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 present application claims benefit under 35 U.S.C. 119(e) to U.S. Provisional Application No. 63/133,257 filed 1 January 2021. Applicants claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365 (c) is acknowledged.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 30 June 2023 and 12 September 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statement is being considered by the examiner. The reference “Conway, S.P. “REVIEW SERIES: Practical management of Cystic Fibrosis” has not been considered due to the reference not being included in the IDS.
Claim Objections
Claim 6 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. 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).
Claim 16 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 14. 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).
Claim 18 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 11. 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).
Claim 24 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 19. 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).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3, 5-6, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al, hereafter “Liu” (“Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria.” Acta Biomater. 2018 Dec;82:133-142. doi: 10.1016/j.actbio.2018.10.013. Epub 2018 Oct 11. PMID: 30316023.), as in the IDS filed 30 June 2023.
Regarding claim 1, Liu teaches a method of reducing toxicity of polymyxins as a therapeutic agent comprising a step of co-administrating a polymyxin (colistin) with PGA (pg. 133 [Abstract] “With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, a nanoformulation is herein developed through coacervate complexation with polyanionic peptides. Upon controlled mixing of cationic colistin with polyglutamic acids, formation of liquid coacervates was demonstrated. … Upon administration over a 7-day period, colistin nanoparticles also exhibited reduced hepatotoxicity as compared to free colistin.”).
Regarding claim 3, Liu teaches a method of reducing the toxicity of polymyxins according to claim 1, and further discloses where the therapeutic agent is used to treat a respiratory infection (pg. 133 [Abstract] “In mouse models of Klebsiella pneumoniae bacteremia and Acinetobacter baumannii pneumonia, treatment with colistin nanoparticles showed equivalent efficacy to free colistin.”; pg. 140 “Notably, colistin nanoparticle treatment showed signs of improved bacterial reduction in organs such as lungs and kidneys.” ).
Regarding claim 5, Liu teaches the therapeutic agent being polymyxin E (colistin) (pg. 133 [Abstract] “With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, a nanoformulation is herein developed through coacervate complexation with polyanionic peptides.”).
Regarding claim 6, Liu teaches the therapeutic agent being administered with polyglutamic acid (pg. 133 [Abstract] “Upon controlled mixing of cationic colistin with polyglutamic acids,...”)
Regarding claim 9, Liu teaches a method of co-formulating polyglutamic acid (PGA) and a polymyxin (pg. 134 “Given the polycationic characteristic of colistin, we herein prepared a colistin nanocomplex through coacervate complexation with anionic polyglutamic acid (PGA).”).
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 2 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (“Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria.”), as applied to claim 1 above, and further in view of Dubashynskaya & Skorik, hereafter “Dubashynskaya” (“Polymyxin Delivery Systems: Recent Advances and Challenges.” Pharmaceuticals (Basel). 2020 Apr 29;13(5):83. doi: 10.3390/ph13050083. PMID: 32365637; PMCID: PMC7281078.).
Regarding claim 2, Liu teaches a method of reducing toxicity of polymyxins, as applied to claim 1 above.
Liu does not teach the method of reducing toxins to be used to attenuate lung toxicity caused by the polymyxins.
Dubashynskaya teaches a method for reducing the toxicity of polymyxins comprising the method taught in Liu, while also teaching that the addition of PGA reduces the toxicity caused by colistin (polymyxin E) (pg. 4, “In addition, solid polymeric particles and liposomes have suitable sizes (1–5 µm, and less than 1 µm) for antibiotics to reach the lower airways and infected foci by inhalation administration. Consequently, these drug carriers improve bioavailability and enhance the drug effect while reducing the required dose and frequency of administration. The end result is a decrease in the toxicity and side effects for both injection and inhalation formulations [80–83].”; pg. 5, “Zashikhina et al. [109] synthesized amphiphilic charged copolymers of amino acids (hydrophilic lysine and glutamic acid, and hydrophobic phenylalanine) to form interpolyelectrolyte complexes with cationic and anionic peptides, including polymyxin B. The resulting particles were stabilized by coating with cationic or anionic polysaccharides (chitosan, heparin, alginate). ... The coatings also decreased the cytotoxicity and increased the stability of the resulting peptide delivery systems in biological media.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu’s teachings with Dubashynskaya’s teachings because both Liu and Dubashynskaya teach the administration of a polymyxin with PGA reduces toxicity. One of ordinary skill would be inclined to believe that the co-administration method taught by Liu combined with the teachings of Dubashynskaya would attenuate lung toxicity due to Dubashynskaya teaching that the co-administration can be inhaled and is known to reduce toxicity in the location it is administered.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Regarding claim 4, the teachings of Liu and Dubashynskaya are described and applied as above.
Further, Dubashynskaya teaches the therapeutic agent being delivered via inhalation helps overcome mucociliary clearance, and contribute to the penetration of antibiotics (pg. 4 “The polymeric particles, conjugates, and liposomes in the form of inhalation formulations protect drugs from the aggressive environment of the inflamed lung (high salt concentrations, changes in oxygen levels), improve interaction with mucus, help overcome mucociliary clearance, and contribute to the penetration of antibiotics into the bacterial biofilm.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu’s teachings with Dubashynskaya’s teachings because both Liu and Dubashynskaya teach the administration of a polymyxin with PGA reduces toxicity. One of ordinary skill would be inclined to believe that the co-administration method taught by Liu would be improved by the administration method taught by Dubashynskaya due to Dubashynskaya teaching that inhaling drugs helps to overcome mucociliary clearance, and contribute to the penetration of antibiotic into bacterial biofilm.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Liu (“Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria.”) as applied to claim 1 above, and further in view of Zhou & Wang, hereafter “Zhou” (WO 2019/213101 A1).
Regarding claim 7, Liu teaches a method of reducing toxicity of polymyxins as a therapeutic agent comprising a step of co-administrating a polymyxin (colistin) with PGA (pg. 133 [Abstract] “With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, a nanoformulation is herein developed through coacervate complexation with polyanionic peptides. Upon controlled mixing of cationic colistin with polyglutamic acids, formation of liquid coacervates was demonstrated. … Upon administration over a 7-day period, colistin nanoparticles also exhibited reduced hepatotoxicity as compared to free colistin.”).
Liu does not teach the method with one or more active ingredients added to the co-administration.
Zhou teaches the addition of an active ingredient (a quinolone) to a polymyxin (colistin or polymyxin B) to treat bacterial infection in the lungs (para. 8-10 “In particular, the present invention utilizes an anionic lipid as an essential component of a liposome for efficient encapsulation of Cip and Col, which affords a stable more efficient pharmaceutical composition for the treatment of a bacterial infection, especially infections of the lungs. … this present invention relates to a pharmaceutical composition comprising polymyxin, quinolone, a phosphatidylcholine (PC), an anionic lipid and cholesterol, wherein polymyxin and quinolone are encapsulated… In some illustrative embodiments, this present invention relates to a pharmaceutical composition disclosed herein, wherein said polymyxin is colistin or polymyxin B or its pharmaceutically acceptable salt; a quinolone ....”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu’s teachings with Zhou’s teachings because both inventions are drawn to treating infections of the lung using a polymyxin. Zhou teaches the addition of an antibiotic, a quinolone, results in a stable, more efficient pharmaceutical composition. One of ordinary skill in the art would think to modify the teachings of Liu with the teaching of Zhou with a reasonable expectation to improve a known technique with predictable results. See MPEP 2143 (D).
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (“Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria.”) as applied to claim 1 above, and further in view of Liu et al, here after “Liu2017” (WO 2017/032236 A1).
Regarding claim 8, Liu teaches a method of reducing toxicity of polymyxins.
Liu does not teach the molar ratio of polymyxin: PGA, PAA or combinations thereof being 1:1 to 1:20.
Liu2017 teaches a method of using a cationic antimicrobial peptide (polymyxin) in combination with polymers (PGA or PAA) to treat bacterial diseases and infections ([Abstract] “Provided in the present invention are a complex prepared from antimicrobial peptides in combination with polymers, the preparation method of the complex, and the use of the complex for preparing drugs for preventing or treating diseases or infections caused by bacteria (such as gram-positive bacteria or gram-negative bacteria), fungi or viruses.”). Liu2017 states that using the combination of cationic antimicrobial peptides and polymers can reduce the hemolytic toxicity of the antimicrobial peptides, which are needed in high doses (pg. 2-3 “Therefore, antimicrobial peptides require high doses when used, which in turn leads to hemolytic toxicity.”).Liu2017 also teaches the molar ratios of these compositions to be from 1:0.04 to 1:5 (pg. 12 “In some preferred embodiments of this application, the molar ratio of the polymer to the antimicrobial peptide is 0.04:1, 0.2:1, 0.3:1, 1:1, 3:1, or 5:1.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu’s teachings with Liu2017’s teachings because both teach a method of using polymyxins and polymers to treat gram-negative bacteria. Liu2017 states that using the combination of cationic antimicrobial peptides and polymers can reduce the hemolytic toxicity of the antimicrobial peptides, which are needed in high doses.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Regarding claim 10, the teaching of Liu are described and applied as above.
Liu does not teach the molar ratio of polymyxin: PGA, PAA or combinations thereof being 1:1 to 1:20.
Liu2017 teaches a method of using a cationic antimicrobial peptide (polymyxin) in combination with polymers (PGA or PAA) to treat bacterial diseases and infections ([Abstract] “Provided in the present invention are a complex prepared from antimicrobial peptides in combination with polymers, the preparation method of the complex, and the use of the complex for preparing drugs for preventing or treating diseases or infections caused by bacteria (such as gram-positive bacteria or gram-negative bacteria), fungi or viruses.”). Liu2017 states that using the combination of cationic antimicrobial peptides and polymers can reduce the hemolytic toxicity of the antimicrobial peptides, which are needed in high doses (pg. 2-3 “Therefore, antimicrobial peptides require high doses when used, which in turn leads to hemolytic toxicity.”). Liu2017 also teaches the molar ratios of these compositions to be from 1:0.04 to 1:5 (pg. 12 “In some preferred embodiments of this application, the molar ratio of the polymer to the antimicrobial peptide is 0.04:1, 0.2:1, 0.3:1, 1:1, 3:1, or 5:1.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu’s teachings with Liu2017’s teachings because both teach a method of using polymyxins and polymers to treat gram-negative bacteria. Liu2017 states that using the combination of cationic antimicrobial peptides and polymers can reduce the hemolytic toxicity of the antimicrobial peptides, which are needed in high doses.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Claims 11-13, 17-21, and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al, hereafter “Liu” (“Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria.” Acta Biomater. 2018 Dec;82:133-142. doi: 10.1016/j.actbio.2018.10.013. Epub 2018 Oct 11. PMID: 30316023.) in view of Vandevanter & Montgomery, hereafter “Vandevanter” (WO 9820836 A2).
Regarding claim 11, Liu teaches a process for manufacturing a therapeutic agent comprising a step of co-administrating a polymyxin (colistin) with PGA (pg. 133 [Abstract] “With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, a nanoformulation is herein developed through coacervate complexation with polyanionic peptides. Upon controlled mixing of cationic colistin with polyglutamic acids, formation of liquid coacervates was demonstrated. … Upon administration over a 7-day period, colistin nanoparticles also exhibited reduced hepatotoxicity as compared to free colistin.”).
Liu does not teach the therapeutic agent being used for nebulization.
Vandevanter teaches colistin being delivered via a dry powder, a nebulizer or an inhaler (pg. 1 lines. 17-29; “The pure colistin is devoid of impurities, has a standard high biological activity per weight of dry powder, a high temperature stability, and is suitable for aerosolization using jet or ultrasonic nebulizers as well as for delivery by dry powder or metered dose inhaler.”). Vandevanter also teaches that inhaled treatment methods are more effective than that of an aerosol therapy (pg. 3, lines. 34-37; “These studies show that combination of oral ciproflaxin with inhaled colimycin was more than five times more effective than aerosol colimycin therapy alone.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu’s teachings with Vandevanter’s teachings because both references are teaching methods of treating respiratory infections using polymyxins. One of ordinary skill in the art would have thought to take the teachings of Liu and combine them with the teachings of Vandevanter due to Vandevanter teaching that inhaled treatments are more than 5 times more effective than an aerosol administration method.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Regarding claim 12, Vandevanter further teaches the solution being for inhalation (pg. 1 lines, 17-22; “The pure colistin is devoid of impurities, has a standard high biological activity per weight of dry powder, a high temperature stability, and is suitable for aerosolization using jet or ultrasonic nebulizers as well as for delivery by dry powder or metered dose inhaler.”).
Regarding claim 13, Vandevanter further teaches the solution being for the treatment of respiratory infection by inhalation (pg. 1, lines. 13-17; “The formulation is suitable for nebulization and in its nebulized form provides an effective treatment and prophylaxis of Pseudomonas aeruginosa and other susceptible pulmonary infections such as Stenotrophomonas maltophilia.”).
Regarding claim 17, with regard to the limitation "wherein said polymyxins are selected from the group consisting of polymyxin B, colistin, or a polymyxin-like lipopeptide”, the combined teachings of Liu and Vandevanter as applied above read on this limitation.
Regarding claim 18, with regard to the limitation "wherein said polyaspartic acid or polyglutamic acid is from the group consisting of polyaspartic acid (PAA), polyglutamic acid (PGA), a combination of PAA and PGA, or a pharmaceutically acceptable salt thereof”, the combined teachings of Liu and Vandevanter as applied above read on this limitation.
Regarding claim 19, Liu teaches the process of manufacturing a dry powder composition of polyglutamic acid (PGA) and a polymyxin via freeze drying (pg. 6 “Colistin nanoparticles were subsequently analyzed for their physicochemical properties. DLS measurements showed that the 8 nm nanoparticles have a zeta potential of −3 mV, and there was no change in size or zeta potential following freeze drying and reconstitution in water (Fig. 2A). ”), but does not teach the freeze-dried product being a powder. Vandevanter teaches the co-administrating a polymyxin (colistin) with PGA ([Abstract] “With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, … complexation with polyanionic peptides.”) in a powder form (pg. 1 lines. 17-29; “The pure colistin is devoid of impurities, has a standard high biological activity per weight of dry powder… and is suitable for aerosolization using jet or ultrasonic nebulizers as well as for delivery by dry powder). Vandevanter also teaches that a dry powder formulation is convenient due to it not requiring any dilution, it having an extended shelf life (pg. 5, lines. 30-34; “The dry powder formulation is convenient because it does not require any dilution, it has an extended shelf-life and the inhalation delivery devices are portable and do not require an air compressor needed by nebulizers.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu’s teachings with Vandevanter’s teachings because both references are teaching methods of treating respiratory infections using polymyxins. One of ordinary skill in the art would have thought to take the teachings of Liu and combine them with the teachings of Vandevanter due to Vandevanter teaching that the use of a dry powder formulation is convenient due to it not requiring any dilution, and its extended shelf life.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Regarding claim 20, Vandevanter teaches a dry powder being for inhalation (pg. 1 lines, 17-22; “The pure colistin is devoid of impurities, has a standard high biological activity per weight of dry powder, a high temperature stability, and is suitable for aerosolization using jet or ultrasonic nebulizers as well as for delivery by dry powder or metered dose inhaler.”). Vandevanter also teaches that inhaled treatment methods are more effective than that of an aerosol therapy (pg. 3, lines. 34-37; “These studies show that combination of oral ciproflaxin with inhaled colimycin was more than five times more effective than aerosol colimycin therapy alone.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu’s teachings with Vandevanter’s teachings because both references are teaching methods of treating respiratory infections using polymyxins. One of ordinary skill in the art would have thought to take the teachings of Liu and combine them with the teachings of Vandevanter due to Vandevanter teaching that inhaled treatments are more than 5 times more effective than an aerosol administration method.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Regarding claim 21, Vandevanter further teaches the dry powder is for the treatment of respiratory infection by inhalation (pg. 1, lines. 13-22 “The formulation is suitable for nebulization and in its nebulized form provides an effective treatment and prophylaxis of Pseudomonas aeruginosa and other susceptible pulmonary infections such as Stenotrophomonas maltophilia. The pure colistin is devoid of impurities, has a standard high biological activity per weight of dry powder, a high temperature stability, and is suitable for aerosolization using jet or ultrasonic nebulizers as well as for delivery by dry powder or metered dose inhaler.”).
Regarding claim 23, with regard to the limitation "wherein said polymyxins are selected from the group consisting of polymyxin B, colistin, or a polymyxin-like lipopeptide”, the combined teachings of Liu and Vandevanter as applied above read on this limitation.
Regarding claim 24, with regard to the limitation "wherein said polyaspartic acid or polyglutamic acid is from the group consisting of polyaspartic acid (PAA), polyglutamic acid (PGA), a combination of PAA and PGA, or a pharmaceutically acceptable salt thereof”, the combined teachings of Liu and Vandevanter as applied above read on this limitation.
Regarding claim 25, Liu teaches the composition of claim 19, mixed into water, a pharmaceutically acceptable excipient (pg. 134 “Coacervate complexation between colistin and PGA was achieved by mixing the two components at varying ratios in water…”)
Regarding claim 26, Liu teaches the process of manufacturing a dry powder composition of polyglutamic acid (PGA) and a polymyxin via freeze drying (pg. 6 “Colistin nanoparticles were subsequently analyzed for their physicochemical properties. DLS measurements showed that the 8 nm nanoparticles have a zeta potential of −3 mV, and there was no change in size or zeta potential following freeze drying and Vandevanter further teaches the dry powder is for the treatment of respiratory infection by inhalation (pg. 1, lines. 13-22 “The formulation is suitable for nebulization and in its nebulized form provides an effective treatment and prophylaxis of Pseudomonas aeruginosa and other susceptible pulmonary infections such as Stenotrophomonas maltophilia. The pure colistin is devoid of impurities, has a standard high biological activity per weight of dry powder, a high temperature stability, and is suitable for aerosolization using jet or ultrasonic nebulizers as well as for delivery by dry powder or metered dose inhaler.”).
Claims 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (“Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria.”) and Vandevanter & Montgomery, hereafter “Vandevanter” (WO 9820836 A2), as applied to claim 11 above, and further in view of Liu et al, here after “Liu2017” (WO 2017/032236 A1).
Regarding claim 14, Liu teaches a process for manufacturing a therapeutic agent comprising a step of co-administrating a polymyxin (colistin) with PGA.
The teachings of Liu and Vandevanter, as applied to claim 11, are described and applied as above.
Liu and Vandevanter do not teach the molar ratio of polymyxin: PGA, PAA or combinations thereof being 1:1 to 1:20.
Liu2017 teaches a method of using a cationic antimicrobial peptide (polymyxin) in combination with polymers (PGA or PAA) to treat bacterial diseases and infections ([Abstract] “Provided in the present invention are a complex prepared from antimicrobial peptides in combination with polymers, the preparation method of the complex, and the use of the complex for preparing drugs for preventing or treating diseases or infections caused by bacteria (such as gram-positive bacteria or gram-negative bacteria), fungi or viruses.”). Liu2017 states that using the combination of cationic antimicrobial peptides and polymers can reduce the hemolytic toxicity of the antimicrobial peptides, which are needed in high doses (pg. 2-3 “Therefore, antimicrobial peptides require high doses when used, which in turn leads to hemolytic toxicity.”). Liu2017 also teaches the molar ratios of these compositions to be from 1:0.04 to 1:5 (pg. 12 “In some preferred embodiments of this application, the molar ratio of the polymer to the antimicrobial peptide is 0.04:1, 0.2:1, 0.3:1, 1:1, 3:1, or 5:1.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu and Vandevanter’s teachings with Liu2017’s teachings because all teach a method of using polymyxins and polymers to treat gram-negative bacteria. Liu2017 states that using the combination of cationic antimicrobial peptides and polymers can reduce the hemolytic toxicity of the antimicrobial peptides, which are needed in high doses.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Regarding claim 15, the teachings of Liu, Vandevanter and Liu2017 are described and applied as above.
Further, Vandevanter teaches the colistin formula ranging from 0.1 to 50 mg/mL (pg. 11, lines. 27-30; “The formulation comprises 1-50 mg/ml, preferably about 2-20 mg/ml in an aqueous solution, preferably saline, ranging from a full (0.9%) to a half strength, so that the formulation is preferably always isotonic.”)
Regarding claim 16, with regard to the limitation " wherein polymyxin and polyaspartic acid and/or polyglutamic acid are at a molar ratio of approximately 1:1 to approximately 1:20”, the combined teachings of Liu, Vandevanter and Liu2017 as applied (claim 14) above read on this limitation.
Claims 22 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (“Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria.”) and Vandevanter & Montgomery, hereafter “Vandevanter” (WO 9820836 A2), as applied to claim 11 above, and further in view of Liu et al, here after “Liu2017” (WO 2017/032236 A1).
Regarding claim 22, Liu teaches a process for manufacturing a therapeutic agent comprising a step of co-administrating a polymyxin (colistin) with PGA.
The teachings of Liu and Vandevanter, as applied to claim 11, are described and applied as above.
Liu and Vandevanter do not teach the molar ratio of polymyxin: PGA, PAA or combinations thereof being 1:1 to 1:20.
Liu2017 teaches a method of using a cationic antimicrobial peptide (polymyxin) in combination with polymers (PGA or PAA) to treat bacterial diseases and infections ([Abstract] “Provided in the present invention are a complex prepared from antimicrobial peptides in combination with polymers, the preparation method of the complex, and the use of the complex for preparing drugs for preventing or treating diseases or infections caused by bacteria (such as gram-positive bacteria or gram-negative bacteria), fungi or viruses.”). Liu2017 states that using the combination of cationic antimicrobial peptides and polymers can reduce the hemolytic toxicity of the antimicrobial peptides, which are needed in high doses (pg. 2-3 “Therefore, antimicrobial peptides require high doses when used, which in turn leads to hemolytic toxicity.”). Liu2017 also teaches the molar ratios of these compositions to be from 1:0.04 to 1:5 (pg. 12 “In some preferred embodiments of this application, the molar ratio of the polymer to the antimicrobial peptide is 0.04:1, 0.2:1, 0.3:1, 1:1, 3:1, or 5:1.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Liu and Vandevanter’s teachings with Liu2017’s teachings because they all teach a method of using polymyxins and polymers to treat gram-negative bacteria. Liu2017 states that using the combination of cationic antimicrobial peptides and polymers can reduce the hemolytic toxicity of the antimicrobial peptides, which are needed in high doses.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Summary
Claim 6, 16, 18, and 24 is objected to under 37 CFR 1.75. Claims 1, 3, 5-6, and 9 are rejected under 35 U.S.C. 102(a)(1). Claims 2, 4, 7-8 and 10-26 are rejected under 35 U.S.C. 103.
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Daliyah M. Brown whose telephone number is (571)272-0136. The examiner can normally be reached Monday-Thursday 9:00 am - 4:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Daliyah M. Brown/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654