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 .
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.
Claim Status
Applicant’s preliminary amendment of 06/30/2023 is acknowledged. Claims 1-5 are cancelled, and claims 6-25 are new. Claims 6-25 are currently pending and are examined on the merits herein.
Priority
The instant application is a 371 of PCT/IB2020/062551 filed on 12/30/2020 as reflected in the filing receipt dated on 12/04/2023.
Claim Objections
Claims 6-7, 9, 11, 13, 20-21, and 23 are objected to because of the following informalities:
Claims 6 and 20 each recite “which formulation comprises”, which appears to be a grammatical error and should read “in which the formulation comprises”.
Claims 6-7 and 20-21 each recite at least one instance wherein the term “Ivermectin” is inappropriately capitalized. The term should read “ivermectin”.
Claims 9 and 23 each recite the term “Caprylic/Capric Triglyceride”, which is inappropriately capitalized and should read “caprylic/capric triglyceride”.
Claim 11 recites the limitation “anydrous ethanol”, which appears to be a typographical error as evidenced by claim 24, and should read “anhydrous ethanol”.
Claim 13 recites the term “anti-oxidant”, which contains an extraneous hyphen and should read “antioxidant” to be consistent with other instant claims which recite the same term.
Appropriate correction is required.
Applicant is advised that should claim 6 be found allowable, claim 20 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. 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). In this case, even though claim 20 recites the limitation “rapidly absorbable”, both claims recite an ivermectin solution requiring the same ingredients at the same concentrations. Therefore, the resulting formulations would be identical in composition and, thus, have the same properties. The same reasoning applies to dependent claims 21, 22, 23, 24, and/or 25 should dependent claims 7, 8, 9, 11, and/or 12, respectively, be found allowable.
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.
Claims 6-25 are 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.
Claims 6 and 20 each recite the limitation “formulation in solution suitable for oral administration”. As written, it is unclear whether the formulation itself, which appears to be in the form of a solution based on the recited ingredients, is sufficient to meet the claim limitation “in solution”, or whether Applicant is claiming a formulation that must then be added into a separate, additionally-required solvent or solution to form a new solution. In the interest of compact prosecution and consistent with Applicant’s instant specification, which states that the claimed formulation is ivermectin as an insoluble active in a liquid solution (Instant Specification, Paragraph 0024), the Examiner is interpreting the claim to mean that the claimed formulation itself is in the form of a solution and is, therefore, sufficient to meet the limitation “in solution”. If Applicant intends for the claim to be interpreted as such, the Examiner recommends amending the claims to recite “formulation in the form of a solution that is suitable for oral administration”.
Claims 7-19 are rejected by virtue of their dependence on claim 6, and claims 21-25 are rejected by virtue of their dependence on claim 20, as the fail to resolve the ambiguity in question.
Claims 6 and 20 recite the plural limitations “flavorings and sweeteners”; however, claims 18 and 19, which depend from claim 6, respectively recite the singular limitations “said flavoring is” and “said sweetener is”, which seemingly contradict the plural limitations recited in the independent claim. Thus, the dependent claims create confusion as to the scope of the independent claims, and vice versa. More specifically, it is unclear the minimum number of ingredients required to meet the claims. For example, is the cherry flavoring recited in claim 18 the only flavoring required, or are additional flavorings required? Is the sucralose recited in claim 19 the only sweetener required, or are additional sweeteners required? Although claim 20 does not have related dependent claims, the formulation as claimed is identical to that recited in claim 6 and, therefore, the intended scope of claim 20 is similarly unclear. In view of the foregoing, each of claims 6, 18, 19, and 20 are indefinite in scope. The Examiner notes that Applicant’s instant specification—specifically Applicant’s only provided example formulation (Instant Specification, Page 11)—appears to permit formulations wherein only one flavoring and only one sweetener is present. If Applicant intends to claim formulations reflecting such, the Examiner recommends amending the independent claims to recite “a flavoring and a sweetener”, which allows for inclusion of one, or more than one, flavoring and/or sweetener. If Applicant intends for more than one flavoring and/or sweetener to be required, dependent claims 18 and 19 should reflect such language.
Claims 7-19 are rejected by virtue of their dependence on claim 6, and claims 21-25 are rejected by virtue of their dependence on claim 20, as the fail to resolve the ambiguity in question.
Claims 6-7 and 20-21 each recite at least one instance of the limitation “by weight”. It is unclear whether the term indicates component weight, w/w of the total composition, w/v of the total composition, etc. Therefore, the metes and bounds of the claim are indefinite. For the purpose of the prior art rejections below and consistent with Applicant’s instant specification, which presents Applicant’s exemplary formulation as measured in g/L (Instant Specification, Page 11), the claim is interpreted to mean “% w/v of the total composition”.
Claims 7-19 are rejected by virtue of their dependence on claim 6, and claims 21-25 are rejected by virtue of their dependence on claim 20, as the fail to resolve the ambiguity in question.
Claims 6 and 20 each recite the plural limitation “effective amounts”; however, claims 7 and 21, which depend from claims 6 and 20, respectively, each recite the singular limitation “said effective amount”, which seemingly contradict the plural limitations recited in the independent claims. Thus, the dependent claims create confusion as to the scope of the independent claims, and vice versa. More specifically, it is unclear whether more than one amount of ivermectin is required to meet the claims. In view of the foregoing, each of claims 6, 7, 20, and 21 are indefinite in scope. The Examiner notes that Applicant’s instant specification—specifically Applicant’s only provided example formulation (Instant Specification, Page 11)—appears to permit formulations wherein a singular amount of ivermectin is present. If Applicant intends to claim formulations reflecting such, the Examiner recommends amending the independent claims to recite “an effective amount”. If Applicant intends for a different interpretation, the claim language should reflect such.
Claim 23 recites the limitation “wherein said medium chain triglycerides”. There is insufficient antecedent basis for this limitation. Claim 23 depends from claim 20, which does not recite medium chain triglycerides. Therefore, it is unclear to which said medium chain triglycerides the claim refers, rendering the scope of the claim is indefinite. For the purposes of compact prosecution, the Examiner is interpreting the claim to depend from claim 22, which provides sufficient antecedent basis for the limitation.
Claim Interpretation
Regarding the limitation “effective amounts” recited in claims 6 and 20, with no limiting definition of the term provided in Applicant’s instant disclosure, the term is being interpreted under broadest reasonable interpretation given the plain meaning of the term in the art. Note: MPEP 2173.01(I). In this case, the term is interpreted to mean any amount of ivermectin deemed suitable for oral administration by the prior art.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 6-9, 12-13, 18-23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al. (US20130090296A1; published: 06/23/2011) in view of de Villiers (Pharmaceutical Excipients, ch. 17 & 21, p. 216-223 & 257-266; published: 10/19/2008) as evidenced by Croda (Polyethylene Glycols & Polyol Esters, p. 1-6; published: 2009).
Cho, throughout the reference, teaches a macrocyclic lactone solution formulation for controlling parasites, wherein preferred formulations comprise: a macrocyclic lactone such as ivermectin or abamectin, a vegetable or mineral oil, levamisole, an organic solvent, and additional components such as preservatives (Abstract, Claims, and Paragraphs 0013, 0063-0072).
Cho further teaches an exemplary formulation comprising: 15.04% w/v levamisole hydrochloride; 1.6% w/v ivermectin; 10% w/v dimethylacetamide; 0.02% w/v butylhydroxytoluene; 50.4% castor oil; and Crodamol GTCC up to 100 mL (Paragraphs 0089-0095, Formulation F2). Crodamol GTCC is caprylic/capric triglyceride, as evidenced by Croda (Page 4, Table).
Regarding the limitation wherein the solution is “suitable for oral administration” as recited in claims 6 and 20: Cho teaches that formulation can be applied to an animal by all application forms known in the art, including oral administration (Paragraph 0077), thereby meeting the limitation.
Regarding the amount of ivermectin recited in claims 6 and 20: As discussed in the “Claim Interpretation” section above, with no limiting definition of “effective amounts” provided in Applicant’s instant disclosure, the amount of ivermectin taught by Cho, which is suitable for oral administration for controlling parasites, meets the claim limitation. In the case that more than one amount is required to meet the claim, Cho teaches that any amount between 0.1 – 10% w/v ivermectin is suitable for use in its formulations. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate the solution using one or more amounts within the range taught by Cho, according to therapeutic need.
Regarding the amount of oily solvent recited in claims 6 and 20: The total amount of oil in Cho’s exemplary formulation is 73.34% w/v (calculated by Examiner), which closely approaches the claimed range. Cho further teaches that the amount of levamisole can be as low as 0.1% w/v and that caprylic/capric triglyceride is used in an amount sufficient to reach total volume (Paragraph 0072, Table), which is this case is 100 mL. Therefore, an ordinarily skilled artisan could at once envisage an embodiment wherein the amount of levamisole is 0.1% w/v, which would result in a total oil concentration of 88.28% w/v, which lies within and thus renders obvious the instantly claimed range.
Regarding the amount of co-solvent recited in claims 6 and 20: Dimethylacetamide is taught as an organic solvent (Paragraph 0072, Table) part of a non-aqueous solvent system comprising oil and an organic solvent (Paragraph 0014), and thus meets the limitation “co-solvent”. The amount of dimethylacetamide lies within and thus renders obvious the instantly claimed range.
Regarding the amount of co-solvent recited in claims 6 and 20: The amount of butylhydroxytoluene, which is an antioxidant as evidenced by instant claim 13, lies within and thus renders obvious the claimed range.
Regarding claims 7 and 21: The amount of ivermectin in Cho’s exemplary formulation closely approaches the claimed range. Cho further teaches that ivermectin may be present in any amount ranging from 0.1 – 10% w/v (Paragraph 0072, Table). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to adjust the amount of ivermectin within the range taught by Cho, which overlaps and thus renders obvious the claimed range, because the reference teaches that any amount within this range is suitable for controlling parasites.
Regarding claims 8, 9, 22, and 23: The caprylic/capric triglyceride of Cho reads on the instantly claimed medium chain triglycerides as evidenced by instant claims 9 and 23. Regarding the amount caprylic/capric triglyceride required by independent claims 6 and 20, Cho teaches that the amount of castor oil can be as low as 1% w/v and that caprylic/capric triglyceride is used in an amount sufficient to reach total volume (Paragraph 0072, Table), which is this case is 100 mL. Therefore, an ordinarily skilled artisan could at once envisage an embodiment wherein the amount of castor oil is 1% w/v, which would result in a concentration of caprylic/capric triglyceride of 87.28% w/v, which lies within and thus renders obvious the instantly claimed range.
Regarding claims 12, 13, and 25: The butylhydroxytoluene of Cho reads on the same as instantly claimed.
However, Cho does not expressly teach that the formulation comprises flavorings and sweeteners as recited in instant claims 6 and 20.
de Villiers teaches that flavors and sweeteners are added to oral dosage forms to improve patient acceptance of the preparation (Page 261).
Regarding the flavorings and sweeteners recited in claims 6 and 20: Because Cho teaches that its formulations can be administered orally to animals, which includes human and non-human animals (Cho, Paragraph 0075), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the formulation of Cho by further including both flavors and sweeteners, as taught by de Villiers, to improve patient acceptance of an oral dosage form of the formulation.
Regarding claim 18: It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the formulation taught by the combination of Cho and de Villiers by selecting cherry as a flavor because de Villiers teaches that this flavor is one of the most commonly used across a variety of drug classes (Page 262) to improve the palatability of a bland preparation or to mask the unpleasant taste of an active ingredient (Page 261).
Regarding claim 19: It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the formulation taught by the combination of Cho and de Villiers by further selecting sucralose, which is a high-intensity sweetener (Page 265), as a sweetener because de Villiers teaches that adding a flavor and/or sweetener that has an intense, long-lasting taste will effectively cover up the taste of a drug (Page 262).
Regarding the limitation “rapidly absorbable” recited in claim 20: The ivermectin solution taught by the combination of Cho and de Villiers, which has the same ingredients at the same concentrations as instantly claimed, would necessarily possess the same physical properties and, thus, result in a rapidly absorbable formulation as claimed. Note: MPEP 2145. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
One of ordinary skill in the art would have a reasonable expectation of success in modifying the prior art teachings as proposed because de Villiers teaches that such excipients are routinely used in oral dosage forms to improve patient acceptance of the formulation.
Claims 6-13 and 18-25 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al. (US20130090296A1; published: 06/23/2011) in view of de Villiers (Pharmaceutical Excipients, ch. 17 & 21, p. 216-223 & 257-266; published: 10/19/2008), as applied to claims 6-9, 12-13, 18-23, and 25 above, and further in view of Wang (CN1219393A; published: 06/16/1999) as evidenced by Croda (Polyethylene Glycols & Polyol Esters, p. 1-6; published: 2009).
The combination of Cho and de Villiers as evidenced by Croda teaches the invention(s) of claims 6-9, 12-13, 18-23, and 25 as discussed in detail above and further incorporated herein.
However, the combination of Cho and de Villiers does not expressly teach that the co-solvent is ethanol as recited in claim 10 or, more specifically, anhydrous ethanol as recited in claims 11 and 24.
Wang, throughout the reference, also teaches an oral liquid for treating parasitosis comprising: ivermectin, co-solvent, and vegetable oil (Abstract, Claims, and Page 0004).
Regarding claim 10: Wang specifically teaches organic solvents such as ethanol and dimethylacetamide, among a limited list of others, as suitable co-solvents for oil-based formulations of ivermectin (Paragraph 0008 and Claim 5), wherein organic solvents are routinely used to prepare oral liquids (Paragraph 0002). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the dimethylacetamide of the formulation taught by the combination of Cho and de Villiers with the ethanol of Wang according to known methods to yield the predictable result of an oil-based ivermectin formulation suitable for oral administration.
Regarding the limitation “anhydrous” recited in claims 11 and 24: Cho teaches that avermectins, including ivermectin (Paragraph 0033), are substantially insoluble in water and require a pH of about 6.6 to achieve stability (Paragraph 0029). As such, Cho teaches that its formulations exclude water (Paragraph 0030). While the combination of Cho, de Villiers, and Wang is silent as to the purity of the ethanol co-solvent, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use an anhydrous ethanol form in order to avoid introducing water, which Cho teaches negatively impacts the solubility and stability of ivermectin, into the solvent system.
One of ordinary skill in the art would have a reasonable expectation of success in modifying the prior art teachings as proposed because Wang teaches ethanol as a suitable alternative organic co-solvent to dimethylacetamide in oil-based ivermectin formulations for oral treatment of parasitosis.
Claims 6-9, 12-23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al. (US20130090296A1; published: 06/23/2011) in view of de Villiers (Pharmaceutical Excipients, ch. 17 & 21, p. 216-223 & 257-266; published: 10/19/2008), as applied to claims 6-9, 12-13, 18-23, and 25 above, and further in view of Waterman et al. (Pharmaceutical Development and Technology, vol. 7, p. 1-32; published: 2002) as evidenced by Croda (Polyethylene Glycols & Polyol Esters, p. 1-6; published: 2009).
The combination of Cho and de Villiers as evidenced by Croda teaches the invention(s) of claims 6-9, 12-13, 18-23, and 25 as discussed in detail above and further incorporated herein.
Cho further teaches that its formulations may comprise additional pharmaceutical excipients such as antioxidants, and specifically teaches butylated hydroxyanisole (same as butylhydroxyanisole) as an exemplary antioxidant (Paragraphs 0061-0062).
However, the combination of Cho and de Villiers does not expressly teach that the formulation comprises butylhydroxyanisole, DL-α-tocopherol, ascorbic acid, or malic acid as recited in dependent claims 14, 15, 16, and 17, respectively, at the concentration required in independent claim 6.
Waterman, throughout the reference, teaches that oxidation is one of the more common modes of degradation in drug products and discusses remedies for different dosage forms, including liquid formulations containing small molecules (Abstract and Page 1).
Regarding claim 14: Waterman teaches that BHA (same as butylhydroxyanisole) effectively reduces oxidation in liquid formulations at concentrations of 0.005 – 0.02% w/v (Page 26, Table 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the formulation taught by the combination of Cho and de Villiers by further including butylhydroxyanisole within the range taught by Waterman, which lies within and thus renders obvious the claimed range, in order to prevent degradation of the ivermectin formulation.
The Examiner notes that the inclusion of butylhydroxyanisole also meets alternative limitations recited in claims 12 and 25.
Regarding claims 15, 16, and 17: Waterman further teaches that other antioxidants, including Vitamin E, ascorbic acid, and malic acid, are suitable alternatives to butylhydroxyanisole for reducing oxidation in liquid formulations comprising an alcohol solvent (Page 26, Table 12). Vitamin E is a form of α-tocopherol that includes D- or DL-α-tocopherol as evidenced by de Villiers (Page 222). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the butylhydroxyanisole of the formulation taught by the combination of Cho, de Villiers, and Waterman with any of the following: Vitamin E (e.g., DL-α-tocopherol), ascorbic acid, or malic acid, as taught by Waterman, according to known methods to yield the predictable result of an ivermectin formulation with reduced degradation.
The Examiner notes that the inclusion of Vitamin E (e.g., DL-α-tocopherol), ascorbic acid, or malic acid also meets alternative limitations recited in claims 12 and 25.
One of ordinary skill in the art would have a reasonable expectation of success in modifying the prior art formulation as proposed because Cho exemplifies butylhydroxyanisole as a preferred antioxidant to be included the formulation. Further, Cho explicitly teaches that its formulations may comprise additional pharmaceutical excipients known in the art, such as an antioxidant, and Waterman teaches that Vitamin E (e.g., DL-α-tocopherol), ascorbic acid, and malic acid are useful alternative antioxidants in liquid drug formulations.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 6-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 10-20 of copending Application No. 18/029,370 (reference application) in view of Wang (CN1219393A; published: 06/16/1999), de Villiers (Pharmaceutical Excipients, ch. 17 & 21, p. 216-223 & 257-266; published: 10/19/2008), Cho et al. (US20130090296A1; published: 06/23/2011), and Waterman et al. (Pharmaceutical Development and Technology, vol. 7, p. 1-32; published: 2002).
Copending ‘370 claims are drawn to a formulation of ivermectin comprising: ivermectin in an amount between 0.5 to 2.0% by weight, wherein 0.5% by weight reads on the amount of ivermectin recited in instant claims 6, 7, 20, and 21; 60 to 80% by weight of an oily solvent, wherein 80% by weight reads on the amount of oily solvent recited in instant claims 6 and 20; 10 to 20% by weight of a surfactant; 10 to 20% by weight of a co-surfactant; and 0.1 to 0.9% by weight of an antioxidant, wherein 0.1% by weight reads on the amount of antioxidant recited in instant claims 6 and 20. Copending ‘370 claim 11 reads on instant claims 8 and 22. Copending ‘370 claim 12 reads on instant claims 9 and 23. Copending ‘370 claim 15 reads on instant claims 12 and 25. Copending ‘370 claim 19 reads on instant claim 14. Copending ‘370 claim 20 reads on instant claim 15.
Although the claims at issue are not identical, they are not patentably distinct from each other because although the copending claims are directed to a formulation to be incorporated into a softgel, which is merely an intended use of the formulation, the only structural difference between the instant and copending formulations is that instant claims 6 and 20 require 10% to 20% by weight of a co-solvent, as well as flavorings and sweeteners. Further, the claims of copending ‘370 do not explicitly recite the limitations of dependent claims 10, 11, 13, 16, 17, 18, 19, or 24.
The teachings of Wang, de Villiers, Cho, and Waterman are as set forth above and further incorporated herein.
Regarding the co-solvent recited instant claims 6, 10, and 20: Wang teaches that it is possible to formulate oil-based ivermectin solutions wherein the concentration of co-solvent ranges from 1 – 40% and the concentration of surfactant ranges from 0.1 – 80% (Claim 2). It would have been obvious to one of ordinary skill in the art to optimize the concentration of ingredients in the formulation recited in the claims of copending ‘370 to allow for incorporation of a co-solvent, such as the ethanol exemplified by Wang, within the range taught by Wang, which overlaps and thus renders obvious the claimed amount of co-solvent, in order to improve the solubility of ivermectin in the formulation.
Regarding the flavorings and sweeteners recited in instant claims 6 and 20: Because the formulation taught by the combination of copending ‘370 and Wang is intended to be administered orally and as such could be tasted by a recipient, it would have been obvious to one of ordinary skill in the art modify the formulation by further including both flavors and sweeteners, as taught by de Villiers, to improve patient acceptance of an oral dosage form of the formulation.
Regarding the limitation “rapidly absorbable” recited in claim 20: The ivermectin solution taught by the combination of copending ‘370, Wang, and de Villiers, which has the same ingredients at the same concentrations as instantly claimed, would necessarily possess the same physical properties and, thus, result in a rapidly absorbable formulation as claimed. Note: MPEP 2145. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Regarding instant claims 11 and 24: While the combination of copending ‘370 claims, Wang, and de Villiers is silent as to the purity of the ethanol co-solvent, it would have been obvious to one of ordinary skill in the art to use an anhydrous ethanol form in order to avoid introducing water, which Cho teaches negatively impacts the solubility and stability of ivermectin, into the solvent system.
Regarding instant claims 13, 16, and 17: Waterman teaches that other antioxidants, including butylhydroxytoluene (BHT), ascorbic acid, and malic acid, are suitable alternatives to butylhydroxyanisole and tocopherols for reducing oxidation in liquid formulations comprising an alcohol solvent (Page 26, Table 12). It would have been obvious to one of ordinary skill in the art to substitute the butylhydroxyanisole or the DL-α-tocopherol of the formulation taught by the combination of copending ‘370 claims, Wang, de Villiers, and Cho with any of the following: butylhydroxytoluene (BHT), ascorbic acid, and malic acid, as taught by Waterman, according to known methods to yield the predictable result of an ivermectin formulation with reduced degradation.
Regarding instant claim 18: It would have been obvious to one of ordinary skill in the art to modify the formulation taught by the combination of copending ‘370 claims, Wang, de Villiers, Cho, and Waterman by selecting cherry as a flavor because de Villiers teaches that this flavor is one of the most commonly used across a variety of drug classes (Page 262) to improve the palatability of a bland preparation or to mask the unpleasant taste of an active ingredient (Page 261).
Regarding claim 19: It would have been obvious to one of ordinary skill in the art to modify the formulation taught by the combination of copending ‘370 claims, Wang, de Villiers, Cho, and Waterman by further selecting sucralose, which is a high-intensity sweetener (Page 265), as a sweetener because de Villiers teaches that adding a flavor and/or sweetener that has an intense, long-lasting taste will effectively cover up the taste of a drug (Page 262).
One of ordinary skill in the art would have a reasonable expectation of success in modifying the claims of copending ‘370 as proposed because all ingredients and concentrations are well known in the prior art to be useful in formulating ivermectin formulations that are intended for oral administration.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH CLINKSCALES WISTNER whose telephone number is (571)270-7715. The examiner can normally be reached Monday - Thursday 8:00 AM - 5:00 PM ET.
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/SARAH C WISTNER/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616