williams and Wilkins 2005. Select Pages. Hereinafter Remington.
5 Shariati et. al. "The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic" Front. Public Health, 2022, 1-28. DOI: 10.3389/fpubh.2022.1025633. Hereinafter Shariati.
Prosecution Insights