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 is the U.S. National Stage Application, pursuant to 35 U.S.C. 371, of PCT International Application No. PCT/US2020/047551, filed August 22, 2020, which claims priority to U.S. App. No. 62/890,517, filed August 22, 2019.
Requirement for Election/Restriction -Status of the Claims
In response to the Restriction Requirement, Applicant elects Group I, identified by the Examiner as embracing claims 1-5, 8-10, and 12.
Group I Claims 1-5 8-10 and 12, are drawn to compositions comprising non-steroidal anti-inflammatory drugs (NSAIDs);
Group II Claims 19, 20, 25-27 and 31 are drawn to a method of treatment of a sore throat;
Group III Claims 13, 15, 17, 18, 25 and 26 are drawn to a product for delivery using the compositions of NSAIDs;
Group IV Claim 23 is drawn to a product for an oral spray.
In response to the Election of Species Requirement, applicant elects a composition comprising apolactoferrin (0.05% w/v), lysozyme (0.5% w/v), glycerol (5% w/v), sweetener (30% w/v), menthol (1% w/v), carboxymethyl cellulose (1% w/v), aqueous aloe extract (1% w/v), and acetylsalicylic acid 0.6% w/v). To the extent necessary (as the Examiner requested "a proper chemical name" for all excipients), Applicant elects wintergreen oil as the sweetener.
Therefore, for the reasons above and those made of record of the Office Action dated May 12, 2025 the requirement remains proper and is hereby made FINAL.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/22/2022 (6 references), 07/08/2024 (8 references) and 9/11/2025 (3 references). The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
Examiner Gauger initiated telephonic interview on December 2, 2025, with Applicant's representative Scott Goncher of Greenberg Traurig, LLP. Per our discussion, the Examiner requested that Groups I (claims 1-5, 8-10, and 12) and III (claims 13, 15, 17-18, 25 and 26) be rejoined with an additional election of either the lozenge form or the oral spray form be provided (more similar to a species election between these two compositional forms). Examiner is rejoining Groups I and III and to reflect the lozenge as the delivery route. Within Groups I and III, claims 1-5, 8-10, 12, 13, 15, and 17 are readable on a lozenge delivery. Applicant makes these elections without acquiescence to any comments made in the Restriction Requirement and do so with traverse at least for the reasons in the October 9, 2025.
Claims 1-5, 8-10, 12-13, 15, 17-20, 23, 25-27 and 31 are pending.
Claims 1-5, 8-10, 12, 13, 15, and 17 are readable on the lozenge election and are the
subject of the Office Action below.
Claim Rejections - 35 USC § 102
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 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 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Radkova, et. al., Radkova, et.al., Efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection: a randomized, non-inferiority trial in the Russian Federation, Journal of Pain Research 2017:10 1591–1600.
Claims 1 and 4 require a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients, carriers, and/or diluents and one or more non-steroidal anti-inflammatory drugs (NSAID), wherein the total concentration of NSAIDs is less than 75 mg/ml (as in claim 1) and total concentration of NSAIDs is less than 20 mg/ml (as in claim 4).
Radkova teaches the efficacy of the NSAID, flurbuprofen, at a concentration of 8.75 mg administered via a lozenge or a spray to treat patients with a sore throat caused by an upper respiratory tract infection in a randomized, multicenter trial of 440 adults with a recent-onset, moderate-to-severe sore throat due to URTI:
“Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) with proven analgesic and anti-inflammatory effects,18,19 and lozenges containing 8.75 mg flurbiprofen have been shown to be safe and effective in relieving the symptoms of a sore throat (including pain).3,20–24 Flurbiprofen 8.75 mg lozenges are available over-the-counter in many countries, and they are the only formulation of flurbiprofen currently available in Russia.”
Radkova, page 1592, paragraph 4 (emphasis added).
The use of NSAIDs in a pharmaceutical composition in the form of a lozenge at a concentration of 8.75 mg anticipates the use of a concentration of NSAIDs of both claims 1 and 4 because flurbiprofen is a NSAID delivered at a concentration of less that 75 mg/ml and 20 mg/ml respectively.
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.
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.
Claims 1-5, 13 and 15 are obvious over Bouroubi and Radkova in further view of Rathod:
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Bouroubi et.al., Pain relief of sore throat with a new anti-inflammatory throat lozenge, ibuprofen 25 mg: A randomised, double-blind, placebo-controlled, international phase III study, Int J Clin Pract. 2017;71: e12961 and in view of Radkova, et.al., Efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection: a randomized, non-inferiority trial in the Russian Federation, Journal of Pain Research 2017:10 1591–1600 and Rathod, et.al., Medicated Lozenges as an Easy to Use Dosage Form, World Journal of Pharmaceutical Research, Volume 7, Issue 16, 2018, 305-322.
By way of background, Pharyngitis, more commonly known as sore throat, is associated
with pharyngeal inflammation and is usually caused by an upper respiratory tract infection (URTI) such as the common cold, characterized by pain and inflammation of the larynx, pharynx and tonsils, is one of the most common complaints encountered in clinical practices and is typically associated with pain upon swallowing. In the majority of cases, the infection that causes the sore throat is viral in nature. Antibiotic agents are therefore not appropriate for first-line treatment. Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for many decades to treat acute pain in different locations and organs. Oral analgesics such as acetaminophen, aspirin or ibuprofen have been widely used to treat an acute sore throat.
Applicants purport a pharmaceutical composition that includes a total concentration of NSAIDs to be used to in a concentration less than 75 mg/mL (as in claim 1) and that the NSAID in the specification is identified as a salicylate derivative that includes acetylsalicylic acid (aspirin) [49] and [50] as in (claim 2), with a total concentration less than 10 mg/ml (as in claim 3) and one or more NSAIDs with a total concentration less than 20 mg/ml (as in claim 4) and a total NSAID concentration of salicylate of more than 90% 95%, to 99% by weight (as in claim 5) delivered as a lozenge (as in claim 13) and a lozenge comprising 0.1 to 10 mg of acetylsalicylic acid; aspirin (as in claim 15).
Claim 1
Bouroubi teaches how the art has used NSAIDs, including acetaminophen, aspirin, and ibuprofen in an oromucosal form for the treatment of sore throat:
“Oral analgesics such as acetaminophen, aspirin or ibuprofen have been widely used to treat acute sore throat. Low-dose topical forms, more appropriate for such a local indication, have been developed. Among these, lozenges provide the highest deposition and longest availability of the active compound in the pharyngeal cavity. Locally delivered NSAIDs for sore throat are available.”
Bouroubi, page 2, column 2 (emphasis added), and describes his goal of making oral lozenges of ibuprofen over systemic modes of administration:
“However, the main limitations of the systemic therapies are the risk of causing systemic adverse reactions whereas the concentration of the drug substance in the target tissue is low.7 To address these issues, an ibuprofen lozenge to be sucked has been developed at the low dose of 25 mg selected from an unpublished dose-range study. Compared with other locally acting forms such as throat sprays and
rinses, the lozenge pharmaceutical form provides a more targeted and longer delivery and hence is more suitable in the management of sore throat.7-9 The lozenge form is available for a variety of active ingredients for treating sore throat,9 but not for ibuprofen, despite its demonstrated efficacy for sore throat relief when administered orally.”
Bouroubi, page 2, column 1, paragraph 2 (emphasis added).
While Bouroubi teaches certain aspects of his 25 mg ibuprofen lozenge, and references other lozenge non-patent literature publications, he does not explicitly disclose the volume of the lozenge (i.e., the 25 mg/mL density limitation). However, one of ordinary skill in the art would have a reasonable expectation of success in arriving at a 25 mg/mL ibuprofen lozenge from the teaching of Bouroubi because, lozenges are generally prepared in the mass range of 1.5 g to 4.5g, and with excipients having an overall density in the range 1.2 g/mL to 1.5 g/mL would lead to Bouroubi’s lozenge meeting the density of claim 1. For example, see the teaching of Ashwini.
Rathod teaches that lozenges are typically formulated between a total mass of 1.5 g to 4.5 g and a size of about 5/8- 3/4 inch, and use many different excipients along to carry the active agent:
“Hard candy lozenges are mixtures of sugar and other carbohydrates in an amorphous (noncrystalline) or glassy state. They can also be regarded as solid syrups of sugars. The moisture content and weight of hard candy lozenge should be between, 0.5 to 1.5% and 1.5-4.5g respectively. These should undergo a slow and uniform dissolution or erosion over 5- 10 min., and should not disintegrate. The temperature requirements for their preparation is usually high hence heat labile materials cannot be incorporated in them.
Rathod, page 310-311, Hard candy lozenges, (emphasis added),
And:
“The lozenge tablets differ from conventional tablets in terms of organolepticity, non-disintegrating characteristics and slower dissolution profiles. The lozenge is made usingheavy compression equipment to give a tablet that is harder than usual, as it is desirable for the troche to dissolve slowly in mouth. They are usually flat faced with sizes, weight, hardness, and erosion time ranging between, 5/8-3/4-inch, 1.5-4 g, 30-50 kg inch2 and 5-10 min, respectively.”
Rathod, page 309 (emphasis added).
Rathod also teaches a vast array of excipients that would be used to prepare the pharmaceutical form of the lozenge.
Although Bouroubi teaches how the art has used NSAIDs including acetaminophen, aspirin, and ibuprofen (with a density limitation of concentration of 25 mg/mL), in an oromucosal form for the treatment of sore throat; including lozenges, they don’t teach the density of the of the lozenge. Rathod teaches that lozenges are typically formulated between a total mass of 1.5 g to 4.5 g and a size of about 5/8- 3/4 inch, and use many different excipients along to carry the active agent. However, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the NSAID composition of less than 75 mg/mL of the instant claim because a 25mg/mL density of the NSAID, ibuprofen, in a lozenge form is taught by Bouroubi and is clearly less than the instant claim. The average lozenge has an average total mass of between 1.5 and 4.5 grams including a range of the excipients, lubricants, binders, coloring and flavoring agents, and humectants as taught by Rathod.
Accordingly, claim 1 is rejected.
Claim 2 limits claim 1, and further requires the NSAID to be aspirin. Although Bouroubi does not exemplify aspirin as the lozenge active agent, he clearly suggests that aspirin could be used as the pharmaceutical active.
Accordingly, claim 2 is rejected.
Claims 4 and 5 limit claim 1 to total concentration of NSAIDs is less than 20 mg/ml (as in claim 4) and the total NSAID content of said composition is more than 90% or more than 95% or more than 99% salicylate and derivatives thereof by weight of the NSAID content (as in claim 5).
Radkova teaches the efficacy of the NSAID, flurbuprofen, at a concentration of 8.75 mg administered via a lozenge or a spray to treat patients with a sore throat caused by an upper respiratory tract infection in a randomized, multicenter trial of 440 adults with a recent-onset, moderate-to-severe sore throat due to URTI.:
“Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) with proven analgesic and anti-inflammatory effects,18,19 and lozenges containing 8.75 mg flurbiprofen have been shown to be safe and effective in relieving the symptoms of a sore throat (including pain).3,20–24 Flurbiprofen 8.75 mg lozenges are available over-the-counter in many countries, and they are the only formulation of flurbiprofen currently available in Russia.”
Radkova, page 1592, paragraph 4 (emphasis added).
“Flurbiprofen 8.75 mg delivered as a spray or lozenge provides effective relief from the pain associated with sore
throats due to URTI. Non-inferiority of the spray versus the
lozenge formulation was established, and both formulations
demonstrated comparable efficacy and safety profiles.”
Radkova, page 1598, Conclusion (emphasis added).
Bouroubi teaches that NSAIDs include oral analgesics such as acetaminophen, aspirin or ibuprofen that have been widely used to treat an acute sore throat and that low dose topical forms have been developed. They also teach that among these, lozenges provide the highest deposition and longest availability of the active compound in the pharyngeal cavity. Locally delivered NSAIDs for sore throat are available. They also teach that an oromucosal form of ibuprofen at a dose of 25 mg/ml is effective at treating an acute sore throat in a Phase III clinical study. Radkova teaches that a different NSAID, Flurbiprofen is delivered via a lozenge or spray to treat a sore throat due to an upper respiratory tract infection at a concentration of 8.75 mg/ml. The concentration of these NASAIDs identified by Bouroubi and Radkova are delivered as 100% of the composition of the lozenge (with unspecified other excipients/components to prepare the drug for delivery as a lozenge) and do not detail a combination of the NSAIDs.
Accordingly, one of ordinary skill in the art would have a reasonable expectation of success because by substituting the NSAID acetylsalicylic acid (aspirin) for the NSAIDs detailed by Bouroubi (ibuprofen) and Radkova (flurbiprofen) both delivered in the form of a lozenge to treat a sore throat. The applicant is substituting a known equivalent acetylsalicylic acid for the NSAIDs identified by Bouroubi and Radkova used for the same purpose of treating a sore throat with a lozenge as taught by both Bouroubi and Radkova. Therefore, the invention of the instant claims was prima facie obvious at the time it was filed.
Claims 1, 8-10, 12, and 17 are obvious over Kutta, and Radkova in further view of Rathod.
Claims 1, 8-10, 12, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Kutta et.al., Distribution of mucins and antimicrobial substances lysozyme and lactoferrin in the laryngeal subglottic region, J. Anat. (2008) 213, pp473–481 in view of Radkova, et.al., Efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection: a randomized, non-inferiority trial in the Russian Federation, Journal of Pain Research 2017:10 1591–1600 and in further view of Rathod, et.al., Medicated Lozenges as an Easy to Use Dosage Form, World Journal of Pharmaceutical Research, Volume 7, Issue 16, 2018, 305-322.
Applicants purport to having invented a pharmaceutical composition that utilizes lactoferrin and lysozyme in (as in claim 8) in a weight ratio of 1:1 to 10:1 (as in claim 9), a ratio of lactoferrin and lysozyme to NSAID is 10:1 to 1:10 (as in claim 10), in combination with one or more NSAIDs and concentrations of non-active ingredients including glycerol, a sweetener, menthol, carboxymethyl cellulose and aloe (as in claims 12 and 17).
Kutta teaches that both lactoferrin and lysozyme are naturally occurring and well-known constituents found in the airway surface and are known for their bactericidal activities; acting synergistically in combination. For example:
“Lysozyme is a low-molecular-weight protein showing bacteriostatic and bactericidal activity. It triggers bacterial autolysis by hydrolyzing the glycoside bond between N-acetylmuramic acid and N-acetylglucosamine, both components of the peptidoglycan in bacterial cell walls and thus counteracts the pathogenicity of gram-negative and gram-positive bacteria (Wilhelmus, 1985). Comparable to the supraglottis (Kutta et al. 2002), lysozyme is supposed to act as a protective agent against microbial infection in the mucous membranes of the subglottis.”
Kutta, pg. 480, column 1 (emphasis added). Further,
“Lactoferrin is another antimicrobial protein that reduces the amount of free iron available for bacteria. It provides both bacteriostatic and bactericidal protection (Legrand et al. 2005; Valenti & Antonini, 2005) and plays a role in the primary antibody response, lymphocyte proliferation, cytokine production, natural killer (NK) cell activity and regulation of complement activation (Valenti & Antonini, 2005). It appears that lactoferrin is actually produced by the serous
cells of seromucous glands of the subglottis. Like lysozyme, lactoferrin has been demonstrated in the larynx only supraglottically in the epithelium and submucosal glands of the false vocal folds (Kutta et al. 2002). The production of several antimicrobial substances, such as lysozyme and lactoferrin, leads to a more effective antimicrobial defense, as the combined action of antimicrobial substances comprises synergistic as well as additive killing effects (Singh
et al. 2000).”
Kutta, pg. 480, column 1 (emphasis added).
Although Kutta teaches that the proteins lysozyme and lactoferrin are naturally occurring in the mucus membranes of the body and have a synergistic or additive effect as antimicrobial agents when evaluated together, they don’t teach the use of them in a lozenge to treat a sore throat. Radkova does teach that the use of NSAIDs in a lozenge is useful to treat a sore throat. However, Rathod does teach that the use of and the formulation of a lozenges for medicaments has considerations including the intended release time of the drug, the use of fillers, sweeteners and binders to deliver a localized treatment to the patient. These ingredients are well known for the creation of a lozenge. For example:
“Lozenges are solid preparations that contain one or more medicaments, usually in a flavored, sweetened base, and are intended to dissolve or disintegrate slowly in the mouth or these are medicated candy intended to be dissolved slowly in the mouth to lubricate and sooth the irritated
tissues of throat”
Rathod, Abstract, pg. 305 (emphasis added), and further,
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542
765
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Rathod, Table 2, pg. 312.
Accordingly, one of ordinary skill in the art would have found that the use of a NSAID as taught by Radkova using a lozenge for delivery, with a combination of lysozyme and lactoferrin, that are both recognized and have a synergistic activity as bactericides as taught by Kutta. Combined with a lozenge formula that has a sweetener, binder (such as carboxymethyl cellulose), a humectant (such as glycerin) and aloe that has bactericidal properties and anti-inflammatory components like bradykinase would be prima facie obvious at the time of the filing because the Applicant is simply combining an OTC NSAID, acetylsalicylic acid; aspirin, with known proteins lysozyme and lactoferrin that are naturally occurring in the mucus membranes of the body and have a synergistic or additive effect as antimicrobial agents in a lozenge using known sweeteners, binders and humectants.
The combination claimed therefore appears little more than an arrangement of old elements with each performing the same function it had been known to perform and yielding no more than one would expect from such an arrangement. KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)) (indicating that “when the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.”).
Conclusion
Claims 1-5, 8-10, 12, 13, 15 and 17 are rejected.
No Claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL RANDALL GAUGER whose telephone number is (571)272-1325. The examiner can normally be reached M-F 7:30-5:00.
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/P.R.G./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629