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 .
Withdrawal of Rejections
The response and amendments filed on 12/05/2025 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality correction and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
The previous nonstatutory double patenting rejection has been withdrawn necessitated by Applicant’s amendments.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
New and/or Maintained Grounds of Rejection Necessitated by Amendments
Claim Rejections - 35 USC § 102, Anticipation
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 6, and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kumar (WO 2018/112548; Date of Publication: June 28, 2018 – cited in IDS filed on 01/27/2023 – previously cited).
Kumar’s general disclosure pertains to “A biofilm disrupting composition for disruption and/or removal of bacterial biofilms from a surface, comprising at least one redox based viscosity modifier, at least one biofilm disruptor, and at least one biocide, wherein the redox based viscosity modifier is capable of reducing disulfide links in biofilm components” (see, e.g., Kumar, abstract). Moreover, Kumar discloses that the biofilm disruptor is a protease (see, e.g., Kumar, [0038]), the redox based viscosity modifier is a disulfide bond breaking agent (see, e.g., Kumar, abstract), and the biocide is an antibiotic (see, e.g., Kumar, [0048]). Kumar discloses that the composition can be formulated for inhalation to treat respiratory diseases and infections (see, e.g., Kumar, [0061]).
Regarding claim 1 pertaining to the composition, Kumar teaches “A biofilm disrupting composition for disruption and/or removal of bacterial biofilms from a surface, comprising at least one redox based viscosity modifier, at least one biofilm disruptor, and at least one biocide, wherein the redox based viscosity modifier is capable of reducing disulfide links in biofilm components” (see, e.g., Kumar, abstract & [0025]). Moreover, Kumar teaches that the biofilm disruptor is a protease (see, e.g., Kumar, [0038]), the redox based viscosity modifier is a disulfide bond breaking agent (see, e.g., Kumar, abstract), and the biocide is an antibiotic (see, e.g., Kumar, [0048]). Moreover, Kumar teaches “In the case of a composition intended for the in-vivo removal of a biofilm, such as that found in the lungs in cystic fibrosis patients, the biocide will be a pharmacologically acceptable antibiotic” (see, e.g., Kumar, [0049]). Additionally, Kumar teaches papain as a biofilm degrading protease and which is a cysteine protease (see, e.g., Kumar, Example 3, [0070]). Furthermore, Kumar teaches “The micronized composition of this particularly preferred embodiment is suitable for inhalation and useful for the disruption and removal of bacterial biofilms found in the lungs in conditions such as cystic fibrosis, bronchitis, chronic obstructive pulmonary disease (COPD), and other airway infections in which biofilms are implicated, such as recurrent rhinosinusitis or pharyngotonsillitis” (see, e.g., Kumar, [0061]); therefore, the composition is a pharmaceutical composition and is adapted for inhalation.
Regarding claims 6 and 8 pertaining to the biofilm degrading agent, Kumar teaches that the biofilm disruptor is DNase (see, e.g., Kumar, [0038]).
Examiner’s Response to Arguments
Applicant's arguments filed 12/05/2025 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments that Kumar does not specify the particular combination of components that would be suitable for therapeutic use (remarks, pages 10-11), this argument is not persuasive because the inhalation composition refers to the “biofilm disrupting composition” (see, e.g., Kumar, [0061]), wherein the “biofilm disrupting composition” comprises “at least one redox based viscosity modifier, at least one biofilm disruptor, and at least one biocide” (see, e.g., Kumar, abstract). Furthermore, Kumar teaches “In the case of a composition intended for the in-vivo removal of a biofilm, such as that found in the lungs in cystic fibrosis patients, the biocide will be a pharmacologically acceptable antibiotic” (see, e.g., Kumar, [0049]). Additionally, Kumar teaches “The micronized composition of this particularly preferred embodiment is suitable for inhalation and useful for the disruption and removal of bacterial biofilms found in the lungs in conditions such as cystic fibrosis, bronchitis, chronic obstructive pulmonary disease (COPD), and other airway infections in which biofilms are implicated, such as recurrent rhinosinusitis or pharyngotonsillitis” (see, e.g., Kumar, [0061]). Therefore, based on the teachings of Kumar, the composition comprising at least one redox based viscosity modifier, at least one biofilm disruptor, and at least one biocide is formulated for inhalation and is suitable for therapeutic use since it is adapted for in vivo administration for treating biofilms in airways.
Regarding Applicant’s arguments pertaining to Kumar not disclosing whether the biofilm disrupter is an enzyme, a blend or surfactants, or a blend of solvents (remarks, page 11), this argument is not persuasive because Kumar teaches that the biofilm disrupter “may be at least one enzyme selected from the group consisting of protease, amylase, cellulase, and DNase. Preferably one or more of the enzymes is DNase” (see, e.g., Kumar, [0038]). Moreover, Kumar teaches in Example 3 that the biofilm disrupter is papain, a cysteine protease (see, e.g., Kumar, Example 3, [0069]). Furthermore, Kumar teaches “Alternatively, or in addition, the biofilm disruptor may comprise a blend of surfactants and/or solvents which preferably lower the surface tension of the composition” (see, e.g., Kumar, [0040]). However, Applicant uses the transitional phrase “comprising”, which is “open-ended and does not exclude additional, unrecited elements or method steps” (see, e.g., MPEP 2111.03(I)); therefore, the claimed invention could also include additional types of biofilm disruptors, such as surfactants and/or solvents along with at least one enzyme, including proteases.
Regarding Applicant’s argument regarding Kumar failing to provide an enabling disclosure that teaches a combination comprising “(i) a redox-based viscosity modifier in the form of a disulfide bond- breaking agent, (ii) a biofilm disrupter in the form of a protease, and (iii) a biocide in the form of an antibiotic” (remarks, page 11), this argument is not persuasive for multiple reasons:
First, Kumar teaches “A biofilm disrupting composition for disruption and/or removal of bacterial biofilms from a surface, comprising at least one redox based viscosity modifier, at least one biofilm disruptor, and at least one biocide, wherein the redox based viscosity modifier is capable of reducing disulfide links in biofilm components” (see, e.g., Kumar, abstract). Therefore, Kumar immediately envisages the instantly claimed invention because Kumar teaches the same three components as the instantly claimed invention, such as a biofilm disrupting composition comprising: (i) at least one redox based viscosity modifier; (ii) at least one biofilm disruptor; and (iii) at least one biocide wherein the redox based viscosity modifier is capable of reducing disulfide links in biofilm components (see, e.g., Kumar, [0017]) (see, e.g., MPEP 2131.02(III)). Therefore, the instantly claimed invention is immediately envisaged by Kumar.
Secondly, Kumar teaches “The composition of the invention comprises at least one redox based viscosity modifier. This is a biologically and pharmaceutically acceptable compound capable of reducing disulphide bonds and therefore is capable of disrupting disulphide cross-links found within glycoproteins and adhesins typically found in the basal layers of most biofilms” (see, e.g., Kumar, [0025]). Moreover, Kumar teaches “The biofilm disruptor may be at least one enzyme selected from the group consisting of protease, amylase, cellulase, and DNase. Preferably one or more of the enzymes is DNase” (see, e.g., Kumar, [0038]). Furthermore, Kumar teaches “The composition of the invention comprises at least one biocide. The biocide may be selected from an antibiotic or a disinfectant, depending on the intended use of the composition” (see, e.g., Kumar, [0048]). Therefore, based on these teachings, Kumar anticipates the instantly claimed invention.
Thirdly, the instantly claimed invention is generically claiming three components that are generically adapted for injection or inhalation. Moreover, the instantly claimed invention does not provide concentration(s) and/or formulation(s) for the instantly claimed invention. Therefore, based on this, the instantly claimed invention is broadly claiming a composition comprising a biofilm degrading protease, a disulfide bond breaking agent, and antibiotic for inhalation or injection. Based on this, as discussed above, Kumar teaches a biofilm disrupting composition comprising: (i) at least one redox based viscosity modifier; (ii) at least one biofilm disruptor; and (iii) at least one biocide wherein the redox based viscosity modifier is capable of reducing disulfide links in biofilm components (see, e.g., Kumar, [0017]). Furthermore, Kumar teaches “The micronized composition of this particularly preferred embodiment is suitable for inhalation and useful for the disruption and removal of bacterial biofilms found in the lungs in conditions such as cystic fibrosis, bronchitis, chronic obstructive pulmonary disease (COPD), and other airway infections in which biofilms are implicated, such as recurrent rhinosinusitis or pharyngotonsillitis” (see, e.g., Kumar, [0061]). Furthermore, the “adapted” language does not requires steps to be performed and does not limit the claim to a particular structure (see, e.g., MPEP 2111.04(I)). Therefore, the prior art only needs to be capable of injection or inhalation, and Kumar teaches that the composition is suitable for inhalation (see, e.g., Kumar, [0061]).
Fourthly, Kumar teaches limited species. For example, for the disulfide bond breaking agent, Kumar teaches that the disulfide bond breaking agent is a redox based viscosity modifier (see, e.g., Kumar, [0025]). For the biofilm disruptor, Kumar teaches that this disruptor is selected from the group consisting of protease, amylase, cellulase, and DNase” (see, e.g., Kumar, [0038]). For the biocide, Kumar teaches that the biocide is either an antibiotic or a disinfectant (see, e.g., Kumar, [0048]). Furthermore, Kumar teaches that if the composition is formulated for in vivo use that it would contain an antibiotic instead of a disinfectant (see, e.g., Kumar, [0049]). Therefore, due to the limited number of species taught by Kumar for each of the three components, the composition would be immediately envisaged (see, e.g., MPEP 2131.02(III)).
Fifthly, Applicant has not provided persuasive arguments that Kumar is not enabling. It is the Applicant’s burden to provide evidence, not just arguments, that the prior art is not enabling (see, e.g., MPEP 716.07 & MPEP 2121). Moreover, the prior art is not required to be exemplified in order to anticipate the claimed invention (see, e.g., MPEP 2131). In order to reject a claim as anticipated by a reference “the disclosure must teach every element required by the claim under its broadest reasonable interpretation” (see, e.g., MPEP 2131). As discussed above, Kumar teaches a biofilm disrupting composition comprising: (i) at least one redox based viscosity modifier; (ii) at least one biofilm disruptor; and (iii) at least one biocide wherein the redox based viscosity modifier is capable of reducing disulfide links in biofilm components (see, e.g., Kumar, [0017]), which anticipates the instantly claimed invention.
Sixthly, Applicant statement that Kumar confines the discussion to surface decontamination formulations is not accurate, as Kumar teaches that the composition can be adapted for in vivo administration to disrupt biofilms, wherein the composition comprises an antibiotic as the biocide (see, e.g., Kumar, [0049]-[0050]). Additionally, as set forth above, Kumar teaches that “The micronized composition of this particularly preferred embodiment is suitable for inhalation and useful for the disruption and removal of bacterial biofilms found in the lungs in conditions such as cystic fibrosis, bronchitis, chronic obstructive pulmonary disease (COPD), and other airway infections in which biofilms are implicated, such as recurrent rhinosinusitis or pharyngotonsillitis” (see, e.g., Kumar, [0061]). Therefore, Kumar does not only teach a surface decontamination formulation, but specifically teaches that the composition is adaptable for in vivo administration as a pharmaceutical composition by using an antibiotic as the biocide.
New and/or Maintained Grounds of Rejection Necessitated by Amendments
Claim Rejections - 35 USC § 103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Kumar as applied to claims 1, 6, and 8 above, and further in view of Morris (WO 2017/063023; Date of Publication: April 20, 2017 – cited in the IDS filed on 01/27/2023 – previously cited).
The teachings of Kumar are discussed above as it pertains to a composition comprising a biofilm degrading protease, a disulfide bond breaking agent, and an antibiotic.
However, Kumar does not teach: wherein the biofilm degrading protease is bromelain (claim 3); or wherein the disulfide bond breaking agent is acetylcysteine (claim 4).
Morris’ general disclosure relates to “synergistic compositions comprising bromelain, or a proteolytic fraction thereof, and cysteamine or a metabolite, pharmaceutically acceptable salt, solvate or prodrug thereof” (see, e.g., Morris, abstract). Moreover, Morris discloses that N-acetylcysteine and bromelain display synergistic mucolytic and anti-cancer effects, wherein “the synergistic combination of bromelain and cysteamine provide one or more of enhanced disintegration and/or solubilization of mucinous material, increased efficacy in reducing the production of mucin, facilitation of the removal of mucinous material from the body, a direct inhibitory effect on tumor cell growth and increased efficacy of an anti-cancer agent” (see, e.g., Morris, [0009]).
Regarding claim 3 pertaining to the biofilm degrading protease, Morris teaches bromelain (see, e.g., Morris, abstract & [0009]).
Regarding claim 4 pertaining to the disulfide bond breaking agent, Morris teaches N-acetylcysteine (see, e.g., Morris, [00102]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Kumar and Morris and utilize a biofilm degrading protease, such as bromelain, and a disulfide bond breaking agent, such as N-acetylcysteine, as taught by Morris. One would have been motivated to do so because Morris teaches “compositions comprising bromelain, or a proteolytic fraction thereof and cysteamine display synergistic mucolytic and anti-cancer effects” (see, e.g., Morris, [0009]). Furthermore, Morris teaches “the synergistic combination of bromelain and cysteamine provide one or more of enhanced disintegration and/or solubilization of mucinous material, increased efficacy in reducing the production of mucin, facilitation of the removal of mucinous material from the body, a direct inhibitory effect on tumor cell growth and increased efficacy of an anti-cancer agent” (see, e.g., Morris, [0009]). Moreover, Kumar teaches a composition comprising a biofilm degrading protease, a disulfide bond breaking agent, and an antibiotic, wherein the composition is used to disrupt and/or remove biofilms (see, e.g., Kumar, abstract), and biofilms are inherently comprised within the mucus layer of the gastrointestinal track (see, e.g., Art of Record, Damianos), . Therefore, based on the teachings of Kumar and Morris, it would have been obvious to produce a composition comprising a biofilm degrading protease, a disulfide bond breaking agent, and an antibiotic, wherein the biofilm degrading protease is bromelain and the disulfide bond breaking agent is N-acetylcysteine.. One would have expected success because Kumar and Morris both teach compositions comprising a biofilm degrading protease, a disulfide bond breaking agent for treatment of infection and/or disease.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Kumar as applied to claims 1-2, 6, and 8-9 above, and further in view of Kumar (WO 2018/112511; Date of Publication: June 28, 2018 – cited in the IDS filed on 01/27/2023 – herein referred to as “Kumar 511” – previously cited).
The teachings of Kumar are discussed above as it pertains to a composition comprising a biofilm degrading protease, a disulfide bond breaking agent, and an antibiotic.
However, Kumar does not teach: wherein the antibiotic is an aminoglycoside (claim 5).
Kumar 511’s general disclosure relates to “A biofilm disrupting composition for use in treating biofilm-mediated infections due to non-Pseudomonas micro-organisms in the Cystic Fibrosis patient. One embodiment of the composition of the invention comprises at least one biologically acceptable thiol based antioxidant and at least one antibiotic” (see, e.g., Kumar 511, abstract). Moreover, Kumar 511 discloses that aminoglycosides are effective in killing Gram-negative bacteria (see, e.g., Kumar 511, [46]) and that antibiotics are used “to kill the organisms responsible for the formation of the biofilm. This will have the secondary effect of removing the propensity of the biofilm to release infectious agents that often lead to chronic illnesses with in-vivo biofilms, or indeed serve as an environmental reservoir of infectious organisms” (see, e.g., Kumar, [0051]).
Regarding claim 5 pertaining to the antibiotic, Kumar 511 teaches that the antibiotic is an aminoglycoside (see, e.g., Kumar, [46]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Kumar’s composition comprising a biofilm degrading protease, a disulfide bond breaking agent, and an antibiotic, wherein the antibiotic is an aminoglycoside, as taught by Kumar 511. One would have been motivated to do so because Kumar 511 teaches that aminoglycosides are effective in killing Gram-negative bacteria (see, e.g., Kumar 511, [46]). Furthermore, Kumar 511 teaches that DNase I and antibiotics are effective in disrupting biofilms (see, e.g., Kumar 511, [28]). Moreover, Kumar teaches that antibiotics are used “to kill the organisms responsible for the formation of the biofilm. This will have the secondary effect of removing the propensity of the biofilm to release infectious agents that often lead to chronic illnesses with in-vivo biofilms, or indeed serve as an environmental reservoir of infectious organisms” (see, e.g., Kumar, [0051]). Therefore, based on the teachings of Kumar and Kumar 511, it would have been obvious to produce a composition comprising a biofilm degrading protease, a disulfide bond breaking agent, and an antibiotic, wherein the antibiotic is an aminoglycoside, because this composition can be used to treat Gram-negative bacteria within biofilms. One would have expected success because Kumar and Kumar 511 both teach compositions comprising antibiotics and DNase for disruption of biofilms.
Examiner’s Response to Arguments
Applicant's arguments filed 12/05/2025 have been fully considered but they are not persuasive.
Regarding Applicant’s argument that bromelain cannot be formulated in the composition for inhalation or injection due to its toxicity (remarks, pages 14-15), this argument is not persuasive for multiple reasons:
First, Applicant is clearly claiming that the biofilm degrading protease in the composition is bromelain, and that the composition is adapted for injection or inhalation by a patient. Therefore, based on Applicant’s argument that there would be toxicity issues when introducing bromelain into a patient’s body, this would result in an enablement issue for the present invention and applicant has not claimed a specific formulation that would supposedly overcome this ‘toxicity issue”. Since Applicant is claiming that bromelain cannot be administered in vivo, systemically due to its toxicity, the claimed invention could not be formulated as a whole without there being toxic side effects when administered to a patient. Furthermore, as discussed above, the claims only require a composition comprising a biofilm degrading protease, a disulfide bond breaking agent, and an antibiotic, and the prior art of Kumar anticipates this claimed invention (see, e.g., Kumar, [0017]).
Secondly, Morris teaches “Bromelain ("Br") is an extract of the pineapple plant (Ananas Comosus) comprises different thiol endopeptidases and other components such as phosphatases, glucosidases, peroxidases, cellulases, glycoproteins, carbohydrates and several protease inhibitors, and is known to have proteolytic activity in vitro and in vivo, and anti-edematous, anti-inflammatory, antithrombotic and fibrinolytic activities. The active factors in Br are biochemically characterized only in part. Nonetheless, due to its efficacy after oral administration, its safety and lack of undesired side effects, Br has good compliance among patients as a therapeutic drug” (see, e.g., Morris, [0008]). Furthermore, Morris teaches that the composition comprising bromelain can be formulated for injection, oral, topical, and intranasal administration (see, e.g., Morris, [00190]); therefore, Morris’ formulation of a composition comprising bromelain for in vivo administration further supports that bromelain is safe to be administered to patients in vivo.
Regarding Applicant’s argument that Kumar’511 does not teach a composition comprising a biofilm-degrading cysteine protease, a disulfide bond breaking agent, and an antibiotic (remarks, page 17), this argument is not persuasive because these limitations are already taught by Kumar, as discussed above. Kumar’511 was relied upon to teach that the antibiotic is an aminoglycoside within the composition, as discussed above.
Conclusion
Claims 1, 3-6, and 8 are rejected.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 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 CFR 1.17(a)) pursuant to 37 CFR 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.
Art of Record
Damianos, John et al. Gut Goo: Physiology, Diet, and Therapy of Intestinal Mucus and Biofilms in Gastrointestinal Health and Disease. Clinical Gastroenterology and Hepatology, Volume 23, Issue 2, 205 - 215
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653